Mathematical Modelling Research in Turkey: A Content Analysis Study

Science.gov (United States)

Çelik, H. Coskun

2017-01-01

The aim of the present study was to examine the mathematical modelling studies done between 2004 and 2015 in Turkey and to reveal their tendencies. Forty-nine studies were selected using purposeful sampling based on the term, "mathematical modelling" with Higher Education Academic Search Engine. They were analyzed with content analysis.…

PhyloChip microarray analysis reveals altered gastrointestinal microbial communities in a rat model of colonic hypersensitivity

Energy Technology Data Exchange (ETDEWEB)

Nelson, T.A.; Holmes, S.; Alekseyenko, A.V.; Shenoy, M.; DeSantis, T.; Wu, C.H.; Andersen, G.L.; Winston, J.; Sonnenburg, J.; Pasricha, P.J.; Spormann, A.

2010-12-01

Irritable bowel syndrome (IBS) is a chronic, episodic gastrointestinal disorder that is prevalent in a significant fraction of western human populations; and changes in the microbiota of the large bowel have been implicated in the pathology of the disease. Using a novel comprehensive, high-density DNA microarray (PhyloChip) we performed a phylogenetic analysis of the microbial community of the large bowel in a rat model in which intracolonic acetic acid in neonates was used to induce long lasting colonic hypersensitivity and decreased stool water content and frequency, representing the equivalent of human constipation-predominant IBS. Our results revealed a significantly increased compositional difference in the microbial communities in rats with neonatal irritation as compared with controls. Even more striking was the dramatic change in the ratio of Firmicutes relative to Bacteroidetes, where neonatally irritated rats were enriched more with Bacteroidetes and also contained a different composition of species within this phylum. Our study also revealed differences at the level of bacterial families and species. The PhyloChip is a useful and convenient method to study enteric microflora. Further, this rat model system may be a useful experimental platform to study the causes and consequences of changes in microbial community composition associated with IBS.

Systems biology integration of proteomic data in rodent models of depression reveals involvement of the immune response and glutamatergic signaling.

Science.gov (United States)

Carboni, Lucia; Nguyen, Thanh-Phuong; Caberlotto, Laura

2016-12-01

The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study is to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease. Network analysis is performed integrating preexisting proteomic data from rodent models of depression. The IntAct mouse and the HRPD are used as reference protein-protein interaction databases. The functionality analyses of the networks are then performed by testing overrepresented GO biological process terms and pathways. Functional enrichment analyses of the networks revealed an association with molecular processes related to depression in humans, such as those involved in the immune response. Pathways impacted by clinically effective antidepressants are modulated, including glutamatergic signaling and neurotrophic responses. Moreover, dysregulations of proteins regulating energy metabolism and circadian rhythms are implicated. The comparison with protein pathways modulated in depressive patients revealed significant overlapping. This systems biology study supports the notion that animal models can contribute to the research into the biology and therapeutics of depression. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Representing Microbial Dormancy in Soil Decomposition Models Improves Model Performance and Reveals Key Ecosystem Controls on Microbial Activity

Science.gov (United States)

He, Y.; Yang, J.; Zhuang, Q.; Wang, G.; Liu, Y.

2014-12-01

Climate feedbacks from soils can result from environmental change and subsequent responses of plant and microbial communities and nutrient cycling. Explicit consideration of microbial life history traits and strategy may be necessary to predict climate feedbacks due to microbial physiology and community changes and their associated effect on carbon cycling. In this study, we developed an explicit microbial-enzyme decomposition model and examined model performance with and without representation of dormancy at six temperate forest sites with observed soil efflux ranged from 4 to 10 years across different forest types. We then extrapolated the model to all temperate forests in the Northern Hemisphere (25-50°N) to investigate spatial controls on microbial and soil C dynamics. Both models captured the observed soil heterotrophic respiration (RH), yet no-dormancy model consistently exhibited large seasonal amplitude and overestimation in microbial biomass. Spatially, the total RH from temperate forests based on dormancy model amounts to 6.88PgC/yr, and 7.99PgC/yr based on no-dormancy model. However, no-dormancy model notably overestimated the ratio of microbial biomass to SOC. Spatial correlation analysis revealed key controls of soil C:N ratio on the active proportion of microbial biomass, whereas local dormancy is primarily controlled by soil moisture and temperature, indicating scale-dependent environmental and biotic controls on microbial and SOC dynamics. These developments should provide essential support to modeling future soil carbon dynamics and enhance the avenue for collaboration between empirical soil experiment and modeling in the sense that more microbial physiological measurements are needed to better constrain and evaluate the models.

Floodplain forest succession reveals fluvial processes: A hydrogeomorphic model for temperate riparian woodlands.

Science.gov (United States)

Egger, Gregory; Politti, Emilio; Lautsch, Erwin; Benjankar, Rohan; Gill, Karen M; Rood, Stewart B

2015-09-15

River valley floodplains are physically-dynamic environments where fluvial processes determine habitat gradients for riparian vegetation. These zones support trees and shrubs whose life stages are adapted to specific habitat types and consequently forest composition and successional stage reflect the underlying hydrogeomorphic processes and history. In this study we investigated woodland vegetation composition, successional stage and habitat properties, and compared these with physically-based indicators of hydraulic processes. We thus sought to develop a hydrogeomorphic model to evaluate riparian woodland condition based on the spatial mosaic of successional phases of the floodplain forest. The study investigated free-flowing and dam-impacted reaches of the Kootenai and Flathead Rivers, in Idaho and Montana, USA and British Columbia, Canada. The analyses revealed strong correspondence between vegetation assessments and metrics of fluvial processes indicating morphodynamics (erosion and shear stress), inundation and depth to groundwater. The results indicated that common successional stages generally occupied similar hydraulic environments along the different river segments. Comparison of the spatial patterns between the free-flowing and regulated reaches revealed greater deviation from the natural condition for the braided channel segment than for the meandering segment. This demonstrates the utility of the hydrogeomorphic approach and suggests that riparian woodlands along braided channels could have lower resilience than those along meandering channels and might be more vulnerable to influences such as from river damming or climate change. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

Science.gov (United States)

Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

2016-08-18

Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

Diverse binding site structures revealed in homology models of polyreactive immunoglobulins

Science.gov (United States)

Ramsland, Paul A.; Guddat, Luke W.; Edmundson, Allen B.; Raison, Robert L.

1997-09-01

We describe here computer-assisted homology models of the combiningsite structure of three polyreactive immunoglobulins. Template-based modelsof Fv (VL-VH) fragments were derived forthe surface IgM expressed by the malignant CD5 positive B cells from threepatients with chronic lymphocytic leukaemia (CLL). The conserved frameworkregions were constructed using crystal coordinates taken from highlyhomologous human variable domain structures (Pot and Hil). Complementaritydetermining regions (CDRs) were predicted by grafting loops, taken fromknown immunoglobulin structures, onto the Fv framework models. The CDRtemplates were chosen, where possible, to be of the same length and of highresidue identity or similarity. LCDR1, 2 and 3 as well as HCDR1 and 2 forthe Fv were constructed using this strategy. For HCDR3 prediction, adatabase containing the Cartesian coordinates of 30 of these loops wascompiled from unliganded antibody X-ray crystallographic structures and anHCDR3 of the same length as that of the B CLL Fv was selected as a template.In one case (Yar), the resulting HCDR3 model gave unfavourable interactionswhen incorporated into the Fv model. This HCDR3 was therefore modelled usingan alternative strategy of construction of the loop stems, using apreviously described HCDR3 conformation (Pot), followed by chain closurewith a β-turn. The template models were subjected to positionalrefinement using energy minimisation and molecular dynamics simulations(X-PLOR). An electrostatic surface description (GRASP) did not reveal acommon structural feature within the binding sites of the three polyreactiveFv. Thus, polyreactive immunoglobulins may recognise similar and multipleantigens through a diverse array of binding site structures.

Landmark Study Reveals Antarctic Glacier's Long History of Retreat

OpenAIRE

Kuska, Dale M.

2016-01-01

Faculty Showcase Archive Article Approved for public release; distribution is unlimited. A major study, released in late November in the journal “Nature,” reveals the history of retreat of the massive Pine Island Glacier (PIG) in western Antarctica, widely considered one of the largest contributors to global sea-level rise.

A Reformulation of the Dual Career Conceptual Model for Analysis in an Organizational Scope: Revealing new Aspects

Directory of Open Access Journals (Sweden)

Heliani Berlato

2017-01-01

Full Text Available Couples who live a dual career, in general, are characterized by their continuing professional engagement and their desire for personal growth together. It is a synergy between career aspirations and family sphere, so that they co-exist; reflecting nowadays, a challenge for people who seek to live this duality. Not exempt from it, it is possible to understand the need for management models of people who are in harmony with the desires of dual career couples who are part of organizations. If in the 1980s the existence of dual career couples was not so common in Brazil, nowadays organizations increasingly receive these couples, which impacts the need for people management models to keep up with these social changes. Therefore, the model recognizes that the personal dimension (impacts on the organizational context cannot be avoided, and also that other factors affect both spheres (personal and organizational when referring to the normative roles that permeate these areas. The main intention of this essay is to construct a theoretical model of dual career to consider the factor - organization, as vital to understand (and accept the need to consider other dimensions on the dual career analytical perspective. The first evidences of dual career studies in Brazil revealed that the look at this movement only from the individual's margin is limited. This way, to consider the existence of other dimensions and consequently the influences they may cause, favors an expansion of the perspective, and also brings a detailing about the external factors (organization, society and culture that influence the dual career couple. To consider that this couple, as well as having personal challenges in the relationship between work and family, is subject to the culture that regulates their roles (men and women and that directly influences how organizations will handle that topic reveals the merit of this study. This, in turn, draws attention to the organizational sphere

Gaussian graphical modeling reveals specific lipid correlations in glioblastoma cells

Science.gov (United States)

Mueller, Nikola S.; Krumsiek, Jan; Theis, Fabian J.; Böhm, Christian; Meyer-Bäse, Anke

2011-06-01

Advances in high-throughput measurements of biological specimens necessitate the development of biologically driven computational techniques. To understand the molecular level of many human diseases, such as cancer, lipid quantifications have been shown to offer an excellent opportunity to reveal disease-specific regulations. The data analysis of the cell lipidome, however, remains a challenging task and cannot be accomplished solely based on intuitive reasoning. We have developed a method to identify a lipid correlation network which is entirely disease-specific. A powerful method to correlate experimentally measured lipid levels across the various samples is a Gaussian Graphical Model (GGM), which is based on partial correlation coefficients. In contrast to regular Pearson correlations, partial correlations aim to identify only direct correlations while eliminating indirect associations. Conventional GGM calculations on the entire dataset can, however, not provide information on whether a correlation is truly disease-specific with respect to the disease samples and not a correlation of control samples. Thus, we implemented a novel differential GGM approach unraveling only the disease-specific correlations, and applied it to the lipidome of immortal Glioblastoma tumor cells. A large set of lipid species were measured by mass spectrometry in order to evaluate lipid remodeling as a result to a combination of perturbation of cells inducing programmed cell death, while the other perturbations served solely as biological controls. With the differential GGM, we were able to reveal Glioblastoma-specific lipid correlations to advance biomedical research on novel gene therapies.

Integrative Analysis of Subcellular Quantitative Proteomics Studies Reveals Functional Cytoskeleton Membrane-Lipid Raft Interactions in Cancer.

Science.gov (United States)

Shah, Anup D; Inder, Kerry L; Shah, Alok K; Cristino, Alexandre S; McKie, Arthur B; Gabra, Hani; Davis, Melissa J; Hill, Michelle M

2016-10-07

Lipid rafts are dynamic membrane microdomains that orchestrate molecular interactions and are implicated in cancer development. To understand the functions of lipid rafts in cancer, we performed an integrated analysis of quantitative lipid raft proteomics data sets modeling progression in breast cancer, melanoma, and renal cell carcinoma. This analysis revealed that cancer development is associated with increased membrane raft-cytoskeleton interactions, with ∼40% of elevated lipid raft proteins being cytoskeletal components. Previous studies suggest a potential functional role for the raft-cytoskeleton in the action of the putative tumor suppressors PTRF/Cavin-1 and Merlin. To extend the observation, we examined lipid raft proteome modulation by an unrelated tumor suppressor opioid binding protein cell-adhesion molecule (OPCML) in ovarian cancer SKOV3 cells. In agreement with the other model systems, quantitative proteomics revealed that 39% of OPCML-depleted lipid raft proteins are cytoskeletal components, with microfilaments and intermediate filaments specifically down-regulated. Furthermore, protein-protein interaction network and simulation analysis showed significantly higher interactions among cancer raft proteins compared with general human raft proteins. Collectively, these results suggest increased cytoskeleton-mediated stabilization of lipid raft domains with greater molecular interactions as a common, functional, and reversible feature of cancer cells.

Landscape effects on demersal fish revealed by field observations and predictive seabed modelling.

Science.gov (United States)

Elliott, Sophie A M; Sabatino, Alessandro D; Heath, Michael R; Turrell, William R; Bailey, David M

2017-01-01

Nature conservation and fisheries management often focus on particular seabed features that are considered vulnerable or important to commercial species. As a result, individual seabed types are protected in isolation, without any understanding of what effect the mixture of seabed types within the landscape has on ecosystem functions. Here we undertook predictive seabed modelling within a coastal marine protected area using observations from underwater stereo-video camera deployments and environmental information (depth, wave fetch, maximum tidal speeds, distance from coast and underlying geology). The effect of the predicted substratum type, extent and heterogeneity or the diversity of substrata, within a radius of 1500 m around each camera deployment of juvenile gadoid relative abundance was analysed. The predicted substratum model performed well with wave fetch and depth being the most influential predictor variables. Gadus morhua (Atlantic cod) were associated with relatively more rugose substrata (Algal-gravel-pebble and seagrass) and heterogeneous landscapes, than Melanogrammus aeglefinus (haddock) or Merlangius merlangus (whiting) (sand and mud). An increase in M. merlangus relative abundance was observed with increasing substratum extent. These results reveal that landscape effects should be considered when protecting the seabed for fish and not just individual seabed types. The landscape approach used in this study therefore has important implications for marine protected area, fisheries management and monitoring advice concerning demersal fish populations.

On the square arc voltage waveform model in magnetic discharge lamp studies

OpenAIRE

Molina, Julio; Sainz Sapera, Luis; Mesas García, Juan José

2011-01-01

The current number of magnetic and electronic ballast discharge lamps in power distribution systems is increasing because they perform better than incandescent lamps. This paper studies the magnetic discharge lamp modeling. In particular, the arc voltage waveform is analyzed and the limitations of the square waveform model are revealed from experimental measurements.

Small angle X-ray scattering study of calreticulin reveals conformational plasticity

DEFF Research Database (Denmark)

Toft, Katrine Nørgaard; Larsen, Nanna; Jørgensen, Flemming Steen

2008-01-01

. The data from the calreticulin monomer reveal the shape of calreticulin in solution: The previously structurally un-described C-terminal is seen as a globular domain, and the P-domain beta-hairpin extends from the N-domain in a spiral like conformation. In the calreticulin solution dimer, the N-, C-, and P......-domains are easily identified, and the P-domain is in an extended conformation connecting to the second calreticulin molecule. The SAXS solution data enables the construction of a medium-resolution model of calreticulin. In the light of the unresolved chaperone mechanism of calreticulin and calnexin, we discuss...

Study on an equivalent continuum model at the Mizunami Underground Research Laboratory

International Nuclear Information System (INIS)

Tanno, Takeo; Sato, Toshinori; Matsui, Hiroya; Sanada, Hiroyuki; Kumasaka, Hiroo; Tada, Hiroyuki

2012-01-01

The Japan Atomic Energy Agency (JAEA) is conducting the MIzunami Underground research laboratory (MIU) Project in order to develop comprehensive geological investigation and engineering techniques for deep underground applications (e.g. geological disposal of HLW). This modelling study has a two-fold objective, to contribute to the evaluation of the mechanical stability of shaft and research drifts, and to plan the future studies. A crack tensor model, a method of an equivalent continuum model, has been studied at the MIU. In this study, the relationship between the estimated crack tensor parameters and the rock mass classification was revealed. (author)

Revealing transboundary and local air pollutant sources affecting Metro Manila through receptor modeling studies

International Nuclear Information System (INIS)

Pabroa, Preciosa Corazon B.; Bautista VII, Angel T.; Santos, Flora L.; Racho, Joseph Michael D.

2011-01-01

Ambient fine particulate matter (PM 2 .5) levels at the Metro Manila air sampling stations of the Philippine Nuclear Research Research Institute were found to be above the WHO guideline value of 10 μg m 3 indicating, in general, very poor air quality in the area. The elemental components of the fine particulate matter were obtained using the energy-dispersive x-ray fluorescence spectrometry. Positive matrix factorization, a receptor modelling tool, was used to identify and apportion air pollution sources. Location of probable transboundary air pollutants were evaluated using HYSPLIT (Hybrid Single Particle Lagrangian Integrated Trajectory Model) while location of probable local air pollutant sources were determined using the conditional probability function (CPF). Air pollutant sources can either be natural or anthropogenic. This study has shown natural air pollutant sources such as volcanic eruptions from Bulusan volcano in 2006 and from Anatahan volcano in 2005 to have impacted on the region. Fine soils was shown to have originated from China's Mu US Desert some time in 2004. Smoke in the fine fraction in 2006 show indications of coming from forest fires in Sumatra and Borneo. Fine particulate Pb in Valenzuela was shown to be coming from the surrounding area. Many more significant air pollution impacts can be evaluated with the identification of probable air pollutant sources with the use of elemental fingerprints and locating these sources with the use of HYSPLIT and CPF. (author)

QUALITY OF AN ACADEMIC STUDY PROGRAMME - EVALUATION MODEL

Directory of Open Access Journals (Sweden)

Mirna Macur

2016-01-01

Full Text Available Quality of an academic study programme is evaluated by many: employees (internal evaluation and by external evaluators: experts, agencies and organisations. Internal and external evaluation of an academic programme follow written structure that resembles on one of the quality models. We believe the quality models (mostly derived from EFQM excellence model don’t fit very well into non-profit activities, policies and programmes, because they are much more complex than environment, from which quality models derive from (for example assembly line. Quality of an academic study programme is very complex and understood differently by various stakeholders, so we present dimensional evaluation in the article. Dimensional evaluation, as opposed to component and holistic evaluation, is a form of analytical evaluation in which the quality of value of the evaluand is determined by looking at its performance on multiple dimensions of merit or evaluation criteria. First stakeholders of a study programme and their views, expectations and interests are presented, followed by evaluation criteria. They are both joined into the evaluation model revealing which evaluation criteria can and should be evaluated by which stakeholder. Main research questions are posed and research method for each dimension listed.

Study on Regional Agro-ecological Risk and Pressure Supported by City Expansion Model and SERA Model - A Case Study of Selangor, Malaysia

OpenAIRE

Shi , Xiaoxia; Zhang , Yaoli; Peng , Cheng

2010-01-01

International audience; This study revealed the influence of city expansion on the agro-ecological risks through the analysis and prediction of city expansion in different periods and study on the change of risk and pressure on the regional agricultural eco-environment. The city expansion of Selangor, Malaysia (as a case) was predicted based on relevant spatial and attribute data as well as simulation prediction models of city expansion. Subsequently, the ecological risk and pressure in the s...

Data-driven modeling of sleep EEG and EOG reveals characteristics indicative of pre-Parkinson's and Parkinson's disease.

Science.gov (United States)

Christensen, Julie A E; Zoetmulder, Marielle; Koch, Henriette; Frandsen, Rune; Arvastson, Lars; Christensen, Søren R; Jennum, Poul; Sorensen, Helge B D

2014-09-30

Manual scoring of sleep relies on identifying certain characteristics in polysomnograph (PSG) signals. However, these characteristics are disrupted in patients with neurodegenerative diseases. This study evaluates sleep using a topic modeling and unsupervised learning approach to identify sleep topics directly from electroencephalography (EEG) and electrooculography (EOG). PSG data from control subjects were used to develop an EOG and an EEG topic model. The models were applied to PSG data from 23 control subjects, 25 patients with periodic leg movements (PLMs), 31 patients with idiopathic REM sleep behavior disorder (iRBD) and 36 patients with Parkinson's disease (PD). The data were divided into training and validation datasets and features reflecting EEG and EOG characteristics based on topics were computed. The most discriminative feature subset for separating iRBD/PD and PLM/controls was estimated using a Lasso-regularized regression model. The features with highest discriminability were the number and stability of EEG topics linked to REM and N3, respectively. Validation of the model indicated a sensitivity of 91.4% and a specificity of 68.8% when classifying iRBD/PD patients. The topics showed visual accordance with the manually scored sleep stages, and the features revealed sleep characteristics containing information indicative of neurodegeneration. This study suggests that the amount of N3 and the ability to maintain NREM and REM sleep have potential as early PD biomarkers. Data-driven analysis of sleep may contribute to the evaluation of neurodegenerative patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Mechanism study of pulsus paradoxus using mechanical models.

Directory of Open Access Journals (Sweden)

Chang-yang Xing

Full Text Available Pulsus paradoxus is an exaggeration of the normal inspiratory decrease in systolic blood pressure. Despite a century of attempts to explain this sign consensus is still lacking. To solve the controversy and reveal the exact mechanism, we reexamined the characteristic anatomic arrangement of the circulation system in the chest and designed these mechanical models based on related hydromechanic principles. Model 1 was designed to observe the primary influence of respiratory intrathoracic pressure change (RIPC on systemic and pulmonary venous return systems (SVR and PVR respectively. Model 2, as an equivalent mechanical model of septal swing, was to study the secondary influence of RIPC on the motion of the interventriclar septum (IVS, which might be the direct cause for pulsus paradoxus. Model 1 demonstrated that the simulated RIPC had different influence on the simulated SVR and PVR. It increased the volume of the simulated right ventricle (SRV when the internal pressure was kept constant (8.16 cmH2O, while it had the opposite effect on PVR. Model 2 revealed the three major factors determining the respiratory displacement of IVS in normal and different pathophysiological conditions: the magnitude of RIPC, the pressure difference between the two ventricles and the intrapericardial pressure. Our models demonstrate that the different anatomical arrangement of the two venous return systems leads to a different effect of RIPC on right and left ventricles, and thus a pressure gradient across IVS that tends to shift IVS left- and rightwards. When the leftward displacement of IVS reaches a considerable amplitude in some pathologic condition such as cardiac tamponade, the pulsus paradoxus occurs.

A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis.

Directory of Open Access Journals (Sweden)

Guillem Casanovas

2014-01-01

Full Text Available Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.

Using animal models to study post-partum psychiatric disorders.

Science.gov (United States)

Perani, C V; Slattery, D A

2014-10-01

The post-partum period represents a time during which all maternal organisms undergo substantial plasticity in a wide variety of systems in order to ensure the well-being of the offspring. Although this time is generally associated with increased calmness and decreased stress responses, for a substantial subset of mothers, this period represents a time of particular risk for the onset of psychiatric disorders. Thus, post-partum anxiety, depression and, to a lesser extent, psychosis may develop, and not only affect the well-being of the mother but also place at risk the long-term health of the infant. Although the risk factors for these disorders, as well as normal peripartum-associated adaptations, are well known, the underlying aetiology of post-partum psychiatric disorders remains poorly understood. However, there have been a number of attempts to model these disorders in basic research, which aim to reveal their underlying mechanisms. In the following review, we first discuss known peripartum adaptations and then describe post-partum mood and anxiety disorders, including their risk factors, prevalence and symptoms. Thereafter, we discuss the animal models that have been designed in order to study them and what they have revealed about their aetiology to date. Overall, these studies show that it is feasible to study such complex disorders in animal models, but that more needs to be done in order to increase our knowledge of these severe and debilitating mood and anxiety disorders. © 2014 The British Pharmacological Society.

Studying the Consistency between and within the Student Mental Models for Atomic Structure

Science.gov (United States)

Zarkadis, Nikolaos; Papageorgiou, George; Stamovlasis, Dimitrios

2017-01-01

Science education research has revealed a number of student mental models for atomic structure, among which, the one based on Bohr's model seems to be the most dominant. The aim of the current study is to investigate the coherence of these models when students apply them for the explanation of a variety of situations. For this purpose, a set of…

Quantitative proteomic study of Aspergillus Fumigatus secretome revealed deamidation of secretory enzymes.

Science.gov (United States)

Adav, Sunil S; Ravindran, Anita; Sze, Siu Kwan

2015-04-24

Aspergillus sp. plays an essential role in lignocellulosic biomass recycling and is also exploited as cell factories for the production of industrial enzymes. This study profiled the secretome of Aspergillus fumigatus when grown with cellulose, xylan and starch by high throughput quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ). Post translational modifications (PTMs) of proteins play a critical role in protein functions. However, our understanding of the PTMs in secretory proteins is limited. Here, we present the identification of PTMs such as deamidation of secreted proteins of A. fumigatus. This study quantified diverse groups of extracellular secreted enzymes and their functional classification revealed cellulases and glycoside hydrolases (32.9%), amylases (0.9%), hemicellulases (16.2%), lignin degrading enzymes (8.1%), peptidases and proteases (11.7%), chitinases, lipases and phosphatases (7.6%), and proteins with unknown function (22.5%). The comparison of quantitative iTRAQ results revealed that cellulose and xylan stimulates expression of specific cellulases and hemicellulases, and their abundance level as a function of substrate. In-depth data analysis revealed deamidation as a major PTM of key cellulose hydrolyzing enzymes like endoglucanases, cellobiohydrolases and glucosidases. Hemicellulose degrading endo-1,4-beta-xylanase, monosidases, xylosidases, lignin degrading laccase, isoamyl alcohol oxidase and oxidoreductases were also found to be deamidated. The filamentous fungi play an essential role in lignocellulosic biomass recycling and fungal strains belonging to Aspergillus were also exploited as cell factories for the production of organic acids, pharmaceuticals, and industrially important enzymes. In this study, extracellular proteins secreted by thermophilic A. fumigatus when grown with cellulose, xylan and starch were profiled using isobaric tags for relative and absolute quantification (iTRAQ) by

Puerto Rico Revealed Preference Survey Data 2004

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Revealed preference models provide insights into recreational angler behavior and the economic value of recreational fishing trips. Revealed preference data is...

Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Xia, Xiaojun [The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Park, Eunmi [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Fischer, Susan M. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78967 (United States); Hu, Yinling, E-mail: huy2@mail.nih.gov [Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701 (United States)

2013-02-15

Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside.

Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

International Nuclear Information System (INIS)

Xia, Xiaojun; Park, Eunmi; Fischer, Susan M.; Hu, Yinling

2013-01-01

Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside

Assessing Asset Pricing Models Using Revealed Preference

OpenAIRE

Jonathan B. Berk; Jules H. van Binsbergen

2014-01-01

We propose a new method of testing asset pricing models that relies on using quantities rather than prices or returns. We use the capital flows into and out of mutual funds to infer which risk model investors use. We derive a simple test statistic that allows us to infer, from a set of candidate models, the model that is closest to the model that investors use in making their capital allocation decisions. Using this methodology, we find that of the models most commonly used in the literature,...

Probabilistic Inference: Task Dependency and Individual Differences of Probability Weighting Revealed by Hierarchical Bayesian Modeling.

Science.gov (United States)

Boos, Moritz; Seer, Caroline; Lange, Florian; Kopp, Bruno

2016-01-01

Cognitive determinants of probabilistic inference were examined using hierarchical Bayesian modeling techniques. A classic urn-ball paradigm served as experimental strategy, involving a factorial two (prior probabilities) by two (likelihoods) design. Five computational models of cognitive processes were compared with the observed behavior. Parameter-free Bayesian posterior probabilities and parameter-free base rate neglect provided inadequate models of probabilistic inference. The introduction of distorted subjective probabilities yielded more robust and generalizable results. A general class of (inverted) S-shaped probability weighting functions had been proposed; however, the possibility of large differences in probability distortions not only across experimental conditions, but also across individuals, seems critical for the model's success. It also seems advantageous to consider individual differences in parameters of probability weighting as being sampled from weakly informative prior distributions of individual parameter values. Thus, the results from hierarchical Bayesian modeling converge with previous results in revealing that probability weighting parameters show considerable task dependency and individual differences. Methodologically, this work exemplifies the usefulness of hierarchical Bayesian modeling techniques for cognitive psychology. Theoretically, human probabilistic inference might be best described as the application of individualized strategic policies for Bayesian belief revision.

Ex-vivo diffusion MRI reveals microstructural alterations in stress-sensitive brain regions: A chronic mild stress recovery study

DEFF Research Database (Denmark)

Khan, Ahmad Raza; Hansen, Brian; Wiborg, Ove

Depression is a leading cause of disability worldwide and causes significant microstructural alterations in stress-sensitive brain regions. However, the potential recovery of these microstructural alterations has not previously been investigated, which we, therefore, set out to do using diffusion...... MRI (d-MRI) in the chronic mild stress (CMS) rat model of depression. This study reveals significant microstructural alterations after 8 weeks of recovery, in the opposite direction to change induced by stress in the acute phase of the experiment. Such findings may be useful in the prognosis...... of depression or for monitoring treatment response....

Automatic generation of predictive dynamic models reveals nuclear phosphorylation as the key Msn2 control mechanism.

Science.gov (United States)

Sunnåker, Mikael; Zamora-Sillero, Elias; Dechant, Reinhard; Ludwig, Christina; Busetto, Alberto Giovanni; Wagner, Andreas; Stelling, Joerg

2013-05-28

Predictive dynamical models are critical for the analysis of complex biological systems. However, methods to systematically develop and discriminate among systems biology models are still lacking. We describe a computational method that incorporates all hypothetical mechanisms about the architecture of a biological system into a single model and automatically generates a set of simpler models compatible with observational data. As a proof of principle, we analyzed the dynamic control of the transcription factor Msn2 in Saccharomyces cerevisiae, specifically the short-term mechanisms mediating the cells' recovery after release from starvation stress. Our method determined that 12 of 192 possible models were compatible with available Msn2 localization data. Iterations between model predictions and rationally designed phosphoproteomics and imaging experiments identified a single-circuit topology with a relative probability of 99% among the 192 models. Model analysis revealed that the coupling of dynamic phenomena in Msn2 phosphorylation and transport could lead to efficient stress response signaling by establishing a rate-of-change sensor. Similar principles could apply to mammalian stress response pathways. Systematic construction of dynamic models may yield detailed insight into nonobvious molecular mechanisms.

Analysis of the fibroblast growth factor system reveals alterations in a mouse model of spinal muscular atrophy.

Science.gov (United States)

Hensel, Niko; Ratzka, Andreas; Brinkmann, Hella; Klimaschewski, Lars; Grothe, Claudia; Claus, Peter

2012-01-01

The monogenetic disease Spinal Muscular Atrophy (SMA) is characterized by a progressive loss of motoneurons leading to muscle weakness and atrophy due to severe reduction of the Survival of Motoneuron (SMN) protein. Several models of SMA show deficits in neurite outgrowth and maintenance of neuromuscular junction (NMJ) structure. Survival of motoneurons, axonal outgrowth and formation of NMJ is controlled by neurotrophic factors such as the Fibroblast Growth Factor (FGF) system. Besides their classical role as extracellular ligands, some FGFs exert also intracellular functions controlling neuronal differentiation. We have previously shown that intracellular FGF-2 binds to SMN and regulates the number of a subtype of nuclear bodies which are reduced in SMA patients. In the light of these findings, we systematically analyzed the FGF-system comprising five canonical receptors and 22 ligands in a severe mouse model of SMA. In this study, we demonstrate widespread alterations of the FGF-system in both muscle and spinal cord. Importantly, FGF-receptor 1 is upregulated in spinal cord at a pre-symptomatic stage as well as in a mouse motoneuron-like cell-line NSC34 based model of SMA. Consistent with that, phosphorylations of FGFR-downstream targets Akt and ERK are increased. Moreover, ERK hyper-phosphorylation is functionally linked to FGFR-1 as revealed by receptor inhibition experiments. Our study shows that the FGF system is dysregulated at an early stage in SMA and may contribute to the SMA pathogenesis.

Local-scale models reveal ecological niche variability in amphibian and reptile communities from two contrasting biogeographic regions

Directory of Open Access Journals (Sweden)

Alberto Muñoz

2016-10-01

Full Text Available Ecological Niche Models (ENMs are widely used to describe how environmental factors influence species distribution. Modelling at a local scale, compared to a large scale within a high environmental gradient, can improve our understanding of ecological species niches. The main goal of this study is to assess and compare the contribution of environmental variables to amphibian and reptile ENMs in two Spanish national parks located in contrasting biogeographic regions, i.e., the Mediterranean and the Atlantic area. The ENMs were built with maximum entropy modelling using 11 environmental variables in each territory. The contributions of these variables to the models were analysed and classified using various statistical procedures (Mann–Whitney U tests, Principal Components Analysis and General Linear Models. Distance to the hydrological network was consistently the most relevant variable for both parks and taxonomic classes. Topographic variables (i.e., slope and altitude were the second most predictive variables, followed by climatic variables. Differences in variable contribution were observed between parks and taxonomic classes. Variables related to water availability had the larger contribution to the models in the Mediterranean park, while topography variables were decisive in the Atlantic park. Specific response curves to environmental variables were in accordance with the biogeographic affinity of species (Mediterranean and non-Mediterranean species and taxonomy (amphibians and reptiles. Interestingly, these results were observed for species located in both parks, particularly those situated at their range limits. Our findings show that ecological niche models built at local scale reveal differences in habitat preferences within a wide environmental gradient. Therefore, modelling at local scales rather than assuming large-scale models could be preferable for the establishment of conservation strategies for herptile species in natural

Local-scale models reveal ecological niche variability in amphibian and reptile communities from two contrasting biogeographic regions

Science.gov (United States)

Santos, Xavier; Felicísimo, Ángel M.

2016-01-01

Ecological Niche Models (ENMs) are widely used to describe how environmental factors influence species distribution. Modelling at a local scale, compared to a large scale within a high environmental gradient, can improve our understanding of ecological species niches. The main goal of this study is to assess and compare the contribution of environmental variables to amphibian and reptile ENMs in two Spanish national parks located in contrasting biogeographic regions, i.e., the Mediterranean and the Atlantic area. The ENMs were built with maximum entropy modelling using 11 environmental variables in each territory. The contributions of these variables to the models were analysed and classified using various statistical procedures (Mann–Whitney U tests, Principal Components Analysis and General Linear Models). Distance to the hydrological network was consistently the most relevant variable for both parks and taxonomic classes. Topographic variables (i.e., slope and altitude) were the second most predictive variables, followed by climatic variables. Differences in variable contribution were observed between parks and taxonomic classes. Variables related to water availability had the larger contribution to the models in the Mediterranean park, while topography variables were decisive in the Atlantic park. Specific response curves to environmental variables were in accordance with the biogeographic affinity of species (Mediterranean and non-Mediterranean species) and taxonomy (amphibians and reptiles). Interestingly, these results were observed for species located in both parks, particularly those situated at their range limits. Our findings show that ecological niche models built at local scale reveal differences in habitat preferences within a wide environmental gradient. Therefore, modelling at local scales rather than assuming large-scale models could be preferable for the establishment of conservation strategies for herptile species in natural parks. PMID

Alveolocapillary model system to study alveolar re-epithelialization

Energy Technology Data Exchange (ETDEWEB)

Willems, Coen H.M.P.; Zimmermann, Luc J.I.; Sanders, Patricia J.L.T.; Wagendorp, Margot; Kloosterboer, Nico [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands); Cohen Tervaert, Jan Willem [Division of Clinical and Experimental Immunology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht (Netherlands); Duimel, Hans J.Q.; Verheyen, Fons K.C.P. [Electron Microscopy Unit, Department of Molecular Cell Biology, Maastricht University Medical Centre, Maastricht (Netherlands); Iwaarden, J. Freek van, E-mail: f.vaniwaarden@maastrichtuniversity.nl [Department of Paediatrics, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Centre, Maastricht (Netherlands)

2013-01-01

In the present study an in vitro bilayer model system of the pulmonary alveolocapillary barrier was established to investigate the role of the microvascular endothelium on re-epithelialization. The model system, confluent monolayer cultures on opposing sides of a porous membrane, consisted of a human microvascular endothelial cell line (HPMEC-ST1.6R) and an alveolar type II like cell line (A549), stably expressing EGFP and mCherry, respectively. These fluorescent proteins allowed the real time assessment of the integrity of the monolayers and the automated analysis of the wound healing process after a scratch injury. The HPMECs significantly attenuated the speed of re-epithelialization, which was associated with the proximity to the A549 layer. Examination of cross-sectional transmission electron micrographs of the model system revealed protrusions through the membrane pores and close contact between the A549 cells and the HPMECs. Immunohistochemical analysis showed that these close contacts consisted of heterocellular gap-, tight- and adherens-junctions. Additional analysis, using a fluorescent probe to assess gap-junctional communication, revealed that the HPMECs and A549 cells were able to exchange the fluorophore, which could be abrogated by disrupting the gap junctions using connexin mimetic peptides. These data suggest that the pulmonary microvascular endothelium may impact the re-epithelialization process. -- Highlights: ► Model system for vital imaging and high throughput screening. ► Microvascular endothelium influences re-epithelialization. ► A549 cells form protrusions through membrane to contact HPMEC. ► A549 cells and HPMECs form heterocellular tight-, gap- and adherens-junctions.

Probabilistic inference: Task dependency and individual differences of probability weighting revealed by hierarchical Bayesian modelling

Directory of Open Access Journals (Sweden)

Moritz eBoos

2016-05-01

Full Text Available Cognitive determinants of probabilistic inference were examined using hierarchical Bayesian modelling techniques. A classic urn-ball paradigm served as experimental strategy, involving a factorial two (prior probabilities by two (likelihoods design. Five computational models of cognitive processes were compared with the observed behaviour. Parameter-free Bayesian posterior probabilities and parameter-free base rate neglect provided inadequate models of probabilistic inference. The introduction of distorted subjective probabilities yielded more robust and generalizable results. A general class of (inverted S-shaped probability weighting functions had been proposed; however, the possibility of large differences in probability distortions not only across experimental conditions, but also across individuals, seems critical for the model’s success. It also seems advantageous to consider individual differences in parameters of probability weighting as being sampled from weakly informative prior distributions of individual parameter values. Thus, the results from hierarchical Bayesian modelling converge with previous results in revealing that probability weighting parameters show considerable task dependency and individual differences. Methodologically, this work exemplifies the usefulness of hierarchical Bayesian modelling techniques for cognitive psychology. Theoretically, human probabilistic inference might be best described as the application of individualized strategic policies for Bayesian belief revision.

Use of a statistical model of the whole femur in a large scale, multi-model study of femoral neck fracture risk.

Science.gov (United States)

Bryan, Rebecca; Nair, Prasanth B; Taylor, Mark

2009-09-18

Interpatient variability is often overlooked in orthopaedic computational studies due to the substantial challenges involved in sourcing and generating large numbers of bone models. A statistical model of the whole femur incorporating both geometric and material property variation was developed as a potential solution to this problem. The statistical model was constructed using principal component analysis, applied to 21 individual computer tomography scans. To test the ability of the statistical model to generate realistic, unique, finite element (FE) femur models it was used as a source of 1000 femurs to drive a study on femoral neck fracture risk. The study simulated the impact of an oblique fall to the side, a scenario known to account for a large proportion of hip fractures in the elderly and have a lower fracture load than alternative loading approaches. FE model generation, application of subject specific loading and boundary conditions, FE processing and post processing of the solutions were completed automatically. The generated models were within the bounds of the training data used to create the statistical model with a high mesh quality, able to be used directly by the FE solver without remeshing. The results indicated that 28 of the 1000 femurs were at highest risk of fracture. Closer analysis revealed the percentage of cortical bone in the proximal femur to be a crucial differentiator between the failed and non-failed groups. The likely fracture location was indicated to be intertrochantic. Comparison to previous computational, clinical and experimental work revealed support for these findings.

Revealed social preference for potable groundwater: An Eastern Iowa case study

Science.gov (United States)

Raunikar, R. P.; Bernknopf, R. L.; Forney, W.; Mishra, S.

2011-12-01

The spatially explicit land use and land cover information provided by Landsat moderate-resolution land imagery (MRLI) is needed to more efficiently balance the production of goods and services over landscapes. For example, economic trade-offs are needed to provide both clean groundwater resources and other non-environmental goods and services produced by activities that affect the vadose zone and thus contribute to contamination of groundwater. These trade-off choices are made by numerous economic agents and are constrained by many social institutions including governmental regulations at many levels, contractual obligations and traditions. In effect, on a social level, society acts as if it values groundwater by foregoing other goods to protect these resources. The result of the protection afforded to groundwater resources is observable by measuring contamination in well samples. This observed level of groundwater contamination risk is the revealed preference of society as a whole for clean groundwater. We observed the risk of groundwater contamination in a sampling of well data from our study area (35 counties of Eastern Iowa.) We used a proportional hazard model to quantify the nitrate contamination survival implied by the panel of 19,873 well data, where remaining below a 10 mg/ml maximum contamination level (MCL) is defined as survival. We tested the data for evidence that the levels of protection provided to these resources is correlated with aquifer and vadose zone characteristics and geographic location and whether it changed over time and with economic and other conditions. We demonstrate the use of a nitrate conditioned hazard function for projecting the survival of wells based on nitrate exposure information over the 1940 to 2010 time period. We discuss results of simulations of the survival process that demonstrate the economic significance of this approach. We find that aquifer survival has been significantly improving over time. The principle of

Model Studies of the Histidine-Tyrosine Cross-Link in Cytochrome c Oxidase Reveal the Flexible Substituent Effect of the Imidazole Moiety

Science.gov (United States)

Pratt, Derek A.; Pesavento, Russell P.; van der Donk, Wilfred A.

2010-01-01

Experimental and theoretical studies were carried out to interrogate the effect of an imidazole substituent in each of the ortho, meta, and para positions on the pKa, E°, and O–H BDE of phenol. The results reveal that imidazole substitution lowers the pKa of phenol and increases the E° of phenoxide due to its σ-electron withdrawing ability (σp− = +0.21, σm− = +0.45) but decreases the O–H BDE and E° of phenol due to its σ-electron-donating ability (σp+ = −0.45). PMID:15957934

Genome association study through nonlinear mixed models revealed new candidate genes for pig growth curves

Directory of Open Access Journals (Sweden)

Fabyano Fonseca e Silva

Full Text Available ABSTRACT: Genome association analyses have been successful in identifying quantitative trait loci (QTLs for pig body weights measured at a single age. However, when considering the whole weight trajectories over time in the context of genome association analyses, it is important to look at the markers that affect growth curve parameters. The easiest way to consider them is via the two-step method, in which the growth curve parameters and marker effects are estimated separately, thereby resulting in a reduction of the statistical power and the precision of estimates. One efficient solution is to adopt nonlinear mixed models (NMM, which enables a joint modeling of the individual growth curves and marker effects. Our aim was to propose a genome association analysis for growth curves in pigs based on NMM as well as to compare it with the traditional two-step method. In addition, we also aimed to identify the nearest candidate genes related to significant SNP (single nucleotide polymorphism markers. The NMM presented a higher number of significant SNPs for adult weight (A and maturity rate (K, and provided a direct way to test SNP significance simultaneously for both the A and K parameters. Furthermore, all significant SNPs from the two-step method were also reported in the NMM analysis. The ontology of the three candidate genes (SH3BGRL2, MAPK14, and MYL9 derived from significant SNPs (simultaneously affecting A and K allows us to make inferences with regards to their contribution to the pig growth process in the population studied.

Mitochondrial dysfunction, oxidative stress and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson’s disease

Energy Technology Data Exchange (ETDEWEB)

Chin, Mark H.; Qian, Weijun; Wang, Haixing; Petyuk, Vladislav A.; Bloom, Joshua S.; Sforza, Daniel M.; Lacan, Goran; Liu, Dahai; Khan, Arshad H.; Cantor, Rita M.; Bigelow, Diana J.; Melega, William P.; Camp, David G.; Smith, Richard D.; Smith, Desmond J.

2008-02-10

The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson disease (PD) are not completely understood. Here we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 85 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response and apoptosis. Additionally, codon usage and miRNAs may play an important role in translational control in the striatum. These results constitute one of the largest datasets integrating protein and transcript changes for these neurotoxin models with many similar endpoint phenotypes but distinct mechanisms.

Diffusion Modelling Reveals the Decision Making Processes Underlying Negative Judgement Bias in Rats.

Directory of Open Access Journals (Sweden)

Claire A Hales

Full Text Available Human decision making is modified by emotional state. Rodents exhibit similar biases during interpretation of ambiguous cues that can be altered by affective state manipulations. In this study, the impact of negative affective state on judgement bias in rats was measured using an ambiguous-cue interpretation task. Acute treatment with an anxiogenic drug (FG7142, and chronic restraint stress and social isolation both induced a bias towards more negative interpretation of the ambiguous cue. The diffusion model was fit to behavioural data to allow further analysis of the underlying decision making processes. To uncover the way in which parameters vary together in relation to affective state manipulations, independent component analysis was conducted on rate of information accumulation and distances to decision threshold parameters for control data. Results from this analysis were applied to parameters from negative affective state manipulations. These projected components were compared to control components to reveal the changes in decision making processes that are due to affective state manipulations. Negative affective bias in rodents induced by either FG7142 or chronic stress is due to a combination of more negative interpretation of the ambiguous cue, reduced anticipation of the high reward and increased anticipation of the low reward.

Diffusion Modelling Reveals the Decision Making Processes Underlying Negative Judgement Bias in Rats.

Science.gov (United States)

Hales, Claire A; Robinson, Emma S J; Houghton, Conor J

2016-01-01

Human decision making is modified by emotional state. Rodents exhibit similar biases during interpretation of ambiguous cues that can be altered by affective state manipulations. In this study, the impact of negative affective state on judgement bias in rats was measured using an ambiguous-cue interpretation task. Acute treatment with an anxiogenic drug (FG7142), and chronic restraint stress and social isolation both induced a bias towards more negative interpretation of the ambiguous cue. The diffusion model was fit to behavioural data to allow further analysis of the underlying decision making processes. To uncover the way in which parameters vary together in relation to affective state manipulations, independent component analysis was conducted on rate of information accumulation and distances to decision threshold parameters for control data. Results from this analysis were applied to parameters from negative affective state manipulations. These projected components were compared to control components to reveal the changes in decision making processes that are due to affective state manipulations. Negative affective bias in rodents induced by either FG7142 or chronic stress is due to a combination of more negative interpretation of the ambiguous cue, reduced anticipation of the high reward and increased anticipation of the low reward.

How Do Multiple-Star Systems Form? VLA Study Reveals "Smoking Gun"

Science.gov (United States)

2006-12-01

system, all the antennas could provide data for us. In addition, we improved the level of detail by using the Pie Town, NM, antenna of the Very Long Baseline Array, as part of an expanded system," Lim said. The implementation and improvement of the 43 GHz receiving system was a collaborative program among the German Max Planck Institute, the Mexican National Autonomous University, and the U.S. National Radio Astronomy Observatory. Two popular theoretical models for the formation of multiple-star systems are, first, that the two protostars and their surrounding dusty disks fragment from a larger parent disk, and, second, that the protostars form independently and then one captures the other into a mutual orbit. "Our new study shows that the disks of the two main protostars are aligned with each other, and also are aligned with the larger, surrounding disk. In addition, their orbital motion resembles the rotation of the larger disk. This is a 'smoking gun' supporting the fragmentation model," Lim said. However, the new study also revealed a third young star with a dust disk. "The disk of this one is misaligned with those of the other two, so it may be the result of either fragmentation or capture," Takakuwa said. The misalignment of the third disk could have come through gravitational interactions with the other two, larger, protostars, the scientists said. They plan further observations to try to resolve the question. "We have a very firm indication that two of these protostars and their dust disks formed from the same, larger disk-like cloud, then broke out from it in a fragmentation process. That strongly supports one theoretical model for how multiple-star systems are formed. The misalignment of the third protostar and its disk leaves open the possibility that it could have formed elsewhere and been captured, and we'll continue to work on reconstructing the history of this fascinating system," Lim summarized. The National Radio Astronomy Observatory is a facility of

Cartilaginous Metabolomic Study Reveals Potential Mechanisms of Osteophyte Formation in Osteoarthritis.

Science.gov (United States)

Xu, Zhongwei; Chen, Tingmei; Luo, Jiao; Ding, Shijia; Gao, Sichuan; Zhang, Jian

2017-04-07

Osteophyte is one of the inevitable consequences of progressive osteoarthritis with the main characteristics of cartilage degeneration and endochondral ossification. The pathogenesis of osteophyte formation is not fully understood to date. In this work, metabolomic approaches were employed to explore potential mechanisms of osteophyte formation by detecting metabolic variations between extracts of osteophyte cartilage tissues (n = 32) and uninvolved control cartilage tissues (n = 34), based on the platform of ultraperformance liquid chromatography tandem quadrupole time-of-flight mass spectrometry, as well as the use of multivariate statistic analysis and univariate statistic analysis. The osteophyte group was significantly separated from the control group by the orthogonal partial least-squares discriminant analysis models, indicating that metabolic state of osteophyte cartilage had been changed. In total, 28 metabolic variations further validated by mass spectrum (MS) match, tandom mass spectrum (MS/MS) match, and standards match mainly included amino acids, sulfonic acids, glycerophospholipids, and fatty acyls. These metabolites were related to some specific physiological or pathological processes (collagen dissolution, boundary layers destroyed, self-restoration triggered, etc.) which might be associated with the procedure of osteophyte formation. Pathway analysis showed phenylalanine metabolism (PI = 0.168, p = 0.004) was highly correlative to this degenerative process. Our findings provided a direction for targeted metabolomic study and an insight into further reveal the molecular mechanisms of ostophyte formation.

Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis

Science.gov (United States)

Broddrick, Jared T.; Rubin, Benjamin E.; Welkie, David G.; Du, Niu; Mih, Nathan; Diamond, Spencer; Lee, Jenny J.; Golden, Susan S.; Palsson, Bernhard O.

2016-01-01

The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting in the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology. PMID:27911809

Food hygiene practices and its associated factors among model and non model households in Abobo district, southwestern Ethiopia: Comparative cross-sectional study.

Science.gov (United States)

Okugn, Akoma; Woldeyohannes, Demelash

2018-01-01

In developing country most of human infectious diseases are caused by eating contaminated food. Estimated nine out ten of the diarrheal disease is attributable to the environment and associated with risk factors of poor food hygiene practice. Understanding the risk of eating unsafe food is the major concern to prevent and control food borne diseases. The main goal of this study was to assessing food hygiene practices and its associated factors among model and non model households at Abobo district. This study was conducted from 18 October 2013 to 13 June 2014. A community-based comparative cross-sectional study design was used. Pretested structured questionnaire was used to collect data. A total of 1247 households (417 model and 830 non model households) were included in the study from Abobo district. Bivariate and multivariate logistic regression analysis was used to identify factors associated with outcome variable. The study revealed that good food hygiene practice was 51%, of which 79% were model and 36.70% were non model households. Type of household [AOR: 2.07, 95% CI: (1.32-3.39)], sex of household head [AOR: 1.63, 95% CI: (1.06-2.48)], Availability of liquid wastes disposal pit [AOR: 2.23, 95% CI: (1.39,3.63)], Knowledge of liquid waste to cause diseases [AOR: 1.95, 95% (1.23,3.08)], and availability of functional hand washing facility [AOR: 3.61, 95% CI: (1.86-7.02)] were the factors associated with food handling practices. This study revealed that good food handling practice is low among model and non model households. While type of household (model versus non model households), sex, knowledge of solid waste to cause diseases, availability of functional hand washing facility, and availability of liquid wastes disposal pit were the factors associated with outcome variable. Health extension workers should play a great role in educating households regarding food hygiene practices to improve their knowledge and practices of the food hygiene.

Neural correlates reveal sub-lexical orthography and phonology during reading aloud: A review

Directory of Open Access Journals (Sweden)

Kalinka eTimmer

2014-08-01

Full Text Available The sub-lexical conversion of graphemes-to-phonemes (GPC during reading has been investigated extensively with behavioral measures, as well as event-related potentials (ERPs. Most research utilizes silent reading (e.g., lexical decision task for which phonological activation is not a necessity. However, recent research employed reading aloud to capture sub-lexical GPC. The masked priming paradigm avoids strategic processing and is therefore well suitable for capturing sub-lexical processing instead of lexical effects. By employing ERPs, the on-line time course of sub-lexical GPC can be observed before the overt response. ERPs have revealed that besides phonological activation, as revealed by behavioral studies, there is also early orthographic activation. This review describes studies in one’s native language, in one’s second language, and in a cross-language situation. We discuss the implications the ERP results have on different (computational models. First, the ERP results show that computational models should assume an early locus of the grapheme-to-phoneme-conversion (GPC. Second, cross-language studies reveal that the phonological representations from both languages of a bilingual become activated automatically and the phonology belonging to the context is selected rapidly. Therefore, it is important to extend the scope of computational models of reading (aloud to multiple lexicons.

Revealed preference with limited consideration

NARCIS (Netherlands)

Demuynck, T.; Seel, C.

2014-01-01

We derive revealed preference tests for models where individuals use consideration sets to simplify their consumption problem. Our basic test provides necessary and sufficient conditions for consistency of observed choices with the existence of consideration set restrictions. The same conditions can

Revealing topographic lineaments through IHS enhancement of DEM data. [Digital Elevation Model

Science.gov (United States)

Murdock, Gary

1990-01-01

Intensity-hue-saturation (IHS) processing of slope (dip), aspect (dip direction), and elevation to reveal subtle topographic lineaments which may not be obvious in the unprocessed data are used to enhance digital elevation model (DEM) data from northwestern Nevada. This IHS method of lineament identification was applied to a mosiac of 12 square degrees using a Cray Y-MP8/864. Square arrays from 3 x 3 to 31 x 31 points were tested as well as several different slope enhancements. When relatively few points are used to fit the plane, lineaments of various lengths are observed and a mechanism for lineament classification is described. An area encompassing the gold deposits of the Carlin trend and including the Rain in the southeast to Midas in the northwest is investigated in greater detail. The orientation and density of lineaments may be determined on the gently sloping pediment surface as well as in the more steeply sloping ranges.

Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma.

Science.gov (United States)

Lescarbeau, Rebecca S; Lei, Liang; Bakken, Katrina K; Sims, Peter A; Sarkaria, Jann N; Canoll, Peter; White, Forest M

2016-06-01

Glioblastoma (GBM) is the most common malignant primary brain cancer. With a median survival of about a year, new approaches to treating this disease are necessary. To identify signaling molecules regulating GBM progression in a genetically engineered murine model of proneural GBM, we quantified phosphotyrosine-mediated signaling using mass spectrometry. Oncogenic signals, including phosphorylated ERK MAPK, PI3K, and PDGFR, were found to be increased in the murine tumors relative to brain. Phosphorylation of CDK1 pY15, associated with the G2 arrest checkpoint, was identified as the most differentially phosphorylated site, with a 14-fold increase in phosphorylation in the tumors. To assess the role of this checkpoint as a potential therapeutic target, syngeneic primary cell lines derived from these tumors were treated with MK-1775, an inhibitor of Wee1, the kinase responsible for CDK1 Y15 phosphorylation. MK-1775 treatment led to mitotic catastrophe, as defined by increased DNA damage and cell death by apoptosis. To assess the extensibility of targeting Wee1/CDK1 in GBM, patient-derived xenograft (PDX) cell lines were also treated with MK-1775. Although the response was more heterogeneous, on-target Wee1 inhibition led to decreased CDK1 Y15 phosphorylation and increased DNA damage and apoptosis in each line. These results were also validated in vivo, where single-agent MK-1775 demonstrated an antitumor effect on a flank PDX tumor model, increasing mouse survival by 1.74-fold. This study highlights the ability of unbiased quantitative phosphoproteomics to reveal therapeutic targets in tumor models, and the potential for Wee1 inhibition as a treatment approach in preclinical models of GBM. Mol Cancer Ther; 15(6); 1332-43. ©2016 AACR. ©2016 American Association for Cancer Research.

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

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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

A Study on a Numerical Modeling of a Friction Pendulum System

International Nuclear Information System (INIS)

Kim, Min Kyu; Choun, Young Sun; Ohtori, Yasuki

2006-01-01

A Friction Pendulum System (FPS) is a well known seismic isolation system. In the case of FPS, the period of a vibration only depends on a radius of a curvature and the gravitational constant, and it does not depend on the mass. For this reason, the FPS is useful for smaller weight equipment and a liquid storage tank which changes its' liquid level. Kim et al. (2004) studied the seismic isolation effect of small equipment by using a natural rubber bearing (NRB), a high damping rubber bearing (HDRB) and a Friction pendulum system (FPS) by an experimental research. In this study, modified Mokha model for a small FPS system was proposed and it was revealed this model matched the experimental results well

Revealing Business Opportunities in the Norwegian Power Industry: How the implementation of AMR facilitates new business models

OpenAIRE

Platou, Rikke Stoud; Sleire, Maren

2011-01-01

This thesis aims to map out the current state of the Norwegian power industry and reveal opportunities that can serve as a fundament for the formation of new business models in the industry post AMR implementation.Demand side management (DSM) arouse to include end customers and give them incentives for having a power consumption pattern which also benefits the power system. Market structure; lack of ICT infrastructure and understanding of the solutions; costs and competitiveness, as well as t...

Unfolding mechanism of thrombin-binding aptamer revealed by molecular dynamics simulation and Markov State Model.

Science.gov (United States)

Zeng, Xiaojun; Zhang, Liyun; Xiao, Xiuchan; Jiang, Yuanyuan; Guo, Yanzhi; Yu, Xinyan; Pu, Xuemei; Li, Menglong

2016-04-05

Thrombin-binding aptamer (TBA) with the sequence 5'GGTTGGTGTGGTTGG3' could fold into G-quadruplex, which correlates with functionally important genomic regionsis. However, unfolding mechanism involved in the structural stability of G-quadruplex has not been satisfactorily elucidated on experiments so far. Herein, we studied the unfolding pathway of TBA by a combination of molecular dynamics simulation (MD) and Markov State Model (MSM). Our results revealed that the unfolding of TBA is not a simple two-state process but proceeds along multiple pathways with multistate intermediates. One high flux confirms some observations from NMR experiment. Another high flux exhibits a different and simpler unfolding pathway with less intermediates. Two important intermediate states were identified. One is similar to the G-triplex reported in the folding of G-quadruplex, but lack of H-bonding between guanines in the upper plane. More importantly, another intermediate state acting as a connector to link the folding region and the unfolding one, was the first time identified, which exhibits higher population and stability than the G-triplex-like intermediate. These results will provide valuable information for extending our understanding the folding landscape of G-quadruplex formation.

High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

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Chiao-Ling Lo

2016-08-01

Full Text Available Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP. This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross resulted in small haplotype blocks (HB with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS, were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50% of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284 and intronic regions (169 with the least in exon's (4, suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a, excitatory receptors (Grin2a, Gria3, Grip1, neurotransmitters (Pomc, and synapses (Snap29. This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model.

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Lo, Chiao-Ling; Lossie, Amy C; Liang, Tiebing; Liu, Yunlong; Xuei, Xiaoling; Lumeng, Lawrence; Zhou, Feng C; Muir, William M

2016-08-01

Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon's (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits.

Study of morphological variation of northern Neotropical Ariidae reveals conservatism despite macrohabitat transitions.

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Stange, Madlen; Aguirre-Fernández, Gabriel; Salzburger, Walter; Sánchez-Villagra, Marcelo R

2018-03-27

Morphological convergence triggered by trophic adaptations is a common pattern in adaptive radiations. The study of shape variation in an evolutionary context is usually restricted to well-studied fish models. We take advantage of the recently revised systematics of New World Ariidae and investigate skull shape evolution in six genera of northern Neotropical Ariidae. They constitute a lineage that diversified in the marine habitat but repeatedly adapted to freshwater habitats. 3D geometric morphometrics was applied for the first time in catfish skulls and phylogenetically informed statistical analyses were performed to test for the impact of habitat on skull diversification after habitat transition in this lineage. We found that skull shape is conserved throughout phylogeny. A morphospace analysis revealed that freshwater and marine species occupy extreme ends of the first principal component axis and that they exhibit similar Procrustes variances. Yet freshwater species occupy the smallest shape space compared to marine and brackish species (based on partial disparity), and marine and freshwater species have the largest Procrustes distance to each other. We observed a single case of shape convergence as derived from 'C-metrics', which cannot be explained by the occupation of the same habitat. Although Ariidae occupy such a broad spectrum of different habitats from sea to freshwater, the morphospace analysis and analyses of shape and co-variation with habitat in a phylogenetic context shows that conservatism dominates skull shape evolution among ariid genera.

A lesion model of envy and Schadenfreude: legal, deservingness and moral dimensions as revealed by neurodegeneration

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Santamaría-García, Hernando; Baez, Sandra; Reyes, Pablo; Santamaría-García, José A; Santacruz-Escudero, José M; Matallana, Diana; Arévalo, Analía; Sigman, Mariano; García, Adolfo M; Ibáñez, Agustín

2017-01-01

Abstract The study of moral emotions (i.e. Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as unified and monolithic emotional domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested a group of patients with behavioural variant frontotemporal dementia (bvFTD), patients with Alzheimer’s disease, as a contrastive neurodegeneration model, and healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the Alzheimer’s disease and control groups, patients with bvFTD obtained significantly higher scores on all dimensions for both emotions. Correlational analyses revealed an association between envy and Schadenfreude scores and greater deficits in social cognition, inhibitory control, and behaviour disturbances in bvFTD patients. Brain anatomy findings (restricted to bvFTD and controls) confirmed the partially dissociable nature of the moral emotions’ experiences and highlighted the importance of socio-moral brain areas in processing those emotions. In all subjects, an association emerged between Schadenfreude and the ventral striatum, and between envy and the anterior cingulate cortex. In addition, the results supported an association between scores for moral and legal transgression and the morphology of areas implicated in emotional appraisal, including the amygdala and the parahippocampus. By contrast, bvFTD patients exhibited a negative association between increased Schadenfreude and envy across dimensions and critical regions supporting social-value rewards and social-moral processes (dorsolateral prefrontal cortex, angular

Mathematics Teachers' Views of Accountability Testing Revealed through Lesson Study

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Yarema, Connie H.

2010-01-01

The practice of lesson study, a professional development model originating in Japan, aligns well with recommendations from research for teacher professional development. Lesson study is also an inductive research method that uncovers student thinking and, in parallel, grants teacher-educators the opportunity to study teachers' thinking about…

Evolutionary Meta-Analysis of Association Studies Reveals Ancient Constraints Affecting Disease Marker Discovery

Science.gov (United States)

Dudley, Joel T.; Chen, Rong; Sanderford, Maxwell; Butte, Atul J.; Kumar, Sudhir

2012-01-01

Genome-wide disease association studies contrast genetic variation between disease cohorts and healthy populations to discover single nucleotide polymorphisms (SNPs) and other genetic markers revealing underlying genetic architectures of human diseases. Despite scores of efforts over the past decade, many reproducible genetic variants that explain substantial proportions of the heritable risk of common human diseases remain undiscovered. We have conducted a multispecies genomic analysis of 5,831 putative human risk variants for more than 230 disease phenotypes reported in 2,021 studies. We find that the current approaches show a propensity for discovering disease-associated SNPs (dSNPs) at conserved genomic positions because the effect size (odds ratio) and allelic P value of genetic association of an SNP relates strongly to the evolutionary conservation of their genomic position. We propose a new measure for ranking SNPs that integrates evolutionary conservation scores and the P value (E-rank). Using published data from a large case-control study, we demonstrate that E-rank method prioritizes SNPs with a greater likelihood of bona fide and reproducible genetic disease associations, many of which may explain greater proportions of genetic variance. Therefore, long-term evolutionary histories of genomic positions offer key practical utility in reassessing data from existing disease association studies, and in the design and analysis of future studies aimed at revealing the genetic basis of common human diseases. PMID:22389448

Simulation study of a rectifying bipolar ion channel: Detailed model versus reduced model

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Z. Ható

2016-02-01

Full Text Available We study a rectifying mutant of the OmpF porin ion channel using both all-atom and reduced models. The mutant was created by Miedema et al. [Nano Lett., 2007, 7, 2886] on the basis of the NP semiconductor diode, in which an NP junction is formed. The mutant contains a pore region with positive amino acids on the left-hand side and negative amino acids on the right-hand side. Experiments show that this mutant rectifies. Although we do not know the structure of this mutant, we can build an all-atom model for it on the basis of the structure of the wild type channel. Interestingly, molecular dynamics simulations for this all-atom model do not produce rectification. A reduced model that contains only the important degrees of freedom (the positive and negative amino acids and free ions in an implicit solvent, on the other hand, exhibits rectification. Our calculations for the reduced model (using the Nernst-Planck equation coupled to Local Equilibrium Monte Carlo simulations reveal a rectification mechanism that is different from that seen for semiconductor diodes. The basic reason is that the ions are different in nature from electrons and holes (they do not recombine. We provide explanations for the failure of the all-atom model including the effect of all the other atoms in the system as a noise that inhibits the response of ions (that would be necessary for rectification to the polarizing external field.

Enhanced limonene production in cyanobacteria reveals photosynthesis limitations.

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Wang, Xin; Liu, Wei; Xin, Changpeng; Zheng, Yi; Cheng, Yanbing; Sun, Su; Li, Runze; Zhu, Xin-Guang; Dai, Susie Y; Rentzepis, Peter M; Yuan, Joshua S

2016-12-13

Terpenes are the major secondary metabolites produced by plants, and have diverse industrial applications as pharmaceuticals, fragrance, solvents, and biofuels. Cyanobacteria are equipped with efficient carbon fixation mechanism, and are ideal cell factories to produce various fuel and chemical products. Past efforts to produce terpenes in photosynthetic organisms have gained only limited success. Here we engineered the cyanobacterium Synechococcus elongatus PCC 7942 to efficiently produce limonene through modeling guided study. Computational modeling of limonene flux in response to photosynthetic output has revealed the downstream terpene synthase as a key metabolic flux-controlling node in the MEP (2-C-methyl-d-erythritol 4-phosphate) pathway-derived terpene biosynthesis. By enhancing the downstream limonene carbon sink, we achieved over 100-fold increase in limonene productivity, in contrast to the marginal increase achieved through stepwise metabolic engineering. The establishment of a strong limonene flux revealed potential synergy between photosynthate output and terpene biosynthesis, leading to enhanced carbon flux into the MEP pathway. Moreover, we show that enhanced limonene flux would lead to NADPH accumulation, and slow down photosynthesis electron flow. Fine-tuning ATP/NADPH toward terpene biosynthesis could be a key parameter to adapt photosynthesis to support biofuel/bioproduct production in cyanobacteria.

Radiation induced muscositis as space flight risk. Model studies on X-ray and heavy ion irradiated typical oral mucosa models

International Nuclear Information System (INIS)

Tschachojan, Viktoria

2014-01-01

Humans in exomagnetospheric space are exposed to highly energetic heavy ion radiation which can be hardly shielded. Since radiation-induced mucositis constitutes a severe complication of heavy ion radiotherapy, it would also implicate a serious medical safety risk for the crew members during prolonged space flights such as missions to Moon or Mars. For assessment of risk developing radiation-induced mucositis, three-dimensional organotypic cultures of immortalized human keratinocytes and fibroblasts were irradiated with a 12 C particle beam at high energies or X-Rays. Immunofluorescence stainings were done from cryosections and radiation induced release of cytokines and chemokines was quantified by ELISA from culture supernatants. The major focuses of this study were on 4, 8, 24 and 48 hours after irradiation. The conducted analyses of our mucosa model showed many structural similarities with the native oral mucosa and authentic immunological responses to radiation exposure. Quantification of the DNA damage in irradiated mucosa models revealed about twice as many DSB after heavy-ion irradiation compared to X-rays at definite doses and time points, suggesting a higher gene toxicity of heavy ions. Nuclear factor κB activation was observed after treatment with X-rays or 12 C particles. An activation of NF κB p65 in irradiated samples could not be detected. ELISA analyses showed significantly higher interleukin 6 and interleukin 8 levels after irradiation with X-rays and 12 C particles compared to non-irradiated controls. However, only X-rays induced significantly higher levels of interleukin 1β. Analyses of TNF-α and IFN-γ showed no radiation-induced effects. Further analyses revealed a radiation-induced reduction in proliferation and loss of compactness in irradiated oral mucosa model, which would lead to local lesions in vivo. In this study we revealed that several pro-inflammatory markers and structural changes are induced by X-rays and heavy-ion irradiation

Statistical modeling reveals the effect of absolute humidity on dengue in Singapore.

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Hai-Yan Xu

2014-05-01

Full Text Available Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM was used to evaluate and compare the impact of weekly Absolute Humidity (AH and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike's Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing

Statistical modeling reveals the effect of absolute humidity on dengue in Singapore.

Science.gov (United States)

Xu, Hai-Yan; Fu, Xiuju; Lee, Lionel Kim Hock; Ma, Stefan; Goh, Kee Tai; Wong, Jiancheng; Habibullah, Mohamed Salahuddin; Lee, Gary Kee Khoon; Lim, Tian Kuay; Tambyah, Paul Anantharajah; Lim, Chin Leong; Ng, Lee Ching

2014-05-01

Weather factors are widely studied for their effects on indicating dengue incidence trends. However, these studies have been limited due to the complex epidemiology of dengue, which involves dynamic interplay of multiple factors such as herd immunity within a population, distinct serotypes of the virus, environmental factors and intervention programs. In this study, we investigate the impact of weather factors on dengue in Singapore, considering the disease epidemiology and profile of virus serotypes. A Poisson regression combined with Distributed Lag Non-linear Model (DLNM) was used to evaluate and compare the impact of weekly Absolute Humidity (AH) and other weather factors (mean temperature, minimum temperature, maximum temperature, rainfall, relative humidity and wind speed) on dengue incidence from 2001 to 2009. The same analysis was also performed on three sub-periods, defined by predominant circulating serotypes. The performance of DLNM regression models were then evaluated through the Akaike's Information Criterion. From the correlation and DLNM regression modeling analyses of the studied period, AH was found to be a better predictor for modeling dengue incidence than the other unique weather variables. Whilst mean temperature (MeanT) also showed significant correlation with dengue incidence, the relationship between AH or MeanT and dengue incidence, however, varied in the three sub-periods. Our results showed that AH had a more stable impact on dengue incidence than temperature when virological factors were taken into consideration. AH appeared to be the most consistent factor in modeling dengue incidence in Singapore. Considering the changes in dominant serotypes, the improvements in vector control programs and the inconsistent weather patterns observed in the sub-periods, the impact of weather on dengue is modulated by these other factors. Future studies on the impact of climate change on dengue need to take all the other contributing factors into

Master stability functions reveal diffusion-driven pattern formation in networks

Science.gov (United States)

Brechtel, Andreas; Gramlich, Philipp; Ritterskamp, Daniel; Drossel, Barbara; Gross, Thilo

2018-03-01

We study diffusion-driven pattern formation in networks of networks, a class of multilayer systems, where different layers have the same topology, but different internal dynamics. Agents are assumed to disperse within a layer by undergoing random walks, while they can be created or destroyed by reactions between or within a layer. We show that the stability of homogeneous steady states can be analyzed with a master stability function approach that reveals a deep analogy between pattern formation in networks and pattern formation in continuous space. For illustration, we consider a generalized model of ecological meta-food webs. This fairly complex model describes the dispersal of many different species across a region consisting of a network of individual habitats while subject to realistic, nonlinear predator-prey interactions. In this example, the method reveals the intricate dependence of the dynamics on the spatial structure. The ability of the proposed approach to deal with this fairly complex system highlights it as a promising tool for ecology and other applications.

Molecular basis of structural make-up of feeds in relation to nutrient absorption in ruminants, revealed with advanced molecular spectroscopy: A review on techniques and models

Energy Technology Data Exchange (ETDEWEB)

Rahman, Md. Mostafizar [Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Yu, Peiqiang [Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

2017-01-31

Progress in ruminant feed research is no more feasible only based on wet chemical analysis, which is merely able to provide information on chemical composition of feeds regardless of their digestive features and nutritive value in ruminants. Studying internal structural make-up of functional groups/feed nutrients is often vital for understanding the digestive behaviors and nutritive values of feeds in ruminant because the intrinsic structure of feed nutrients is more related to its overall absorption. In this article, the detail information on the recent developments in molecular spectroscopic techniques to reveal microstructural information of feed nutrients and the use of nutrition models in regards to ruminant feed research was reviewed. The emphasis of this review was on (1) the technological progress in the use of molecular spectroscopic techniques in ruminant feed research; (2) revealing spectral analysis of functional groups of biomolecules/feed nutrients; (3) the use of advanced nutrition models for better prediction of nutrient availability in ruminant systems; and (4) the application of these molecular techniques and combination of nutrient models in cereals, co-products and pulse crop research. The information described in this article will promote better insight in the progress of research on molecular structural make-up of feed nutrients in ruminants.

Using a nursing theory or a model in nursing PhD dissertations: a qualitative study from Turkey.

Science.gov (United States)

Mete, Samiye; Gokçe İsbir, Gozde

2015-04-01

The aim of this study was to reveal experiences of nursing students and their advisors using theories and models in their PhD dissertations. The study adopted a descriptive qualitative approach. This study was performed with 10 PhD candidates and their five advisors from nursing faculty. The results of the study were categorized into four. These are reasons for using a theory/model in a PhD dissertation, reasons for preferring a given model, causes of difficulties in using models in PhD dissertations, and facilitating factors of using theories and models in PhD of dissertations. It was also reported to contribute to the methodology of research and professional development of the students and advisors. © 2014 NANDA International, Inc.

The pattern and time course of somatosensory changes in the human UVB sunburn model reveal the presence of peripheral and central sensitization.

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Gustorff, Burkhard; Sycha, Thomas; Lieba-Samal, Doris; Rolke, Roman; Treede, Rolf-Detlef; Magerl, Walter

2013-04-01

The ultraviolet B (UVB) sunburn model was characterized with a comprehensive battery of quantitative sensory testing (QST). Primary hyperalgesia in UVB-irradiated skin and secondary hyperalgesia in adjacent nonirradiated skin were studied in 22 healthy subjects 24h after irradiation with UVB at 3-fold minimal erythema dose of a skin area 5 cm in diameter at the thigh and compared to mirror-image contralateral control areas. The time course of hyperalgesia over 96 h was studied in a subgroup of 12 subjects. Within the sunburn area, cold hyperesthesia (P=.01), profound generalized hyperalgesia to heat (Psunburn was surrounded by large areas of pinprick hyperalgesia (mean±SEM, 218±32 cm(2)) and a small rim of dynamic mechanical allodynia but no other sensory changes. Although of smaller magnitude, secondary hyperalgesia and dynamic mechanical allodynia adjacent to the UVB-irradiated area were statistically highly significant. Primary and secondary hyperalgesia developed in parallel within hours, peaked after 24-32 h, and lasted for more than 96 h. These data reveal that the UVB sunburn model activates a broad spectrum of peripheral and central sensitization mechanisms and hence is a useful human surrogate model to be used as a screening tool for target engagement in phases 1 and 2a of drug development. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost Advantages for Continuous Methods for a Broad Range of Manufacturing Scales.

Science.gov (United States)

Hummel, Jonathan; Pagkaliwangan, Mark; Gjoka, Xhorxhi; Davidovits, Terence; Stock, Rick; Ransohoff, Thomas; Gantier, Rene; Schofield, Mark

2018-01-17

The biopharmaceutical industry is evolving in response to changing market conditions, including increasing competition and growing pressures to reduce costs. Single-use (SU) technologies and continuous bioprocessing have attracted attention as potential facilitators of cost-optimized manufacturing for monoclonal antibodies. While disposable bioprocessing has been adopted at many scales of manufacturing, continuous bioprocessing has yet to reach the same level of implementation. In this study, the cost of goods of Pall Life Science's integrated, continuous bioprocessing (ICB) platform is modeled, along with that of purification processes in stainless-steel and SU batch formats. All three models include costs associated with downstream processing only. Evaluation of the models across a broad range of clinical and commercial scenarios reveal that the cost savings gained by switching from stainless-steel to SU batch processing are often amplified by continuous operation. The continuous platform exhibits the lowest cost of goods across 78% of all scenarios modeled here, with the SU batch process having the lowest costs in the rest of the cases. The relative savings demonstrated by the continuous process are greatest at the highest feed titers and volumes. These findings indicate that existing and imminent continuous technologies and equipment can become key enablers for more cost effective manufacturing of biopharmaceuticals. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dynamical study of a chaotic predator-prey model with an omnivore

Science.gov (United States)

Al-khedhairi, A.; Elsadany, A. A.; Elsonbaty, A.; Abdelwahab, A. G.

2018-01-01

In this paper, the dynamics and bifurcations of a three-species predator-prey model with an omnivore are further investigated. The food web considered in this work comprises prey, predator and a third species, which consumes the carcasses of the predator along with predation of the original prey. The conditions for existence, uniqueness and continuous dependence on initial conditions for the solution of the model are derived. Analytical and numerical bifurcation studies reveal that the system undergoes transcritical and Hopf bifurcations around its equilibrium points. Further, the Hopf bifurcation curves in the parameters' space along with codimension two bifurcations of equilibrium points and bifurcation of limit cycles that arise in the system are investigated. In particular, the occurrence of generalized Hopf, fold Hopf and Neimarck-Sacker bifurcations is unveiled and illustrates the rich dynamics of the model. Finally, bifurcation diagrams, phase portraits and Lyapunov exponents of the model are presented.

Imaging mass spectrometry reveals elevated nigral levels of dynorphin neuropeptides in L-DOPA-induced dyskinesia in rat model of Parkinson's disease.

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Anna Ljungdahl

Full Text Available L-DOPA-induced dyskinesia is a troublesome complication of L-DOPA pharmacotherapy of Parkinson's disease and has been associated with disturbed brain opioid transmission. However, so far the results of clinical and preclinical studies on the effects of opioids agonists and antagonists have been contradictory at best. Prodynorphin mRNA levels correlate well with the severity of dyskinesia in animal models of Parkinson's disease; however the identities of the actual neuroactive opioid effectors in their target basal ganglia output structures have not yet been determined. For the first time MALDI-TOF imaging mass spectrometry (IMS was used for unbiased assessment and topographical elucidation of prodynorphin-derived peptides in the substantia nigra of a unilateral rat model of Parkinson's disease and L-DOPA induced dyskinesia. Nigral levels of dynorphin B and alpha-neoendorphin strongly correlated with the severity of dyskinesia. Even if dynorphin peptide levels were elevated in both the medial and lateral part of the substantia nigra, MALDI IMS analysis revealed that the most prominent changes were localized to the lateral part of the substantia nigra. MALDI IMS is advantageous compared with traditional molecular methods, such as radioimmunoassay, in that neither the molecular identity analyzed, nor the specific localization needs to be predetermined. Indeed, MALDI IMS revealed that the bioconverted metabolite leu-enkephalin-arg also correlated positively with severity of dyskinesia. Multiplexing DynB and leu-enkephalin-arg ion images revealed small (0.25 by 0.5 mm nigral subregions with complementing ion intensities, indicating localized peptide release followed by bioconversion. The nigral dynorphins associated with L-DOPA-induced dyskinesia were not those with high affinity to kappa opioid receptors, but consisted of shorter peptides, mainly dynorphin B and alpha-neoendorphin that are known to bind and activate mu and delta opioid receptors

Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit.

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Ashoori, Maryam; Burns, Catherine M; d'Entremont, Barbara; Momtahan, Kathryn

2014-01-01

Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamwork and leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams.

Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit

Science.gov (United States)

Ashoori, Maryam; Burns, Catherine M.; d'Entremont, Barbara; Momtahan, Kathryn

2014-01-01

Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamworkand leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. Practitioner Summary: This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams PMID:24837514

A predictive coding account of bistable perception - a model-based fMRI study.

Science.gov (United States)

Weilnhammer, Veith; Stuke, Heiner; Hesselmann, Guido; Sterzer, Philipp; Schmack, Katharina

2017-05-01

In bistable vision, subjective perception wavers between two interpretations of a constant ambiguous stimulus. This dissociation between conscious perception and sensory stimulation has motivated various empirical studies on the neural correlates of bistable perception, but the neurocomputational mechanism behind endogenous perceptual transitions has remained elusive. Here, we recurred to a generic Bayesian framework of predictive coding and devised a model that casts endogenous perceptual transitions as a consequence of prediction errors emerging from residual evidence for the suppressed percept. Data simulations revealed close similarities between the model's predictions and key temporal characteristics of perceptual bistability, indicating that the model was able to reproduce bistable perception. Fitting the predictive coding model to behavioural data from an fMRI-experiment on bistable perception, we found a correlation across participants between the model parameter encoding perceptual stabilization and the behaviourally measured frequency of perceptual transitions, corroborating that the model successfully accounted for participants' perception. Formal model comparison with established models of bistable perception based on mutual inhibition and adaptation, noise or a combination of adaptation and noise was used for the validation of the predictive coding model against the established models. Most importantly, model-based analyses of the fMRI data revealed that prediction error time-courses derived from the predictive coding model correlated with neural signal time-courses in bilateral inferior frontal gyri and anterior insulae. Voxel-wise model selection indicated a superiority of the predictive coding model over conventional analysis approaches in explaining neural activity in these frontal areas, suggesting that frontal cortex encodes prediction errors that mediate endogenous perceptual transitions in bistable perception. Taken together, our current work

A predictive coding account of bistable perception - a model-based fMRI study.

Directory of Open Access Journals (Sweden)

Veith Weilnhammer

2017-05-01

Full Text Available In bistable vision, subjective perception wavers between two interpretations of a constant ambiguous stimulus. This dissociation between conscious perception and sensory stimulation has motivated various empirical studies on the neural correlates of bistable perception, but the neurocomputational mechanism behind endogenous perceptual transitions has remained elusive. Here, we recurred to a generic Bayesian framework of predictive coding and devised a model that casts endogenous perceptual transitions as a consequence of prediction errors emerging from residual evidence for the suppressed percept. Data simulations revealed close similarities between the model's predictions and key temporal characteristics of perceptual bistability, indicating that the model was able to reproduce bistable perception. Fitting the predictive coding model to behavioural data from an fMRI-experiment on bistable perception, we found a correlation across participants between the model parameter encoding perceptual stabilization and the behaviourally measured frequency of perceptual transitions, corroborating that the model successfully accounted for participants' perception. Formal model comparison with established models of bistable perception based on mutual inhibition and adaptation, noise or a combination of adaptation and noise was used for the validation of the predictive coding model against the established models. Most importantly, model-based analyses of the fMRI data revealed that prediction error time-courses derived from the predictive coding model correlated with neural signal time-courses in bilateral inferior frontal gyri and anterior insulae. Voxel-wise model selection indicated a superiority of the predictive coding model over conventional analysis approaches in explaining neural activity in these frontal areas, suggesting that frontal cortex encodes prediction errors that mediate endogenous perceptual transitions in bistable perception. Taken together

Per-pixel bias-variance decomposition of continuous errors in data-driven geospatial modeling: A case study in environmental remote sensing

Science.gov (United States)

Gao, Jing; Burt, James E.

2017-12-01

This study investigates the usefulness of a per-pixel bias-variance error decomposition (BVD) for understanding and improving spatially-explicit data-driven models of continuous variables in environmental remote sensing (ERS). BVD is a model evaluation method originated from machine learning and have not been examined for ERS applications. Demonstrated with a showcase regression tree model mapping land imperviousness (0-100%) using Landsat images, our results showed that BVD can reveal sources of estimation errors, map how these sources vary across space, reveal the effects of various model characteristics on estimation accuracy, and enable in-depth comparison of different error metrics. Specifically, BVD bias maps can help analysts identify and delineate model spatial non-stationarity; BVD variance maps can indicate potential effects of ensemble methods (e.g. bagging), and inform efficient training sample allocation - training samples should capture the full complexity of the modeled process, and more samples should be allocated to regions with more complex underlying processes rather than regions covering larger areas. Through examining the relationships between model characteristics and their effects on estimation accuracy revealed by BVD for both absolute and squared errors (i.e. error is the absolute or the squared value of the difference between observation and estimate), we found that the two error metrics embody different diagnostic emphases, can lead to different conclusions about the same model, and may suggest different solutions for performance improvement. We emphasize BVD's strength in revealing the connection between model characteristics and estimation accuracy, as understanding this relationship empowers analysts to effectively steer performance through model adjustments.

Communication Games Reveal Preparation Contextuality

Science.gov (United States)

Hameedi, Alley; Tavakoli, Armin; Marques, Breno; Bourennane, Mohamed

2017-12-01

A communication game consists of distributed parties attempting to jointly complete a task with restricted communication. Such games are useful tools for studying limitations of physical theories. A theory exhibits preparation contextuality whenever its predictions cannot be explained by a preparation noncontextual model. Here, we show that communication games performed in operational theories reveal the preparation contextuality of that theory. For statistics obtained in a particular family of communication games, we show a direct correspondence with correlations in spacelike separated events obeying the no-signaling principle. Using this, we prove that all mixed quantum states of any finite dimension are preparation contextual. We report on an experimental realization of a communication game involving three-level quantum systems from which we observe a strong violation of the constraints of preparation noncontextuality.

Fourier decomposition of spatial localization errors reveals an idiotropic dominance of an internal model of gravity.

Science.gov (United States)

De Sá Teixeira, Nuno Alexandre

2014-12-01

Given its conspicuous nature, gravity has been acknowledged by several research lines as a prime factor in structuring the spatial perception of one's environment. One such line of enquiry has focused on errors in spatial localization aimed at the vanishing location of moving objects - it has been systematically reported that humans mislocalize spatial positions forward, in the direction of motion (representational momentum) and downward in the direction of gravity (representational gravity). Moreover, spatial localization errors were found to evolve dynamically with time in a pattern congruent with an anticipated trajectory (representational trajectory). The present study attempts to ascertain the degree to which vestibular information plays a role in these phenomena. Human observers performed a spatial localization task while tilted to varying degrees and referring to the vanishing locations of targets moving along several directions. A Fourier decomposition of the obtained spatial localization errors revealed that although spatial errors were increased "downward" mainly along the body's longitudinal axis (idiotropic dominance), the degree of misalignment between the latter and physical gravity modulated the time course of the localization responses. This pattern is surmised to reflect increased uncertainty about the internal model when faced with conflicting cues regarding the perceived "downward" direction.

The elastic network model reveals a consistent picture on intrinsic functional dynamics of type II restriction endonucleases

International Nuclear Information System (INIS)

Uyar, A; Kurkcuoglu, O; Doruker, P; Nilsson, L

2011-01-01

The vibrational dynamics of various type II restriction endonucleases, in complex with cognate/non-cognate DNA and in the apo form, are investigated with the elastic network model in order to reveal common functional mechanisms in this enzyme family. Scissor-like and tong-like motions observed in the slowest modes of all enzymes and their complexes point to common DNA recognition and cleavage mechanisms. Normal mode analysis further points out that the scissor-like motion has an important role in differentiating between cognate and non-cognate sequences at the recognition site, thus implying its catalytic relevance. Flexible regions observed around the DNA-binding site of the enzyme usually concentrate on the highly conserved β-strands, especially after DNA binding. These β-strands may have a structurally stabilizing role in functional dynamics for target site recognition and cleavage. In addition, hot spot residues based on high-frequency modes reveal possible communication pathways between the two distant cleavage sites in the enzyme family. Some of these hot spots also exist on the shortest path between the catalytic sites and are highly conserved

Experimental study and modelling of iron ore reduction by hydrogen

International Nuclear Information System (INIS)

Wagner, D.

2008-01-01

In an effort to find new ways to drastically reduce the CO 2 emissions from the steel industry (ULCOS project), the reduction of iron ore by pure hydrogen in a shaft furnace was investigated. The work consisted of literature, experimental, and modelling studies. The chemical reaction and its kinetics were analysed on the basis of thermogravimetric experiments and physicochemical characterizations of partially reduced samples. A specific kinetic model was designed, which simulates the successive reactions, the different steps of mass transport, and possible iron sintering, at the particle scale. Finally, a 2-dimensional numerical model of a shaft furnace was developed. It depicts the variation of the solid and gas temperatures and compositions throughout the reactor. One original feature of the model is using the law of additive characteristic times for calculating the reaction rates. This allowed us to handle both the particle and the reactor scale, while keeping reasonable calculation time. From the simulation results, the influence of the process parameters was assessed. Optimal operating conditions were concluded, which reveal the efficiency of the hydrogen process. (author)

Climate model biases in seasonality of continental water storage revealed by satellite gravimetry

Science.gov (United States)

Swenson, Sean; Milly, P.C.D.

2006-01-01

Satellite gravimetric observations of monthly changes in continental water storage are compared with outputs from five climate models. All models qualitatively reproduce the global pattern of annual storage amplitude, and the seasonal cycle of global average storage is reproduced well, consistent with earlier studies. However, global average agreements mask systematic model biases in low latitudes. Seasonal extrema of low‐latitude, hemispheric storage generally occur too early in the models, and model‐specific errors in amplitude of the low‐latitude annual variations are substantial. These errors are potentially explicable in terms of neglected or suboptimally parameterized water stores in the land models and precipitation biases in the climate models.

A lesion model of envy and Schadenfreude: legal, deservingness and moral dimensions as revealed by neurodegeneration.

Science.gov (United States)

Santamaría-García, Hernando; Baez, Sandra; Reyes, Pablo; Santamaría-García, José A; Santacruz-Escudero, José M; Matallana, Diana; Arévalo, Analía; Sigman, Mariano; García, Adolfo M; Ibáñez, Agustín

2017-12-01

The study of moral emotions (i.e. Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as unified and monolithic emotional domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested a group of patients with behavioural variant frontotemporal dementia (bvFTD), patients with Alzheimer's disease, as a contrastive neurodegeneration model, and healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the Alzheimer's disease and control groups, patients with bvFTD obtained significantly higher scores on all dimensions for both emotions. Correlational analyses revealed an association between envy and Schadenfreude scores and greater deficits in social cognition, inhibitory control, and behaviour disturbances in bvFTD patients. Brain anatomy findings (restricted to bvFTD and controls) confirmed the partially dissociable nature of the moral emotions' experiences and highlighted the importance of socio-moral brain areas in processing those emotions. In all subjects, an association emerged between Schadenfreude and the ventral striatum, and between envy and the anterior cingulate cortex. In addition, the results supported an association between scores for moral and legal transgression and the morphology of areas implicated in emotional appraisal, including the amygdala and the parahippocampus. By contrast, bvFTD patients exhibited a negative association between increased Schadenfreude and envy across dimensions and critical regions supporting social-value rewards and social-moral processes (dorsolateral prefrontal cortex, angular gyrus and

Imitation Modeling and Institutional Studies

Directory of Open Access Journals (Sweden)

Maksim Y. Barbashin

2017-09-01

Full Text Available This article discusses the use of imitation modeling in the conduct of institutional research. The institutional approach is based on the observation of social behavior. To understand a social process means to determine the key rules that individuals use, undertaking social actions associated with this process or phenomenon. This does not mean that institutions determine behavioral reactions, although there are a number of social situations where the majority of individuals follow the dominant rules. If the main laws of development of the institutional patterns are known, one can describe most of the social processes accurately. The author believes that the main difficulty with the analysis of institutional processes is their recursive nature: from the standards of behavior one may find the proposed actions of social agents who follow, obey or violate institutions, but the possibility of reconstructive analysis is not obvious. The author demonstrates how the institutional approach is applied to the analysis of social behavior. The article describes the basic principles and methodology of imitation modeling. Imitation modeling reveals the importance of institutions in structuring social transactions. The article concludes that in the long term institutional processes are not determined by initial conditions.

Topic Modeling Reveals Distinct Interests within an Online Conspiracy Forum

Directory of Open Access Journals (Sweden)

Colin Klein

2018-02-01

Full Text Available Conspiracy theories play a troubling role in political discourse. Online forums provide a valuable window into everyday conspiracy theorizing, and can give a clue to the motivations and interests of those who post in such forums. Yet this online activity can be difficult to quantify and study. We describe a unique approach to studying online conspiracy theorists which used non-negative matrix factorization to create a topic model of authors' contributions to the main conspiracy forum on Reddit.com. This subreddit provides a large corpus of comments which spans many years and numerous authors. We show that within the forum, there are multiple sub-populations distinguishable by their loadings on different topics in the model. Further, we argue, these differences are interpretable as differences in background beliefs and motivations. The diversity of the distinct subgroups places constraints on theories of what generates conspiracy theorizing. We argue that traditional “monological” believers are only the tip of an iceberg of commenters. Neither simple irrationality nor common preoccupations can account for the observed diversity. Instead, we suggest, those who endorse conspiracies seem to be primarily brought together by epistemological concerns, and that these central concerns link an otherwise heterogenous group of individuals.

An evolutionary-network model reveals stratified interactions in the V3 loop of the HIV-1 envelope.

Directory of Open Access Journals (Sweden)

Art F Y Poon

2007-11-01

Full Text Available The third variable loop (V3 of the human immunodeficiency virus type 1 (HIV-1 envelope is a principal determinant of antibody neutralization and progression to AIDS. Although it is undoubtedly an important target for vaccine research, extensive genetic variation in V3 remains an obstacle to the development of an effective vaccine. Comparative methods that exploit the abundance of sequence data can detect interactions between residues of rapidly evolving proteins such as the HIV-1 envelope, revealing biological constraints on their variability. However, previous studies have relied implicitly on two biologically unrealistic assumptions: (1 that founder effects in the evolutionary history of the sequences can be ignored, and; (2 that statistical associations between residues occur exclusively in pairs. We show that comparative methods that neglect the evolutionary history of extant sequences are susceptible to a high rate of false positives (20%-40%. Therefore, we propose a new method to detect interactions that relaxes both of these assumptions. First, we reconstruct the evolutionary history of extant sequences by maximum likelihood, shifting focus from extant sequence variation to the underlying substitution events. Second, we analyze the joint distribution of substitution events among positions in the sequence as a Bayesian graphical model, in which each branch in the phylogeny is a unit of observation. We perform extensive validation of our models using both simulations and a control case of known interactions in HIV-1 protease, and apply this method to detect interactions within V3 from a sample of 1,154 HIV-1 envelope sequences. Our method greatly reduces the number of false positives due to founder effects, while capturing several higher-order interactions among V3 residues. By mapping these interactions to a structural model of the V3 loop, we find that the loop is stratified into distinct evolutionary clusters. We extend our model to

Study of the 'non-Abelian' current algebra of a non-linear σ-model

International Nuclear Information System (INIS)

Ghosh, Subir

2006-01-01

A particular form of non-linear σ-model, having a global gauge invariance, is studied. The detailed discussion on current algebra structures reveals the non-Abelian nature of the invariance, with field dependent structure functions. Reduction of the field theory to a point particle framework yields a non-linear harmonic oscillator, which is a special case of similar models studied before in [J.F. Carinena et al., Nonlinearity 17 (2004) 1941, math-ph/0406002; J.F. Carinena et al., in: Proceedings of 10th International Conference in Modern Group Analysis, Larnaca, Cyprus, 2004, p. 39, math-ph/0505028; J.F. Carinena et al., Rep. Math. Phys. 54 (2004) 285, hep-th/0501106]. The connection with non-commutative geometry is also established

Effects of Business Model Development Projects on Organizational Culture: A Multiple Case Study of SMEs

OpenAIRE

Ulla Santti; Tuomo Eskelinen; Mervi Rajahonka; Kaija Villman; Ari Happonen

2017-01-01

Previous research has shown that links between organizational culture and innovativeness/performance may act as a “social glue” that helps a company develop organizational culture as a competitive advantage. In this study of three case companies, the organizational culture change due business model development projects is studied using the Competing Values Framework (CVF) tool and interviews with respondents about discovered changes. To reveal intervention and implied effects between business...

Evaluating the governance model of hardware-dependent software ecosystems - a case study of the axis ecosystem

DEFF Research Database (Denmark)

Wnuk, Krzysztof; Manikas, Konstantinos; Runeson, Per

2014-01-01

specifically, we evaluate the governance model applied by Axis, a network video and surveillance camera producer, that is the platform owner and orchestrator of the Application Development Partner (ADP) software ecosystem. We conduct an exploratory case study collecting data from observations and interviews...... and apply the governance model for prevention and improvement of the software ecosystem health proposed by Jansen and Cusumano. Our results reveal that although the governance actions do not address the majority of their governance model, the ADP ecosystem is considered a growing ecosystem providing...

Revealing conceptual understanding of international business

NARCIS (Netherlands)

Sue Ashley; Dr. Harmen Schaap; Prof.Dr. Elly de Bruijn

2017-01-01

This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students’ conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual

Modeling discharge and water quality in a temporary river basin using SWAT model: A case-study on the Ardila river

OpenAIRE

Durão, Anabela; Serafim, António; Brito, David; Morais, Manuela

2012-01-01

Temporary rivers have a hydrologic variability, which are characterized by long drought periods and short floods events, that influences water quality. Analysis of river flow generated in the Ardila river basin (temporary regime) using precipitation data (from 1931 to 2003) from a weather station, located within the basin, at the Portuguese side (which represents only 22% of the study area) showed a discrepancy between the modeled and observed runoff since 1981. It was also revealed a satisfa...

Studies of transformational leadership: evaluating two alternative models of trust and satisfaction.

Science.gov (United States)

Yang, Yi-Feng

2014-06-01

This study evaluates the influence of leadership style and employee trust in their leaders on job satisfaction. 341 personnel (164 men, 177 women; M age = 33.5 yr., SD = 5.1) from four large insurance companies in Taiwan completed the transformational leadership behavior inventory, the leadership trust scale and a short version of the Minnesota (Job) Satisfaction Questionnaire. A bootstrapping mediation and structural equation modeling revealed that the effect of transformational leadership on job satisfaction was mediated by leadership trust. This study highlights the importance of leadership trust in leadership-satisfaction relationships, and provides managers with practical ways to enhance job satisfaction.

Selectivity of primary events in the radiation chemistry of organic solids and polymers as revealed by model studies of ionized molecules

International Nuclear Information System (INIS)

Feldman, V.

2006-01-01

Selectivity of the primary chemical events induced by ionizing radiation in molecular systems is the key issue of basic radiation chemistry, which is crucially important for controlling the radiation sensitivity of various-type organic and polymeric materials and designing new effective approaches to the radiation modification. In the past decade we have demonstrated that many features of selective localization of the radiation-induced effects in molecular solids can be understood on the basis of model studies of the primary ionized molecules in rigid low-temperature matrices. This talk will outline the key results of these studies and possible implications for radiation chemistry of vatious systems. In particular, the following aspects will be considered: (1) Spectroscopic characteristics of ustable ionized molecules in low-temperature matrices and their correlations with the site-selective reactivity. (2) Experimental modeling of the effect of excess energy on the properties of primary ionized molecules in condensed phases. (3) Intramolecular long-range effects with particular impact on the properties of ionized bifunctional molecules of X-(CH 2 ) n -X and X-(CH 2 ) n -Y types. (4) Modeling of intermolecular long-range positive hole transfer between molecular traps with close ionization energy and manifestations of 'fine tuning' effects resulting from conformation variations and intermolecular interactions. Several illustrative examples of correlation between the properties of primary ionized molecules and selectivity of the radiation-chemical transformations in organic solids and macromolecules will be presented. Finally, the problem of prediction of the radiation-chemical behaviour of complex organic systems on the basis of limited spectroscopic information and quantum-chemical data obtained for model systems will be addressed. This work was supported by the Russian Foundation for Basic Research (Project No. 06-03-33104) and the Russian Academy of Sciences

Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

Science.gov (United States)

Gregory, Elaine K; Vercammen, Janet M; Flynn, Megan E; Kibbe, Melina R

2016-12-01

Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species. A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting. We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 μm 2 ; P guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 μm 2 ; P guinea pig, and describe a unique distribution of intimal formation that results in both species

A dynamic uranium-leaching model for process-control studies

International Nuclear Information System (INIS)

Vetter, D.A.; Barker, I.J.; Turner, G.A.

1989-01-01

The modelling of the uranium-leaching process, and the logging of data from a plant for the evaluation of the model, are reported. A phenomenological approach was adopted in the development of the model. A set of eight chemical reactions was chosen to represent the complex chemistry of the process, and kinetic expressions for these reactions were incorporated in differential equations representing mass and energy balances. These equations were coded in FORTRAN to form a program that simulated the process, and that allowed averaged and continuous data from the plant to be compared with the model. This allowed the model to be 'tuned', and to reveal a number of minor problems with the control infrastructure on the plant. 7 figs., 21 refs

Non-parametric Bayesian graph models reveal community structure in resting state fMRI

DEFF Research Database (Denmark)

Andersen, Kasper Winther; Madsen, Kristoffer H.; Siebner, Hartwig Roman

2014-01-01

Modeling of resting state functional magnetic resonance imaging (rs-fMRI) data using network models is of increasing interest. It is often desirable to group nodes into clusters to interpret the communication patterns between nodes. In this study we consider three different nonparametric Bayesian...... models for node clustering in complex networks. In particular, we test their ability to predict unseen data and their ability to reproduce clustering across datasets. The three generative models considered are the Infinite Relational Model (IRM), Bayesian Community Detection (BCD), and the Infinite...... between clusters. BCD restricts the between-cluster link probabilities to be strictly lower than within-cluster link probabilities to conform to the community structure typically seen in social networks. IDM only models a single between-cluster link probability, which can be interpreted as a background...

Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.

Science.gov (United States)

Berkes, Pietro; Orbán, Gergo; Lengyel, Máté; Fiser, József

2011-01-07

The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.

A Collective Case Study of Secondary Students' Model-Based Inquiry on Natural Selection through Programming in an Agent-Based Modeling Environment

Science.gov (United States)

Xiang, Lin

incomplete and many relationships among the model ideas had not been well established by the end of the study. Most of them did not treat the natural selection model as a whole but only focused on some ideas within the model. Very few of them could scientifically apply the natural selection model to interpret other evolutionary phenomena. The findings about participating students' programming processes revealed these processes were composed of consecutive programming cycles. The cycle typically included posing a task, constructing and running program codes, and examining the resulting simulation. Students held multiple ideas and applied various programming strategies in these cycles. Students were involved in MBI at each step of a cycle. Three types of ideas, six programming strategies and ten MBI actions were identified out of the processes. The relationships among these ideas, strategies and actions were also identified and described. Findings suggested that ABPM activities could support MBI by (1) exposing students' personal models and understandings, (2) provoking and supporting a series of model-based inquiry activities, such as elaborating target phenomena, abstracting patterns, and revising conceptual models, and (3) provoking and supporting tangible and productive conversations among students, as well as between the instructor and students. Findings also revealed three programming behaviors that appeared to impede productive MBI, including (1) solely phenomenon-orientated programming, (2) transplanting program codes, and (3) blindly running procedures. Based on the findings, I propose a general modeling process in ABPM activities, summarize the ways in which MBI can be supported in ABPM activities and constrained by multiple factors, and suggest the implications of this study in the future ABPM-assisted science instructional design and research.

A modeling study of the impact of urban trees on ozone

Science.gov (United States)

David J. Nowak; Kevin L. Civerolo; S. Trivikrama Rao; Gopal Sistla; Christopher J. Luley; Daniel E. Crane

2000-01-01

Modeling the effects of increased urban tree cover on ozone concentrations (July 13-15, 1995) from Washington, DC, to central Massachusetts reveals that urban trees generally reduce ozone concentrations in cities, but tend to increase average ozone concentrations in the overall modeling domain. During the daytime, average ozone reductions in urban areas (1 ppb) were...

Human iPSC-Derived Neuronal Model of Tau-A152T Frontotemporal Dementia Reveals Tau-Mediated Mechanisms of Neuronal Vulnerability

Directory of Open Access Journals (Sweden)

M. Catarina Silva

2016-09-01

Full Text Available Frontotemporal dementia (FTD and other tauopathies characterized by focal brain neurodegeneration and pathological accumulation of proteins are commonly associated with tau mutations. However, the mechanism of neuronal loss is not fully understood. To identify molecular events associated with tauopathy, we studied induced pluripotent stem cell (iPSC-derived neurons from individuals carrying the tau-A152T variant. We highlight the potential of in-depth phenotyping of human neuronal cell models for pre-clinical studies and identification of modulators of endogenous tau toxicity. Through a panel of biochemical and cellular assays, A152T neurons showed accumulation, redistribution, and decreased solubility of tau. Upregulation of tau was coupled to enhanced stress-inducible markers and cell vulnerability to proteotoxic, excitotoxic, and mitochondrial stressors, which was rescued upon CRISPR/Cas9-mediated targeting of tau or by pharmacological activation of autophagy. Our findings unmask tau-mediated perturbations of specific pathways associated with neuronal vulnerability, revealing potential early disease biomarkers and therapeutic targets for FTD and other tauopathies.

Modeling reveals bistability and low-pass filtering in the network module determining blood stem cell fate.

Directory of Open Access Journals (Sweden)

Jatin Narula

2010-05-01

Full Text Available Combinatorial regulation of gene expression is ubiquitous in eukaryotes with multiple inputs converging on regulatory control elements. The dynamic properties of these elements determine the functionality of genetic networks regulating differentiation and development. Here we propose a method to quantitatively characterize the regulatory output of distant enhancers with a biophysical approach that recursively determines free energies of protein-protein and protein-DNA interactions from experimental analysis of transcriptional reporter libraries. We apply this method to model the Scl-Gata2-Fli1 triad-a network module important for cell fate specification of hematopoietic stem cells. We show that this triad module is inherently bistable with irreversible transitions in response to physiologically relevant signals such as Notch, Bmp4 and Gata1 and we use the model to predict the sensitivity of the network to mutations. We also show that the triad acts as a low-pass filter by switching between steady states only in response to signals that persist for longer than a minimum duration threshold. We have found that the auto-regulation loops connecting the slow-degrading Scl to Gata2 and Fli1 are crucial for this low-pass filtering property. Taken together our analysis not only reveals new insights into hematopoietic stem cell regulatory network functionality but also provides a novel and widely applicable strategy to incorporate experimental measurements into dynamical network models.

A study on dynamic model of steady-state visual evoked potentials.

Science.gov (United States)

Zhang, Shangen; Han, Xu; Chen, Xiaogang; Wang, Yijun; Gao, Shangkai; Gao, Xiaorong

2018-04-04

Significant progress has been made in the past two decades to considerably improve the performance of steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI). However, there are still some unsolved problems that may help us to improve BCI performance, one of which is that our understanding of the dynamic process of SSVEP is still superficial, especially for the transient-state response. This study introduced an antiphase stimulation method (antiphase: phase 0/π), which can simultaneously separate and extract SSVEP and event-related potential (ERP) signals from EEG, and eliminate the interference of ERP to SSVEP. Based on the SSVEP signals obtained by the antiphase stimulation method, the envelope of SSVEP was extracted by the Hilbert transform, and the dynamic model of SSVEP was quantitatively studied by mathematical modeling. The step response of a second-order linear system was used to fit the envelope of SSVEP, and its characteristics were represented by four parameters with physical and physiological meanings: one was amplitude related, one was latency related and two were frequency related. This study attempted to use pre-stimulation paradigms to modulate the dynamic model parameters, and quantitatively analyze the results by applying the dynamic model to further explore the pre-stimulation methods that had the potential to improve BCI performance. The results showed that the dynamic model had good fitting effect with SSVEP under three pre-stimulation paradigms. The test results revealed that the parameters of SSVEP dynamic models could be modulated by the pre-stimulation baseline luminance, and the gray baseline luminance pre-stimulation obtained the highest performance. This study proposed a dynamic model which was helpful to understand and utilize the transient characteristics of SSVEP. This study also found that pre-stimulation could be used to adjust the parameters of SSVEP model, and had the potential to improve the performance

Revealing Conceptual Understanding of International Business

Science.gov (United States)

Ashley, Sue; Schaap, Harmen; de Bruijn, Elly

2017-01-01

This study aims to identify an adequate approach for revealing conceptual understanding in higher professional education. Revealing students' conceptual understanding is an important step towards developing effective curricula, assessment and aligned teaching strategies to enhance conceptual understanding in higher education. Essays and concept…

End-to-side neurorraphy: a long-term study of neural regeneration in a rat model.

Science.gov (United States)

Tarasidis, G; Watanabe, O; Mackinnon, S E; Strasberg, S R; Haughey, B H; Hunter, D A

1998-10-01

This study evaluated long-term reinnervation of an end-to-side neurorraphy and the resultant functional recovery in a rat model. The divided distal posterior tibial nerve was repaired to the side of an intact peroneal nerve. Control groups included a cut-and-repair of the posterior tibial nerve and an end-to-end repair of the peroneal nerve to the posterior tibial nerve. Evaluations included walking-track analysis, nerve conduction studies, muscle mass measurements, retrograde nerve tracing, and histologic evaluation. Walking tracks indicated poor recovery of posterior tibial nerve function in the experimental group. No significant difference in nerve conduction velocities was seen between the experimental and control groups. Gastrocnemius muscle mass measurements revealed no functional recovery in the experimental group. Similarly, retrograde nerve tracing revealed minimal motor neuron staining in the experimental group. However, some sensory staining was seen within the dorsal root ganglia of the end-to-side group. Histologic study revealed minimal myelinated axonal regeneration in the experimental group as compared with findings in the other groups. These results suggest that predominantly sensory regeneration occurs in an end-to-side neurorraphy at an end point of 6 months.

A crowdsourcing model for creating preclinical medical education study tools.

Science.gov (United States)

Bow, Hansen C; Dattilo, Jonathan R; Jonas, Andrea M; Lehmann, Christoph U

2013-06-01

During their preclinical course work, medical students must memorize and recall substantial amounts of information. Recent trends in medical education emphasize collaboration through team-based learning. In the technology world, the trend toward collaboration has been characterized by the crowdsourcing movement. In 2011, the authors developed an innovative approach to team-based learning that combined students' use of flashcards to master large volumes of content with a crowdsourcing model, using a simple informatics system to enable those students to share in the effort of generating concise, high-yield study materials. The authors used Google Drive and developed a simple Java software program that enabled students to simultaneously access and edit sets of questions and answers in the form of flashcards. Through this crowdsourcing model, medical students in the class of 2014 at the Johns Hopkins University School of Medicine created a database of over 16,000 questions that corresponded to the Genes to Society basic science curriculum. An analysis of exam scores revealed that students in the class of 2014 outperformed those in the class of 2013, who did not have access to the flashcard system, and a survey of students demonstrated that users were generally satisfied with the system and found it a valuable study tool. In this article, the authors describe the development and implementation of their crowdsourcing model for creating study materials, emphasize its simplicity and user-friendliness, describe its impact on students' exam performance, and discuss how students in any educational discipline could implement a similar model of collaborative learning.

The unconvincing product - Consumer versus expert hazard identification: A mental models study of novel foods

DEFF Research Database (Denmark)

Hagemann, Kit; Scholderer, Joachim

and experts understanding of benefits and risks associated with three Novel foods (a potato, rice and functional food ingredients) using a relatively new methodology for the study of risk perception called Mental models. Mental models focus on the way people conceptualise hazardous processes and allows...... researchers to pit a normative analysis (expert mental models) against a descriptive analysis (consumer mental models). Expert models were elicited by means of a three-wave Delphi procedure from altogether 24 international experts and consumers models from in-dept interviews with Danish consumers. The results...... revealed that consumers´ and experts' mental models differed in connection to scope. Experts focused on the types of hazards for which risk assessments can be conducted under current legal frameworks whereas consumers were concerned about issues that lay outside the scope of current legislation. Experts...

A genome-wide study reveals rare CNVs exclusive to extreme phenotypes of Alzheimer disease.

Science.gov (United States)

Rovelet-Lecrux, Anne; Legallic, Solenn; Wallon, David; Flaman, Jean-Michel; Martinaud, Olivier; Bombois, Stéphanie; Rollin-Sillaire, Adeline; Michon, Agnès; Le Ber, Isabelle; Pariente, Jérémie; Puel, Michèle; Paquet, Claire; Croisile, Bernard; Thomas-Antérion, Catherine; Vercelletto, Martine; Lévy, Richard; Frébourg, Thierry; Hannequin, Didier; Campion, Dominique

2012-06-01

Studying rare extreme forms of Alzheimer disease (AD) may prove to be a useful strategy in identifying new genes involved in monogenic determinism of AD. Amyloid precursor protein (APP), PSEN1, and PSEN2 mutations account for only 85% of autosomal dominant early-onset AD (ADEOAD) families. We hypothesised that rare copy number variants (CNVs) could be involved in ADEOAD families without mutations in known genes, as well as in rare sporadic young-onset AD cases. Using high-resolution array comparative genomic hybridisation, we assessed the presence of rare CNVs in 21 unrelated ADEOAD cases, having no alteration on known genes, and 12 sporadic AD cases, with an age of onset younger than 55 years. The analysis revealed the presence of 7 singleton CNVs (4 in ADEOAD and 3 in sporadic cases) absent in 1078 controls and 912 late-onset AD cases. Strikingly, 4 out of 7 rearrangements target genes (KLK6, SLC30A3, MEOX2, and FPR2) encoding proteins that are tightly related to amyloid-β peptide metabolism or signalling. Although these variants are individually rare and restricted to particular subgroups of patients, these findings support the causal role, in human pathology, of a set of genes coding for molecules suspected for a long time to modify Aβ metabolism or signalling, and for which animal or cellular models have already been developed.

On combining revealed and stated preferences to forecast customer behaviour: three case studies

NARCIS (Netherlands)

Ph.H.B.F. Franses (Philip Hans); P.C. Verhoef (Peter)

2002-01-01

textabstractMany companies collect stated preference data (SP) like intentions and satisfaction as well as revealed preference data (RP) like actual purchasing behavior. It seems relevant to examine the predictive usefulness of this information for future revealed preferences, that is, customer

Application of REVEAL-W to risk-based configuration control

International Nuclear Information System (INIS)

Dezfuli, H.; Meyer, J.; Modarres, M.

1994-01-01

Over the past two years, the concept of risk-based configuration control has been introduced to the US Nuclear Regulatory Commission and the nuclear industry. Converting much of the current, deterministically based regulation of nuclear power plants to risk-based regulation can result in lower levels of risk while relieving unnecessary burdens on power plant operators and regulatory staff. To achieve the potential benefits of risk-based configuration control, the risk models developed for nuclear power plants should be (1) flexible enough to effectively support necessary risk calculations, and (2) transparent enough to encourage their use by all parties. To address these needs, SCIENTECH, Inc., has developed the PC-based REVEAL W (formerly known as SMART). This graphic-oriented and user-friendly application software allows the user to develop transparent complex logic models based on the concept of the master plant logic diagram. The logic model is success-oriented and compact. The analytical capability built into REVEAL W is generic, so the software can support different types of risk-based evaluations, such as probabilistic safety assessment, accident sequence precursor analysis, design evaluation and configuration management. In this paper, we focus on the application of REVEAL W to support risk-based configuration control of nuclear power plants. (author)

Plants as models for the study of human pathogenesis.

Science.gov (United States)

Guttman, David S

2004-05-01

There are many common disease mechanisms used by bacterial pathogens of plants and humans. They use common means of attachment, secretion and genetic regulation. They share many virulence factors, such as extracellular polysaccharides and some type III secreted effectors. Plant and human innate immune systems also share many similarities. Many of these shared bacterial virulence mechanisms are homologous, but even more appear to have independently converged on a common function. This combination of homologous and analogous systems reveals conserved and critical steps in the disease process. Given these similarities, and the many experimental advantages of plant biology, including ease of replication, stringent genetic and reproductive control, and high throughput with low cost, it is proposed that plants would make excellent models for the study of human pathogenesis.

Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells

International Nuclear Information System (INIS)

Askmyr, M; Ågerstam, H; Lilljebjörn, H; Hansen, N; Karlsson, C; Palffy, S von; Landberg, N; Högberg, C; Lassen, C; Rissler, M; Richter, J; Ehinger, M; Järås, M; Fioretos, T

2014-01-01

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanized CML model, we retrovirally expressed BCR-ABL1 in the cord blood CD34 + cells and transplanted these into NOD-SCID (non-obese diabetic/severe-combined immunodeficient) interleukin-2-receptor γ-deficient mice. In primary mice, BCR-ABL1 expression induced an inflammatory-like state in the bone marrow and spleen, and mast cells were the only myeloid lineage specifically expanded by BCR-ABL1. Upon secondary transplantation, the pronounced inflammatory phenotype was lost and mainly human mast cells and macrophages were found in the bone marrow. Moreover, a striking block at the pre-B-cell stage was observed in primary mice, resulting in an accumulation of pre-B cells. A similar block in B-cell differentiation could be confirmed in primary cells from CML patients. Hence, this humanized mouse model of CML reveals previously unexplored features of CP CML and should be useful for further studies to understand the disease pathogenesis of CML

Environmental Sound Perception: Metadescription and Modeling Based on Independent Primary Studies

Directory of Open Access Journals (Sweden)

Stephen McAdams

2010-01-01

Full Text Available The aim of the study is to transpose and extend to a set of environmental sounds the notion of sound descriptors usually used for musical sounds. Four separate primary studies dealing with interior car sounds, air-conditioning units, car horns, and closing car doors are considered collectively. The corpus formed by these initial stimuli is submitted to new experimental studies and analyses, both for revealing metacategories and for defining more precisely the limits of each of the resulting categories. In a second step, the new structure is modeled: common and specific dimensions within each category are derived from the initial results and new investigations of audio features are performed. Furthermore, an automatic classifier based on two audio descriptors and a multinomial logistic regression procedure is implemented and validated with the corpus.

Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

NARCIS (Netherlands)

B. Schumacher (Björn); V. Bartels (Valerie); P. Frommolt (Peter); B. Habermann (Bianca); F. Braun (Fabian); J.L. Schultze (Joachim); M. Roodbergen (Marianne); J.H.J. Hoeijmakers (Jan); P. Nürnberg (Peter); M.E.T. Dollé (Martijn); T. Benzing (Thomas); R.-U. Müller (Roman-Ulrich); C.E. Kurschat (Christine)

2013-01-01

textabstractBackground: Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome

A whole-body model for glycogen regulation reveals a critical role for substrate cycling in maintaining blood glucose homeostasis.

Directory of Open Access Journals (Sweden)

Ke Xu

2011-12-01

Full Text Available Timely, and sometimes rapid, metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state, and vice versa. These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from ingested carbohydrates, through hepatic glycogen stores, towards gluconeogenesis. The integration of hepatic glycogen regulation with extra-hepatic energetics is a key aspect of these adaptive mechanisms. Here we use computational modeling to explore hepatic glycogen regulation under fed and fasting conditions in the context of a whole-body model. The model was validated against previous experimental results concerning glycogen phosphorylase a (active and glycogen synthase a dynamics. The model qualitatively reproduced physiological changes that occur during transition from the fed to the fasted state. Analysis of the model reveals a critical role for the inhibition of glycogen synthase phosphatase by glycogen phosphorylase a. This negative regulation leads to high levels of glycogen synthase activity during fasting conditions, which in turn increases substrate (futile cycling, priming the system for a rapid response once an external source of glucose is restored. This work demonstrates that a mechanistic understanding of the design principles used by metabolic control circuits to maintain homeostasis can benefit from the incorporation of mathematical descriptions of these networks into "whole-body" contextual models that mimic in vivo conditions.

Revealing effective classifiers through network comparison

Science.gov (United States)

Gallos, Lazaros K.; Fefferman, Nina H.

2014-11-01

The ability to compare complex systems can provide new insight into the fundamental nature of the processes captured, in ways that are otherwise inaccessible to observation. Here, we introduce the n-tangle method to directly compare two networks for structural similarity, based on the distribution of edge density in network subgraphs. We demonstrate that this method can efficiently introduce comparative analysis into network science and opens the road for many new applications. For example, we show how the construction of a “phylogenetic tree” across animal taxa according to their social structure can reveal commonalities in the behavioral ecology of the populations, or how students create similar networks according to the University size. Our method can be expanded to study many additional properties, such as network classification, changes during time evolution, convergence of growth models, and detection of structural changes during damage.

Stochastic modelling of shifts in allele frequencies reveals a strongly polygynous mating system in the re-introduced Asiatic wild ass.

Science.gov (United States)

Renan, Sharon; Greenbaum, Gili; Shahar, Naama; Templeton, Alan R; Bouskila, Amos; Bar-David, Shirli

2015-04-01

Small populations are prone to loss of genetic variation and hence to a reduction in their evolutionary potential. Therefore, studying the mating system of small populations and its potential effects on genetic drift and genetic diversity is of high importance for their viability assessments. The traditional method for studying genetic mating systems is paternity analysis. Yet, as small populations are often rare and elusive, the genetic data required for paternity analysis are frequently unavailable. The endangered Asiatic wild ass (Equus hemionus), like all equids, displays a behaviourally polygynous mating system; however, the level of polygyny has never been measured genetically in wild equids. Combining noninvasive genetic data with stochastic modelling of shifts in allele frequencies, we developed an alternative approach to paternity analysis for studying the genetic mating system of the re-introduced Asiatic wild ass in the Negev Desert, Israel. We compared the shifts in allele frequencies (as a measure of genetic drift) that have occurred in the wild ass population since re-introduction onset to simulated scenarios under different proportions of mating males. We revealed a strongly polygynous mating system in which less than 25% of all males participate in the mating process each generation. This strongly polygynous mating system and its potential effect on the re-introduced population's genetic diversity could have significant consequences for the long-term persistence of the population in the Negev. The stochastic modelling approach and the use of allele-frequency shifts can be further applied to systems that are affected by genetic drift and for which genetic data are limited. © 2015 John Wiley & Sons Ltd.

Novel cancer gene variants and gene fusions of triple-negative breast cancers (TNBCs) reveal their molecular diversity conserved in the patient-derived xenograft (PDX) model.

Science.gov (United States)

Jung, Jaeyun; Jang, Kiwon; Ju, Jung Min; Lee, Eunji; Lee, Jong Won; Kim, Hee Jung; Kim, Jisun; Lee, Sae Byul; Ko, Beom Seok; Son, Byung Ho; Lee, Hee Jin; Gong, Gyungyup; Ahn, Sei Yeon; Choi, Jung Kyoon; Singh, Shree Ram; Chang, Suhwan

2018-04-20

Despite the improved 5-year survival rate of breast cancer, triple-negative breast cancer (TNBC) remains a challenge due to lack of effective targeted therapy and higher recurrence and metastasis than other subtypes. To identify novel druggable targets and to understand its unique biology, we tried to implement 24 patient-derived xenografts (PDXs) of TNBC. The overall success rate of PDX implantation was 45%, much higher than estrogen receptor (ER)-positive cases. Immunohistochemical analysis revealed conserved ER/PR/Her2 negativity (with two exceptions) between the original and PDX tumors. Genomic analysis of 10 primary tumor-PDX pairs with Ion AmpliSeq CCP revealed high degree of variant conservation (85.0% to 96.9%) between primary and PDXs. Further analysis showed 44 rare variants with a predicted high impact in 36 genes including Trp53, Pten, Notch1, and Col1a1. Among them, we confirmed frequent Notch1 variant. Furthermore, RNA-seq analysis of 24 PDXs revealed 594 gene fusions, of which 163 were in-frame, including AZGP1-GJC3 and NF1-AARSD1. Finally, western blot analysis of oncogenic signaling proteins supporting molecular diversity of TNBC PDXs. Overall, our report provides a molecular basis for the usefulness of the TNBC PDX model in preclinical study. Copyright © 2018. Published by Elsevier B.V.

Modeling autosomal recessive cutis laxa type 1C in mice reveals distinct functions for Ltbp-4 isoforms

DEFF Research Database (Denmark)

Bultmann-Mellin, Insa; Conradi, Anne; Maul, Alexandra C

2015-01-01

Recent studies have revealed an important role for LTBP-4 in elastogenesis. Its mutational inactivation in humans causes autosomal recessive cutis laxa type 1C (ARCL1C), which is a severe disorder caused by defects of the elastic fiber network. Although the human gene involved in ARCL1C has been ...

Prediction of paddy drying kinetics: A comparative study between mathematical and artificial neural network modelling

Directory of Open Access Journals (Sweden)

Beigi Mohsen

2017-01-01

Full Text Available The present study aimed at investigation of deep bed drying of rough rice kernels at various thin layers at different drying air temperatures and flow rates. A comparative study was performed between mathematical thin layer models and artificial neural networks to estimate the drying curves of rough rice. The suitability of nine mathematical models in simulating the drying kinetics was examined and the Midilli model was determined as the best approach for describing drying curves. Different feed forward-back propagation artificial neural networks were examined to predict the moisture content variations of the grains. The ANN with 4-18-18-1 topology, transfer function of hyperbolic tangent sigmoid and a Levenberg-Marquardt back propagation training algorithm provided the best results with the maximum correlation coefficient and the minimum mean square error values. Furthermore, it was revealed that ANN modeling had better performance in prediction of drying curves with lower root mean square error values.

A study on basic theory for CDCC method for three-body model of deuteron scattering

International Nuclear Information System (INIS)

Kawai, Mitsuji

1988-01-01

Recent studies have revealed that the CDCC method is valid for treating the decomposition process involved in deuteron scattering on the basis of a three-body model. However, theoretical support has not been developed for this method. The present study is aimed at determining whether a solution by the CDCC method can be obtained 'correctly' from a 'realistic' model Hamiltonian for deuteron scattering. Some researchers have recently pointed out that there are some problems with the conventional CDCC calculation procedure in view of the general scattering theory. These problems are associated with asymptotic froms of the wave functions, convergence of calculations, and boundary conditions. Considerations show that the problem with asymptotic forms of the wave function is not a fatal defect, though some compromise is necessary. The problem with the convergence of calculations is not very serious either. Discussions are made of the handling of boundary conditions. Thus, the present study indicates that the CDCC method can be applied satisfactorily to actual deuteron scattering, and that the model wave function for the CDCC method is consistent with the model Hamiltonian. (Nogami, K.)

Experimental study and modelization of a propane storage tank depressurization

International Nuclear Information System (INIS)

Veneau, Tania

1995-01-01

The risks associated with the fast depressurization of propane storage tanks reveals the importance of the 'source term' determination. This term is directly linked, among others, to the characteristics of the jet developed downstream of the breach. The first aim of this work was to provide an original data bank concerning drop velocity and diameter distributions in a propane jet. For this purpose, a phase Doppler anemometer bas been implemented on an experimental set-up. Propane blowdowns have been performed with different breach sizes and several initial pressures in the storage tank. Drop diameter and velocity distributions have been investigated at different locations in the jet zone. These measurements exhibited the fragmentation and vaporisation trends in the jet. The second aim of this work concerned the 'source term'. lt required to study the coupling between the fluid behaviour inside the tank and the flow through the breach. This model took into account the phase exchange when flashing occurred in the tank. The flow at the breach was described with an homogeneous relaxation model. This coupled modelization has been successfully and exhaustively validated. lt originality lies on the application to propane flows. (author) [fr

Assessing cross-national invariance of the three-component model of organizational commitment : a six-country study of European university employees

NARCIS (Netherlands)

Eisinga, R.; Teelken, Ch.; Doorewaard, H.

2010-01-01

This study examined cross-national invariance of Meyer and Allen’s three-component model of organizational commitment using samples of university faculty from six European countries. The analysis revealed strict factorial measurement invariance of affective, continuance, and normative organizational

Studies on DANESS Code Modeling

International Nuclear Information System (INIS)

Jeong, Chang Joon

2009-09-01

The DANESS code modeling study has been performed. DANESS code is widely used in a dynamic fuel cycle analysis. Korea Atomic Energy Research Institute (KAERI) has used the DANESS code for the Korean national nuclear fuel cycle scenario analysis. In this report, the important models such as Energy-demand scenario model, New Reactor Capacity Decision Model, Reactor and Fuel Cycle Facility History Model, and Fuel Cycle Model are investigated. And, some models in the interface module are refined and inserted for Korean nuclear fuel cycle model. Some application studies have also been performed for GNEP cases and for US fast reactor scenarios with various conversion ratios

Sexually dimorphic distribution of Prokr2 neurons revealed by the Prokr2-Cre mouse model.

Science.gov (United States)

Mohsen, Zaid; Sim, Hosung; Garcia-Galiano, David; Han, Xingfa; Bellefontaine, Nicole; Saunders, Thomas L; Elias, Carol F

2017-12-01

Prokineticin receptor 2 (PROKR2) is predominantly expressed in the mammalian central nervous system. Loss-of-function mutations of PROKR2 in humans are associated with Kallmann syndrome due to the disruption of gonadotropin releasing hormone neuronal migration and deficient olfactory bulb morphogenesis. PROKR2 has been also implicated in the neuroendocrine control of GnRH neurons post-migration and other physiological systems. However, the brain circuitry and mechanisms associated with these actions have been difficult to investigate mainly due to the widespread distribution of Prokr2-expressing cells, and the lack of animal models and molecular tools. Here, we describe the generation, validation and characterization of a new mouse model that expresses Cre recombinase driven by the Prokr2 promoter, using CRISPR-Cas9 technology. Cre expression was visualized using reporter genes, tdTomato and GFP, in males and females. Expression of Cre-induced reporter genes was found in brain sites previously described to express Prokr2, e.g., the paraventricular and the suprachiasmatic nuclei, and the area postrema. The Prokr2-Cre mouse model was further validated by colocalization of Cre-induced GFP and Prokr2 mRNA. No disruption of Prokr2 expression, GnRH neuronal migration or fertility was observed. Comparative analysis of Prokr2-Cre expression in male and female brains revealed a sexually dimorphic distribution confirmed by in situ hybridization. In females, higher Cre activity was found in the medial preoptic area, ventromedial nucleus of the hypothalamus, arcuate nucleus, medial amygdala and lateral parabrachial nucleus. In males, Cre was higher in the amygdalo-hippocampal area. The sexually dimorphic pattern of Prokr2 expression indicates differential roles in reproductive function and, potentially, in other physiological systems.

Pedestrian Walking Behavior Revealed through a Random Walk Model

Directory of Open Access Journals (Sweden)

Hui Xiong

2012-01-01

Full Text Available This paper applies method of continuous-time random walks for pedestrian flow simulation. In the model, pedestrians can walk forward or backward and turn left or right if there is no block. Velocities of pedestrian flow moving forward or diffusing are dominated by coefficients. The waiting time preceding each jump is assumed to follow an exponential distribution. To solve the model, a second-order two-dimensional partial differential equation, a high-order compact scheme with the alternating direction implicit method, is employed. In the numerical experiments, the walking domain of the first one is two-dimensional with two entrances and one exit, and that of the second one is two-dimensional with one entrance and one exit. The flows in both scenarios are one way. Numerical results show that the model can be used for pedestrian flow simulation.

Memory functions reveal structural properties of gene regulatory networks

Science.gov (United States)

Perez-Carrasco, Ruben

2018-01-01

Gene regulatory networks (GRNs) control cellular function and decision making during tissue development and homeostasis. Mathematical tools based on dynamical systems theory are often used to model these networks, but the size and complexity of these models mean that their behaviour is not always intuitive and the underlying mechanisms can be difficult to decipher. For this reason, methods that simplify and aid exploration of complex networks are necessary. To this end we develop a broadly applicable form of the Zwanzig-Mori projection. By first converting a thermodynamic state ensemble model of gene regulation into mass action reactions we derive a general method that produces a set of time evolution equations for a subset of components of a network. The influence of the rest of the network, the bulk, is captured by memory functions that describe how the subnetwork reacts to its own past state via components in the bulk. These memory functions provide probes of near-steady state dynamics, revealing information not easily accessible otherwise. We illustrate the method on a simple cross-repressive transcriptional motif to show that memory functions not only simplify the analysis of the subnetwork but also have a natural interpretation. We then apply the approach to a GRN from the vertebrate neural tube, a well characterised developmental transcriptional network composed of four interacting transcription factors. The memory functions reveal the function of specific links within the neural tube network and identify features of the regulatory structure that specifically increase the robustness of the network to initial conditions. Taken together, the study provides evidence that Zwanzig-Mori projections offer powerful and effective tools for simplifying and exploring the behaviour of GRNs. PMID:29470492

Biochemistry and structural studies of kynurenine 3-monooxygenase reveal allosteric inhibition by Ro 61-8048.

Science.gov (United States)

Gao, Jingjing; Yao, Licheng; Xia, Tingting; Liao, Xuebin; Zhu, Deyu; Xiang, Ye

2018-04-01

The human kynurenine 3-monooxygenase (hKMO) is a potential therapeutic target for neurodegenerative and neurologic disorders. Inhibition of KMO by Ro 61-8048, a potent, selective, and the most widely used inhibitor of KMO, was shown effective in various models of neurodegenerative or neurologic disorders. However, the molecular basis of hKMO inhibition by Ro 61-8048 is not clearly understood. Here, we report biochemistry studies on hKMO and crystal structures of an hKMO homolog, pfKMO from Pseudomonas fluorescens, in complex with the substrate l-kynurenine and Ro 61-8048. We found that the C-terminal ∼110 aa are essential for the enzymatic activity of hKMO and the homologous C-terminal region of pfKMO folds into a distinct, all-α-helical domain, which associates with the N-terminal catalytic domain to form a unique tunnel in proximity to the substrate-binding pocket. The tunnel binds the Ro 61-8048 molecule, which fills most of the tunnel, and Ro 61-8048 is hydrogen bonded with several completely conserved residues, including an essential catalytic residue. Modification of Ro 61-8048 and biochemical studies of the modified Ro 61-8048 derivatives suggested that Ro 61-8048 inhibits the enzyme in an allosteric manner by affecting the conformation of the essential catalytic residue and by blocking entry of the substrate or product release. The unique binding sites distinguish Ro 61-8048 as a noncompetitive and highly selective inhibitor from other competitive inhibitors, which should facilitate further optimization of Ro 61-8048 and the development of new inhibitory drugs to hKMO.-Gao, J., Yao, L., Xia, T., Liao, X., Zhu, D., Xiang, Y. Biochemistry and structural studies of kynurenine 3-monooxygenase reveal allosteric inhibition by Ro 61-8048.

Cross-species transcriptomic approach reveals genes in hamster implantation sites.

Science.gov (United States)

Lei, Wei; Herington, Jennifer; Galindo, Cristi L; Ding, Tianbing; Brown, Naoko; Reese, Jeff; Paria, Bibhash C

2014-12-01

The mouse model has greatly contributed to understanding molecular mechanisms involved in the regulation of progesterone (P4) plus estrogen (E)-dependent blastocyst implantation process. However, little is known about contributory molecular mechanisms of the P4-only-dependent blastocyst implantation process that occurs in species such as hamsters, guineapigs, rabbits, pigs, rhesus monkeys, and perhaps humans. We used the hamster as a model of P4-only-dependent blastocyst implantation and carried out cross-species microarray (CSM) analyses to reveal differentially expressed genes at the blastocyst implantation site (BIS), in order to advance the understanding of molecular mechanisms of implantation. Upregulation of 112 genes and downregulation of 77 genes at the BIS were identified using a mouse microarray platform, while use of the human microarray revealed 62 up- and 38 down-regulated genes at the BIS. Excitingly, a sizable number of genes (30 up- and 11 down-regulated genes) were identified as a shared pool by both CSMs. Real-time RT-PCR and in situ hybridization validated the expression patterns of several up- and down-regulated genes identified by both CSMs at the hamster and mouse BIS to demonstrate the merit of CSM findings across species, in addition to revealing genes specific to hamsters. Functional annotation analysis found that genes involved in the spliceosome, proteasome, and ubiquination pathways are enriched at the hamster BIS, while genes associated with tight junction, SAPK/JNK signaling, and PPARα/RXRα signalings are repressed at the BIS. Overall, this study provides a pool of genes and evidence of their participation in up- and down-regulated cellular functions/pathways at the hamster BIS. © 2014 Society for Reproduction and Fertility.

Mouse models for the study of postnatal cardiac hypertrophy

Directory of Open Access Journals (Sweden)

A. Del Olmo-Turrubiarte

2015-06-01

Full Text Available The main objective of this study was to create a postnatal model for cardiac hypertrophy (CH, in order to explain the mechanisms that are present in childhood cardiac hypertrophy. Five days after implantation, intraperitoneal (IP isoproterenol (ISO was injected for 7 days to pregnant female mice. The fetuses were obtained at 15, 17 and 19 dpc from both groups, also newborns (NB, neonates (7–15 days and young adults (6 weeks of age. Histopathological exams were done on the hearts. Immunohistochemistry and western blot demonstrated GATA4 and PCNA protein expression, qPCR real time the mRNA of adrenergic receptors (α-AR and β-AR, alpha and beta myosins (α-MHC, β-MHC and GATA4. After the administration of ISO, there was no change in the number of offsprings. We observed significant structural changes in the size of the offspring hearts. Morphometric analysis revealed an increase in the size of the left ventricular wall and interventricular septum (IVS. Histopathological analysis demonstrated loss of cellular compaction and presence of left ventricular small fibrous foci after birth. Adrenergic receptors might be responsible for changing a physiological into a pathological hypertrophy. However GATA4 seemed to be the determining factor in the pathology. A new animal model was established for the study of pathologic CH in early postnatal stages.

Multi-omics reveal the lifestyle of the acidophilic, mineral-oxidizing model species Leptospirillum ferriphilumT.

Science.gov (United States)

Christel, Stephan; Herold, Malte; Bellenberg, Sören; El Hajjami, Mohamed; Buetti-Dinh, Antoine; Pivkin, Igor V; Sand, Wolfgang; Wilmes, Paul; Poetsch, Ansgar; Dopson, Mark

2017-11-17

Leptospirillum ferriphilum plays a major role in acidic, metal rich environments where it represents one of the most prevalent iron oxidizers. These milieus include acid rock and mine drainage as well as biomining operations. Despite its perceived importance, no complete genome sequence of this model species' type strain is available, limiting the possibilities to investigate the strategies and adaptations Leptospirillum ferriphilum T applies to survive and compete in its niche. This study presents a complete, circular genome of Leptospirillum ferriphilum T DSM 14647 obtained by PacBio SMRT long read sequencing for use as a high quality reference. Analysis of the functionally annotated genome, mRNA transcripts, and protein concentrations revealed a previously undiscovered nitrogenase cluster for atmospheric nitrogen fixation and elucidated metabolic systems taking part in energy conservation, carbon fixation, pH homeostasis, heavy metal tolerance, oxidative stress response, chemotaxis and motility, quorum sensing, and biofilm formation. Additionally, mRNA transcript counts and protein concentrations were compared between cells grown in continuous culture using ferrous iron as substrate and bioleaching cultures containing chalcopyrite (CuFeS 2 ). Leptospirillum ferriphilum T adaptations to growth on chalcopyrite included a possibly enhanced production of reducing power, reduced carbon dioxide fixation, as well as elevated RNA transcripts and proteins involved in heavy metal resistance, with special emphasis on copper efflux systems. Finally, expression and translation of genes responsible for chemotaxis and motility were enhanced. IMPORTANCE Leptospirillum ferriphilum is one of the most important iron-oxidizers in the context of acidic and metal rich environments during moderately thermophilic biomining. A high-quality circular genome of Leptospirillum ferriphilum T coupled with functional omics data provides new insights into its metabolic properties, such as the

Use of a Regression Model to Study Host-Genomic Determinants of Phage Susceptibility in MRSA

DEFF Research Database (Denmark)

Zschach, Henrike; Larsen, Mette V; Hasman, Henrik

2018-01-01

strains to 12 (nine monovalent) different therapeutic phage preparations and subsequently employed linear regression models to estimate the influence of individual host gene families on resistance to phages. Specifically, we used a two-step regression model setup with a preselection step based on gene...... family enrichment. We show that our models are robust and capture the data's underlying signal by comparing their performance to that of models build on randomized data. In doing so, we have identified 167 gene families that govern phage resistance in our strain set and performed functional analysis...... on them. This revealed genes of possible prophage or mobile genetic element origin, along with genes involved in restriction-modification and transcription regulators, though the majority were genes of unknown function. This study is a step in the direction of understanding the intricate host...

Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

Science.gov (United States)

2013-01-01

Background Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1-/Δ progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. Results In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1-/Δ mice showed cluster formation between young WT and Ercc1-/Δ as well as old WT and Ercc1-/Δ samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1-/Δ mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1-/Δ mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies. PMID:23947592

Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging.

Science.gov (United States)

Schermer, Bernhard; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Braun, Fabian; Schultze, Joachim L; Roodbergen, Marianne; Hoeijmakers, Jan Hj; Schumacher, Björn; Nürnberg, Peter; Dollé, Martijn Et; Benzing, Thomas; Müller, Roman-Ulrich; Kurschat, Christine E

2013-08-16

Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1(-/Δ) progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1(-/Δ) mice showed cluster formation between young WT and Ercc1(-/Δ) as well as old WT and Ercc1(-/Δ) samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1(-/Δ) mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1(-/Δ) mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies.

Ultra-low input transcriptomics reveal the spore functional content and phylogenetic affiliations of poorly studied arbuscular mycorrhizal fungi.

Science.gov (United States)

Beaudet, Denis; Chen, Eric C H; Mathieu, Stephanie; Yildirir, Gokalp; Ndikumana, Steve; Dalpé, Yolande; Séguin, Sylvie; Farinelli, Laurent; Stajich, Jason E; Corradi, Nicolas

2017-12-02

Arbuscular mycorrhizal fungi (AMF) are a group of soil microorganisms that establish symbioses with the vast majority of land plants. To date, generation of AMF coding information has been limited to model genera that grow well axenically; Rhizoglomus and Gigaspora. Meanwhile, data on the functional gene repertoire of most AMF families is non-existent. Here, we provide primary large-scale transcriptome data from eight poorly studied AMF species (Acaulospora morrowiae, Diversispora versiforme, Scutellospora calospora, Racocetra castanea, Paraglomus brasilianum, Ambispora leptoticha, Claroideoglomus claroideum and Funneliformis mosseae) using ultra-low input ribonucleic acid (RNA)-seq approaches. Our analyses reveals that quiescent spores of many AMF species harbour a diverse functional diversity and solidify known evolutionary relationships within the group. Our findings demonstrate that RNA-seq data obtained from low-input RNA are reliable in comparison to conventional RNA-seq experiments. Thus, our methodology can potentially be used to deepen our understanding of fungal microbial function and phylogeny using minute amounts of RNA material. © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer’s Disease Not Evident in Mouse Models

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Brad A. Friedman

2018-01-01

Full Text Available Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer’s disease (AD model, we identified microglial subsets—distinct from previously reported “disease-associated microglia”—expressing interferon-related or proliferation modules. We then analyzed whole-tissue RNA profiles from human neurodegenerative diseases, including a new AD dataset. Correcting for altered cellular composition of AD tissue, we observed elevated expression of the neurodegeneration-related modules, but also modules not implicated using expression profiles from mouse models alone. We provide a searchable, interactive database for exploring gene expression in all these datasets (http://research-pub.gene.com/BrainMyeloidLandscape. Understanding the dimensions of CNS myeloid cell activation in human disease may reveal opportunities for therapeutic intervention.

Can the business model of Handelsbanken be an archetype for small and medium sized banks? A comparative case study

DEFF Research Database (Denmark)

Kousgaard Larsen, Morten; Lange Nissen, Jacob; Lueg, Rainer

2014-01-01

strengthening of the financial and non-financial position can serve as a blueprint for small- and medium sized banks. We conduct a comparative case study by interviewing Handelsbanken and the disguised ‘Danish Local Bank’ (DLB), where the DLB is a representative example of a small- and medium sized Danish bank......The Danish Banking sector faces increasing requirements regarding regulation and profitability, which especially threatens small- and medium sized banks. This study analyzes whether the successful business model of Handelsbanken (‘The Handelsbanken Way’) to banking in regard to the needed....... This study is structured according to the frameworks from Business Model implementations and from implied organizational structures. Using the notion of Osterwalder and Pigneur (2010), this study reveals only minor differences in the Business Models of Handelsbanken and DLB. Despite the supposedly obvious...

Structure of the dimeric N-glycosylated form of fungal β-N-acetylhexosaminidase revealed by computer modeling, vibrational spectroscopy, and biochemical studies

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Sklenář Jan

2007-05-01

Full Text Available Abstract Background Fungal β-N-acetylhexosaminidases catalyze the hydrolysis of chitobiose into its constituent monosaccharides. These enzymes are physiologically important during the life cycle of the fungus for the formation of septa, germ tubes and fruit-bodies. Crystal structures are known for two monomeric bacterial enzymes and the dimeric human lysosomal β-N-acetylhexosaminidase. The fungal β-N-acetylhexosaminidases are robust enzymes commonly used in chemoenzymatic syntheses of oligosaccharides. The enzyme from Aspergillus oryzae was purified and its sequence was determined. Results The complete primary structure of the fungal β-N-acetylhexosaminidase from Aspergillus oryzae CCF1066 was used to construct molecular models of the catalytic subunit of the enzyme, the enzyme dimer, and the N-glycosylated dimer. Experimental data were obtained from infrared and Raman spectroscopy, and biochemical studies of the native and deglycosylated enzyme, and are in good agreement with the models. Enzyme deglycosylated under native conditions displays identical kinetic parameters but is significantly less stable in acidic conditions, consistent with model predictions. The molecular model of the deglycosylated enzyme was solvated and a molecular dynamics simulation was run over 20 ns. The molecular model is able to bind the natural substrate – chitobiose with a stable value of binding energy during the molecular dynamics simulation. Conclusion Whereas the intracellular bacterial β-N-acetylhexosaminidases are monomeric, the extracellular secreted enzymes of fungi and humans occur as dimers. Dimerization of the fungal β-N-acetylhexosaminidase appears to be a reversible process that is strictly pH dependent. Oligosaccharide moieties may also participate in the dimerization process that might represent a unique feature of the exclusively extracellular enzymes. Deglycosylation had only limited effect on enzyme activity, but it significantly affected

Modeling of the Dorsal Gradient across Species Reveals Interaction between Embryo Morphology and Toll Signaling Pathway during Evolution

Science.gov (United States)

Koslen, Hannah R.; Chiel, Hillel J.; Mizutani, Claudia Mieko

2014-01-01

Morphogenetic gradients are essential to allocate cell fates in embryos of varying sizes within and across closely related species. We previously showed that the maternal NF-κB/Dorsal (Dl) gradient has acquired different shapes in Drosophila species, which result in unequally scaled germ layers along the dorso-ventral axis and the repositioning of the neuroectodermal borders. Here we combined experimentation and mathematical modeling to investigate which factors might have contributed to the fast evolutionary changes of this gradient. To this end, we modified a previously developed model that employs differential equations of the main biochemical interactions of the Toll (Tl) signaling pathway, which regulates Dl nuclear transport. The original model simulations fit well the D. melanogaster wild type, but not mutant conditions. To broaden the applicability of this model and probe evolutionary changes in gradient distributions, we adjusted a set of 19 independent parameters to reproduce three quantified experimental conditions (i.e. Dl levels lowered, nuclear size and density increased or decreased). We next searched for the most relevant parameters that reproduce the species-specific Dl gradients. We show that adjusting parameters relative to morphological traits (i.e. embryo diameter, nuclear size and density) alone is not sufficient to reproduce the species Dl gradients. Since components of the Tl pathway simulated by the model are fast-evolving, we next asked which parameters related to Tl would most effectively reproduce these gradients and identified a particular subset. A sensitivity analysis reveals the existence of nonlinear interactions between the two fast-evolving traits tested above, namely the embryonic morphological changes and Tl pathway components. Our modeling further suggests that distinct Dl gradient shapes observed in closely related melanogaster sub-group lineages may be caused by similar sequence modifications in Tl pathway components, which

Revealed Preference Methods for Studying Bicycle Route Choice—A Systematic Review

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Ray Pritchard

2018-03-01

Full Text Available One fundamental aspect of promoting utilitarian bicycle use involves making modifications to the built environment to improve the safety, efficiency and enjoyability of cycling. Revealed preference data on bicycle route choice can assist greatly in understanding the actual behaviour of a highly heterogeneous group of users, which in turn assists the prioritisation of infrastructure or other built environment initiatives. This systematic review seeks to compare the relative strengths and weaknesses of the empirical approaches for evaluating whole journey route choices of bicyclists. Two electronic databases were systematically searched for a selection of keywords pertaining to bicycle and route choice. In total seven families of methods are identified: GPS devices, smartphone applications, crowdsourcing, participant-recalled routes, accompanied journeys, egocentric cameras and virtual reality. The study illustrates a trade-off in the quality of data obtainable and the average number of participants. Future additional methods could include dockless bikeshare, multiple camera solutions using computer vision and immersive bicycle simulator environments.

Four studies of economic behavior : integrating revealed and stated preferences data

NARCIS (Netherlands)

de Ree, J.J.

2010-01-01

This thesis estimates equivalence scales for Indonesia, proposes a new type of test of the life-cycle model, shows how important economic and demographic characteristics of Dutch households evolve over age, cohorts and time, and studies the decision problem to when and how much to work, save and

Molecular interaction of PCB153 to human serum albumin: Insights from spectroscopic and molecular modeling studies

Energy Technology Data Exchange (ETDEWEB)

Han, Chao; Fang, Senbiao; Cao, Huiming; Lu, Yan; Ma, Yaqiong [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Wei, Dongfeng [Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700 (China); Xie, Xiaoyun [College of Earth and Environmental Science, Lanzhou University, Lanzhou 730000 (China); Liu, Xiaohua [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Li, Xin [College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471003 (China); Fei, Dongqing [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China); Zhao, Chunyan, E-mail: zhaochy07@lzu.edu.cn [School of Pharmacy, Lanzhou University, Lanzhou 730000 (China)

2013-03-15

Highlights: ► We identify the binding mode of PCB153 to human serum albumin (HSA). ► Spectroscopic and molecular modeling results reveal that PCB153 binds at the site II. ► The interaction is mainly governed by hydrophobic and hydrogen bond forces. ► The work helps to probe transporting, distribution and toxicity effect of PCBs. -- Abstract: Polychlorinated biphenyls (PCBs) possessed much potential hazard to environment because of its chemical stability and biological toxicity. Here, we identified the binding mode of a representative compound, PCB153, to human serum albumin (HSA) using fluorescence and molecular dynamics simulation methods. The fluorescence study showed that the intrinsic fluorescence of HSA was quenched by addition of PCB153 through a static quenching mechanism. The thermodynamic analysis proved the binding behavior was mainly governed by hydrophobic force. Furthermore, as evidenced by site marker displacement experiments using two probe compounds, it revealed that PCB153 acted exactly on subdomain IIIA (site II) of HSA. On the other hand, the molecular dynamics studies as well as free energy calculations made another important contribution to understand the conformational changes of HSA and the stability of HSA-PCB153 system. Molecular docking revealed PCB153 can bind in a large hydrophobic activity of subdomain IIIA by the hydrophobic interaction and hydrogen bond interactions between chlorine atoms and residue ASN391. The present work provided reasonable models helping us further understand the transporting, distribution and toxicity effect of PCBs when it spread into human blood serum.

Omics strategies for revealing Yersinia pestis virulence

Science.gov (United States)

Yang, Ruifu; Du, Zongmin; Han, Yanping; Zhou, Lei; Song, Yajun; Zhou, Dongsheng; Cui, Yujun

2012-01-01

Omics has remarkably changed the way we investigate and understand life. Omics differs from traditional hypothesis-driven research because it is a discovery-driven approach. Mass datasets produced from omics-based studies require experts from different fields to reveal the salient features behind these data. In this review, we summarize omics-driven studies to reveal the virulence features of Yersinia pestis through genomics, trascriptomics, proteomics, interactomics, etc. These studies serve as foundations for further hypothesis-driven research and help us gain insight into Y. pestis pathogenesis. PMID:23248778

Effects of Business Model Development Projects on Organizational Culture: A Multiple Case Study of SMEs

Directory of Open Access Journals (Sweden)

Ulla Santti

2017-08-01

Full Text Available Previous research has shown that links between organizational culture and innovativeness/performance may act as a “social glue” that helps a company develop organizational culture as a competitive advantage. In this study of three case companies, the organizational culture change due business model development projects is studied using the Competing Values Framework (CVF tool and interviews with respondents about discovered changes. To reveal intervention and implied effects between business model development project and organizational culture changes, we used CIMO logic (context, intervention, mechanism, and outcome to bridge practice and theory by explanatory, backward-looking research. Our case studies of companies in relatively short-duration business model development projects indicate that organizational culture may have some dynamic characteristics, for example, an increase of the adhocracy organizational type in all case companies or an increase in the hierarchical leadership type in one case company. Thus, the development of an organizational culture type can be partly controlled. Our results also indicated business model development projects do have a minor effect on organizational culture, even when development activities have not been put fully into practice. However, the more comprehensively business model development project activities have been put into practice, the larger the effect on organizational culture.

How causal analysis can reveal autonomy in models of biological systems

Science.gov (United States)

Marshall, William; Kim, Hyunju; Walker, Sara I.; Tononi, Giulio; Albantakis, Larissa

2017-11-01

Standard techniques for studying biological systems largely focus on their dynamical or, more recently, their informational properties, usually taking either a reductionist or holistic perspective. Yet, studying only individual system elements or the dynamics of the system as a whole disregards the organizational structure of the system-whether there are subsets of elements with joint causes or effects, and whether the system is strongly integrated or composed of several loosely interacting components. Integrated information theory offers a theoretical framework to (1) investigate the compositional cause-effect structure of a system and to (2) identify causal borders of highly integrated elements comprising local maxima of intrinsic cause-effect power. Here we apply this comprehensive causal analysis to a Boolean network model of the fission yeast (Schizosaccharomyces pombe) cell cycle. We demonstrate that this biological model features a non-trivial causal architecture, whose discovery may provide insights about the real cell cycle that could not be gained from holistic or reductionist approaches. We also show how some specific properties of this underlying causal architecture relate to the biological notion of autonomy. Ultimately, we suggest that analysing the causal organization of a system, including key features like intrinsic control and stable causal borders, should prove relevant for distinguishing life from non-life, and thus could also illuminate the origin of life problem. This article is part of the themed issue 'Reconceptualizing the origins of life'.

An approach to the interpretation of backpropagation neural network models in QSAR studies.

Science.gov (United States)

Baskin, I I; Ait, A O; Halberstam, N M; Palyulin, V A; Zefirov, N S

2002-03-01

An approach to the interpretation of backpropagation neural network models for quantitative structure-activity and structure-property relationships (QSAR/QSPR) studies is proposed. The method is based on analyzing the first and second moments of distribution of the values of the first and the second partial derivatives of neural network outputs with respect to inputs calculated at data points. The use of such statistics makes it possible not only to obtain actually the same characteristics as for the case of traditional "interpretable" statistical methods, such as the linear regression analysis, but also to reveal important additional information regarding the non-linear character of QSAR/QSPR relationships. The approach is illustrated by an example of interpreting a backpropagation neural network model for predicting position of the long-wave absorption band of cyane dyes.

Comparison of conventional study model measurements and 3D digital study model measurements from laser scanned dental impressions

Science.gov (United States)

Nugrahani, F.; Jazaldi, F.; Noerhadi, N. A. I.

2017-08-01

The field of orthodontics is always evolving,and this includes the use of innovative technology. One type of orthodontic technology is the development of three-dimensional (3D) digital study models that replace conventional study models made by stone. This study aims to compare the mesio-distal teeth width, intercanine width, and intermolar width measurements between a 3D digital study model and a conventional study model. Twelve sets of upper arch dental impressions were taken from subjects with non-crowding teeth. The impressions were taken twice, once with alginate and once with polivinylsiloxane. The alginate impressions used in the conventional study model and the polivinylsiloxane impressions were scanned to obtain the 3D digital study model. Scanning was performed using a laser triangulation scanner device assembled by the School of Electrical Engineering and Informatics at the Institut Teknologi Bandung and David Laser Scan software. For the conventional model, themesio-distal width, intercanine width, and intermolar width were measured using digital calipers; in the 3D digital study model they were measured using software. There were no significant differences between the mesio-distal width, intercanine width, and intermolar width measurments between the conventional and 3D digital study models (p>0.05). Thus, measurements using 3D digital study models are as accurate as those obtained from conventional study models

Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.

Science.gov (United States)

Bolton, Helen; Graham, Sarah J L; Van der Aa, Niels; Kumar, Parveen; Theunis, Koen; Fernandez Gallardo, Elia; Voet, Thierry; Zernicka-Goetz, Magdalena

2016-03-29

Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.

Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

Science.gov (United States)

López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M.; Gibert, Isidre

2015-01-01

Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host–pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host–pathogen interactions. PMID:25699030

Statistical power of model selection strategies for genome-wide association studies.

Directory of Open Access Journals (Sweden)

Zheyang Wu

2009-07-01

Full Text Available Genome-wide association studies (GWAS aim to identify genetic variants related to diseases by examining the associations between phenotypes and hundreds of thousands of genotyped markers. Because many genes are potentially involved in common diseases and a large number of markers are analyzed, it is crucial to devise an effective strategy to identify truly associated variants that have individual and/or interactive effects, while controlling false positives at the desired level. Although a number of model selection methods have been proposed in the literature, including marginal search, exhaustive search, and forward search, their relative performance has only been evaluated through limited simulations due to the lack of an analytical approach to calculating the power of these methods. This article develops a novel statistical approach for power calculation, derives accurate formulas for the power of different model selection strategies, and then uses the formulas to evaluate and compare these strategies in genetic model spaces. In contrast to previous studies, our theoretical framework allows for random genotypes, correlations among test statistics, and a false-positive control based on GWAS practice. After the accuracy of our analytical results is validated through simulations, they are utilized to systematically evaluate and compare the performance of these strategies in a wide class of genetic models. For a specific genetic model, our results clearly reveal how different factors, such as effect size, allele frequency, and interaction, jointly affect the statistical power of each strategy. An example is provided for the application of our approach to empirical research. The statistical approach used in our derivations is general and can be employed to address the model selection problems in other random predictor settings. We have developed an R package markerSearchPower to implement our formulas, which can be downloaded from the

Experimental study and modelling of the high temperature mechanical behavior of oxide dispersion strengthened ferritic steels

International Nuclear Information System (INIS)

Steckmeyer, A.

2012-01-01

The strength of metals, and therefore their maximum operating temperature, can be improved by oxide dispersion strengthening (ODS). Numerous research studies are carried out at the French Atomic Energy Commission (CEA) in order to develop a cladding tube material for Gen IV nuclear power reactors. Oxide dispersion strengthened steels appear to be the most promising candidates for such application, which demands a minimum operating temperature of 650 C. The present dissertation intends to improve the understanding of the mechanical properties of ODS steels, in terms of creep lifetime and mechanical anisotropy. The methodology of this work includes mechanical tests between room temperature and 900 C as well as macroscopic and polycrystalline modelling. These tests are carried out on a Fe-14Cr1W0,26Ti + 0,3 Y 2 O 3 ODS ferritic steel processed at CEA by mechanical alloying and hot extrusion. The as-received material is a bar with a circular section. The mechanical tests reveal the high mechanical strength of this steel at high temperature. A strong influence of the strain rate on the ductility and the mechanical strength is also observed. A macroscopic mechanical model has been developed on the basis of some experimental statements such as the high kinematic contribution to the flow stress. This model has a strong ability to reproduce the mechanical behaviour of the studied material. Two different polycrystalline models have also been developed in order to reproduce the mechanical anisotropy of the material. They are based on its specific grain morphology and crystallographic texture. The discrepancy between the predictions of both models and experimental results reveal the necessity to formulate alternate assumptions on the deformation mechanisms of ODS ferritic steels. (author) [fr

Reveal genes functionally associated with ACADS by a network study.

Science.gov (United States)

Chen, Yulong; Su, Zhiguang

2015-09-15

Establishing a systematic network is aimed at finding essential human gene-gene/gene-disease pathway by means of network inter-connecting patterns and functional annotation analysis. In the present study, we have analyzed functional gene interactions of short-chain acyl-coenzyme A dehydrogenase gene (ACADS). ACADS plays a vital role in free fatty acid β-oxidation and regulates energy homeostasis. Modules of highly inter-connected genes in disease-specific ACADS network are derived by integrating gene function and protein interaction data. Among the 8 genes in ACADS web retrieved from both STRING and GeneMANIA, ACADS is effectively conjoined with 4 genes including HAHDA, HADHB, ECHS1 and ACAT1. The functional analysis is done via ontological briefing and candidate disease identification. We observed that the highly efficient-interlinked genes connected with ACADS are HAHDA, HADHB, ECHS1 and ACAT1. Interestingly, the ontological aspect of genes in the ACADS network reveals that ACADS, HAHDA and HADHB play equally vital roles in fatty acid metabolism. The gene ACAT1 together with ACADS indulges in ketone metabolism. Our computational gene web analysis also predicts potential candidate disease recognition, thus indicating the involvement of ACADS, HAHDA, HADHB, ECHS1 and ACAT1 not only with lipid metabolism but also with infant death syndrome, skeletal myopathy, acute hepatic encephalopathy, Reye-like syndrome, episodic ketosis, and metabolic acidosis. The current study presents a comprehensible layout of ACADS network, its functional strategies and candidate disease approach associated with ACADS network. Copyright © 2015 Elsevier B.V. All rights reserved.

Inhibition of thrombin by functionalized C60 nanoparticles revealed via in vitro assays and in silico studies.

Science.gov (United States)

Liu, Yanyan; Fu, Jianjie; Pan, Wenxiao; Xue, Qiao; Liu, Xian; Zhang, Aiqian

2018-01-01

The studies on the human toxicity of nanoparticles (NPs) are far behind the rapid development of engineered functionalized NPs. Fullerene has been widely used as drug carrier skeleton due to its reported low risk. However, different from other kinds of NPs, fullerene-based NPs (C 60 NPs) have been found to have an anticoagulation effect, although the potential target is still unknown. In the study, both experimental and computational methods were adopted to gain mechanistic insight into the modulation of thrombin activity by nine kinds of C 60 NPs with diverse surface chemistry properties. In vitro enzyme activity assays showed that all tested surface-modified C 60 NPs exhibited thrombin inhibition ability. Kinetic studies coupled with competitive testing using 3 known inhibitors indicated that six of the C 60 NPs, of greater hydrophobicity and hydrogen bond (HB) donor acidity or acceptor basicity, acted as competitive inhibitors of thrombin by directly interacting with the active site of thrombin. A simple quantitative nanostructure-activity relationship model relating the surface substituent properties to the inhibition potential was then established for the six competitive inhibitors. Molecular docking analysis revealed that the intermolecular HB interactions were important for the specific binding of C 60 NPs to the active site canyon, while the additional stability provided by the surface groups through van der Waals interaction also play a key role in the thrombin binding affinity of the NPs. Our results suggest that thrombin is a possible target of the surface-functionalized C 60 NPs relevant to their anticoagulation effect. Copyright © 2017. Published by Elsevier B.V.

High School Students' Epistemological Beliefs, Conceptions of Learning, and Self-Efficacy for Learning Biology: A Study of Their Structural Models

Science.gov (United States)

Sadi, Özlem; Dagyar, Miray

2015-01-01

The current work reveals the data of the study which examines the relationships among epistemological beliefs, conceptions of learning, and self-efficacy for biology learning with the help of the Structural Equation Modeling. Three questionnaires, the Epistemological Beliefs, the Conceptions of Learning Biology and the Self-efficacy for Learning…

Can Environmental Regulations Promote Corporate Environmental Responsibility? Evidence from the Moderated Mediating Effect Model and an Empirical Study in China

Directory of Open Access Journals (Sweden)

Benhong Peng

2018-02-01

Full Text Available Based on the Stakeholder theory, a moderated mediating effect model is developed to reach the study objective, revealing an important connection that suggests environmental regulations (ERs influence corporate environmental responsibility (CER (Porter Hypothesis. In building the model, the validity of the questionnaire data was analyzed with factor analysis. By employing a two-step approach, a regression analysis is utilized to discuss the mediating effect of altruistic motivation and moderating effect of green innovation, and a structural equation model is used to explore the interactive mechanism of different variables. It is found that altruistic motivation plays a medium role in the relationship between ERs and CER, and green innovation engages a positive coordination in the relationship. The empirical study identifies factors affecting enterprises’ willingness to undertake environmental responsibility, including environment policies, corporate culture, and personal characters among others. It is also revealed that altruistic motivation is conducive to forming a community interests among enterprises and enhancing their resistance to market risks, which explains and corroborates the Stakeholder theory; and the higher the level of green innovation, the more willing enterprises are to implement environmentally friendly operations.

Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers.

Science.gov (United States)

Ahuja, Naveen; Katare, Om Prakash; Singh, Bhupinder

2007-01-01

Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed AL type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-à-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug-poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate.

Heavy Metal Exposure and Metabolic Syndrome: Evidence from Human and Model System Studies.

Science.gov (United States)

Planchart, Antonio; Green, Adrian; Hoyo, Cathrine; Mattingly, Carolyn J

2018-03-01

Metabolic syndrome (MS) describes the co-occurrence of conditions that increase one's risk for heart disease and other disorders such as diabetes and stroke. The worldwide increase in the prevalence of MS cannot be fully explained by lifestyle factors such as sedentary behavior and caloric intake alone. Environmental exposures, such as heavy metals, have been implicated, but results are conflicting and possible mechanisms remain unclear. To assess recent progress in determining a possible role between heavy metal exposure and MS, we reviewed epidemiological and model system data for cadmium (Cd), lead (Pb), and mercury (Hg) from the last decade. Data from 36 epidemiological studies involving 17 unique countries/regions and 13 studies leveraging model systems are included in this review. Epidemiological and model system studies support a possible association between heavy metal exposure and MS or comorbid conditions; however, results remain conflicting. Epidemiological studies were predominantly cross-sectional and collectively, they highlight a global interest in this question and reveal evidence of differential susceptibility by sex and age to heavy metal exposures. In vivo studies in rats and mice and in vitro cell-based assays provide insights into potential mechanisms of action relevant to MS including altered regulation of lipid and glucose homeostasis, adipogenesis, and oxidative stress. Heavy metal exposure may contribute to MS or comorbid conditions; however, available data are conflicting. Causal inference remains challenging as epidemiological data are largely cross-sectional; and variation in study design, including samples used for heavy metal measurements, age of subjects at which MS outcomes are measured; the scope and treatment of confounding factors; and the population demographics vary widely. Prospective studies, standardization or increased consistency across study designs and reporting, and consideration of molecular mechanisms informed by model

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. Copyright © 2016 Elsevier Inc. All rights reserved.

On the spatial structure and time evolution of shamal winds over the Arabian Sea – a case study through numerical modelling.

Digital Repository Service at National Institute of Oceanography (India)

VinodKumar, K.; Seemanth, M.; Vethamony, P.; Aboobacker, V.M.

and Forecasting (WRF) model to simulate a major winter shamal event (having duration of 3–5?days), which occurred in 2008 and analysed the spatial structure and time evolution of shamal winds over the Arabian Sea (AS). The study reveals that horizontally, shamal...

A passionate way of being: A qualitative study revealing the passion spiral

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Susanna M. Halonen

2014-06-01

Full Text Available Being engaged in an activity one is passionate about has been tied to feeling life is worth living for. Existing research in passion has explored this phenomenon purely using quantitative research methodology, and by tying an individual’s passion to a specific activity. In this study, passion was explored in semi-structured interviews with 12 participants. The qualitative grounded theory analysis revealed a passionate way of being, with passion being located in the individual rather than in a specific activity. A new phenomenon to positive psychology, a passionate way of being is about having a purpose, creating positive impact, and pursuing variety. These key elements, amongst others, created a reinforcing, self-sustaining spiral, which offered a route to hedonic and eudaimonic happiness, generally serving to enhance life (though it could also detract from life if it became overpowering.

A vegetation modeling concept for Building and Environmental Aerodynamics wind tunnel tests and its application in pollutant dispersion studies

International Nuclear Information System (INIS)

Gromke, Christof

2011-01-01

A new vegetation modeling concept for Building and Environmental Aerodynamics wind tunnel investigations was developed. The modeling concept is based on fluid dynamical similarity aspects and allows the small-scale modeling of various kinds of vegetation, e.g. field crops, shrubs, hedges, single trees and forest stands. The applicability of the modeling concept was validated in wind tunnel pollutant dispersion studies. Avenue trees in urban street canyons were modeled and their implications on traffic pollutant dispersion were investigated. The dispersion experiments proved the modeling concept to be practicable for wind tunnel studies and suggested to provide reliable concentration results. Unfavorable effects of trees on pollutant dispersion and natural ventilation in street canyons were revealed. Increased traffic pollutant concentrations were found in comparison to the tree-free reference case. - Highlights: → A concept for aerodynamic modelling of vegetation in small scale wind tunnel studies is presented. → The concept was applied to study pollutant dispersion in urban street canyons with avenue tress. → The wind tunnel studies show that modelling the aerodynamic effects of vegetation is important. → Avenue trees give rise to increased pollutant concentrations in urban street canyons. - Avenue trees in urban street canyons affect the pollutant dispersion and result in increased traffic exhaust concentrations.

Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells.

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Armitage, Emily G; Kotze, Helen L; Allwood, J William; Dunn, Warwick B; Goodacre, Royston; Williams, Kaye J

2015-10-28

Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments.

Simple analytical model reveals the functional role of embodied sensorimotor interaction in hexapod gaits

Science.gov (United States)

Aoi, Shinya; Nachstedt, Timo; Manoonpong, Poramate; Wörgötter, Florentin; Matsuno, Fumitoshi

2018-01-01

Insects have various gaits with specific characteristics and can change their gaits smoothly in accordance with their speed. These gaits emerge from the embodied sensorimotor interactions that occur between the insect’s neural control and body dynamic systems through sensory feedback. Sensory feedback plays a critical role in coordinated movements such as locomotion, particularly in stick insects. While many previously developed insect models can generate different insect gaits, the functional role of embodied sensorimotor interactions in the interlimb coordination of insects remains unclear because of their complexity. In this study, we propose a simple physical model that is amenable to mathematical analysis to explain the functional role of these interactions clearly. We focus on a foot contact sensory feedback called phase resetting, which regulates leg retraction timing based on touchdown information. First, we used a hexapod robot to determine whether the distributed decoupled oscillators used for legs with the sensory feedback generate insect-like gaits through embodied sensorimotor interactions. The robot generated two different gaits and one had similar characteristics to insect gaits. Next, we proposed the simple model as a minimal model that allowed us to analyze and explain the gait mechanism through the embodied sensorimotor interactions. The simple model consists of a rigid body with massless springs acting as legs, where the legs are controlled using oscillator phases with phase resetting, and the governed equations are reduced such that they can be explained using only the oscillator phases with some approximations. This simplicity leads to analytical solutions for the hexapod gaits via perturbation analysis, despite the complexity of the embodied sensorimotor interactions. This is the first study to provide an analytical model for insect gaits under these interaction conditions. Our results clarified how this specific foot contact sensory

Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars.

Science.gov (United States)

Lin, Hong; Rao, Jun; Shi, Jianxin; Hu, Chaoyang; Cheng, Fang; Wilson, Zoe A; Zhang, Dabing; Quan, Sheng

2014-09-01

Soybean [Glycine max (L.) Merr.] is one of the world's major crops, and soybean seeds are a rich and important resource for proteins and oils. While "omics" studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especially in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetically related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield. © 2014 Institute of Botany, Chinese Academy of Sciences.

Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars

Institute of Scientific and Technical Information of China (English)

Hong Lin; Jun Rao; Jianxin Shi; Chaoyang Hu; Fang Cheng; Zoe AWilson; Dabing Zhang; Sheng Quan

2014-01-01

Soybean [Glycine max (L.) Merr.] is one of the world’s major crops, and soybean seeds are a rich and important resource for proteins and oils. While “omics”studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especial y in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetical y related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield.

Modeling and cellular studies

International Nuclear Information System (INIS)

Anon.

1982-01-01

Testing the applicability of mathematical models with carefully designed experiments is a powerful tool in the investigations of the effects of ionizing radiation on cells. The modeling and cellular studies complement each other, for modeling provides guidance for designing critical experiments which must provide definitive results, while the experiments themselves provide new input to the model. Based on previous experimental results the model for the accumulation of damage in Chlamydomonas reinhardi has been extended to include various multiple two-event combinations. Split dose survival experiments have shown that models tested to date predict most but not all the observed behavior. Stationary-phase mammalian cells, required for tests of other aspects of the model, have been shown to be at different points in the cell cycle depending on how they were forced to stop proliferating. These cultures also demonstrate different capacities for repair of sublethal radiation damage

Crizotinib-Resistant ROS1 Mutations Reveal a Predictive Kinase Inhibitor Sensitivity Model for ROS1- and ALK-Rearranged Lung Cancers.

Science.gov (United States)

Facchinetti, Francesco; Loriot, Yohann; Kuo, Mei-Shiue; Mahjoubi, Linda; Lacroix, Ludovic; Planchard, David; Besse, Benjamin; Farace, Françoise; Auger, Nathalie; Remon, Jordi; Scoazec, Jean-Yves; André, Fabrice; Soria, Jean-Charles; Friboulet, Luc

2016-12-15

The identification of molecular mechanisms conferring resistance to tyrosine kinase inhibitor (TKI) is a key step to improve therapeutic results for patients with oncogene addiction. Several alterations leading to EGFR and anaplastic lymphoma kinase (ALK) resistance to TKI therapy have been described in non-small cell lung cancer (NSCLC). Only two mutations in the ROS1 kinase domain responsible for crizotinib resistance have been described in patients thus far. A patient suffering from a metastatic NSCLC harboring an ezrin (EZR)-ROS1 fusion gene developed acquired resistance to the ALK/ROS1 inhibitor crizotinib. Molecular analysis (whole-exome sequencing, CGH) and functional studies were undertaken to elucidate the mechanism of resistance. Based on this case, we took advantage of the structural homology of ROS1 and ALK to build a predictive model for drug sensitivity regarding future ROS1 mutations. Sequencing revealed a dual mutation, S1986Y and S1986F, in the ROS1 kinase domain. Functional in vitro studies demonstrated that ROS1 harboring either the S1986Y or the S1986F mutation, while conferring resistance to crizotinib and ceritinib, was inhibited by lorlatinib (PF-06463922). The patient's clinical response confirmed the potency of lorlatinib against S1986Y/F mutations. The ROS1 S1986Y/F and ALK C1156Y mutations are homologous and displayed similar sensitivity patterns to ALK/ROS1 TKIs. We extended this analogy to build a model predicting TKI efficacy against potential ROS1 mutations. Clinical evidence, in vitro validation, and homology-based prediction provide guidance for treatment decision making for patients with ROS1-rearranged NSCLC who progressed on crizotinib. Clin Cancer Res; 22(24); 5983-91. ©2016 AACR. ©2016 American Association for Cancer Research.

BIOMOVS: an international model validation study

International Nuclear Information System (INIS)

Haegg, C.; Johansson, G.

1988-01-01

BIOMOVS (BIOspheric MOdel Validation Study) is an international study where models used for describing the distribution of radioactive and nonradioactive trace substances in terrestrial and aquatic environments are compared and tested. The main objectives of the study are to compare and test the accuracy of predictions between such models, explain differences in these predictions, recommend priorities for future research concerning the improvement of the accuracy of model predictions and act as a forum for the exchange of ideas, experience and information. (author)

BIOMOVS: An international model validation study

International Nuclear Information System (INIS)

Haegg, C.; Johansson, G.

1987-01-01

BIOMOVS (BIOspheric MOdel Validation Study) is an international study where models used for describing the distribution of radioactive and nonradioactive trace substances in terrestrial and aquatic environments are compared and tested. The main objectives of the study are to compare and test the accuracy of predictions between such models, explain differences in these predictions, recommend priorities for future research concerning the improvement of the accuracy of model predictions and act as a forum for the exchange of ideas, experience and information. (orig.)

A numerical modelling study on regional mercury budget for eastern North America

Directory of Open Access Journals (Sweden)

X. Lin

2003-01-01

Full Text Available In this study, we have integrated an up-to-date physio-chemical transformation mechanism of Hg into the framework of US EPA's CMAQ model system. In addition, the model adapted detailed calculations of the air-surface exchange for Hg to properly describe Hg re-emissions and dry deposition from and to natural surfaces. The mechanism covers Hg in three categories, elemental Hg (Hg0, reactive gaseous Hg (RGM and particulate Hg (HgP. With interfacing to MM5 (meteorology processor and SMOKE (emission processor, we applied the model to a 4-week period in June/July 1995 on a domain covering most of eastern North America. Results indicate that the model simulates reasonably well the levels of total gaseous Hg (TGM and the specific Hg wet deposition measurements made by the Hg deposition network (MDN. Moreover, results from various scenario runs reveal that the Hg system behaves in a closely linear way in terms of contributions from different source categories, i.e. anthropogenic emissions, natural re-emissions and background. Analyses of the scenario results suggest that 37% of anthropogenically emitted Hg was deposited back in the model domain with 5155 kg of anthropogenic Hg moving out of the domain during the simulation period. Overall, the domain served as a net source, which supplied ~a half ton of Hg to the global background pool over the period. Our model validation and a sensitivity test further rationalized the rate constant for gaseous oxidation of Hg0 by hydroxyl radical OH used in the global scale modelling study by Bergan and Rodhe (2001. A further laboratory determination of the reaction rate constant, including its temperature dependence, stands as one of the important issues critical to improving our knowledge on the budget and cycling of Hg.

Multivariate EMD-Based Modeling and Forecasting of Crude Oil Price

Directory of Open Access Journals (Sweden)

Kaijian He

2016-04-01

Full Text Available Recent empirical studies reveal evidence of the co-existence of heterogeneous data characteristics distinguishable by time scale in the movement crude oil prices. In this paper we propose a new multivariate Empirical Mode Decomposition (EMD-based model to take advantage of these heterogeneous characteristics of the price movement and model them in the crude oil markets. Empirical studies in benchmark crude oil markets confirm that more diverse heterogeneous data characteristics can be revealed and modeled in the projected time delayed domain. The proposed model demonstrates the superior performance compared to the benchmark models.

Submillisecond Elastic Recoil Reveals Molecular Origins of Fibrin Fiber Mechanics

Science.gov (United States)

Hudson, Nathan E.; Ding, Feng; Bucay, Igal; O’Brien, E. Timothy; Gorkun, Oleg V.; Superfine, Richard; Lord, Susan T.; Dokholyan, Nikolay V.; Falvo, Michael R.

2013-01-01

Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin’s elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin’s mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. PMID:23790375

Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling

Science.gov (United States)

Liu, Alan S.; Wang, Hailong; Copeland, Craig R.; Chen, Christopher S.; Shenoy, Vivek B.; Reich, Daniel H.

2016-01-01

The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues’ response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells’ shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics. PMID:27671239

Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures

Directory of Open Access Journals (Sweden)

Peter A. Bell

2013-06-01

Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal diseases resulting from mutations in cartilage structural proteins. Electron microscopy and immunohistochemistry previously showed that the appearance of the cartilage extracellular matrix (ECM in targeted mouse models of these diseases is disrupted; however, the precise changes in ECM organization and the pathological consequences remain unknown. Our aim was to determine the effects of matrilin-3 and COMP mutations on the composition and extractability of ECM components to inform how these detrimental changes might influence cartilage organization and degeneration. Cartilage was sequentially extracted using increasing denaturants and the extraction profiles of specific proteins determined using SDS-PAGE/Western blotting. Furthermore, the relative composition of protein pools was determined using mass spectrometry for a non-biased semi-quantitative analysis. Western blotting revealed changes in the extraction of matrilins, COMP and collagen IX in mutant cartilage. Mass spectrometry confirmed quantitative changes in the extraction of structural and non-structural ECM proteins, including proteins with roles in cellular processes such as protein folding and trafficking. In particular, genotype-specific differences in the extraction of collagens XII and XIV and tenascins C and X were identified; interestingly, increased expression of several of these genes has recently been implicated in susceptibility and/or progression of murine osteoarthritis. We demonstrated that mutation of matrilin-3 and COMP caused changes in the extractability of other cartilage proteins and that proteomic analyses of Matn3 V194D, Comp T585M and Comp DelD469 mouse models revealed both common and discrete disease signatures that provide novel insight into skeletal disease mechanisms and cartilage degradation.

Cardiac c-Kit Biology Revealed by Inducible Transgenesis.

Science.gov (United States)

Gude, Natalie A; Firouzi, Fareheh; Broughton, Kathleen M; Ilves, Kelli; Nguyen, Kristine P; Payne, Christina R; Sacchi, Veronica; Monsanto, Megan M; Casillas, Alexandria R; Khalafalla, Farid G; Wang, Bingyan J; Ebeid, David E; Alvarez, Roberto; Dembitsky, Walter P; Bailey, Barbara A; van Berlo, Jop; Sussman, Mark A

2018-06-22

Biological significance of c-Kit as a cardiac stem cell marker and role(s) of c-Kit+ cells in myocardial development or response to pathological injury remain unresolved because of varied and discrepant findings. Alternative experimental models are required to contextualize and reconcile discordant published observations of cardiac c-Kit myocardial biology and provide meaningful insights regarding clinical relevance of c-Kit signaling for translational cell therapy. The main objectives of this study are as follows: demonstrating c-Kit myocardial biology through combined studies of both human and murine cardiac cells; advancing understanding of c-Kit myocardial biology through creation and characterization of a novel, inducible transgenic c-Kit reporter mouse model that overcomes limitations inherent to knock-in reporter models; and providing perspective to reconcile disparate viewpoints on c-Kit biology in the myocardium. In vitro studies confirm a critical role for c-Kit signaling in both cardiomyocytes and cardiac stem cells. Activation of c-Kit receptor promotes cell survival and proliferation in stem cells and cardiomyocytes of either human or murine origin. For creation of the mouse model, the cloned mouse c-Kit promoter drives Histone2B-EGFP (enhanced green fluorescent protein; H2BEGFP) expression in a doxycycline-inducible transgenic reporter line. The combination of c-Kit transgenesis coupled to H2BEGFP readout provides sensitive, specific, inducible, and persistent tracking of c-Kit promoter activation. Tagging efficiency for EGFP+/c-Kit+ cells is similar between our transgenic versus a c-Kit knock-in mouse line, but frequency of c-Kit+ cells in cardiac tissue from the knock-in model is 55% lower than that from our transgenic line. The c-Kit transgenic reporter model reveals intimate association of c-Kit expression with adult myocardial biology. Both cardiac stem cells and a subpopulation of cardiomyocytes express c-Kit in uninjured adult heart

Kinetic modeling studies of SOA formation from α-pinene ozonolysis

Science.gov (United States)

Gatzsche, Kathrin; Iinuma, Yoshiteru; Tilgner, Andreas; Mutzel, Anke; Berndt, Torsten; Wolke, Ralf

2017-11-01

This paper describes the implementation of a kinetic gas-particle partitioning approach used for the simulation of secondary organic aerosol (SOA) formation within the SPectral Aerosol Cloud Chemistry Interaction Model (SPACCIM). The kinetic partitioning considers the diffusion of organic compounds into aerosol particles and the subsequent chemical reactions in the particle phase. The basic kinetic partitioning approach is modified by the implementation of chemical backward reaction of the solute within the particle phase as well as a composition-dependent particle-phase bulk diffusion coefficient. The adapted gas-phase chemistry mechanism for α-pinene oxidation has been updated due to the recent findings related to the formation of highly oxidized multifunctional organic compounds (HOMs). Experimental results from a LEAK (Leipziger Aerosolkammer) chamber study for α-pinene ozonolysis were compared with the model results describing this reaction system.The performed model studies reveal that the particle-phase bulk diffusion coefficient and the particle-phase reactivity are key parameters for SOA formation. Using the same particle-phase reactivity for both cases, we find that liquid particles with higher particle-phase bulk diffusion coefficients have 310 times more organic material formed in the particle phase compared to higher viscous semi-solid particles with lower particle-phase bulk diffusion coefficients. The model results demonstrate that, even with a moderate particle-phase reactivity, about 61 % of the modeled organic mass consists of reaction products that are formed in the liquid particles. This finding emphasizes the potential role of SOA processing. Moreover, the initial organic aerosol mass concentration and the particle radius are of minor importance for the process of SOA formation in liquid particles. A sensitivity study shows that a 22-fold increase in particle size merely leads to a SOA increase of less than 10 %.Due to two additional

Negative differential mobility for negative carriers as revealed by space charge measurements on crosslinked polyethylene insulated model cables

International Nuclear Information System (INIS)

Teyssedre, G.; Laurent, C.; Vu, T. T. N.

2015-01-01

Among features observed in polyethylene materials under relatively high field, space charge packets, consisting in a pulse of net charge that remains in the form of a pulse as it crosses the insulation, are repeatedly observed but without complete theory explaining their formation and propagation. Positive charge packets are more often reported, and the models based on negative differential mobility(NDM) for the transport of holes could account for some charge packets phenomenology. Conversely, NDM for electrons transport has never been reported so far. The present contribution reports space charge measurements by pulsed electroacoustic method on miniature cables that are model of HVDC cables. The measurements were realized at room temperature or with a temperature gradient of 10 °C through the insulation under DC fields on the order 30–60 kV/mm. Space charge results reveal systematic occurrence of a negative front of charges generated at the inner electrode that moves toward the outer electrode at the beginning of the polarization step. It is observed that the transit time of the front of negative charge increases, and therefore the mobility decreases, with the applied voltage. Further, the estimated mobility, in the range 10 −14 –10 −13  m 2  V −1  s −1 for the present results, increases when the temperature increases for the same condition of applied voltage. The features substantiate the hypothesis of negative differential mobility used for modelling space charge packets

RNA Virus Evolution via a Quasispecies-Based Model Reveals a Drug Target with a High Barrier to Resistance

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Richard J. Bingham

2017-11-01

Full Text Available The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly. We introduce here a quasispecies-based model of a viral infection that incorporates structural and mechanistic knowledge of packaging signal function in assembly to construct a phenotype-fitness map, capturing the impact of this RNA code on assembly yield and efficiency. Details of viral replication and assembly inside an infected host cell are coupled with a population model of a viral infection, allowing the occurrence of therapy resistance to be assessed in response to drugs inhibiting packaging signal recognition. Stochastic simulations of viral quasispecies evolution in chronic HCV infection under drug action and/or immune clearance reveal that drugs targeting all RNA signals in the assembly code collectively have a high barrier to drug resistance, even though each packaging signal in isolation has a lower barrier than conventional drugs. This suggests that drugs targeting the RNA signals in the assembly code could be promising routes for exploitation in anti-viral drug design.

RNA Virus Evolution via a Quasispecies-Based Model Reveals a Drug Target with a High Barrier to Resistance.

Science.gov (United States)

Bingham, Richard J; Dykeman, Eric C; Twarock, Reidun

2017-11-17

The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly. We introduce here a quasispecies-based model of a viral infection that incorporates structural and mechanistic knowledge of packaging signal function in assembly to construct a phenotype-fitness map, capturing the impact of this RNA code on assembly yield and efficiency. Details of viral replication and assembly inside an infected host cell are coupled with a population model of a viral infection, allowing the occurrence of therapy resistance to be assessed in response to drugs inhibiting packaging signal recognition. Stochastic simulations of viral quasispecies evolution in chronic HCV infection under drug action and/or immune clearance reveal that drugs targeting all RNA signals in the assembly code collectively have a high barrier to drug resistance, even though each packaging signal in isolation has a lower barrier than conventional drugs. This suggests that drugs targeting the RNA signals in the assembly code could be promising routes for exploitation in anti-viral drug design.

Negative differential mobility for negative carriers as revealed by space charge measurements on crosslinked polyethylene insulated model cables

Science.gov (United States)

Teyssedre, G.; Vu, T. T. N.; Laurent, C.

2015-12-01

Among features observed in polyethylene materials under relatively high field, space charge packets, consisting in a pulse of net charge that remains in the form of a pulse as it crosses the insulation, are repeatedly observed but without complete theory explaining their formation and propagation. Positive charge packets are more often reported, and the models based on negative differential mobility(NDM) for the transport of holes could account for some charge packets phenomenology. Conversely, NDM for electrons transport has never been reported so far. The present contribution reports space charge measurements by pulsed electroacoustic method on miniature cables that are model of HVDC cables. The measurements were realized at room temperature or with a temperature gradient of 10 °C through the insulation under DC fields on the order 30-60 kV/mm. Space charge results reveal systematic occurrence of a negative front of charges generated at the inner electrode that moves toward the outer electrode at the beginning of the polarization step. It is observed that the transit time of the front of negative charge increases, and therefore the mobility decreases, with the applied voltage. Further, the estimated mobility, in the range 10-14-10-13 m2 V-1 s-1 for the present results, increases when the temperature increases for the same condition of applied voltage. The features substantiate the hypothesis of negative differential mobility used for modelling space charge packets.

Analytical modelling and study of the stability characteristics of the Advanced Heavy Water Reactor

International Nuclear Information System (INIS)

Nayak, A.K.; Vijayan, P.K.; Saha, D.

2000-04-01

An analytical model has been developed to study the thermohydraulic and neutronic-coupled density-wave instability in the Indian Advanced Heavy Water Reactor (AHWR) which is a natural circulation pressure tube type boiling water reactor. The model considers a point kinetics model for the neutron dynamics and a lumped parameter model for the fuel thermal dynamics along with the conservation equations of mass, momentum and energy and equation of state for the coolant. In addition, to study the effect of neutron interactions between different parts of the core, the model considers a coupled multipoint kinetics equation in place of simple point kinetics equation. Linear stability theory was applied to reveal the instability of in-phase and out-of-phase modes in the boiling channels of the AHWR. The results indicate that the design configuration considered may experience both Ledinegg and Type I and Type II density-wave instabilities depending on the operating condition. Some methods of suppressing these instabilities were found out. In addition, it was found that the stability behavior of the reactor is greatly influenced by the void reactivity coefficient, fuel time constant, radial power distribution and channel inlet orificing. The delayed neutrons were found to have strong influence on the Type I and Type II instabilities. Decay ratio maps were predicted considering various operating parameters of the reactor, which are useful for its design. (author)

Reduced ENSO Variability at the LGM Revealed by an Isotope-Enabled Earth System Model

Science.gov (United States)

Zhu, Jiang; Liu, Zhengyu; Brady, Esther; Otto-Bliesner, Bette; Zhang, Jiaxu; Noone, David; Tomas, Robert; Nusbaumer, Jesse; Wong, Tony; Jahn, Alexandra;

Lipid clustering correlates with membrane curvature as revealed by molecular simulations of complex lipid bilayers.

Directory of Open Access Journals (Sweden)

Heidi Koldsø

2014-10-01

Full Text Available Cell membranes are complex multicomponent systems, which are highly heterogeneous in the lipid distribution and composition. To date, most molecular simulations have focussed on relatively simple lipid compositions, helping to inform our understanding of in vitro experimental studies. Here we describe on simulations of complex asymmetric plasma membrane model, which contains seven different lipids species including the glycolipid GM3 in the outer leaflet and the anionic lipid, phosphatidylinositol 4,5-bisphophate (PIP2, in the inner leaflet. Plasma membrane models consisting of 1500 lipids and resembling the in vivo composition were constructed and simulations were run for 5 µs. In these simulations the most striking feature was the formation of nano-clusters of GM3 within the outer leaflet. In simulations of protein interactions within a plasma membrane model, GM3, PIP2, and cholesterol all formed favorable interactions with the model α-helical protein. A larger scale simulation of a model plasma membrane containing 6000 lipid molecules revealed correlations between curvature of the bilayer surface and clustering of lipid molecules. In particular, the concave (when viewed from the extracellular side regions of the bilayer surface were locally enriched in GM3. In summary, these simulations explore the nanoscale dynamics of model bilayers which mimic the in vivo lipid composition of mammalian plasma membranes, revealing emergent nanoscale membrane organization which may be coupled both to fluctuations in local membrane geometry and to interactions with proteins.

Landslide-susceptibility analysis using light detection and ranging-derived digital elevation models and logistic regression models: a case study in Mizunami City, Japan

Science.gov (United States)

Wang, Liang-Jie; Sawada, Kazuhide; Moriguchi, Shuji

2013-01-01

To mitigate the damage caused by landslide disasters, different mathematical models have been applied to predict landslide spatial distribution characteristics. Although some researchers have achieved excellent results around the world, few studies take the spatial resolution of the database into account. Four types of digital elevation model (DEM) ranging from 2 to 20 m derived from light detection and ranging technology to analyze landslide susceptibility in Mizunami City, Gifu Prefecture, Japan, are presented. Fifteen landslide-causative factors are considered using a logistic-regression approach to create models for landslide potential analysis. Pre-existing landslide bodies are used to evaluate the performance of the four models. The results revealed that the 20-m model had the highest classification accuracy (71.9%), whereas the 2-m model had the lowest value (68.7%). In the 2-m model, 89.4% of the landslide bodies fit in the medium to very high categories. For the 20-m model, only 83.3% of the landslide bodies were concentrated in the medium to very high classes. When the cell size decreases from 20 to 2 m, the area under the relative operative characteristic increases from 0.68 to 0.77. Therefore, higher-resolution DEMs would provide better results for landslide-susceptibility mapping.

Typhoon Effect on Kuroshio and Green Island Wakes: A Modelling Study

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Tai-Wen Hsu

2018-01-01

Full Text Available Green Island, located in the typhoon-active eastern Taiwan coastal water, is the potential Kuroshio power plant site. In this study, a high resolution (250–2250 m shallow-water equations model is used to investigate the effect of typhoon on the hydro-dynamics of Kuroshio and Green Island wakes. Two typhoon–Kuroshio interactions—typhoon Soulik and Holland’s typhoon model—are studied. Simulation results of typhoon Soulik indicate salient characteristics of Kuroshio, and downstream island wakes seems less affected by the typhoon Soulik, because the shortest distance of typhoon Soulik is 250 km away from Green Island and wind speed near Green Island is small. Moreover, Kuroshio currents increase when flow is in the same direction as the counterclockwise rotation of typhoon, and vice versa. This finding is in favorable agreement with the TOROS (Taiwan Ocean Radar Observing System observed data. Simulations of Kuroshio and Holland’s typhoon model successfully reproduces the downstream recirculation and vortex street. Numerical results reveal that the slow moving typhoon has a more significant impact on the Kuroshio and downstream Green Island wakes than the fast moving typhoon does. The rightward bias phenomenon is evident—Kuroshio currents increase (decrease in the right (left of the moving typhoon’s track, due to the counterclockwise rotation of typhoon.

A comparative study on the forming limit diagram prediction between Marciniak-Kuczynski model and modified maximum force criterion by using the evolving non-associated Hill48 plasticity model

Science.gov (United States)

Shen, Fuhui; Lian, Junhe; Münstermann, Sebastian

2018-05-01

Experimental and numerical investigations on the forming limit diagram (FLD) of a ferritic stainless steel were performed in this study. The FLD of this material was obtained by Nakajima tests. Both the Marciniak-Kuczynski (MK) model and the modified maximum force criterion (MMFC) were used for the theoretical prediction of the FLD. From the results of uniaxial tensile tests along different loading directions with respect to the rolling direction, strong anisotropic plastic behaviour was observed in the investigated steel. A recently proposed anisotropic evolving non-associated Hill48 (enHill48) plasticity model, which was developed from the conventional Hill48 model based on the non-associated flow rule with evolving anisotropic parameters, was adopted to describe the anisotropic hardening behaviour of the investigated material. In the previous study, the model was coupled with the MMFC for FLD prediction. In the current study, the enHill48 was further coupled with the MK model. By comparing the predicted forming limit curves with the experimental results, the influences of anisotropy in terms of flow rule and evolving features on the forming limit prediction were revealed and analysed. In addition, the forming limit predictive performances of the MK and the MMFC models in conjunction with the enHill48 plasticity model were compared and evaluated.

Hydra meiosis reveals unexpected conservation of structural synaptonemal complex proteins across metazoans.

Science.gov (United States)

Fraune, Johanna; Alsheimer, Manfred; Volff, Jean-Nicolas; Busch, Karoline; Fraune, Sebastian; Bosch, Thomas C G; Benavente, Ricardo

2012-10-09

The synaptonemal complex (SC) is a key structure of meiosis, mediating the stable pairing (synapsis) of homologous chromosomes during prophase I. Its remarkable tripartite structure is evolutionarily well conserved and can be found in almost all sexually reproducing organisms. However, comparison of the different SC protein components in the common meiosis model organisms Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealed no sequence homology. This discrepancy challenged the hypothesis that the SC arose only once in evolution. To pursue this matter we focused on the evolution of SYCP1 and SYCP3, the two major structural SC proteins of mammals. Remarkably, our comparative bioinformatic and expression studies revealed that SYCP1 and SYCP3 are also components of the SC in the basal metazoan Hydra. In contrast to previous assumptions, we therefore conclude that SYCP1 and SYCP3 form monophyletic groups of orthologous proteins across metazoans.

Model quality and safety studies

DEFF Research Database (Denmark)

Petersen, K.E.

1997-01-01

The paper describes the EC initiative on model quality assessment and emphasizes some of the problems encountered in the selection of data from field tests used in the evaluation process. Further, it discusses the impact of model uncertainties in safety studies of industrial plants. The model...... that most of these have never been through a procedure of evaluation, but nonetheless are used to assist in making decisions that may directly affect the safety of the public and the environment. As a major funder of European research on major industrial hazards, DGXII is conscious of the importance......-tain model is appropriate for use in solving a given problem. Further, the findings from the REDIPHEM project related to dense gas dispersion will be highlighted. Finally, the paper will discuss the need for model quality assessment in safety studies....

Mathematical modeling reveals kinetics of lymphocyte recirculation in the whole organism.

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Vitaly V Ganusov

2014-05-01

Full Text Available The kinetics of recirculation of naive lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct lymphocytes (TDLs via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95% of lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5% migrate to secondary lymphoid tissues such as lymph nodes, Peyer's patches, or the spleen. Interestingly, our analysis suggests that lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours and a longer average residence time of TDLs in major lymph nodes and Peyer's patches (10 hours. Surprisingly, we find that the average residence time of lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs or the gut (mesenteric LNs or in Peyer's patches. Applying our model to an additional dataset on lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of recirculation kinetics of thoracic duct lymphocytes in the whole organism.

Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

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Hua Wan

2016-01-01

Full Text Available TAL effectors (TALEs contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE.

Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism

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Camilla Ceccatelli Berti

2015-04-01

Full Text Available Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA, namely PKAN and CoPAN. PKAN are defined by mutations in PANK2, encoding the pantothenate kinase 2 enzyme, that account for about 50% of cases of NBIA, whereas mutations in CoA synthase COASY have been recently reported as the second inborn error of CoA synthesis leading to CoPAN. As reported previously, yeast cells expressing the pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.

Seasonal succession in zooplankton feeding traits reveals trophic trait coupling

DEFF Research Database (Denmark)

Kenitz, Kasia; Visser, Andre; Mariani, Patrizio

2017-01-01

non-motile cells flourishing in spring and motile community dominating during summer. The zooplankton community is dominated by active feeding-current feeders with peak biomass in the late spring declining during summer. The model reveals how zooplankton grazing reinforces protist plankton seasonal...

Modeling study on the effects of pulse rise rate in atmospheric pulsed discharges

Science.gov (United States)

Zhang, Yuan-Tao; Wang, Yan-Hui

2018-02-01

In this paper, we present a modeling study on the discharge characteristics driven by short pulsed voltages, focusing on the effects of pulse rise rate based on the fluid description of atmospheric plasmas. The numerical results show that the breakdown voltage of short pulsed discharge is almost linearly dependent on the pulse rise rate, which is also confirmed by the derived equations from the fluid model. In other words, if the pulse rise rate is fixed as a constant, the simulation results clearly suggest that the breakdown voltage is almost unchanged, although the amplitude of pulsed voltage increases significantly. The spatial distribution of the electric field and electron density are given to reveal the underpinning physics. Additionally, the computational data and the analytical expression also indicate that an increased repetition frequency can effectively decrease the breakdown voltage and current density, which is consistent with the experimental observation.

Comments and corrections on 3D modeling studies of locomotor muscle moment arms in archosaurs

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Karl Bates

2015-10-01

Full Text Available In a number of recent studies we used computer modeling to investigate the evolution of muscle leverage (moment arms and function in extant and extinct archosaur lineages (crocodilians, dinosaurs including birds and pterosaurs. These studies sought to quantify the level of disparity and convergence in muscle moment arms during the evolution of bipedal and quadrupedal posture in various independent archosaur lineages, and in doing so further our understanding of changes in anatomy, locomotion and ecology during the group’s >250 million year evolutionary history. Subsequent work by others has led us to re-evaluate our models, which revealed a methodological error that impacted on the results obtained from the abduction–adduction and long-axis rotation moment arms in our published studies. In this paper we present corrected abduction–adduction and long axis rotation moment arms for all our models, and evaluate the impact of this new data on the conclusions of our previous studies. We find that, in general, our newly corrected data differed only slightly from that previously published, with very few qualitative changes in muscle moments (e.g., muscles originally identified as abductors remained abductors. As a result the majority of our previous conclusions regarding the functional evolution of key muscles in these archosaur groups are upheld.

Structural modelling and phylogenetic analyses of PgeIF4A2 (Eukaryotic translation initiation factor) from Pennisetum glaucum reveal signature motifs with a role in stress tolerance and development.

Science.gov (United States)

Agarwal, Aakrati; Mudgil, Yashwanti; Pandey, Saurabh; Fartyal, Dhirendra; Reddy, Malireddy K

2016-01-01

Eukaryotic translation initiation factor 4A (eIF4A) is an indispensable component of the translation machinery and also play a role in developmental processes and stress alleviation in plants and animals. Different eIF4A isoforms are present in the cytosol of the cell, namely, eIF4A1, eIF4A2, and eIF4A3 and their expression is tightly regulated in cap-dependent translation. We revealed the structural model of PgeIF4A2 protein using the crystal structure of Homo sapiens eIF4A3 (PDB ID: 2J0S) as template by Modeller 9.12. The resultant PgeIF4A2 model structure was refined by PROCHECK, ProSA, Verify3D and RMSD that showed the model structure is reliable with 77 % amino acid sequence identity with template. Investigation revealed two conserved signatures for ATP-dependent RNA Helicase DEAD-box conserved site (VLDEADEML) and RNA helicase DEAD-box type, Q-motif in sheet-turn-helix and α-helical region respectively. All these conserved motifs are responsible for response during developmental stages and stress tolerance in plants.

Numerical modeling of carrier gas flow in atomic layer deposition vacuum reactor: A comparative study of lattice Boltzmann models

International Nuclear Information System (INIS)

Pan, Dongqing; Chien Jen, Tien; Li, Tao; Yuan, Chris

2014-01-01

This paper characterizes the carrier gas flow in the atomic layer deposition (ALD) vacuum reactor by introducing Lattice Boltzmann Method (LBM) to the ALD simulation through a comparative study of two LBM models. Numerical models of gas flow are constructed and implemented in two-dimensional geometry based on lattice Bhatnagar–Gross–Krook (LBGK)-D2Q9 model and two-relaxation-time (TRT) model. Both incompressible and compressible scenarios are simulated and the two models are compared in the aspects of flow features, stability, and efficiency. Our simulation outcome reveals that, for our specific ALD vacuum reactor, TRT model generates better steady laminar flow features all over the domain with better stability and reliability than LBGK-D2Q9 model especially when considering the compressible effects of the gas flow. The LBM-TRT is verified indirectly by comparing the numerical result with conventional continuum-based computational fluid dynamics solvers, and it shows very good agreement with these conventional methods. The velocity field of carrier gas flow through ALD vacuum reactor was characterized by LBM-TRT model finally. The flow in ALD is in a laminar steady state with velocity concentrated at the corners and around the wafer. The effects of flow fields on precursor distributions, surface absorptions, and surface reactions are discussed in detail. Steady and evenly distributed velocity field contribute to higher precursor concentration near the wafer and relatively lower particle velocities help to achieve better surface adsorption and deposition. The ALD reactor geometry needs to be considered carefully if a steady and laminar flow field around the wafer and better surface deposition are desired

Numerical modeling of carrier gas flow in atomic layer deposition vacuum reactor: A comparative study of lattice Boltzmann models

Energy Technology Data Exchange (ETDEWEB)

Pan, Dongqing; Chien Jen, Tien [Department of Mechanical Engineering, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201 (United States); Li, Tao [School of Mechanical Engineering, Dalian University of Technology, Dalian 116024 (China); Yuan, Chris, E-mail: cyuan@uwm.edu [Department of Mechanical Engineering, University of Wisconsin-Milwaukee, 3200 North Cramer Street, Milwaukee, Wisconsin 53211 (United States)

2014-01-15

This paper characterizes the carrier gas flow in the atomic layer deposition (ALD) vacuum reactor by introducing Lattice Boltzmann Method (LBM) to the ALD simulation through a comparative study of two LBM models. Numerical models of gas flow are constructed and implemented in two-dimensional geometry based on lattice Bhatnagar–Gross–Krook (LBGK)-D2Q9 model and two-relaxation-time (TRT) model. Both incompressible and compressible scenarios are simulated and the two models are compared in the aspects of flow features, stability, and efficiency. Our simulation outcome reveals that, for our specific ALD vacuum reactor, TRT model generates better steady laminar flow features all over the domain with better stability and reliability than LBGK-D2Q9 model especially when considering the compressible effects of the gas flow. The LBM-TRT is verified indirectly by comparing the numerical result with conventional continuum-based computational fluid dynamics solvers, and it shows very good agreement with these conventional methods. The velocity field of carrier gas flow through ALD vacuum reactor was characterized by LBM-TRT model finally. The flow in ALD is in a laminar steady state with velocity concentrated at the corners and around the wafer. The effects of flow fields on precursor distributions, surface absorptions, and surface reactions are discussed in detail. Steady and evenly distributed velocity field contribute to higher precursor concentration near the wafer and relatively lower particle velocities help to achieve better surface adsorption and deposition. The ALD reactor geometry needs to be considered carefully if a steady and laminar flow field around the wafer and better surface deposition are desired.

Separating foliar physiology from morphology reveals the relative roles of vertically structured transpiration factors within red maple crowns and limitations of larger scale models

Science.gov (United States)

Bauerle, William L.; Bowden, Joseph D.

2011-01-01

A spatially explicit mechanistic model, MAESTRA, was used to separate key parameters affecting transpiration to provide insights into the most influential parameters for accurate predictions of within-crown and within-canopy transpiration. Once validated among Acer rubrum L. genotypes, model responses to different parameterization scenarios were scaled up to stand transpiration (expressed per unit leaf area) to assess how transpiration might be affected by the spatial distribution of foliage properties. For example, when physiological differences were accounted for, differences in leaf width among A. rubrum L. genotypes resulted in a 25% difference in transpiration. An in silico within-canopy sensitivity analysis was conducted over the range of genotype parameter variation observed and under different climate forcing conditions. The analysis revealed that seven of 16 leaf traits had a ≥5% impact on transpiration predictions. Under sparse foliage conditions, comparisons of the present findings with previous studies were in agreement that parameters such as the maximum Rubisco-limited rate of photosynthesis can explain ∼20% of the variability in predicted transpiration. However, the spatial analysis shows how such parameters can decrease or change in importance below the uppermost canopy layer. Alternatively, model sensitivity to leaf width and minimum stomatal conductance was continuous along a vertical canopy depth profile. Foremost, transpiration sensitivity to an observed range of morphological and physiological parameters is examined and the spatial sensitivity of transpiration model predictions to vertical variations in microclimate and foliage density is identified to reduce the uncertainty of current transpiration predictions. PMID:21617246

Instability of Nagaoka's Theorem within The Hubbard Model ...

African Journals Online (AJOL)

Hence the t – J model is a better model for studying magnetism than the t – U model. Investigation also revealed that the inclusion of the on-site Coulomb interaction term U, in the t – J model enhances ferromagnetic tendencies in the systems studied. In this work, Nagaoka's theorem on ferromagnetism has been extended ...

Modelling Difficulties and Their Overcoming Strategies in the Solution of a Modelling Problem

Science.gov (United States)

Dede, Ayse Tekin

2016-01-01

The purpose of the study is to reveal the elementary mathematics student teachers' difficulties encountered in the solution of a modelling problem, the strategies to overcome those difficulties and whether the strategies worked or not. Nineteen student teachers solved the modelling problem in their four or five-person groups, and the video records…

Compartmentation of glycogen metabolism revealed from 13C isotopologue distributions

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Marin de Mas Igor

2011-10-01

Full Text Available Abstract Background Stable isotope tracers are used to assess metabolic flux profiles in living cells. The existing methods of measurement average out the isotopic isomer distribution in metabolites throughout the cell, whereas the knowledge of compartmental organization of analyzed pathways is crucial for the evaluation of true fluxes. That is why we accepted a challenge to create a software tool that allows deciphering the compartmentation of metabolites based on the analysis of average isotopic isomer distribution. Results The software Isodyn, which simulates the dynamics of isotopic isomer distribution in central metabolic pathways, was supplemented by algorithms facilitating the transition between various analyzed metabolic schemes, and by the tools for model discrimination. It simulated 13C isotope distributions in glucose, lactate, glutamate and glycogen, measured by mass spectrometry after incubation of hepatocytes in the presence of only labeled glucose or glucose and lactate together (with label either in glucose or lactate. The simulations assumed either a single intracellular hexose phosphate pool, or also channeling of hexose phosphates resulting in a different isotopic composition of glycogen. Model discrimination test was applied to check the consistency of both models with experimental data. Metabolic flux profiles, evaluated with the accepted model that assumes channeling, revealed the range of changes in metabolic fluxes in liver cells. Conclusions The analysis of compartmentation of metabolic networks based on the measured 13C distribution was included in Isodyn as a routine procedure. The advantage of this implementation is that, being a part of evaluation of metabolic fluxes, it does not require additional experiments to study metabolic compartmentation. The analysis of experimental data revealed that the distribution of measured 13C-labeled glucose metabolites is inconsistent with the idea of perfect mixing of hexose

Mechanistic species distribution modeling reveals a niche shift during invasion.

Science.gov (United States)

Chapman, Daniel S; Scalone, Romain; Štefanić, Edita; Bullock, James M

2017-06-01

Niche shifts of nonnative plants can occur when they colonize novel climatic conditions. However, the mechanistic basis for niche shifts during invasion is poorly understood and has rarely been captured within species distribution models. We quantified the consequence of between-population variation in phenology for invasion of common ragweed (Ambrosia artemisiifolia L.) across Europe. Ragweed is of serious concern because of its harmful effects as a crop weed and because of its impact on public health as a major aeroallergen. We developed a forward mechanistic species distribution model based on responses of ragweed development rates to temperature and photoperiod. The model was parameterized and validated from the literature and by reanalyzing data from a reciprocal common garden experiment in which native and invasive populations were grown within and beyond the current invaded range. It could therefore accommodate between-population variation in the physiological requirements for flowering, and predict the potentially invaded ranges of individual populations. Northern-origin populations that were established outside the generally accepted climate envelope of the species had lower thermal requirements for bud development, suggesting local adaptation of phenology had occurred during the invasion. The model predicts that this will extend the potentially invaded range northward and increase the average suitability across Europe by 90% in the current climate and 20% in the future climate. Therefore, trait variation observed at the population scale can trigger a climatic niche shift at the biogeographic scale. For ragweed, earlier flowering phenology in established northern populations could allow the species to spread beyond its current invasive range, substantially increasing its risk to agriculture and public health. Mechanistic species distribution models offer the possibility to represent niche shifts by varying the traits and niche responses of individual

Study on sand particles creep model and open pit mine landslide mechanism caused by sand fatigue liquefaction

Science.gov (United States)

Du, Dong-Ning; Wang, Lai-Gui; Zhang, Xiang-Dong; Zhang, Shu-Kun

2017-06-01

The sand particles in the sand - rock composite slope of the open pit mine occurs creep deformation and fatigue liquefaction under the action of vehicle load vibration and hydraulic gradient, which causes landslide geological disasters and it destroys the surface environment. To reveal the mechanism, a mechanics model based on the model considering the soil structural change with a new “plastic hinge” element is developed, to improve its constitutive and creep curve equations. Data from sand creep experiments are used to identify the parameters in the model and to validate the model. The results show that the mechanical model can describe the rotation progress between the sand particles, disclose the negative acceleration creep deformation stage during the third phase, and require fewer parameters while maintaining accuracy. It provides a new creep model considering rotation to analyze sand creep mechanism, which provides a theoretical basis for revealing the open pit mine landslide mechanism induced by creep deformation and fatigue liquefaction of sandy soil.

Robotic assessment of neuromuscular characteristics using musculoskeletal models: A pilot study.

Science.gov (United States)

Jayaneththi, V R; Viloria, J; Wiedemann, L G; Jarrett, C; McDaid, A J

2017-07-01

Non-invasive neuromuscular characterization aims to provide greater insight into the effectiveness of existing and emerging rehabilitation therapies by quantifying neuromuscular characteristics relating to force production, muscle viscoelasticity and voluntary neural activation. In this paper, we propose a novel approach to evaluate neuromuscular characteristics, such as muscle fiber stiffness and viscosity, by combining robotic and HD-sEMG measurements with computational musculoskeletal modeling. This pilot study investigates the efficacy of this approach on a healthy population and provides new insight on potential limitations of conventional musculoskeletal models for this application. Subject-specific neuromuscular characteristics of the biceps and triceps brachii were evaluated using robot-measured kinetics, kinematics and EMG activity as inputs to a musculoskeletal model. Repeatability experiments in five participants revealed large variability within each subjects evaluated characteristics, with almost all experiencing variation greater than 50% of full scale when repeating the same task. The use of robotics and HD-sEMG, in conjunction with musculoskeletal modeling, to quantify neuromuscular characteristics has been explored. Despite the ability to predict joint kinematics with relatively high accuracy, parameter characterization was inconsistent i.e. many parameter combinations gave rise to minimal kinematic error. The proposed technique is a novel approach for in vivo neuromuscular characterization and is a step towards the realization of objective in-home robot-assisted rehabilitation. Importantly, the results have confirmed the technical (robot and HD-sEMG) feasibility while highlighting the need to develop new musculoskeletal models and optimization techniques capable of achieving consistent results across a range of dynamic tasks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Animal models.

Science.gov (United States)

Walker, Ellen A

2010-01-01

As clinical studies reveal that chemotherapeutic agents may impair several different cognitive domains in humans, the development of preclinical animal models is critical to assess the degree of chemotherapy-induced learning and memory deficits and to understand the underlying neural mechanisms. In this chapter, the effects of various cancer chemotherapeutic agents in rodents on sensory processing, conditioned taste aversion, conditioned emotional response, passive avoidance, spatial learning, cued memory, discrimination learning, delayed-matching-to-sample, novel-object recognition, electrophysiological recordings and autoshaping is reviewed. It appears at first glance that the effects of the cancer chemotherapy agents in these many different models are inconsistent. However, a literature is emerging that reveals subtle or unique changes in sensory processing, acquisition, consolidation and retrieval that are dose- and time-dependent. As more studies examine cancer chemotherapeutic agents alone and in combination during repeated treatment regimens, the animal models will become more predictive tools for the assessment of these impairments and the underlying neural mechanisms. The eventual goal is to collect enough data to enable physicians to make informed choices about therapeutic regimens for their patients and discover new avenues of alternative or complementary therapies that reduce or eliminate chemotherapy-induced cognitive deficits.

Structural equation modeling in the genetically informative study of the covariation of intelligence, working memory and planning

Directory of Open Access Journals (Sweden)

Voronin I.

2016-01-01

Full Text Available Structural equation modelling (SEM has become an important tool in behaviour genetic research. The application of SEM for multivariate twin analysis allows revealing the structure of genetic and environmental factors underlying individual differences in human traits. We outline the framework of twin method and SEM, describe SEM implementation of a multivariate twin model and provide an example of a multivariate twin study. The study included 901 adolescent twin pairs from Russia. We measured general cognitive ability and characteristics of working memory and planning. The individual differences in working memory and planning were explained mostly by person-specific environment. The variability of intelligence is related to genes, family environment, and person specific environment. Moderate and weak associations between intelligence, working memory, and planning were entirely explained by shared environmental effects.

Kinetics of ethylcyclohexane pyrolysis and oxidation: An experimental and detailed kinetic modeling study

KAUST Repository

Wang, Zhandong

2015-07-01

Ethylcyclohexane (ECH) is a model compound for cycloalkanes with long alkyl side-chains. A preliminary investigation on ECH (Wang et al., Proc. Combust. Inst., 35, 2015, 367-375) revealed that an accurate ECH kinetic model with detailed fuel consumption mechanism and aromatic growth pathways, as well as additional ECH pyrolysis and oxidation data with detailed species concentration covering a wide pressure and temperature range are required to understand the ECH combustion kinetics. In this work, the flow reactor pyrolysis of ECH at various pressures (30, 150 and 760Torr) was studied using synchrotron vacuum ultraviolet (VUV) photoionization mass spectrometry (PIMS) and gas chromatography (GC). The mole fraction profiles of numerous major and minor species were evaluated, and good agreement was observed between the PIMS and GC data sets. Furthermore, a fuel-rich burner-stabilized laminar premixed ECH/O2/Ar flame at 30Torr was studied using synchrotron VUV PIMS. A detailed kinetic model for ECH high temperature pyrolysis and oxidation was developed and validated against the pyrolysis and flame data performed in this work. Further validation of the kinetic model is presented against literature data including species concentrations in jet-stirred reactor oxidation, ignition delay times in a shock tube, and laminar flame speeds at various pressures and equivalence ratios. The model well predicts the consumption of ECH, the growth of aromatics, and the global combustion properties. Reaction flux and sensitivity analysis were utilized to elucidate chemical kinetic features of ECH combustion under various reaction conditions. © 2015 The Combustion Institute.

Seismic tomography model reveals mantle magma sources of recent volcanic activity at El Hierro Island (Canary Islands, Spain)

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García-Yeguas, Araceli; Ibáñez, Jesús M.; Koulakov, Ivan; Jakovlev, Andrey; Romero-Ruiz, M. Carmen; Prudencio, Janire

2014-12-01

We present a 3-D model of P and S velocities beneath El Hierro Island, constructed using the traveltime data of more than 13 000 local earthquakes recorded by the Instituto Geográfico Nacional (IGN, Spain) in the period from 2011 July to 2012 September. The velocity models were performed using the LOTOS code for iterative passive source tomography. The results of inversion were thoroughly verified using different resolution and robustness tests. The results reveal that the majority of the onshore area of El Hierro is associated with a high-velocity anomaly observed down to 10-12-km depth. This anomaly is interpreted as the accumulation of solid igneous rocks erupted during the last 1 Myr and intrusive magmatic bodies. Below this high-velocity pattern, we observe a low-velocity anomaly, interpreted as a batch of magma coming from the mantle located beneath El Hierro. The boundary between the low- and high-velocity anomalies is marked by a prominent seismicity cluster, thought to represent anomalous stresses due to the interaction of the batch of magma with crust material. The areas of recent eruptions, Orchilla and La Restinga, are associated with low-velocity anomalies surrounding the main high-velocity block. These eruptions took place around the island where the crust is much weaker than the onshore area and where the melted material cannot penetrate. These results put constraints on the geological model that could explain the origin of the volcanism in oceanic islands, such as in the Canaries, which is not yet clearly understood.

Negative differential mobility for negative carriers as revealed by space charge measurements on crosslinked polyethylene insulated model cables

Energy Technology Data Exchange (ETDEWEB)

Teyssedre, G., E-mail: gilbert.teyssedre@laplace.univ-tlse.fr; Laurent, C. [Université de Toulouse, UPS, INPT, LAPLACE (Laboratoire Plasma et Conversion d' Energie), 118 route de Narbonne, F-31062 Toulouse cedex 9 (France); CNRS, LAPLACE, F-31062 Toulouse (France); Vu, T. T. N. [Université de Toulouse, UPS, INPT, LAPLACE (Laboratoire Plasma et Conversion d' Energie), 118 route de Narbonne, F-31062 Toulouse cedex 9 (France); Electric Power University, 235 Hoang Quoc Viet, 10000 Hanoi (Viet Nam)

2015-12-21

Among features observed in polyethylene materials under relatively high field, space charge packets, consisting in a pulse of net charge that remains in the form of a pulse as it crosses the insulation, are repeatedly observed but without complete theory explaining their formation and propagation. Positive charge packets are more often reported, and the models based on negative differential mobility(NDM) for the transport of holes could account for some charge packets phenomenology. Conversely, NDM for electrons transport has never been reported so far. The present contribution reports space charge measurements by pulsed electroacoustic method on miniature cables that are model of HVDC cables. The measurements were realized at room temperature or with a temperature gradient of 10 °C through the insulation under DC fields on the order 30–60 kV/mm. Space charge results reveal systematic occurrence of a negative front of charges generated at the inner electrode that moves toward the outer electrode at the beginning of the polarization step. It is observed that the transit time of the front of negative charge increases, and therefore the mobility decreases, with the applied voltage. Further, the estimated mobility, in the range 10{sup −14}–10{sup −13} m{sup 2} V{sup −1} s{sup −1} for the present results, increases when the temperature increases for the same condition of applied voltage. The features substantiate the hypothesis of negative differential mobility used for modelling space charge packets.

Integrative demographic modeling reveals population level impacts of PCB toxicity to juvenile snapping turtles

International Nuclear Information System (INIS)

Salice, Christopher J.; Rowe, Christopher L.; Eisenreich, Karen M.

2014-01-01

A significant challenge in ecotoxicology and risk assessment lies in placing observed contaminant effects in a meaningful ecological context. Polychlorinated biphenyls (PCBs) have been shown to affect juvenile snapping turtle survival and growth but the ecological significance of these effects is difficult to discern without a formal, population-level assessment. We used a demographic matrix model to explore the potential population-level effects of PCBs on turtles. Our model showed that effects of PCBs on juvenile survival, growth and size at hatching could translate to negative effects at the population level despite the fact that these life cycle components do not typically contribute strongly to population level processes. This research points to the utility of using integrative demographic modeling approaches to better understand contaminant effects in wildlife. The results indicate that population-level effects are only evident after several years, suggesting that for long-lived species, detecting adverse contaminant effects could prove challenging. -- Highlights: • Previous studies have shown the PCBs can impact juvenile snapping turtles. • We used a demographic model of turtles to evaluate population-level PCB effects. • PCB effects on turtles may translate to negative population responses. • Long-term monitoring is needed to detect contaminant effects on natural turtle populations. • Demographic models can improve our understanding contaminant ecotoxicity. -- A demographic model was used to show that PCB induced effects on young snapping turtles can result in adverse effects at the population level

Studying shocks in model astrophysical flows

International Nuclear Information System (INIS)

Chakrabarti, S.K.

1989-01-01

We briefly discuss some properties of the shocks in the existing models for quasi two-dimensional astrophysical flows. All of these models which allow the study of shock analytically have some unphysical characteristics due to inherent assumptions made. We propose a hybrid model for a thin flow which has fewer unpleasant features and is suitable for the study of shocks. (author). 5 refs

Studies on 16α-Hydroxylation of Steroid Molecules and Regioselective Binding Mode in Homology-Modeled Cytochrome P450-2C11

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Hamed I. Ali

2011-01-01

Full Text Available We investigated the 16α-hydroxylation of steroid molecules and regioselective binding mode in homology-modeled cytochrome P450-2C11 to correlate the biological study with the computational molecular modeling. It revealed that there was a positive relationship between the observed inhibitory potencies and the binding free energies. Docking of steroid molecules into this homology-modeled CYP2C11 indicated that 16α-hydroxylation is favored with steroidal molecules possessing the following components, (1 a bent A-B ring configuration (5β-reduced, (2 C-3 α-hydroxyl group, (3 C-17β-acetyl group, and (4 methyl group at both the C-18 and C-19. These respective steroid components requirements were defined as the inhibitory contribution factor. Overall studies of the male rat CYP2C11 metabolism revealed that the above-mentioned steroid components requirements were essential to induce an effective inhibition of [3H]progesterone 16α-hydroxylation. As far as docking of homology-modeled CYP2C11 against investigated steroids is concerned, they are docked at the active site superimposed with flurbiprofen. It was also found that the distance between heme iron and C16α-H was between 4 to 6 Å and that the related angle was in the range of 180±45∘.

Results from an acoustic modelling study of seismic airgun survey noise in Queen Charlotte Basin

Energy Technology Data Exchange (ETDEWEB)

MacGillivray, A.O.; Chapman, N.R. [Victoria Univ., BC (Canada). School of Earth and Ocean Sciences

2005-12-07

An acoustic modelling study was conducted to examine seismic survey noise propagation in the Queen Charlotte Basin (QCB) and better understand the physical aspects of sound transmission. The study results are intended to help determine the potential physiological and behavioural effects of airgun noise on marine mammals and fish. The scope of the study included a numerical simulation of underwater sound transmission in QCB in areas where oil and gas exploration activities may be conducted; a forecast of received noise levels by combining acoustic transmission loss computations with acoustic source levels representative of seismic exploration activity and, the use of received forecasts to estimate zones of impact for marine mammals. The critical environmental parameters in the QCB are the bathymetry of the ocean, the sound speed profile in the water and the geoacoustic profile of the seabed. The RAM acoustic propagation model developed by the United States Naval Research Laboratory was used to compute acoustic transmission loss in the QCB. The source level and directionality of the seismic array was determined by a full-waveform array source signature model. This modelling study of noise propagation from seismic surveys revealed several key findings. Among them, it showed that received noise levels in the water are affected by the source location, array orientation and the shape of the sound speed profile with respect to water depth. It also showed that noise levels are lowest in shallow bathymetry. 30 refs., 5 tabs., 13 figs.

TreeNetViz: revealing patterns of networks over tree structures.

Science.gov (United States)

Gou, Liang; Zhang, Xiaolong Luke

2011-12-01

Network data often contain important attributes from various dimensions such as social affiliations and areas of expertise in a social network. If such attributes exhibit a tree structure, visualizing a compound graph consisting of tree and network structures becomes complicated. How to visually reveal patterns of a network over a tree has not been fully studied. In this paper, we propose a compound graph model, TreeNet, to support visualization and analysis of a network at multiple levels of aggregation over a tree. We also present a visualization design, TreeNetViz, to offer the multiscale and cross-scale exploration and interaction of a TreeNet graph. TreeNetViz uses a Radial, Space-Filling (RSF) visualization to represent the tree structure, a circle layout with novel optimization to show aggregated networks derived from TreeNet, and an edge bundling technique to reduce visual complexity. Our circular layout algorithm reduces both total edge-crossings and edge length and also considers hierarchical structure constraints and edge weight in a TreeNet graph. These experiments illustrate that the algorithm can reduce visual cluttering in TreeNet graphs. Our case study also shows that TreeNetViz has the potential to support the analysis of a compound graph by revealing multiscale and cross-scale network patterns. © 2011 IEEE

The Evaluation of Bivariate Mixed Models in Meta-analyses of Diagnostic Accuracy Studies with SAS, Stata and R.

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Vogelgesang, Felicitas; Schlattmann, Peter; Dewey, Marc

2018-05-01

Meta-analyses require a thoroughly planned procedure to obtain unbiased overall estimates. From a statistical point of view not only model selection but also model implementation in the software affects the results. The present simulation study investigates the accuracy of different implementations of general and generalized bivariate mixed models in SAS (using proc mixed, proc glimmix and proc nlmixed), Stata (using gllamm, xtmelogit and midas) and R (using reitsma from package mada and glmer from package lme4). Both models incorporate the relationship between sensitivity and specificity - the two outcomes of interest in meta-analyses of diagnostic accuracy studies - utilizing random effects. Model performance is compared in nine meta-analytic scenarios reflecting the combination of three sizes for meta-analyses (89, 30 and 10 studies) with three pairs of sensitivity/specificity values (97%/87%; 85%/75%; 90%/93%). The evaluation of accuracy in terms of bias, standard error and mean squared error reveals that all implementations of the generalized bivariate model calculate sensitivity and specificity estimates with deviations less than two percentage points. proc mixed which together with reitsma implements the general bivariate mixed model proposed by Reitsma rather shows convergence problems. The random effect parameters are in general underestimated. This study shows that flexibility and simplicity of model specification together with convergence robustness should influence implementation recommendations, as the accuracy in terms of bias was acceptable in all implementations using the generalized approach. Schattauer GmbH.

Behavioural Comparison of Driverswhen Driving a Motorcycle or a Car: A Structural Equation Modelling Study

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Darja Topolšek

2015-12-01

Full Text Available The goal of the study was to investigate if the drivers behave in the same way when they are driving a motorcycle or a car. For this purpose, the Motorcycle Rider Behaviour Questionnaire and Driver Behaviour Questionnaire were conducted among the same drivers population. Items of questionnaires were used to develop a structural equation model with two factors, one for the motorcyclist’s behaviour, and the other for the car driver’s behaviour. Exploratory and confirmatory factor analyses were also applied in this study. Results revealed a certain difference in driving behaviour. The principal reason lies probably in mental consciousness that the risk-taking driving of a motorbike can result in much more catastrophic consequences than when driving a car. The drivers also pointed out this kind of thinking and the developed model has statistically confirmed the behavioural differences. The implications of these findings are also argued in relation to the validation of the appropriateness of the existing traffic regulations.

A Study on Logistics Cluster Competitiveness among Asia Main Countries using the Porter's Diamond Model

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Tae Won Chung

2016-12-01

Full Text Available Measurement and discussions of logistics cluster competitiveness with a national approach are required to boost agglomeration effects and potentially create logistics efficiency and productivity. This study developed assessment criteria of logistics cluster competitiveness based on Porter's diamond model, calculated the weight of each criterion by the AHP method, and finally evaluated and discussed logistics cluster competitiveness among Asia main countries. The results indicate that there was a large difference in logistics cluster competitiveness among six countries. The logistics cluster competitiveness scores of Singapore (7.93, Japan (7.38, and Hong Kong (7.04 are observably different from those of China (5.40, Korea (5.08, and Malaysia (3.46. Singapore, with the highest competitiveness score, revealed its absolute advantage in logistics cluster indices. These research results intend to provide logistics policy makers with some strategic recommendations, and may serve as a baseline for further logistics cluster studies using Porter's diamond model.

Grainyhead-like 2 (GRHL2) distribution reveals novel pathophysiological differences between human idiopathic pulmonary fibrosis and mouse models of pulmonary fibrosis

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Mahavadi, Poornima; Sasikumar, Satish; Cushing, Leah; Hyland, Tessa; Rosser, Ann E.; Riccardi, Daniela; Lu, Jining; Kalin, Tanya V.; Kalinichenko, Vladimir V.; Guenther, Andreas; Ramirez, Maria I.; Pardo, Annie; Selman, Moisés; Warburton, David

2013-01-01

Chronic injury of alveolar lung epithelium leads to epithelial disintegrity in idiopathic pulmonary fibrosis (IPF). We had reported earlier that Grhl2, a transcriptional factor, maintains alveolar epithelial cell integrity by directly regulating components of adherens and tight junctions and thus hypothesized an important role of GRHL2 in pathogenesis of IPF. Comparison of GRHL2 distribution at different stages of human lung development showed its abundance in developing lung epithelium and in adult lung epithelium. However, GRHL2 is detected in normal human lung mesenchyme only at early fetal stage (week 9). Similar mesenchymal reexpression of GRHL2 was also observed in IPF. Immunofluorescence analysis in serial sections from three IPF patients revealed at least two subsets of alveolar epithelial cells (AEC), based on differential GRHL2 expression and the converse fluorescence intensities for epithelial vs. mesenchymal markers. Grhl2 was not detected in mesenchyme in intraperitoneal bleomycin-induced injury as well as in spontaneously occurring fibrosis in double-mutant HPS1 and HPS2 mice, whereas in contrast in a radiation-induced fibrosis model, with forced Forkhead box M1 (Foxm1) expression, an overlap of Grhl2 with a mesenchymal marker was observed in fibrotic regions. Grhl2's role in alveolar epithelial cell plasticity was confirmed by altered Grhl2 gene expression analysis in IPF and further validated by in vitro manipulation of its expression in alveolar epithelial cell lines. Our findings reveal important pathophysiological differences between human IPF and specific mouse models of fibrosis and support a crucial role of GRHL2 in epithelial activation in lung fibrosis and perhaps also in epithelial plasticity. PMID:24375798

Submillisecond elastic recoil reveals molecular origins of fibrin fiber mechanics.

Science.gov (United States)

Hudson, Nathan E; Ding, Feng; Bucay, Igal; O'Brien, E Timothy; Gorkun, Oleg V; Superfine, Richard; Lord, Susan T; Dokholyan, Nikolay V; Falvo, Michael R

2013-06-18

Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin's elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin's mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The new galaxy evolution paradigm revealed by the Herschel surveys

Science.gov (United States)

Eales, Stephen; Smith, Dan; Bourne, Nathan; Loveday, Jon; Rowlands, Kate; van der Werf, Paul; Driver, Simon; Dunne, Loretta; Dye, Simon; Furlanetto, Cristina; Ivison, R. J.; Maddox, Steve; Robotham, Aaron; Smith, Matthew W. L.; Taylor, Edward N.; Valiante, Elisabetta; Wright, Angus; Cigan, Philip; De Zotti, Gianfranco; Jarvis, Matt J.; Marchetti, Lucia; Michałowski, Michał J.; Phillipps, Steven; Viaene, Sebastien; Vlahakis, Catherine

2018-01-01

The Herschel Space Observatory has revealed a very different galaxyscape from that shown by optical surveys which presents a challenge for galaxy-evolution models. The Herschel surveys reveal (1) that there was rapid galaxy evolution in the very recent past and (2) that galaxies lie on a single Galaxy Sequence (GS) rather than a star-forming 'main sequence' and a separate region of 'passive' or 'red-and-dead' galaxies. The form of the GS is now clearer because far-infrared surveys such as the Herschel ATLAS pick up a population of optically red star-forming galaxies that would have been classified as passive using most optical criteria. The space-density of this population is at least as high as the traditional star-forming population. By stacking spectra of H-ATLAS galaxies over the redshift range 0.001 high stellar masses, high star-formation rates but, even several billion years in the past, old stellar populations - they are thus likely to be relatively recent ancestors of early-type galaxies in the Universe today. The form of the GS is inconsistent with rapid quenching models and neither the analytic bathtub model nor the hydrodynamical EAGLE simulation can reproduce the rapid cosmic evolution. We propose a new gentler model of galaxy evolution that can explain the new Herschel results and other key properties of the galaxy population.

Validation of an Experimental Model to Study Less Severe Chronic Renal Failure.

Science.gov (United States)

Fernandes-Charpiot, Ida Mária Maximina; Caldas, Heloisa Cristina; Mendes, Glória Elisa Florido; Gomes de Sá Neto, Luiz; Oliveira, Henrique Lacativa; Baptista, Maria Alice Sperto Ferreira; Abbud-Filho, Mario

2016-10-01

The 5/6 nephrectomy, mimics the stages of human chronic renal failure (CRF), but the procedure causes severe renal functional and morphological damage that could interfere with the evaluation of therapies for slowing the progression of the disease. This study summarizes the results of renal function, histology, and immunohistochemical findings in rats undergoing a 2/3 nephrectomy. The rats were distributed in groups according to the type of nephrectomy: CRF5/6: induced by a 5/6 renal mass reduction and CRF2/3: less severe CRF. The body weight and blood pressure were monitored, and the serum creatinine (SCr), creatinine clearance (CCr), urine osmolality, and 24-h proteinuria (PT24h) were measured. CRF progression was evaluated by the rate of decline of CCr (RCCr). Histology and immunohistochemistry were performed in the remnant kidneys. Statistical analysis was done by unpaired t-test, and a P-value renal histopathological findings revealed fewer chronic lesions in rats with CRF2/3. Similarly, we observed less macrophage accumulation as well as lower proliferative activity and expression of fibronectin and a-smooth muscle-actin in the CRF2/3 model. The CRF2/3 model presented with a pattern of less severe CRF, functionally and morphologically, compared to the classical CRF5/6 model, and the CRF2/3 model may be useful for evaluating therapeutic interventions that target the early stages of CRF.

Large revealing similarity in multihadron production in nuclear and particle collisions

International Nuclear Information System (INIS)

Mishra, Aditya Nath; Sahoo, Raghunath; Sarkisyan, Edward K.G.; Sakharov, Alexander S.; )

2016-01-01

The dependencies of charged particle pseudorapidity density and transverse energy pseudorapidity density at midrapidity as well as of charged particle total multiplicity on the collision energy and on the number of nucleon participants, or centrality, measured in nucleus-nucleus collisions are studied in the energy range spanning a few GeV to a few TeV per nucleon. The model in which the multiparticle production is driven by the dissipating effective energy of participants is considered. The model extends the earlier proposed approach, combining the constituent quark picture together with Landau relativistic hydrodynamics shown to interrelate the measurements from different types of collisions. Within this model, the dependence of the charged particle pseudorapidity density and transverse energy pseudorapidity density at midrapidity on the number of participants in heavy-ion collisions are found to be well described in terms of the effective energy defined as a centrality-dependent fraction of the collision energy. For both variables the effective energy approach reveals a similarity in the energy dependence obtained for the most central collisions and centrality data in the entire available energy range

Islamic Counselling Model to Increase Religious Commitment (Study of Students at the University UIN Bandung

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Fenti Hikmawati

2014-06-01

Full Text Available The study aims to test the effectiveness of Islamic counseling model for helping the students to tight their religious commitment. The religious commitment is covered in three major Islamic teachings: Iman (faith, Islam (surrender to Allah, and lhsan (state of being observed by Allah. The model of Islamic counseling aims to tight students' religious commitment must to be applied immediately because the preface study reveals some students' religious commitment were not strong enough, their behavior and thinking symptoms tend to not appropriate yet with Islam norm among their association and conception toward the truth of God. To achieve the aim, the study was carried out with three steps: (1 designing a model of counseling; (2 trying out field study, using pretest-post test control group experimental design with 140 students of Islamic Religion Education, the Faculty of Tarbiyah and Teaching, State Islamic University, Sunan Gunung Djati, Bandung. Of 140 students, 70 students are from the classes: A (32 people, B (38 people, involved in control group and the test; 37 people from class C, and 33 students from class D involved in the experiment group, and; (3 designing a final model by revising the model tried-out. The variable involved three major Islamic dimensions: the iman, Islam, and ihsan of the students. The model was designed based on the theory put forward by Musfir bin Said Az-Zalmmi, that is, an integrated counseling model. The model combines and employs the ideas from other concepts into a tightly united concept, called Islamic concept. Upon completing analysis, it was found that the new concept is significantly effective to enhance students' religious commitment. A Model of Islamic Counseling (MIC is an alternative-counseling model that can be employed for teenagers/ students to enhance their religious commitment. The study recommends that: (1 MIC can be applied to fifth semester students in the Faculty of Tarbiyah State Islamic

Study of mathematical models for fatigue crack propagation

International Nuclear Information System (INIS)

Yarema, S.Ya.; Mel'nichok, L.S.

1982-01-01

Complex composition of mathematical models for description of experimental diagrams of fatigue fracture (EDFF) for different steels and alloys from the view point of their correspondence to experimental data is conducted. 5 simple formulas for EDFF description have been chosen from the known ones. It is revealed that the analytical expression should contain 6 parameters for the main peculiarities of typical EDFF. This conclusion agrees with the fact that the 6-parametric formula provides the best quality of experimental data approximation. It should be also noted that the necessary number of parameters coincides with the number of all the standard characteristics (main and additional) of cyclic crack resistance of materials

Proposing an Aggregate Production Planning Model by Goal Programming Approach, a Case Study

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Mansoureh Farzam Rad

2014-06-01

Full Text Available Production planning is one of the most important functions in the process of production management. Production planning in the intermediate range of time is termed as aggregate production planning (APP. Aggregate production planning is an important upper level planning activity in a production management system. The present study tries to suggest an aggregate production planning model for products of Hafez tile factory during one year. Due to this fact that the director of the company seeks 3 main objectives to determine the optimal production rate, the linear goal planning method was employed. After solving the problem, in order to examine the efficiency and the distinctiveness of this method in compare to linear programming, the problem was modeled just by considering one objective then was solved by linear programming approach. The findings revealed the goal programming with multi objectives resulted more appropriate solution rather than linear programming with just one objective.

Systems genomics study reveals expression quantitative trait loci, regulator genes and pathways associated with boar taint in pigs.

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Markus Drag

Full Text Available Boar taint is an offensive odour and/or taste from a proportion of non-castrated male pigs caused by skatole and androstenone accumulation during sexual maturity. Castration is widely used to avoid boar taint but is currently under debate because of animal welfare concerns. This study aimed to identify expression quantitative trait loci (eQTLs with potential effects on boar taint compounds to improve breeding possibilities for reduced boar taint. Danish Landrace male boars with low, medium and high genetic merit for skatole and human nose score (HNS were slaughtered at ~100 kg. Gene expression profiles were obtained by RNA-Seq, and genotype data were obtained by an Illumina 60K Porcine SNP chip. Following quality control and filtering, 10,545 and 12,731 genes from liver and testis were included in the eQTL analysis, together with 20,827 SNP variants. A total of 205 and 109 single-tissue eQTLs associated with 102 and 58 unique genes were identified in liver and testis, respectively. By employing a multivariate Bayesian hierarchical model, 26 eQTLs were identified as significant multi-tissue eQTLs. The highest densities of eQTLs were found on pig chromosomes SSC12, SSC1, SSC13, SSC9 and SSC14. Functional characterisation of eQTLs revealed functions within regulation of androgen and the intracellular steroid hormone receptor signalling pathway and of xenobiotic metabolism by cytochrome P450 system and cellular response to oestradiol. A QTL enrichment test revealed 89 QTL traits curated by the Animal Genome PigQTL database to be significantly overlapped by the genomic coordinates of cis-acting eQTLs. Finally, a subset of 35 cis-acting eQTLs overlapped with known boar taint QTL traits. These eQTLs could be useful in the development of a DNA test for boar taint but careful monitoring of other overlapping QTL traits should be performed to avoid any negative consequences of selection.

Binding of carbendazim to bovine serum albumin: Insights from experimental and molecular modeling studies

Science.gov (United States)

Li, Jinhua; Zhang, Yulei; Hu, Lin; Kong, Yaling; Jin, Changqing; Xi, Zengzhe

2017-07-01

Carbendazim (CBZ) is a widely used benzimidazole fungicide in agriculture to control a wide range of fruit and vegetable pathogens, which may lead to potential health hazards. To evaluate the potential toxicity of CBZ, the binding mechanism of bovine serum albumin (BSA) with CBZ was investigated by the fluorescence quenching technology, UV absorbance spectra, circular dichroism (CD), and molecular modeling. The fluorescence titration and UV absorbance spectra revealed that the fluorescence quenching mechanism of BSA by CBZ was a combined quenching process. In addition, the studies of CD spectra suggested that the binding of CBZ to BSA changed the secondary structure of protein. Furthermore, the thermodynamic functions of enthalpy change (ΔH0) and entropy change (ΔS0) for the reaction were calculated to be 24.87 kJ mol-1 and 162.95 J mol-1 K-1 according to Van't Hoff equation. These data suggested that hydrophobic interaction play a major role in the binding of CBZ to BSA, which was in good agreement with the result of molecular modeling study.

Evaluation of precipitation extremes over the Asian domain: observation and modelling studies

Science.gov (United States)

Kim, In-Won; Oh, Jaiho; Woo, Sumin; Kripalani, R. H.

2018-04-01

In this study, a comparison in the precipitation extremes as exhibited by the seven reference datasets is made to ascertain whether the inferences based on these datasets agree or they differ. These seven datasets, roughly grouped in three categories i.e. rain-gauge based (APHRODITE, CPC-UNI), satellite-based (TRMM, GPCP1DD) and reanalysis based (ERA-Interim, MERRA, and JRA55), having a common data period 1998-2007 are considered. Focus is to examine precipitation extremes in the summer monsoon rainfall over South Asia, East Asia and Southeast Asia. Measures of extreme precipitation include the percentile thresholds, frequency of extreme precipitation events and other quantities. Results reveal that the differences in displaying extremes among the datasets are small over South Asia and East Asia but large differences among the datasets are displayed over the Southeast Asian region including the maritime continent. Furthermore, precipitation data appear to be more consistent over East Asia among the seven datasets. Decadal trends in extreme precipitation are consistent with known results over South and East Asia. No trends in extreme precipitation events are exhibited over Southeast Asia. Outputs of the Coupled Model Intercomparison Project Phase 5 (CMIP5) simulation data are categorized as high, medium and low-resolution models. The regions displaying maximum intensity of extreme precipitation appear to be dependent on model resolution. High-resolution models simulate maximum intensity of extreme precipitation over the Indian sub-continent, medium-resolution models over northeast India and South China and the low-resolution models over Bangladesh, Myanmar and Thailand. In summary, there are differences in displaying extreme precipitation statistics among the seven datasets considered here and among the 29 CMIP5 model data outputs.

Metabolomics Reveals Relationship between Plasma Inositols and Birth Weight: Possible Markers for Fetal Programming of Type 2 Diabetes

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Pia Marlene Nissen

2011-01-01

Full Text Available Epidemiological studies in man and with experimental animal models have shown that intrauterine growth restriction (IUGR resulting in low birth weight is associated with higher risk of programming welfare diseases in later life. In the pig, severe IUGR occurs naturally and contribute substantially to a large intralitter variation in birth weight and may therefore be a good model for man. In the present paper the natural form of IUGR in pigs was studied close to term by nuclear magnetic resonance (NMR-based metabolomics. The NMR-based investigations revealed different metabolic profiles of plasma samples from low-birth weight (LW and high-birth weight (HW piglets, respectively, and differences were assigned to levels of glucose and myo-inositol. Further studies by GC-MS revealed that LW piglets had a significant higher concentration of myoinositol and D-chiro-inositol in plasma compared to larger littermates. Myo-inositol and D-chiro-inositol have been coupled with glucose intolerance and insulin resistance in adults, and the present paper therefore suggests that IUGR is related to impaired glucose metabolism during fetal development, which may cause type 2 diabetes in adulthood.

Revealing skill of the MiKlip decadal prediction system by three-dimensional probabilistic evaluation

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Sophie Stolzenberger

2016-12-01

Full Text Available Decadal climate predictions and their verification are part of ongoing research. This article studies different methods applied to decadal hindcasts of three-dimensional atmospheric variables to evaluate the MiKlip (Mittelfristige Klimaprognosen prediction system. Variables such as upper air temperature are tight to the core of the prediction system and hence help to reveal its power and deficiencies. The verification uses both, necessary and sufficient probabilistic measures. We analyze annual and multi-year averages of air temperature and geopotential height and the parametrized quantity net water flux at the ocean surface, the so-called freshwater flux, also known as E‑P (evaporation minus precipitation, as an important variable for atmosphere-ocean coupling. The model data stem from various versions of the MiKlip prediction system and constitute different sets of ensemble hindcasts covering 1979–2012. The results reveal that the freshwater flux is far more sensitive to model deficiencies than the basic dynamical variables and the predictability decays much earlier with prediction lead time. Initializing the atmospheric component is more important for the predictability than the difference in resolution between two model versions. The combined initialization of atmosphere and ocean has the effect of increasing the predictability in the inner tropics from 1 to 2 years compared to the ocean only initialization. For prediction year 7–10, the hindcasts are still closer to each other than to the uninitialized historical runs indicating that the prediction system is still influenced by the initial conditions. The skill for prediction year 7–10 is, however, only marginally larger than the skill of the uninitialized ensemble. The three-dimensional skill analysis reveals a clear indication of a mid-tropospheric temperature error developing in the tropical Pacific area.

Learning Gene Expression Through Modelling and Argumentation. A Case Study Exploring the Connections Between the Worlds of Knowledge

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Puig, Blanca; Ageitos, Noa; Jiménez-Aleixandre, María Pilar

2017-12-01

There is emerging interest on the interactions between modelling and argumentation in specific contexts, such as genetics learning. It has been suggested that modelling might help students understand and argue on genetics. We propose modelling gene expression as a way to learn molecular genetics and diseases with a genetic component. The study is framed in Tiberghien's (2000) two worlds of knowledge, the world of "theories & models" and the world of "objects & events", adding a third component, the world of representations. We seek to examine how modelling and argumentation interact and connect the three worlds of knowledge while modelling gene expression. It is a case study of 10th graders learning about diseases with a genetic component. The research questions are as follows: (1) What argumentative and modelling operations do students enact in the process of modelling gene expression? Specifically, which operations allow connecting the three worlds of knowledge? (2) What are the interactions between modelling and argumentation in modelling gene expression? To what extent do these interactions help students connect the three worlds of knowledge and modelling gene expression? The argumentative operation of using evidence helps students to relate the three worlds of knowledge, enacted in all the connections. It seems to be a relationship among the number of interactions between modelling and argumentation, the connections between world of knowledge and students' capacity to develop a more sophisticated representation. Despite this is a case study, this approach of analysis reveals potentialities for a deeper understanding of learning genetics though scientific practices.

Neuronal model with distributed delay: analysis and simulation study for gamma distribution memory kernel.

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Karmeshu; Gupta, Varun; Kadambari, K V

2011-06-01

A single neuronal model incorporating distributed delay (memory)is proposed. The stochastic model has been formulated as a Stochastic Integro-Differential Equation (SIDE) which results in the underlying process being non-Markovian. A detailed analysis of the model when the distributed delay kernel has exponential form (weak delay) has been carried out. The selection of exponential kernel has enabled the transformation of the non-Markovian model to a Markovian model in an extended state space. For the study of First Passage Time (FPT) with exponential delay kernel, the model has been transformed to a system of coupled Stochastic Differential Equations (SDEs) in two-dimensional state space. Simulation studies of the SDEs provide insight into the effect of weak delay kernel on the Inter-Spike Interval(ISI) distribution. A measure based on Jensen-Shannon divergence is proposed which can be used to make a choice between two competing models viz. distributed delay model vis-á-vis LIF model. An interesting feature of the model is that the behavior of (CV(t))((ISI)) (Coefficient of Variation) of the ISI distribution with respect to memory kernel time constant parameter η reveals that neuron can switch from a bursting state to non-bursting state as the noise intensity parameter changes. The membrane potential exhibits decaying auto-correlation structure with or without damped oscillatory behavior depending on the choice of parameters. This behavior is in agreement with empirically observed pattern of spike count in a fixed time window. The power spectral density derived from the auto-correlation function is found to exhibit single and double peaks. The model is also examined for the case of strong delay with memory kernel having the form of Gamma distribution. In contrast to fast decay of damped oscillations of the ISI distribution for the model with weak delay kernel, the decay of damped oscillations is found to be slower for the model with strong delay kernel.

Cellobiose as a model system to reveal cellulose dissolution mechanism in acetate-based ionic liquids: Density functional theory study substantiated by NMR spectra.

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Cao, Bobo; Du, Jiuyao; Du, Dongmei; Sun, Haitao; Zhu, Xiao; Fu, Hui

2016-09-20

Cellulose dissolution mechanism in acetate-based ionic liquids was systematically studied in Nuclear Magnetic Resonance (NMR) spectra and Density Functional Theory (DFT) methods by using cellobiose and 1-butyl-3-methylimidazolium acetate (BmimAc) as a model system. The solubility of cellulose in ionic liquid increased with temperature increase in the range of 90-140°C. NMR spectra suggested OAc(-) preferred to form stronger hydrogen bonds with hydrogen of hydroxyl in cellulose. Electrostatic potential method was employed to predict the most possible reaction sites and locate the most stable configuration. Atoms in molecules (AIM) theory was used to study the features of bonds at bond critical points and the variations of bond types. Simultaneously, noncovalent interactions were characterized and visualized by employing reduced density gradient analysis combined with Visual Molecular Dynamics (VMD) program. Natural bond orbital (NBO) theory was applied to study the noncovalent nature and characterize the orbital interactions between cellobiose and Bmim[OAc]. Copyright © 2016 Elsevier Ltd. All rights reserved.

Kuala Kemaman hydraulic model study

International Nuclear Information System (INIS)

Abdul Kadir Ishak

2005-01-01

There The problems facing the area of Kuala Kemaman are siltation and erosion at shoreline. The objectives of study are to assess the best alignment of the groyne alignment, to ascertain the most stable shoreline regime and to investigate structural measures to overcome the erosion. The scope of study are data collection, wave analysis, hydrodynamic simulation and sediment transport simulation. Numerical models MIKE 21 are used - MIKE 21 NSW, for wind-wave model, which describes the growth, decay and transformation of wind-generated waves and swell in nearshore areas. The study takes into account effects of refraction and shoaling due to varying depth, energy dissipation due to bottom friction and wave breaking, MIKE 21 HD - modelling system for 2D free-surface flow which to stimulate the hydraulics phenomena in estuaries, coastal areas and seas. Predicted tidal elevation and waves (radiation stresses) are considered into study while wind is not considered. MIKE 21 ST - the system that calculates the rates of non-cohesive (sand) sediment transport for both pure content and combined waves and current situation

Comparison of Bolton analysis and Little’s irregularity index on laser scanned three-dimensional digital study models with conventional study models

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Kurnia, H.; Noerhadi, N. A. I.

2017-08-01

Three-dimensional digital study models were introduced following advances in digital technology. This study was carried out to assess the reliability of digital study models scanned by a laser scanning device newly assembled. The aim of this study was to compare the digital study models and conventional models. Twelve sets of dental impressions were taken from patients with mild-to-moderate crowding. The impressions were taken twice, one with alginate and the other with polyvinylsiloxane. The alginate impressions were made into conventional models, and the polyvinylsiloxane impressions were scanned to produce digital models. The mesiodistal tooth width and Little’s irregularity index (LII) were measured manually with digital calipers on the conventional models and digitally on the digital study models. Bolton analysis was performed on each study models. Each method was carried out twice to check for intra-observer variability. The reproducibility (comparison of the methods) was assessed using independent-sample t-tests. The mesiodistal tooth width between conventional and digital models did not significantly differ (p > 0.05). Independent-sample t-tests did not identify statistically significant differences for Bolton analysis and LII (p = 0.603 for Bolton and p = 0894 for LII). The measurements of the digital study models are as accurate as those of the conventional models.

EXPLORATORY DATA ANALYSIS AND MULTIVARIATE STRATEGIES FOR REVEALING MULTIVARIATE STRUCTURES IN CLIMATE DATA

Directory of Open Access Journals (Sweden)

2016-12-01

Full Text Available This paper is on data analysis strategy in a complex, multidimensional, and dynamic domain. The focus is on the use of data mining techniques to explore the importance of multivariate structures; using climate variables which influences climate change. Techniques involved in data mining exercise vary according to the data structures. The multivariate analysis strategy considered here involved choosing an appropriate tool to analyze a process. Factor analysis is introduced into data mining technique in order to reveal the influencing impacts of factors involved as well as solving for multicolinearity effect among the variables. The temporal nature and multidimensionality of the target variables is revealed in the model using multidimensional regression estimates. The strategy of integrating the method of several statistical techniques, using climate variables in Nigeria was employed. R2 of 0.518 was obtained from the ordinary least square regression analysis carried out and the test was not significant at 5% level of significance. However, factor analysis regression strategy gave a good fit with R2 of 0.811 and the test was significant at 5% level of significance. Based on this study, model building should go beyond the usual confirmatory data analysis (CDA, rather it should be complemented with exploratory data analysis (EDA in order to achieve a desired result.

Studies on phenomenological hadron models with chiral symmetry

International Nuclear Information System (INIS)

Rathske, E.

1991-12-01

In this report we consider, in the context of phenomenological models for hadrons, several aspects of Skyrme-type and hybrid bag models. In the first of the two central parts we discuss two qualitatively different generalizations of the minimal SU(2) Skyrme model. One of these consists in adding to the Lagrangian density a symmetric term of fourth order in the field derivatives. Its consequences are determined for solutions and observables by analytical and numerical investigations. In the other we propose a contribution for explicit isospin symmetry breaking in the mesonic as well as the baryonic sector. Together with the standard nonlinear σ-model term it allows for exact time-dependent classical soliton solutions. Their quantization leads to a quantitative connection between the hadronic isospin mass differenced of pions and nucleons. The second main part of this report is devoted to the generalization of SU(2) bag models under the aspect of chiral symmetry. We first show that the construction of appropriate surface terms in the Lagrangian density necessitates the introduction of dynamical bosonic degrees of freedom. This allows for a variety of bag scenarios (including the 'endopionic' bag). We then consider explicit isospin symmetry breaking for hybrid bag models with a nonlinear mesonic sector. An intimate relationship is revealed between the effects of a quark mass difference and the time-dependent bosonic solutions found for the purely mesonic case. It is reflected in a nontrivial interdependence between quark and meson masses, bag radius and chiral angle. We provide an especially extensive list of references for the topics discussed in this report. (orig.) [de

Economic choices reveal probability distortion in macaque monkeys.

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Stauffer, William R; Lak, Armin; Bossaerts, Peter; Schultz, Wolfram

2015-02-18

Economic choices are largely determined by two principal elements, reward value (utility) and probability. Although nonlinear utility functions have been acknowledged for centuries, nonlinear probability weighting (probability distortion) was only recently recognized as a ubiquitous aspect of real-world choice behavior. Even when outcome probabilities are known and acknowledged, human decision makers often overweight low probability outcomes and underweight high probability outcomes. Whereas recent studies measured utility functions and their corresponding neural correlates in monkeys, it is not known whether monkeys distort probability in a manner similar to humans. Therefore, we investigated economic choices in macaque monkeys for evidence of probability distortion. We trained two monkeys to predict reward from probabilistic gambles with constant outcome values (0.5 ml or nothing). The probability of winning was conveyed using explicit visual cues (sector stimuli). Choices between the gambles revealed that the monkeys used the explicit probability information to make meaningful decisions. Using these cues, we measured probability distortion from choices between the gambles and safe rewards. Parametric modeling of the choices revealed classic probability weighting functions with inverted-S shape. Therefore, the animals overweighted low probability rewards and underweighted high probability rewards. Empirical investigation of the behavior verified that the choices were best explained by a combination of nonlinear value and nonlinear probability distortion. Together, these results suggest that probability distortion may reflect evolutionarily preserved neuronal processing. Copyright © 2015 Stauffer et al.

Fibrillation mechanism of a model intrinsically disordered protein revealed by 2D correlation deep UV resonance Raman spectroscopy.

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Sikirzhytski, Vitali; Topilina, Natalya I; Takor, Gaius A; Higashiya, Seiichiro; Welch, John T; Uversky, Vladimir N; Lednev, Igor K

2012-05-14

Understanding of numerous biological functions of intrinsically disordered proteins (IDPs) is of significant interest to modern life science research. A large variety of serious debilitating diseases are associated with the malfunction of IDPs including neurodegenerative disorders and systemic amyloidosis. Here we report on the molecular mechanism of amyloid fibrillation of a model IDP (YE8) using 2D correlation deep UV resonance Raman spectroscopy. YE8 is a genetically engineered polypeptide, which is completely unordered at neutral pH yet exhibits all properties of a fibrillogenic protein at low pH. The very first step of the fibrillation process involves structural rearrangements of YE8 at the global structure level without the detectable appearance of secondary structural elements. The formation of β-sheet species follows the global structural changes and proceeds via the simultaneous formation of turns and β-strands. The kinetic mechanism revealed is an important new contribution to understanding of the general fibrillation mechanism proposed for IDP.

A Numerical Study of Water Loss Rate Distributions in MDCT-based Human Airway Models

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Wu, Dan; Miyawaki, Shinjiro; Tawhai, Merryn H.; Hoffman, Eric A.; Lin, Ching-Long

2015-01-01

Both three-dimensional (3D) and one-dimensional (1D) computational fluid dynamics (CFD) methods are applied to study regional water loss in three multi-detector row computed-tomography (MDCT)-based human airway models at the minute ventilations of 6, 15 and 30 L/min. The overall water losses predicted by both 3D and 1D models in the entire respiratory tract agree with available experimental measurements. However, 3D and 1D models reveal different regional water loss rate distributions due to the 3D secondary flows formed at bifurcations. The secondary flows cause local skewed temperature and humidity distributions on inspiration acting to elevate the local water loss rate; and the secondary flow at the carina tends to distribute more cold air to the lower lobes. As a result, the 3D model predicts that the water loss rate first increases with increasing airway generation, and then decreases as the air approaches saturation, while the 1D model predicts a monotonic decrease of water loss rate with increasing airway generation. Moreover, the 3D (or 1D) model predicts relatively higher water loss rates in lower (or upper) lobes. The regional water loss rate can be related to the non-dimensional wall shear stress (τ*) by the non-dimensional mass transfer coefficient (h0*) as h0* = 1.15 τ*0.272, R = 0.842. PMID:25869455

Building v/s Exploring Models: Comparing Learning of Evolutionary Processes through Agent-based Modeling

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Wagh, Aditi

Two strands of work motivate the three studies in this dissertation. Evolutionary change can be viewed as a computational complex system in which a small set of rules operating at the individual level result in different population level outcomes under different conditions. Extensive research has documented students' difficulties with learning about evolutionary change (Rosengren et al., 2012), particularly in terms of levels slippage (Wilensky & Resnick, 1999). Second, though building and using computational models is becoming increasingly common in K-12 science education, we know little about how these two modalities compare. This dissertation adopts agent-based modeling as a representational system to compare these modalities in the conceptual context of micro-evolutionary processes. Drawing on interviews, Study 1 examines middle-school students' productive ways of reasoning about micro-evolutionary processes to find that the specific framing of traits plays a key role in whether slippage explanations are cued. Study 2, which was conducted in 2 schools with about 150 students, forms the crux of the dissertation. It compares learning processes and outcomes when students build their own models or explore a pre-built model. Analysis of Camtasia videos of student pairs reveals that builders' and explorers' ways of accessing rules, and sense-making of observed trends are of a different character. Builders notice rules through available blocks-based primitives, often bypassing their enactment while explorers attend to rules primarily through the enactment. Moreover, builders' sense-making of observed trends is more rule-driven while explorers' is more enactment-driven. Pre and posttests reveal that builders manifest a greater facility with accessing rules, providing explanations manifesting targeted assembly. Explorers use rules to construct explanations manifesting non-targeted assembly. Interviews reveal varying degrees of shifts away from slippage in both

Molecular shape and binding force of Mycoplasma mobile's leg protein Gli349 revealed by an AFM study

International Nuclear Information System (INIS)

Lesoil, Charles; Nonaka, Takahiro; Sekiguchi, Hiroshi; Osada, Toshiya; Miyata, Makoto; Afrin, Rehana; Ikai, Atsushi

2010-01-01

Recent studies of the gliding bacteria Mycoplasma mobile have identified a family of proteins called the Gli family which was considered to be involved in this novel and yet fairly unknown motility system. The 349 kDa protein called Gli349 was successfully isolated and purified from the bacteria, and electron microscopy imaging and antibody experiments led to the hypothesis that it acts as the 'leg' of M. mobile, responsible for attachment to the substrate as well as for gliding motility. However, more precise evidence of the molecular shape and function of this protein was required to asses this theory any further. In this study, an atomic force microscope (AFM) was used both as an imaging and a force measurement device to provide new information about Gli349 and its role in gliding motility. AFM images of the protein were obtained revealing a complex structure with both rigid and flexible parts, consistent with previous electron micrographs of the protein. Single-molecular force spectroscopy experiments were also performed, revealing that Gli349 is able to specifically bind to sialyllactose molecules and withstand unbinding forces around 70 pN. These findings strongly support the idea that Gli349 is the 'leg' protein of M. mobile, responsible for binding and also most probably force generation during gliding motility.

A comprehensive experimental and kinetic modeling study of n -propylbenzene combustion

KAUST Repository

Yuan, Wenhao

2017-09-05

This work presents a comprehensive experimental and kinetic modeling study on the combustion of n-propylbenzene. Flow reactor pyrolysis of n-propylbenzene at 0.04, 0.2 and 1 atm and laminar premixed flames of n-propylbenzene at 0.04 atm with equivalence ratios of 0.75 and 1.00 were investigated with synchrotron vacuum ultraviolet photoionization mass spectrometry. Jet stirred reactor (JSR) oxidation of n-propylbenzene at 10 atm with equivalence ratios of 0.5, 1.0, 1.5 and 2.0 was investigated with gas chromatography. A detailed kinetic model for n-propylbenzene combustion with 340 species and 2069 reactions was developed and validated against the data measured in this work. Model analyses such as rate of production analysis and sensitivity analysis were also performed to reveal the key pathways in the consumption of fuel and formation of polycyclic aromatic hydrocarbons (PAHs). The analysis results demonstrate that the benzylic Csingle bondC bond dissociation reaction is crucial for the decomposition of n-propylbenzene in the pyrolysis and rich flame. Low temperature oxidation reactions play important roles in the high pressure JSR oxidation of n-propylbenzene. In addition, the formation pathways of PAHs are strongly related to the fuel structure, especially for the formation of bicyclic PAHs such as indene and naphthalene. Furthermore, the present model was also validated against previous experimental data of n-propylbenzene combustion under a wide range of conditions, including ignition delay times, laminar flame speeds, extinction strain rates, speciation profiles in atmospheric pressure JSR oxidation, flow reactor oxidation and high pressure shock tube pyrolysis and oxidation.

A comprehensive experimental and kinetic modeling study of n -propylbenzene combustion

KAUST Repository

Yuan, Wenhao; Li, Yuyang; Dagaut, Philippe; Wang, Yizun; Wang, Zhandong; Qi, Fei

2017-01-01

This work presents a comprehensive experimental and kinetic modeling study on the combustion of n-propylbenzene. Flow reactor pyrolysis of n-propylbenzene at 0.04, 0.2 and 1 atm and laminar premixed flames of n-propylbenzene at 0.04 atm with equivalence ratios of 0.75 and 1.00 were investigated with synchrotron vacuum ultraviolet photoionization mass spectrometry. Jet stirred reactor (JSR) oxidation of n-propylbenzene at 10 atm with equivalence ratios of 0.5, 1.0, 1.5 and 2.0 was investigated with gas chromatography. A detailed kinetic model for n-propylbenzene combustion with 340 species and 2069 reactions was developed and validated against the data measured in this work. Model analyses such as rate of production analysis and sensitivity analysis were also performed to reveal the key pathways in the consumption of fuel and formation of polycyclic aromatic hydrocarbons (PAHs). The analysis results demonstrate that the benzylic Csingle bondC bond dissociation reaction is crucial for the decomposition of n-propylbenzene in the pyrolysis and rich flame. Low temperature oxidation reactions play important roles in the high pressure JSR oxidation of n-propylbenzene. In addition, the formation pathways of PAHs are strongly related to the fuel structure, especially for the formation of bicyclic PAHs such as indene and naphthalene. Furthermore, the present model was also validated against previous experimental data of n-propylbenzene combustion under a wide range of conditions, including ignition delay times, laminar flame speeds, extinction strain rates, speciation profiles in atmospheric pressure JSR oxidation, flow reactor oxidation and high pressure shock tube pyrolysis and oxidation.

Revealing the regime of shallow coral reefs at patch scale by continuous spatial modeling

Directory of Open Access Journals (Sweden)

Antoine eCollin

2014-11-01

Full Text Available Reliably translating real-world spatial patterns of ecosystems is critical for understanding processes susceptible to reinforce resilience. However the great majority of studies in spatial ecology use thematic maps to describe habitats and species in a binary scheme. By discretizing the transitional areas and neglecting the gradual replacement across a given space, the thematic approach may suffer from substantial limitations when interpreting patterns created by many continuous variables. Here, local and regional spectral proxies were used to design and spatially map at very fine scale a continuous index dedicated to one of the most complex seascapes, the coral reefscape. Through a groundbreaking merge of bottom-up and top-down approach, we demonstrate that three to seven-habitat continuous indices can be modeled by nine, six, four and three spectral proxies, respectively, at 0.5 m spatial resolution using hand- and spaceborne measurements. We map the seven-habitat continuous index, spanning major Indo-Pacific coral reef habitats through the far red-green normalized difference ratio over the entire lagoon of a low (Tetiaroa atoll and a high volcanic (Moorea island in French Polynesia with 84% and 82% accuracy, respectively. Further examinations of the two resulting spatial models using a customized histoscape (density function of model values distributed on a concentric strip across the reef crest-coastline distance show that Tetiaroa exhibits a greater variety of coral reef habitats than Moorea. By designing such easy-to-implement, transferrable spectral proxies of coral reef regime, this study initiates a framework for spatial ecologists tackling coral reef biodiversity, responses to stresses, perturbations and shifts. We discuss the limitations and contributions of our findings towards the study of worldwide coral reef resilience following stochastic environmental change.

Surface phenomena revealed by in situ imaging: studies from adhesion, wear and cutting

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Viswanathan, Koushik; Mahato, Anirban; Yeung, Ho; Chandrasekar, Srinivasan

2017-03-01

Surface deformation and flow phenomena are ubiquitous in mechanical processes. In this work we present an in situ imaging framework for studying a range of surface mechanical phenomena at high spatial resolution and across a range of time scales. The in situ framework is capable of resolving deformation and flow fields quantitatively in terms of surface displacements, velocities, strains and strain rates. Three case studies are presented demonstrating the power of this framework for studying surface deformation. In the first, the origin of stick-slip motion in adhesive polymer interfaces is investigated, revealing a intimate link between stick-slip and surface wave propagation. Second, the role of flow in mediating formation of surface defects and wear particles in metals is analyzed using a prototypical sliding process. It is shown that conventional post-mortem observation and inference can lead to erroneous conclusions with regard to formation of surface cracks and wear particles. The in situ framework is shown to unambiguously capture delamination wear in sliding. Third, material flow and surface deformation in a typical cutting process is analyzed. It is shown that a long-standing problem in the cutting of annealed metals is resolved by the imaging, with other benefits such as estimation of energy dissipation and power from the flow fields. In closure, guidelines are provided for profitably exploiting in situ observations to study large-strain deformation, flow and friction phenomena at surfaces that display a variety of time-scales.

Genome-wide investigation reveals high evolutionary rates in annual model plants.

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Yue, Jia-Xing; Li, Jinpeng; Wang, Dan; Araki, Hitoshi; Tian, Dacheng; Yang, Sihai

2010-11-09

associated with annual/perennial life history. Although we acknowledge current limitations of this kind of study, mainly due to a small sample size available and a distant taxonomic relationship of the model organisms, our results indicate that the genome-wide survey is a promising approach toward further understanding of the mechanism determining the molecular evolutionary rate at the genomic level.

High efficiency bio-hydrogen production from glucose revealed in an inoculum of heat-pretreated landfill leachate sludge

International Nuclear Information System (INIS)

Wong, Y.M.; Juan, J.C.; Ting, Adeline; Wu, T.Y.

2014-01-01

Bio-hydrogen is a promising sustainable energy to replace fossil fuels. This study investigated bio-H 2 production from the inoculum of heat-pretreated landfill leachate sludge using glucose as model substrate. The seed sludge pretreated at 65 °C showed the highest amount of H 2 at the optimum condition of pH 6 and 37 °C. The maximum H 2 yield estimated by the modified Gompertz model was 6.43 mol H 2 /mol glucose. The high efficient of H 2 production is thermodynamically feasible with the Gibbs free energy of −34 kJ/mol. This study reveals that pretreated landfill leachate sludge has considerable potential for H 2 production. - Highlights: • Heat retreated landfill leachate sludge revealed high efficient H 2 production. • High efficient H 2 yield, 6.4 mol H 2 /mol glucose. • The synergisms between H 2 -producing bacteria may responsible for the high H 2 yield. • High H 2 yield is thermodynamically feasible with Gibbs free energy of −34 kJ/mol

Catchment tracers reveal discharge, recharge and sources of groundwater-borne pollutants in a novel lake modelling approach

Science.gov (United States)

Kristensen, Emil; Madsen-Østerbye, Mikkel; Massicotte, Philippe; Pedersen, Ole; Markager, Stiig; Kragh, Theis

2018-02-01

Groundwater-borne contaminants such as nutrients, dissolved organic carbon (DOC), coloured dissolved organic matter (CDOM) and pesticides can have an impact the biological quality of lakes. The sources of pollutants can, however, be difficult to identify due to high heterogeneity in groundwater flow patterns. This study presents a novel approach for fast hydrological surveys of small groundwater-fed lakes using multiple groundwater-borne tracers. Water samples were collected from the lake and temporary groundwater wells, installed every 50 m within a distance of 5-45 m to the shore, were analysed for tracer concentrations of CDOM, DOC, total dissolved nitrogen (TDN, groundwater only), total nitrogen (TN, lake only), total dissolved phosphorus (TDP, groundwater only), total phosphorus (TP, lake only), δ18O / δ16O isotope ratios and fluorescent dissolved organic matter (FDOM) components derived from parallel factor analysis (PARAFAC). The isolation of groundwater recharge areas was based on δ18O measurements and areas with a high groundwater recharge rate were identified using a microbially influenced FDOM component. Groundwater discharge sites and the fractions of water delivered from the individual sites were isolated with the Community Assembly via Trait Selection model (CATS). The CATS model utilized tracer measurements of TDP, TDN, DOC and CDOM from the groundwater samples and related these to the tracer measurements of TN, TP, DOC and CDOM in the lake. A direct comparison between the lake and the inflowing groundwater was possible as degradation rates of the tracers in the lake were taken into account and related to a range of water retention times (WRTs) of the lake (0.25-3.5 years in 0.25-year increments). These estimations showed that WRTs above 2 years required a higher tracer concentration of inflowing water than found in any of the groundwater wells around the lake. From the estimations of inflowing tracer concentration, the CATS model isolated

Quantitative imaging reveals heterogeneous growth dynamics and treatment-dependent residual tumor distributions in a three-dimensional ovarian cancer model

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Celli, Jonathan P.; Rizvi, Imran; Evans, Conor L.; Abu-Yousif, Adnan O.; Hasan, Tayyaba

2010-09-01

Three-dimensional tumor models have emerged as valuable in vitro research tools, though the power of such systems as quantitative reporters of tumor growth and treatment response has not been adequately explored. We introduce an approach combining a 3-D model of disseminated ovarian cancer with high-throughput processing of image data for quantification of growth characteristics and cytotoxic response. We developed custom MATLAB routines to analyze longitudinally acquired dark-field microscopy images containing thousands of 3-D nodules. These data reveal a reproducible bimodal log-normal size distribution. Growth behavior is driven by migration and assembly, causing an exponential decay in spatial density concomitant with increasing mean size. At day 10, cultures are treated with either carboplatin or photodynamic therapy (PDT). We quantify size-dependent cytotoxic response for each treatment on a nodule by nodule basis using automated segmentation combined with ratiometric batch-processing of calcein and ethidium bromide fluorescence intensity data (indicating live and dead cells, respectively). Both treatments reduce viability, though carboplatin leaves micronodules largely structurally intact with a size distribution similar to untreated cultures. In contrast, PDT treatment disrupts micronodular structure, causing punctate regions of toxicity, shifting the distribution toward smaller sizes, and potentially increasing vulnerability to subsequent chemotherapeutic treatment.

Systems genomics study reveals expression quantitative trait loci, regulator genes and pathways associated with boar taint in pigs

DEFF Research Database (Denmark)

Drag, Markus; Hansen, Mathias B.; Kadarmideen, Haja N.

2018-01-01

Boar taint is an offensive odour and/or taste from a proportion of non-castrated male pigs caused by skatole and androstenone accumulation during sexual maturity. Castration is widely used to avoid boar taint but is currently under debate because of animal welfare concerns. This study aimed...... to identify expression quantitative trait loci (eQTLs) with potential effects on boar taint compounds to improve breeding possibilities for reduced boar taint. Danish Landrace male boars with low, medium and high genetic merit for skatole and human nose score (HNS) were slaughtered at similar to 100 kg. Gene...... and SSC14. Functional characterisation of eQTLs revealed functions within regulation of androgen and the intracellular steroid hormone receptor signalling pathway and of xenobiotic metabolism by cytochrome P450 system and cellular response to oestradiol. A QTL enrichment test revealed 89 QTL traits...

Neonatal Seizure Models to Study Epileptogenesis

Directory of Open Access Journals (Sweden)

Yuka Kasahara

2018-04-01

Full Text Available Current therapeutic strategies for epilepsy include anti-epileptic drugs and surgical treatments that are mainly focused on the suppression of existing seizures rather than the occurrence of the first spontaneous seizure. These symptomatic treatments help a certain proportion of patients, but these strategies are not intended to clarify the cellular and molecular mechanisms underlying the primary process of epilepsy development, i.e., epileptogenesis. Epileptogenic changes include reorganization of neural and glial circuits, resulting in the formation of an epileptogenic focus. To achieve the goal of developing “anti-epileptogenic” drugs, we need to clarify the step-by-step mechanisms underlying epileptogenesis for patients whose seizures are not controllable with existing “anti-epileptic” drugs. Epileptogenesis has been studied using animal models of neonatal seizures because such models are useful for studying the latent period before the occurrence of spontaneous seizures and the lowering of the seizure threshold. Further, neonatal seizure models are generally easy to handle and can be applied for in vitro studies because cells in the neonatal brain are suitable for culture. Here, we review two animal models of neonatal seizures for studying epileptogenesis and discuss their features, specifically focusing on hypoxia-ischemia (HI-induced seizures and febrile seizures (FSs. Studying these models will contribute to identifying the potential therapeutic targets and biomarkers of epileptogenesis.

Structural and functional studies of the modulator NS9283 reveal agonist-like mechanism of action at α4β2 nicotinic acetylcholine receptors

DEFF Research Database (Denmark)

Olsen, Jeppe A; Ahring, Philip K; Kastrup, Jette Sandholm Jensen

2014-01-01

Modulation of Cys loop receptor ion channels is a proven drug discovery strategy, but many underlying mechanisms of the mode of action are poorly understood. We report the x-ray structure of the acetylcholine-binding protein from Lymnaea stagnalis with NS9283, a stoichiometry selective positive...... on efficacy. The shared modulatory profile along with a binding site located in an extracellular subunit interface suggest that modulation via an agonist-like mechanism may be a common mechanism of action that potentially could apply to Cys loop receptors beyond the α4β2 nAChRs....... modulator that targets the α4-α4 interface of α4β2 nicotinic acetylcholine receptors (nAChRs). Together with homology modeling, mutational data, quantum mechanical calculations, and pharmacological studies on α4β2 nAChRs, the structure reveals a modulator binding mode that overlaps the α4-α4 interface...

Extensive small-angle X-ray scattering studies of blood coagulation factor VIIa reveal interdomain flexibility

DEFF Research Database (Denmark)

Mosbæk, Charlotte Rode; Nolan, David; Persson, Egon

2010-01-01

Blood coagulation factor VIIa (FVIIa) is used in the treatment of replacement therapy resistant hemophilia patients, and FVIIa is normally activated upon complex formation with tissue factor (TF), potentially in context with structural rearrangements. The solution behavior of uncomplexed FVIIa...... is important for understanding the mechanism of activation and for the stability and activity of the pharmaceutical product. However, crystal structures of FVIIa in complex with TF and of truncated free FVIIa reveal different overall conformations while previous small-angle scattering studies suggest FVIIa...... causing resistance to activation, thereby emphasizing the connection between the distribution of different conformations of FVII and the mechanism of activation....

Integrated Experimental and Model-based Analysis Reveals the Spatial Aspects of EGFR Activation Dynamics

Energy Technology Data Exchange (ETDEWEB)

Shankaran, Harish; Zhang, Yi; Chrisler, William B.; Ewald, Jonathan A.; Wiley, H. S.; Resat, Haluk

2012-10-02

The epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinases, and controls a diverse set of cellular responses relevant to development and tumorigenesis. ErbB activation is a complex process involving receptor-ligand binding, receptor dimerization, phosphorylation, and trafficking (internalization, recycling and degradation), which together dictate the spatio-temporal distribution of active receptors within the cell. The ability to predict this distribution, and elucidation of the factors regulating it, would help to establish a mechanistic link between ErbB expression levels and the cellular response. Towards this end, we constructed mathematical models for deconvolving the contributions of receptor dimerization and phosphorylation to EGFR activation, and to examine the dependence of these processes on sub-cellular location. We collected experimental datasets for EGFR activation dynamics in human mammary epithelial cells, with the specific goal of model parameterization, and used the data to estimate parameters for several alternate models. Model-based analysis indicated that: 1) signal termination via receptor dephosphorylation in late endosomes, prior to degradation, is an important component of the response, 2) less than 40% of the receptors in the cell are phosphorylated at any given time, even at saturating ligand doses, and 3) receptor dephosphorylation rates at the cell surface and early endosomes are comparable. We validated the last finding by measuring EGFR dephosphorylation rates at various times following ligand addition both in whole cells, and in endosomes using ELISAs and fluorescent imaging. Overall, our results provide important information on how EGFR phosphorylation levels are regulated within cells. Further, the mathematical model described here can be extended to determine receptor dimer abundances in cells co-expressing various levels of ErbB receptors. This study demonstrates that an iterative cycle of

Purchasing portfolio models: a critique and update

NARCIS (Netherlands)

Gelderman, C.J.; Weele, van A.J.

2005-01-01

Purchasing portfolio models have spawned considerable discussion in the literature. Many advantages and disadvantages have been put forward, revealing considerable divergence in opinion on the merits of portfolio models. This study addresses the question of whether or not the use of purchasing

Revealing the Driving Forces of Mid-Cities Urban Growth Patterns Using Spatial Modeling: a Case Study of Los Ángeles, Chile

Directory of Open Access Journals (Sweden)

Mauricio I. Aguayo

2007-06-01

Full Text Available City growth and changes in land-use patterns cause various important social and environmental impacts. To understand the spatial and temporal dynamics of these processes, the factors that drive urban development must be identified and analyzed, especially those factors that can be used to predict future changes and their potential environmental effects. Our objectives were to quantify the relationship between urban growth and its driving forces and to predict the spatial growth pattern based on historical land-use changes for the city of Los Ángeles in central Chile. This involved the analysis of images from 1978, 1992, and 1998 and characterization of the spatial pattern of land-use change; the construction of digital coverage in GIS; the selection of predictive variables through univariate analysis; the construction of logistic regression models using growth vs. nongrowth for 1978-1992 as the dependent variable; and the prediction of the probability of land-use change by applying the regression model to the 1992-1998 period. To investigate the influence of spatial scale, we constructed several sets of models that contained (1 only distance variables, e.g., distance to highways; (2 only scale-dependent density variables, e.g., density of urban area within a 600-m radius; (3 both distance and density variables; and (4 both distance and density variables at several spatial scales. The environmental variables were included in all models. The combination of distance and density variables at several scales is required to appropriately capture the multiscale urban growth process. The best models correctly predict ~90% of the observed land-use changes for 1992-1998. The distance to access roads, densities of the urban road system and urbanized area at various scales, and soil type were the strongest predictors of the growth pattern. Other variables were less important or not significant in explaining the urban growth process. Our approach, which

Evaluation of adamantane hydroxamates as botulinum neurotoxin inhibitors: synthesis, crystallography, modeling, kinetic and cellular based studies.

Science.gov (United States)

Šilhár, Peter; Silvaggi, Nicholas R; Pellett, Sabine; Čapková, Kateřina; Johnson, Eric A; Allen, Karen N; Janda, Kim D

2013-03-01

Botulinum neurotoxins (BoNTs) are the most lethal biotoxins known to mankind and are responsible for the neuroparalytic disease botulism. Current treatments for botulinum poisoning are all protein based and thus have a limited window of treatment opportunity. Inhibition of the BoNT light chain protease (LC) has emerged as a therapeutic strategy for the treatment of botulism as it may provide an effective post exposure remedy. Using a combination of crystallographic and modeling studies a series of hydroxamates derived from 1-adamantylacetohydroxamic acid (3a) were prepared. From this group of compounds, an improved potency of about 17-fold was observed for two derivatives. Detailed mechanistic studies on these structures revealed a competitive inhibition model, with a K(i)=27 nM, which makes these compounds some of the most potent small molecule, non-peptidic BoNT/A LC inhibitors reported to date. Copyright © 2012 Elsevier Ltd. All rights reserved.

A mouse model of visual perceptual learning reveals alterations in neuronal coding and dendritic spine density in the visual cortex

Directory of Open Access Journals (Sweden)

Yan eWang

2016-03-01

Full Text Available Visual perceptual learning (VPL can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS and a 55% gain in visual acuity (VA. Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1 than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL.

A Mouse Model of Visual Perceptual Learning Reveals Alterations in Neuronal Coding and Dendritic Spine Density in the Visual Cortex.

Science.gov (United States)

Wang, Yan; Wu, Wei; Zhang, Xian; Hu, Xu; Li, Yue; Lou, Shihao; Ma, Xiao; An, Xu; Liu, Hui; Peng, Jing; Ma, Danyi; Zhou, Yifeng; Yang, Yupeng

2016-01-01

Visual perceptual learning (VPL) can improve spatial vision in normally sighted and visually impaired individuals. Although previous studies of humans and large animals have explored the neural basis of VPL, elucidation of the underlying cellular and molecular mechanisms remains a challenge. Owing to the advantages of molecular genetic and optogenetic manipulations, the mouse is a promising model for providing a mechanistic understanding of VPL. Here, we thoroughly evaluated the effects and properties of VPL on spatial vision in C57BL/6J mice using a two-alternative, forced-choice visual water task. Briefly, the mice underwent prolonged training at near the individual threshold of contrast or spatial frequency (SF) for pattern discrimination or visual detection for 35 consecutive days. Following training, the contrast-threshold trained mice showed an 87% improvement in contrast sensitivity (CS) and a 55% gain in visual acuity (VA). Similarly, the SF-threshold trained mice exhibited comparable and long-lasting improvements in VA and significant gains in CS over a wide range of SFs. Furthermore, learning largely transferred across eyes and stimulus orientations. Interestingly, learning could transfer from a pattern discrimination task to a visual detection task, but not vice versa. We validated that this VPL fully restored VA in adult amblyopic mice and old mice. Taken together, these data indicate that mice, as a species, exhibit reliable VPL. Intrinsic signal optical imaging revealed that mice with perceptual training had higher cut-off SFs in primary visual cortex (V1) than those without perceptual training. Moreover, perceptual training induced an increase in the dendritic spine density in layer 2/3 pyramidal neurons of V1. These results indicated functional and structural alterations in V1 during VPL. Overall, our VPL mouse model will provide a platform for investigating the neurobiological basis of VPL.

Optimization of rootkit revealing system resources – A game theoretic approach

Directory of Open Access Journals (Sweden)

K. Muthumanickam

2015-10-01

Full Text Available Malicious rootkit is a collection of programs designed with the intent of infecting and monitoring the victim computer without the user’s permission. After the victim has been compromised, the remote attacker can easily cause further damage. In order to infect, compromise and monitor, rootkits adopt Native Application Programming Interface (API hooking technique. To reveal the hidden rootkits, current rootkit detection techniques check different data structures which hold reference to Native APIs. To verify these data structures, a large amount of system resources are required. This is because of the number of APIs in these data structures being quite large. Game theoretic approach is a useful mathematical tool to simulate network attacks. In this paper, a mathematical model is framed to optimize resource consumption using game-theory. To the best of our knowledge, this is the first work to be proposed for optimizing resource consumption while revealing rootkit presence using game theory. Non-cooperative game model is taken to discuss the problem. Analysis and simulation results show that our game theoretic model can effectively reduce the resource consumption by selectively monitoring the number of APIs in windows platform.

A study of gradient strengthening based on a finite-deformation gradient crystal-plasticity model

Science.gov (United States)

Pouriayevali, Habib; Xu, Bai-Xiang

2017-11-01

A comprehensive study on a finite-deformation gradient crystal-plasticity model which has been derived based on Gurtin's framework (Int J Plast 24:702-725, 2008) is carried out here. This systematic investigation on the different roles of governing components of the model represents the strength of this framework in the prediction of a wide range of hardening behaviors as well as rate-dependent and scale-variation responses in a single crystal. The model is represented in the reference configuration for the purpose of numerical implementation and then implemented in the FEM software ABAQUS via a user-defined subroutine (UEL). Furthermore, a function of accumulation rates of dislocations is employed and viewed as a measure of formation of short-range interactions. Our simulation results reveal that the dissipative gradient strengthening can be identified as a source of isotropic-hardening behavior, which may represent the effect of irrecoverable work introduced by Gurtin and Ohno (J Mech Phys Solids 59:320-343, 2011). Here, the variation of size dependency at different magnitude of a rate-sensitivity parameter is also discussed. Moreover, an observation of effect of a distinctive feature in the model which explains the effect of distortion of crystal lattice in the reference configuration is reported in this study for the first time. In addition, plastic flows in predefined slip systems and expansion of accumulation of GNDs are distinctly observed in varying scales and under different loading conditions.

Amblypygids: Model Organisms for the Study of Arthropod Navigation Mechanisms in Complex Environments?

Directory of Open Access Journals (Sweden)

Daniel D Wiegmann

2016-03-01

Full Text Available Navigation is an ideal behavioral model for the study of sensory system integration and the neural substrates associated with complex behavior. For this broader purpose, however, it may be profitable to develop new model systems that are both tractable and sufficiently complex to ensure that information derived from a single sensory modality and path integration are inadequate to locate a goal. Here, we discuss some recent discoveries related to navigation by amblypygids, nocturnal arachnids that inhabit the tropics and sub-tropics. Nocturnal displacement experiments under the cover of a tropical rainforest reveal that these animals possess navigational abilities that are reminiscent, albeit on a smaller spatial scale, of true-navigating vertebrates. Specialized legs, called antenniform legs, which possess hundreds of olfactory and tactile sensory hairs, and vision appear to be involved. These animals also have enormous mushroom bodies, higher-order brain regions that, in insects, integrate contextual cues and may be involved in spatial memory. In amblypygids, the complexity of a nocturnal rainforest may impose navigational challenges that favor the integration of information derived from multimodal cues. Moreover, the movement of these animals is easily studied in the laboratory and putative neural integration sites of sensory information can be manipulated. Thus, amblypygids could serve as a model system for the discovery of neural substrates associated with a unique and potentially sophisticated navigational capability. The diversity of habitats in which amblypygids are found also offers an opportunity for comparative studies of sensory integration and ecological selection pressures on navigation mechanisms.

A Novel 3D Skin Explant Model to Study Anaerobic Bacterial Infection

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Grazieli Maboni

2017-09-01

Full Text Available Skin infection studies are often limited by financial and ethical constraints, and alternatives, such as monolayer cell culture, do not reflect many cellular processes limiting their application. For a more functional replacement, 3D skin culture models offer many advantages such as the maintenance of the tissue structure and the cell types present in the host environment. A 3D skin culture model can be set up using tissues acquired from surgical procedures or post slaughter, making it a cost effective and attractive alternative to animal experimentation. The majority of 3D culture models have been established for aerobic pathogens, but currently there are no models for anaerobic skin infections. Footrot is an anaerobic bacterial infection which affects the ovine interdigital skin causing a substantial animal welfare and financial impact worldwide. Dichelobacter nodosus is a Gram-negative anaerobic bacterium and the causative agent of footrot. The mechanism of infection and host immune response to D. nodosus is poorly understood. Here we present a novel 3D skin ex vivo model to study anaerobic bacterial infections using ovine skin explants infected with D. nodosus. Our results demonstrate that D. nodosus can invade the skin explant, and that altered expression of key inflammatory markers could be quantified in the culture media. The viability of explants was assessed by tissue integrity (histopathological features and cell death (DNA fragmentation over 76 h showing the model was stable for 28 h. D. nodosus was quantified in all infected skin explants by qPCR and the bacterium was visualized invading the epidermis by Fluorescent in situ Hybridization. Measurement of pro-inflammatory cytokines/chemokines in the culture media revealed that the explants released IL1β in response to bacteria. In contrast, levels of CXCL8 production were no different to mock-infected explants. The 3D skin model realistically simulates the interdigital skin and has

Talaromyces marneffei Genomic, Transcriptomic, Proteomic and Metabolomic Studies Reveal Mechanisms for Environmental Adaptations and Virulence

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Susanna K. P. Lau

2017-06-01

Full Text Available Talaromyces marneffei is a thermally dimorphic fungus causing systemic infections in patients positive for HIV or other immunocompromised statuses. Analysis of its ~28.9 Mb draft genome and additional transcriptomic, proteomic and metabolomic studies revealed mechanisms for environmental adaptations and virulence. Meiotic genes and genes for pheromone receptors, enzymes which process pheromones, and proteins involved in pheromone response pathway are present, indicating its possibility as a heterothallic fungus. Among the 14 Mp1p homologs, only Mp1p is a virulence factor binding a variety of host proteins, fatty acids and lipids. There are 23 polyketide synthase genes, one for melanin and two for mitorubrinic acid/mitorubrinol biosynthesis, which are virulence factors. Another polyketide synthase is for biogenesis of the diffusible red pigment, which consists of amino acid conjugates of monascorubin and rubropunctatin. Novel microRNA-like RNAs (milRNAs and processing proteins are present. The dicer protein, dcl-2, is required for biogenesis of two milRNAs, PM-milR-M1 and PM-milR-M2, which are more highly expressed in hyphal cells. Comparative transcriptomics showed that tandem repeat-containing genes were overexpressed in yeast phase, generating protein polymorphism among cells, evading host’s immunity. Comparative proteomics between yeast and hyphal cells revealed that glyceraldehyde-3-phosphate dehydrogenase, up-regulated in hyphal cells, is an adhesion factor for conidial attachment.

Integrative analysis and expression profiling of secondary cell wall genes in C4 biofuel model Setaria italica reveals targets for lignocellulose bioengineering

Directory of Open Access Journals (Sweden)

Mehanathan eMuthamilarasan

2015-11-01

Full Text Available Several underutilized grasses have excellent potential for use as bioenergy feedstock due to their lignocellulosic biomass. Genomic tools have enabled identification of lignocellulose biosynthesis genes in several sequenced plants. However, the non-availability of whole genome sequence of bioenergy grasses hinders the study on bioenergy genomics and their genomics-assisted crop improvement. Foxtail millet (Setaria italica L.; Si is a model crop for studying systems biology of bioenergy grasses. In the present study, a systematic approach has been used for identification of gene families involved in cellulose (CesA/Csl, callose (Gsl and monolignol biosynthesis (PAL, C4H, 4CL, HCT, C3H, CCoAOMT, F5H, COMT, CCR, CAD and construction of physical map of foxtail millet. Sequence alignment and phylogenetic analysis of identified proteins showed that monolignol biosynthesis proteins were highly diverse, whereas CesA/Csl and Gsl proteins were homologous to rice and Arabidopsis. Comparative mapping of foxtail millet lignocellulose biosynthesis genes with other C4 panicoid genomes revealed maximum homology with switchgrass, followed by sorghum and maize. Expression profiling of candidate lignocellulose genes in response to different abiotic stresses and hormone treatments showed their differential expression pattern, with significant higher expression of SiGsl12, SiPAL2, SiHCT1, SiF5H2 and SiCAD6 genes. Further, due to the evolutionary conservation of grass genomes, the insights gained from the present study could be extrapolated for identifying genes involved in lignocellulose biosynthesis in other biofuel species for further characterization.

Integrative analysis and expression profiling of secondary cell wall genes in C4 biofuel model Setaria italica reveals targets for lignocellulose bioengineering.

Science.gov (United States)

Muthamilarasan, Mehanathan; Khan, Yusuf; Jaishankar, Jananee; Shweta, Shweta; Lata, Charu; Prasad, Manoj

2015-01-01

Several underutilized grasses have excellent potential for use as bioenergy feedstock due to their lignocellulosic biomass. Genomic tools have enabled identification of lignocellulose biosynthesis genes in several sequenced plants. However, the non-availability of whole genome sequence of bioenergy grasses hinders the study on bioenergy genomics and their genomics-assisted crop improvement. Foxtail millet (Setaria italica L.; Si) is a model crop for studying systems biology of bioenergy grasses. In the present study, a systematic approach has been used for identification of gene families involved in cellulose (CesA/Csl), callose (Gsl) and monolignol biosynthesis (PAL, C4H, 4CL, HCT, C3H, CCoAOMT, F5H, COMT, CCR, CAD) and construction of physical map of foxtail millet. Sequence alignment and phylogenetic analysis of identified proteins showed that monolignol biosynthesis proteins were highly diverse, whereas CesA/Csl and Gsl proteins were homologous to rice and Arabidopsis. Comparative mapping of foxtail millet lignocellulose biosynthesis genes with other C4 panicoid genomes revealed maximum homology with switchgrass, followed by sorghum and maize. Expression profiling of candidate lignocellulose genes in response to different abiotic stresses and hormone treatments showed their differential expression pattern, with significant higher expression of SiGsl12, SiPAL2, SiHCT1, SiF5H2, and SiCAD6 genes. Further, due to the evolutionary conservation of grass genomes, the insights gained from the present study could be extrapolated for identifying genes involved in lignocellulose biosynthesis in other biofuel species for further characterization.

Short-Term Wind Speed Forecasting Study and Its Application Using a Hybrid Model Optimized by Cuckoo Search

Directory of Open Access Journals (Sweden)

Xuejun Chen

2015-01-01

Full Text Available The support vector regression (SVR and neural network (NN are both new tools from the artificial intelligence field, which have been successfully exploited to solve various problems especially for time series forecasting. However, traditional SVR and NN cannot accurately describe intricate time series with the characteristics of high volatility, nonstationarity, and nonlinearity, such as wind speed and electricity price time series. This study proposes an ensemble approach on the basis of 5-3 Hanning filter (5-3H and wavelet denoising (WD techniques, in conjunction with artificial intelligence optimization based SVR and NN model. So as to confirm the validity of the proposed model, two applicative case studies are conducted in terms of wind speed series from Gansu Province in China and electricity price from New South Wales in Australia. The computational results reveal that cuckoo search (CS outperforms both PSO and GA with respect to convergence and global searching capacity, and the proposed CS-based hybrid model is effective and feasible in generating more reliable and skillful forecasts.

Modeled distribution and abundance of a pelagic seabird reveal trends in relation to fisheries

Science.gov (United States)

Renner, Martin; Parrish, Julia K.; Piatt, John F.; Kuletz, Kathy J.; Edwards, Ann E.; Hunt, George L.

2013-01-01

The northern fulmar Fulmarus glacialis is one of the most visible and widespread seabirds in the eastern Bering Sea and Aleutian Islands. However, relatively little is known about its abundance, trends, or the factors that shape its distribution. We used a long-term pelagic dataset to model changes in fulmar at-sea distribution and abundance since the mid-1970s. We used an ensemble model, based on a weighted average of generalized additive model (GAM), multivariate adaptive regression splines (MARS), and random forest models to estimate the pelagic distribution and density of fulmars in the waters of the Aleutian Archipelago and Bering Sea. The most important predictor variables were colony effect, sea surface temperature, distribution of fisheries, location, and primary productivity. We calculated a time series from the ratio of observed to predicted values and found that fulmar at-sea abundance declined from the 1970s to the 2000s at a rate of 0.83% (± 0.39% SE) per annum. Interpolating fulmar densities on a spatial grid through time, we found that the center of fulmar distribution in the Bering Sea has shifted north, coinciding with a northward shift in fish catches and a warming ocean. Our study shows that fisheries are an important, but not the only factor, shaping fulmar distribution and abundance trends in the eastern Bering Sea and Aleutian Islands.

DIGE proteome analysis reveals suitability of ischemic cardiac in vitro model for studying cellular response to acute ischemia and regeneration.

Directory of Open Access Journals (Sweden)

Sina Haas

Full Text Available Proteomic analysis of myocardial tissue from patient population is suited to yield insights into cellular and molecular mechanisms taking place in cardiovascular diseases. However, it has been limited by small sized biopsies and complicated by high variances between patients. Therefore, there is a high demand for suitable model systems with the capability to simulate ischemic and cardiotoxic effects in vitro, under defined conditions. In this context, we established an in vitro ischemia/reperfusion cardiac disease model based on the contractile HL-1 cell line. To identify pathways involved in the cellular alterations induced by ischemia and thereby defining disease-specific biomarkers and potential target structures for new drug candidates we used fluorescence 2D-difference gel electrophoresis. By comparing spot density changes in ischemic and reperfusion samples we detected several protein spots that were differentially abundant. Using MALDI-TOF/TOF-MS and ESI-MS the proteins were identified and subsequently grouped by functionality. Most prominent were changes in apoptosis signalling, cell structure and energy-metabolism. Alterations were confirmed by analysis of human biopsies from patients with ischemic cardiomyopathy.With the establishment of our in vitro disease model for ischemia injury target identification via proteomic research becomes independent from rare human material and will create new possibilities in cardiac research.

Recent studies of uranium and plutonium chemistry in alkaline radioactive waste solutions

International Nuclear Information System (INIS)

King, William D.; Wilmarth, William R.; Hobbs, David T.; Edwards, Thomas B.

2008-01-01

Solubility studies of uranium and plutonium in a caustic, radioactive Savannah River Site tank waste solution revealed the existence of uranium supersaturation in the as-received sample. Comparison of the results to predictions generated from previously published models for solubility in these waste types revealed that the U model poorly predicts solubility while Pu model predictions are quite consistent with experimental observations. Separate studies using simulated Savannah River Site evaporator feed solution revealed that the known formation of sodium aluminosilicate solids in waste evaporators can promote rapid precipitation of uranium from supersaturated solutions

Effective Connectivity Reveals Right-Hemisphere Dominance in Audiospatial Perception: Implications for Models of Spatial Neglect

Science.gov (United States)

Friston, Karl J.; Mattingley, Jason B.; Roepstorff, Andreas; Garrido, Marta I.

2014-01-01

Detecting the location of salient sounds in the environment rests on the brain's ability to use differences in sounds arriving at both ears. Functional neuroimaging studies in humans indicate that the left and right auditory hemispaces are coded asymmetrically, with a rightward attentional bias that reflects spatial attention in vision. Neuropsychological observations in patients with spatial neglect have led to the formulation of two competing models: the orientation bias and right-hemisphere dominance models. The orientation bias model posits a symmetrical mapping between one side of the sensorium and the contralateral hemisphere, with mutual inhibition of the ipsilateral hemisphere. The right-hemisphere dominance model introduces a functional asymmetry in the brain's coding of space: the left hemisphere represents the right side, whereas the right hemisphere represents both sides of the sensorium. We used Dynamic Causal Modeling of effective connectivity and Bayesian model comparison to adjudicate between these alternative network architectures, based on human electroencephalographic data acquired during an auditory location oddball paradigm. Our results support a hemispheric asymmetry in a frontoparietal network that conforms to the right-hemisphere dominance model. We show that, within this frontoparietal network, forward connectivity increases selectively in the hemisphere contralateral to the side of sensory stimulation. We interpret this finding in light of hierarchical predictive coding as a selective increase in attentional gain, which is mediated by feedforward connections that carry precision-weighted prediction errors during perceptual inference. This finding supports the disconnection hypothesis of unilateral neglect and has implications for theories of its etiology. PMID:24695717

The experimental study of heat transfer around molds inside a model autoclave

Science.gov (United States)

Ghamlouch, Taleb; Roux, Stéphane; Lefèvre, Nicolas; Bailleul, Jean-Luc; Sobotka, Vincent

2018-05-01

The temperature distribution within composite parts manufactured inside autoclaves plays a key role in determining the parts quality at the end of the curing cycle. Indeed, heat transfer between the parts and the surroundings inside an autoclave is strongly coupled with the flow field around the molds and can be modeled through the convective heat transfer coefficient (HTC). The aerodynamically unsuitable geometry of the molds generates complex turbulent non-uniform flows around them accompanied with the presence of dead zones. This heterogeneity can imply non-uniform convective heat transfers leading to temperature gradients inside parts that can be prejudicial. Given this fact, the purpose of this study is to perform experimental measurements in order to describe the flow field and the convective heat transfer behavior around representative industrial molds installed inside a home-made model. A key point of our model autoclave is the ease of use of non-intrusive measuring instruments: the Particle Image Velocimetry (PIV) technique and infrared imaging camera for the study of the flow field and the heat transfer coefficient distribution around the molds respectively. The experimental measurements are then compared to computational fluid dynamics (CFD) calculations performed on the computer code ANSYS Fluent 16.0®. This investigation has revealed, as expected, a non-uniform distribution of the convective heat transfer coefficient around the molds and therefore the presence of thermal gradients which can reduce the composite parts quality during an autoclave process. A good agreement has been achieved between the experimental and the numerical results leading then to the validation of the performed numerical simulations.

Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

Energy Technology Data Exchange (ETDEWEB)

Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

2012-07-01

Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

Demand effects of consumers’ stated and revealed preferences

OpenAIRE

Engström, Per; Forsell, Eskil

2013-01-01

Knowledge of how consumers react to different quality signals is fundamental for understanding how markets work. We study the online market- place for Android apps where we compare the causal effects on demand from two quality related signals; other consumers' stated and revealed preferences toward an app. Our main result is that consumers are much more responsive to other consumers' revealed preferences, compared to others' stated preferences. A 10 percentile increase in displayed average ra...

Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells

DEFF Research Database (Denmark)

Kirstetter, Peggy; Schuster, Mikkel B; Bereshchenko, Oksana

2008-01-01

Mutations in the CEBPA gene are present in 7%-10% of human patients with acute myeloid leukemia (AML). However, no genetic models exist that demonstrate their etiological relevance. To mimic the most common mutations affecting CEBPA-that is, those leading to loss of the 42 kDa C/EBPalpha isoform (p...... penetrance. p42-deficient leukemia could be transferred by a Mac1+c-Kit+ population that gave rise only to myeloid cells in recipient mice. Expression profiling of this population against normal Mac1+c-Kit+ progenitors revealed a signature shared with MLL-AF9-transformed AML.......42) while retaining the 30kDa isoform (p30)-we modified the mouse Cebpa locus to express only p30. p30 supported the formation of granulocyte-macrophage progenitors. However, p42 was required for control of myeloid progenitor proliferation, and p42-deficient mice developed AML with complete...

Sorption mechanism of U(VI) on to natural soil system: a study using intra-particle diffusion model

International Nuclear Information System (INIS)

Rout, S.; Kumar, A.; Ravi, P.M.; Tripathi, R.M.

2015-01-01

The rate of U(VI) adsorption onto natural soils from different parent materials has been studied experimentally using the batch adsorption method at five different initial U(VI) concentrations. The utility of Weber and Morris Interparticle diffusion model for describing the mechanism and kinetics of sorption is discussed. The study reveals that the mechanism of U(VI) sorption involves three steps such as: external surface adsorption, gradual adsorption stage which is the rate determining step and the last portion refers to the final equilibrium stage. The steps involved in sorption of U(VI) on to soil is same irrespective of soil types and initial U(VI) concentration. (author)

Commensurate comparisons of models with energy budget observations reveal consistent climate sensitivities

Science.gov (United States)

Armour, K.

2017-12-01

Global energy budget observations have been widely used to constrain the effective, or instantaneous climate sensitivity (ICS), producing median estimates around 2°C (Otto et al. 2013; Lewis & Curry 2015). A key question is whether the comprehensive climate models used to project future warming are consistent with these energy budget estimates of ICS. Yet, performing such comparisons has proven challenging. Within models, values of ICS robustly vary over time, as surface temperature patterns evolve with transient warming, and are generally smaller than the values of equilibrium climate sensitivity (ECS). Naively comparing values of ECS in CMIP5 models (median of about 3.4°C) to observation-based values of ICS has led to the suggestion that models are overly sensitive. This apparent discrepancy can partially be resolved by (i) comparing observation-based values of ICS to model values of ICS relevant for historical warming (Armour 2017; Proistosescu & Huybers 2017); (ii) taking into account the "efficacies" of non-CO2 radiative forcing agents (Marvel et al. 2015); and (iii) accounting for the sparseness of historical temperature observations and differences in sea-surface temperature and near-surface air temperature over the oceans (Richardson et al. 2016). Another potential source of discrepancy is a mismatch between observed and simulated surface temperature patterns over recent decades, due to either natural variability or model deficiencies in simulating historical warming patterns. The nature of the mismatch is such that simulated patterns can lead to more positive radiative feedbacks (higher ICS) relative to those engendered by observed patterns. The magnitude of this effect has not yet been addressed. Here we outline an approach to perform fully commensurate comparisons of climate models with global energy budget observations that take all of the above effects into account. We find that when apples-to-apples comparisons are made, values of ICS in models are

Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

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Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

2016-05-01

Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Digital Elevation Models of Patterned Ground in the Canadian Arctic and Implications for the Study of Mars

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Knightly, P.; Murakami, Y.; Clarke, J.; Sizemore, H.; Siegler, M.; Rupert, S.; Chevrier, V.

2017-12-01

Patterned ground forms in periglacial zones from both expansion and contraction of permafrost by freeze-thaw and sub-freezing temperature changes and has been observed on both Earth and Mars from orbital and the surface at the Phoneix and Viking 2 landing sites. The Phoenix mission to Mars studied patterned ground in the vicinity of the spacecraft including the excavation of a trench revealing water permafrost beneath the surface. A study of patterned ground at the Haughton Impact structure on Devon Island used stereo-pair imaging and three-dimensional photographic models to catalog the type and occurrence of patterned ground in the study area. This image catalog was then used to provide new insight into photographic observations gathered by Phoenix. Stereo-pair imagery has been a valuable geoscience tool for decades and it is an ideal tool for comparative planetary geology studies. Stereo-pair images captured on Devon Island were turned into digital elevation models (DEMs) and comparisons were noted between the permafrost and patterned ground environment of Earth and Mars including variations in grain sorting, active layer thickness, and ice table depth. Recent advances in 360° cameras also enabled the creation of a detailed, immersive site models of patterned ground at selected sites in Haughton crater on Devon Island. The information from this ground truth study will enable the development and refinement of existing models to better evaluate patterned ground on Mars and predict its evolution.

Inter-species activity correlations reveal functional correspondences between monkey and human brain areas

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Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G.; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A.; Vanduffel, Wim

2012-01-01

Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. In cases where functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assess similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by means of temporal correlation. Using natural vision data, we reveal regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This novel framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models. PMID:22306809

Using means-end chain analysis to reveal consumers' motivation for buying local foods: An exploratory study

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Poppy Arsil

2016-11-01

Full Text Available This article utilizes and discusses specific aspects of Means-End Chain (MEC analysis for understanding of the motives of Indonesian consumers who are involved in purchasing local foods. The MEC theory is used as a measure of attributes, consequences, and values of locally produced products involving specific aspects of this theory namely laddering methods of administration, content analysis procedure, constructing and interpreting Hierarchy Value Map (HVM. The results of the study indicate that MEC approach is a powerful method to reveal consumer motivation of local foods when associated with the various cultural groupings identified by the study particular between Javanese and Non-Javanese consumers. This study offers a practical implication and source of knowledge for other future studies and policies in term of (a a new approach for understanding the motives behind purchasing local foods for Indonesia consumers, and (b developing new categories of attributes, consequences and values of local foods.

Spatial models reveal the microclimatic buffering capacity of old-growth forests.

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Frey, Sarah J K; Hadley, Adam S; Johnson, Sherri L; Schulze, Mark; Jones, Julia A; Betts, Matthew G

2016-04-01

Climate change is predicted to cause widespread declines in biodiversity, but these predictions are derived from coarse-resolution climate models applied at global scales. Such models lack the capacity to incorporate microclimate variability, which is critical to biodiversity microrefugia. In forested montane regions, microclimate is thought to be influenced by combined effects of elevation, microtopography, and vegetation, but their relative effects at fine spatial scales are poorly known. We used boosted regression trees to model the spatial distribution of fine-scale, under-canopy air temperatures in mountainous terrain. Spatial models predicted observed independent test data well (r = 0.87). As expected, elevation strongly predicted temperatures, but vegetation and microtopography also exerted critical effects. Old-growth vegetation characteristics, measured using LiDAR (light detection and ranging), appeared to have an insulating effect; maximum spring monthly temperatures decreased by 2.5°C across the observed gradient in old-growth structure. These cooling effects across a gradient in forest structure are of similar magnitude to 50-year forecasts of the Intergovernmental Panel on Climate Change and therefore have the potential to mitigate climate warming at local scales. Management strategies to conserve old-growth characteristics and to curb current rates of primary forest loss could maintain microrefugia, enhancing biodiversity persistence in mountainous systems under climate warming.

Care Models of eHealth Services: A Case Study on the Design of a Business Model for an Online Precare Service.

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van Meeuwen, Dorine Pd; van Walt Meijer, Quirine J; Simonse, Lianne Wl

2015-03-24

With a growing population of health care clients in the future, the organization of high-quality and cost-effective service providing becomes an increasing challenge. New online eHealth services are proposed as innovative options for the future. Yet, a major barrier to these services appears to be the lack of new business model designs. Although design efforts generally result in visual models, no such artifacts have been found in the literature on business model design. This paper investigates business model design in eHealth service practices from a design perspective. It adopts a research by design approach and seeks to unravel what characteristics of business models determine an online service and what are important value exchanges between health professionals and clients. The objective of the study was to analyze the construction of care models in-depth, framing the essential elements of a business model, and design a new care model that structures these elements for the particular context of an online pre-care service in practice. This research employs a qualitative method of an in-depth case study in which different perspectives on constructing a care model are investigated. Data are collected by using the visual business modeling toolkit, designed to cocreate and visualize the business model. The cocreated models are transcribed and analyzed per actor perspective, transactions, and value attributes. We revealed eight new actors in the business model for providing the service. Essential actors are: the intermediary network coordinator connecting companies, the service dedicated information technology specialists, and the service dedicated health specialist. In the transactions for every service providing we found a certain type of contract, such as a license contract and service contracts for precare services and software products. In addition to the efficiency, quality, and convenience, important value attributes appeared to be: timelines, privacy and

A zebrafish model of lethal congenital contracture syndrome 1 reveals Gle1 function in spinal neural precursor survival and motor axon arborization.

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Jao, Li-En; Appel, Bruce; Wente, Susan R

2012-04-01

In humans, GLE1 is mutated in lethal congenital contracture syndrome 1 (LCCS1) leading to prenatal death of all affected fetuses. Although the molecular roles of Gle1 in nuclear mRNA export and translation have been documented, no animal models for this disease have been reported. To elucidate the function of Gle1 in vertebrate development, we used the zebrafish (Danio rerio) model system. gle1 mRNA is maternally deposited and widely expressed. Altering Gle1 using an insertional mutant or antisense morpholinos results in multiple defects, including immobility, small eyes, diminished pharyngeal arches, curved body axis, edema, underdeveloped intestine and cell death in the central nervous system. These phenotypes parallel those observed in LCCS1 human fetuses. Gle1 depletion also results in reduction of motoneurons and aberrant arborization of motor axons. Unexpectedly, the motoneuron deficiency results from apoptosis of neural precursors, not of differentiated motoneurons. Mosaic analyses further indicate that Gle1 activity is required extrinsically in the environment for normal motor axon arborization. Importantly, the zebrafish phenotypes caused by Gle1 deficiency are only rescued by expressing wild-type human GLE1 and not by the disease-linked Fin(Major) mutant form of GLE1. Together, our studies provide the first functional characterization of Gle1 in vertebrate development and reveal its essential role in actively dividing cells. We propose that defective GLE1 function in human LCCS1 results in both neurogenic and non-neurogenic defects linked to the apoptosis of proliferative organ precursors.

Generative models versus underlying symmetries to explain biological pattern.

Science.gov (United States)

Frank, S A

2014-06-01

Mathematical models play an increasingly important role in the interpretation of biological experiments. Studies often present a model that generates the observations, connecting hypothesized process to an observed pattern. Such generative models confirm the plausibility of an explanation and make testable hypotheses for further experiments. However, studies rarely consider the broad family of alternative models that match the same observed pattern. The symmetries that define the broad class of matching models are in fact the only aspects of information truly revealed by observed pattern. Commonly observed patterns derive from simple underlying symmetries. This article illustrates the problem by showing the symmetry associated with the observed rate of increase in fitness in a constant environment. That underlying symmetry reveals how each particular generative model defines a single example within the broad class of matching models. Further progress on the relation between pattern and process requires deeper consideration of the underlying symmetries. © 2014 The Author. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Revealing driving factors of China's PM2.5 pollution

Science.gov (United States)

Zheng, Y.; Zhao, H.; Zhang, Q.; Geng, G.; Tong, D.; Peng, L.; He, K.

2017-12-01

China's rapid economic development and intensive energy consumption are deteriorating the air quality significantly. Understanding the key driving factors behind China's growing emissions of air pollutants and the accompanying PM2.5 pollution is critical for the development of China's clean air policies and also provides insight into how other emerging economies may develop a clear sky future. Here we reveal the socioeconomic drivers of the variations of China's PM2.5 concentrations during 2002-2012 by using an interdisciplinary framework that integrates an emission inventory model, an index decomposition analysis model, and a regional air quality model. The decomposition results demostrate that the improvements in emission efficiency and energy efficiency failed to offset the increased emissions of both primary PM2.5 and gaseous PM2.5 precursors (including SO2 NOx, and volatile organic compounds) triggered by the surging economic growth during 2002-2012. During the same time, the effects of energy structure, production structure and population growth were relatively less significant to all pollutants, which indicates the potential of large emission abatements through energy structure and production structure adjustment. Sensitivity simulations by the air quality model based on the provincial decomposition results also show that the economic growth have outpaced efficiency improvements in the increments of PM2.5 concentrations during the study years. As China continues to develop rapidly, future policies should promote further improvements in efficiency and accelerate the adjustments toward clean energy and production structures, which are critical for reducing China's emissions and alleviating the severe PM2.5 pollution.

The Comparative Study of Collaborative Learning and SDLC Model to develop IT Group Projects

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Sorapak Pukdesree

2017-11-01

Full Text Available The main objectives of this research were to compare the attitudes of learners between applying SDLC model with collaborative learning and typical SDLC model and to develop electronic courseware as group projects. The research was a quasi-experimental research. The populations of the research were students who took Computer Organization and Architecture course in the academic year 2015. There were 38 students who participated to the research. The participants were divided voluntary into two groups including an experimental group with 28 students using SDLC model with collaborative learning and a control group with 10 students using typical SDLC model. The research instruments were attitude questionnaire, semi-structured interview and self-assessment questionnaire. The collected data was analysed by arithmetic mean, standard deviation, and independent sample t-test. The results of the questionnaire revealed that the attitudes of the learners using collaborative learning and SDLC model were statistically significant difference between the mean score for experimental group and control group at a significance level of 0.05. The independent statistical analyses were significantly different between the two groups at a significance level of 0.05. The results of the interviewing revealed that most of the learners had the corresponding opinions that collaborative learning was very useful with highest level of their attitudes comparing with the previous methodology. Learners had left some feedbacks that collaborative learning should be applied to other courses.

Study The role of latent variables in lost working days by Structural Equation Modeling Approach

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Meysam Heydari

2016-12-01

Full Text Available Background: Based on estimations, each year about 250 million work-related injuries and many temporary or permanent disabilities occur which most are preventable. Oil and Gas industries are among industries with high incidence of injuries in the world. The aim of this study has investigated  the role and effect of different risk management variables on lost working days (LWD in the seismic projects. Methods: This study was a retrospective, cross-sectional and systematic analysis, which was carried out on occupational accidents between 2008-2015(an 8 years period in different seismic projects for oilfield exploration at Dana Energy (Iranian Seismic Company. The preliminary sample size of the study were 487accidents. A systems analysis approach were applied by using root case analysis (RCA and structural equation modeling (SEM. Tools for the data analysis were included, SPSS23 and AMOS23  software. Results: The mean of lost working days (LWD, was calculated 49.57, the final model of structural equation modeling showed that latent variables of, safety and health training factor(-0.33, risk assessment factor(-0.55 and risk control factor (-0.61 as direct causes significantly affected of lost working days (LWD in the seismic industries (p< 0.05. Conclusion: The finding of present study revealed that combination of variables affected in lost working days (LWD. Therefore,the role of these variables in accidents should be investigated and suitable programs should be considered for them.

Example of emergency response model evaluation of studies using the Mathew/Adpic models

International Nuclear Information System (INIS)

Dickerson, M.H.; Lange, R.

1986-04-01

This report summarizes model evaluation studies conducted for the MATHEW/ADPIC transport and diffusion models during the past ten years. These models support the US Department of Energy Atmospheric Release Advisory Capability, an emergency response service for atmospheric releases of nuclear material. Field studies involving tracer releases used in these studies cover a broad range of meteorology, terrain and tracer release heights, the three most important aspects of estimating air concentration values resulting from airborne releases of toxic material. Results of these studies show that these models can estimate air concentration values within a factor of 2 20% to 50% of the time and a factor of 5 40% to 80% of the time. As the meterology and terrain become more complex and the release height of the tracer is increased, the accuracy of the model calculations degrades. This band of uncertainty appears to correctly represent the capability of these models at this time. A method for estimating angular uncertainty in the model calculations is described and used to suggest alternative methods for evaluating emergency response models

Modeling the Financial Distress of Microenterprise StartUps Using Support Vector Machines: A Case Study

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Antonio Blanco-Oliver

2014-10-01

Full Text Available Despite the leading role that micro-entrepreneurship plays in economic development, and the high failure rate of microenterprise start-ups in their early years, very few studies have designed financial distress models to detect the financial problems of micro-entrepreneurs. Moreover, due to a lack of research, nothing is known about whether non-financial information and nonparametric statistical techniques improve the predictive capacity of these models. Therefore, this paper provides an innovative financial distress model specifically designed for microenterprise startups via support vector machines (SVMs that employs financial, non-financial, and macroeconomic variables. Based on a sample of almost 5,500 micro- entrepreneurs from a Peruvian Microfinance Institution (MFI, our findings show that the introduction of non-financial information related to the zone in which the entrepreneurs live and situate their business, the duration of the MFI-entrepreneur relationship, the number of loans granted by the MFI in the last year, the loan destination, and the opinion of experts on the probability that microenterprise start-ups may experience financial problems, significantly increases the accuracy performance of our financial distress model. Furthermore, the results reveal that the models that use SVMs outperform those which employ traditional logistic regression (LR analysis.

In vitro radiosensitivity of six human cell lines. A comparative study with different statistical models

International Nuclear Information System (INIS)

Fertil, B.; Deschavanne, P.J.; Lachet, B.; Malaise, E.P.

1980-01-01

The intrinsic radiosensitivity of human cell lines (five tumor and one nontransformed fibroblastic) was studied in vitro. The survival curves were fitted by the single-hit multitarget, the two-hit multitarget, the single-hit multitarget with initial slope, and the quadratic models. The accuracy of the experimental results permitted evaluation of the various fittings. Both a statistical test (comparison of variances left unexplained by the four models) and a biological consideration (check for independence of the fitted parameters vis-a-vis the portion of the survival curve in question) were carried out. The quadratic model came out best with each of them. It described the low-dose effects satisfactorily, revealing a single-hit lethal component. This finding and the fact that the six survival curves displayed a continuous curvature ruled out the adoption of the target models as well as the widely used linear regression. As calculated by the quadratic model, the parameters of the six cell lines lead to the following conclusions: (a) the intrinsic radiosensitivity varies greatly among the different cell lines; (b) the interpretation of the fibroblast survival curve is not basically different from that of the tumor cell lines; and (c) the radiosensitivity of these human cell lines is comparable to that of other mammalian cell lines

Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

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Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

2016-03-01

Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood

Mathematical modelling with case studies using Maple and Matlab

CERN Document Server

Barnes, B

2014-01-01

Introduction to Mathematical ModelingMathematical models An overview of the book Some modeling approaches Modeling for decision makingCompartmental Models Introduction Exponential decay and radioactivity Case study: detecting art forgeries Case study: Pacific rats colonize New Zealand Lake pollution models Case study: Lake Burley Griffin Drug assimilation into the blood Case study: dull, dizzy, or dead? Cascades of compartments First-order linear DEs Equilibrium points and stability Case study: money, money, money makes the world go aroundModels of Single PopulationsExponential growth Density-

Human primary erythroid cells as a more sensitive alternative in vitro hematological model for nanotoxicity studies: Toxicological effects of silver nanoparticles.

Science.gov (United States)

Rujanapun, Narawadee; Aueviriyavit, Sasitorn; Boonrungsiman, Suwimon; Rosena, Apiwan; Phummiratch, Duangkamol; Riolueang, Suchada; Chalaow, Nipon; Viprakasit, Vip; Maniratanachote, Rawiwan

2015-12-01

Although immortalized cells established from cancerous cells have been widely used for studies in nanotoxicology studies, the reliability of the results derived from immortalized cells has been questioned because of their different characteristics from normal cells. In the present study, human primary erythroid cells in liquid culture were used as an in vitro hematological cell model for investigation of the nanotoxicity of silver nanoparticles (AgNPs) and comparing the results to the immortalized hematological cell lines HL60 and K562. The AgNPs caused significant cytotoxic effects in the primary erythroid cells, as shown by the decreased cell viability and induction of intracellular ROS generation and apoptosis, whereas they showed much lower cytotoxic and apoptotic effects in HL60 and K562 cells and did not induced ROS generation in these cell lines. Scanning electron microcopy revealed an interaction of AgNPs to the cell membrane in both primary erythroid and immortalized cells. In addition, AgNPs induced hemolysis in the primary erythroid cells in a dose-dependent manner, and transmission electron microcopy analysis revealed that AgNPs damaged the erythroid cell membrane. Taken together, these results suggest that human primary erythroid cells in liquid culture are a more sensitive alternative in vitro hematological model for nanotoxicology studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin.

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Vasyl V Mykuliak

2018-04-01

Full Text Available Mechanical stability is a key feature in the regulation of structural scaffolding proteins and their functions. Despite the abundance of α-helical structures among the human proteome and their undisputed importance in health and disease, the fundamental principles of their behavior under mechanical load are poorly understood. Talin and α-catenin are two key molecules in focal adhesions and adherens junctions, respectively. In this study, we used a combination of atomistic steered molecular dynamics (SMD simulations, polyprotein engineering, and single-molecule atomic force microscopy (smAFM to investigate unfolding of these proteins. SMD simulations revealed that talin rod α-helix bundles as well as α-catenin α-helix domains unfold through stable 3-helix intermediates. While the 5-helix bundles were found to be mechanically stable, a second stable conformation corresponding to the 3-helix state was revealed. Mechanically weaker 4-helix bundles easily unfolded into a stable 3-helix conformation. The results of smAFM experiments were in agreement with the findings of the computational simulations. The disulfide clamp mutants, designed to protect the stable state, support the 3-helix intermediate model in both experimental and computational setups. As a result, multiple discrete unfolding intermediate states in the talin and α-catenin unfolding pathway were discovered. Better understanding of the mechanical unfolding mechanism of α-helix proteins is a key step towards comprehensive models describing the mechanoregulation of proteins.

Building the Nanoplasmonics Toolbox Through Shape Modeling and Single Particle Optical Studies

Science.gov (United States)

Ringe, Emilie

Interest in nanotechnology is driven by unprecedented properties tailorability, achievable by controlling particle structure and composition. Unlike bulk components, minute changes in size and shape affect the optical and electronic properties of nanoparticles. Characterization of such structure-function relationships and better understanding of structure control mechanisms is crucial to the development of applications such as plasmonic sensors and devices. The objective of the current research is thus twofold: to theoretically predict and understand how shape is controlled by synthesis conditions, and to experimentally unravel, through single particle studies, how shape, composition, size, and surrounding environment affect plasmonic properties in noble metal particles. Quantitative, predictive rules and fundamental knowledge obtained from this research contributes to the "nanoplasmonics toolbox", a library designed to provide scientists and engineers the tools to create and optimize novel nanotechnology applications. In this dissertation, single particle approaches are developed and used to unravel the effects of size, shape, substrate, aggregation state and surrounding environment on the optical response of metallic nanoparticles. Ag and Au nanocubes on different substrates are first presented, followed by the discussion of the concept of plasmon length, a universal parameter to describe plasmon energy for a variety of particle shapes and plasmon modes. Plasmonic sensing (both refractive index sensing and surface-enhanced Raman spectroscopy) and polarization effects are then studied at the single particle level. In the last two Chapters, analytical shape models based on the Wulff construction provide unique modeling tools for alloy and kinetically grown nanoparticles. The former reveals a size-dependence of the shape of small alloy particles (such as those used in catalysis) because of surface segregation, while the latter uniquely models the shape of many

Comparative Study of Lectin Domains in Model Species: New Insights into Evolutionary Dynamics

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Sofie Van Holle

2017-05-01

Full Text Available Lectins are present throughout the plant kingdom and are reported to be involved in diverse biological processes. In this study, we provide a comparative analysis of the lectin families from model species in a phylogenetic framework. The analysis focuses on the different plant lectin domains identified in five representative core angiosperm genomes (Arabidopsis thaliana, Glycine max, Cucumis sativus, Oryza sativa ssp. japonica and Oryza sativa ssp. indica. The genomes were screened for genes encoding lectin domains using a combination of Basic Local Alignment Search Tool (BLAST, hidden Markov models, and InterProScan analysis. Additionally, phylogenetic relationships were investigated by constructing maximum likelihood phylogenetic trees. The results demonstrate that the majority of the lectin families are present in each of the species under study. Domain organization analysis showed that most identified proteins are multi-domain proteins, owing to the modular rearrangement of protein domains during evolution. Most of these multi-domain proteins are widespread, while others display a lineage-specific distribution. Furthermore, the phylogenetic analyses reveal that some lectin families evolved to be similar to the phylogeny of the plant species, while others share a closer evolutionary history based on the corresponding protein domain architecture. Our results yield insights into the evolutionary relationships and functional divergence of plant lectins.

Architecture of cognitive flexibility revealed by lesion mapping

Science.gov (United States)

Barbey, Aron K.; Colom, Roberto; Grafman, Jordan

2013-01-01

Neuroscience has made remarkable progress in understanding the architecture of human intelligence, identifying a distributed network of brain structures that support goal-directed, intelligent behavior. However, the neural foundations of cognitive flexibility and adaptive aspects of intellectual function remain to be well characterized. Here, we report a human lesion study (n = 149) that investigates the neural bases of key competencies of cognitive flexibility (i.e., mental flexibility and the fluent generation of new ideas) and systematically examine their contributions to a broad spectrum of cognitive and social processes, including psychometric intelligence (Wechsler Adult Intelligence Scale), emotional intelligence (Mayer, Salovey, Caruso Emotional Intelligence Test), and personality (Neuroticism–Extraversion–Openness Personality Inventory). Latent variable modeling was applied to obtain error-free indices of each factor, followed by voxel-based lesion-symptom mapping to elucidate their neural substrates. Regression analyses revealed that latent scores for psychometric intelligence reliably predict latent scores for cognitive flexibility (adjusted R2 = 0.94). Lesion mapping results further indicated that these convergent processes depend on a shared network of frontal, temporal, and parietal regions, including white matter association tracts, which bind these areas into an integrated system. A targeted analysis of the unique variance explained by cognitive flexibility further revealed selective damage within the right superior temporal gyrus, a region known to support insight and the recognition of novel semantic relations. The observed findings motivate an integrative framework for understanding the neural foundations of adaptive behavior, suggesting that core elements of cognitive flexibility emerge from a distributed network of brain regions that support specific competencies for human intelligence. PMID:23721727

Four not six: Revealing culturally common facial expressions of emotion.

Science.gov (United States)

Jack, Rachael E; Sun, Wei; Delis, Ioannis; Garrod, Oliver G B; Schyns, Philippe G

2016-06-01

As a highly social species, humans generate complex facial expressions to communicate a diverse range of emotions. Since Darwin's work, identifying among these complex patterns which are common across cultures and which are culture-specific has remained a central question in psychology, anthropology, philosophy, and more recently machine vision and social robotics. Classic approaches to addressing this question typically tested the cross-cultural recognition of theoretically motivated facial expressions representing 6 emotions, and reported universality. Yet, variable recognition accuracy across cultures suggests a narrower cross-cultural communication supported by sets of simpler expressive patterns embedded in more complex facial expressions. We explore this hypothesis by modeling the facial expressions of over 60 emotions across 2 cultures, and segregating out the latent expressive patterns. Using a multidisciplinary approach, we first map the conceptual organization of a broad spectrum of emotion words by building semantic networks in 2 cultures. For each emotion word in each culture, we then model and validate its corresponding dynamic facial expression, producing over 60 culturally valid facial expression models. We then apply to the pooled models a multivariate data reduction technique, revealing 4 latent and culturally common facial expression patterns that each communicates specific combinations of valence, arousal, and dominance. We then reveal the face movements that accentuate each latent expressive pattern to create complex facial expressions. Our data questions the widely held view that 6 facial expression patterns are universal, instead suggesting 4 latent expressive patterns with direct implications for emotion communication, social psychology, cognitive neuroscience, and social robotics. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Comparative study between 2 methods of mounting models in semiadjustable articulator for orthognathic surgery.

Science.gov (United States)

Mayrink, Gabriela; Sawazaki, Renato; Asprino, Luciana; de Moraes, Márcio; Fernandes Moreira, Roger William

2011-11-01

Compare the traditional method of mounting dental casts on a semiadjustable articulator and the new method suggested by Wolford and Galiano, 1 analyzing the inclination of maxillary occlusal plane in relation to FHP. Two casts of 10 patients were obtained. One of them was used for mounting of models on a traditional articulator, by using a face bow transfer system and the other one was used to mounting models at Occlusal Plane Indicator platform (OPI), using the SAM articulator. After that, na analysis of the accuracy of mounting models was performed. The angle made by de occlusal plane and FHP on the cephalogram should be equal the angle between the occlusal plane and the upper member of the articulator. The measures were tabulated in Microsoft Excell(®) and calculated using a 1-way analysis variance. Statistically, the results did not reveal significant differences among the measures. OPI and face bow presents similar results but more studies are needed to verify its accuracy relative to the maxillary cant in OPI or develop new techniques able to solve the disadvantages of each technique. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Mentoring and role models in recruitment and retention: a study of junior medical faculty perceptions.

Science.gov (United States)

Steele, Margaret M; Fisman, Sandra; Davidson, Brenda

2013-05-01

This study explored the views of junior faculty toward informing mentorship program development. Mixed sampling methodologies including questionnaires (n = 175), focus groups (female, n = 4; male, n = 4), and individual interviews (female n = 10; male, n = 9) of junior faculty were conducted in clinical departments at one academic health sciences center. Questionnaire results indicated that having role models increased commitment to an academic career; mentorship experience during residency training was a high incentive to pursue an academic career; and junior faculty did have identifiable mentorship experiences. Focus group results revealed that mentoring as well as the presence of role models a few years ahead of the junior faculty would promote career development. Females preferred similar age role models who spoke the same language, particularly in the area of promotion. Females identified several challenges and issues including a lack of researcher role models, a range of perceptions regarding the merits of formal versus informal mentoring, and the idea that mentors should provide advice on promotion and grants. Males valued advice on finances while females wanted advice on work-life balance. Mentorship emerged as an important factor in academic faculty recruitment and retention, with varying perceptions of how it should be institutionalized. Role models were viewed as important for retention, and a paucity of mid-career, female researcher role models suggests a gap to be filled in future programmatic efforts.

Systems biology modeling reveals a possible mechanism of the tumor cell death upon oncogene inactivation in EGFR addicted cancers.

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Jian-Ping Zhou

Full Text Available Despite many evidences supporting the concept of "oncogene addiction" and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK and phosphoinositol-3 kinase (PI3K/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential due to the elevated level of reactive oxygen species (ROS is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers.

Development of the electromagnetic tomography system. Sensitivity study of anomalous body by model studies; EM tomography system no kaihatsu. Model kaiseki ni yoru ijotai no kando chosa kekka

Energy Technology Data Exchange (ETDEWEB)

Kumekawa, Y; Miura, Y; Takasugi, S [Geothermal Energy Research and Development Co. Ltd., Tokyo (Japan); Arai, E [Metal Mining Agency of Japan, Tokyo (Japan)

1996-05-01

An examination was made by a model analysis on sensitivity and the like against a resistive anomalous body, in connection with an electromagnetic tomography system with surface earthquake sources and underground receiver arrangements. A resistivity model was of a three-dimensional structure, and built with a 5 ohm{center_dot}m low resistivity anomalous body assembled in a 100 ohm{center_dot}m homogeneous medium. As a result of the examination, it was shown that the size limitation of an analyzable anomalous body was 50{times}50{times}20m at a frequency of 8 to 10kHz and that a system with high precision in a high frequency range was necessary. The examination of effects under a shallow anomalous body revealed, for example, that the fluctuation of a low frequency response was large compared with a deep anomalous body and that, where a second anomalous body existed under it, the effect also appeared with a surface earthquake source positioned in the opposite side from the anomalous body. The examination of effects under the three dimensional structure revealed, for example, that a remarkable change appeared in the data with the change in the inclined angle of the transmission line against the strike of the anomalous body. 4 refs., 7 figs.

Attention-dependent modulation of cortical taste circuits revealed by Granger causality with signal-dependent noise.

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Qiang Luo

2013-10-01

Full Text Available We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention.

EVALUATION OF THE HTA CORE MODEL FOR NATIONAL HEALTH TECHNOLOGY ASSESSMENT REPORTS: COMPARATIVE STUDY AND EXPERIENCES FROM EUROPEAN COUNTRIES.

Science.gov (United States)

Kõrge, Kristina; Berndt, Nadine; Hohmann, Juergen; Romano, Florence; Hiligsmann, Mickael

2017-01-01

The health technology assessment (HTA) Core Model® is a tool for defining and standardizing the elements of HTA analyses within several domains for producing structured reports. This study explored the parallels between the Core Model and a national HTA report. Experiences from various European HTA agencies were also investigated to determine the Core Model's adaptability to national reports. A comparison between a national report on Genetic Counseling, produced by the Cellule d'expertise médicale Luxembourg, and the Core Model was performed to identify parallels in terms of relevant and comparable assessment elements (AEs). Semi-structured interviews with five representatives from European HTA agencies were performed to assess their user experiences with the Core Model. The comparative study revealed that 50 percent of the total number (n = 144) of AEs in the Core Model were relevant for the national report. Of these 144 AEs from the Core Model, 34 (24 percent) were covered in the national report. Some AEs were covered only partly. The interviewees emphasized flexibility in using the Core Model and stated that the most important aspects to be evaluated include characteristics of the disease and technology, clinical effectiveness, economic aspects, and safety. In the present study, the national report covered an acceptable number of AEs of the Core Model. These results need to be interpreted with caution because only one comparison was performed. The Core Model can be used in a flexible manner, applying only those elements that are relevant from the perspective of the technology assessment and specific country context.

A large study reveals no Association between APOE and Parkinson’s disease

Science.gov (United States)

Federoff, Monica; Jimenez-Rolando, Belen; Nalls, Michael A; Singleton, Andrew B

2012-01-01

Background Research focusing on the role of APOE in Parkinson’s disease (PD) has been largely inconclusive, creating a broad discrepancy in association studies. Objective To elucidate the role of APOE alleles in PD risk by studying a large sample size and controlling for population substructure. Patients and Methods In total, 3465 case and control samples were genotyped, obtained from the NINDS Neurogenetics repository. Results No significant differences in ε4 dosages exist between PD cases and controls. The frequency of ε4 carriers differed slightly between cases and controls at 24% (580/2412) and 26% (270/1053), respectively. Likewise, mean dosages of APOE ε2 were not significantly different between cases and controls. APOE ε2 carriers were observed at a frequency of 13.6% (329/2412) among cases and 15% (158/1053) among controls. Logistic regression models evaluating PD as possibly associated with ε4 or ε2 carrier status and allele dosages yielded no significant results. The mean MMSE score among all PD cases was 28.35 (SD = 2.58) and memory loss was reported in only 11.9% (105/879) of cases. Linear regression models comparing MMSE scores as predicted by ε4 or ε2 carrier status and allele dosages were not significant. Conclusions There is no association between APOE epsilon alleles and Parkinson’s disease. PMID:22349451

Study of a model for gamma radiation effects on chlorella

International Nuclear Information System (INIS)

Delforge, Jacques; Fabre, Henri; CEA Centre d'Etudes Nucleaires de Grenoble, 38

1977-01-01

The experimental data obtained by 60 Co γ irradiation of chlorella are especially interesting because they show a dose rate effect (change in the survival curve plotted versus dose as the dose rate varies) and a change in the survival fraction as a function of the time separating the end of irradiation and the starting of culture. The radiobiological models published until now are not able to illustrate all these experimental phenomena. An attempt is made here to find a model within the scope of P. DELATTRE's transformation system theory. The use of this precise theoretical framework enables to propose an experimental procedure which offers no special practical difficulty but leads to much more abundant information than the standard procedures. The model obtained reveals the existence of at least three different states amongst chlorella still able to multiply, and only one state amongst those temporarily deprived of their multiplying capacity. It shows the possibility of internal restorations in the elements still capable of multiplying, but also confirms the existence of non-lethal but irreparable lesions [fr

Mixed models in cerebral ischemia study

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Matheus Henrique Dal Molin Ribeiro

2016-06-01

Full Text Available The data modeling from longitudinal studies stands out in the current scientific scenario, especially in the areas of health and biological sciences, which induces a correlation between measurements for the same observed unit. Thus, the modeling of the intra-individual dependency is required through the choice of a covariance structure that is able to receive and accommodate the sample variability. However, the lack of methodology for correlated data analysis may result in an increased occurrence of type I or type II errors and underestimate/overestimate the standard errors of the model estimates. In the present study, a Gaussian mixed model was adopted for the variable response latency of an experiment investigating the memory deficits in animals subjected to cerebral ischemia when treated with fish oil (FO. The model parameters estimation was based on maximum likelihood methods. Based on the restricted likelihood ratio test and information criteria, the autoregressive covariance matrix was adopted for errors. The diagnostic analyses for the model were satisfactory, since basic assumptions and results obtained corroborate with biological evidence; that is, the effectiveness of the FO treatment to alleviate the cognitive effects caused by cerebral ischemia was found.

A study of modelling simplifications in ground vibration predictions for railway traffic at grade

Science.gov (United States)

Germonpré, M.; Degrande, G.; Lombaert, G.

2017-10-01

Accurate computational models are required to predict ground-borne vibration due to railway traffic. Such models generally require a substantial computational effort. Therefore, much research has focused on developing computationally efficient methods, by either exploiting the regularity of the problem geometry in the direction along the track or assuming a simplified track structure. This paper investigates the modelling errors caused by commonly made simplifications of the track geometry. A case study is presented investigating a ballasted track in an excavation. The soil underneath the ballast is stiffened by a lime treatment. First, periodic track models with different cross sections are analyzed, revealing that a prediction of the rail receptance only requires an accurate representation of the soil layering directly underneath the ballast. A much more detailed representation of the cross sectional geometry is required, however, to calculate vibration transfer from track to free field. Second, simplifications in the longitudinal track direction are investigated by comparing 2.5D and periodic track models. This comparison shows that the 2.5D model slightly overestimates the track stiffness, while the transfer functions between track and free field are well predicted. Using a 2.5D model to predict the response during a train passage leads to an overestimation of both train-track interaction forces and free field vibrations. A combined periodic/2.5D approach is therefore proposed in this paper. First, the dynamic axle loads are computed by solving the train-track interaction problem with a periodic model. Next, the vibration transfer to the free field is computed with a 2.5D model. This combined periodic/2.5D approach only introduces small modelling errors compared to an approach in which a periodic model is used in both steps, while significantly reducing the computational cost.

Development of the Artistic Supervision Model Scale (ASMS)

Science.gov (United States)

Kapusuzoglu, Saduman; Dilekci, Umit

2017-01-01

The purpose of the study is to develop the Artistic Supervision Model Scale in accordance with the perception of inspectors and the elementary and secondary school teachers on artistic supervision. The lack of a measuring instrument related to the model of artistic supervision in the field of literature reveals the necessity of such study. 290…

Study on models for gap conductance between fuel and sheath for CANDU reactors

International Nuclear Information System (INIS)

Lee, K.M.; Ohn, M.Y.; Lim, H.S.; Choi, J.H.; Hwang, S.T.

1995-01-01

The gap conductance between the fuel and the sheath depends strongly on the gap width and has a significant influence on the amount of initial stored energy. The modified Ross and Stoute gap conductance model in ELESTRES is based on a simplified thermal deformation model for steady-state fuel temperature calculations. A review on a series of experiments reveals that fuel pellets crack, relocate, and are eccentrically positioned within the sheath rather than solid concentric cylinders. In this paper, the two recently-proposed gap conductance models (offset gap model and relocated gap model) are described and are applied to calculate the fuel-sheath gap conductances under experimental conditions and normal operating conditions in CANDU reactors. The good agreement between the experimentally-inferred and calculated gap conductance values demonstrates that the modified Ross and Stoute model was implemented correctly in ELESTRES. The predictions of the modified Ross and Stoute model provide conservative values for gap heat transfer and fuel surface temperature compared to the offset gap and relocated gap models for a limiting power envelope. (author)

Ecological succession reveals potential signatures of marine-terrestrial transition in salt marsh fungal communities.

Science.gov (United States)

Dini-Andreote, Francisco; Pylro, Victor Satler; Baldrian, Petr; van Elsas, Jan Dirk; Salles, Joana Falcão

2016-08-01

Marine-to-terrestrial transition represents one of the most fundamental shifts in microbial life. Understanding the distribution and drivers of soil microbial communities across coastal ecosystems is critical given the roles of microbes in soil biogeochemistry and their multifaceted influence on landscape succession. Here, we studied the fungal community dynamics in a well-established salt marsh chronosequence that spans over a century of ecosystem development. We focussed on providing high-resolution assessments of community composition, diversity and ecophysiological shifts that yielded patterns of ecological succession through soil formation. Notably, despite containing 10- to 100-fold lower fungal internal transcribed spacer abundances, early-successional sites revealed fungal richnesses comparable to those of more mature soils. These newly formed sites also exhibited significant temporal variations in β-diversity that may be attributed to the highly dynamic nature of the system imposed by the tidal regime. The fungal community compositions and ecophysiological assignments changed substantially along the successional gradient, revealing a clear signature of ecological replacement and gradually transforming the environment from a marine into a terrestrial system. Moreover, distance-based linear modelling revealed soil physical structure and organic matter to be the best predictors of the shifts in fungal β-diversity along the chronosequence. Taken together, our study lays the basis for a better understanding of the spatiotemporally determined fungal community dynamics in salt marshes and highlights their ecophysiological traits and adaptation in an evolving ecosystem.

Model Servqual Dengan Pendekatan Structural Equation Modeling (Studi Pada Mahasiswa Sistem Informasi)

OpenAIRE

Nurfaizal, Yusmedi

2015-01-01

Penelitian ini berjudul “MODEL SERVQUAL DENGAN PENDEKATAN STRUCTURAL EQUATION MODELING (Studi Pada Mahasiswa Sistem Informasi)”. Tujuan penelitian ini adalah untuk mengetahui model Servqual dengan pendekatan Structural Equation Modeling pada mahasiswa sistem informasi. Peneliti memutuskan untuk mengambil sampel sebanyak 100 responden. Untuk menguji model digunakan analisis SEM. Hasil penelitian menunjukkan bahwa tangibility, reliability responsiveness, assurance dan emphaty mempunyai pengaruh...

Air Pollution Exposure Modeling for Health Studies | Science ...

Science.gov (United States)

Dr. Michael Breen is leading the development of air pollution exposure models, integrated with novel personal sensor technologies, to improve exposure and risk assessments for individuals in health studies. He is co-investigator for multiple health studies assessing the exposure and effects of air pollutants. These health studies include participants with asthma, diabetes, and coronary artery disease living in various U.S. cities. He has developed, evaluated, and applied novel exposure modeling and time-activity tools, which includes the Exposure Model for Individuals (EMI), GPS-based Microenvironment Tracker (MicroTrac) and Exposure Tracker models. At this seminar, Dr. Breen will present the development and application of these models to predict individual-level personal exposures to particulate matter (PM) for two health studies in central North Carolina. These health studies examine the association between PM and adverse health outcomes for susceptible individuals. During Dr. Breen’s visit, he will also have the opportunity to establish additional collaborations with researchers at Harvard University that may benefit from the use of exposure models for cohort health studies. These research projects that link air pollution exposure with adverse health outcomes benefit EPA by developing model-predicted exposure-dose metrics for individuals in health studies to improve the understanding of exposure-response behavior of air pollutants, and to reduce participant

Case studies, cross-site comparisons, and the challenge of generalization: comparing agent-based models of land-use change in frontier regions.

Science.gov (United States)

Parker, Dawn C; Entwisle, Barbara; Rindfuss, Ronald R; Vanwey, Leah K; Manson, Steven M; Moran, Emilio; An, Li; Deadman, Peter; Evans, Tom P; Linderman, Marc; Rizi, S Mohammad Mussavi; Malanson, George

2008-01-01

Cross-site comparisons of case studies have been identified as an important priority by the land-use science community. From an empirical perspective, such comparisons potentially allow generalizations that may contribute to production of global-scale land-use and land-cover change projections. From a theoretical perspective, such comparisons can inform development of a theory of land-use science by identifying potential hypotheses and supporting or refuting evidence. This paper undertakes a structured comparison of four case studies of land-use change in frontier regions that follow an agent-based modeling approach. Our hypothesis is that each case study represents a particular manifestation of a common process. Given differences in initial conditions among sites and the time at which the process is observed, actual mechanisms and outcomes are anticipated to differ substantially between sites. Our goal is to reveal both commonalities and differences among research sites, model implementations, and ultimately, conclusions derived from the modeling process.

Experimental transmission electron microscopy studies and phenomenological model of bismuth-based superconducting compounds

International Nuclear Information System (INIS)

Elboussiri, Khalid

1991-01-01

The main part of this thesis is devoted to an experimental study by transmission electron microscopy of the different phases of the superconducting bismuth cuprates Bi_2Sr_2Ca_n_-_1Cu_nO_2_n_+_4. In high resolution electron microscopy, the two types of incommensurate modulation realized in these compounds have been observed. A model of structure has been proposed from which the simulated images obtained are consistent with observations. The medium resolution images correlated with the electron diffraction data have revealed existence of a multi-soliton regime with latent lock in phases of commensurate periods between 4b and 10b. At last, a description of different phases of these compounds as a result of superstructures from a disordered perovskite type structure is proposed (author) [fr

Genome-Wide Association Study Reveals Natural Variations Contributing to Drought Resistance in Crops

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Hongwei Wang

2017-06-01

Full Text Available Crops are often cultivated in regions where they will face environmental adversities; resulting in substantial yield loss which can ultimately lead to food and societal problems. Thus, significant efforts have been made to breed stress tolerant cultivars in an attempt to minimize these problems and to produce more stability with respect to crop yields across broad geographies. Since stress tolerance is a complex and multi-genic trait, advancements with classical breeding approaches have been challenging. On the other hand, molecular breeding, which is based on transgenics, marker-assisted selection and genome editing technologies; holds great promise to enable farmers to better cope with these challenges. However, identification of the key genetic components underlying the trait is critical and will serve as the foundation for future crop genetic improvement. Recently, genome-wide association studies have made significant contributions to facilitate the discovery of natural variation contributing to stress tolerance in crops. From these studies, the identified loci can serve as targets for genomic selection or editing to enable the molecular design of new cultivars. Here, we summarize research progress on this issue and focus on the genetic basis of drought tolerance as revealed by genome-wide association studies and quantitative trait loci mapping. Although many favorable loci have been identified, elucidation of their molecular mechanisms contributing to increased stress tolerance still remains a challenge. Thus, continuous efforts are still required to functionally dissect this complex trait through comprehensive approaches, such as system biological studies. It is expected that proper application of the acquired knowledge will enable the development of stress tolerant cultivars; allowing agricultural production to become more sustainable under dynamic environmental conditions.

Thai students' mental model of chemical bonding

Science.gov (United States)

Sarawan, Supawadee; Yuenyong, Chokchai

2018-01-01

This Research was finding the viewing about concept of chemical bonding is fundamental to subsequent learning of various other topics related to this concept in chemistry. Any conceptions about atomic structures that students have will be shown their further learning. The purpose of this study is to interviews conceptions held by high school chemistry students about metallic bonding and to reveal mental model of atomic structures show according to the educational level. With this aim, the questionnaire prepared making use of the literature and administered for analysis about mental model of chemical bonding. It was determined from the analysis of answers of questionnaire the 10th grade, 11th grade and 12th grade students. Finally, each was shown prompts in the form of focus cards derived from curriculum material that showed ways in which the bonding in specific metallic substances had been depicted. Students' responses revealed that learners across all three levels prefer simple, realistic mental models for metallic bonding and reveal to chemical bonding.

Sparse Modeling Reveals miRNA Signatures for Diagnostics of Inflammatory Bowel Disease.

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Matthias Hübenthal

Full Text Available The diagnosis of inflammatory bowel disease (IBD still remains a clinical challenge and the most accurate diagnostic procedure is a combination of clinical tests including invasive endoscopy. In this study we evaluated whether systematic miRNA expression profiling, in conjunction with machine learning techniques, is suitable as a non-invasive test for the major IBD phenotypes (Crohn's disease (CD and ulcerative colitis (UC. Based on microarray technology, expression levels of 863 miRNAs were determined for whole blood samples from 40 CD and 36 UC patients and compared to data from 38 healthy controls (HC. To further discriminate between disease-specific and general inflammation we included miRNA expression data from other inflammatory diseases (inflammation controls (IC: 24 chronic obstructive pulmonary disease (COPD, 23 multiple sclerosis, 38 pancreatitis and 45 sarcoidosis cases as well as 70 healthy controls from previous studies. Classification problems considering 2, 3 or 4 groups were solved using different types of penalized support vector machines (SVMs. The resulting models were assessed regarding sparsity and performance and a subset was selected for further investigation. Measured by the area under the ROC curve (AUC the corresponding median holdout-validated accuracy was estimated as ranging from 0.75 to 1.00 (including IC and 0.89 to 0.98 (excluding IC, respectively. In combination, the corresponding models provide tools for the distinction of CD and UC as well as CD, UC and HC with expected classification error rates of 3.1 and 3.3%, respectively. These results were obtained by incorporating not more than 16 distinct miRNAs. Validated target genes of these miRNAs have been previously described as being related to IBD. For others we observed significant enrichment for IBD susceptibility loci identified in earlier GWAS. These results suggest that the proposed miRNA signature is of relevance for the etiology of IBD. Its diagnostic

Mechanism of porcine liver xanthine oxidoreductase mediated N-oxide reduction of cyadox as revealed by docking and mutagenesis studies.

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Chigang Chen

Full Text Available Xanthine oxidoreductase (XOR is a cytoplasmic molybdenum-containing oxidoreductase, catalyzing both endogenous purines and exogenous compounds. It is suggested that XOR in porcine hepatocytes catalyzes the N-oxide reduction of quinoxaline 1,4-di-N-oxides (QdNOs. To elucidate the molecular mechanism underlying this metabolism, the cDNA of porcine XOR was cloned and heterologously expressed in Spodoptera frugiperda insect cells. The bovine XOR, showing sequence identity of 91% to porcine XOR, was employed as template for homology modeling. By docking cyadox, a representative compound of QdNOs, into porcine XOR model, eight amino acid residues, Gly47, Asn352, Ser360, Arg427, Asp430, Asp431, Ser1227 and Lys1230, were located at distances of less than 4Å to cyadox. Site-directed mutagenesis was performed to analyze their catalytic functions. Compared with wild type porcine XOR, G47A, S360P, D431A, S1227A, and K1230A displayed altered kinetic parameters in cyadox reduction, similarly to that in xanthine oxidation, indicating these mutations influenced electron-donating process of xanthine before subsequent electron transfer to cyadox to fulfill the N-oxide reduction. Differently, R427E and D430H, both located in the 424-434 loop, exhibited a much lower K(m and a decreased V(max respectively in cyadox reduction. Arg427 may be related to the substrate binding of porcine XOR to cyadox, and Asp430 is suggested to be involved in the transfer of electron to cyadox. This study initially reveals the possible catalytic mechanism of porcine XOR in cyadox metabolism, providing with novel insights into the structure-function relationship of XOR in the reduction of exogenous di-N-oxides.

Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models

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Dominik Schreiber

2017-08-01

Full Text Available Inflammatory bowel diseases (IBD, which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml, TNF-α (10 ng/ml, and IL-1β (5 ng/ml. Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD.

Chain networking revealed by molecular dynamics simulation

Science.gov (United States)

Zheng, Yexin; Tsige, Mesfin; Wang, Shi-Qing

Based on Kremer-Grest model for entangled polymer melts, we demonstrate how the response of a polymer glass depends critically on the chain length. After quenching two melts of very different chain lengths (350 beads per chain and 30 beads per chain) into deeply glassy states, we subject them to uniaxial extension. Our MD simulations show that the glass of long chains undergoes stable necking after yielding whereas the system of short chains is unable to neck and breaks up after strain localization. During ductile extension of the polymer glass made of long chain significant chain tension builds up in the load-bearing strands (LBSs). Further analysis is expected to reveal evidence of activation of the primary structure during post-yield extension. These results lend support to the recent molecular model 1 and are the simulations to demonstrate the role of chain networking. This work is supported, in part, by a NSF Grant (DMR-EAGER-1444859)

Brand Marketing Model on Social Networks

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Jolita Jezukevičiūtė

2014-04-01

Full Text Available The paper analyzes the brand and its marketing solutions onsocial networks. This analysis led to the creation of improvedbrand marketing model on social networks, which will contributeto the rapid and cheap organization brand recognition, increasecompetitive advantage and enhance consumer loyalty. Therefore,the brand and a variety of social networks are becoming a hotresearch area for brand marketing model on social networks.The world‘s most successful brand marketing models exploratoryanalysis of a single case study revealed a brand marketingsocial networking tools that affect consumers the most. Basedon information analysis and methodological studies, develop abrand marketing model on social networks.

In vitro protease cleavage and computer simulations reveal the HIV-1 capsid maturation pathway

Science.gov (United States)

Ning, Jiying; Erdemci-Tandogan, Gonca; Yufenyuy, Ernest L.; Wagner, Jef; Himes, Benjamin A.; Zhao, Gongpu; Aiken, Christopher; Zandi, Roya; Zhang, Peijun

2016-12-01

HIV-1 virions assemble as immature particles containing Gag polyproteins that are processed by the viral protease into individual components, resulting in the formation of mature infectious particles. There are two competing models for the process of forming the mature HIV-1 core: the disassembly and de novo reassembly model and the non-diffusional displacive model. To study the maturation pathway, we simulate HIV-1 maturation in vitro by digesting immature particles and assembled virus-like particles with recombinant HIV-1 protease and monitor the process with biochemical assays and cryoEM structural analysis in parallel. Processing of Gag in vitro is accurate and efficient and results in both soluble capsid protein and conical or tubular capsid assemblies, seemingly converted from immature Gag particles. Computer simulations further reveal probable assembly pathways of HIV-1 capsid formation. Combining the experimental data and computer simulations, our results suggest a sequential combination of both displacive and disassembly/reassembly processes for HIV-1 maturation.

Geometric phase effects in excited state dynamics through a conical intersection in large molecules: N-dimensional linear vibronic coupling model study

Science.gov (United States)

Li, Jiaru; Joubert-Doriol, Loïc; Izmaylov, Artur F.

2017-08-01

We investigate geometric phase (GP) effects in nonadiabatic transitions through a conical intersection (CI) in an N-dimensional linear vibronic coupling (ND-LVC) model. This model allows for the coordinate transformation encompassing all nonadiabatic effects within a two-dimensional (2D) subsystem, while the other N - 2 dimensions form a system of uncoupled harmonic oscillators identical for both electronic states and coupled bi-linearly with the subsystem coordinates. The 2D subsystem governs ultra-fast nonadiabatic dynamics through the CI and provides a convenient model for studying GP effects. Parameters of the original ND-LVC model define the Hamiltonian of the transformed 2D subsystem and thus influence GP effects directly. Our analysis reveals what values of ND-LVC parameters can introduce symmetry breaking in the 2D subsystem that diminishes GP effects.

Assessing Reliability of Cellulose Hydrolysis Models to Support Biofuel Process Design – Identifiability and Uncertainty Analysis

DEFF Research Database (Denmark)

Sin, Gürkan; Meyer, Anne S.; Gernaey, Krist

2010-01-01

The reliability of cellulose hydrolysis models is studied using the NREL model. An identifiability analysis revealed that only 6 out of 26 parameters are identifiable from the available data (typical hydrolysis experiments). Attempting to identify a higher number of parameters (as done in the ori......The reliability of cellulose hydrolysis models is studied using the NREL model. An identifiability analysis revealed that only 6 out of 26 parameters are identifiable from the available data (typical hydrolysis experiments). Attempting to identify a higher number of parameters (as done...

A Study of Simple Diffraction Models

DEFF Research Database (Denmark)

Agerkvist, Finn

In this paper two simple methods for cabinet edge diffraction are examined. Calculations with both models are compared with more sophisticated theoretical models and with measured data. The parameters involved are studied and their importance for normal loudspeaker box designs is examined....

Core-level photoemission revealing the Mott transition

International Nuclear Information System (INIS)

Kim, Hyeong-Do; Noh, Han-Jin; Kim, K.H.; Oh, S.-J.

2005-01-01

Ru 3d core-level X-ray photoemission spectra of various ruthenates are examined. They show in general two-peak structures, which can be assigned as the screened and unscreened peaks. The screened peak is absent in a Mott insulator, but develops into a main peak as the correlation strength becomes weak. This spectral behavior is well explained by the dynamical mean-field theory calculation for the single-band Hubbard model with the on-site core-hole potential using the exact diagonalization method. The new mechanism of the core-level photoemission satellite can be utilized to reveal the Mott transition phenomenon in various strongly correlated electron systems

ISOCT study of collagen crosslinking of collagen in cancer models (Conference Presentation)

Science.gov (United States)

Spicer, Graham; Young, Scott T.; Yi, Ji; Shea, Lonnie D.; Backman, Vadim

2016-03-01

The role of extracellular matrix modification and signaling in cancer progression is an increasingly recognized avenue for the progression of the disease. Previous study of field effect carcinogenesis with Inverse Spectroscopic Optical Coherence Tomography (ISOCT) has revealed pronounced changes in the nanoscale-sensitive mass fractal dimension D measured from field effect tissue when compared to healthy tissue. However, the origin of this difference in tissue ultrastructure in field effect carcinogenesis has remained poorly understood. Here, we present findings supporting the idea that enzymatic crosslinking of the extracellular matrix is an effect that presents at the earliest stages of carcinogenesis. We use a model of collagen gel with crosslinking induced by lysyl oxidase (LOXL4) to recapitulate the difference in D previously reported from healthy and cancerous tissue biopsies. Furthermore, STORM imaging of this collagen gel model verifies the morphologic effects of enzymatic crosslinking at length scales as small as 40 nm, close to the previously reported lower length scale sensitivity threshold of 35 nm for ISOCT. Analysis of the autocorrelation function from STORM images of collagen gels and subsequent fitting to the Whittle-Matérn correlation function shows a similar effect of LOXL4 on D from collagen measured with ISOCT and STORM. We extend this to mass spectrometric study of tissue to directly measure concentrations of collagen crosslink residues. The validation of ISOCT as a viable tool for non-invasive rapid quantification of collagen ultrastructure lends it to study other physiological phenomena involving ECM restructuring such as atherosclerotic plaque screening or cervical ripening during pregnancy.

Principles of proteome allocation are revealed using proteomic data and genome-scale models

DEFF Research Database (Denmark)

Yang, Laurence; Yurkovich, James T.; Lloyd, Colton J.

2016-01-01

to metabolism and fitness. Using proteomics data, we formulated allocation constraints for key proteome sectors in the ME model. The resulting calibrated model effectively computed the "generalist" (wild-type) E. coli proteome and phenotype across diverse growth environments. Across 15 growth conditions......Integrating omics data to refine or make context-specific models is an active field of constraint-based modeling. Proteomics now cover over 95% of the Escherichia coli proteome by mass. Genome-scale models of Metabolism and macromolecular Expression (ME) compute proteome allocation linked...... of these sectors for the general stress response sigma factor sigma(S). Finally, the sector constraints represent a general formalism for integrating omics data from any experimental condition into constraint-based ME models. The constraints can be fine-grained (individual proteins) or coarse-grained (functionally...

Microspectroscopic Study of Liposome-to-cell Interaction Revealed by Förster Resonance Energy Transfer.

Science.gov (United States)

Yefimova, Svetlana L; Kurilchenko, Irina Yu; Tkacheva, Tatyana N; Kavok, Nataliya S; Todor, Igor N; Lukianova, Nataliya Yu; Chekhun, Vasyl F; Malyukin, Yuriy V

2014-03-01

We report the Förster resonance energy transfer (FRET)-labeling of liposomal vesicles as an effective approach to study in dynamics the interaction of liposomes with living cells of different types (rat hepatocytes, rat bone marrow, mouse fibroblast-like cells and human breast cancer cells) and cell organelles (hepatocyte nuclei). The in vitro experiments were performed using fluorescent microspectroscopic technique. Two fluorescent dyes (DiO as the energy donor and DiI as an acceptor) were preloaded in lipid bilayers of phosphatidylcholine liposomes that ensures the necessary distance between the dyes for effective FRET. The change in time of the donor and acceptor relative fluorescence intensities was used to visualize and trace the liposome-to-cell interaction. We show that FRET-labeling of liposome vesicles allows one to reveal the differences in efficiency and dynamics of these interactions, which are associated with composition, fluidity, and metabolic activity of cell plasma membranes.

Homology modeling and docking of AahII-Nanobody complexes reveal the epitope binding site on AahII scorpion toxin.

Science.gov (United States)

Ksouri, Ayoub; Ghedira, Kais; Ben Abderrazek, Rahma; Shankar, B A Gowri; Benkahla, Alia; Bishop, Ozlem Tastan; Bouhaouala-Zahar, Balkiss

2018-02-19

Scorpion envenoming and its treatment is a public health problem in many parts of the world due to highly toxic venom polypeptides diffusing rapidly within the body of severely envenomed victims. Recently, 38 AahII-specific Nanobody sequences (Nbs) were retrieved from which the performance of NbAahII10 nanobody candidate, to neutralize the most poisonous venom compound namely AahII acting on sodium channels, was established. Herein, structural computational approach is conducted to elucidate the Nb-AahII interactions that support the biological characteristics, using Nb multiple sequence alignment (MSA) followed by modeling and molecular docking investigations (RosettaAntibody, ZDOCK software tools). Sequence and structural analysis showed two dissimilar residues of NbAahII10 CDR1 (Tyr27 and Tyr29) and an inserted polar residue Ser30 that appear to play an important role. Indeed, CDR3 region of NbAahII10 is characterized by a specific Met104 and two negatively charged residues Asp115 and Asp117. Complex dockings reveal that NbAahII17 and NbAahII38 share one common binding site on the surface of the AahII toxin divergent from the NbAahII10 one's. At least, a couple of NbAahII10 - AahII residue interactions (Gln38 - Asn44 and Arg62, His64, respectively) are mainly involved in the toxic AahII binding site. Altogether, this study gives valuable insights in the design and development of next generation of antivenom. Copyright © 2018 Elsevier Inc. All rights reserved.

A Novel Combined Model Based on an Artificial Intelligence Algorithm—A Case Study on Wind Speed Forecasting in Penglai, China

Directory of Open Access Journals (Sweden)

Feiyu Zhang

2016-06-01

Full Text Available Wind speed forecasting plays a key role in wind-related engineering studies and is important in the management of wind farms. Current forecasting models based on different optimization algorithms can be adapted to various wind speed time series data. However, these methodologies cannot aggregate different hybrid forecasting methods and take advantage of the component models. To avoid these limitations, we propose a novel combined forecasting model called SSA-PSO-DWCM, i.e., particle swarm optimization (PSO determined weight coefficients model. This model consisted of three main steps: one is the decomposition of the original wind speed signals to discard the noise, the second is the parameter optimization of the forecasting method, and the last is the combination of different models in a nonlinear way. The proposed combined model is examined by forecasting the wind speed (10-min intervals of wind turbine 5 located in the Penglai region of China. The simulations reveal that the proposed combined model demonstrates a more reliable forecast than the component forecasting engines and the traditional combined method, which is based on a linear method.

Association Study Reveals Novel Genes Related to Yield and Quality of Fruit in Cape Gooseberry (Physalis peruviana L.

Directory of Open Access Journals (Sweden)

Francy L. García-Arias

2018-03-01

Full Text Available Association mapping has been proposed as an efficient approach to assist plant breeding programs to investigate the genetic basis of agronomic traits. In this study, we evaluated 18 traits related to yield, (FWP, NF, FWI, and FWII, fruit size-shape (FP, FA, MW, WMH, MH, HMW, DI, FSI, FSII, OVO, OBO, and fruit quality (FIR, CF, and SST, in a diverse collection of 100 accessions of Physalis peruviana including wild, landraces, and anther culture derived lines. We identified seven accessions with suitable traits: fruit weight per plant (FWP > 7,000 g/plant and cracked fruits (CF < 4%, to be used as parents in cape gooseberry breeding program. In addition, the accessions were also characterized using Genotyping By Sequencing (GBS. We discovered 27,982 and 36,142 informative SNP markers based on the alignment against the two cape gooseberry references transcriptomes. Besides, 30,344 SNPs were identified based on alignment to the tomato reference genome. Genetic structure analysis showed that the population could be divided into two or three sub-groups, corresponding to landraces-anther culture and wild accessions for K = 2 and wild, landraces, and anther culture plants for K = 3. Association analysis was carried out using a Mixed Linear Model (MLM and 34 SNP markers were significantly associated. These results reveal the basis of the genetic control of important agronomic traits and may facilitate marker-based breeding in P. peruviana.

Mathematical study of mixing models

International Nuclear Information System (INIS)

Lagoutiere, F.; Despres, B.

1999-01-01

This report presents the construction and the study of a class of models that describe the behavior of compressible and non-reactive Eulerian fluid mixtures. Mixture models can have two different applications. Either they are used to describe physical mixtures, in the case of a true zone of extensive mixing (but then this modelization is incomplete and must be considered only as a point of departure for the elaboration of models of mixtures actually relevant). Either they are used to solve the problem of the numerical mixture. This problem appears during the discretization of an interface which separates fluids having laws of different state: the zone of numerical mixing is the set of meshes which cover the interface. The attention is focused on numerical mixtures, for which the hypothesis of non-miscibility (physics) will bring two equations (the sixth and the eighth of the system). It is important to emphasize that even in the case of the only numerical mixture, the presence in one and same place (same mesh) of several fluids have to be taken into account. This will be formalized by the possibility for mass fractions to take all values between 0 and 1. This is not at odds with the equations that derive from the hypothesis of non-miscibility. One way of looking at things is to consider that there are two scales of observation: the physical scale at which one observes the separation of fluids, and the numerical scale, given by the fineness of the mesh, to which a mixture appears. In this work, mixtures are considered from the mathematical angle (both in the elaboration phase and during their study). In particular, Chapter 5 shows a result of model degeneration for a non-extended mixing zone (case of an interface): this justifies the use of models in the case of numerical mixing. All these models are based on the classical model of non-viscous compressible fluids recalled in Chapter 2. In Chapter 3, the central point of the elaboration of the class of models is

A comparative study of mixed exponential and Weibull distributions in a stochastic model replicating a tropical rainfall process

Science.gov (United States)

Abas, Norzaida; Daud, Zalina M.; Yusof, Fadhilah

2014-11-01

A stochastic rainfall model is presented for the generation of hourly rainfall data in an urban area in Malaysia. In view of the high temporal and spatial variability of rainfall within the tropical rain belt, the Spatial-Temporal Neyman-Scott Rectangular Pulse model was used. The model, which is governed by the Neyman-Scott process, employs a reasonable number of parameters to represent the physical attributes of rainfall. A common approach is to attach each attribute to a mathematical distribution. With respect to rain cell intensity, this study proposes the use of a mixed exponential distribution. The performance of the proposed model was compared to a model that employs the Weibull distribution. Hourly and daily rainfall data from four stations in the Damansara River basin in Malaysia were used as input to the models, and simulations of hourly series were performed for an independent site within the basin. The performance of the models was assessed based on how closely the statistical characteristics of the simulated series resembled the statistics of the observed series. The findings obtained based on graphical representation revealed that the statistical characteristics of the simulated series for both models compared reasonably well with the observed series. However, a further assessment using the AIC, BIC and RMSE showed that the proposed model yields better results. The results of this study indicate that for tropical climates, the proposed model, using a mixed exponential distribution, is the best choice for generation of synthetic data for ungauged sites or for sites with insufficient data within the limit of the fitted region.

Sensitivity of fluvial sediment source apportionment to mixing model assumptions: A Bayesian model comparison.

Science.gov (United States)

Cooper, Richard J; Krueger, Tobias; Hiscock, Kevin M; Rawlins, Barry G

2014-11-01

Mixing models have become increasingly common tools for apportioning fluvial sediment load to various sediment sources across catchments using a wide variety of Bayesian and frequentist modeling approaches. In this study, we demonstrate how different model setups can impact upon resulting source apportionment estimates in a Bayesian framework via a one-factor-at-a-time (OFAT) sensitivity analysis. We formulate 13 versions of a mixing model, each with different error assumptions and model structural choices, and apply them to sediment geochemistry data from the River Blackwater, Norfolk, UK, to apportion suspended particulate matter (SPM) contributions from three sources (arable topsoils, road verges, and subsurface material) under base flow conditions between August 2012 and August 2013. Whilst all 13 models estimate subsurface sources to be the largest contributor of SPM (median ∼76%), comparison of apportionment estimates reveal varying degrees of sensitivity to changing priors, inclusion of covariance terms, incorporation of time-variant distributions, and methods of proportion characterization. We also demonstrate differences in apportionment results between a full and an empirical Bayesian setup, and between a Bayesian and a frequentist optimization approach. This OFAT sensitivity analysis reveals that mixing model structural choices and error assumptions can significantly impact upon sediment source apportionment results, with estimated median contributions in this study varying by up to 21% between model versions. Users of mixing models are therefore strongly advised to carefully consider and justify their choice of model structure prior to conducting sediment source apportionment investigations. An OFAT sensitivity analysis of sediment fingerprinting mixing models is conductedBayesian models display high sensitivity to error assumptions and structural choicesSource apportionment results differ between Bayesian and frequentist approaches.

Care Models of eHealth Services: A Case Study on the Design of a Business Model for an Online Precare Service

Science.gov (United States)

2015-01-01

Background With a growing population of health care clients in the future, the organization of high-quality and cost-effective service providing becomes an increasing challenge. New online eHealth services are proposed as innovative options for the future. Yet, a major barrier to these services appears to be the lack of new business model designs. Although design efforts generally result in visual models, no such artifacts have been found in the literature on business model design. This paper investigates business model design in eHealth service practices from a design perspective. It adopts a research by design approach and seeks to unravel what characteristics of business models determine an online service and what are important value exchanges between health professionals and clients. Objective The objective of the study was to analyze the construction of care models in-depth, framing the essential elements of a business model, and design a new care model that structures these elements for the particular context of an online pre-care service in practice. Methods This research employs a qualitative method of an in-depth case study in which different perspectives on constructing a care model are investigated. Data are collected by using the visual business modeling toolkit, designed to cocreate and visualize the business model. The cocreated models are transcribed and analyzed per actor perspective, transactions, and value attributes. Results We revealed eight new actors in the business model for providing the service. Essential actors are: the intermediary network coordinator connecting companies, the service dedicated information technology specialists, and the service dedicated health specialist. In the transactions for every service providing we found a certain type of contract, such as a license contract and service contracts for precare services and software products. In addition to the efficiency, quality, and convenience, important value attributes

Experimental study and modelling of X-ray photo-triggering of a discharge for exciplex laser

International Nuclear Information System (INIS)

Louvet, Yolande

1986-01-01

As the excitation of the laser medium by using a photo-triggered discharge revealed to be more reliable that an excitation by pre-ionised discharge, this research thesis reports the use of such an excitation and the study of initiation mechanisms for discharges photo-triggered by X rays. The author first recalls the main characteristics of excimer and exciplex systems, and presents the principle of discharge photo-triggering. He presents the experimental set-up, and reports the use of an original method to characterise the X radiation. This method uses theoretical data related to Bremsstrahlung emission, and results are validated by experimental tests. Realistic data regarding X ray properties are introduced into the theoretical model which also takes X-ray-induced ionisation reactions and photo-electron energetic degradation into account. By using this model, the author determines the electron distribution function produced by the X pre-ionisation, and the resulting thermalized electron density [fr

Genome-wide allelotyping of a new in vitro model system reveals early events in breast cancer progression.

Science.gov (United States)

Li, Zheng; Meng, Zhen Hang; Sayeed, Aejaz; Shalaby, Refaat; Ljung, Britt-Marie; Dairkee, Shanaz H

2002-10-15

Toward the goal of identifying early genetic losses, which mediate the release of human breast epithelium from replicative suppression leading to cellular immortalization, we have used a newly developed in vitro model system. This system consists of epithelial cultures derived from noncancerous breast tissue, treated with the chemical carcinogen N-ethyl-N-nitrosourea, and continuously passaged to yield cell populations culminating in the immortal phenotype. Genome-wide allelotyping of early passage N-ethyl-N-nitrosourea-exposed cell populations revealed aberrations at >10% (18 of 169) loci examined. Allelic losses encompassing chromosomes 6q24-6q27, implicating immortalization-associated candidate genes, hZAC and SEN6, occurred in two independently derived cell lines before the Hayflick limit. Additional LOH sites were present in one cell line at 3p11-3p26, 11p15, and 20p12-13. Allelic losses reported in this cell line preceded detectable levels of telomerase activity and the occurrence of p53-related aberrations. Information gained from the search for early immortalization-associated genetic deletions in cultured cells was applied in a novel approach toward the analysis of morphologically normal terminal ductal lobular units microdissected from 20 cases of ductal carcinoma in situ. Notably, clonal allelic losses at chromosome 3p24 and 6q24 were an early occurrence in adjoining terminal ductal lobular units of a proportion of primary tumors, which displayed loss of heterozygosity (3 of 11 and 3 of 6, respectively). The biological insights provided by the new model system reported here strongly suggest that early allelic losses delineated in immortalized cultures and validated in vivo could serve as surrogate endpoints to assist in the identification and intervention of high-risk benign breast tissue, which sustains the potential for continuous proliferation.

Radiation induced muscositis as space flight risk. Model studies on X-ray and heavy ion irradiated typical oral mucosa models; Strahlungsinduzierte Mukositis als Risiko der Raumfahrt. Modelluntersuchungen an Roentgen- und Schwerionen-bestrahlten organotypischen Mundschleimhaut-Modellen

Energy Technology Data Exchange (ETDEWEB)

Tschachojan, Viktoria

2014-07-29

Humans in exomagnetospheric space are exposed to highly energetic heavy ion radiation which can be hardly shielded. Since radiation-induced mucositis constitutes a severe complication of heavy ion radiotherapy, it would also implicate a serious medical safety risk for the crew members during prolonged space flights such as missions to Moon or Mars. For assessment of risk developing radiation-induced mucositis, three-dimensional organotypic cultures of immortalized human keratinocytes and fibroblasts were irradiated with a {sup 12}C particle beam at high energies or X-Rays. Immunofluorescence stainings were done from cryosections and radiation induced release of cytokines and chemokines was quantified by ELISA from culture supernatants. The major focuses of this study were on 4, 8, 24 and 48 hours after irradiation. The conducted analyses of our mucosa model showed many structural similarities with the native oral mucosa and authentic immunological responses to radiation exposure. Quantification of the DNA damage in irradiated mucosa models revealed about twice as many DSB after heavy-ion irradiation compared to X-rays at definite doses and time points, suggesting a higher gene toxicity of heavy ions. Nuclear factor κB activation was observed after treatment with X-rays or {sup 12}C particles. An activation of NF κB p65 in irradiated samples could not be detected. ELISA analyses showed significantly higher interleukin 6 and interleukin 8 levels after irradiation with X-rays and {sup 12}C particles compared to non-irradiated controls. However, only X-rays induced significantly higher levels of interleukin 1β. Analyses of TNF-α and IFN-γ showed no radiation-induced effects. Further analyses revealed a radiation-induced reduction in proliferation and loss of compactness in irradiated oral mucosa model, which would lead to local lesions in vivo. In this study we revealed that several pro-inflammatory markers and structural changes are induced by X-rays and heavy

Study and discretization of kinetic models and fluid models at low Mach number

International Nuclear Information System (INIS)

Dellacherie, Stephane

2011-01-01

This thesis summarizes our work between 1995 and 2010. It concerns the analysis and the discretization of Fokker-Planck or semi-classical Boltzmann kinetic models and of Euler or Navier-Stokes fluid models at low Mach number. The studied Fokker-Planck equation models the collisions between ions and electrons in a hot plasma, and is here applied to the inertial confinement fusion. The studied semi-classical Boltzmann equations are of two types. The first one models the thermonuclear reaction between a deuterium ion and a tritium ion producing an α particle and a neutron particle, and is also in our case used to describe inertial confinement fusion. The second one (known as the Wang-Chang and Uhlenbeck equations) models the transitions between electronic quantified energy levels of uranium and iron atoms in the AVLIS isotopic separation process. The basic properties of these two Boltzmann equations are studied, and, for the Wang-Chang and Uhlenbeck equations, a kinetic-fluid coupling algorithm is proposed. This kinetic-fluid coupling algorithm incited us to study the relaxation concept for gas and immiscible fluids mixtures, and to underline connections with classical kinetic theory. Then, a diphasic low Mach number model without acoustic waves is proposed to model the deformation of the interface between two immiscible fluids induced by high heat transfers at low Mach number. In order to increase the accuracy of the results without increasing computational cost, an AMR algorithm is studied on a simplified interface deformation model. These low Mach number studies also incited us to analyse on cartesian meshes the inaccuracy at low Mach number of Godunov schemes. Finally, the LBM algorithm applied to the heat equation is justified

Systems Perturbation Analysis of a Large-Scale Signal Transduction Model Reveals Potentially Influential Candidates for Cancer Therapeutics

Science.gov (United States)

Puniya, Bhanwar Lal; Allen, Laura; Hochfelder, Colleen; Majumder, Mahbubul; Helikar, Tomáš

2016-01-01

Dysregulation in signal transduction pathways can lead to a variety of complex disorders, including cancer. Computational approaches such as network analysis are important tools to understand system dynamics as well as to identify critical components that could be further explored as therapeutic targets. Here, we performed perturbation analysis of a large-scale signal transduction model in extracellular environments that stimulate cell death, growth, motility, and quiescence. Each of the model’s components was perturbed under both loss-of-function and gain-of-function mutations. Using 1,300 simulations under both types of perturbations across various extracellular conditions, we identified the most and least influential components based on the magnitude of their influence on the rest of the system. Based on the premise that the most influential components might serve as better drug targets, we characterized them for biological functions, housekeeping genes, essential genes, and druggable proteins. The most influential components under all environmental conditions were enriched with several biological processes. The inositol pathway was found as most influential under inactivating perturbations, whereas the kinase and small lung cancer pathways were identified as the most influential under activating perturbations. The most influential components were enriched with essential genes and druggable proteins. Moreover, known cancer drug targets were also classified in influential components based on the affected components in the network. Additionally, the systemic perturbation analysis of the model revealed a network motif of most influential components which affect each other. Furthermore, our analysis predicted novel combinations of cancer drug targets with various effects on other most influential components. We found that the combinatorial perturbation consisting of PI3K inactivation and overactivation of IP3R1 can lead to increased activity levels of apoptosis

A zebrafish larval model reveals early tissue-specific innate immune responses to Mucor circinelloides.

Science.gov (United States)

Voelz, Kerstin; Gratacap, Remi L; Wheeler, Robert T

2015-11-01

-animal model system will contribute greatly to the study of molecular mechanisms involved in the interaction of the host innate immune system with fungal spores during mucormycosis. © 2015. Published by The Company of Biologists Ltd.

Comparative Study of Bancruptcy Prediction Models

Directory of Open Access Journals (Sweden)

Isye Arieshanti

2013-09-01

Full Text Available Early indication of bancruptcy is important for a company. If companies aware of  potency of their bancruptcy, they can take a preventive action to anticipate the bancruptcy. In order to detect the potency of a bancruptcy, a company can utilize a a model of bancruptcy prediction. The prediction model can be built using a machine learning methods. However, the choice of machine learning methods should be performed carefully. Because the suitability of a model depends on the problem specifically. Therefore, in this paper we perform a comparative study of several machine leaning methods for bancruptcy prediction. According to the comparative study, the performance of several models that based on machine learning methods (k-NN, fuzzy k-NN, SVM, Bagging Nearest Neighbour SVM, Multilayer Perceptron(MLP, Hybrid of MLP + Multiple Linear Regression, it can be showed that fuzzy k-NN method achieve the best performance with accuracy 77.5%

Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a Target for Diabetes Mellitus

Directory of Open Access Journals (Sweden)

Pawan Kaushik

2014-01-01

Full Text Available The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP-1β, dipeptidyl peptidase-IV (DPP-IV, aldose reductase (AR, and insulin receptor (IR with help of docking software Molegro virtual docker (MVD. From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

Applications of the Regional Atmospheric Modeling System (RAMS) to provide input to photochemical grid models for the Lake Michigan Ozone Study (LMOS)

Energy Technology Data Exchange (ETDEWEB)

Lyons, W.A.; Tremback, C.J.; Pielke, R.A. [ASTeR, Inc., Ft. Collins, CO (United States); Eastman, J.L. [Colorado State Univ., Ft. Collins, CO (United States)

1994-12-31

In spite of stringent emission controls, numerous exceedances of the US ozone air quality standard have continued in the Lake Michigan region, especially during the very hot summers of 1987 and 1988. Analyses revealed that exceedances of the 120 PPB hourly standard were 400% more likely at monitors located within 20 km of the lakeshore. While the role of Lake Michigan in exacerbating regional air quality problems has been investigated for almost 20 years, the relative impacts of various phenomena upon regional photochemical air quality have yet to be quantified. In order to design a defensible regional emission control policy, LMOS sponsored the development of a comprehensive regional photochemical modeling system. This is comprised of an emission model, an advanced regional photochemical model, and a prognostic meteorological model.

Multi-process Late Quaternary landscape evolution modelling reveals lags in climate response over small spatial scales

NARCIS (Netherlands)

Temme, A.J.A.M.; Veldkamp, A.

2009-01-01

Landscapes evolve in complex, non-linear ways over Quaternary timespans. Integrated geomorphological field studies usually yield plausible hypotheses about timing and impact of process activity. Landscape Evolution Models (LEMs) have the potential to test and falsify these landscape evolution

Opening the Big Black Box: European study reveals visitors' impressions of science laboratories

CERN Multimedia

2004-01-01

"On 29 - 30 March the findings of 'Inside the Big Black Box'- a Europe-wide science and society project - will be revealed during a two-day seminar hosted by CERN*. The principle aim of Inside the Big Black Box (IN3B) is to determine whether a working scientific laboratory can capture the curiosity of the general public through visits" (1 page)

Dosage and dose schedule screening of drug combinations in agent-based models reveals hidden synergies

Directory of Open Access Journals (Sweden)

Lisa Corina Barros de Andrade e Sousa1

2016-01-01

Full Text Available The fungus Candida albicans is the most common causative agent of human fungal infections and better drugs or drug combination strategies are urgently needed. Here, we present an agent-based model of the interplay of C. albicans with the host immune system and with the microflora of the host. We took into account the morphological change of C. albicans from the yeast to hyphae form and its dynamics during infection. The model allowed us to follow the dynamics of fungal growth and morphology, of the immune cells and of microflora in different perturbing situations. We specifically focused on the consequences of microflora reduction following antibiotic treatment. Using the agent-based model, different drug types have been tested for their effectiveness, namely drugs that inhibit cell division and drugs that constrain the yeast-to-hyphae transition. Applied individually, the division drug turned out to successfully decrease hyphae while the transition drug leads to a burst in hyphae after the end of the treatment. To evaluate the effect of different drug combinations, doses, and schedules, we introduced a measure for the return to a healthy state, the infection score. Using this measure, we found that the addition of a transition drug to a division drug treatment can improve the treatment reliability while minimizing treatment duration and drug dosage. In this work we present a theoretical study. Although our model has not been calibrated to quantitative experimental data, the technique of computationally identifying synergistic treatment combinations in an agent based model exemplifies the importance of computational techniques in translational research.

Geomagnetic field models for satellite angular motion studies

Science.gov (United States)

Ovchinnikov, M. Yu.; Penkov, V. I.; Roldugin, D. S.; Pichuzhkina, A. V.

2018-03-01

Four geomagnetic field models are discussed: IGRF, inclined, direct and simplified dipoles. Geomagnetic induction vector expressions are provided in different reference frames. Induction vector behavior is compared for different models. Models applicability for the analysis of satellite motion is studied from theoretical and engineering perspectives. Relevant satellite dynamics analysis cases using analytical and numerical techniques are provided. These cases demonstrate the benefit of a certain model for a specific dynamics study. Recommendations for models usage are summarized in the end.

Dynamic Modelling Reveals 'Hotspots' on the Pathway to Enzyme-Substrate Complex Formation.

Directory of Open Access Journals (Sweden)

Shane E Gordon

2016-03-01

Full Text Available Dihydrodipicolinate synthase (DHDPS catalyzes the first committed step in the diaminopimelate pathway of bacteria, yielding amino acids required for cell wall and protein biosyntheses. The essentiality of the enzyme to bacteria, coupled with its absence in humans, validates DHDPS as an antibacterial drug target. Conventional drug design efforts have thus far been unsuccessful in identifying potent DHDPS inhibitors. Here, we make use of contemporary molecular dynamics simulation and Markov state models to explore the interactions between DHDPS from the human pathogen Staphylococcus aureus and its cognate substrate, pyruvate. Our simulations recover the crystallographic DHDPS-pyruvate complex without a priori knowledge of the final bound structure. The highly conserved residue Arg140 was found to have a pivotal role in coordinating the entry of pyruvate into the active site from bulk solvent, consistent with previous kinetic reports, indicating an indirect role for the residue in DHDPS catalysis. A metastable binding intermediate characterized by multiple points of intermolecular interaction between pyruvate and key DHDPS residue Arg140 was found to be a highly conserved feature of the binding trajectory when comparing alternative binding pathways. By means of umbrella sampling we show that these binding intermediates are thermodynamically metastable, consistent with both the available experimental data and the substrate binding model presented in this study. Our results provide insight into an important enzyme-substrate interaction in atomistic detail that offers the potential to be exploited for the discovery of more effective DHDPS inhibitors and, in a broader sense, dynamic protein-drug interactions.

Aquatic insect ecophysiological traits reveal phylogenetically based differences in dissolved cadmium susceptibility.

Science.gov (United States)

Buchwalter, David B; Cain, Daniel J; Martin, Caitrin A; Xie, Lingtian; Luoma, Samuel N; Garland, Theodore

2008-06-17

We used a phylogenetically based comparative approach to evaluate the potential for physiological studies to reveal patterns of diversity in traits related to susceptibility to an environmental stressor, the trace metal cadmium (Cd). Physiological traits related to Cd bioaccumulation, compartmentalization, and ultimately susceptibility were measured in 21 aquatic insect species representing the orders Ephemeroptera, Plecoptera, and Trichoptera. We mapped these experimentally derived physiological traits onto a phylogeny and quantified the tendency for related species to be similar (phylogenetic signal). All traits related to Cd bioaccumulation and susceptibility exhibited statistically significant phylogenetic signal, although the signal strength varied among traits. Conventional and phylogenetically based regression models were compared, revealing great variability within orders but consistent, strong differences among insect families. Uptake and elimination rate constants were positively correlated among species, but only when effects of body size and phylogeny were incorporated in the analysis. Together, uptake and elimination rates predicted dramatic Cd bioaccumulation differences among species that agreed with field-based measurements. We discovered a potential tradeoff between the ability to eliminate Cd and the ability to detoxify it across species, particularly mayflies. The best-fit regression models were driven by phylogenetic parameters (especially differences among families) rather than functional traits, suggesting that it may eventually be possible to predict a taxon's physiological performance based on its phylogenetic position, provided adequate physiological information is available for close relatives. There appears to be great potential for evolutionary physiological approaches to augment our understanding of insect responses to environmental stressors in nature.

Comparing Reasons for Quitting Substance Abuse with the Constructs of Behavioral Models: A Qualitative Study

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Hamid Tavakoli Ghouchani

2015-03-01

Full Text Available Background and Objectives: The world population has reached over seven billion people. Of these, 230 million individuals abuse substances. Therefore, substance abuse prevention and treatment programs have received increasing attention during the past two decades. Understanding people’s motivations for quitting drug abuse is essential to the success of treatment. This study hence sought to identify major motivations for quitting and to compare them with the constructs of health education models. Materials and Methods: In the present study, qualitative content analysis was used to determine the main motivations for quitting substance abuse. Overall, 22 patients, physicians, and psychotherapists were selected from several addiction treatment clinics in Bojnord (Iran during 2014. Purposeful sampling method was applied and continued until data saturation was achieved. Data were collected through semi-structured, face-to-face interviews and field notes. All interviews were recorded and transcribed. Results: Content analysis revealed 33 sub-categories and nine categories including economic problems, drug-related concerns, individual problems, family and social problems, family expectations, attention to social status, beliefs about drug addiction, and valuing the quitting behavior. Accordingly, four themes, i.e. perceived threat, perceived barriers, attitude toward the behavior, and subjective norms, were extracted. Conclusion: Reasons for quitting substance abuse match the constructs of different behavioral models (e.g. the health belief model and the theory of planned behavior.

Ellipsometry study on Pd thin film grown by atomic layer deposition with Maxwell–Garnett effective medium approximation model

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yihang; Zhou, Xueqi; Cao, Kun [State Key Laboratory of Digital of Manufacturing Equipment and Technology, School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Chen, Xiuguo; Deng, Zhang [State Key Laboratory of Digital of Manufacturing Equipment and Technology, School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Liu, Shiyuan, E-mail: shyliu@hust.edu.cn [State Key Laboratory of Digital of Manufacturing Equipment and Technology, School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Shan, Bin [State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Chen, Rong, E-mail: rongchen@mail.hust.edu.cn [State Key Laboratory of Digital of Manufacturing Equipment and Technology, School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan 430074 (China)

2015-10-30

Maxwell–Garnett effective medium approximation (MG-EMA) model is chosen to study Pd ultrathin film grown on Si substrate, as well as its growth on self-assembled monolayers (SAMs) modified substrate respectively. The general oscillator (GO) model with one Drude and two Lorentz oscillators is firstly applied to fix the optical constants of Pd. Compared with Pd bulk model, MG-EMA model with GO is more reliable to predict the film thickness verified by X-ray reflection test. The stable growth rate on Si substrate reveals our methods are feasible and the quartz crystal microbalance measurement confirms the stability of the ALD chamber. For Pd coverage, MG-EMA fitting result is similar to the statistical computation from scanning electron microscope when Pd ALD cycles are over 400, while large bias exists for cycles under 400, might be due to that air is not the proper filling medium between nanoparticles. Then we change the filling medium into SAMs as a comparison, better fitting performance is obtained. It is demonstrated that the filling medium between nanoparticles is important for the application of MG-EMA model. - Highlights: • Ultrathin Pd thin films were grown by atomic layer deposition. • The measurement of thin film was important to understand initial growth behavior. • Maxwell–Garnett effective medium approximation model was applied. • Pd nanoparticle size and coverage were studied. • The filling medium between nanoparticles was important for model application.

The Effect of Small Sample Size on Measurement Equivalence of Psychometric Questionnaires in MIMIC Model: A Simulation Study

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Jamshid Jamali

2017-01-01

Full Text Available Evaluating measurement equivalence (also known as differential item functioning (DIF is an important part of the process of validating psychometric questionnaires. This study aimed at evaluating the multiple indicators multiple causes (MIMIC model for DIF detection when latent construct distribution is nonnormal and the focal group sample size is small. In this simulation-based study, Type I error rates and power of MIMIC model for detecting uniform-DIF were investigated under different combinations of reference to focal group sample size ratio, magnitude of the uniform-DIF effect, scale length, the number of response categories, and latent trait distribution. Moderate and high skewness in the latent trait distribution led to a decrease of 0.33% and 0.47% power of MIMIC model for detecting uniform-DIF, respectively. The findings indicated that, by increasing the scale length, the number of response categories and magnitude DIF improved the power of MIMIC model, by 3.47%, 4.83%, and 20.35%, respectively; it also decreased Type I error of MIMIC approach by 2.81%, 5.66%, and 0.04%, respectively. This study revealed that power of MIMIC model was at an acceptable level when latent trait distributions were skewed. However, empirical Type I error rate was slightly greater than nominal significance level. Consequently, the MIMIC was recommended for detection of uniform-DIF when latent construct distribution is nonnormal and the focal group sample size is small.

The Effect of Small Sample Size on Measurement Equivalence of Psychometric Questionnaires in MIMIC Model: A Simulation Study.

Science.gov (United States)

Jamali, Jamshid; Ayatollahi, Seyyed Mohammad Taghi; Jafari, Peyman

2017-01-01

Evaluating measurement equivalence (also known as differential item functioning (DIF)) is an important part of the process of validating psychometric questionnaires. This study aimed at evaluating the multiple indicators multiple causes (MIMIC) model for DIF detection when latent construct distribution is nonnormal and the focal group sample size is small. In this simulation-based study, Type I error rates and power of MIMIC model for detecting uniform-DIF were investigated under different combinations of reference to focal group sample size ratio, magnitude of the uniform-DIF effect, scale length, the number of response categories, and latent trait distribution. Moderate and high skewness in the latent trait distribution led to a decrease of 0.33% and 0.47% power of MIMIC model for detecting uniform-DIF, respectively. The findings indicated that, by increasing the scale length, the number of response categories and magnitude DIF improved the power of MIMIC model, by 3.47%, 4.83%, and 20.35%, respectively; it also decreased Type I error of MIMIC approach by 2.81%, 5.66%, and 0.04%, respectively. This study revealed that power of MIMIC model was at an acceptable level when latent trait distributions were skewed. However, empirical Type I error rate was slightly greater than nominal significance level. Consequently, the MIMIC was recommended for detection of uniform-DIF when latent construct distribution is nonnormal and the focal group sample size is small.

Why hasn't studying perception in autism spectrum disorders helped us create a cognitive model?

Science.gov (United States)

Adlam, Jonathan

2015-09-01

. Here, poor study design has created results leading to an "eagle-eyed visual acuity" hypothesis of autism. Errors in the initial study are revealed, suggesting that the model should be abandoned. Finally, a general issue is the assumption of homogeneity of perceptual ability and genetics in autism, where the reality is that subgroups exist within the population of people with autism, and significant variation exists between them. The evidence for this is summarised and the issues that it creates explored.

Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit

OpenAIRE

Ashoori, Maryam; Burns, Catherine M.; d'Entremont, Barbara; Momtahan, Kathryn

2014-01-01

Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamworkand leverage the exis...

Experimental and Modeling Study of Liquid-Assisted—Laser Beam Micromachining of Smart Ceramic Materials

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Mayur Parmar

2018-05-01

Full Text Available Smart ceramic materials are next generation materials with the inherent intelligence to adapt to change in the external environment. These materials are destined to play an essential role in several critical engineering applications. Machining these materials using traditional machining processes is a challenge. The laser beam micromachining (LBMM process has the potential to machine such smart materials. However, laser machining when performed in air induces high thermal stress on the surface, often leading to crack formation, recast and re-deposition of ablated material, and large heat-affected zones (HAZ. Performing laser beam machining in the presence of a liquid medium could potentially resolve these issues. This research investigates the possibility of using a Liquid Assisted—Laser Beam Micromachining (LA-LBMM process for micromachining smart ceramic materials. Experimental studies are performed to compare the machining quality of laser beam machining process in air and in a liquid medium. The study reveals that the presence of liquid medium helps in controlling the heat-affected zone and the taper angle of the cavity drilled, thereby enhancing the machining quality. Analytical modeling is developed for the prediction of HAZ and cavity diameter both in air and underwater conditions, and the model is capable of predicting the experimental results to within 10% error.

Experimental and modelling studies of infiltration

International Nuclear Information System (INIS)

Giudici, M.

2004-01-01

This presentation describes a study of infiltration in the unsaturated soil with the objective of estimating the recharge to a phreatic aquifer. The study area is at the border of the city of Milan (Northern Italy), which draws water for both domestic and industrial purposes from ground water resources located beneath the urban area. The rate of water pumping from the aquifer system has been varying during the XX century, depending upon the number of inhabitants and the development of industrial activities. This caused variations with time of the depth of the water table below the ground surface and in turn some emergencies: the two most prominent episodes correspond to the middle '70s, when the water table in the city centre was about 30 m below the undisturbed natural conditions, and to the last decade, when the water table has raised at a rate of approximately 1 m/year and caused infiltrations in deep constructions (garages and building foundations, the underground railways, etc.). We have developed four ground water flow models at different scales, which share some characteristics: they are based on quasi-3D approximation (horizontal flow in the aquifers and vertical flow in the aquitards), conservative finite-differences schemes for regular grid with square cells in the horizontal plane and are implemented with proprietary computer codes. Among the problems that were studied for the development of these models, I recall some numerical problems, related to the behaviour of the phreatic aquifer under conditions of strong exploitation. Model calibration and validation for ModMil has been performed with a two-stage process, i.e., using some of the available data for model calibration and the remaining data for model validation. The application of geophysical exploration techniques, in particular seismic and geo-electrical prospecting, has been very useful to complete the data and information on the hydro-geological structure obtained from stratigraphic logs

A SYSTEMATIC STUDY OF SOFTWARE QUALITY MODELS

OpenAIRE

Dr.Vilas. M. Thakare; Ashwin B. Tomar

2011-01-01

This paper aims to provide a basis for software quality model research, through a systematic study ofpapers. It identifies nearly seventy software quality research papers from journals and classifies paper asper research topic, estimation approach, study context and data set. The paper results combined withother knowledge provides support for recommendations in future software quality model research, toincrease the area of search for relevant studies, carefully select the papers within a set ...

On discourse space modeling

OpenAIRE

Казыдуб, Надежда

2013-01-01

Discourse space is a complex structure that incorporates different levels and dimensions. The paper focuses on developing a multidisciplinary approach that is congruent to the complex character of the modern discourse. Two models of discourse space are proposed here. The Integrated Model reveals the interaction of different categorical mechanisms in the construction of the discourse space. The Evolutionary Model describes the historical roots of the modern discourse. It also reveals historica...

Image based 3D city modeling : Comparative study

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S. P. Singh

2014-06-01

Full Text Available 3D city model is a digital representation of the Earth’s surface and it’s related objects such as building, tree, vegetation, and some manmade feature belonging to urban area. The demand of 3D city modeling is increasing rapidly for various engineering and non-engineering applications. Generally four main image based approaches were used for virtual 3D city models generation. In first approach, researchers were used Sketch based modeling, second method is Procedural grammar based modeling, third approach is Close range photogrammetry based modeling and fourth approach is mainly based on Computer Vision techniques. SketchUp, CityEngine, Photomodeler and Agisoft Photoscan are the main softwares to represent these approaches respectively. These softwares have different approaches & methods suitable for image based 3D city modeling. Literature study shows that till date, there is no complete such type of comparative study available to create complete 3D city model by using images. This paper gives a comparative assessment of these four image based 3D modeling approaches. This comparative study is mainly based on data acquisition methods, data processing techniques and output 3D model products. For this research work, study area is the campus of civil engineering department, Indian Institute of Technology, Roorkee (India. This 3D campus acts as a prototype for city. This study also explains various governing parameters, factors and work experiences. This research work also gives a brief introduction, strengths and weakness of these four image based techniques. Some personal comment is also given as what can do or what can’t do from these softwares. At the last, this study shows; it concluded that, each and every software has some advantages and limitations. Choice of software depends on user requirements of 3D project. For normal visualization project, SketchUp software is a good option. For 3D documentation record, Photomodeler gives good

A comparative study of 3D FZI and electrofacies modeling using seismic attribute analysis and neural network technique: A case study of Cheshmeh-Khosh Oil field in Iran

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Mahdi Rastegarnia

2016-09-01

Full Text Available Electrofacies are used to determine reservoir rock properties, especially permeability, to simulate fluid flow in porous media. These are determined based on classification of similar logs among different groups of logging data. Data classification is accomplished by different statistical analysis such as principal component analysis, cluster analysis and differential analysis. The aim of this study is to predict 3D FZI (flow zone index and Electrofacies (EFACT volumes from a large volume of 3D seismic data. This study is divided into two parts. In the first part of the study, in order to make the EFACT model, nuclear magnetic resonance (NMR log parameters were employed for developing an Electrofacies diagram based on pore size distribution and porosity variations. Then, a graph-based clustering method, known as multi resolution graph-based clustering (MRGC, was employed to classify and obtain the optimum number of Electrofacies. Seismic attribute analysis was then applied to model each relaxation group in order to build the initial 3D model which was used to reach the final model by applying Probabilistic Neural Network (PNN. In the second part of the study, the FZI 3D model was created by multi attributes technique. Then, this model was improved by three different artificial intelligence systems including PNN, multilayer feed-forward network (MLFN and radial basis function network (RBFN. Finally, models of FZI and EFACT were compared. Results obtained from this study revealed that the two models are in good agreement and PNN method is successful in modeling FZI and EFACT from 3D seismic data for which no Stoneley data or NMR log data are available. Moreover, they may be used to detect hydrocarbon-bearing zones and locate the exact place for producing wells for the future development plans. In addition, the result provides a geologically realistic spatial FZI and reservoir facies distribution which helps to understand the subsurface reservoirs

Integrated travel network model for studying epidemics: Interplay between journeys and epidemic

Science.gov (United States)

Ruan, Zhongyuan; Wang, Chaoqing; Ming Hui, Pak; Liu, Zonghua

2015-06-01

The ease of travelling between cities has contributed much to globalization. Yet, it poses a threat on epidemic outbreaks. It is of great importance for network science and health control to understand the impact of frequent journeys on epidemics. We stress that a new framework of modelling that takes a traveller’s viewpoint is needed. Such integrated travel network (ITN) model should incorporate the diversity among links as dictated by the distances between cities and different speeds of different modes of transportation, diversity among nodes as dictated by the population and the ease of travelling due to infrastructures and economic development of a city, and round-trip journeys to targeted destinations via the paths of shortest travel times typical of human journeys. An example is constructed for 116 cities in China with populations over one million that are connected by high-speed train services and highways. Epidemic spread on the constructed network is studied. It is revealed both numerically and theoretically that the traveling speed and frequency are important factors of epidemic spreading. Depending on the infection rate, increasing the traveling speed would result in either an enhanced or suppressed epidemic, while increasing the traveling frequency enhances the epidemic spreading.

An Elaboration of a Strategic Alignment Model of University Information Systems based on SAM Model

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S. Ahriz

2018-02-01

Full Text Available Information system is a guarantee of the universities' ability to anticipate the essential functions to their development and durability. The alignment of information system, one of the pillars of IT governance, has become a necessity. In this paper, we consider the problem of strategic alignment model implementation in Moroccan universities. Literature revealed that few studies have examined strategic alignment in the public sector, particularly in higher education institutions. Hence we opted for an exploratory approach that aims to better understanding the strategic alignment and to evaluate the degree of its use within Moroccan universities. The data gained primarily through interviews with top managers and IT managers reveal that the alignment is not formalized and that it would be appropriate to implement an alignment model. It is found that the implementation of our proposed model can help managers to maximize returns of IT investment and to increase their efficiency.

NeuCode Proteomics Reveals Bap1 Regulation of Metabolism

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Joshua M. Baughman

2016-07-01

Full Text Available We introduce neutron-encoded (NeuCode amino acid labeling of mice as a strategy for multiplexed proteomic analysis in vivo. Using NeuCode, we characterize an inducible knockout mouse model of Bap1, a tumor suppressor and deubiquitinase whose in vivo roles outside of cancer are not well established. NeuCode proteomics revealed altered metabolic pathways following Bap1 deletion, including profound elevation of cholesterol biosynthetic machinery coincident with reduced expression of gluconeogenic and lipid homeostasis proteins in liver. Bap1 loss increased pancreatitis biomarkers and reduced expression of mitochondrial proteins. These alterations accompany a metabolic remodeling with hypoglycemia, hypercholesterolemia, hepatic lipid loss, and acinar cell degeneration. Liver-specific Bap1 null mice present with fully penetrant perinatal lethality, severe hypoglycemia, and hepatic lipid deficiency. This work reveals Bap1 as a metabolic regulator in liver and pancreas, and it establishes NeuCode as a reliable proteomic method for deciphering in vivo biology.

Cryogenic EBSD reveals structure of directionally solidified ice–polymer composite

Energy Technology Data Exchange (ETDEWEB)

Donius, Amalie E., E-mail: amalie.donius@gmail.com [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Obbard, Rachel W., E-mail: Rachel.W.Obbard@dartmouth.edu [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Burger, Joan N., E-mail: ridge.of.the.ancients@gmail.com [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Hunger, Philipp M., E-mail: philipp.m.hunger@gmail.com [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Baker, Ian, E-mail: Ian.Baker@dartmouth.edu [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States); Doherty, Roger D., E-mail: dohertrd@drexel.edu [Department of Materials Science and Engineering, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Wegst, Ulrike G.K., E-mail: ulrike.wegst@dartmouth.edu [Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755 (United States)

2014-07-01

Despite considerable research efforts on directionally solidified or freeze-cast materials in recent years, little fundamental knowledge has been gained that links model with experiment. In this contribution, the cryogenic characterization of directionally solidified polymer solutions illustrates, how powerful cryo-scanning electron microscopy combined with electron backscatter diffraction is for the structural characterization of ice–polymer composite materials. Under controlled sublimation, the freeze-cast polymer scaffold structure is revealed and imaged with secondary electrons. Electron backscatter diffraction fabric analysis shows that the ice crystals, which template the polymer scaffold and create the lamellar structure, have a-axes oriented parallel to the direction of solidification and the c-axes perpendicular to it. These results indicate the great potential of both cryo-scanning electron microscopy and cryo-electron backscatter diffraction in gaining fundamental knowledge of structure–property–processing correlations. - Highlights: • Cryo-SEM of freeze-cast polymer solution reveals an ice-templated structure. • Cryo-EBSD reveals the ice crystal a-axis to parallel the solidification direction. • The honeycomb-like polymer phase favors columnar ridges only on one side. • Combining cryo-SEM with EBSD links solidification theory with experiment.

Cryogenic EBSD reveals structure of directionally solidified ice–polymer composite

International Nuclear Information System (INIS)

Donius, Amalie E.; Obbard, Rachel W.; Burger, Joan N.; Hunger, Philipp M.; Baker, Ian; Doherty, Roger D.; Wegst, Ulrike G.K.

2014-01-01

Despite considerable research efforts on directionally solidified or freeze-cast materials in recent years, little fundamental knowledge has been gained that links model with experiment. In this contribution, the cryogenic characterization of directionally solidified polymer solutions illustrates, how powerful cryo-scanning electron microscopy combined with electron backscatter diffraction is for the structural characterization of ice–polymer composite materials. Under controlled sublimation, the freeze-cast polymer scaffold structure is revealed and imaged with secondary electrons. Electron backscatter diffraction fabric analysis shows that the ice crystals, which template the polymer scaffold and create the lamellar structure, have a-axes oriented parallel to the direction of solidification and the c-axes perpendicular to it. These results indicate the great potential of both cryo-scanning electron microscopy and cryo-electron backscatter diffraction in gaining fundamental knowledge of structure–property–processing correlations. - Highlights: • Cryo-SEM of freeze-cast polymer solution reveals an ice-templated structure. • Cryo-EBSD reveals the ice crystal a-axis to parallel the solidification direction. • The honeycomb-like polymer phase favors columnar ridges only on one side. • Combining cryo-SEM with EBSD links solidification theory with experiment

Study of solar radiation prediction and modeling of relationships between solar radiation and meteorological variables

International Nuclear Information System (INIS)

Sun, Huaiwei; Zhao, Na; Zeng, Xiaofan; Yan, Dong

2015-01-01

Highlights: • We investigate relationships between solar radiation and meteorological variables. • A strong relationship exists between solar radiation and sunshine duration. • Daily global radiation can be estimated accurately with ARMAX–GARCH models. • MGARCH model was applied to investigate time-varying relationships. - Abstract: The traditional approaches that employ the correlations between solar radiation and other measured meteorological variables are commonly utilized in studies. It is important to investigate the time-varying relationships between meteorological variables and solar radiation to determine which variables have the strongest correlations with solar radiation. In this study, the nonlinear autoregressive moving average with exogenous variable–generalized autoregressive conditional heteroscedasticity (ARMAX–GARCH) and multivariate GARCH (MGARCH) time-series approaches were applied to investigate the associations between solar radiation and several meteorological variables. For these investigations, the long-term daily global solar radiation series measured at three stations from January 1, 2004 until December 31, 2007 were used in this study. Stronger relationships were observed to exist between global solar radiation and sunshine duration than between solar radiation and temperature difference. The results show that 82–88% of the temporal variations of the global solar radiation were captured by the sunshine-duration-based ARMAX–GARCH models and 55–68% of daily variations were captured by the temperature-difference-based ARMAX–GARCH models. The advantages of the ARMAX–GARCH models were also confirmed by comparison of Auto-Regressive and Moving Average (ARMA) and neutral network (ANN) models in the estimation of daily global solar radiation. The strong heteroscedastic persistency of the global solar radiation series was revealed by the AutoRegressive Conditional Heteroscedasticity (ARCH) and Generalized Auto

Mining Product Data Models: A Case Study

Directory of Open Access Journals (Sweden)

Cristina-Claudia DOLEAN

2014-01-01

Full Text Available This paper presents two case studies used to prove the validity of some data-flow mining algorithms. We proposed the data-flow mining algorithms because most part of mining algorithms focuses on the control-flow perspective. First case study uses event logs generated by an ERP system (Navision after we set several trackers on the data elements needed in the process analyzed; while the second case study uses the event logs generated by YAWL system. We offered a general solution of data-flow model extraction from different data sources. In order to apply the data-flow mining algorithms the event logs must comply a certain format (using InputOutput extension. But to respect this format, a set of conversion tools is needed. We depicted the conversion tools used and how we got the data-flow models. Moreover, the data-flow model is compared to the control-flow model.

Computer modelling reveals new conformers of the ATP binding loop of Na+/K+-ATPase involved in the transphosphorylation process of the sodium pump.

Science.gov (United States)

Tejral, Gracian; Sopko, Bruno; Necas, Alois; Schoner, Wilhelm; Amler, Evzen

2017-01-01

Hydrolysis of ATP by Na + /K + -ATPase, a P-Type ATPase, catalyzing active Na + and K + transport through cellular membranes leads transiently to a phosphorylation of its catalytical α -subunit. Surprisingly, three-dimensional molecular structure analysis of P-type ATPases reveals that binding of ATP to the N-domain connected by a hinge to the P-domain is much too far away from the Asp 369 to allow the transfer of ATP's terminal phosphate to its aspartyl-phosphorylation site. In order to get information for how the transfer of the γ -phosphate group of ATP to the Asp 369 is achieved, analogous molecular modeling of the M 4 -M 5 loop of ATPase was performed using the crystal data of Na + /K + -ATPase of different species. Analogous molecular modeling of the cytoplasmic loop between Thr 338 and Ile 760 of the α 2 -subunit of Na + /K + -ATPase and the analysis of distances between the ATP binding site and phosphorylation site revealed the existence of two ATP binding sites in the open conformation; the first one close to Phe 475 in the N-domain, the other one close to Asp 369 in the P-domain. However, binding of Mg 2+ •ATP to any of these sites in the "open conformation" may not lead to phosphorylation of Asp 369 . Additional conformations of the cytoplasmic loop were found wobbling between "open conformation"  "semi-open conformation  "closed conformation" in the absence of 2Mg 2+ •ATP. The cytoplasmic loop's conformational change to the "semi-open conformation"-characterized by a hydrogen bond between Arg 543 and Asp 611 -triggers by binding of 2Mg 2+ •ATP to a single ATP site and conversion to the "closed conformation" the phosphorylation of Asp 369 in the P-domain, and hence the start of Na + /K + -activated ATP hydrolysis.

Molecular modeling and docking studies of human 5-hydroxytryptamine 2A (5-HT2A) receptor for the identification of hotspots for ligand binding.

Science.gov (United States)

Kanagarajadurai, Karuppiah; Malini, Manoharan; Bhattacharya, Aditi; Panicker, Mitradas M; Sowdhamini, Ramanathan

2009-12-01

The serotonergic system has been implicated in emotional and cognitive function. In particular, 5-HT(2A) (5-hydroxytrytamine receptor 2A) is attributed to a number of disorders like schizophrenia, depression, eating disorders and anxiety. 5-HT(2A), being a GPCR (G-protein coupled receptor), is important in the pharmaceutical industry as a proven target for these disorders. Despite their extensive clinical importance, the structural studies of this protein is lacking due to difficulties in determining its crystal structure. We have performed sequence analysis and molecular modeling of 5-HT(2A) that has revealed a set of conserved residues and motifs considered to play an important role in maintaining structural integrity and function of the receptor. The analysis also revealed a set of residues specific to the receptor which distinguishes them from other members of the subclass and their orthologs. Further, starting from the model structure of human 5-HT(2A) receptor, docking studies were attempted to envisage how it might interact with eight of its ligands (such as serotonin, dopamine, DOI, LSD, haloperidol, ketanserin, risperidone and clozapine). The binding studies of dopamine to 5-HT(2A) receptor can bring up better understanding in the etiology of a number of neurological disorders involving both these two receptors. Our sequence analysis and study of interactions of this receptor with other ligands reveal additional residue hotspots such as Asn 363 and Tyr 370. The function of these residues can be further analyzed by rational design of site-directed mutagenesis. Two distinct binding sites are identified which could play important roles in ligand binding and signaling.

Use of field experimental studies to evaluate emergency response models

International Nuclear Information System (INIS)

Gudiksen, P.H.; Lange, R.; Rodriguez, D.J.; Nasstrom, J.S.

1985-01-01

The three-dimensional diagnostic wind field model (MATHEW) and the particle-in-cell atmospheric transport and diffusion model (ADPIC) are used by the Atmospheric Release Advisory Capability to estimate the environmental consequences of accidental releases of radioactivity into the atmosphere. These models have undergone extensive evaluations against field experiments conducted in a variety of environmental settings ranging from relatively flat to very complex terrain areas. Simulations of tracer experiments conducted in a complex mountain valley setting revealed that 35 to 50% of the comparisons between calculated and measured tracer concentrations were within a factor of 5. This may be compared with a factor of 2 for 50% of the comparisons for relatively flat terrain. This degradation of results in complex terrain is due to a variety of factors such as the limited representativeness of measurements in complex terrain, the limited spatial resolution afforded by the models, and the turbulence parameterization based on sigma/sub theta/ measurements to evaluate the eddy diffusivities. Measurements of sigma/sub theta/ in complex terrain exceed those measured over flat terrain by a factor of 2 to 3 leading to eddy diffusivities that are unrealistically high. The results of model evaluations are very sensitive to the quality and the representativeness of the meteorological data. This is particularly true for measurements near the source. The capability of the models to simulate the dispersion of an instantaneously produced cloud of particulates was illustrated to be generally within a factor of 2 over flat terrain. 19 refs., 16 figs

The OH-initiated oxidation of atmospheric peroxyacetic acid: Experimental and model studies

Science.gov (United States)

Wu, Huihui; Wang, Yin; Li, Huan; Huang, Liubin; Huang, Dao; Shen, Hengqing; Xing, Yanan; Chen, Zhongming

2017-09-01

Peroxyacetic acid (PAA, CH3C(O)OOH) plays an important role in atmospheric chemistry, serving as reactive oxidant and affecting radical recycling. However, previous studies revealed an obvious gap between modelled and observed concentrations of atmospheric PAA, which may be partly ascribed to the uncertainty in the kinetics and mechanism of OH-oxidation. In this study, we measured the rate constant of OH radical reaction with PAA (kPAA+OH) and investigated the products in order to develop a more robust atmospheric PAA chemistry. Using the relative rates technique and employing toluene and meta-xylene as reference compounds, the kPAA+OH was determined to be (9.4-11.9) × 10-12 cm3 molecule-1 s-1 at 298 K and 1 atm, which is about (2.5-3.2) times larger than that parameter used in Master Chemical Mechanism v3.3.1 (MCM v3.3.1) (3.70 × 10-12 cm3 molecule-1 s-1). Incorporation of a box model and MCM v3.3.1 with revised PAA chemistry represented a better simulation of atmospheric PAA observed during Wangdu Campaign 2014, a rural site in North China Plain. It is found that OH-oxidation is an important sink of atmospheric PAA in this rural area, accounting for ∼30% of the total loss. Moreover, the major terminal products of PAA-OH reaction were identified as formaldehyde (HCHO) and formic acid (HC(O)OH). The modelled results show that both primary and secondary chemistry play an important role in the large HCHO and HC(O)OH formation under experimental conditions. There should exist the channel of methyl H-abstraction for PAA-OH reaction, which may also provide routes to HCHO and HC(O)OH formation.

Raman spectroscopy reveals biophysical markers in skin cancer surgical margins

Science.gov (United States)

Feng, Xu; Moy, Austin J.; Nguyen, Hieu T. M.; Zhang, Yao; Fox, Matthew C.; Sebastian, Katherine R.; Reichenberg, Jason S.; Markey, Mia K.; Tunnell, James W.

2018-02-01

The recurrence rate of nonmelanoma skin cancer is highly related to the residual tumor after surgery. Although tissueconserving surgery, such as Mohs surgery, is a standard method for the treatment of nonmelanoma skin cancer, they are limited by lengthy and costly frozen-section histopathology. Raman spectroscopy (RS) is proving to be an objective, sensitive, and non-destructive tool for detecting skin cancer. Previous studies demonstrated the high sensitivity of RS in detecting tumor margins of basal cell carcinoma (BCC). However, those studies rely on statistical classification models and do not elucidate the skin biophysical composition. As a result, we aim to discover the biophysical differences between BCC and primary normal skin structures (including epidermis, dermis, hair follicle, sebaceous gland and fat). We obtained freshly resected ex vivo skin samples from fresh resection specimens from 14 patients undergoing Mohs surgery. Raman images were acquired from regions containing one or more structures using a custom built 830nm confocal Raman microscope. The spectra were grouped using K-means clustering analysis and annotated as either BCC or each of the five normal structures by comparing with the histopathology image of the serial section. The spectral data were then fit by a previously established biophysical model with eight primary skin constituents. Our results show that BCC has significant differences in the fit coefficients of nucleus, collagen, triolein, keratin and elastin compared with normal structures. Our study reveals RS has the potential to detect biophysical changes in resection margins, and supports the development of diagnostic algorithms for future intraoperative implementation of RS during Mohs surgery.

Rat models of 17β-estradiol-induced mammary cancer reveal novel insights into breast cancer etiology and prevention.

Science.gov (United States)

Shull, James D; Dennison, Kirsten L; Chack, Aaron C; Trentham-Dietz, Amy

2018-03-01

Numerous laboratory and epidemiologic studies strongly implicate endogenous and exogenous estrogens in the etiology of breast cancer. Data summarized herein suggest that the ACI rat model of 17β-estradiol (E2)-induced mammary cancer is unique among rodent models in the extent to which it faithfully reflects the etiology and biology of luminal types of breast cancer, which together constitute ~70% of all breast cancers. E2 drives cancer development in this model through mechanisms that are largely dependent upon estrogen receptors and require progesterone and its receptors. Moreover, mammary cancer development appears to be associated with generation of oxidative stress and can be modified by multiple dietary factors, several of which may attenuate the actions of reactive oxygen species. Studies of susceptible ACI rats and resistant COP or BN rats provide novel insights into the genetic bases of susceptibility and the biological processes regulated by genetic determinants of susceptibility. This review summarizes research progress resulting from use of these physiologically relevant rat models to advance understanding of breast cancer etiology and prevention.

Models hosts for the study of oral candidiasis.

Science.gov (United States)

Junqueira, Juliana Campos

2012-01-01

Oral candidiasis is an opportunistic infection caused by yeast of the Candida genus, primarily Candida albicans. It is generally associated with predisposing factors such as the use of immunosuppressive agents, antibiotics, prostheses, and xerostomia. The development of research in animal models is extremely important for understanding the nature of the fungal pathogenicity, host interactions, and treatment of oral mucosal Candida infections. Many oral candidiasis models in rats and mice have been developed with antibiotic administration, induction of xerostomia, treatment with immunosuppressive agents, or the use of germ-free animals, and all these models has both benefits and limitations. Over the past decade, invertebrate model hosts, including Galleria mellonella, Caenorhabditis elegans, and Drosophila melanogaster, have been used for the study of Candida pathogenesis. These invertebrate systems offer a number of advantages over mammalian vertebrate models, predominantly because they allow the study of strain collections without the ethical considerations associated with studies in mammals. Thus, the invertebrate models may be useful to understanding of pathogenicity of Candida isolates from the oral cavity, interactions of oral microorganisms, and study of new antifungal compounds for oral candidiasis.

Adaptation to High Ethanol Reveals Complex Evolutionary Pathways.

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Karin Voordeckers

2015-11-01

Full Text Available Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts.

Title Epidemic Model of a Concept within the Subject Classes of Patents: A Case Study on the Term RFID

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Mohammad Tavakolizade Ravari

2016-12-01

Full Text Available The current research aims at studying the epidemic model of the term RFID within the classes of patents. Methodology: The research is descriptive and has been conducted based on the mathematical models of diseases. Research population consists of 35,627 granted patents from the USPTO database those which the terms RFID or Radio Frequency Identification occur in their titles or abstracts. Data analysis was performed through software like Excel, SPSS, and Ravar-Matrix. Findings show that the cumulative growth of sub-classes with the term RFID follows an S-logistic model. This is an evidence of natural growth rate for assigning the term RFID to the USPTO sub-classes over the years.  Other finding reveals that the term RFID has been entered into and exited from the sub-classes of patents like the SIS epidemic model of diseases. As a final conclusion, the most technical fields those that are susceptible for RFID technology, have been met this technology. On the base of SIS model, the epidemic of RFID technology has been reached a balance.

Techno-economic Study

DEFF Research Database (Denmark)

Sigurdsson, Halldór Matthias; Point, J.C.; Million, P.

A techno-economic model for analysing and comparing broadband deployment strategies has been established. The resulting simulation model can compare Capital Expenditure (CAPEX) of dominating broadband technologies in different types of demographic areas. The study reveals the competitiveness...... and applicability of different access technologies in the future broadband market as well as providing sensitivity analysis of the most influential factors controlling market development....

Crowding in Visual Working Memory Reveals Its Spatial Resolution and the Nature of Its Representations.

Science.gov (United States)

Tamber-Rosenau, Benjamin J; Fintzi, Anat R; Marois, René

2015-09-01

Spatial resolution fundamentally limits any image representation. Although this limit has been extensively investigated for perceptual representations by assessing how neighboring flankers degrade the perception of a peripheral target with visual crowding, the corresponding limit for representations held in visual working memory (VWM) is unknown. In the present study, we evoked crowding in VWM and directly compared resolution in VWM and perception. Remarkably, the spatial resolution of VWM proved to be no worse than that of perception. However, mixture modeling of errors caused by crowding revealed the qualitatively distinct nature of these representations. Perceptual crowding errors arose from both increased imprecision in target representations and substitution of flankers for targets. By contrast, VWM crowding errors arose exclusively from substitutions, which suggests that VWM transforms analog perceptual representations into discrete items. Thus, although perception and VWM share a common resolution limit, exceeding this limit reveals distinct mechanisms for perceiving images and holding them in mind. © The Author(s) 2015.

'Big bang' of B-cell development revealed.

Science.gov (United States)

Murre, Cornelis

2018-01-15

Earlier studies have identified transcription factors that specify B-cell fate, but the underlying mechanisms remain to be revealed. Two new studies by Miyai and colleagues (pp. 112-126) and Li and colleagues (pp. 96-111) in this issue of Genes & Development provide new and unprecedented insights into the genetic and epigenetic mechanisms that establish B-cell identity. © 2018 Murre; Published by Cold Spring Harbor Laboratory Press.

Machine learning methods reveal the temporal pattern of dengue incidence using meteorological factors in metropolitan Manila, Philippines.

Science.gov (United States)

Carvajal, Thaddeus M; Viacrusis, Katherine M; Hernandez, Lara Fides T; Ho, Howell T; Amalin, Divina M; Watanabe, Kozo

2018-04-17

Several studies have applied ecological factors such as meteorological variables to develop models and accurately predict the temporal pattern of dengue incidence or occurrence. With the vast amount of studies that investigated this premise, the modeling approaches differ from each study and only use a single statistical technique. It raises the question of whether which technique would be robust and reliable. Hence, our study aims to compare the predictive accuracy of the temporal pattern of Dengue incidence in Metropolitan Manila as influenced by meteorological factors from four modeling techniques, (a) General Additive Modeling, (b) Seasonal Autoregressive Integrated Moving Average with exogenous variables (c) Random Forest and (d) Gradient Boosting. Dengue incidence and meteorological data (flood, precipitation, temperature, southern oscillation index, relative humidity, wind speed and direction) of Metropolitan Manila from January 1, 2009 - December 31, 2013 were obtained from respective government agencies. Two types of datasets were used in the analysis; observed meteorological factors (MF) and its corresponding delayed or lagged effect (LG). After which, these datasets were subjected to the four modeling techniques. The predictive accuracy and variable importance of each modeling technique were calculated and evaluated. Among the statistical modeling techniques, Random Forest showed the best predictive accuracy. Moreover, the delayed or lag effects of the meteorological variables was shown to be the best dataset to use for such purpose. Thus, the model of Random Forest with delayed meteorological effects (RF-LG) was deemed the best among all assessed models. Relative humidity was shown to be the top-most important meteorological factor in the best model. The study exhibited that there are indeed different predictive outcomes generated from each statistical modeling technique and it further revealed that the Random forest model with delayed meteorological

Catchment tracers reveal discharge, recharge and sources of groundwater-borne pollutants in a novel lake modelling approach

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E. Kristensen

2018-02-01

Full Text Available Groundwater-borne contaminants such as nutrients, dissolved organic carbon (DOC, coloured dissolved organic matter (CDOM and pesticides can have an impact the biological quality of lakes. The sources of pollutants can, however, be difficult to identify due to high heterogeneity in groundwater flow patterns. This study presents a novel approach for fast hydrological surveys of small groundwater-fed lakes using multiple groundwater-borne tracers. Water samples were collected from the lake and temporary groundwater wells, installed every 50 m within a distance of 5–45 m to the shore, were analysed for tracer concentrations of CDOM, DOC, total dissolved nitrogen (TDN, groundwater only, total nitrogen (TN, lake only, total dissolved phosphorus (TDP, groundwater only, total phosphorus (TP, lake only, δ18O ∕ δ16O isotope ratios and fluorescent dissolved organic matter (FDOM components derived from parallel factor analysis (PARAFAC. The isolation of groundwater recharge areas was based on δ18O measurements and areas with a high groundwater recharge rate were identified using a microbially influenced FDOM component. Groundwater discharge sites and the fractions of water delivered from the individual sites were isolated with the Community Assembly via Trait Selection model (CATS. The CATS model utilized tracer measurements of TDP, TDN, DOC and CDOM from the groundwater samples and related these to the tracer measurements of TN, TP, DOC and CDOM in the lake. A direct comparison between the lake and the inflowing groundwater was possible as degradation rates of the tracers in the lake were taken into account and related to a range of water retention times (WRTs of the lake (0.25–3.5 years in 0.25-year increments. These estimations showed that WRTs above 2 years required a higher tracer concentration of inflowing water than found in any of the groundwater wells around the lake. From the estimations of inflowing tracer concentration

Spatial model of land use change related to sediment yield (case study: Cipeles and Cilutung watershed, West Java)

Science.gov (United States)

Wulandari, D. W.; Kusratmoko, E.; Indra, T. L.

2018-05-01

Land use changes (LUC) as a result of increasing human need for space are likely to destroy the hydrological function of the watershed, increase land degradation, stimulate erosion and drive the process of sedimentation. This study aimed to predict LUC during the period 1990 to 2030 in relation to sediment yield in Cilutung and Cipeles Watershed, West Java. LUC were simulated following the model of Cellular Automata-Marcov Chain, whereas land use composition in 2030 was predicted using Land Change Modeler on Idrisi Selva Software. Elevation, slope, distance from road, distance from river, and distance from settlement were selected as driving factors for LUC in this study. Erosion and sediment yield were predicted using WATEM/SEDEM model based on land use, rainfall, soil texture and topography. The results showed that the areas of forest and shrub have slightly declined up to 5% during the period 1990 to 2016, generally being converted into rice fields, settlements, non-irrigated fields and plantations. In addition, rice fields, settlements, and plantations were expected to substantially increase up to 50% in 2030. Furthermore, the study also revealed that erosion and sediment yield tend to increase every year. This is likely associated with LUC occurring in Cipeles and Cilutung Watershed.

Experimental and modeling study of Portland cement paste degradation in boric acid

International Nuclear Information System (INIS)

Benakli, A.; Chomat, L.; Le Bescop, P.; Wall, J.

2015-01-01

In the framework of Spent Fuel Pools (SFP) lifetime studies, an investigation of the Portland cement degradation in boric acid has been requested by the Electric Power Research Institute. The main goal of this study is to identify the physico-chemical degradation mechanisms involved in boric acid media. Both experimental and modeling approaches are considered. Concerning degradation experiments, sample of cement paste are immersed during three and nine months in a boric acid solution at 2400 ppm that is periodically renewed. Boric acid concentration has been chosen to be representative of SFP solution. Results will be confronted with reactive transport numerical calculations performed by the reactive transport code HYTEC associated with a dedicated extended database called Thermoddem. The analysis of degradation solution revealed a main ions release mechanism driven by diffusion especially for calcium, nitrate, sodium and sulfate. Leaching behavior of magnesium seems to be more complex. Decalcification is the major degradation process involved, even if a non-negligible contribution of further cations (Mg 2+ , Na + ) and anions (SO 4 2- ) has been noticed. Analysis of degradation soution also revealed that kinetic of Portland cement paste degradation in boric acid is higher than in pure water, regarding the degraded depths measured and calcium leaching rate. This observation has been confirmed by solid characterization. Microstructure analysis of degraded Portland cement paste showed a global porosity increase in the degraded zone that might be mainly attributed to Portlandite dissolution. An Ettringite reprecipitation in the degraded zone has been suspected but could also be Ettringite-like phases containing boron. The analysis techniques used did not allow us to differentiate it, and no others specific mineral phases containing boron has been identified. Profile pattern by XRD analysis allowed us to identify four zones composing the degraded Portland cement paste

The Chlamydomonas Genome Reveals the Evolution of Key Animal and Plant Functions

Energy Technology Data Exchange (ETDEWEB)

Merchant, Sabeeha S

2007-04-09

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the 120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.

Global terrestrial water storage connectivity revealed using complex climate network analyses

Science.gov (United States)

Sun, A. Y.; Chen, J.; Donges, J.

2015-07-01

Terrestrial water storage (TWS) exerts a key control in global water, energy, and biogeochemical cycles. Although certain causal relationship exists between precipitation and TWS, the latter quantity also reflects impacts of anthropogenic activities. Thus, quantification of the spatial patterns of TWS will not only help to understand feedbacks between climate dynamics and the hydrologic cycle, but also provide new insights and model calibration constraints for improving the current land surface models. This work is the first attempt to quantify the spatial connectivity of TWS using the complex network theory, which has received broad attention in the climate modeling community in recent years. Complex networks of TWS anomalies are built using two global TWS data sets, a remote sensing product that is obtained from the Gravity Recovery and Climate Experiment (GRACE) satellite mission, and a model-generated data set from the global land data assimilation system's NOAH model (GLDAS-NOAH). Both data sets have 1° × 1° grid resolutions and cover most global land areas except for permafrost regions. TWS networks are built by first quantifying pairwise correlation among all valid TWS anomaly time series, and then applying a cutoff threshold derived from the edge-density function to retain only the most important features in the network. Basinwise network connectivity maps are used to illuminate connectivity of individual river basins with other regions. The constructed network degree centrality maps show the TWS anomaly hotspots around the globe and the patterns are consistent with recent GRACE studies. Parallel analyses of networks constructed using the two data sets reveal that the GLDAS-NOAH model captures many of the spatial patterns shown by GRACE, although significant discrepancies exist in some regions. Thus, our results provide further measures for constraining the current land surface models, especially in data sparse regions.

Modelling and control of variable speed wind turbines for power system studies

DEFF Research Database (Denmark)

Michalke, Gabriele; Hansen, Anca Daniela

2010-01-01

and implemented in the power system simulation tool DIgSILENT. Important issues like the fault ride-through and grid support capabilities of these wind turbine concepts are addressed. The paper reveals that advanced control of variable speed wind turbines can improve power system stability. Finally......, it will be shown in the paper that wind parks consisting of variable speed wind turbines can help nearby connected fixed speed wind turbines to ride-through grid faults. Copyright © 2009 John Wiley & Sons, Ltd.......Modern wind turbines are predominantly variable speed wind turbines with power electronic interface. Emphasis in this paper is therefore on the modelling and control issues of these wind turbine concepts and especially on their impact on the power system. The models and control are developed...

Computational study of the fibril organization of polyglutamine repeats reveals a common motif identified in beta-helices.

Science.gov (United States)

Zanuy, David; Gunasekaran, Kannan; Lesk, Arthur M; Nussinov, Ruth

2006-04-21

The formation of fibril aggregates by long polyglutamine sequences is assumed to play a major role in neurodegenerative diseases such as Huntington. Here, we model peptides rich in glutamine, through a series of molecular dynamics simulations. Starting from a rigid nanotube-like conformation, we have obtained a new conformational template that shares structural features of a tubular helix and of a beta-helix conformational organization. Our new model can be described as a super-helical arrangement of flat beta-sheet segments linked by planar turns or bends. Interestingly, our comprehensive analysis of the Protein Data Bank reveals that this is a common motif in beta-helices (termed beta-bend), although it has not been identified so far. The motif is based on the alternation of beta-sheet and helical conformation as the protein sequence is followed from the N to the C termini (beta-alpha(R)-beta-polyPro-beta). We further identify this motif in the ssNMR structure of the protofibril of the amyloidogenic peptide Abeta(1-40). The recurrence of the beta-bend suggests a general mode of connecting long parallel beta-sheet segments that would allow the growth of partially ordered fibril structures. The design allows the peptide backbone to change direction with a minimal loss of main chain hydrogen bonds. The identification of a coherent organization beyond that of the beta-sheet segments in different folds rich in parallel beta-sheets suggests a higher degree of ordered structure in protein fibrils, in agreement with their low solubility and dense molecular packing.

Self-harming behavior of a parent with borderline personality disorder assessed using revealed preference and attributional approaches: a case study.

Science.gov (United States)

Tustin, R Don

2002-08-01

This article discusses a case study involving a parent with Borderline Personality Disorder who exhibited self-harming behaviors. Assessment and intervention were based both on a review of the client's attributions about causes of her own behavior as being either internalizing or externalizing, and on a review of motivation of the behaviors using functional analysis. Antecedent situations for self-harming behaviors were identified to provide a basis for reviewing the client's attributions of reasons for disordered behavior. A new technique of functional analysis was applied using the principle of revealed preference arising from behavioral economics. Revealed preference identified outcomes that were valued by the client, enabling new responses to be identified to attain these reinforcers. Attribution re-training was provided. Significant reductions in self-harming behaviors were achieved during brief therapy and were maintained during follow-up.

Equation-free analysis of two-component system signalling model reveals the emergence of co-existing phenotypes in the absence of multistationarity.

Directory of Open Access Journals (Sweden)

Rebecca B Hoyle

Full Text Available Phenotypic differences of genetically identical cells under the same environmental conditions have been attributed to the inherent stochasticity of biochemical processes. Various mechanisms have been suggested, including the existence of alternative steady states in regulatory networks that are reached by means of stochastic fluctuations, long transient excursions from a stable state to an unstable excited state, and the switching on and off of a reaction network according to the availability of a constituent chemical species. Here we analyse a detailed stochastic kinetic model of two-component system signalling in bacteria, and show that alternative phenotypes emerge in the absence of these features. We perform a bifurcation analysis of deterministic reaction rate equations derived from the model, and find that they cannot reproduce the whole range of qualitative responses to external signals demonstrated by direct stochastic simulations. In particular, the mixed mode, where stochastic switching and a graded response are seen simultaneously, is absent. However, probabilistic and equation-free analyses of the stochastic model that calculate stationary states for the mean of an ensemble of stochastic trajectories reveal that slow transcription of either response regulator or histidine kinase leads to the coexistence of an approximate basal solution and a graded response that combine to produce the mixed mode, thus establishing its essential stochastic nature. The same techniques also show that stochasticity results in the observation of an all-or-none bistable response over a much wider range of external signals than would be expected on deterministic grounds. Thus we demonstrate the application of numerical equation-free methods to a detailed biochemical reaction network model, and show that it can provide new insight into the role of stochasticity in the emergence of phenotypic diversity.

Comparative study of economics of different models of family size biogas plants for state of Punjab, India

International Nuclear Information System (INIS)

Singh, K. Jatinder; Sooch, Sarbjit Singh

2004-01-01

Biogas, the end product of anaerobic digestion of cattle dung, can successfully supplement the cooking fuels in the countryside areas of India, where the raw material needed for its production is plentifully available. Because of the lack of awareness regarding selection of a suitable model and size of biogas plant, the full potential of the biogas producing material is not harnessed, and the economic viability of biogas technology is rendered doubtful. To facilitate this decision making, the economics of family size biogas plants, i.e. with capacity from 1 to 6 m 3 , was studied, and three prevalent models, viz. KVIC, Janta and Deenbandu, were compared. Calculations for installation cost and annual operational cost were made for the state of Punjab, India, where the hydraulic retention time is 40 days, and current market prices were taken into account. Comparison of the economics revealed that the cost of installation and annual operational cost of each capacity were higher for the KVIC model, followed by the Janta and then the Deenbandhu model. Irrespective of the model, as the capacity of the biogas plant increases, the installation, as well as the annual operational cost increase proportionately. With increase in capacity, the payback period decreased exponentially with the exponential character being highest for the KVIC model, followed by the Janta and then the Deenbandhu model. However, on the basis of comparative economics, the Deenbandhu model was found to be the cheapest and most viable model of biogas plant

THE FLIPPED WRITING CLASSROOM IN TURKISH EFL CONTEXT: A COMPARATIVE STUDY ON A NEW MODEL

Directory of Open Access Journals (Sweden)

Emrah EKMEKCI

2017-04-01

Full Text Available Flipped learning, one of the most popular and conspicuous instructional models of recent time, can be considered as a pedagogical approach in which the typical lecture and homework elements of a course are reversed. Flipped learning transforms classrooms into interactive and dynamic places where the teacher guides the students and facilitates their learning. The current study explores the impact of flipped instruction on students’ foreign language writing skill which is often perceived as boring, complex and difficult by English as a Foreign Language (EFL learners. The study compares flipped and traditional face-to-face writing classes on the basis of writing performances. Employing a pre- and post-test true experimental design with a control group, the study is based on a mixed-method research. The experimental group consisting of 23 English Language Teaching (ELT students attending preparatory class were instructed for fifteen weeks through Flipped Writing Class Model while the control group comprising 20 ELT preparatory class students followed traditional face-to-face lecture-based writing class. Independent and paired samples t-tests were carried out for the analyses of the data gathered through the pre-and post-tests. The results indicated that there was a statistically significant difference between the experimental and control groups in terms of their writing performances based on the employed rubric. It was found that the students in the experimental group outperformed the students in the control group after the treatment process. The results of the study also revealed that the great majority of the students in the experimental group held positive attitudes towards Flipped Writing Class Model.

Small-scale density variations in the lunar crust revealed by GRAIL

Science.gov (United States)

Jansen, J. C.; Andrews-Hanna, J. C.; Li, Y.; Lucey, P. G.; Taylor, G. J.; Goossens, S.; Lemoine, F. G.; Mazarico, E.; Head, J. W.; Milbury, C.; Kiefer, W. S.; Soderblom, J. M.; Zuber, M. T.

2017-07-01

Data from the Gravity Recovery and Interior Laboratory (GRAIL) mission have revealed that ∼98% of the power of the gravity signal of the Moon at high spherical harmonic degrees correlates with the topography. The remaining 2% of the signal, which cannot be explained by topography, contains information about density variations within the crust. These high-degree Bouguer gravity anomalies are likely caused by small-scale (10‧s of km) shallow density variations. Here we use gravity inversions to model the small-scale three-dimensional variations in the density of the lunar crust. Inversion results from three non-descript areas yield shallow density variations in the range of 100-200 kg/m3. Three end-member scenarios of variations in porosity, intrusions into the crust, and variations in bulk crustal composition were tested as possible sources of the density variations. We find that the density anomalies can be caused entirely by changes in porosity. Characteristics of density anomalies in the South Pole-Aitken basin also support porosity as a primary source of these variations. Mafic intrusions into the crust could explain many, but not all of the anomalies. Additionally, variations in crustal composition revealed by spectral data could only explain a small fraction of the density anomalies. Nevertheless, all three sources of density variations likely contribute. Collectively, results from this study of GRAIL gravity data, combined with other studies of remote sensing data and lunar samples, show that the lunar crust exhibits variations in density by ± 10% over scales ranging from centimeters to 100‧s of kilometers.

Transcriptomic analysis reveals ethylene as stimulator and auxin as regulator of adventitious root formation in petunia cuttings

OpenAIRE

Druege, Uwe; Franken, Philipp; Lischewski, Sandra; Ahkami, Amir H.; Zerche, Siegfried; Hause, Bettina; Hajirezaei, Mohammad R.

2014-01-01

Adventitious root (AR) formation in the stem base of cuttings is the basis for propagation of many plant species and petunia is used as model to study this developmental process. Following AR formation from 2 to 192 hours after excision (hpe) of cuttings, transcriptome analysis by microarray revealed a change of the character of the rooting zone from stem base to root identity. The greatest shift in the number of differentially expressed genes was observed between 24 and 72 hpe, when the cate...

An Exploratory Study on the Development of an Animal Model of Acute Pancreatitis Following Nicotine Exposure