WorldWideScience

Sample records for previously derived model

  1. Previous Experience a Model of Practice UNAE

    OpenAIRE

    Ruiz, Ormary Barberi; Pesántez Palacios, María Dolores

    2017-01-01

    The statements presented in this article represents a preliminary version of the proposed model of pre-professional practices (PPP) of the National University of Education (UNAE) of Ecuador, an urgent institutional necessity is revealed in the descriptive analyzes conducted from technical support - administrative (reports, interviews, testimonials), pedagogical foundations of UNAE (curricular directionality, transverse axes in practice, career plan, approach and diagnostic examination as subj...

  2. Battery failure model derived from flaw theory

    Science.gov (United States)

    Schulman, I.

    1981-01-01

    A previously derived failure model for battery lifetime is discussed in terms of growth rate of the flaw, distribution of flaw sizes, and number of flaws. Equations are presented for determining the failure model for a nickel cadmium battery.

  3. Reference Values for Spirometry Derived Using Lambda, Mu, Sigma (LMS) Method in Korean Adults: in Comparison with Previous References.

    Science.gov (United States)

    Jo, Bum Seak; Myong, Jun Pyo; Rhee, Chin Kook; Yoon, Hyoung Kyu; Koo, Jung Wan; Kim, Hyoung Ryoul

    2018-01-15

    The present study aimed to update the prediction equations for spirometry and their lower limits of normal (LLN) by using the lambda, mu, sigma (LMS) method and to compare the outcomes with the values of previous spirometric reference equations. Spirometric data of 10,249 healthy non-smokers (8,776 females) were extracted from the fourth and fifth versions of the Korea National Health and Nutrition Examination Survey (KNHANES IV, 2007-2009; V, 2010-2012). Reference equations were derived using the LMS method which allows modeling skewness (lambda [L]), mean (mu [M]), and coefficient of variation (sigma [S]). The outcome equations were compared with previous reference values. Prediction equations were presented in the following form: predicted value = e{a + b × ln(height) + c × ln(age) + M - spline}. The new predicted values for spirometry and their LLN derived using the LMS method were shown to more accurately reflect transitions in pulmonary function in young adults than previous prediction equations derived using conventional regression analysis in 2013. There were partial discrepancies between the new reference values and the reference values from the Global Lung Function Initiative in 2012. The results should be interpreted with caution for young adults and elderly males, particularly in terms of the LLN for forced expiratory volume in one second/forced vital capacity in elderly males. Serial spirometry follow-up, together with correlations with other clinical findings, should be emphasized in evaluating the pulmonary function of individuals. Future studies are needed to improve the accuracy of reference data and to develop continuous reference values for spirometry across all ages. © 2018 The Korean Academy of Medical Sciences.

  4. Aggregation of thrombin-derived C-terminal fragments as a previously undisclosed host defense mechanism

    DEFF Research Database (Denmark)

    Petrlova, Jitka; Hansen, Finja C; van der Plas, Mariena J A

    2017-01-01

    Effective control of endotoxins and bacteria is crucial for normal wound healing. During injury, the key enzyme thrombin is formed, leading to generation of fibrin. Here, we show that human neutrophil elastase cleaves thrombin, generating 11-kDa thrombin-derived C-terminal peptides (TCPs), which ...

  5. A variable-order fractal derivative model for anomalous diffusion

    Directory of Open Access Journals (Sweden)

    Liu Xiaoting

    2017-01-01

    Full Text Available This paper pays attention to develop a variable-order fractal derivative model for anomalous diffusion. Previous investigations have indicated that the medium structure, fractal dimension or porosity may change with time or space during solute transport processes, results in time or spatial dependent anomalous diffusion phenomena. Hereby, this study makes an attempt to introduce a variable-order fractal derivative diffusion model, in which the index of fractal derivative depends on temporal moment or spatial position, to characterize the above mentioned anomalous diffusion (or transport processes. Compared with other models, the main advantages in description and the physical explanation of new model are explored by numerical simulation. Further discussions on the dissimilitude such as computational efficiency, diffusion behavior and heavy tail phenomena of the new model and variable-order fractional derivative model are also offered.

  6. Validation of SWAT+ at field level and comparison with previous SWAT models in simulating hydrologic quantity

    Science.gov (United States)

    GAO, J.; White, M. J.; Bieger, K.; Yen, H.; Arnold, J. G.

    2017-12-01

    Over the past 20 years, the Soil and Water Assessment Tool (SWAT) has been adopted by many researches to assess water quantity and quality in watersheds around the world. As the demand increases in facilitating model support, maintenance, and future development, the SWAT source code and data have undergone major modifications over the past few years. To make the model more flexible in terms of interactions of spatial units and processes occurring in watersheds, a completely revised version of SWAT (SWAT+) was developed to improve SWAT's ability in water resource modelling and management. There are only several applications of SWAT+ in large watersheds, however, no study pays attention to validate the new model at field level and assess its performance. To test the basic hydrologic function of SWAT+, it was implemented in five field cases across five states in the U.S. and compared the SWAT+ created results with that from the previous models at the same fields. Additionally, an automatic calibration tool was used to test which model is easier to be calibrated well in a limited number of parameter adjustments. The goal of the study was to evaluate the performance of SWAT+ in simulating stream flow on field level at different geographical locations. The results demonstrate that SWAT+ demonstrated similar performance with previous SWAT model, but the flexibility offered by SWAT+ via the connection of different spatial objects can result in a more accurate simulation of hydrological processes in spatial, especially for watershed with artificial facilities. Autocalibration shows that SWAT+ is much easier to obtain a satisfied result compared with the previous SWAT. Although many capabilities have already been enhanced in SWAT+, there exist inaccuracies in simulation. This insufficiency will be improved with advancements in scientific knowledge on hydrologic process in specific watersheds. Currently, SWAT+ is prerelease, and any errors are being addressed.

  7. The Importance of Business Model Factors for Cloud Computing Adoption: Role of Previous Experiences

    Directory of Open Access Journals (Sweden)

    Bogataj Habjan Kristina

    2017-08-01

    Full Text Available Background and Purpose: Bringing several opportunities for more effective and efficient IT governance and service exploitation, cloud computing is expected to impact the European and global economies significantly. Market data show that despite many advantages and promised benefits the adoption of cloud computing is not as fast and widespread as foreseen. This situation shows the need for further exploration of the potentials of cloud computing and its implementation on the market. The purpose of this research was to identify individual business model factors with the highest impact on cloud computing adoption. In addition, the aim was to identify the differences in opinion regarding the importance of business model factors on cloud computing adoption according to companies’ previous experiences with cloud computing services.

  8. Rational Models for Inflation-Linked Derivatives

    DEFF Research Database (Denmark)

    Dam, Henrik; Macrina, Andrea; Skovmand, David

    2018-01-01

    We construct models for the pricing and risk management of inflation-linked derivatives. The model is rational in the sense that affine payoffs written on the consumer price index have prices that are rational functions of the state variables. The nominal pricing kernel is constructed in a multip......We construct models for the pricing and risk management of inflation-linked derivatives. The model is rational in the sense that affine payoffs written on the consumer price index have prices that are rational functions of the state variables. The nominal pricing kernel is constructed...... in a multiplicative manner that allows for closed-form pricing of vanilla inflation products suchlike zero-coupon swaps, caps and floors, year-on-year swaps, caps and floors, and the exotic limited price index swap. The model retains the attractive features of a nominal multi-curve interest rate model such as closed...

  9. Schwinger model with higher derivative couplings

    Energy Technology Data Exchange (ETDEWEB)

    Barcelos-Neto, J.; Natividade, C.P. (Universidade Federal do Rio de Janeiro, RJ (Brazil). Inst. de Fisica)

    1991-02-01

    We study a version of the Schwinger model where fermion and gauge fields are coupled by means of higher derivatives. We show that, regardless of possible existence of ghosts and non-unitarity, the model is completely soluble and the anomalous axial divergence and the mass generated for the photon field are the same as in the usual model. The confinement of the electric charge is also discussed. (orig.).

  10. Modelling Environment Changes for Pricing Weather Derivatives

    Directory of Open Access Journals (Sweden)

    Kabaivanov Stanimir

    2017-12-01

    Full Text Available This paper focuses on modelling environment changes in a way that allows to price weather derivatives in a flexible and efficient way. Applications and importance of climate and weather contracts extends beyond financial markets and hedging as they can be used as complementary tools for risk assessment. In addition, option-based approach toward resource management can offer very special insights on rare-events and allow to reuse derivative pricing methods to improve natural resources management. To demonstrate this general concept, we use Monte Carlo and stochastic modelling of temperatures to evaluate weather options. Research results are accompanied by R and Python code.

  11. Temperature stochastic modeling and weather derivatives pricing ...

    African Journals Online (AJOL)

    ... over a sufficient period to apply a stochastic process that describes the evolution of the temperature. A numerical example of a swap contract pricing is presented, using an approximation formula as well as Monte Carlo simulations. Keywords: Weather derivatives, temperature stochastic model, Monte Carlo simulation.

  12. Testing Expected Shortfall Models for Derivative Positions

    NARCIS (Netherlands)

    Kerkhof, F.L.J.; Melenberg, B.; Schumacher, J.M.

    2003-01-01

    In this paper we test several risk management models for computing expected shortfall for one-period hedge errors of hedged derivatives positions.Contrary to value-at-risk, expected shortfall cannot be tested using the standard binomial test, since we need information of the distribution in the

  13. Modelling ocean-colour-derived chlorophyll a

    Science.gov (United States)

    Dutkiewicz, Stephanie; Hickman, Anna E.; Jahn, Oliver

    2018-01-01

    This article provides a proof of concept for using a biogeochemical/ecosystem/optical model with a radiative transfer component as a laboratory to explore aspects of ocean colour. We focus here on the satellite ocean colour chlorophyll a (Chl a) product provided by the often-used blue/green reflectance ratio algorithm. The model produces output that can be compared directly to the real-world ocean colour remotely sensed reflectance. This model output can then be used to produce an ocean colour satellite-like Chl a product using an algorithm linking the blue versus green reflectance similar to that used for the real world. Given that the model includes complete knowledge of the (model) water constituents, optics and reflectance, we can explore uncertainties and their causes in this proxy for Chl a (called derived Chl a in this paper). We compare the derived Chl a to the actual model Chl a field. In the model we find that the mean absolute bias due to the algorithm is 22 % between derived and actual Chl a. The real-world algorithm is found using concurrent in situ measurement of Chl a and radiometry. We ask whether increased in situ measurements to train the algorithm would improve the algorithm, and find a mixed result. There is a global overall improvement, but at the expense of some regions, especially in lower latitudes where the biases increase. Not surprisingly, we find that region-specific algorithms provide a significant improvement, at least in the annual mean. However, in the model, we find that no matter how the algorithm coefficients are found there can be a temporal mismatch between the derived Chl a and the actual Chl a. These mismatches stem from temporal decoupling between Chl a and other optically important water constituents (such as coloured dissolved organic matter and detrital matter). The degree of decoupling differs regionally and over time. For example, in many highly seasonal regions, the timing of initiation and peak of the spring bloom in

  14. Discovery of previously unrecognised local faults in London, UK, using detailed 3D geological modelling

    Science.gov (United States)

    Aldiss, Don; Haslam, Richard

    2013-04-01

    In parts of London, faulting introduces lateral heterogeneity to the local ground conditions, especially where construction works intercept the Palaeogene Lambeth Group. This brings difficulties to the compilation of a ground model that is fully consistent with the ground investigation data, and so to the design and construction of engineering works. However, because bedrock in the London area is rather uniform at outcrop, and is widely covered by Quaternary deposits, few faults are shown on the geological maps of the area. This paper discusses a successful resolution of this problem at a site in east central London, where tunnels for a new underground railway station are planned. A 3D geological model was used to provide an understanding of the local geological structure, in faulted Lambeth Group strata, that had not been possible by other commonly-used methods. This model includes seven previously unrecognised faults, with downthrows ranging from about 1 m to about 12 m. The model was constructed in the GSI3D geological modelling software using about 145 borehole records, including many legacy records, in an area of 850 m by 500 m. The basis of a GSI3D 3D geological model is a network of 2D cross-sections drawn by a geologist, generally connecting borehole positions (where the borehole records define the level of the geological units that are present), and outcrop and subcrop lines for those units (where shown by a geological map). When the lines tracing the base of each geological unit within the intersecting cross-sections are complete and mutually consistent, the software is used to generate TIN surfaces between those lines, so creating a 3D geological model. Even where a geological model is constructed as if no faults were present, changes in apparent dip between two data points within a single cross-section can indicate that a fault is present in that segment of the cross-section. If displacements of similar size with the same polarity are found in a series

  15. Price models for oil derivates in Slovenia

    International Nuclear Information System (INIS)

    Nemac, F.; Saver, A.

    1995-01-01

    In Slovenia, a law is currently applied according to which any change in the price of oil derivatives is subject to the Governmental approval. Following the target of getting closer to the European Union, the necessity has arisen of finding ways for the introduction of liberalization or automated approach to price modifications depending on oscillations of oil derivative prices on the world market and the rate of exchange of the American dollar. It is for this reason that at the Agency for Energy Restructuring we made a study for the Ministry of Economic Affairs and Development regarding this issue. We analysed the possible models for the formation of oil derivative prices for Slovenia. Based on the assessment of experiences of primarily the west European countries, we proposed three models for the price formation for Slovenia. In future, it is expected that the Government of the Republic of Slovenia will make a selection of one of the proposed models to be followed by enforcement of price liberalization. The paper presents two representative models for price formation as used in Austria and Portugal. In the continuation the authors analyse the application of three models that they find suitable for the use in Slovenia. (author)

  16. Derivative processes for modelling metabolic fluxes

    Science.gov (United States)

    Žurauskienė, Justina; Kirk, Paul; Thorne, Thomas; Pinney, John; Stumpf, Michael

    2014-01-01

    Motivation: One of the challenging questions in modelling biological systems is to characterize the functional forms of the processes that control and orchestrate molecular and cellular phenotypes. Recently proposed methods for the analysis of metabolic pathways, for example, dynamic flux estimation, can only provide estimates of the underlying fluxes at discrete time points but fail to capture the complete temporal behaviour. To describe the dynamic variation of the fluxes, we additionally require the assumption of specific functional forms that can capture the temporal behaviour. However, it also remains unclear how to address the noise which might be present in experimentally measured metabolite concentrations. Results: Here we propose a novel approach to modelling metabolic fluxes: derivative processes that are based on multiple-output Gaussian processes (MGPs), which are a flexible non-parametric Bayesian modelling technique. The main advantages that follow from MGPs approach include the natural non-parametric representation of the fluxes and ability to impute the missing data in between the measurements. Our derivative process approach allows us to model changes in metabolite derivative concentrations and to characterize the temporal behaviour of metabolic fluxes from time course data. Because the derivative of a Gaussian process is itself a Gaussian process, we can readily link metabolite concentrations to metabolic fluxes and vice versa. Here we discuss how this can be implemented in an MGP framework and illustrate its application to simple models, including nitrogen metabolism in Escherichia coli. Availability and implementation: R code is available from the authors upon request. Contact: j.norkunaite@imperial.ac.uk; m.stumpf@imperial.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24578401

  17. Effects of previous severe exercise on two and three parameter critical power modeling

    Directory of Open Access Journals (Sweden)

    Eduardo Kokubun

    2007-09-01

    Full Text Available The purpose of this study was to apply the two and three-parameter critical power model equations after depletion of a fi xed amount of anaerobic work capacity (AWC, followed by a short rest period. Sixteen subjects underwent: (1 two practice trials for ergometer familiarization to severe exercise; (2 4-5 exercise bouts on different days for the estimation of critical power (CP and AWC using the two and three parameter models; (3 the same procedures as described in stage 2 were repeated after 30 s recovery from 180 s of exercise completed at an intensity that would have elicited exhaustion in around 300 s. The CP2parameter (130-174 W versus 131-170 W and CP3parameter (108 versus 100 W estimated after prior severe exercise followed by a short rest period remained stable compared to the fatigue-free tests. The AWC2parameter was reduced in response to prior severe exercise. The AWC3parameter was not significantly reduced. The correlations between CP2parameter derived from the same equation with and without prior AWC2parameter reduction were strong (r = 0.97-0.99, P ABSTRACT O propósito do presente estudo foi aplicar as equações do modelo de potência crítica de dois e três parâmetros após a depleção de uma quantia fi xa de capacidade de trabalho anaeróbio (AWC, seguido de um período curto de repouso. Dezesseis sujeitos realizaram: (1 duas familiarizações ao exercício severo no cicloergômetro; (2 4-5 exercícios máximos em dias diferentes para a estimativa da CP e AWC por meio dos modelos de dois e três parâmetros; (3 os mesmos procedimentos descritos no #2 foram realizados após 30 s de repouso e de um exercício de 180 s a uma intensidade em que a exaustão provavelmente ocorreria em ~300 s. A CP2parameter (130-174 W versus 131-170 W e CP3parameter (108 versus 100 W estimadas após o exercício prévio severo e seguido por um curto período de repouso permaneceu estável quando comparado às estimativas sem o exercício pr

  18. Trashepatic left gastric vein embolization in the treatment of recurrent hemorrhaging in patients with schistosomiasis previously submitted to non-derivative surgery

    Directory of Open Access Journals (Sweden)

    Paulo Fernandes Saad

    2012-12-01

    Full Text Available CONTEXT: Non-derivative surgical techniques are the treatment of choice for the control of upper digestive tract hemorrhages after schistosomotic portal hypertension. However, recurrent hemorrhaging due to gastroesophagic varices is frequent. OBJECTIVE: To evaluate the outcome of treatment based on embolization of the left gastric vein to control the reoccurrence of hemorrhages caused by gastroesophagic varices in patients with schistosomiasis previously submitted to non-derivative surgery. METHODS: Rates of reoccurrence of hemorrhages and the qualitative and quantitative reduction of gastroesophagic varices in patients undergoing transhepatic embolization of the left gastric vein between December 1999 and January 2009 were studied based on medical charts and follow-up reports. RESULTS: Seven patients with a mean age of 39.3 years underwent percutaneous transhepatic embolization of the left gastric vein. The mean time between azigoportal disconnections employed in combination with splenectomy and the percutaneous approach was 8.4 ± 7.3 years, and the number of episodes of digestive hemorrhaging ranged from 1 to 7 years. No episodes of reoccurrence of hemorrhaging were found during a follow-up period which ranged from 6 months to 7 years. Endoscopic postembolization studies revealed reductions in gastroesophagic varices in all patients compared to preembolization endoscopy. CONCLUSIONS: Percutaneous transhepatic embolization of the left gastric vein in patients with schistosomiasis previously submitted to surgery resulted in a decrease in gastroesophagic varices and was shown to be effective in controlling hemorrhage reoccurrence.

  19. Structure activity relationships of quinoxalin-2-one derivatives as platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors, derived from molecular modeling.

    Science.gov (United States)

    Mori, Yoshikazu; Hirokawa, Takatsugu; Aoki, Katsuyuki; Satomi, Hisanori; Takeda, Shuichi; Aburada, Masaki; Miyamoto, Ken-ichi

    2008-05-01

    We previously reported a quinoxalin-2-one compound (Compound 1) that had inhibitory activity equivalent to existing platelet-derived growth factor-beta receptor (PDGFbeta R) inhibitors. Lead optimization of Compound 1 to increase its activity and selectivity, using structural information regarding PDGFbeta R-ligand interactions, is urgently needed. Here we present models of the PDGFbeta R kinase domain complexed with quinoxalin-2-one derivatives. The models were constructed using comparative modeling, molecular dynamics (MD) and ligand docking. In particular, conformations derived from MD, and ligand binding site information presented by alpha-spheres in the pre-docking processing, allowed us to identify optimal protein structures for docking of target ligands. By carrying out molecular modeling and MD of PDGFbeta R in its inactive state, we obtained two structural models having good Compound 1 binding potentials. In order to distinguish the optimal candidate, we evaluated the structural activity relationships (SAR) between the ligand-binding free energies and inhibitory activity values (IC50 values) for available quinoxalin-2-one derivatives. Consequently, a final model with a high SAR was identified. This model included a molecular interaction between the hydrophobic pocket behind the ATP binding site and the substitution region of the quinoxalin-2-one derivatives. These findings should prove useful in lead optimization of quinoxalin-2-one derivatives as PDGFb R inhibitors.

  20. Third metacarpal condylar fatigue fractures in equine athletes occur within previously modelled subchondral bone.

    Science.gov (United States)

    Whitton, R Christopher; Trope, Gareth D; Ghasem-Zadeh, Ali; Anderson, Garry A; Parkin, Timothy D H; Mackie, Eleanor J; Seeman, Ego

    2010-10-01

    Bone modelling and remodelling reduce the risk of fatigue fractures; the former by adapting bone to its loading circumstances, the latter by replacing fatigued bone. Remodelling transiently increases porosity because of the normal delay in onset of the formation phase of the remodelling sequence. Protracted intense loading suppresses remodelling leaving modelling as the only means of maintaining bone strength. We therefore hypothesized that race horses with fatigue fractures of the distal third metacarpal bone (MC3) will have reduced porosity associated with suppressed remodelling while continued adaptive modelling will result in higher volume fraction (BV/TV) at this site. Using high resolution peripheral quantitative computed tomography (HR-pQCT), we measured the distal aspect of the MC3 obtained at postmortem from 13 thoroughbred race horses with condylar fractures of the MC3 (cases), 8 horses without fractures (training controls), 14 horses with a fracture at another site (fractured controls) and 9 horses resting from training (resting controls). Porosity of the subchondral bone of MC3 was lower in cases than resting controls (12±1.4% vs. 18±1.6%, P=0.017) although areas of focal porosity were observed adjacent to fractures in 6/13 horses. BV/TV of the distal metacarpal epiphysis tended to be higher in horses with condylar fractures (0.79±0.015) than training controls (0.74±0.019, P=0.070), but also higher in controls with a fracture elsewhere (0.79±0.014) than the training controls (0.74±0.019, P=0.040). BV/TV was higher in horses over three years of age than those aged two or three years (0.79±0.01 vs. 0.74±0.01, P=0.016). All metacarpal condylar fractures occurred within focal areas of high BV/TV. We infer that intense training in equine athletes suppresses remodelling of third metacarpal subchondral bone limiting damage repair while modelling increases regional bone volume in an attempt to minimise local stresses but may fail to offset bone

  1. A tracer diffusion model derived from microstructure

    International Nuclear Information System (INIS)

    Lehikoinen, Jarmo; Muurinen, Arto; Olin, Markus

    2012-01-01

    of reference, is shown to be given by the ratio of the effective diffusivity to the apparent diffusivity for an assumed non-interacting solute, such as tritiated water. Finally, the utility of the model and derivation of the model parameters are demonstrated with tracer diffusion data from the open literature for compacted bentonite. (authors)

  2. Liver growth factor treatment reverses emphysema previously established in a cigarette smoke exposure mouse model.

    Science.gov (United States)

    Pérez-Rial, Sandra; Del Puerto-Nevado, Laura; Girón-Martínez, Alvaro; Terrón-Expósito, Raúl; Díaz-Gil, Juan J; González-Mangado, Nicolás; Peces-Barba, Germán

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease largely associated with cigarette smoke exposure (CSE) and characterized by pulmonary and extrapulmonary manifestations, including systemic inflammation. Liver growth factor (LGF) is an albumin-bilirubin complex with demonstrated antifibrotic, antioxidant, and antihypertensive actions even at extrahepatic sites. We aimed to determine whether short LGF treatment (1.7 μg/mouse ip; 2 times, 2 wk), once the lung damage was established through the chronic CSE, contributes to improvement of the regeneration of damaged lung tissue, reducing systemic inflammation. We studied AKR/J mice, divided into three groups: control (air-exposed), CSE (chronic CSE), and CSE + LGF (LGF-treated CSE mice). We assessed pulmonary function, morphometric data, and levels of various systemic inflammatory markers to test the LGF regenerative capacity in this system. Our results revealed that the lungs of the CSE animals showed pulmonary emphysema and inflammation, characterized by increased lung compliance, enlargement of alveolar airspaces, systemic inflammation (circulating leukocytes and serum TNF-α level), and in vivo lung matrix metalloproteinase activity. LGF treatment was able to reverse all these parameters, decreasing total cell count in bronchoalveolar lavage fluid and T-lymphocyte infiltration in peripheral blood observed in emphysematous mice and reversing the decrease in monocytes observed in chronic CSE mice, and tends to reduce the neutrophil population and serum TNF-α level. In conclusion, LGF treatment normalizes the physiological and morphological parameters and levels of various systemic inflammatory biomarkers in a chronic CSE AKR/J model, which may have important pathophysiological and therapeutic implications for subjects with stable COPD. Copyright © 2014 the American Physiological Society.

  3. Impact of Scattering Model on Disdrometer Derived Attenuation Scaling

    Science.gov (United States)

    Zemba, Michael; Luini, Lorenzo; Nessel, James; Riva, Carlo (Compiler)

    2016-01-01

    NASA Glenn Research Center (GRC), the Air Force Research Laboratory (AFRL), and the Politecnico di Milano (POLIMI) are currently entering the third year of a joint propagation study in Milan, Italy utilizing the 20 and 40 GHz beacons of the Alphasat TDP5 Aldo Paraboni scientific payload. The Ka- and Q-band beacon receivers were installed at the POLIMI campus in June of 2014 and provide direct measurements of signal attenuation at each frequency. Collocated weather instrumentation provides concurrent measurement of atmospheric conditions at the receiver; included among these weather instruments is a Thies Clima Laser Precipitation Monitor (optical disdrometer) which records droplet size distributions (DSD) and droplet velocity distributions (DVD) during precipitation events. This information can be used to derive the specific attenuation at frequencies of interest and thereby scale measured attenuation data from one frequency to another. Given the ability to both predict the 40 GHz attenuation from the disdrometer and the 20 GHz timeseries as well as to directly measure the 40 GHz attenuation with the beacon receiver, the Milan terminal is uniquely able to assess these scaling techniques and refine the methods used to infer attenuation from disdrometer data.In order to derive specific attenuation from the DSD, the forward scattering coefficient must be computed. In previous work, this has been done using the Mie scattering model, however, this assumes a spherical droplet shape. The primary goal of this analysis is to assess the impact of the scattering model and droplet shape on disdrometer derived attenuation predictions by comparing the use of the Mie scattering model to the use of the T-matrix method, which does not assume a spherical droplet. In particular, this paper will investigate the impact of these two scattering approaches on the error of the resulting predictions as well as on the relationship between prediction error and rain rate.

  4. Deriving minimal models for resource utilization

    NARCIS (Netherlands)

    te Brinke, Steven; Bockisch, Christoph; Bergmans, Lodewijk; Malakuti Khah Olun Abadi, Somayeh; Aksit, Mehmet; Katz, Shmuel

    2013-01-01

    We show how compact Resource Utilization Models (RUMs) can be extracted from concrete overly-detailed models of systems or sub-systems in order to model energy-aware software. Using the Counterexample-Guided Abstraction Refinement (CEGAR) approach, along with model-checking tools, abstract models

  5. A Derivative Based Estimator for Semiparametric Index Models

    NARCIS (Netherlands)

    Donkers, A.C.D.; Schafgans, M.

    2003-01-01

    This paper proposes a semiparametric estimator for single- and multiple index models.It provides an extension of the average derivative estimator to the multiple index model setting.The estimator uses the average of the outer product of derivatives and is shown to be root-N consistent and

  6. Remarks on the microscopic derivation of the collective model

    International Nuclear Information System (INIS)

    Toyoda, T.; Wildermuth, K.

    1984-01-01

    The rotational part of the phenomenological collective model of Bohr and Mottelson and others is derived microscopically, starting with the Schrodinger equation written in projection form and introducing a new set of 'relative Euler angles'. In order to derive the local Schrodinger equation of the collective model, it is assumed that the intrinsic wave functions give strong peaking properties to the overlapping kernels

  7. Previously published midazolam-alfentanil response surface model cannot predict patient response well in gastrointestinal endoscopy sedation.

    Science.gov (United States)

    Liou, Jing-Yang; Ting, Chien-Kun; Huang, Yu-Ying; Tsou, Mei-Yung

    2016-03-01

    A response surface model is a mathematical model used to predict multiple-drug pharmacodynamic interactions. With the use of a previously published volunteer model, we tested the accuracy of the midazolam-alfentanil response surface model during gastrointestinal endoscopy. We enrolled 35 adult patients scheduled for combined endoscopic procedures. Patients were sedated with intravenous midazolam and alfentanil, and monitored with real-time auditory evoked potential. Sedation Observer's Assessment of Alertness/Sedation (OAA/S) scores were recorded by an independent observer every 2 minutes. Patients with OAA/S scores of ≥ 4 were designated as "awake". Pharmacokinetic profiles were calculated using the TIVA trainer. The published response surface model was modified to make estimations more reasonable. Patient response (OAA/S score ≥ 4 or response during gastrointestinal endoscopic procedure sedation. Accuracy in predicting an OAA/S score of response ranged from 0.04% to 2.94% at the time of arousal (OAA/S score ≥ 4) and from 0.24% to 15.55% when the patient was asleep (OAA/S score response of patients undergoing sedated gastrointestinal endoscopic procedures. Future model parameter adjustments are required. Copyright © 2016. Published by Elsevier Taiwan LLC.

  8. Validation of a Previously Developed Geospatial Model That Predicts the Prevalence of Listeria monocytogenes in New York State Produce Fields.

    Science.gov (United States)

    Weller, Daniel; Shiwakoti, Suvash; Bergholz, Peter; Grohn, Yrjo; Wiedmann, Martin; Strawn, Laura K

    2016-02-01

    Technological advancements, particularly in the field of geographic information systems (GIS), have made it possible to predict the likelihood of foodborne pathogen contamination in produce production environments using geospatial models. Yet, few studies have examined the validity and robustness of such models. This study was performed to test and refine the rules associated with a previously developed geospatial model that predicts the prevalence of Listeria monocytogenes in produce farms in New York State (NYS). Produce fields for each of four enrolled produce farms were categorized into areas of high or low predicted L. monocytogenes prevalence using rules based on a field's available water storage (AWS) and its proximity to water, impervious cover, and pastures. Drag swabs (n = 1,056) were collected from plots assigned to each risk category. Logistic regression, which tested the ability of each rule to accurately predict the prevalence of L. monocytogenes, validated the rules based on water and pasture. Samples collected near water (odds ratio [OR], 3.0) and pasture (OR, 2.9) showed a significantly increased likelihood of L. monocytogenes isolation compared to that for samples collected far from water and pasture. Generalized linear mixed models identified additional land cover factors associated with an increased likelihood of L. monocytogenes isolation, such as proximity to wetlands. These findings validated a subset of previously developed rules that predict L. monocytogenes prevalence in produce production environments. This suggests that GIS and geospatial models can be used to accurately predict L. monocytogenes prevalence on farms and can be used prospectively to minimize the risk of preharvest contamination of produce. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  9. Policy advice derived from simulation models

    NARCIS (Netherlands)

    Brenner, T.; Werker, C.

    2009-01-01

    When advising policy we face the fundamental problem that economic processes are connected with uncertainty and thus policy can err. In this paper we show how the use of simulation models can reduce policy errors. We suggest that policy is best based on socalled abductive simulation models, which

  10. Ignition and Growth Modeling of Detonating LX-04 (85% HMX / 15% VITON) Using New and Previously Obtained Experimental Data

    Science.gov (United States)

    Tarver, Craig

    2017-06-01

    An Ignition and Growth reactive flow model for detonating LX-04 (85% HMX / 15% Viton) was developed using new and previously obtained experimental data on: cylinder test expansion; wave curvature; failure diameter; and laser interferometric copper and tantalum foil free surface velocities and LiF interface particle velocity histories. A reaction product JWL EOS generated by the CHEETAH code compared favorably with the existing, well normalized LX-04 product JWL when both were used with the Ignition and Growth model. Good agreement with all existing experimental data was obtained. Keywords: LX-04, HMX, detonation, Ignition and Growth PACS:82.33.Vx, 82.40.Fp This work was performed under the auspices of the U. S. Department of Energy by the Lawrence Livermore National Laboratory under Contract No. DE-AC52-07NA27344.

  11. Weather Derivatives and Stochastic Modelling of Temperature

    Directory of Open Access Journals (Sweden)

    Fred Espen Benth

    2011-01-01

    Full Text Available We propose a continuous-time autoregressive model for the temperature dynamics with volatility being the product of a seasonal function and a stochastic process. We use the Barndorff-Nielsen and Shephard model for the stochastic volatility. The proposed temperature dynamics is flexible enough to model temperature data accurately, and at the same time being analytically tractable. Futures prices for commonly traded contracts at the Chicago Mercantile Exchange on indices like cooling- and heating-degree days and cumulative average temperatures are computed, as well as option prices on them.

  12. Silicon Carbide Derived Carbons: Experiments and Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Kertesz, Miklos [Georgetown University, Washington DC 20057

    2011-02-28

    The main results of the computational modeling was: 1. Development of a new genealogical algorithm to generate vacancy clusters in diamond starting from monovacancies combined with energy criteria based on TBDFT energetics. The method revealed that for smaller vacancy clusters the energetically optimal shapes are compact but for larger sizes they tend to show graphitized regions. In fact smaller clusters of the size as small as 12 already show signatures of this graphitization. The modeling gives firm basis for the slit-pore modeling of porous carbon materials and explains some of their properties. 2. We discovered small vacancy clusters and their physical characteristics that can be used to spectroscopically identify them. 3. We found low barrier pathways for vacancy migration in diamond-like materials by obtaining for the first time optimized reaction pathways.

  13. Wind gust models derived from field data

    Science.gov (United States)

    Gawronski, W.

    1995-01-01

    Wind data measured during a field experiment were used to verify the analytical model of wind gusts. Good coincidence was observed; the only discrepancy occurred for the azimuth error in the front and back winds, where the simulated errors were smaller than the measured ones. This happened because of the assumption of the spatial coherence of the wind gust model, which generated a symmetric antenna load and, in consequence, a low azimuth servo error. This result indicates a need for upgrading the wind gust model to a spatially incoherent one that will reflect the real gusts in a more accurate manner. In order to design a controller with wind disturbance rejection properties, the wind disturbance should be known at the input to the antenna rate loop model. The second task, therefore, consists of developing a digital filter that simulates the wind gusts at the antenna rate input. This filter matches the spectrum of the measured servo errors. In this scenario, the wind gusts are generated by introducing white noise to the filter input.

  14. Clinical CVVH model removes endothelium-derived microparticles from circulation

    Directory of Open Access Journals (Sweden)

    Abdelhafeez H. Abdelhafeez

    2014-02-01

    Full Text Available Background: Endothelium-derived microparticles (EMPs are submicron vesicles released from the plasma membrane of endothelial cells in response to injury, apoptosis or activation. We have previously demonstrated EMP-induced acute lung injury (ALI in animal models and endothelial barrier dysfunction in vitro. Current treatment options for ALI are limited and consist of supportive therapies. We hypothesize that standard clinical continuous venovenous hemofiltration (CVVH reduces serum EMP levels and may be adapted as a potential therapeutic intervention. Materials and methods: EMPs were generated from plasminogen activation inhibitor-1 (PAI-1-stimulated human umbilical vein endothelial cells (HUVECs. Flow cytometric analysis was used to characterize EMPs as CD31- and annexin V-positive events in a submicron size gate. Enumeration was completed against a known concentration of latex beads. Ultimately, a concentration of ~650,000 EMP/mL perfusate fluid (total 470 mL was circulated through a standard CVVH filter (pore size 200 μm, flow rate 250 mL/hr for a period of 70 minutes. 0.5 mL aliquots were removed at 5- to 10-minute intervals for flow cytometric analysis. EMP concentration in the dialysate was measured at the end of 4 hours to better understand the fate of EMPs. Results: A progressive decrease in circulating EMP concentration was noted using standard CVVH at 250 mL/hr (a clinical standard rate from a 470 mL volume modelling a patient's circulation. A 50% reduction was noted within the first 30 minutes. EMPs entering the dialysate after 4 hours were 5.7% of the EMP original concentration. Conclusion: These data demonstrate that standard CVVH can remove EMPs from circulation in a circuit modelling a patient. An animal model of hemofiltration with induction of EMP release is required to test the therapeutic potential of this finding and potential of application in early treatment of ALI.

  15. Cancer treatment model with the Caputo-Fabrizio fractional derivative

    Science.gov (United States)

    Ali Dokuyucu, Mustafa; Celik, Ercan; Bulut, Hasan; Mehmet Baskonus, Haci

    2018-03-01

    In this article, a model for cancer treatment is examined. The model is integrated into the Caputo-Fabrizio fractional derivative first, to examine the existence of the solution. Then, the uniqueness of the solution is investigated and we identified under which conditions the model provides a unique solution.

  16. New empirically-derived solar radiation pressure model for GPS satellites

    Science.gov (United States)

    Bar-Sever, Y.; Kuang, D.

    2003-04-01

    We derive a new and improved GPS solar pressure model by estimating model parameters using least square approximation to four and a half years of GPS precise orbit data. The new solar radiation model for Block IIR satellites provides 90% improvement over to the best pre-launch model, as measured by orbit fits and orbit prediction quality. The new model of Block II/IIA realizes a more modest improvement of the previous JPL empirical model. The empirical model is constructed as a set of Fourier functions of the Earth-Probe-Sun angle, to represent the solar radiation pressure forces in the coordinate system tied to the nominal solar panel surface orientation. The model derivation reveals a number of systematic patterns, some of which can be explained in terms of properties of the GPS attitude control system, and some are yet to be explained. Finally, we will discuss the overall orbit determination improvements using the new models.

  17. Simultaneous inference for model averaging of derived parameters

    DEFF Research Database (Denmark)

    Jensen, Signe Marie; Ritz, Christian

    2015-01-01

    Model averaging is a useful approach for capturing uncertainty due to model selection. Currently, this uncertainty is often quantified by means of approximations that do not easily extend to simultaneous inference. Moreover, in practice there is a need for both model averaging and simultaneous...... inference for derived parameters calculated in an after-fitting step. We propose a method for obtaining asymptotically correct standard errors for one or several model-averaged estimates of derived parameters and for obtaining simultaneous confidence intervals that asymptotically control the family...

  18. Large deflection of viscoelastic beams using fractional derivative model

    International Nuclear Information System (INIS)

    Bahranini, Seyed Masoud Sotoodeh; Eghtesad, Mohammad; Ghavanloo, Esmaeal; Farid, Mehrdad

    2013-01-01

    This paper deals with large deflection of viscoelastic beams using a fractional derivative model. For this purpose, a nonlinear finite element formulation of viscoelastic beams in conjunction with the fractional derivative constitutive equations has been developed. The four-parameter fractional derivative model has been used to describe the constitutive equations. The deflected configuration for a uniform beam with different boundary conditions and loads is presented. The effect of the order of fractional derivative on the large deflection of the cantilever viscoelastic beam, is investigated after 10, 100, and 1000 hours. The main contribution of this paper is finite element implementation for nonlinear analysis of viscoelastic fractional model using the storage of both strain and stress histories. The validity of the present analysis is confirmed by comparing the results with those found in the literature.

  19. Interpreting "Personality" Taxonomies: Why Previous Models Cannot Capture Individual-Specific Experiencing, Behaviour, Functioning and Development. Major Taxonomic Tasks Still Lay Ahead.

    Science.gov (United States)

    Uher, Jana

    2015-12-01

    As science seeks to make generalisations, a science of individual peculiarities encounters intricate challenges. This article explores these challenges by applying the Transdisciplinary Philosophy-of-Science Paradigm for Research on Individuals (TPS-Paradigm) and by exploring taxonomic "personality" research as an example. Analyses of researchers' interpretations of the taxonomic "personality" models, constructs and data that have been generated in the field reveal widespread erroneous assumptions about the abilities of previous methodologies to appropriately represent individual-specificity in the targeted phenomena. These assumptions, rooted in everyday thinking, fail to consider that individual-specificity and others' minds cannot be directly perceived, that abstract descriptions cannot serve as causal explanations, that between-individual structures cannot be isomorphic to within-individual structures, and that knowledge of compositional structures cannot explain the process structures of their functioning and development. These erroneous assumptions and serious methodological deficiencies in widely used standardised questionnaires have effectively prevented psychologists from establishing taxonomies that can comprehensively model individual-specificity in most of the kinds of phenomena explored as "personality", especially in experiencing and behaviour and in individuals' functioning and development. Contrary to previous assumptions, it is not universal models but rather different kinds of taxonomic models that are required for each of the different kinds of phenomena, variations and structures that are commonly conceived of as "personality". Consequently, to comprehensively explore individual-specificity, researchers have to apply a portfolio of complementary methodologies and develop different kinds of taxonomies, most of which have yet to be developed. Closing, the article derives some meta-desiderata for future research on individuals' "personality".

  20. Transcriptomic analysis in a Drosophila model identifies previously implicated and novel pathways in the therapeutic mechanism in neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Priyanka eSingh

    2011-03-01

    Full Text Available We have taken advantage of a newly described Drosophila model to gain insights into the potential mechanism of antiepileptic drugs (AEDs, a group of drugs that are widely used in the treatment of several neurological and psychiatric conditions besides epilepsy. In the recently described Drosophila model that is inspired by pentylenetetrazole (PTZ induced kindling epileptogenesis in rodents, chronic PTZ treatment for seven days causes a decreased climbing speed and an altered CNS transcriptome, with the latter mimicking gene expression alterations reported in epileptogenesis. In the model, an increased climbing speed is further observed seven days after withdrawal from chronic PTZ. We used this post-PTZ withdrawal regime to identify potential AED mechanism. In this regime, treatment with each of the five AEDs tested, namely, ethosuximide (ETH, gabapentin (GBP, vigabatrin (VGB, sodium valproate (NaVP and levetiracetam (LEV, resulted in rescuing of the altered climbing behavior. The AEDs also normalized PTZ withdrawal induced transcriptomic perturbation in fly heads; whereas AED untreated flies showed a large number of up- and down-regulated genes which were enriched in several processes including gene expression and cell communication, the AED treated flies showed differential expression of only a small number of genes that did not enrich gene expression and cell communication processes. Gene expression and cell communication related upregulated genes in AED untreated flies overrepresented several pathways - spliceosome, RNA degradation, and ribosome in the former category, and inositol phosphate metabolism, phosphatidylinositol signaling, endocytosis and hedgehog signaling in the latter. Transcriptome remodeling effect of AEDs was overall confirmed by microarray clustering that clearly separated the profiles of AED treated and untreated flies. Besides being consistent with previously implicated pathways, our results provide evidence for a role of

  1. CHAOS-2-a geomagnetic field model derived from one decade of continuous satellite data

    DEFF Research Database (Denmark)

    Olsen, Nils; Mandea, M.; Sabaka, T.J.

    2009-01-01

    We have derived a model of the near-Earth's magnetic field using more than 10 yr of high-precision geomagnetic measurements from the three satellites Orsted, CHAMP and SAC-C. This model is an update of the two previous models, CHAOS (Olsen et al. 2006) and xCHAOS (Olsen & Mandea 2008). Data...... coefficients up to n = 20 are described by order 5 splines (with 6-month knot spacing) spanning the years from 1997.0 to 2009.5. Compared to its predecessors, the temporal regularization of the CHAOS-2 model is also modified. Indeed, second and higher order time derivatives of the core field are damped...... by minimizing the second time derivative of the squared magnetic field intensity at the core-mantle boundary. The CHAOS-2 model describes rapid time changes, as monitored by the ground magnetic observatories, much better than its predecessors....

  2. Deriving the Dividend Discount Model in the Intermediate Microeconomics Class

    Science.gov (United States)

    Norman, Stephen; Schlaudraff, Jonathan; White, Karianne; Wills, Douglas

    2013-01-01

    In this article, the authors show that the dividend discount model can be derived using the basic intertemporal consumption model that is introduced in a typical intermediate microeconomics course. This result will be of use to instructors who teach microeconomics to finance students in that it demonstrates the value of utility maximization in…

  3. Vulnerable Derivatives and Good Deal Bounds: A Structural Model

    DEFF Research Database (Denmark)

    Murgoci, Agatha

    2013-01-01

    We price vulnerable derivatives -- i.e. derivatives where the counterparty may default. These are basically the derivatives traded on the over-the-counter (OTC) markets. Default is modeled in a structural framework. The technique employed for pricing is good deal bounds (GDBs). The method imposes...... can be obtained. We provide a link between the objective probability measure and the range of potential risk-neutral measures, which has an intuitive economic meaning. We also provide tight pricing bounds for European calls and show how to extend the call formula to pricing other financial products...

  4. An extended car-following model considering the acceleration derivative in some typical traffic environments

    Science.gov (United States)

    Zhou, Tong; Chen, Dong; Liu, Weining

    2018-03-01

    Based on the full velocity difference and acceleration car-following model, an extended car-following model is proposed by considering the vehicle’s acceleration derivative. The stability condition is given by applying the control theory. Considering some typical traffic environments, the results of theoretical analysis and numerical simulation show the extended model has a more actual acceleration of string vehicles than that of the previous models in starting process, stopping process and sudden brake. Meanwhile, the traffic jams more easily occur when the coefficient of vehicle’s acceleration derivative increases, which is presented by space-time evolution. The results confirm that the vehicle’s acceleration derivative plays an important role in the traffic jamming transition and the evolution of traffic congestion.

  5. Modelling the response of stable water isotopes in Greenland precipitation to orbital configurations of the previous interglacial

    Directory of Open Access Journals (Sweden)

    Jesper Sjolte

    2014-09-01

    Full Text Available The relation between δ 18O of precipitation and temperature has been used in numerous studies to reconstruct past temperatures at ice core sites in Greenland and Antarctica. During the past two decades, it has become clear that the slope between δ 18O and temperature varies in both space and time. Here, we use a general circulation model driven by changes in orbital parameters to investigate the Greenland δ 18O–temperature relation for the previous interglacial, the Eemian. In our analysis, we focus on changes in the moisture source regions, and the results underline the importance of taking the seasonality of climate change into account. The orbitally driven experiments show that continental evaporation over North America increases during summer in the warm parts of the Eemian, while marine evaporation decreases. This likely flattens the Greenland δ 18O response to temperature during summer. Since the main climate change in the experiments occurs during summer this adds to a limited response of δ 18O, which is more strongly tied to temperature during winter than during summer. A south–west to north–east gradient in the δ 18O–temperature slope is also evident for Greenland, with low slopes in the south–west and steeper slopes in the north–east. This probably reflects the proportion of continental moisture and Arctic moisture arriving in Greenland, with more continental moisture in the south–west and less in the north–east, and vice versa for the Arctic moisture.

  6. State-Space Modelling of Loudspeakers using Fractional Derivatives

    DEFF Research Database (Denmark)

    King, Alexander Weider; Agerkvist, Finn T.

    2015-01-01

    This work investigates the use of fractional order derivatives in modeling moving-coil loudspeakers. A fractional order state-space solution is developed, leading the way towards incorporating nonlinearities into a fractional order system. The method is used to calculate the response of a fractio......This work investigates the use of fractional order derivatives in modeling moving-coil loudspeakers. A fractional order state-space solution is developed, leading the way towards incorporating nonlinearities into a fractional order system. The method is used to calculate the response...... of a fractional harmonic oscillator, representing the mechanical part of a loudspeaker, showing the effect of the fractional derivative and its relationship to viscoelasticity. Finally, a loudspeaker model with a fractional order viscoelastic suspension and fractional order voice coil is fit to measurement data...

  7. Previous exercise training has a beneficial effect on renal and cardiovascular function in a model of diabetes.

    Directory of Open Access Journals (Sweden)

    Kleiton Augusto dos Santos Silva

    Full Text Available Exercise training (ET is an important intervention for chronic diseases such as diabetes mellitus (DM. However, it is not known whether previous exercise training intervention alters the physiological and medical complications of these diseases. We investigated the effects of previous ET on the progression of renal disease and cardiovascular autonomic control in rats with streptozotocin (STZ-induced DM. Male Wistar rats were divided into five groups. All groups were followed for 15 weeks. Trained control and trained diabetic rats underwent 10 weeks of exercise training, whereas previously trained diabetic rats underwent 14 weeks of exercise training. Renal function, proteinuria, renal sympathetic nerve activity (RSNA and the echocardiographic parameters autonomic modulation and baroreflex sensitivity (BRS were evaluated. In the previously trained group, the urinary albumin/creatinine ratio was reduced compared with the sedentary diabetic and trained diabetic groups (p<0.05. Additionally, RSNA was normalized in the trained diabetic and previously trained diabetic animals (p<0.05. The ejection fraction was increased in the previously trained diabetic animals compared with the diabetic and trained diabetic groups (p<0.05, and the myocardial performance index was improved in the previously trained diabetic group compared with the diabetic and trained diabetic groups (p<0.05. In addition, the previously trained rats had improved heart rate variability and BRS in the tachycardic response and bradycardic response in relation to the diabetic group (p<0.05. This study demonstrates that previous ET improves the functional damage that affects DM. Additionally, our findings suggest that the development of renal and cardiac dysfunction can be minimized by 4 weeks of ET before the induction of DM by STZ.

  8. Previous exercise training has a beneficial effect on renal and cardiovascular function in a model of diabetes.

    Science.gov (United States)

    Silva, Kleiton Augusto dos Santos; Luiz, Rafael da Silva; Rampaso, Rodolfo Rosseto; de Abreu, Nayda Parísio; Moreira, Édson Dias; Mostarda, Cristiano Teixeira; De Angelis, Kátia; de Paulo Castro Teixeira, Vicente; Irigoyen, Maria Cláudia; Schor, Nestor

    2012-01-01

    Exercise training (ET) is an important intervention for chronic diseases such as diabetes mellitus (DM). However, it is not known whether previous exercise training intervention alters the physiological and medical complications of these diseases. We investigated the effects of previous ET on the progression of renal disease and cardiovascular autonomic control in rats with streptozotocin (STZ)-induced DM. Male Wistar rats were divided into five groups. All groups were followed for 15 weeks. Trained control and trained diabetic rats underwent 10 weeks of exercise training, whereas previously trained diabetic rats underwent 14 weeks of exercise training. Renal function, proteinuria, renal sympathetic nerve activity (RSNA) and the echocardiographic parameters autonomic modulation and baroreflex sensitivity (BRS) were evaluated. In the previously trained group, the urinary albumin/creatinine ratio was reduced compared with the sedentary diabetic and trained diabetic groups (ptrained diabetic and previously trained diabetic animals (ptrained diabetic animals compared with the diabetic and trained diabetic groups (ptrained diabetic group compared with the diabetic and trained diabetic groups (ptrained rats had improved heart rate variability and BRS in the tachycardic response and bradycardic response in relation to the diabetic group (p<0.05). This study demonstrates that previous ET improves the functional damage that affects DM. Additionally, our findings suggest that the development of renal and cardiac dysfunction can be minimized by 4 weeks of ET before the induction of DM by STZ.

  9. A model for acoustic absorbent materials derived from coconut fiber

    Directory of Open Access Journals (Sweden)

    Ramis, J.

    2014-03-01

    Full Text Available In the present paper, a methodology is proposed for obtaining empirical equations describing the sound absorption characteristics of an absorbing material obtained from natural fibers, specifically from coconut. The method, which was previously applied to other materials, requires performing measurements of air-flow resistivity and of acoustic impedance for samples of the material under study. The equations that govern the acoustic behavior of the material are then derived by means of a least-squares fit of the acoustic impedance and of the propagation constant. These results can be useful since they allow the empirically obtained analytical equations to be easily incorporated in prediction and simulation models of acoustic systems for noise control that incorporate the studied materials.En este trabajo se describe el proceso seguido para obtener ecuaciones empíricas del comportamiento acústico de un material absorbente obtenido a partir de fibras naturales, concretamente el coco. El procedimiento, que ha sido ensayado con éxito en otros materiales, implica la realización de medidas de impedancia y resistencia al flujo de muestras del material bajo estudio. Las ecuaciones que gobiernan el comportamiento desde el punto de vista acústico del material se obtienen a partir del ajuste de ecuaciones de comportamiento de la impedancia acústica y la constante de propagación del material. Los resultados son útiles ya que, al disponer de ecuaciones analíticas obtenidas empíricamente, facilitan la incorporación de estos materiales en predicciones mediante métodos numéricos del comportamiento cuando son instalados formando parte de dispositivos para el control del ruido.

  10. Turbulence modeling with fractional derivatives: Derivation from first principles and initial results

    Science.gov (United States)

    Epps, Brenden; Cushman-Roisin, Benoit

    2017-11-01

    Fluid turbulence is an outstanding unsolved problem in classical physics, despite 120+ years of sustained effort. Given this history, we assert that a new mathematical framework is needed to make a transformative breakthrough. This talk offers one such framework, based upon kinetic theory tied to the statistics of turbulent transport. Starting from the Boltzmann equation and ``Lévy α-stable distributions'', we derive a turbulence model that expresses the turbulent stresses in the form of a fractional derivative, where the fractional order is tied to the transport behavior of the flow. Initial results are presented herein, for the cases of Couette-Poiseuille flow and 2D boundary layers. Among other results, our model is able to reproduce the logarithmic Law of the Wall in shear turbulence.

  11. Modeling and Forecasting Average Temperature for Weather Derivative Pricing

    Directory of Open Access Journals (Sweden)

    Zhiliang Wang

    2015-01-01

    Full Text Available The main purpose of this paper is to present a feasible model for the daily average temperature on the area of Zhengzhou and apply it to weather derivatives pricing. We start by exploring the background of weather derivatives market and then use the 62 years of daily historical data to apply the mean-reverting Ornstein-Uhlenbeck process to describe the evolution of the temperature. Finally, Monte Carlo simulations are used to price heating degree day (HDD call option for this city, and the slow convergence of the price of the HDD call can be found through taking 100,000 simulations. The methods of the research will provide a frame work for modeling temperature and pricing weather derivatives in other similar places in China.

  12. QSAR models for antioxidant activity of new coumarin derivatives.

    Science.gov (United States)

    Erzincan, P; Saçan, M T; Yüce-Dursun, B; Danış, Ö; Demir, S; Erdem, S S; Ogan, A

    2015-01-01

    This study presents 37 new antioxidant coumarin derivatives and strategies for structural modification to improve their antioxidant activities, the main ferric-reducing antioxidant power (FRAP) assay used to evaluate their antioxidant properties and the generation of validated quantitative structure-activity (antioxidant activity) relationship (QSAR) models. In an attempt to generate QSAR models, structures of all coumarin derivatives in the data set were fully optimized by semi-empirical PM6 method using SPARTAN 10 software. Descriptors were calculated by DRAGON 6.0 software. Multiple linear regression (MLR) models were developed with different training/test set combinations using QSARINS 2.2.1 software. Robustness, reliability and predictive power of the models were tested by internal and external validations. Applicability domain of the best two-descriptor model (nTR = 30; r(2) = 0.924; RMSETR = 0.213; nTEST = 7; r(2)ext = 0.887; RMSEext = 0.255; CCCext = 0.939) was determined. Descriptors appeared in the model revealed that complexity, H-bond donor and lipophilic character are important parameters in describing the antioxidant activity. Apart from the compounds in the data set, we also designed 31 new antioxidant coumarin derivatives and predicted their antioxidant activity using the best two-descriptor model. Most of these compounds are promising antioxidants.

  13. A Consistent Pricing Model for Index Options and Volatility Derivatives

    DEFF Research Database (Denmark)

    Kokholm, Thomas

    We propose a flexible modeling framework for the joint dynamics of an index and a set of forward variance swap rates written on this index. Our model reproduces various empirically observed properties of variance swap dynamics and enables volatility derivatives and options on the underlying index...... to be priced consistently, while allowing for jumps in volatility and returns. An affine specification using Lévy processes as building blocks leads to analytically tractable pricing formulas for volatility derivatives, such as VIX options, as well as efficient numerical methods for pricing of European options...... on the underlying asset. The model has the convenient feature of decoupling the vanilla skews from spot/volatility correlations and allowing for different conditional correlations in large and small spot/volatility moves. We show that our model can simultaneously fit prices of European options on S&P 500 across...

  14. A Consistent Pricing Model for Index Options and Volatility Derivatives

    DEFF Research Database (Denmark)

    Cont, Rama; Kokholm, Thomas

    2013-01-01

    We propose a flexible modeling framework for the joint dynamics of an index and a set of forward variance swap rates written on this index. Our model reproduces various empirically observed properties of variance swap dynamics and enables volatility derivatives and options on the underlying index...... to be priced consistently, while allowing for jumps in volatility and returns. An affine specification using Lévy processes as building blocks leads to analytically tractable pricing formulas for volatility derivatives, such as VIX options, as well as efficient numerical methods for pricing of European options...... on the underlying asset. The model has the convenient feature of decoupling the vanilla skews from spot/volatility correlations and allowing for different conditional correlations in large and small spot/volatility moves. We show that our model can simultaneously fit prices of European options on S&P 500 across...

  15. Modelling of the Blood Plasma Species of Biguanide Derivatives ...

    African Journals Online (AJOL)

    NJD

    Modelling of the Blood Plasma Species of. Biguanide Derivatives Exhibiting Potential as. Diagnostic Radiopharmaceuticals. Judith M. Wagenera*, Midred K. Dithebea, Daniel Moganob, Ignacy Cukrowskib and Jan Rijn Zeevaartc. aRadiochemistry, NECSA, P.O. Box 582, Pretoria 0001, South Africa. bDepartment of ...

  16. Microscopic Derivation of the Ginzburg-Landau Model

    DEFF Research Database (Denmark)

    Frank, Rupert; Hainzl, Christian; Seiringer, Robert

    2014-01-01

    We present a summary of our recent rigorous derivation of the celebrated Ginzburg-Landau (GL) theory, starting from the microscopic Bardeen-Cooper-Schrieffer (BCS) model. Close to the critical temperature, GL arises as an effective theory on the macroscopic scale. The relevant scaling limit...

  17. Modelling ocean-colour-derived chlorophyll a

    Directory of Open Access Journals (Sweden)

    S. Dutkiewicz

    2018-01-01

    Full Text Available This article provides a proof of concept for using a biogeochemical/ecosystem/optical model with a radiative transfer component as a laboratory to explore aspects of ocean colour. We focus here on the satellite ocean colour chlorophyll a (Chl a product provided by the often-used blue/green reflectance ratio algorithm. The model produces output that can be compared directly to the real-world ocean colour remotely sensed reflectance. This model output can then be used to produce an ocean colour satellite-like Chl a product using an algorithm linking the blue versus green reflectance similar to that used for the real world. Given that the model includes complete knowledge of the (model water constituents, optics and reflectance, we can explore uncertainties and their causes in this proxy for Chl a (called derived Chl a in this paper. We compare the derived Chl a to the actual model Chl a field. In the model we find that the mean absolute bias due to the algorithm is 22 % between derived and actual Chl a. The real-world algorithm is found using concurrent in situ measurement of Chl a and radiometry. We ask whether increased in situ measurements to train the algorithm would improve the algorithm, and find a mixed result. There is a global overall improvement, but at the expense of some regions, especially in lower latitudes where the biases increase. Not surprisingly, we find that region-specific algorithms provide a significant improvement, at least in the annual mean. However, in the model, we find that no matter how the algorithm coefficients are found there can be a temporal mismatch between the derived Chl a and the actual Chl a. These mismatches stem from temporal decoupling between Chl a and other optically important water constituents (such as coloured dissolved organic matter and detrital matter. The degree of decoupling differs regionally and over time. For example, in many highly seasonal regions, the timing of initiation

  18. A Consistent Pricing Model for Index Options and Volatility Derivatives

    DEFF Research Database (Denmark)

    Kokholm, Thomas

    We propose a flexible modeling framework for the joint dynamics of an index and a set of forward variance swap rates written on this index. Our model reproduces various empirically observed properties of variance swap dynamics and enables volatility derivatives and options on the underlying index...... on the underlying asset. The model has the convenient feature of decoupling the vanilla skews from spot/volatility correlations and allowing for different conditional correlations in large and small spot/volatility moves. We show that our model can simultaneously fit prices of European options on S&P 500 across...

  19. Derivation of Output Power of Induction Heater Model

    Directory of Open Access Journals (Sweden)

    Riyadh K. Chillab

    2016-12-01

    Full Text Available The work is concerned with the study of the single phase cylindrical induction heating systems and derive equation power. The presented analysis is analytical and a multi-layer model using cylindrical geometry which is used to obtain the theoretical results. To validate the theoretical results, a practical model is constructed, tested and the results are compared with the theoretical ones. Comparison showed that the adopted analytical method is efficient in describing the performance of such induction heater systems

  20. Empirically derived neighbourhood rules for urban land-use modelling

    DEFF Research Database (Denmark)

    Hansen, Henning Sten

    2012-01-01

    interaction between neighbouring land uses is an important component in urban cellular automata. Nevertheless, this component is often calibrated through trial-and-error estimation. The aim of this project has been to develop an empirically derived landscape metric supporting cellular-automata-based land......-use modelling. Through access to very detailed urban land-use data it has been possible to derive neighbourhood rules empirically, and test their sensitivity to the land-use classification applied, the regional variability of the rules, and their time variance. The developed methodology can be implemented...

  1. Operational derivation of Boltzmann distribution with Maxwell's demon model.

    Science.gov (United States)

    Hosoya, Akio; Maruyama, Koji; Shikano, Yutaka

    2015-11-24

    The resolution of the Maxwell's demon paradox linked thermodynamics with information theory through information erasure principle. By considering a demon endowed with a Turing-machine consisting of a memory tape and a processor, we attempt to explore the link towards the foundations of statistical mechanics and to derive results therein in an operational manner. Here, we present a derivation of the Boltzmann distribution in equilibrium as an example, without hypothesizing the principle of maximum entropy. Further, since the model can be applied to non-equilibrium processes, in principle, we demonstrate the dissipation-fluctuation relation to show the possibility in this direction.

  2. Evolution of Geometric Sensitivity Derivatives from Computer Aided Design Models

    Science.gov (United States)

    Jones, William T.; Lazzara, David; Haimes, Robert

    2010-01-01

    The generation of design parameter sensitivity derivatives is required for gradient-based optimization. Such sensitivity derivatives are elusive at best when working with geometry defined within the solid modeling context of Computer-Aided Design (CAD) systems. Solid modeling CAD systems are often proprietary and always complex, thereby necessitating ad hoc procedures to infer parameter sensitivity. A new perspective is presented that makes direct use of the hierarchical associativity of CAD features to trace their evolution and thereby track design parameter sensitivity. In contrast to ad hoc methods, this method provides a more concise procedure following the model design intent and determining the sensitivity of CAD geometry directly to its respective defining parameters.

  3. Modeling Temperature and Pricing Weather Derivatives Based on Temperature

    Directory of Open Access Journals (Sweden)

    Birhan Taştan

    2017-01-01

    Full Text Available This study first proposes a temperature model to calculate the temperature indices upon which temperature-based derivatives are written. The model is designed as a mean-reverting process driven by a Levy process to represent jumps and other features of temperature. Temperature indices are mainly measured as deviations from a base temperature, and, hence, the proposed model includes jumps because they may constitute an important part of this deviation for some locations. The estimated value of a temperature index and its distribution in this model apply an inversion formula to the temperature model. Second, this study develops a pricing process over calculated index values, which returns a customized price for temperature-based derivatives considering that temperature has unique effects on every economic entity. This personalized price is also used to reveal the trading behavior of a hypothesized entity in a temperature-based derivative trade with profit maximization as the objective. Thus, this study presents a new method that does not need to evaluate the risk-aversion behavior of any economic entity.

  4. A fractal derivative model for the characterization of anomalous diffusion in magnetic resonance imaging

    Science.gov (United States)

    Liang, Yingjie; Ye, Allen Q.; Chen, Wen; Gatto, Rodolfo G.; Colon-Perez, Luis; Mareci, Thomas H.; Magin, Richard L.

    2016-10-01

    Non-Gaussian (anomalous) diffusion is wide spread in biological tissues where its effects modulate chemical reactions and membrane transport. When viewed using magnetic resonance imaging (MRI), anomalous diffusion is characterized by a persistent or 'long tail' behavior in the decay of the diffusion signal. Recent MRI studies have used the fractional derivative to describe diffusion dynamics in normal and post-mortem tissue by connecting the order of the derivative with changes in tissue composition, structure and complexity. In this study we consider an alternative approach by introducing fractal time and space derivatives into Fick's second law of diffusion. This provides a more natural way to link sub-voxel tissue composition with the observed MRI diffusion signal decay following the application of a diffusion-sensitive pulse sequence. Unlike previous studies using fractional order derivatives, here the fractal derivative order is directly connected to the Hausdorff fractal dimension of the diffusion trajectory. The result is a simpler, computationally faster, and more direct way to incorporate tissue complexity and microstructure into the diffusional dynamics. Furthermore, the results are readily expressed in terms of spectral entropy, which provides a quantitative measure of the overall complexity of the heterogeneous and multi-scale structure of biological tissues. As an example, we apply this new model for the characterization of diffusion in fixed samples of the mouse brain. These results are compared with those obtained using the mono-exponential, the stretched exponential, the fractional derivative, and the diffusion kurtosis models. Overall, we find that the order of the fractal time derivative, the diffusion coefficient, and the spectral entropy are potential biomarkers to differentiate between the microstructure of white and gray matter. In addition, we note that the fractal derivative model has practical advantages over the existing models from the

  5. Differential geometry of viscoelastic models with fractional-order derivatives

    International Nuclear Information System (INIS)

    Yajima, Takahiro; Nagahama, Hiroyuki

    2010-01-01

    Viscoelastic materials with memory effect are studied based on the fractional rheonomic geometry. The geometric objects are regarded as basic quantities of fractional viscoelastic models, i.e. the metric tensor and torsion tensor are interpreted as the strain and the fractional strain rate, respectively. The generalized viscoelastic equations are expressed by the geometric objects. Especially, the basic constitutive equations such as Voigt and Maxwell models can be derived geometrically from the generalized equation. This leads to the fact that various viscoelastic models can be unified into one geometric expression.

  6. Relativistic nuclear matter with alternative derivative coupling models

    International Nuclear Information System (INIS)

    Delfino, A.; Coelho, C.T.; Malheiro, M.

    1994-01-01

    Effective Lagrangians involving nucleons coupled to scalar and vector fields are investigated within the framework of relativistic mean-field theory. The study presents the traditional Walecka model and different kinds of scalar derivative coupling suggested by Zimanyi and Moszkowski. The incompressibility (presented in an analytical form), scalar potential, and vector potential at the saturation point of nuclear matter are compared for these models. The real optical potential for the models are calculated and one of the models fits well the experimental curve from-50 to 400 MeV while also gives a soft equation of state. By varying the coupling constants and keeping the saturation point of nuclear matter approximately fixed, only the Walecka model presents a first order phase transition of finite temperature at zero density. (author)

  7. Novel Thiazole Derivatives of Medicinal Potential: Synthesis and Modeling

    Directory of Open Access Journals (Sweden)

    Nour E. A. Abdel-Sattar

    2017-01-01

    Full Text Available This paper reports on the synthesis of new thiazole derivatives that could be profitably exploited in medical treatment of tumors. Molecular electronic structures have been modeled within density function theory (DFT framework. Reactivity indices obtained from the frontier orbital energies as well as electrostatic potential energy maps are discussed and correlated with the molecular structure. X-ray crystallographic data of one of the new compounds is measured and used to support and verify the theoretical results.

  8. Initialization of a mesoscale model with satellite derived temperature profiles

    Science.gov (United States)

    Kalb, Michael W.

    1986-01-01

    The abilities of rawinsonde data and Tiros-N satellite derived temperature profile data to depict mesoscale precipitation accumulation are evaluated. Four mesoscale simulations using combinations of temperature, low-level wind, and low-level wind initialization were performed with the limited area mesoscale prediction system (LAMPS) model. Comparisons of the simulations with operational LFM forecast accumulations reveal that the LAMPS model simulations provide a better depiction of the observed precipitation accumulation than the LFM forecasts, and the satellite temperature profiles produce better mesoscale precipitation accumulation forecasts than the rawinsonde temperature data.

  9. Per-Oral Endoscopic Myotomy (POEM) After Previous Laparoscopic Heller Myotomy Is Feasible and Safe in a Porcine Model.

    Science.gov (United States)

    Miles, Luke F; Frelich, Matthew J; Gould, Jon C; Dua, Kulwinder S; Jensen, Eric S; Kastenmeier, Andrew S

    2015-10-01

    We sought to evaluate the feasibility, safety, and difficulty of performing the per-oral endoscopic myotomy (POEM) procedure in the setting of a prior Heller myotomy using a survival porcine model. Four pigs underwent laparoscopic Heller myotomy with Dor partial anterior fundoplication followed by the POEM performed 4 weeks later. Two additional pigs served as controls, undergoing only the POEM. All procedures were completed without complications. The revisional POEM was not significantly more difficult than POEM controls based on procedure time, POEM procedure components, or procedure difficulty scores. Revisional POEM had a longer mean operative time when compared with Heller myotomy (126.0 vs. 83.8 min; Pmyotomy is safe and feasible in the porcine model and has potential as an option for patients suffering from recurrent or persistent symptoms after failed surgical myotomy.

  10. Use of a PBPK model with dose-dependent elimination rates predicts higher peak dioxin exposures than previously estimated

    Energy Technology Data Exchange (ETDEWEB)

    Emond, C. [NRC, NAS, WA, DC (United States); Michalek, J.E. [Air Force Research Lab., Brooks City-Base, TX (United States); Birnbaum, L.S.; DeVito, M.J. [PKB, ETD, ORD, NHEERL U.S. EPA, RTP, NC (United States)

    2004-09-15

    Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with increased risk for cancer, diabetes and reproductive toxicities in numerous epidemiological studies. Several of these studies base exposure estimates on measurements of blood levels years after the accidental or occupational exposures. Peak exposures have been estimated in these studies assuming a mono or biphasic elimination rate for TCDD, with estimates of half-life ranging from 5 to 12 years. Recent clinical studies suggest that the elimination rate of TCDD is dose dependent. To address this question a physiologically based pharmacokinetic (PBPK) model can be used to predict the concentration of TCDD with a dose-dependent elimination rate. The aims of this study were to validate a dose-dependent elimination rate by using a PBPK model and to adequately predict the concentration of TCDD shortly after the exposure.

  11. QSAR MODELING OF ANTIBACTERIAL ACTIVITY OF SOME BENZIMIDAZOLE DERIVATIVES

    Directory of Open Access Journals (Sweden)

    SANJA O. PODUNAVAC-KUZMANOVIĆ

    2011-03-01

    Full Text Available A quantitative structure-activity relationship (QSAR study has been carried out for a training set of 12 benzimidazole derivatives to correlate and predict the antibacterial activity of studied compounds against Gram-negative bacteria Pseudomonas aeruginosa. Multiple linear regression was used to select the descriptors and to generate the best prediction model that relates the structural features to inhibitory activity. The predictivity of the model was estimated by cross-validation with the leave-one-out method. Our results suggest a QSAR model based on the following descriptors: parameter of lipophilicity (logP and hydration energy (HE. Good agreement between experimental and predicted inhibitory values, obtained in the validation procedure, indicated the good quality of the generated QSAR model.

  12. COMPARISON OF HUMAN ADIPOSE-DERIVED STEM CELLS AND BONE MARROW-DERIVED STEM CELLS IN A MYOCARDIAL INFARCTION MODEL

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Holst-Hansen, Claus

    2012-01-01

    Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... randomised to receive intramyocardial injections of adipose-derived stem cells, bone marrow derived mesenchymal stem cells or phosphate-buffered saline one week following induction of myocardial infarction. Results: After four weeks, left ventricular ejection fraction was improved in the adipose-derived stem...

  13. Modeling Human Cardiac Hypertrophy in Stem Cell-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Ekaterina Ovchinnikova

    2018-03-01

    Full Text Available Summary: Cardiac hypertrophy accompanies many forms of cardiovascular diseases. The mechanisms behind the development and regulation of cardiac hypertrophy in the human setting are poorly understood, which can be partially attributed to the lack of a human cardiomyocyte-based preclinical test system recapitulating features of diseased myocardium. The objective of our study is to determine whether human embryonic stem cell-derived cardiomyocytes (hESC-CMs subjected to mechanical stretch can be used as an adequate in vitro model for studying molecular mechanisms of cardiac hypertrophy. We show that hESC-CMs subjected to cyclic stretch, which mimics mechanical overload, exhibit essential features of a hypertrophic state on structural, functional, and gene expression levels. The presented hESC-CM stretch approach provides insight into molecular mechanisms behind mechanotransduction and cardiac hypertrophy and lays groundwork for the development of pharmacological approaches as well as for discovering potential circulating biomarkers of cardiac dysfunction. : In this article, Berezikov, van der Meer, and colleagues used stem cell-derived cardiomyocytes to model human cardiac hypertrophy. Their approach provides novel insights into molecular mechanisms behind mechanotransduction and cardiac hypertrophy and lays groundwork for the development of new pharmacological approaches as well as for discovering new potential circulating biomarkers of cardiac dysfunction. Keywords: stem cells, human cardiomyocytes, hypertrophy, in vitro disease modeling, cardiomyocytes stretch response, mechanotransduction

  14. Deriving a model for influenza epidemics from historical data.

    Energy Technology Data Exchange (ETDEWEB)

    Ray, Jaideep; Lefantzi, Sophia

    2011-09-01

    In this report we describe how we create a model for influenza epidemics from historical data collected from both civilian and military societies. We derive the model when the population of the society is unknown but the size of the epidemic is known. Our interest lies in estimating a time-dependent infection rate to within a multiplicative constant. The model form fitted is chosen for its similarity to published models for HIV and plague, enabling application of Bayesian techniques to discriminate among infectious agents during an emerging epidemic. We have developed models for the progression of influenza in human populations. The model is framed as a integral, and predicts the number of people who exhibit symptoms and seek care over a given time-period. The start and end of the time period form the limits of integration. The disease progression model, in turn, contains parameterized models for the incubation period and a time-dependent infection rate. The incubation period model is obtained from literature, and the parameters of the infection rate are fitted from historical data including both military and civilian populations. The calibrated infection rate models display a marked difference in which the 1918 Spanish Influenza pandemic differed from the influenza seasons in the US between 2001-2008 and the progression of H1N1 in Catalunya, Spain. The data for the 1918 pandemic was obtained from military populations, while the rest are country-wide or province-wide data from the twenty-first century. We see that the initial growth of infection in all cases were about the same; however, military populations were able to control the epidemic much faster i.e., the decay of the infection-rate curve is much higher. It is not clear whether this was because of the much higher level of organization present in a military society or the seriousness with which the 1918 pandemic was addressed. Each outbreak to which the influenza model was fitted yields a separate set of

  15. Mathematical modeling of wastewater-derived biodegradable dissolved organic nitrogen.

    Science.gov (United States)

    Simsek, Halis

    2016-11-01

    Wastewater-derived dissolved organic nitrogen (DON) typically constitutes the majority of total dissolved nitrogen (TDN) discharged to surface waters from advanced wastewater treatment plants (WWTPs). When considering the stringent regulations on nitrogen discharge limits in sensitive receiving waters, DON becomes problematic and needs to be reduced. Biodegradable DON (BDON) is a portion of DON that is biologically degradable by bacteria when the optimum environmental conditions are met. BDON in a two-stage trickling filter WWTP was estimated using artificial intelligence techniques, such as adaptive neuro-fuzzy inference systems, multilayer perceptron, radial basis neural networks (RBNN), and generalized regression neural networks. Nitrite, nitrate, ammonium, TDN, and DON data were used as input neurons. Wastewater samples were collected from four different locations in the plant. Model performances were evaluated using root mean square error, mean absolute error, mean bias error, and coefficient of determination statistics. Modeling results showed that the R(2) values were higher than 0.85 in all four models for all wastewater samples, except only R(2) in the final effluent sample for RBNN modeling was low (0.52). Overall, it was found that all four computing techniques could be employed successfully to predict BDON.

  16. Derivation of Event-B Models from OWL Ontologies

    Directory of Open Access Journals (Sweden)

    Alkhammash Eman H.

    2016-01-01

    Full Text Available The derivation of formal specifications from large and complex requirements is a key challenge in systems engineering. In this paper we present an approach that aims to address this challenge by building formal models from OWL ontologies. An ontology is used in the field of knowledge representation to capture a clear view of the domain and to produce a concise and unambiguous set of domain requirements. We harness the power of ontologies to handle inconsistency of domain requirements and produce clear, concise and unambiguous set of domain requirements for Event-B modelling. The proposed approach works by generating Attempto Controlled English (ACE from the OWL ontology and then maps the ACE requirements to develop Event-B models. ACE is a subset of English that can be unambiguously translated into first-order logic. There is an injective mapping between OWL ontology and a subset of ACE. ACE is a suitable interlingua for producing the mapping between OWL and Event-B models for many reasons. Firstly, ACE is easy to learn and understand, it hides the math of OWL and would be natural to use by everybody. Secondly ACE has a parser that converts ACE texts into Discourse Representation Structures (DRS. Finally, ACE can be extended to target a richer syntactic subset of Event-B which ultimately would facilitate the translation of ACE requirements to Event-B.

  17. MSC-derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune Murine Models: Type 1 Diabetes and Uveoretinitis

    Directory of Open Access Journals (Sweden)

    Taeko Shigemoto-Kuroda

    2017-05-01

    Full Text Available Accumulating evidence shows that extracellular vesicles (EVs produced by mesenchymal stem/stromal cells (MSCs exert their therapeutic effects in several disease models. We previously demonstrated that MSCs suppress autoimmunity in models of type 1 diabetes (T1D and experimental autoimmune uveoretinitis (EAU. Therefore, here, we investigated the therapeutic potential of MSC-derived EVs using our established mouse models for autoimmune diseases affecting the pancreas and the eye: T1D and EAU. The data demonstrate that MSC-derived EVs effectively prevent the onset of disease in both T1D and EAU. In addition, the mixed lymphocyte reaction assay with MSC-derived EVs indicated that EVs inhibit activation of antigen-presenting cells and suppress development of T helper 1 (Th1 and Th17 cells. These results raise the possibility that MSC-derived EVs may be an alternative to cell therapy for autoimmune disease prevention.

  18. Game Theory for Speculative Derivatives: A Possible Stabilizing Regulatory Model

    Directory of Open Access Journals (Sweden)

    Francesco Musolino

    2012-10-01

    Full Text Available The aim of this paper is to propose a methodology to stabilize the financial markets using Game Theory, specifically the Complete Study of a Differentiable Game. Initially, we intend to make a quick discussion of peculiarities and recent development of derivatives, and then we move on to the main topic of the paper: forwards and futures. We illustrate their pricing and the functioning of markets for this particular derivatives type. We also will examine the short or long hedging strategies, used by companies to try to cancel the risk associated with market variables. At this purpose, we present a game theory model. Specifically, we focus on two economic operators: a real economic subject and a financial institute (a bank, for example with a big economic availability. For this purpose, we discuss about an interaction between the two above economic subjects: the Enterprise, our first player, and the Financial Institute, our second player. We propose a tax on financial transactions with speculative purposes in order to stabilize the financial market, protecting it from speculations. This tax hits only the speculative profits and we find a cooperative solution that allows, however, both players to obtain a gain.

  19. Comparing pharmacophore models derived from crystallography and NMR ensembles

    Science.gov (United States)

    Ghanakota, Phani; Carlson, Heather A.

    2017-11-01

    NMR and X-ray crystallography are the two most widely used methods for determining protein structures. Our previous study examining NMR versus X-Ray sources of protein conformations showed improved performance with NMR structures when used in our Multiple Protein Structures (MPS) method for receptor-based pharmacophores (Damm, Carlson, J Am Chem Soc 129:8225-8235, 2007). However, that work was based on a single test case, HIV-1 protease, because of the rich data available for that system. New data for more systems are available now, which calls for further examination of the effect of different sources of protein conformations. The MPS technique was applied to Growth factor receptor bound protein 2 (Grb2), Src SH2 homology domain (Src-SH2), FK506-binding protein 1A (FKBP12), and Peroxisome proliferator-activated receptor-γ (PPAR-γ). Pharmacophore models from both crystal and NMR ensembles were able to discriminate between high-affinity, low-affinity, and decoy molecules. As we found in our original study, NMR models showed optimal performance when all elements were used. The crystal models had more pharmacophore elements compared to their NMR counterparts. The crystal-based models exhibited optimum performance only when pharmacophore elements were dropped. This supports our assertion that the higher flexibility in NMR ensembles helps focus the models on the most essential interactions with the protein. Our studies suggest that the "extra" pharmacophore elements seen at the periphery in X-ray models arise as a result of decreased protein flexibility and make very little contribution to model performance.

  20. Comparison of digital elevation models and relevant derived attributes

    Science.gov (United States)

    Li, Xinchuan; Zhang, Youjing; Jin, Xiuliang; He, Qiaoning; Zhang, Xiuping

    2017-10-01

    The digital elevation model (DEM) and its derivative attributes are important parameters for evaluating any process using digital terrain analysis. Five freely available global DEM products including Advanced Spaceborne Thermal Emission and Reflection Radiometer-Global Digital Elevation Model version 2 (ASTER GDEM2), Shuttle Radar Topographic Mission version 4.1 (SRTM V4.1), Global Multiresolution Terrain Elevation Data 2010 (GMTED2010), EarthEnv-DEM90, and Global 30 Arc-Second Elevation (GTOPO30) were assessed in this study. The objective of this study was to compare the differences of elevations, slopes, and topographic wetness indices (TWIs) derived from these five DEM products. SRTM V4.1 showed a better accuracy [root mean square error (RMSE)=4.87 m] than ASTER GDEM2 (RMSE=7.08 m) based on ICESat/GLAS (the Ice, Cloud, and land Elevation Satellite/Geoscience Laser Altimeter System) laser altimetry points. ICESat/GLAS data were then selected as the benchmark to rectify the SRTM V4.1 data using the simple kriging (SK) interpolation method. The corrected high-accuracy SRTM V4.1 data (RMSE=1.14 m) were then regarded as the reference data. EarthEnv-DEM90 displayed the best accuracy in the DEM and slope, whereas the TWI accuracy of GMTED2010 was best. The accuracy of topographic attributes was sensitive to the roughness of the terrain. DEM and slope displayed a larger error variance as the elevation increased. DEM was sensitive to the data source and slope was sensitive to the data source and spatial resolution. TWI was influenced by data source and spatial resolution. As the spatial resolution decreased, the differences of topographic attributes tended to decrease.

  1. Protein model discrimination using mutational sensitivity derived from deep sequencing.

    Science.gov (United States)

    Adkar, Bharat V; Tripathi, Arti; Sahoo, Anusmita; Bajaj, Kanika; Goswami, Devrishi; Chakrabarti, Purbani; Swarnkar, Mohit K; Gokhale, Rajesh S; Varadarajan, Raghavan

    2012-02-08

    A major bottleneck in protein structure prediction is the selection of correct models from a pool of decoys. Relative activities of ∼1,200 individual single-site mutants in a saturation library of the bacterial toxin CcdB were estimated by determining their relative populations using deep sequencing. This phenotypic information was used to define an empirical score for each residue (RankScore), which correlated with the residue depth, and identify active-site residues. Using these correlations, ∼98% of correct models of CcdB (RMSD ≤ 4Å) were identified from a large set of decoys. The model-discrimination methodology was further validated on eleven different monomeric proteins using simulated RankScore values. The methodology is also a rapid, accurate way to obtain relative activities of each mutant in a large pool and derive sequence-structure-function relationships without protein isolation or characterization. It can be applied to any system in which mutational effects can be monitored by a phenotypic readout. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Vegetation root zone storage and rooting depth, derived from local calibration of a global hydrological model

    Science.gov (United States)

    van der Ent, R.; Van Beek, R.; Sutanudjaja, E.; Wang-Erlandsson, L.; Hessels, T.; Bastiaanssen, W.; Bierkens, M. F.

    2017-12-01

    The storage and dynamics of water in the root zone control many important hydrological processes such as saturation excess overland flow, interflow, recharge, capillary rise, soil evaporation and transpiration. These processes are parameterized in hydrological models or land-surface schemes and the effect on runoff prediction can be large. Root zone parameters in global hydrological models are very uncertain as they cannot be measured directly at the scale on which these models operate. In this paper we calibrate the global hydrological model PCR-GLOBWB using a state-of-the-art ensemble of evaporation fields derived by solving the energy balance for satellite observations. We focus our calibration on the root zone parameters of PCR-GLOBWB and derive spatial patterns of maximum root zone storage. We find these patterns to correspond well with previous research. The parameterization of our model allows for the conversion of maximum root zone storage to root zone depth and we find that these correspond quite well to the point observations where available. We conclude that climate and soil type should be taken into account when regionalizing measured root depth for a certain vegetation type. We equally find that using evaporation rather than discharge better allows for local adjustment of root zone parameters within a basin and thus provides orthogonal data to diagnose and optimize hydrological models and land surface schemes.

  3. DFT application for chlorin derivatives photosensitizer drugs modeling

    Science.gov (United States)

    Machado, Neila; Carvalho, B. G.; Téllez Soto, C. A.; Martin, A. A.; Favero, P. P.

    2018-04-01

    Photodynamic therapy is an alternative form of cancer treatment that meets the desire for a less aggressive approach to the body. It is based on the interaction between a photosensitizer, activating light, and molecular oxygen. This interaction results in a cascade of reactions that leads to localized cell death. Many studies have been conducted to discover an ideal photosensitizer, which aggregates all the desirable characteristics of a potent cell killer and generates minimal side effects. Using Density Functional Theory (DFT) implemented in the program Vienna Ab-initio Simulation Package, new chlorin derivatives with different functional groups were simulated to evaluate the different absorption wavelengths to permit resonant absorption with the incident laser. Gaussian 09 program was used to determine vibrational wave numbers and Natural Bond Orbitals. The chosen drug with the best characteristics for the photosensitizer was a modified model of the original chlorin, which was called as Thiol chlorin. According to our calculations it is stable and is 19.6% more efficient at optical absorption in 708 nm in comparison to the conventional chlorin e6. Vibrational modes, optical and electronic properties were predicted. In conclusion, this study is an attempt to improve the development of new photosensitizer drugs through computational methods that save time and contribute to decrease the numbers of animals for model application.

  4. Modeling bleaching of tomato derivatives at subzero temperatures.

    Science.gov (United States)

    Manzocco, Lara; Calligaris, Sonia; Nicoli, Maria Cristina

    2006-02-22

    This work was addressed to obtain a predictive model of the rate of bleaching in tomato derivatives at subzero temperatures. To this aim, a tomato puree was freeze-dried and equilibrated at increasing solid fractions. The bleaching rate was assessed by measuring tomato color during storage for up to 18 months at temperatures from -30 to 0 degrees C. The temperature dependence of the tomato-bleaching rate was neither predictable using the Arrhenius equation nor simply related to tomato physical state. The lack of a clear Arrhenius relation was attributed to the occurrence of temperature-dependent phenomena, such as ice crystallization and oxygen solubility modifications, which strongly changed the local concentration of reactants. A modified Arrhenius equation predicting the tomato-bleaching rate in the entire temperature range was proposed. Tomato concentration, and hence its physical state, affected the temperature dependence of bleaching, modifying apparent activation energy and frequency factor of the modified Arrhenius equation. In light of these considerations, a mathematical model was set up and validated to accurately predict the tomato-bleaching rate on the basis of only its concentration and storage temperature.

  5. Estimation efficiency of usage satellite derived and modelled biophysical products for yield forecasting

    Science.gov (United States)

    Kolotii, Andrii; Kussul, Nataliia; Skakun, Sergii; Shelestov, Andrii; Ostapenko, Vadim; Oliinyk, Tamara

    2015-04-01

    Efficient and timely crop monitoring and yield forecasting are important tasks for ensuring of stability and sustainable economic development [1]. As winter crops pay prominent role in agriculture of Ukraine - the main focus of this study is concentrated on winter wheat. In our previous research [2, 3] it was shown that usage of biophysical parameters of crops such as FAPAR (derived from Geoland-2 portal as for SPOT Vegetation data) is far more efficient for crop yield forecasting to NDVI derived from MODIS data - for available data. In our current work efficiency of usage such biophysical parameters as LAI, FAPAR, FCOVER (derived from SPOT Vegetation and PROBA-V data at resolution of 1 km and simulated within WOFOST model) and NDVI product (derived from MODIS) for winter wheat monitoring and yield forecasting is estimated. As the part of crop monitoring workflow (vegetation anomaly detection, vegetation indexes and products analysis) and yield forecasting SPIRITS tool developed by JRC is used. Statistics extraction is done for landcover maps created in SRI within FP-7 SIGMA project. Efficiency of usage satellite based and modelled with WOFOST model biophysical products is estimated. [1] N. Kussul, S. Skakun, A. Shelestov, O. Kussul, "Sensor Web approach to Flood Monitoring and Risk Assessment", in: IGARSS 2013, 21-26 July 2013, Melbourne, Australia, pp. 815-818. [2] F. Kogan, N. Kussul, T. Adamenko, S. Skakun, O. Kravchenko, O. Kryvobok, A. Shelestov, A. Kolotii, O. Kussul, and A. Lavrenyuk, "Winter wheat yield forecasting in Ukraine based on Earth observation, meteorological data and biophysical models," International Journal of Applied Earth Observation and Geoinformation, vol. 23, pp. 192-203, 2013. [3] Kussul O., Kussul N., Skakun S., Kravchenko O., Shelestov A., Kolotii A, "Assessment of relative efficiency of using MODIS data to winter wheat yield forecasting in Ukraine", in: IGARSS 2013, 21-26 July 2013, Melbourne, Australia, pp. 3235 - 3238.

  6. PREVIOUS SECOND TRIMESTER ABORTION

    African Journals Online (AJOL)

    PNLC

    PREVIOUS SECOND TRIMESTER ABORTION: A risk factor for third trimester uterine rupture in three ... for accurate diagnosis of uterine rupture. KEY WORDS: Induced second trimester abortion - Previous uterine surgery - Uterine rupture. ..... scarred uterus during second trimester misoprostol- induced labour for a missed ...

  7. Derivation of a Clinical Model to Predict Unchanged Inpatient Echocardiograms.

    Science.gov (United States)

    Gunderson, Craig G; Gromisch, Elizabeth S; Chang, John J; Malm, Brian J

    2018-03-01

    Transthoracic echocardiography (TTE) is one of the most commonly ordered tests in healthcare. Repeat TTE, defined as a TTE done within 1 year of a prior TTE, represents 24% to 42% of all studies. The purpose of this study was to derive a clinical prediction model to predict unchanged repeat TTE, with the goal of defining a subset of studies that are unnecessary. Single-center retrospective cohort study of all hospitalized patients who had a repeat TTE between October 1, 2013, and September 30, 2014. Two hundred eleven of 601 TTEs were repeat studies, of which 78 (37%) had major changes. Five variables were independent predictors of major new TTE changes, including history of intervening acute myocardial infarction, cardiothoracic surgery, major new electrocardiogram (ECG) changes, prior valve disease, and chronic kidney disease. Using the β-coefficient for each of these variables, we defined a clinical prediction model that we named the CAVES score. The acronym CAVES stands for chronic kidney disease, acute myocardial infarction, valvular disease, ECG changes, and surgery (cardiac). The prevalence of major TTE change for the full cohort was 35%. For the group with a CAVES score of -1, that probability was only 5.6%; for the group with a score of 0, the probability was 17.7%; and for the group with a score ≥1, the probability was 55.3%. The bootstrap corrected C statistic for the model was 0.78 (95% confidence interval, 0.72-0.85), indicating good discrimination. Overall, the CAVES score had good discrimination and calibration. If further validated, it may be useful to predict repeat TTEs that are unlikely to have major changes.

  8. Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Gun-Sik Cho

    2017-01-01

    Full Text Available Pluripotent stem cells (PSCs offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs. Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which manifests predominantly in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases.

  9. Rescue of neural crest-derived phenotypes in a zebrafish CHARGE model by Sox10 downregulation

    Science.gov (United States)

    Asad, Zainab; Pandey, Aditi; Babu, Aswini; Sun, Yuhan; Shevade, Kaivalya; Kapoor, Shruti; Ullah, Ikram; Ranjan, Shashi; Scaria, Vinod; Bajpai, Ruchi; Sachidanandan, Chetana

    2016-01-01

    CHD7 mutations are implicated in a majority of cases of the congenital disorder, CHARGE syndrome. CHARGE, an autosomal dominant syndrome, is known to affect multiple tissues including eye, heart, ear, craniofacial nerves and skeleton and genital organs. Using a morpholino-antisense-oligonucleotide-based zebrafish model for CHARGE syndrome, we uncover a complex spectrum of abnormalities in the neural crest and the crest-derived cell types. We report for the first time, defects in myelinating Schwann cells, enteric neurons and pigment cells in a CHARGE model. We also observe defects in the specification of peripheral neurons and the craniofacial skeleton as previously reported. Chd7 morphants have impaired migration of neural crest cells and deregulation of sox10 expression from the early stages. Knocking down Sox10 in the zebrafish CHARGE model rescued the defects in Schwann cells and craniofacial cartilage. Our zebrafish CHARGE model thus reveals important regulatory roles for Chd7 at multiple points of neural crest development viz., migration, fate choice and differentiation and we suggest that sox10 deregulation is an important driver of the neural crest-derived aspects of Chd7 dependent CHARGE syndrome. PMID:27418670

  10. Gravity field models derived from Swarm GPS data

    Science.gov (United States)

    Teixeira da Encarnação, João; Arnold, Daniel; Bezděk, Aleš; Dahle, Christoph; Doornbos, Eelco; van den IJssel, Jose; Jäggi, Adrian; Mayer-Gürr, Torsten; Sebera, Josef; Visser, Pieter; Zehentner, Norbert

    2017-04-01

    The Swarm satellites, with primary mission to measure Earth's Magnetic Field, continue to provide high-quality hl-SST data. We use these data to derive the time-varying gravity field of the Earth up to Spherical Harmonic degree and order 12, on a monthly basis since December 2013. We combine the gravity field solutions computed with the data of all three satellites, as provided by a number of institutes, namely at the Astronomical Institute (ASU) of the Czech Academy of Sciences (Bezděk et al., 2016), the Astronomical Institute of the University of Bern (AIUB, Jäggi et al., 2016) and the Institute of Geodesy (IfG) of the Graz University of Technology (Zehentner et al., 2015) and demonstrate that this uninterrupted time series of gravity field models are in good agreement with the temporal variations observed by the GRACE satellites. Therefore, these data can be used to study large-scale mass changes globally, e.g. i) in the context of low-latency applications, such as the European Gravity Service for Improved Emergency Management project (http://egsiem.eu), ii) in those months where GRACE solutions are not available, and iii) as an important source of independent information for mitigating the GRACE/GRACE Follow-On gap.

  11. Modeling marbled murrelet (Brachyramphus marmoratus) habitat using LiDAR-derived canopy data

    Science.gov (United States)

    Hagar, Joan C.; Eskelson, Bianca N.I.; Haggerty, Patricia K.; Nelson, S. Kim; Vesely, David G.

    2014-01-01

    LiDAR (Light Detection And Ranging) is an emerging remote-sensing tool that can provide fine-scale data describing vertical complexity of vegetation relevant to species that are responsive to forest structure. We used LiDAR data to estimate occupancy probability for the federally threatened marbled murrelet (Brachyramphus marmoratus) in the Oregon Coast Range of the United States. Our goal was to address the need identified in the Recovery Plan for a more accurate estimate of the availability of nesting habitat by developing occupancy maps based on refined measures of nest-strand structure. We used murrelet occupancy data collected by the Bureau of Land Management Coos Bay District, and canopy metrics calculated from discrete return airborne LiDAR data, to fit a logistic regression model predicting the probability of occupancy. Our final model for stand-level occupancy included distance to coast, and 5 LiDAR-derived variables describing canopy structure. With an area under the curve value (AUC) of 0.74, this model had acceptable discrimination and fair agreement (Cohen's κ = 0.24), especially considering that all sites in our sample were regarded by managers as potential habitat. The LiDAR model provided better discrimination between occupied and unoccupied sites than did a model using variables derived from Gradient Nearest Neighbor maps that were previously reported as important predictors of murrelet occupancy (AUC = 0.64, κ = 0.12). We also evaluated LiDAR metrics at 11 known murrelet nest sites. Two LiDAR-derived variables accurately discriminated nest sites from random sites (average AUC = 0.91). LiDAR provided a means of quantifying 3-dimensional canopy structure with variables that are ecologically relevant to murrelet nesting habitat, and have not been as accurately quantified by other mensuration methods.

  12. Mapping vulnerability of multiple aquifers using multiple models and fuzzy logic to objectively derive model structures.

    Science.gov (United States)

    Nadiri, Ata Allah; Sedghi, Zahra; Khatibi, Rahman; Gharekhani, Maryam

    2017-09-01

    Driven by contamination risks, mapping Vulnerability Indices (VI) of multiple aquifers (both unconfined and confined) is investigated by integrating the basic DRASTIC framework with multiple models overarched by Artificial Neural Networks (ANN). The DRASTIC framework is a proactive tool to assess VI values using the data from the hydrosphere, lithosphere and anthroposphere. However, a research case arises for the application of multiple models on the ground of poor determination coefficients between the VI values and non-point anthropogenic contaminants. The paper formulates SCFL models, which are derived from the multiple model philosophy of Supervised Committee (SC) machines and Fuzzy Logic (FL) and hence SCFL as their integration. The Fuzzy Logic-based (FL) models include: Sugeno Fuzzy Logic (SFL), Mamdani Fuzzy Logic (MFL), Larsen Fuzzy Logic (LFL) models. The basic DRASTIC framework uses prescribed rating and weighting values based on expert judgment but the four FL-based models (SFL, MFL, LFL and SCFL) derive their values as per internal strategy within these models. The paper reports that FL and multiple models improve considerably on the correlation between the modeled vulnerability indices and observed nitrate-N values and as such it provides evidence that the SCFL multiple models can be an alternative to the basic framework even for multiple aquifers. The study area with multiple aquifers is in Varzeqan plain, East Azerbaijan, northwest Iran. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. A model composition for Mars derived from the oxygen isotopic ratios of martian/SNC meteorites. [Abstract only

    Science.gov (United States)

    Delaney, J. S.

    1994-01-01

    Oxygen is the most abundant element in most meteorites, yet the ratios of its isotopes are seldom used to constrain the compositional history of achondrites. The two major achondrite groups have O isotope signatures that differ from any plausible chondritic precursors and lie between the ordinary and carbonaceous chondrite domains. If the assumption is made that the present global sampling of chondritic meteorites reflects the variability of O reservoirs at the time of planetessimal/planet aggregation in the early nebula, then the O in these groups must reflect mixing between known chondritic reservoirs. This approach, in combination with constraints based on Fe-Mn-Mg systematics, has been used previously to model the composition of the basaltic achondrite parent body (BAP) and provides a model precursor composition that is generally consistent with previous eucrite parent body (EPB) estimates. The same approach is applied to Mars exploiting the assumption that the SNC and related meteorites sample the martian lithosphere. Model planet and planetesimal compositions can be derived by mixing of known chondritic components using O isotope ratios as the fundamental compositional constraint. The major- and minor-element composition for Mars derived here and that derived previously for the basaltic achondrite parent body are, in many respects, compatible with model compositions generated using completely independent constraints. The role of volatile elements and alkalis in particular remains a major difficulty in applying such models.

  14. Currents, HF Radio-derived, SF Bay Outlet, Normal Model, Zonal, EXPERIMENTAL

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The data is the zonal component of ocean surface currents derived from High Frequency Radio-derived measurements, with missing values filled in by a normal model....

  15. Currents, HF Radio-derived, Ano Nuevo, Normal Model, Zonal, EXPERIMENTAL

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The data is the zonal component of ocean surface currents derived from High Frequency Radio-derived measurements, with missing values filled in by a normal model....

  16. Currents, HF Radio-derived, Monterey Bay, Normal Model, Zonal, EXPERIMENTAL

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The data is the zonal component of ocean surface currents derived from High Frequency Radio-derived measurements, with missing values filled in by a normal model....

  17. Accounting for misclassification in electronic health records-derived exposures using generalized linear finite mixture models.

    Science.gov (United States)

    Hubbard, Rebecca A; Johnson, Eric; Chubak, Jessica; Wernli, Karen J; Kamineni, Aruna; Bogart, Andy; Rutter, Carolyn M

    2017-06-01

    Exposures derived from electronic health records (EHR) may be misclassified, leading to biased estimates of their association with outcomes of interest. An example of this problem arises in the context of cancer screening where test indication, the purpose for which a test was performed, is often unavailable. This poses a challenge to understanding the effectiveness of screening tests because estimates of screening test effectiveness are biased if some diagnostic tests are misclassified as screening. Prediction models have been developed for a variety of exposure variables that can be derived from EHR, but no previous research has investigated appropriate methods for obtaining unbiased association estimates using these predicted probabilities. The full likelihood incorporating information on both the predicted probability of exposure-class membership and the association between the exposure and outcome of interest can be expressed using a finite mixture model. When the regression model of interest is a generalized linear model (GLM), the expectation-maximization algorithm can be used to estimate the parameters using standard software for GLMs. Using simulation studies, we compared the bias and efficiency of this mixture model approach to alternative approaches including multiple imputation and dichotomization of the predicted probabilities to create a proxy for the missing predictor. The mixture model was the only approach that was unbiased across all scenarios investigated. Finally, we explored the performance of these alternatives in a study of colorectal cancer screening with colonoscopy. These findings have broad applicability in studies using EHR data where gold-standard exposures are unavailable and prediction models have been developed for estimating proxies.

  18. Evidence for the Formation of Benzacridine Derivatives in Alkaline-Treated Sunflower Meal and Model Solutions

    Directory of Open Access Journals (Sweden)

    Verena Bongartz

    2016-01-01

    Full Text Available Sunflower extraction meal (SEM is an economically interesting protein source. During alkaline extraction of proteins, the presence of chlorogenic acid (CQA in the meal gives rise to the formation of o-quinones. Reactions with nucleophiles present in proteins can lead to green discoloration. Although such reactions have been known for a long time, there is a lack of information on the chemical nature of the reaction products. SEM and model systems consisting of amino acids and CQA were subjected to alkaline treatment and, for comparison, to oxidation of CQA by polyphenoloxidase (PPO. Several green trihydroxy benzacridine (TBA derivatives were tentatively identified in all samples by UHPLC-DAD-MS/MS. Surprisingly, in alkaline-treated samples of particular amino acids as well as in SEM, the same six TBA isomers were detected. In contrast, the enzymatically oxidized samples resulted in only three TBA derivatives. Contrary to previous findings, neither peptide nor amino acid residues were attached to the resultant benzacridine core. The results indicate that the formation of TBA derivatives is caused by the reaction between CQA quinones and free NH2 groups. Further research is necessary to elucidate the structure of the addition products for a comprehensive evaluation of food and feed safety aspects.

  19. Finite BRST Mapping in Higher-Derivative Models

    Science.gov (United States)

    Moshin, Pavel Yu.; Upadhyay, Sudhaker; Castro, Ricardo A.

    2017-08-01

    We continue the study of finite field-dependent BRST (FFBRST) symmetry in the quantum theory of gauge fields. An expression for the Jacobian of path integral measure is presented, depending on a finite field-dependent parameter, and the FFBRST symmetry is then applied to a number of well-established quantum gauge theories in a form which incudes higher-derivative terms. Specifically, we examine the corresponding versions of the Maxwell theory, non-Abelian vector field theory, and gravitation theory. We present a systematic mapping between different forms of gauge-fixing, including those with higher-derivative terms, for which these theories have better renormalization properties. In doing so, we also provide the independence of the S-matrix from a particular gauge-fixing with higher derivatives. Following this method, a higher-derivative quantum action can be constructed for any gauge theory in the FFBRST framework.

  20. Derivation of the mean annual water-energy balance model based on an Ohms-type law

    Science.gov (United States)

    Li, X.; Shan, X.; Yang, H.

    2017-12-01

    The Budyko Hypothesis is used to describe the water partition and energy partition. Many empirical and analytical solutions have been proposed to evaluate the general solution which can be described as E/P = F(E0/P, c), where c is a parameter. And previous studies have given a derivation of Mezentsev-Choudhruy-Yang (MCY) model, based on dimensional analysis and mathematic reasoning, however, little hydrological process. Thus further hydrological meaning is limited to the boundary conditions which are difficult to explore. Note that hydrologic cycle is always forced by the energy conversions and atmospheric transportation, and the parallel in the electric circuits and the atmospheric motions, therefore we try to give a new derivation of MCY model from a conceptual model, considering hydrologic fluxes and atmospheric motions. Here an analogy of Ohms Law and the atmospheric cycle is used to aim at describing the partition of water in a long-term timescale. Then MCY model is derived in a new form, which is based on more physical explanation than mathematic reasoning proposed in previous studies. The implications of this derivation are also explored.

  1. Laparoscopy After Previous Laparotomy

    Directory of Open Access Journals (Sweden)

    Zulfo Godinjak

    2006-11-01

    Full Text Available Following the abdominal surgery, extensive adhesions often occur and they can cause difficulties during laparoscopic operations. However, previous laparotomy is not considered to be a contraindication for laparoscopy. The aim of this study is to present that an insertion of Veres needle in the region of umbilicus is a safe method for creating a pneumoperitoneum for laparoscopic operations after previous laparotomy. In the last three years, we have performed 144 laparoscopic operations in patients that previously underwent one or two laparotomies. Pathology of digestive system, genital organs, Cesarean Section or abdominal war injuries were the most common causes of previouslaparotomy. During those operations or during entering into abdominal cavity we have not experienced any complications, while in 7 patients we performed conversion to laparotomy following the diagnostic laparoscopy. In all patients an insertion of Veres needle and trocar insertion in the umbilical region was performed, namely a technique of closed laparoscopy. Not even in one patient adhesions in the region of umbilicus were found, and no abdominal organs were injured.

  2. Adipose-Derived Stem Cell-Derived Exosomes Ameliorate Erectile Dysfunction in a Rat Model of Type 2 Diabetes.

    Science.gov (United States)

    Chen, Fengzhi; Zhang, Haibo; Wang, Zhiqiang; Ding, Wei; Zeng, Qinyu; Liu, Wenbing; Huang, Can; He, Shuhua; Wei, Anyang

    2017-09-01

    The efficacy of adipose-derived stem cells (ADSCs) in alleviating erectile dysfunction (ED) of diabetic rats has been demonstrated mainly through a paracrine effect. However, exosomes (EXOs), which are important bioactive substance vectors secreted by ADSCs, have never been associated with ED. To investigate the effect of ADSC-derived EXOs on erectile function in a type 2 diabetic ED rat model. EXOs were isolated from the supernatants of cultured ADSCs by ultracentrifugation. We constructed a type 2 diabetic rat model using a high-fat diet and low-dose streptozotocin administered by intraperitoneal injection. In total, 24 diabetic rats were randomly assigned to three groups and were treated with an intracavernous injection of ADSC-derived EXOs, ADSCs, or phosphate buffered saline. Another eight age-matched rats underwent sham operation and composed the normal control group. Intracavernous pressure and mean arterial pressure testing and histologic and western blot analyses were performed 4 weeks after the intracavernous injection. ADSC-derived EXOs and ADSCs administered by intracavernous injection led to an increase in the ratio of intracavernous pressure to mean arterial pressure compared with that for phosphate buffered saline treatment. Histologic and western blot analyses demonstrated an increased ratio of smooth muscle to collagen, increased expression of an endothelial marker (CD31), a smooth muscle marker (α-smooth muscle actin), and antiapoptotic protein Bcl-2 and decreased the expression of the apoptotic protein cleaved caspase-3 and apoptosis of endothelial and smooth muscle cells in the corpus cavernosum tissue after EXO or ADSC injection compared with values for the phosphate buffered saline treatment. The present results are expected to provide a scientific foundation for clinical application in the near future. Although the results demonstrated that intracavernous injection of ADSC-derived EXOs could ameliorate ED of diabetic rats, the optimum dose

  3. Modeling the ascent of sounding balloons: derivation of the vertical air motion

    Directory of Open Access Journals (Sweden)

    A. Gallice

    2011-10-01

    Full Text Available A new model to describe the ascent of sounding balloons in the troposphere and lower stratosphere (up to ∼30–35 km altitude is presented. Contrary to previous models, detailed account is taken of both the variation of the drag coefficient with altitude and the heat imbalance between the balloon and the atmosphere. To compensate for the lack of data on the drag coefficient of sounding balloons, a reference curve for the relationship between drag coefficient and Reynolds number is derived from a dataset of flights launched during the Lindenberg Upper Air Methods Intercomparisons (LUAMI campaign. The transfer of heat from the surrounding air into the balloon is accounted for by solving the radial heat diffusion equation inside the balloon. In its present state, the model does not account for solar radiation, i.e. it is only able to describe the ascent of balloons during the night. It could however be adapted to also represent daytime soundings, with solar radiation modeled as a diffusive process. The potential applications of the model include the forecast of the trajectory of sounding balloons, which can be used to increase the accuracy of the match technique, and the derivation of the air vertical velocity. The latter is obtained by subtracting the ascent rate of the balloon in still air calculated by the model from the actual ascent rate. This technique is shown to provide an approximation for the vertical air motion with an uncertainty error of 0.5 m s−1 in the troposphere and 0.2 m s−1 in the stratosphere. An example of extraction of the air vertical velocity is provided in this paper. We show that the air vertical velocities derived from the balloon soundings in this paper are in general agreement with small-scale atmospheric velocity fluctuations related to gravity waves, mechanical turbulence, or other small-scale air motions measured during the SUCCESS campaign (Subsonic Aircraft: Contrail and Cloud Effects

  4. Antitumor Activity of Fascaplysin Derivatives on Glioblastoma Model In Vitro.

    Science.gov (United States)

    Lyakhova, I A; Bryukhovetsky, I S; Kudryavtsev, I V; Khotimchenko, Yu S; Zhidkov, M E; Kantemirov, A V

    2018-03-01

    Antitumor efficiency of fascaplysin synthetic derivatives (7-phenylfascaplysin, 3-chlorofascaplysin, 3-bromofascaplysin, and 10-bromofascaplysin) was compared out in vitro on C6 glioma cells. The cytotoxic efficiency of all tested compounds was higher than that of unsubstituted fascaplysin; 3-bromofascaplysin and 7-phenylfascaplysin exhibited the best capacity to kill glioma C6 cells. Apoptosis was the main mechanism of glioma cell death. The cytotoxic activity of these compounds increased with prolongation of exposure to the substance and increase of its concentration. Fascaplysin derivatives modified all phases of glioma cell vital cycle. The count of viable tumor cell in G0 phase remained minimum by the end of experiment under the effects of 3-bromofascaplysin and 7-phenylfascaplysin.

  5. Study of neuroprotective function of Ginkgo biloba extract (EGb761) derived-flavonoid monomers using a three-dimensional stem cell-derived neural model.

    Science.gov (United States)

    Wu, Yueting; Sun, Jiachen; George, Julian; Ye, Hua; Cui, Zhanfeng; Li, Zhaohui; Liu, Qingxi; Zhang, Yaozhou; Ge, Dan; Liu, Yang

    2016-05-01

    An in vitro three-dimensional (3D) cell culture system that can mimic organ and tissue structure and function in vivo will be of great benefit for drug discovery and toxicity testing. In this study, the neuroprotective properties of the three most prevalent flavonoid monomers extracted from EGb 761 (isorharmnetin, kaempferol, and quercetin) were investigated using the developed 3D stem cell-derived neural co-culture model. Rat neural stem cells were differentiated into co-culture of both neurons and astrocytes at an equal ratio in the developed 3D model and standard two-dimensional (2D) model using a two-step differentiation protocol for 14 days. The level of neuroprotective effect offered by each flavonoid was found to be aligned with its effect as an antioxidant and its ability to inhibit Caspase-3 activity in a dose-dependent manner. Cell exposure to quercetin (100 µM) following oxidative insult provided the highest levels of neuroprotection in both 2D and 3D models, comparable with exposure to 100 µM of Vitamin E, whilst exposure to isorhamnetin and kaempferol provided a reduced level of neuroprotection in both 2D and 3D models. At lower dosages (10 µM flavonoid concentration), the 3D model was more representative of results previously reported in vivo. The co-cultures of stem cell derived neurons and astrocytes in 3D hydrogel scaffolds as an in vitro neural model closely replicates in vivo results for routine neural drug toxicity and efficacy testing. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:735-744, 2016. © 2016 American Institute of Chemical Engineers.

  6. Physically-Derived Dynamical Cores in Atmospheric General Circulation Models

    Science.gov (United States)

    Rood, Richard B.; Lin, Shian-Kiann

    1999-01-01

    The algorithm chosen to represent the advection in atmospheric models is often used as the primary attribute to classify the model. Meteorological models are generally classified as spectral or grid point, with the term grid point implying discretization using finite differences. These traditional approaches have a number of shortcomings that render them non-physical. That is, they provide approximate solutions to the conservation equations that do not obey the fundamental laws of physics. The most commonly discussed shortcomings are overshoots and undershoots which manifest themselves most overtly in the constituent continuity equation. For this reason many climate models have special algorithms to model water vapor advection. This talk focuses on the development of an atmospheric general circulation model which uses a consistent physically-based advection algorithm in all aspects of the model formulation. The shallow-water model of Lin and Rood (QJRMS, 1997) is generalized to three dimensions and combined with the physics parameterizations of NCAR's Community Climate Model. The scientific motivation for the development is to increase the integrity of the underlying fluid dynamics so that the physics terms can be more effectively isolated, examined, and improved. The expected benefits of the new model are discussed and results from the initial integrations will be presented.

  7. Normal Mode Derived Models of the Physical Properties of Earth's Outer Core

    Science.gov (United States)

    Irving, J. C. E.; Cottaar, S.; Lekic, V.; Wu, W.

    2017-12-01

    Earth's outer core, the largest reservoir of metal in our planet, is comprised of an iron alloy of an uncertain composition. Its dynamical behaviour is responsible for the generation of Earth's magnetic field, with convection driven both by thermal and chemical buoyancy fluxes. Existing models of the seismic velocity and density of the outer core exhibit some variation, and there are only a small number of models which aim to represent the outer core's density.It is therefore important that we develop a better understanding of the physical properties of the outer core. Though most of the outer core is likely to be well mixed, it is possible that the uppermost outer core is stably stratified: it may be enriched in light elements released during the growth of the solid, iron enriched, inner core; by elements dissolved from the mantle into the outer core; or by exsolution of compounds previously dissolved in the liquid metal which will eventually be swept into the mantle. The stratified layer may host MAC or Rossby waves and it could impede communication between the chemically differentiated mantle and outer core, including screening out some of the geodynamo's signal. We use normal mode center frequencies to estimate the physical properties of the outer core in a Bayesian framework. We estimate the mineral physical parameters needed to best produce velocity and density models of the outer core which are consistent with the normal mode observations. We require that our models satisfy realistic physical constraints. We create models of the outer core with and without a distinct uppermost layer and assess the importance of this region.Our normal mode-derived models are compared with observations of body waves which travel through the outer core. In particular, we consider SmKS waves which are especially sensitive to the uppermost outer core and are therefore an important way to understand the robustness of our models.

  8. Molecular and mathematical modeling analyses of inter-island transmission of rabies into a previously rabies-free island in the Philippines.

    Science.gov (United States)

    Tohma, Kentaro; Saito, Mariko; Demetria, Catalino S; Manalo, Daria L; Quiambao, Beatriz P; Kamigaki, Taro; Oshitani, Hitoshi

    2016-03-01

    Rabies is endemic in the Philippines and dog bites are a major cause of rabies cases in humans. The rabies control program has not been successful in eliminating rabies because of low vaccination coverage among dogs. Therefore, more effective and feasible strategies for rabies control are urgently required in the country. To control rabies, it is very important to know if inter-island transmission can occur because rabies can become endemic once the virus is introduced in areas that previously had no reported cases. Our molecular epidemiological study suggests that inter-island transmission events can occur; therefore, we further investigated these inter-island transmission using phylogenetic and modeling approaches. We investigate inter-island transmission between Luzon and Tablas Islands in the Philippines. Phylogenetic analysis and mathematical modeling demonstrate that there was a time lag of several months to a year from rabies introduction to initial case detection, indicating the difficulties in recognizing the initial rabies introductory event. There had been no rabies cases reported in Tablas Island; however, transmission chain was sustained on this island after the introduction of rabies virus because of low vaccination coverage among dogs. Across the islands, a rabies control program should include control of inter-island dog transportation and rabies vaccination to avoid viral introduction from the outside and to break transmission chains after viral introduction. However, this program has not yet been completely implemented and transmission chains following inter-island virus transmission are still observed. Local government units try to control dog transport; however, it should be more strictly controlled, and a continuous rabies control program should be implemented to prevent rabies spread even in rabies-free areas. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Chesapeake Bay nitrogen fluxes derived from a land‐estuarine ocean biogeochemical modeling system: Model description, evaluation, and nitrogen budgets

    Science.gov (United States)

    Friedrichs, Marjorie A. M.; Wilkin, John; Tian, Hanqin; Yang, Qichun; Hofmann, Eileen E.; Wiggert, Jerry D.; Hood, Raleigh R.

    2015-01-01

    Abstract The Chesapeake Bay plays an important role in transforming riverine nutrients before they are exported to the adjacent continental shelf. Although the mean nitrogen budget of the Chesapeake Bay has been previously estimated from observations, uncertainties associated with interannually varying hydrological conditions remain. In this study, a land‐estuarine‐ocean biogeochemical modeling system is developed to quantify Chesapeake riverine nitrogen inputs, within‐estuary nitrogen transformation processes and the ultimate export of nitrogen to the coastal ocean. Model skill was evaluated using extensive in situ and satellite‐derived data, and a simulation using environmental conditions for 2001–2005 was conducted to quantify the Chesapeake Bay nitrogen budget. The 5 year simulation was characterized by large riverine inputs of nitrogen (154 × 109 g N yr−1) split roughly 60:40 between inorganic:organic components. Much of this was denitrified (34 × 109 g N yr−1) and buried (46 × 109 g N yr−1) within the estuarine system. A positive net annual ecosystem production for the bay further contributed to a large advective export of organic nitrogen to the shelf (91 × 109 g N yr−1) and negligible inorganic nitrogen export. Interannual variability was strong, particularly for the riverine nitrogen fluxes. In years with higher than average riverine nitrogen inputs, most of this excess nitrogen (50–60%) was exported from the bay as organic nitrogen, with the remaining split between burial, denitrification, and inorganic export to the coastal ocean. In comparison to previous simulations using generic shelf biogeochemical model formulations inside the estuary, the estuarine biogeochemical model described here produced more realistic and significantly greater exports of organic nitrogen and lower exports of inorganic nitrogen to the shelf. PMID:27668137

  10. Chesapeake Bay nitrogen fluxes derived from a land-estuarine ocean biogeochemical modeling system: Model description, evaluation, and nitrogen budgets.

    Science.gov (United States)

    Feng, Yang; Friedrichs, Marjorie A M; Wilkin, John; Tian, Hanqin; Yang, Qichun; Hofmann, Eileen E; Wiggert, Jerry D; Hood, Raleigh R

    2015-08-01

    The Chesapeake Bay plays an important role in transforming riverine nutrients before they are exported to the adjacent continental shelf. Although the mean nitrogen budget of the Chesapeake Bay has been previously estimated from observations, uncertainties associated with interannually varying hydrological conditions remain. In this study, a land-estuarine-ocean biogeochemical modeling system is developed to quantify Chesapeake riverine nitrogen inputs, within-estuary nitrogen transformation processes and the ultimate export of nitrogen to the coastal ocean. Model skill was evaluated using extensive in situ and satellite-derived data, and a simulation using environmental conditions for 2001-2005 was conducted to quantify the Chesapeake Bay nitrogen budget. The 5 year simulation was characterized by large riverine inputs of nitrogen (154 × 10 9  g N yr -1 ) split roughly 60:40 between inorganic:organic components. Much of this was denitrified (34 × 10 9  g N yr -1 ) and buried (46 × 10 9  g N yr -1 ) within the estuarine system. A positive net annual ecosystem production for the bay further contributed to a large advective export of organic nitrogen to the shelf (91 × 10 9  g N yr -1 ) and negligible inorganic nitrogen export. Interannual variability was strong, particularly for the riverine nitrogen fluxes. In years with higher than average riverine nitrogen inputs, most of this excess nitrogen (50-60%) was exported from the bay as organic nitrogen, with the remaining split between burial, denitrification, and inorganic export to the coastal ocean. In comparison to previous simulations using generic shelf biogeochemical model formulations inside the estuary, the estuarine biogeochemical model described here produced more realistic and significantly greater exports of organic nitrogen and lower exports of inorganic nitrogen to the shelf.

  11. UV Stellar Distribution Model for the Derivation of Payload

    Directory of Open Access Journals (Sweden)

    Young-Jun Choi

    1999-12-01

    Full Text Available We present the results of a model calculation of the stellar distribution in a UV and centered at 2175Å corresponding to the well-known bump in the interstellar extinction curve. The stellar distribution model used here is based on the Bahcall-Soneira galaxy model (1980. The source code for model calculation was designed by Brosch (1991 and modified to investigate various designing factors for UV satellite payload. The model predicts UV stellar densities in different sky directions, and its results are compared with the TD-1 star counts for a number of sky regions. From this study, we can determine the field of view, size of optics, angular resolution, and number of stars in one orbit. There will provide the basic constrains in designing a satellite payload for UV observations.

  12. Derivation of Distributed Models of Atomic Polarizability for Molecular Simulations.

    Science.gov (United States)

    Soteras, Ignacio; Curutchet, Carles; Bidon-Chanal, Axel; Dehez, François; Ángyán, János G; Orozco, Modesto; Chipot, Christophe; Luque, F Javier

    2007-11-01

    The main thrust of this investigation is the development of models of distributed atomic polarizabilities for the treatment of induction effects in molecular mechanics simulations. The models are obtained within the framework of the induced dipole theory by fitting the induction energies computed via a fast but accurate MP2/Sadlej-adjusted perturbational approach in a grid of points surrounding the molecule. Particular care is paid in the examination of the atomic quantities obtained from models of implicitly and explicitly interacting polarizabilities. Appropriateness and accuracy of the distributed models are assessed by comparing the molecular polarizabilities recovered from the models and those obtained experimentally and from MP2/Sadlej calculations. The behavior of the models is further explored by computing the polarization energy for aromatic compounds in the context of cation-π interactions and for selected neutral compounds in a TIP3P aqueous environment. The present results suggest that the computational strategy described here constitutes a very effective tool for the development of distributed models of atomic polarizabilities and can be used in the generation of new polarizable force fields.

  13. Rigorous theoretical derivation of lumped models to transmission line systems

    International Nuclear Information System (INIS)

    Zhao Jixiang

    2012-01-01

    By virtue of the negative electric parameter concept, i.e. negative lumped resistance, inductance, conductance and capacitance (N-RLGC), the lumped equivalent models of transmission line systems, including the circuit model, two-port π-network and T-network, are given. We start from the N-segment-ladder-like equivalent networks composed distributed parameters, and achieve the input impedance in the form of a continued fraction. Utilizing the continued fraction theory, the expressions of input impedance are obtained under three kinds of extreme cases, i.e. the load impedances are equal to zero, infinity and characteristic impedance, respectively. When the number of segment N is limited to infinity, they are transformed to lumped elements. Comparison between the distributed model and lumped model of transmission lines, the expression of tanh γd, which is the key term in the transmission line equations, are obtained by RLGC, furthermore, according to input admittance, admittance matrix and ABCD matrix of transmission lines, the lumped equivalent circuit models, π-networks and T-networks have been given. The models are verified in the frequency and time domain, respectively, showing that the models are accurate and efficient. (semiconductor integrated circuits)

  14. Position Dependence of Fractional Derivative Models for Loudspeaker Voice Coils with Lossy Inductance

    DEFF Research Database (Denmark)

    King, Alexander Weider; Agerkvist, Finn T.

    2017-01-01

    Commonly used models of moving-coil loudspeaker voice coils, which include effects from eddy current losses, are either inaccurate or contain an abundance of parameters, and are difficult to extend to the nonlinear domain. On the contrary, fractional derivative models accurately describe...... order derivative approaches a value of 1, corresponding to an ideal inductance, when the voice coil is completely outside the magnetic system. Finally, the developed model reveals details about the effect of conductive voice coil formers...

  15. Generic UAV Modeling to Obtain Its Aerodynamic and Control Derivatives

    National Research Council Canada - National Science Library

    Chua, Choon S

    2008-01-01

    ...). These data has a dual application. Firstly, it is required in the Mathworks Simulink 6-degree-of-freedom model of a generic unmanned air vehicle to develop a robust controller and do a variety of trade-offs...

  16. A Consistent Pricing Model for Index Options and Volatility Derivatives

    DEFF Research Database (Denmark)

    Cont, Rama; Kokholm, Thomas

    We propose and study a flexible modeling framework for the joint dynamics of an index and a set of forward variance swap rates written on this index, allowing options on forward variance swaps and options on the underlying index to be priced consistently. Our model reproduces various empirically...... observed properties of variance swap dynamics and allows for jumps in volatility and returns. An affine specification using L´evy processes as building blocks leads to analytically tractable pricing formulas for options on variance swaps as well as efficient numerical methods for pricing of European...... options on the underlying asset. The model has the convenient feature of decoupling the vanilla skews from spot/volatility correlations and allowing for different conditional correlations in large and small spot/volatility moves. We show that our model can simultaneously fit prices of European options...

  17. Modeling neurodegenerative diseases with patient-derived induced pluripotent cells

    DEFF Research Database (Denmark)

    Poon, Anna; Zhang, Yu; Chandrasekaran, Abinaya

    2017-01-01

    The rising prevalence of progressive neurodegenerative diseases coupled with increasing longevity poses an economic burden at individual and societal levels. There is currently no effective cure for the majority of neurodegenerative diseases and disease-affected tissues from patients have been...... the opportunity to model disease development, uncover novel mechanisms and test potential therapeutics. Here we review findings from iPSC-based modeling of selected neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and spinocerebellar ataxia. Furthermore, we discuss...

  18. Modeling ramp-hold indentation measurements based on Kelvin-Voigt fractional derivative model

    Science.gov (United States)

    Zhang, Hongmei; zhe Zhang, Qing; Ruan, Litao; Duan, Junbo; Wan, Mingxi; Insana, Michael F.

    2018-03-01

    Interpretation of experimental data from micro- and nano-scale indentation testing is highly dependent on the constitutive model selected to relate measurements to mechanical properties. The Kelvin-Voigt fractional derivative model (KVFD) offers a compact set of viscoelastic features appropriate for characterizing soft biological materials. This paper provides a set of KVFD solutions for converting indentation testing data acquired for different geometries and scales into viscoelastic properties of soft materials. These solutions, which are mostly in closed-form, apply to ramp-hold relaxation, load-unload and ramp-load creep-testing protocols. We report on applications of these model solutions to macro- and nano-indentation testing of hydrogels, gastric cancer cells and ex vivo breast tissue samples using an atomic force microscope (AFM). We also applied KVFD models to clinical ultrasonic breast data using a compression plate as required for elasticity imaging. Together the results show that KVFD models fit a broad range of experimental data with a correlation coefficient typically R 2  >  0.99. For hydrogel samples, estimation of KVFD model parameters from test data using spherical indentation versus plate compression as well as ramp relaxation versus load-unload compression all agree within one standard deviation. Results from measurements made using macro- and nano-scale indentation agree in trend. For gastric cell and ex vivo breast tissue measurements, KVFD moduli are, respectively, 1/3-1/2 and 1/6 of the elasticity modulus found from the Sneddon model. In vivo breast tissue measurements yield model parameters consistent with literature results. The consistency of results found for a broad range of experimental parameters suggest the KVFD model is a reliable tool for exploring intrinsic features of the cell/tissue microenvironments.

  19. The phantom derivative method when a structure model is available: about its theoretical basis.

    Science.gov (United States)

    Burla, Maria Cristina; Cascarano, Giovanni Luca; Giacovazzo, Carmelo; Polidori, Giampiero

    2017-05-01

    This study clarifies why, in the phantom derivative (PhD) approach, randomly created structures can help in refining phases obtained by other methods. For this purpose the joint probability distribution of target, model, ancil and phantom derivative structure factors and its conditional distributions have been studied. Since PhD may use n phantom derivatives, with n ≥ 1, a more general distribution taking into account all the ancil and derivative structure factors has been considered, from which the conditional distribution of the target phase has been derived. The corresponding conclusive formula contains two components. The first is the classical Srinivasan & Ramachandran term, relating the phases of the target structure with the model phases. The second arises from the combination of two correlations: that between model and derivative (the first is a component of the second) and that between derivative and target. The second component mathematically codifies the information on the target phase arising from model and derivative electron-density maps. The result is new, and explains why a random structure, uncorrelated with the target structure, adds useful information on the target phases, provided a model structure is known. Some experimental tests aimed at checking if the second component really provides information on ϕ (the target phase) were performed; the favourable results confirm the correctness of the theoretical calculations and of the corresponding analysis.

  20. Modeling spot markets for electricity and pricing electricity derivatives

    Science.gov (United States)

    Ning, Yumei

    Spot prices for electricity have been very volatile with dramatic price spikes occurring in restructured market. The task of forecasting electricity prices and managing price risk presents a new challenge for market players. The objectives of this dissertation are: (1) to develop a stochastic model of price behavior and predict price spikes; (2) to examine the effect of weather forecasts on forecasted prices; (3) to price electricity options and value generation capacity. The volatile behavior of prices can be represented by a stochastic regime-switching model. In the model, the means of the high-price and low-price regimes and the probabilities of switching from one regime to the other are specified as functions of daily peak load. The probability of switching to the high-price regime is positively related to load, but is still not high enough at the highest loads to predict price spikes accurately. An application of this model shows how the structure of the Pennsylvania-New Jersey-Maryland market changed when market-based offers were allowed, resulting in higher price spikes. An ARIMA model including temperature, seasonal, and weekly effects is estimated to forecast daily peak load. Forecasts of load under different assumptions about weather patterns are used to predict changes of price behavior given the regime-switching model of prices. Results show that the range of temperature forecasts from a normal summer to an extremely warm summer cause relatively small increases in temperature (+1.5%) and load (+3.0%). In contrast, the increases in prices are large (+20%). The conclusion is that the seasonal outlook forecasts provided by NOAA are potentially valuable for predicting prices in electricity markets. The traditional option models, based on Geometric Brownian Motion are not appropriate for electricity prices. An option model using the regime-switching framework is developed to value a European call option. The model includes volatility risk and allows changes

  1. Strategies to Automatically Derive a Process Model from a Configurable Process Model Based on Event Data

    Directory of Open Access Journals (Sweden)

    Mauricio Arriagada-Benítez

    2017-10-01

    Full Text Available Configurable process models are frequently used to represent business workflows and other discrete event systems among different branches of large organizations: they unify commonalities shared by all branches and describe their differences, at the same time. The configuration of such models is usually done manually, which is challenging. On the one hand, when the number of configurable nodes in the configurable process model grows, the size of the search space increases exponentially. On the other hand, the person performing the configuration may lack the holistic perspective to make the right choice for all configurable nodes at the same time, since choices influence each other. Nowadays, information systems that support the execution of business processes create event data reflecting how processes are performed. In this article, we propose three strategies (based on exhaustive search, genetic algorithms and a greedy heuristic that use event data to automatically derive a process model from a configurable process model that better represents the characteristics of the process in a specific branch. These strategies have been implemented in our proposed framework and tested in both business-like event logs as recorded in a higher educational enterprise resource planning system and a real case scenario involving a set of Dutch municipalities.

  2. A fractal derivative constitutive model for three stages in granite creep

    Directory of Open Access Journals (Sweden)

    R. Wang

    Full Text Available In this paper, by replacing the Newtonian dashpot with the fractal dashpot and considering damage effect, a new constitutive model is proposed in terms of time fractal derivative to describe the full creep regions of granite. The analytic solutions of the fractal derivative creep constitutive equation are derived via scaling transform. The conventional triaxial compression creep tests are performed on MTS 815 rock mechanics test system to verify the efficiency of the new model. The granite specimen is taken from Beishan site, the most potential area for the China’s high-level radioactive waste repository. It is shown that the proposed fractal model can characterize the creep behavior of granite especially in accelerating stage which the classical models cannot predict. The parametric sensitivity analysis is also conducted to investigate the effects of model parameters on the creep strain of granite. Keywords: Beishan granite, Fractal derivative, Damage evolution, Scaling transformation

  3. Calculus for cognitive scientists derivatives, integrals and models

    CERN Document Server

    Peterson, James K

    2016-01-01

    This book provides a self-study program on how mathematics, computer science and science can be usefully and seamlessly intertwined. Learning to use ideas from mathematics and computation is essential for understanding approaches to cognitive and biological science. As such the book covers calculus on one variable and two variables and works through a number of interesting first-order ODE models. It clearly uses MatLab in computational exercises where the models cannot be solved by hand, and also helps readers to understand that approximations cause errors – a fact that must always be kept in mind.

  4. Understanding forest-derived biomass supply with GIS modelling

    DEFF Research Database (Denmark)

    Hock, B. K.; Blomqvist, L.; Hall, P.

    2012-01-01

    distribution, and the cost of delivery as forests are frequently remote from energy users. A GIS-based model was developed to predict supply curves of forest biomass material for a site or group of sites, both now and in the future. The GIS biomass supply model was used to assist the New Zealand Energy...... Efficiency and Conservation Authority's development of a national target for biomass use for industrial heat production, to determine potential forest residue volumes for industrial heat and their delivery costs for 19 processing plants of the dairy company Fonterra, and towards investigating options...

  5. Using statistical compatibility to derive advanced probabilistic fatigue models

    Czech Academy of Sciences Publication Activity Database

    Fernández-Canteli, A.; Castillo, E.; López-Aenlle, M.; Seitl, Stanislav

    2010-01-01

    Roč. 2, č. 1 (2010), s. 1131-1140 E-ISSN 1877-7058. [Fatigue 2010. Praha, 06.06.2010-11.06.2010] Institutional research plan: CEZ:AV0Z20410507 Keywords : Fatigue models * Statistical compatibility * Functional equations Subject RIV: JL - Materials Fatigue, Friction Mechanics

  6. Derivation of Monotone Decision Models from Non-Monotone Data

    NARCIS (Netherlands)

    Daniëls, H.A.M.; Velikova, M.V.

    2003-01-01

    The objective of data mining is the extraction of knowledge from databases. In practice, one often encounters difficulties with models that are constructed purely by search, without incorporation of knowledge about the domain of application.In economic decision making such as credit loan approval or

  7. Relating Derived Relations as a Model of Analogical Reasoning: Reaction Times and Event-Related Potentials

    Science.gov (United States)

    Barnes-Holmes, Dermot; Regan, Donal; Barnes-Holmes, Yvonne; Commins, Sean; Walsh, Derek; Stewart, Ian; Smeets, Paul M.; Whelan, Robert; Dymond, Simon

    2005-01-01

    The current study aimed to test a Relational Frame Theory (RFT) model of analogical reasoning based on the relating of derived same and derived difference relations. Experiment 1 recorded reaction time measures of similar-similar (e.g., "apple is to orange as dog is to cat") versus different-different (e.g., "he is to his brother as…

  8. Simple Entropic Derivation of a Generalized Black-Scholes Option Pricing Model

    Directory of Open Access Journals (Sweden)

    Michael J. Stutzer

    2000-04-01

    Full Text Available Abstract: A straightforward derivation of the celebrated Black-Scholes Option Pricing model is obtained by solution of a simple constrained minimization of relative entropy. The derivation leads to a natural generalization of it, which is consistent with some evidence from stock index option markets.

  9. Integrating ecological insight derived from individual-based simulations and physiologically structured population models

    NARCIS (Netherlands)

    Nisbet, R.M.; Martin, B.T.; de Roos, A.M.

    2016-01-01

    Two contrasting approaches are widely used to derive population dynamics as an emergent property deriving from the physiology and behavior of individual organisms. "Individual-based models" (IBMs) are computer simulations where the "state" (e.g., age, size) of each individual in a population is fol-

  10. Protective effects of a dimeric derivative of ferulic acid in animal models of Alzheimer's disease.

    Science.gov (United States)

    Jung, Jun-Sub; Yan, Ji-Jing; Li, Hong-Mei; Sultan, Md Tipu; Yu, Jaehoon; Lee, Hee-Sul; Shin, Kye-Jung; Song, Dong-Keun

    2016-07-05

    Ferulic acid is a compound with potent anti-oxidant and anti-inflammatory activities. We previously reported the protective effects of ferulic acid administration against two animal models of Alzheimer's disease (AD): intracerebroventricular (i.c.v.) injection of Aß1-42 in mice and APP/PS1 mutant transgenic mice. In this study using the same AD animal models, we examined the effect of KMS4001, one of dimeric derivatives of ferulic acid. Intragastric pretreatment of mice with KMS4001 (30mg/kg/day) for 5 days significantly attenuated the Aß1-42 (i.c.v.)-induced memory impairment both in passive avoidance test and in Y-maze test. APP/PS1 mutant transgenic mice at KMS4001 doses of 3 and 30mg/kg/day via drinking water showed the significantly enhanced novel-object recognition memory at both 1.5 and 3 months after the start of KMS4001 treatment. Treatment of APP/PS1 mutant transgenic mice with KMS4001 for 3 months at the doses of 3 and 30mg/kg/day markedly decreased Aβ1-40 and Aβ1-42 levels in the frontal cortex. The KMS4001 dose-response relationships for Aβ decrease and for improvement in novel-object recognition test corresponded to each other. Taken together, these results suggest that KMS4001 could be an effective drug candidate against AD. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Deriving dynamic marketing effectiveness from econometric time series models

    OpenAIRE

    Horváth, C.; Franses, Ph.H.B.F.

    2003-01-01

    textabstractTo understand the relevance of marketing efforts, it has become standard practice to estimate the long-run and short-run effects of the marketing-mix, using, say, weekly scanner data. A common vehicle for this purpose is an econometric time series model. Issues that are addressed in the literature are unit roots, cointegration, structural breaks and impulse response functions. In this paper we summarize the most important concepts by reviewing all possible empirical cases that can...

  12. An Emprical Point Error Model for Tls Derived Point Clouds

    Science.gov (United States)

    Ozendi, Mustafa; Akca, Devrim; Topan, Hüseyin

    2016-06-01

    The random error pattern of point clouds has significant effect on the quality of final 3D model. The magnitude and distribution of random errors should be modelled numerically. This work aims at developing such an anisotropic point error model, specifically for the terrestrial laser scanner (TLS) acquired 3D point clouds. A priori precisions of basic TLS observations, which are the range, horizontal angle and vertical angle, are determined by predefined and practical measurement configurations, performed at real-world test environments. A priori precision of horizontal (𝜎𝜃) and vertical (𝜎𝛼) angles are constant for each point of a data set, and can directly be determined through the repetitive scanning of the same environment. In our practical tests, precisions of the horizontal and vertical angles were found as 𝜎𝜃=±36.6𝑐𝑐 and 𝜎𝛼=±17.8𝑐𝑐, respectively. On the other hand, a priori precision of the range observation (𝜎𝜌) is assumed to be a function of range, incidence angle of the incoming laser ray, and reflectivity of object surface. Hence, it is a variable, and computed for each point individually by employing an empirically developed formula varying as 𝜎𝜌=±2-12 𝑚𝑚 for a FARO Focus X330 laser scanner. This procedure was followed by the computation of error ellipsoids of each point using the law of variance-covariance propagation. The direction and size of the error ellipsoids were computed by the principal components transformation. The usability and feasibility of the model was investigated in real world scenarios. These investigations validated the suitability and practicality of the proposed method.

  13. Rifalazil and derivative compounds show potent efficacy in a mouse model of H. pylori colonization.

    Science.gov (United States)

    Rothstein, David M; Mullin, Steve; Sirokman, Klari; Söndergaard, Karen L; Johnson, Starrla; Gwathmey, Judith K; van Duzer, John; Murphy, Christopher K

    2008-08-01

    The rifamycin rifalazil (RFZ), and derivatives (NCEs) were efficacious in a mouse model of Helicobacter pylori colonization. Select NCEs were more active in vitro and showed greater efficacy than RFZ. A systemic component contributes to efficacy.

  14. Experimentally derived model to predict permeability behavior of mudstones

    Science.gov (United States)

    Schneider, J.; Flemings, P. B.; Day-Stirrat, R.; Germaine, J. T.

    2010-12-01

    We use uniaxial consolidation experiments to analyze the permeability evolution during consolidation for mudstones with varying composition to develop a predictive permeability model for mudstones. We admixed silt-sized silica to dry, natural Boston Blue Clay (BBC) powder in five different mass ratios. The result is mixtures of silty clay and clayey silt with percentages of clay-sized particles varying between 36 % and 57 %. To recreate natural conditions yet remove variability and soil disturbance, we resedimented all mixtures to a total stress of 100 kPa. We then loaded them to a vertical effective stress of 2.4 MPa in an uniaxial, constant-rate-of-strain consolidation device. We show that vertical permeability increases exponentially with void ratio and decreasing clay content. There is an order of magnitude difference in permeability at a given void ratio for clay contents varying from 36 % to 57 % (by mass). We developed a model that predicts the permeability of silt-clay mixtures based on knowledge of the composition and void ratio alone. The model assumes that flow occurs through the clay-matrix. Thus, the effective permeability is controlled by the void ratio of the clay fraction. At a given stress level, the clay void ratio increases with silt content: large pores are preserved in silty samples due to stress-bridging which does not allow the clay particles to consolidate. Mudstones are important to practical and fundamental programs. They are a key cap rock for subsurface hydrocarbons and geologic storage of CO2. Over the last decade, large amounts of natural gas have been produced from mudstone (shale) gas fields.

  15. A critical view on temperature modelling for application in weather derivatives markets

    International Nuclear Information System (INIS)

    Šaltytė Benth, Jūratė; Benth, Fred Espen

    2012-01-01

    In this paper we present a stochastic model for daily average temperature. The model contains seasonality, a low-order autoregressive component and a variance describing the heteroskedastic residuals. The model is estimated on daily average temperature records from Stockholm (Sweden). By comparing the proposed model with the popular model of Campbell and Diebold (2005), we point out some important issues to be addressed when modelling the temperature for application in weather derivatives market. - Highlights: ► We present a stochastic model for daily average temperature, containing seasonality, a low-order autoregressive component and a variance describing the heteroskedastic residuals. ► We compare the proposed model with the popular model of Campbell and Diebold (2005). ► Some important issues to be addressed when modelling the temperature for application in weather derivatives market are pointed out.

  16. Development of a neutral network model to predict the excretion of purine derivatives in the urine of cows

    International Nuclear Information System (INIS)

    Volpe, V.; Stefanon, B.; Moscardini, S.; Susmel, P.; Gruber, L.

    1999-01-01

    A Neural Network Model to predict the urinary excretion of purine derivative nitrogen (UPDN) in cows is presented. The input variables of the model are dry matter intake (DMINT), NDF intake (NDFINT), total soluble nitrogen (SP), total soluble non-protein dry matter (SNPDM), total degradable nitrogen (DCP), total degradable non-protein dry matter (DNPDM), hourly available CP in the rumen (HACP), hourly available non-protein dry matter (HANPDM), three different gross indexes of synchronization, namely SYNCA (SP/SNPDM), SYNCB (DCP/DNPDM) and SYNCK (HACP/HANPDM) and two variables describing some metabolic aspects of purine derivative excretion such as live weight of the cow (LW) and milk yield (MILKY). The Model developed uses the Multi Layer Perceptron (MLP) utility, with 13 nodes in the input layer, 8 nodes in the hidden layer and 1 node in the output layer. The Model performances have been tested over 24 observations not previously used to train the model. When compared to a linear regression approach, the Neural Network model showed better performance but under predicted the daily excretion of UPDN for values around 20 g/day. When evaluated in terms of behaviour and depicted scenario the model responded to changes of live weight (LW) and milk yield (MILKY) and to modifications of the pattern of nutrients supplied to rumen microbes. (author)

  17. A nonlinear fractional derivative model of impulse motion for viscoelastic materials

    International Nuclear Information System (INIS)

    Fukunaga, Masataka; Shimizu, Nobuyuki; Nasuno, Hiroshi

    2009-01-01

    Generally, force can be described as a function of displacement in the mechanical model. A nonlinear fractional derivative model with respect to displacement is proposed to describe force for a viscoelastic material based on the measured data of impulsive motion. In the model, the nonlinearity is assumed to appear in the term of the fractional derivative. Three types of nonlinearity in the fractional derivative term are considered as candidates for a suitable model for reproducing the impulsive responses of the measured data. The first one is the case where the nonlinearity appears in the coefficient of the fractional derivative and the second in the fractionally differentiated term. The third one is the case where the nonlinearity appears as the combination of the above two types. The equation of motion and the initial conditions are derived by employing the above nonlinear models for head-on collisions of a rigid body onto the viscoelastic material. The property of the impulsive responses for the system that is derived above is characterized by the time when the acceleration shows its maximum. The symmetry property of increasing and decreasing acceleration response about the time of maximum acceleration is also considered. The second-type nonlinearity in the model seems to be adequate for reproducing the measured response.

  18. Solar Energy Deposition Rates in the Mesosphere Derived from Airglow Measurements: Implications for the Ozone Model Deficit Problem

    Science.gov (United States)

    Mlynczak, Martin G.; Garcia, Rolando R.; Roble, Raymond G.; Hagan, Maura

    2000-01-01

    We derive rates of energy deposition in the mesosphere due to the absorption of solar ultraviolet radiation by ozone. The rates are derived directly from measurements of the 1.27-microns oxygen dayglow emission, independent of knowledge of the ozone abundance, the ozone absorption cross sections, and the ultraviolet solar irradiance in the ozone Hartley band. Fifty-six months of airglow data taken between 1982 and 1986 by the near-infrared spectrometer on the Solar-Mesosphere Explorer satellite are analyzed. The energy deposition rates exhibit altitude-dependent annual and semi-annual variations. We also find a positive correlation between temperatures and energy deposition rates near 90 km at low latitudes. This correlation is largely due to the semiannual oscillation in temperature and ozone and is consistent with model calculations. There is also a suggestion of possible tidal enhancement of this correlation based on recent theoretical and observational analyses. The airglow-derived rates of energy deposition are then compared with those computed by multidimensional numerical models. The observed and modeled deposition rates typically agree to within 20%. This agreement in energy deposition rates implies the same agreement exists between measured and modeled ozone volume mixing ratios in the mesosphere. Only in the upper mesosphere at midlatitudes during winter do we derive energy deposition rates (and hence ozone mixing ratios) consistently and significantly larger than the model calculations. This result is contrary to previous studies that have shown a large model deficit in the ozone abundance throughout the mesosphere. The climatology of solar energy deposition and heating presented in this paper is available to the community at the Middle Atmosphere Energy Budget Project web site at http://heat-budget.gats-inc.com.

  19. On a business cycle model with fractional derivative under narrow-band random excitation

    International Nuclear Information System (INIS)

    Lin, Zifei; Li, Jiaorui; Li, Shuang

    2016-01-01

    This paper analyzes the dynamics of a business cycle model with fractional derivative of order  α (0 < α < 1) subject to narrow-band random excitation, in which fractional derivative describes the memory property of the economic variables. Stochastic dynamical system concepts are integrated into the business cycle model for understanding the economic fluctuation. Firstly, the method of multiple scales is applied to derive the model to obtain the approximate analytical solution. Secondly, the effect of economic policy with fractional derivative on the amplitude of the economic fluctuation and the effect on stationary probability density are studied. The results show macroeconomic regulation and control can lower the stable amplitude of economic fluctuation. While in the process of equilibrium state, the amplitude is magnified. Also, the macroeconomic regulation and control improves the stability of the equilibrium state. Thirdly, how externally stochastic perturbation affects the dynamics of the economy system is investigated.

  20. In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models.

    Science.gov (United States)

    Asadzadeh, Fatemeh; Ferrucci, Veronica; DE Antonellis, Pasqualino; Zollo, Massimo

    2017-03-01

    Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub

  1. Mechanisms of Therapy Resistance in Patient-Derived Xenograft Models of BRCA1-Deficient Breast Cancer.

    Science.gov (United States)

    Ter Brugge, Petra; Kristel, Petra; van der Burg, Eline; Boon, Ute; de Maaker, Michiel; Lips, Esther; Mulder, Lennart; de Ruiter, Julian; Moutinho, Catia; Gevensleben, Heidrun; Marangoni, Elisabetta; Majewski, Ian; Józwiak, Katarzyna; Kloosterman, Wigard; van Roosmalen, Markus; Duran, Karen; Hogervorst, Frans; Turner, Nick; Esteller, Manel; Cuppen, Edwin; Wesseling, Jelle; Jonkers, Jos

    2016-11-01

    Although BRCA1-deficient tumors are extremely sensitive to DNA-damaging drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, recurrences do occur and, consequently, resistance to therapy remains a serious clinical problem. To study the underlying mechanisms, we induced therapy resistance in patient-derived xenograft (PDX) models of BRCA1-mutated and BRCA1-methylated triple-negative breast cancer. A cohort of 75 mice carrying BRCA1-deficient breast PDX tumors was treated with cisplatin, melphalan, nimustine, or olaparib, and treatment sensitivity was determined. In tumors that acquired therapy resistance, BRCA1 expression was investigated using quantitative real-time polymerase chain reaction and immunoblotting. Next-generation sequencing, methylation-specific multiplex ligation-dependent probe amplification (MLPA) and Target Locus Amplification (TLA)-based sequencing were used to determine mechanisms of BRCA1 re-expression in therapy-resistant tumors. BRCA1 protein was not detected in therapy-sensitive tumors but was found in 31 out of 42 resistant cases. Apart from previously described mechanisms involving BRCA1-intragenic deletions and loss of BRCA1 promoter hypermethylation, a novel resistance mechanism was identified in four out of seven BRCA1-methylated PDX tumors that re-expressed BRCA1 but retained BRCA1 promoter hypermethylation. In these tumors, we found de novo gene fusions that placed BRCA1 under the transcriptional control of a heterologous promoter, resulting in re-expression of BRCA1 and acquisition of therapy resistance. In addition to previously described clinically relevant resistance mechanisms in BRCA1-deficient tumors, we describe a novel resistance mechanism in BRCA1-methylated PDX tumors involving de novo rearrangements at the BRCA1 locus, demonstrating that BRCA1-methylated breast cancers may acquire therapy resistance via both epigenetic and genetic mechanisms. © The Author 2016. Published by Oxford University Press. All rights reserved

  2. Preventive effects of tonsil-derived mesenchymal stem cells on osteoradionecrosis in a rat model.

    Science.gov (United States)

    Park, Hae Sang; Lee, Jihae; Kim, Jin-Woo; Kim, Ha Young; Jung, Soo Yeon; Lee, Sung Min; Park, Chan Hum; Kim, Han Su

    2018-03-01

    The purpose of this study was to investigate the effects of tonsil-derived mesenchymal stem cells (MSCs) on osteoradionecrosis (ORN). We generated a mandibular ORN rat model using a combination of 20-Gy single-dose irradiation and tooth extraction. Study groups were negative control (tooth extraction only), ORN group (irradiation, tooth extraction), Matrigel-1 group (Matrigel; BD Biosciences, San Jose, CA; irradiation, Matrigel application immediately after tooth extraction), tonsil-derived MSC-1 group (irradiation, tonsil-derived MSC application immediately after tooth extraction), Matrigel-4 group (irradiation, Matrigel application 4 weeks after tooth extraction), and tonsil-derived MSC-4 group (irradiation, tonsil-derived MSC application 4 weeks after tooth extraction). Bone mineral density was significantly lower in the ORN group than in the negative control group. The tonsil-derived MSC-1 group showed significantly higher bone mineral density than did the ORN and tonsil-derived MSC-4 groups. A single 20-Gy dose of irradiation combined with tooth extraction successfully generated ORN in the rat model. The tonsil-derived MSCs can be effective for bone regeneration in ORN, particularly when applied immediately after dentoalveolar trauma or surgery. © 2017 Wiley Periodicals, Inc.

  3. The effect of adipose derived stromal vascular fraction on stasis zone in an experimental burn model.

    Science.gov (United States)

    Eyuboglu, Atilla Adnan; Uysal, Cagri A; Ozgun, Gonca; Coskun, Erhan; Markal Ertas, Nilgun; Haberal, Mehmet

    2018-03-01

    Stasis zone is the surrounding area of the coagulation zone which is an important part determining the extent of the necrosis in burn patients. In our study we aim to salvage the stasis zone by injecting adipose derived stromal vascular fraction (ADSVF). Thermal injury was applied on dorsum of Sprague-Dawley rats (n=20) by the "comb burn" model as described previously. When the burn injury was established on Sprague-Dawley rats (30min); rat dorsum was separated into 2 equal parts consisting of 4 burn zones (3 stasis zone) on each pair. ADSVF cells harvested from inguinal fat pads of Sprague-Dawley rats (n=5) were injected on the right side while same amount of phosphate buffered saline (PBS) injected on the left side of the same animal. One week later, average vital tissue on the statis zone was determined by macroscopy, angiography and microscopy. Vascular density, inflammatory cell density, gradient of fibrosis and epithelial thickness were determined via immunohistochemical assay. Macroscopic stasis zone tissue viability (32±3.28%, 57±4.28%) (p51, 1.50±0.43) (pzone on acute burn injuries. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  4. Finite element analysis of an atomistically derived cohesive model for brittle fracture

    International Nuclear Information System (INIS)

    Lloyd, J T; McDowell, D L; Zimmerman, J A; Jones, R E; Zhou, X W

    2011-01-01

    In order to apply information from molecular dynamics (MD) simulations in problems governed by engineering length and time scales, a coarse graining methodology must be used. In previous work by Zhou et al (2009 Acta Mater. 57 4671–86), a traction-separation cohesive model was developed using results from MD simulations with atomistic-to-continuum measures of stress and displacement. Here, we implement this cohesive model within a combined finite element/cohesive surface element framework (referred to as a finite element approach or FEA), and examine the ability for the atomistically informed FEA to directly reproduce results from MD. We find that FEA shows close agreement of both stress and crack opening displacement profiles at the cohesive interface, although some differences do exist that can be attributed to the stochastic nature of finite temperature MD. The FEA methodology is then used to study slower loading rates that are computationally expensive for MD. We find that the crack growth process initially exhibits a rate-independent relationship between crack length and boundary displacement, followed by a rate-dependent regime where, at a given amount of boundary displacement, a lower applied strain rate produces a longer crack length. Our method is also extended to larger length scales by simulating a compact tension fracture-mechanics specimen with sub-micrometer dimensions. Such a simulation shows a computational speedup of approximately four orders of magnitude over conventional atomistic simulation, while exhibiting the expected fracture-mechanics response. Finally, differences between FEA and MD are explored with respect to ensemble and temperature effects in MD, and their impact on the cohesive model and crack growth behavior. These results enable us to make several recommendations to improve the methodology used to derive cohesive laws from MD simulations. In light of this work, which has critical implications for efforts to derive continuum laws

  5. Use of remote sensing derived parameters in a crop model for biomass prediction of hay crop

    Science.gov (United States)

    El Hajj, Mohammad; Baghdadi, Nicolas; Cheviron, Bruno; Belaud, Gilles; Zribi, Mehrez

    2016-04-01

    Pre-harvest yield forecasting is a critical challenge for producers, especially for large agricultural areas. During previous decades, numerous crop models were developed to predict crop growth and yield at daily time, most often for wheat or maize, and also for grasslands. Crop models require several input parameters that describe soil properties (e.g. field capacity), plant characteristics (e.g. maximal rooting depth) and management options (e.g. sowing dates, irrigation and harvest dates), which are referred to as the soil, plant and management families of parameters. Remote sensing technology has been extensively applied to identify spatially distributed values of some of the accessible parameters in the soil, plant and management families. The aim of this study was to address the feasibility, merits and limitations of forcing remote-sensing-derived parameters (LAI values, harvest and irrigation dates) in the PILOTE crop model, targeting the Total Dry Matter (TDM) of hay crops. Results show that optical images are suitable to feed PILOTE with LAI values without inducing significant errors on the predicted Total Dry Matter (TDM) values (Root Mean Square Error "RMSE" = 0.41 t/ha and Mean Absolute Percentage Error "MAPE" = 22%). Moreover, optical images with revisit times lower than 16 days are adequate to feed PILOTE with remotely sensed harvest dates (RMSE irrigation dates that were estimated from SAR images also enabled reliable model predictions, at least when attaching a random uncertainty of "only" 3 days to the real known irrigation dates. The case of one or several undetected irrigations has also been explored, with the expected conclusion that undetected irrigations significantly affect model predictions only in dry periods. For the tested soil properties and climatic conditions, a maximum underestimation of TDM of approximately 1.55 t/ha (reference TDM of 3.43 t/ha) was observed in the second crop growth cycle when ignoring two irrigations out of four in

  6. Effects of Film Modeling on the Reduction of Anxiety-Related Behaviors in Individuals Varying in Level of Previous Experience in the Stress Situation.

    Science.gov (United States)

    Melamed, Barbara G.; And Others

    1978-01-01

    Evaluated influence of film preparation on children undergoing dental sessions with respect to peer modeling v demonstration of procedures and amount of information. Children exposed to peer-model videotaped presentations immediately preceding their restorative treatment exhibited fewer disruptive behaviors and less apprehension than those…

  7. Establishment and characterization of uterine sarcoma and carcinosarcoma patient-derived xenograft models

    NARCIS (Netherlands)

    Cuppens, Tine; Depreeuw, Jeroen; Annibali, Daniela; Thomas, Debby; Hermans, Els; Gommé, Ellen; Trinh, Xuan Bich; Debruyne, David; Moerman, Philippe; Lambrechts, Diether; Amant, Frédéric

    2017-01-01

    Uterine sarcomas (US) and carcinosarcomas (CS) are rare, aggressive cancers. The lack of reliable preclinical models hampers the search for new treatment strategies and predictive biomarkers. To this end, we established and characterized US and CS patient-derived xenograft (PDX) models. Tumor

  8. Patient-Derived Xenograft Models : An Emerging Platform for Translational Cancer Research

    NARCIS (Netherlands)

    Hidalgo, Manuel; Amant, Frederic; Biankin, Andrew V.; Budinska, Eva; Byrne, Annette T.; Caldas, Carlos; Clarke, Robert B.; de Jong, Steven; Jonkers, Jos; Maelandsmo, Gunhild Mari; Roman-Roman, Sergio; Seoane, Joan; Trusolino, Livio; Villanueva, Alberto

    Recently, there has been an increasing interest in the development and characterization of patient-derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histologic and genetic characteristics of their donor tumor and remain stable across passages. These

  9. Relational Understanding of the Derivative Concept through Mathematical Modeling: A Case Study

    Science.gov (United States)

    Sahin, Zulal; Aydogan Yenmez, Arzu; Erbas, Ayhan Kursat

    2015-01-01

    The purpose of this study was to investigate three second-year graduate students' awareness and understanding of the relationships among the "big ideas" that underlie the concept of derivative through modeling tasks and Skemp's distinction between relational and instrumental understanding. The modeling tasks consisting of warm-up,…

  10. A direct derivation of the exact Fisther information matrix of Gaussian vector state space models

    NARCIS (Netherlands)

    Klein, A.A.B.; Neudecker, H.

    2000-01-01

    This paper deals with a direct derivation of Fisher's information matrix of vector state space models for the general case, by which is meant the establishment of the matrix as a whole and not element by element. The method to be used is matrix differentiation, see [4]. We assume the model to be

  11. Interaction of hematoporphyrin derivative, light, and ionizing radiation in a rat glioma model

    International Nuclear Information System (INIS)

    Kostron, H.; Swartz, M.R.; Miller, D.C.; Martuza, R.L.

    1986-01-01

    The effects of hematoporphyrin derivative, light, and cobalt 60 ( 60 Co) irradiation were studied in a rat glioma model using an in vivo and an in vitro clonogenic assay. There was no effect on tumor growth by visible light or by a single dose of 60 Co irradiation at 4 Gy or 8 Gy, whereas 16 Gy inhibited tumor growth to 40% versus the control. Hematoporphyrin derivative alone slightly stimulated growth (P less than 0.1). Light in the presence of 10 mg hematoporphyrin derivative/kg inhibited tumor growth to 32%. 60 Co irradiation in the presence of hematoporphyrin derivative produced a significant tumor growth inhibition (P less than 0.02). This growth inhibition was directly related to the concentration of hematoporphyrin derivative. The addition of 60 Co to light in the presence of hematoporphyrin derivative produced a greater growth inhibition than light or 60 Co irradiation alone. This effect was most pronounced when light was applied 30 minutes before 60 Co irradiation. Our experiments in a subcutaneous rat glioma model suggest a radiosensitizing effect of hematoporphyrin derivative. Furthermore, the photodynamic inactivation is enhanced by the addition of 60 Co irradiation. These findings may be of importance in planning new treatment modalities in malignant brain tumors

  12. Analysis of the Keller–Segel Model with a Fractional Derivative without Singular Kernel

    Directory of Open Access Journals (Sweden)

    Abdon Atangana

    2015-06-01

    Full Text Available Using some investigations based on information theory, the model proposed by Keller and Segel was extended to the concept of fractional derivative using the derivative with fractional order without singular kernel recently proposed by Caputo and Fabrizio. We present in detail the existence of the coupled-solutions using the fixed-point theorem. A detailed analysis of the uniqueness of the coupled-solutions is also presented. Using an iterative approach, we derive special coupled-solutions of the modified system and we present some numerical simulations to see the effect of the fractional order.

  13. Variables influencing the use of derivatives in South Africa – the development of a conceptual model

    Directory of Open Access Journals (Sweden)

    Stefan Schwegler

    2011-03-01

    Full Text Available This paper, which is the first in a two-part series, sets out the development of a conceptual model on the variables influencing investors’ decisions to use derivatives in their portfolios. Investor-specific variables include: the investor’s needs, goals and return expectations, the investor’s knowledge of financial markets, familiarity with different asset classes including derivative instruments, and the investor’s level of wealth and level of risk tolerance. Market-specific variables include: the level of volatility, standardisation, regulation and liquidity in a market, the level of information available on derivatives, the transparency of price determination, taxes, brokerage costs and product availability.

  14. Impacts of supersymmetric higher derivative terms on inflation models in supergravity

    International Nuclear Information System (INIS)

    Aoki, Shuntaro; Yamada, Yusuke

    2015-01-01

    We show the effects of supersymmetric higher derivative terms on inflation models in supergravity. The results show that such terms generically modify the effective kinetic coefficient of the inflaton during inflation if the cut off scale of the higher derivative operators is sufficiently small. In such a case, the η-problem in supergravity does not occur, and we find that the effective potential of the inflaton generically becomes a power type potential with a power smaller than two

  15. Fractional derivatives of constant and variable orders applied to anomalous relaxation models in heat transfer problems

    Directory of Open Access Journals (Sweden)

    Yang Xiao-Jun

    2017-01-01

    Full Text Available In this paper, we address a class of the fractional derivatives of constant and variable orders for the first time. Fractional-order relaxation equations of constants and variable orders in the sense of Caputo type are modeled from mathematical view of point. The comparative results of the anomalous relaxation among the various fractional derivatives are also given. They are very efficient in description of the complex phenomenon arising in heat transfer.

  16. Modelling of near-field radionuclide transport phenomena in a KBS-3V type of repository for nuclear waste with Goldsim Code - and verification against previous methods

    International Nuclear Information System (INIS)

    Pulkkanen, V.-M.; Nordman, H.

    2010-03-01

    Traditional radionuclide transport models overestimate significantly some phenomena, or completely ignore them. This motivates the development of new more precise models. As a result, this work is a description of commissioning of a new KBS-3V near-field radionuclide transport model, which has been done with a commercial software called GoldSim. According to earlier models, GoldSim model uses rz coordinates, but the solubilities of radionuclides have been treated more precisely. To begin with, the physical phenomena concerning near-field transport have been introduced according to GoldSim way of thinking. Also, the computational methods of GoldSim have been introduced and compared to methods used earlier. The actual verification of GoldSim model has been carried out by comparing the GoldSim results from simple cases to the corresponding results obtained with REPCOM, a software developed by VTT and used in several safety assessments. The results agree well. Finally, a few complicated cases were studied. In these cases, the REPCOM's limitations in handling of some phenomena become evident. The differences in the results are caused especially by the extension of the solubility limit to the whole computational domain, and the element-wise treatment of the solubilities which was used instead of nuclide-wise treatment. This work has been carried out as a special assignment to the former laboratory of Advanced Energy Systems in Helsinki University of Technology. The work was done at VTT. (orig.)

  17. Modelling of near-field radionuclide transport phenomena in a KBS-3V type of repository for nuclear waste with Goldsim Code - and verification against previous methods

    Energy Technology Data Exchange (ETDEWEB)

    Pulkkanen, V.-M.; Nordman, H. (VTT Technical Research Centre, Espoo (Finland))

    2010-03-15

    Traditional radionuclide transport models overestimate significantly some phenomena, or completely ignore them. This motivates the development of new more precise models. As a result, this work is a description of commissioning of a new KBS-3V near-field radionuclide transport model, which has been done with a commercial software called GoldSim. According to earlier models, GoldSim model uses rz coordinates, but the solubilities of radionuclides have been treated more precisely. To begin with, the physical phenomena concerning near-field transport have been introduced according to GoldSim way of thinking. Also, the computational methods of GoldSim have been introduced and compared to methods used earlier. The actual verification of GoldSim model has been carried out by comparing the GoldSim results from simple cases to the corresponding results obtained with REPCOM, a software developed by VTT and used in several safety assessments. The results agree well. Finally, a few complicated cases were studied. In these cases, the REPCOM's limitations in handling of some phenomena become evident. The differences in the results are caused especially by the extension of the solubility limit to the whole computational domain, and the element-wise treatment of the solubilities which was used instead of nuclide-wise treatment. This work has been carried out as a special assignment to the former laboratory of Advanced Energy Systems in Helsinki University of Technology. The work was done at VTT. (orig.)

  18. An equilibrium pricing model for weather derivatives in a multi-commodity setting

    International Nuclear Information System (INIS)

    Lee, Yongheon; Oren, Shmuel S.

    2009-01-01

    Many industries are exposed to weather risk. Weather derivatives can play a key role in hedging and diversifying such risk because the uncertainty in a company's profit function can be correlated to weather condition which affects diverse industry sectors differently. Unfortunately the weather derivatives market is a classical example of an incomplete market that is not amenable to standard methodologies used for derivative pricing in complete markets. In this paper, we develop an equilibrium pricing model for weather derivatives in a multi-commodity setting. The model is constructed in the context of a stylized economy where agents optimize their hedging portfolios which include weather derivatives that are issued in a fixed quantity by a financial underwriter. The supply and demand resulting from hedging activities and the supply by the underwriter are combined in an equilibrium pricing model under the assumption that all agents maximize some risk averse utility function. We analyze the gains due to the inclusion of weather derivatives in hedging portfolios and examine the components of that gain attributable to hedging and to risk sharing. (author)

  19. How to derive and validate clinical prediction models for use in intensive care medicine.

    Science.gov (United States)

    Labarère, José; Renaud, Bertrand; Bertrand, Renaud; Fine, Michael J

    2014-04-01

    Clinical prediction models are formal combinations of historical, physical examination and laboratory or radiographic test data elements designed to accurately estimate the probability that a specific illness is present (diagnostic model), will respond to a form of treatment (therapeutic model) or will have a well-defined outcome (prognostic model) in an individual patient. They are derived and validated using empirical data and used to assist physicians in their clinical decision-making that requires a quantitative assessment of diagnostic, therapeutic or prognostic probabilities at the bedside. To provide intensivists with a comprehensive overview of the empirical development and testing phases that a clinical prediction model must satisfy before its implementation into clinical practice. The development of a clinical prediction model encompasses three consecutive phases, namely derivation, (external) validation and impact analysis. The derivation phase consists of building a multivariable model, estimating its apparent predictive performance in terms of both calibration and discrimination, and assessing the potential for statistical over-fitting using internal validation techniques (i.e. split-sampling, cross-validation or bootstrapping). External validation consists of testing the predictive performance of a model by assessing its calibration and discrimination in different but plausibly related patients. Impact analysis involves comparative research [i.e. (cluster) randomized trials] to determine whether clinical use of a prediction model affects physician practices, patient outcomes or the cost of healthcare delivery. This narrative review introduces a checklist of 19 items designed to help intensivists develop and transparently report valid clinical prediction models.

  20. Modeling the Interest Rate Term Structure: Derivatives Contracts Dynamics and Evaluation

    Directory of Open Access Journals (Sweden)

    Pedro L. Valls Pereira

    2005-06-01

    Full Text Available This article deals with a model for the term structure of interest rates and the valuation of derivative contracts directly dependent on it. The work is of a theoretical nature and deals, exclusively, with continuous time models, making ample use of stochastic calculus results and presents original contributions that we consider relevant to the development of the fixed income market modeling. We develop a new multifactorial model of the term structure of interest rates. The model is based on the decomposition of the yield curve into the factors level, slope, curvature, and the treatment of their collective dynamics. We show that this model may be applied to serve various objectives: analysis of bond price dynamics, valuation of derivative contracts and also market risk management and formulation of operational strategies which is presented in another article.

  1. In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses.

    Directory of Open Access Journals (Sweden)

    Ying Chen

    Full Text Available There is a need for functional in vitro 3D human intestine systems that can bridge the gap between conventional cell culture studies and human trials. The successful engineering in vitro of human intestinal tissues relies on the use of the appropriate cell sources, biomimetic scaffolds, and 3D culture conditions to support vital organ functions. We previously established a compartmentalized scaffold consisting of a hollow space within a porous bulk matrix, in which a functional and physiologically relevant intestinal epithelium system was generated using intestinal cell lines. In this study, we adopt the 3D scaffold system for the cultivation of stem cell-derived human small intestinal enteriods (HIEs to engineer an in vitro 3D model of a nonstransformed human small intestinal epithelium. Characterization of tissue properties revealed a mature HIE-derived epithelium displaying four major terminally differentiated epithelial cell types (enterocytes, Goblet cells, Paneth cells, enteroendocrine cells, with tight junction formation, microvilli polarization, digestive enzyme secretion, and low oxygen tension in the lumen. Moreover, the tissue model demonstrates significant antibacterial responses to E. coli infection, as evidenced by the significant upregulation of genes involved in the innate immune response. Importantly, many of these genes are activated in human patients with inflammatory bowel disease (IBD, implicating the potential application of the 3D stem-cell derived epithelium for the in vitro study of host-microbe-pathogen interplay and IBD pathogenesis.

  2. In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses.

    Science.gov (United States)

    Chen, Ying; Zhou, Wenda; Roh, Terrence; Estes, Mary K; Kaplan, David L

    2017-01-01

    There is a need for functional in vitro 3D human intestine systems that can bridge the gap between conventional cell culture studies and human trials. The successful engineering in vitro of human intestinal tissues relies on the use of the appropriate cell sources, biomimetic scaffolds, and 3D culture conditions to support vital organ functions. We previously established a compartmentalized scaffold consisting of a hollow space within a porous bulk matrix, in which a functional and physiologically relevant intestinal epithelium system was generated using intestinal cell lines. In this study, we adopt the 3D scaffold system for the cultivation of stem cell-derived human small intestinal enteriods (HIEs) to engineer an in vitro 3D model of a nonstransformed human small intestinal epithelium. Characterization of tissue properties revealed a mature HIE-derived epithelium displaying four major terminally differentiated epithelial cell types (enterocytes, Goblet cells, Paneth cells, enteroendocrine cells), with tight junction formation, microvilli polarization, digestive enzyme secretion, and low oxygen tension in the lumen. Moreover, the tissue model demonstrates significant antibacterial responses to E. coli infection, as evidenced by the significant upregulation of genes involved in the innate immune response. Importantly, many of these genes are activated in human patients with inflammatory bowel disease (IBD), implicating the potential application of the 3D stem-cell derived epithelium for the in vitro study of host-microbe-pathogen interplay and IBD pathogenesis.

  3. Conference Innovations in Derivatives Market : Fixed Income Modeling, Valuation Adjustments, Risk Management, and Regulation

    CERN Document Server

    Grbac, Zorana; Scherer, Matthias; Zagst, Rudi

    2016-01-01

    This book presents 20 peer-reviewed chapters on current aspects of derivatives markets and derivative pricing. The contributions, written by leading researchers in the field as well as experienced authors from the financial industry, present the state of the art in: • Modeling counterparty credit risk: credit valuation adjustment, debit valuation adjustment, funding valuation adjustment, and wrong way risk. • Pricing and hedging in fixed-income markets and multi-curve interest-rate modeling. • Recent developments concerning contingent convertible bonds, the measuring of basis spreads, and the modeling of implied correlations. The recent financial crisis has cast tremendous doubts on the classical view on derivative pricing. Now, counterparty credit risk and liquidity issues are integral aspects of a prudent valuation procedure and the reference interest rates are represented by a multitude of curves according to their different periods and maturities. A panel discussion included in the book (featuring D...

  4. Scenario and modelling uncertainty in global mean temperature change derived from emission driven Global Climate Models

    Science.gov (United States)

    Booth, B. B. B.; Bernie, D.; McNeall, D.; Hawkins, E.; Caesar, J.; Boulton, C.; Friedlingstein, P.; Sexton, D.

    2012-09-01

    We compare future changes in global mean temperature in response to different future scenarios which, for the first time, arise from emission driven rather than concentration driven perturbed parameter ensemble of a Global Climate Model (GCM). These new GCM simulations sample uncertainties in atmospheric feedbacks, land carbon cycle, ocean physics and aerosol sulphur cycle processes. We find broader ranges of projected temperature responses arising when considering emission rather than concentration driven simulations (with 10-90 percentile ranges of 1.7 K for the aggressive mitigation scenario up to 3.9 K for the high end business as usual scenario). A small minority of simulations resulting from combinations of strong atmospheric feedbacks and carbon cycle responses show temperature increases in excess of 9 degrees (RCP8.5) and even under aggressive mitigation (RCP2.6) temperatures in excess of 4 K. While the simulations point to much larger temperature ranges for emission driven experiments, they do not change existing expectations (based on previous concentration driven experiments) on the timescale that different sources of uncertainty are important. The new simulations sample a range of future atmospheric concentrations for each emission scenario. Both in case of SRES A1B and the Representative Concentration Pathways (RCPs), the concentration pathways used to drive GCM ensembles lies towards the lower end of our simulated distribution. This design decision (a legecy of previous assessments) is likely to lead concentration driven experiments to under-sample strong feedback responses in concentration driven projections. Our ensemble of emission driven simulations span the global temperature response of other multi-model frameworks except at the low end, where combinations of low climate sensitivity and low carbon cycle feedbacks lead to responses outside our ensemble range. The ensemble simulates a number of high end responses which lie above the CMIP5 carbon

  5. Position Dependence of Fractional Derivative Models for Loudspeaker Voice Coils with Lossy Inductance

    DEFF Research Database (Denmark)

    King, Alexander Weider; Agerkvist, Finn T.

    2017-01-01

    Commonly used models of moving-coil loudspeaker voice coils, which include effects from eddy current losses, are either inaccurate or contain an abundance of parameters, and are difficult to extend to the nonlinear domain. On the contrary, fractional derivative models accurately describe the freq......Commonly used models of moving-coil loudspeaker voice coils, which include effects from eddy current losses, are either inaccurate or contain an abundance of parameters, and are difficult to extend to the nonlinear domain. On the contrary, fractional derivative models accurately describe...... the frequency and position dependence of the lossy inductance, with meaningful connections to the underlying physics, while keeping the number of parameters low. These fractional derivatives are also compatible with state-space polynomial methods of modeling nonlinear behavior. It is shown that the fractional...... order derivative approaches a value of 1, corresponding to an ideal inductance, when the voice coil is completely outside the magnetic system. Finally, the developed model reveals details about the effect of conductive voice coil formers...

  6. Modeling Neurodegenerative Microenvironment Using Cortical Organoids Derived from Human Stem Cells.

    Science.gov (United States)

    Yan, Yuanwei; Song, Liqing; Bejoy, Julie; Zhao, Jing; Kanekiyo, Takahisa; Bu, Guojun; Zhou, Yi; Li, Yan

    2018-02-27

    Alzheimer's disease (AD) is one of the most common neurodegenerative disorders and causes cognitive impairment and memory deficits of the patients. The mechanism of AD is not well known, due to lack of human brain models. Recently, mini-brain tissues called organoids have been derived from human induced pluripotent stem cells (hiPSCs) for modeling human brain development and neurological diseases. Thus, the objective of this research is to model and characterize neural degeneration microenvironment using three-dimensional (3D) forebrain cortical organoids derived from hiPSCs and study the response to the drug treatment. It is hypothesized that the 3D forebrain organoids derived from hiPSCs with AD-associated genetic background may partially recapitulate the extracellular microenvironment in neural degeneration. To test this hypothesis, AD-patient derived hiPSCs with presenilin-1 mutation were used for cortical organoid generation. AD-related inflammatory responses, matrix remodeling and the responses to DAPT, heparin (completes with heparan sulfate proteoglycans [HSPGs] to bind Aβ42), and heparinase (digests HSPGs) treatments were investigated. The results indicate that the cortical organoids derived from AD-associated hiPSCs exhibit a high level of Aβ42 comparing with healthy control. In addition, the AD-derived organoids result in an elevated gene expression of proinflammatory cytokines interleukin-6 and tumor necrosis factor-α, upregulate syndecan-3, and alter matrix remodeling protein expression. Our study demonstrates the capacity of hiPSC-derived organoids for modeling the changes of extracellular microenvironment and provides a potential approach for AD-related drug screening.

  7. Activity Exerted by a Testosterone Derivative on Myocardial Injury Using an Ischemia/Reperfusion Model

    Science.gov (United States)

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Betty, Sarabia-Alcocer; Monica, Velázquez-Sarabia Betty

    2014-01-01

    Some reports indicate that several steroid derivatives have activity at cardiovascular level; nevertheless, there is scarce information about the activity exerted by the testosterone derivatives on cardiac injury caused by ischemia/reperfusion (I/R). Analyzing these data, in this study, a new testosterone derivative was synthetized with the objective of evaluating its effect on myocardial injury using an ischemia/reperfusion model. In addition, perfusion pressure and coronary resistance were evaluated in isolated rat hearts using the Langendorff technique. Additionally, molecular mechanism involved in the activity exerted by the testosterone derivative on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in the absence or presence of the following compounds: flutamide, prazosin, metoprolol, nifedipine, indomethacin, and PINANE TXA2. The results showed that the testosterone derivative significantly increases (P = 0.05) the perfusion pressure and coronary resistance in isolated heart. Other data indicate that the testosterone derivative increases left ventricular pressure in a dose-dependent manner (0.001–100 nM); however, this phenomenon was significantly inhibited (P = 0.06) by indomethacin and PINANE-TXA2  (P = 0.05) at a dose of 1 nM. In conclusion, these data suggest that testosterone derivative induces changes in the left ventricular pressure levels through thromboxane receptor activation. PMID:24839599

  8. Novel pancreatic cancer cell lines derived from genetically engineered mouse models of spontaneous pancreatic adenocarcinoma: applications in diagnosis and therapy.

    Directory of Open Access Journals (Sweden)

    María P Torres

    Full Text Available Pancreatic cancer (PC remains one of the most lethal human malignancies with poor prognosis. Despite all advances in preclinical research, there have not been significant translation of novel therapies into the clinics. The development of genetically engineered mouse (GEM models that produce spontaneous pancreatic adenocarcinoma (PDAC have increased our understanding of the pathogenesis of the disease. Although these PDAC mouse models are ideal for studying potential therapies and specific genetic mutations, there is a need for developing syngeneic cell lines from these models. In this study, we describe the successful establishment and characterization of three cell lines derived from two (PDAC mouse models. The cell line UN-KC-6141 was derived from a pancreatic tumor of a Kras(G12D;Pdx1-Cre (KC mouse at 50 weeks of age, whereas UN-KPC-960 and UN-KPC-961 cell lines were derived from pancreatic tumors of Kras(G12D;Trp53(R172H;Pdx1-Cre (KPC mice at 17 weeks of age. The cancer mutations of these parent mice carried over to the daughter cell lines (i.e. Kras(G12D mutation was observed in all three cell lines while Trp53 mutation was observed only in KPC cell lines. The cell lines showed typical cobblestone epithelial morphology in culture, and unlike the previously established mouse PDAC cell line Panc02, expressed the ductal marker CK19. Furthermore, these cell lines expressed the epithelial-mesenchymal markers E-cadherin and N-cadherin, and also, Muc1 and Muc4 mucins. In addition, these cell lines were resistant to the chemotherapeutic drug Gemcitabine. Their implantation in vivo produced subcutaneous as well as tumors in the pancreas (orthotopic. The genetic mutations in these cell lines mimic the genetic compendium of human PDAC, which make them valuable models with a high potential of translational relevance for examining diagnostic markers and therapeutic drugs.

  9. Discovery of Antibiotics-derived Polymers for Gene Delivery using Combinatorial Synthesis and Cheminformatics Modeling

    Science.gov (United States)

    Potta, Thrimoorthy; Zhen, Zhuo; Grandhi, Taraka Sai Pavan; Christensen, Matthew D.; Ramos, James; Breneman, Curt M.; Rege, Kaushal

    2014-01-01

    We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in high transgene expression levels in cells. The role of polymer physicochemical properties in determining efficacy of transgene expression was investigated using Quantitative Structure-Activity Relationship (QSAR) cheminformatics models based on Support Vector Regression (SVR) and ‘building block’ polymer structures. The QSAR model exhibited high predictive ability, and investigation of descriptors in the model, using molecular visualization and correlation plots, indicated that physicochemical attributes related to both, aminoglycosides and diglycidyl ethers facilitated transgene expression. This work synergistically combines combinatorial synthesis and parallel screening with cheminformatics-based QSAR models for discovery and physicochemical elucidation of effective antibiotics-derived polymers for transgene delivery in medicine and biotechnology. PMID:24331709

  10. Discovery of antibiotics-derived polymers for gene delivery using combinatorial synthesis and cheminformatics modeling.

    Science.gov (United States)

    Potta, Thrimoorthy; Zhen, Zhuo; Grandhi, Taraka Sai Pavan; Christensen, Matthew D; Ramos, James; Breneman, Curt M; Rege, Kaushal

    2014-02-01

    We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in high transgene expression levels in cells. The role of polymer physicochemical properties in determining efficacy of transgene expression was investigated using Quantitative Structure-Activity Relationship (QSAR) cheminformatics models based on Support Vector Regression (SVR) and 'building block' polymer structures. The QSAR model exhibited high predictive ability, and investigation of descriptors in the model, using molecular visualization and correlation plots, indicated that physicochemical attributes related to both, aminoglycosides and diglycidyl ethers facilitated transgene expression. This work synergistically combines combinatorial synthesis and parallel screening with cheminformatics-based QSAR models for discovery and physicochemical elucidation of effective antibiotics-derived polymers for transgene delivery in medicine and biotechnology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. A model for the derivation of new transport limits for non-fixed contamination

    Energy Technology Data Exchange (ETDEWEB)

    Thierfeldt, S. [Brenk Systemplanung GmbH, Aachen (Germany); Lorenz, B. [GNS Gesellschaft fuer Nuklearservice, Essen (Germany); Hesse, J. [RWE Power AG, Essen (Germany)

    2004-07-01

    The IAEA Regulations for the Safe Transport of Radioactive Material contain requirements for contamination limits on packages and conveyances used for the transport of radioactive material. Current contamination limits for packages and conveyances under routine transport conditions have been derived from a model proposed by Fairbairn more than 40 years ago. This model has proven effective if used with pragmatism, but is based on very conservative as well as extremely simple assumptions which is in no way appropriate any more and which is not compatible with ICRP recommendations regarding radiation protection standards. Therefore, a new model has now been developed which reflects all steps of the transport process. The derivation of this model has been fostered by the IAEA by initiating a Co-ordinated Research Project. The results of the calculations using this model could be directly applied as new nuclide specific transport limits for the non-fixed contamination.

  12. A model for the derivation of new transport limits for non-fixed contamination

    International Nuclear Information System (INIS)

    Thierfeldt, S.; Lorenz, B.; Hesse, J.

    2004-01-01

    The IAEA Regulations for the Safe Transport of Radioactive Material contain requirements for contamination limits on packages and conveyances used for the transport of radioactive material. Current contamination limits for packages and conveyances under routine transport conditions have been derived from a model proposed by Fairbairn more than 40 years ago. This model has proven effective if used with pragmatism, but is based on very conservative as well as extremely simple assumptions which is in no way appropriate any more and which is not compatible with ICRP recommendations regarding radiation protection standards. Therefore, a new model has now been developed which reflects all steps of the transport process. The derivation of this model has been fostered by the IAEA by initiating a Co-ordinated Research Project. The results of the calculations using this model could be directly applied as new nuclide specific transport limits for the non-fixed contamination

  13. Rituximab, Cyclophosphamide, Dexamethasone (RCD) regimen induces cure in WSU-WM xenograft model and a partial remission in previously treated Waldenstrom's macroglobulinemia patient.

    Science.gov (United States)

    Mohammad, Ramzi M; Aboukameel, Amro; Nabha, Sanaa; Ibrahim, Dina; Al-Katib, Ayad

    2002-08-01

    Waldenstrom's macroglobulinemia (WM) is an uncommon lymphoproliferative disease which remains incurable with current treatment protocols. We have previously established a permanent WM cell line, WSU-WM, which grows as a xenograft in severe combined immune deficient (SCID) mice. In this study, we investigated the antitumor effects of Rituximab (RTX), Cyclophosphamide (CTX), Dexamethasone (DEX) [RCD]-Regimen in vivo WSU-WM SCID xenograft and in a patient with WM. For the pre-clinical efficacy study, WSU-WM-bearing SCID mice were randomly assigned to receive RTX (150 mg/kg/inj, i.v., QDX5), CTX (90 mg/kg/inj, s.c. QDX5) as single agents or diluent. The combination group received RTX at 150 mg/kg/inj, QDX5; CTX at 150 mg/kg/inj, QODX3 and DEX at 1.0 mg/kg/inj, i.v., QDX5. Tumor growth inhibition (T/C), tumor growth delay (T - C), and log10 kill (net) for RTX and CTX were 24.5%, 37 days, 5.52 and 88%, 0.0 days, 0.0log10 kill, respectively. No cures were observed with either agent; however, all mice (6/6, with bilateral tumors) were cured when treated with RCD-regimen. A 57-year-old patient with relapsed WM was treated with the RCD-regimen and showed an excellent partial remission for seven months. The patient tolerated the treatment very well, the hemoglobin improved dramatically, platelets remained stable, the IgM level normalized and there was only minimal involvement of bone marrow. Based on these results, the RCD regimen is effective against WM and its activity should be further evaluated in clinical trials.

  14. Comment on "Assessing Discrepancies Between Previous Plate Kinematic Models of Mesozoic Iberia and Their Constraints" by Barnett-Moore Et Al.

    Science.gov (United States)

    van Hinsbergen, Douwe J. J.; Spakman, Wim; Vissers, Reinoud L. M.; van der Meer, Douwe G.

    2017-12-01

    In their recent paper, Barnett-Moore et al. (2016) reflect on current models of Iberian plate motion in the Jurassic and Cretaceous as well as ongoing debates on the reliability of the various types of kinematic data that form independent constraints on Iberia's motion relative to Eurasia. They question the validity of various marine geophysical, seismic, tomographic, geological, and paleomagnetic data sets from the Bay of Biscay, Central Atlantic Ocean, and Iberia for kinematic reconstruction of Iberia and conclude that neither models invoking Aptian-Albian transtension, nor compression, are consistent with currently available data. An important element in their analysis is that they discard the large paleomagnetic data set from the Jurassic and Cretaceous from Iberia based on perceived limitations of that data set. In addition, they argue that seismic tomographic images exclude a scenario of subduction in the Aptian-Albian in the Pyrenees, and based on this "question the validity of current plate reconstructions, their constraints, and geodynamic scenarios, which are in support of this scenario [e.g., Vissers et al., 2016]." We welcome the discussion raised by Barnett-Moore et al. (2016) on the reliability and usefulness of paleomagnetic data as independent constraint for Iberia's plate motion in the Mesozoic. Taking these paleomagnetic data at face value, Vissers et al. (2016) recently showed that these are consistent with an 40° counterclockwise rotation of Iberia in the Aptian, requiring up to 500 km of Aptian convergence across the Pyrenees, that is, through subduction. In this comment, we aim to critically assess whether and how the concerns on the quality of paleomagnetic data raised by Barnett-Moore et al. (2016) may allow for an alternative explanation, particularly one with a Mesozoic rotation of Iberia that is small enough so as to not requiring subduction. We also reassess whether seismic tomographic images indeed refute subduction scenarios, using 8

  15. Hydrologic Derivatives for Modeling and Analysis—A new global high-resolution database

    Science.gov (United States)

    Verdin, Kristine L.

    2017-07-17

    The U.S. Geological Survey has developed a new global high-resolution hydrologic derivative database. Loosely modeled on the HYDRO1k database, this new database, entitled Hydrologic Derivatives for Modeling and Analysis, provides comprehensive and consistent global coverage of topographically derived raster layers (digital elevation model data, flow direction, flow accumulation, slope, and compound topographic index) and vector layers (streams and catchment boundaries). The coverage of the data is global, and the underlying digital elevation model is a hybrid of three datasets: HydroSHEDS (Hydrological data and maps based on SHuttle Elevation Derivatives at multiple Scales), GMTED2010 (Global Multi-resolution Terrain Elevation Data 2010), and the SRTM (Shuttle Radar Topography Mission). For most of the globe south of 60°N., the raster resolution of the data is 3 arc-seconds, corresponding to the resolution of the SRTM. For the areas north of 60°N., the resolution is 7.5 arc-seconds (the highest resolution of the GMTED2010 dataset) except for Greenland, where the resolution is 30 arc-seconds. The streams and catchments are attributed with Pfafstetter codes, based on a hierarchical numbering system, that carry important topological information. This database is appropriate for use in continental-scale modeling efforts. The work described in this report was conducted by the U.S. Geological Survey in cooperation with the National Aeronautics and Space Administration Goddard Space Flight Center.

  16. Global history of the ancient monocot family Araceae inferred with models accounting for past continental positions and previous ranges based on fossils.

    Science.gov (United States)

    Nauheimer, Lars; Metzler, Dirk; Renner, Susanne S

    2012-09-01

    The family Araceae (3790 species, 117 genera) has one of the oldest fossil records among angiosperms. Ecologically, members of this family range from free-floating aquatics (Pistia and Lemna) to tropical epiphytes. Here, we infer some of the macroevolutionary processes that have led to the worldwide range of this family and test how the inclusion of fossil (formerly occupied) geographical ranges affects biogeographical reconstructions. Using a complete genus-level phylogeny from plastid sequences and outgroups representing the 13 other Alismatales families, we estimate divergence times by applying different clock models and reconstruct range shifts under different models of past continental connectivity, with or without the incorporation of fossil locations. Araceae began to diversify in the Early Cretaceous (when the breakup of Pangea was in its final stages), and all eight subfamilies existed before the K/T boundary. Early lineages persist in Laurasia, with several relatively recent entries into Africa, South America, South-East Asia and Australia. Water-associated habitats appear to be ancestral in the family, and DNA substitution rates are especially high in free-floating Araceae. Past distributions inferred when fossils are included differ in nontrivial ways from those without fossils. Our complete genus-level time-scale for the Araceae may prove to be useful for ecological and physiological studies. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  17. Equilibrium stochastic dynamics of a Brownian particle in inhomogeneous space: Derivation of an alternative model

    Science.gov (United States)

    Bhattacharyay, A.

    2018-03-01

    An alternative equilibrium stochastic dynamics for a Brownian particle in inhomogeneous space is derived. Such a dynamics can model the motion of a complex molecule in its conformation space when in equilibrium with a uniform heat bath. The derivation is done by a simple generalization of the formulation due to Zwanzig for a Brownian particle in homogeneous heat bath. We show that, if the system couples to different number of bath degrees of freedom at different conformations then the alternative model gets derived. We discuss results of an experiment by Faucheux and Libchaber which probably has indicated possible limitation of the Boltzmann distribution as equilibrium distribution of a Brownian particle in inhomogeneous space and propose experimental verification of the present theory using similar methods.

  18. Constitutive modeling of jugular vein-derived venous valve leaflet tissues.

    Science.gov (United States)

    Kaul, Nayyan; Huang, Hsiao-Ying Shadow

    2017-11-01

    Venous valve tissues, though used in vein reconstruction surgeries and bioprosthetic valves with moderate success, have not been extensively studied with respect to their structure. Their inherent anisotropic, non-linear behavior combined with severe diseases which affect veins, such as chronic venous insufficiency, warrant understanding the structure and material behavior of these tissues. Hence, before any bioprosthetic grafts may be used in place of tissues, it is of the utmost importance to understand the mechanical and structural properties of these tissues as this may lead to higher success rates for valve replacement surgeries. The longevity of the bioprosthetics may also increase if the manufactured grafts behave the same as native valves. Building on the scant information about the uniaxial and biaxial mechanical properties of jugular venous valves and wall tissues from previous studies, the current focus of our investigation lies in understanding the material behavior by establishing a phenomenological strain energy-based constitutive relation for the tissues. We used bovine veins to study the behavior of valve leaflet tissue and adjoining wall tissue (from the proximal and distal ends of the veins) under different biaxial testing protocols. We looked at the behavior of numerical partial derivatives of the strain energy to select a suitable functional form for the strain energy for wall and valve tissues. Using this strain energy descriptor, we determined the Cauchy stress and compared it with experimental results under additional sets of displacement-controlled biaxial testing protocols to find material specific model parameters by the Powell's method algorithm. Results show that whereas wall tissue strain energy can be explained using a polynomial non-linear function, the valve tissue, due to higher non-linearities, requires an exponential function. This study may provide useful information for the primary stages of bioprosthetic designs and replacement

  19. Modeling of a three-phase reactor for bitumen-derived gas oil hydrotreating

    Directory of Open Access Journals (Sweden)

    R. Chacón

    2012-03-01

    Full Text Available A three-phase reactor model for describing the hydrotreating reactions of bitumen-derived gas oil was developed. The model incorporates the mass-transfer resistance at the gas-liquid and liquid-solid interfaces and a kinetic rate expression based on a Langmuir-Hinshelwood-type model. We derived three correlations for determining the solubility of hydrogen (H2, hydrogen sulfide (H2S and ammonia (NH3 in hydrocarbon mixtures and the calculation of the catalyst effectiveness factor was included. Experimental data taken from the literature were used to determine the kinetic parameters (stoichiometric coefficients, reaction orders, reaction rate and adsorption constants for hydrodesulfuration (HDS and hydrodenitrogenation (HDN and to validate the model under various operating conditions. Finally, we studied the effect of operating conditions such as pressure, temperature, LHSV, H2/feed ratio and the inhibiting effect of H2S on HDS and NH3 on HDN.

  20. Synthesis and Molecular modeling of some new chalcones derived from coumarine as CDC25 phosphatases inhibitors

    Directory of Open Access Journals (Sweden)

    Delel Dridi

    2016-01-01

    Full Text Available New chalcones derived from coumarines were synthesized and tested as CDC25 phosphatase inhibitors. Molecular modeling of these new compounds was also presented in aim to study the mode of compounds orientation within CDC25 A and B. The reversibility of compounds 3, 4 and 5 was confirmed by application of MALDI–TOFMS technique.

  1. Integrating Developmental Theory and Methodology: Using Derivatives to Articulate Change Theories, Models, and Inferences

    Science.gov (United States)

    Deboeck, Pascal R.; Nicholson, Jody; Kouros, Chrystyna; Little, Todd D.; Garber, Judy

    2015-01-01

    Matching theories about growth, development, and change to appropriate statistical models can present a challenge, which can result in misuse, misinterpretation, and underutilization of different analytical approaches. We discuss the use of "derivatives": the change of a construct with respect to the change in another construct.…

  2. Equity and Foreign Exchange Hybrid Models for Pricing Long-Maturity Financial Derivatives

    NARCIS (Netherlands)

    Grzelak, L.A.

    2011-01-01

    Modelling derivative products in Finance usually starts with the specification of a system of Stochastic Differential Equations (SDEs), that corresponds to state variables like stock, interest rate, Foreign Exchange (FX) rate and volatility. By correlating the SDEs for the different asset classes

  3. Arabic Language Modeling with Stem-Derived Morphemes for Automatic Speech Recognition

    Science.gov (United States)

    Heintz, Ilana

    2010-01-01

    The goal of this dissertation is to introduce a method for deriving morphemes from Arabic words using stem patterns, a feature of Arabic morphology. The motivations are three-fold: modeling with morphemes rather than words should help address the out-of-vocabulary problem; working with stem patterns should prove to be a cross-dialectally valid…

  4. Evaluation of MSG-derived global radiation estimates for application in a regional crop model

    NARCIS (Netherlands)

    Roerink, G.J.; Bojanowski, J.S.; Wit, de A.J.W.; Eerens, H.; Supit, I.; Leo, O.; Boogaard, H.L.

    2012-01-01

    Crop monitoring systems that rely on agrometeorologic models require estimates of global radiation. These estimates are difficult to obtain due to the limited number of weather stations that measure this variable. In the present study, we validated the global radiation estimates derived from

  5. A generalized one-factor term structure model and pricing of interest rate derivative securities

    NARCIS (Netherlands)

    Jiang, George J.

    1997-01-01

    The purpose of this paper is to propose a nonparametric interest rate term structure model and investigate its implications on term structure dynamics and prices of interest rate derivative securities. The nonparametric spot interest rate process is estimated from the observed short-term interest

  6. Market segment derivation and profiling via a finite mixture model framework

    NARCIS (Netherlands)

    Wedel, M; Desarbo, WS

    The Marketing literature has shown how difficult it is to profile market segments derived with finite mixture models. especially using traditional descriptor variables (e.g., demographics). Such profiling is critical for the proper implementation of segmentation strategy. we propose a new finite

  7. Pathway computation in models derived from bio-science text sources

    DEFF Research Database (Denmark)

    Andreasen, Troels; Bulskov, Henrik; Jensen, Per Anker

    2017-01-01

    This paper outlines a system, OntoScape, serving to accomplish complex inference tasks on knowledge bases and bio-models derived from life-science text corpora. The system applies so-called natural logic, a form of logic which is readable for humans. This logic affords ontological representations...

  8. Crop growth modelling and crop yield forecasting using satellite derived meteorological inputs

    NARCIS (Netherlands)

    Wit, de A.J.W.; Diepen, van K.

    2006-01-01

    One of the key challenges for operational crop monitoring and yield forecasting using crop models is to find spatially representative meteorological input data. Currently, weather inputs are often interpolated from low density networks of weather stations or derived from output from coarse (0.5

  9. Computing Pathways in Bio-Models Derived from Bio-Science Text Sources

    DEFF Research Database (Denmark)

    Andreasen, Troels; Bulskov, Henrik; Nilsson, Jørgen Fischer

    2015-01-01

    This paper outlines a system, OntoScape, serving to accomplish complex inference tasks on knowledge bases and bio-models derived from life-science text corpora. The system applies so-called natural logic, a form of logic which is readable for humans. This logic affords ontological representations...

  10. A new fractional derivative without singular kernel: Application to the modelling of the steady heat flow

    Directory of Open Access Journals (Sweden)

    Yang Xiao-Jun

    2016-01-01

    Full Text Available In this article we propose a new fractional derivative without singular kernel. We consider the potential application for modeling the steady heat-conduction problem. The analytical solution of the fractional-order heat flow is also obtained by means of the Laplace transform.

  11. Polling models with renewal arrivals: a new method to derive heavy-traffic asymptotics

    NARCIS (Netherlands)

    van der Mei, R.D.; Winands, E.M.M.

    2008-01-01

    We consider asymmetric cyclic polling systems with an arbitrary number of queues, general service-time distributions, zero switch-over times, gated service at each queue, and with general renewal arrival processes at each of the queues. For this classical model, we propose a new method to derive

  12. Measurements on 3D models of human skulls derived from two different cone beam CT scanners

    NARCIS (Netherlands)

    van Vlijmen, Olivier J. C.; Rangel, Frits A.; Bergé, Stefaan J.; Bronkhorst, Ewald M.; Becking, Alfred G.; Kuijpers-Jagtman, Anne Marie

    2011-01-01

    The aims of this study were to compare measurements on three-dimensional (3D) models of human skulls derived from two different cone beam CT scanners (CBCT) and to evaluate if the used hardware can influence the performed measurements. CBCT scans of 40 dry human skulls with both the i-CAT and the

  13. Precise troposphere delay model for Egypt, as derived from radiosonde data

    Directory of Open Access Journals (Sweden)

    M.A. Abdelfatah

    2015-06-01

    Real GPS data of six stations in 8-day period were used for the assessment of zenith part of PTD model against the available international models. These international models include Saastamoinen, Hopfield, and the local Egyptian dry model proposed by Mousa & El-Fiky. The data were processed using Bernese software version 5.0. The closure error results indicate that the PTD model is the best model in all session, but when the available radiosonde stations are less, the accuracy of PTD model is near to classic models. As radiosonde data for all ten stations are not available every session, it is recommended to use one of the regularization techniques for database to overcome missing data and derive consistent tropospheric delay information.

  14. Evaluating measurement of dynamic constructs: defining a measurement model of derivatives.

    Science.gov (United States)

    Estabrook, Ryne

    2015-03-01

    While measurement evaluation has been embraced as an important step in psychological research, evaluating measurement structures with longitudinal data is fraught with limitations. This article defines and tests a measurement model of derivatives (MMOD), which is designed to assess the measurement structure of latent constructs both for analyses of between-person differences and for the analysis of change. Simulation results indicate that MMOD outperforms existing models for multivariate analysis and provides equivalent fit to data generation models. Additional simulations show MMOD capable of detecting differences in between-person and within-person factor structures. Model features, applications, and future directions are discussed. (c) 2015 APA, all rights reserved).

  15. Patient Derived Xenograft Models: An Emerging Platform for Translational Cancer Research

    Science.gov (United States)

    Hidalgo, Manuel; Amant, Frederic; Biankin, Andrew V.; Budinská, Eva; Byrne, Annette T.; Caldas, Carlos; Clarke, Robert B.; de Jong, Steven; Jonkers, Jos; Mælandsmo, Gunhild Mari; Roman-Roman, Sergio; Seoane, Joan; Trusolino, Livio; Villanueva, Alberto

    2014-01-01

    Recently, there has been increasing interest in the development and characterization of patient derived tumor xenograft (PDX) models for cancer research. PDX models mostly retain the principal histological and genetic characteristics of their donor tumor and remain stable across passages. These models have been shown to be predictive of clinical outcomes and are being used for preclinical drug evaluation, biomarker identification, biological studies, and personalized medicine strategies. This paper summarizes the current state of the art in this field including methodological issues, available collections, practical applications, challenges and shortcoming, and future directions, and introduces a European consortium of PDX models. PMID:25185190

  16. Duplication in a model of rock fracture with fractional derivative without singular kernel

    OpenAIRE

    Goufo Emile F. Doungmo; Pene Morgan Kamga; Mwambakana Jeanine N.

    2015-01-01

    We provide a mathematical analysis of a break-up model with the newly developed Caputo-Fabrizio fractional order derivative with no singular kernel, modeling rock fracture in the ecosystem. Recall that rock fractures play an important role in ecological and geological events, such as groundwater contamination, earthquakes and volcanic eruptions. Hence, in the theory of rock division, especially in eco-geology, open problems like phenomenon of shattering, which remains partially un...

  17. Modeling the diurnal tide with dissipation derived from UARS/HRDI measurements

    Directory of Open Access Journals (Sweden)

    M. A. Geller

    1997-09-01

    Full Text Available This paper uses dissipation values derived from UARS/HRDI observations in a recently published diurnal-tide model. These model structures compare quite well with the UARS/HRDI observations with respect to the annual variation of the diurnal tidal amplitudes and the size of the amplitudes themselves. It is suggested that the annual variation of atmospheric dissipation in the mesosphere-lower thermosphere is a major controlling factor in determining the annual variation of the diurnal tide.

  18. Modeling of the influence of transparency of the derivatives market on financial depth

    Directory of Open Access Journals (Sweden)

    Irina Burdenko

    2016-07-01

    Full Text Available The market of derivative tools becomes an integral part of the financial market, the functions which are carrying out in it peculiar only to it: hedging, distribution of risks, ensuring liquidity of basic assets, information support of future movement of the prices, decrease in asymmetry of information in the financial markets. However, the insufficiency or lack of transparent information can lead to emergence of the crisis phenomena, shocks in the financial market and growth of system risk. Emergence of need for strengthening of information function of the market of derivatives changes of requirements to transparency of information had been caused by financial crisis of 2008-2009. In this article the attempt of an assessment of influence was made by means of autoregressive models the change of requirements to standard transparency, such as qualitative characteristic of the derivatives market, on quantitative indices of the financial market, in particular financial depth. The results of research demonstrate that reforming of the legislation concerning strengthening of transparency in the derivatives market positively influences the growth of financial depth. The research of this question will promote the best understanding of importance of reforming of regulation of the derivatives market, in particular strengthening of requirements to transparency. Recommendations of the further researches concern the needs of input of reforms of financial regulation in the derivatives market in Ukraine, and, thus, to provide the corresponding conditions for his development

  19. Deformation analysis of polymers composites: rheological model involving time-based fractional derivative

    Science.gov (United States)

    Zhou, H. W.; Yi, H. Y.; Mishnaevsky, L.; Wang, R.; Duan, Z. Q.; Chen, Q.

    2017-05-01

    A modeling approach to time-dependent property of Glass Fiber Reinforced Polymers (GFRP) composites is of special interest for quantitative description of long-term behavior. An electronic creep machine is employed to investigate the time-dependent deformation of four specimens of dog-bond-shaped GFRP composites at various stress level. A negative exponent function based on structural changes is introduced to describe the damage evolution of material properties in the process of creep test. Accordingly, a new creep constitutive equation, referred to fractional derivative Maxwell model, is suggested to characterize the time-dependent behavior of GFRP composites by replacing Newtonian dashpot with the Abel dashpot in the classical Maxwell model. The analytic solution for the fractional derivative Maxwell model is given and the relative parameters are determined. The results estimated by the fractional derivative Maxwell model proposed in the paper are in a good agreement with the experimental data. It is shown that the new creep constitutive model proposed in the paper needs few parameters to represent various time-dependent behaviors.

  20. A 3D-QSAR Study on Betulinic Acid Derivatives as Anti-Tumor Agents and the Synthesis of Novel Derivatives for Modeling Validation.

    Science.gov (United States)

    Ding, Weimin; Zhang, Sheng; Zhu, Meixuan; Wang, Shaoming; Xu, Tao; Qu, Haijing; Yu, Tao; Yan, Xiufeng; Wang, Yang

    2017-01-01

    Betulinic acid is a lupane-type triterpene firstly extracted from the bark of white birch. It has displayed anti-inflammatory, antioxidant, anti-HIV and selective cytotoxicity. To understand the structure- anti-tumor activity relationship of betulinic acid and betulin derivatives and to synthesize novel anti-tumor derivatives of betulinic acid and betulin. The 3D-QSAR methods including CoMFA and CoMSIA methods were performed to study the structureanti- tumor activity relationship of betulinic acid (BA) and betulin (BE) derivatives. According to the models, near the C-3 site, non-bulky, negatively charged electron-donating, hydrophobic, non-hydrogen-bond-donating and hydrogen-bond-accepting groups are favored to the activity. Around the C-28 site, the bulky, positively charged electron-withdrawing and hydrophobic groups are favored, whereas hydrophilic groups may be introduced at the terminal of the side chain. Based on the models, BA and BE were esterified with substituted amino acid derivatives achieving novel derivatives for the modeling validation. The experimental results verified the modeling rules, and showed when different rules may apply to the new structures, the steric effects might be more important. The synthesized derivatives were showed promising cytotoxicity against tested cancer cell lines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Statistical modeling of phenological phases in Poland based on coupling satellite derived products and gridded meteorological data

    Science.gov (United States)

    Czernecki, Bartosz; Jabłońska, Katarzyna; Nowosad, Jakub

    2016-04-01

    ), average monthly temperatures for each month over the previous year for each site, etc. A few commonly applied statistical methods, including multiple regression, random forest, and neural network techniques were tested and evaluated against the onset dates of phenophases. To avoid overfitting of the models, the dataset was divided into a calibration and a validation period using leave-one-out cross-validation method. The obtained results show good potential of using statistical models in filling the temporal and spatial gaps in data, as well as, for forecasting selected phenological phases. However, there are some clear limitations of applying modern satellite observation in plant phenology modelling. Therefore, most of the created phenology models are primarily based on agrometeorological indices with only slightly improvements while using satellite derived products.

  2. Thermal vacuum state for the two-coupled-oscillator model at finite temperature: Derivation and application

    International Nuclear Information System (INIS)

    Xu Xue-Xiang; Hu Li-Yun; Guo Qin; Fan Hong-Yi

    2013-01-01

    Following the spirit of thermo field dynamics initiated by Takahashi and Umezawa, we employ the technique of integration within an ordered product of operators to derive the thermal vacuum state (TVS) for the Hamiltonian H of the two-coupled-oscillator model. The ensemble averages of the system are derived conveniently by using the TVS. In addition, the entropy for this system is discussed based on the relation between the generalized Hellmann—Feynman theorem and the entroy variation in the context of the TVS. (general)

  3. A new visco-elasto-plastic model via time-space fractional derivative

    Science.gov (United States)

    Hei, X.; Chen, W.; Pang, G.; Xiao, R.; Zhang, C.

    2018-02-01

    To characterize the visco-elasto-plastic behavior of metals and alloys we propose a new constitutive equation based on a time-space fractional derivative. The rheological representative of the model can be analogous to that of the Bingham-Maxwell model, while the dashpot element and sliding friction element are replaced by the corresponding fractional elements. The model is applied to describe the constant strain rate, stress relaxation and creep tests of different metals and alloys. The results suggest that the proposed simple model can describe the main characteristics of the experimental observations. More importantly, the model can also provide more accurate predictions than the classic Bingham-Maxwell model and the Bingham-Norton model.

  4. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model.

    Science.gov (United States)

    Kikuchi, Tetsuhiro; Morizane, Asuka; Doi, Daisuke; Magotani, Hiroaki; Onoe, Hirotaka; Hayashi, Takuya; Mizuma, Hiroshi; Takara, Sayuki; Takahashi, Ryosuke; Inoue, Haruhisa; Morita, Satoshi; Yamamoto, Michio; Okita, Keisuke; Nakagawa, Masato; Parmar, Malin; Takahashi, Jun

    2017-08-30

    Induced pluripotent stem cells (iPS cells) are a promising source for a cell-based therapy to treat Parkinson's disease (PD), in which midbrain dopaminergic neurons progressively degenerate. However, long-term analysis of human iPS cell-derived dopaminergic neurons in primate PD models has never been performed to our knowledge. Here we show that human iPS cell-derived dopaminergic progenitor cells survived and functioned as midbrain dopaminergic neurons in a primate model of PD (Macaca fascicularis) treated with the neurotoxin MPTP. Score-based and video-recording analyses revealed an increase in spontaneous movement of the monkeys after transplantation. Histological studies showed that the mature dopaminergic neurons extended dense neurites into the host striatum; this effect was consistent regardless of whether the cells were derived from patients with PD or from healthy individuals. Cells sorted by the floor plate marker CORIN did not form any tumours in the brains for at least two years. Finally, magnetic resonance imaging and positron emission tomography were used to monitor the survival, expansion and function of the grafted cells as well as the immune response in the host brain. Thus, this preclinical study using a primate model indicates that human iPS cell-derived dopaminergic progenitors are clinically applicable for the treatment of patients with PD.

  5. Transplantation of human stem cell-derived hepatocytes in an animal model of acute liver failure.

    Science.gov (United States)

    Ramanathan, Rajesh; Pettinato, Giuseppe; Beeston, John T; Lee, David D; Wen, Xuejun; Mangino, Martin J; Fisher, Robert A

    2015-08-01

    Hepatocyte cell transplantation can be life-saving in patients with acute liver failure (ALF); however, primary human hepatocyte transplantation is limited by the scarcity of donor hepatocytes. We investigated the effect of stem cell-derived, hepatocyte-like cells in an animal xenotransplant model of ALF. Intraperitoneal d-galactosamine was used to develop a lethal model of ALF in the rat. Human induced pluripotent stem cells (iPSC), human mesenchymal stem cells, and human iPSC combined with human endothelial cells (iPSC + EC) were differentiated into hepatocyte-like cells and transplanted into the spleens of athymic nude rats with ALF. A reproducible lethal model of ALF was achieved with nearly 90% death within 3 days. Compared with negative controls, rats transplanted with stem cell-derived, hepatocyte-like cells were associated with increased survival. Human albumin was detected in the rat serum 3 days after transplantation in more than one-half the animals transplanted with hepatocyte-like cells. Only animals transplanted with iPSC + EC-derived hepatocytes had serum human albumin at 14 days posttransplant. Transplanted hepatocyte-like cells homed to the injured rat liver, whereas the ECs were only detected in the spleen. Transplantation of stem cell-derived, hepatocyte-like cells improved survival with evidence of in vivo human albumin production. Combining ECs may prolong cell function after transplantation. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Drainage Structure Datasets and Effects on LiDAR-Derived Surface Flow Modeling

    Directory of Open Access Journals (Sweden)

    Ruopu Li

    2013-12-01

    Full Text Available With extraordinary resolution and accuracy, Light Detection and Ranging (LiDAR-derived digital elevation models (DEMs have been increasingly used for watershed analyses and modeling by hydrologists, planners and engineers. Such high-accuracy DEMs have demonstrated their effectiveness in delineating watershed and drainage patterns at fine scales in low-relief terrains. However, these high-resolution datasets are usually only available as topographic DEMs rather than hydrologic DEMs, presenting greater land roughness that can affect natural flow accumulation. Specifically, locations of drainage structures such as road culverts and bridges were simulated as barriers to the passage of drainage. This paper proposed a geospatial method for producing LiDAR-derived hydrologic DEMs, which incorporates data collection of drainage structures (i.e., culverts and bridges, data preprocessing and burning of the drainage structures into DEMs. A case study of GIS-based watershed modeling in South Central Nebraska showed improved simulated surface water derivatives after the drainage structures were burned into the LiDAR-derived topographic DEMs. The paper culminates in a proposal and discussion of establishing a national or statewide drainage structure dataset.

  7. Solutions of Cattaneo-Hristov model of elastic heat diffusion with Caputo-Fabrizio and Atangana-Baleanu fractional derivatives

    Directory of Open Access Journals (Sweden)

    Koca Ilknur

    2017-01-01

    Full Text Available Recently Hristov using the concept of a relaxation kernel with no singularity developed a new model of elastic heat diffusion equation based on the Caputo-Fabrizio fractional derivative as an extended version of Cattaneo model of heat diffusion equation. In the present article, we solve exactly the Cattaneo-Hristov model and extend it by the concept of a derivative with non-local and non-singular kernel by using the new Atangana-Baleanu derivative. The Cattaneo-Hristov model with the extended derivative is solved analytically with the Laplace transform, and numerically using the Crank-Nicholson scheme.

  8. A constitutive rheological model for agglomerating blood derived from nonequilibrium thermodynamics

    Science.gov (United States)

    Tsimouri, Ioanna Ch.; Stephanou, Pavlos S.; Mavrantzas, Vlasis G.

    2018-03-01

    Red blood cells tend to aggregate in the presence of plasma proteins, forming structures known as rouleaux. Here, we derive a constitutive rheological model for human blood which accounts for the formation and dissociation of rouleaux using the generalized bracket formulation of nonequilibrium thermodynamics. Similar to the model derived by Owens and co-workers ["A non-homogeneous constitutive model for human blood. Part 1. Model derivation and steady flow," J. Fluid Mech. 617, 327-354 (2008)] through polymer network theory, each rouleau in our model is represented as a dumbbell; the corresponding structural variable is the conformation tensor of the dumbbell. The kinetics of rouleau formation and dissociation is treated as in the work of Germann et al. ["Nonequilibrium thermodynamic modeling of the structure and rheology of concentrated wormlike micellar solutions," J. Non-Newton. Fluid Mech. 196, 51-57 (2013)] by assuming a set of reversible reactions, each characterized by a forward and a reverse rate constant. The final set of evolution equations for the microstructure of each rouleau and the expression for the stress tensor turn out to be very similar to those of Owens and co-workers. However, by explicitly considering a mechanism for the formation and breakage of rouleaux, our model further provides expressions for the aggregation and disaggregation rates appearing in the final transport equations, which in the kinetic theory-based network model of Owens were absent and had to be specified separately. Despite this, the two models are found to provide similar descriptions of experimental data on the size distribution of rouleaux.

  9. Vertical Distribution of Suspended Sediment under Steady Flow: Existing Theories and Fractional Derivative Model

    Directory of Open Access Journals (Sweden)

    Shiqian Nie

    2017-01-01

    Full Text Available The fractional advection-diffusion equation (fADE model is a new approach to describe the vertical distribution of suspended sediment concentration in steady turbulent flow. However, the advantages and parameter definition of the fADE model in describing the sediment suspension distribution are still unclear. To address this knowledge gap, this study first reviews seven models, including the fADE model, for the vertical distribution of suspended sediment concentration in steady turbulent flow. The fADE model, among others, describes both Fickian and non-Fickian diffusive characteristics of suspended sediment, while the other six models assume that the vertical diffusion of suspended sediment follows Fick’s first law. Second, this study explores the sensitivity of the fractional index of the fADE model to the variation of particle sizes and sediment settling velocities, based on experimental data collected from the literatures. Finally, empirical formulas are developed to relate the fractional derivative order to particle size and sediment settling velocity. These formulas offer river engineers a substitutive way to estimate the fractional derivative order in the fADE model.

  10. Ability of silybin and its derivatives to prevent protein oxidation in different model systems

    DEFF Research Database (Denmark)

    Purchartová, K.; Baron, C.P.; Křen, V.

    2013-01-01

    to prevent activation of hemoglobin (Hb) to highly reactive hypervalent heme protein species (ferrylHb and perferrylHb) was examined. Indeed, Hb cytotoxicity has been associated with the generation of protein radicals, which are formed when the ferric iron of Hb (Fe3+) is oxidised by H2O2 to (Fe4+) to form...... perferrylHb and ferrylHb, with the later also bearing a radical on its protein. The relationship between the structural properties of silybin and its derivatives and their ability to prevent oxidation of Hb was investigated in model system in the presence or the absence of lipids. The antioxidant activities...... of silybin, dehydrosilybin, 23-O-butanoyl and 23-O-palmitoyl silybin derivatives were correlated with their interaction with Hb species. Results are discussed in relation to the potential of dehydrosilybin, silybin and C4 and C16 derivates to prevent activation of Hb to hypevalent heme protein species....

  11. The Impact of Microwave-Derived Surface Soil Moisture on Watershed Hydrological Modeling

    Science.gov (United States)

    ONeill, P. E.; Hsu, A. Y.; Jackson, T. J.; Wood, E. F.; Zion, M.

    1997-01-01

    The usefulness of incorporating microwave-derived soil moisture information in a semi-distributed hydrological model was demonstrated for the Washita '92 experiment in the Little Washita River watershed in Oklahoma. Initializing the hydrological model with surface soil moisture fields from the ESTAR airborne L-band microwave radiometer on a single wet day at the start of the study period produced more accurate model predictions of soil moisture than a standard hydrological initialization with streamflow data over an eight-day soil moisture drydown.

  12. Using Multiple Satellite-derived Water Levels to Inform Hydrodynamic Model in Sparsely Gauged Areas

    Science.gov (United States)

    Pham, H. T.; Marshall, L. A.; Johnson, F.; Sharma, A.

    2017-12-01

    Satellite radar altimetry from different orbits such as ENVISAT (35-day), Jason-2 (10-day), or CryoSat-2 (369-day) have been used as input data in hydrodynamic models for calibration, parameter estimation, or data assimilation. Due to coarse temporal resolutions, satellite altimeters are usually combined with in-situ data to improve their temporal resolutions and thereby improve model outputs. However, in sparsely gauged areas, using only low temporal resolution satellite altimeters without any complementation of in-situ river heights causes poor model performances. To improve hydrodynamic models in such areas, a method is required to complement high frequent satellite altimeters without using in-situ data. Here we propose a method to supplement 10-day Jason-2 satellite altimetry to produce daily water levels using multiple remotely sensed datasets rather than using in-situ data. A simple seasonal linear regression model is developed of the relationship between Jason-2 satellite altimetry to the difference in day and night land surface temperature (ΔLST) derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) Aqua land surface temperature products, satellite precipitation obtained from the Global Satellite Mapping of Precipitation (GSMAP) product, and satellite soil moisture retrieved from the Soil Moisture and Ocean Salinity (SMOS) product. The main aims of this study are (1) to evaluate the applicability of the daily multiple satellite-derived water levels in hydrodynamic models, and (2) to assess the propagation of uncertainty of multiple satellite datasets to model outputs. A Monte Carlo approach is used to incorporate the errors from multiple satellite input datasets. We apply the methodology at several locations to ensure that the proposed method is robust and reliable. The results indicate the potential of using multiple satellite-derived water levels for hydrodynamic models and other applications in sparsely gauged areas.

  13. Conceptual aspects: analyses law, ethical, human, technical, social factors of development ICT, e-learning and intercultural development in different countries setting out the previous new theoretical model and preliminary findings

    NARCIS (Netherlands)

    Kommers, Petrus A.M.; Smyrnova-Trybulska, Eugenia; Morze, Natalia; Issa, Tomayess; Issa, Theodora

    2015-01-01

    This paper, prepared by an international team of authors focuses on the conceptual aspects: analyses law, ethical, human, technical, social factors of ICT development, e-learning and intercultural development in different countries, setting out the previous and new theoretical model and preliminary

  14. Mint3 in bone marrow-derived cells promotes lung metastasis in breast cancer model mice.

    Science.gov (United States)

    Hara, Toshiro; Murakami, Yoshinori; Seiki, Motoharu; Sakamoto, Takeharu

    2017-08-26

    Breast cancer is one of the most common cancers in women in the world. Although breast cancer is well treatable at the early stage, patients with distant metastases show a poor prognosis. Data from recent studies using transplantation models indicate that Mint3/APBA3 might promote breast cancer malignancy. However, whether Mint3 indeed contributes to tumor development, progression, or metastasis in vivo remains unclear. To address this, here we examined whether Mint3 depletion affects tumor malignancy in MMTV-PyMT breast cancer model mice. In MMTV-PyMT mice, Mint3 depletion did not affect tumor onset and tumor growth, but attenuated lung metastases. Experimental lung metastasis of breast cancer Met-1 cells derived from MMTV-PyMT mice also decreased in Mint3-depleted mice, indicating that host Mint3 expression affected lung metastasis of MMTV-PyMT-derived breast cancer cells. Further bone marrow transplant experiments revealed that Mint3 in bone marrow-derived cells promoted lung metastasis in MMTV-PyMT mice. Thus, targeting Mint3 in bone marrow-derived cells might be a good strategy for preventing metastasis and improving the prognosis of breast cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening.

    Science.gov (United States)

    Broutier, Laura; Mastrogiovanni, Gianmarco; Verstegen, Monique Ma; Francies, Hayley E; Gavarró, Lena Morrill; Bradshaw, Charles R; Allen, George E; Arnes-Benito, Robert; Sidorova, Olga; Gaspersz, Marcia P; Georgakopoulos, Nikitas; Koo, Bon-Kyoung; Dietmann, Sabine; Davies, Susan E; Praseedom, Raaj K; Lieshout, Ruby; IJzermans, Jan N M; Wigmore, Stephen J; Saeb-Parsy, Kourosh; Garnett, Mathew J; van der Laan, Luc Jw; Huch, Meritxell

    2017-12-01

    Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumor, allowing for discrimination between different tumor tissues and subtypes, even after long-term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumorogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug-screening testing and led to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease.

  16. Relating derived relations as a model of analogical reasoning: reaction times and event-related potentials.

    Science.gov (United States)

    Barnes-Holmes, Dermot; Regan, Donal; Barnes-Holmes, Yvonne; Commins, Sean; Walsh, Derek; Stewart, Ian; Smeets, Paul M; Whelan, Robert; Dymond, Simon

    2005-11-01

    The current study aimed to test a Relational Frame Theory (RFT) model of analogical reasoning based on the relating of derived same and derived difference relations. Experiment 1 recorded reaction time measures of similar-similar (e.g., "apple is to orange as dog is to cat") versus different-different (e.g., "he is to his brother as chalk is to cheese") derived relational responding, in both speed-contingent and speed-noncontingent conditions. Experiment 2 examined the event-related potentials (ERPs) associated with these two response patterns. Both experiments showed similar-similar responding to be significantly faster than different-different responding. Experiment 2 revealed significant differences between the waveforms of the two response patterns in the left-hemispheric prefrontal regions; different-different waveforms were significantly more negative than similar-similar waveforms. The behavioral and neurophysiological data support the RFT prediction that, all things being equal, similar-similar responding is relationally "simpler" than, and functionally distinct from, different-different analogical responding. The ERP data were fully consistent with findings in the neurocognitive literature on analogy. These findings strengthen the validity of the RFT model of analogical reasoning and supplement the behavior-analytic approach to analogy based on the relating of derived relations.

  17. A non-local structural derivative model for characterization of ultraslow diffusion in dense colloids

    Science.gov (United States)

    Liang, Yingjie; Chen, Wen

    2018-03-01

    Ultraslow diffusion has been observed in numerous complicated systems. Its mean squared displacement (MSD) is not a power law function of time, but instead a logarithmic function, and in some cases grows even more slowly than the logarithmic rate. The distributed-order fractional diffusion equation model simply does not work for the general ultraslow diffusion. Recent study has used the local structural derivative to describe ultraslow diffusion dynamics by using the inverse Mittag-Leffler function as the structural function, in which the MSD is a function of inverse Mittag-Leffler function. In this study, a new stretched logarithmic diffusion law and its underlying non-local structural derivative diffusion model are proposed to characterize the ultraslow diffusion in aging dense colloidal glass at both the short and long waiting times. It is observed that the aging dynamics of dense colloids is a class of the stretched logarithmic ultraslow diffusion processes. Compared with the power, the logarithmic, and the inverse Mittag-Leffler diffusion laws, the stretched logarithmic diffusion law has better precision in fitting the MSD of the colloidal particles at high densities. The corresponding non-local structural derivative diffusion equation manifests clear physical mechanism, and its structural function is equivalent to the first-order derivative of the MSD.

  18. A Modified Groundwater Flow Model Using the Space Time Riemann-Liouville Fractional Derivatives Approximation

    Directory of Open Access Journals (Sweden)

    Abdon Atangana

    2014-01-01

    Full Text Available The notion of uncertainty in groundwater hydrology is of great importance as it is known to result in misleading output when neglected or not properly accounted for. In this paper we examine this effect in groundwater flow models. To achieve this, we first introduce the uncertainties functions u as function of time and space. The function u accounts for the lack of knowledge or variability of the geological formations in which flow occur (aquifer in time and space. We next make use of Riemann-Liouville fractional derivatives that were introduced by Kobelev and Romano in 2000 and its approximation to modify the standard version of groundwater flow equation. Some properties of the modified Riemann-Liouville fractional derivative approximation are presented. The classical model for groundwater flow, in the case of density-independent flow in a uniform homogeneous aquifer is reformulated by replacing the classical derivative by the Riemann-Liouville fractional derivatives approximations. The modified equation is solved via the technique of green function and the variational iteration method.

  19. Derivation of simplified basic equations of gas-liquid two-phase dispersed flow based on two-fluid model

    International Nuclear Information System (INIS)

    Kataoka, Isao; Tomiyama, Akio

    2004-01-01

    The simplified and physically reasonable basic equations for the gas-liquid dispersed flow were developed based on some appropriate assumptions and the treatment of dispersed phase as isothermal rigid particles. Based on the local instant formulation of mass, momentum and energy conservation of the dispersed flow, time-averaged equations were obtained assuming that physical quantities in the dispersed phase are uniform. These assumptions are approximately valid when phase change rate and/or chemical reaction rate are not so large at gas-liquid interface and there is no heat generation in within the dispersed phase. Detailed discussions were made on the characteristics of obtained basic equations and physical meanings of terms consisting the basic equations. It is shown that, in the derived averaged momentum equation, the terms of pressure gradient and viscous momentum diffusion do not appear and, in the energy equation, the term of molecular thermal diffusion heat flux does not appear. These characteristics of the derived equations were shown to be very consistent concerning the physical interpretation of the gas-liquid dispersed flow. Furthermore, the obtained basic equations are consistent with experiments for the dispersed flow where most of averaged physical quantities are obtained assuming that the distributions of those are uniform within the dispersed phase. Investigation was made on the problem whether the obtained basic equations are well-posed or ill-posed for the initial value problem. The eigenvalues of the simplified mass and momentum equations are calculated for basic equations obtained here and previous two-fluid basic equations with one pressure model. Well-posedness and ill-posedness are judged whether the eigenvalues are real or imaginary. The result indicated the newly developed basic equations always constitute the well-posed initial value problem while the previous two-fluid basic equations based on one pressure model constitutes ill

  20. Influence of satellite-derived photolysis rates and NOx emissions on Texas ozone modeling

    Science.gov (United States)

    Tang, W.; Cohan, D. S.; Pour-Biazar, A.; Lamsal, L. N.; White, A. T.; Xiao, X.; Zhou, W.; Henderson, B. H.; Lash, B. F.

    2015-02-01

    Uncertain photolysis rates and emission inventory impair the accuracy of state-level ozone (O3) regulatory modeling. Past studies have separately used satellite-observed clouds to correct the model-predicted photolysis rates, or satellite-constrained top-down NOx emissions to identify and reduce uncertainties in bottom-up NOx emissions. However, the joint application of multiple satellite-derived model inputs to improve O3 state implementation plan (SIP) modeling has rarely been explored. In this study, Geostationary Operational Environmental Satellite (GOES) observations of clouds are applied to derive the photolysis rates, replacing those used in Texas SIP modeling. This changes modeled O3 concentrations by up to 80 ppb and improves O3 simulations by reducing modeled normalized mean bias (NMB) and normalized mean error (NME) by up to 0.1. A sector-based discrete Kalman filter (DKF) inversion approach is incorporated with the Comprehensive Air Quality Model with extensions (CAMx)-decoupled direct method (DDM) model to adjust Texas NOx emissions using a high-resolution Ozone Monitoring Instrument (OMI) NO2 product. The discrepancy between OMI and CAMx NO2 vertical column densities (VCDs) is further reduced by increasing modeled NOx lifetime and adding an artificial amount of NO2 in the upper troposphere. The region-based DKF inversion suggests increasing NOx emissions by 10-50% in most regions, deteriorating the model performance in predicting ground NO2 and O3, while the sector-based DKF inversion tends to scale down area and nonroad NOx emissions by 50%, leading to a 2-5 ppb decrease in ground 8 h O3 predictions. Model performance in simulating ground NO2 and O3 are improved using sector-based inversion-constrained NOx emissions, with 0.25 and 0.04 reductions in NMBs and 0.13 and 0.04 reductions in NMEs, respectively. Using both GOES-derived photolysis rates and OMI-constrained NOx emissions together reduces modeled NMB and NME by 0.05, increases the model

  1. The role of the Gordon-Schowalter derivative term in the constitutive models - improved flexibility of the modified XPP model

    Czech Academy of Sciences Publication Activity Database

    Pivokonský, Radek; Filip, Petr; Zelenková, Jana

    2015-01-01

    Roč. 4, č. 293 (2015), s. 1227-1236 ISSN 0303-402X Institutional support: RVO:67985874 Keywords : constitutive model * Gordon-Schowalter derivative * PTT model * PTT-XPP model * shear flow * elongational flow Subject RIV: BK - Fluid Dynamics Impact factor: 1.890, year: 2015 http://download.springer.com/ static /pdf/707/art%253A10.1007%252Fs00396-015-3498-7.pdf?auth66=1426682430_7112efb47b46fdc0a8ab81568fe83505&ext=.pdf

  2. Testing sensitivity of the LISFLOOD subgrid hydraulic model to SAR image derived information

    Science.gov (United States)

    Wood, Melissa; Bates, Paul; Neal, Jeff; Hostache, Renaud; Matgen, Patrick; Chini, Marco; Giustarini, Laura

    2013-04-01

    There has been much interest in the use of Synthetic Aperture Radar (SAR) images to indirectly estimate flood extent and flood elevation to aid the understanding of fluvial flood inundation processes. SAR remote sensing satellites are capable of all-weather day/night observations that can discriminate between land and smooth open water surfaces over large scales. By combining SAR derived information with 2D hydraulic models and terrain data, the mechanisms of flooding can be better simulated therefore enabling more accurate and reliable flood forecasting. The objective of this study is to test the sensitivity of a LISFLOOD subgrid 2D model to its main parameters (i.e. roughness coefficient, river bathymetry) using SAR derived flood extent maps. Because of SAR imaging techniques and processing steps used to derive the flood information, any SAR-derived flood extent image will contain inherent uncertainty. We therefore use the uncertainty of the SAR information to obtain a range of plausible parameters to test sensitivity of the hydraulic model. LISFLOOD is a distributed 2D model developed at the University of Bristol and designed for use with larger ungauged river catchments. The version used employs a subgrid procedure which allows any size of river channel below that of the grid resolution to be represented. This procedure has been shown to improve hydraulic connectivity within the modelled flooded area and thus improve flood prediction for data sparse areas. A hydrodynamic LISFLOOD subgrid model of the River Severn at Tewkesbury covering a domain area of 50x70km and including the confluence with a major tributary (the River Avon) will be utilised. A complete storm hydrograph will be used as inflow to the model to simulate the full flood event. Surveyed cross section and gauged daily flows are also available for the River Severn. Therefore, the model results using variable parameters can be compared against results obtained from ground observations to further

  3. In vitro eye irritancy test of polyoxyethylene alkyl derivatives using a reconstructed rabbit corneal epithelium model.

    Science.gov (United States)

    Matsuda, Sanae; Hisama, Masayoshi; Shibayama, Hiroharu; Itou, Norihiko; Iwaki, Masahiro

    2009-05-01

    We have developed the Rabbit Corneal Epithelial (RCE) Model to evaluate the in vitro eye irritation potential of chemicals including pharmaceuticals, cosmetics and their raw ingredients. In the model, a stratified culture of rabbit corneal epithelial cells is grown at the air-liquid interface on an amnion acting as a parabasal membrane. The alkaline exposure was restored each day in the presence of no irritants, although with the addition of sodium lauryl sulfate (SLS), which is a major irritant, the restoration of deficit was inhibited on the RCE model in a dose-dependent manner. The results of this test were comparable with those of the Draize test, and thus, this method using the RCE model may prove to be a useful and sensitive in vitro eye irritation test. The in vitro eye irritation potential of polyoxyethylene alkyl derivatives, polyoxyethylene lauryl ether (PLE), polyoxyethylene cetyl ether (PCE), polyoxyethylene stearyl ether (PSE), polyoxyethylene oleyl ether (POE), and polyoxyethylene behenyl ether (PBE) were evaluated using the RCE model containing an alkaline exposure. POE inhibited 90.2% of the restoration of deficit at a concentration of 0.5% on the 4th day after addition. Depending on the structure, an activity relationship was defined. The polyoxyethylene alkyl derivatives had distinctly different inhibitory potencies against the restoration of deficit, according to their substitution patterns. POE inhibited the restoration of deficit greater than other polyoxyethylene alkyl derivatives on the RCE model. These results indicated that the oleyl chain of POE is an important factor for inhibiting the restoration of deficit on the RCE model.

  4. using explanatory models to derive simple tools for Avanced Life Support system studies - Crop Modelling

    Science.gov (United States)

    Cavazzoni, J.

    System-level analyses for Advanced Life Support (ALS) require mathematical models for various processes, such as biomass production and waste management, which would ideally be integrated into overall system models. Explanatory models (also referred to as mechanistic or process models) would provide the basis for a more robust system model, as these would be based on an understanding of processes specific to ALS studies. However, integrating such models may not always be practicable because of their complexity, especially for initial system-level analyses where simple sub-models may be satisfactory. One way to address this is to capture important features of explanatory models in simple models that may be readily integrated for system-level analyses. In this paper, explanatory crop models were used to generate parameters and multi-variable polynomial equations for basic models that are suitable for estimating the direction and magnitude of daily changes in canopy gas-exchange, harvest index, and production scheduling due to off- nominal conditions for ALS system studies. The simplest variant of these models consists of only a few equations, and has been integrated into a top-level SIMULINK model for the Bioregenerative Planetary Life Support Systems Test Complex (BIO-Plex), a large-scale human-rated test facility under development at NASA Johnson Space Center. When included in systems studies, the simple crop models may help identify issues that need to be addressed using more detailed modeling studies and specific experiments. Similar modeling simplifications may also prove useful for other ALS sub-systems, as well as for Earth system applications.

  5. Modelling and simulation of a dynamical system with the Atangana-Baleanu fractional derivative

    Science.gov (United States)

    Owolabi, Kolade M.

    2018-01-01

    In this paper, we model an ecological system consisting of a predator and two preys with the newly derived two-step fractional Adams-Bashforth method via the Atangana-Baleanu derivative in the Caputo sense. We analyze the dynamical system for correct choice of parameter values that are biologically meaningful. The local analysis of the main model is based on the application of qualitative theory for ordinary differential equations. By using the fixed point theorem idea, we establish the existence and uniqueness of the solutions. Convergence results of the new scheme are verified in both space and time. Dynamical wave phenomena of solutions are verified via some numerical results obtained for different values of the fractional index, which have some interesting ecological implications.

  6. Spin models inferred from patient-derived viral sequence data faithfully describe HIV fitness landscapes.

    Science.gov (United States)

    Shekhar, Karthik; Ruberman, Claire F; Ferguson, Andrew L; Barton, John P; Kardar, Mehran; Chakraborty, Arup K

    2013-12-01

    Mutational escape from vaccine-induced immune responses has thwarted the development of a successful vaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus' fitness as a function of its proteomic sequence can enable rational design of potent vaccines, as this information can focus vaccine-induced immune responses to target mutational vulnerabilities of the virus. Spin models have been proposed as a means to infer intrinsic fitness landscapes of HIV proteins from patient-derived viral protein sequences. These sequences are the product of nonequilibrium viral evolution driven by patient-specific immune responses and are subject to phylogenetic constraints. How can such sequence data allow inference of intrinsic fitness landscapes? We combined computer simulations and variational theory á la Feynman to show that, in most circumstances, spin models inferred from patient-derived viral sequences reflect the correct rank order of the fitness of mutant viral strains. Our findings are relevant for diverse viruses.

  7. Spin models inferred from patient-derived viral sequence data faithfully describe HIV fitness landscapes

    Science.gov (United States)

    Shekhar, Karthik; Ruberman, Claire F.; Ferguson, Andrew L.; Barton, John P.; Kardar, Mehran; Chakraborty, Arup K.

    2013-12-01

    Mutational escape from vaccine-induced immune responses has thwarted the development of a successful vaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus' fitness as a function of its proteomic sequence can enable rational design of potent vaccines, as this information can focus vaccine-induced immune responses to target mutational vulnerabilities of the virus. Spin models have been proposed as a means to infer intrinsic fitness landscapes of HIV proteins from patient-derived viral protein sequences. These sequences are the product of nonequilibrium viral evolution driven by patient-specific immune responses and are subject to phylogenetic constraints. How can such sequence data allow inference of intrinsic fitness landscapes? We combined computer simulations and variational theory á la Feynman to show that, in most circumstances, spin models inferred from patient-derived viral sequences reflect the correct rank order of the fitness of mutant viral strains. Our findings are relevant for diverse viruses.

  8. Genomic predictors for recurrence patterns of hepatocellular carcinoma: model derivation and validation.

    Directory of Open Access Journals (Sweden)

    Ji Hoon Kim

    2014-12-01

    Full Text Available BACKGROUND: Typically observed at 2 y after surgical resection, late recurrence is a major challenge in the management of hepatocellular carcinoma (HCC. We aimed to develop a genomic predictor that can identify patients at high risk for late recurrence and assess its clinical implications. METHODS AND FINDINGS: Systematic analysis of gene expression data from human liver undergoing hepatic injury and regeneration revealed a 233-gene signature that was significantly associated with late recurrence of HCC. Using this signature, we developed a prognostic predictor that can identify patients at high risk of late recurrence, and tested and validated the robustness of the predictor in patients (n = 396 who underwent surgery between 1990 and 2011 at four centers (210 recurrences during a median of 3.7 y of follow-up. In multivariate analysis, this signature was the strongest risk factor for late recurrence (hazard ratio, 2.2; 95% confidence interval, 1.3-3.7; p = 0.002. In contrast, our previously developed tumor-derived 65-gene risk score was significantly associated with early recurrence (p = 0.005 but not with late recurrence (p = 0.7. In multivariate analysis, the 65-gene risk score was the strongest risk factor for very early recurrence (<1 y after surgical resection (hazard ratio, 1.7; 95% confidence interval, 1.1-2.6; p = 0.01. The potential significance of STAT3 activation in late recurrence was predicted by gene network analysis and validated later. We also developed and validated 4- and 20-gene predictors from the full 233-gene predictor. The main limitation of the study is that most of the patients in our study were hepatitis B virus-positive. Further investigations are needed to test our prediction models in patients with different etiologies of HCC, such as hepatitis C virus. CONCLUSIONS: Two independently developed predictors reflected well the differences between early and late recurrence of HCC at the molecular level and provided new

  9. Anomalous Advection-Dispersion Equations within General Fractional-Order Derivatives: Models and Series Solutions

    Directory of Open Access Journals (Sweden)

    Xin Liang

    2018-01-01

    Full Text Available In this paper, an anomalous advection-dispersion model involving a new general Liouville–Caputo fractional-order derivative is addressed for the first time. The series solutions of the general fractional advection-dispersion equations are obtained with the aid of the Laplace transform. The results are given to demonstrate the efficiency of the proposed formulations to describe the anomalous advection dispersion processes.

  10. Using induced pluripotent stem cells derived neurons to model brain diseases

    Directory of Open Access Journals (Sweden)

    Cindy E McKinney

    2017-01-01

    Full Text Available The ability to use induced pluripotent stem cells (iPSC to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders. Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology. iPSC derived neurons, or other neural cell types, provide the ability to access pathology in cells derived directly from a patient's blood sample or skin biopsy where availability of brain tissue is limiting. Thus, utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future. Many brain diseases across the spectrum of neurodevelopment, neurodegenerative and neuropsychiatric are being approached by iPSC models. The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells. In this mini-review, the importance of iPSC cell models validated for pluripotency, germline competency and function assessments is discussed. Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.

  11. Radiopharmacology of iminodiacetic acid N-derivatives analysis in biological models and comparison to human beings

    International Nuclear Information System (INIS)

    Canellas, C.O.; Arguelles, M.G.; Mitta, A.E.A.

    1987-01-01

    It was studied the influence of chemical structures and molecular weight in the distribution of several iminodiacetic acid N-derivatives and to determine the potential use of these radiopharmaceuticals in humans. The study was performed with the following derivatives: N-(2,6 dimetyphenylcarbamoylmethy) iminodiacetic acid, N(2.6 dietylphenyl-carbamoylmethy) iminodiacetic acid, N-(2,6 diisopropylphenylcarbamoylmethy) iminodiacetic acid and the previously unknown N-derivative N-(2,6 diisopropyl, phenylcarbamoylethyl) iminodiacetic aced. These were sinthesized by a modified procedure by MITTA et al. and controlled by NMR, mass spectrometry, elemental composition and also toxicity pirogens, lethal dose and the chelate's radiochemical dose were determined. Liver gallbladder, intestinal and renal kinetics were studied in mice. In order to evaluate the metabolic pathways of the radiopharmaceuticals, the content of gallbladder and the urine were reinjected. Plasma kinetics and the plasmatic half life was determined by extracorporeal circulation in Wistar rats. For the use in human beings, test were carried out in different branches of nuclear medicine, in normal volunteers and carriers of different pathologic disorders. The patients were divided into four groups: acute and chronic cholecystitis, cirrhosis and jaundice. It was obtained the liver/heart activity ratio and estimated the appearance times of the intrahepatic ducts, gallbladder, duodenum and renal persistence. (M.E.L.) [es

  12. Therapeutic effect of transplanted human Wharton's jelly stem cell-derived oligodendrocyte progenitor cells (hWJ-MSC-derived OPCs) in an animal model of multiple sclerosis.

    Science.gov (United States)

    Mikaeili Agah, Elmira; Parivar, Kazem; Joghataei, Mohammad Taghi

    2014-04-01

    Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS). A potential new therapeutic approach for MS is cell transplantation which may promote remyelination. We transplanted human Wharton's jelly stem cell-derived oligodendrocyte progenitor cells (hWJ-MSC-derived OPCs) into the brain ventricles of mice induced with experimental autoimmune encephalomyelitis (EAE), the animal model of MS. We studied the effect of the transplanted OPCs on the functional and pathological manifestations of the disease. Transplanted hWJ-MSC-derived OPCs significantly reduced the clinical signs of EAE. Histological examinations showed that remyelination was significantly increased after transplantation. These results suggest that hWJ-MSC-derived OPCs promote the regeneration of myelin sheaths in the brain.

  13. Mixing height derived from the DMI-HIRLAM NWP model, and used for ETEX dispersion modelling

    Energy Technology Data Exchange (ETDEWEB)

    Soerensen, J.H.; Rasmussen, A. [Danish Meteorological Inst., Copenhagen (Denmark)

    1997-10-01

    For atmospheric dispersion modelling it is of great significance to estimate the mixing height well. Mesoscale and long-range diffusion models using output from numerical weather prediction (NWP) models may well use NWP model profiles of wind, temperature and humidity in computation of the mixing height. This is dynamically consistent, and enables calculation of the mixing height for predicted states of the atmosphere. In autumn 1994, the European Tracer Experiment (ETEX) was carried out with the objective to validate atmospheric dispersion models. The Danish Meteorological Institute (DMI) participates in the model evaluations with the Danish Emergency Response Model of the Atmosphere (DERMA) using NWP model data from the DMI version of the High Resolution Limited Area Model (HIRLAM) as well as from the global model of the European Centre for Medium-Range Weather Forecast (ECMWF). In DERMA, calculation of mixing heights are performed based on a bulk Richardson number approach. Comparing with tracer gas measurements for the first ETEX experiment, a sensitivity study is performed for DERMA. Using DMI-HIRLAM data, the study shows that optimum values of the critical bulk Richardson number in the range 0.15-0.35 are adequate. These results are in agreement with recent mixing height verification studies against radiosonde data. The fairly large range of adequate critical values is a signature of the robustness of the method. Direct verification results against observed missing heights from operational radio-sondes released under the ETEX plume are presented. (au) 10 refs.

  14. Effect of ECG-derived respiration (EDR) on modeling ventricular repolarization dynamics in different physiological and psychological conditions.

    Science.gov (United States)

    Imam, M H; Karmakar, C K; Khandoker, A H; Palaniswami, M

    2014-10-01

    Ventricular repolarization dynamics is an important predictor of the outcome in cardiovascular diseases. Mathematical modeling of the heart rate variability (RR interval variability) and ventricular repolarization variability (QT interval variability) is one of the popular methods to understand the dynamics of ventricular repolarization. Although ECG derived respiration (EDR) was previously suggested as a surrogate of respiration, but the effect of respiratory movement on ventricular repolarization dynamics was not studied. In this study, the importance of considering the effect of respiration and the validity of using EDR as a surrogate of respiration for linear parametric modeling of ventricular repolarization variability is studied in two cases with different physiological and psychological conditions. In the first case study, we used 20 young and 20 old healthy subjects' ECG and respiration data from Fantasia database at Physionet to analyze a bivariate QT-RR and a trivariate [Formula: see text] model structure to study the aging effect on cardiac repolarization variability. In the second study, we used 16 healthy subjects' data from drivedb (stress detection for automobile drivers) database at Physionet to do the same analysis for different psychological condition (i.e., in stressed and no stress condition). The results of our study showed that model having respiratory information (QT-RR-RESP and QT-RR-EDR) gave significantly better fit value (p 0.05) performance as that of respiration as an exogenous model input in describing repolarization variability irrespective of age and different mental conditions. Another finding of our study is that both respiration and EDR-based models can significantly (p < 0.05) differentiate the ventricular repolarization dynamics between healthy subjects of different age groups and with different psychological conditions, whereas models without respiration or EDR cannot distinguish between the groups. These results established

  15. Intermediate modeling between kinetic equations and hydrodynamic limits: derivation, analysis and simulations

    International Nuclear Information System (INIS)

    Parisot, M.

    2011-01-01

    This work is dedicated study of a problem resulting from plasma physics: the thermal transfer of electrons in a plasma close to equilibrium Maxwellian. Firstly, a dimensional study of the Vlasov-Fokker-Planck-Maxwell system is performed, allowing one hand to identify a physically relevant parameter of scale and also to define mathematically the contours of validity domain. The asymptotic regime called Spitzer-Harm is studied for a relatively general class of collision operator. The following part of this work is devoted to the derivation and study of the hydrodynamic limit of the system of Vlasov-Maxwell-Landau outside the strictly asymptotic. A model proposed by Schurtz and Nicolais located in this context and analyzed. The particularity of this model lies in the application of a delocalization operation in the heat flux. The link with non-local models of Luciani and Mora is established as well as mathematics properties as the principle of maximum and entropy dissipation. Then a formal derivation from the Vlasov equations with a simplified collision operator, is proposed. The derivation, inspired by the recent work of D. Levermore, involves decomposition methods according to the spherical harmonics and methods of closing called diffusion methods. A hierarchy of intermediate models between the kinetic equations and the hydrodynamic limit is described. In particular a new hydrodynamic system integro-differential by nature, is proposed. The Schurtz and Nicolai model appears as a simplification of the system resulting from the derivation, assuming a steady flow of heat. The above results are then generalized to account for the internal energy dependence which appears naturally in the equation establishment. The existence and uniqueness of the solution of the nonstationary system are established in a simplified framework. The last part is devoted was the implementation of a specific numerical scheme to solve these models. We propose a finite volume approach can be

  16. Large Differences in Terrestrial Vegetation Production Derived from Satellite-Based Light Use Efficiency Models

    Directory of Open Access Journals (Sweden)

    Wenwen Cai

    2014-09-01

    Full Text Available Terrestrial gross primary production (GPP is the largest global CO2 flux and determines other ecosystem carbon cycle variables. Light use efficiency (LUE models may have the most potential to adequately address the spatial and temporal dynamics of GPP, but recent studies have shown large model differences in GPP simulations. In this study, we investigated the GPP differences in the spatial and temporal patterns derived from seven widely used LUE models at the global scale. The result shows that the global annual GPP estimates over the period 2000–2010 varied from 95.10 to 139.71 Pg C∙yr−1 among models. The spatial and temporal variation of global GPP differs substantially between models, due to different model structures and dominant environmental drivers. In almost all models, water availability dominates the interannual variability of GPP over large vegetated areas. Solar radiation and air temperature are not the primary controlling factors for interannual variability of global GPP estimates for most models. The disagreement among the current LUE models highlights the need for further model improvement to quantify the global carbon cycle.

  17. In silico modeling predicts drug sensitivity of patient-derived cancer cells.

    Science.gov (United States)

    Pingle, Sandeep C; Sultana, Zeba; Pastorino, Sandra; Jiang, Pengfei; Mukthavaram, Rajesh; Chao, Ying; Bharati, Ila Sri; Nomura, Natsuko; Makale, Milan; Abbasi, Taher; Kapoor, Shweta; Kumar, Ansu; Usmani, Shahabuddin; Agrawal, Ashish; Vali, Shireen; Kesari, Santosh

    2014-05-21

    Glioblastoma (GBM) is an aggressive disease associated with poor survival. It is essential to account for the complexity of GBM biology to improve diagnostic and therapeutic strategies. This complexity is best represented by the increasing amounts of profiling ("omics") data available due to advances in biotechnology. The challenge of integrating these vast genomic and proteomic data can be addressed by a comprehensive systems modeling approach. Here, we present an in silico model, where we simulate GBM tumor cells using genomic profiling data. We use this in silico tumor model to predict responses of cancer cells to targeted drugs. Initially, we probed the results from a recent hypothesis-independent, empirical study by Garnett and co-workers that analyzed the sensitivity of hundreds of profiled cancer cell lines to 130 different anticancer agents. We then used the tumor model to predict sensitivity of patient-derived GBM cell lines to different targeted therapeutic agents. Among the drug-mutation associations reported in the Garnett study, our in silico model accurately predicted ~85% of the associations. While testing the model in a prospective manner using simulations of patient-derived GBM cell lines, we compared our simulation predictions with experimental data using the same cells in vitro. This analysis yielded a ~75% agreement of in silico drug sensitivity with in vitro experimental findings. These results demonstrate a strong predictability of our simulation approach using the in silico tumor model presented here. Our ultimate goal is to use this model to stratify patients for clinical trials. By accurately predicting responses of cancer cells to targeted agents a priori, this in silico tumor model provides an innovative approach to personalizing therapy and promises to improve clinical management of cancer.

  18. Development of models for prediction of the antioxidant activity of derivatives of natural compounds.

    Science.gov (United States)

    Martinčič, Rok; Kuzmanovski, Igor; Wagner, Alain; Novič, Marjana

    2015-04-08

    Antioxidants are important for maintaining the appropriate balance between oxidizing and reducing species in the body and thus preventing oxidative stress. Many natural compounds are being screened for their possible antioxidant activity. It was found that a mushroom pigment Norbadione A, which is a pulvinic acid derivative, shows an antioxidant activity; the same was found for other pulvinic acid derivatives and structurally related coumarines. Based on the results of in vitro studies performed on these compounds as a part of this study quantitative structure-activity relationship (QSAR) predictive models were constructed using multiple linear regression, counter-propagation artificial neural networks and support vector regression (SVR). The models have been developed in accordance with current QSAR guidelines, including the assessment of the models applicability domains. A new approach for the graphical evaluation of the applicability domain for SVR models is suggested. The developed models show sufficient predictive abilities for the screening of virtual libraries for new potential antioxidants. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Testing an Inflation Model with Nonminimal Derivative Coupling in the Light of Planck 2015 Data

    Directory of Open Access Journals (Sweden)

    Kourosh Nozari

    2016-01-01

    Full Text Available We study the dynamics of a generalized inflationary model in which both the scalar field and its derivatives are coupled with the gravity. We consider a general form of the nonminimal derivative coupling in order to have a complete treatment of the model. By expanding the action up to the second order in perturbation, we study the spectrum of the primordial modes of the perturbations. Also, by expanding the action up to the third order and considering the three-point correlation functions, the amplitude of the non-Gaussianity of the primordial perturbations is studied in both equilateral and orthogonal configurations. Finally, by adopting some sort of potentials, we compare the model in hand with the Planck 2015 released observational data and obtain some constraints on the model’s parameters space. As an important result, we show that the nonminimal couplings help to make models of chaotic inflation that would otherwise be in tension with Planck data, in better agreement with the data. This model is consistent with observation at weak coupling limit.

  20. Deriving albedo maps for HAPEX-Sahel from ASAS data using kernel-driven BRDF models

    Directory of Open Access Journals (Sweden)

    P. Lewis

    1999-01-01

    Full Text Available This paper describes the application and testing of a method for deriving spatial estimates of albedo from multi-angle remote sensing data. Linear kernel-driven models of surface bi-directional reflectance have been inverted against high spatial resolution multi-angular, multi- spectral airborne data of the principal cover types within the HAPEX-Sahel study site in Niger, West Africa. The airborne data are obtained from the NASA Airborne Solid-state Imaging Spectrometer (ASAS instrument, flown in Niger in September and October 1992. The maps of model parameters produced are used to estimate integrated reflectance properties related to spectral albedo. Broadband albedo has been estimated from this by weighting the spectral albedo for each pixel within the map as a function of the appropriate spectral solar irradiance and proportion of direct and diffuse illumination. Partial validation of the results was performed by comparing ASAS reflectance and derived directional-hemispherical reflectance with simulations of a millet canopy made with a complex geometric canopy reflectance model, the Botanical Plant Modelling System (BPMS. Both were found to agree well in magnitude. Broadband albedo values derived from the ASAS data were compared with ground-based (point sample albedo measurements and found to agree extremely well. These results indicate that the linear kernel-driven modelling approach, which is to be used operationally to produce global 16 day, 1 km albedo maps from forthcoming NASA Earth Observing System spaceborne data, is both sound and practical for the estimation of angle-integrated spectral reflectance quantities related to albedo. Results for broadband albedo are dependent on spectral sampling and on obtaining the correct spectral weigthings.

  1. Deformation analysis of polymers composites: rheological model involving time-based fractional derivative

    DEFF Research Database (Denmark)

    Zhou, H. W.; Yi, H. Y.; Mishnaevsky, Leon

    2017-01-01

    A modeling approach to time-dependent property of Glass Fiber Reinforced Polymers (GFRP) composites is of special interest for quantitative description of long-term behavior. An electronic creep machine is employed to investigate the time-dependent deformation of four specimens of dog-bond-shaped......A modeling approach to time-dependent property of Glass Fiber Reinforced Polymers (GFRP) composites is of special interest for quantitative description of long-term behavior. An electronic creep machine is employed to investigate the time-dependent deformation of four specimens of dog......, is suggested to characterize the time-dependent behavior of GFRP composites by replacing Newtonian dashpot with the Abel dashpot in the classical Maxwell model. The analytic solution for the fractional derivative Maxwell model is given and the relative parameters are determined. The results estimated...

  2. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Afford New Opportunities in Inherited Cardiovascular Disease Modeling

    Directory of Open Access Journals (Sweden)

    Daniel R. Bayzigitov

    2016-01-01

    Full Text Available Fundamental studies of molecular and cellular mechanisms of cardiovascular disease pathogenesis are required to create more effective and safer methods of their therapy. The studies can be carried out only when model systems that fully recapitulate pathological phenotype seen in patients are used. Application of laboratory animals for cardiovascular disease modeling is limited because of physiological differences with humans. Since discovery of induced pluripotency generating induced pluripotent stem cells has become a breakthrough technology in human disease modeling. In this review, we discuss a progress that has been made in modeling inherited arrhythmias and cardiomyopathies, studying molecular mechanisms of the diseases, and searching for and testing drug compounds using patient-specific induced pluripotent stem cell-derived cardiomyocytes.

  3. Antitumor activity of the multikinase inhibitor regorafenib in patient-derived xenograft models of gastric cancer.

    Science.gov (United States)

    Huynh, Hung; Ong, Richard; Zopf, Dieter

    2015-10-29

    Unresectable gastric cancer is associated with poor outcomes, with few treatment options available after failure of cytotoxic chemotherapy. Clinical trials of targeted therapies have generally shown no survival benefit in gastric cancer, with the exceptions of the antibodies ramucirumab (anti-VEGFR2) and trastuzumab (anti-HER2/neu). Given the efficacy of the multikinase inhibitor regorafenib in other gastrointestinal tumors, we investigated its potential in gastric cancer. The antitumor activity of oral regorafenib was assessed in eight murine patient-derived gastric cancer xenograft models. Dose-response experiments assessed the efficacy and tolerability of oral regorafenib 5, 10, and 15 mg/kg/day in two models, with 10 mg/kg/day selected for further investigation in all eight models. Tumor weight and volume was monitored during treatment; tumor cell proliferation, angiogenesis, apoptosis, and intracellular signaling were assessed using immunohistochemistry and Western blotting of total tumor lysates at the end of treatment. Regorafenib showed dose-dependent inhibition of tumor growth and was well tolerated, with no significant decreases in bodyweight or evident toxicity. Regorafenib 10 mg/kg/day significantly inhibited tumor growth in all eight models (72 to 96 %; all p Regorafenib reduced tumor angiogenesis 3- to 11-fold versus controls in all models (all p Regorafenib was effective in patient-derived models of gastric cancer of different histological subtypes, with inhibition of tumor growth, angiogenesis, and tumor-cell proliferation observed in almost all models. These findings are consistent with the observed activity of regorafenib in preclinical models of other gastrointestinal tumors, and support further clinical investigation in gastric cancer.

  4. Human bone marrow-derived and umbilical cord-derived mesenchymal stem cells for alleviating neuropathic pain in a spinal cord injury model

    OpenAIRE

    Yousefifard, Mahmoud; Nasirinezhad, Farinaz; Shardi Manaheji, Homa; Janzadeh, Atousa; Hosseini, Mostafa; Keshavarz, Mansoor

    2016-01-01

    Background Stem cell therapy can be used for alleviating the neuropathic pain induced by spinal cord injuries (SCIs). However, survival and differentiation of stem cells following their transplantation vary depending on the host and intrinsic factors of the cell. Therefore, the present study aimed to determine the effect of stem cells derived from bone marrow (BM-MSC) and umbilical cord (UC-MSC) on neuropathic pain relief. Methods A compression model was used to induce SCI in a rat model. A w...

  5. Integrating hydrodynamic models and COSMO-SkyMed derived products for flood damage assessment

    Science.gov (United States)

    Giuffra, Flavio; Boni, Giorgio; Pulvirenti, Luca; Pierdicca, Nazzareno; Rudari, Roberto; Fiorini, Mattia

    2015-04-01

    Floods are the most frequent weather disasters in the world and probably the most costly in terms of social and economic losses. They may have a strong impact on infrastructures and health because the range of possible damages includes casualties, loss of housing and destruction of crops. Presently, the most common approach for remotely sensing floods is the use of synthetic aperture radar (SAR) images. Key features of SAR data for inundation mapping are the synoptic view, the capability to operate even in cloudy conditions and during both day and night time and the sensitivity of the microwave radiation to water. The launch of a new generation of instruments, such as TerraSAR-X and COSMO-SkyMed (CSK) allows producing near real time flood maps having a spatial resolution in the order of 1-5 m. Moreover, the present (CSK) and upcoming (Sentinel-1) constellations permit the acquisition of radar data characterized by a short revisit time (in the order of some hours for CSK), so that the production of frequent inundation maps can be envisaged. Nonetheless, gaps might be present in the SAR-derived flood maps because of the limited area imaged by SAR; moreover, the detection of floodwater may be complicated by the presence of very dense vegetation or urban settlements. Hence the need to complement SAR-derived flood maps with the outputs of physical models. Physical models allow delivering to end users very useful information for a complete flood damage assessment, such as data on water depths and flow directions, which cannot be directly derived from satellite remote sensing images. In addition, the flood extent predictions of hydraulic models can be compared to SAR-derived inundation maps to calibrate the models, or to fill the aforementioned gaps that can be present in the SAR-derived maps. Finally, physical models enable the construction of risk scenarios useful for emergency managers to take their decisions and for programming additional SAR acquisitions in order to

  6. Characterization of a Murine Pressure Ulcer Model to Assess Efficacy of Adipose-derived Stromal Cells.

    Science.gov (United States)

    Strong, Amy L; Bowles, Annie C; MacCrimmon, Connor P; Lee, Stephen J; Frazier, Trivia P; Katz, Adam J; Gawronska-Kozak, Barbara; Bunnell, Bruce A; Gimble, Jeffrey M

    2015-03-01

    As the world's population lives longer, the number of individuals at risk for pressure ulcers will increase considerably in the coming decades. In developed countries, up to 18% of nursing home residents suffer from pressure ulcers and the resulting hospital costs can account for up to 4% of a nation's health care budget. Although full-thickness surgical skin wounds have been used as a model, preclinical rodent studies have demonstrated that repeated cycles of ischemia and reperfusion created by exposure to magnets most closely mimic the human pressure ulcer condition. This study uses in vivo and in vitro quantitative parameters to characterize the temporal kinetics and histology of pressure ulcers in young, female C57BL/6 mice exposed to 2 or 3 ischemia-reperfusion cycles. This pressure ulcer model was validated further in studies examining the efficacy of adipose-derived stromal/stem cell administration. Optimal results were obtained with the 2-cycle model based on the wound size, histology, and gene expression profile of representative angiogenic and reparative messenger RNAs. When treated with adipose-derived stromal/stem cells, pressure ulcer wounds displayed a dose-dependent and significant acceleration in wound closure rates and improved tissue histology. These findings document the utility of this simplified preclinical model for the evaluation of novel tissue engineering and medical approaches to treat pressure ulcers in humans.

  7. Covariance matrices for nuclear cross sections derived from nuclear model calculations

    International Nuclear Information System (INIS)

    Smith, D. L.

    2005-01-01

    The growing need for covariance information to accompany the evaluated cross section data libraries utilized in contemporary nuclear applications is spurring the development of new methods to provide this information. Many of the current general purpose libraries of evaluated nuclear data used in applications are derived either almost entirely from nuclear model calculations or from nuclear model calculations benchmarked by available experimental data. Consequently, a consistent method for generating covariance information under these circumstances is required. This report discusses a new approach to producing covariance matrices for cross sections calculated using nuclear models. The present method involves establishing uncertainty information for the underlying parameters of nuclear models used in the calculations and then propagating these uncertainties through to the derived cross sections and related nuclear quantities by means of a Monte Carlo technique rather than the more conventional matrix error propagation approach used in some alternative methods. The formalism to be used in such analyses is discussed in this report along with various issues and caveats that need to be considered in order to proceed with a practical implementation of the methodology

  8. Modeling of a three-phase reactor for bitumen-derived gas oil hydrotreating

    Energy Technology Data Exchange (ETDEWEB)

    Chacon, R.; Canale, A.; Bouza, A. [Departamento de Termodinamica y Fenomenos de Transporte. Universidad Simon Bolivar, Caracas (Venezuela, Bolivarian Republic of); Sanchez, Y. [Departamento de Procesos y Sistemas. Universidad Simon Bolivar (Venezuela, Bolivarian Republic of)

    2012-01-15

    A three-phase reactor model for describing the hydrotreating reactions of bitumen-derived gas oil was developed. The model incorporates the mass-transfer resistance at the gas-liquid and liquid-solid interfaces and a kinetic rate expression based on a Langmuir-Hinshelwood-type model. We derived three correlations for determining the solubility of hydrogen (H{sub 2}), hydrogen sulfide (H{sub 2}S) and ammonia (NH{sub 3}) in hydrocarbon mixtures and the calculation of the catalyst effectiveness factor was included. Experimental data taken from the literature were used to determine the kinetic parameters (stoichiometric coefficients, reaction orders, reaction rate and adsorption constants for hydrodesulfuration (HDS) and hydrodenitrogenation (HDN)) and to validate the model under various operating conditions. Finally, we studied the effect of operating conditions such as pressure, temperature, LHSV, H{sub 2}/feed ratio and the inhibiting effect of H{sub 2}S on HDS and NH{sub 3} on HDN. (author)

  9. Mathematical modeling of tetrahydroimidazole benzodiazepine-1-one derivatives as an anti HIV agent

    Science.gov (United States)

    Ojha, Lokendra Kumar

    2017-07-01

    The goal of the present work is the study of drug receptor interaction via QSAR (Quantitative Structure-Activity Relationship) analysis for 89 set of TIBO (Tetrahydroimidazole Benzodiazepine-1-one) derivatives. MLR (Multiple Linear Regression) method is utilized to generate predictive models of quantitative structure-activity relationships between a set of molecular descriptors and biological activity (IC50). The best QSAR model was selected having a correlation coefficient (r) of 0.9299 and Standard Error of Estimation (SEE) of 0.5022, Fisher Ratio (F) of 159.822 and Quality factor (Q) of 1.852. This model is statistically significant and strongly favours the substitution of sulphur atom, IS i.e. indicator parameter for -Z position of the TIBO derivatives. Two other parameter logP (octanol-water partition coefficient) and SAG (Surface Area Grid) also played a vital role in the generation of best QSAR model. All three descriptor shows very good stability towards data variation in leave-one-out (LOO).

  10. One in vitro model for visceral adipose-derived fibroblasts in chronic inflammation

    International Nuclear Information System (INIS)

    Yue Guiping; Du Lirui; Xia Tao; He Xianhui; Qiu Huan; Xu Lihui; Chen Xiaodong; Feng Shengqiu; Yang Zaiqing

    2005-01-01

    One pathogenesis of the obesity-associated complications is that consistent with increased body fat mass, the elevation of adipose tissue-derived cytokines inflicts a low-grade chronic inflammation, which ultimately leads to metabolic disorders. Adipocytes and macrophages in visceral adipose (VA) have been confirmed to contribute to the chronic inflammation; however, the role of the resident fibroblasts is still unknown. We established one VA fibroblast cell line, termed VAFC. Morphological analysis indicated that there were large numbers of pits at the cell plasma membrane. In vitro VAFC cells promoted bone marrow cells to differentiate into macrophages and protected them from apoptosis in the serum-free conditions. Additionally, they also interfered in lymphocytes proliferation. On the basis of these results, this cell line might be an in vitro model for understanding the role of adipose-derived fibroblasts in obesity-associated chronic inflammation

  11. Direct phase derivative estimation using difference equation modeling in holographic interferometry

    International Nuclear Information System (INIS)

    Kulkarni, Rishikesh; Rastogi, Pramod

    2014-01-01

    A new method is proposed for the direct phase derivative estimation from a single spatial frequency modulated carrier fringe pattern in holographic interferometry. The fringe intensity in a given row/column is modeled as a difference equation of intensity with spatially varying coefficients. These coefficients carry the information on the phase derivative. Consequently, the accurate estimation of the coefficients is obtained by approximating the coefficients as a linear combination of the predefined linearly independent basis functions. Unlike Fourier transform based fringe analysis, the method does not call for performing the filtering of the Fourier spectrum of fringe intensity. Moreover, the estimation of the carrier frequency is performed by applying the proposed method to a reference interferogram. The performance of the proposed method is insensitive to the fringe amplitude modulation and is validated with the simulation results. (paper)

  12. Development of a Model for Dynamic Recrystallization Consistent with the Second Derivative Criterion

    Directory of Open Access Journals (Sweden)

    Muhammad Imran

    2017-11-01

    Full Text Available Dynamic recrystallization (DRX processes are widely used in industrial hot working operations, not only to keep the forming forces low but also to control the microstructure and final properties of the workpiece. According to the second derivative criterion (SDC by Poliak and Jonas, the onset of DRX can be detected from an inflection point in the strain-hardening rate as a function of flow stress. Various models are available that can predict the evolution of flow stress from incipient plastic flow up to steady-state deformation in the presence of DRX. Some of these models have been implemented into finite element codes and are widely used for the design of metal forming processes, but their consistency with the SDC has not been investigated. This work identifies three sources of inconsistencies that models for DRX may exhibit. For a consistent modeling of the DRX kinetics, a new strain-hardening model for the hardening stages III to IV is proposed and combined with consistent recrystallization kinetics. The model is devised in the Kocks-Mecking space based on characteristic transition in the strain-hardening rate. A linear variation of the transition and inflection points is observed for alloy 800H at all tested temperatures and strain rates. The comparison of experimental and model results shows that the model is able to follow the course of the strain-hardening rate very precisely, such that highly accurate flow stress predictions are obtained.

  13. Development of a Model for Dynamic Recrystallization Consistent with the Second Derivative Criterion.

    Science.gov (United States)

    Imran, Muhammad; Kühbach, Markus; Roters, Franz; Bambach, Markus

    2017-11-02

    Dynamic recrystallization (DRX) processes are widely used in industrial hot working operations, not only to keep the forming forces low but also to control the microstructure and final properties of the workpiece. According to the second derivative criterion (SDC) by Poliak and Jonas, the onset of DRX can be detected from an inflection point in the strain-hardening rate as a function of flow stress. Various models are available that can predict the evolution of flow stress from incipient plastic flow up to steady-state deformation in the presence of DRX. Some of these models have been implemented into finite element codes and are widely used for the design of metal forming processes, but their consistency with the SDC has not been investigated. This work identifies three sources of inconsistencies that models for DRX may exhibit. For a consistent modeling of the DRX kinetics, a new strain-hardening model for the hardening stages III to IV is proposed and combined with consistent recrystallization kinetics. The model is devised in the Kocks-Mecking space based on characteristic transition in the strain-hardening rate. A linear variation of the transition and inflection points is observed for alloy 800H at all tested temperatures and strain rates. The comparison of experimental and model results shows that the model is able to follow the course of the strain-hardening rate very precisely, such that highly accurate flow stress predictions are obtained.

  14. Improving evapotranspiration in a land surface model using biophysical variables derived from MSG/SEVIRI satellite

    Directory of Open Access Journals (Sweden)

    N. Ghilain

    2012-08-01

    Full Text Available Monitoring evapotranspiration over land is highly dependent on the surface state and vegetation dynamics. Data from spaceborn platforms are desirable to complement estimations from land surface models. The success of daily evapotranspiration monitoring at continental scale relies on the availability, quality and continuity of such data. The biophysical variables derived from SEVIRI on board the geostationary satellite Meteosat Second Generation (MSG and distributed by the Satellite Application Facility on Land surface Analysis (LSA-SAF are particularly interesting for such applications, as they aimed at providing continuous and consistent daily time series in near-real time over Africa, Europe and South America. In this paper, we compare them to monthly vegetation parameters from a database commonly used in numerical weather predictions (ECOCLIMAP-I, showing the benefits of the new daily products in detecting the spatial and temporal (seasonal and inter-annual variability of the vegetation, especially relevant over Africa. We propose a method to handle Leaf Area Index (LAI and Fractional Vegetation Cover (FVC products for evapotranspiration monitoring with a land surface model at 3–5 km spatial resolution. The method is conceived to be applicable for near-real time processes at continental scale and relies on the use of a land cover map. We assess the impact of using LSA-SAF biophysical variables compared to ECOCLIMAP-I on evapotranspiration estimated by the land surface model H-TESSEL. Comparison with in-situ observations in Europe and Africa shows an improved estimation of the evapotranspiration, especially in semi-arid climates. Finally, the impact on the land surface modelled evapotranspiration is compared over a north–south transect with a large gradient of vegetation and climate in Western Africa using LSA-SAF radiation forcing derived from remote sensing. Differences are highlighted. An evaluation against remote sensing derived land

  15. Modelling dengue fever risk in the State of Yucatan, Mexico using regional-scale satellite-derived sea surface temperature.

    Science.gov (United States)

    Laureano-Rosario, Abdiel E; Garcia-Rejon, Julian E; Gomez-Carro, Salvador; Farfan-Ale, Jose A; Muller-Karger, Frank E

    2017-08-01

    Accurately predicting vector-borne diseases, such as dengue fever, is essential for communities worldwide. Changes in environmental parameters such as precipitation, air temperature, and humidity are known to influence dengue fever dynamics. Furthermore, previous studies have shown how oceanographic variables, such as El Niño Southern Oscillation (ENSO)-related sea surface temperature from the Pacific Ocean, influences dengue fever in the Americas. However, literature is lacking on the use of regional-scale satellite-derived sea surface temperature (SST) to assess its relationship with dengue fever in coastal areas. Data on confirmed dengue cases, demographics, precipitation, and air temperature were collected. Incidence of weekly dengue cases was examined. Stepwise multiple regression analyses (AIC model selection) were used to assess which environmental variables best explained increased dengue incidence rates. SST, minimum air temperature, precipitation, and humidity substantially explained 42% of the observed variation (r 2 =0.42). Infectious diseases are characterized by the influence of past cases on current cases and results show that previous dengue cases alone explained 89% of the variation. Ordinary least-squares analyses showed a positive trend of 0.20±0.03°C in SST from 2006 to 2015. An important element of this study is to help develop strategic recommendations for public health officials in Mexico by providing a simple early warning capability for dengue incidence. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. LCS-1: a high-resolution global model of the lithospheric magnetic field derived from CHAMP and Swarm satellite observations

    Science.gov (United States)

    Olsen, Nils; Ravat, Dhananjay; Finlay, Christopher C.; Kother, Livia K.

    2017-12-01

    We derive a new model, named LCS-1, of Earth's lithospheric field based on four years (2006 September-2010 September) of magnetic observations taken by the CHAMP satellite at altitudes lower than 350 km, as well as almost three years (2014 April-2016 December) of measurements taken by the two lower Swarm satellites Alpha and Charlie. The model is determined entirely from magnetic 'gradient' data (approximated by finite differences): the north-south gradient is approximated by first differences of 15 s along-track data (for CHAMP and each of the two Swarm satellites), while the east-west gradient is approximated by the difference between observations taken by Swarm Alpha and Charlie. In total, we used 6.2 mio data points. The model is parametrized by 35 000 equivalent point sources located on an almost equal-area grid at a depth of 100 km below the surface (WGS84 ellipsoid). The amplitudes of these point sources are determined by minimizing the misfit to the magnetic satellite 'gradient' data together with the global average of |Br| at the ellipsoid surface (i.e. applying an L1 model regularization of Br). In a final step, we transform the point-source representation to a spherical harmonic expansion. The model shows very good agreement with previous satellite-derived lithospheric field models at low degree (degree correlation above 0.8 for degrees n ≤ 133). Comparison with independent near-surface aeromagnetic data from Australia yields good agreement (coherence >0.55) at horizontal wavelengths down to at least 250 km, corresponding to spherical harmonic degree n ≈ 160. The LCS-1 vertical component and field intensity anomaly maps at Earth's surface show similar features to those exhibited by the WDMAM2 and EMM2015 lithospheric field models truncated at degree 185 in regions where they include near-surface data and provide unprecedented detail where they do not. Example regions of improvement include the Bangui anomaly region in central Africa, the west African

  17. High-resolution mutational profiling suggests the genetic validity of glioblastoma patient-derived pre-clinical models.

    Directory of Open Access Journals (Sweden)

    Shawn E Yost

    Full Text Available Recent advances in the ability to efficiently characterize tumor genomes is enabling targeted drug development, which requires rigorous biomarker-based patient selection to increase effectiveness. Consequently, representative DNA biomarkers become equally important in pre-clinical studies. However, it is still unclear how well these markers are maintained between the primary tumor and the patient-derived tumor models. Here, we report the comprehensive identification of somatic coding mutations and copy number aberrations in four glioblastoma (GBM primary tumors and their matched pre-clinical models: serum-free neurospheres, adherent cell cultures, and mouse xenografts. We developed innovative methods to improve the data quality and allow a strict comparison of matched tumor samples. Our analysis identifies known GBM mutations altering PTEN and TP53 genes, and new actionable mutations such as the loss of PIK3R1, and reveals clear patient-to-patient differences. In contrast, for each patient, we do not observe any significant remodeling of the mutational profile between primary to model tumors and the few discrepancies can be attributed to stochastic errors or differences in sample purity. Similarly, we observe ∼96% primary-to-model concordance in copy number calls in the high-cellularity samples. In contrast to previous reports based on gene expression profiles, we do not observe significant differences at the DNA level between in vitro compared to in vivo models. This study suggests, at a remarkable resolution, the genome-wide conservation of a patient's tumor genetics in various pre-clinical models, and therefore supports their use for the development and testing of personalized targeted therapies.

  18. Using an Altimeter-Derived Internal Tide Model to Remove Tides from in Situ Data

    Science.gov (United States)

    Zaron, Edward D.; Ray, Richard D.

    2017-01-01

    Internal waves at tidal frequencies, i.e., the internal tides, are a prominent source of variability in the ocean associated with significant vertical isopycnal displacements and currents. Because the isopycnal displacements are caused by ageostrophic dynamics, they contribute uncertainty to geostrophic transport inferred from vertical profiles in the ocean. Here it is demonstrated that a newly developed model of the main semidiurnal (M2) internal tide derived from satellite altimetry may be used to partially remove the tide from vertical profile data, as measured by the reduction of steric height variance inferred from the profiles. It is further demonstrated that the internal tide model can account for a component of the near-surface velocity as measured by drogued drifters. These comparisons represent a validation of the internal tide model using independent data and highlight its potential use in removing internal tide signals from in situ observations.

  19. Highly Accurate Tree Models Derived from Terrestrial Laser Scan Data: A Method Description

    Directory of Open Access Journals (Sweden)

    Jan Hackenberg

    2014-05-01

    Full Text Available This paper presents a method for fitting cylinders into a point cloud, derived from a terrestrial laser-scanned tree. Utilizing high scan quality data as the input, the resulting models describe the branching structure of the tree, capable of detecting branches with a diameter smaller than a centimeter. The cylinders are stored as a hierarchical tree-like data structure encapsulating parent-child neighbor relations and incorporating the tree’s direction of growth. This structure enables the efficient extraction of tree components, such as the stem or a single branch. The method was validated both by applying a comparison of the resulting cylinder models with ground truth data and by an analysis between the input point clouds and the models. Tree models were accomplished representing more than 99% of the input point cloud, with an average distance from the cylinder model to the point cloud within sub-millimeter accuracy. After validation, the method was applied to build two allometric models based on 24 tree point clouds as an example of the application. Computation terminated successfully within less than 30 min. For the model predicting the total above ground volume, the coefficient of determination was 0.965, showing the high potential of terrestrial laser-scanning for forest inventories.

  20. A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties

    Directory of Open Access Journals (Sweden)

    Christine Dorothee Schmeitz

    2013-09-01

    Full Text Available Fate decision processes of T lymphocytes are crucial for health and disease. Whether a T lymphocyte is activated, divides, gets anergic or initiates apoptosis depends on extracellular triggers and intracellular signalling. Free cytosolic calcium dynamics plays an important role in this context. The relative contributions of store-derived calcium entry and calcium entry from extracellular space to T lymphocyte activation are still a matter of debate. Here we develop a quantitative mathematical model of T lymphocyte calcium dynamics in order to establish a tool which allows to disentangle cause-effect relationships between ion fluxes and observed calcium time courses. The model is based on single transmembrane protein characteristics which have been determined in independent experiments. This reduces the number of unknown parameters in the model to a minimum and ensures the predictive power of the model. Simulation results are subsequently used for an analysis of whole cell calcium dynamics measured under various experimental conditions. The model accounts for a variety of these conditions, which supports the suitability of the modelling approach. The simulation results suggest a model in which calcium dynamics dominantly relies on the opening of channels in calcium stores while calcium entry through calcium-release activated channels (CRAC is more associated with the maintenance of the T lymphocyte calcium levels and prevents the cell from calcium depletion. Our findings indicate that CRAC guarantees a long-term stable calcium level which is required for cell survival and sustained calcium enhancement.

  1. Evaluation of Bias Associated with Capture Maps Derived from Nonlinear Groundwater Flow Models.

    Science.gov (United States)

    Nadler, Cara; Allander, Kip; Pohll, Greg; Morway, Eric; Naranjo, Ramon; Huntington, Justin

    2017-09-21

    The impact of groundwater withdrawal on surface water is a concern of water users and water managers, particularly in the arid western United States. Capture maps are useful tools to spatially assess the impact of groundwater pumping on water sources (e.g., streamflow depletion) and are being used more frequently for conjunctive management of surface water and groundwater. Capture maps have been derived using linear groundwater flow models and rely on the principle of superposition to demonstrate the effects of pumping in various locations on resources of interest. However, nonlinear models are often necessary to simulate head-dependent boundary conditions and unconfined aquifers. Capture maps developed using nonlinear models with the principle of superposition may over- or underestimate capture magnitude and spatial extent. This paper presents new methods for generating capture difference maps, which assess spatial effects of model nonlinearity on capture fraction sensitivity to pumping rate, and for calculating the bias associated with capture maps. The sensitivity of capture map bias to selected parameters related to model design and conceptualization for the arid western United States is explored. This study finds that the simulation of stream continuity, pumping rates, stream incision, well proximity to capture sources, aquifer hydraulic conductivity, and groundwater evapotranspiration extinction depth substantially affect capture map bias. Capture difference maps demonstrate that regions with large capture fraction differences are indicative of greater potential capture map bias. Understanding both spatial and temporal bias in capture maps derived from nonlinear groundwater flow models improves their utility and defensibility as conjunctive-use management tools. © 2017, National Ground Water Association.

  2. Recapitulation of metabolic defects in a model of propionic acidemia using patient-derived primary hepatocytes.

    Science.gov (United States)

    Chapman, Kimberly A; Collado, Maria S; Figler, Robert A; Hoang, Stephen A; Armstrong, Allison J; Cui, Wanxing; Purdy, Michael; Simmers, Michael B; Yazigi, Nada A; Summar, Marshall L; Wamhoff, Brian R; Dash, Ajit

    2016-03-01

    Propionic acidemia (PA) is a disorder of intermediary metabolism with defects in the alpha or beta subunits of propionyl CoA carboxylase (PCCA and PCCB respectively) enzyme. We previously described a liver culture system that uses liver-derived hemodynamic blood flow and transport parameters to restore and maintain primary human hepatocyte biology and metabolism utilizing physiologically relevant milieu concentrations. In this study, primary hepatocytes isolated from the explanted liver of an 8-year-old PA patient were cultured in the liver system for 10 days and evaluated for retention of differentiated polarized morphology. The expression of PCCA and PCCB was assessed at a gene and protein level relative to healthy donor controls. Ammonia and urea levels were measured in the presence and absence of amino acid supplements to assess the metabolic consequences of branched-chain amino acid metabolism in this disease. Primary hepatocytes from the PA patient maintained a differentiated polarized morphology (peripheral actin staining) over 10 days of culture in the system. We noted lower levels of PCCA and PCCB relative to normal healthy controls at the mRNA and protein level. Supplementation of branched-chain amino acids, isoleucine (5mM) and valine (5mM) in the medium, resulted in increased ammonia and decreased urea in the PA patient hepatocyte system, but no such response was seen in healthy hepatocytes or patient-derived fibroblasts. We demonstrate for the first time the successful culture of PA patient-derived primary hepatocytes in a differentiated state, that stably retain the PCCA and PCCB enzyme defects at a gene and protein level. Phenotypic response of the system to an increased load of branched-chain amino acids, not possible with fibroblasts, underscores the utility of this system in the better understanding of the molecular pathophysiology of PA and examining the effectiveness of potential therapeutic agents in the most relevant tissue. Copyright © 2015

  3. Recapitulation of metabolic defects in a model of propionic acidemia using patient-derived primary hepatocytes☆

    Science.gov (United States)

    Figler, Robert A.; Hoang, Stephen A.; Armstrong, Allison J.; Cui, Wanxing; Purdy, Michael; Simmers, Michael B.; Yazigi, Nada A.; Summar, Marshall L.; Wamhoff, Brian R.; Dash, Ajit

    2016-01-01

    Background Propionic acidemia (PA) is a disorder of intermediary metabolism with defects in the alpha or beta subunits of propionyl CoA carboxylase (PCCA and PCCB respectively) enzyme. We previously described a liver culture system that uses liver-derived hemodynamic blood flow and transport parameters to restore and maintain primary human hepatocyte biology and metabolism utilizing physiologically relevant milieu concentrations. Methods In this study, primary hepatocytes isolated from the explanted liver of an 8-year-old PA patient were cultured in the liver system for 10 days and evaluated for retention of differentiated polarized morphology. The expression of PCCA and PCCB was assessed at a gene and protein level relative to healthy donor controls. Ammonia and urea levels were measured in the presence and absence of amino acid supplements to assess the metabolic consequences of branched-chain amino acid metabolism in this disease. Results Primary hepatocytes from the PA patient maintained a differentiated polarized morphology (peripheral actin staining) over 10 days of culture in the system. We noted lower levels of PCCA and PCCB relative to normal healthy controls at the mRNA and protein level. Supplementation of branched-chain amino acids, isoleucine (5 mM) and valine (5 mM) in the medium, resulted in increased ammonia and decreased urea in the PA patient hepatocyte system, but no such response was seen in healthy hepatocytes or patient-derived fibroblasts. Conclusions We demonstrate for the first time the successful culture of PA patient-derived primary hepatocytes in a differentiated state, that stably retain the PCCA and PCCB enzyme defects at a gene and protein level. Phenotypic response of the system to an increased load of branched-chain amino acids, not possible with fibroblasts, underscores the utility of this system in the better understanding of the molecular pathophysiology of PA and examining the effectiveness of potential therapeutic agents in the

  4. Modeling Fanconi Anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs

    Science.gov (United States)

    Montserrat, Nuria; Tarantino, Carolina; Gu, Ying; Yi, Fei; Xu, Xiuling; Zhang, Weiqi; Ruiz, Sergio; Plongthongkum, Nongluk; Zhang, Kun; Masuda, Shigeo; Nivet, Emmanuel; Tsunekawa, Yuji; Soligalla, Rupa Devi; Goebl, April; Aizawa, Emi; Kim, Na Young; Kim, Jessica; Dubova, Ilir; Li, Ying; Ren, Ruotong; Benner, Chris; del Sol, Antonio; Bueren, Juan; Trujillo, Juan Pablo; Surralles, Jordi; Cappelli, Enrico; Dufour, Carlo; Esteban, Concepcion Rodriguez; Belmonte, Juan Carlos Izpisua

    2014-01-01

    Fanconi Anemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration-free induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA-patient bone marrow cells. PMID:24999918

  5. Disease Modeling Using 3D Organoids Derived from Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Ho, Beatrice Xuan; Pek, Nicole Min Qian; Soh, Boon-Seng

    2018-03-21

    The rising interest in human induced pluripotent stem cell (hiPSC)-derived organoid culture has stemmed from the manipulation of various combinations of directed multi-lineage differentiation and morphogenetic processes that mimic organogenesis. Organoids are three-dimensional (3D) structures that are comprised of multiple cell types, self-organized to recapitulate embryonic and tissue development in vitro. This model has been shown to be superior to conventional two-dimensional (2D) cell culture methods in mirroring functionality, architecture, and geometric features of tissues seen in vivo. This review serves to highlight recent advances in the 3D organoid technology for use in modeling complex hereditary diseases, cancer, host-microbe interactions, and possible use in translational and personalized medicine where organoid cultures were used to uncover diagnostic biomarkers for early disease detection via high throughput pharmaceutical screening. In addition, this review also aims to discuss the advantages and shortcomings of utilizing organoids in disease modeling. In summary, studying human diseases using hiPSC-derived organoids may better illustrate the processes involved due to similarities in the architecture and microenvironment present in an organoid, which also allows drug responses to be properly recapitulated in vitro.

  6. A QSAR model of Olanzapine derivatives as potential inhibitors for 5-HT2A Receptor.

    Science.gov (United States)

    Mitra, Pooja; Rastogi, Aishwarya; Rajpoot, Mayank; Kumar, Ajay; Srivastava, Vivek

    2017-01-01

    Schizophrenia is a complex, chronic mental disorder, affecting about 21 million people worldwide. It is characterized by symptoms, including distortions in thinking, perception, emotions, disorganized speech, sense of self and behavior. Recently, a numbers of marketed drugs for Schizophrenia are available against dopamine D2 and serotonin 5-HT2A receptors. Here, we docked Olanzapine derivatives (collected from literature) with 5-HT2A Receptor using the program AutoDock 4.2. The docked protein inhibitor complex structure was optimized using molecular dynamics simulation for 5ps with the CHARMM-22 force field using NAMD (NAnoscale Molecular Dynamics program) incorporated in visual molecular dynamics (VMD 1.9.2) and then evaluating the stability of complex structure by calculating RMSD values. NAMD is a parallel, object-oriented molecular dynamics code designed for high-performance simulation of large biomolecular systems. A quantitative structure activity relationship (QSAR) model was built using energy-based descriptors as independent variable and pKi value as dependent variable of eleven known Olanzapine derivatives with 5-HT2A Receptor, yielding correlation coefficient r2 of 0.63861. The predictive performance of QSAR model was assessed using different crossvalidation procedures. Our results suggest that a ligand-receptor binding interaction for 5-HT2A receptor using a QSAR model is promising approach to design more potent 5-HT2A receptor inhibitors prior to their synthesis.

  7. Disease Modeling Using 3D Organoids Derived from Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Beatrice Xuan Ho

    2018-03-01

    Full Text Available The rising interest in human induced pluripotent stem cell (hiPSC-derived organoid culture has stemmed from the manipulation of various combinations of directed multi-lineage differentiation and morphogenetic processes that mimic organogenesis. Organoids are three-dimensional (3D structures that are comprised of multiple cell types, self-organized to recapitulate embryonic and tissue development in vitro. This model has been shown to be superior to conventional two-dimensional (2D cell culture methods in mirroring functionality, architecture, and geometric features of tissues seen in vivo. This review serves to highlight recent advances in the 3D organoid technology for use in modeling complex hereditary diseases, cancer, host–microbe interactions, and possible use in translational and personalized medicine where organoid cultures were used to uncover diagnostic biomarkers for early disease detection via high throughput pharmaceutical screening. In addition, this review also aims to discuss the advantages and shortcomings of utilizing organoids in disease modeling. In summary, studying human diseases using hiPSC-derived organoids may better illustrate the processes involved due to similarities in the architecture and microenvironment present in an organoid, which also allows drug responses to be properly recapitulated in vitro.

  8. Computing Pathways in Bio-Models Derived from Bio-Science Text Sources

    DEFF Research Database (Denmark)

    Andreasen, Troels; Bulskov, Henrik; Nilsson, Jørgen Fischer

    2015-01-01

    This paper outlines a system, OntoScape, serving to accomplish complex inference tasks on knowledge bases and bio-models derived from life-science text corpora. The system applies so-called natural logic, a form of logic which is readable for humans. This logic affords ontological representations...... of complex terms appearing in the text sources. Along with logical propositions, the system applies a semantic graph representation facilitating calculation of bio-pathways. More generally, the system aords means of query answering appealing to general and domain specic inference rules....

  9. Higher derivative extensions of 3d Chern-Simons models: conservation laws and stability

    Energy Technology Data Exchange (ETDEWEB)

    Kaparulin, D.S.; Karataeva, I.Yu.; Lyakhovich, S.L. [Tomsk State University, Physics Faculty, Tomsk (Russian Federation)

    2015-11-15

    We consider the class of higher derivative 3d vector field models with the field equation operator being a polynomial of the Chern-Simons operator. For the nth-order theory of this type, we provide a general recipe for constructing n-parameter family of conserved second rank tensors. The family includes the canonical energy-momentum tensor, which is unbounded, while there are bounded conserved tensors that provide classical stability of the system for certain combinations of the parameters in the Lagrangian. We also demonstrate the examples of consistent interactions which are compatible with the requirement of stability. (orig.)

  10. Modelling and computation in the valuation of carbon derivatives with stochastic convenience yields.

    Directory of Open Access Journals (Sweden)

    Shuhua Chang

    Full Text Available The anthropogenic greenhouse gas (GHG emission has risen dramatically during the last few decades, which mainstream researchers believe to be the main cause of climate change, especially the global warming. The mechanism of market-based carbon emission trading is regarded as a policy instrument to deal with global climate change. Although several empirical researches about the carbon allowance and its derivatives price have been made, theoretical results seem to be sparse. In this paper, we theoretically develop a mathematical model to price the CO2 emission allowance derivatives with stochastic convenience yields by the principle of absence of arbitrage opportunities. In the case of American options, we formulate the pricing problem to a linear parabolic variational inequality (VI in two spatial dimensions and develop a power penalty method to solve it. Then, a fitted finite volume method is designed to solve the nonlinear partial differential equation (PDE resulting from the power penalty method and governing the futures, European and American option valuation. Moreover, some numerical results are performed to illustrate the efficiency and usefulness of this method. We find that the stochastic convenience yield does effect the valuation of carbon emission derivatives. In addition, some sensitivity analyses are also made to examine the effects of some parameters on the valuation results.

  11. Modelling and Computation in the Valuation of Carbon Derivatives with Stochastic Convenience Yields

    Science.gov (United States)

    Chang, Shuhua; Wang, Xinyu

    2015-01-01

    The anthropogenic greenhouse gas (GHG) emission has risen dramatically during the last few decades, which mainstream researchers believe to be the main cause of climate change, especially the global warming. The mechanism of market-based carbon emission trading is regarded as a policy instrument to deal with global climate change. Although several empirical researches about the carbon allowance and its derivatives price have been made, theoretical results seem to be sparse. In this paper, we theoretically develop a mathematical model to price the CO2 emission allowance derivatives with stochastic convenience yields by the principle of absence of arbitrage opportunities. In the case of American options, we formulate the pricing problem to a linear parabolic variational inequality (VI) in two spatial dimensions and develop a power penalty method to solve it. Then, a fitted finite volume method is designed to solve the nonlinear partial differential equation (PDE) resulting from the power penalty method and governing the futures, European and American option valuation. Moreover, some numerical results are performed to illustrate the efficiency and usefulness of this method. We find that the stochastic convenience yield does effect the valuation of carbon emission derivatives. In addition, some sensitivity analyses are also made to examine the effects of some parameters on the valuation results. PMID:26010900

  12. Leveraging North Carolina's QL2 Lidar to Quantify Sensitivity of National Water Model Derived Flood Inundation Extent to DEM Resolution

    Science.gov (United States)

    Lovette, J. P.; Lenhardt, W. C.; Blanton, B.; Duncan, J. M.; Stillwell, L.

    2017-12-01

    The National Water Model (NWM) has provided a novel framework for near real time flood inundation mapping across CONUS at a 10m resolution. In many regions, this spatial scale is quickly being surpassed through the collection of high resolution lidar (1 - 3m). As one of the leading states in data collection for flood inundation mapping, North Carolina is currently improving their previously available 20 ft statewide elevation product to a Quality Level 2 (QL2) product with a nominal point spacing of 0.7 meters. This QL2 elevation product increases the ground points by roughly ten times over the previous statewide lidar product, and by over 250 times when compared to the 10m NED elevation grid. When combining these new lidar data with the discharge estimates from the NWM, we can further improve statewide flood inundation maps and predictions of at-risk areas. In the context of flood risk management, these improved predictions with higher resolution elevation models consistently represent an improvement on coarser products. Additionally, the QL2 lidar also includes coarse land cover classification data for each point return, opening the possibility for expanding analysis beyond the use of only digital elevation models (e.g. improving estimates of surface roughness, identifying anthropogenic features in floodplains, characterizing riparian zones, etc.). Using the NWM Height Above Nearest Drainage approach, we compare flood inundation extents derived from multiple lidar-derived grid resolutions to assess the tradeoff between precision and computational load in North Carolina's coastal river basins. The elevation data distributed through the state's new lidar collection program provide spatial resolutions ranging from 5-50 feet, with most inland areas also including a 3 ft product. Data storage increases by almost two orders of magnitude across this range, as does processing load. In order to further assess the validity of the higher resolution elevation products on

  13. Physical Property Modeling of Concentrated Cesium Eluate Solutions, Part I - Derivation of Models

    Energy Technology Data Exchange (ETDEWEB)

    Choi, A.S.; Pierce, R. A.; Edwards, T. B.; Calloway, T. B.

    2005-09-15

    Major analytes projected to be present in the Hanford Waste Treatment Plant cesium ion-exchange eluate solutions were identified from the available analytical data collected during radioactive bench-scale runs, and a test matrix of cesium eluate solutions was designed within the bounding concentrations of those analytes. A computer model simulating the semi-batch evaporation of cesium eluate solutions was run in conjunction with a multi-electrolyte aqueous system database to calculate the physical properties of each test matrix solution concentrated to the target endpoints of 80% and 100% saturation. The calculated physical properties were analyzed statistically and fitted into mathematical expressions for the bulk solubility, density, viscosity, heat capacity and volume reduction factor as a function of temperature and concentration of each major analyte in the eluate feed. The R{sup 2} of the resulting physical property models ranged from 0.89 to 0.99.

  14. Scenario and modelling uncertainty in global mean temperature change derived from emission driven Global Climate Models

    OpenAIRE

    B. B. B. Booth; D. Bernie; D. McNeall; E. Hawkins; J. Caesar; C. Boulton; P. Friedlingstein; D. Sexton

    2012-01-01

    We compare future changes in global mean temperature in response to different future scenarios which, for the first time, arise from emission driven rather than concentration driven perturbed parameter ensemble of a Global Climate Model (GCM). These new GCM simulations sample uncertainties in atmospheric feedbacks, land carbon cycle, ocean physics and aerosol sulphur cycle processes. We find broader ranges of projected temperature responses arising when considering emission rather than concen...

  15. Patient-Derived Gastric Carcinoma Xenograft Mouse Models Faithfully Represent Human Tumor Molecular Diversity.

    Directory of Open Access Journals (Sweden)

    Tianwei Zhang

    Full Text Available Patient-derived cancer xenografts (PDCX generally represent more reliable models of human disease in which to evaluate a potential drugs preclinical efficacy. However to date, only a few patient-derived gastric cancer xenograft (PDGCX models have been reported. In this study, we aimed to establish additional PDGCX models and to evaluate whether these models accurately reflected the histological and genetic diversities of the corresponding patient tumors. By engrafting fresh patient gastric cancer (GC tissues into immune-compromised mice (SCID and/or nude mice, thirty two PDGCX models were established. Histological features were assessed by a qualified pathologist based on H&E staining. Genomic comparison was performed for several biomarkers including ERBB1, ERBB2, ERBB3, FGFR2, MET and PTEN. These biomarkers were profiled to assess gene copy number by fluorescent in situ hybridization (FISH and/or protein expression by immunohistochemistry (IHC. All 32 PDGCX models retained the histological features of the corresponding human tumors. Furthermore, among the 32 models, 78% (25/32 highly expressed ERBB1 (EGFR, 22% (7/32 were ERBB2 (HER2 positive, 78% (25/32 showed ERBB3 (HER3 high expression, 66% (21/32 lost PTEN expression, 3% (1/32 harbored FGFR2 amplification, 41% (13/32 were positive for MET expression and 16% (5/32 were MET gene amplified. Between the PDGCX models and their parental tumors, a high degree of similarity was observed for FGFR2 and MET gene amplification, and also for ERBB2 status (agreement rate = 94~100%; kappa value = 0.81~1. Protein expression of PTEN and MET also showed moderate agreement (agreement rate = 78%; kappa value = 0.46~0.56, while ERBB1 and ERBB3 expression showed slight agreement (agreement rate = 59~75%; kappa value = 0.18~0.19. ERBB2 positivity, FGFR2 or MET gene amplification was all maintained until passage 12 in mice. The stability of the molecular profiles observed across subsequent passages within the

  16. Identification of myeloproliferative neoplasm drug agents via predictive simulation modeling: assessing responsiveness with micro-environment derived cytokines.

    Science.gov (United States)

    Kobayashi, Susumu S; Vali, Shireen; Kumar, Ansu; Singh, Neeraj; Abbasi, Taher; Sayeski, Peter P

    2016-06-14

    Previous studies have shown that the bone marrow micro-environment supports the myeloproliferative neoplasms (MPN) phenotype including via the production of cytokines that can induce resistance to frontline MPN therapies. However, the mechanisms by which this occurs are poorly understood. Moreover, the ability to rapidly identify drug agents that can act as adjuvants to existing MPN frontline therapies is virtually non-existent. Here, using a novel predictive simulation approach, we sought to determine the effect of various drug agents on MPN cell lines, both with and without the micro-environment derived inflammatory cytokines. We first created individual simulation models for two representative MPN cell lines; HEL and SET-2, based on their genomic mutation and copy number variation (CNV) data. Running computational simulations on these virtual cell line models, we identified a synergistic effect of two drug agents on cell proliferation and viability; namely, the Jak2 kinase inhibitor, G6, and the Bcl-2 inhibitor, ABT737. IL-6 did not show any impact on the cells due to the predicted lack of IL-6 signaling within these cells. Interestingly, TNFα increased the sensitivity of the single drug agents and their use in combination while IFNγ decreased the sensitivity. In summary, this study predictively identified two drug agents that reduce MPN cell viability via independent mechanisms that was prospectively validated. Moreover, their efficacy is either potentiated or inhibited, by some of the micro-environment derived cytokines. Lastly, this study has validated the use of this simulation based technology to prospectively determine such responses.

  17. Derivation of Maxwell's Equations Based on a Continuum Mechanical Model of Vacuum and a Singularity Model of Electric Charges

    Directory of Open Access Journals (Sweden)

    Wang X.-S.

    2008-04-01

    Full Text Available The main purpose of this paper is to seek a mechanical interpretation of electromagnetic phenomena. We suppose that vacuum is filled with a kind of continuously distributed material which may be called Omega(1 substratum. Further, we speculate that the Omega(1 substratum might behave like a fluid with respect to translational motion of large bod- ies through it, but would still posses elasticity to produce small transverse vibrations. Thus, we propose a visco-elastic constitutive relation of the Omega(1 substratum. Further- more, we speculate that electric charges are emitting or absorbing the Omega(1 substratum continuously and establish a fluidic source and sink model of electric charges. Thus, Maxwell’s equations in vacuum are derived by methods of continuum mechanics based on this mechanical model of vacuum and the singularity model of electric charges.

  18. Derivation of Maxwell's Equations Based on a Continuum Mechanical Model of Vacuum and a Singularity Model of Electric Charges

    Directory of Open Access Journals (Sweden)

    Xiao-Song Wang

    2008-04-01

    Full Text Available The main purpose of this paper is to seek a mechanical interpretation of electromagnetic phenomena. We suppose that vacuumis filled with a kind of continuously distributed material which may be called $Omega (1$ substratum. Further, we speculate that the $Omega (1$ substratum might behave like a fluid with respect to translational motion of large bodies through it, but would still posses elasticity to produce small transverse vibrations. Thus, we propose a visco-elastic constitutive relation of the $Omega (1$ substratum. Furthermore, we speculate that electric charges are emitting or absorbing the $Omega (1$ substratum continuously and establish a fluidic source and sink model of electric charges. Thus,Maxwell's equations in vacuum are derived by methods of continuum mechanics based on this mechanical model of vacuum and the singularity model of electric charges.

  19. QSAR models for thiophene and imidazopyridine derivatives inhibitors of the Polo-Like Kinase 1.

    Science.gov (United States)

    Comelli, Nieves C; Duchowicz, Pablo R; Castro, Eduardo A

    2014-10-01

    The inhibitory activity of 103 thiophene and 33 imidazopyridine derivatives against Polo-Like Kinase 1 (PLK1) expressed as pIC50 (-logIC50) was predicted by QSAR modeling. Multivariate linear regression (MLR) was employed to model the relationship between 0D and 3D molecular descriptors and biological activities of molecules using the replacement method (MR) as variable selection tool. The 136 compounds were separated into several training and test sets. Two splitting approaches, distribution of biological data and structural diversity, and the statistical experimental design procedure D-optimal distance were applied to the dataset. The significance of the training set models was confirmed by statistically higher values of the internal leave one out cross-validated coefficient of determination (Q2) and external predictive coefficient of determination for the test set (Rtest2). The model developed from a training set, obtained with the D-optimal distance protocol and using 3D descriptor space along with activity values, separated chemical features that allowed to distinguish high and low pIC50 values reasonably well. Then, we verified that such model was sufficient to reliably and accurately predict the activity of external diverse structures. The model robustness was properly characterized by means of standard procedures and their applicability domain (AD) was analyzed by leverage method. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model

    DEFF Research Database (Denmark)

    Tønnesen, Jan; Parish, Clare L; Sørensen, Andreas T

    2011-01-01

    Intrastriatal grafts of stem cell-derived dopamine (DA) neurons induce behavioral recovery in animal models of Parkinson's disease (PD), but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral...

  1. CHAOS-a model of the Earth's magnetic field derived from CHAMP, Orsted, and SAC-C magnetic satellite data

    DEFF Research Database (Denmark)

    Olsen, Nils; Luhr, H.; Sabaka, T.J.

    2006-01-01

    We have derived a model of the near-Earth magnetic field (up to spherical harmonic degree n= 50 for the static field, and up to n = 18 for the first time derivative) using more than 6.5 yr of high-precision geomagnetic measurements from the three satellites Orsted, CHAMP and SAC-C taken between...

  2. More on the Computation of Higher-Order Derivatives of the Elementary Symmetric Functions in the Rasch Model.

    Science.gov (United States)

    Liou, Michelle

    1994-01-01

    A recursive equation is proposed for computing higher order derivatives of elementary symmetric functions in the Rasch model. A simulation study indicates a small loss in accuracy for the proposed formula compared to Gustafsson's sum algorithm (1980) for computing higher order derivatives when tests contain 60 items or less. (SLD)

  3. Free energy models for ice VII and liquid water derived from pressure, entropy, and heat capacity relations.

    Science.gov (United States)

    Myint, Philip C; Benedict, Lorin X; Belof, Jonathan L

    2017-08-28

    We present equations of state relevant to conditions encountered in ramp and multiple-shock compression experiments of water. These experiments compress water from ambient conditions to pressures as high as about 14 GPa and temperatures of up to several hundreds of Kelvin. Water may freeze into ice VII during this process. Although there are several studies on the thermodynamic properties of ice VII, an accurate and analytic free energy model from which all other properties may be derived in a thermodynamically consistent manner has not been previously determined. We have developed such a free energy model for ice VII that is calibrated with pressure-volume-temperature measurements and melt curve data. Furthermore, we show that liquid water in the pressure and temperature range of interest is well-represented by a simple Mie-Grüneisen equation of state. Our liquid water and ice VII equations of state are validated by comparing to sound speed and Hugoniot data. Although they are targeted towards ramp and multiple-shock compression experiments, we demonstrate that our equations of state also behave reasonably well at pressures and temperatures that lie somewhat beyond those found in the experiments.

  4. Potential of Multitemporal Tandem-X Derived Crop Surface Models for Maize Growth Monitoring

    Science.gov (United States)

    Hütt, C.; Tilly, N.; Schiedung, H.; Bareth, G.

    2016-06-01

    In this study, first results of retrieving plant heights of maize fields from multitemporal TanDEM-X images are shown. Three TanDEM-X dual polarization spotlight acquisitions were taken over a rural area in Germany in the growing season 2014. By interferometric processing, digital terrain models (DTM) were derived for each date with 5m resolution. From the data of the first acquisition (June 1st) taken before planting, a DTM of the bare ground is generated. The data of the following acquisition dates (July 15th, July 26th) are used to establish crop surface models (CSM). A CSM represents the crop surface of a whole field in a high resolution. By subtracting the DTM of the ground from each CSM, the actual plant height is calculated. Within these data sets 30 maize fields in the area of interest could be detected and verified by external land use data. Besides the spaceborne measurements, one of the maize fields was intensively investigated using terrestrial laser scanning (TLS), which was carried out at the same dates as the predicted TanDEM-X acquisitions. Visual inspection of the derived plant heights, and accordance of the individually processed polarisations over the maize fields, demonstrate the feasibility of the proposed method. Unfortunately, the infield variability of the intensively monitored field could not be successfully captured in the TanDEM-X derived plant heights and merely the general trend is visible. Nevertheless, the study shows the potential of the TanDEM-X constellation for maize height monitoring on field level.

  5. Synthesis, experimental evaluation and molecular modelling of hydroxamate derivatives as zinc metalloproteinase inhibitors.

    Science.gov (United States)

    Sjøli, Stian; Nuti, Elisa; Camodeca, Caterina; Bilto, Irina; Rossello, Armando; Winberg, Jan-Olof; Sylte, Ingebrigt; Adekoya, Olayiwola A

    2016-01-27

    Enzymes of the M4 family of zinc-metalloproteinases are virulence factors secreted from gram-positive or gram-negative bacteria, and putative drug targets in the treatment of bacterial infections. In order to have a therapeutic value such inhibitors should not interfere with endogenous zinc-metalloproteinases. In the present study we have synthesised a series of hydroxamate derivatives and validated the compounds as inhibitors of the M4 enzymes thermolysin and pseudolysin, and the endogenous metalloproteinases ADAM-17, MMP-2 and MMP-9 using experimental binding studies and molecular modelling. In general, the compounds are stronger inhibitors of the MMPs than of the M4 enzymes, however, an interesting exception is LM2. The compounds bound stronger to pseudolysin than to thermolysin, and the molecular modelling studies showed that occupation of the S2(') subpocket by an aromatic group is favourable for strong interactions with pseudolysin. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Efficient Model Order Reduction for the Dynamics of Nonlinear Multilayer Sheet Structures with Trial Vector Derivatives

    Directory of Open Access Journals (Sweden)

    Wolfgang Witteveen

    2014-01-01

    Full Text Available The mechanical response of multilayer sheet structures, such as leaf springs or car bodies, is largely determined by the nonlinear contact and friction forces between the sheets involved. Conventional computational approaches based on classical reduction techniques or the direct finite element approach have an inefficient balance between computational time and accuracy. In the present contribution, the method of trial vector derivatives is applied and extended in order to obtain a-priori trial vectors for the model reduction which are suitable for determining the nonlinearities in the joints of the reduced system. Findings show that the result quality in terms of displacements and contact forces is comparable to the direct finite element method but the computational effort is extremely low due to the model order reduction. Two numerical studies are presented to underline the method’s accuracy and efficiency. In conclusion, this approach is discussed with respect to the existing body of literature.

  7. Derivative Trade Optimizing Model Utilizing GP Based on Behavioral Finance Theory

    Science.gov (United States)

    Matsumura, Koki; Kawamoto, Masaru

    This paper proposed a new technique which makes the strategy trees for the derivative (option) trading investment decision based on the behavioral finance theory and optimizes it using evolutionary computation, in order to achieve high profitability. The strategy tree uses a technical analysis based on a statistical, experienced technique for the investment decision. The trading model is represented by various technical indexes, and the strategy tree is optimized by the genetic programming(GP) which is one of the evolutionary computations. Moreover, this paper proposed a method using the prospect theory based on the behavioral finance theory to set psychological bias for profit and deficit and attempted to select the appropriate strike price of option for the higher investment efficiency. As a result, this technique produced a good result and found the effectiveness of this trading model by the optimized dealings strategy.

  8. Modeling of the reburning process using sewage sludge-derived syngas.

    Science.gov (United States)

    Werle, Sebastian

    2012-04-01

    Gasification of sewage sludge can provide clean and effective reburning fuel for combustion applications. The motivation of this work was to define the reburning potential of the sewage sludge gasification gas (syngas). A numerical simulation of the co-combustion process of syngas in a hard coal-fired boiler was done. All calculations were performed using the Chemkin programme and a plug-flow reactor model was used. The calculations were modelled using the GRI-Mech 2.11 mechanism. The highest conversions for nitric oxide (NO) were obtained at temperatures of approximately 1000-1200K. The combustion of hard coal with sewage sludge-derived syngas reduces NO emissions. The highest reduction efficiency (>90%) was achieved when the molar flow ratio of the syngas was 15%. Calculations show that the analysed syngas can provide better results than advanced reburning (connected with ammonia injection), which is more complicated process. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Deforming the Starobinsky model in ghost-free higher derivative supergravities

    Science.gov (United States)

    Diamandis, G. A.; Georgalas, B. C.; Kaskavelis, K.; Lahanas, A. B.; Pavlopoulos, G.

    2017-08-01

    We consider higher derivative supergravities that are dual to ghost-free N =1 supergravity theories in the Einstein frame. The duality is implemented by deforming the Kähler function, and/or the superpotential, to include nonlinear dependences on chiral fields that, in other approaches, play the role of the Lagrange multipliers employed to establish this duality. These models are of the no-scale type, and in the minimal case, they require the presence of four chiral multiplets, with a Kähler potential having the structure of the S U (4 ,1 )/S U (4 )×U (1 ) coset manifold. In the standard N =1 supergravity formulation, these models are described by a multifield scalar potential, featuring Starobinsky-like behavior in particular directions.

  10. F-Nets and Software Cabling: Deriving a Formal Model and Language for Portable Parallel Programming

    Science.gov (United States)

    DiNucci, David C.; Saini, Subhash (Technical Monitor)

    1998-01-01

    Parallel programming is still being based upon antiquated sequence-based definitions of the terms "algorithm" and "computation", resulting in programs which are architecture dependent and difficult to design and analyze. By focusing on obstacles inherent in existing practice, a more portable model is derived here, which is then formalized into a model called Soviets which utilizes a combination of imperative and functional styles. This formalization suggests more general notions of algorithm and computation, as well as insights into the meaning of structured programming in a parallel setting. To illustrate how these principles can be applied, a very-high-level graphical architecture-independent parallel language, called Software Cabling, is described, with many of the features normally expected from today's computer languages (e.g. data abstraction, data parallelism, and object-based programming constructs).

  11. Specific binding of a dihydropyrimidinone derivative with DNA: Spectroscopic, calorimetric and modeling investigations

    Energy Technology Data Exchange (ETDEWEB)

    Wang Gongke, E-mail: wanggongke@126.com [School of Chemistry and Environmental Science, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan 453007 (China); Yan Changling; Wang Dongchao; Li Dan [School of Chemistry and Environmental Science, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan 453007 (China); Lu Yan, E-mail: yanlu2001@sohu.com [School of Chemistry and Environmental Science, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan 453007 (China)

    2012-07-15

    One of the dihydropyrimidinone derivative 5-(ethoxycarbonyl)-6-methyl-4-(4-methoxyphenyl) -3,4-dihydropyrimidin-2(1H)-one (EMMD) was synthesized, and its binding properties with calf-thymus DNA (ctDNA) were investigated using spectroscopic, viscometric, isothermal titration calorimetric (ITC) and molecular modeling techniques. Fluorescence spectra suggested that the fluorescence enhancement of the binding interaction of EMMD to ctDNA was a static process with ground state complex formation. The binding constant determined with spectroscopic titration and ITC was found to be in the same order of 10{sup 4} M{sup -1}. According to the results of the viscosity analysis, fluorescence competitive binding experiment, fluorescence quenching studies, absorption spectral and ITC investigations, it can be concluded that EMMD is intercalative binding to ctDNA. Furthermore, the results of molecular modeling confirmed those obtained from spectroscopic, viscosimetric and ITC investigations. Additionally, ITC studies also indicated that the binding interaction is predominantly enthalpy driven. - Highlights: Black-Right-Pointing-Pointer Medically important dihydropyrimidinones derivative EMMD is synthesized. Black-Right-Pointing-Pointer EMMD is intercalative binding into ctDNA helix. Black-Right-Pointing-Pointer Hydrogen bonding may play an essential role in the binding of EMCD with ctDNA. Black-Right-Pointing-Pointer This binding interaction is predominantly enthalpy driven.

  12. Steady-state non-linear vibrations of plates using Zener material model with fractional derivative

    Science.gov (United States)

    Litewka, Przemysław; Lewandowski, Roman

    2017-08-01

    The paper is devoted to non-linear vibrations of plates, made of the Zener viscoelastic material modelled with the Caputo fractional derivative, and in particular to their response to harmonic excitation. The plate geometric non-linearity is of the von Kármán type. In the formulation shear effects and rotary inertia are considered, too. The problem is solved in the frequency domain. A one-harmonic form of the solution for plate displacements corresponding to the plate formulation is assumed. The amplitude equation is obtained from the time averaged principle of virtual work. The time averaging precedes the use of the harmonic balance method. In the space discretization the finite element method is used involving 8-noded rectangular plate elements with selective-reduced integration. Several numerical examples are analyzed and the response curves are found using a path-following method. The purpose of these analyses is to identify material features of the adopted model of viscoelasticity with the fractional derivative.

  13. Regionalization of subsurface stormflow parameters of hydrologic models: Derivation from regional analysis of streamflow recession curves

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Sheng; Li, Hongyi; Huang, Maoyi; Ali, Melkamu; Leng, Guoyong; Leung, Lai-Yung R.; Wang, Shaowen; Sivapalan, Murugesu

    2014-07-21

    Subsurface stormflow is an important component of the rainfall–runoff response, especially in steep terrain. Its contribution to total runoff is, however, poorly represented in the current generation of land surface models. The lack of physical basis of these common parameterizations precludes a priori estimation of the stormflow (i.e. without calibration), which is a major drawback for prediction in ungauged basins, or for use in global land surface models. This paper is aimed at deriving regionalized parameterizations of the storage–discharge relationship relating to subsurface stormflow from a top–down empirical data analysis of streamflow recession curves extracted from 50 eastern United States catchments. Detailed regression analyses were performed between parameters of the empirical storage–discharge relationships and the controlling climate, soil and topographic characteristics. The regression analyses performed on empirical recession curves at catchment scale indicated that the coefficient of the power-law form storage–discharge relationship is closely related to the catchment hydrologic characteristics, which is consistent with the hydraulic theory derived mainly at the hillslope scale. As for the exponent, besides the role of field scale soil hydraulic properties as suggested by hydraulic theory, it is found to be more strongly affected by climate (aridity) at the catchment scale. At a fundamental level these results point to the need for more detailed exploration of the co-dependence of soil, vegetation and topography with climate.

  14. Multi-site assimilation of a terrestrial biosphere model (BETHY) using satellite derived soil moisture data

    Science.gov (United States)

    Wu, Mousong; Sholze, Marko

    2017-04-01

    We investigated the importance of soil moisture data on assimilation of a terrestrial biosphere model (BETHY) for a long time period from 2010 to 2015. Totally, 101 parameters related to carbon turnover, soil respiration, as well as soil texture were selected for optimization within a carbon cycle data assimilation system (CCDAS). Soil moisture data from Soil Moisture and Ocean Salinity (SMOS) product was derived for 10 sites representing different plant function types (PFTs) as well as different climate zones. Uncertainty of SMOS soil moisture data was also estimated using triple collocation analysis (TCA) method by comparing with ASCAT dataset and BETHY forward simulation results. Assimilation of soil moisture to the system improved soil moisture as well as net primary productivity(NPP) and net ecosystem productivity (NEP) when compared with soil moisture derived from in-situ measurements and fluxnet datasets. Parameter uncertainties were largely reduced relatively to prior values. Using SMOS soil moisture data for assimilation of a terrestrial biosphere model proved to be an efficient approach in reducing uncertainty in ecosystem fluxes simulation. It could be further used in regional an global assimilation work to constrain carbon dioxide concentration simulation by combining with other sources of measurements.

  15. A unified mechanism for plant polyketide biosynthesis derived from in silico modeling.

    Science.gov (United States)

    Healy, Eamonn F; Cervantes, Luis; Nabona, Barret; Williams, Jacob

    2018-03-18

    The polyketide synthases found in a variety of plants and fungi provide a varied source of biologically active compounds of pharmacological and medicinal interest. Stilbene synthase and chalcone synthase catalyze the formation of a common tetraketide intermediate, but use different cyclization mechanisms to produce distinct and separate natural products. While key structural differences have been identified to explain this functional diversity, a fuller explication of the factors responsible for this mechanistic disparity is required. Based on the energetics of our models of the bound tetraketides, and our structural analysis of the active sites we propose that a key tautomeric conversion provides a mechanistic framework common to both cyclizations. A previously unidentified active water molecule facilitates cyclization in chalcone synthase through a Claisen mechanism. Such a "Claisen switch" is comparable to the previously characterized "aldol switch" mechanism proposed for the biosynthesis of resveratrol in stilbene synthase. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. The geometrical precision of virtual bone models derived from clinical computed tomography data for forensic anthropology.

    Science.gov (United States)

    Colman, Kerri L; Dobbe, Johannes G G; Stull, Kyra E; Ruijter, Jan M; Oostra, Roelof-Jan; van Rijn, Rick R; van der Merwe, Alie E; de Boer, Hans H; Streekstra, Geert J

    2017-07-01

    Almost all European countries lack contemporary skeletal collections for the development and validation of forensic anthropological methods. Furthermore, legal, ethical and practical considerations hinder the development of skeletal collections. A virtual skeletal database derived from clinical computed tomography (CT) scans provides a potential solution. However, clinical CT scans are typically generated with varying settings. This study investigates the effects of image segmentation and varying imaging conditions on the precision of virtual modelled pelves. An adult human cadaver was scanned using varying imaging conditions, such as scanner type and standard patient scanning protocol, slice thickness and exposure level. The pelvis was segmented from the various CT images resulting in virtually modelled pelves. The precision of the virtual modelling was determined per polygon mesh point. The fraction of mesh points resulting in point-to-point distance variations of 2 mm or less (95% confidence interval (CI)) was reported. Colour mapping was used to visualise modelling variability. At almost all (>97%) locations across the pelvis, the point-to-point distance variation is less than 2 mm (CI = 95%). In >91% of the locations, the point-to-point distance variation was less than 1 mm (CI = 95%). This indicates that the geometric variability of the virtual pelvis as a result of segmentation and imaging conditions rarely exceeds the generally accepted linear error of 2 mm. Colour mapping shows that areas with large variability are predominantly joint surfaces. Therefore, results indicate that segmented bone elements from patient-derived CT scans are a sufficiently precise source for creating a virtual skeletal database.

  17. An Optimization Principle for Deriving Nonequilibrium Statistical Models of Hamiltonian Dynamics

    Science.gov (United States)

    Turkington, Bruce

    2013-08-01

    A general method for deriving closed reduced models of Hamiltonian dynamical systems is developed using techniques from optimization and statistical estimation. Given a vector of resolved variables, selected to describe the macroscopic state of the system, a family of quasi-equilibrium probability densities on phase space corresponding to the resolved variables is employed as a statistical model, and the evolution of the mean resolved vector is estimated by optimizing over paths of these densities. Specifically, a cost function is constructed to quantify the lack-of-fit to the microscopic dynamics of any feasible path of densities from the statistical model; it is an ensemble-averaged, weighted, squared-norm of the residual that results from submitting the path of densities to the Liouville equation. The path that minimizes the time integral of the cost function determines the best-fit evolution of the mean resolved vector. The closed reduced equations satisfied by the optimal path are derived by Hamilton-Jacobi theory. When expressed in terms of the macroscopic variables, these equations have the generic structure of governing equations for nonequilibrium thermodynamics. In particular, the value function for the optimization principle coincides with the dissipation potential that defines the relation between thermodynamic forces and fluxes. The adjustable closure parameters in the best-fit reduced equations depend explicitly on the arbitrary weights that enter into the lack-of-fit cost function. Two particular model reductions are outlined to illustrate the general method. In each example the set of weights in the optimization principle contracts into a single effective closure parameter.

  18. Assessing composition and structure of soft biphasic media from Kelvin-Voigt fractional derivative model parameters.

    Science.gov (United States)

    Zhang, Hong Mei; Wang, Yue; Fatemi, Mostafa; Insana, Michael F

    2017-03-01

    Kelvin-Voigt fractional derivative (KVFD) model parameters have been used to describe viscoelastic properties of soft tissues. However, translating model parameters into a concise set of intrinsic mechanical properties related to tissue composition and structure remains challenging. This paper begins by exploring these relationships using a biphasic emulsion materials with known composition. Mechanical properties are measured by analyzing data from two indentation techniques - ramp-stress relaxation and load-unload hysteresis tests. Material composition is predictably correlated with viscoelastic model parameters. Model parameters estimated from the tests reveal that elastic modulus E 0 closely approximates the shear modulus for pure gelatin. Fractional-order parameter α and time constant τ vary monotonically with the volume fraction of the material's fluid component. α characterizes medium fluidity and the rate of energy dissipation, and τ is a viscous time constant. Numerical simulations suggest that the viscous coefficient η is proportional to the energy lost during quasi-static force-displacement cycles, E A . The slope of E A versus η is determined by α and the applied indentation ramp time T r . Experimental measurements from phantom and ex vivo liver data show close agreement with theoretical predictions of the η - E A relation. The relative error is less than 20% for emulsions 22% for liver. We find that KVFD model parameters form a concise features space for biphasic medium characterization that described time-varying mechanical properties.

  19. Nursing opinion leadership: a preliminary model derived from philosophic theories of rational belief.

    Science.gov (United States)

    Anderson, Christine A; Whall, Ann L

    2013-10-01

    Opinion leaders are informal leaders who have the ability to influence others' decisions about adopting new products, practices or ideas. In the healthcare setting, the importance of translating new research evidence into practice has led to interest in understanding how opinion leaders could be used to speed this process. Despite continued interest, gaps in understanding opinion leadership remain. Agent-based models are computer models that have proven to be useful for representing dynamic and contextual phenomena such as opinion leadership. The purpose of this paper is to describe the work conducted in preparation for the development of an agent-based model of nursing opinion leadership. The aim of this phase of the model development project was to clarify basic assumptions about opinions, the individual attributes of opinion leaders and characteristics of the context in which they are effective. The process used to clarify these assumptions was the construction of a preliminary nursing opinion leader model, derived from philosophical theories about belief formation. © 2013 John Wiley & Sons Ltd.

  20. Patient-derived Xenograft (PDX) Models In Basic and Translational Breast Cancer Research

    Science.gov (United States)

    Dobrolecki, Lacey E.; Airhart, Susie D.; Alferez, Denis G.; Aparicio, Samuel; Behbod, Fariba; Bentires-Alj, Mohamed; Brisken, Cathrin; Bult, Carol J.; Cai, Shirong; Clarke, Robert B.; Dowst, Heidi; Ellis, Matthew J.; Gonzalez-Suarez, Eva; Iggo, Richard D.; Kabos, Peter; Li, Shunqiang; Lindeman, Geoffrey J.; Marangoni, Elisabetta; McCoy, Aaron; Meric-Bernstam, Funda; Piwnica-Worms, Helen; Poupon, Marie-France; Reis-Filho, Jorge; Sartorius, Carol A.; Scabia, Valentina; Sflomos, George; Tu, Yizheng; Vaillant, François; Visvader, Jane E.; Welm, Alana; Wicha, Max S.

    2017-01-01

    Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational pre-clinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and “Triple-negative” (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward “credentialing” of PDX models as surrogates to represent individual patients for use in pre-clinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research. PMID:28025748

  1. An Atomistic Carbide-Derived Carbon Model Generated Using ReaxFF-Based Quenched Molecular Dynamics

    Directory of Open Access Journals (Sweden)

    Matthew W. Thompson

    2017-10-01

    Full Text Available We report a novel atomistic model of carbide-derived carbons (CDCs, which are nanoporous carbons with high specific surface areas, synthesis-dependent degrees of graphitization, and well-ordered, tunable porosities. These properties make CDCs viable substrates in several energy-relevant applications, such as gas storage media, electrochemical capacitors, and catalytic supports. These materials are heterogenous, non-ideal structures and include several important parameters that govern their performance. Therefore, a realistic model of the CDC structure is needed in order to study these systems and their nanoscale and macroscale properties with molecular simulation. We report the use of the ReaxFF reactive force field in a quenched molecular dynamics routine to generate atomistic CDC models. The pair distribution function, pore size distribution, and adsorptive properties of this model are reported and corroborated with experimental data. Simulations demonstrate that compressing the system after quenching changes the pore size distribution to better match the experimental target. Ring size distributions of this model demonstrate the prevalence of non-hexagonal carbon rings in CDCs. These effects may contrast the properties of CDCs against those of activated carbons with similar pore size distributions and explain higher energy densities of CDC-based supercapacitors.

  2. Investigating the performance of LiDAR-derived biomass information in hydromechanic slope stability modelling

    Science.gov (United States)

    Schmaltz, Elmar; Steger, Stefan; Bogaard, Thom; Van Beek, Rens; Glade, Thomas

    2017-04-01

    Hydromechanic slope stability models are often used to assess the landslide susceptibility of hillslopes. Some of these models are able to account for vegetation related effects when assessing slope stability. However, spatial information of required vegetation parameters (especially of woodland) that are defined by land cover type, tree species and stand density are mostly underrepresented compared to hydropedological and geomechanical parameters. The aim of this study is to assess how LiDAR-derived biomass information can help to distinguish distinct tree stand-immanent properties (e.g. stand density and diversity) and further improve the performance of hydromechanic slope stability models. We used spatial vegetation data produced from sophisticated algorithms that are able to separate single trees within a stand based on LiDAR point clouds and thus allow an extraordinary detailed determination of the aboveground biomass. Further, this information is used to estimate the species- and stand-related distribution of the subsurface biomass using an innovative approach to approximate root system architecture and development. The hydrological tree-soil interactions and their impact on the geotechnical stability of the soil mantle are then reproduced in the dynamic and spatially distributed slope stability model STARWARS/PROBSTAB. This study highlights first advances in the approximation of biomechanical reinforcement potential of tree root systems in tree stands. Based on our findings, we address the advantages and limitations of highly detailed biomass information in hydromechanic modelling and physically based slope failure prediction.

  3. Integrative evaluation of data derived from biomonitoring and models indicating atmospheric deposition of heavy metals.

    Science.gov (United States)

    Nickel, Stefan; Schröder, Winfried

    2017-05-01

    Atmospheric deposition of heavy metals (HM) can be determined by use of numeric models, technical devices and biomonitors. Mainly focussing on Germany, this paper aims at evaluating data from deposition modelling and biomonitoring programmes. The model LOTOS-EUROS (LE) yielded data on HM deposition at a spatial resolution of 25 km by 25 km throughout Europe. The European Monitoring and Evaluation Programme (EMEP) provided model calculations on 50 km by 50 km grids. Corresponding data on HM concentration in moss, leaves and needles and soil were derived from the European Moss Survey (EMS), the German Environmental Specimen Bank (ESB) and the International Co-operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (iCP Forests). The modelled HM deposition and respective concentrations in moss (EMS), leaves and needles (ESB, iCP Forests) and soil (iCP Forests) were investigated for their statistical relationships. Regression equations were applied on geostatistical surface estimations of HM concentration in moss and then the residuals were interpolated by use of kriging interpolation. Both maps were summed up to a map of cadmium (Cd) and lead (Pb) deposition across Germany. Biomonitoring data were strongly correlated to LE than to EMEP. For HM concentrations in moss, the highest correlations were found for the association between geostatistical surface estimations of HM concentration in moss and deposition (LE).

  4. Effect of tropospheric models on derived precipitable water vapor over Southeast Asia

    Science.gov (United States)

    Rahimi, Zhoobin; Mohd Shafri, Helmi Zulhaidi; Othman, Faridah; Norman, Masayu

    2017-05-01

    An interesting subject in the field of GPS technology is estimating variation of precipitable water vapor (PWV). This estimation can be used as a data source to assess and monitor rapid changes in meteorological conditions. So far, numerous GPS stations are distributed across the world and the number of GPS networks is increasing. Despite these developments, a challenging aspect of estimating PWV through GPS networks is the need of tropospheric parameters such as temperature, pressure, and relative humidity (Liu et al., 2015). To estimate the tropospheric parameters, global pressure temperature (GPT) model developed by Boehm et al. (2007) is widely used in geodetic analysis for GPS observations. To improve the accuracy, Lagler et al. (2013) introduced GPT2 model by adding annual and semi-annual variation effects to GPT model. Furthermore, Boehm et al. (2015) proposed the GPT2 wet (GPT2w) model which uses water vapor pressure to improve the calculations. The global accuracy of GPT2 and GPT2w models has been evaluated by previous researches (Fund et al., 2011; Munekane and Boehm, 2010); however, investigations to assess the accuracy of global tropospheric models in tropical regions such as Southeast Asia is not sufficient. This study tests and examines the accuracy of GPT2w as one of the most recent versions of tropospheric models (Boehm et al., 2015). We developed a new regional model called Malaysian Pressure Temperature (MPT) model, and compared this model with GPT2w model. The compared results at one international GNSS service (IGS) station located in the south of Peninsula Malaysia shows that MPT model has a better performance than GPT2w model to produce PWV during monsoon season. According to the results, MPT has improved the accuracy of estimated pressure and temperature by 30% and 10%, respectively, in comparison with GPT2w model. These results indicate that MPT model can be a good alternative tool in the absence of meteorological sensors at GPS stations in

  5. In vitro eye irritancy test of lauryl derivatives using the reconstructed rabbit corneal epithelium model.

    Science.gov (United States)

    Matsuda, Sanae; Hisama, Masayoshi; Shibayama, Hiroharu; Itou, Norihiko; Iwaki, Masahiro

    2009-06-01

    The rabbit corneal epithelium model (RCE model) was developed as a three-dimensional in vitro model to replace animal testing for the assessment of eye tolerance. In the model, a stratified culture of rabbit corneal epithelial cells is grown at the air-liquid interface on an amniotic membrane acting as a parabasal membrane. The alkaline exposure was restored each day in the presence of no irritants, although with the addition of SLS, which is a major irritant, the restoration of deficit was inhibited on the RCE model in a dose-dependent manner. The results of this test were comparable with those of the Draize test, and thus, this method using the RCE model may prove to be a useful and sensitive in vitro eye irritation test. The lauryl fatty chain derivatives, such as polyoxyethylene (9) lauryl ether (PLE), sodium polyoxyethylene (2) lauryl ether sulfate (SPLE), mono glyceryl laurate (MGL), and sodium N-lauroyl-l-glutaminate (SLG), which are widely used as surfactants for toiletry products and cosmetics, were evaluated for in vitro eye irritation potential using the RCE model. SLS, PLE, SPLE, MGL, and SLG inhibited 88.7%, 59.2%, 69.0%, 47.5%, and 15.7% of the restoration of deletion 24h after treatment at a concentration of 0.05%. The IC(50) (50% inhibitory concentration) values of SLS, PLE, SPLE, MGL, and SLG were 0.002%, 0.021%, 0.005%, 0.056%, and 0.448%, respectively. These results indicated that a functional group at the end of lauryl chain is an important factor for inhibiting the restoration of deletion using the RCE model.

  6. Data-derived modeling characterizes plasticity of MAPK signaling in melanoma.

    Directory of Open Access Journals (Sweden)

    Marti Bernardo-Faura

    2014-09-01

    Full Text Available The majority of melanomas have been shown to harbor somatic mutations in the RAS-RAF-MEK-MAPK and PI3K-AKT pathways, which play a major role in regulation of proliferation and survival. The prevalence of these mutations makes these kinase signal transduction pathways an attractive target for cancer therapy. However, tumors have generally shown adaptive resistance to treatment. This adaptation is achieved in melanoma through its ability to undergo neovascularization, migration and rearrangement of signaling pathways. To understand the dynamic, nonlinear behavior of signaling pathways in cancer, several computational modeling approaches have been suggested. Most of those models require that the pathway topology remains constant over the entire observation period. However, changes in topology might underlie adaptive behavior to drug treatment. To study signaling rearrangements, here we present a new approach based on Fuzzy Logic (FL that predicts changes in network architecture over time. This adaptive modeling approach was used to investigate pathway dynamics in a newly acquired experimental dataset describing total and phosphorylated protein signaling over four days in A375 melanoma cell line exposed to different kinase inhibitors. First, a generalized strategy was established to implement a parameter-reduced FL model encoding non-linear activity of a signaling network in response to perturbation. Next, a literature-based topology was generated and parameters of the FL model were derived from the full experimental dataset. Subsequently, the temporal evolution of model performance was evaluated by leaving time-defined data points out of training. Emerging discrepancies between model predictions and experimental data at specific time points allowed the characterization of potential network rearrangement. We demonstrate that this adaptive FL modeling approach helps to enhance our mechanistic understanding of the molecular plasticity of melanoma.

  7. Establishment and characterization of uterine sarcoma and carcinosarcoma patient-derived xenograft models.

    Science.gov (United States)

    Cuppens, Tine; Depreeuw, Jeroen; Annibali, Daniela; Thomas, Debby; Hermans, Els; Gommé, Ellen; Trinh, Xuan Bich; Debruyne, David; Moerman, Philippe; Lambrechts, Diether; Amant, Frédéric

    2017-09-01

    Uterine sarcomas (US) and carcinosarcomas (CS) are rare, aggressive cancers. The lack of reliable preclinical models hampers the search for new treatment strategies and predictive biomarkers. To this end, we established and characterized US and CS patient-derived xenograft (PDX) models. Tumor fragments of US and CS were subcutaneously implanted into immunocompromised mice. Engrafted xenograft and original tumors were compared by means of histology, immunohistochemistry, whole-genome low-coverage sequencing for copy number variations, and RNA sequencing. Of 13 implanted leiomyosarcomas (LMS), 10 engrafted (engraftment rate of 77%). Also 2 out of 7 CS (29%) and one high-grade US (not otherwise specified) models were successfully established. LMS xenografts showed high histological similarity to their corresponding human tumors. Expression of desmin and/or H-caldesmon was detected in 8/10 LMS PDX models. We noticed that in CS models, characterized by the concomitant presence of a mesenchymal and an epithelial component, the relative distribution of the components is varying over the generations, as confirmed by changes in vimentin and cytokeratin expression. The similarity in copy number profiles between original and xenograft tumors ranged from 57.7% to 98.2% for LMS models and from 47.4 to 65.8% for CS models. Expression pattern stability was assessed by clustering RNA expression levels of original and xenograft tumors. Six xenografts clustered together with their original tumor, while 3 (all LMS) clustered apart. We present here a panel of clinically annotated uterine sarcoma and carcinosarcoma PDX models, which will be a useful tool for preclinical testing of new therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Optimal temperature for malaria transmission is dramaticallylower than previously predicted

    Science.gov (United States)

    Mordecai, Eerin A.; Paaijmans, Krijin P.; Johnson, Leah R.; Balzer, Christian; Ben-Horin, Tal; de Moor, Emily; McNally, Amy; Pawar, Samraat; Ryan, Sadie J.; Smith, Thomas C.; Lafferty, Kevin D.

    2013-01-01

    The ecology of mosquito vectors and malaria parasites affect the incidence, seasonal transmission and geographical range of malaria. Most malaria models to date assume constant or linear responses of mosquito and parasite life-history traits to temperature, predicting optimal transmission at 31 °C. These models are at odds with field observations of transmission dating back nearly a century. We build a model with more realistic ecological assumptions about the thermal physiology of insects. Our model, which includes empirically derived nonlinear thermal responses, predicts optimal malaria transmission at 25 °C (6 °C lower than previous models). Moreover, the model predicts that transmission decreases dramatically at temperatures > 28 °C, altering predictions about how climate change will affect malaria. A large data set on malaria transmission risk in Africa validates both the 25 °C optimum and the decline above 28 °C. Using these more accurate nonlinear thermal-response models will aid in understanding the effects of current and future temperature regimes on disease transmission.

  9. Predicting Collateral Status With Magnetic Resonance Perfusion Parameters: Probabilistic Approach With a Tmax-Derived Prediction Model.

    Science.gov (United States)

    Lee, Mi Ji; Son, Jeong Pyo; Kim, Suk Jae; Ryoo, Sookyung; Woo, Sook-Young; Cha, Jihoon; Kim, Gyeong-Moon; Chung, Chin-Sang; Lee, Kwang Ho; Bang, Oh Young

    2015-10-01

    Good collateral flow is an important predictor for favorable responses to recanalization therapy and successful outcomes after acute ischemic stroke. Magnetic resonance perfusion-weighted imaging (MRP) is widely used in patients with stroke. However, it is unclear whether the perfusion parameters and thresholds would predict collateral status. The present study evaluated the relationship between hypoperfusion severity and collateral status to develop a predictive model for good collaterals using MRP parameters. Patients who were eligible for recanalization therapy that underwent both serial diffusion-weighted imaging and serial MRP were enrolled into the study. A collateral flow map derived from MRP source data was generated through automatic postprocessing. Hypoperfusion severity, presented as proportions of every 2-s Tmax strata to the entire hypoperfusion volume (Tmax≥2 s), was compared between patients with good and poor collaterals. Prediction models for good collaterals were developed with each Tmax strata proportion and cerebral blood volumes. Among 66 patients, 53 showed good collaterals based on MRP-based collateral grading. Although no difference was noted in delays within 16 s, more severe Tmax delays (Tmax16-18 s, Tmax18-22 s, Tmax22-24 s, and Tmax>24 s) were associated with poor collaterals. The probability equation model using Tmax strata proportion demonstrated high predictive power in a receiver operating characteristic analysis (area under the curve=0.9303; 95% confidence interval, 0.8682-0.9924). The probability score was negatively correlated with the volume of infarct growth (P=0.030). Collateral status is associated with more severe Tmax delays than previously defined. The present Tmax severity-weighted model can determine good collaterals and subsequent infarct growth. © 2015 American Heart Association, Inc.

  10. Testing Brain Overgrowth and Synaptic Models of Autism Using NPC’s and Neurons from Patient-Derived IPS Cells

    Science.gov (United States)

    2014-10-01

    Zikopoulos, B. & Barbas, H. Altered neural connectivity in excitatory and inhibitory cortical circuits in autism . Frontiers in human neuroscience 7, 609, doi:10.3389/fnhum.2013.00609 (2013). 11. APPENDICES: Nothing to report ...Models of Autism Using NPC’s and Neurons from Patient- Derived IPS Cells PRINCIPAL INVESTIGATOR: Fred H. Gage, Ph.D...SUBTITLE Testing Brain Overgrowth and Synaptic Models of Autism Using NPC’s and Neurons from Patient- Derived IPS Cells 5a. CONTRACT

  11. Derivative Process Model of Development Power in Industry: Empirical Research and Forecast for Chinese Software Industry and US Economy

    OpenAIRE

    Feng Dai; Bao- hua Sun; Jie Sun

    2004-01-01

    Based on concept and theory of Development Power [1], this paper analyzes the transferability and the diffusibility of industrial development power, points out that the chaos is the extreme of DP releasing and order is the highest degree of DP accumulating, puts forward A-C strength, the index of adjusting and controlling strength, and sets up the derivative process model for industrial development power on the Partial Distribution [2]-[4]. By the derivative process model, a kind of time seri...

  12. Using Whole-House Field Tests to Empirically Derive Moisture Buffering Model Inputs

    Energy Technology Data Exchange (ETDEWEB)

    Woods, J.; Winkler, J.; Christensen, D.; Hancock, E.

    2014-08-01

    Building energy simulations can be used to predict a building's interior conditions, along with the energy use associated with keeping these conditions comfortable. These models simulate the loads on the building (e.g., internal gains, envelope heat transfer), determine the operation of the space conditioning equipment, and then calculate the building's temperature and humidity throughout the year. The indoor temperature and humidity are affected not only by the loads and the space conditioning equipment, but also by the capacitance of the building materials, which buffer changes in temperature and humidity. This research developed an empirical method to extract whole-house model inputs for use with a more accurate moisture capacitance model (the effective moisture penetration depth model). The experimental approach was to subject the materials in the house to a square-wave relative humidity profile, measure all of the moisture transfer terms (e.g., infiltration, air conditioner condensate) and calculate the only unmeasured term: the moisture absorption into the materials. After validating the method with laboratory measurements, we performed the tests in a field house. A least-squares fit of an analytical solution to the measured moisture absorption curves was used to determine the three independent model parameters representing the moisture buffering potential of this house and its furnishings. Follow on tests with realistic latent and sensible loads showed good agreement with the derived parameters, especially compared to the commonly-used effective capacitance approach. These results show that the EMPD model, once the inputs are known, is an accurate moisture buffering model.

  13. Optimization of Catheter Ablation of Atrial Fibrillation: Insights Gained from Clinically-Derived Computer Models

    Directory of Open Access Journals (Sweden)

    Jichao Zhao

    2015-05-01

    Full Text Available Atrial fibrillation (AF is the most common heart rhythm disturbance, and its treatment is an increasing economic burden on the health care system. Despite recent intense clinical, experimental and basic research activity, the treatment of AF with current antiarrhythmic drugs and catheter/surgical therapies remains limited. Radiofrequency catheter ablation (RFCA is widely used to treat patients with AF. Current clinical ablation strategies are largely based on atrial anatomy and/or substrate detected using different approaches, and they vary from one clinical center to another. The nature of clinical ablation leads to ambiguity regarding the optimal patient personalization of the therapy partly due to the fact that each empirical configuration of ablation lines made in a patient is irreversible during one ablation procedure. To investigate optimized ablation lesion line sets, in silico experimentation is an ideal solution. 3D computer models give us a unique advantage to plan and assess the effectiveness of different ablation strategies before and during RFCA. Reliability of in silico assessment is ensured by inclusion of accurate 3D atrial geometry, realistic fiber orientation, accurate fibrosis distribution and cellular kinetics; however, most of this detailed information in the current computer models is extrapolated from animal models and not from the human heart. The predictive power of computer models will increase as they are validated with human experimental and clinical data. To make the most from a computer model, one needs to develop 3D computer models based on the same functionally and structurally mapped intact human atria with high spatial resolution. The purpose of this review paper is to summarize recent developments in clinically-derived computer models and the clinical insights they provide for catheter ablation.

  14. Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders.

    Science.gov (United States)

    Lazzeri, Elena; Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura; Romagnani, Paola

    2015-08-01

    The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. Copyright © 2015 by the American Society of Nephrology.

  15. 2D lattice model of a lipid bilayer: Microscopic derivation and thermodynamic exploration

    Science.gov (United States)

    Hakobyan, Davit; Heuer, Andreas

    2017-02-01

    Based on all-atom Molecular Dynamics (MD) simulations of a lipid bilayer we present a systematic mapping on a 2D lattice model. Keeping the lipid type and the chain order parameter as key variables we derive a free energy functional, containing the enthalpic interaction of adjacent lipids as well as the tail entropy. The functional form of both functions is explicitly determined for saturated and polyunsaturated lipids. By studying the lattice model via Monte Carlo simulations it is possible to reproduce the temperature dependence of the distribution of order parameters of the pure lipids, including the prediction of the gel transition. Furthermore, application to a mixture of saturated and polyunsaturated lipids yields the correct phase separation behavior at lower temperatures with a simulation time reduced by approximately 7 orders of magnitude as compared to the corresponding MD simulations. Even the time-dependence of the de-mixing is reproduced on a semi-quantitative level. Due to the generality of the approach we envisage a large number of further applications, ranging from modeling larger sets of lipids, sterols, and solvent proteins to predicting nucleation barriers for the melting of lipids. Particularly, from the properties of the 2D lattice model one can directly read off the enthalpy and entropy change of the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine gel-to-liquid transition in excellent agreement with experimental and MD results.

  16. QSAR models for predicting the toxicity of piperidine derivatives against Aedes aegypti.

    Science.gov (United States)

    Doucet, J P; Papa, E; Doucet-Panaye, A; Devillers, J

    2017-06-01

    QSAR models are proposed for predicting the toxicity of 33 piperidine derivatives against Aedes aegypti. From 2D topological descriptors, calculated with the PaDEL software, ordinary least squares multilinear regression (OLS-MLR) treatment from the QSARINS software and machine learning and related approaches including linear and radial support vector machine (SVM), projection pursuit regression (PPR), radial basis function neural network (RBFNN), general regression neural network (GRNN) and k-nearest neighbours (k-NN), led to four-variable models. Their robustness and predictive ability were evaluated through both internal and external validation. Determination coefficients (r 2 ) greater than 0.85 on the training sets and 0.8 on the test sets were obtained with OLS-MLR and linear SVM. They slightly outperform PPR, radial SVM and RBFNN, whereas GRNN and k-NN showed lower performance. The easy availability of the involved structural descriptors and the simplicity of the MLR model make the corresponding model attractive at an exploratory level for proposing, from this limited dataset, guidelines in the design of new potentially active molecules.

  17. Validation of mixing heights derived from the operational NWP models at the German weather service

    Energy Technology Data Exchange (ETDEWEB)

    Fay, B.; Schrodin, R.; Jacobsen, I. [Deutscher Wetterdienst, Offenbach (Germany); Engelbart, D. [Deutscher Wetterdienst, Meteorol. Observ. Lindenberg (Germany)

    1997-10-01

    NWP models incorporate an ever-increasing number of observations via four-dimensional data assimilation and are capable of providing comprehensive information about the atmosphere both in space and time. They describe not only near surface parameters but also the vertical structure of the atmosphere. They operate daily, are well verified and successfully used as meteorological pre-processors in large-scale dispersion modelling. Applications like ozone forecasts, emission or power plant control calculations require highly resolved, reliable, and routine values of the temporal evolution of the mixing height (MH) which is a critical parameter in determining the mixing and transformation of substances and the resulting pollution levels near the ground. The purpose of development at the German Weather Service is a straightforward mixing height scheme that uses only parameters derived from NWP model variables and thus automatically provides spatial and temporal fields of mixing heights on an operational basis. An universal parameter to describe stability is the Richardson number Ri. Compared to the usual diagnostic or rate equations, the Ri number concept of determining mixing heights has the advantage of using not only surface layer parameters but also regarding the vertical structure of the boundary layer resolved in the NWP models. (au)

  18. An improved pre-clinical patient-derived liquid xenograft mouse model for acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Zhisheng Her

    2017-10-01

    Full Text Available Abstract Background Xenotransplantation of patient-derived AML (acute myeloid leukemia cells in NOD-scid Il2rγ null (NSG mice is the method of choice for evaluating this human hematologic malignancy. However, existing models constructed using intravenous injection in adult or newborn NSG mice have inferior engraftment efficiency, poor peripheral blood engraftment, or are difficult to construct. Methods Here, we describe an improved AML xenograft model where primary human AML cells were injected into NSG newborn pups intrahepatically. Results Introduction of primary cells from AML patients resulted in high levels of engraftment in peripheral blood, spleen, and bone marrow (BM of recipient mice. The phenotype of engrafted AML cells remained unaltered during serial transplantation. The mice developed features that are consistent with human AML including spleen enlargement and infiltration of AML cells into multiple organs. Importantly, we demonstrated that although leukemic stem cell activity is enriched and mediated by CD34+CD117+ subpopulation, CD34+CD117− subpopulation can acquire CD34+CD117+ phenotype through de-differentiation. Lastly, we evaluated the therapeutic potential of Sorafenib and Regorafenib in this AML model and found that periphery and spleen AML cells are sensitive to these treatments, whereas BM provides a protective environment to AML. Conclusions Collectively, our improved model is robust, easy-to-construct, and reliable for pre-clinical AML studies.

  19. Atomistic modeling of zirconium hydride precipitation: methodology for deriving a tight-binding potential

    International Nuclear Information System (INIS)

    Dufresne, Alice

    2014-01-01

    The zirconium-hydrogen system is of nuclear safety interest, as the hydride precipitation leads to the cladding embrittlement, which is made of zirconium-based alloys. The cladding is the first safety barrier confining the radioactive products: its integrity shall be kept during the entire fuel-assemblies life, in reactor, including accidental situation, and post-operation (transport and storage). Many uncertainties remain regarding the hydrides precipitation kinetics and the local stress impact on their precipitation. The atomic scale modeling of this system would bring clarifications on the relevant mechanisms. The usual atomistic modeling methods are based on thermo-statistic approaches, whose precision and reliability depend on the interatomic potential used. However, there was no potential allowing a rigorous study of the Zr-H system. The present work has indeed addressed this issue: a new tight-binding potential for zirconium hydrides modeling is now available. Moreover, this thesis provides a detailed manual for deriving such potentials accounting for spd hybridization, and fitted here on DFT results. This guidebook has be written in light of modeling a pure transition metal followed by a metal-covalent coupling (metallic carbides, nitrides and silicides). (author)

  20. Derivation of the tunnelling exchange time for the model of trap-assisted tunnelling

    International Nuclear Information System (INIS)

    Racko, J.; Ballo, P.; Benko, P.; Harmatha, L.; Grmanova, A.; Breza, J.

    2014-01-01

    We present derivation of the tunnelling exchange times that play the key role in the model of trap assisted tunnelling (TAT) considering the electron and hole exchange processes between the trapping centre lying in the forbidden band of the semiconductor and the conduction band, valence band or a metal. All exchange processes are quantitatively described by respective exchange times. The reciprocal values of these exchange times represent the frequency with which the exchange processes contribute to the probability of occupation of the trap by free charge carriers. The crucial problem in any model of TAT is the calculation of the occupation probability. In our approach this probability is expressed in terms of only thermal and tunnelling exchange times. The concept of tunnelling exchange times presents a dominant contribution to our model of TAT. The new approach allows to simply calculate the probability of occupation of the trapping centre by a free charge carrier and subsequently to get the thermal and tunnelling generation-recombination rates occurring in the continuity equations. This is why the TAT model based on thermal and tunnelling exchange times is suitable for simulating the electrical properties of semiconductor nanostructures in which quantum mechanical phenomena play a key role. (authors)

  1. Analyzing dynamic fault trees derived from model-based system architectures

    International Nuclear Information System (INIS)

    Dehlinger, Josh; Dugan, Joanne Bechta

    2008-01-01

    Dependability-critical systems, such as digital instrumentation and control systems in nuclear power plants, necessitate engineering techniques and tools to provide assurances of their safety and reliability. Determining system reliability at the architectural design phase is important since it may guide design decisions and provide crucial information for trade-off analysis and estimating system cost. Despite this, reliability and system engineering remain separate disciplines and engineering processes by which the dependability analysis results may not represent the designed system. In this article we provide an overview and application of our approach to build architecture-based, dynamic system models for dependability-critical systems and then automatically generate Dynamic Fault Trees (DFT) for comprehensive, toolsupported reliability analysis. Specifically, we use the Architectural Analysis and Design Language (AADL) to model the structural, behavioral and failure aspects of the system in a composite architecture model. From the AADL model, we seek to derive the DFT(s) and use Galileo's automated reliability analyses to estimate system reliability. This approach alleviates the dependability engineering - systems engineering knowledge expertise gap, integrates the dependability and system engineering design and development processes and enables a more formal, automated and consistent DFT construction. We illustrate this work using an example based on a dynamic digital feed-water control system for a nuclear reactor

  2. Modeling Protein Aggregation and the Heat Shock Response in ALS iPSC-Derived Motor Neurons.

    Science.gov (United States)

    Seminary, Emily R; Sison, Samantha L; Ebert, Allison D

    2018-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder caused by the selective loss of the upper and lower motor neurons. Only 10% of all cases are caused by a mutation in one of the two dozen different identified genes, while the remaining 90% are likely caused by a combination of as yet unidentified genetic and environmental factors. Mutations in C9orf72, SOD1 , or TDP-43 are the most common causes of familial ALS, together responsible for at least 60% of these cases. Remarkably, despite the large degree of heterogeneity, all cases of ALS have protein aggregates in the brain and spinal cord that are immunopositive for SOD1, TDP-43, OPTN, and/or p62. These inclusions are normally prevented and cleared by heat shock proteins (Hsps), suggesting that ALS motor neurons have an impaired ability to induce the heat shock response (HSR). Accordingly, there is evidence of decreased induction of Hsps in ALS mouse models and in human post-mortem samples compared to unaffected controls. However, the role of Hsps in protein accumulation in human motor neurons has not been fully elucidated. Here, we generated motor neuron cultures from human induced pluripotent stem cell (iPSC) lines carrying mutations in SOD1, TDP-43 , or C9orf72 . In this study, we provide evidence that despite a lack of overt motor neuron loss, there is an accumulation of insoluble, aggregation-prone proteins in iPSC-derived motor neuron cultures but that content and levels vary with genetic background. Additionally, although iPSC-derived motor neurons are generally capable of inducing the HSR when exposed to a heat stress, protein aggregation itself is not sufficient to induce the HSR or stress granule formation. We therefore conclude that ALS iPSC-derived motor neurons recapitulate key early pathological features of the disease and fail to endogenously upregulate the HSR in response to increased protein burden.

  3. Development of West-European PM2.5 and NO2 land use regression models incorporating satellite-derived and chemical transport modelling data

    NARCIS (Netherlands)

    de Hoogh, Kees; Gulliver, John; Donkelaar, Aaron van; Martin, Randall V; Marshall, Julian D; Bechle, Matthew J; Cesaroni, Giulia; Pradas, Marta Cirach; Dedele, Audrius; Eeftens, Marloes|info:eu-repo/dai/nl/315028300; Forsberg, Bertil; Galassi, Claudia; Heinrich, Joachim; Hoffmann, Barbara; Jacquemin, Bénédicte; Katsouyanni, Klea; Korek, Michal; Künzli, Nino; Lindley, Sarah J; Lepeule, Johanna; Meleux, Frederik; de Nazelle, Audrey; Nieuwenhuijsen, Mark; Nystad, Wenche; Raaschou-Nielsen, Ole; Peters, Annette; Peuch, Vincent-Henri; Rouil, Laurence; Udvardy, Orsolya; Slama, Rémy; Stempfelet, Morgane; Stephanou, Euripides G; Tsai, Ming Y; Yli-Tuomi, Tarja; Weinmayr, Gudrun; Brunekreef, Bert|info:eu-repo/dai/nl/067548180; Vienneau, Danielle; Hoek, Gerard|info:eu-repo/dai/nl/069553475

    2016-01-01

    Satellite-derived (SAT) and chemical transport model (CTM) estimates of PM2.5 and NO2 are increasingly used in combination with Land Use Regression (LUR) models. We aimed to compare the contribution of SAT and CTM data to the performance of LUR PM2.5 and NO2 models for Europe. Four sets of models,

  4. Chick embryo xenograft model reveals a novel perineural niche for human adipose-derived stromal cells

    Directory of Open Access Journals (Sweden)

    Ingrid R. Cordeiro

    2015-09-01

    Full Text Available Human adipose-derived stromal cells (hADSC are a heterogeneous cell population that contains adult multipotent stem cells. Although it is well established that hADSC have skeletal potential in vivo in adult organisms, in vitro assays suggest further differentiation capacity, such as into glia. Thus, we propose that grafting hADSC into the embryo can provide them with a much more instructive microenvironment, allowing the human cells to adopt diverse fates or niches. Here, hADSC spheroids were grafted into either the presumptive presomitic mesoderm or the first branchial arch (BA1 regions of chick embryos. Cells were identified without previous manipulations via human-specific Alu probes, which allows efficient long-term tracing of heterogeneous primary cultures. When grafted into the trunk, in contrast to previous studies, hADSC were not found in chondrogenic or osteogenic territories up to E8. Surprisingly, 82.5% of the hADSC were associated with HNK1+ tissues, such as peripheral nerves. Human skin fibroblasts showed a smaller tropism for nerves. In line with other studies, hADSC also adopted perivascular locations. When grafted into the presumptive BA1, 74.6% of the cells were in the outflow tract, the final goal of cardiac neural crest cells, and were also associated with peripheral nerves. This is the first study showing that hADSC could adopt a perineural niche in vivo and were able to recognize cues for neural crest cell migration of the host. Therefore, we propose that xenografts of human cells into chick embryos can reveal novel behaviors of heterogeneous cell populations, such as response to migration cues.

  5. Functional Characterization of IPSC-Derived Brain Cells as a Model for X-Linked Adrenoleukodystrophy.

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    Mauhamad Baarine

    Full Text Available X-ALD is an inherited neurodegenerative disorder where mutations in the ABCD1 gene result in clinically diverse phenotypes: the fatal disorder of cerebral childhood ALD (cALD or a milder disorder of adrenomyeloneuropathy (AMN. The various models used to study the pathobiology of X-ALD disease lack the appropriate presentation for different phenotypes of cALD vs AMN. This study demonstrates that induced pluripotent stem cells (IPSC derived brain cells astrocytes (Ast, neurons and oligodendrocytes (OLs express morphological and functional activities of the respective brain cell types. The excessive accumulation of saturated VLCFA, a "hallmark" of X-ALD, was observed in both AMN OLs and cALD OLs with higher levels observed in cALD OLs than AMN OLs. The levels of ELOVL1 (ELOVL Fatty Acid Elongase 1 mRNA parallel the VLCFA load in AMN and cALD OLs. Furthermore, cALD Ast expressed higher levels of proinflammatory cytokines than AMN Ast and control Ast with or without stimulation with lipopolysaccharide. These results document that IPSC-derived Ast and OLs from cALD and AMN fibroblasts mimic the respective biochemical disease phenotypes and thus provide an ideal platform to investigate the mechanism of VLCFA load in cALD OLs and VLCFA-induced inflammatory disease mechanisms of cALD Ast and thus for testing of new therapeutics for AMN and cALD disease of X-ALD.

  6. Molecular structure and modeling studies of azobenzene derivatives containing maleimide groups.

    Science.gov (United States)

    Cojocaru, Corneliu; Airinei, Anton; Fifere, Nicusor

    2013-01-01

    The molecular orbital calculations have been carried out to investigate the structure and stability of (E) / (Z) isomers of some azobenzene derivatives containing maleimide groups. A special attention has been devoted to the compound (E)-1, (E)-1-(4-(phenyldiazenyl)phenyl)-1H-pyrrole-2,5-dione, for which the available crystallographic experimental data have been used to validate the modeling structures computed at the theoretical levels AM1, PM3, RHF/6-31+G(d,p) and B3LYP/6-31+G(d,p). To this end, the discrepancy between experimental and calculated structural parameters has been ascertained in terms of root-mean-square deviation (RMSD). The quantum calculations at the level RHF/6-31+G(d,p) yield the most accurate results on (E)-1 structure giving a deviation error from crystallographic data of about 5.00% for bond lengths and 0.97% for interatomic angles. The theoretical electronic absorption spectra of azobenzene derivatives of concern have been computed by means of configuration-interaction method (CI) at the level of semi-empirical Hamiltonians (AM1 and PM3). Likewise, the molecular energy spectra, electrostatic potential and some quantitative structure activity relationship (QSAR) properties of studied molecules have been computed and discussed in the paper.

  7. Enamel matrix derivative for replanted teeth in animal models: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Sahng G. Kim

    2013-11-01

    Full Text Available Objectives To investigate the effect of enamel matrix derivative (EMD on periodontal healing of replanted teeth in animal models. Materials and Methods The authors searched MEDLINE, PubMed, EMBASE, Cochrane Library, Web of Knowledge and Scopus for articles published up to Oct 2012. Animal studies in which EMD was applied in transplanted or replanted teeth with adequate controls and histological data were considered. Normal periodontal healing or root resorption determined by histology after EMD was applied in replanted teeth with adequate controls was used as outcome measures. The following search strategy was used: ('Emdogain' OR 'enamel matrix proteins' OR 'enamel matrix derivative' AND ('avulsion' OR 'transplantion' OR 'autotransplantation' OR 'replantation'. Results Six animal studies were included in the final review. There was great heterogeneity in study design among included studies. Two studies with similar study designs were identified and analyzed by a meta-analysis. The pooled estimates showed a significantly higher normal healing and surface resorption and significantly less inflammatory and replacement resorption in EMD-treated groups compared with non-EMD-treated groups. Conclusions With the limitations of this systematic review, the use of EMD led to greater normal periodontal healing and surface root resorption and less inflammatory and replacement root resorption in the presence of periodontal ligaments. However, no definite conclusion could be drawn with regard to the effect of EMD on periodontal healing and root resorption when no periodontal ligaments exist.

  8. Morphological comparison of the craniofacial phenotypes of mouse models expressing the Apert FGFR2 S252W mutation in neural crest- or mesoderm-derived tissues.

    Science.gov (United States)

    Heuzé, Yann; Singh, Nandini; Basilico, Claudio; Jabs, Ethylin Wang; Holmes, Greg; Richtsmeier, Joan T

    2014-06-01

    Bones of the craniofacial skeleton are derived from two distinct cell lineages, cranial neural crest and mesoderm, and articulate at sutures and synchondroses which represent major bone growth sites. Premature fusion of cranial suture(s) is associated with craniofacial dysmorphogenesis caused in part by alteration in the growth potential at sutures and can occur as an isolated birth defect or as part of a syndrome, such as Apert syndrome. Conditional expression of the Apert FGFR2 S252W mutation in cells derived from mesoderm was previously shown to be necessary and sufficient to cause coronal craniosynostosis. Here we used micro computed tomography images of mice expressing the Apert mutation constitutively in either mesoderm- or neural crest-derived cells to quantify craniofacial shape variation and suture fusion patterns, and to identify shape changes in craniofacial bones derived from the lineage not expressing the mutation, referred to here as secondary shape changes. Our results show that at postnatal day 0: (i) conditional expression of the FGFR2 S252W mutation in neural crest-derived tissues causes a more severe craniofacial phenotype than when expressed in mesoderm-derived tissues; and (ii) both mesoderm- and neural crest-specific mouse models display secondary shape changes. We also show that premature suture fusion is not necessarily dependent on the expression of the FGFR2 S252W mutation in the sutural mesenchyme. More specifically, it appears that suture fusion patterns in both mouse models are suture-specific resulting from a complex combination of the influence of primary abnormalities of biogenesis or signaling within the sutures, and timing. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Global distribution of urban parameters derived from high-resolution global datasets for weather modelling

    Science.gov (United States)

    Kawano, N.; Varquez, A. C. G.; Dong, Y.; Kanda, M.

    2016-12-01

    Numerical model such as Weather Research and Forecasting model coupled with single-layer Urban Canopy Model (WRF-UCM) is one of the powerful tools to investigate urban heat island. Urban parameters such as average building height (Have), plain area index (λp) and frontal area index (λf), are necessary inputs for the model. In general, these parameters are uniformly assumed in WRF-UCM but this leads to unrealistic urban representation. Distributed urban parameters can also be incorporated into WRF-UCM to consider a detail urban effect. The problem is that distributed building information is not readily available for most megacities especially in developing countries. Furthermore, acquiring real building parameters often require huge amount of time and money. In this study, we investigated the potential of using globally available satellite-captured datasets for the estimation of the parameters, Have, λp, and λf. Global datasets comprised of high spatial resolution population dataset (LandScan by Oak Ridge National Laboratory), nighttime lights (NOAA), and vegetation fraction (NASA). True samples of Have, λp, and λf were acquired from actual building footprints from satellite images and 3D building database of Tokyo, New York, Paris, Melbourne, Istanbul, Jakarta and so on. Regression equations were then derived from the block-averaging of spatial pairs of real parameters and global datasets. Results show that two regression curves to estimate Have and λf from the combination of population and nightlight are necessary depending on the city's level of development. An index which can be used to decide which equation to use for a city is the Gross Domestic Product (GDP). On the other hand, λphas less dependence on GDP but indicated a negative relationship to vegetation fraction. Finally, a simplified but precise approximation of urban parameters through readily-available, high-resolution global datasets and our derived regressions can be utilized to estimate a

  10. Synthesis, molecular modeling and structural characterization of vanillin derivatives as antimicrobial agents

    Science.gov (United States)

    Sun, Juan; Yin, Yong; Sheng, Gui-Hua; Yang, Zhi-Bo; Zhu, Hai-Liang

    2013-05-01

    Two vanillin derivatives have been designed and synthesized and their biological activities were also evaluated for antimicrobial activity. Their chemical structures are characterized by single crystal X-ray diffraction studies, 1H NMR, MS, and elemental analysis. Structural stabilization of them followed by intramolecular as well as intermolecular H-bonds makes these molecules as perfect examples in molecular recognition with self-complementary donor and acceptor units within a single molecule. Docking simulations have been performed to position compounds into the FtsZ active site to determine their probable binding model. Compound 3a shows the most potent biological activity, which may be a promising antimicrobial leading compound for the further research.

  11. Lattice Model to Derive the Fluctuating Hydrodynamics of Active Particles with Inertia.

    Science.gov (United States)

    Manacorda, A; Puglisi, A

    2017-11-17

    We derive the hydrodynamic equations with fluctuating currents for the density, momentum, and energy fields for an active system in the dilute limit. In our model, nonoverdamped self-propelled particles (such as grains or birds) move on a lattice, interacting by means of aligning dissipative forces and excluded volume repulsion. Our macroscopic equations, in a specific case, reproduce a transition line from a disordered phase to a swarming phase and a linear dispersion law accounting for underdamped wave propagation. Numerical simulations up to a packing fraction ∼10% are in fair agreement with the theory, including the macroscopic noise amplitudes. At a higher packing fraction, a dense-diluted coexistence emerges. We underline the analogies with the granular kinetic theories, elucidating the relation between the active swarming phase and granular shear instability.

  12. Plant-derived extracts in the neuroscience of anxiety on animal models: biases and comments.

    Science.gov (United States)

    Chirumbolo, Salvatore

    2012-04-01

    Generalized anxiety disorders probably represent one of the world's biggest mental health problems. A large number of studies have also shown that anxiety disorders and depression are often associated with quality of life impairments. As anxiety represents a big concern in public health, a substantial literature supports clinically important associations between psychiatric illness and chronic medical conditions. Actually, most research focuses on depression, finding that depression can adversely affect self-care and increase the risk of incident medical illness, complications, and mortality. Anxiety disorders are less well studied, but robust epidemiological and clinical evidences show that they play an equally important role. Recent reported articles have raised a debate about the effectiveness of some plant-derived extracts in anxiety-like models in mice. Biases about several aspects related with experimental setting, animal selection, environments, operators and investigators, selection and performance of behavioral tests, controls, results managing, and statistics are here discussed.

  13. Refuse-derived fuel as a secondary energy in Taiwan - Using Hotelling space allocation model

    International Nuclear Information System (INIS)

    Kwodong Wey; Sheueching Hong

    2006-01-01

    Most Taiwanese farmers usually blend rice straws into the soil after harvest. However, rice straws possess great thermal energy, which can be used to produce refuse-derived fuel (RDF-5). As Taiwan faces energy shortage, the development benefits of the RDF-5 industry are tempting. This study employs the Hotelling model to design the locations and the optimal numbers of RDF-5 plants. From the technology and material supply point of view, turning waste rice straws into RDF-5 is feasible in Taiwan. Nevertheless, from the business operation perspective, even if the RDF-5 plant is willing to lower its profit rate, its selling price is still hard to compete with imported RDF-5. If the Taiwanese government decides to pursue RDF-5 as an alternative energy, they might need to take a step further to subsidize entrepreneurs or provide appropriate tax benefits. Otherwise, the RDF-5 industry is hard to survive in Taiwan. (Author)

  14. The neuroprotective effect of a triazine derivative in an Alzheimer's rat model.

    Directory of Open Access Journals (Sweden)

    Fatemeh Alipour

    2015-01-01

    Full Text Available Alzheimer's disease (AD is the most prevalent neurodegenerative disorder. It is characterized by formation of amyloid plaques and neurofibrillary tangles in the brain, degeneration of the cholinergic neurons and neural cell death. This study was aimed to investigate the effect of a triazine derivative, C16H12Cl2N3S, on learning in an Alzheimer's rat model. Animals were divided into seven groups; each group contained seven animals.animals received no surgery and treatment; saline group: animals received normal saline after recovery; sham group: animals received 10% DMSO after recovery; STZ group (Alzheimer's model: animals received streptozotocin (STZ in four and six days after recovery; T5, T10 and T15 groups: animals were treated with triazine derivative, C16H12Cl2N3S, at doses of 5, 10 and 15 µM, respectively. All drugs were injected intracerebroventricular. The spatial learning and histological assessment were performed in all groups. Animals in STZ group had more deficits in spatial learning than the control group in Morris water maze. C16H12Cl2N3S improved spatial learning significantly compared to STZ group. The CA1 pyramidal layer thicknesses in STZ group were reduced significantly compared to control group. C16H12Cl2N3S increased the CA1 pyramidal layer thickness in T15 group compared to STZ group. Current findings suggest C16H12Cl2N3S may have a protective effect on learning deficit and hippocampal structure in AD.

  15. Analytic derivation of bacterial growth laws from a simple model of intracellular chemical dynamics.

    Science.gov (United States)

    Pandey, Parth Pratim; Jain, Sanjay

    2016-09-01

    Experiments have found that the growth rate and certain other macroscopic properties of bacterial cells in steady-state cultures depend upon the medium in a surprisingly simple manner; these dependencies are referred to as 'growth laws'. Here we construct a dynamical model of interacting intracellular populations to understand some of the growth laws. The model has only three population variables: an amino acid pool, a pool of enzymes that transport an external nutrient and produce the amino acids, and ribosomes that catalyze their own and the enzymes' production from the amino acids. We assume that the cell allocates its resources between the enzyme sector and the ribosomal sector to maximize its growth rate. We show that the empirical growth laws follow from this assumption and derive analytic expressions for the phenomenological parameters in terms of the more basic model parameters. Interestingly, the maximization of the growth rate of the cell as a whole implies that the cell allocates resources to the enzyme and ribosomal sectors in inverse proportion to their respective 'efficiencies'. The work introduces a mathematical scheme in which the cellular growth rate can be explicitly determined and shows that two large parameters, the number of amino acid residues per enzyme and per ribosome, are useful for making approximations.

  16. Mathematical models for prediction of rheological parameters in vinasses derived from sugar cane

    Science.gov (United States)

    Chacua, Leidy M.; Ayala, Germán; Rojas, Hernán; Agudelo, Ana C.

    2016-04-01

    The rheological behaviour of vinasses derived from sugar cane was studied as a function of time (0 and 600 s), soluble solids content (44 and 60 °Brix), temperature (10 and 50°C), and shear rate (0.33 and 1.0 s-1). The results indicated that vinasses were time-independent at 25°C, where shear stress values ranged between 0.01 and 0.08 Pa. Flow curves showed a shear-thinning rheological behaviour in vinasses with a flow behaviour index between 0.69 and 0.89, for temperature between 10 and 20°C. With increasing temperature, the flow behaviour index was modified, reaching values close to 1.0. The Arrhenius model described well the thermal activation of shear stress and the consistency coefficient as a function of temperature. Activation energy from the Arrhenius model ranged between 31 and 45 kJ mol-1. Finally, the consistency coefficient as a function of the soluble solids content and temperature was well fitted using an exponential model (R2 = 0.951), showing that the soluble solids content and temperature have an opposite effect on consistency coefficient values.

  17. Development of risk-based computer models for deriving criteria on residual radioactivity and recycling

    International Nuclear Information System (INIS)

    Chen, S.Y.

    1994-01-01

    Argonne National Laboratory (ANL) is developing multimedia environmental pathway and health risk computer models to assess radiological risks to human health and to derive cleanup guidelines for environmental restoration, decommissioning, and recycling activities. These models are based on the existing RESRAD code, although each has a separate design and serves different objectives. Two such codes are RESRAD-BUILD and RESRAD-PROBABILISTIC. The RESRAD code was originally developed to implement the US Department of Energy's (DOE's) residual radioactive materials guidelines for contaminated soils. RESRAD has been successfully used by DOE and its contractors to assess health risks and develop cleanup criteria for several sites selected for cleanup or restoration programs. RESRAD-BUILD analyzes human health risks from radioactive releases during decommissioning or rehabilitation of contaminated buildings. Risks to workers are assessed for dismantling activities; risks to the public are assessed for occupancy. RESRAD-BUILD is based on a room compartmental model analyzing the effects on room air quality of contaminant emission and resuspension (as well as radon emanation), the external radiation pathway, and other exposure pathways. RESRAD-PROBABILISTIC, currently under development, is intended to perform uncertainty analysis for RESRAD by using the Monte Carlo approach based on the Latin-Hypercube sampling scheme. The codes being developed at ANL are tailored to meet a specific objective of human health risk assessment and require specific parameter definition and data gathering. The combined capabilities of these codes satisfy various risk assessment requirements in environmental restoration and remediation activities

  18. Modeling and simulation of microalgae derived hydrogen production in compact large scale photobioreactors

    Science.gov (United States)

    Vargas, Jose; Dias, Fernando; Mariano, Andre; Balmant, Wellington; Rosa, Marcos; Savi, Daiani; Kava, Vanessa; Glienke, Chirlei; Ordonez, Juan

    This study predicts microalgae derived hydrogen production in compact large scale photobioreactors (PBR). A transient mathematical model for the cultivation medium is developed. The tool determines the whole system temperature, and mass fractions distribution. A mathematical correlation is proposed to calculate the resulting effect on H2 production rate after genetically modifying the microalgae species. An indigenous microalgae strain was selected to be robust under different weather conditions. This strain was identified through rDNA sequence analysis, including ITS1, 5.8S and ITS2 (Internal Transcribed Spacer). The ITS analysis showed no genetic divergence between the utilized strain and Acutodesmus obliquus. A coarse mesh was used (6048 volume elements) to obtain results for a large compact PBR (2m x 5m x 8m). The largest computational time required for obtaining results was 560 s. The numerical results for the wild species microalgal growth are validated by direct comparison to experiments. Tests were conducted in the laboratory to assess H2 production model numerical results, which are in good qualitative agreement with measurements. Therefore, the model could be used as an efficient tool for H2 production PBR systems design and control. CNPq.

  19. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  20. Direct Neuronal Reprogramming for Disease Modeling Studies Using Patient-Derived Neurons: What Have We Learned?

    Directory of Open Access Journals (Sweden)

    Janelle Drouin-Ouellet

    2017-09-01

    Full Text Available Direct neuronal reprogramming, by which a neuron is formed via direct conversion from a somatic cell without going through a pluripotent intermediate stage, allows for the possibility of generating patient-derived neurons. A unique feature of these so-called induced neurons (iNs is the potential to maintain aging and epigenetic signatures of the donor, which is critical given that many diseases of the CNS are age related. Here, we review the published literature on the work that has been undertaken using iNs to model human brain disorders. Furthermore, as disease-modeling studies using this direct neuronal reprogramming approach are becoming more widely adopted, it is important to assess the criteria that are used to characterize the iNs, especially in relation to the extent to which they are mature adult neurons. In particular: i what constitutes an iN cell, ii which stages of conversion offer the earliest/optimal time to assess features that are specific to neurons and/or a disorder and iii whether generating subtype-specific iNs is critical to the disease-related features that iNs express. Finally, we discuss the range of potential biomedical applications that can be explored using patient-specific models of neurological disorders with iNs, and the challenges that will need to be overcome in order to realize these applications.

  1. Development of risk-based computer models for deriving criteria on residual radioactivity and recycling

    International Nuclear Information System (INIS)

    Chen, Shih-Yew

    1995-01-01

    Argonne National Laboratory (ANL) is developing multimedia environmental pathway and health risk computer models to assess radiological risks to human health and to derive cleanup guidelines for environmental restoration, decommissioning, and recycling activities. These models are based on the existing RESRAD code, although each has a separate design and serves different objectives. Two such codes are RESRAD-BUILD and RESRAD-PROBABILISTIC. The RESRAD code was originally developed to implement the U.S. Department of Energy's (DOE's) residual radioactive materials guidelines for contaminated soils. RESRAD has been successfully used by DOE and its contractors to assess health risks and develop cleanup criteria for several sites selected for cleanup or restoration programs. RESRAD-BUILD analyzes human health risks from radioactive releases during decommissioning or rehabilitation of contaminated buildings. Risks to workers are assessed for dismantling activities; risks to the public are assessed for occupancy. RESRAD-BUILD is based on a room compartmental model analyzing the effects on room air quality of contaminant emission and resuspension (as well as radon emanation), the external radiation pathway, and other exposure pathways. RESRAD-PROBABILISTIC, currently under development, is intended to perform uncertainty analysis for RESRAD by using the Monte Carlo approach based on the Latin-Hypercube sampling scheme. The codes being developed at ANL are tailored to meet a specific objective of human health risk assessment and require specific parameter definition and data gathering. The combined capabilities of these codes satisfy various risk assessment requirements in environmental restoration and remediation activities. (author)

  2. Estimating Biomass of Barley Using Crop Surface Models (CSMs Derived from UAV-Based RGB Imaging

    Directory of Open Access Journals (Sweden)

    Juliane Bendig

    2014-10-01

    Full Text Available Crop monitoring is important in precision agriculture. Estimating above-ground biomass helps to monitor crop vitality and to predict yield. In this study, we estimated fresh and dry biomass on a summer barley test site with 18 cultivars and two nitrogen (N-treatments using the plant height (PH from crop surface models (CSMs. The super-high resolution, multi-temporal (1 cm/pixel CSMs were derived from red, green, blue (RGB images captured from a small unmanned aerial vehicle (UAV. Comparison with PH reference measurements yielded an R2 of 0.92. The test site with different cultivars and treatments was monitored during “Biologische Bundesanstalt, Bundessortenamt und CHemische Industrie” (BBCH Stages 24–89. A high correlation was found between PH from CSMs and fresh biomass (R2 = 0.81 and dry biomass (R2 = 0.82. Five models for above-ground fresh and dry biomass estimation were tested by cross-validation. Modelling biomass between different N-treatments for fresh biomass produced the best results (R2 = 0.71. The main limitation was the influence of lodging cultivars in the later growth stages, producing irregular plant heights. The method has potential for future application by non-professionals, i.e., farmers.

  3. Tumor-Derived Cell Lines as Molecular Models of Cancer Pharmacogenomics.

    Science.gov (United States)

    Goodspeed, Andrew; Heiser, Laura M; Gray, Joe W; Costello, James C

    2016-01-01

    Compared with normal cells, tumor cells have undergone an array of genetic and epigenetic alterations. Often, these changes underlie cancer development, progression, and drug resistance, so the utility of model systems rests on their ability to recapitulate the genomic aberrations observed in primary tumors. Tumor-derived cell lines have long been used to study the underlying biologic processes in cancer, as well as screening platforms for discovering and evaluating the efficacy of anticancer therapeutics. Multiple -omic measurements across more than a thousand cancer cell lines have been produced following advances in high-throughput technologies and multigroup collaborative projects. These data complement the large, international cancer genomic sequencing efforts to characterize patient tumors, such as The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). Given the scope and scale of data that have been generated, researchers are now in a position to evaluate the similarities and differences that exist in genomic features between cell lines and patient samples. As pharmacogenomics models, cell lines offer the advantages of being easily grown, relatively inexpensive, and amenable to high-throughput testing of therapeutic agents. Data generated from cell lines can then be used to link cellular drug response to genomic features, where the ultimate goal is to build predictive signatures of patient outcome. This review highlights the recent work that has compared -omic profiles of cell lines with primary tumors, and discusses the advantages and disadvantages of cancer cell lines as pharmacogenomic models of anticancer therapies. ©2015 American Association for Cancer Research.

  4. DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling.

    Science.gov (United States)

    de Boni, Laura; Gasparoni, Gilles; Haubenreich, Carolin; Tierling, Sascha; Schmitt, Ina; Peitz, Michael; Koch, Philipp; Walter, Jörn; Wüllner, Ullrich; Brüstle, Oliver

    2018-01-01

    Genetic predisposition and epigenetic alterations are both considered to contribute to sporadic neurodegenerative diseases (NDDs) such as Parkinson's disease (PD). Since cell reprogramming and the generation of induced pluripotent stem cells (iPSCs) are themselves associated with major epigenetic remodeling, it remains unclear to what extent iPSC-derived neurons lend themselves to model epigenetic disease-associated changes. A key question to be addressed in this context is whether iPSC-derived neurons exhibit epigenetic signatures typically observed in neurons derived from non-reprogrammed human embryonic stem cells (hESCs). Here, we compare mature neurons derived from hESC and isogenic human iPSC generated from hESC-derived neural stem cells. Genome-wide 450 K-based DNA methylation and HT12v4 gene array expression analyses were complemented by a deep analysis of selected genes known to be involved in NDD. Our studies show that DNA methylation and gene expression patterns of isogenic hESC- and iPSC-derived neurons are markedly preserved on a genome-wide and single gene level. Overall, iPSC-derived neurons exhibit similar DNA methylation patterns compared to isogenic hESC-derived neurons. Further studies will be required to explore whether the epigenetic patterns observed in iPSC-derived neurons correspond to those detectable in native brain neurons.

  5. Assessing composition and structure of soft biphasic media from Kelvin-Voigt fractional derivative model parameters

    Science.gov (United States)

    Zhang, Hongmei; Wang, Yue; Fatemi, Mostafa; Insana, Michael F.

    2017-03-01

    Kelvin-Voigt fractional derivative (KVFD) model parameters have been used to describe viscoelastic properties of soft tissues. However, translating model parameters into a concise set of intrinsic mechanical properties related to tissue composition and structure remains challenging. This paper begins by exploring these relationships using a biphasic emulsion materials with known composition. Mechanical properties are measured by analyzing data from two indentation techniques—ramp-stress relaxation and load-unload hysteresis tests. Material composition is predictably correlated with viscoelastic model parameters. Model parameters estimated from the tests reveal that elastic modulus E 0 closely approximates the shear modulus for pure gelatin. Fractional-order parameter α and time constant τ vary monotonically with the volume fraction of the material’s fluid component. α characterizes medium fluidity and the rate of energy dissipation, and τ is a viscous time constant. Numerical simulations suggest that the viscous coefficient η is proportional to the energy lost during quasi-static force-displacement cycles, E A . The slope of E A versus η is determined by α and the applied indentation ramp time T r. Experimental measurements from phantom and ex vivo liver data show close agreement with theoretical predictions of the η -{{E}A} relation. The relative error is less than 20% for emulsions 22% for liver. We find that KVFD model parameters form a concise features space for biphasic medium characterization that described time-varying mechanical properties. The experimental work was carried out at the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Methodological development, including numerical simulation and all data analysis, were carried out at the school of Life Science and Technology, Xi’an JiaoTong University, 710049, China.

  6. Local Application of Isogenic Adipose-Derived Stem Cells Restores Bone Healing Capacity in a Type 2 Diabetes Model.

    Science.gov (United States)

    Wallner, Christoph; Abraham, Stephanie; Wagner, Johannes Maximilian; Harati, Kamran; Ismer, Britta; Kessler, Lukas; Zöllner, Hannah; Lehnhardt, Marcus; Behr, Björn

    2016-06-01

    Bone regeneration is typically a reliable process without scar formation. The endocrine disease type 2 diabetes prolongs and impairs this healing process. In a previous work, we showed that angiogenesis and osteogenesis-essential steps of bone regeneration-are deteriorated, accompanied by reduced proliferation in type 2 diabetic bone regeneration. The aim of the study was to improve these mechanisms by local application of adipose-derived stem cells (ASCs) and facilitate bone regeneration in impaired diabetic bone regeneration. The availability of ASCs in great numbers and the relative ease of harvest offers unique advantages over other mesenchymal stem cell entities. A previously described unicortical tibial defect model was utilized in diabetic mice (Lepr(db-/-)). Isogenic mouse adipose-derived stem cells (mASCs)(db-/db-) were harvested, transfected with a green fluorescent protein vector, and isografted into tibial defects (150,000 living cells per defect). Alternatively, control groups were treated with Dulbecco's modified Eagle's medium or mASCs(WT). In addition, wild-type mice were identically treated. By means of immunohistochemistry, proteins specific for angiogenesis, cell proliferation, cell differentiation, and bone formation were analyzed at early (3 days) and late (7 days) stages of bone regeneration. Additionally, histomorphometry was performed to examine bone formation rate and remodeling. Histomorphometry revealed significantly increased bone formation in mASC(db-/db-)-treated diabetic mice as compared with the respective control groups. Furthermore, locally applied mASCs(db-/db-) significantly enhanced neovascularization and osteogenic differentiation. Moreover, bone remodeling was upregulated in stem cell treatment groups. Local application of mACSs can restore impaired diabetic bone regeneration and may represent a therapeutic option for the future. This study showed that stem cells obtained from fat pads of type 2 diabetic mice are capable of

  7. Books average previous decade of economic misery.

    Science.gov (United States)

    Bentley, R Alexander; Acerbi, Alberto; Ormerod, Paul; Lampos, Vasileios

    2014-01-01

    For the 20(th) century since the Depression, we find a strong correlation between a 'literary misery index' derived from English language books and a moving average of the previous decade of the annual U.S. economic misery index, which is the sum of inflation and unemployment rates. We find a peak in the goodness of fit at 11 years for the moving average. The fit between the two misery indices holds when using different techniques to measure the literary misery index, and this fit is significantly better than other possible correlations with different emotion indices. To check the robustness of the results, we also analysed books written in German language and obtained very similar correlations with the German economic misery index. The results suggest that millions of books published every year average the authors' shared economic experiences over the past decade.

  8. Currents, HF Radio-derived, SF Bay Outlet, Normal Model, Meridional, EXPERIMENTAL

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The data is the meridional component of ocean surface currents derived from High Frequency Radio-derived measurements, with missing values filled in by a normal...

  9. Induced pluripotent stem cell derived cardiomyocytes as models for cardiac arrhythmias

    Directory of Open Access Journals (Sweden)

    Maaike eHoekstra

    2012-08-01

    Full Text Available Cardiac arrhythmias are a major cause of morbidity and mortality. In younger patients, the majority of sudden cardiac deaths have an underlying Mendelian genetic cause. Over the last 15 years, enormous progress has been made in identifying the distinct clinical phenotypes and in studying the basic cellular and genetic mechanisms associated with the primary Mendelian (monogenic arrhythmia syndromes. Investigation of the electrophysiological consequences of an ion channel mutation is ideally done in the native cardiomyocyte environment. However, the majority of such studies so far have relied on heterologous expression systems in which single ion channel genes are expressed in non-cardiac cells. In some cases, transgenic mouse models haven been generated, but these also have significant shortcomings, primarily related to species differences.The discovery that somatic cells can be reprogrammed to pluripotency as induced pluripotent stem cells (iPSC has generated much interest since it presents an opportunity to generate patient- and disease-specific cell lines from which normal and diseased human cardiomyocytes can be obtained These genetically diverse human model systems can be studied in vitro and used to decipher mechanisms of disease and identify strategies and reagents for new therapies. Here we review the present state of the art with respect to cardiac disease models already generated using IPSC technology and which have been (partially characterized.Human iPSC (hiPSC models have been described for the cardiac arrhythmia syndromes, including LQT1, LQT2, LQT3-Brugada Syndrome, LQT8/Timothy syndrome and catecholaminergic polymorphic ventricular tachycardia. In most cases, the hiPSC-derived cardiomyoctes recapitulate the disease phenotype and have already provided opportunities for novel insight into cardiac pathophysiology. It is expected that the lines will be useful in the development of pharmacological agents for the management of these

  10. Observed and Model-Derived Ozone Production Efficiency over Urban and Rural New York State

    Directory of Open Access Journals (Sweden)

    Matthew Ninneman

    2017-07-01

    Full Text Available This study examined the model-derived and observed ozone production efficiency (OPE = ∆Ox/∆NOz in one rural location, Pinnacle State Park (PSP in Addison, New York (NY, and one urban location, Queens College (QC in Flushing, NY, in New York State (NYS during photo-chemically productive hours (11 a.m.–4 p.m. Eastern Standard Time (EST in summer 2016. Measurement data and model predictions from National Oceanic and Atmospheric Administration National Air Quality Forecast Capability (NOAA NAQFC—Community Multiscale Air Quality (CMAQ model versions 4.6 (v4.6 and 5.0.2 (v5.0.2 were used to assess the OPE at both sites. CMAQ-predicted and observed OPEs were often in poor agreement at PSP and in reasonable agreement at QC, with model-predicted and observed OPEs, ranging from approximately 5–11 and 10–13, respectively, at PSP; and 4–7 and 6–8, respectively, at QC. The observed relationship between OPE and oxides of nitrogen (NOx was studied at PSP to examine where the OPE downturn may have occurred. Summer 2016 observations at PSP did not reveal a distinct OPE downturn, but they did indicate that the OPE at PSP remained high (10 or greater regardless of the [NOx] level. The observed OPEs at QC were found by using species-specific reactive odd nitrogen (NOy instruments and an estimated value for nitrogen dioxide (NO2, since observed OPEs determined using non-specific NOx and NOy instruments yielded observed OPE results that (1 varied from approximately 11–25, (2 sometimes had negative [NOz] concentrations, and (3 were inconsistent with CMAQ-predicted OPE. This difference in observed OPEs at QC depending on the suite of instruments used suggests that species-specific NOx and NOy instruments may be needed to obtain reliable urban OPEs.

  11. The eHealth Enhanced Chronic Care Model: a theory derivation approach.

    Science.gov (United States)

    Gee, Perry M; Greenwood, Deborah A; Paterniti, Debora A; Ward, Deborah; Miller, Lisa M Soederberg

    2015-04-01

    Chronic illnesses are significant to individuals and costly to society. When systematically implemented, the well-established and tested Chronic Care Model (CCM) is shown to improve health outcomes for people with chronic conditions. Since the development of the original CCM, tremendous information management, communication, and technology advancements have been established. An opportunity exists to improve the time-honored CCM with clinically efficacious eHealth tools. The first goal of this paper was to review research on eHealth tools that support self-management of chronic disease using the CCM. The second goal was to present a revised model, the eHealth Enhanced Chronic Care Model (eCCM), to show how eHealth tools can be used to increase efficiency of how patients manage their own chronic illnesses. Using Theory Derivation processes, we identified a "parent theory", the Chronic Care Model, and conducted a thorough review of the literature using CINAHL, Medline, OVID, EMBASE PsychINFO, Science Direct, as well as government reports, industry reports, legislation using search terms "CCM or Chronic Care Model" AND "eHealth" or the specific identified components of eHealth. Additionally, "Chronic Illness Self-management support" AND "Technology" AND several identified eHealth tools were also used as search terms. We then used a review of the literature and specific components of the CCM to create the eCCM. We identified 260 papers at the intersection of technology, chronic disease self-management support, the CCM, and eHealth and organized a high-quality subset (n=95) using the components of CCM, self-management support, delivery system design, clinical decision support, and clinical information systems. In general, results showed that eHealth tools make important contributions to chronic care and the CCM but that the model requires modification in several key areas. Specifically, (1) eHealth education is critical for self-care, (2) eHealth support needs to be

  12. Error estimates for near-Real-Time Satellite Soil Moisture as Derived from the Land Parameter Retrieval Model

    NARCIS (Netherlands)

    Parinussa, R.M.; Meesters, A.G.C.A.; Liu, Y.Y.; Dorigo, W.; Wagner, W.; de Jeu, R.A.M.

    2011-01-01

    A time-efficient solution to estimate the error of satellite surface soil moisture from the land parameter retrieval model is presented. The errors are estimated using an analytical solution for soil moisture retrievals from this radiative-transfer-based model that derives soil moisture from

  13. Statistical correction of lidar-derived digital elevation models with multispectral airborne imagery in tidal marshes

    Science.gov (United States)

    Buffington, Kevin J.; Dugger, Bruce D.; Thorne, Karen M.; Takekawa, John Y.

    2016-01-01

    Airborne light detection and ranging (lidar) is a valuable tool for collecting large amounts of elevation data across large areas; however, the limited ability to penetrate dense vegetation with lidar hinders its usefulness for measuring tidal marsh platforms. Methods to correct lidar elevation data are available, but a reliable method that requires limited field work and maintains spatial resolution is lacking. We present a novel method, the Lidar Elevation Adjustment with NDVI (LEAN), to correct lidar digital elevation models (DEMs) with vegetation indices from readily available multispectral airborne imagery (NAIP) and RTK-GPS surveys. Using 17 study sites along the Pacific coast of the U.S., we achieved an average root mean squared error (RMSE) of 0.072 m, with a 40–75% improvement in accuracy from the lidar bare earth DEM. Results from our method compared favorably with results from three other methods (minimum-bin gridding, mean error correction, and vegetation correction factors), and a power analysis applying our extensive RTK-GPS dataset showed that on average 118 points were necessary to calibrate a site-specific correction model for tidal marshes along the Pacific coast. By using available imagery and with minimal field surveys, we showed that lidar-derived DEMs can be adjusted for greater accuracy while maintaining high (1 m) resolution.

  14. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids

    Science.gov (United States)

    Freedman, Benjamin S.; Brooks, Craig R.; Lam, Albert Q.; Fu, Hongxia; Morizane, Ryuji; Agrawal, Vishesh; Saad, Abdelaziz F.; Li, Michelle K.; Hughes, Michael R.; Werff, Ryan Vander; Peters, Derek T.; Lu, Junjie; Baccei, Anna; Siedlecki, Andrew M.; Valerius, M. Todd; Musunuru, Kiran; McNagny, Kelly M.; Steinman, Theodore I.; Zhou, Jing; Lerou, Paul H.; Bonventre, Joseph V.

    2015-01-01

    Human-pluripotent-stem-cell-derived kidney cells (hPSC-KCs) have important potential for disease modelling and regeneration. Whether the hPSC-KCs can reconstitute tissue-specific phenotypes is currently unknown. Here we show that hPSC-KCs self-organize into kidney organoids that functionally recapitulate tissue-specific epithelial physiology, including disease phenotypes after genome editing. In three-dimensional cultures, epiblast-stage hPSCs form spheroids surrounding hollow, amniotic-like cavities. GSK3β inhibition differentiates spheroids into segmented, nephron-like kidney organoids containing cell populations with characteristics of proximal tubules, podocytes and endothelium. Tubules accumulate dextran and methotrexate transport cargoes, and express kidney injury molecule-1 after nephrotoxic chemical injury. CRISPR/Cas9 knockout of podocalyxin causes junctional organization defects in podocyte-like cells. Knockout of the polycystic kidney disease genes PKD1 or PKD2 induces cyst formation from kidney tubules. All of these functional phenotypes are distinct from effects in epiblast spheroids, indicating that they are tissue specific. Our findings establish a reproducible, versatile three-dimensional framework for human epithelial disease modelling and regenerative medicine applications. PMID:26493500

  15. Modeling the dynamics of radionuclide concentration in animal derived products after an accident in tropical areas

    International Nuclear Information System (INIS)

    Vinhas, Denise M.; Rochedo, Elaine R.R.; Wasserman, Maria A.V.; Conti, Luiz F.C.

    2005-01-01

    Following an accidental release of radionuclides to the atmosphere with the contamination of large areas, a detailed and fast methodology to assess the prognosis of public exposure is needed to estimate radiological consequences and optimize decisions to the protection of the public. The German model ECOSYS has been chosen to integrate the SIEM - Integrated Emergency System, developed by IRD/CNEN to assess the doses to the public after an accidental contamination of rural areas. The use the model demands a considerable effort in adapting scenarios to fit the specific conditions of a location, considering the differences related to climate, environmental characteristics, agricultural calendar and practices, along with population diet. The area selected to start this adaptation considers the characteristics of the 50 km radius area surrounding the nuclear power plants at Angra dos Reis, Rio de Janeiro. At a first stage, the concentration on vegetal food products has been studied. This work describes the methodology used to select scenarios and presents results of the dynamics of the predicted concentration of radionuclides in different kinds of animal derived food products. The work provides guidance to the need of radioecological research needed to improve the adequacy of the estimates to actual Brazilian scenarios. (author)

  16. Tryptophan PET Imaging of the Kynurenine Pathway in Patient-Derived Xenograft Models of Glioblastoma.

    Science.gov (United States)

    Guastella, Anthony R; Michelhaugh, Sharon K; Klinger, Neil V; Kupsky, William J; Polin, Lisa A; Muzik, Otto; Juhász, Csaba; Mittal, Sandeep

    2016-01-01

    Increasing evidence demonstrates the immunosuppressive kynurenine pathway's (KP) role in the pathophysiology of human gliomas. To study the KP in vivo, we used the noninvasive molecular imaging tracer α-[(11)C]-methyl-l-tryptophan (AMT). The AMT-positron emission tomography (PET) has shown high uptake in high-grade gliomas and predicted survival in patients with recurrent glioblastoma (GBM). We generated patient-derived xenograft (PDX) models from dissociated cells, or tumor fragments, from 5 patients with GBM. Mice bearing subcutaneous tumors were imaged with AMT-PET, and tumors were analyzed to detect the KP enzymes indoleamine 2,3-dioxygenase (IDO) 1, IDO2, tryptophan 2,3-dioxygenase, kynureninase, and kynurenine 3-monooxygenase. Overall, PET imaging showed robust tumoral AMT uptake in PDX mice with prolonged tracer accumulation over 60 minutes, consistent with AMT trapping seen in humans. Immunostained tumor tissues demonstrated positive detection of multiple KP enzymes. Furthermore, intracranial implantation of GBM cells was performed with imaging at both 9 and 14 days postimplant, with a marked increase in AMT uptake at 14 days and a corresponding high level of tissue immunostaining for KP enzymes. These results indicate that our PDX mouse models recapitulate human GBM, including aberrant tryptophan metabolism, and offer an in vivo system for development of targeted therapeutics for patients with GBM. © The Author(s) 2016.

  17. Lithology-derived structure classification from the joint interpretation of magnetotelluric and seismic models

    Science.gov (United States)

    Bedrosian, P.A.; Maercklin, N.; Weckmann, U.; Bartov, Y.; Ryberg, T.; Ritter, O.

    2007-01-01

    Magnetotelluric and seismic methods provide complementary information about the resistivity and velocity structure of the subsurface on similar scales and resolutions. No global relation, however, exists between these parameters, and correlations are often valid for only a limited target area. Independently derived inverse models from these methods can be combined using a classification approach to map geologic structure. The method employed is based solely on the statistical correlation of physical properties in a joint parameter space and is independent of theoretical or empirical relations linking electrical and seismic parameters. Regions of high correlation (classes) between resistivity and velocity can in turn be mapped back and re-examined in depth section. The spatial distribution of these classes, and the boundaries between them, provide structural information not evident in the individual models. This method is applied to a 10 km long profile crossing the Dead Sea Transform in Jordan. Several prominent classes are identified with specific lithologies in accordance with local geology. An abrupt change in lithology across the fault, together with vertical uplift of the basement suggest the fault is sub-vertical within the upper crust. ?? 2007 The Authors Journal compilation ?? 2007 RAS.

  18. The development of stochastic process modeling through risk analysis derived from scheduling of NPP project

    International Nuclear Information System (INIS)

    Lee, Kwang Ho; Roh, Myung Sub

    2013-01-01

    There are so many different factors to consider when constructing a nuclear power plant successfully from planning to decommissioning. According to PMBOK, all projects have nine domains from a holistic project management perspective. They are equally important to all projects, however, this study focuses mostly on the processes required to manage timely completion of the project and conduct risk management. The overall objective of this study is to let you know what the risk analysis derived from scheduling of NPP project is, and understand how to implement the stochastic process modeling through risk management. Building the Nuclear Power Plant is required a great deal of time and fundamental knowledge related to all engineering. That means that integrated project scheduling management with so many activities is necessary and very important. Simulation techniques for scheduling of NPP project using Open Plan program, Crystal Ball program, and Minitab program can be useful tools for designing optimal schedule planning. Thus far, Open Plan and Monte Carlo programs have been used to calculate the critical path for scheduling network analysis. And also, Minitab program has been applied to monitor the scheduling risk. This approach to stochastic modeling through risk analysis of project activities is very useful for optimizing the schedules of activities using Critical Path Method and managing the scheduling control of NPP project. This study has shown new approach to optimal scheduling of NPP project, however, this does not consider the characteristic of activities according to the NPP site conditions. Hence, this study needs more research considering those factors

  19. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.

    Science.gov (United States)

    Vlachogiannis, Georgios; Hedayat, Somaieh; Vatsiou, Alexandra; Jamin, Yann; Fernández-Mateos, Javier; Khan, Khurum; Lampis, Andrea; Eason, Katherine; Huntingford, Ian; Burke, Rosemary; Rata, Mihaela; Koh, Dow-Mu; Tunariu, Nina; Collins, David; Hulkki-Wilson, Sanna; Ragulan, Chanthirika; Spiteri, Inmaculada; Moorcraft, Sing Yu; Chau, Ian; Rao, Sheela; Watkins, David; Fotiadis, Nicos; Bali, Maria; Darvish-Damavandi, Mahnaz; Lote, Hazel; Eltahir, Zakaria; Smyth, Elizabeth C; Begum, Ruwaida; Clarke, Paul A; Hahne, Jens C; Dowsett, Mitchell; de Bono, Johann; Workman, Paul; Sadanandam, Anguraj; Fassan, Matteo; Sansom, Owen J; Eccles, Suzanne; Starling, Naureen; Braconi, Chiara; Sottoriva, Andrea; Robinson, Simon P; Cunningham, David; Valeri, Nicola

    2018-02-23

    Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  20. The development of stochastic process modeling through risk analysis derived from scheduling of NPP project

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kwang Ho; Roh, Myung Sub [KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

    2013-10-15

    There are so many different factors to consider when constructing a nuclear power plant successfully from planning to decommissioning. According to PMBOK, all projects have nine domains from a holistic project management perspective. They are equally important to all projects, however, this study focuses mostly on the processes required to manage timely completion of the project and conduct risk management. The overall objective of this study is to let you know what the risk analysis derived from scheduling of NPP project is, and understand how to implement the stochastic process modeling through risk management. Building the Nuclear Power Plant is required a great deal of time and fundamental knowledge related to all engineering. That means that integrated project scheduling management with so many activities is necessary and very important. Simulation techniques for scheduling of NPP project using Open Plan program, Crystal Ball program, and Minitab program can be useful tools for designing optimal schedule planning. Thus far, Open Plan and Monte Carlo programs have been used to calculate the critical path for scheduling network analysis. And also, Minitab program has been applied to monitor the scheduling risk. This approach to stochastic modeling through risk analysis of project activities is very useful for optimizing the schedules of activities using Critical Path Method and managing the scheduling control of NPP project. This study has shown new approach to optimal scheduling of NPP project, however, this does not consider the characteristic of activities according to the NPP site conditions. Hence, this study needs more research considering those factors.

  1. Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model.

    Directory of Open Access Journals (Sweden)

    Chenjie Yang

    Full Text Available Exosomes are endosome-derived small membrane vesicles that are secreted by most cell types including tumor cells. Tumor-derived exosomes usually contain tumor antigens and have been used as a source of tumor antigens to stimulate anti-tumor immune responses. However, many reports also suggest that tumor-derived exosomes can facilitate tumor immune evasion through different mechanisms, most of which are antigen-independent. In the present study we used a mouse model of delayed-type hypersensitivity (DTH and demonstrated that local administration of tumor-derived exosomes carrying the model antigen chicken ovalbumin (OVA resulted in the suppression of DTH response in an antigen-specific manner. Analysis of exosome trafficking demonstrated that following local injection, tumor-derived exosomes were internalized by CD11c+ cells and transported to the draining LN. Exosome-mediated DTH suppression is associated with increased mRNA levels of TGF-β1 and IL-4 in the draining LN. The tumor-derived exosomes examined were also found to inhibit DC maturation. Taken together, our results suggest a role for tumor-derived exosomes in inducing tumor antigen-specific immunosuppression, possibly by modulating the function of APCs.

  2. Comparison of Surface Flow Features from Lidar-Derived Digital Elevation Models with Historical Elevation and Hydrography Data for Minnehaha County, South Dakota

    Science.gov (United States)

    Poppenga, Sandra K.; Worstell, Bruce B.; Stoker, Jason M.; Greenlee, Susan K.

    2009-01-01

    The U.S. Geological Survey (USGS) has taken the lead in the creation of a valuable remote sensing product by incorporating digital elevation models (DEMs) derived from Light Detection and Ranging (lidar) into the National Elevation Dataset (NED), the elevation layer of 'The National Map'. High-resolution lidar-derived DEMs provide the accuracy needed to systematically quantify and fully integrate surface flow including flow direction, flow accumulation, sinks, slope, and a dense drainage network. In 2008, 1-meter resolution lidar data were acquired in Minnehaha County, South Dakota. The acquisition was a collaborative effort between Minnehaha County, the city of Sioux Falls, and the USGS Earth Resources Observation and Science (EROS) Center. With the newly acquired lidar data, USGS scientists generated high-resolution DEMs and surface flow features. This report compares lidar-derived surface flow features in Minnehaha County to 30- and 10-meter elevation data previously incorporated in the NED and ancillary hydrography datasets. Surface flow features generated from lidar-derived DEMs are consistently integrated with elevation and are important in understanding surface-water movement to better detect surface-water runoff, flood inundation, and erosion. Many topographic and hydrologic applications will benefit from the increased availability of accurate, high-quality, and high-resolution surface-water data. The remotely sensed data provide topographic information and data integration capabilities needed for meeting current and future human and environmental needs.

  3. Earth's gravity field modelling based on satellite accelerations derived from onboard GPS phase measurements

    Science.gov (United States)

    Guo, X.; Ditmar, P.; Zhao, Q.; Klees, R.; Farahani, H. H.

    2017-09-01

    GPS data collected by satellite gravity missions can be used for extracting the long-wavelength part of the Earth's gravity field. We propose a new data processing method which makes use of the `average acceleration' approach to gravity field modelling. In this method, satellite accelerations are directly derived from GPS carrier phase measurements with an epoch-differenced scheme. As a result, no ambiguity solutions are needed and the systematic errors that do not change much from epoch to epoch are largely eliminated. The GPS data collected by the Gravity Field and Steady-State Ocean Circulation Explorer (GOCE) satellite mission are used to demonstrate the added value of the proposed method. An analysis of the residual accelerations shows that accelerations derived in this way are more precise, with noise being reduced by about 20 and 5% at the cross-track component and the other two components, respectively, as compared to those based on kinematic orbits. The accelerations obtained in this way allow the recovery of the gravity field to a slightly higher maximum degree compared to the solution based on kinematic orbits. Furthermore, the gravity field solution has an overall better performance. Errors in spherical harmonic coefficients are smaller, especially at low degrees. The cumulative geoid height error is reduced by about 15 and 5% up to degree 50 and 150, respectively. An analysis in the spatial domain shows that large errors along the geomagnetic equator, which are caused by a high electron density coupled with large short-term variations, are substantially reduced. Finally, the new method allows for a better observation of mass transport signals. In particular, sufficiently realistic signatures of regional mass anomalies in North America and south-west Africa are obtained.

  4. Bifunctional Molybdenum Polyoxometalates for the Combined Hydrodeoxygenation and Alkylation of Lignin-Derived Model Phenolics.

    Science.gov (United States)

    Anderson, Eric; Crisci, Anthony; Murugappan, Karthick; Román-Leshkov, Yuriy

    2017-05-22

    Reductive catalytic fractionation of biomass has recently emerged as a powerful lignin extraction and depolymerization method to produce monomeric aromatic oxygenates in high yields. Here, bifunctional molybdenum-based polyoxometalates supported on titania (POM/TiO 2 ) are shown to promote tandem hydrodeoxygenation (HDO) and alkylation reactions, converting lignin-derived oxygenated aromatics into alkylated benzenes and alkylated phenols in high yields. In particular, anisole and 4-propylguaiacol were used as model compounds for this gas-phase study using a packed-bed flow reactor. For anisole, 30 % selectivity for alkylated aromatic compounds (54 % C-alkylation of the methoxy groups by methyl balance) with an overall 72 % selectivity for HDO at 82 % anisole conversion was observed over H 3 PMo 12 O 40 /TiO 2 at 7 h on stream. Under similar conditions, 4-propylguaiacol was mainly converted into 4-propylphenol and alkylated 4-propylphenols with a selectivity to alkylated 4-propylphenols of 42 % (77 % C-alkylation) with a total HDO selectivity to 4-propylbenzene and alkylated 4-propylbenzenes of 4 % at 92 % conversion (7 h on stream). Higher catalyst loadings pushed the 4-propylguaiacol conversion to 100 % and resulted in a higher selectivity to propylbenzene of 41 %, alkylated aromatics of 21 % and alkylated phenols of 17 % (51 % C-alkylation). The reactivity studies coupled with catalyst characterization revealed that Lewis acid sites act synergistically with neighboring Brønsted acid sites to simultaneously promote alkylation and hydrodeoxygenation activity. A reaction mechanism is proposed involving activation of the ether bond on a Lewis acid site, followed by methyl transfer and C-alkylation. Mo-based POMs represent a versatile catalytic platform to simultaneously upgrade lignin-derived oxygenated aromatics into alkylated arenes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Skeletal Muscle Regeneration in a Rat (Rattus norvegicus) Model with CorMatrix and Adipose Derived Stem Cells

    Science.gov (United States)

    2015-07-16

    Model with CorMatrix and Adipose Derived Stem Cells ." PRINCIPAL INVESTIGATOR (Pl) I TRAINING COORDINATOR (TC): Major Lucas Neff DEPARTMENT...ability of the matrix to work in concert with adipose derived stem cells for further augmentation of healing. 3 FDGXXX Attachments: Attachment 1...Introduction: The increasing use of explosive devices has led to a dramatic increase in traumatic injury accompanied by severe tissue trauma and

  6. TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase-10 in an organotypic model of human skin

    Energy Technology Data Exchange (ETDEWEB)

    De Abrew, K. Nadira [Molecular and Environmental Toxicology Center, University of Wisconsin—Madison, Madison, WI 53706 (United States); Thomas-Virnig, Christina L.; Rasmussen, Cathy A. [Department of Pathology, University of Wisconsin—Madison, Madison, WI 53706 (United States); Bolterstein, Elyse A. [Molecular and Environmental Toxicology Center, University of Wisconsin—Madison, Madison, WI 53706 (United States); Schlosser, Sandy J. [Department of Pathology, University of Wisconsin—Madison, Madison, WI 53706 (United States); Allen-Hoffmann, B. Lynn, E-mail: blallenh@wisc.edu [Molecular and Environmental Toxicology Center, University of Wisconsin—Madison, Madison, WI 53706 (United States); Department of Pathology, University of Wisconsin—Madison, Madison, WI 53706 (United States)

    2014-05-01

    The epidermis of skin is the first line of defense against the environment. A three dimensional model of human skin was used to investigate tissue-specific phenotypes induced by the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Continuous treatment of organotypic cultures of human keratinocytes with TCDD resulted in intracellular spaces between keratinocytes of the basal and immediately suprabasal layers as well as thinning of the basement membrane, in addition to the previously reported hyperkeratinization. These tissue remodeling events were preceded temporally by changes in expression of the extracellular matrix degrading enzyme, matrix metalloproteinase-10 (MMP-10). In organotypic cultures MMP-10 mRNA and protein were highly induced following TCDD treatment. Q-PCR and immunoblot results from TCDD-treated monolayer cultures, as well as indirect immunofluorescence and immunoblot analysis of TCDD-treated organotypic cultures, showed that MMP-10 was specifically contributed by the epidermal keratinocytes but not the dermal fibroblasts. Keratinocyte-derived MMP-10 protein accumulated over time in the dermal compartment of organotypic cultures. TCDD-induced epidermal phenotypes in organotypic cultures were attenuated by the keratinocyte-specific expression of tissue inhibitor of metalloproteinase-1, a known inhibitor of MMP-10. These studies suggest that MMP-10 and possibly other MMP-10-activated MMPs are responsible for the phenotypes exhibited in the basement membrane, the basal keratinocyte layer, and the cornified layer of TCDD-treated organotypic cultures. Our studies reveal a novel mechanism by which the epithelial–stromal microenvironment is altered in a tissue-specific manner thereby inducing structural and functional pathology in the interfollicular epidermis of human skin. - Highlights: • TCDD causes hyperkeratosis and basement membrane changes in a model of human skin. • TCDD induces MMP-10 expression in organotypic cultures

  7. A rhenium tris-carbonyl derivative as a model molecule for incorporation into phospholipid assemblies for skin applications.

    Science.gov (United States)

    Fernández, Estibalitz; Rodríguez, Gelen; Hostachy, Sarah; Clède, Sylvain; Cócera, Mercedes; Sandt, Christophe; Lambert, François; de la Maza, Alfonso; Policar, Clotilde; López, Olga

    2015-07-01

    A rhenium tris-carbonyl derivative (fac-[Re(CO)3Cl(2-(1-dodecyl-1H-1,2,3,triazol-4-yl)-pyridine)]) was incorporated into phospholipid assemblies, called bicosomes, and the penetration of this molecule into skin was monitored using Fourier-transform infrared microspectroscopy (FTIR). To evaluate the capacity of bicosomes to promote the penetration of this derivative, the skin penetration of the Re(CO)3 derivative dissolved in dimethyl sulfoxide (DMSO), a typical enhancer, was also studied. Dynamic light scattering results (DLS) showed an increase in the size of the bicosomes with the incorporation of the Re(CO)3 derivative, and the FTIR microspectroscopy showed that the Re(CO)3 derivative incorporated in bicosomes penetrated deeper into the skin than when dissolved in DMSO. When this molecule was applied on the skin using the bicosomes, 60% of the Re(CO)3 derivative was retained in the stratum corneum (SC) and 40% reached the epidermis (Epi). Otherwise, the application of this molecule via DMSO resulted in 95% of the Re(CO)3 derivative being in the SC and only 5% reaching the Epi. Using a Re(CO)3 derivative with a dodecyl-chain as a model molecule, it was possible to determine the distribution of molecules with similar physicochemical characteristics in the skin using bicosomes. This fact makes these nanostructures promising vehicles for the application of lipophilic molecules inside the skin. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Comparison of different statistical modelling approaches for deriving spatial air temperature patterns in an urban environment

    Science.gov (United States)

    Straub, Annette; Beck, Christoph; Breitner, Susanne; Cyrys, Josef; Geruschkat, Uta; Jacobeit, Jucundus; Kühlbach, Benjamin; Kusch, Thomas; Richter, Katja; Schneider, Alexandra; Umminger, Robin; Wolf, Kathrin

    2017-04-01

    Frequently spatial variations of air temperature of considerable magnitude occur within urban areas. They correspond to varying land use/land cover characteristics and vary with season, time of day and synoptic conditions. These temperature differences have an impact on human health and comfort directly by inducing thermal stress as well as indirectly by means of affecting air quality. Therefore, knowledge of the spatial patterns of air temperature in cities and the factors causing them is of great importance, e.g. for urban planners. A multitude of studies have shown statistical modelling to be a suitable tool for generating spatial air temperature patterns. This contribution presents a comparison of different statistical modelling approaches for deriving spatial air temperature patterns in the urban environment of Augsburg, Southern Germany. In Augsburg there exists a measurement network for air temperature and humidity currently comprising 48 stations in the city and its rural surroundings (corporately operated by the Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health and the Institute of Geography, University of Augsburg). Using different datasets for land surface characteristics (Open Street Map, Urban Atlas) area percentages of different types of land cover were calculated for quadratic buffer zones of different size (25, 50, 100, 250, 500 m) around the stations as well for source regions of advective air flow and used as predictors together with additional variables such as sky view factor, ground level and distance from the city centre. Multiple Linear Regression and Random Forest models for different situations taking into account season, time of day and weather condition were applied utilizing selected subsets of these predictors in order to model spatial distributions of mean hourly and daily air temperature deviations from a rural reference station. Furthermore, the different model setups were

  9. Opening of the Aden Gulf Ridge Derived from GPS Constraints and Plate Tectonic Models

    Science.gov (United States)

    Fernandes, R. M.; Rolandone, F.; Leroy, S.; Alothman, A.; Al-Aydrus, A.; Khalil, H.; Ahmed, A.; Khanbari, K.; Bos, M. S.; Nicolon, P.; Heydel, L.

    2012-12-01

    The Aden Gulf Ridge forms, together with the Red Sea and the Ethiopian Rift, the only emerged RRR-type (Ridge/Ridge/Ridge) triple junction in the globe: the Afar Triple Junction. The Aden Gulf Ridge defines the boundary between two major tectonic blocks: Arabia and Somalia, being Nubia the third unit in the triple junction (bordering Arabia along the Red Sea and Somalia along the Ethiopian Rift). Although the extensional behaviour of these structures are well known, the present-day magnitudes of their opening rates are still under evaluation, in particular for the opening rate between the Arabia and Somalia plates. This work uses GPS observations acquired in campaign and continuous mode in order to better constrain the opening rates of the three plate boundaries. For the Nubia-Arabia and Nubia-Somalia boundary plates, we use solely the velocity predictions given by our computed angular velocity models using the available continuous stations in Nubia, Somalia and Arabia. The available data set is augmented here with several stations in Saudi Arabia, which allow us to better constrain the angular velocity for the stable part of the Arabia plate. We estimate the angular velocity model with respect to ITRF2008 (the latest realization of the International Terrestrial Reference System) using the value of 2.5 years (although most of the stations have already a significantly longer time-series) as threshold data span for the processed time-series. Temporal correlations are used to properly estimate the uncertainty of the time-series and derived angular velocity model. In addition, to study the near-field in the Aden Gulf, data acquired in denser campaign networks in Yemen and Oman are used to also directly compute the extension rate in the Red Sea. We show that most of the Arabian Peninsula is stable (within the uncertainties) but the southwest part (Yemen) is influenced by the proximity with the Afar Triple Junction.

  10. Consistent Pricing of VIX and Equity Derivatives with the 4/2 Stochastic Volatility Plus Jumps Model

    OpenAIRE

    Lin, Wei; Li, Shenghong; Luo, Xingguo; Chern, Shane

    2015-01-01

    In this paper, we develop a 4/2 stochastic volatility plus jumps model, namely, a new stochastic volatility model including the Heston model and 3/2 model as special cases. Our model is highly tractable by applying the Lie symmetries theory for PDEs, which means that the pricing procedure can be performed efficiently. In fact, we obtain a closed-form solution for the joint Fourier-Laplace transform so that equity and realized-variance derivatives can be priced. We also employ our model to con...

  11. The Importance of Physical Models for Deriving Dust Masses and Grain Size Distributions in Supernova Ejecta. I. Radiatively Heated Dust in the Crab Nebula

    Science.gov (United States)

    Temim, Tea; Dwek, Eli

    2013-01-01

    Recent far-infrared (IR) observations of supernova remnants (SNRs) have revealed significantly large amounts of newly condensed dust in their ejecta, comparable to the total mass of available refractory elements. The dust masses derived from these observations assume that all the grains of a given species radiate at the same temperature, regardless of the dust heating mechanism or grain radius. In this paper, we derive the dust mass in the ejecta of the Crab Nebula, using a physical model for the heating and radiation from the dust. We adopt a power-law distribution of grain sizes and two different dust compositions (silicates and amorphous carbon), and calculate the heating rate of each dust grain by the radiation from the pulsar wind nebula. We find that the grains attain a continuous range of temperatures, depending on their size and composition. The total mass derived from the best-fit models to the observed IR spectrum is 0.019-0.13 Solar Mass, depending on the assumed grain composition. We find that the power-law size distribution of dust grains is characterized by a power-law index of 3.5-4.0 and a maximum grain size larger than 0.1 micron. The grain sizes and composition are consistent with what is expected for dust grains formed in a Type IIP supernova (SN). Our derived dust mass is at least a factor of two less than the mass reported in previous studies of the Crab Nebula that assumed more simplified two-temperature models. These models also require a larger mass of refractory elements to be locked up in dust than was likely available in the ejecta. The results of this study show that a physical model resulting in a realistic distribution of dust temperatures can constrain the dust properties and affect the derived dust masses. Our study may also have important implications for deriving grain properties and mass estimates in other SNRs and for the ultimate question of whether SNe are major sources of dust in the Galactic interstellar medium and in

  12. A space-jump derivation for non-local models of cell-cell adhesion and non-local chemotaxis.

    Science.gov (United States)

    Buttenschön, Andreas; Hillen, Thomas; Gerisch, Alf; Painter, Kevin J

    2018-01-01

    Cellular adhesion provides one of the fundamental forms of biological interaction between cells and their surroundings, yet the continuum modelling of cellular adhesion has remained mathematically challenging. In 2006, Armstrong et al. proposed a mathematical model in the form of an integro-partial differential equation. Although successful in applications, a derivation from an underlying stochastic random walk has remained elusive. In this work we develop a framework by which non-local models can be derived from a space-jump process. We show how the notions of motility and a cell polarization vector can be naturally included. With this derivation we are able to include microscopic biological properties into the model. We show that particular choices yield the original Armstrong model, while others lead to more general models, including a doubly non-local adhesion model and non-local chemotaxis models. Finally, we use random walk simulations to confirm that the corresponding continuum model represents the mean field behaviour of the stochastic random walk.

  13. VCE-003.2, a novel cannabigerol derivative, enhances neuronal progenitor cell survival and alleviates symptomatology in murine models of Huntington's disease.

    Science.gov (United States)

    Díaz-Alonso, Javier; Paraíso-Luna, Juan; Navarrete, Carmen; Del Río, Carmen; Cantarero, Irene; Palomares, Belén; Aguareles, José; Fernández-Ruiz, Javier; Bellido, María Luz; Pollastro, Federica; Appendino, Giovanni; Calzado, Marco A; Galve-Roperh, Ismael; Muñoz, Eduardo

    2016-07-19

    Cannabinoids have shown to exert neuroprotective actions in animal models by acting at different targets including canonical cannabinoid receptors and PPARγ. We previously showed that VCE-003, a cannabigerol (CBG) quinone derivative, is a novel neuroprotective and anti-inflammatory cannabinoid acting through PPARγ. We have now generated a non-thiophilic VCE-003 derivative named VCE-003.2 that preserves the ability to activate PPARγ and analyzed its neuroprotective activity. This compound exerted a prosurvival action in progenitor cells during neuronal differentiation, which was prevented by a PPARγ antagonist, without affecting neural progenitor cell proliferation. In addition, VCE-003.2 attenuated quinolinic acid (QA)-induced cell death and caspase-3 activation and also reduced mutant huntingtin aggregates in striatal cells. The neuroprotective profile of VCE-003.2 was analyzed using in vivo models of striatal neurodegeneration induced by QA and 3-nitropropionic acid (3NP) administration. VCE-003.2 prevented medium spiny DARPP32(+) neuronal loss in these Huntington's-like disease mice models improving motor deficits, reactive astrogliosis and microglial activation. In the 3NP model VCE-003.2 inhibited the upregulation of proinflammatory markers and improved antioxidant defenses in the brain. These data lead us to consider VCE-003.2 to have high potential for the treatment of Huntington's disease (HD) and other neurodegenerative diseases with neuroinflammatory traits.

  14. Personality correlates of pathological gambling derived from Big Three and Big Five personality models.

    Science.gov (United States)

    Miller, Joshua D; Mackillop, James; Fortune, Erica E; Maples, Jessica; Lance, Charles E; Keith Campbell, W; Goodie, Adam S

    2013-03-30

    Personality traits have proved to be consistent and important factors in a variety of externalizing behaviors including addiction, aggression, and antisocial behavior. Given the comorbidity of these behaviors with pathological gambling (PG), it is important to test the degree to which PG shares these trait correlates. In a large community sample of regular gamblers (N=354; 111 with diagnoses of pathological gambling), the relations between measures of two major models of personality - Big Three and Big Five - were examined in relation to PG symptoms derived from a semi-structured diagnostic interview. Across measures, traits related to the experience of strong negative emotions were the most consistent correlates of PG, regardless of whether they were analyzed using bivariate or multivariate analyses. In several instances, however, the relations between personality and PG were moderated by demographic variable such as gender, race, and age. It will be important for future empirical work of this nature to pay closer attention to potentially important moderators of these relations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Dual Binding Site and Selective Acetylcholinesterase Inhibitors Derived from Integrated Pharmacophore Models and Sequential Virtual Screening

    Directory of Open Access Journals (Sweden)

    Shikhar Gupta

    2014-01-01

    Full Text Available In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer’s randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties.

  16. Interpolation Routines Assessment in ALS-Derived Digital Elevation Models for Forestry Applications

    Directory of Open Access Journals (Sweden)

    Antonio Luis Montealegre

    2015-07-01

    Full Text Available Airborne Laser Scanning (ALS is capable of estimating a variety of forest parameters using different metrics extracted from the normalized heights of the point cloud using a Digital Elevation Model (DEM. In this study, six interpolation routines were tested over a range of land cover and terrain roughness in order to generate a collection of DEMs with spatial resolution of 1 and 2 m. The accuracy of the DEMs was assessed twice, first using a test sample extracted from the ALS point cloud, second using a set of 55 ground control points collected with a high precision Global Positioning System (GPS. The effects of terrain slope, land cover, ground point density and pulse penetration on the interpolation error were examined stratifying the study area with these variables. In addition, a Classification and Regression Tree (CART analysis allowed the development of a prediction uncertainty map to identify in which areas DEMs and Airborne Light Detection and Ranging (LiDAR derived products may be of low quality. The Triangulated Irregular Network (TIN to raster interpolation method produced the best result in the validation process with the training data set while the Inverse Distance Weighted (IDW routine was the best in the validation with GPS (RMSE of 2.68 cm and RMSE of 37.10 cm, respectively.

  17. Chiral dimethylamine flutamide derivatives-modeling, synthesis, androgen receptor affinities and carbon-11 labeling

    International Nuclear Information System (INIS)

    Jacobson, Orit; Laky, Desideriu; Carlson, Kathryn E.; Elgavish, Sharona; Gozin, Michael; Even-Sapir, Einat; Leibovitc, Ilan; Gutman, Mordechai; Chisin, Roland; Katzenellenbogen, John A.; Mishani, Eyal

    2006-01-01

    Most prostate cancers are androgen dependent upon initial diagnosis. On the other hand, some very aggressive forms of prostate cancer were shown to have lost the expression of the androgen receptor (AR). Although the AR is routinely targeted in endocrine treatment, the clinical outcome remains suboptimal. Therefore, it is crucial to demonstrate the presence and activity of the AR in each case of prostate cancer, before and after treatment. While noninvasive positron emission tomography (PET) has the potential to determine AR expression of tumor cells in vivo, fully optimized PET imaging agents are not yet available. Based on molecular modeling, three novel derivatives of hydroxyflutamide (Compounds 1-3) were designed and synthesized. They contain an electron-rich group (dimethylamine) located on the methyl moiety, which may confer a better stability to the molecule in vivo. Compounds 1-3 have AR binding that is similar or higher than that of the currently used commercial drugs. An automated carbon-11 radiolabeling route was developed, and the compounds were successfully labeled with a 10-15% decay-corrected radiochemical yield, 99% radiochemical purity and a specific activity of 4Ci/μmol end of bombardment (n=15). These labeled biomarkers may facilitate the future quantitative molecular imaging of AR-positive prostate cancer using PET and may also allow for image-guided treatment of prostate cancer

  18. Derivation of a Vacuum Refractive Index in a Stringy Space-Time Foam Model

    CERN Document Server

    Ellis, Jonathan Richard; Nanopoulos, D V

    2008-01-01

    It has been suggested that energetic photons propagating in vacuo should experience a non-trivial refractive index due to the foamy structure of space-time induced by quantum-gravitational fluctuations. The sensitivity of recent astrophysical observations, particularly of AGN Mk501 by the MAGIC Collaboration, approaches the Planck scale for a refractive index depending linearly on the photon energy. We present here a new derivation of this quantum-gravitational vacuum refraction index, based on a stringy analogue of the interaction of a photon with internal degrees of freedom in a conventional medium. We model the space-time foam as a gas of D-particles in the bulk space-time of a higher-dimensional cosmology where the observable Universe is a D3-brane. The interaction of an open string representing a photon with a D-particle stretches and excites the string, which subsequently decays and re-emits the photon with a time delay that increases linearly with the photon energy and is related to stringy uncertainty...

  19. New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies.

    Science.gov (United States)

    Doğan, İnci Selin; Saraç, Selma; Sari, Suat; Kart, Didem; Eşsiz Gökhan, Şebnem; Vural, İmran; Dalkara, Sevim

    2017-04-21

    Azole antifungals are potent inhibitors of fungal lanosterol 14α demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design, synthesis, and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl)ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 μg/mL against Candida albicans. Additionally, some of our compounds, such as 19 (MIC: 0.25 μg/mL), were potent against resistant C. glabrata, a fungal strain less susceptible to some first-line antifungal drugs. We confirmed their antifungal efficacy by antibiofilm test and their safety against human monocytes by cytotoxicity assay. To rationalize their mechanism of action, we performed computational analysis utilizing molecular docking and dynamics simulations on the C. albicans and C. glabrata CYP51 (CACYP51 and CGCYP51) homology models we built. Leu130 and T131 emerged as possible key residues for inhibition of CGCYP51 by 19. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Autologous adipocyte derived stem cells favour healing in a minipig model of cutaneous radiation syndrome.

    Directory of Open Access Journals (Sweden)

    Fabien Forcheron

    Full Text Available Cutaneous radiation syndrome (CRS is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Here we examined for the first time in a large animal model the therapeutic potential of autologous adipose tissue-derived stroma cells (ASCs. For experiments, Göttingen minipigs were locally gamma irradiated using a (60Co source at the dose of 50 Gy and grafted (n = 5 or not (n = 8. ASCs were cultured in MEM-alpha with 10% fetal calf serum and basic fibroblast growth factor (2 ng.mL(-1 and post irradiation were intradermally injected on days 25, 46, 67 and finally between days 95 and 115 (50 × 10(6 ASCs each time into the exposed area. All controls exhibited a clinical evolution with final necrosis (day 91. In grafted pigs an ultimate wound healing was observed in four out of five grafted animals (day 130 +/- 28. Immunohistological analysis of cytokeratin expression showed a complete epidermis recovery. Grafted ASCs accumulated at the dermis/subcutis barrier in which they attracted numerous immune cells, and even an increased vasculature in one pig. Globally this study suggests that local injection of ASCs may represent a useful strategy to mitigate CRS.

  1. Effect of triazine derivative added to denture materials on a microcosm biofilm model.

    Science.gov (United States)

    de Moraes, Aline Pinheiro; Barwaldt, Caroline Konzgen; Nunes, Thaís Zorzoli; Sarkis-Onofre, Rafael; Ogliari, Fabrício Aulo; Boscato, Noéli; Pereira-Cenci, Tatiana

    2012-07-01

    The aim of this study was to assess the effect of triazine incorporation to denture materials on biofilm formation of saliva derived from microcosms of patients who are positive for Candida albicans. Biofilms were formed on microwave-cured acrylic resin, one hard denture liner, and two soft denture liners containing 0, 2.5, 5, and 10% triazine. For experimental subset (n = 10), mechanical properties of the materials and colony-forming unit counts from the biofilms formed on the materials were assessed. Flexural strength and modulus decreased with the addition of 2.5% triazine (p < 0.01). In general, the addition of 5 and 10% triazine leaded to more soluble materials (p < 0.001). Saliva donor with candidiasis resulted in higher counts of total microorganisms (p = 0.0294) and Streptococci (p = 0.0008). Soft denture liners showed the highest counts for total microorganisms, Streptococci, and Candida species (p < 0.001). The addition of triazine directly to denture materials was not beneficial in reducing biofilm formation in a complex biofilm model. Copyright © 2012 Wiley Periodicals, Inc.

  2. Fractional derivative and hereditary combined model for memory effects on flexible polyurethane foam

    Science.gov (United States)

    Elfarhani, Makram; Jarraya, Abdessalem; Abid, Said; Haddar, Mohamed

    2016-06-01

    In a quasi-static regime with cyclic loading, the force-displacement curve of flexible polyurethane exhibits complicated behavior: nonlinearity, visco-elasticity, hysteresis, residual force, etc. Beside nonlinearity and visco-elasticity, this material displays high dependence on the displacement rate and past loading history. Its dependence on compression rate helps to appropriately identify the force-displacement curve. Based on the new curve identification, the overall foam response is assumed to be a composite of a nonlinear elastic component and a visco-elastic component. The elastic component is expressed as a polynomial function in displacement, while the visco-elastic one is formulated according to the hereditary approach to represent the foam visco-elastic damping force during the loading phase and according to the fractional derivative approach during unloading to represent the visco-elastic residual force in the material. The focus of this study was to develop mathematical formulations and identification parameters to faithfully characterize the visco-elastic behavior of flexible polyurethane foam under multi-cycle compressive tests. A parameter calibration methodology based on the separation of the measurement data of each component force was established. This optimization process helps to avoid the parameter values admixture problem during the phase of numeric calculations of the same component force. The validity of the model results is checked according to the simulation accuracy, the physical significance of results and their agreement with the obtained force-displacement curve identification.

  3. Astronaut Bone Medical Standards Derived from Finite Element (FE) Models of QCT Scans from Population Studies

    Science.gov (United States)

    Sibonga, J. D.; Feiveson, A. H.

    2014-01-01

    This work was accomplished in support of the Finite Element [FE] Strength Task Group, NASA Johnson Space Center [JSC], Houston, TX. This group was charged with the task of developing rules for using finite-element [FE] bone-strength measures to construct operating bands for bone health that are relevant to astronauts following exposure to spaceflight. FE modeling is a computational tool used by engineers to estimate the failure loads of complex structures. Recently, some engineers have used this tool to characterize the failure loads of the hip in population studies that also monitored fracture outcomes. A Directed Research Task was authorized in July, 2012 to investigate FE data from these population studies to derive these proposed standards of bone health as a function of age and gender. The proposed standards make use of an FE-based index that integrates multiple contributors to bone strength, an expanded evaluation that is critical after an astronaut is exposed to spaceflight. The current index of bone health used by NASA is the measurement of areal BMD. There was a concern voiced by a research and clinical advisory panel that the sole use of areal BMD would be insufficient to fully evaluate the effects of spaceflight on the hip. Hence, NASA may not have a full understanding of fracture risk, both during and after a mission, and may be poorly estimating in-flight countermeasure efficacy. The FE Strength Task Group - composed of principal investigators of the aforementioned population studies and of FE modelers -donated some of its population QCT data to estimate of hip bone strength by FE modeling for this specific purpose. Consequently, Human Health Countermeasures [HHC] has compiled a dataset of FE hip strengths, generated by a single FE modeling approach, from human subjects (approx.1060) with ages covering the age range of the astronauts. The dataset has been analyzed to generate a set of FE strength cutoffs for the following scenarios: a) Qualify an

  4. EVALUASI MODEL-MODEL PENDUGAAN UMUR SIMPAN PANGAN DARI DIFUSI HUKUM FICK UNIDIREKSIONAL EVALUATION OF SHELF-LIFE EQUATION MODELS DERIVED FROM UNIDIRECTIONAL FICK’S LAW

    Directory of Open Access Journals (Sweden)

    M. Arpah

    2000-04-01

    Full Text Available The aim of this research was to study the variation of shelf-life values, obtained in quantifying shelf-life of biscuits among models of accelerated storage studies (ASS from unidirectional Fick’S law. Shelf-life of biscuits is defined as the length of time of a packaged biscuits can be stored before the onset quality change appears.Four models: Heiss-Eichner (1971, Labuza (1983, Rudolph (1986 and Half Value Period or HVP model (Syarief, 1986 were evaluated. These models shared a common basic principle that they were all derived and developed from unidirectional Fick’s law. Therefore, each parameter of individual model can be compared to the athers. A semi empirical approach using reaction kinetics through Arrhenius plot was used as a real shelf-life values.Quantification resulted in two categories of shelf-life values, First those which higher than expected value and second, were lower than expected. Parameter evaluation of components of Heiss-Eichner and Labuza models clearly shown less in number than components of Rudolph and HVP models. This led to a conclusion that the more sophisticated models gave higher shelf-life values as compared to the Arhenius model.

  5. Therapeutic Potential of Human-Derived Endothelial Colony-Forming Cells in Animal Models.

    Science.gov (United States)

    Tasev, Dimitar; Koolwijk, Pieter; van Hinsbergh, Victor W M

    2016-10-01

    Tissue regeneration requires proper vascularization. In vivo studies identified that the endothelial colony-forming cells (ECFCs), a subtype of endothelial progenitor cells that can be isolated from umbilical cord or peripheral blood, represent a promising cell source for therapeutic neovascularization. ECFCs not only are able to initiate and facilitate neovascularization in diseased tissue but also can, by acting in a paracrine manner, contribute to the creation of favorable conditions for efficient and appropriate differentiation of tissue-resident stem or progenitor cells. This review outlines the progress in the field of in vivo regenerative and tissue engineering studies and surveys why, when, and how ECFCs can be used for tissue regeneration. Reviewed literature that regard human-derived ECFCs in xenogeneic animal models implicates that ECFCs should be considered as an endothelial cell source of preference for induction of neovascularization. Their neovascularization and regenerative potential is augmented in combination with other types of stem or progenitor cells. Biocompatible scaffolds prevascularized with ECFCs interconnect faster and better with the host vasculature. The physical incorporation of ECFCs in newly formed blood vessels grants prolonged release of trophic factors of interest, which also makes ECFCs an interesting cell source candidate for gene therapy and delivery of bioactive compounds in targeted area. ECFCs possess all biological features to be considered as a cell source of preference for tissue engineering and repair of blood supply. Investigation of regenerative potential of ECFCs in autologous settings in large animal models before clinical application is the next step to clearly outline the most efficient strategy for using ECFCs as treatment.

  6. QSAR Modeling of COX -2 Inhibitory Activity of Some Dihydropyridine and Hydroquinoline Derivatives Using Multiple Linear Regression (MLR) Method.

    Science.gov (United States)

    Akbari, Somaye; Zebardast, Tannaz; Zarghi, Afshin; Hajimahdi, Zahra

    2017-01-01

    COX-2 inhibitory activities of some 1,4-dihydropyridine and 5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives were modeled by quantitative structure-activity relationship (QSAR) using stepwise-multiple linear regression (SW-MLR) method. The built model was robust and predictive with correlation coefficient (R 2 ) of 0.972 and 0.531 for training and test groups, respectively. The quality of the model was evaluated by leave-one-out (LOO) cross validation (LOO correlation coefficient (Q 2 ) of 0.943) and Y-randomization. We also employed a leverage approach for the defining of applicability domain of model. Based on QSAR models results, COX-2 inhibitory activity of selected data set had correlation with BEHm6 (highest eigenvalue n. 6 of Burden matrix/weighted by atomic masses), Mor03u (signal 03/unweighted) and IVDE (Mean information content on the vertex degree equality) descriptors which derived from their structures.

  7. Comparison of cloud forcing derived from the Earth Radiation Budget Experiment with that simulated by the NCAR Community Climate Model

    Science.gov (United States)

    Kiehl, J. T.; Ramanathan, V.

    1990-01-01

    The cloud radiative forcing derived from the Earth Radiation Budget Experiment (ERBE) data was compared with cloud forcing simulated by a T42 version of the NCAR Community Climate Model (CCM). The comparison indicates a number of deficiencies in the CCM. Namely, it is shown that the model emits substantially more long-wave radiation than is observed by ERBE. This overestimation is attributed to two model characteristics: (1) the model is too dry and thus reduces the greenhouse longwave radiation effect of the atmosphere (permitting more longwave radiation to escape into space); and (2) the effective high cloud amount is quite small in the model.

  8. Virtual reality publication of spiral ct-derived three-dimensional models: or, creation of spiral, CT-derived, three-dimensional VRML objects.

    Science.gov (United States)

    Tyszka, J M

    1997-01-01

    Three-dimensional models can be generated from slice images, such as those obtained from computed tomography (CT) and magnetic resonance imaging (MRI) using a variety of techniques. A popular method for rendering 3D anatomical models is the creation of polygonal mesh surfaces representing the boundary between tissues. Mesh surfaces can be rendered extremely quickly using conventional personal computers, without recourse to more expensive graphic workstations. The dissemination of three-dimensional (3D) models across the Internet has been made significantly easier by the definition of the Virtual Reality Markup Language (VRML) format. The VRML definition allows the parameters and relationships of 3D objects to be described in a text format. The text file can be transfered from a host computer to a remote client computer through the World Wide Web and viewed using readily available software (See Appendix). VRML is based on the definition of primitive 3D objects such as polygons and spheres. Consequently, the transition from a mesh surface derived from a clinical image data set to a VRML object is relatively simple, allowing for convenient and cost-effective dissemination of 3D clinical models across the internet.

  9. Automatic Service Derivation from Business Process Model Repositories via Semantic Technology

    NARCIS (Netherlands)

    Leopold, H.; Pittke, F.; Mendling, J.

    2015-01-01

    Although several approaches for service identification have been defined in research and practice, there is a notable lack of fully automated techniques. In this paper, we address the problem of manual work in the context of service derivation and present an approach for automatically deriving

  10. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources

    Science.gov (United States)

    Lippmann, Ethan S.; Al-Ahmad, Abraham; Azarin, Samira M.; Palecek, Sean P.; Shusta, Eric V.

    2014-02-01

    Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm2). Overall, this scalable human BBB model may enable a wide range of neuroscience studies.

  11. Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.

    Science.gov (United States)

    Shah, Sandeep N; Gelderman, Monique P; Lewis, Emily M A; Farrel, John; Wood, Francine; Strader, Michael Brad; Alayash, Abdu I; Vostal, Jaroslav G

    2016-01-01

    Reliance on volunteer blood donors can lead to transfusion product shortages, and current liquid storage of red blood cells (RBCs) is associated with biochemical changes over time, known as 'the storage lesion'. Thus, there is a need for alternative sources of transfusable RBCs to supplement conventional blood donations. Extracorporeal production of stem cell-derived RBCs (stemRBCs) is a potential and yet untapped source of fresh, transfusable RBCs. A number of groups have attempted RBC differentiation from CD34+ cells. However, it is still unclear whether these stemRBCs could eventually be effective substitutes for traditional RBCs due to potential differences in oxygen carrying capacity, viability, deformability, and other critical parameters. We have generated ex vivo stemRBCs from primary human cord blood CD34+ cells and compared them to donor-derived RBCs based on a number of in vitro parameters. In vivo, we assessed stemRBC circulation kinetics in an animal model of transfusion and oxygen delivery in a mouse model of exercise performance. Our novel, chronically anemic, SCID mouse model can evaluate the potential of stemRBCs to deliver oxygen to tissues (muscle) under resting and exercise-induced hypoxic conditions. Based on our data, stem cell-derived RBCs have a similar biochemical profile compared to donor-derived RBCs. While certain key differences remain between donor-derived RBCs and stemRBCs, the ability of stemRBCs to deliver oxygen in a living organism provides support for further development as a transfusion product.

  12. Neuroprotective Effect of the Marine-Derived Compound 11-Dehydrosinulariolide through DJ-1-Related Pathway in In Vitro and In Vivo Models of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Chien-Wei Feng

    2016-10-01

    Full Text Available Parkinson’s disease (PD is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways. Additionally, we found that 11-de could reverse the 6-OHDA-induced downregulation of total swimming distance in a zebrafish model of PD. Using a rat model of PD, we showed that a 6-OHDA-induced increase in the number of turns, and increased time spent by rats on the beam, could be reversed by 11-de treatment. Lastly, we showed that 6-OHDA-induced attenuation in tyrosine hydroxylase (TH, a dopaminergic neuronal marker, in zebrafish and rat models of PD could also be reversed by treatment with 11-de. Moreover, the patterns of DJ-1 expression observed in this study in the zebrafish and rat models of PD corroborated the trend noted in previous in vitro studies.

  13. Topogrid Derived 10 Meter Resolution Digital Elevation Model of the Shenandoah National Park and Surrounding Region, Virginia

    Science.gov (United States)

    Chirico, Peter G.; Tanner, Seth D.

    2004-01-01

    Explanation The purpose of developing a new 10m resolution DEM of the Shenandoah National Park Region was to more accurately depict geologic structure, surfical geology, and landforms of the Shenandoah National Park Region in preparation for automated landform classification. Previously, only a 30m resolution DEM was available through the National Elevation Dataset (NED). During production of the Shenandoah10m DEM of the Park the Geography Discipline of the USGS completed a revised 10m DEM to be included into the NED. However, different methodologies were used to produce the two similar DEMs. The ANUDEM algorithm was used to develop the Shenadoah DEM data. This algorithm allows for the inclusion of contours, streams, rivers, lake and water body polygons as well as spot height data to control the elevation model. A statistical analysis using over 800 National Geodetic Survey (NGS) first and second order vertical control points reveals that the Shenandoah10m DEM, produced as a part of the Appalachian Blue Ridge Landscape project, has a vertical accuracy of ?4.87 meters. The metadata for the 10m NED data reports a vertical accuracy of ?7m. A table listing the NGS control points, the elevation comparison, and the RMSE for the Shenandoah10m DEM is provided. The process of automated terrain classification involves developing statistical signatures from the DEM for each type of surficial deposit and landform type. The signature will be a measure of several characteristics derived from the elevation data including slope, aspect, planform curvature, and profile curvature. The quality of the DEM is of critical importance when extracting terrain signatures. The highest possible horizontal and vertical accuracy is required. The more accurate Shenandoah 10m DEM can now be analyzed and integrated with the geologic observations to yield statistical correlations between the two in the development of landform and surface geology mapping projects.

  14. Short-term dispersal of Fukushima-derived radionuclides off Japan: modeling efforts and model-data intercomparison

    Directory of Open Access Journals (Sweden)

    I. I. Rypina

    2013-07-01

    Full Text Available The Great East Japan Earthquake and tsunami that caused a loss of power at the Fukushima nuclear power plants (FNPP resulted in emission of radioactive isotopes into the atmosphere and the ocean. In June of 2011, an international survey measuring a variety of radionuclide isotopes, including 137Cs, was conducted in surface and subsurface waters off Japan. This paper presents the results of numerical simulations specifically aimed at interpreting these observations and investigating the spread of Fukushima-derived radionuclides off the coast of Japan and into the greater Pacific Ocean. Together, the simulations and observations allow us to study the dominant mechanisms governing this process, and to estimate the total amount of radionuclides in discharged coolant waters and atmospheric airborne radionuclide fallout. The numerical simulations are based on two different ocean circulation models, one inferred from AVISO altimetry and NCEP/NCAR reanalysis wind stress, and the second generated numerically by the NCOM model. Our simulations determine that > 95% of 137Cs remaining in the water within ~600 km of Fukushima, Japan in mid-June 2011 was due to the direct oceanic discharge. The estimated strength of the oceanic source is 16.2 ± 1.6 PBq, based on minimizing the model-data mismatch. We cannot make an accurate estimate for the atmospheric source strength since most of the fallout cesium had left the survey area by mid-June. The model explained several key features of the observed 137Cs distribution. First, the absence of 137Cs at the southernmost stations is attributed to the Kuroshio Current acting as a transport barrier against the southward progression of 137Cs. Second, the largest 137Cs concentrations were associated with a semi-permanent eddy that entrained 137Cs-rich waters, collecting and stirring them around the eddy perimeter. Finally, the intermediate 137Cs concentrations at the westernmost stations are attributed to younger, and

  15. Flood Damage Analysis: First Floor Elevation Uncertainty Resulting from LiDAR-Derived Digital Surface Models

    Directory of Open Access Journals (Sweden)

    José María Bodoque

    2016-07-01

    Full Text Available The use of high resolution ground-based light detection and ranging (LiDAR datasets provides spatial density and vertical precision for obtaining highly accurate Digital Surface Models (DSMs. As a result, the reliability of flood damage analysis has improved significantly, owing to the increased accuracy of hydrodynamic models. In addition, considerable error reduction has been achieved in the estimation of first floor elevation, which is a critical parameter for determining structural and content damages in buildings. However, as with any discrete measurement technique, LiDAR data contain object space ambiguities, especially in urban areas where the presence of buildings and the floodplain gives rise to a highly complex landscape that is largely corrected by using ancillary information based on the addition of breaklines to a triangulated irregular network (TIN. The present study provides a methodological approach for assessing uncertainty regarding first floor elevation. This is based on: (i generation an urban TIN from LiDAR data with a density of 0.5 points·m−2, complemented with the river bathymetry obtained from a field survey with a density of 0.3 points·m−2. The TIN was subsequently improved by adding breaklines and was finally transformed to a raster with a spatial resolution of 2 m; (ii implementation of a two-dimensional (2D hydrodynamic model based on the 500-year flood return period. The high resolution DSM obtained in the previous step, facilitated addressing the modelling, since it represented suitable urban features influencing hydraulics (e.g., streets and buildings; and (iii determination of first floor elevation uncertainty within the 500-year flood zone by performing Monte Carlo simulations based on geostatistics and 1997 control elevation points in order to assess error. Deviations in first floor elevation (average: 0.56 m and standard deviation: 0.33 m show that this parameter has to be neatly characterized in order

  16. CD4+ cell-derived interleukin-17 in a model of dysregulated, Borrelia-induced arthritis.

    Science.gov (United States)

    Hansen, Emily S; Johnson, Megan E; Schell, Ronald F; Nardelli, Dean T

    2016-10-01

    Lyme borreliosis, which is caused in the United States by the spirochete Borrelia burgdorferi, may manifest as different arrays of signs, symptoms and severities between infected individuals. Recent studies have indicated that particularly severe forms of Lyme borreliosis in humans are associated with an increased Th17 response. Here, we hypothesized that a murine model combining the dysregulated immune response of an environment lacking interleukin-10 (IL-10) with a robust T-cell-driven inflammatory response would reflect arthritis associated with the production of IL-17 by CD4+ cells. We demonstrate that IL-10 regulates the production of IL-17 by Borrelia-primed CD4+ cells early after interaction with Lyme spirochetes in vitro and that infection of Borrelia-primed mice with B. burgdorferi leads to significant production of IL-17 that contributes to the development of severe arthritis. These results extend our previous findings by demonstrating that a dysregulated adaptive immune response to Lyme spirochetes can contribute to severe, Th17-associated arthritis. These findings may lead to therapeutic measures for individuals with particularly severe symptoms of Lyme borreliosis. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. CT-guided Irreversible Electroporation in an Acute Porcine Liver Model: Effect of Previous Transarterial Iodized Oil Tissue Marking on Technical Parameters, 3D Computed Tomographic Rendering of the Electroporation Zone, and Histopathology

    Energy Technology Data Exchange (ETDEWEB)

    Sommer, C. M., E-mail: christof.sommer@med.uni-heidelberg.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany); Fritz, S., E-mail: stefan.fritz@med.uni-heidelberg.de [University Hospital Heidelberg, Department of General Visceral and Transplantation Surgery (Germany); Vollherbst, D., E-mail: dominikvollherbst@web.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany); Zelzer, S., E-mail: s.zelzer@dkfz-heidelberg.de [German Cancer Research Center (dkfz), Medical and Biological Informatics (Germany); Wachter, M. F., E-mail: fredericwachter@googlemail.com; Bellemann, N., E-mail: nadine.bellemann@med.uni-heidelberg.de; Gockner, T., E-mail: theresa.gockner@med.uni-heidelberg.de; Mokry, T., E-mail: theresa.mokry@med.uni-heidelberg.de; Schmitz, A., E-mail: anne.schmitz@med.uni-heidelberg.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany); Aulmann, S., E-mail: sebastian.aulmann@mail.com [University Hospital Heidelberg, Department of General Pathology (Germany); Stampfl, U., E-mail: ulrike.stampfl@med.uni-heidelberg.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany); Pereira, P., E-mail: philippe.pereira@slk-kliniken.de [SLK Kliniken Heilbronn GmbH, Clinic for Radiology, Minimally-invasive Therapies and Nuclear Medicine (Germany); Kauczor, H. U., E-mail: hu.kauczor@med.uni-heidelberg.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany); Werner, J., E-mail: jens.werner@med.uni-heidelberg.de [University Hospital Heidelberg, Department of General Visceral and Transplantation Surgery (Germany); Radeleff, B. A., E-mail: boris.radeleff@med.uni-heidelberg.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany)

    2015-02-15

    PurposeTo evaluate the effect of previous transarterial iodized oil tissue marking (ITM) on technical parameters, three-dimensional (3D) computed tomographic (CT) rendering of the electroporation zone, and histopathology after CT-guided irreversible electroporation (IRE) in an acute porcine liver model as a potential strategy to improve IRE performance.MethodsAfter Ethics Committee approval was obtained, in five landrace pigs, two IREs of the right and left liver (RL and LL) were performed under CT guidance with identical electroporation parameters. Before IRE, transarterial marking of the LL was performed with iodized oil. Nonenhanced and contrast-enhanced CT examinations followed. One hour after IRE, animals were killed and livers collected. Mean resulting voltage and amperage during IRE were assessed. For 3D CT rendering of the electroporation zone, parameters for size and shape were analyzed. Quantitative data were compared by the Mann–Whitney test. Histopathological differences were assessed.ResultsMean resulting voltage and amperage were 2,545.3 ± 66.0 V and 26.1 ± 1.8 A for RL, and 2,537.3 ± 69.0 V and 27.7 ± 1.8 A for LL without significant differences. Short axis, volume, and sphericity index were 16.5 ± 4.4 mm, 8.6 ± 3.2 cm{sup 3}, and 1.7 ± 0.3 for RL, and 18.2 ± 3.4 mm, 9.8 ± 3.8 cm{sup 3}, and 1.7 ± 0.3 for LL without significant differences. For RL and LL, the electroporation zone consisted of severely widened hepatic sinusoids containing erythrocytes and showed homogeneous apoptosis. For LL, iodized oil could be detected in the center and at the rim of the electroporation zone.ConclusionThere is no adverse effect of previous ITM on technical parameters, 3D CT rendering of the electroporation zone, and histopathology after CT-guided IRE of the liver.

  18. CT-guided Irreversible Electroporation in an Acute Porcine Liver Model: Effect of Previous Transarterial Iodized Oil Tissue Marking on Technical Parameters, 3D Computed Tomographic Rendering of the Electroporation Zone, and Histopathology

    International Nuclear Information System (INIS)

    Sommer, C. M.; Fritz, S.; Vollherbst, D.; Zelzer, S.; Wachter, M. F.; Bellemann, N.; Gockner, T.; Mokry, T.; Schmitz, A.; Aulmann, S.; Stampfl, U.; Pereira, P.; Kauczor, H. U.; Werner, J.; Radeleff, B. A.

    2015-01-01

    PurposeTo evaluate the effect of previous transarterial iodized oil tissue marking (ITM) on technical parameters, three-dimensional (3D) computed tomographic (CT) rendering of the electroporation zone, and histopathology after CT-guided irreversible electroporation (IRE) in an acute porcine liver model as a potential strategy to improve IRE performance.MethodsAfter Ethics Committee approval was obtained, in five landrace pigs, two IREs of the right and left liver (RL and LL) were performed under CT guidance with identical electroporation parameters. Before IRE, transarterial marking of the LL was performed with iodized oil. Nonenhanced and contrast-enhanced CT examinations followed. One hour after IRE, animals were killed and livers collected. Mean resulting voltage and amperage during IRE were assessed. For 3D CT rendering of the electroporation zone, parameters for size and shape were analyzed. Quantitative data were compared by the Mann–Whitney test. Histopathological differences were assessed.ResultsMean resulting voltage and amperage were 2,545.3 ± 66.0 V and 26.1 ± 1.8 A for RL, and 2,537.3 ± 69.0 V and 27.7 ± 1.8 A for LL without significant differences. Short axis, volume, and sphericity index were 16.5 ± 4.4 mm, 8.6 ± 3.2 cm 3 , and 1.7 ± 0.3 for RL, and 18.2 ± 3.4 mm, 9.8 ± 3.8 cm 3 , and 1.7 ± 0.3 for LL without significant differences. For RL and LL, the electroporation zone consisted of severely widened hepatic sinusoids containing erythrocytes and showed homogeneous apoptosis. For LL, iodized oil could be detected in the center and at the rim of the electroporation zone.ConclusionThere is no adverse effect of previous ITM on technical parameters, 3D CT rendering of the electroporation zone, and histopathology after CT-guided IRE of the liver

  19. Development of a LiDAR derived digital elevation model (DEM) as Input to a METRANS geographic information system (GIS).

    Science.gov (United States)

    2011-05-01

    This report describes an assessment of digital elevation models (DEMs) derived from : LiDAR data for a subset of the Ports of Los Angeles and Long Beach. A methodology : based on Monte Carlo simulation was applied to investigate the accuracy of DEMs ...

  20. Antidepressant Effects of Pharmacopuncture on Behavior and Brain-Derived Neurotrophic Factor (BDNF Expression in Chronic Stress Model of Mice

    Directory of Open Access Journals (Sweden)

    Yunna Kim

    2017-12-01

    Conclusion: HJ11 improves depressive-like behaviors in the stress-induced mouse model of depression, and the results indicate that the neuroprotective effect of HJ11, identified by brain-derived neurotrophic factor expression, may play a critical role in its antidepressant effect.

  1. Accuracy of linear measurements from cone-beam computed tomography-derived surface models of different voxel sizes

    NARCIS (Netherlands)

    Damstra, Janalt; Fourie, Zacharias; Huddleston Slater, James J R; Ren, Yijin

    INTRODUCTION: The aims of this study were to determine the linear accuracy of 3-dimensional surface models derived from a commercially available cone-beam computed tomography (CBCT) dental imaging system and volumetric rendering software and to investigate the influence of voxel resolution on the

  2. OSGM02: A new model for converting GPS-derived heights to local height datums in Great Britain and Ireland

    DEFF Research Database (Denmark)

    Iliffe, J.C.; Ziebart, M.; Cross, P.A.

    2003-01-01

    The background to the recent computation of a new vertical datum model for the British Isles (OSGM02) is described After giving a brief description of the computational techniques and the data sets used for the derivation of the gravimetric geoid, the paper focuses on the fitting of this surface...

  3. Gene expression profiling in a mouse model identifies fetal liver- and placenta-derived potential biomarkers for Down syndrome screening

    NARCIS (Netherlands)

    Pennings, J.L.A.; Rodenburg, W.; Imholz, S.; Koster, M.P.H.; van Oostrom, C.T.M.; Breit, T.M.; Schielen, P.C.J.I.; de Vries, A.

    2011-01-01

    Background: As a first step to identify novel potential biomarkers for prenatal Down Syndrome screening, we analyzed gene expression in embryos of wild type mice and the Down Syndrome model Ts1Cje. Since current Down Syndrome screening markers are derived from placenta and fetal liver, these tissues

  4. Deriving spatially explicit water uses from land use change modelling results in four river basins across Europe

    NARCIS (Netherlands)

    Huber García, Verena; Meyer, Swen; Kok, Kasper; Verweij, Peter; Ludwig, Ralf

    2018-01-01

    The objective of this study is to provide spatially distributed water use maps at a high spatial and thematic resolution as detailed input data for further modelling purposes. The maps were derived on the basis of official water statistics and land use maps to represent the current conditions in

  5. One-dimensional and two-dimensional hydrodynamic modelling derived flow properties: Impacts on aquatic habitat quality predictions

    Science.gov (United States)

    Rohan Benjankar; Daniele Tonina; James McKean

    2014-01-01

    Studies of the effects of hydrodynamic model dimensionality on simulated flow properties and derived quantities such as aquatic habitat quality are limited. It is important to close this knowledge gap especially now that entire river networks can be mapped at the microhabitat scale due to the advent of point-cloud techniques. This study compares flow properties, such...

  6. Induced pluripotent stem cell-derived neuron as a human model for testing environmentally induced developmental neurotoxicity

    Science.gov (United States)

    Induced pluripotent stem cell-derived neurons as a human model for testing environmentally induced developmental neurotoxicity Ingrid L. Druwe1, Timothy J. Shafer2, Kathleen Wallace2, Pablo Valdivia3 ,and William R. Mundy2. 1University of North Carolina, Curriculum in Toxicology...

  7. A Derivation of the Long-Term Degradation of a Pulsed Atomic Frequency Standard from a Control-Loop Model

    Science.gov (United States)

    Greenhall, C. A.

    1996-01-01

    The phase of a frequency standard that uses periodic interrogation and control of a local oscillator (LO) is degraded by a long-term random-walk component induced by downconversion of LO noise into the loop passband. The Dick formula for the noise level of this degradation is derived from an explicit solution of an LO control-loop model.

  8. The influence of the segmentation process on 3D measurements from cone beam computed tomography-derived surface models

    NARCIS (Netherlands)

    Engelbrecht, Willem P.; Fourie, Zacharias; Damstra, Janalt; Gerrits, Peter O.; Ren, Yijin

    2013-01-01

    To compare the accuracy of linear and angular measurements between cephalometric and anatomic landmarks on surface models derived from 3D cone beam computed tomography (CBCT) with two different segmentation protocols was the aim of this study. CBCT scans were made of cadaver heads and 3D surface

  9. Segmentation process significantly influences the accuracy of 3D surface models derived from cone beam computed tomography

    NARCIS (Netherlands)

    Fourie, Zacharias; Damstra, Janalt; Schepers, Rutger H; Gerrits, Pieter; Ren, Yijin

    AIMS: To assess the accuracy of surface models derived from 3D cone beam computed tomography (CBCT) with two different segmentation protocols. MATERIALS AND METHODS: Seven fresh-frozen cadaver heads were used. There was no conflict of interests in this study. CBCT scans were made of the heads and 3D

  10. Derivation and application of mathematical model for well test analysis with variable skin factor in hydrocarbon reservoirs

    Science.gov (United States)

    Liu, Pengcheng; Li, Wenhui; Xia, Jing; Jiao, Yuwei; Bie, Aifang

    2016-06-01

    Skin factor is often regarded as a constant in most of the mathematical model for well test analysis in oilfields, but this is only a kind of simplified treatment with the actual skin factor changeable. This paper defined the average permeability of a damaged area as a function of time by using the definition of skin factor. Therefore a relationship between a variable skin factor and time was established. The variable skin factor derived was introduced into existing traditional models rather than using a constant skin factor, then, this newly derived mathematical model for well test analysis considering variable skin factor was solved by Laplace transform. The dimensionless wellbore pressure and its derivative changed with dimensionless time were plotted with double logarithm and these plots can be used for type curve fitting. The effects of all the parameters in the expression of variable skin factor were analyzed based on the dimensionless wellbore pressure and its derivative. Finally, actual well testing data were used to fit the type curves developed which validates the applicability of the mathematical model from Sheng-2 Block, Shengli Oilfield, China.

  11. Conditioned Media From Adipose Tissue Derived Mesenchymal Stem Cells Reverse Insulin Resistance in Cellular Models.

    Science.gov (United States)

    Shree, Nitya; Bhonde, Ramesh R

    2017-08-01

    The link between insulin resistance (IR) and type 2 diabetes has been recognized for a long time. Type 2 diabetes is often associated with basal hyperinsulinemia, reduced sensitivity to insulin, and disturbances in insulin release. There are evidences showing the reversal of IR by mesenchymal stem cells. However, the effect of conditioned media from adipose derived mesenchymal stem cells (ADSCs-CM) in reversal of IR has not been established. We established an insulin resistant model of 3T3L1 and C2C12 cells and treated with ADSCs-CM. 2-NBDG (2-[N-[7-Nitrobenz-2-oxa-1,3-diazol-4-yl]Amino]-2-Deoxyglucose) uptake was performed to assess improvement in glucose uptake. Genes involved in glucose transport and in inflammation were also analysed. Western blot for glucose transporter-4 and Akt was performed to evaluate translocation of Glut4 and insulin signaling respectively. We found that the ADSCs-CM treated cells restored insulin, stimulated glucose uptake as compared to the untreated control indicating the insulin sensitizing effect of the CM. The treated cells also showed inhibition adipogenesis in 3T3L1 cells and significant reduction of intramuscular triglyceride accumulation in C2C12 cells. Gene expressions studies revealed the drastic upregulation of GLUT4 gene and significant reduction in IL6 and PAI1 gene in both 3T3L1 and C2C12 cells, indicating possible mechanism of glucose uptake with concomitant decrease in inflammation. Enhancement of GLUT4 and phospho Akt protein expression seems to be responsible for the increment in glucose uptake and enhanced insulin signaling, respectively. Our study revealed for the first time that ADSCs-CM acts as an alternative insulin sensitizer providing stem cell solution to IR. J. Cell. Biochem. 118: 2037-2043,2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Biological variation of homeostasis model assessment-derived insulin resistance in type 2 diabetes.

    Science.gov (United States)

    Jayagopal, Vijay; Kilpatrick, Eric S; Jennings, Paul E; Hepburn, David A; Atkin, Stephen L

    2002-11-01

    Individuals with type 2 diabetes are particularly vulnerable to cardiovascular disease. Insulin resistance is a major determinant of this increased risk and is a potential therapeutic target. This study was undertaken to establish the natural biological variation of insulin resistance in individuals with type 2 diabetes. The biological variation of insulin resistance was assessed by measuring insulin resistance at 4-day intervals on 10 consecutive occasions in 12 postmenopausal women with diet-controlled type 2 diabetes and in 11 weight- and age-matched postmenopausal women without type 2 diabetes. Insulin resistance was derived using the homeostasis model assessment for insulin resistance (HOMA-IR) method. The distribution of HOMA-IR was log Gaussian in the type 2 diabetic study group and Gaussian in the control group. The HOMA-IR in the type 2 diabetic group was significantly greater than that of the control group (mean +/- SD: 4.33 +/- 2.3 vs. 2.11 +/- 0.79 units, P = 0.001). After accounting for analytical variation, the mean intraindividual variation was also substantially greater in the type 2 diabetic group than in the control group (mean 1.05 vs. 0.15, P = 0.001). Consequently, at any level of HOMA-IR, a subsequent sample must increase by >90% or decrease by >47% to be considered significantly different from the first. HOMA-IR is significantly greater and more variable for individuals with type 2 diabetes. Therefore, this inherent variability needs to be accounted for in studies evaluating therapeutic reduction of HOMA-IR in this group.

  13. Significance of uncertainties derived from settling tank model structure and parameters on predicting WWTP performance - A global sensitivity analysis study

    DEFF Research Database (Denmark)

    Ramin, Elham; Sin, Gürkan; Mikkelsen, Peter Steen

    2011-01-01

    Uncertainty derived from one of the process models – such as one-dimensional secondary settling tank (SST) models – can impact the output of the other process models, e.g., biokinetic (ASM1), as well as the integrated wastewater treatment plant (WWTP) models. The model structure and parameter...... uncertainty of settler models can therefore propagate, and add to the uncertainties in prediction of any plant performance criteria. Here we present an assessment of the relative significance of secondary settling model performance in WWTP simulations. We perform a global sensitivity analysis (GSA) based....... The outcome of this study contributes to a better understanding of uncertainty in WWTPs, and explicitly demonstrates the significance of secondary settling processes that are crucial elements of model prediction under dry and wet-weather loading conditions....

  14. Human Suprapatellar Fat Pad-Derived Mesenchymal Stem Cells Induce Chondrogenesis and Cartilage Repair in a Model of Severe Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Ignacio Muñoz-Criado

    2017-01-01

    Full Text Available Cartilage degeneration is associated with degenerative bone and joint processes in severe osteoarthritis (OA. Spontaneous cartilage regeneration is extremely limited. Often the treatment consists of a partial or complete joint implant. Adipose-derived stem cell (ASC transplantation has been shown to restore degenerated cartilage; however, regenerative differences of ASC would depend on the source of adipose tissue. The infra- and suprapatellar fat pads surrounding the knee offer a potential autologous source of ASC for patients after complete joint substitution. When infrapatellar- and suprapatellar-derived stromal vascular fractions (SVF were compared, a significantly higher CD105 (+ population was found in the suprapatellar fat. In addition, the suprapatellar SVF exhibited increased numbers of colony formation units and a higher population doubling in culture compared to the infrapatellar fraction. Both the suprapatellar- and infrapatellar-derived ASC were differentiated in vitro into mature adipocytes, osteocytes, and chondrocytes. However, the suprapatellar-derived ASC showed higher osteogenic and chondrogenic efficiency. Suprapatellar-derived ASC transplantation in a severe OA mouse model significantly diminished the OA-associated knee inflammation and cartilage degenerative grade, significantly increasing the production of glycosaminoglycan and inducing endogenous chondrogenesis in comparison with the control group. Overall, suprapatellar-derived ASC offer a potential autologous regenerative treatment for patients with multiple degenerative OA.

  15. A generic probability based model to derive regional patterns of crops in time and space

    Science.gov (United States)

    Wattenbach, Martin; Luedtke, Stefan; Redweik, Richard; van Oijen, Marcel; Balkovic, Juraj; Reinds, Gert Jan

    2015-04-01

    Croplands are not only the key to human food supply, they also change the biophysical and biogeochemical properties of the land surface leading to changes in the water cycle, energy portioning, they influence soil erosion and substantially contribute to the amount of greenhouse gases entering the atmosphere. The effects of croplands on the environment depend on the type of crop and the associated management which both are related to the site conditions, economic boundary settings as well as preferences of individual farmers. The method described here is designed to predict the most probable crop to appear at a given location and time. The method uses statistical crop area information on NUTS2 level from EUROSTAT and the Common Agricultural Policy Regionalized Impact Model (CAPRI) as observation. These crops are then spatially disaggregated to the 1 x 1 km grid scale within the region, using the assumption that the probability of a crop appearing at a given location and a given year depends on a) the suitability of the land for the cultivation of the crop derived from the MARS Crop Yield Forecast System (MCYFS) and b) expert knowledge of agricultural practices. The latter includes knowledge concerning the feasibility of one crop following another (e.g. a late-maturing crop might leave too little time for the establishment of a winter cereal crop) and the need to combat weed infestations or crop diseases. The model is implemented in R and PostGIS. The quality of the generated crop sequences per grid cell is evaluated on the basis of the given statistics reported by the joint EU/CAPRI database. The assessment is given on NUTS2 level using per cent bias as a measure with a threshold of 15% as minimum quality. The results clearly indicates that crops with a large relative share within the administrative unit are not as error prone as crops that allocate only minor parts of the unit. However, still roughly 40% show an absolute per cent bias above the 15% threshold. This

  16. The geometrical precision of virtual bone models derived from clinical computed tomography data for forensic anthropology

    NARCIS (Netherlands)

    Colman, Kerri L.; Dobbe, Johannes G. G.; Stull, Kyra E.; Ruijter, Jan M.; Oostra, Roelof-Jan; van Rijn, Rick R.; van der Merwe, Alie E.; de Boer, Hans H.; Streekstra, Geert J.

    2017-01-01

    Almost all European countries lack contemporary skeletal collections for the development and validation of forensic anthropological methods. Furthermore, legal, ethical and practical considerations hinder the development of skeletal collections. A virtual skeletal database derived from clinical

  17. Tumor-targeting Salmonella typhimurium A1-R is a highly effective general therapeutic for undifferentiated soft tissue sarcoma patient-derived orthotopic xenograft nude-mouse models.

    Science.gov (United States)

    Igarashi, Kentaro; Kawaguchi, Kei; Kiyuna, Tasuku; Miyake, Kentaro; Miyake, Masuyo; Singh, Arun S; Eckardt, Mark A; Nelson, Scott D; Russell, Tara A; Dry, Sarah M; Li, Yunfeng; Yamamoto, Norio; Hayashi, Katsuhiro; Kimura, Hiroaki; Miwa, Shinji; Tsuchiya, Hiroyuki; Singh, Shree Ram; Eilber, Fritz C; Hoffman, Robert M

    2018-03-18

    Undifferentiated soft tissue sarcoma (USTS) is a recalcitrant and heterogeneous subgroup of soft tissue sarcoma with high risk of metastasis and recurrence. Due to heterogeneity of USTS, there is no reliably effective first-line therapy. We have generated tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R), which previously showed strong efficacy on single patient-derived orthotopic xenograft (PDOX) models of Ewing's sarcoma and follicular dendritic cell sarcoma. In the present study, tumor resected from 4 patients with a biopsy-proven USTS (2 undifferentiated pleomorphic sarcoma [UPS], 1 undifferentiated sarcoma not otherwise specified [NOS] and 1 undifferentiated spindle cell sarcoma [USS]) were grown orthotopically in the biceps femoris muscle of mice to establish PDOX models. One USS model and one UPS model were doxorubicin (DOX) resistant. One UPS and the NOS model were partially sensitive to DOX. DOX is first-line therapy for these diseases. S. typhimurium A1-R arrested tumor growth all 4 models. In addition to arresting tumor growth in each case, S. typhimurium A1-R was significantly more efficacious than DOX in each case, thereby surpassing first-line therapy. These results suggest that S. typhimurium A1-R can be a general therapeutic for USTS and possibly sarcoma in general. Published by Elsevier Inc.

  18. In silico modelling of thiazolidine derivatives with antioxidant potency: Models quantify the degree of contribution of molecular fragments towards the free radical scavenging ability

    Science.gov (United States)

    De, Biplab; Adhikari, Indrani; Nandy, Ashis; Saha, Achintya; Goswami, Binoy Behari

    2017-06-01

    Design and development of antioxidant supplements constitute an essential aspect of research in order to derive molecules that would help to combat the free radical invasion to the human body and curb oxidative stress related diseases. The present work deals with the development of in silico models for a series of thiazolidine derivatives having antioxidant potential. The objective of the work is to obtain models that would help to design new thazolidine derivatives based on substituent modification and thereby predict their activity profile. The QSAR model thus developed helps in quantification of the extent of contribution of the various molecular fragments towards the activity of the molecules, while the 3D pharmacophore model provides a brief idea of the essential molecular features that help the molecules to interact with the neighbouring free radicals. Both the models have been extensively validated which ensures their predictive ability as well the potential to search molecular databases for selection of thiazolidine derivatives with potent antioxidant activity. The models can thus be utilised effectively for database searching with the aim to isolate active antioxidants belonging to the thiazolidine group.

  19. Calibration of Deterministic Streamflow Models in Ungaged Basins Using Statistically-Derived At-Site Streamflow Simulations

    Science.gov (United States)

    Farmer, William; Hay, Lauren; Kiang, Julie

    2017-04-01

    The continental-scale streamflow network provides vital information for quantifying water resources in the U.S., however, large portions of the U.S. remain ungaged and require streamflow to be estimated. Validation of streamflow models in ungaged basins is difficult due to the lack of observed daily streamflow data for model calibration. This difficulty often leads researchers to rely on regional statistical models (regionalizations) that are limited to the time series of the streamflow variable of interest and offer limited additional hydrologic outputs beyond the variable of interest compared to deterministic streamflow models, which are capable of modeling multiple elements of the water budget simultaneously. This work combines statistically-derived streamflows at ungaged locations to calibrate a popular hydrologic model, PRMS (Precipitation-Runoff Modeling System). Combining this statistically-derived, at-site information with observations of other hydrologic variables, including evapotranspiration and snow covered area, produced simulations as reasonable as alternative approaches to ungaged calibration. Improvements from calibrating to statistical time series are limited by maximum performance of an idealized at-site calibration, i.e., if observed streamflows were known for calibration. The degree of performance when calibrated with observed data is correlated with the degree of performance when calibrated with statistically-derived alternatives. Regionally-varying hydrologic processes limit the applicability of deterministic models, statistical models and the combination thereof; coupled calibration may improve identification of these underlying processes. The advantages and disadvantages of statistically-informed calibration of deterministic models are discussed with emphasis on continental application across the conterminous United States.

  20. Impeller-pump model derived from conservation laws applied to the simulation of the cardiovascular system coupled to heart-assist pumps.

    Science.gov (United States)

    Shi, Yubing; Korakianitis, Theodosios

    2018-02-01

    Previous numerical models of impeller pumps for ventricular assist devices utilize curve-fitted polynomials to simulate experimentally-obtained pressure difference versus flow rate characteristics of the pumps, with pump rotational speed as a parameter. In this paper the numerical model for the pump pressure difference versus flow rate characteristics is obtained by analytic derivation. The mass, energy and angular momentum conservation laws are applied to the working fluid passing through the impeller geometry and coupled with the turbomachine's velocity diagram. This results in the construction of a pressure difference versus flow rate characteristic for the specific pump geometry, with pump rotational speed as parameter. Overall this model allows modifications of the pump geometry, so that the pump avoids undesirable operating conditions, such as regurgitant flow. The HeartMate III centrifugal pump is used as an example to demonstrate the application of the technique. The parameterised numerical model for HeartMate III derived by this technique is coupled with a numerical model for the human cardiovascular system, and the combination is used to investigate the cardiovascular response under different conditions of impeller pump support. Conditions resulting in regurgitant pump flow, the pump resulting in aortic valve closure and taking over completely the pumping action from the diseased heart, and inner ventricular wall suction at pump inlet are predicted by the model. The simulation results suggest that for normal HeartMate III operation the pump speed should be maintained between 3,100 and 4,500 rpm to avoid regurgitant pump flow and ventricular suction. To obtain optimal overall cardiovascular system plus pump response, the pump operating speed should be 3,800 rpm. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Evaluation of Pharmacokinetic Models for the Disposition of Lead (Pb) in Humans, in Support of Application to Occupational Exposure Limit Derivation

    Science.gov (United States)

    2015-11-09

    Evaluation of Pharmacokinetic Models for the Disposition of Lead (Pb) in Humans, in Support of Application to Occupational Exposure Limit...Derivation Naval Medical Research Unit Dayton EVALUATION OF PHARMACOKINETIC MODELS FOR THE DISPOSITION OF LEAD (PB) IN HUMANS, IN SUPPORT OF... pharmacokinetic models for the disposition of lead (Pb) in humans, in support of application to occupational exposure limit derivation 5a. Contract

  2. Scenario and modelling uncertainty in global mean temperature change derived from emission-driven global climate models

    Directory of Open Access Journals (Sweden)

    B. B. B. Booth

    2013-04-01

    Full Text Available We compare future changes in global mean temperature in response to different future scenarios which, for the first time, arise from emission-driven rather than concentration-driven perturbed parameter ensemble of a global climate model (GCM. These new GCM simulations sample uncertainties in atmospheric feedbacks, land carbon cycle, ocean physics and aerosol sulphur cycle processes. We find broader ranges of projected temperature responses arising when considering emission rather than concentration-driven simulations (with 10–90th percentile ranges of 1.7 K for the aggressive mitigation scenario, up to 3.9 K for the high-end, business as usual scenario. A small minority of simulations resulting from combinations of strong atmospheric feedbacks and carbon cycle responses show temperature increases in excess of 9 K (RCP8.5 and even under aggressive mitigation (RCP2.6 temperatures in excess of 4 K. While the simulations point to much larger temperature ranges for emission-driven experiments, they do not change existing expectations (based on previous concentration-driven experiments on the timescales over which different sources of uncertainty are important. The new simulations sample a range of future atmospheric concentrations for each emission scenario. Both in the case of SRES A1B and the Representative Concentration Pathways (RCPs, the concentration scenarios used to drive GCM ensembles, lies towards the lower end of our simulated distribution. This design decision (a legacy of previous assessments is likely to lead concentration-driven experiments to under-sample strong feedback responses in future projections. Our ensemble of emission-driven simulations span the global temperature response of the CMIP5 emission-driven simulations, except at the low end. Combinations of low climate sensitivity and low carbon cycle feedbacks lead to a number of CMIP5 responses to lie below our ensemble range. The ensemble simulates a number of high

  3. Rapid Mantle-Crust Transit Times Derived From Crystal Zonation Modeling

    Science.gov (United States)

    Ruprecht, P.; Plank, T.

    2012-12-01

    The timescales of magma transit through the entire crustal column in mature volcanic plumbing systems have been elusive, as both geophysical and geochemical techniques are most sensitive to upper crustal processes. Geophysical studies of the lower crust are often hampered by the small signal-to-noise ratio and the absence of intrinsically large earthquakes as a result of limited stress build-up. However, new approaches in seismic studies (Shelly and Hill, 2011; Tarasewicz et al., 2012) use waveform cross correlation techniques to augment existing earthquake catalogs and document hypocenter migration associated with fluid movement within the entire crust and even within the uppermost mantle. This technique is limited to (1) well-monitored volcanic systems and (2) transient magma transport that may or may not be associated with current volcanic activity. Complementary to these seismic approaches, we have developed a geochemical speedometer on the basis of trace element diffusion modeling (primarily Ni) in primitive olivine "phenocrysts" that integrates over the entire crustal ascent path and can be used to extract ascent rates from both current and older eruptions. Underlying the use of the geochemical speedometer is the assumption that primitive (> Fo88) olivines crystallize close to the Moho and then are transported without long-term (> one year) storage in the crust. We present thermal dike models showing that the conditions in the crust are unfavorable for the long-term preservation of primitive olivine crystals as cooling, differentiation, and diffusive re-equilibration inevitably lead to lower Fo olivines. Furthermore, distinct trace element signatures (e.g., Ni, Cr, Ca) in individual phenocrysts require the presence of compositionally distinct mantle-derived melts that most likely pool at the rheologic boundary of the Moho. Crystallizing olivine then captures these distinct melts during a first episode of cooling. Their magmatic origin is supported by high Ca

  4. Synthesis of New Perhydropyrrolo[1,2-a]pyrazine Derivatives and Their Evaluation in Animal Models of Epilepsy

    Directory of Open Access Journals (Sweden)

    Maciej Dawidowski

    2014-10-01

    Full Text Available A series of novel stereochemically pure derivatives of the investigative broad-spectrum anticonvulsant ADD408003 was designed and synthesized. Five-center four-component (U-5C-4CR and four-center three-component (U-4C-3CR variants of Ugi reaction were used in the key step of the synthetic pathways. The compounds obtained were evaluated for the anticonvulsant activitiy in the maximal electroshock seizure (MES, subcutaneous Metrazole (scMET and minimal clonic seizure (6 Hz animal models of epilepsy. The efficacies of most derivatives in the 6 Hz model of pharmacoresistant partial seizures were markedly higher than in the ‘classical’ MES and scMET models. The most active compounds, (4R,8aR-3a, and (4S,8aS-6 displayed median effective doses (ED50 of 47.90 and 126.19 mg/kg, respectively, for the 6 Hz test.

  5. Study on Time-Dependent Behavior of Granite and the Creep Model Based on Fractional Derivative Approach Considering Temperature

    Directory of Open Access Journals (Sweden)

    Zhilei He

    2016-01-01

    Full Text Available Based on mineral components and the creep experimental studies of Three Gorges granite and Beishan granite from different regions of China at various temperatures, the strength and creep property of two types of granites are compared and analyzed. Considering the damage evolution process, a new creep constitutive model is proposed to describe the creep property of granite at different temperatures based on fractional derivative. The parameters of the new creep model are determined on the basis of the experimental results of the two granites. In addition, a sensitivity study is carried out, showing effects of stress level, fractional derivative order, and the exponent m. The results indicate that the proposed creep model can describe the three creep stages of granite at different temperatures and contribute to further research on the creep property of granite.

  6. Deriving Behaviour of Hodgkin Huxley model with fever dynamics: A computational study

    Directory of Open Access Journals (Sweden)

    Hasan ESKALEN

    2017-10-01

    Full Text Available A single neuron can be modeled by the set of differential equations. Hodgkin-Huxley (HH model, the one of the most famous neuron model, can be considered as a dynamical system with four independent variables. Here we studied to reduce the number of differential equation required for conductance based HH model under strong inhibitory noise. Exponential Integrate and Fire (EIF model, one independent variable, is used as a reduced model of HH model by using current-voltage (I-V curve of the original model. The required reduction parameters are determined from this curve. The behaviour of HH model and its reduced EIF (rEIF model are in good agreement in sub-threshold level. Above-threshold behaviour of reduced EIF model and original model compared in terms of threshold voltage under strong inhibitory noise. Our numerical simulations clearly show that sub-threshold behaviour of HH model perfectly reduced to rEIF model.

  7. Outcome of nursing home-acquired pneumonia: derivation and application of a practical model to predict 30 day mortality.

    Science.gov (United States)

    Naughton, B J; Mylotte, J M; Tayara, A

    2000-10-01

    To derive a prediction model of 30 day mortality for nursing home-acquired pneumonia (NHAP) based on factors that can be readily identified by nursing home staff at the time of diagnosis and to apply the model to management issues related to NHAP including clarifying the importance of prepneumonia functional status as a predictor of outcome of NHAP. This was a retrospective chart review of 378 episodes of NHAP treated in the nursing home or hospital during two periods: November 1997 to April 1998 and November 1998 to April 1999. Eleven nursing homes in the greater Buffalo, NY region. Nursing home residents with radiographically proven pneumonia who had at least one of the following signs/symptoms: cough, fever, purulent sputum, respiratory rate > or =25 breaths/minute, localized auscultatory findings, or pleuritic pain. Status (alive or dead) of each resident at 30 days (30 day mortality) after diagnosis of NHAP was the dependent variable. Factors predicting 30 day mortality were identified by logistic regression analysis. A scoring system was developed based on the results of the logistic model. Each episode of NHAP in the derivation cohort was scored using the model and the cohort was stratified by the model score into six categories or risk for mortality (0-5). The predictability of the model in the derivation cohort was measured using receiver operator characteristics curve analysis. Of 378 episodes of NHAP, 74% were treated initially in the nursing home and 26% were hospitalized initially for treatment. The overall 30 day mortality was 21.4%; however, the mortality rate was significantly higher for those treated initially in the hospital (29.6% vs 16.6%; P = .012). Logistic regression analysis identified four predictors of 30 day mortality: (1) respiratory rate >30 breaths/minute (2 points), (2) pulse > 125 beats/minute (1 point), (3) altered mental status (1 point), and (4) a history of dementia (1 point). Applying the scoring system to each episode in the

  8. Adipose-Derived Stem Cells Improve Collagenase-Induced Tendinopathy in a Rat Model.

    Science.gov (United States)

    Oshita, Takashi; Tobita, Morikuni; Tajima, Satoshi; Mizuno, Hiroshi

    2016-08-01

    Tendinopathy is a common and highly prevalent musculoskeletal disorder characterized by repetitive activity-related pain and focal tendon tenderness. Histopathologically, tendinopathic tissue mainly shows degenerative changes. Therefore, tendinopathy is not affected by anti-inflammatory therapies. A novel approach, including a stem cell-based therapy, may be beneficial for its treatment. The purpose of this study was to evaluate the effects of adipose-derived stem cells (ASCs) on tendon healing in a rat tendinopathy model. The hypothesis was that ASC transplantation would improve degeneration in collagenase-induced tendinopathy. Controlled laboratory study. Sixteen F344/NSlc rats underwent collagenase injection into the Achilles tendon to induce tendinopathy. At 1 week after collagenase injection, 8 rats received ASCs (ASC group) and 8 received phosphate-buffered saline alone (PBS group). Animals were sacrificed at 4 or 12 weeks after ASC administration, and the degree of degeneration in each tendon was histologically evaluated according to the Bonar scale. The microstructure of healing tendons was observed by scanning electron microscopy. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to measure the ratio of type III collagen messenger RNA (mRNA) to type I collagen mRNA in tendons. The median Bonar scale score in the ASC and PBS groups was 2.5 and 5.33 at 4 weeks after treatment and 1.0 and 4.0 at 12 weeks after treatment, respectively. Histologically, the ASC group showed a significantly lower degree of tendon degeneration than the PBS group at both time points. In the RT-PCR analysis, the ratio of type III collagen to type I collagen was significantly lower in the ASC group than in the PBS group at 12 weeks after treatment. Moreover, this ratio decreased over time in the ASC group, whereas it increased over time in the PBS group. The study findings demonstrate that the application of ASCs results in significant improvement in the

  9. Effect of enamel matrix derivative on periodontal wound healing and regeneration in an osteoporotic model.

    Science.gov (United States)

    Miron, Richard J; Wei, Lingfei; Yang, Shuang; Caluseru, Oana M; Sculean, Anton; Zhang, Yufeng

    2014-11-01

    Despite the worldwide increased prevalence of osteoporosis, no data are available evaluating the effect of an enamel matrix derivative (EMD) on the healing of periodontal defects in patients with osteoporosis. This study aims to evaluate whether the regenerative potential of EMD may be suitable for osteoporosis-related periodontal defects. Forty female Wistar rats (mean body weight: 200 g) were used for this study. An osteoporosis animal model was carried out by bilateral ovariectomy (OVX) in 20 animals. Ten weeks after OVX, bilateral fenestration defects were created at the buccal aspect of the first mandibular molar. Animals were randomly assigned to four groups of 10 animals per group: 1) control animals with unfilled periodontal defects; 2) control animals with EMD-treated defects; 3) OVX animals with unfilled defects; and 4) OVX animals with EMD-treated defects. The animals were euthanized 28 days later, and the percentage of defect fill and thickness of newly formed bone and cementum were assessed by histomorphometry and microcomputed tomography (micro-CT) analysis. The number of osteoclasts was determined by tartrate-resistant acid phosphatase (TRAP), and angiogenesis was assessed by analyzing formation of blood vessels. OVX animals demonstrated significantly reduced bone volume in unfilled defects compared with control defects (18.9% for OVX animals versus 27.2% for control animals) as assessed by micro-CT. The addition of EMD in both OVX and control animals resulted in significantly higher bone density (52.4% and 69.2%, respectively) and bone width (134 versus 165μm) compared with untreated defects; however, the healing in OVX animals treated with EMD was significantly lower than that in control animals treated with EMD. Animals treated with EMD also demonstrated significantly higher cementum formation in both control and OVX animals. The number of TRAP-positive osteoclasts did not vary between untreated and EMD-treated animals; however, a significant

  10. Congruency sequence effects are driven by previous-trial congruency, not previous-trial response conflict

    OpenAIRE

    Weissman, Daniel H.; Carp, Joshua

    2013-01-01

    Congruency effects in distracter interference tasks are often smaller after incongruent trials than after congruent trials. However, the sources of such congruency sequence effects (CSEs) are controversial. The conflict monitoring model of cognitive control links CSEs to the detection and resolution of response conflict. In contrast, competing theories attribute CSEs to attentional or affective processes that vary with previous-trial congruency (incongruent vs. congruent). The present study s...

  11. Trashepatic left gastric vein embolization in the treatment of recurrent hemorrhaging in patients with schistosomiasis previously submitted to non-derivative surgery Embolização transhepática da veia gástrica esquerda no tratamento da recidiva hemorrágica em esquistossomóticos submetidos previamente a cirurgia não derivativa

    Directory of Open Access Journals (Sweden)

    Paulo Fernandes Saad

    2012-12-01

    Full Text Available CONTEXT: Non-derivative surgical techniques are the treatment of choice for the control of upper digestive tract hemorrhages after schistosomotic portal hypertension. However, recurrent hemorrhaging due to gastroesophagic varices is frequent. OBJECTIVE: To evaluate the outcome of treatment based on embolization of the left gastric vein to control the reoccurrence of hemorrhages caused by gastroesophagic varices in patients with schistosomiasis previously submitted to non-derivative surgery. METHODS: Rates of reoccurrence of hemorrhages and the qualitative and quantitative reduction of gastroesophagic varices in patients undergoing transhepatic embolization of the left gastric vein between December 1999 and January 2009 were studied based on medical charts and follow-up reports. RESULTS: Seven patients with a mean age of 39.3 years underwent percutaneous transhepatic embolization of the left gastric vein. The mean time between azigoportal disconnections employed in combination with splenectomy and the percutaneous approach was 8.4 ± 7.3 years, and the number of episodes of digestive hemorrhaging ranged from 1 to 7 years. No episodes of reoccurrence of hemorrhaging were found during a follow-up period which ranged from 6 months to 7 years. Endoscopic postembolization studies revealed reductions in gastroesophagic varices in all patients compared to preembolization endoscopy. CONCLUSIONS: Percutaneous transhepatic embolization of the left gastric vein in patients with schistosomiasis previously submitted to surgery resulted in a decrease in gastroesophagic varices and was shown to be effective in controlling hemorrhage reoccurrence.INTRODUÇÃO: A cirurgia por técnicas não derivativas é o tratamento de escolha para o controle da hemorragia digestiva alta secundária à hipertensão portal esquistossomótica. Contudo, a recidiva hemorrágica em decorrência das varizes gastroesofágicas é um evento frequente. O programa de erradicação endosc

  12. Influence of agro-ecosystem modeling approach on the greenhouse gas profiles of wheat-derived biopolymer products.

    Science.gov (United States)

    Guo, Miao; Li, ChangSheng; Bell, J Nigel B; Murphy, Richard J

    2012-01-03

    An approach is presented to include a wider range of factors involved in the nitrogen and carbon cycles in agro-ecosystems than is typical of many Life Cycle Assessments (LCAs) of agriculture-based products. This use results from the process-oriented Denitrification-Decomposition (DNDC, modified version) model. Here we evaluate the effects of using site-specific N(2)O emissions derived from the DNDC model rather than the values derived from the commonly used Intergovernmental Panel on Climate Change (IPCC) Tier 1 empirical model on the results of whole life cycle greenhouse gas (GHG) profiles for wheat-based biopolymer products. Statistical methods were also used to analyze the quality of the DNDC and IPCC outputs and to characterize the uncertainty in the GHG results. The results confirm that the GHG profiles of the wheat-derived biopolymer products are sensitive to how the agricultural system is modeled and uncertainty analyses indicate that DNDC is preferred over the IPCC Tier 1 approach for site-specific LCAs. The former allows inclusion of a wider range of important site-specific agricultural parameters in the LCA, provides for improved quality in the LCA data, and permits better calibration of uncertainty in the LCA inventory.

  13. Methodology for deriving hydrogeological input parameters for safety-analysis models - application to fractured crystalline rocks of Northern Switzerland

    International Nuclear Information System (INIS)

    Vomvoris, S.; Andrews, R.W.; Lanyon, G.W.; Voborny, O.; Wilson, W.

    1996-04-01

    Switzerland is one of many nations with nuclear power that is seeking to identify rock types and locations that would be suitable for the underground disposal of nuclear waste. A common challenge among these programs is to provide engineering designers and safety analysts with a reasonably representative hydrogeological input dataset that synthesizes the relevant information from direct field observations as well as inferences and model results derived from those observations. Needed are estimates of the volumetric flux through a volume of rock and the distribution of that flux into discrete pathways between the repository zones and the biosphere. These fluxes are not directly measurable but must be derived based on understandings of the range of plausible hydrogeologic conditions expected at the location investigated. The methodology described in this report utilizes conceptual and numerical models at various scales to derive the input dataset. The methodology incorporates an innovative approach, called the geometric approach, in which field observations and their associated uncertainty, together with a conceptual representation of those features that most significantly affect the groundwater flow regime, were rigorously applied to generate alternative possible realizations of hydrogeologic features in the geosphere. In this approach, the ranges in the output values directly reflect uncertainties in the input values. As a demonstration, the methodology is applied to the derivation of the hydrogeological dataset for the crystalline basement of Northern Switzerland. (author) figs., tabs., refs

  14. 3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders.

    Science.gov (United States)

    Lee, Chun-Ting; Bendriem, Raphael M; Wu, Wells W; Shen, Rong-Fong

    2017-08-20

    Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials. Studies using patient-derived brain organoids have already revealed novel insights into molecular and genetic mechanisms of certain complex human neurological disorders such as microcephaly, autism, and Alzheimer's disease. Furthermore, the combination of hiPSC technology and small-molecule high-throughput screening (HTS) facilitates the development of novel pharmacotherapeutic strategies, while transcriptome sequencing enables the transcriptional profiling of patient-derived brain organoids. Finally, the addition of CRISPR/Cas9 genome editing provides incredible potential for personalized cell replacement therapy with genetically corrected hiPSCs. This review describes the history and current state of 3D brain organoid differentiation strategies, a survey of applications of organoids towards studies of neurodevelopmental and neurodegenerative disorders, and the challenges associated with their use as in vitro models of neurological disorders.

  15. Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models

    NARCIS (Netherlands)

    Arntz, O.J.; Pieters, B.C.; Oliveira, M.C.; Broeren, M.G.A.; Bennink, M.B.; Vries, M. de; Lent, P.L.E.M. van; Koenders, M.I.; Berg, W.B. van den; Kraan, P.M. van der; Loo, F.A.J. van de

    2015-01-01

    SCOPE: This study shows the effect of bovine milk derived extracellular vesicles (BMEVs) on spontaneous polyarthritis in IL-1Ra-deficient mice and collagen-induced arthritis. METHODS AND RESULTS: BMEVs were isolated from semi-skimmed milk by ultracentrifugation and the particle size was around 100

  16. Adult Stem Cell-Derived Kidney Organoids to Model Tissue Physiology and Disease

    NARCIS (Netherlands)

    Schutgens, Frans

    2017-01-01

    “Organoid” is defined as a 3D structure grown from stem cells and consisting of organ-specific cell types that self-organizes through cell sorting and spatially restricted lineage commitment. Organoids can be derived from either adult stem cells (ASCs) or pluripotent stem cells (PSCs). The

  17. Deriving Rich Coastal Morphology and Shore Zone Classification from LIDAR Terrain Models

    NARCIS (Netherlands)

    Nijland, Wiebe|info:eu-repo/dai/nl/304823643; Reshitnyk, Luba Y.; Starzomski, Brian M.; Reynolds, John D.; Darimont, Chris T.; Nelson, Trisalyn A.

    2017-01-01

    Comprehensive mapping of shore-zone morphology supports evaluation of shore habitat, monitoring of environmental hazards, and characterization of the transfer of nutrients between marine and terrestrial environments. This article shows how rich shore-zone morphological metrics can be derived from

  18. Wave climatology of the Indian Ocean derived from altimetry and wave model

    Digital Repository Service at National Institute of Oceanography (India)

    Vethamony, P.; Rao, L.V.G.; Kumar, R.; Sarkar, A.; Mohan, M.; Sudheesh, K.; Karthikeyan, S.B.

    GEOSAT altimeter data for the period 1986-1989 have been utilised to derive wave climatology for the Indian Ocean region bounded by 20 degrees S to 25 degrees N and 40 degrees E to 110 degrees E. The results are presented in the form of mean monthly...

  19. Explicit macroscopic singlet oxygen modeling for benzoporphyrin derivative monoacid ring A (BPD)-mediated photodynamic therapy.

    Science.gov (United States)

    Kim, Michele M; Penjweini, Rozhin; Liang, Xing; Zhu, Timothy C

    2016-11-01

    Photodynamic therapy (PDT) is an effective non-ionizing treatment modality that is currently being used for various malignant and non-malignant diseases. In type II PDT with photosensitizers such as benzoporphyrin monoacid ring A (BPD), cell death is based on the creation of singlet oxygen ( 1 O 2 ). With a previously proposed empirical five-parameter macroscopic model, the threshold dose of singlet oxygen ([ 1 O 2 ] rx,sh ]) to cause tissue necrosis in tumors treated with PDT was determined along with a range of the magnitude of the relevant photochemical parameters: the photochemical oxygen consumption rate per light fluence rate and photosensitizer concentration (ξ), the probability ratio of 1 O 2 to react with ground state photosensitizer compared to a cellular target (σ), the ratio of the monomolecular decay rate of the triplet state photosensitizer (β), the low photosensitizer concentration correction factor (δ), and the macroscopic maximum oxygen supply rate (g). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated interstitially with a linear light source at 690nm with total energy released per unit length of 22.5-135J/cm and source power per unit length of 12-150mW/cm to induce different radii of necrosis. A fitting algorithm was developed to determine the photochemical parameters by minimizing the error function involving the range between the calculated reacted singlet oxygen ([ 1 O 2 ] rx ) at necrosis radius and the [ 1 O 2 ] rx,sh . [ 1 O 2 ] rx was calculated based on explicit dosimetry of the light fluence distribution, the tissue optical properties, and the BPD concentration. The initial ground state oxygen concentration ([ 3 O 2 ] 0 ) was set to be 40μM in this study. The photochemical parameters were found to be ξ=(55±40)×10 -3 cm 2 mW -1 s -1 , σ=(1.8±3)×10 -5 μM -1 , and g=1.7±0.7μMs -1 . We have taken the literature values for δ=33μM, and β=11.9μM. [ 1 O 2 ] rx has shown promise to be a more effective

  20. Electricity derivatives

    CERN Document Server

    Aïd, René

    2015-01-01

    Offering a concise but complete survey of the common features of the microstructure of electricity markets, this book describes the state of the art in the different proposed electricity price models for pricing derivatives and in the numerical methods used to price and hedge the most prominent derivatives in electricity markets, namely power plants and swings. The mathematical content of the book has intentionally been made light in order to concentrate on the main subject matter, avoiding fastidious computations. Wherever possible, the models are illustrated by diagrams. The book should allow prospective researchers in the field of electricity derivatives to focus on the actual difficulties associated with the subject. It should also offer a brief but exhaustive overview of the latest techniques used by financial engineers in energy utilities and energy trading desks.

  1. Amazon rainforest responses to elevated CO2: Deriving model-based hypotheses for the AmazonFACE experiment

    Science.gov (United States)

    Rammig, A.; Fleischer, K.; Lapola, D.; Holm, J.; Hoosbeek, M.

    2017-12-01

    Increasing atmospheric CO2 concentration is assumed to have a stimulating effect ("CO2 fertilization effect") on forest growth and resilience. Empirical evidence, however, for the existence and strength of such a tropical CO2 fertilization effect is scarce and thus a major impediment for constraining the uncertainties in Earth System Model projections. The implications of the tropical CO2 effect are far-reaching, as it strongly influences the global carbon and water cycle, and hence future global climate. In the scope of the Amazon Free Air CO2 Enrichment (FACE) experiment, we addressed these uncertainties by assessing the CO2 fertilization effect at ecosystem scale. AmazonFACE is the first FACE experiment in an old-growth, highly diverse tropical rainforest. Here, we present a priori model-based hypotheses for the experiment derived from a set of 12 ecosystem models. Model simulations identified key uncertainties in our understanding of limiting processes and derived model-based hypotheses of expected ecosystem responses to elevated CO2 that can directly be tested during the experiment. Ambient model simulations compared satisfactorily with in-situ measurements of ecosystem carbon fluxes, as well as carbon, nitrogen, and phosphorus stocks. Models consistently predicted an increase in photosynthesis with elevated CO2, which declined over time due to developing limitations. The conversion of enhanced photosynthesis into biomass, and hence ecosystem carbon sequestration, varied strongly among the models due to different assumptions on nutrient limitation. Models with flexible allocation schemes consistently predicted an increased investment in belowground structures to alleviate nutrient limitation, in turn accelerating turnover rates of soil organic matter. The models diverged on the prediction for carbon accumulation after 10 years of elevated CO2, mainly due to contrasting assumptions in their phosphorus cycle representation. These differences define the expected

  2. Mind the gap - Deriving a compatible user mental model of the home heating system to encourage sustainable behaviour.

    Science.gov (United States)

    Revell, Kirsten M A; Stanton, Neville A

    2016-11-01

    Householders' behaviour with their home heating systems is a considerable contributor to domestic energy consumption. To create a design specification for the 'scaffolding' needed for sustainable behaviour with home heating controls, Norman's (1986) Gulf of Execution and Evaluation was applied to the home heating system. A Home Heating Design Model (DM) was produced with a home heating expert. Norman's (1986) 7 Stages of Activity were considered to derive a Compatible User Mental Model (CUMM) of a typical Heating System. Considerable variation in the concepts needed at each stage was found. Elements that could be derived from the DM supported stages relating to action specification, execution, perception and interpretation, but many are not communicated in the design of typical heating controls. Stages relating to goals, intentions and evaluation required concepts beyond the DM. A systems view that tackles design for sustainable behaviour from a variety of levels is needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Human bone marrow-derived and umbilical cord-derived mesenchymal stem cells for alleviating neuropathic pain in a spinal cord injury model.

    Science.gov (United States)

    Yousefifard, Mahmoud; Nasirinezhad, Farinaz; Shardi Manaheji, Homa; Janzadeh, Atousa; Hosseini, Mostafa; Keshavarz, Mansoor

    2016-03-08

    Stem cell therapy can be used for alleviating the neuropathic pain induced by spinal cord injuries (SCIs). However, survival and differentiation of stem cells following their transplantation vary depending on the host and intrinsic factors of the cell. Therefore, the present study aimed to determine the effect of stem cells derived from bone marrow (BM-MSC) and umbilical cord (UC-MSC) on neuropathic pain relief. A compression model was used to induce SCI in a rat model. A week after SCI, about 1 million cells were transplanted into the spinal cord. Behavioral tests, including motor function recovery, mechanical allodynia, cold allodynia, mechanical hyperalgesia, and thermal hyperalgesia, were carried out every week for 8 weeks after SCI induction. A single unit recording and histological evaluation were then performed. We show that BM-MSC and UC-MSC transplantations led to improving functional recovery, allodynia, and hyperalgesia. No difference was seen between the two cell groups regarding motor recovery and alleviating the allodynia and hyperalgesia. These cells survived in the tissue at least 8 weeks and prevented cavity formation due to SCI. However, survival rate of UC-MSC was significantly higher than BM-MSC. Electrophysiological evaluations showed that transplantation of UC-MSC brings about better results than BM-MSCs in wind up of wide dynamic range neurons. The results of the present study show that BM-MSC and UC-MSC transplantations alleviated the symptoms of neuropathic pain and resulted in subsequent motor recovery after SCI. However, survival rate and electrophysiological findings of UC-MSC were significantly better than BM-MSC.

  4. Controversies in Cardiovascular Research: Induced pluripotent stem cell-derived cardiomyocytes – boutique science or valuable arrhythmia model?

    Science.gov (United States)

    Knollmann, Björn C

    2013-01-01

    As part of the series on Controversies in Cardiovascular Research, the article reviews the strengths and limitations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) as models of cardiac arrhythmias. Specifically, the article attempts to answer the following questions: Which clinical arrhythmias can be modeled by iPSC-CM? How well can iPSC-CM model adult ventricular myocytes? What are the strengths and limitations of published iPSC-CM arrhythmia models? What new mechanistic insight has been gained? What is the evidence that would support using iPSC-CM to personalize anti-arrhythmic drug therapy? The review also discusses the pros and cons of using the iPSC-CM technology for modeling specific genetic arrhythmia disorders such as long QT syndrome, Brugada Syndrome or Catecholaminergic Polymorphic Ventricular Tachycardia. PMID:23569106

  5. Comparison of representational spaces based on structural information in the development of QSAR models for benzylamino enaminone derivatives.

    Science.gov (United States)

    García, G Cerruela; Palacios-Bejarano, B; Ruiz, I Luque; Gómez-Nieto, M Á

    2012-10-01

    In this paper we study different representational spaces of molecule data sets based on 2D representation models for the building of QSAR models for the prediction of the activity of 37 benzylamino enaminone derivatives. Approximations based on classical similarity calculated from fingerprint representation of molecules and isomorphism obtained using sub-graph matching algorithms are compared to fragmentation-based approximations using partial least squares and genetic algorithms. The influence of the anchored position of a non-common moiety and the kind of substituents in the common core structure of the data set are analysed, demonstrating the anomalous behaviour of some molecules and therefore the difficulty in building prediction models. These problems are solved by considering approximate similarity models. These models tune the prediction equations based on the size of the substituent and the anchored position, by adjusting the contribution of each substituent in similarity measurements calculated between the molecule data sets.

  6. OSGM02: A new model for converting GPS-derived heights to local height datums in Great Britain and Ireland

    DEFF Research Database (Denmark)

    Iliffe, J.C.; Ziebart, M.; Cross, P.A.

    2003-01-01

    The background to the recent computation of a new vertical datum model for the British Isles (OSGM02) is described After giving a brief description of the computational techniques and the data sets used for the derivation of the gravimetric geoid, the paper focuses on the fitting of this surface ...... procedure. Results for each major region (Great Britain, Ireland, and Northern Ireland) as well as the various independent island datums are described The problems to be expected when working between datums are discussed....

  7. Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons From Patient Derived iPS Cells

    Science.gov (United States)

    2015-12-01

    impaired social interaction, as well as limited and repetitive interests and behavior . Recent studies have led to two major hypotheses for autism ...10-12, we next applied a Weighted Gene Co-expression Network Analysis (WGCNA) to provide a higher order view of the biological processes altered in...AWARD NUMBER: W81XWH-13-1-0414 TITLE: Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons From Patient-Derived iPS

  8. Testing Brain Overgrowth and Synaptic Models of Autism Using NPCs and Neurons from Patient-Derived IPS Cells

    Science.gov (United States)

    2015-12-01

    Award Number: W81XWH-13-1-0415 TITLE: Testing Brain Overgrowth and Synaptic Models of Autism Using NPC’s and Neurons from Patient-Derived IPS...Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Autism and autism spectrum disorders (ASD) are complex...impaired social interaction, and limited and repetitive interests and behavior. Recent studies have led to two major hypotheses for autism

  9. Muscle-derived Decellularised Extracellular Matrix Improves Functional Recovery in a Rat Latissimus Dorsi Muscle Defect Model

    Science.gov (United States)

    2013-12-01

    in vivo torque production from EMG in mouse muscles injured by eccentric contractions. J Physiol 1999;515(Pt 2):609e19. 27. Gamba PG, Conconi MT, Lo... Muscle -derived decellularised extracellular matrix improves functional recovery in a rat latissimus dorsi muscle defect model Xiaoyu K. Chen a,b...maxillary injuries; Muscle function; Skeletal muscle ; Volumetric muscle loss Summary Purpose: Craniofacial maxillary injuries represent nearly 30% of all

  10. Time-lapse Imaging of Primary Preneoplastic Mammary Epithelial Cells Derived from Genetically Engineered Mouse Models of Breast Cancer

    OpenAIRE

    Nakles, Rebecca E.; Millman, Sarah L.; Cabrera, M. Carla; Johnson, Peter; Mueller, Susette; Hoppe, Philipp S.; Schroeder, Timm; Furth, Priscilla A.

    2013-01-01

    Time-lapse imaging can be used to compare behavior of cultured primary preneoplastic mammary epithelial cells derived from different genetically engineered mouse models of breast cancer. For example, time between cell divisions (cell lifetimes), apoptotic cell numbers, evolution of morphological changes, and mechanism of colony formation can be quantified and compared in cells carrying specific genetic lesions. Primary mammary epithelial cell cultures are generated from mammary glands without...

  11. Electricity derivatives

    OpenAIRE

    Barone-Adesi, Giovanni; Gigli, Andrea

    2006-01-01

    In this paper we propose an algorithm for pricing derivatives written on electricity in an incomplete market setting. A discrete time model for price dynamics which embodies the main features of electricity price revealed by simple time series analysis is considered. We use jointly Binomial and Monte Carlo methods for pricing under a risk-neutral measure of which we prove the existence.

  12. Modeling electro-magneto-hydrodynamic thermo-fluidic transport of biofluids with new trend of fractional derivative without singular kernel

    Science.gov (United States)

    Abdulhameed, M.; Vieru, D.; Roslan, R.

    2017-10-01

    This paper investigates the electro-magneto-hydrodynamic flow of the non-Newtonian behavior of biofluids, with heat transfer, through a cylindrical microchannel. The fluid is acted by an arbitrary time-dependent pressure gradient, an external electric field and an external magnetic field. The governing equations are considered as fractional partial differential equations based on the Caputo-Fabrizio time-fractional derivatives without singular kernel. The usefulness of fractional calculus to study fluid flows or heat and mass transfer phenomena was proven. Several experimental measurements led to conclusion that, in such problems, the models described by fractional differential equations are more suitable. The most common time-fractional derivative used in Continuum Mechanics is Caputo derivative. However, two disadvantages appear when this derivative is used. First, the definition kernel is a singular function and, secondly, the analytical expressions of the problem solutions are expressed by generalized functions (Mittag-Leffler, Lorenzo-Hartley, Robotnov, etc.) which, generally, are not adequate to numerical calculations. The new time-fractional derivative Caputo-Fabrizio, without singular kernel, is more suitable to solve various theoretical and practical problems which involve fractional differential equations. Using the Caputo-Fabrizio derivative, calculations are simpler and, the obtained solutions are expressed by elementary functions. Analytical solutions of the biofluid velocity and thermal transport are obtained by means of the Laplace and finite Hankel transforms. The influence of the fractional parameter, Eckert number and Joule heating parameter on the biofluid velocity and thermal transport are numerically analyzed and graphic presented. This fact can be an important in Biochip technology, thus making it possible to use this analysis technique extremely effective to control bioliquid samples of nanovolumes in microfluidic devices used for biological

  13. Verification of the reflective model of first order factorsfor reward and empowerment constructs based on questionnaires derived from Lawler et al. (1991

    Directory of Open Access Journals (Sweden)

    Juan A. Marin-Garcia

    2012-12-01

    Full Text Available Purpose: High involvement practices have traditionally been classified in four main categories: training, communication, rewards and empowerment. In order to measure the degree of implementation of these programs, different questionnaires have been developed. In this paper, we have identified 3 types of questionnaires and we have deeply analyzed the psychometrical properties of one of these types: questionnaires derived from Lawler et al. (1991. The most recent investigation seems to show that psychometrical properties of both training and communication constructs are appropriate. However, it is necessary to work on rewards and empowerment scales. This research  analyzes, by means of confirmatory factorial, two reflective measurement models, already present in the previous literature of rewards and empowerment scales.Design/methodology/approach: Spanish samples from 1997 (n=105, as well as United States ones (n=212 dating 1996 and n=143 dating 1999 have been used. Convergent and discriminant validity were tested.Findings and Originality/value: None of the models presents and acceptable adjustment in the used samples. Therefore, a possible future line of investigation in order to check whether the measurement model of rewards and empowerment constructs is formative instead of reflective, has been opened.Practical implications: Practitioners can profit from the results of this research because questionnaires validity will allow companies to have measurement and good practices diagnosis tools that can be used either for internal benchmarking or for the comparison with reference groups of companies.Originality/value: Our paper identifies three questionnaire typologies used in the field of investigations of rewards and empowerment practices. We show that the point of view with which the scales of theses questionnaires have been treated has always been reflective. Moreover, this is one of the few papers that have checked the validity of the

  14. Design, synthesis and molecular modeling of aloe-emodin derivatives as potent xanthine oxidase inhibitors.

    Science.gov (United States)

    Shi, Da-Hua; Huang, Wei; Li, Chao; Liu, Yu-Wei; Wang, Shi-Fan

    2014-03-21

    A series of aloe-emodin derivatives were synthesized and evaluated as xanthine oxidase inhibitors. Among them, four aloe-emodin derivatives showed significant inhibitory activities against xanthine oxidase. The compound 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carbaldehyde (A1) possessed the best xanthine oxidase inhibitory activity with IC50 of 2.79 μM. Lineweaver-Burk plot analysis revealed that A1 acted as a mixed-type inhibitor for xanthine oxidase. The docking study revealed that the molecule A1 had strong interactions with the active site of xanthine oxidase and this result was in agreement with kinetic study. Consequently, compound A1 is a new-type candidate for further development for the treatment of gout. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  15. Efficient automatic OCR word validation using word partial format derivation and language model

    Science.gov (United States)

    Chen, Siyuan; Misra, Dharitri; Thoma, George R.

    2010-01-01

    In this paper we present an OCR validation module, implemented for the System for Preservation of Electronic Resources (SPER) developed at the U.S. National Library of Medicine.1 The module detects and corrects suspicious words in the OCR output of scanned textual documents through a procedure of deriving partial formats for each suspicious word, retrieving candidate words by partial-match search from lexicons, and comparing the joint probabilities of N-gram and OCR edit transformation corresponding to the candidates. The partial format derivation, based on OCR error analysis, efficiently and accurately generates candidate words from lexicons represented by ternary search trees. In our test case comprising a historic medico-legal document collection, this OCR validation module yielded the correct words with 87% accuracy and reduced the overall OCR word errors by around 60%.

  16. Derivative chameleons

    International Nuclear Information System (INIS)

    Noller, Johannes

    2012-01-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂ μ φ∂ μ φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂ μ φ∂ μ φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type

  17. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

    Directory of Open Access Journals (Sweden)

    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  18. Modeling Cerebrovascular Pathophysiology in Amyloid-β Metabolism using Neural-Crest-Derived Smooth Muscle Cells

    Directory of Open Access Journals (Sweden)

    Christine Cheung

    2014-10-01

    Full Text Available Summary: There is growing recognition of cerebrovascular contributions to neurodegenerative diseases. In the walls of cerebral arteries, amyloid-beta (Aβ accumulation is evident in a majority of aged people and patients with cerebral amyloid angiopathy. Here, we leverage human pluripotent stem cells to generate vascular smooth muscle cells (SMCs from neural crest progenitors, recapitulating brain-vasculature-specific attributes of Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural-crest-derived SMCs to mediate Aβ uptake and intracellular lysosomal degradation. Hypoxia significantly compromises the contribution of SMCs to Aβ clearance by suppressing LRP1 expression. This enabled us to develop an assay of Aβ uptake by using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high-throughput format, demonstrating the value of stem-cell-based phenotypic screening for novel therapeutics and drug repurposing, aimed at alleviating amyloid burden. : The contribution of blood vessel pathologies to neurodegenerative disorders is relatively neglected, partly due to inadequate human tissues for research. By using human stem cells, Cheung et al. establish a method of generating vascular smooth muscle cells (SMCs from neural crest progenitors, the primary precursors that give rise to brain blood vessels. These stem-cell-derived SMCs display defective amyloid processing under chronic hypoxia, a phenomenon well documented in the cerebral vasculatures of aged people and patients with Alzheimer’s disease.

  19. LCS-1: A high-resolution global model of the lithospheric magnetic field derived from CHAMP and Swarm satellite observations

    DEFF Research Database (Denmark)

    Olsen, Nils; Ravat, Dhananjay; Finlay, Chris

    2017-01-01

    We derive a new model, named LCS-1, of Earth’s lithospheric field based on four years (Sept 2006 – Sept 2010) of magnetic observations taken by the CHAMP satellite at altitudes lower than 350 km, as well as almost three years (April 2014 to December 2016) of measurements taken by the two lower...... Swarm satellites Alpha and Charlie. The model is determined entirely from magnetic “gradient” data (approximated by finite differences): the North-South gradient is approximated by first differences of 15 second along-track data (for CHAMP and each of the two Swarm satellites), while the East...

  20. ARCB/GSSR M RADIO TELESC DERIVED RADAR MODEL UNIT MAP V1.0

    Data.gov (United States)

    National Aeronautics and Space Administration — A model for Mars depolarized radar echo power that (1) matches the observed variation of total radar cross section with longitude and (2) produces model spectra that...

  1. Maintenance of pulmonary vasculature tone by blood derived from the inferior vena cava in a rabbit model of cavopulmonary shunt.

    Science.gov (United States)

    Ikai, Akio; Shirai, Mikiyasu; Nishimura, Kazunobu; Ikeda, Tadashi; Kameyama, Takayuki; Ueyama, Koji; Komeda, Masashi

    2005-01-01

    After cavopulmonary shunt in which the superior vena cava is anastomosed to the right pulmonary artery, the right lung is in a unique condition without flow pulsatility and hepatic venous effluent. In a previous study, we reported that hypoxic pulmonary vasoconstriction disappeared in the pulmonary circulation after cavopulmonary shunt. In this study, however, to investigate the influence of pulsatility and hepatic venous effluent on hypoxic pulmonary vasoconstriction in the pulmonary circulation, we developed an alternative cavopulmonary shunt rabbit model that included hepatic venous effluent in the pulmonary circulation and reduced the pulsatility of the pulmonary arterial blood flow. We then observed the physiologic characteristics of the peripheral pulmonary artery after cavopulmonary shunt, specifically the disappearance of hypoxic pulmonary vasoconstriction. Sixteen Japanese white rabbits (12-16 weeks old) were used in this study. With general anesthesia, a cavopulmonary shunt was established by anastomosing the right superior vena cava to the right pulmonary artery in an end-to-side fashion. Of the 16 rabbits for the study, the proximal right pulmonary artery was completely ligated in 5 (atresia group) and partially ligated in 6 (stenosis group). Sham operation was performed in the remaining 5 rabbits. Two weeks later, we analyzed the response of the pulmonary artery (which was divided into three categories: segmental, lobular, and acinar level artery) to hypoxia (8% oxygen inhalation) with a specially designed video radiographic system. Morphometric analysis of the resistance pulmonary artery was done in each group after angiography. Mean pressure and pulse pressure in the right pulmonary artery were not significantly different between the atresia and stenosis groups. The mean pulmonary artery pressures in the atresia and stenosis groups were 8 and 11 mm Hg, respectively. However, the pulse pressure was less than 2 mm Hg in both groups. The baseline

  2. Design and synthesis of new antioxidants predicted by the model developed on a set of pulvinic acid derivatives.

    Science.gov (United States)

    Le Roux, Antoine; Kuzmanovski, Igor; Habrant, Damien; Meunier, Stéphane; Bischoff, Pierre; Nadal, Brice; Thetiot-Laurent, Sophie A-L; Le Gall, Thierry; Wagner, Alain; Novič, Marjana

    2011-12-27

    Antioxidative activity expressed as protection of thymidine has been investigated for a set of 30 pulvinic acid derivatives. A combination of in vitro testing and in silico modeling was used for synthesis of new potential antioxidants. Experimental data obtained from a primary screening test based on oxidation under Fenton conditions and by an UV exposure followed by back-titration of the amount of thymidine remaining intact have been used to develop a computer model for prediction of antioxidant activity. Structural descriptors of 30 compounds tested for their thymidine protection activity were calculated in order to define the structure-property relationship and to construct predictive models. Due to the potential nonlinearity, the counter-propagation artificial neural networks were assessed for modeling of the antioxidant activity of these compounds. The optimized model was challenged with 80 new molecules not present in the initial training set. The compounds with the highest predicted antioxidant activity were considered for synthesis. Among the predicted structures, some coumarine derivatives appeared to be especially interesting. One of them was synthesized and tested on in vitro assays and showed some antioxidant and radioprotective activities, which turned out as a promising lead toward more potent antioxidants.

  3. Base-metal dental casting alloy biocompatibility assessment using a human-derived three-dimensional oral mucosal model.

    LENUS (Irish Health Repository)

    McGinley, E L

    2012-01-01

    Nickel-chromium (Ni-Cr) alloys used in fixed prosthodontics have been associated with type IV Ni-induced hypersensitivity. We hypothesised that the full-thickness human-derived oral mucosa model employed for biocompatibility testing of base-metal dental alloys would provide insights into the mechanisms of Ni-induced toxicity. Primary oral keratinocytes and gingival fibroblasts were seeded onto Alloderm™ and maintained until full thickness was achieved prior to Ni-Cr and cobalt-chromium (Co-Cr) alloy disc exposure (2-72 h). Biocompatibility assessment involved histological analyses with cell viability measurements, oxidative stress responses, inflammatory cytokine expression and cellular toxicity analyses. Inductively coupled plasma mass spectrometry analysis determined elemental ion release levels. We detected adverse morphology with significant reductions in cell viability, significant increases in oxidative stress, inflammatory cytokine expression and cellular toxicity for the Ni-Cr alloy-treated oral mucosal models compared with untreated oral mucosal models, and adverse effects were increased for the Ni-Cr alloy that leached the most Ni. Co-Cr demonstrated significantly enhanced biocompatibility compared with Ni-Cr alloy-treated oral mucosal models. The human-derived full-thickness oral mucosal model discriminated between dental alloys and provided insights into the mechanisms of Ni-induced toxicity, highlighting potential clinical relevance.

  4. Parametric Cognitive Modeling of Information and Computer Technology Usage by People with Aging- and Disability-Derived Functional Impairments.

    Science.gov (United States)

    García-Betances, Rebeca I; Cabrera-Umpiérrez, María Fernanda; Ottaviano, Manuel; Pastorino, Matteo; Arredondo, María T

    2016-02-22

    Despite the speedy evolution of Information and Computer Technology (ICT), and the growing recognition of the importance of the concept of universal design in all domains of daily living, mainstream ICT-based product designers and developers still work without any truly structured tools, guidance or support to effectively adapt their products and services to users' real needs. This paper presents the approach used to define and evaluate parametric cognitive models that describe interaction and usage of ICT by people with aging- and disability-derived functional impairments. A multisensorial training platform was used to train, based on real user measurements in real conditions, the virtual parameterized user models that act as subjects of the test-bed during all stages of simulated disabilities-friendly ICT-based products design. An analytical study was carried out to identify the relevant cognitive functions involved, together with their corresponding parameters as related to aging- and disability-derived functional impairments. Evaluation of the final cognitive virtual user models in a real application has confirmed that the use of these models produce concrete valuable benefits to the design and testing process of accessible ICT-based applications and services. Parameterization of cognitive virtual user models allows incorporating cognitive and perceptual aspects during the design process.

  5. Investigation of the interaction between isomeric derivatives and human serum albumin by fluorescence spectroscopy and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ruiyong, E-mail: wangry@zzu.edu.cn; Dou, Huanjing; Yin, Yujing; Xie, Yuanzhe; Sun, Li; Liu, Chunmei; Dong, Jingjing; Huang, Gang; Zhu, Yanyan; Song, Chuanjun, E-mail: chjsong@zzu.edu.cn; Chang, Junbiao, E-mail: changjunbiao@zzu.edu.cn

    2014-10-15

    In this paper, we have synthesized 9H-pyrrolo[1,2-a]indol-9-ones and the isomeric indeno[2,1-b]pyrrol-8-ones. The interactions of human serum albumin with series of isomeric derivatives have been studied by spectrophotometric methods. Results show the intrinsic fluorescence is quenched by the derivatives with a static quenching procedure. The thermodynamics parameters indicate that van der Waals forces and hydrogen bonds play a major role in the interactions. The results of synchronous fluorescence spectra demonstrate that the microenvironments of Trp residue of human serum albumin are disturbed by most derivatives. Thermodynamic results showed that the 9H-pyrrolo[1,2-a]indol-9-ones are stronger quenchers and bind to human serum albumin with the higher affinity than isomeric indeno[2,1-b]pyrrol-8-ones. The influence of molecular structure on the binding aspects has been investigated. - Highlights: • The interactions between isomeric derivatives and HSA have been investigated. • Results reveal that 9H-pyrrolo[1,2-a]indol-9-ones are stronger quenchers for HSA. • Hydrogen bonds and van der Waals forces play major role in the binding process. • The influence of molecular structure on the binding aspects has been investigated. • The binding study was also modeled by molecular docking.

  6. Assessing the accuracy of satellite-derived urban extent over major urban clusters in the WRF model

    Science.gov (United States)

    Xu, Ronghan; Pan, Zharong; Gao, Hao

    2017-07-01

    Urban land use data play a central role in climate change assessments of urbanization process. The Moderate Resolution Imaging Spectroradiometer (MODIS) land use data is employed in the Weather Research and Forecasting (WRF) model. It is important to understand scaling effects of the MODIS urban data before applying to regional climate modelling. In this study, we took the Landsat derived National Land-Use/Land-Cover Dataset (NLCD) of China as the reference data to assess the accuracy of the MODIS urban map. Urban area sizes and spatial agreement of urban pixels were investigated as assessment methods at the national and metropolitan levels over China. Results showed that the accuracies vary from region to region and highlighted strengths and weaknesses of the MODIS data in different metropolitan area. The study provides insights to model communities with the suitability of the MODIS urban data for specific regional modeling.

  7. Mefloquine and its oxazolidine derivative compound are active against drug-resistant Mycobacterium tuberculosis strains and in a murine model of tuberculosis infection.

    Science.gov (United States)

    Rodrigues-Junior, Valnês S; Villela, Anne D; Gonçalves, Raoni S B; Abbadi, Bruno Lopes; Trindade, Rogério Valim; López-Gavín, Alexandre; Tudó, Griselda; González-Martín, Julian; Basso, Luiz Augusto; de Souza, Marcus V N; Campos, Maria Martha; Santos, Diógenes Santiago

    2016-08-01

    Repurposing of drugs to treat tuberculosis (TB) has been considered an alternative to overcome the global TB epidemic, especially to combat drug-resistant forms of the disease. Mefloquine has been reported as a potent drug to kill drug-resistant strains of Mycobacterium tuberculosis. In addition, mefloquine-derived molecules have been synthesised and their effectiveness against mycobacteria has been assessed. In this work, we demonstrate for the first time the activities of mefloquine and its oxazolidine derivative compound 1E in a murine model of TB infection following administration of both drugs by the oral route. The effects of associations between mefloquine or 1E with the clinically used antituberculosis drugs isoniazid, rifampicin, ethambutol, moxifloxacin and streptomycin were also investigated. Importantly, combination of mefloquine with isoniazid and of 1E with streptomycin showed a two-fold decrease in their minimum inhibitory concentrations (MICs). Moreover, no tested combinations demonstrated antagonist interactions. Here we describe novel evidence on the activity of mefloquine and 1E against a series of quinolone-resistant M. tuberculosis strains. These data show MICs against quinolone-resistant strains (0.5-8 µg/mL) similar to or lower than those previously reported for multidrug-resistant strains. Taking these results together, we can suggest the use of mefloquine or 1E in combination with clinically available drugs, especially in the case of resistant forms of TB. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  8. In Vitro Modeling of Blood-Brain Barrier with Human iPSC-Derived Endothelial Cells, Pericytes, Neurons, and Astrocytes via Notch Signaling

    Directory of Open Access Journals (Sweden)

    Kohei Yamamizu

    2017-03-01

    Full Text Available The blood-brain barrier (BBB is composed of four cell populations, brain endothelial cells (BECs, pericytes, neurons, and astrocytes. Its role is to precisely regulate the microenvironment of the brain through selective substance crossing. Here we generated an in vitro model of the BBB by differentiating human induced pluripotent stem cells (hiPSCs into all four populations. When the four hiPSC-derived populations were co-cultured, endothelial cells (ECs were endowed with features consistent with BECs, including a high expression of nutrient transporters (CAT3, MFSD2A and efflux transporters (ABCA1, BCRP, PGP, MRP5, and strong barrier function based on tight junctions. Neuron-derived Dll1, which activates Notch signaling in ECs, was essential for the BEC specification. We performed in vitro BBB permeability tests and assessed ten clinical drugs by nanoLC-MS/MS, finding a good correlation with the BBB permeability reported in previous cases. This technology should be useful for research on human BBB physiology, pathology, and drug development.

  9. Mesenchymal Stem Cells Engineered to Secrete Pigment Epithelium-Derived Factor Inhibit Tumor Metastasis and the Formation of Malignant Ascites in a Murine Colorectal Peritoneal Carcinomatosis Model.

    Science.gov (United States)

    Yang, Liping; Zhang, Yuwei; Cheng, Liuliu; Yue, Dan; Ma, Jinhu; Zhao, Da; Hou, Xiaoming; Xiang, Rong; Cheng, Ping

    2016-03-01

    The therapeutic effects of conventional treatments for advanced colorectal cancer with colorectal peritoneal carcinomatosis (CRPC) and malignant ascites are not very encouraging. Vascular endothelial growth factor-A/vascular permeability factors (VEGF-A/VPF) play key roles in the formation of malignant ascites. In previous work, we demonstrated that pigment epithelium-derived factor (PEDF) antagonized VEGF-A and could repress tumor growth and suppress metastasis in several cancer types. Thus, PEDF may be a therapeutic candidate for treating malignant ascites. Mesenchymal stem cells (MSCs) are promising tools for delivering therapeutic agents in cancer treatment. In the study, MSCs derived from bone marrow were efficiently engineered to secrete human PEDF by adenoviral transduction. Then, intraperitoneal Ad-PEDF-transduced MSCs were analyzed with respect to CRPC and malignant ascites in a CT26 CRPC model. MSCs engineered to secrete PEDF through adenoviral transduction significantly inhibited tumor metastasis and malignant ascites formation in CT26 CRPC mice. Antitumor mechanisms of MSCs-PEDF (MSCs transduced with Ad-PEDF: MOI 500) were associated with inhibiting tumor angiogenesis, inducing apoptosis, and restoring the VEGF-A/sFLT-1 ratio in ascites. Moreover, MSC-mediated Ad-PEDF delivery reduced production of adenovirus-neutralizing antibodies, prolonged PEDF expression, and induced MSCs-PEDF migration toward tumor cells. As a conclusion, MSCs engineered to secrete PEDF by adenoviral transduction may be a therapeutic approach for suppressing tumor metastasis and inhibiting malignant ascites production in CRPC.

  10. Placental complications after a previous cesarean section

    OpenAIRE

    Milošević Jelena; Lilić Vekoslav; Tasić Marija; Radović-Janošević Dragana; Stefanović Milan; Antić Vladimir

    2009-01-01

    Introduction The incidence of cesarean section has been rising in the past 50 years. With the increased number of cesarean sections, the number of pregnancies with the previous cesarean section rises as well. The aim of this study was to establish the influence of the previous cesarean section on the development of placental complications: placenta previa, placental abruption and placenta accreta, as well as to determine the influence of the number of previous cesarean sections on the complic...

  11. Deriving a light use efficiency model from eddy covariance flux data for predicting daily gross primary production across biomes

    Science.gov (United States)

    Yuan, W.; Liu, S.; Zhou, G.; Tieszen, L.L.; Baldocchi, D.; Bernhofer, C.; Gholz, H.; Goldstein, Allen H.; Goulden, M.L.; Hollinger, D.Y.; Hu, Y.; Law, B.E.; Stoy, Paul C.; Vesala, T.; Wofsy, S.C.

    2007-01-01

    The quantitative simulation of gross primary production (GPP) at various spatial and temporal scales has been a major challenge in quantifying the global carbon cycle. We developed a light use efficiency (LUE) daily GPP model from eddy covariance (EC) measurements. The model, called EC-LUE, is driven by only four variables: normalized difference vegetation index (NDVI), photosynthetically active radiation (PAR), air temperature, and the Bowen ratio of sensible to latent heat flux (used to calculate moisture stress). The EC-LUE model relies on two assumptions: First, that the fraction of absorbed PAR (fPAR) is a linear function of NDVI; Second, that the realized light use efficiency, calculated from a biome-independent invariant potential LUE, is controlled by air temperature or soil moisture, whichever is most limiting. The EC-LUE model was calibrated and validated using 24,349 daily GPP estimates derived from 28 eddy covariance flux towers from the AmeriFlux and EuroFlux networks, covering a variety of forests, grasslands and savannas. The model explained 85% and 77% of the observed variations of daily GPP for all the calibration and validation sites, respectively. A comparison with GPP calculated from the Moderate Resolution Imaging Spectroradiometer (MODIS) indicated that the EC-LUE model predicted GPP that better matched tower data across these sites. The realized LUE was predominantly controlled by moisture conditions throughout the growing season, and controlled by temperature only at the beginning and end of the growing season. The EC-LUE model is an alternative approach that makes it possible to map daily GPP over large areas because (1) the potential LUE is invariant across various land cover types and (2) all driving forces of the model can be derived from remote sensing data or existing climate observation networks.

  12. Cholinesterases inhibition and molecular modeling studies of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones.

    Science.gov (United States)

    Shah, Muhammad Shakil; Khan, Shafi Ullah; Ejaz, Syeda Abida; Afridi, Saifullah; Rizvi, Syed Umar Farooq; Najam-Ul-Haq, Muhammad; Iqbal, Jamshed

    2017-01-22

    Super-activation of cholinesterases (acetylcholinesterase and butyrylcholinesterase) are linked to various neurological problems most precisely Alzheimer's disease (AD), which leads to senile dementia. Therefore, cholinesterases (AChE & BChE) inhibition are considered as a promising strategy for the treatment of Alzheimer's disease. FDA approved drugs for the treatment of AD, belong to a group of cholinesterase inhibitors. However, none of them is able to combat or completely abrogate the disease progression. Herein, we report a series of newly synthesized chalcone derivatives with anti-AD potential. For this purpose, a series of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones were tested for their cholinesterases (AChE & BChE) inhibitory activity. All compounds were found as selective inhibitor of AChE. In piperidyl chalcones derivatives compound 1e having IC 50 of 0.16 ± 0.008 μM and 2m in 2-pyrazoline chalcones with IC 50 of 0.13 ± 0.006 μM, were found to be the most potent inhibitors of AChE, exhibiting ≈142 and ≈ 173-fold greater inhibitory potential compared to the reference inhibitor i.e., Neostigmine (IC 50  ± SEM = 22.2 ± 3.2 μM). Molecular docking studies of most potent inhibitors were carried out to investigate the binding interactions inside the active site. Molecular docking study revealed that potent compounds and co-crystalized ligand had same binding orientation within the active site of target enzyme. Most of these compounds are selective inhibitors of AChE with a potential use against progressive neurodegenerative disorder and age related problems. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Coronary CT Angiography-derived Fractional Flow Reserve: Machine Learning Algorithm versus Computational Fluid Dynamics Modeling.

    Science.gov (United States)

    Tesche, Christian; De Cecco, Carlo N; Baumann, Stefan; Renker, Matthias; McLaurin, Tindal W; Duguay, Taylor M; Bayer, Richard R; Steinberg, Daniel H; Grant, Katharine L; Canstein, Christian; Schwemmer, Chris; Schoebinger, Max; Itu, Lucian M; Rapaka, Saikiran; Sharma, Puneet; Schoepf, U Joseph

    2018-04-10

    Purpose To compare two technical approaches for determination of coronary computed tomography (CT) angiography-derived fractional flow reserve (FFR)-FFR derived from coronary CT angiography based on computational fluid dynamics (hereafter, FFR CFD ) and FFR derived from coronary CT angiography based on machine learning algorithm (hereafter, FFR ML )-against coronary CT angiography and quantitative coronary angiography (QCA). Materials and Methods A total of 85 patients (mean age, 62 years ± 11 [standard deviation]; 62% men) who had undergone coronary CT angiography followed by invasive FFR were included in this single-center retrospective study. FFR values were derived on-site from coronary CT angiography data sets by using both FFR CFD and FFR ML . The performance of both techniques for detecting lesion-specific ischemia was compared against visual stenosis grading at coronary CT angiography, QCA, and invasive FFR as the reference standard. Results On a per-lesion and per-patient level, FFR ML showed a sensitivity of 79% and 90% and a specificity of 94% and 95%, respectively, for detecting lesion-specific ischemia. Meanwhile, FFR CFD resulted in a sensitivity of 79% and 89% and a specificity of 93% and 93%, respectively, on a per-lesion and per-patient basis (P = .86 and P = .92). On a per-lesion level, the area under the receiver operating characteristics curve (AUC) of 0.89 for FFR ML and 0.89 for FFR CFD showed significantly higher discriminatory power for detecting lesion-specific ischemia compared with that of coronary CT angiography (AUC, 0.61) and QCA (AUC, 0.69) (all P < .0001). Also, on a per-patient level, FFR ML (AUC, 0.91) and FFR CFD (AUC, 0.91) performed significantly better than did coronary CT angiography (AUC, 0.65) and QCA (AUC, 0.68) (all P < .0001). Processing time for FFR ML was significantly shorter compared with that of FFR CFD (40.5 minutes ± 6.3 vs 43.4 minutes ± 7.1; P = .042). Conclusion The FFR ML algorithm performs equally in

  14. Considerations for pre-clinical models and clinical trials of pluripotent stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Hulot, Jean-Sébastien; Stillitano, Francesca; Salem, Joe Elie; Kovacic, Jason C; Fuster, Valentin; Hajjar, Roger J

    2014-01-09

    Pluripotent stem cells (PSCs) represent an appealing source from which to develop cell replacement therapies. Different initiatives have been launched to promote their development toward clinical applications. This article will review the main questions that should be considered before translating PSC-derived cardiomyocytes into clinical investigations, including the development of good manufacturing practice-level PSC lines, the development of efficient protocols to generate pure populations of cardiac myocytes, and the development of techniques to improve the retention and survival rate of transplanted cells.

  15. Incorporation of poly-saccharidic derivatives in model biological systems: monolayers, lamellar phases and vesicles

    International Nuclear Information System (INIS)

    Deme, Bruno

    1995-01-01

    Our aim is to introduce a soluble polymer in a lyotropic lamellar phase, and to modify the force balance in the case of a collapsed system where no repulsive contribution overcomes the van der Waals attraction, except at very short distances where hydration forces dominate (i.e. a collapsed stack of membranes). Mixed layers of a synthetic lecithin (DMPC) and a hydrophobically modified polysaccharide (cholesteryl-pullulan, CHP) have been investigated at the air-water interface by surface tension experiments and by specular reflection of neutrons. The DMPC/CHP/water ternary phase diagram has been determined by small angle X-ray scattering (SAXS) and small angle neutron scattering (SANS). CHP derivatives are associative polymers bearing lateral cholesterol groups that interact with a polar phases such as phospholipid monolayers and biological membranes. These derivatives are surface active and self-aggregate in solution leading to the formation of soluble micellar type aggregates. The interaction of CHP derivatives with lipidic structures involves the anchoring of the cholesterol groups that yields to the tethering of the poly-saccharidic backbones at lipid/water interfaces. These poly-saccharidic backbones are flexible chains in good solvent in water. Using these derivatives and a new preparation procedure, we show that it is possible to avoid the depletion of the polysaccharide due to its steric exclusion by the collapsed DMPC lamellar phase. We are able to prepare samples at thermodynamic equilibrium with the polysaccharide solubilized in the lamellar phase, a situation opposed to the well known behavior of mixed polysaccharide/lecithin Systems commonly used in osmotic stress experiments. Here, the osmotic pressure of the chains confined in the lamellar lattice acts as a new long range repulsive contribution in the DMPC lyotropic L α phase and results in the swelling of the lamellar phase at large membrane separations (570 A). Such bilayer separations allow out of

  16. No-ghost theorem for the fourth-order derivative Pais-Uhlenbeck oscillator model.

    Science.gov (United States)

    Bender, Carl M; Mannheim, Philip D

    2008-03-21

    A new realization of the fourth-order derivative Pais-Uhlenbeck oscillator is constructed. This realization possesses no states of negative norm and has a real energy spectrum that is bounded below. The key to this construction is the recognition that in this realization the Hamiltonian is not Dirac Hermitian. However, the Hamiltonian is symmetric under combined space reflection P and time reversal T. The Hilbert space that is appropriate for this PT-symmetric Hamiltonian is identified and it is found to have a positive-definite inner product. Furthermore, the time-evolution operator is unitary.

  17. DESIGN OF LOW CYTOTOXICITY DIARYLANILINE DERIVATIVES BASED ON QSAR RESULTS: AN APPLICATION OF ARTIFICIAL NEURAL NETWORK MODELLING

    Directory of Open Access Journals (Sweden)

    Ihsanul Arief

    2016-11-01

    Full Text Available Study on cytotoxicity of diarylaniline derivatives by using quantitative structure-activity relationship (QSAR has been done. The structures and cytotoxicities of  diarylaniline derivatives were obtained from the literature. Calculation of molecular and electronic parameters was conducted using Austin Model 1 (AM1, Parameterized Model 3 (PM3, Hartree-Fock (HF, and density functional theory (DFT methods.  Artificial neural networks (ANN analysis used to produce the best equation with configuration of input data-hidden node-output data = 5-8-1, value of r2 = 0.913; PRESS = 0.069. The best equation used to design and predict new diarylaniline derivatives.  The result shows that compound N1-(4′-Cyanophenyl-5-(4″-cyanovinyl-2″,6″-dimethyl-phenoxy-4-dimethylether benzene-1,2-diamine is the best-proposed compound with cytotoxicity value (CC50 of 93.037 μM.

  18. Functional integration of grafted neural stem cell-derived dopaminergic neurons monitored by optogenetics in an in vitro Parkinson model.

    Directory of Open Access Journals (Sweden)

    Jan Tønnesen

    Full Text Available Intrastriatal grafts of stem cell-derived dopamine (DA neurons induce behavioral recovery in animal models of Parkinson's disease (PD, but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D₂ autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation or inhibition of grafted cells and host neurons using channelrhodopsin-2 (ChR2 and halorhodopsin (NpHR, respectively, revealed complex, bi-directional synaptic interactions between grafted cells and host neurons and extensive synaptic connectivity within the graft. Our data demonstrate for the first time using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying behavioral recovery as well as adverse effects following stem cell-based DA cell replacement strategies in PD.

  19. Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models

    Directory of Open Access Journals (Sweden)

    Wu Xianhua

    2012-08-01

    Full Text Available Abstract Background Trastuzumab is currently approved for the clinical treatment of breast and gastric cancer patients with HER-2 positive tumors, but not yet for the treatment of esophageal carcinoma patients, whose tumors typically show 5 ~ 35% HER-2 gene amplification and 0 ~ 56% HER-2 protein expression. This study aimed to investigate the therapeutic efficacy of Trastuzumab in patient-derived esophageal squamous cell carcinoma xenograft (PDECX mouse models. Methods PDECX models were established by implanting patient esophageal squamous cell carcinoma (ESCC tissues into immunodeficient (SCID/nude mice. HER-2 gene copy number (GCN and protein expression were determined in xenograft tissues and corresponding patient EC samples by FISH and IHC analysis. Trastuzumab anti-tumor efficacy was evaluated within these PDECX models (n = 8 animals/group. Furthermore, hotspot mutations of EGFR, K-ras, B-raf and PIK3CA genes were screened for in the PDECX models and their corresponding patient’s ESCC tissues. Similarity between the PDECX models and their corresponding patient’s ESCC tissue was confirmed by histology, morphology, HER-2 GCN and mutation. Results None of the PDECX models (or their corresponding patient’s ESCC tissues harbored HER-2 gene amplification. IHC staining showed HER-2 positivity (IHC 2+ in 2 PDECX models and negativity in 3 PDECX models. Significant tumor regression was observed in the Trastuzumab-treated EC044 HER-2 positive model (IHC 2+. A second HER-2 positive (IHC 2+ model, EC039, harbored a known PIK3CA mutation and showed strong activation of the AKT signaling pathway and was insensitive to Trastuzumab treatment, but could be resensitised using a combination of Trastuzumab and AKT inhibitor AZD5363. In summary, we established 5 PDECX mouse models and demonstrated tumor regression in response to Trastuzumab treatment in a HER-2 IHC 2+ model, but resistance in a HER-2 IHC 2+/PIK3CA mutated model. Conclusions

  20. A modified simple dynamic model: Derived from the information embedded in observed streamflows

    Science.gov (United States)

    Li, Wei; Nieber, John L.

    2017-09-01

    A zero-dimension hydrological model has been developed to simulate the discharge (Q) from watershed groundwater storage(S). The model is a modified version of the original model developed by Kirchner in 2009 which uses a unique sensitivity function, g (Q) to represent the relation between rate of flow recession and the instantaneous flow rate. The modified dynamic model instead uses a normalized sensitivity function g (Qnorm) which provides the model the flexibility to encompass the hysteretic effect of initial water storage on flow during recession periods. The sensitivity function is normalized based on a correlation function F (Q) which implicitly quantifies the influence of initial storage conditions on recession flow dynamics. For periods of either positive or negative net recharge to groundwater the model applies a term similar in form to an analytical solution based on solution to the linearized Boussinesq equation. The combination of these two streamflow components, the recession component and the net recharge response, provides the model with the flexibility to realistically mimic the hysteresis in the Q vs. S relations for a watershed. The model is applied to the Sagehen Creek watershed, a hilly watershed located in the Sierra Mountains of California. The results show that the modified model has an improved performance to simulate the discharge dynamic encompassing a wide range of water storage (degree of wetness) representing an almost ten-fold variation in annual streamflow.

  1. Markov Modeling of Component Fault Growth Over A Derived Domain of Feasible Output Control Effort Modifications

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper introduces a novel Markov process formulation of stochastic fault growth modeling, in order to facilitate the development and analysis of...

  2. Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha

    Directory of Open Access Journals (Sweden)

    Muchtaridi Muchtaridi

    2017-10-01

    Full Text Available Tamoxifen is the most frequently used anti-estrogen adjuvant treatment for estrogen receptor-positive breast cancer. However, it is associated with an increased risk of several serious side–effects, such as uterine cancer, stroke, and pulmonary embolism. The 2′,4′-dihydroxy-6-methoxy-3,5-dimethylchalcone (ChalcEA from plant leaves of Eugenia aquea, has been found to inhibit the proliferation of MCF-7 human breast cancer cells in a dose-dependent manner, with an IC50 of 74.5 μg/mL (250 μM. The aim of this work was to study the molecular interactions of new ChalcEA derivatives formed with the Estrogen Receptor α (ERα using computer aided drug design approaches. Molecular docking using Autodock 4.2 was employed to explore the modes of binding of ChalcEA derivatives with ERα. The 3D structure-based pharmacophore model was derived using LigandScout 4.1 Advanced to investigate the important chemical interactions of the ERα-tamoxifen complex structure. The binding energy and the tamoxifen-pharmacophore fit score of the best ChalcEA derivative (HNS10 were −12.33 kcal/mol and 67.07 kcal/mol, respectively. The HNS10 interacted with Leu346, Thr347, Leu349, Ala350, Glu353, Leu387, Met388, Leu391, Arg394, Met421, and Leu525. These results suggest that the new ChalcEA derivatives could serve as the lead compound for potent ERα inhibitor in the fight against breast cancer.

  3. Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha.

    Science.gov (United States)

    Muchtaridi, Muchtaridi; Syahidah, Hasna Nur; Subarnas, Anas; Yusuf, Muhammad; Bryant, Sharon D; Langer, Thierry

    2017-10-16

    Tamoxifen is the most frequently used anti-estrogen adjuvant treatment for estrogen receptor-positive breast cancer. However, it is associated with an increased risk of several serious side-effects, such as uterine cancer, stroke, and pulmonary embolism. The 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone (ChalcEA) from plant leaves of Eugenia aquea , has been found to inhibit the proliferation of MCF-7 human breast cancer cells in a dose-dependent manner, with an IC 50 of 74.5 μg/mL (250 μM). The aim of this work was to study the molecular interactions of new ChalcEA derivatives formed with the Estrogen Receptor α (ERα) using computer aided drug design approaches. Molecular docking using Autodock 4.2 was employed to explore the modes of binding of ChalcEA derivatives with ERα. The 3D structure-based pharmacophore model was derived using LigandScout 4.1 Advanced to investigate the important chemical interactions of the ERα-tamoxifen complex structure. The binding energy and the tamoxifen-pharmacophore fit score of the best ChalcEA derivative (HNS10) were -12.33 kcal/mol and 67.07 kcal/mol, respectively. The HNS10 interacted with Leu346, Thr347, Leu349, Ala350, Glu353, Leu387, Met388, Leu391, Arg394, Met421, and Leu525. These results suggest that the new ChalcEA derivatives could serve as the lead compound for potent ERα inhibitor in the fight against breast cancer.

  4. Derivation of the expressions for γ50 and D50 for different individual TCP and NTCP models

    International Nuclear Information System (INIS)

    Stavreva, N.; Stavrev, P.; Warkentin, B.; Fallone, B.G.

    2002-01-01

    This paper presents a complete set of formulae for the position (D 50 ) and the normalized slope (γ 50 ) of the dose-response relationship based on the most commonly used radiobiological models for tumours as well as for normal tissues. The functional subunit response models (critical element and critical volume) are used in the derivation of the formulae for the normal tissue. Binomial statistics are used to describe the tumour control probability, the functional subunit response as well as the normal tissue complication probability. The formulae are derived for the single hit and linear quadratic models of cell kill in terms of the number of fractions and dose per fraction. It is shown that the functional subunit models predict very steep, almost step-like, normal tissue individual dose-response relationships. Furthermore, the formulae for the normalized gradient depend on the cellular parameters α and β when written in terms of number of fractions, but not when written in terms of dose per fraction. (author)

  5. Recent Developments of Hydrazide/Hydrazone Derivatives and Their Analogs as Anticonvulsant Agents in Animal Models.

    Science.g