[Ideas and methods of two-dimensional zebrafish model combined with chromatographic techniques in high-throughput screening of active anti-osteoporosis components of traditional Chinese medicines].

Science.gov (United States)

Wei, Ying-Jie; Jing, Li-Jun; Zhan, Yang; Sun, E; Jia, Xiao-Bin

2014-05-01

To break through the restrictions of the evaluation model and the quantity of compounds by using the two-dimensional zebrafish model combined with chromatographic techniques, and establish a new method for the high-throughput screening of active anti-osteoporosis components. According to the research group-related studies and relevant foreign literatures, on the basis of the fact that the zebrafish osteoporosis model could efficiently evaluate the activity, the zebrafish metabolism model could efficiently enrich metabolites and the chromatographic techniques could efficiently separate and analyze components of traditional Chinese medicines, we proposed that the inherent combination of the three methods is expected to efficiently decode in vivo and in vitro efficacious anti-osteoporosis materials of traditional Chinese medicines. The method makes it simple and efficient in the enrichment, separation and analysis on components of traditional Chinese medicines, particularly micro-components and metabolites and the screening anti-osteoporosis activity, fully reflects that efficacious materials of traditional Chinese medicines contain original components and metabolites, with characteristic of "multi-components, multi-targets and integral effect", which provides new ideas and methods for the early and rapid discovery of active anti-osteoporosis components of traditional Chinese medicines.

Activity of levofloxacin in combination with colistin against Acinetobacter baumannii: In vitro and in a Galleria mellonella model.

Science.gov (United States)

Wei, Wenjuan; Yang, Haifei; Hu, Lifen; Ye, Ying; Li, Jiabin

2017-12-01

Treatment of Acinetobacter baumannii infections is challenging owing to widespread multidrug-resistant A. baumannii (MDR-AB) and the lack of novel agents. Although recent data suggest that levofloxacin (LVX) may have unique activity against MDR-AB in combination with colistin (CST), further preclinical work is needed. We used a A. baumannii type strain ATCC19606, a CST-resistant strain AB19606R, and two clinical isolates (GN0624 and GN1115) of MDR-AB to investigate the in vitro and in vivo efficacy of LVX-CST combination. Synergy studies were performed using the microtiter plate chequerboard assay and time-kill methodology. Inhibitory activity of antibiotics against biofilms and the mutant prevention concentrations were also studied in vitro. A simple invertebrate model (Galleria mellonella) has been used to assess the in vivo activity of antimicrobial therapies. The LVX-CST combination was bactericidal against the CST-susceptible clinical isolate (GN0624). In checkerboard assays, synergy (defined as a fractional inhibitory concentration index of baumanni. Treatment of G. mellonella larvae infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when LVX was given with CST compared with CST treatment alone (p < 0.05). In summary, a synergistic or additive effect between CST and LVX was observed in vitro and in vivo against CST-susceptible A. baumannii strains, although not against CST-resistant ones. Copyright © 2015. Published by Elsevier B.V.

A combined system for measuring animal motion activities.

Science.gov (United States)

Young, M S; Young, C W; Li, Y C

2000-01-31

In this study, we have developed a combined animal motion activity measurement system that combines an infrared light matrix subsystem with an ultrasonic phase shift subsystem for animal activity measurement. Accordingly, in conjunction with an IBM PC/AT compatible personal computer, the combined system has the advantages of both infrared and ultrasonic subsystems. That is, it can at once measure and directly analyze detailed changes in animal activity ranging from locomotion to tremor. The main advantages of this combined system are that it features real time data acquisition with the option of animated real time or recorded display/playback of the animal's motion. Additionally, under the multi-task operating condition of IBM PC, it can acquire and process behavior using both IR and ultrasound systems simultaneously. Traditional systems have had to make separate runs for gross and fine movement recording. This combined system can be profitably employed for normative behavioral activity studies and for neurological and pharmacological research.

Multi-day activity scheduling reactions to planned activities and future events in a dynamic agent-based model of activity-travel behavior

NARCIS (Netherlands)

Nijland, E.W.L.; Arentze, T.A.; Timmermans, H.J.P.

2009-01-01

Modeling multi-day planning has received scarce attention today in activity-based transport demand modeling. Elaborating and combining previous work on event-driven activity generation, the aim of this paper is to develop and illustrate an extension of a need-based model of activity generation that

Fire, Climate, and Human Activity: A Combustive Combination

Science.gov (United States)

Kehrwald, N. M.; Battistel, D.; Argiriadis, E.; Barbante, C.; Barber, L. B.; Fortner, S. K.; Jasmann, J.; Kirchgeorg, T.; Zennaro, P.

2017-12-01

Ice and lake core records demonstrate that fires caused by human activity can dominate regional biomass burning records in the Common Era. These major increases in fires are often associated with extensive land use change such as an expansion in agriculture. Regions with few humans, relatively stable human populations and/or unvarying land use often have fire histories that are dominated by climate parameters such as temperature and precipitation. Here, we examine biomass burning recorded in ice cores from northern Greenland (NEEM, (77°27'N; 51°3.6'W), Alaska (Juneau Icefield, 58° 35' N; 134° 29'W) and East Antarctica (EPICA DOME C; 75°06'S; 123°21'E), along with New Zealand lake cores to investigate interactions between climate, fire and human activity. Biomarkers such as levoglucosan, and its isomers mannosan and galactosan, can only be produced by cellulose combustion and therefore are specific indicators of past fire activity archived in ice and lake cores. These fire histories add another factor to climate proxies from the same core, and provide a comparison to regional fire syntheses from charcoal records and climate models. For example, fire data from the JSBACH-Spitfire model for the past 2000 years demonstrates that a climate-only scenario would not increase biomass burning in high northern latitudes for the past 2000 years, while NEEM ice core and regional pollen records demonstrate both increased fire activity and land use change that may be ascribed to human activity. Additional biomarkers such as fecal sterols in lake sediments can determine when people were in an area, and can help establish if an increased human presence in an area corresponds with intensified fire activity. This combination of specific biomarkers, other proxy data, and model output can help determine the relative impact of humans versus climate factors on regional fire activity.

Using Active Learning for Speeding up Calibration in Simulation Models.

Science.gov (United States)

Cevik, Mucahit; Ergun, Mehmet Ali; Stout, Natasha K; Trentham-Dietz, Amy; Craven, Mark; Alagoz, Oguzhan

2016-07-01

Most cancer simulation models include unobservable parameters that determine disease onset and tumor growth. These parameters play an important role in matching key outcomes such as cancer incidence and mortality, and their values are typically estimated via a lengthy calibration procedure, which involves evaluating a large number of combinations of parameter values via simulation. The objective of this study is to demonstrate how machine learning approaches can be used to accelerate the calibration process by reducing the number of parameter combinations that are actually evaluated. Active learning is a popular machine learning method that enables a learning algorithm such as artificial neural networks to interactively choose which parameter combinations to evaluate. We developed an active learning algorithm to expedite the calibration process. Our algorithm determines the parameter combinations that are more likely to produce desired outputs and therefore reduces the number of simulation runs performed during calibration. We demonstrate our method using the previously developed University of Wisconsin breast cancer simulation model (UWBCS). In a recent study, calibration of the UWBCS required the evaluation of 378 000 input parameter combinations to build a race-specific model, and only 69 of these combinations produced results that closely matched observed data. By using the active learning algorithm in conjunction with standard calibration methods, we identify all 69 parameter combinations by evaluating only 5620 of the 378 000 combinations. Machine learning methods hold potential in guiding model developers in the selection of more promising parameter combinations and hence speeding up the calibration process. Applying our machine learning algorithm to one model shows that evaluating only 1.49% of all parameter combinations would be sufficient for the calibration. © The Author(s) 2015.

Combined active-passive immunisation of horses against tetanus.

Science.gov (United States)

Liefman, C E

1980-03-01

The protection afforded by active, passive and combined active-passive methods of immunisation against tetanus was examined in previously unimmunised horses. Three groups of horses were injected; one with tetanus toxoid alone, one with tetanus antitoxin alone and one in which the tetanus toxoid and tetanus antitoxin were injected simultaneously. The protection afforded was determined by monitoring the levels of antitoxin achieved in the horses by each of these methods. The results obtained demonstrated the effectiveness of the combined active-passive method in affording rapid and prolonged protection and enabled the examination of some of the factors involved in active and in passive immunisation when used alone. The advantages obtained by the use of the combined active-passive method in protecting unimmunised horses suddenly placed at risk to infection are outlined.

Capstone Teaching Models: Combining Simulation, Analytical Intuitive Learning Processes, History and Effectiveness

Science.gov (United States)

Reid, Maurice; Brown, Steve; Tabibzadeh, Kambiz

2012-01-01

For the past decade teaching models have been changing, reflecting the dynamics, complexities, and uncertainties of today's organizations. The traditional and the more current active models of learning have disadvantages. Simulation provides a platform to combine the best aspects of both types of teaching practices. This research explores the…

Evaluation of analgesic and anti-inflammatory activity of a combination of tramadol-ibuprofen in experimental animals.

Science.gov (United States)

Suthakaran, Chidambarann; Kayalvizhi, Muniyagounder K; Nithya, Karnam; Raja, Thozhudalangudy Ar

2017-01-01

Pain is the major concern of patients attending dental clinics, and satisfactory pain relief has always been difficult to achieve. Since the pathophysiology of pain is a complex, central and peripheral nervous system process, combined analgesic regimens with different mechanisms of action as a multimodal approach are becoming popular among the clinicians and dentists. The aim of the present study was to evaluate the analgesic and anti-inflammatory activity of ibuprofen and tramadol when used alone or in combination in animal models of pain and inflammation. The animals were divided into six groups with six animals in each group. Analgesic activity was assessed by hot plate method in rats and by acetic acid-induced writhing test in mice. Paw edema model in rats after induction with 0.1 mL of 1% carrageenan was used to assess the anti-inflammatory activity. Analysis of variance followed by Tukey's honestly significant difference post hoc test was used for statistical analysis. Combined use of tramadol and ibuprofen provided enhanced analgesic and anti-inflammatory effects in animal models of pain and inflammation.

Comparing droplet activation parameterisations against adiabatic parcel models using a novel inverse modelling framework

Science.gov (United States)

Partridge, Daniel; Morales, Ricardo; Stier, Philip

2015-04-01

Many previous studies have compared droplet activation parameterisations against adiabatic parcel models (e.g. Ghan et al., 2001). However, these have often involved comparisons for a limited number of parameter combinations based upon certain aerosol regimes. Recent studies (Morales et al., 2014) have used wider ranges when evaluating their parameterisations, however, no study has explored the full possible multi-dimensional parameter space that would be experienced by droplet activations within a global climate model (GCM). It is important to be able to efficiently highlight regions of the entire multi-dimensional parameter space in which we can expect the largest discrepancy between parameterisation and cloud parcel models in order to ascertain which regions simulated by a GCM can be expected to be a less accurate representation of the process of cloud droplet activation. This study provides a new, efficient, inverse modelling framework for comparing droplet activation parameterisations to more complex cloud parcel models. To achieve this we couple a Markov Chain Monte Carlo algorithm (Partridge et al., 2012) to two independent adiabatic cloud parcel models and four droplet activation parameterisations. This framework is computationally faster than employing a brute force Monte Carlo simulation, and allows us to transparently highlight which parameterisation provides the closest representation across all aerosol physiochemical and meteorological environments. The parameterisations are demonstrated to perform well for a large proportion of possible parameter combinations, however, for certain key parameters; most notably the vertical velocity and accumulation mode aerosol concentration, large discrepancies are highlighted. These discrepancies correspond for parameter combinations that result in very high/low simulated values of maximum supersaturation. By identifying parameter interactions or regimes within the multi-dimensional parameter space we hope to guide

Evaluation of analgesic and anti-inflammatory activity of a combination of tramadol-ibuprofen in experimental animals

Directory of Open Access Journals (Sweden)

Chidambarann Suthakaran

2017-01-01

Full Text Available Background: Pain is the major concern of patients attending dental clinics, and satisfactory pain relief has always been difficult to achieve. Since the pathophysiology of pain is a complex, central and peripheral nervous system process, combined analgesic regimens with different mechanisms of action as a multimodal approach are becoming popular among the clinicians and dentists. Objectives: The aim of the present study was to evaluate the analgesic and anti-inflammatory activity of ibuprofen and tramadol when used alone or in combination in animal models of pain and inflammation. Animals and Methods: The animals were divided into six groups with six animals in each group. Analgesic activity was assessed by hot plate method in rats and by acetic acid-induced writhing test in mice. Paw edema model in rats after induction with 0.1 mL of 1% carrageenan was used to assess the anti-inflammatory activity. Statistical Analysis: Analysis of variance followed by Tukey's honestly significant difference post hoc test was used for statistical analysis. Results and Conclusion: Combined use of tramadol and ibuprofen provided enhanced analgesic and anti-inflammatory effects in animal models of pain and inflammation.

Design strategy for the combined system of shunt passive and series active filters

OpenAIRE

Fujita, Hideki; Akagi, Hirofumi

1991-01-01

A design strategy for the combined power filter for a three-phase twelve-pulse thyristor rectifier is proposed. The shunt passive filter, which can minimize the output voltage of the series active filter, is designed and tested in a prototype model. A specially designed shunt passive filter makes it possible to reduce the required rating of the series active filter to 60% compared with a conventional shunt passive filter

QSAR modelling using combined simple competitive learning networks and RBF neural networks.

Science.gov (United States)

Sheikhpour, R; Sarram, M A; Rezaeian, M; Sheikhpour, E

2018-04-01

The aim of this study was to propose a QSAR modelling approach based on the combination of simple competitive learning (SCL) networks with radial basis function (RBF) neural networks for predicting the biological activity of chemical compounds. The proposed QSAR method consisted of two phases. In the first phase, an SCL network was applied to determine the centres of an RBF neural network. In the second phase, the RBF neural network was used to predict the biological activity of various phenols and Rho kinase (ROCK) inhibitors. The predictive ability of the proposed QSAR models was evaluated and compared with other QSAR models using external validation. The results of this study showed that the proposed QSAR modelling approach leads to better performances than other models in predicting the biological activity of chemical compounds. This indicated the efficiency of simple competitive learning networks in determining the centres of RBF neural networks.

Novel qsar combination forecast model for insect repellent coupling support vector regression and k-nearest-neighbor

International Nuclear Information System (INIS)

Wang, L.F.; Bai, L.Y.

2013-01-01

To improve the precision of quantitative structure-activity relationship (QSAR) modeling for aromatic carboxylic acid derivatives insect repellent, a novel nonlinear combination forecast model was proposed integrating support vector regression (SVR) and K-nearest neighbor (KNN): Firstly, search optimal kernel function and nonlinearly select molecular descriptors by the rule of minimum MSE value using SVR. Secondly, illuminate the effects of all descriptors on biological activity by multi-round enforcement resistance-selection. Thirdly, construct the sub-models with predicted values of different KNN. Then, get the optimal kernel and corresponding retained sub-models through subtle selection. Finally, make prediction with leave-one-out (LOO) method in the basis of reserved sub-models. Compared with previous widely used models, our work shows significant improvement in modeling performance, which demonstrates the superiority of the present combination forecast model. (author)

Antitumor Efficacy of Dual Blockade of EGFR Signaling by Osimertinib in Combination With Selumetinib or Cetuximab in Activated EGFR Human NCLC Tumor Models.

Science.gov (United States)

Della Corte, Carminia Maria; Ciaramella, Vincenza; Cardone, Claudia; La Monica, Silvia; Alfieri, Roberta; Petronini, Pier Giorgio; Malapelle, Umberto; Vigliar, Elena; Pepe, Francesco; Troncone, Giancarlo; Castellone, Maria Domenica; Troiani, Teresa; Martinelli, Erika; Ciardiello, Fortunato; Morgillo, Floriana

2018-03-08

Osimertinib showed great clinical efficacy for activated-EGFR NCLC patient treatment. The aim of this work was to test the efficacy of a complete EGFR-inhibition by osimertinib plus the monoclonal antibody cetuximab or the MEK1/2-inhibitor selumetinib in EGFR-mutated NCLC in vivo models. We evaluated combinations of osimertinib plus selumetinib/cetuximab in HCC827 (E746-A759del/T790M-), H1975 (L858R/T790M+), and PC9-T790M (E746-A759del /T790M+) xenografts in second-line therapy after the development of resistance to osimertinib, and in first-line therapy, and we explored mechanisms of resistance to these treatments. The addition of selumetinib or cetuximab to osimertinib in second-line therapy reverted the sensibility to osimertinib in the majority of mice, with a response rate (RR) of 50% to 80%, and a median progression-free survival (mPFS) of first- plus second-line of therapy of 28 weeks. The early use of combinations in first-line therapy increased the RR to 90%, with an mPFS not reached in all combination arms in the three xenografts models, with a statistically significant superiority (p < 0.005) as compared to osimertinib, achieving in first-line therapy an mPFS time of 17 to 18 weeks. Moreover, in ex vivo primary cell cultures obtained from osimertinib plus selumetinib-resistant tumors, we found Hedgehog pathway activation and we showed that therapy with an SMO inhibitor plus osimertinib and selumetinib inhibited proliferation and migratory and invasive properties of resistant cells. We showed that a dual vertical EGFR blockade with osimertinib plus selumetinib/cetuximab is a novel effective therapeutic option in EGFR-mutated NCLC and that hedgehog pathway activation and its interplay with MAPK is involved in resistance to these combination treatments. Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Seepage characteristics of the second tertiary combined model

Directory of Open Access Journals (Sweden)

Huan ZHAO

2015-08-01

Full Text Available The second tertiary combined model experiment zone has been developed in Block B, Field L. The percolation feature of the second tertiary combined develop model shows great importance to rational and efficient development of the reservoir. In order to clearly illuminate its percolation feature, the typical reservoir numerical model is built by Eclipse, which is a reservoir numerical simulation software. The percolation features of original and added perforation interval under the second tertiary combined model are studied, and the variation features of general water-cut, recovery percentage, wellbore pressure, reservoir pressure and water saturation on condition of higher injection rate under the second tertiary combined model are analyzed. The research indicates that the second tertiary combined enhances the recovery of remaining oil on top of thick reservoir by developing and enhancing original perforation interval under water drive, then improves development results by polymer flooding, and gains higher recovery rate by synthetic action of water driver and polymer flooding.

Human Activity-Understanding: A Multilayer Approach Combining Body Movements and Contextual Descriptors Analysis

Directory of Open Access Journals (Sweden)

Consuelo Granata

2015-07-01

Full Text Available A deep understanding of human activity is key to successful human-robot interaction (HRI. The translation of sensed human behavioural signals/cues and context descriptors into an encoded human activity remains a challenge because of the complex nature of human actions. In this paper, we propose a multilayer framework for the understanding of human activity to be implemented in a mobile robot. It consists of a perception layer which exploits a D-RGB-based skeleton tracking output used to simulate a physical model of virtual human dynamics in order to compensate for the inaccuracy and inconsistency of the raw data. A multi-support vector machine (MSVM model trained with features describing the human motor coordination through temporal segments in combination with environment descriptors (object affordance is used to recognize each sub-activity (classification layer. The interpretation of sequences of classified elementary actions is based on discrete hidden Markov models (DHMMs (interpretation layer. The framework assessment was performed on the Cornell Activity Dataset (CAD-120 [1]. The performances of our method are comparable with those presented in [2] and clearly show the relevance of this model-based approach.

A rat model of concurrent combined injuries (polytrauma)

Science.gov (United States)

Akscyn, Robert M; Franklin, J Lee; Gavrikova, Tatyana A; Schwacha, Martin G; Messina, Joseph L

2015-01-01

Polytrauma, a combination of injuries to more than one body part or organ system, is common in modern warfare and in automobile and industrial accidents. The combination of injuries can include burn injury, fracture, hemorrhage, trauma to the extremities, and trauma to specific organ systems. To investigate the effects of combined injuries, we have developed a new and highly reproducible model of polytrauma. This model combines burn injury with soft tissue and gastrointestinal (GI) tract trauma. Male Sprague Dawley rats were subjected to a 15-20% total body surface area scald burn, or a single puncture of the cecum with a G30 needle, or the combination of both injuries (polytrauma). Unlike many ‘double hit’ models, the injuries in our model were performed simultaneously. We asked whether multiple minor injuries, when combined, would result in a distinct phenotype, different from single minor injuries or a more severe single injury. There were differences between the single injuries and polytrauma in the maintenance of blood glucose, body temperature, body weight, hepatic mRNA and circulating levels of TNF-α, IL-1β and IL-6, and hepatic ER-stress. It has been suggested that models utilizing combinatorial injuries may be needed to more accurately model the human condition. We believe our model is ideal for studying the complex sequelae of polytrauma, which differs from single injuries. Insights gained from this model may suggest better treatment options to improve patient outcomes. PMID:26884923

Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.

Science.gov (United States)

Vilas-Zornoza, A; Agirre, X; Abizanda, G; Moreno, C; Segura, V; De Martino Rodriguez, A; José-Eneriz, E S; Miranda, E; Martín-Subero, J I; Garate, L; Blanco-Prieto, M J; García de Jalón, J A; Rio, P; Rifón, J; Cigudosa, J C; Martinez-Climent, J A; Román-Gómez, J; Calasanz, M J; Ribera, J M; Prósper, F

2012-07-01

Histone deacetylases (HDACs) have been identified as therapeutic targets due to their regulatory function in chromatin structure and organization. Here, we analyzed the therapeutic effect of LBH589, a class I-II HDAC inhibitor, in acute lymphoblastic leukemia (ALL). In vitro, LBH589 induced dose-dependent antiproliferative and apoptotic effects, which were associated with increased H3 and H4 histone acetylation. Intravenous administration of LBH589 in immunodeficient BALB/c-RAG2(-/-)γc(-/-) mice in which human-derived T and B-ALL cell lines were injected induced a significant reduction in tumor growth. Using primary ALL cells, a xenograft model of human leukemia in BALB/c-RAG2(-/-)γc(-/-) mice was established, allowing continuous passages of transplanted cells to several mouse generations. Treatment of mice engrafted with T or B-ALL cells with LBH589 induced an in vivo increase in the acetylation of H3 and H4, which was accompanied with prolonged survival of LBH589-treated mice in comparison with those receiving vincristine and dexamethasone. Notably, the therapeutic efficacy of LBH589 was significantly enhanced in combination with vincristine and dexamethasone. Our results show the therapeutic activity of LBH589 in combination with standard chemotherapy in pre-clinical models of ALL and suggest that this combination may be of clinical value in the treatment of patients with ALL.

78 FR 15894 - Draft Qualitative Risk Assessment of Risk of Activity/Food Combinations for Activities (Outside...

Science.gov (United States)

2013-03-13

.... FDA-2012-N-1258] Draft Qualitative Risk Assessment of Risk of Activity/Food Combinations for... comment period for a document entitled ``Draft Qualitative Risk Assessment of Risk of Activity/ [[Page... ``Draft Qualitative Risk Assessment of Risk of Activity/Food Combinations for Activities (Outside the Farm...

Estimating Net Primary Production of Swedish Forest Landscapes by Combining Mechanistic Modeling and Remote Sensing

DEFF Research Database (Denmark)

Tagesson, Håkan Torbern; Smith, Benjamin; Løfgren, Anders

2009-01-01

and the Beer-Lambert law. LAI estimates were compared with satellite-extrapolated field estimates of LAI, and the results were generally acceptable. NPP estimates directly from the dynamic vegetation model and estimates obtained by combining the model estimates with remote sensing information were, on average......The aim of this study was to investigate a combination of satellite images of leaf area index (LAI) with processbased vegetation modeling for the accurate assessment of the carbon balances of Swedish forest ecosystems at the scale of a landscape. Monthly climatologic data were used as inputs...... in a dynamic vegetation model, the Lund Potsdam Jena-General Ecosystem Simulator. Model estimates of net primary production (NPP) and the fraction of absorbed photosynthetic active radiation were constrained by combining them with satellite-based LAI images using a general light use efficiency (LUE) model...

Allosteric MEK1/2 Inhibitor Refametinib (BAY 86-9766 in Combination with Sorafenib Exhibits Antitumor Activity in Preclinical Murine and Rat Models of Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Roberta Schmieder

2013-10-01

Full Text Available OBJECTIVE: The objectives of the study were to evaluate the allosteric mitogen-activated protein kinase kinase (MEK inhibitor BAY 86-9766 in monotherapy and in combination with sorafenib in orthotopic and subcutaneous hepatocellular carcinoma (HCC models with different underlying etiologies in two species. DESIGN: Antiproliferative potential of BAY 86-9766 and synergistic effects with sorafenib were studied in several HCC cell lines. Relevant pathway signaling was studied in MH3924a cells. For in vivo testing, the HCC cells were implanted subcutaneously or orthotopically. Survival and mode of action (MoA were analyzed. RESULTS: BAY 86-9766 exhibited potent antiproliferative activity in HCC cell lines with half-maximal inhibitory concentration values ranging from 33 to 762 nM. BAY 86-9766 was strongly synergistic with sorafenib in suppressing tumor cell proliferation and inhibiting phosphorylation of the extracellular signal-regulated kinase (ERK. BAY 86-9766 prolonged survival in Hep3B xenografts, murine Hepa129 allografts, and MH3924A rat allografts. Additionally, tumor growth, ascites formation, and serum alpha-fetoprotein levels were reduced. Synergistic effects in combination with sorafenib were shown in Huh-7, Hep3B xenografts, and MH3924A allografts. On the signaling pathway level, the combination of BAY 86-9766 and sorafenib led to inhibition of the upregulatory feedback loop toward MEK phosphorylation observed after BAY 86-9766 monotreatment. With regard to the underlying MoA, inhibition of ERK phosphorylation, tumor cell proliferation, and microvessel density was observed in vivo. CONCLUSION: BAY 86-9766 shows potent single-agent antitumor activity and acts synergistically in combination with sorafenib in preclinical HCC models. These results support the ongoing clinical development of BAY 86-9766 and sorafenib in advanced HCC.

Multi-day activity scheduling reactions to planned activities and future events in a dynamic model of activity-travel behavior

Science.gov (United States)

Nijland, Linda; Arentze, Theo; Timmermans, Harry

2014-01-01

Modeling multi-day planning has received scarce attention in activity-based transport demand modeling so far. However, new dynamic activity-based approaches are being developed at the current moment. The frequency and inflexibility of planned activities and events in activity schedules of individuals indicate the importance of incorporating those pre-planned activities in the new generation of dynamic travel demand models. Elaborating and combining previous work on event-driven activity generation, the aim of this paper is to develop and illustrate an extension of a need-based model of activity generation that takes into account possible influences of pre-planned activities and events. This paper describes the theory and shows the results of simulations of the extension. The simulation was conducted for six different activities, and the parameter values used were consistent with an earlier estimation study. The results show that the model works well and that the influences of the parameters are consistent, logical, and have clear interpretations. These findings offer further evidence of face and construct validity to the suggested modeling approach.

Quantitative Structure-Activity Relationship Modeling Coupled with Molecular Docking Analysis in Screening of Angiotensin I-Converting Enzyme Inhibitory Peptides from Qula Casein Hydrolysates Obtained by Two-Enzyme Combination Hydrolysis.

Science.gov (United States)

Lin, Kai; Zhang, Lanwei; Han, Xue; Meng, Zhaoxu; Zhang, Jianming; Wu, Yifan; Cheng, Dayou

2018-03-28

In this study, Qula casein derived from yak milk casein was hydrolyzed using a two-enzyme combination approach, and high angiotensin I-converting enzyme (ACE) inhibitory activity peptides were screened by quantitative structure-activity relationship (QSAR) modeling integrated with molecular docking analysis. Hydrolysates (casein presents an excellent source to produce ACE inhibitory peptides.

Activated by Combined Magnrtic Field Gravitropic Reaction Reply on Nanodose of Biologicaly Active Compounds

Science.gov (United States)

Sheykina, Nadezhda; Bogatina, Nina

The new science direction nanotechnologies initiated a big jump in the pharmacology and medicine. This leads to the big development of homeopathy. The most interest appeared while investigating of the reaction of biological object on the nano dose of iologically substances. The changing of concentration (in nmol/l) of biologically active material is also possible during weak energy action. For instance, weak combined magnetic field may change a little the concentration of ions that are oriented parallel to the external magnetic field and, by the analogy with said above, lead to the similar effects. Simple estimations give the value for the threshold to the magnetic field by two orders smaller than the geomagnetic field. By this investigation we wanted to understand whether the analogy in the action of nano dose of biologically active substances and weak combined magnetic field presents and whether the action of one of these factors may be replaced by other one. The effect of one of biologically active substances NPA (Naphtyl-Phtalame Acid) solution with the concentration 0.01 mol/l on the gravitropic reaction of cress roots was investigated. It was shown that its effect was the inhibition of cress roots gravitropic reaction. The same inhibition was achieved by the combined magnetic field action on the cress roots, germinated in water. The alternative component of the combined magnetic field coincided formally with the cyclotron frequency of NPA ions. So the analogy in the action of nano dose of biologically active substances and weak combined magnetic field was shown. The combined magnetic field using allows to decrease sufficiently the dose of biologically active substances. This fact can be of great importance in pharmacy and medicine.

Combining multimedia models with integrated urban water system models for micropollutants

DEFF Research Database (Denmark)

De Keyser, W.; Gevaert, V.; Verdonck, F.

2010-01-01

Integrated urban water system (IUWS) modeling aims at assessing the quality of the surface water receiving the urban emissions through sewage treatment plants, combined sewer overflows (CSOS) and stormwater drainage systems However, some micropollutants tend to appear in more than one environmental...... medium (air, water, sediment, soil, groundwater, etc) In this work, a multimedia fate and transport model (MFTM) is "wrapped around" a dynamic IUWS model for organic micropollutants to enable integrated environmental assessment The combined model was tested on a hypothetical catchment using two scenarios...... on the one hand a reference scenario with a combined sewerage system and on the other hand a stormwater infiltration pond scenario, as an example of a sustainable urban drainage system (SUDS) A case for Bis(2-ethylhexyl) phthalate (DEHP) was simulated and resulted in reduced surface water concentrations...

78 FR 3824 - Draft Qualitative Risk Assessment of Risk of Activity/Food Combinations for Activities (Outside...

Science.gov (United States)

2013-01-16

.... FDA-2012-N-1258] Draft Qualitative Risk Assessment of Risk of Activity/Food Combinations for... entitled ``Draft Qualitative Risk Assessment of Risk of Activity/Food Combinations for Activities (Outside... defined in the regulation promulgated under section 418(n) of the FD&C Act. II. Qualitative Risk...

Active Learning of Classification Models with Likert-Scale Feedback.

Science.gov (United States)

Xue, Yanbing; Hauskrecht, Milos

2017-01-01

Annotation of classification data by humans can be a time-consuming and tedious process. Finding ways of reducing the annotation effort is critical for building the classification models in practice and for applying them to a variety of classification tasks. In this paper, we develop a new active learning framework that combines two strategies to reduce the annotation effort. First, it relies on label uncertainty information obtained from the human in terms of the Likert-scale feedback. Second, it uses active learning to annotate examples with the greatest expected change. We propose a Bayesian approach to calculate the expectation and an incremental SVM solver to reduce the time complexity of the solvers. We show the combination of our active learning strategy and the Likert-scale feedback can learn classification models more rapidly and with a smaller number of labeled instances than methods that rely on either Likert-scale labels or active learning alone.

78 FR 64428 - Draft Qualitative Risk Assessment of Risk of Activity/Animal Food Combinations for Activities...

Science.gov (United States)

2013-10-29

.... FDA-2013-N-1043] Draft Qualitative Risk Assessment of Risk of Activity/Animal Food Combinations for... entitled ``Draft Qualitative Risk Assessment of Risk of Activity/Animal Food Combinations for Activities...(n) of the FD&C Act. II. Qualitative Risk Assessment As explained in the draft RA, we conducted the...

Modelling equilibrium adsorption of single, binary, and ternary combinations of Cu, Pb, and Zn onto granular activated carbon.

Science.gov (United States)

Loganathan, Paripurnanda; Shim, Wang Geun; Sounthararajah, Danious Pratheep; Kalaruban, Mahatheva; Nur, Tanjina; Vigneswaran, Saravanamuthu

2018-03-30

Elevated concentrations of heavy metals in water can be toxic to humans, animals, and aquatic organisms. A study was conducted on the removal of Cu, Pb, and Zn by a commonly used water treatment adsorbent, granular activated carbon (GAC), from three single, three binary (Cu-Pb, Cu-Zn, Pb-Zn), and one ternary (Cu-Pb-Zn) combination of metals. It also investigated seven mathematical models on their suitability to predict the metals adsorption capacities. Adsorption of Cu, Pb, and Zn increased with pH with an abrupt increase in adsorption at around pH 5.5, 4.5, and 6.0, respectively. At all pHs tested (2.5-7.0), the adsorption capacity followed the order Pb > Cu > Zn. The Langmuir and Sips models fitted better than the Freundlich model to the data in the single-metal system at pH 5. The Langmuir maximum adsorption capacities of Pb, Cu, and Zn (mmol/g) obtained from the model's fits were 0.142, 0.094, and 0.058, respectively. The adsorption capacities (mmol/g) for these metals at 0.01 mmol/L equilibrium liquid concentration were 0.130, 0.085, and 0.040, respectively. Ideal Adsorbed Solution (IAS)-Langmuir and IAS-Sips models fitted well to the binary and ternary metals adsorption data, whereas the Extended Langmuir and Extended Sips models' fits to the data were poor. The selectivity of adsorption followed the same order as the metals' capacities and affinities of adsorption in the single-metal systems.

Model for Atmospheric Propagation of Spatially Combined Laser Beams

Science.gov (United States)

2016-09-01

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS MODEL FOR ATMOSPHERIC PROPAGATION OF SPATIALLY COMBINED LASER BEAMS by Kum Leong Lee September...MODEL FOR ATMOSPHERIC PROPAGATION OF SPATIALLY COMBINED LASER BEAMS 5. FUNDING NUMBERS 6. AUTHOR(S) Kum Leong Lee 7. PERFORMING ORGANIZATION NAME(S) AND...BLANK ii Approved for public release. Distribution is unlimited. MODEL FOR ATMOSPHERIC PROPAGATION OF SPATIALLY COMBINED LASER BEAMS Kum Leong Lee

Activity of Colistin in Combination with Meropenem, Tigecycline, Fosfomycin, Fusidic Acid, Rifampin or Sulbactam against Extensively Drug-Resistant Acinetobacter baumannii in a Murine Thigh-Infection Model.

Directory of Open Access Journals (Sweden)

Bing Fan

Full Text Available Few effective therapeutic options are available for treating severe infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB. Using a murine thigh-infection model, we examined the in vivo efficacy of colistin in combination with meropenem, tigecycline, fosfomycin, fusidic acid, rifampin, or sulbactam against 12 XDR-AB strains. Colistin, tigecycline, rifampin, and sulbactam monotherapy significantly decreased bacterial counts in murine thigh infections compared with those observed in control mice receiving no treatment. Colistin was the most effective agent tested, displaying bactericidal activity against 91.7% of strains at 48 h post-treatment. With strains showing a relatively low minimum inhibitory concentration (MIC for meropenem (MIC ≤ 32 mg/L, combination therapy with colistin plus meropenem caused synergistic inhibition at both 24 h and 48 h post-treatment. However, when the meropenem MIC was ≥64 mg/L, meropenem did not significantly alter the efficacy of colistin. The addition of rifampin and fusidic acid significantly improved the efficacy of colistin, showing a synergistic effect in 100% and 58.3% of strains after 24 h of treatment, respectively, while the addition of tigecycline, fosfomycin, or sulbactam did not show obvious synergistic activity. No clear differences in activities were observed between colistin-rifampin and colistin-fusidic acid combination therapy with most strains. Overall, our in vivo study showed that administering colistin in combination with rifampin or fusidic acid is more efficacious in treating XDR-AB infections than other combinations. The colistin-meropenem combination may be another appropriate option if the MIC is ≤32 mg/L. Further clinical studies are urgently needed to confirm the relevance of these findings.

Effect of combined function of temperature and water activity on the growth of Vibrio harveyi

Directory of Open Access Journals (Sweden)

Kang Zhou

2012-12-01

Full Text Available Vibrio harveyi is considered as a causative agent of the systemic disease, vibriosis, which occurs in many biological fields. The effects of temperatures (12.9-27.1 ºC and water activity (NaCl% 0.6%-3.4% on V. harveyi were investigated. The behavior and growth characteristics of V. harveyi was studied and modeled. Growth curves were fitted by using Gompertz and Baranyi models, and the Baranyi model showed a better fittness. Then, the maximum growth rates (µmax and lag phase durations (LPD, λ obtained from both Gompertz and Baranyi model were modeled as a combination function of temperature and water activity using the response surface and Arrhenius-Davey models for secondary model. The value of r², MSE, bias and accuracy factor suggest Baranyi model has better fitness than Gompertz model. Furthermore, validation of the developed models with independent data from ComBase also shown better interrelationship between observed and predicted growth parameter when using Baranyi model.

Effect of combined function of temperature and water activity on the growth of Vibrio harveyi.

Science.gov (United States)

Zhou, Kang; Gui, Meng; Li, Pinglan; Xing, Shaohua; Cui, Tingting; Peng, Zhaohui

2012-10-01

Vibrio harveyi is considered as a causative agent of the systemic disease, vibriosis, which occurs in many biological fields. The effects of temperatures (12.9-27.1 °C) and water activity (NaCl% 0.6%-3.4%) on V. harveyi were investigated. The behavior and growth characteristics of V. harveyi was studied and modeled. Growth curves were fitted by using Gompertz and Baranyi models, and the Baranyi model showed a better fittness. Then, the maximum growth rates (μmax) and lag phase durations (LPD, λ) obtained from both Gompertz and Baranyi model were modeled as a combination function of temperature and water activity using the response surface and Arrhenius-Davey models for secondary model. The value of r(2), MSE, bias and accuracy factor suggest Baranyi model has better fitness than Gompertz model. Furthermore, validation of the developed models with independent data from ComBase also shown better interrelationship between observed and predicted growth parameter when using Baranyi model.

COMBINE archive and OMEX format: one file to share all information to reproduce a modeling project.

Science.gov (United States)

Bergmann, Frank T; Adams, Richard; Moodie, Stuart; Cooper, Jonathan; Glont, Mihai; Golebiewski, Martin; Hucka, Michael; Laibe, Camille; Miller, Andrew K; Nickerson, David P; Olivier, Brett G; Rodriguez, Nicolas; Sauro, Herbert M; Scharm, Martin; Soiland-Reyes, Stian; Waltemath, Dagmar; Yvon, Florent; Le Novère, Nicolas

2014-12-14

With the ever increasing use of computational models in the biosciences, the need to share models and reproduce the results of published studies efficiently and easily is becoming more important. To this end, various standards have been proposed that can be used to describe models, simulations, data or other essential information in a consistent fashion. These constitute various separate components required to reproduce a given published scientific result. We describe the Open Modeling EXchange format (OMEX). Together with the use of other standard formats from the Computational Modeling in Biology Network (COMBINE), OMEX is the basis of the COMBINE Archive, a single file that supports the exchange of all the information necessary for a modeling and simulation experiment in biology. An OMEX file is a ZIP container that includes a manifest file, listing the content of the archive, an optional metadata file adding information about the archive and its content, and the files describing the model. The content of a COMBINE Archive consists of files encoded in COMBINE standards whenever possible, but may include additional files defined by an Internet Media Type. Several tools that support the COMBINE Archive are available, either as independent libraries or embedded in modeling software. The COMBINE Archive facilitates the reproduction of modeling and simulation experiments in biology by embedding all the relevant information in one file. Having all the information stored and exchanged at once also helps in building activity logs and audit trails. We anticipate that the COMBINE Archive will become a significant help for modellers, as the domain moves to larger, more complex experiments such as multi-scale models of organs, digital organisms, and bioengineering.

Unpacking "Active Learning": A Combination of Flipped Classroom and Collaboration Support Is More Effective but Collaboration Support Alone Is Not

Science.gov (United States)

Rau, Martina A.; Kennedy, Kristopher; Oxtoby, Lucas; Bollom, Mark; Moore, John W.

2017-01-01

Much evidence shows that instruction that actively engages students with learning materials is more effective than traditional, lecture-centric instruction. These "active learning" models comprise an extremely heterogeneous set of instructional methods: they often include collaborative activities, flipped classrooms, or a combination of…

The Combined Strength of Thermodynamics and Comparative Planetology: Application of Activity Models to Core Formation in Terrestrial Bodies

Science.gov (United States)

Righter, K.; Pando, K. M.; Danielson, L. R.

2015-01-01

how large the effect of Si can be, these epsilon values correspond to activity coefficients (gamma) for As of 0.01 when XSi = 0, and up to gamma = 23 when XSi = 0.2. Combining these new results with previous determinations [5,6] of epsilon parameters for S and C for these elements allows us calculate activity of Ge, In, As, and Sb in Fe-Ni-Si-S-C-O metallic liquids. We apply this new model to sever-al terrestrial bodies such as Earth (Si-rich core), Mars (S-rich core), Moon (S-, C-, and Si-poor core), and Vesta, and examine the resulting core and mantle concentrations of these elements. Mantle concentrations of these four elements are well explained for Earth and Mars in models that call for mid-mantle equilibration between Si-bearing and S-bearing FeNi cores, respectively. Modeling results for the Moon and Vesta will also be presented.

Combining multimedia models with integrated urban water system models for micropollutants

DEFF Research Database (Denmark)

De Keyser, W.; Gevaert, V.; Verdonck, F.

2009-01-01

Integrated urban water system (IUWS) modelling aims at assessing the quality of the surface water receiving the urban emissions through sewage treatment plants, combined sewer overflows (CSOs) and stormwater drainage systems. However, some micropollutants have the tendency to occur in more than one...... environmental medium. In this work, a multimedia fate and transport model (MFTM) is “wrapped around” a dynamic IUWS model for organic micropollutants to enable integrated environmental assessment. The combined model was tested on a hypothetical catchment using two scenarios: a reference scenario...... and a stormwater infiltration pond scenario, as an example of a sustainable urban drainage system (SUDS). A case for Bis(2-ethylhexyl) phthalate (DEHP) was simulated and resulted in a reduced surface water concentration for the latter scenario. However, the model also showed that this was at the expense...

Superheated water pretreatment combined with CO2 activation/regeneration of the exhausted activated carbon used in the treatment of industrial wastewater.

Science.gov (United States)

Xiao, Jin; Yu, Bailie; Zhong, Qifan; Yuan, Jie; Yao, Zhen; Zhang, Liuyun

2017-10-01

This paper examines a novel method of regenerating saturated activated carbon after adsorption of complex phenolic, polycyclic aromatic hydrocarbons with low energy consumption by using superheated water pretreatment combined with CO 2 activation. The effects of the temperature of the superheated water, liquid-solid ratio, soaking time, activation temperature, activation time, and CO 2 flow rate of regeneration and adsorption of coal-powdered activated carbon (CPAC) were studied. The results show that the adsorption capacity of iodine values on CPAC recovers to 102.25% of the fresh activated carbon, and the recovery rate is 79.8% under optimal experimental conditions. The adsorption model and adsorption kinetics of methylene blue on regenerated activated carbon (RAC) showed that the adsorption process was in accordance with the Langmuir model and the pseudo-second-order kinetics model. Furthermore, the internal diffusion process was the main controlling step. The surface properties, Brunauer-Emmett-Teller (BET) surface area, and pore size distribution were characterized by Fourier transform infrared spectroscopy (FT-IR) and BET, which show that the RAC possesses more oxygen-containing functional groups with a specific surface area of 763.39 m 2 g -1 and a total pore volume of 0.3039 cm 3 g -1 . Micropores account for 79.8% and mesopores account for 20.2%.

Quantification of left ventricular volumes from cardiac cine MRI using active contour model combined with gradient vector flow

International Nuclear Information System (INIS)

Tanki, Nobuyoshi; Murase, Kenya; Kumashiro, Masayuki; Momoi, Risa; Yang, Xiaomei; Tabuchi, Takashi; Nagayama, Masako; Watanabe, Yuji

2005-01-01

We investigated the feasibility of combining the active contour model with gradient vector flow (Snakes-GVF) to estimate left ventricular (LV) volumes from cardiac cine magnetic resonance imaging (MRI). MRI data were acquired from 27 patients, including 14 adults (9 men, 5 women, 55.0±23.3 years) and 13 children (10 boys, 3 girls, 2.7±2.1 years) using Gyroscan Intera (1.5 Tesla, Philips Medical Systems). LV volumes were calculated by adding the areas surrounded by the contour extracted by Snakes-GVF and compared with volumes estimated by manual tracing. Those estimated by Snakes-GVF [y (mL)] correlated well with those estimated by manual tracing [x (mL)]. In adult cases, the regression equation and correlation coefficient were y=1.008x-0.517 and 0.996, respectively. In pediatric cases, they were y=1.174x-2.542 and 0.992, respectively. In conclusion, Snakes-GVF is a powerful and useful tool for quantifying LV volumes using cardiac MRI. (author)

Does birth weight influence physical activity in youth? A combined analysis of four studies using objectively measured physical activity

DEFF Research Database (Denmark)

Ridgway, Charlotte L; Brage, Søren; Sharp, Stephen J

2011-01-01

Animal models suggest growth restriction in utero leads to lower levels of motor activity. Furthermore, individuals with very low birth weight report lower levels of physical activity as adults. The aim of this study was to examine whether birth weight acts as a biological determinant of physical...... activity and sedentary time. This study uses combined analysis of three European cohorts and one from South America (n = 4,170). Birth weight was measured or parentally reported. Height and weight were measured and used to calculate Body Mass Index (BMI). PA was objectively measured using accelerometry...... for ≥3 days, ≥10 hours day. Data was standardized to allow comparisons between different monitors. Total physical activity was assessed as counts per minute (cpm), with time spent above moderate activity (MVPA) >2,000 counts and time spent sedentary (...

Bayesian screening for active compounds in high-dimensional chemical spaces combining property descriptors and molecular fingerprints.

Science.gov (United States)

Vogt, Martin; Bajorath, Jürgen

2008-01-01

Bayesian classifiers are increasingly being used to distinguish active from inactive compounds and search large databases for novel active molecules. We introduce an approach to directly combine the contributions of property descriptors and molecular fingerprints in the search for active compounds that is based on a Bayesian framework. Conventionally, property descriptors and fingerprints are used as alternative features for virtual screening methods. Following the approach introduced here, probability distributions of descriptor values and fingerprint bit settings are calculated for active and database molecules and the divergence between the resulting combined distributions is determined as a measure of biological activity. In test calculations on a large number of compound activity classes, this methodology was found to consistently perform better than similarity searching using fingerprints and multiple reference compounds or Bayesian screening calculations using probability distributions calculated only from property descriptors. These findings demonstrate that there is considerable synergy between different types of property descriptors and fingerprints in recognizing diverse structure-activity relationships, at least in the context of Bayesian modeling.

Object Oriented Modeling : A method for combining model and software development

NARCIS (Netherlands)

Van Lelyveld, W.

2010-01-01

When requirements for a new model cannot be met by available modeling software, new software can be developed for a specific model. Methods for the development of both model and software exist, but a method for combined development has not been found. A compatible way of thinking is required to

In-vitro activity of ciprofloxacin combined with flomoxef against Bacteroides fragilis, compared with that of ciprofloxacin combined with clindamycin.

Science.gov (United States)

Kato, Komei; Iwai, Shigetomi; Sato, Takeshi; Harada, Tomohide; Nakagawa, Yoshiteru; Iwanaga, Hitomi; Ito, Yumiko; Takayama, Tadatoshi

2002-06-01

Using checkerboard and time-kill assays, the in-vitro activity of ciprofloxacin alone and in combination with flomoxef against clinical Bacteroides fragilis strains was evaluated. In addition, the microbiological efficacy of this combination was compared with that of ciprofloxacin plus clindamycin. In 88% of the 25 strains tested, the combination of ciprofloxacin plus flomoxef exhibited a synergistic or an additive effect, whereas only 56% of the 25 strains ( Pflomoxef was observed in all 7 strains. In conclusion, the combination of ciprofloxacin plus flomoxef is very active against B. fragilis, suggesting that this combination may be very useful in the treatment of aerobic and B. fragilis mixed infections, because ciprofloxacin has an expanded spectrum against aerobes.

Use of a combined effect model approach for discriminating between ABCB1- and ABCC1-type efflux activities in native bivalve gill tissue

Energy Technology Data Exchange (ETDEWEB)

Faria, Melissa [Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); CESAM & Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro (Portugal); Pavlichenko, Vasiliy [Siberian Institute of Plant Physiology and Biochemistry, Siberian Branch of Russian Academy of Sciences (SIPPB SB RAS), Lermontov Str. 132, 664033, Irkutsk (Russian Federation); Department of Bioanalytical Ecotoxicology, UFZ — Helmholtz Centre for Environmental Research, Permoserstr. 15, D-04318 Leipzig (Germany); Burkhardt-Medicke, Kathleen [Department of Bioanalytical Ecotoxicology, UFZ — Helmholtz Centre for Environmental Research, Permoserstr. 15, D-04318 Leipzig (Germany); Institute of Hydrobiology, Dresden University of Technology, D-01062 Dresden (Germany); Soares, Amadeu M.V.M. [CESAM & Departamento de Biologia, Universidade de Aveiro, 3810-193 Aveiro (Portugal); Altenburger, Rolf [Department of Bioanalytical Ecotoxicology, UFZ — Helmholtz Centre for Environmental Research, Permoserstr. 15, D-04318 Leipzig (Germany); Barata, Carlos [Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Luckenbach, Till, E-mail: till.luckenbach@ufz.de [Department of Bioanalytical Ecotoxicology, UFZ — Helmholtz Centre for Environmental Research, Permoserstr. 15, D-04318 Leipzig (Germany)

2016-04-15

Aquatic organisms, such as bivalves, employ ATP binding cassette (ABC) transporters for efflux of potentially toxic chemicals. Anthropogenic water contaminants can, as chemosensitizers, disrupt efflux transporter function enabling other, putatively toxic compounds to enter the organism. Applying rapid amplification of cDNA ends (RACE) PCR we identified complete cDNAs encoding ABCB1- and ABCC1-type transporter homologs from zebra mussel providing the molecular basis for expression of both transporter types in zebra mussel gills. Further, efflux activities of both transporter types in gills were indicated with dye accumulation assays where efflux of the dye calcein-am was sensitive to both ABCB1- (reversin 205, verapamil) and ABCC1- (MK571) type specific inhibitors. The assumption that different inhibitors targeted different efflux pump types was confirmed when comparing measured effects of binary inhibitor compound mixtures in dye accumulation assays with predictions from mixture effect models. Effects by the MK571/reversin 205 mixture corresponded better with independent action, whereas reversin 205/verapamil joint effects were better predicted by the concentration addition model indicating different and equal targets, respectively. The binary mixture approach was further applied to identify the efflux pump type targeted by environmentally relevant chemosensitizing compounds. Pentachlorophenol and musk ketone, which were selected after a pre-screen of twelve compounds that previously had been identified as chemosensitizers, showed mixture effects that corresponded better with concentration addition when combined with reversine 205 but with independent action predictions when combined with MK571 indicating targeting of an ABCB1-type efflux pump by these compounds. - Highlights: • Sequences and function of ABC efflux transporters in bivalve gills were explored. • Full length Dreissena polymorpha abcb1 and abcc1 cDNA sequences were identified. • A mixture effect

Use of a combined effect model approach for discriminating between ABCB1- and ABCC1-type efflux activities in native bivalve gill tissue

International Nuclear Information System (INIS)

Faria, Melissa; Pavlichenko, Vasiliy; Burkhardt-Medicke, Kathleen; Soares, Amadeu M.V.M.; Altenburger, Rolf; Barata, Carlos; Luckenbach, Till

2016-01-01

Aquatic organisms, such as bivalves, employ ATP binding cassette (ABC) transporters for efflux of potentially toxic chemicals. Anthropogenic water contaminants can, as chemosensitizers, disrupt efflux transporter function enabling other, putatively toxic compounds to enter the organism. Applying rapid amplification of cDNA ends (RACE) PCR we identified complete cDNAs encoding ABCB1- and ABCC1-type transporter homologs from zebra mussel providing the molecular basis for expression of both transporter types in zebra mussel gills. Further, efflux activities of both transporter types in gills were indicated with dye accumulation assays where efflux of the dye calcein-am was sensitive to both ABCB1- (reversin 205, verapamil) and ABCC1- (MK571) type specific inhibitors. The assumption that different inhibitors targeted different efflux pump types was confirmed when comparing measured effects of binary inhibitor compound mixtures in dye accumulation assays with predictions from mixture effect models. Effects by the MK571/reversin 205 mixture corresponded better with independent action, whereas reversin 205/verapamil joint effects were better predicted by the concentration addition model indicating different and equal targets, respectively. The binary mixture approach was further applied to identify the efflux pump type targeted by environmentally relevant chemosensitizing compounds. Pentachlorophenol and musk ketone, which were selected after a pre-screen of twelve compounds that previously had been identified as chemosensitizers, showed mixture effects that corresponded better with concentration addition when combined with reversine 205 but with independent action predictions when combined with MK571 indicating targeting of an ABCB1-type efflux pump by these compounds. - Highlights: • Sequences and function of ABC efflux transporters in bivalve gills were explored. • Full length Dreissena polymorpha abcb1 and abcc1 cDNA sequences were identified. • A mixture effect

Modelling the combined impact of radionuclide discharges reaching rivers

International Nuclear Information System (INIS)

Hilton, J.; Small, S.; Hornby, D.; Scarlett, P.; Harvey, M.; Simmonds, J.; Bexon, A.; Jones, A.

2003-01-01

The Agency currently authorises direct and indirect (via sewerage systems) discharges of liquid radioactive wastes to rivers from nuclear sites and other registered users of radioactivity. Discharges are normally authorised on a site-by-site basis, taking into account the radiological assessment. Radiological assessments are normally made using dilution models to estimate radionuclide activities in the effluents themselves and in the receiving rivers. These data are then combined with information on habits and dose factor information to give a dose assessment for individuals exposed to the discharge. For each site the highest radiological impact is expected immediately downstream of the disposal point where concentrations of radionuclides and resulting doses are highest. The concentration and doses are expected to decline with increasing distance downstream of the disposal point. However, if discharges are made into the river from other establishments higher up the catchment, the total dose may be higher. Recent Environment Agency research projects provided evidence of the potential radiological significance of multiple discharges to a single river. In the light of these studies, the Agency require a robust modelling tool to assist in the assessment of the effects of combined discharges to river systems. The aim of this R and D project was to develop and test modelling tools that could be used to make assessments of the impact of multiple radiological discharge into river systems and to trial them on the upper Thames river system

TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules.

Science.gov (United States)

Liu, Qian; Sun, Jessica D; Wang, Jingli; Ahluwalia, Dharmendra; Baker, Amanda F; Cranmer, Lee D; Ferraro, Damien; Wang, Yan; Duan, Jian-Xin; Ammons, W Steve; Curd, John G; Matteucci, Mark D; Hart, Charles P

2012-06-01

Subregional hypoxia is a common feature of tumors and is recognized as a limiting factor for the success of radiotherapy and chemotherapy. TH-302, a hypoxia-activated prodrug selectively targeting hypoxic regions of solid tumors, delivers a cytotoxic warhead to the tumor, while maintaining relatively low systemic toxicity. The antitumor activity, different dosing sequences, and dosing regimens of TH-302 in combination with commonly used conventional chemotherapeutics were investigated in human tumor xenograft models. Seven chemotherapeutic drugs (docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide) were tested in combination with TH-302 in eleven human xenograft models, including non-small cell lung cancer (NSCLC), colon cancer, prostate cancer, fibrosarcoma, melanoma, and pancreatic cancer. The antitumor activity of docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide was increased when combined with TH-302 in nine out of eleven models tested. Administration of TH-302 2-8 h prior to the other chemotherapeutics yielded superior efficacy versus other sequences tested. Simultaneous administration of TH-302 and chemotherapeutics increased toxicity versus schedules with dosing separations. In a dosing optimization study, TH-302 administered daily at 50 mg/kg intraperitoneally for 5 days per week in the H460 NSCLC model showed the optimal response with minimal toxicity. TH-302 enhances the activity of a wide range of conventional anti-neoplastic agents in a broad panel of in vivo xenograft models. These data highlight in vivo effects of schedule and order of drug administration in regimen efficacy and toxicity and have relevance to the design of human regimens incorporating TH-302.

On Combining Language Models: Oracle Approach

National Research Council Canada - National Science Library

Hacioglu, Kadri; Ward, Wayne

2001-01-01

In this paper, we address the of combining several language models (LMs). We find that simple interpolation methods, like log-linear and linear interpolation, improve the performance but fall short of the performance of an oracle...

Exotic hadron production in a quark combination model

International Nuclear Information System (INIS)

Han Wei; Shao Fenglan; Li Shiyuan; Shang Yonghui; Yao Tao

2009-01-01

The philosophy on production of exotic hadrons (multiquark states) in the framework of the quark combination model is investigated, taking f 0 (980) as an example. The production rate and p T spectra of f 0 (980) considered as (ss) or (sqsq), respectively, are calculated and compared in Au+Au collisions at √(s NN )=200 GeV. The unitarity of various combination models, when open for exotic hadron production, is addressed.

Bi-dimension decomposed hidden Markov models for multi-person activity recognition

Institute of Scientific and Technical Information of China (English)

Wei-dong ZHANG; Feng CHEN; Wen-li XU

2009-01-01

We present a novel model for recognizing long-term complex activities involving multiple persons. The proposed model, named 'decomposed hidden Markov model' (DHMM), combines spatial decomposition and hierarchical abstraction to capture multi-modal, long-term dependent and multi-scale characteristics of activities. Decomposition in space and time offers conceptual advantages of compaction and clarity, and greatly reduces the size of state space as well as the number of parameters.DHMMs are efficient even when the number of persons is variable. We also introduce an efficient approximation algorithm for inference and parameter estimation. Experiments on multi-person activities and multi-modal individual activities demonstrate that DHMMs are more efficient and reliable than familiar models, such as coupled HMMs, hierarchical HMMs, and multi-observation HMMs.

The combination of IL-21 and IFN-alpha boosts STAT3 activation, cytotoxicity and experimental tumor therapy

DEFF Research Database (Denmark)

Eriksen, Karsten W; Søndergaard, Henrik; Woetmann, Anders

2008-01-01

such as IFN-alpha and IL-2 have multiple and severe side effects. Accordingly, they are generally used at sub-optimal doses, which limit their clinical efficacy. Here we hypothesized that a combination of IFN-alpha and IL-21, a novel cytokine of the IL-2 family with anti-cancer effects, will increase the anti......-cancer efficacy at sub-optimal cytokine doses. We show that the combined stimulation of target-cells with IFN-alpha and IL-21 triggers an increased STAT3 activation whereas the activation of other STATs including STAT1/2 is unaffected. In parallel, the combined stimulation with IFN-alpha and IL-21 triggers...... a selective increase in MHC class I expression and NK- and CD8(+) T-cell-mediated cytotoxicity. In an experimental in vivo model of renal carcinoma, the combined treatment of IFN-alpha and IL-21 also produces a significant anti-cancer effect as judged by an inhibition of tumor growth and an increased survival...

Simulation of Mercury's magnetosheath with a combined hybrid-paraboloid model

Science.gov (United States)

Parunakian, David; Dyadechkin, Sergey; Alexeev, Igor; Belenkaya, Elena; Khodachenko, Maxim; Kallio, Esa; Alho, Markku

2017-08-01

In this paper we introduce a novel approach for modeling planetary magnetospheres that involves a combination of the hybrid model and the paraboloid magnetosphere model (PMM); we further refer to it as the combined hybrid model. While both of these individual models have been successfully applied in the past, their combination enables us both to overcome the traditional difficulties of hybrid models to develop a self-consistent magnetic field and to compensate the lack of plasma simulation in the PMM. We then use this combined model to simulate Mercury's magnetosphere and investigate the geometry and configuration of Mercury's magnetosheath controlled by various conditions in the interplanetary medium. The developed approach provides a unique comprehensive view of Mercury's magnetospheric environment for the first time. Using this setup, we compare the locations of the bow shock and the magnetopause as determined by simulations with the locations predicted by stand-alone PMM runs and also verify the magnetic and dynamic pressure balance at the magnetopause. We also compare the results produced by these simulations with observational data obtained by the magnetometer on board the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft along a dusk-dawn orbit and discuss the signatures of the magnetospheric features that appear in these simulations. Overall, our analysis suggests that combining the semiempirical PMM with a self-consistent global kinetic model creates new modeling possibilities which individual models cannot provide on their own.

Combination of Bayesian Network and Overlay Model in User Modeling

Directory of Open Access Journals (Sweden)

Loc Nguyen

2009-12-01

Full Text Available The core of adaptive system is user model containing personal information such as knowledge, learning styles, goals… which is requisite for learning personalized process. There are many modeling approaches, for example: stereotype, overlay, plan recognition… but they don’t bring out the solid method for reasoning from user model. This paper introduces the statistical method that combines Bayesian network and overlay modeling so that it is able to infer user’s knowledge from evidences collected during user’s learning process.

Science Letters：Synergetic effects for p-nitrophenol abatement using a combined activated carbon adsorption-electrooxidation process

Institute of Scientific and Technical Information of China (English)

周明华; 戴启洲; 雷乐成; 汪大翚

2004-01-01

A novel fluidized electrochemical reactor that integrated advanced electrochemical oxidation with activated carbon (AC) fluidization in a single cell was developed to model pollutant p-nitrophenol (PNP) abatement. AC fluidization could enhance COD removal by 22%-30%. In such a combined process, synergetic effects on PNP and COD removal was found, with their removal rate being enhanced by 137.8% and 97.8%, respectively. AC could be electrochemically regenerated and reused, indicating the combined process would be promising for treatment of biorefractory organic pollutants.

The combination of sorafenib and everolimus shows antitumor activity in preclinical models of malignant pleural mesothelioma

International Nuclear Information System (INIS)

Pignochino, Ymera; Dell’Aglio, Carmine; Inghilleri, Simona; Zorzetto, Michele; Basiricò, Marco; Capozzi, Federica; Canta, Marta; Piloni, Davide; Cemmi, Francesca; Sangiolo, Dario; Gammaitoni, Loretta; Soster, Marco; Marchiò, Serena; Pozzi, Ernesto; Morbini, Patrizia; Luisetti, Maurizio; Aglietta, Massimo; Grignani, Giovanni; Stella, Giulia M

2015-01-01

Malignant Pleural Mesothelioma (MPM) is an aggressive tumor arising from mesothelial cells lining the pleural cavities characterized by resistance to standard therapies. Most of the molecular steps responsible for pleural transformation remain unclear; however, several growth factor signaling cascades are known to be altered during MPM onset and progression. Transducers of these pathways, such as PIK3CA-mTOR-AKT, MAPK, and ezrin/radixin/moesin (ERM) could therefore be exploited as possible targets for pharmacological intervention. This study aimed to identify ‘druggable’ pathways in MPM and to formulate a targeted approach based on the use of commercially available molecules, such as the multikinase inhibitor sorafenib and the mTOR inhibitor everolimus. We planned a triple approach based on: i) analysis of immunophenotypes and mutational profiles in a cohort of thoracoscopic MPM samples, ii) in vitro pharmacological assays, ii) in vivo therapeutic approaches on MPM xenografts. No mutations were found in ‘hot spot’ regions of the mTOR upstream genes (e.g. EGFR, KRAS and PIK3CA). Phosphorylated mTOR and ERM were specifically overexpressed in the analyzed MPM samples. Sorafenib and everolimus combination was effective in mTOR and ERM blockade; exerted synergistic effects on the inhibition of MPM cell proliferation; triggered ROS production and consequent AMPK-p38 mediated-apoptosis. The antitumor activity was displayed when orally administered to MPM-bearing NOD/SCID mice. ERM and mTOR pathways are activated in MPM and ‘druggable’ by a combination of sorafenib and everolimus. Combination therapy is a promising therapeutic strategy against MPM. The online version of this article (doi:10.1186/s12885-015-1363-1) contains supplementary material, which is available to authorized users

A muscle model for hybrid muscle activation

Directory of Open Access Journals (Sweden)

Klauer Christian

2015-09-01

Full Text Available To develop model-based control strategies for Functional Electrical Stimulation (FES in order to support weak voluntary muscle contractions, a hybrid model for describing joint motions induced by concurrent voluntary-and FES induced muscle activation is proposed. It is based on a Hammerstein model – as commonly used in feedback controlled FES – and exemplarily applied to describe the shoulder abduction joint angle. Main component of a Hammerstein muscle model is usually a static input nonlinearity depending on the stimulation intensity. To additionally incorporate voluntary contributions, we extended the static non-linearity by a second input describing the intensity of the voluntary contribution that is estimated by electromyography (EMG measurements – even during active FES. An Artificial Neural Network (ANN is used to describe the static input non-linearity. The output of the ANN drives a second-order linear dynamical system that describes the combined muscle activation and joint angle dynamics. The tunable parameters are adapted to the individual subject by a system identification approach using previously recorded I/O-data. The model has been validated in two healthy subjects yielding RMS values for the joint angle error of 3.56° and 3.44°, respectively.

Comparing models of the combined-stimulation advantage for speech recognition.

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Micheyl, Christophe; Oxenham, Andrew J

2012-05-01

The "combined-stimulation advantage" refers to an improvement in speech recognition when cochlear-implant or vocoded stimulation is supplemented by low-frequency acoustic information. Previous studies have been interpreted as evidence for "super-additive" or "synergistic" effects in the combination of low-frequency and electric or vocoded speech information by human listeners. However, this conclusion was based on predictions of performance obtained using a suboptimal high-threshold model of information combination. The present study shows that a different model, based on Gaussian signal detection theory, can predict surprisingly large combined-stimulation advantages, even when performance with either information source alone is close to chance, without involving any synergistic interaction. A reanalysis of published data using this model reveals that previous results, which have been interpreted as evidence for super-additive effects in perception of combined speech stimuli, are actually consistent with a more parsimonious explanation, according to which the combined-stimulation advantage reflects an optimal combination of two independent sources of information. The present results do not rule out the possible existence of synergistic effects in combined stimulation; however, they emphasize the possibility that the combined-stimulation advantages observed in some studies can be explained simply by non-interactive combination of two information sources.

Antifungal activities of diphenyl diselenide and ebselen alone and in combination with antifungal agents against Fusarium spp.

Science.gov (United States)

Venturini, Tarcieli Pozzebon; Chassot, Francieli; Loreto, Érico Silva; Keller, Jéssica Tairine; Azevedo, Maria Izabel; Zeni, Gilson; Santurio, Janio Morais; Alves, Sydney Hartz

2016-07-01

Herein, we describe the in vitro activity of a combination of the organoselenium compounds diphenyl diselenide and ebselen alone and in combination with amphotericin B, caspofungin, itraconazole, and voriconazole against 25 clinical isolates of Fusarium spp. For this analysis, we used the broth microdilution method based on the M38-A2 technique and checkerboard microdilution method. Diphenyl diselenide (MIC range = 4-32 μg/ml) and ebselen (MIC range = 2-8 μg/ml) showed in vitro activity against the isolates tested. The most effective combinations were (synergism rates): ebselen + amphotericin B (88%), ebselen + voriconazole (80%), diphenyl diselenide + amphotericin B (72%), and diphenyl diselenide + voriconazole (64%). Combination with caspofungin resulted in low rates of synergism: ebselen + caspofungin, 36%, and diphenyl diselenide + caspofungin, 28%; combination with itraconazole demonstrated indifferent interactions. Antagonistic effects were not observed for any of the combinations tested. Our findings suggest that the antifungal potential of diphenyl diselenide and ebselen deserves further investigation in in vivo experimental models, especially in combination with amphotericin B and voriconazole. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

SPR imaging combined with cyclic voltammetry for the detection of neural activity

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Hui Li

2014-03-01

Full Text Available Surface plasmon resonance (SPR detects changes in refractive index at a metal-dielectric interface. In this study, SPR imaging (SPRi combined with cyclic voltammetry (CV was applied to detect neural activity in isolated bullfrog sciatic nerves. The neural activities induced by chemical and electrical stimulation led to an SPR response, and the activities were recorded in real time. The activities of different parts of the sciatic nerve were recorded and compared. The results demonstrated that SPR imaging combined with CV is a powerful tool for the investigation of neural activity.

Anoxic Activated Sludge Monitoring with Combined Nitrate and Titrimetric Measurements

DEFF Research Database (Denmark)

Petersen, B.; Gernaey, Krist; Vanrolleghem, P.A.

2002-01-01

was with the carbon source in excess, since excess nitrate provoked nitrite build-up thereby complicating the data interpretation. A conceptual model could quantitatively describe the experimental observations and thus link the experimentally measured proton production with the consumption of electron acceptor......An experimental procedure for anoxic activated sludge monitoring with combined nitrate and titrimetric measurements is proposed and evaluated successfully with two known carbon sources, (-)acetate and dextrose. For nitrate measurements an ion-selective nitrate electrode is applied to allow...... for frequent measurements, and thereby the possibility for detailed determination of the denitrification biokinetics. An internal nitrate electrode calibration is implemented in the experiments to avoid the often-encountered electrode drift problem. It was observed that the best experimental design...

Wind gust estimation by combining numerical weather prediction model and statistical post-processing

Science.gov (United States)

Patlakas, Platon; Drakaki, Eleni; Galanis, George; Spyrou, Christos; Kallos, George

2017-04-01

The continuous rise of off-shore and near-shore activities as well as the development of structures, such as wind farms and various offshore platforms, requires the employment of state-of-the-art risk assessment techniques. Such analysis is used to set the safety standards and can be characterized as a climatologically oriented approach. Nevertheless, a reliable operational support is also needed in order to minimize cost drawbacks and human danger during the construction and the functioning stage as well as during maintenance activities. One of the most important parameters for this kind of analysis is the wind speed intensity and variability. A critical measure associated with this variability is the presence and magnitude of wind gusts as estimated in the reference level of 10m. The latter can be attributed to different processes that vary among boundary-layer turbulence, convection activities, mountain waves and wake phenomena. The purpose of this work is the development of a wind gust forecasting methodology combining a Numerical Weather Prediction model and a dynamical statistical tool based on Kalman filtering. To this end, the parameterization of Wind Gust Estimate method was implemented to function within the framework of the atmospheric model SKIRON/Dust. The new modeling tool combines the atmospheric model with a statistical local adaptation methodology based on Kalman filters. This has been tested over the offshore west coastline of the United States. The main purpose is to provide a useful tool for wind analysis and prediction and applications related to offshore wind energy (power prediction, operation and maintenance). The results have been evaluated by using observational data from the NOAA's buoy network. As it was found, the predicted output shows a good behavior that is further improved after the local adjustment post-process.

Tardos fingerprinting codes in the combined digit model

NARCIS (Netherlands)

Skoric, B.; Katzenbeisser, S.; Schaathun, H.G.; Celik, M.U.

2009-01-01

We introduce a new attack model for collusion-secure codes, called the combined digit model, which represents signal processing attacks against the underlying watermarking level better than existing models. In this paper, we analyze the performance of two variants of the Tardos code and show that

Evaluation of combination therapy for Burkholderia cenocepacia lung infection in different in vitro and in vivo models.

Directory of Open Access Journals (Sweden)

Freija Van den Driessche

Full Text Available Burkholderia cenocepacia is an opportunistic pathogen responsible for life-threatening infections in cystic fibrosis patients. B. cenocepacia is extremely resistant towards antibiotics and therapy is complicated by its ability to form biofilms. We investigated the efficacy of an alternative antimicrobial strategy for B. cenocepacia lung infections using in vitro and in vivo models. A screening of the NIH Clinical Collection 1&2 was performed against B. cenocepacia biofilms formed in 96-well microtiter plates in the presence of tobramycin to identify repurposing candidates with potentiator activity. The efficacy of selected hits was evaluated in a three-dimensional (3D organotypic human lung epithelial cell culture model. The in vivo effect was evaluated in the invertebrate Galleria mellonella and in a murine B. cenocepacia lung infection model. The screening resulted in 60 hits that potentiated the activity of tobramycin against B. cenocepacia biofilms, including four imidazoles of which econazole and miconazole were selected for further investigation. However, a potentiator effect was not observed in the 3D organotypic human lung epithelial cell culture model. Combination treatment was also not able to increase survival of infected G. mellonella. Also in mice, there was no added value for the combination treatment. Although potentiators of tobramycin with activity against biofilms of B. cenocepacia were identified in a repurposing screen, the in vitro activity could not be confirmed nor in a more sophisticated in vitro model, neither in vivo. This stresses the importance of validating hits resulting from in vitro studies in physiologically relevant model systems.

Developing an active implementation model for a chronic disease management program.

Science.gov (United States)

Smidth, Margrethe; Christensen, Morten Bondo; Olesen, Frede; Vedsted, Peter

2013-04-01

Introduction and diffusion of new disease management programs in healthcare is usually slow, but active theory-driven implementation seems to outperform other implementation strategies. However, we have only scarce evidence on the feasibility and real effect of such strategies in complex primary care settings where municipalities, general practitioners and hospitals should work together. The Central Denmark Region recently implemented a disease management program for chronic obstructive pulmonary disease (COPD) which presented an opportunity to test an active implementation model against the usual implementation model. The aim of the present paper is to describe the development of an active implementation model using the Medical Research Council's model for complex interventions and the Chronic Care Model. We used the Medical Research Council's five-stage model for developing complex interventions to design an implementation model for a disease management program for COPD. First, literature on implementing change in general practice was scrutinised and empirical knowledge was assessed for suitability. In phase I, the intervention was developed; and in phases II and III, it was tested in a block- and cluster-randomised study. In phase IV, we evaluated the feasibility for others to use our active implementation model. The Chronic Care Model was identified as a model for designing efficient implementation elements. These elements were combined into a multifaceted intervention, and a timeline for the trial in a randomised study was decided upon in accordance with the five stages in the Medical Research Council's model; this was captured in a PaTPlot, which allowed us to focus on the structure and the timing of the intervention. The implementation strategies identified as efficient were use of the Breakthrough Series, academic detailing, provision of patient material and meetings between providers. The active implementation model was tested in a randomised trial

Improving model predictions for RNA interference activities that use support vector machine regression by combining and filtering features

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Peek Andrew S

2007-06-01

Full Text Available Abstract Background RNA interference (RNAi is a naturally occurring phenomenon that results in the suppression of a target RNA sequence utilizing a variety of possible methods and pathways. To dissect the factors that result in effective siRNA sequences a regression kernel Support Vector Machine (SVM approach was used to quantitatively model RNA interference activities. Results Eight overall feature mapping methods were compared in their abilities to build SVM regression models that predict published siRNA activities. The primary factors in predictive SVM models are position specific nucleotide compositions. The secondary factors are position independent sequence motifs (N-grams and guide strand to passenger strand sequence thermodynamics. Finally, the factors that are least contributory but are still predictive of efficacy are measures of intramolecular guide strand secondary structure and target strand secondary structure. Of these, the site of the 5' most base of the guide strand is the most informative. Conclusion The capacity of specific feature mapping methods and their ability to build predictive models of RNAi activity suggests a relative biological importance of these features. Some feature mapping methods are more informative in building predictive models and overall t-test filtering provides a method to remove some noisy features or make comparisons among datasets. Together, these features can yield predictive SVM regression models with increased predictive accuracy between predicted and observed activities both within datasets by cross validation, and between independently collected RNAi activity datasets. Feature filtering to remove features should be approached carefully in that it is possible to reduce feature set size without substantially reducing predictive models, but the features retained in the candidate models become increasingly distinct. Software to perform feature prediction and SVM training and testing on nucleic acid

Combining Off-the-Job Productivity Regression Model with EPA’s NONROAD Model in Estimating CO2 Emissions from Bulldozer

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Apif M. Hajji

2017-09-01

Full Text Available Heavy duty diesel (HDD construction equipment which includes bulldozer is important in infrastructure development. This equipment consumes large amount of diesel fuel and emits high level of carbon dioxide (CO2. The total emissions are dependent upon the fuel use, and the fuel use is dependent upon the productivity of the equipment. This paper proposes a methodology and tool for estimating CO2 emissions from bulldozer based on the productivity rate. The methodology is formulated by using the result of multiple linear regressions (MLR of CAT’s data for obtaining the productivity model and combined with the EPA’s NONROAD model. The emission factors from NONROAD model were used to quantify the CO2 emissions. To display the function of the model, a case study and sensitivity analysis for a bulldozer’s activity is also presented. MLR results indicate that the productivity model generated from CAT’s data can be used as the basis for quantifying the total CO2 emissions for an earthwork activity.

Pesticide Removal by Combined Ozonation and Granular Activated Carbon Filtration

NARCIS (Netherlands)

Orlandini, E.

1999-01-01

This research aimed to idendfy and understand mechanisms that underlie the beneficial effect of ozonation on removal of pesdcides and other micropoUutants by Granular Activated Carbon (GAC) filtradon. This allows optimization of the combination of these two processes, termed Biological Activated

Combined influence of healthy diet and active lifestyle on cardiovascular disease risk factors in adolescents.

Science.gov (United States)

Cuenca-García, M; Ortega, F B; Ruiz, J R; González-Gross, M; Labayen, I; Jago, R; Martínez-Gómez, D; Dallongeville, J; Bel-Serrat, S; Marcos, A; Manios, Y; Breidenassel, C; Widhalm, K; Gottrand, F; Ferrari, M; Kafatos, A; Molnár, D; Moreno, L A; De Henauw, S; Castillo, M J; Sjöström, M

2014-06-01

To investigate the combined influence of diet quality and physical activity on cardiovascular disease (CVD) risk factors in adolescents, adolescents (n = 1513; 12.5-17.5 years) participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence study were studied. Dietary intake was registered using a 24-h recall and a diet quality index was calculated. Physical activity was assessed by accelerometry. Lifestyle groups were computed as: healthy diet and active, unhealthy diet but active, healthy diet but inactive, and unhealthy diet and inactive. CVD risk factor measurements included cardiorespiratory fitness, adiposity indicators, blood lipid profile, blood pressure, and insulin resistance. A CVD risk score was computed. The healthy diet and active group had a healthier cardiorespiratory profile, fat mass index (FMI), triglycerides, and high-density lipoprotein cholesterol (HDL-C) levels and total cholesterol (TC)/HDL-C ratio (all P ≤ 0.05). Overall, active adolescents showed higher cardiorespiratory fitness, lower FMI, TC/HDL-C ratio, and homeostasis model assessment index and healthier blood pressure than their inactive peers with either healthy or unhealthy diet (all P ≤ 0.05). Healthy diet and active group had healthier CVD risk score compared with the inactive groups (all P ≤ 0.02). Thus, a combination of healthy diet and active lifestyle is associated with decreased CVD risk in adolescents. Moreover, an active lifestyle may reduce the adverse consequences of an unhealthy diet. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Disentangling the Complexity of HGF Signaling by Combining Qualitative and Quantitative Modeling.

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Lorenza A D'Alessandro

2015-04-01

Full Text Available Signaling pathways are characterized by crosstalk, feedback and feedforward mechanisms giving rise to highly complex and cell-context specific signaling networks. Dissecting the underlying relations is crucial to predict the impact of targeted perturbations. However, a major challenge in identifying cell-context specific signaling networks is the enormous number of potentially possible interactions. Here, we report a novel hybrid mathematical modeling strategy to systematically unravel hepatocyte growth factor (HGF stimulated phosphoinositide-3-kinase (PI3K and mitogen activated protein kinase (MAPK signaling, which critically contribute to liver regeneration. By combining time-resolved quantitative experimental data generated in primary mouse hepatocytes with interaction graph and ordinary differential equation modeling, we identify and experimentally validate a network structure that represents the experimental data best and indicates specific crosstalk mechanisms. Whereas the identified network is robust against single perturbations, combinatorial inhibition strategies are predicted that result in strong reduction of Akt and ERK activation. Thus, by capitalizing on the advantages of the two modeling approaches, we reduce the high combinatorial complexity and identify cell-context specific signaling networks.

Combining structure-based pharmacophore modeling, virtual screening, and in silico ADMET analysis to discover novel tetrahydro-quinoline based pyruvate kinase isozyme M2 activators with antitumor activity

Directory of Open Access Journals (Sweden)

Chen C

2014-09-01

Full Text Available Can Chen,1,2,* Ting Wang,1,3,* Fengbo Wu,1,* Wei Huang,4 Gu He,1 Liang Ouyang,1 Mingli Xiang,1 Cheng Peng,4 Qinglin Jiang1,2 1State Key Laboratory of Biotherapy and Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 2College of Pharmacy and the First Affiliated Hospital, Chengdu Medical College, Chengdu, 3Department of Cardiology, Genenal Hospital of Chengdu Military Command, Chengdu, 4State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China*These authors contributed equally to this workAbstract: Compared with normal differentiated cells, cancer cells upregulate the expression of pyruvate kinase isozyme M2 (PKM2 to support glycolytic intermediates for anabolic processes, including the synthesis of nucleic acids, amino acids, and lipids. In this study, a combination of the structure-based pharmacophore modeling and a hybrid protocol of virtual screening methods comprised of pharmacophore model-based virtual screening, docking-based virtual screening, and in silico ADMET (absorption, distribution, metabolism, excretion and toxicity analysis were used to retrieve novel PKM2 activators from commercially available chemical databases. Tetrahydroquinoline derivatives were identified as potential scaffolds of PKM2 activators. Thus, the hybrid virtual screening approach was applied to screen the focused tetrahydroquinoline derivatives embedded in the ZINC database. Six hit compounds were selected from the final hits and experimental studies were then performed. Compound 8 displayed a potent inhibitory effect on human lung cancer cells. Following treatment with Compound 8, cell viability, apoptosis, and reactive oxygen species (ROS production were examined in A549 cells. Finally, we evaluated the effects of Compound 8 on mice xenograft tumor models in vivo. These results may provide important

An Automatic Segmentation Method Combining an Active Contour Model and a Classification Technique for Detecting Polycomb-group Proteinsin High-Throughput Microscopy Images.

Science.gov (United States)

Gregoretti, Francesco; Cesarini, Elisa; Lanzuolo, Chiara; Oliva, Gennaro; Antonelli, Laura

2016-01-01

The large amount of data generated in biological experiments that rely on advanced microscopy can be handled only with automated image analysis. Most analyses require a reliable cell image segmentation eventually capable of detecting subcellular structures.We present an automatic segmentation method to detect Polycomb group (PcG) proteins areas isolated from nuclei regions in high-resolution fluorescent cell image stacks. It combines two segmentation algorithms that use an active contour model and a classification technique serving as a tool to better understand the subcellular three-dimensional distribution of PcG proteins in live cell image sequences. We obtained accurate results throughout several cell image datasets, coming from different cell types and corresponding to different fluorescent labels, without requiring elaborate adjustments to each dataset.

A control oriental model for combined compression-ejector refrigeration system

International Nuclear Information System (INIS)

Liu, Jiapeng; Wang, Lei; Jia, Lei; Li, Zhen; Zhao, Hongxia

2017-01-01

Highlights: • A control oriental model for combined compression-ejector refrigeration system is proposed. • The pressure pulsating phenomenon in the system is investigated based on the model. • The results show that the model can reflect the system performance under variable operating conditions. - Abstract: Combined compression-ejector refrigeration systems have attracted lots of attention in recent years. In order to improve the running stability of the complex refrigeration system, it is necessary to obtain a simple and accuracy mathematical model for system control. In this paper, a control oriental model for combined compression ejector system is proposed. By analyzing the inner relationship between compressor and ejector, a hybrid model is built based on thermodynamic principles and lumped parameter method. Comparing with traditional theoretical models, the model is more suitable for system control due to its simpler structure and less parameters. Then the pressure pulsating phenomenon inside the piping system between compressor and ejector is investigated based on the model. The effectiveness of the proposed model is validated by experimental data. It is shown that the model can reflect the system performance under variable operating conditions.

Experimental design and modelling approach to evaluate efficacy of β-lactam/β-lactamase inhibitor combinations.

Science.gov (United States)

Sy, S K B; Derendorf, H

2017-07-29

A β-lactamase inhibitor (BLI) confers susceptibility of β-lactamase-expressing multidrug resistant (MDR) organisms to the partnering β-lactam (BL). To discuss the experimental design and modelling strategies for two-drug combinations, using ceftazidime- and aztreonam-avibactam combinations, as examples. The information came from several publications on avibactam in vitro time-kill studies and corresponding pharmacodynamic models. The experimental design to optimally gather crucial information from constant-concentration time-kill studies is to use an agile matrix of two-drug concentration combinations that cover 0.25- to 4-fold BL minimum inhibitory concentration (MIC) relative to the BLI concentrations to be tested against the particular isolate. This shifting agile design can save substantial costs and resources, without sacrificing crucial information needed for model development. The complex synergistic BL/BLI interaction is quantitatively explored using a semi-mechanistic pharmacokinetic-pharmacodynamic (PK/PD) mathematical model that accounts for antimicrobial activities in the combination, bacteria-mediated BL degradation and inhibition of BL degradation by BLI. A predictive mathematical formulation for the two-drug killing effects preserves the correlation between the model-derived EC 50 of BL and the BL MIC. The predictive value of PK/PD model is evaluated against external data that were not used for model development, including but not limited to in vitro hollow fibre and in vivo murine infection models. As a framework for translational predictions, the goal of this modelling strategy is to significantly decrease the decision-making time by running clinical trial simulations with MIC-substituted EC 50 function for isolates of comparable susceptibility through established correlation between BL MIC and EC 50 values. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Effects of blood-activating and stasis-removing drugs combined with VEGF gene transfer on angiogenesis in ischemic necrosis of the femoral head.

Science.gov (United States)

Li, Jun-Hui; Wu, Ya-Ling; Ye, Jian-Hong; Ning, Ya-Gong; Yu, Hai-Ying; Peng, Zhong-Jie; Luan, Xiao-Wen

2009-09-01

To observe the promoting effects of blood-activating and stasis-removing Chinese drugs combined with vascular endothelial growth factor (VEGF) gene transfer on angiogenesis in ischemic necrosis of the femoral head. Forty Japanese giant-ear rabbits were randomly divided into a control group, a model group, a Chinese drug group, a gene group, and a combined group. After 8 weeks of treatment, the rate of VEGF positive cell expression in the synovium of the femoral head was measured using the immunohistochemical method, and the number of blood vessels in the femoral head was measured by digital subtraction angiography. The rate of VEGF positive cell expression in the model group was significantly lower than that in the Chinese drug group (P 0.05). Either the blood-activating and stasis-removing Chinese drugs or VEGF gene transfer can promote the angiogenesis and building of collateral circulation for femoral head ischemic necrosis, and the combined therapy with Chinese drugs or VEGF gene transfer may show a better therapeutic effect. The present study provides an experimental basis for clinical application of the combined therapy with the blood-activating and stasis-removing Chinese drugs and VEGF gene transfer.

Renewable Molecular Flasks with NADH Models: Combination of Light-Driven Proton Reduction and Biomimetic Hydrogenation of Benzoxazinones.

Science.gov (United States)

Zhao, Liang; Wei, Jianwei; Lu, Junhua; He, Cheng; Duan, Chunying

2017-07-17

Using small molecules with defined pockets to catalyze chemical transformations resulted in attractive catalytic syntheses that echo the remarkable properties of enzymes. By modulating the active site of a nicotinamide adenine dinucleotide (NADH) model in a redox-active molecular flask, we combined biomimetic hydrogenation with in situ regeneration of the active site in a one-pot transformation using light as a clean energy source. This molecular flask facilitates the encapsulation of benzoxazinones for biomimetic hydrogenation of the substrates within the inner space of the flask using the active sites of the NADH models. The redox-active metal centers provide an active hydrogen source by light-driven proton reduction outside the pocket, allowing the in situ regeneration of the NADH models under irradiation. This new synthetic platform, which offers control over the location of the redox events, provides a regenerating system that exhibits high selectivity and efficiency and is extendable to benzoxazinone and quinoxalinone systems. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Science.gov (United States)

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

2016-01-01

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

In vitro activity and in vivo animal model efficacy of IB-367 alone and in combination with imipenem and colistin against Gram-negative bacteria.

Science.gov (United States)

Simonetti, Oriana; Cirioni, Oscar; Ghiselli, Roberto; Orlando, Fiorenza; Silvestri, Carmela; Mazzocato, Susanna; Kamysz, Wojciech; Kamysz, Elzbieta; Provinciali, Mauro; Giacometti, Andrea; Guerrieri, Mario; Offidani, Annamaria

2014-05-01

The aim of our study was to evaluate the in vitro activity of IB-367 and its bactericidal effect for Pseudomonas aeruginosa and Escherichia coli, associated to a synergic study to test the antibiotic combinations between the peptide and colistin or imipenem. Minimum inhibitory concentrations (MICs), the minimum bactericidal concentrations (MBCs), the synergy test and killing study were carried out to evaluate the IB-367 activity. In the in vivo model, a wound was incised through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 107 colony-forming units of P. aeruginosa and E. coli. For each strain, the study included an infected or not infected group that did not receive any treatment, and five contaminated groups treated with local IB- 367, intraperitoneal imipenem, intraperitoneal colistin, topical IB-367 local plus intraperitoneal imipenem or intraperitoneal colistin. All isolates were inhibited by IB-367 at concentrations of 4-64 mg/l. Killing by IB-367 was shown to be very rapid: its activity on all Gram-negative bacteria was completed within a 40 min exposure period at a concentration of 2 × MIC/l. Synergy was demonstrated when IB-367 was combined with colistin or imipenem. In in vivo studies, the groups treated with topical IB-367 and intraperitoneal colistin showed the best results in terms of bacterial load inhibition either for Pseudomonas or for E. coli. The good in vitro activity and in vivo efficacy, as well as, the synergic interactions with antibiotics suggest that IB-367 is a promising candidate for potential application in the treatment of wound Gram-negative infections. Copyright © 2014 Elsevier Inc. All rights reserved.

Symbolic Processing Combined with Model-Based Reasoning

Science.gov (United States)

James, Mark

2009-01-01

A computer program for the detection of present and prediction of future discrete states of a complex, real-time engineering system utilizes a combination of symbolic processing and numerical model-based reasoning. One of the biggest weaknesses of a purely symbolic approach is that it enables prediction of only future discrete states while missing all unmodeled states or leading to incorrect identification of an unmodeled state as a modeled one. A purely numerical approach is based on a combination of statistical methods and mathematical models of the applicable physics and necessitates development of a complete model to the level of fidelity required for prediction. In addition, a purely numerical approach does not afford the ability to qualify its results without some form of symbolic processing. The present software implements numerical algorithms to detect unmodeled events and symbolic algorithms to predict expected behavior, correlate the expected behavior with the unmodeled events, and interpret the results in order to predict future discrete states. The approach embodied in this software differs from that of the BEAM methodology (aspects of which have been discussed in several prior NASA Tech Briefs articles), which provides for prediction of future measurements in the continuous-data domain.

Pricing Mining Concessions Based on Combined Multinomial Pricing Model

Directory of Open Access Journals (Sweden)

Chang Xiao

2017-01-01

Full Text Available A combined multinomial pricing model is proposed for pricing mining concession in which the annualized volatility of the price of mineral products follows a multinomial distribution. First, a combined multinomial pricing model is proposed which consists of binomial pricing models calculated according to different volatility values. Second, a method is provided to calculate the annualized volatility and the distribution. Third, the value of convenience yields is calculated based on the relationship between the futures price and the spot price. The notion of convenience yields is used to adjust our model as well. Based on an empirical study of a Chinese copper mine concession, we verify that our model is easy to use and better than the model with constant volatility when considering the changing annualized volatility of the price of the mineral product.

A day in the city : using conjoint choice experiments to model urban tourists' choice of activity packages

NARCIS (Netherlands)

Dellaert, B.G.C.; Borgers, A.W.J.; Timmermans, H.J.P.

1995-01-01

This paper introduces and tests a conjoint choice experiment approach to modeling urban tourists' choice of activity packages. The joint logit model is introduced as a tool to model choices between combinations of activities and an experimental design approach is proposed that includes attributes

Combination of Vaccine-Strain Measles and Mumps Viruses Enhances Oncolytic Activity against Human Solid Malignancies.

Science.gov (United States)

Son, Ho Anh; Zhang, LiFeng; Cuong, Bui Khac; Van Tong, Hoang; Cuong, Le Duy; Hang, Ngo Thu; Nhung, Hoang Thi My; Yamamoto, Naoki; Toan, Nguyen Linh

2018-02-07

Oncolytic measles and mumps viruses (MeV, MuV) have a potential for anti-cancer treatment. We examined the anti-tumor activity of MeV, MuV, and MeV-MuV combination (MM) against human solid malignancies (HSM). MeV, MuV, and MM targeted and significantly killed various cancer cell lines of HSM but not normal cells. MM demonstrated a greater anti-tumor effect and prolonged survival in a human prostate cancer xenograft tumor model compared to MeV and MuV. MeV, MuV, and MM significantly induced the expression of immunogenic cell death markers and enhanced spleen-infiltrating immune cells. In conclusion, MM combination significantly improves the treatment of human solid malignancies.

System Identification and Steering Control Characteristic of Rice Combine Harvester Model

Science.gov (United States)

Sutisna, S. P.; Setiawan, R. P. A.; Subrata, I. D. M.; Mandang, T.

2018-05-01

This study is a preliminary research of rice combine harvester trajectory. A vehicle model of rice combine used crawler with differential steering. Turning process of differential steering used speed difference of right and left tracks This study aims to learn of rice combine harvester steering control. In real condition, the hydraulic break on each track produced the speed difference. The model used two DC motors with maximum speed 100 rpm for each tracks. A rotary encoder with resolution 600 pulse/rotation was connected to each DC motors shaft to monitor the speed of tracks and connected to the input shaft of a gearbox with ratio 1:46. The motor speed control for each track used pulse width modulation to produce the speed difference. A gyroscope sensor with resolution 0.01° was used to determine the model orientation angle. Like the real rice combine, the tracks can not rotate to the opposite direction at the same time so it makes the model can not perform the pivot turn. The turn radius of the model was 28 cm and the forward maximum speed was 17.8 cm/s. The model trajectory control used PID odometry controller. Parameters input were the speed of each track and the orientation of the vehicle. The straight line test showed the controller can control the rice combine model trajectory with the average error 0.67 cm.

A Combined Random Forests and Active Contour Model Approach for Fully Automatic Segmentation of the Left Atrium in Volumetric MRI

Directory of Open Access Journals (Sweden)

Chao Ma

2017-01-01

Full Text Available Segmentation of the left atrium (LA from cardiac magnetic resonance imaging (MRI datasets is of great importance for image guided atrial fibrillation ablation, LA fibrosis quantification, and cardiac biophysical modelling. However, automated LA segmentation from cardiac MRI is challenging due to limited image resolution, considerable variability in anatomical structures across subjects, and dynamic motion of the heart. In this work, we propose a combined random forests (RFs and active contour model (ACM approach for fully automatic segmentation of the LA from cardiac volumetric MRI. Specifically, we employ the RFs within an autocontext scheme to effectively integrate contextual and appearance information from multisource images together for LA shape inferring. The inferred shape is then incorporated into a volume-scalable ACM for further improving the segmentation accuracy. We validated the proposed method on the cardiac volumetric MRI datasets from the STACOM 2013 and HVSMR 2016 databases and showed that it outperforms other latest automated LA segmentation methods. Validation metrics, average Dice coefficient (DC and average surface-to-surface distance (S2S, were computed as 0.9227±0.0598 and 1.14±1.205 mm, versus those of 0.6222–0.878 and 1.34–8.72 mm, obtained by other methods, respectively.

Effect of combined activation on the preparation of high porous active carbons from granulated post-consumer polyethyleneterephthalate

International Nuclear Information System (INIS)

Sych, N.V.; Kartel, N.T.; Tsyba, N.N.; Strelko, V.V.

2006-01-01

Activated carbons were prepared from granulated post-consumer PET by combined activation including heat treatment with sulphuric acid (chemical activation) followed by steam activation. The effect of activation time, temperature, impregnation coefficient in the activation process was studied in order to optimize those reception parameters. One of the most important parameter in combined activation of crushed PET was found to be impregnation coefficient. It was defined that the optimal impregnation coefficient is equal 28%. Activation temperature is another variability which has a significant effect on the pore volume evolution. The increasing of activation temperature enhances the surface area and pore volumes of active carbons. The yield of final product which composes of nearly 15% is the factor limited the activation temperature above 800 deg. C. Textural characteristics of the samples were carried out by performing N 2 adsorption isotherm at -196 deg. C. The obtained active carbons were mainly micro- and mesoporous and with BET apparent surface areas of up to 1030 m 2 /g. The adsorption capacity on methylene blue reaches 1.0 mmol/g, the sorption activity on iodine comes to 77%

Combination of Accumulated Motion and Color Segmentation for Human Activity Analysis

Directory of Open Access Journals (Sweden)

Briassouli Alexia

2008-01-01

Full Text Available Abstract The automated analysis of activity in digital multimedia, and especially video, is gaining more and more importance due to the evolution of higher-level video processing systems and the development of relevant applications such as surveillance and sports. This paper presents a novel algorithm for the recognition and classification of human activities, which employs motion and color characteristics in a complementary manner, so as to extract the most information from both sources, and overcome their individual limitations. The proposed method accumulates the flow estimates in a video, and extracts "regions of activity" by processing their higher-order statistics. The shape of these activity areas can be used for the classification of the human activities and events taking place in a video and the subsequent extraction of higher-level semantics. Color segmentation of the active and static areas of each video frame is performed to complement this information. The color layers in the activity and background areas are compared using the earth mover's distance, in order to achieve accurate object segmentation. Thus, unlike much existing work on human activity analysis, the proposed approach is based on general color and motion processing methods, and not on specific models of the human body and its kinematics. The combined use of color and motion information increases the method robustness to illumination variations and measurement noise. Consequently, the proposed approach can lead to higher-level information about human activities, but its applicability is not limited to specific human actions. We present experiments with various real video sequences, from sports and surveillance domains, to demonstrate the effectiveness of our approach.

Combination of Accumulated Motion and Color Segmentation for Human Activity Analysis

Directory of Open Access Journals (Sweden)

Ioannis Kompatsiaris

2008-03-01

Full Text Available The automated analysis of activity in digital multimedia, and especially video, is gaining more and more importance due to the evolution of higher-level video processing systems and the development of relevant applications such as surveillance and sports. This paper presents a novel algorithm for the recognition and classification of human activities, which employs motion and color characteristics in a complementary manner, so as to extract the most information from both sources, and overcome their individual limitations. The proposed method accumulates the flow estimates in a video, and extracts “regions of activity” by processing their higher-order statistics. The shape of these activity areas can be used for the classification of the human activities and events taking place in a video and the subsequent extraction of higher-level semantics. Color segmentation of the active and static areas of each video frame is performed to complement this information. The color layers in the activity and background areas are compared using the earth mover's distance, in order to achieve accurate object segmentation. Thus, unlike much existing work on human activity analysis, the proposed approach is based on general color and motion processing methods, and not on specific models of the human body and its kinematics. The combined use of color and motion information increases the method robustness to illumination variations and measurement noise. Consequently, the proposed approach can lead to higher-level information about human activities, but its applicability is not limited to specific human actions. We present experiments with various real video sequences, from sports and surveillance domains, to demonstrate the effectiveness of our approach.

The ACTIVE conceptual framework as a structural equation model

Science.gov (United States)

Gross, Alden L.; Payne, Brennan R.; Casanova, Ramon; Davoudzadeh, Pega; Dzierzewski, Joseph M.; Farias, Sarah; Giovannetti, Tania; Ip, Edward H.; Marsiske, Michael; Rebok, George W.; Schaie, K. Warner; Thomas, Kelsey; Willis, Sherry; Jones, Richard N.

2018-01-01

Background/Study Context Conceptual frameworks are analytic models at a high level of abstraction. Their operationalization can inform randomized trial design and sample size considerations. Methods The Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) conceptual framework was empirically tested using structural equation modeling (N=2,802). ACTIVE was guided by a conceptual framework for cognitive training in which proximal cognitive abilities (memory, inductive reasoning, speed of processing) mediate treatment-related improvement in primary outcomes (everyday problem-solving, difficulty with activities of daily living, everyday speed, driving difficulty), which in turn lead to improved secondary outcomes (health-related quality of life, health service utilization, mobility). Measurement models for each proximal, primary, and secondary outcome were developed and tested using baseline data. Each construct was then combined in one model to evaluate fit (RMSEA, CFI, normalized residuals of each indicator). To expand the conceptual model and potentially inform future trials, evidence of modification of structural model parameters was evaluated by age, years of education, sex, race, and self-rated health status. Results Preconceived measurement models for memory, reasoning, speed of processing, everyday problem-solving, instrumental activities of daily living (IADL) difficulty, everyday speed, driving difficulty, and health-related quality of life each fit well to the data (all RMSEA .95). Fit of the full model was excellent (RMSEA = .038; CFI = .924). In contrast with previous findings from ACTIVE regarding who benefits from training, interaction testing revealed associations between proximal abilities and primary outcomes are stronger on average by nonwhite race, worse health, older age, and less education (p conceptual model. Findings suggest that the types of people who show intervention effects on cognitive performance potentially may be

The ACTIVE conceptual framework as a structural equation model.

Science.gov (United States)

Gross, Alden L; Payne, Brennan R; Casanova, Ramon; Davoudzadeh, Pega; Dzierzewski, Joseph M; Farias, Sarah; Giovannetti, Tania; Ip, Edward H; Marsiske, Michael; Rebok, George W; Schaie, K Warner; Thomas, Kelsey; Willis, Sherry; Jones, Richard N

2018-01-01

Background/Study Context: Conceptual frameworks are analytic models at a high level of abstraction. Their operationalization can inform randomized trial design and sample size considerations. The Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) conceptual framework was empirically tested using structural equation modeling (N=2,802). ACTIVE was guided by a conceptual framework for cognitive training in which proximal cognitive abilities (memory, inductive reasoning, speed of processing) mediate treatment-related improvement in primary outcomes (everyday problem-solving, difficulty with activities of daily living, everyday speed, driving difficulty), which in turn lead to improved secondary outcomes (health-related quality of life, health service utilization, mobility). Measurement models for each proximal, primary, and secondary outcome were developed and tested using baseline data. Each construct was then combined in one model to evaluate fit (RMSEA, CFI, normalized residuals of each indicator). To expand the conceptual model and potentially inform future trials, evidence of modification of structural model parameters was evaluated by age, years of education, sex, race, and self-rated health status. Preconceived measurement models for memory, reasoning, speed of processing, everyday problem-solving, instrumental activities of daily living (IADL) difficulty, everyday speed, driving difficulty, and health-related quality of life each fit well to the data (all RMSEA .95). Fit of the full model was excellent (RMSEA = .038; CFI = .924). In contrast with previous findings from ACTIVE regarding who benefits from training, interaction testing revealed associations between proximal abilities and primary outcomes are stronger on average by nonwhite race, worse health, older age, and less education (p conceptual model. Findings suggest that the types of people who show intervention effects on cognitive performance potentially may be different from

Monitoring Soil Microbial Activities in Different Cropping Systems Using Combined Methods

Institute of Scientific and Technical Information of China (English)

YUAN Zhimin; LIU Haijun; HAN Jun; SUN Jingjing; WU Xiaoying; YAO Jun

2017-01-01

Cropping activities may affect soil microbial activities and biomass,which would affect C and N cycling in soil and thus the crop yields and quality.In the present study,a combination of microcalorimetric,enzyme activity (sucrase,urease,catalase,and fluorescein diacetate hydrolysis),and real-time polymerase chain reaction (RT-PCR) analyses was used to investigate microbial status of farmland soils,collected from 5 different sites in Huazhong Agriculture University,China.Our results showed that among the 5 sites,both positive and negative impacts of cropping activities on soil microbial activity were observed.Enzyme activity analysis showed that cropping activities reduced soil sucrase and urease activities,which would influence the C and N cycles in soil.Much more attentions should be given to microbial status affected by cropping activities in future.According to the correlation analysis,fluorescein diacetate hydrolysis showed a significantly (P ＜ 0.05) negative correlation with the time to reach the maximum power output (R =--0.898),but a significantly (P ＜ 0.05) positive correlation with bacterial gene copy number (R =0.817).Soil catalase activity also showed a significantly (P ＜ 0.05) positive correlation with bacterial gene copy number (R =0.965).Using combined methods would provide virtual information of soil microbial status.

Urban Saturated Power Load Analysis Based on a Novel Combined Forecasting Model

Directory of Open Access Journals (Sweden)

Huiru Zhao

2015-03-01

Full Text Available Analysis of urban saturated power loads is helpful to coordinate urban power grid construction and economic social development. There are two different kinds of forecasting models: the logistic curve model focuses on the growth law of the data itself, while the multi-dimensional forecasting model considers several influencing factors as the input variables. To improve forecasting performance, a novel combined forecasting model for saturated power load analysis was proposed in this paper, which combined the above two models. Meanwhile, the weights of these two models in the combined forecasting model were optimized by employing a fruit fly optimization algorithm. Using Hubei Province as the example, the effectiveness of the proposed combined forecasting model was verified, demonstrating a higher forecasting accuracy. The analysis result shows that the power load of Hubei Province will reach saturation in 2039, and the annual maximum power load will reach about 78,630 MW. The results obtained from this proposed hybrid urban saturated power load analysis model can serve as a reference for sustainable development for urban power grids, regional economies, and society at large.

The Generalized Hill Model: A Kinematic Approach Towards Active Muscle Contraction

Science.gov (United States)

Menzel, Andreas; Kuhl, Ellen

2014-01-01

Excitation-contraction coupling is the physiological process of converting an electrical stimulus into a mechanical response. In muscle, the electrical stimulus is an action potential and the mechanical response is active contraction. The classical Hill model characterizes muscle contraction though one contractile element, activated by electrical excitation, and two non-linear springs, one in series and one in parallel. This rheology translates into an additive decomposition of the total stress into a passive and an active part. Here we supplement this additive decomposition of the stress by a multiplicative decomposition of the deformation gradient into a passive and an active part. We generalize the one-dimensional Hill model to the three-dimensional setting and constitutively define the passive stress as a function of the total deformation gradient and the active stress as a function of both the total deformation gradient and its active part. We show that this novel approach combines the features of both the classical stress-based Hill model and the recent active-strain models. While the notion of active stress is rather phenomenological in nature, active strain is micro-structurally motivated, physically measurable, and straightforward to calibrate. We demonstrate that our model is capable of simulating excitation-contraction coupling in cardiac muscle with its characteristic features of wall thickening, apical lift, and ventricular torsion. PMID:25221354

Modeling Li I and K I sensitivity to Pleiades activity

NARCIS (Netherlands)

Stuik, R.; Bruls, J.H.M.J.; Rutten, R.J.

1996-01-01

We compare schematic modeling of spots and plage on the surface of cool dwarfs with Pleiades data to assess effects of magnetic activity on the strengths of the L II and K I resonance lines in Pleiades spectra. Comprehensive L II and K I NLTE line formation computation is combined with comparatively

Global emissions and models of photochemically active compounds

International Nuclear Information System (INIS)

Penner, J.E.; Atherton, C.S.; Graedel, T.E.

1993-01-01

Anthropogenic emissions from industrial activity, fossil fuel combustion, and biomass burning are now known to be large enough (relative to natural sources) to perturb the chemistry of vast regions of the troposphere. A goal of the IGAC Global Emissions Inventory Activity (GEIA) is to provide authoritative and reliable emissions inventories on a 1 degree x 1 degree grid. When combined with atmospheric photochemical models, these high quality emissions inventories may be used to predict the concentrations of major photochemical products. Comparison of model results with measurements of pertinent species allows us to understand whether there are major shortcomings in our understanding of tropospheric photochemistry, the budgets and transport of trace species, and their effects in the atmosphere. Through this activity, we are building the capability to make confident predictions of the future consequences of anthropogenic emissions. This paper compares IGAC recommended emissions inventories for reactive nitrogen and sulfur dioxide to those that have been in use previously. We also present results from the three-dimensional LLNL atmospheric chemistry model that show how emissions of anthropogenic nitrogen oxides might potentially affect tropospheric ozone and OH concentrations and how emissions of anthropogenic sulfur increase sulfate aerosol loadings

Model FT631 moisture/density combined gauge

International Nuclear Information System (INIS)

Ji Changsong; Dai Zhude; Zhang Jianguo; Zhang Enshang; Huang Jiling; Meng Qingbao

1990-01-01

Model FT631 Moisture/Density Combined Gauge has been developed, with which both water content and density, the two parameters of measured medium (soil), are obtained in one act of measurement at the same time. A China patent has been taken for this invention

78 FR 24693 - Draft Qualitative Risk Assessment of Risk of Activity/Food Combinations for Activities (Outside...

Science.gov (United States)

2013-04-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 117 [Docket No. FDA-2012-N-1258] Draft Qualitative Risk Assessment of Risk of Activity/Food Combinations for..., and requesting comment on, a document entitled ``Draft Qualitative Risk Assessment of Risk of Activity...

An Analytical Tire Model with Flexible Carcass for Combined Slips

Directory of Open Access Journals (Sweden)

Nan Xu

2014-01-01

Full Text Available The tire mechanical characteristics under combined cornering and braking/driving situations have significant effects on vehicle directional controls. The objective of this paper is to present an analytical tire model with flexible carcass for combined slip situations, which can describe tire behavior well and can also be used for studying vehicle dynamics. The tire forces and moments come mainly from the shear stress and sliding friction at the tread-road interface. In order to describe complicated tire characteristics and tire-road friction, some key factors are considered in this model: arbitrary pressure distribution; translational, bending, and twisting compliance of the carcass; dynamic friction coefficient; anisotropic stiffness properties. The analytical tire model can describe tire forces and moments accurately under combined slip conditions. Some important properties induced by flexible carcass can also be reflected. The structural parameters of a tire can be identified from tire measurements and the computational results using the analytical model show good agreement with test data.

Adaptive rival penalized competitive learning and combined linear predictor model for financial forecast and investment.

Science.gov (United States)

Cheung, Y M; Leung, W M; Xu, L

1997-01-01

We propose a prediction model called Rival Penalized Competitive Learning (RPCL) and Combined Linear Predictor method (CLP), which involves a set of local linear predictors such that a prediction is made by the combination of some activated predictors through a gating network (Xu et al., 1994). Furthermore, we present its improved variant named Adaptive RPCL-CLP that includes an adaptive learning mechanism as well as a data pre-and-post processing scheme. We compare them with some existing models by demonstrating their performance on two real-world financial time series--a China stock price and an exchange-rate series of US Dollar (USD) versus Deutschmark (DEM). Experiments have shown that Adaptive RPCL-CLP not only outperforms the other approaches with the smallest prediction error and training costs, but also brings in considerable high profits in the trading simulation of foreign exchange market.

Electricity Price Forecast Using Combined Models with Adaptive Weights Selected and Errors Calibrated by Hidden Markov Model

Directory of Open Access Journals (Sweden)

Da Liu

2013-01-01

Full Text Available A combined forecast with weights adaptively selected and errors calibrated by Hidden Markov model (HMM is proposed to model the day-ahead electricity price. Firstly several single models were built to forecast the electricity price separately. Then the validation errors from every individual model were transformed into two discrete sequences: an emission sequence and a state sequence to build the HMM, obtaining a transmission matrix and an emission matrix, representing the forecasting ability state of the individual models. The combining weights of the individual models were decided by the state transmission matrixes in HMM and the best predict sample ratio of each individual among all the models in the validation set. The individual forecasts were averaged to get the combining forecast with the weights obtained above. The residuals of combining forecast were calibrated by the possible error calculated by the emission matrix of HMM. A case study of day-ahead electricity market of Pennsylvania-New Jersey-Maryland (PJM, USA, suggests that the proposed method outperforms individual techniques of price forecasting, such as support vector machine (SVM, generalized regression neural networks (GRNN, day-ahead modeling, and self-organized map (SOM similar days modeling.

Traditional, Cyber and Combined Bullying Roles: Differences in Risky Online and Offline Activities

Directory of Open Access Journals (Sweden)

Sebastian Wachs

2015-02-01

Full Text Available This study (1 reports frequency rates of mutually exclusive traditional, cyber and combined (both traditional and cyber bullying roles; and (2 investigates whether adolescents belonging to particular bullying roles show higher levels of involvement in risky online activities (Compulsive Internet Use (CIU, online grooming victimization, and sexting and risky offline activities (bad behavior in school, drinking alcohol and truancy than non-involved adolescents. The sample comprised self-reports of 1928 German, Dutch and Thai adolescents (Age = 12–18; M = 14.52; SD = 1.6. The results revealed age, sex and country differences in bullying frequency rates. CIU, sending of sexts and risky offline activities were most strongly associated with combined bully-victims. The receiving of sexts was most strongly associated with combined bullies; and online grooming victimization was most strongly related to cyber bully-victims. Another important finding is that the associations between risky offline activities and combined bullying are stronger than for traditional and cyber bullying. The findings contribute to better understanding of the associations between varying bullying roles and risky online and offline activities among adolescents. In sum, the results underscore the need to promote life skills rather than adopting more conventional approaches, which focus almost exclusively on reduction of risks.

Synergistic Role of Balanced Scorecard/Activity Based Costing and Goal Programming Combined Model on Strategic Cost Management

OpenAIRE

Taleghani, Mohammad

2017-01-01

During the past few years, we have seen a significant shift in cost accounting and management. In the new business environment, cost management has become a critical skill, but it is not sufficient for simply reducing costs; instead, costs must be managed strategically. Application of a successful Strategic Cost Management (StraCM) system plays the significant role in success of organization performance. In this study, we want to illustrate how the goal programming model in combination with t...

Where and what TMS activates: Experiments and modeling.

Science.gov (United States)

Laakso, Ilkka; Murakami, Takenobu; Hirata, Akimasa; Ugawa, Yoshikazu

Despite recent developments in navigation and modeling techniques, the type and location of the structures that are activated by transcranial magnetic stimulation (TMS) remain unknown. We studied the relationships between electrophysiological measurements and electric fields induced in the brain to locate the TMS activation site. The active and resting motor thresholds of the first dorsal interosseous muscle were recorded in 19 subjects (7 female, 12 male, age 22 ± 4 years) using anteromedially oriented monophasic TMS at multiple locations over the left primary motor cortex (M1). Structural MR images were used to construct electric field models of each subject's head and brain. The cortical activation site was estimated by finding where the calculated electric fields best explained the coil-location dependency of the measured MTs. The experiments and modeling showed individual variations both in the measured motor thresholds (MTs) and in the computed electric fields. When the TMS coil was moved on the scalp, the calculated electric fields in the hand knob region were shown to vary consistently with the measured MTs. Group-level analysis indicated that the electric fields were significantly correlated with the measured MTs. The strongest correlations (R 2  = 0.69), which indicated the most likely activation site, were found in the ventral and lateral part of the hand knob. The site was independent of voluntary contractions of the target muscle. The study showed that TMS combined with personalized electric field modeling can be used for high-resolution mapping of the motor cortex. Copyright © 2017 Elsevier Inc. All rights reserved.

Behavioral phenotypes in schizophrenic animal models with multiple combinations of genetic and environmental factors.

Science.gov (United States)

Hida, Hirotake; Mouri, Akihiro; Noda, Yukihiro

2013-01-01

Schizophrenia is a multifactorial psychiatric disorder in which both genetic and environmental factors play a role. Genetic [e.g., Disrupted-in-schizophrenia 1 (DISC1), Neuregulin-1 (NRG1)] and environmental factors (e.g., maternal viral infection, obstetric complications, social stress) may act during the developmental period to increase the incidence of schizophrenia. In animal models, interactions between susceptibility genes and the environment can be controlled in ways not possible in humans; therefore, such models are useful for investigating interactions between or within factors in the pathogenesis and pathophysiology of schizophrenia. We provide an overview of schizophrenic animal models investigating interactions between or within factors. First, we reviewed gene-environment interaction animal models, in which schizophrenic candidate gene mutant mice were subjected to perinatal immune activation or adolescent stress. Next, environment-environment interaction animal models, in which mice were subjected to a combination of perinatal immune activation and adolescent administration of drugs, were described. These animal models showed interaction between or within factors; behavioral changes, which were obscured by each factor, were marked by interaction of factors and vice versa. Appropriate behavioral approaches with such models will be invaluable for translational research on novel compounds, and also for providing insight into the pathogenesis and pathophysiology of schizophrenia.

Antipityrosporum Ovale Activity Of A Herbal Drug Combination Of Wrightia Tinctoria And Hisbiscus Rosasinensis

Directory of Open Access Journals (Sweden)

Kirshnamoorthy J R

2000-01-01

Full Text Available Antipityosporum activity of a herbal drug combination of Wrighria tinctoria and Hibiscus rosasinensis was tested in vitro against the isolates of Pityrosporum ovale recovered from dandruff. The drug combination exhibited fungicidal activity at a concentration ranging between 500 to1000 pg/ml.

[Evaluation of effects of combination intervention model to men who have sex with men].

Science.gov (United States)

Tan, Jing-guang; Cheng, Jin-quan; Lu, Zu-xun

2012-08-01

This study aimed to explore and evaluate the effects of combination intervention model conducted by Center for Disease Control and Prevention and activity place to men who have sex with men (MSM). To implement one-year combination intervention in 4 MSM venues during May, 2009 and April, 2010. Meanwhile, 3 similar MSM venues were chosen as control. MSM places introduced CDC to consumption crowds. Experts and volunteers sent by CDC undertook health education programme on site and condom, lubricant, pamphlet, consultation, test were provided at the same time. The intervention measures applied to control only included providing pamphlet, condom, lubricant by volunteers. Investigations were conducted among subjects of combination intervention group and control group before (111, 120 subjects) and after (105, 98 subjects) the intervention with questions related to knowledge and behavior of AIDS prevention. After one-year intervention, among MSM with combination intervention, the awareness rate of knowledge level about acquired immune deficiency syndrome (AIDS) increased from 73.0% (81/111) to 91.7% (110/120), proportion of condom-use with male at last anal intercourse increased from 73.0% (81/111) to 85.0% (102/120), ratio of never-use condom with male decreased from 10.8% (11/102) to 1.7% (2/112), percentage of acquiring AIDS-related service and intervention improved significantly, acquiring condom (lubricant) increased from 70.3% (78/111) to 85.0% (102/120), acquiring peer education increased from 10.8% (12/111) to 24.2% (29/120), the proportion of acquiring counseling and testing of HIV increased from 69.4% (77/111) to 90.8% (109/120) (all P values 0.05) in control MSM venues. Combination intervention model was an effective intervention model contributing to an increase in knowledge of AIDS prevention and decreasing high risk behavior in MSM population.

Active illumination and appearance model for face alignment

DEFF Research Database (Denmark)

Kahraman, Fatih; Gokmen, M.; Darkner, Sune

2010-01-01

Illumination conditions have an explicit effect on the performance of face recognition systems. In particular, varying the illumination upon the face imposes such, complex effects that the identification often fails to provide a stable performance level. In this paper, we propose an approach......, integrating face identity and illumination models in order to reach acceptable and stable face recognition rates. For this purpose, Active Appearance Model (A AM) and illumination model of faces are combined in order to obtain an illumination invariant face localization. The proposed method is an integrated......, is sufficient. There is no need to build complex models for illumination. As a result, this paper has presented a simple and efficient method for face modeling and face alignment in order to increase the performance of face localization by means of the proposed illumination invariant AIA method for face...

Functional copmponents produced by multi-jet modelling combined with electroforming and machining

Directory of Open Access Journals (Sweden)

Baier, Oliver

2014-08-01

Full Text Available In fuel cell technology, certain components are used that are responsible for guiding liquid media. When these components are produced by conventional manufacturing, there are often sealing issues, and trouble- and maintenance-free deployment cannot be ensured. Against this background, a new process combination has been developed in a joint project between the University of Duisburg-Essen, the Center for Fuel Cell Technology (ZBT, and the company Galvano-T electroplating forming GmbH. The approach is to combine multi-jet modelling (MJM, electroforming and milling in order to produce a defined external geometry. The wax models are generated on copper base plates and copper-coated to a desirable thickness. Following this, the undefined electroplated surfaces are machined to achieve the desired measurement, and the wax is melted out. This paper presents, first, how this process is technically feasible, then describes how the MJM on a 3-D Systems ThermoJet was adapted to stabilise the process.In the AiF-sponsored ZIM project, existing limits and possibilities are shown and different approaches of electroplating are investigated. This paper explores whether or not activation of the wax structure by a conductive initial layer is required. Using the described process chain, different parts were built: a heat exchanger, a vaporiser, and a reformer (in which pellets were integrated in an intermediate step. In addition, multiple-layer parts with different functions were built by repeating the process combination several times.

Research on NC laser combined cutting optimization model of sheet metal parts

Science.gov (United States)

Wu, Z. Y.; Zhang, Y. L.; Li, L.; Wu, L. H.; Liu, N. B.

2017-09-01

The optimization problem for NC laser combined cutting of sheet metal parts was taken as the research object in this paper. The problem included two contents: combined packing optimization and combined cutting path optimization. In the problem of combined packing optimization, the method of “genetic algorithm + gravity center NFP + geometric transformation” was used to optimize the packing of sheet metal parts. In the problem of combined cutting path optimization, the mathematical model of cutting path optimization was established based on the parts cutting constraint rules of internal contour priority and cross cutting. The model played an important role in the optimization calculation of NC laser combined cutting.

The comparative analysis of antiparkinsonian activity of glycine combined with amantadine in conditions of changing neurosynaptic transmission

Directory of Open Access Journals (Sweden)

Mamchur V.I.

2017-10-01

Full Text Available Parkinson's disease is traditionally viewed as a disease which affects the human motor sphere. Besides motor manifestations in the clinical picture of the disease, non-motor manifestations with dementia as the most common are present. The purpose of the work – experimental evaluation of the possible antiparkinsonian action of glycine in terms of experimental models of Parkinson's disease equivalents (akinetic-rigid and tremor forms on the background of antiparkinsonian correction by amantadine. Methods: catalepsy model (inhibition of dopaminergic transmission, equivalents of hypokinesia and rigidity states and model of arekolyn tremor (activation of cholinergic transmission that corresponds to parkinsonian tremor on the background of amantadine administration (50 mg/kg, glycine (100 mg/kg and 200 mg/kg and their combined introduction. The research results show a positive dynamic in combined using of amantadine with glycine at a dose of 100 mg/kg and 200 mg/kg, which was is determined by the low percentage of animals with symptoms of catalepsy (50-70% with evaluation criteria of 0.5-1.8 points with maximum possible 6 points. Similar results were obtained in terms of activation of the cholinergic system (arekolyn tremor. Glycine at a dose of 100 mg/kg and 200 mg/kg facilitated to optimization of antitremor action of amantadine, that is registered in increased latent period of tremor, reduction of its duration and intensity attenuation almost by 2,1 times in comparison with indicators of the control group. Thus, studied combinations of amantadine with glycine at a dose of 100 mg/kg and 200 mg/kg are promising in studying of their influence on dementia in Parkinson's syndrome, and this study will be continued.

Optimizing Combinations of Flavonoids Deriving from Astragali Radix in Activating the Regulatory Element of Erythropoietin by a Feedback System Control Scheme

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Hui Yu

2013-01-01

Full Text Available Identifying potent drug combination from a herbal mixture is usually quite challenging, due to a large number of possible trials. Using an engineering approach of the feedback system control (FSC scheme, we identified the potential best combinations of four flavonoids, including formononetin, ononin, calycosin, and calycosin-7-O-β-D-glucoside deriving from Astragali Radix (AR; Huangqi, which provided the best biological action at minimal doses. Out of more than one thousand possible combinations, only tens of trials were required to optimize the flavonoid combinations that stimulated a maximal transcriptional activity of hypoxia response element (HRE, a critical regulator for erythropoietin (EPO transcription, in cultured human embryonic kidney fibroblast (HEK293T. By using FSC scheme, 90% of the work and time can be saved, and the optimized flavonoid combinations increased the HRE mediated transcriptional activity by ~3-fold as compared with individual flavonoid, while the amount of flavonoids was reduced by ~10-fold. Our study suggests that the optimized combination of flavonoids may have strong effect in activating the regulatory element of erythropoietin at very low dosage, which may be used as new source of natural hematopoietic agent. The present work also indicates that the FSC scheme is able to serve as an efficient and model-free approach to optimize the drug combination of different ingredients within a herbal decoction.

Combining SKU-level sales forecasts from models and experts

NARCIS (Netherlands)

Ph.H.B.F. Franses (Philip Hans); R. Legerstee (Rianne)

2009-01-01

textabstractWe study the performance of SKU-level sales forecasts which linearly combine statistical model forecasts and expert forecasts. Using a large and unique database containing model forecasts for monthly sales of various pharmaceutical products and forecasts given by about fifty experts, we

Combination of PKCε Activation and PTP1B Inhibition Effectively Suppresses Aβ-Induced GSK-3β Activation and Tau Phosphorylation.

Science.gov (United States)

Kanno, Takeshi; Tsuchiya, Ayako; Tanaka, Akito; Nishizaki, Tomoyuki

2016-09-01

Glycogen synthase kinase-3β (GSK-3β) is a key element to phosphorylate tau and form neurofibrillary tangles (NFTs) found in tauopathies including Alzheimer's disease (AD). A current topic for AD therapy is focused upon how to prevent tau phosphorylation. In the present study, PKCε activated Akt and inactivated GSK-3β by directly interacting with each protein. Inhibition of protein tyrosine phosphatase 1B (PTP1B), alternatively, caused an enhancement in the tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), allowing activation of Akt through a pathway along an IRS-1/phosphatidylinositol 3 kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1 (PDK1)/Akt axis, to phosphorylate and inactivate GSK-3β. Combination of PKCε activation and PTP1B inhibition more sufficiently activated Akt and inactivated GSK-3β than each independent treatment, to suppress amyloid β (Aβ)-induced tau phosphorylation and ameliorate spatial learning and memory impairment in 5xFAD transgenic mice, an animal model of AD. This may represent an innovative strategy for AD therapy.

A combined Fisher and Laplacian score for feature selection in QSAR based drug design using compounds with known and unknown activities.

Science.gov (United States)

Valizade Hasanloei, Mohammad Amin; Sheikhpour, Razieh; Sarram, Mehdi Agha; Sheikhpour, Elnaz; Sharifi, Hamdollah

2018-02-01

Quantitative structure-activity relationship (QSAR) is an effective computational technique for drug design that relates the chemical structures of compounds to their biological activities. Feature selection is an important step in QSAR based drug design to select the most relevant descriptors. One of the most popular feature selection methods for classification problems is Fisher score which aim is to minimize the within-class distance and maximize the between-class distance. In this study, the properties of Fisher criterion were extended for QSAR models to define the new distance metrics based on the continuous activity values of compounds with known activities. Then, a semi-supervised feature selection method was proposed based on the combination of Fisher and Laplacian criteria which exploits both compounds with known and unknown activities to select the relevant descriptors. To demonstrate the efficiency of the proposed semi-supervised feature selection method in selecting the relevant descriptors, we applied the method and other feature selection methods on three QSAR data sets such as serine/threonine-protein kinase PLK3 inhibitors, ROCK inhibitors and phenol compounds. The results demonstrated that the QSAR models built on the selected descriptors by the proposed semi-supervised method have better performance than other models. This indicates the efficiency of the proposed method in selecting the relevant descriptors using the compounds with known and unknown activities. The results of this study showed that the compounds with known and unknown activities can be helpful to improve the performance of the combined Fisher and Laplacian based feature selection methods.

A combined Preisach–Hyperbolic Tangent model for magnetic hysteresis of Terfenol-D

Energy Technology Data Exchange (ETDEWEB)

Talebian, Soheil [Department of Mechanical Engineering, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Hojjat, Yousef, E-mail: yhojjat@modares.ac.ir [Department of Mechanical Engineering, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Ghodsi, Mojtaba [Department of Mechanical and Industrial Engineering, Sultan Qaboos University, Muscat (Oman); Karafi, Mohammad Reza [Department of Mechanical Engineering, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Mirzamohammadi, Shahed [Department of Mechanical Engineering, Shahid Rajaee University, Tehran (Iran, Islamic Republic of)

2015-12-15

This study presents a new model using the combination of Preisach and Hyperbolic Tangent models, to predict the magnetic hysteresis of Terfenol-D at different frequencies. Initially, a proper experimental setup was fabricated and used to obtain different magnetic hysteresis curves of Terfenol-D; such as major, minor and reversal loops. Then, it was shown that the Hyperbolic Tangent model is precisely capable of modeling the magnetic hysteresis of the Terfenol-D for both rate-independent and rate-dependent cases. Empirical equations were proposed with respect to magnetic field frequency which can calculate the non-dimensional coefficients needed by the model. These empirical equations were validated at new frequencies of 100 Hz and 300 Hz. Finally, the new model was developed through the combination of Preisach and Hyperbolic Tangent models. In the combined model, analytical relations of the Hyperbolic Tangent model for the first order reversal loops determined the weighting function of the Preisach model. This model reduces the required experiments and errors due to numerical differentiations generally needed for characterization of the Preisach function. In addition, it can predict the rate-dependent hysteresis as well as rate-independent hysteresis. - Highlights: • Different hysteresis curves of Terfenol-D are experimentally obtained at 0–200 Hz. • A new model is presented using combination of Preisach and Hyperbolic Tangent models. • The model predicts both rate-independent and rate-dependent hystereses of Terfenol-D. • The analytical model reduces the numerical errors and number of required experiments.

Combination strategies for pandemic influenza response - a systematic review of mathematical modeling studies

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Lee Vernon J

2009-12-01

Full Text Available Abstract Background Individual strategies in pandemic preparedness plans may not reduce the impact of an influenza pandemic. Methods We searched modeling publications through PubMed and associated references from 1990 to 30 September 2009. Inclusion criteria were modeling papers quantifying the effectiveness of combination strategies, both pharmaceutical and non-pharmaceutical. Results Nineteen modeling papers on combination strategies were selected. Four studies examined combination strategies on a global scale, 14 on single countries, and one on a small community. Stochastic individual-based modeling was used in nine studies, stochastic meta-population modeling in five, and deterministic compartmental modeling in another five. As part of combination strategies, vaccination was explored in eight studies, antiviral prophylaxis and/or treatment in 16, area or household quarantine in eight, case isolation in six, social distancing measures in 10 and air travel restriction in six studies. Two studies suggested a high probability of successful influenza epicenter containment with combination strategies under favorable conditions. During a pandemic, combination strategies delayed spread, reduced overall number of cases, and delayed and reduced peak attack rate more than individual strategies. Combination strategies remained effective at high reproductive numbers compared with single strategy. Global cooperative strategies, including redistribution of antiviral drugs, were effective in reducing the global impact and attack rates of pandemic influenza. Conclusion Combination strategies increase the effectiveness of individual strategies. They include pharmaceutical (antiviral agents, antibiotics and vaccines and non-pharmaceutical interventions (case isolation, quarantine, personal hygiene measures, social distancing and travel restriction. Local epidemiological and modeling studies are needed to validate efficacy and feasibility.

21 CFR 352.20 - Permitted combinations of active ingredients.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Permitted combinations of active ingredients. 352.20 Section 352.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... effective date was stayed until further notice. For the convenience of the user, the text is set forth as...

Combined effects of water temperature and copper ion concentration on catalase activity in Crassostrea ariakensis

Science.gov (United States)

Wang, Hui; Yang, Hongshuai; Liu, Jiahui; Li, Yanhong; Liu, Zhigang

2015-07-01

A central composite experimental design and response surface method were used to investigate the combined effects of water temperature (18-34°C) and copper ion concentration (0.1-1.5 mg/L) on the catalase (CAT) activity in the digestive gland of Crassostrea ariakensis. The results showed that the linear effects of temperature were significant ( P0.05), and the quadratic effects of copper ion concentration were significant ( P0.05), and the effect of temperature was greater than that of copper ion concentration. A model equation of CAT enzyme activity in the digestive gland of C. ariakensis toward the two factors of interest was established, with R 2, Adj. R 2 and Pred. R 2 values as high as 0.943 7, 0.887 3 and 0.838 5, respectively. These findings suggested that the goodness of fit to experimental data and predictive capability of the model were satisfactory, and could be practically applied for prediction under the conditions of the study. Overall, the results suggest that the simultaneous variation of temperature and copper ion concentration alters the activity of the antioxidant enzyme CAT by modulating active oxygen species metabolism, which may be utilized as a biomarker to detect the effects of copper pollution.

21 CFR 333.320 - Permitted combinations of active ingredients.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Permitted combinations of active ingredients. 333.320 Section 333.320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Note: At 75 FR 9776, Mar. 4, 2010, § 333.320 was revised, effective Mar. 4, 2011. For the convenience...

A joint calibration model for combining predictive distributions

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Patrizia Agati

2013-05-01

Full Text Available In many research fields, as for example in probabilistic weather forecasting, valuable predictive information about a future random phenomenon may come from several, possibly heterogeneous, sources. Forecast combining methods have been developed over the years in order to deal with ensembles of sources: the aim is to combine several predictions in such a way to improve forecast accuracy and reduce risk of bad forecasts.In this context, we propose the use of a Bayesian approach to information combining, which consists in treating the predictive probability density functions (pdfs from the individual ensemble members as data in a Bayesian updating problem. The likelihood function is shown to be proportional to the product of the pdfs, adjusted by a joint “calibration function” describing the predicting skill of the sources (Morris, 1977. In this paper, after rephrasing Morris’ algorithm in a predictive context, we propose to model the calibration function in terms of bias, scale and correlation and to estimate its parameters according to the least squares criterion. The performance of our method is investigated and compared with that of Bayesian Model Averaging (Raftery, 2005 on simulated data.

Recognizing stationary and locomotion activities using combinational of spectral analysis with statistical descriptors features

Science.gov (United States)

Zainudin, M. N. Shah; Sulaiman, Md Nasir; Mustapha, Norwati; Perumal, Thinagaran

2017-10-01

Prior knowledge in pervasive computing recently garnered a lot of attention due to its high demand in various application domains. Human activity recognition (HAR) considered as the applications that are widely explored by the expertise that provides valuable information to the human. Accelerometer sensor-based approach is utilized as devices to undergo the research in HAR since their small in size and this sensor already build-in in the various type of smartphones. However, the existence of high inter-class similarities among the class tends to degrade the recognition performance. Hence, this work presents the method for activity recognition using our proposed features from combinational of spectral analysis with statistical descriptors that able to tackle the issue of differentiating stationary and locomotion activities. The noise signal is filtered using Fourier Transform before it will be extracted using two different groups of features, spectral frequency analysis, and statistical descriptors. Extracted signal later will be classified using random forest ensemble classifier models. The recognition results show the good accuracy performance for stationary and locomotion activities based on USC HAD datasets.

Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings.

Science.gov (United States)

Schmid, Florian; Wachsmuth, Lydia; Schwalm, Miriam; Prouvot, Pierre-Hugues; Jubal, Eduardo Rosales; Fois, Consuelo; Pramanik, Gautam; Zimmer, Claus; Faber, Cornelius; Stroh, Albrecht

2016-11-01

Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca 2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca 2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca 2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca 2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping. © The Author(s) 2015.

Assessing sensory versus optogenetic network activation by combining (o)fMRI with optical Ca2+ recordings

Science.gov (United States)

Schmid, Florian; Wachsmuth, Lydia; Schwalm, Miriam; Prouvot, Pierre-Hugues; Jubal, Eduardo Rosales; Fois, Consuelo; Pramanik, Gautam; Zimmer, Claus; Stroh, Albrecht

2015-01-01

Encoding of sensory inputs in the cortex is characterized by sparse neuronal network activation. Optogenetic stimulation has previously been combined with fMRI (ofMRI) to probe functional networks. However, for a quantitative optogenetic probing of sensory-driven sparse network activation, the level of similarity between sensory and optogenetic network activation needs to be explored. Here, we complement ofMRI with optic fiber-based population Ca2+ recordings for a region-specific readout of neuronal spiking activity in rat brain. Comparing Ca2+ responses to the blood oxygenation level-dependent signal upon sensory stimulation with increasing frequencies showed adaptation of Ca2+ transients contrasted by an increase of blood oxygenation level-dependent responses, indicating that the optical recordings convey complementary information on neuronal network activity to the corresponding hemodynamic response. To study the similarity of optogenetic and sensory activation, we quantified the density of cells expressing channelrhodopsin-2 and modeled light propagation in the tissue. We estimated the effectively illuminated volume and numbers of optogenetically stimulated neurons, being indicative of sparse activation. At the functional level, upon either sensory or optogenetic stimulation we detected single-peak short-latency primary Ca2+ responses with similar amplitudes and found that blood oxygenation level-dependent responses showed similar time courses. These data suggest that ofMRI can serve as a representative model for functional brain mapping. PMID:26661247

Improved working memory following novel combinations of physical and cognitive activity.

Science.gov (United States)

Langdon, Kristopher D; Corbett, Dale

2012-06-01

In humans, retrospective studies suggest that habitual physical activity (PA) or cognitive activity (CA) can help maintain or improve cognitive function. Similar findings have been reported using physical exercise in animal studies; however, the exercise paradigms differ markedly in duration and frequency, making extrapolation difficult. Here, the authors present a novel PA and CA paradigm that combines voluntary wheel running with Hebb-Williams and radial arm maze (RAM) training. A total of 57 male Sprague-Dawley rats were divided into 4 treatment groups: the PA, CA, and combined PA and CA groups and sedentary controls. PA (voluntary wheel running) and CA (Hebb-Williams mazes) consisted of a moderate 2 h/d, 5 d/wk treatment paradigm. Animals exposed to a combination of PA and CA made significantly fewer working memory errors and exhibited superior choice accuracy when compared with animals exposed to either PA or CA alone in the 8-arm baited configuration of the RAM. Additional analyses revealed that the cognitive improvements were independent of exercise intensity/duration. Assessment of brain-derived neurotrophic factor (BDNF) levels revealed a significant increase in hippocampal BDNF only in the PA-alone group. A novel combination of PA and CA improves learning and memory abilities independent of activity intensity, BDNF, or phosphorylated cyclic AMP response element binding protein levels. This is the first report of significant changes in cognitive ability using a paradigm involving moderate levels of PA plus cognitive stimulation. An adaptation of this paradigm may be particularly beneficial in slowing the development of mild cognitive impairment and subsequent dementia in elderly people.

Combining the pan-aurora kinase inhibitor AMG 900 with histone deacetylase inhibitors enhances antitumor activity in prostate cancer

International Nuclear Information System (INIS)

Paller, Channing J; Wissing, Michel D; Mendonca, Janet; Sharma, Anup; Kim, Eugene; Kim, Hea-Soo; Kortenhorst, Madeleine S Q; Gerber, Stephanie; Rosen, Marc; Shaikh, Faraz; Zahurak, Marianna L; Rudek, Michelle A; Hammers, Hans; Rudin, Charles M; Carducci, Michael A; Kachhap, Sushant K

2014-01-01

Histone deacetylase inhibitors (HDACIs) are being tested in clinical trials for the treatment of solid tumors. While most studies have focused on the reexpression of silenced tumor suppressor genes, a number of genes/pathways are downregulated by HDACIs. This provides opportunities for combination therapy: agents that further disable these pathways through inhibition of residual gene function are speculated to enhance cell death in combination with HDACIs. A previous study from our group indicated that mitotic checkpoint kinases such as PLK1 and Aurora A are downregulated by HDACIs. We used in vitro and in vivo xenograft models of prostate cancer (PCA) to test whether combination of HDACIs with the pan-aurora kinase inhibitor AMG 900 can synergistically or additively kill PCA cells. AMG 900 and HDACIs synergistically decreased cell proliferation activity and clonogenic survival in DU-145, LNCaP, and PC3 PCA cell lines compared to single-agent treatment. Cellular senescence, polyploidy, and apoptosis was significantly increased in all cell lines after combination treatment. In vivo xenograft studies indicated decreased tumor growth and decreased aurora B kinase activity in mice treated with low-dose AMG 900 and vorinostat compared to either agent alone. Pharmacodynamics was assessed by scoring for phosphorylated histone H3 through immunofluorescence. Our results indicate that combination treatment with low doses of AMG 900 and HDACIs could be a promising therapy for future clinical trials against PCA

Regorafenib (BAY 73-4506): antitumor and antimetastatic activities in preclinical models of colorectal cancer.

Science.gov (United States)

Schmieder, Roberta; Hoffmann, Jens; Becker, Michael; Bhargava, Ajay; Müller, Tina; Kahmann, Nicole; Ellinghaus, Peter; Adams, Robert; Rosenthal, André; Thierauch, Karl-Heinz; Scholz, Arne; Wilhelm, Scott M; Zopf, Dieter

2014-09-15

Regorafenib, a novel multikinase inhibitor, has recently demonstrated overall survival benefits in metastatic colorectal cancer (CRC) patients. Our study aimed to gain further insight into the molecular mechanisms of regorafenib and to assess its potential in combination therapy. Regorafenib was tested alone and in combination with irinotecan in patient-derived (PD) CRC models and a murine CRC liver metastasis model. Mechanism of action was investigated using in vitro functional assays, immunohistochemistry and correlation with CRC-related oncogenes. Regorafenib demonstrated significant inhibition of growth-factor-mediated vascular endothelial growth factor receptor (VEGFR) 2 and VEGFR3 autophosphorylation, and intracellular VEGFR3 signaling in human umbilical vascular endothelial cells (HuVECs) and lymphatic endothelial cells (LECs), and also blocked migration of LECs. Furthermore, regorafenib inhibited proliferation in 19 of 25 human CRC cell lines and markedly slowed tumor growth in five of seven PD xenograft models. Combination of regorafenib with irinotecan significantly delayed tumor growth after extended treatment in four xenograft models. Reduced CD31 staining indicates that the antiangiogenic effects of regorafenib contribute to its antitumor activity. Finally, regorafenib significantly delayed disease progression in a murine CRC liver metastasis model by inhibiting the growth of established liver metastases and preventing the formation of new metastases in other organs. In addition, our results suggest that regorafenib displays antimetastatic activity, which may contribute to its efficacy in patients with metastatic CRC. Combination of regorafenib and irinotecan demonstrated an increased antitumor effect and could provide a future treatment option for CRC patients. © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

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Herrera Maria

2006-04-01

Full Text Available Abstract Background Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG in vitro. Methods and results TG was quantified by time parameters: lag time (LT and time to peak (TTP, and by amount of TG: peak of TG (PTG and area under thrombin formation curve after 35 minutes (AUC→35min in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA, ADP, and collagen (Col. In addition, the effects of recombinant activated FVII (rFVIIa alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p 35min were significantly increased (p 35min (but not PTG when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. Conclusion Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis.

Research of combination model for prediction of the trend of outbreak of hepatitis B

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Yin-ping CHEN

2014-03-01

Full Text Available Objective　To establish a combination model of autoregressive integrated moving average model and the grey dynamics (ARIMA-GM of hepatitis B incidence rate (1/100 000 to predict the trend of outbreak of hepatitis B, as to provide a scientific basis for the early discovery of the infectious diseases for the performance of countermeasures of controlling its spread. Methods　The monthly incidence of hepatitis B in Qian'an city, Hebei province, was collected from Jan 2004 to Dec 2012, and a model (ARIMA was reproduced with SPSS software. The GM (1,1 model was used to correct the residual sequence with a threshold value, and a combined forecasting model was reproduced. This combination model was used to predict the monthly incidence rate in this city in 2013. Results　The model ARIMA(0,1,1(0,1,112 was established successfully and the residual sequence was a white noise sequence. Then the GM (1,1 model with a threshold of 3 was used to correct its residuals and obtain its nonlinear feature extraction of information. The forecasting model met required precision standards (C=0.673, P=0.877, the fitting accuracy of which was basically qualified. The results showed that the MAE, MAPE of the ARIMA-GM combined model were smaller than that of a single model, and the combined model could improve the prediction accuracy. Using the combined model to forecast the incidence of hepatitis B during Jan 2013 to Dec 2013, the overall trend was relatively consistent with the condition of previous years. Conclusion　The ARIMA-GM combined model can better fit the incidence rate of hepatitis B with a greater accuracy than the seasonal ARIMA model. The prediction results can provide the reference for the early warning system of HBV. DOI: 10.11855/j.issn.0577-7402.2014.01.12

Quinolinic acid induced neurodegeneration in the striatum: a combined in vivo and in vitro analysis of receptor changes and microglia activation

International Nuclear Information System (INIS)

Moresco, R.M.; Lavazza, T.; Belloli, S.; Todde, S.; Matarrese, M.; Carpinelli, A.; Turolla, E.; Fazio, F.; Lecchi, M.; Pezzola, A.; Popoli, P.; Zimarino, V.; Malgaroli, A.

2008-01-01

Huntington's disease (HD) is a progressive neurodegenerative disorder, which is characterised by prominent neuronal cell loss in the basal ganglia with motor and cognitive disturbances. One of the most well-studied pharmacological models of HD is produced by local injection in the rat brain striatum of the excitotoxin quinolinic acid (QA), which produces many of the distinctive features of this human neurodegenerative disorder. Here, we report a detailed analysis, obtained both in vivo and in vitro of this pharmacological model of HD. By combining emission tomography (PET) with autoradiographic and immunocytochemical confocal laser techniques, we quantified in the QA-injected striatum the temporal behavior (from 1 to 60 days from the excitotoxic insult) of neuronal cell density and receptor availability (adenosine A 2A and dopamine D 2 receptors) together with the degree of microglia activation. Both approaches showed a loss of adenosine A 2A and dopamine D 2 receptors paralleled by an increase of microglial activation. This combined longitudinal analysis of the disease progression, which suggested an impairment of neurotransmission, neuronal integrity and a reversible activation of brain inflammatory processes, might represent a more quantitative approach to compare the differential effects of treatments in slowing down or reversing HD in rodent models with potential applications to human patients. (orig.)

Key Characteristics of Combined Accident including TLOFW accident for PSA Modeling

Energy Technology Data Exchange (ETDEWEB)

Kim, Bo Gyung; Kang, Hyun Gook [KAIST, Daejeon (Korea, Republic of); Yoon, Ho Joon [Khalifa University of Science, Technology and Research, Abu Dhabi (United Arab Emirates)

2015-05-15

The conventional PSA techniques cannot adequately evaluate all events. The conventional PSA models usually focus on single internal events such as DBAs, the external hazards such as fire, seismic. However, the Fukushima accident of Japan in 2011 reveals that very rare event is necessary to be considered in the PSA model to prevent the radioactive release to environment caused by poor treatment based on lack of the information, and to improve the emergency operation procedure. Especially, the results from PSA can be used to decision making for regulators. Moreover, designers can consider the weakness of plant safety based on the quantified results and understand accident sequence based on human actions and system availability. This study is for PSA modeling of combined accidents including total loss of feedwater (TLOFW) accident. The TLOFW accident is a representative accident involving the failure of cooling through secondary side. If the amount of heat transfer is not enough due to the failure of secondary side, the heat will be accumulated to the primary side by continuous core decay heat. Transients with loss of feedwater include total loss of feedwater accident, loss of condenser vacuum accident, and closure of all MSIVs. When residual heat removal by the secondary side is terminated, the safety injection into the RCS with direct primary depressurization would provide alternative heat removal. This operation is called feed and bleed (F and B) operation. Combined accidents including TLOFW accident are very rare event and partially considered in conventional PSA model. Since the necessity of F and B operation is related to plant conditions, the PSA modeling for combined accidents including TLOFW accident is necessary to identify the design and operational vulnerabilities.The PSA is significant to assess the risk of NPPs, and to identify the design and operational vulnerabilities. Even though the combined accident is very rare event, the consequence of combined

Design of optimized hypoxia-activated prodrugs using pharmacokinetic/pharmacodynamic modeling

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Annika Bettina Foehrenbacher

2013-12-01

Full Text Available Hypoxia contributes to resistance of tumors to some cytotoxic drugs and to radiotherapy, but can in principle be exploited with hypoxia-activated prodrugs (HAP. HAP in clinical development fall into two broad groups. Class I HAP (like the benzotriazine N-oxides tirapazamine and SN30000, are activated under relatively mild hypoxia. In contrast, Class II HAP (such as the nitro compounds PR-104A or TH-302 are maximally activated only under extreme hypoxia, but their active metabolites (effectors diffuse to cells at intermediate O2 and thus also eliminate moderately hypoxic cells. Here, we use a spatially resolved pharmacokinetic/pharmacodynamic (SR-PK/PD model to compare these two strategies and to identify the features required in an optimal Class II HAP. The model uses a Green’s function approach to calculate spatial and longitudinal gradients of O2, prodrug and effector concentrations, and resulting killing in a digitized 3D tumor microregion to estimate activity as monotherapy and in combination with radiotherapy. An analogous model for a normal tissue with mild hypoxia and short intervesssel distances (based on a cremaster muscle microvessel network was used to estimate tumor selectivity of cell killing. This showed that Class II HAP offer advantages over Class I including higher tumor selectivity and greater freedom to vary prodrug diffusibility and rate of metabolic activation. The model suggests that the largest gains in class II HAP antitumor activity could be realized by optimizing effector stability and prodrug activation rates. We also use the model to show that diffusion of effector into blood vessels is unlikely to materially increase systemic exposure for realistic tumor burdens and effector clearances. However, we show that the tumor selectivity achievable by hypoxia-dependent prodrug activation alone is limited if dose-limiting normal tissues are even mildly hypoxic

Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel

OpenAIRE

Wein, Alexander N.; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T.; Leppla, Stephen H.

2012-01-01

PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wild-type lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6,...

Activated aging dynamics and effective trap model description in the random energy model

Science.gov (United States)

Baity-Jesi, M.; Biroli, G.; Cammarota, C.

2018-01-01

We study the out-of-equilibrium aging dynamics of the random energy model (REM) ruled by a single spin-flip Metropolis dynamics. We focus on the dynamical evolution taking place on time-scales diverging with the system size. Our aim is to show to what extent the activated dynamics displayed by the REM can be described in terms of an effective trap model. We identify two time regimes: the first one corresponds to the process of escaping from a basin in the energy landscape and to the subsequent exploration of high energy configurations, whereas the second one corresponds to the evolution from a deep basin to the other. By combining numerical simulations with analytical arguments we show why the trap model description does not hold in the former but becomes exact in the second.

Atmospheric Boundary Layer Modeling for Combined Meteorology and Air Quality Systems

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Atmospheric Eulerian grid models for mesoscale and larger applications require sub-grid models for turbulent vertical exchange processes, particularly within the Planetary Boundary Layer (PSL). In combined meteorology and air quality modeling systems consistent PSL modeling of wi...

A comparison of methods to assess the antimicrobial activity of nanoparticle combinations on bacterial cells.

Directory of Open Access Journals (Sweden)

Claire Bankier

Full Text Available Bacterial cell quantification after exposure to antimicrobial compounds varies widely throughout industry and healthcare. Numerous methods are employed to quantify these antimicrobial effects. With increasing demand for new preventative methods for disease control, we aimed to compare and assess common analytical methods used to determine antimicrobial effects of novel nanoparticle combinations on two different pathogens.Plate counts of total viable cells, flow cytometry (LIVE/DEAD BacLight viability assay and qPCR (viability qPCR were used to assess the antimicrobial activity of engineered nanoparticle combinations (NPCs on Gram-positive (Staphylococcus aureus and Gram-negative (Pseudomonas aeruginosa bacteria at different concentrations (0.05, 0.10 and 0.25 w/v%. Results were analysed using linear models to assess the effectiveness of different treatments.Strong antimicrobial effects of the three NPCs (AMNP0-2 on both pathogens could be quantified using the plate count method and flow cytometry. The plate count method showed a high log reduction (>8-log for bacteria exposed to high NPC concentrations. We found similar antimicrobial results using the flow cytometry live/dead assay. Viability qPCR analysis of antimicrobial activity could not be quantified due to interference of NPCs with qPCR amplification.Flow cytometry was determined to be the best method to measure antimicrobial activity of the novel NPCs due to high-throughput, rapid and quantifiable results.

A comparison of methods to assess the antimicrobial activity of nanoparticle combinations on bacterial cells.

Science.gov (United States)

Bankier, Claire; Cheong, Yuen; Mahalingam, Suntharavathanan; Edirisinghe, Mohan; Ren, Guogang; Cloutman-Green, Elaine; Ciric, Lena

2018-01-01

Bacterial cell quantification after exposure to antimicrobial compounds varies widely throughout industry and healthcare. Numerous methods are employed to quantify these antimicrobial effects. With increasing demand for new preventative methods for disease control, we aimed to compare and assess common analytical methods used to determine antimicrobial effects of novel nanoparticle combinations on two different pathogens. Plate counts of total viable cells, flow cytometry (LIVE/DEAD BacLight viability assay) and qPCR (viability qPCR) were used to assess the antimicrobial activity of engineered nanoparticle combinations (NPCs) on Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria at different concentrations (0.05, 0.10 and 0.25 w/v%). Results were analysed using linear models to assess the effectiveness of different treatments. Strong antimicrobial effects of the three NPCs (AMNP0-2) on both pathogens could be quantified using the plate count method and flow cytometry. The plate count method showed a high log reduction (>8-log) for bacteria exposed to high NPC concentrations. We found similar antimicrobial results using the flow cytometry live/dead assay. Viability qPCR analysis of antimicrobial activity could not be quantified due to interference of NPCs with qPCR amplification. Flow cytometry was determined to be the best method to measure antimicrobial activity of the novel NPCs due to high-throughput, rapid and quantifiable results.

A Chimeric Antibody against ACKR3/CXCR7 in Combination with TMZ Activates Immune Responses and Extends Survival in Mouse GBM Models.

Science.gov (United States)

Salazar, Nicole; Carlson, Jeffrey C; Huang, Kexin; Zheng, Yayue; Oderup, Cecilia; Gross, Julia; Jang, Andrew D; Burke, Thomas M; Lewén, Susanna; Scholz, Alexander; Huang, Serina; Nease, Leona; Kosek, Jon; Mittelbronn, Michel; Butcher, Eugene C; Tu, Hua; Zabel, Brian A

2018-05-02

Glioblastoma (GBM) is the least treatable type of brain tumor, afflicting over 15,000 people per year in the United States. Patients have a median survival of 16 months, and over 95% die within 5 years. The chemokine receptor ACKR3 is selectively expressed on both GBM cells and tumor-associated blood vessels. High tumor expression of ACKR3 correlates with poor prognosis and potential treatment resistance, making it an attractive therapeutic target. We engineered a single chain FV-human FC-immunoglobulin G1 (IgG 1 ) antibody, X7Ab, to target ACKR3 in human and mouse GBM cells. We used hydrodynamic gene transfer to overexpress the antibody, with efficacy in vivo. X7Ab kills GBM tumor cells and ACKR3-expressing vascular endothelial cells by engaging the cytotoxic activity of natural killer (NK) cells and complement and the phagocytic activity of macrophages. Combining X7Ab with TMZ allows the TMZ dosage to be lowered, without compromising therapeutic efficacy. Mice treated with X7Ab and in combination with TMZ showed significant tumor reduction by MRI and longer survival overall. Brain-tumor-infiltrating leukocyte analysis revealed that X7Ab enhances the activation of M1 macrophages to support anti-tumor immune response in vivo. Targeting ACKR3 with immunotherapeutic monoclonal antibodies (mAbs) in combination with standard of care therapies may prove effective in treating GBM. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

A combined model based on CEEMDAN and modified flower pollination algorithm for wind speed forecasting

International Nuclear Information System (INIS)

Zhang, Wenyu; Qu, Zongxi; Zhang, Kequan; Mao, Wenqian; Ma, Yining; Fan, Xu

2017-01-01

Highlights: • A CEEMDAN-CLSFPA combined model is proposed for short-term wind speed forecasting. • The CEEMDAN technique is used to decompose the original wind speed series. • A modified optimization algorithm-CLSFPA is proposed to optimize the weights of the combined model. • The no negative constraint theory is applied to the combined model. • Robustness of the proposed model is validated by data sampled from four different wind farms. - Abstract: Wind energy, which is stochastic and intermittent by nature, has a significant influence on power system operation, power grid security and market economics. Precise and reliable wind speed prediction is vital for wind farm planning and operational planning for power grids. To improve wind speed forecasting accuracy, a large number of forecasting approaches have been proposed; however, these models typically do not account for the importance of data preprocessing and are limited by the use of individual models. In this paper, a novel combined model – combining complete ensemble empirical mode decomposition adaptive noise (CEEMDAN), flower pollination algorithm with chaotic local search (CLSFPA), five neural networks and no negative constraint theory (NNCT) – is proposed for short-term wind speed forecasting. First, a recent CEEMDAN is employed to divide the original wind speed data into a finite set of IMF components, and then a combined model, based on NNCT, is proposed for forecasting each decomposition signal. To improve the forecasting capacity of the combined model, a modified flower pollination algorithm (FPA) with chaotic local search (CLS) is proposed and employed to determine the optimal weight coefficients of the combined model, and the final prediction values were obtained by reconstructing the refined series. To evaluate the forecasting ability of the proposed combined model, 15-min wind speed data from four wind farms in the eastern coastal areas of China are used. The experimental results of

Activity-based DEVS modeling

DEFF Research Database (Denmark)

Alshareef, Abdurrahman; Sarjoughian, Hessam S.; Zarrin, Bahram

2018-01-01

architecture and the UML concepts. In this paper, we further this work by grounding Activity-based DEVS modeling and developing a fully-fledged modeling engine to demonstrate applicability. We also detail the relevant aspects of the created metamodel in terms of modeling and simulation. A significant number......Use of model-driven approaches has been increasing to significantly benefit the process of building complex systems. Recently, an approach for specifying model behavior using UML activities has been devised to support the creation of DEVS models in a disciplined manner based on the model driven...... of the artifacts of the UML 2.5 activities and actions, from the vantage point of DEVS behavioral modeling, is covered in details. Their semantics are discussed to the extent of time-accurate requirements for simulation. We characterize them in correspondence with the specification of the atomic model behavior. We...

Local Inflammation in Fracture Hematoma: Results from a Combined Trauma Model in Pigs

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K. Horst

2015-01-01

Full Text Available Background. Previous studies showed significant interaction between the local and systemic inflammatory response after severe trauma in small animal models. The purpose of this study was to establish a new combined trauma model in pigs to investigate fracture-associated local inflammation and gain information about the early inflammatory stages after polytrauma. Material and Methods. Combined trauma consisted of tibial fracture, lung contusion, liver laceration, and controlled hemorrhage. Animals were mechanically ventilated and under ICU-monitoring for 48 h. Blood and fracture hematoma samples were collected during the time course of the study. Local and systemic levels of serum cytokines and diverse alarmins were measured by ELISA kit. Results. A statistical significant difference in the systemic serum values of IL-6 and HMGB1 was observed when compared to the sham. Moreover, there was a statistical significant difference in the serum values of the fracture hematoma of IL-6, IL-8, IL-10, and HMGB1 when compared to the systemic inflammatory response. However a decrease of local proinflammatory concentrations was observed while anti-inflammatory mediators increased. Conclusion. Our data showed a time-dependent activation of the local and systemic inflammatory response. Indeed it is the first study focusing on the local and systemic inflammatory response to multiple-trauma in a large animal model.

Discriminative latent models for recognizing contextual group activities.

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Lan, Tian; Wang, Yang; Yang, Weilong; Robinovitch, Stephen N; Mori, Greg

2012-08-01

In this paper, we go beyond recognizing the actions of individuals and focus on group activities. This is motivated from the observation that human actions are rarely performed in isolation; the contextual information of what other people in the scene are doing provides a useful cue for understanding high-level activities. We propose a novel framework for recognizing group activities which jointly captures the group activity, the individual person actions, and the interactions among them. Two types of contextual information, group-person interaction and person-person interaction, are explored in a latent variable framework. In particular, we propose three different approaches to model the person-person interaction. One approach is to explore the structures of person-person interaction. Differently from most of the previous latent structured models, which assume a predefined structure for the hidden layer, e.g., a tree structure, we treat the structure of the hidden layer as a latent variable and implicitly infer it during learning and inference. The second approach explores person-person interaction in the feature level. We introduce a new feature representation called the action context (AC) descriptor. The AC descriptor encodes information about not only the action of an individual person in the video, but also the behavior of other people nearby. The third approach combines the above two. Our experimental results demonstrate the benefit of using contextual information for disambiguating group activities.

Combining a popularity-productivity stochastic block model with a discriminative-content model for general structure detection.

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Chai, Bian-fang; Yu, Jian; Jia, Cai-Yan; Yang, Tian-bao; Jiang, Ya-wen

2013-07-01

Latent community discovery that combines links and contents of a text-associated network has drawn more attention with the advance of social media. Most of the previous studies aim at detecting densely connected communities and are not able to identify general structures, e.g., bipartite structure. Several variants based on the stochastic block model are more flexible for exploring general structures by introducing link probabilities between communities. However, these variants cannot identify the degree distributions of real networks due to a lack of modeling of the differences among nodes, and they are not suitable for discovering communities in text-associated networks because they ignore the contents of nodes. In this paper, we propose a popularity-productivity stochastic block (PPSB) model by introducing two random variables, popularity and productivity, to model the differences among nodes in receiving links and producing links, respectively. This model has the flexibility of existing stochastic block models in discovering general community structures and inherits the richness of previous models that also exploit popularity and productivity in modeling the real scale-free networks with power law degree distributions. To incorporate the contents in text-associated networks, we propose a combined model which combines the PPSB model with a discriminative model that models the community memberships of nodes by their contents. We then develop expectation-maximization (EM) algorithms to infer the parameters in the two models. Experiments on synthetic and real networks have demonstrated that the proposed models can yield better performances than previous models, especially on networks with general structures.

Mechanism of Sporicidal Activity for the Synergistic Combination of Peracetic Acid and Hydrogen Peroxide.

Science.gov (United States)

Leggett, Mark J; Schwarz, J Spencer; Burke, Peter A; McDonnell, Gerald; Denyer, Stephen P; Maillard, Jean-Yves

2016-02-15

There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity. Copyright © 2016 Leggett et al.

Efficient pan-European river flood hazard modelling through a combination of statistical and physical models

NARCIS (Netherlands)

Paprotny, D.; Morales Napoles, O.; Jonkman, S.N.

2017-01-01

Flood hazard is currently being researched on continental and global scales, using models of increasing complexity. In this paper we investigate a different, simplified approach, which combines statistical and physical models in place of conventional rainfall-run-off models to carry out flood

Modeling of a combined cycle power plant

International Nuclear Information System (INIS)

Faridah Mohamad Idris

2001-01-01

The combined cycle power plant is a non-linear, closed loop system, which consists of high-pressure (HP) superheater, HP evaporator, HP economizer, low-pressure (LP) evaporator, HP drum, HP deaerator, condenser, HP and LP steam turbine and gas turbine. The two types of turbines in the plant for example the gas turbine and the HP and LP steam turbines operate concurrently to generate power to the plant. The exhaust gas which originate from the combustion chamber drives the gas turbine, after which it flows into the heat recovery steam generator (HRSG) to generate superheated steam to be used in driving the HP and LP steam turbines. In this thesis, the combined cycle power plant is modeled at component level using the physical method. Assuming that there is delay in transport, except for the gas turbine system, the mass and heat balances are applied on the components of the plant to derive the governing equations of the components. These time dependent equations, which are of first order differential types, are then solved for the mass and enthalpy of the components. The solutions were simulated using Matlab Simulink using measured plant data. Where necessary there is no plant data available, approximated data were used. The generalized regression neural networks are also used to generate extra sets of simulation data for the HRSG system. Comparisons of the simulation results with its corresponding plant data showed good agreements between the two and indicated that the models developed for the components could be used to represent the combined cycle power plant under study. (author)

Language Model Combination and Adaptation Using Weighted Finite State Transducers

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Liu, X.; Gales, M. J. F.; Hieronymus, J. L.; Woodland, P. C.

2010-01-01

In speech recognition systems language model (LMs) are often constructed by training and combining multiple n-gram models. They can be either used to represent different genres or tasks found in diverse text sources, or capture stochastic properties of different linguistic symbol sequences, for example, syllables and words. Unsupervised LM adaption may also be used to further improve robustness to varying styles or tasks. When using these techniques, extensive software changes are often required. In this paper an alternative and more general approach based on weighted finite state transducers (WFSTs) is investigated for LM combination and adaptation. As it is entirely based on well-defined WFST operations, minimum change to decoding tools is needed. A wide range of LM combination configurations can be flexibly supported. An efficient on-the-fly WFST decoding algorithm is also proposed. Significant error rate gains of 7.3% relative were obtained on a state-of-the-art broadcast audio recognition task using a history dependently adapted multi-level LM modelling both syllable and word sequences

Fibrin-specific and effective clot lysis requires both plasminogen activators and for them to be in a sequential rather than simultaneous combination.

Science.gov (United States)

Pannell, R; Li, S; Gurewich, V

2017-08-01

Thrombolysis with tissue plasminogen activator (tPA) has been a disappointment and has now been replaced by an endovascular procedure whenever possible. Nevertheless, thrombolysis remains the only means by which circulation in a thrombosed artery can be restored rapidly. In contrast to tPA monotherapy, endogenous fibrinolysis uses both tPA and urokinase plasminogen activator (uPA), whose native form is a proenzyme, prouPA. This combination is remarkably effective as evidenced by the fibrin degradation product, D-dimer, which is invariably present in plasma. The two activators have complementary mechanisms of plasminogen activation and are synergistic in combination. Since tPA initiates fibrinolysis when released from the vessel wall and prouPA is in the blood, they induce fibrinolysis sequentially. It was postulated that this may be more effective and fibrin-specific. The hypothesis was tested in a model of clot lysis in plasma in which a clot was first exposed to tPA for 5 min, washed and incubated with prouPA. Lysis was compared with that of clots incubated with both activators simultaneously. The sequential combination was almost twice as effective and caused less fibrinogenolysis than the simultaneous combination (p < 0.0001) despite having significantly less tPA, as a result of the wash. A mechanism is described by which this phenomenon can be explained. The findings are believed to have significant therapeutic implications.

A NEW COMBINED LOCAL AND NON-LOCAL PBL MODEL FOR METEOROLOGY AND AIR QUALITY MODELING

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A new version of the Asymmetric Convective Model (ACM) has been developed to describe sub-grid vertical turbulent transport in both meteorology models and air quality models. The new version (ACM2) combines the non-local convective mixing of the original ACM with local eddy diff...

Can a model of study activity increase didactic dialogue and students' understanding of learning in IPE?

DEFF Research Database (Denmark)

Hansen, Bodil Winther; Hatt, Camusa

at Metropolitan University College. Since 2013 all UCS have worked with a nationally decided study activity model. The model outlines four different types of learning activities. Students are introduced to courses via the model to heighten their understanding of course design and the expectations...... combining quantitative surveys, interviews, observation and focus groups. Comparisonldiscussion: The presentation will discuss the ambition to optimize dialogue about learning between lecturers and students by using a model of study activity. Results related to the value and potential of the model as seen...... by both lecturers and students will be presented. Findings/results/outcomes/effects: Students point out that the model can be a useful tool to gain an overview of learning activities and the amount of time they are expected to spend in courses. When lecturers introduce courses via the model it deepens...

Oriented active shape models.

Science.gov (United States)

Liu, Jiamin; Udupa, Jayaram K

2009-04-01

Active shape models (ASM) are widely employed for recognizing anatomic structures and for delineating them in medical images. In this paper, a novel strategy called oriented active shape models (OASM) is presented in an attempt to overcome the following five limitations of ASM: 1) lower delineation accuracy, 2) the requirement of a large number of landmarks, 3) sensitivity to search range, 4) sensitivity to initialization, and 5) inability to fully exploit the specific information present in the given image to be segmented. OASM effectively combines the rich statistical shape information embodied in ASM with the boundary orientedness property and the globally optimal delineation capability of the live wire methodology of boundary segmentation. The latter characteristics allow live wire to effectively separate an object boundary from other nonobject boundaries with similar properties especially when they come very close in the image domain. The approach leads to a two-level dynamic programming method, wherein the first level corresponds to boundary recognition and the second level corresponds to boundary delineation, and to an effective automatic initialization method. The method outputs a globally optimal boundary that agrees with the shape model if the recognition step is successful in bringing the model close to the boundary in the image. Extensive evaluation experiments have been conducted by utilizing 40 image (magnetic resonance and computed tomography) data sets in each of five different application areas for segmenting breast, liver, bones of the foot, and cervical vertebrae of the spine. Comparisons are made between OASM and ASM based on precision, accuracy, and efficiency of segmentation. Accuracy is assessed using both region-based false positive and false negative measures and boundary-based distance measures. The results indicate the following: 1) The accuracy of segmentation via OASM is considerably better than that of ASM; 2) The number of landmarks

Combining molecular docking and QSAR studies for modeling the anti-tyrosinase activity of aromatic heterocycle thiosemicarbazone analogues

Science.gov (United States)

Dong, Huanhuan; Liu, Jing; Liu, Xiaoru; Yu, Yanying; Cao, Shuwen

2018-01-01

A collection of thirty-six aromatic heterocycle thiosemicarbazone analogues presented a broad span of anti-tyrosinase activities were designed and obtained. A robust and reliable two-dimensional quantitative structure-activity relationship model, as evidenced by the high q2 and r2 values (0.848 and 0.893, respectively), was gained based on the analogues to predict the quantitative chemical-biological relationship and the new modifier direction. Inhibitory activities of the compounds were found to greatly depend on molecular shape and orbital energy. Substituents brought out large ovality and high highest-occupied molecular orbital energy values helped to improve the activity of these analogues. The molecular docking results provided visual evidence for QSAR analysis and inhibition mechanism. Based on these, two novel tyrosinase inhibitors O04 and O05 with predicted IC50 of 0.5384 and 0.8752 nM were designed and suggested for further research.

Validation of Quantitative Structure-Activity Relationship (QSAR Model for Photosensitizer Activity Prediction

Directory of Open Access Journals (Sweden)

Sharifuddin M. Zain

2011-11-01

Full Text Available Photodynamic therapy is a relatively new treatment method for cancer which utilizes a combination of oxygen, a photosensitizer and light to generate reactive singlet oxygen that eradicates tumors via direct cell-killing, vasculature damage and engagement of the immune system. Most of photosensitizers that are in clinical and pre-clinical assessments, or those that are already approved for clinical use, are mainly based on cyclic tetrapyrroles. In an attempt to discover new effective photosensitizers, we report the use of the quantitative structure-activity relationship (QSAR method to develop a model that could correlate the structural features of cyclic tetrapyrrole-based compounds with their photodynamic therapy (PDT activity. In this study, a set of 36 porphyrin derivatives was used in the model development where 24 of these compounds were in the training set and the remaining 12 compounds were in the test set. The development of the QSAR model involved the use of the multiple linear regression analysis (MLRA method. Based on the method, r2 value, r2 (CV value and r2 prediction value of 0.87, 0.71 and 0.70 were obtained. The QSAR model was also employed to predict the experimental compounds in an external test set. This external test set comprises 20 porphyrin-based compounds with experimental IC50 values ranging from 0.39 µM to 7.04 µM. Thus the model showed good correlative and predictive ability, with a predictive correlation coefficient (r2 prediction for external test set of 0.52. The developed QSAR model was used to discover some compounds as new lead photosensitizers from this external test set.

Simulation of neuro-fuzzy model for optimization of combine header setting

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S Zareei

2016-09-01

Full Text Available Introduction The noticeable proportion of producing wheat losses occur during production and consumption steps and the loss due to harvesting with combine harvester is regarded as one of the main factors. A grain combines harvester consists of different sets of equipment and one of the most important parts is the header which comprises more than 50% of the entire harvesting losses. Some researchers have presented regression equation to estimate grain loss of combine harvester. The results of their study indicated that grain moisture content, reel index, cutter bar speed, service life of cutter bar, tine spacing, tine clearance over cutter bar, stem length were the major parameters affecting the losses. On the other hand, there are several researchswhich have used the variety of artificial intelligence methods in the different aspects of combine harvester. In neuro-fuzzy control systems, membership functions and if-then rules were defined through neural networks. Sugeno- type fuzzy inference model was applied to generate fuzzy rules from a given input-output data set due to its less time-consuming and mathematically tractable defuzzification operation for sample data-based fuzzy modeling. In this study, neuro-fuzzy model was applied to develop forecasting models which can predict the combine header loss for each set of the header parameter adjustments related to site-specific information and therefore can minimize the header loss. Materials and Methods The field experiment was conducted during the harvesting season of 2011 at the research station of the Faulty of Agriculture, Shiraz University, Shiraz, Iran. The wheat field (CV. Shiraz was harvested with a Claas Lexion-510 combine harvester. The factors which were selected as main factors influenced the header performance were three levels of reel index (RI (forward speed of combine harvester divided by peripheral speed of reel (1, 1.2, 1.5, three levels of cutting height (CH(25, 30, 35 cm, three

Complex motion of elevators in piecewise map model combined with circle map

Science.gov (United States)

Nagatani, Takashi

2013-11-01

We study the dynamic behavior in the elevator traffic controlled by capacity when the inflow rate of passengers into elevators varies periodically with time. The dynamics of elevators is described by the piecewise map model combined with the circle map. The motion of the elevators depends on the inflow rate, its period, and the number of elevators. The motion in the piecewise map model combined with the circle map shows a complex behavior different from the motion in the piecewise map model.

Focal radiation therapy combined with 4-1BB activation and CTLA-4 blockade yields long-term survival and a protective antigen-specific memory response in a murine glioma model.

Directory of Open Access Journals (Sweden)

Zineb Belcaid

Full Text Available Glioblastoma (GBM is the most common malignant brain tumor in adults and is associated with a poor prognosis. Cytotoxic T lymphocyte antigen -4 (CTLA-4 blocking antibodies have demonstrated an ability to generate robust antitumor immune responses against a variety of solid tumors. 4-1BB (CD137 is expressed by activated T lymphocytes and served as a co-stimulatory signal, which promotes cytotoxic function. Here, we evaluate a combination immunotherapy regimen involving 4-1BB activation, CTLA-4 blockade, and focal radiation therapy in an immune-competent intracranial GBM model.GL261-luciferace cells were stereotactically implanted in the striatum of C57BL/6 mice. Mice were treated with a triple therapy regimen consisted of 4-1BB agonist antibodies, CTLA-4 blocking antibodies, and focal radiation therapy using a small animal radiation research platform and mice were followed for survival. Numbers of brain-infiltrating lymphocytes were analyzed by FACS analysis. CD4 or CD8 depleting antibodies were administered to determine the relative contribution of T helper and cytotoxic T cells in this regimen. To evaluate the ability of this immunotherapy to generate an antigen-specific memory response, long-term survivors were re-challenged with GL261 glioma en B16 melanoma flank tumors.Mice treated with triple therapy had increased survival compared to mice treated with focal radiation therapy and immunotherapy with 4-1BB activation and CTLA-4 blockade. Animals treated with triple therapy exhibited at least 50% long-term tumor free survival. Treatment with triple therapy resulted in a higher density of CD4+ and CD8+ tumor infiltrating lymphocytes. Mechanistically, depletion of CD4+ T cells abrogated the antitumor efficacy of triple therapy, while depletion of CD8+ T cells had no effect on the treatment response.Combination therapy with 4-1BB activation and CTLA-4 blockade in the setting of focal radiation therapy improves survival in an orthotopic mouse

Music-induced emotions can be predicted from a combination of brain activity and acoustic features.

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Daly, Ian; Williams, Duncan; Hallowell, James; Hwang, Faustina; Kirke, Alexis; Malik, Asad; Weaver, James; Miranda, Eduardo; Nasuto, Slawomir J

2015-12-01

It is widely acknowledged that music can communicate and induce a wide range of emotions in the listener. However, music is a highly-complex audio signal composed of a wide range of complex time- and frequency-varying components. Additionally, music-induced emotions are known to differ greatly between listeners. Therefore, it is not immediately clear what emotions will be induced in a given individual by a piece of music. We attempt to predict the music-induced emotional response in a listener by measuring the activity in the listeners electroencephalogram (EEG). We combine these measures with acoustic descriptors of the music, an approach that allows us to consider music as a complex set of time-varying acoustic features, independently of any specific music theory. Regression models are found which allow us to predict the music-induced emotions of our participants with a correlation between the actual and predicted responses of up to r=0.234,pmusic induced emotions can be predicted by their neural activity and the properties of the music. Given the large amount of noise, non-stationarity, and non-linearity in both EEG and music, this is an encouraging result. Additionally, the combination of measures of brain activity and acoustic features describing the music played to our participants allows us to predict music-induced emotions with significantly higher accuracies than either feature type alone (p<0.01). Copyright © 2015 Elsevier Inc. All rights reserved.

Clearance measurements on activated parts of accelerators by combined methods; Verfahrenskombinierte Freigabemessung aktivierter Beschleunigerteile

Energy Technology Data Exchange (ETDEWEB)

Jansen, S.; Friedemann, S. [VKTA, Dresden (Germany); Enghardt, W. [Technische Univ. Dresden (Germany). OncoRay

2016-07-01

The process of clearance of radioactive materials according to paragraph 29 StrlSchV contents the comparison of activity to mass and surface of the material. To avoid a borderless assessment of activity of activation it is often necessary to use combined measurement methods: For clearance of collimators of a medical proton accelerator (energy range up to 200 MeV) it needs to know the nuclide composition. The energetical and geometrical calibration was fixed by experiments. The clearance based on measurements of activity distribution, gammaspectroscopy verification of nuclide composition and gamma-counting detectors. Parts of medical electron-accelerators achieved its clearance by combination of abovementioned methods and in-situ-gammaspectroscopy. Activated und contaminated lead stones achieved its clearance by measurements of fluence, laboratory evaluation of samples, in-situ-gammaspectroscopy and wipe tests.

Modeling and experiment to threshing unit of stripper combine ...

African Journals Online (AJOL)

Modeling and experiment to threshing unit of stripper combine. ... were conducted with the different feed rates and drum rotator speeds for the rice stripped mixtures. ... and damage as well as for threshing unit design and process optimization.

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

Science.gov (United States)

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2015-01-01

Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

Directory of Open Access Journals (Sweden)

Jing Hao

Full Text Available Fixed-dose combinations (FDC contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed.Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients.New molecular entities (NMEs, new therapeutic biologics license applications (BLAs and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC and only already marketed drugs (Non-NMEs-FDC. Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed.During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31 after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39 before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24 years to the patent and exclusivity life of the single active ingredients in the combination.FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

Combined influence of leisure time physical activity and hip circumference on all-cause mortality

DEFF Research Database (Denmark)

Østergaard, Jane Nautrup; Grønbæk, Morten; Ängquist, Lars Henrik

2013-01-01

Hip circumference has been shown to be inversely associated with mortality. Muscle atrophy in the gluteofemoral region may be a possible explanation and thus physical activity is likely to play an important role. We aimed to estimate the combined effects of hip circumference and physical activity...... followed to 2009 in the Danish Civil Registration System, with 1.3% loss to follow-up and 2513 deaths. Hazard ratios (HR) were estimated for combinations of physical activity and hip circumference. Hip circumference was inversely associated with mortality irrespective of being physically active or not....... However, being physically active seemed to counterbalance some of the adverse health effects of a small hip circumference; when comparing inactive to active, the excess mortality at the 25(th) percentile of hip circumference is 40% in men (HR= 1.40, 95% CI: 1.14-1.72) and 33% in women (HR= 1.33, CI: 1...

A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library.

Science.gov (United States)

Feng, Jie; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Auwaerter, Paul G; Zhang, Ying

2016-01-01

Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi

The post-activation potentiation effect on sprint performance after combined resistance/sprint training in junior basketball players.

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Tsimachidis, Constantinos; Patikas, Dimitrios; Galazoulas, Christos; Bassa, Eleni; Kotzamanidis, Christos

2013-01-01

The aim of this study was to examine the effect of a 10-week combined resistance/sprint training programme in the post-activation potentiation of sprint performance before, between and after resistance training sets. Twenty-six junior basketball players were randomly divided into a control and a combined training group. The combined training group performed a combined training programme consisting of 5 sets at 5-8 RM (Repetition Maximum) half-squats with sprints performed between each set. Post-activation potentiation was considered as the increase in sprint velocity in trials executed between and after the resistance sets compared with the sprint trial performed before the resistance sets of the respective first and last training session. For sprint evaluation the running distances 0-10 and 0-30 m were selected. The intervention increased both strength and sprint performance. No post-activation potentiation effect was observed during the first training session in either group. Post-activation potentiation appeared in the combined training group during the last training session of the intervention in both 0-10 and 0-30 m sprint. This study illustrates that post-activation potentiation effect on sprint performance in junior basketball players, who did not previously follow systematic resistance training, emerges after a 10-week resistance/sprint combined training programme.

Synergistic activity profile of carbosilane dendrimer G2-STE16 in combination with other dendrimers and antiretrovirals as topical anti-HIV-1 microbicide.

Science.gov (United States)

Sepúlveda-Crespo, Daniel; Lorente, Raquel; Leal, Manuel; Gómez, Rafael; De la Mata, Francisco J; Jiménez, José Luis; Muñoz-Fernández, M Ángeles

2014-04-01

Polyanionic carbosilane dendrimers represent opportunities to develop new anti-HIV microbicides. Dendrimers and antiretrovirals (ARVs) acting at different stages of HIV replication have been proposed as compounds to decrease new HIV infections. Thus, we determined the potential use of our G2-STE16 carbosilane dendrimer in combination with other carbosilane dendrimers and ARVs for the use as topical microbicide against HIV-1. We showed that these combinations obtained 100% inhibition and displayed a synergistic profile against different HIV-1 isolates in our model of TZM.bl cells. Our results also showed their potent activity in the presence of an acidic vaginal or seminal fluid environment and did not activate an inflammatory response. This study is the first step toward exploring the use of different anionic carbosilane dendrimers in combination and toward making a safe microbicide. Therefore, our results support further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicide. This paper describes the first steps toward the use of anionic carbosilane dendrimers in combination with antivirals to address HIV-1, paving the way to further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicides. © 2014.

The in vitro and in vivo efficacy of fluconazole in combination with farnesol against Candida albicans isolates using a murine vulvovaginitis model.

Science.gov (United States)

Bozó, Aliz; Domán, Marianna; Majoros, László; Kardos, Gábor; Varga, István; Kovács, Renátó

2016-11-01

Farnesol is a quorum-sensing molecule that inhibits biofilm formation in Candida albicans. Previous in vitro data suggest that, in combination with certain antifungals, farnesol may have an adjuvant anti-biofilm agent. However, the in vivo efficacy of farnesol is very questionable. Therefore, the in vitro and in vivo activity of fluconazole combined with farnesol was evaluated against C. albicans biofilms using fractional inhibitory concentration index (FICI) determination, time-kill experiments and a murine vulvovaginitis model. The median biofilm MICs of fluconazole-sensitive C. albicans isolates ranged between 4 -> 512 mg/L and 150-300 μM for fluconazole and farnesol, respectively. These values were 512 -> 512 mg/L and > 300 μM for fluconazole-resistant clinical isolates. Farnesol decreased the median MICs of fluconazole by 2-64-fold for biofilms. Based on FICI, synergistic interaction was observed only in the case of the sessile SC5314 reference strain (FICIs: 0.16-0.27). In time-kill studies, only the 512 mg/L fluconazole and 512 mg/L fluconazole + 75 μM farnesol reduced biofilm mass significantly at each time point in the case of all isolates. The combination reduced the metabolic activity of biofilms for all isolates in a concentration- and time-dependent manner. Our findings revealed that farnesol alone was not protective in a murine vulvovaginitis model. Farnesol was not beneficial in combination with fluconazole for fluconazole-susceptible isolates, but partially increased fluconazole activity against one fluconazole-resistant isolate, but not the other one.

Combining Bayesian Networks and Agent Based Modeling to develop a decision-support model in Vietnam

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Nong, Bao Anh; Ertsen, Maurits; Schoups, Gerrit

2016-04-01

Complexity and uncertainty in natural resources management have been focus themes in recent years. Within these debates, with the aim to define an approach feasible for water management practice, we are developing an integrated conceptual modeling framework for simulating decision-making processes of citizens, in our case in the Day river area, Vietnam. The model combines Bayesian Networks (BNs) and Agent-Based Modeling (ABM). BNs are able to combine both qualitative data from consultants / experts / stakeholders, and quantitative data from observations on different phenomena or outcomes from other models. Further strengths of BNs are that the relationship between variables in the system is presented in a graphical interface, and that components of uncertainty are explicitly related to their probabilistic dependencies. A disadvantage is that BNs cannot easily identify the feedback of agents in the system once changes appear. Hence, ABM was adopted to represent the reaction among stakeholders under changes. The modeling framework is developed as an attempt to gain better understanding about citizen's behavior and factors influencing their decisions in order to reduce uncertainty in the implementation of water management policy.

Combining region- and network-level brain-behavior relationships in a structural equation model.

Science.gov (United States)

Bolt, Taylor; Prince, Emily B; Nomi, Jason S; Messinger, Daniel; Llabre, Maria M; Uddin, Lucina Q

2018-01-15

Brain-behavior associations in fMRI studies are typically restricted to a single level of analysis: either a circumscribed brain region-of-interest (ROI) or a larger network of brain regions. However, this common practice may not always account for the interdependencies among ROIs of the same network or potentially unique information at the ROI-level, respectively. To account for both sources of information, we combined measurement and structural components of structural equation modeling (SEM) approaches to empirically derive networks from ROI activity, and to assess the association of both individual ROIs and their respective whole-brain activation networks with task performance using three large task-fMRI datasets and two separate brain parcellation schemes. The results for working memory and relational tasks revealed that well-known ROI-performance associations are either non-significant or reversed when accounting for the ROI's common association with its corresponding network, and that the network as a whole is instead robustly associated with task performance. The results for the arithmetic task revealed that in certain cases, an ROI can be robustly associated with task performance, even when accounting for its associated network. The SEM framework described in this study provides researchers additional flexibility in testing brain-behavior relationships, as well as a principled way to combine ROI- and network-levels of analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Combining Cattle Activity and Progesterone Measurements Using Hidden Semi-Markov Models

DEFF Research Database (Denmark)

O'Connell, Jared Michael; Tøgersen, Frede Aakmann; Friggens, Nic

2011-01-01

, the ability to identify oestrus is investigated as this is of great importance to farm management. Progesterone concentration is a more accurate but more expensive method than pedometer counts, and we evaluate the added benefits of a model that includes this variable. The resulting model is biologically...

Hysteresis modeling and identification of a dielectric electro-active polymer actuator using an APSO-based nonlinear Preisach NARX fuzzy model

International Nuclear Information System (INIS)

Truong, Bui Ngoc Minh; Nam, Doan Ngoc Chi; Ahn, Kyoung Kwan

2013-01-01

Dielectric electro-active polymer (DEAP) materials are attractive since they are low cost, lightweight and have a large deformation capability. They have no operating noise, very low electric power consumption and higher performance and efficiency than competing technologies. However, DEAP materials generally have strong hysteresis as well as uncertain and nonlinear characteristics. These disadvantages can limit the efficiency in the use of DEAP materials. To address these limitations, this research will present the combination of the Preisach model and the dynamic nonlinear autoregressive exogenous (NARX) fuzzy model-based adaptive particle swarm optimization (APSO) identification algorithm for modeling and identification of the nonlinear behavior of one typical type of DEAP actuator. Firstly, open loop input signals are applied to obtain nonlinear features and to investigate the responses of the DEAP actuator system. Then, a Preisach model can be combined with a dynamic NARX fuzzy structure to estimate the tip displacement of a DEAP actuator. To optimize all unknown parameters of the designed combination, an identification scheme based on a least squares method and an APSO algorithm is carried out. Finally, experimental validation research is carefully completed, and the effectiveness of the proposed model is evaluated by employing various input signals. (paper)

In vitro activities of beta-lactam antibiotics alone and in combination with sulbactam against Gram-negative bacteria.

Science.gov (United States)

Wang, Fu-Der; Lin, Mei-Lin; Lee, Wen-Sen; Liu, Cheng-Yi

2004-06-01

The resistance rates of ampicillin/sulbactam 2:1 against imipenem-susceptible and -resistant Acinetobacter baumannii were 23.5 and 30%, respectively. Ceftazidime/sulbactam combination showed significant reduction of resistant rates against Enterobacter cloacae, A. baumannii, ESBL Klebsiella pneumoniae. MIC90 of cefoperazone against E. cloacae, Serratia marcescens, A. baumannii and ESBL K. pneumoniae were > 128 mg/l. Addition of sulbactam enhanced the antimicrobial activities significantly. When imipenem was combined with sulbactam, the resistant rates against imipenem-resistant A. baumanni were significantly reduced. Cefepime/sulbactam combination was active against imipenem-resistant A. baumanni. The resistance rates of aztreonam/sulbactam combination against E. cloacae, imipenem-sensitive and resistant A. baumannii, ESBL K. pneumoniae were lowered significantly. The cefotaxime/sulbactam combination showed a significant improvement of activities against E. cloacae, S. marcescens, A. baumannii and ESBL K. pneumoniae. Copyright 2004 Elsevier B.V.

In Vitro Activity of MK-7655, a Novel β-Lactamase Inhibitor, in Combination with Imipenem against Carbapenem-Resistant Gram-Negative Bacteria

Science.gov (United States)

Hirsch, Elizabeth B.; Ledesma, Kimberly R.; Chang, Kai-Tai; Schwartz, Michael S.; Motyl, Mary R.

2012-01-01

Carbapenem-resistant bacteria represent a significant treatment challenge due to the lack of active antimicrobials available. MK-7655 is a novel β-lactamase inhibitor under clinical development. We investigated the combined killing activity of imipenem and MK-7655 against four imipenem-resistant bacterial strains, using a mathematical model previously evaluated in our laboratory. Time-kill studies (TKS) were conducted with imipenem and MK-7655 against a KPC-2-producing Klebsiella pneumoniae isolate (KP6339) as well as 3 Pseudomonas aeruginosa isolates (PA24226, PA24227, and PA24228) with OprD porin deletions and overexpression of AmpC. TKS were performed using 25 clinically achievable concentration combinations in a 5-by-5 array. Bacterial burden at 24 h was determined in triplicate by quantitative culture and mathematically modeled using a three-dimensional response surface. Mathematical model assessments were evaluated experimentally using clinically relevant dosing regimens of imipenem, with or without MK-7655, in a hollow-fiber infection model (HFIM). The combination of imipenem and MK-7655 was synergistic for all strains. Interaction indices were as follows: for KP6339, 0.50 (95% confidence interval [CI], 0.42 to 0.58); for PA24226, 0.60 (95% CI, 0.58 to 0.62); for PA24227, 0.70 (95% CI, 0.66 to 0.74); and for PA24228, 0.55 (95% CI, 0.49 to 0.61). In the HFIM, imipenem plus MK-7655 considerably reduced the bacterial burden at 24 h, while failure with imipenem alone was seen against all isolates. Sustained suppression of bacterial growth at 72 h was achieved with simulated doses of 500 mg imipenem plus 500 mg MK-7655 in 2 (KP6339 and PA24227) strains, and it was achieved in an additional strain (PA24228) when the imipenem dose was increased to 1,000 mg. Additional studies are being conducted to determine the optimal dose and combinations to be used in clinical investigations. PMID:22526311

Focal Adhesion Kinase Inhibitors in Combination with Erlotinib Demonstrate Enhanced Anti-Tumor Activity in Non-Small Cell Lung Cancer.

Directory of Open Access Journals (Sweden)

Grant A Howe

Full Text Available Blockade of epidermal growth factor receptor (EGFR activity has been a primary therapeutic target for non-small cell lung cancers (NSCLC. As patients with wild-type EGFR have demonstrated only modest benefit from EGFR tyrosine kinase inhibitors (TKIs, there is a need for additional therapeutic approaches in patients with wild-type EGFR. As a key component of downstream integrin signalling and known receptor cross-talk with EGFR, we hypothesized that targeting focal adhesion kinase (FAK activity, which has also been shown to correlate with aggressive stage in NSCLC, would lead to enhanced activity of EGFR TKIs. As such, EGFR TKI-resistant NSCLC cells (A549, H1299, H1975 were treated with the EGFR TKI erlotinib and FAK inhibitors (PF-573,228 or PF-562,271 both as single agents and in combination. We determined cell viability, apoptosis and 3-dimensional growth in vitro and assessed tumor growth in vivo. Treatment of EGFR TKI-resistant NSCLC cells with FAK inhibitor alone effectively inhibited cell viability in all cell lines tested; however, its use in combination with the EGFR TKI erlotinib was more effective at reducing cell viability than either treatment alone when tested in both 2- and 3-dimensional assays in vitro, with enhanced benefit seen in A549 cells. This increased efficacy may be due in part to the observed inhibition of Akt phosphorylation when the drugs were used in combination, where again A549 cells demonstrated the most inhibition following treatment with the drug combination. Combining erlotinib with FAK inhibitor was also potent in vivo as evidenced by reduced tumor growth in the A549 mouse xenograft model. We further ascertained that the enhanced sensitivity was irrespective of the LKB1 mutational status. In summary, we demonstrate the effectiveness of combining erlotinib and FAK inhibitors for use in known EGFR wild-type, EGFR TKI resistant cells, with the potential that a subset of cell types, which includes A549, could be

IASM: Individualized activity space modeler

Science.gov (United States)

Hasanzadeh, Kamyar

2018-01-01

Researchers from various disciplines have long been interested in analyzing and describing human mobility patterns. Activity space (AS), defined as an area encapsulating daily human mobility and activities, has been at the center of this interest. However, given the applied nature of research in this field and the complexity that advanced geographical modeling can pose to its users, the proposed models remain simplistic and inaccurate in many cases. Individualized Activity Space Modeler (IASM) is a geographic information system (GIS) toolbox, written in Python programming language using ESRI's Arcpy module, comprising four tools aiming to facilitate the use of advanced activity space models in empirical research. IASM provides individual-based and context-sensitive tools to estimate home range distances, delineate activity spaces, and model place exposures using individualized geographical data. In this paper, we describe the design and functionality of IASM, and provide an example of how it performs on a spatial dataset collected through an online map-based survey.

Short-term traffic flow prediction model using particle swarm optimization–based combined kernel function-least squares support vector machine combined with chaos theory

Directory of Open Access Journals (Sweden)

Qiang Shang

2016-08-01

Full Text Available Short-term traffic flow prediction is an important part of intelligent transportation systems research and applications. For further improving the accuracy of short-time traffic flow prediction, a novel hybrid prediction model (multivariate phase space reconstruction–combined kernel function-least squares support vector machine based on multivariate phase space reconstruction and combined kernel function-least squares support vector machine is proposed. The C-C method is used to determine the optimal time delay and the optimal embedding dimension of traffic variables’ (flow, speed, and occupancy time series for phase space reconstruction. The G-P method is selected to calculate the correlation dimension of attractor which is an important index for judging chaotic characteristics of the traffic variables’ series. The optimal input form of combined kernel function-least squares support vector machine model is determined by multivariate phase space reconstruction, and the model’s parameters are optimized by particle swarm optimization algorithm. Finally, case validation is carried out using the measured data of an expressway in Xiamen, China. The experimental results suggest that the new proposed model yields better predictions compared with similar models (combined kernel function-least squares support vector machine, multivariate phase space reconstruction–generalized kernel function-least squares support vector machine, and phase space reconstruction–combined kernel function-least squares support vector machine, which indicates that the new proposed model exhibits stronger prediction ability and robustness.

Hyperbolastic modeling of tumor growth with a combined treatment of iodoacetate and dimethylsulphoxide

International Nuclear Information System (INIS)

Eby, Wayne M; Tabatabai, Mohammad A; Bursac, Zoran

2010-01-01

An understanding of growth dynamics of tumors is important in understanding progression of cancer and designing appropriate treatment strategies. We perform a comparative study of the hyperbolastic growth models with the Weibull and Gompertz models, which are prevalently used in the field of tumor growth. The hyperbolastic growth models H1, H2, and H3 are applied to growth of solid Ehrlich carcinoma under several different treatments. These are compared with results from Gompertz and Weibull models for the combined treatment. The growth dynamics of the solid Ehrlich carcinoma with the combined treatment are studied using models H1, H2, and H3, and the models are highly accurate in representing the growth. The growth dynamics are also compared with the untreated tumor, the tumor treated with only iodoacetate, and the tumor treated with only dimethylsulfoxide, and the combined treatment. The hyperbolastic models prove to be effective in representing and analyzing the growth dynamics of the solid Ehrlich carcinoma. These models are more precise than Gompertz and Weibull and show less error for this data set. The precision of H3 allows for its use in a comparative analysis of tumor growth rates between the various treatments

Combined effects of weight loss and physical activity on all-cause mortality of overweight men and women

DEFF Research Database (Denmark)

Østergaard, J N; Grønbaek, M; Schnohr, Peter

2010-01-01

To estimate the excess deaths associated with weight loss in combination with leisure time physical activity among overweight or obese people.......To estimate the excess deaths associated with weight loss in combination with leisure time physical activity among overweight or obese people....

A space-fractional Monodomain model for cardiac electrophysiology combining anisotropy and heterogeneity on realistic geometries

Science.gov (United States)

Cusimano, N.; Gerardo-Giorda, L.

2018-06-01

Classical models of electrophysiology do not typically account for the effects of high structural heterogeneity in the spatio-temporal description of excitation waves propagation. We consider a modification of the Monodomain model obtained by replacing the diffusive term of the classical formulation with a fractional power of the operator, defined in the spectral sense. The resulting nonlocal model describes different levels of tissue heterogeneity as the fractional exponent is varied. The numerical method for the solution of the fractional Monodomain relies on an integral representation of the nonlocal operator combined with a finite element discretisation in space, allowing to handle in a natural way bounded domains in more than one spatial dimension. Numerical tests in two spatial dimensions illustrate the features of the model. Activation times, action potential duration and its dispersion throughout the domain are studied as a function of the fractional parameter: the expected peculiar behaviour driven by tissue heterogeneities is recovered.

Model-based efficiency evaluation of combine harvester traction drives

Directory of Open Access Journals (Sweden)

Steffen Häberle

2015-08-01

Full Text Available As part of the research the drive train of the combine harvesters is investigated in detail. The focus on load and power distribution, energy consumption and usage distribution are explicitly explored on two test machines. Based on the lessons learned during field operations, model-based studies of energy saving potential in the traction train of combine harvesters can now be quantified. Beyond that the virtual machine trial provides an opportunity to compare innovative drivetrain architectures and control solutions under reproducible conditions. As a result, an evaluation method is presented and generically used to draw comparisons under local representative operating conditions.

Combining turbine blade-strike and life cycle models to assess mitigation strategies for fish passing dams

Energy Technology Data Exchange (ETDEWEB)

Ferguson, J.W. [National Marine Fisheries Service, Seattle, WA (United States). Fish Ecology Div.; Swedish Univ. of Agricultural Sciences, Umea (Sweden). Dept. of Wildlife, Fish and Environmental Studies; Ploskey, G.R. [Battelle-Pacific Northwest National Laboratory, Richland, WA (United States); Zabel, R.W. [National Marine Fisheries Service, Seattle, WA (United States). Fish Ecology Div.; Lundqvist, H. [Swedish Univ. of Agricultural Sciences, Umea (Sweden). Dept. of Wildlife, Fish and Environmental Studies

2008-08-15

Many diadromous and resident fish populations migrate within riverine, freshwater, and marine habitats that have been altered by human activities. This paper developed a tool designed to analyze the effects of dams on fish populations. The model combined a blade-strike model of a hydroelectric turbine and a life cycle model in order to generate point estimates of mortality and incorporate dam passage impacts. The modelling tool was used to study populations of Atlantic salmon and sea trout populations in Sweden which were depressed due to damming, dredging, pollution, and siltation of the rivers. The downstream migrating fish in the rivers passed through a single dam and power station containing Kaplan and Francis turbines. A blade-strike model was developed as the primary mechanism of mortality for the fish. The mortality of juvenile and adult fish and mortality rates from blade-strikes were then entered into salmon life cycle models that incorporated life history variability in age of reproduction and spawning activities. The life cycle model populations in the river were then modelled in hypothetical scenarios. Results of the scenarios were compared with effects from the blade-strike mortality results. Results of the study showed that increases in the number of female salmon escaping above the dam after 20 years was significantly higher when both juveniles and adult fish populations were protected. The model will be used to evaluate strategies designed to conserve fish populations impacted by dams. 49 refs., 9 tabs., 6 figs.

Combining turbine blade-strike and life cycle models to assess mitigation strategies for fish passing dams

International Nuclear Information System (INIS)

Ferguson, J.W.; Zabel, R.W.; Lundqvist, H.

2008-01-01

Many diadromous and resident fish populations migrate within riverine, freshwater, and marine habitats that have been altered by human activities. This paper developed a tool designed to analyze the effects of dams on fish populations. The model combined a blade-strike model of a hydroelectric turbine and a life cycle model in order to generate point estimates of mortality and incorporate dam passage impacts. The modelling tool was used to study populations of Atlantic salmon and sea trout populations in Sweden which were depressed due to damming, dredging, pollution, and siltation of the rivers. The downstream migrating fish in the rivers passed through a single dam and power station containing Kaplan and Francis turbines. A blade-strike model was developed as the primary mechanism of mortality for the fish. The mortality of juvenile and adult fish and mortality rates from blade-strikes were then entered into salmon life cycle models that incorporated life history variability in age of reproduction and spawning activities. The life cycle model populations in the river were then modelled in hypothetical scenarios. Results of the scenarios were compared with effects from the blade-strike mortality results. Results of the study showed that increases in the number of female salmon escaping above the dam after 20 years was significantly higher when both juveniles and adult fish populations were protected. The model will be used to evaluate strategies designed to conserve fish populations impacted by dams. 49 refs., 9 tabs., 6 figs

A combined statistical model for multiple motifs search

International Nuclear Information System (INIS)

Gao Lifeng; Liu Xin; Guan Shan

2008-01-01

Transcription factor binding sites (TFBS) play key roles in genebior 6.8 wavelet expression and regulation. They are short sequence segments with definite structure and can be recognized by the corresponding transcription factors correctly. From the viewpoint of statistics, the candidates of TFBS should be quite different from the segments that are randomly combined together by nucleotide. This paper proposes a combined statistical model for finding over-represented short sequence segments in different kinds of data set. While the over-represented short sequence segment is described by position weight matrix, the nucleotide distribution at most sites of the segment should be far from the background nucleotide distribution. The central idea of this approach is to search for such kind of signals. This algorithm is tested on 3 data sets, including binding sites data set of cyclic AMP receptor protein in E.coli, PlantProm DB which is a non-redundant collection of proximal promoter sequences from different species, collection of the intergenic sequences of the whole genome of E.Coli. Even though the complexity of these three data sets is quite different, the results show that this model is rather general and sensible. (general)

Assessment of synergistic antibacterial activity of combined biosurfactants revealed by bacterial cell envelop damage.

Science.gov (United States)

Sana, Santanu; Datta, Sriparna; Biswas, Dipa; Sengupta, Dipanjan

2018-02-01

Besides potential surface activity and some beneficial physical properties, biosurfactants express antibacterial activity. Bacterial cell membrane disrupting ability of rhamnolipid produced by Pseudomonas aeruginosa C2 and a lipopeptide type biosurfactant, BS15 produced by Bacillus stratosphericus A15 was examined against Staphylococcus aureus ATCC 25923 and Escherichia coli K8813. Broth dilution technique was followed to examine minimum inhibitory concentration (MIC) of both the biosurfactants. The combined effect of rhamnolipid and BS15 against S. aureus and E. coli showed synergistic activity by expressing fractional inhibitory concentration (FIC) index of 0.43 and 0.5. Survival curve of both the bacteria showed bactericidal activity after treating with biosurfactants at their MIC obtained from FIC index study as it killed >90% of initial population. The lesser value of MIC than minimum bactericidal concentration (MBC) of the biosurfactants also supported their bactericidal activity against both the bacteria. Membrane permeability against both the bacteria was supported by amplifying protein release, increasing of cell surface hydrophobicity, withholding capacity of crystal violet dye and leakage of intracellular materials. Finally cell membrane disruption was confirmed by scanning electron microscopy (SEM). All these experiments expressed synergism and effective bactericidal activity of the combination of rhamnolipid and BS15 by enhancing the bacterial cell membrane permeability. Such effect of the combination of rhamnolipid and BS15 could make them promising alternatives to traditional antibiotic in near future. Copyright © 2017 Elsevier B.V. All rights reserved.

Achieving bifunctional cloak via combination of passive and active schemes

Science.gov (United States)

Lan, Chuwen; Bi, Ke; Gao, Zehua; Li, Bo; Zhou, Ji

2016-11-01

In this study, a simple and delicate approach to realizing manipulation of multi-physics field simultaneously through combination of passive and active schemes is proposed. In the design, one physical field is manipulated with passive scheme while the other with active scheme. As a proof of this concept, a bifunctional device is designed and fabricated to behave as electric and thermal invisibility cloak simultaneously. It is found that the experimental results are consistent with the simulated ones well, confirming the feasibility of our method. Furthermore, the proposed method could also be extended to other multi-physics fields, which might lead to potential applications in thermal, electric, and acoustic areas.

Promotion of active ageing combining sensor and social network data.

Science.gov (United States)

Bilbao, Aritz; Almeida, Aitor; López-de-Ipiña, Diego

2016-12-01

The increase of life expectancy in modern society has caused an increase in elderly population. Elderly people want to live independently in their home environment for as long as possible. However, as we age, our physical skills tend to worsen and our social circle tends to become smaller, something that often leads to a considerable decrease of both our physical and social activities. In this paper, we present an AAL framework developed within the SONOPA project, whose objective is to promote active ageing by combining a social network with information inferred using in-home sensors. Copyright © 2016 Elsevier Inc. All rights reserved.

Antibacterial activity of combined medicinal plants extract against multiple drug resistant strains

Directory of Open Access Journals (Sweden)

Rafiqul Islam

2015-06-01

Full Text Available Objective: To find out the combined antibacterial efficacy of Aegle marmelos, Aphanamixis polystachya, Cuscuta reflexa and Aesclynomene indica against bacterial pathogens. Methods: Antibacterial potency of combined plant extracts has been tested against Bacillus subtilis IFO 3026, Sarcina lutea IFO 3232, Xanthomonas campestris IAM 1671, Escherichia coli IFO 3007, Klebsiella pneumoniae ATTC 10031, Proteus vulgaris MTCC 321 and Pseudomonas denitrificans KACC 32026 by disc diffusion assay. Commercially available standard antibiotic discs were also used to find out antibiotic resistance pattern of test organisms. Results: Among the test organisms, Escherichia coli, Proteus vulgaris, Klebsiella pneumoniae and Proteus denitrificans showed resistance against multiple commercially available antibiotics. On the other hand, these multiple drug resistant organisms showed susceptibility against combined plant extracts. Conclusions: These combined plants extracts showed synergistic antibacterial activity and could lead to new antibacterial drug designing.

Combining balneotherapy and health promotion to promote active and healthy ageing: the Balaruc-MACVIA-LR® approach.

Science.gov (United States)

Blain, H; Bernard, P L; Canovas, G; Raffort, N; Desfour, H; Soriteau, L; Noguès, M; Camuzat, T; Mercier, J; Dupeyron, A; Quéré, I; Laffont, I; Hérisson, C; Solimene, H; Bousquet, J

2016-12-01

Scaling up and replication of successful innovative integrated care models for chronic diseases is one of the targets of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). MACVIA-LR ® (MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon) is a Reference Site of the EIP on AHA. The main objective of MACVIA-LR ® is to develop innovative solutions in order to (1) improve the care of patients affected by chronic diseases, (2) reduce avoidable hospitalization and (3) scale up the innovation to regions of Europe. The MACVIA-LR ® project also aims to assess all possible aspects of medicine-including non-pharmacologic approaches-in order to maintain health and prevent chronic diseases. These approaches include hydrotherapy and balneotherapy which can be of great importance if health promotion strategies are considered. Balneotherapy at Balaruc-les-Bains focusses on musculoskeletal diseases and chronic venous insufficiency of the lower limbs. Each year, over 46,000 people attend an 18-day course related to a new falls prevention initiative combining balneotherapy and education. On arrival, each person receives a flyer providing information on the risk of fall and, depending on this risk, a course is proposed combining education and physical activity. A pilot study assesses the impact of the course 6 and 12 months later. This health promotion strategy for active and healthy ageing follows the FEMTEC (World Federation of Hydrotherapy and Climatotherapy) concept.

Effects of ginsenoside of stem and leaf combined with choline on learning and memory ability of rat models with Alzheimer diseases

Institute of Scientific and Technical Information of China (English)

Xiaomin Zhao; Xianglin Xie; Zuoli Xia; Yunsheng Gao; Yuyun Zhu; Hongxia Gu

2006-01-01

alternating current. If rats jumped down from the platform and the feet touched railings, the response was wrong. Numbers of wrong response were recorded within 3 minutes, and then the test was redone after 24 hours. ② Morris water-maze spatial localization task:Swimming from jumping-off to platform directly was regarded as right response. Additionally, 4 successively right responses were regarded as the standard. Each rat was trained 10 times a day with 120 s per time for 3successive days. The interval was 30 s. Three days later, numbers of right response were recorded. The traincortex: Rats were sacrificed at 17 days after operation to obtain cerebral cortex to measure activity of choilne acetylase with radiochemistry technique. ④ Synergistic effect: It was expressed as Q value: Q value = factual incorporative effect/anticipant incorporative effect; Q ≥ 1 was regarded as synergistic effect. Anticipant incorporative effect = (EA+EB-EA· EB), EA and EB were single timing effect, respectively in GSL group and choline group. E(step-down test and Morris water maze test) = (x in model group - factual value in medicine groups)/x in model group; E (activity of choiine acetylase) = (factual value in medicine groups -xin model group)/x in model group.MATN OUTCOME MEASURES : ① Passive avoidance step-down test and Morris water-maze spatial localization task in the study of learning and memory; ② activity of choiine acetylase.RESULTS: All 40 rats were involved in the final analysis. ① Passive avoidance response: At learning phase on first day and retesting phase on the next day, numbers of wrong responses within 3 minutes were more in model group than sham operation group, and there was significant difference [(5.88±1.46), (2.25±0.87) times;(2.63±1.06), (0.50±0.53) times; P＜ 0.01]; numbers of wrong responses within 3 minutes were less in combination group than model group, and there was significant difference [learning phase: (1.12±0.83), (5.88±1.46)times; retesting

Activated sludge model No. 3

DEFF Research Database (Denmark)

Gujer, W.; Henze, M.; Mino, T.

1999-01-01

The Activated Sludge Model No. 3 (ASM3) can predict oxygen consumption, sludge production, nitrification and denitrification of activated sludge systems. It relates to the Activated Sludge Model No. 1 (ASM1) and corrects for some defects of ASM I. In addition to ASM1, ASM3 includes storage of org...

Time-Varying Combinations of Bayesian Dynamic Models and Equity Momentum Strategies

NARCIS (Netherlands)

N. Basturk (Nalan); S. Grassi (Stefano); L.F. Hoogerheide (Lennart); H.K. van Dijk (Herman)

2016-01-01

markdownabstractA novel dynamic asset-allocation approach is proposed where portfolios as well as portfolio strategies are updated at every decision period based on their past performance. For modeling, a general class of models is specified that combines a dynamic factor and a vector autoregressive

A Bayesian Combined Model for Time-Dependent Turning Movement Proportions Estimation at Intersections

Directory of Open Access Journals (Sweden)

Pengpeng Jiao

2014-01-01

Full Text Available Time-dependent turning movement flows are very important input data for intelligent transportation systems but are impossible to be detected directly through current traffic surveillance systems. Existing estimation models have proved to be not accurate and reliable enough during all intervals. An improved way to address this problem is to develop a combined model framework that can integrate multiple submodels running simultaneously. This paper first presents a back propagation neural network model to estimate dynamic turning movements, as well as the self-adaptive learning rate approach and the gradient descent with momentum method for solving. Second, this paper develops an efficient Kalman filtering model and designs a revised sequential Kalman filtering algorithm. Based on the Bayesian method using both historical data and currently estimated results for error calibration, this paper further integrates above two submodels into a Bayesian combined model framework and proposes a corresponding algorithm. A field survey is implemented at an intersection in Beijing city to collect both time series of link counts and actual time-dependent turning movement flows, including historical and present data. The reported estimation results show that the Bayesian combined model is much more accurate and stable than other models.

Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study.

Science.gov (United States)

Sanmukhani, Jayesh; Anovadiya, Ashish; Tripathi, Chandrabhanu B

2011-01-01

Curcumin is the active ingredient of commonly used spice Curuma longa Linn. In the present study, the antidepressant like activity of curcumin and its combination with fluoxetine and imipramine was studied in acute model (three doses 24, 5 and 1 h before test) of forced swimming test (FST) in glass jar and tail suspension test (TST) in mice and in chronic model (14 day study) of FST with water wheel in rats. All the tests were carried out in the following seven groups (n = 6 in each group), drugs being given orally (doses for mice): Group 1 (vehicle), group 2 (curcumin 50 mg/kg), group 3 (curcumin 100 mg/kg), group 4 (fluoxetine 20 mg/kg), group 5 (imipramine 15 mg/kg), group 6 (curcumin 100 mg/kg plus fluoxetine 20 mg/kg) and group 7 (curcumin 100 mg/kg plus imipramine 15 mg/kg). Equivalent doses for rats were used. Both the acute model of FST and TST, and the chronic model of FST with water wheel showed significant antidepressant like activity of curcumin in 100 mg/kg dose as compared to vehicle control (p fluoxetine and imipramine (p > 0.05) but its addition to fluoxetine and imipramine did not improve their antidepressant activity (p > 0.05). Curcumin increased both the swimming and climbing behavior in FST, thus its antidepressant like activity could be due to an increase in serotonin, norepinephrine and dopamine levels in the brain. Curcumin can be a useful antidepressant especially in cases which respond to drugs having mixed effects on serotonin and catecholamines levels in the brain.

Modeling biological gradient formation: combining partial differential equations and Petri nets.

Science.gov (United States)

Bertens, Laura M F; Kleijn, Jetty; Hille, Sander C; Heiner, Monika; Koutny, Maciej; Verbeek, Fons J

2016-01-01

Both Petri nets and differential equations are important modeling tools for biological processes. In this paper we demonstrate how these two modeling techniques can be combined to describe biological gradient formation. Parameters derived from partial differential equation describing the process of gradient formation are incorporated in an abstract Petri net model. The quantitative aspects of the resulting model are validated through a case study of gradient formation in the fruit fly.

Combining Spatial Models for Shallow Landslides and Debris-Flows Prediction

Directory of Open Access Journals (Sweden)

Eurípedes Vargas do Amaral

2013-05-01

Full Text Available Mass movements in Brazil are common phenomena, especially during strong rainfall events that occur frequently in the summer season. These phenomena cause losses of lives and serious damage to roads, bridges, and properties. Moreover, the illegal occupation by slums on the slopes around the cities intensifies the effect of the mass movement. This study aimed to develop a methodology that combines models of shallow landslides and debris-flows in order to create a map with landslides initiation and debris-flows volume and runout distance. The study area comprised of two catchments in Rio de Janeiro city: Quitite and Papagaio that drained side by side the west flank of the Maciço da Tijuca, with an area of 5 km2. The method included the following steps: (a location of the susceptible areas to landslides using SHALSTAB model; (b determination of rheological parameters of debris-flow from the back-analysis technique; and (c combination of SHALSTAB and FLO-2D models to delineate the areas more susceptible to mass movements. These scenarios were compared with the landslide and debris-flow event of February 1996. Many FLO-2D simulations were exhaustively made to estimate the rheological parameters from the back-analysis technique. Those rheological coefficients of single simulation were back-calculated by adjusting with area and depth of the debris-flow obtained from field data. The initial material volume in the FLO-2D simulations was estimated from SHALSTAB model. The combination of these two mathematical models, SHALSTAB and FLO-2D, was able to predict both landslides and debris-flow events. Such procedures can reduce the casualties and property damage, delineating hazard areas, to estimate hazard intensities for input into risk studies providing information for public policy and planning.

Stochastic E2F activation and reconciliation of phenomenological cell-cycle models.

Science.gov (United States)

Lee, Tae J; Yao, Guang; Bennett, Dorothy C; Nevins, Joseph R; You, Lingchong

2010-09-21

The transition of the mammalian cell from quiescence to proliferation is a highly variable process. Over the last four decades, two lines of apparently contradictory, phenomenological models have been proposed to account for such temporal variability. These include various forms of the transition probability (TP) model and the growth control (GC) model, which lack mechanistic details. The GC model was further proposed as an alternative explanation for the concept of the restriction point, which we recently demonstrated as being controlled by a bistable Rb-E2F switch. Here, through a combination of modeling and experiments, we show that these different lines of models in essence reflect different aspects of stochastic dynamics in cell cycle entry. In particular, we show that the variable activation of E2F can be described by stochastic activation of the bistable Rb-E2F switch, which in turn may account for the temporal variability in cell cycle entry. Moreover, we show that temporal dynamics of E2F activation can be recast into the frameworks of both the TP model and the GC model via parameter mapping. This mapping suggests that the two lines of phenomenological models can be reconciled through the stochastic dynamics of the Rb-E2F switch. It also suggests a potential utility of the TP or GC models in defining concise, quantitative phenotypes of cell physiology. This may have implications in classifying cell types or states.

Prediction of Combine Economic Life Based on Repair and Maintenance Costs Model

Directory of Open Access Journals (Sweden)

A Rohani

2014-09-01

Full Text Available Farm machinery managers often need to make complex economic decisions on machinery replacement. Repair and maintenance costs can have significant impacts on this economic decision. The farm manager must be able to predict farm machinery repair and maintenance costs. This study aimed to identify a regression model that can adequately represent the repair and maintenance costs in terms of machine age in cumulative hours of use. The regression model has the ability to predict the repair and maintenance costs for longer time periods. Therefore, it can be used for the estimation of the economic life. The study was conducted using field data collected from 11 John-Deer 955 combine harvesters used in several western provinces of Iran. It was found that power model has a better performance for the prediction of combine repair and maintenance costs. The results showed that the optimum replacement age of John-Deer 955 combine was 54300 cumulative hours.

A unified internal model theory to resolve the paradox of active versus passive self-motion sensation.

Science.gov (United States)

Laurens, Jean; Angelaki, Dora E

2017-10-18

Brainstem and cerebellar neurons implement an internal model to accurately estimate self-motion during externally generated ('passive') movements. However, these neurons show reduced responses during self-generated ('active') movements, indicating that predicted sensory consequences of motor commands cancel sensory signals. Remarkably, the computational processes underlying sensory prediction during active motion and their relationship to internal model computations during passive movements remain unknown. We construct a Kalman filter that incorporates motor commands into a previously established model of optimal passive self-motion estimation. The simulated sensory error and feedback signals match experimentally measured neuronal responses during active and passive head and trunk rotations and translations. We conclude that a single sensory internal model can combine motor commands with vestibular and proprioceptive signals optimally. Thus, although neurons carrying sensory prediction error or feedback signals show attenuated modulation, the sensory cues and internal model are both engaged and critically important for accurate self-motion estimation during active head movements.

Physical mechanisms of collective expansion in confluent tissues in an Active Vertex Model

Science.gov (United States)

Czajkowski, Michael; Bi, Dapeng; Yang, Xingbo; Merkel, Matthias; Manning, M. Lisa; Marchetti, M. Cristina

Living tissues form many novel patterns due to the active forces exerted by the constituent cells. How these forces combine with proliferation (changing number density) and boundary conditions to control the resultant patterns is an interesting open question. This question arises naturally for in vitro wound healing experiments, where an initially confined monolayer is allowed to expand freely. As the cells interact, proliferate and advance laterally, a characteristic pattern of traction stresses is formed on the substrate. We have developed an Active Vertex Model to make predictions about active confluent tissues with free boundaries. The model incorporates active forces, flocking interactions, and simple rules for cell division within the vertex model geometry. It also exhibits a fluid-solid transition, with qualitatively distinct stress profiles in the solid and in the liquid. Furthermore, under the assumption that cells proliferate more when stretched, we find that polar alignment interactions strongly enhance cell proliferation. Our model suggests that wound healing assays may provide a useful rheological tool for tissues, as well as a novel system for studying the connection between proliferation and flocking. We acknowledge support from NSF-DGE-1068780 and The Simons Foundation for the Investigator Award in MMLS as well as the Targeted Grant in the Mathematical Modeling of Living Systems Number: 342354.

A sequential Monte Carlo model of the combined GB gas and electricity network

International Nuclear Information System (INIS)

Chaudry, Modassar; Wu, Jianzhong; Jenkins, Nick

2013-01-01

A Monte Carlo model of the combined GB gas and electricity network was developed to determine the reliability of the energy infrastructure. The model integrates the gas and electricity network into a single sequential Monte Carlo simulation. The model minimises the combined costs of the gas and electricity network, these include gas supplies, gas storage operation and electricity generation. The Monte Carlo model calculates reliability indices such as loss of load probability and expected energy unserved for the combined gas and electricity network. The intention of this tool is to facilitate reliability analysis of integrated energy systems. Applications of this tool are demonstrated through a case study that quantifies the impact on the reliability of the GB gas and electricity network given uncertainties such as wind variability, gas supply availability and outages to energy infrastructure assets. Analysis is performed over a typical midwinter week on a hypothesised GB gas and electricity network in 2020 that meets European renewable energy targets. The efficacy of doubling GB gas storage capacity on the reliability of the energy system is assessed. The results highlight the value of greater gas storage facilities in enhancing the reliability of the GB energy system given various energy uncertainties. -- Highlights: •A Monte Carlo model of the combined GB gas and electricity network was developed. •Reliability indices are calculated for the combined GB gas and electricity system. •The efficacy of doubling GB gas storage capacity on reliability of the energy system is assessed. •Integrated reliability indices could be used to assess the impact of investment in energy assets

Combined Prediction Model of Death Toll for Road Traffic Accidents Based on Independent and Dependent Variables

Directory of Open Access Journals (Sweden)

Feng Zhong-xiang

2014-01-01

Full Text Available In order to build a combined model which can meet the variation rule of death toll data for road traffic accidents and can reflect the influence of multiple factors on traffic accidents and improve prediction accuracy for accidents, the Verhulst model was built based on the number of death tolls for road traffic accidents in China from 2002 to 2011; and car ownership, population, GDP, highway freight volume, highway passenger transportation volume, and highway mileage were chosen as the factors to build the death toll multivariate linear regression model. Then the two models were combined to be a combined prediction model which has weight coefficient. Shapley value method was applied to calculate the weight coefficient by assessing contributions. Finally, the combined model was used to recalculate the number of death tolls from 2002 to 2011, and the combined model was compared with the Verhulst and multivariate linear regression models. The results showed that the new model could not only characterize the death toll data characteristics but also quantify the degree of influence to the death toll by each influencing factor and had high accuracy as well as strong practicability.

Combined prediction model of death toll for road traffic accidents based on independent and dependent variables.

Science.gov (United States)

Feng, Zhong-xiang; Lu, Shi-sheng; Zhang, Wei-hua; Zhang, Nan-nan

2014-01-01

In order to build a combined model which can meet the variation rule of death toll data for road traffic accidents and can reflect the influence of multiple factors on traffic accidents and improve prediction accuracy for accidents, the Verhulst model was built based on the number of death tolls for road traffic accidents in China from 2002 to 2011; and car ownership, population, GDP, highway freight volume, highway passenger transportation volume, and highway mileage were chosen as the factors to build the death toll multivariate linear regression model. Then the two models were combined to be a combined prediction model which has weight coefficient. Shapley value method was applied to calculate the weight coefficient by assessing contributions. Finally, the combined model was used to recalculate the number of death tolls from 2002 to 2011, and the combined model was compared with the Verhulst and multivariate linear regression models. The results showed that the new model could not only characterize the death toll data characteristics but also quantify the degree of influence to the death toll by each influencing factor and had high accuracy as well as strong practicability.

Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

International Nuclear Information System (INIS)

Wada, Satoshi; Harris, Timothy J.; Tryggestad, Erik; Yoshimura, Kiyoshi; Zeng, Jing; Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F.; Bruno, Tullia C.; De Marzo, Angelo M.

2013-01-01

Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting

Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

Energy Technology Data Exchange (ETDEWEB)

Wada, Satoshi [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Harris, Timothy J.; Tryggestad, Erik [Department of Radiation Oncology and Molecular Radiation Sciences, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Yoshimura, Kiyoshi [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Zeng, Jing [Department of Radiation Oncology and Molecular Radiation Sciences, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Yen, Hung-Rong; Getnet, Derese; Grosso, Joseph F.; Bruno, Tullia C. [Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); De Marzo, Angelo M. [Department of Pathology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); and others

2013-11-15

Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting.

Competing intermolecular interactions of artemisinin-type agents and aspirin with membrane phospholipids: Combined model mass spectrometry and quantum-chemical study

International Nuclear Information System (INIS)

Pashynska, Vlada; Stepanian, Stepan; Gömöry, Agnes; Vekey, Karoly; Adamowicz, Ludwik

2015-01-01

Highlights: • Competitive binding of artemisinin agents and aspirin with phospholipids is shown. • Complexation between the antimalarial drugs and aspirin molecules is also found. • Energetically favorable structures of the model complexes are identified by DFT. • Membranotropic activity of the studied drugs can be modified under joint usage. - Abstract: Study of intermolecular interactions of antimalarial artemisinin-type drugs and aspirin with membrane phospholipids is important in term of elucidation of the drugs activity modification under their joint usage. Combined experimental and computational study of the interaction of dihydroartemisinin, α-artemether, and artesunate with aspirin (ASP) and dipalmitoylphosphatidylcholine (DPPC) is performed by electrospray ionization (ESI) mass spectrometry and by DFT B3LYP/aug-cc-pVDZ methods. The results of the ESI investigation of systems containing artemisinin-type agent, ASP and DPPC, reveal a competition between the antimalarial agents and ASP for binding with DPPC molecules. The complexation between the antimalarial drugs and ASP is also found. Observed phenomena suggest that membranotropic activity of artemisin-type agents and aspirin is modified under their combined usage. To elucidate structure-energy characteristics of the non-covalent complexes studied the model DFT calculations are performed for dihydroartemisinin · ASP complex and complexes of the each drug with phosphatidylcholine head of DPPC in neutral and cationized forms

Competing intermolecular interactions of artemisinin-type agents and aspirin with membrane phospholipids: Combined model mass spectrometry and quantum-chemical study

Energy Technology Data Exchange (ETDEWEB)

Pashynska, Vlada, E-mail: vlada@vl.kharkov.ua [B.Verkin Institute for Low Temperature Physics and Engineering of the National Academy of Sciences of Ukraine, Lenin Ave., 47, 61103 Kharkov (Ukraine); Stepanian, Stepan [B.Verkin Institute for Low Temperature Physics and Engineering of the National Academy of Sciences of Ukraine, Lenin Ave., 47, 61103 Kharkov (Ukraine); Gömöry, Agnes; Vekey, Karoly [Institute of Organic Chemistry of Research Centre for Natural Sciences of the Hungarian Academy of Sciences, Magyar tudosok korutja, 2, Budapest H-1117 (Hungary); Adamowicz, Ludwik [University of Arizona, Department of Chemistry and Biochemistry, Tucson, AZ 85721 (United States)

2015-07-09

Highlights: • Competitive binding of artemisinin agents and aspirin with phospholipids is shown. • Complexation between the antimalarial drugs and aspirin molecules is also found. • Energetically favorable structures of the model complexes are identified by DFT. • Membranotropic activity of the studied drugs can be modified under joint usage. - Abstract: Study of intermolecular interactions of antimalarial artemisinin-type drugs and aspirin with membrane phospholipids is important in term of elucidation of the drugs activity modification under their joint usage. Combined experimental and computational study of the interaction of dihydroartemisinin, α-artemether, and artesunate with aspirin (ASP) and dipalmitoylphosphatidylcholine (DPPC) is performed by electrospray ionization (ESI) mass spectrometry and by DFT B3LYP/aug-cc-pVDZ methods. The results of the ESI investigation of systems containing artemisinin-type agent, ASP and DPPC, reveal a competition between the antimalarial agents and ASP for binding with DPPC molecules. The complexation between the antimalarial drugs and ASP is also found. Observed phenomena suggest that membranotropic activity of artemisin-type agents and aspirin is modified under their combined usage. To elucidate structure-energy characteristics of the non-covalent complexes studied the model DFT calculations are performed for dihydroartemisinin · ASP complex and complexes of the each drug with phosphatidylcholine head of DPPC in neutral and cationized forms.

Bayesian analysis for erosion modelling of sediments in combined sewer systems.

Science.gov (United States)

Kanso, A; Chebbo, G; Tassin, B

2005-01-01

Previous research has confirmed that the sediments at the bed of combined sewer systems are the main source of particulate and organic pollution during rain events contributing to combined sewer overflows. However, existing urban stormwater models utilize inappropriate sediment transport formulas initially developed from alluvial hydrodynamics. Recently, a model has been formulated and profoundly assessed based on laboratory experiments to simulate the erosion of sediments in sewer pipes taking into account the increase in strength with depth in the weak layer of deposits. In order to objectively evaluate this model, this paper presents a Bayesian analysis of the model using field data collected in sewer pipes in Paris under known hydraulic conditions. The test has been performed using a MCMC sampling method for calibration and uncertainty assessment. Results demonstrate the capacity of the model to reproduce erosion as a direct response to the increase in bed shear stress. This is due to the model description of the erosional strength in the deposits and to the shape of the measured bed shear stress. However, large uncertainties in some of the model parameters suggest that the model could be over-parameterised and necessitates a large amount of informative data for its calibration.

A linear combination of pharmacophore hypotheses as a new tool in search of new active compounds--an application for 5-HT1A receptor ligands.

Directory of Open Access Journals (Sweden)

Dawid Warszycki

Full Text Available This study explores a new approach to pharmacophore screening involving the use of an optimized linear combination of models instead of a single hypothesis. The implementation and evaluation of the developed methodology are performed for a complete known chemical space of 5-HT1AR ligands (3616 active compounds with K i < 100 nM acquired from the ChEMBL database. Clusters generated from three different methods were the basis for the individual pharmacophore hypotheses, which were assembled into optimal combinations to maximize the different coefficients, namely, MCC, accuracy and recall, to measure the screening performance. Various factors that influence filtering efficiency, including clustering methods, the composition of test sets (random, the most diverse and cluster population-dependent and hit mode (the compound must fit at least one or two models from a final combination were investigated. This method outmatched both single hypothesis and random linear combination approaches.

Effects of environmental variables on invasive amphibian activity: Using model selection on quantiles for counts

Science.gov (United States)

Muller, Benjamin J.; Cade, Brian S.; Schwarzkoph, Lin

2018-01-01

Many different factors influence animal activity. Often, the value of an environmental variable may influence significantly the upper or lower tails of the activity distribution. For describing relationships with heterogeneous boundaries, quantile regressions predict a quantile of the conditional distribution of the dependent variable. A quantile count model extends linear quantile regression methods to discrete response variables, and is useful if activity is quantified by trapping, where there may be many tied (equal) values in the activity distribution, over a small range of discrete values. Additionally, different environmental variables in combination may have synergistic or antagonistic effects on activity, so examining their effects together, in a modeling framework, is a useful approach. Thus, model selection on quantile counts can be used to determine the relative importance of different variables in determining activity, across the entire distribution of capture results. We conducted model selection on quantile count models to describe the factors affecting activity (numbers of captures) of cane toads (Rhinella marina) in response to several environmental variables (humidity, temperature, rainfall, wind speed, and moon luminosity) over eleven months of trapping. Environmental effects on activity are understudied in this pest animal. In the dry season, model selection on quantile count models suggested that rainfall positively affected activity, especially near the lower tails of the activity distribution. In the wet season, wind speed limited activity near the maximum of the distribution, while minimum activity increased with minimum temperature. This statistical methodology allowed us to explore, in depth, how environmental factors influenced activity across the entire distribution, and is applicable to any survey or trapping regime, in which environmental variables affect activity.

Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection

Energy Technology Data Exchange (ETDEWEB)

Koizumi, Yoshiki [School of Medicine, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan; Nakajim, Syo [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan; Department of Applied Biological Sciences, Faculty of Science and Technology, Tokyo University of Sciences, Chiba, J; Ohash, Hirofumi [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan: Department of Applied Biological Sciences, Faculty of Science and Technology, Tokyo University of Sciences, Chiba, J; Tanaka, Yasuhito [Department of Virology and Liver Unit, Nagoya City University Graduate School of Medicinal Sciences, Nagoya, Japan; Wakita, Takaji [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan; Perelson, Alan S. [Los Alamos National Laboratory; Iwami, Shingo [Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan: PRESTO, JST, Saitama, Japan: CREST, JST, Saitama, Japan; Watashi, Koichi [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan: Department of Applied Biological Sciences, Faculty of Science and Technology, Tokyo University of Sciences, Chiba, J

2016-03-21

Cell culture study combing a mathematical model and computer simulation quantifies the anti-hepatitis C virus drug efficacy at any concentrations and any combinations in preclinical settings, and can obtain rich basic evidences for selecting optimal treatments prior to costly clinical trials.

Combination of supervised and semi-supervised regression models for improved unbiased estimation

DEFF Research Database (Denmark)

Arenas-Garía, Jeronimo; Moriana-Varo, Carlos; Larsen, Jan

2010-01-01

In this paper we investigate the steady-state performance of semisupervised regression models adjusted using a modified RLS-like algorithm, identifying the situations where the new algorithm is expected to outperform standard RLS. By using an adaptive combination of the supervised and semisupervi......In this paper we investigate the steady-state performance of semisupervised regression models adjusted using a modified RLS-like algorithm, identifying the situations where the new algorithm is expected to outperform standard RLS. By using an adaptive combination of the supervised...

Similitude Modeling in RDC Activities

International Nuclear Information System (INIS)

Rosli Darmawan

2015-01-01

Research and development activities would involve the scaled modelling activities in order to investigate theory, facts, thesis or concepts. In commercialisation activities, scaling-up proses is necessary for the development of pilot plants or prototypes. The issue with scaled modelling is the similarity between the small scaled model and the full scaled prototype in all aspects of the system such as physical appearance, dimension and the system behaviour. Similarly, for scaling-up process, physical parameters and behaviour of a smaller model need to be developed into a bigger prototype with similar system. Either way, the modelling process must be able to produce a reliable representation of the system or process so that the objectives or functions of the system can be achieved. This paper discusses a modelling method which may be able to produce similar representation of any system or process either in scaled-model testing or scaling-up processes. (author)

Energy Model of Neuron Activation.

Science.gov (United States)

Romanyshyn, Yuriy; Smerdov, Andriy; Petrytska, Svitlana

2017-02-01

On the basis of the neurophysiological strength-duration (amplitude-duration) curve of neuron activation (which relates the threshold amplitude of a rectangular current pulse of neuron activation to the pulse duration), as well as with the use of activation energy constraint (the threshold curve corresponds to the energy threshold of neuron activation by a rectangular current pulse), an energy model of neuron activation by a single current pulse has been constructed. The constructed model of activation, which determines its spectral properties, is a bandpass filter. Under the condition of minimum-phase feature of the neuron activation model, on the basis of Hilbert transform, the possibilities of phase-frequency response calculation from its amplitude-frequency response have been considered. Approximation to the amplitude-frequency response by the response of the Butterworth filter of the first order, as well as obtaining the pulse response corresponding to this approximation, give us the possibility of analyzing the efficiency of activating current pulses of various shapes, including analysis in accordance with the energy constraint.

Modeling Ethanol Decomposition on Transition Metals: A Combined Application of Scaling and Bronsted-Evans-Polanyi Relations

DEFF Research Database (Denmark)

Ferrin, P.; Simonetti, D.; Kandoi, S.

2009-01-01

calculations necessary to describe trends in activity and selectivity across metal and alloy surfaces, thus extending the reach of DFT to more complex systems. In-this work, the well-known family of Bronsted-Evans-Polanyi (BEP) correlations, connecting minima with maxima in the potential energy surface...... on a subset of these surfaces are calculated. Experiments on supported catalysts verify that this simple model is reasonably accurate in describing reactivity trends across metals, suggesting that the combination of BEP and scaling relations may substantially reduce the cost of DFT calculations required...

Modeling the Non-Linear Response of Fiber-Reinforced Laminates Using a Combined Damage/Plasticity Model

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Schuecker, Clara; Davila, Carlos G.; Pettermann, Heinz E.

2008-01-01

The present work is concerned with modeling the non-linear response of fiber reinforced polymer laminates. Recent experimental data suggests that the non-linearity is not only caused by matrix cracking but also by matrix plasticity due to shear stresses. To capture the effects of those two mechanisms, a model combining a plasticity formulation with continuum damage has been developed to simulate the non-linear response of laminates under plane stress states. The model is used to compare the predicted behavior of various laminate lay-ups to experimental data from the literature by looking at the degradation of axial modulus and Poisson s ratio of the laminates. The influence of residual curing stresses and in-situ effect on the predicted response is also investigated. It is shown that predictions of the combined damage/plasticity model, in general, correlate well with the experimental data. The test data shows that there are two different mechanisms that can have opposite effects on the degradation of the laminate Poisson s ratio which is captured correctly by the damage/plasticity model. Residual curing stresses are found to have a minor influence on the predicted response for the cases considered here. Some open questions remain regarding the prediction of damage onset.

A Drug Combination Screen Identifies Drugs Active against Amoxicillin-induced Round Bodies of Borrelia burgdorferi Persisters from an FDA Drug Library

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Jie eFeng

2016-05-01

Full Text Available Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that are not killed by current Lyme antibiotics. To identify more effective drugs that are active against the round bodies of B. burgdorferi, we established a round body persister model induced by amoxicillin and screened the Food and Drug Administration (FDA drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide (PI viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven of these scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. While some drug candidates such as daptomycin and clofazimine overlapped with a previous screen against stationary phase B. burgdorferi persisters, additional drug candidates active against round bodies we identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi persisters in vitro, even if pre-treated with amoxicillin. These findings may have implications for improved treatment of Lyme disease.

Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel.

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Wein, Alexander N; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T; Leppla, Stephen H

2013-02-01

PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wildtype lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6, paclitaxel showed a dose response in vitro, but cells remained resistant to PA-U2/LF even in the presence of paclitaxel. In vivo, each therapy slowed tumor progression, and an additive effect between the two was observed. Since LF targets tumor vasculature while paclitaxel is an antimitotic, it is possible the agents were acting against different cells in the stroma, precluding a synergistic effect. The engineered anthrax toxin PA-U2/LF warrants further development and testing, possibly in combination with an antiangiogenesis therapy such as sunitinib or sorafinib.

Modeling plant interspecific interactions from experiments with perennial crop mixtures to predict optimal combinations.

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Halty, Virginia; Valdés, Matías; Tejera, Mauricio; Picasso, Valentín; Fort, Hugo

2017-12-01

The contribution of plant species richness to productivity and ecosystem functioning is a longstanding issue in ecology, with relevant implications for both conservation and agriculture. Both experiments and quantitative modeling are fundamental to the design of sustainable agroecosystems and the optimization of crop production. We modeled communities of perennial crop mixtures by using a generalized Lotka-Volterra model, i.e., a model such that the interspecific interactions are more general than purely competitive. We estimated model parameters -carrying capacities and interaction coefficients- from, respectively, the observed biomass of monocultures and bicultures measured in a large diversity experiment of seven perennial forage species in Iowa, United States. The sign and absolute value of the interaction coefficients showed that the biological interactions between species pairs included amensalism, competition, and parasitism (asymmetric positive-negative interaction), with various degrees of intensity. We tested the model fit by simulating the combinations of more than two species and comparing them with the polycultures experimental data. Overall, theoretical predictions are in good agreement with the experiments. Using this model, we also simulated species combinations that were not sown. From all possible mixtures (sown and not sown) we identified which are the most productive species combinations. Our results demonstrate that a combination of experiments and modeling can contribute to the design of sustainable agricultural systems in general and to the optimization of crop production in particular. © 2017 by the Ecological Society of America.

BAYESIAN FORECASTS COMBINATION TO IMPROVE THE ROMANIAN INFLATION PREDICTIONS BASED ON ECONOMETRIC MODELS

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Mihaela Simionescu

2014-12-01

Full Text Available There are many types of econometric models used in predicting the inflation rate, but in this study we used a Bayesian shrinkage combination approach. This methodology is used in order to improve the predictions accuracy by including information that is not captured by the econometric models. Therefore, experts’ forecasts are utilized as prior information, for Romania these predictions being provided by Institute for Economic Forecasting (Dobrescu macromodel, National Commission for Prognosis and European Commission. The empirical results for Romanian inflation show the superiority of a fixed effects model compared to other types of econometric models like VAR, Bayesian VAR, simultaneous equations model, dynamic model, log-linear model. The Bayesian combinations that used experts’ predictions as priors, when the shrinkage parameter tends to infinite, improved the accuracy of all forecasts based on individual models, outperforming also zero and equal weights predictions and naïve forecasts.

Thin Cloud Detection Method by Linear Combination Model of Cloud Image

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Liu, L.; Li, J.; Wang, Y.; Xiao, Y.; Zhang, W.; Zhang, S.

2018-04-01

The existing cloud detection methods in photogrammetry often extract the image features from remote sensing images directly, and then use them to classify images into cloud or other things. But when the cloud is thin and small, these methods will be inaccurate. In this paper, a linear combination model of cloud images is proposed, by using this model, the underlying surface information of remote sensing images can be removed. So the cloud detection result can become more accurate. Firstly, the automatic cloud detection program in this paper uses the linear combination model to split the cloud information and surface information in the transparent cloud images, then uses different image features to recognize the cloud parts. In consideration of the computational efficiency, AdaBoost Classifier was introduced to combine the different features to establish a cloud classifier. AdaBoost Classifier can select the most effective features from many normal features, so the calculation time is largely reduced. Finally, we selected a cloud detection method based on tree structure and a multiple feature detection method using SVM classifier to compare with the proposed method, the experimental data shows that the proposed cloud detection program in this paper has high accuracy and fast calculation speed.

Validation and calibration of structural models that combine information from multiple sources.

Science.gov (United States)

Dahabreh, Issa J; Wong, John B; Trikalinos, Thomas A

2017-02-01

Mathematical models that attempt to capture structural relationships between their components and combine information from multiple sources are increasingly used in medicine. Areas covered: We provide an overview of methods for model validation and calibration and survey studies comparing alternative approaches. Expert commentary: Model validation entails a confrontation of models with data, background knowledge, and other models, and can inform judgments about model credibility. Calibration involves selecting parameter values to improve the agreement of model outputs with data. When the goal of modeling is quantitative inference on the effects of interventions or forecasting, calibration can be viewed as estimation. This view clarifies issues related to parameter identifiability and facilitates formal model validation and the examination of consistency among different sources of information. In contrast, when the goal of modeling is the generation of qualitative insights about the modeled phenomenon, calibration is a rather informal process for selecting inputs that result in model behavior that roughly reproduces select aspects of the modeled phenomenon and cannot be equated to an estimation procedure. Current empirical research on validation and calibration methods consists primarily of methodological appraisals or case-studies of alternative techniques and cannot address the numerous complex and multifaceted methodological decisions that modelers must make. Further research is needed on different approaches for developing and validating complex models that combine evidence from multiple sources.

A Combined Cooperative Braking Model with a Predictive Control Strategy in an Electric Vehicle

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Hongqiang Guo

2013-12-01

Full Text Available Cooperative braking with regenerative braking and mechanical braking plays an important role in electric vehicles for energy-saving control. Based on the parallel and the series cooperative braking models, a combined model with a predictive control strategy to get a better cooperative braking performance is presented. The balance problem between the maximum regenerative energy recovery efficiency and the optimum braking stability is solved through an off-line process optimization stream with the collaborative optimization algorithm (CO. To carry out the process optimization stream, the optimal Latin hypercube design (Opt LHD is presented to discrete the continuous design space. To solve the poor real-time problem of the optimization, a high-precision predictive model based on the off-line optimization data of the combined model is built, and a predictive control strategy is proposed and verified through simulation. The simulation results demonstrate that the predictive control strategy and the combined model are reasonable and effective.

Activities of colistin- and minocycline-based combinations against extensive drug resistant Acinetobacter baumannii isolates from intensive care unit patients

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Li Jian

2011-04-01

Full Text Available Abstract Background Extensive drug resistance of Acinetobacter baumannii is a serious problem in the clinical setting. It is therefore important to find active antibiotic combinations that could be effective in the treatment of infections caused by this problematic 'superbug'. In this study, we analyzed the in vitro activities of three colistin-based combinations and a minocycline-based combination against clinically isolated extensive drug resistant Acinetobacter baumannii (XDR-AB strains. Methods Fourteen XDR-AB clinical isolates were collected. The clonotypes were determined by polymerase chain reaction-based fingerprinting. Susceptibility testing was carried out according to the standards of the Clinical and Laboratory Standards Institute. Activities of drug combinations were investigated against four selected strains and analyzed by mean survival time over 12 hours (MST12 h in a time-kill study. Results The time-kill studies indicated that the minimum inhibitory concentration (MIC of colistin (0.5 or 0.25 μg/mL completely killed all strains at 2 to 4 hours, but 0.5×MIC colistin showed no bactericidal activity. Meropenem (8 μg/mL, minocycline (1 μg/mL or rifampicin (0.06 μg/mL did not show bactericidal activity. However, combinations of colistin at 0.5×MIC (0.25 or 0.125 μg/mL with each of the above were synergistic and shown bactericidal activities against all test isolates. A combination of meropenem (16 μg/mL with minocycline (0.5×MIC, 4 or 2 μg/mL was synergitic to all test isolates, but neither showed bactericidal activity alone. The MST12 h values of drug combinations (either colistin- or minocycline-based combinations were significantly shorter than those of the single drugs (p Conclusions This study indicates that combinations of colistin/meropenem, colistin/rifampicin, colistin/minocycline and minocycline/meropenem are synergistic in vitro against XDR-AB strains.

Hepatoprotective activity of aqueous extract of Portulaca oleracea in combination with lycopene in rats

Science.gov (United States)

Anusha, M.; Venkateswarlu, M.; Prabhakaran, V.; Taj, S. Shareen; Kumari, B. Pushpa; Ranganayakulu, D.

2011-01-01

Objective: To investigate the hepatoprotective activity of the aqueous extract of the aerial parts of Portulaca oleracea (P. oleracea) in combination with lycopene against carbon tetrachloride induced hepatotoxicity in rats. Materials and Methods: Hepatotoxicity was induced in male Wistar rats by intraperitoneal injection of carbon tetrachloride (0.1 ml/kg b.w for 14 days). The aqueous extract of P. oleracea in combination with lycopene (50 mg/kg b.w) was administered to the experimental animals at two selected doses for 14 days. The hepatoprotective activity of the combination was evaluated by the liver function marker enzymes in the serum [aspartate transaminases (AST), alanine transaminases (ALT), alkaline phosphatase (Alk.P), total bilirubin (TB), total protein (TP) and total cholesterol (TC)], pentobarbitone induced sleeping time (PST) and histopathological studies of liver. Results: Both the treatment groups showed hepatoprotective effect against carbon tetrachloride induced hepatotoxicity by significantly restoring the levels of serum enzymes to normal which was comparable to that of silymarin group. Besides, the results obtained from PST and histopathological results also support the study. Conclusions: The oral administration of P. oleracea in combination with lycopene significantly ameliorates CCl4 hepatotoxicity in rats. PMID:22022001

New Insight into Combined Model and Revised Model for RTD Curves in a Multi-strand Tundish

Science.gov (United States)

Lei, Hong

2015-12-01

The analysis for the residence time distribution (RTD) curve is one of the important experimental technologies to optimize the tundish design. But there are some issues about RTD analysis model. Firstly, the combined (or mixed) model and the revised model give different analysis results for the same RTD curve. Secondly, different upper limits of integral in the numerator for the mean residence time give different results for the same RTD curve. Thirdly, the negative dead volume fraction sometimes appears at the outer strand of the multi-strand tundish. In order to solve the above problems, it is necessary to have a deep insight into the RTD curve and to propose a reasonable method to analyze the RTD curve. The results show that (1) the revised model is not appropriate to treat with the RTD curve; (2) the conception of the visual single-strand tundish and the combined model with the dimensionless time at the cut-off point are applied to estimate the flow characteristics in the multi-strand tundish; and that (3) the mean residence time at each exit is the key parameter to estimate the similarity of fluid flow among strands.

Evaluation of Activity and Combination Strategies with the Microtubule-Targeting Drug Sagopilone in Breast Cancer Cell Lines

International Nuclear Information System (INIS)

Eschenbrenner, Julia; Winsel, Sebastian; Hammer, Stefanie; Sommer, Anette; Mittelstaedt, Kevin; Drosch, Michael; Klar, Ulrich; Sachse, Christoph; Hannus, Michael; Seidel, Monika; Weiss, Bertram; Merz, Claudia; Siemeister, Gerhard; Hoffmann, Jens

2011-01-01

Sagopilone, a fully synthetic epothilone, is a microtubule-stabilizing agent optimized for high in vitro and in vivo activity against a broad range of tumor models, including those resistant to paclitaxel and other systemic treatments. Sagopilone development is accompanied by translational research studies to evaluate the molecular mode of action, to recognize mechanisms leading to resistance, to identify predictive response biomarkers, and to establish a rationale for combination with different therapies. Here, we profiled sagopilone activity in breast cancer cell lines. To analyze the mechanisms of mitotic arrest and apoptosis and to identify additional targets and biomarkers, an siRNA-based RNAi drug modifier screen interrogating 300 genes was performed in four cancer cell lines. Defects of the spindle assembly checkpoint (SAC) were identified to cause resistance against sagopilone-induced mitotic arrest and apoptosis. Potential biomarkers for resistance could therefore be functional defects like polymorphisms or mutations in the SAC, particularly in the central SAC kinase BUB1B. Moreover, chromosomal heterogeneity and polyploidy are also potential biomarkers of sagopilone resistance since they imply an increased tolerance for aberrant mitosis. RNAi screening further demonstrated that the sagopilone-induced mitotic arrest can be enhanced by concomitant inhibition of mitotic kinesins, thus suggesting a potential combination therapy of sagopilone with a KIF2C (MCAK) kinesin inhibitor. However, the combination of sagopilone and inhibition of the prophase kinesin KIF11 (EG5) is antagonistic, indicating that the kinesin inhibitor has to be highly specific to bring about the required therapeutic benefit.

Evaluation of Activity and Combination Strategies with the Microtubule-Targeting Drug Sagopilone in Breast Cancer Cell Lines

Energy Technology Data Exchange (ETDEWEB)

Eschenbrenner, Julia [Global Drug Discovery, Therapeutic Research Group Oncology, Bayer Healthcare Pharmaceuticals, Berlin (Germany); Institute for Biotechnology, Technical University Berlin, Berlin (Germany); Winsel, Sebastian [Global Drug Discovery, Therapeutic Research Group Oncology, Bayer Healthcare Pharmaceuticals, Berlin (Germany); Institute for Chemistry and Biochemistry, Free University Berlin, Berlin (Germany); Medical Biotechnology, VTT Technical Research Centre of Finland, Turku (Finland); Hammer, Stefanie [Global Drug Discovery, Therapeutic Research Group Oncology, Bayer Healthcare Pharmaceuticals, Berlin (Germany); Sommer, Anette [Global Drug Discovery, Target Discovery, Bayer Healthcare Pharmaceuticals, Berlin (Germany); Mittelstaedt, Kevin [Global Drug Discovery, Therapeutic Research Group Oncology, Bayer Healthcare Pharmaceuticals, Berlin (Germany); Institute for Chemistry and Biochemistry, Free University Berlin, Berlin (Germany); Department of Medicine, The University of Melbourne, Melbourne, VIC (Australia); Drosch, Michael [Global Drug Discovery, Therapeutic Research Group Oncology, Bayer Healthcare Pharmaceuticals, Berlin (Germany); Center of Human Genetics, University of Bremen, Bremen (Germany); Klar, Ulrich [Global Drug Discovery, Therapeutic Research Group Oncology, Bayer Healthcare Pharmaceuticals, Berlin (Germany); Sachse, Christoph; Hannus, Michael; Seidel, Monika [Cenix BioScience GmbH, Dresden (Germany); Weiss, Bertram; Merz, Claudia [Global Drug Discovery, Target Discovery, Bayer Healthcare Pharmaceuticals, Berlin (Germany); Siemeister, Gerhard [Global Drug Discovery, Therapeutic Research Group Oncology, Bayer Healthcare Pharmaceuticals, Berlin (Germany); Hoffmann, Jens, E-mail: jens.hoffmann@epo-berlin.com [Global Drug Discovery, Therapeutic Research Group Oncology, Bayer Healthcare Pharmaceuticals, Berlin (Germany); Experimentelle Pharmakologie und Onkologie Berlin-Buch GmbH, Berlin (Germany)

2011-11-16

Sagopilone, a fully synthetic epothilone, is a microtubule-stabilizing agent optimized for high in vitro and in vivo activity against a broad range of tumor models, including those resistant to paclitaxel and other systemic treatments. Sagopilone development is accompanied by translational research studies to evaluate the molecular mode of action, to recognize mechanisms leading to resistance, to identify predictive response biomarkers, and to establish a rationale for combination with different therapies. Here, we profiled sagopilone activity in breast cancer cell lines. To analyze the mechanisms of mitotic arrest and apoptosis and to identify additional targets and biomarkers, an siRNA-based RNAi drug modifier screen interrogating 300 genes was performed in four cancer cell lines. Defects of the spindle assembly checkpoint (SAC) were identified to cause resistance against sagopilone-induced mitotic arrest and apoptosis. Potential biomarkers for resistance could therefore be functional defects like polymorphisms or mutations in the SAC, particularly in the central SAC kinase BUB1B. Moreover, chromosomal heterogeneity and polyploidy are also potential biomarkers of sagopilone resistance since they imply an increased tolerance for aberrant mitosis. RNAi screening further demonstrated that the sagopilone-induced mitotic arrest can be enhanced by concomitant inhibition of mitotic kinesins, thus suggesting a potential combination therapy of sagopilone with a KIF2C (MCAK) kinesin inhibitor. However, the combination of sagopilone and inhibition of the prophase kinesin KIF11 (EG5) is antagonistic, indicating that the kinesin inhibitor has to be highly specific to bring about the required therapeutic benefit.

Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts.

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Barbara Szymanska

Full Text Available Current regimens for induction therapy of pediatric acute lymphoblastic leukemia (ALL, or for re-induction post relapse, use a combination of vincristine (VCR, a glucocorticoid, and L-asparaginase (ASP with or without an anthracycline. With cure rates now approximately 80%, robust pre-clinical models are necessary to prioritize active new drugs for clinical trials in relapsed/refractory patients, and the ability of these models to predict synergy/antagonism with established therapy is an essential attribute. In this study, we report optimization of an induction-type regimen by combining VCR, dexamethasone (DEX and ASP (VXL against ALL xenograft models established from patient biopsies in immune-deficient mice. We demonstrate that the VXL combination was synergistic in vitro against leukemia cell lines as well as in vivo against ALL xenografts. In vivo, VXL treatment caused delays in progression of individual xenografts ranging from 22 to >146 days. The median progression delay of xenografts derived from long-term surviving patients was 2-fold greater than that of xenografts derived from patients who died of their disease. Pharmacokinetic analysis revealed that systemic DEX exposure in mice increased 2-fold when administered in combination with VCR and ASP, consistent with clinical findings, which may contribute to the observed synergy between the 3 drugs. Finally, as proof-of-principle we tested the in vivo efficacy of combining VXL with either the Bcl-2/Bcl-xL/Bcl-w inhibitor, ABT-737, or arsenic trioxide to provide evidence of a robust in vivo platform to prioritize new drugs for clinical trials in children with relapsed/refractory ALL.

The effects of whole body vibration combined computerized postural control training on the lower extremity muscle activity and cerebral cortex activity in stroke patients.

Science.gov (United States)

Uhm, Yo-Han; Yang, Dae-Jung

2018-02-01

[Purpose] The purpose of this study was to examine the effect of computerized postural control training using whole body vibration on lower limb muscle activity and cerebral cortical activation in acute stroke patients. [Subjects and Methods] Thirty stroke patients participated and were divided into groups of 10, a group of the computerized postural control training using whole body vibration (Group I), the computerized postural control training combined with aero step (Group II) and computerized postural control training (Group III). MP100 was used to measure lower limb muscle activity, and QEEG-8 was used to measure cerebral cortical activation. [Results] Comparison of muscle activity and cerebral cortical activation before and after intervention between groups showed that Group I had significant differences in lower limb muscle activity and cerebral cortical activation compared to Groups II and III. [Conclusion] This study showed that whole body vibration combined computerized postural control training is effective for improving muscle activity and cerebral cortex activity in stroke patients.

COMBINING SEMIANALYTIC MODELS WITH SIMULATIONS OF GALAXY CLUSTERS: THE NEED FOR HEATING FROM ACTIVE GALACTIC NUCLEI

International Nuclear Information System (INIS)

Short, C. J.; Thomas, P. A.

2009-01-01

We present hydrodynamical N-body simulations of clusters of galaxies with feedback taken from semianalytic models of galaxy formation. The advantage of this technique is that the source of feedback in our simulations is a population of galaxies that closely resembles that found in the real universe. We demonstrate that, to achieve the high entropy levels found in clusters, active galactic nuclei must inject a large fraction of their energy into the intergalactic/intracluster media throughout the growth period of the central black hole. These simulations reinforce the argument of Bower et al., who arrived at the same conclusion on the basis of purely semianalytic reasoning.

ECONOMIC EVALUATION OF COMBINED THERAPY OF ARTERIAL HYPERTENSION BY MARKOV’S MODELING

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N. S. Maksimchuk-Kolobova

2015-09-01

Full Text Available Aim. To evaluate the economic effectiveness of the combined two-drug antihypertensive therapy in patients with arterial hypertension (HT and high cardiovascular risk by Markov’s modeling.Material and methods. Patients (n= 65; 19 males and 46 females with essential HT accompanied by metabolic disorders, history of previous ineffective antihypertensive therapy were included into the study. Patients were randomized into 2 groups. Group V/A was treated with valsartan and amlodipine in fixed-dose combinations of 160/5 and 160/10 mg depending on blood pressure (BP level. Patients of group L/A were treated with losartan 100 mg and amlodipine 5 or 10 mg daily. Treatment duration was 24 weeks. Changes in BP level, and left ventricular hypertrophy (LVH regression were assessed. Economic evaluation was performed on the basis of modeling with specialized software Decision Tree 4.xla.Results. Effect of the two variants of combination therapy on LVH was used to estimate treatment effectiveness and to build the model. Patients were distributed according to the left ventricular mass (LVM at baseline and after 24 weeks of therapy. Significant decrease in LVM was observed in V/A group: from 225.1±71.7 to 186.3±44.5 g (p<0.05. There was no LVM dynamics in L/A group. The model took into account economic and frequency factors for 10 years forecast. V/A therapy is able to prevent 94 deaths, 22 strokes, and 64 myocardial infarction per 1000 patients. Absence of need in treatment of these prevented events can save about 5.5 million RUR for every 1000 patients. It would reduce the total costs per patient during 10 years. V/A therapy is able to save maximal number of quality adjusted life years (QALY due to LVM regression (5.016 years. L/A combination is the most economical variant of pharmacotherapy due to low cost of treatment (16.491.25 RUR per 1 QALY. It would take 286.698.7 RUR additionally for one additional QALY in the treatment with V/A, and it is

Combating Combination of Hypertension and Diabetes in Different Rat Models

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Talma Rosenthal

2010-03-01

Full Text Available Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD, and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH rats. The use of various drugs, such as angiotensin-converting enzyme (ACE inhibitors (ACEIs, various angiotensin receptor blockers (ARBs, and calcium channel blockers (CCBs, to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment.

Modeling interdisciplinary activities involving Mathematics

DEFF Research Database (Denmark)

Iversen, Steffen Møllegaard

2006-01-01

In this paper a didactical model is presented. The goal of the model is to work as a didactical tool, or conceptual frame, for developing, carrying through and evaluating interdisciplinary activities involving the subject of mathematics and philosophy in the high schools. Through the terms...... of Horizontal Intertwining, Vertical Structuring and Horizontal Propagation the model consists of three phases, each considering different aspects of the nature of interdisciplinary activities. The theoretical modelling is inspired by work which focuses on the students abilities to concept formation in expanded...... domains (Michelsen, 2001, 2005a, 2005b). Furthermore the theoretical description rest on a series of qualitative interviews with teachers from the Danish high school (grades 9-11) conducted recently. The special case of concrete interdisciplinary activities between mathematics and philosophy is also...

Target and Tissue Selectivity Prediction by Integrated Mechanistic Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling.

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Vlot, Anna H C; de Witte, Wilhelmus E A; Danhof, Meindert; van der Graaf, Piet H; van Westen, Gerard J P; de Lange, Elizabeth C M

2017-12-04

Selectivity is an important attribute of effective and safe drugs, and prediction of in vivo target and tissue selectivity would likely improve drug development success rates. However, a lack of understanding of the underlying (pharmacological) mechanisms and availability of directly applicable predictive methods complicates the prediction of selectivity. We explore the value of combining physiologically based pharmacokinetic (PBPK) modeling with quantitative structure-activity relationship (QSAR) modeling to predict the influence of the target dissociation constant (K D ) and the target dissociation rate constant on target and tissue selectivity. The K D values of CB1 ligands in the ChEMBL database are predicted by QSAR random forest (RF) modeling for the CB1 receptor and known off-targets (TRPV1, mGlu5, 5-HT1a). Of these CB1 ligands, rimonabant, CP-55940, and Δ 8 -tetrahydrocanabinol, one of the active ingredients of cannabis, were selected for simulations of target occupancy for CB1, TRPV1, mGlu5, and 5-HT1a in three brain regions, to illustrate the principles of the combined PBPK-QSAR modeling. Our combined PBPK and target binding modeling demonstrated that the optimal values of the K D and k off for target and tissue selectivity were dependent on target concentration and tissue distribution kinetics. Interestingly, if the target concentration is high and the perfusion of the target site is low, the optimal K D value is often not the lowest K D value, suggesting that optimization towards high drug-target affinity can decrease the benefit-risk ratio. The presented integrative structure-pharmacokinetic-pharmacodynamic modeling provides an improved understanding of tissue and target selectivity.

Uncovering stability mechanisms in microbial ecosystems - combining microcosm experiments, computational modelling and ecological theory in a multidisciplinary approach

Science.gov (United States)

Worrich, Anja; König, Sara; Banitz, Thomas; Centler, Florian; Frank, Karin; Kästner, Matthias; Miltner, Anja; Thullner, Martin; Wick, Lukas

2015-04-01

Although bacterial degraders in soil are commonly exposed to fluctuating environmental conditions, the functional performance of the biodegradation processes can often be maintained by resistance and resilience mechanisms. However, there is still a gap in the mechanistic understanding of key factors contributing to the stability of such an ecosystem service. Therefore we developed an integrated approach combining microcosm experiments, simulation models and ecological theory to directly make use of the strengths of these disciplines. In a continuous interplay process, data, hypotheses, and central questions are exchanged between disciplines to initiate new experiments and models to ultimately identify buffer mechanisms and factors providing functional stability. We focus on drying and rewetting-cycles in soil ecosystems, which are a major abiotic driver for bacterial activity. Functional recovery of the system was found to depend on different spatial processes in the computational model. In particular, bacterial motility is a prerequisite for biodegradation if either bacteria or substrate are heterogeneously distributed. Hence, laboratory experiments focussing on bacterial dispersal processes were conducted and confirmed this finding also for functional resistance. Obtained results will be incorporated into the model in the next step. Overall, the combination of computational modelling and laboratory experiments identified spatial processes as the main driving force for functional stability in the considered system, and has proved a powerful methodological approach.

The role of the time-kill kinetics assay as part of a preclinical modeling framework for assessing the activity of anti-tuberculosis drugs.

Science.gov (United States)

Bax, Hannelore I; Bakker-Woudenberg, Irma A J M; de Vogel, Corné P; van der Meijden, Aart; Verbon, Annelies; de Steenwinkel, Jurriaan E M

2017-07-01

Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework. Copyright © 2017 Elsevier Ltd. All rights reserved.

An in vitro model for screening estrogen activity of environmental samples after metabolism

Energy Technology Data Exchange (ETDEWEB)

Chahbane, N.; Schramm, K.W. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Oekologische Chemie; Kettrup, A. [Technische Univ. Muenchen, Freising (Germany). Lehrstuhl fuer Oekologische Chemie

2004-09-15

For a few years, yeast estrogen assay (YES) was accepted as a reliable and economic model for screening of environmental estrogens. Though the chemicals directly act with estrogen receptor (ER) can be filtered out by this model, there are still chemicals act with ER only after metabolism and some chemicals eliminate their estrogen activities after metabolism. That is to say, their metabolites exert or have stronger estrogen activities than themselves, which can be called bio-activation. In this case, for the lack of the metabolism enzyme system as human and other animals, only the assay with recombinant yeast cells is insufficient. So, it is necessary to combine the YES with metabolism procedure to evaluate the estrogen activities of these chemicals. The most common method used currently for in vitro metabolic activation in mutagenicity testing and also be applied to the estrogen screening field is S-9 mixture. Also, there is an attempt to develop a chemical model for cytochrome P450 as a bio-mimetic metabolic activation system. All these methods can be used as in vitro models for metabolism. Compare with these models, using whole H4II E cells for metabolism is an alternative and with superiorities. It has the excellence of short experiment period as all other in vitro models, but is much more close to the real surroundings as in vivo. Furthermore, the activity of 7-ethoxyresorufin-O-deethylase (EROD) can be easily measured during the whole incubation period for us to discuss the metabolic activities in a quantitative foundation, not only in qualitative. Methoxychlor is one of the chemicals with bio-activation ability. When directly used in the YES, it shows weak estrogen activity. But a main metabolite of methoxychlor, 2,2-bis (p-hydroxyphenyl) - 1,1,1-trichloroethane (HPTE) is a known estrogen mimic. For the long time using methoxychlor as a pesticide and its clear background, it is an ideal chemical to establish this in vitro system.

Polypeptide-based nanogels co-encapsulating a synergistic combination of doxorubicin with 17-AAG show potent anti-tumor activity in ErbB2-driven breast cancer models.

Science.gov (United States)

Desale, Swapnil S; Raja, Srikumar M; Kim, Jong Oh; Mohapatra, Bhopal; Soni, Kruti S; Luan, Haitao; Williams, Stetson H; Bielecki, Timothy A; Feng, Dan; Storck, Matthew; Band, Vimla; Cohen, Samuel M; Band, Hamid; Bronich, Tatiana K

2015-06-28

ErbB2-driven breast cancers constitute 20-25% of the cases diagnosed within the USA. The humanized anti-ErbB2 monoclonal antibody, Trastuzumab (Herceptin™; Genentech), with chemotherapy is the current standard of treatment. Novel agents and strategies continue to be explored, given the challenges posed by Trastuzumab-resistance development in most patients. The HSP90 inhibitor, 17-allylaminodemethoxygeldanamycin (17-AAG), which induces ErbB2 degradation and attenuates downstream oncogenic signaling, is one such agent that showed significant promise in early phase I and II clinical trials. Its low water solubility, potential toxicities and undesirable side effects observed in patients, partly due to the Cremophor-based formulation, have been discouraging factors in the advancement of this promising drug into clinical use. Encapsulation of 17-AAG into polymeric nanoparticle formulations, particularly in synergistic combination with conventional chemotherapeutics, represents an alternative approach to overcome these problems. Herein, we report an efficient co-encapsulation of 17-AAG and doxorubicin, a clinically well-established and effective modality in breast cancer treatment, into biodegradable and biocompatible polypeptide-based nanogels. Dual drug-loaded nanogels displayed potent cytotoxicity in a breast cancer cell panel and exerted selective synergistic anticancer activity against ErbB2-overexpressing breast cancer cell lines. Analysis of ErbB2 degradation confirmed efficient 17-AAG release from nanogels with activity comparable to free 17-AAG. Furthermore, nanogels containing both 17-AAG and doxorubicin exhibited superior antitumor efficacy in vivo in an ErbB2-driven xenograft model compared to the combination of free drugs. These studies demonstrate that polypeptide-based nanogels can serve as novel nanocarriers for encapsulating 17-AAG along with other chemotherapeutics, providing an opportunity to overcome solubility issues and thereby exploit its full

Finding identifiable parameter combinations in nonlinear ODE models and the rational reparameterization of their input-output equations.

Science.gov (United States)

Meshkat, Nicolette; Anderson, Chris; Distefano, Joseph J

2011-09-01

When examining the structural identifiability properties of dynamic system models, some parameters can take on an infinite number of values and yet yield identical input-output data. These parameters and the model are then said to be unidentifiable. Finding identifiable combinations of parameters with which to reparameterize the model provides a means for quantitatively analyzing the model and computing solutions in terms of the combinations. In this paper, we revisit and explore the properties of an algorithm for finding identifiable parameter combinations using Gröbner Bases and prove useful theoretical properties of these parameter combinations. We prove a set of M algebraically independent identifiable parameter combinations can be found using this algorithm and that there exists a unique rational reparameterization of the input-output equations over these parameter combinations. We also demonstrate application of the procedure to a nonlinear biomodel. Copyright © 2011 Elsevier Inc. All rights reserved.

Modeling the future evolution of the virtual water trade network: A combination of network and gravity models

Science.gov (United States)

Sartori, Martina; Schiavo, Stefano; Fracasso, Andrea; Riccaboni, Massimo

2017-12-01

The paper investigates how the topological features of the virtual water (VW) network and the size of the associated VW flows are likely to change over time, under different socio-economic and climate scenarios. We combine two alternative models of network formation -a stochastic and a fitness model, used to describe the structure of VW flows- with a gravity model of trade to predict the intensity of each bilateral flow. This combined approach is superior to existing methodologies in its ability to replicate the observed features of VW trade. The insights from the models are used to forecast future VW flows in 2020 and 2050, under different climatic scenarios, and compare them with future water availability. Results suggest that the current trend of VW exports is not sustainable for all countries. Moreover, our approach highlights that some VW importers might be exposed to "imported water stress" as they rely heavily on imports from countries whose water use is unsustainable.

Antihyperalgesic effects of dexketoprofen and tramadol in a model of postoperative pain in mice - effects on glial cell activation.

Science.gov (United States)

Romero-Alejo, Elizabeth; Puig, Margarita M; Romero, Asunción

2016-08-01

To define likely targets (i.e. glia) and protocols (analgesic combinations) to improve postoperative pain outcomes and reduce chronic pain after surgery. Specifically, to assess the antihyperalgesic effects of the dexketoprofen : tramadol (DEX : TRM) combination, exploring the implication of glial activation. In a mouse model of postincisional pain, we evaluated mechanical nociceptive thresholds (Von Frey) for 21 days postoperatively. We assessed DEX and TRM alone and combined (1 : 1 ratio) on postoperative hyperalgesia (POH, day 1) and delayed latent pain sensitisation (substantiated by a naloxone challenge; PS, day 21). The interactions were analysed using isobolograms, and concomitant changes in spinal glial cell activation were measured. On day 1, DEX completely blocked POH, whereas TRM induced 32% inhibition. TRM, but not DEX, partially (47%) protected against PS, at 21 days. Co-administration of DEX : TRM (1 : 1 ratio) showed additivity for antihyperalgesia. Both drugs and their combination totally inhibited surgery-induced microglia activation on day 1, but had no effect on surgery-induced astrocyte activation (1 day) or re-activation after naloxone (21 days). The DEX : TRM combination could have clinical advantages: a complete prevention of POH after surgery, together with a substantial (48%) inhibition of the development of PS by TRM. Microglia, but not astrocyte activation, could play a relevant role in the development of postoperative pain hypersensitivity. © 2016 Royal Pharmaceutical Society.

Active Vertex Model for cell-resolution description of epithelial tissue mechanics.

Science.gov (United States)

Barton, Daniel L; Henkes, Silke; Weijer, Cornelis J; Sknepnek, Rastko

2017-06-01

We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cell-specific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies.

A combined AHP-GP model to allocate internal auditing time to ...

African Journals Online (AJOL)

Analytic hierarchy process, goal programming, internal audit, risk assessment. ..... Services area and are listed, together with their associated management ..... [2] Badri MA, 2001, A combined AHP-GP model for quality control systems, Interna-.

Combining Activity DSM with Temporal Logic for Collaborative Planning and Scheduling

Directory of Open Access Journals (Sweden)

Mathieu Baudin

2013-09-01

Full Text Available This work presents an approach that implements enhanced scheduling algorithms to plan and schedule interventions in scientific facilities emitting various types of ionizing radiation such as the ones present at CERN in Geneva, (Switzerland or at GSI in Darmstadt (Germany. To deal with the collaborative process of activity creation and submission used in those organizations, we propose a framework to set the appropriate sequence or skeleton for the activities. This framework combines Allen's Interval Algebra and DSM (Design Structure Matrix. It enables the sequence of activities to be automatically computed while gathering and taking into account the needs of users and testing their compatibility. It also deals with technical-type or resource-type constraints between activities as well as incompatible submissions. The work described in this paper includes details of the collaborative submission process and introduces suggestions for compromising as well as temporal calculations with the introduction of parameterized DSMs rather than binary ones.

Combining multi-objective optimization and bayesian model averaging to calibrate forecast ensembles of soil hydraulic models

Energy Technology Data Exchange (ETDEWEB)

Vrugt, Jasper A [Los Alamos National Laboratory; Wohling, Thomas [NON LANL

2008-01-01

Most studies in vadose zone hydrology use a single conceptual model for predictive inference and analysis. Focusing on the outcome of a single model is prone to statistical bias and underestimation of uncertainty. In this study, we combine multi-objective optimization and Bayesian Model Averaging (BMA) to generate forecast ensembles of soil hydraulic models. To illustrate our method, we use observed tensiometric pressure head data at three different depths in a layered vadose zone of volcanic origin in New Zealand. A set of seven different soil hydraulic models is calibrated using a multi-objective formulation with three different objective functions that each measure the mismatch between observed and predicted soil water pressure head at one specific depth. The Pareto solution space corresponding to these three objectives is estimated with AMALGAM, and used to generate four different model ensembles. These ensembles are post-processed with BMA and used for predictive analysis and uncertainty estimation. Our most important conclusions for the vadose zone under consideration are: (1) the mean BMA forecast exhibits similar predictive capabilities as the best individual performing soil hydraulic model, (2) the size of the BMA uncertainty ranges increase with increasing depth and dryness in the soil profile, (3) the best performing ensemble corresponds to the compromise (or balanced) solution of the three-objective Pareto surface, and (4) the combined multi-objective optimization and BMA framework proposed in this paper is very useful to generate forecast ensembles of soil hydraulic models.

Anti-tumour efficacy of etoposide alone and in combination with piroxicam against canine osteosarcoma in a xenograft model.

Science.gov (United States)

Ong, S M; Saeki, K; Kok, M K; Tanaka, Y; Choisunirachon, N; Yoshitake, R; Nishimura, R; Nakagawa, T

2017-08-01

Osteosarcoma (OSA) in dogs is locally invasive and highly malignant. Distant metastasis is the most common cause of death. To date, the survival rate in dogs with OSA remains poor. The cytotoxic effects of etoposide against canine OSA cell lines, either alone or in combination with piroxicam, have been previously demonstrated in vitro. The aim of this study was to evaluate the anti-tumour effect of etoposide alone and in combination with piroxicam on canine OSA using murine models. Etoposide single agent treatment significantly delayed tumour progression with a marked reduction in Ki-67 immunoreactivity in tumour tissue. Concomitant treatment with piroxicam did not enhance the anti-tumour efficacy of etoposide. Etoposide single agent treatment and combination treatment with piroxicam down-regulated survivin expression, but was not followed by increased apoptotic activity. These findings indicate that etoposide might be a promising novel therapeutic for canine OSA. Further investigations into its potential for clinical application in veterinary oncology are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro activity of flomoxef and cefazolin in combination with vancomycin.

Science.gov (United States)

Simon, C; Simon, M

1991-01-01

207 clinical isolates from strains of patients from the University Children's Hospital of Kiel were investigated for their in vitro activity with the agar dilution method against flomoxef and cefazolin (alone and partially in combination with vancomycin). Staphylococci were also tested with other cephalosporins (cefoxitin, cefamandole, cefotaxime, cefotetan and latamoxef). Flomoxef and cefazolin always acted more vigorously on staphylococci than the other cephalosporins. Resistance of Staphylococcus aureus strains against flomoxef and cefazolin did not occur but was found in 15 and 5 of 98 Staphylococcus epidermidis strains, respectively. Enterococcus faecalis strains were always resistant against both drugs; Streptococcus faecium strains were only moderately sensitive. Combined testing of flomoxef or cefazolin with vancomycin showed synergism in almost all staphylococcal strains. Synergism was stronger when S. epidermidis strains were only weakly sensitive to or resistant against flomoxef and cefazolin in comparison to highly sensitive strains. Flomoxef (or cefazolin) acted synergistically in combination with vancomycin on E. faecalis and S. faecium with the exception of two strains of E. faecalis which showed an additive effect of both drugs.

In vitro activities of amphotericin-b in combination with rifampin against

International Nuclear Information System (INIS)

Zarrin, M.; Najafi, M.R.; Najafi, M.R.

2007-01-01

The main goal of study was finding the synergism effect of amphotricin B (AMB) and rifampin (RIF) on 3 species of Aspergillus. Activities of amphotericin B in combination with rifampin were tested in buffered yeast-nitrogen base using checkerboard method. Plates were inoculated with 20 micro liter spores suspensions of each organism and incubated at 30 degree C for 24h. For this method, the MICs were defined as the lowest antimicrobial concentration inhibiting visible fungal growth on the plates. Minimal fungicidal concentration was defined as the first tube showing no growth on the plate.The MIC of amphotericin B for 100% of isolates of A. fumigatus and A. flavus were inhibited by 4mg/lit amphotericin B. 100% of isolates of A. niger were inhibited by 8mg/lit amphotericin B. When amphotericin B was combined with rifampin, amphotericin B MICs decreased to 2, 1 and 4 mg/lit in A. fumigatus, A. flavus rephrase and A. niger respectively. The results indicate that combination of amphotreicin B and rifampin was synergistic on A. fumigatus, A. flavus and A. niger. (author)

A phenomenological SMA model for combined axial–torsional proportional/non-proportional loading conditions

International Nuclear Information System (INIS)

Bodaghi, M.; Damanpack, A.R.; Aghdam, M.M.; Shakeri, M.

2013-01-01

In this paper, a simple and robust phenomenological model for shape memory alloys (SMAs) is proposed to simulate main features of SMAs under uniaxial as well as biaxial combined axial–torsional proportional/non-proportional loadings. The constitutive model for polycrystalline SMAs is developed within the framework of continuum thermodynamics of irreversible processes. The model nominates the volume fractions of self-accommodated and oriented martensite as scalar internal variables and the preferred direction of oriented martensitic variants as directional internal variable. An algorithm is introduced to develop explicit relationships for the thermo-mechanical behavior of SMAs under uniaxial and biaxial combined axial–torsional proportional/non-proportional loading conditions and also thermal loading. It is shown that the model is able to simulate main aspects of SMAs including self-accommodation, martensitic transformation, orientation and reorientation of martensite, shape memory effect, ferro-elasticity and pseudo-elasticity. A description of the time-discrete counterpart of the proposed SMA model is presented. Experimental results of uniaxial tension and biaxial combined tension–torsion non-proportional tests are simulated and a good qualitative correlation between numerical and experimental responses is achieved. Due to simplicity and accuracy, the model is expected to be used in the future studies dealing with the analysis of SMA devices in which two stress components including one normal and one shear stress are dominant

A general model for preload calculation and stiffness analysis for combined angular contact ball bearings

Science.gov (United States)

Zhang, Jinhua; Fang, Bin; Hong, Jun; Wan, Shaoke; Zhu, Yongsheng

2017-12-01

The combined angular contact ball bearings are widely used in automatic, aerospace and machine tools, but few researches on the combined angular contact ball bearings have been reported. It is shown that the preload and stiffness of combined bearings are mutual influenced rather than simply the superposition of multiple single bearing, therefore the characteristic calculation of combined bearings achieved by coupling the load and deformation analysis of a single bearing. In this paper, based on the Jones quasi-static model and stiffness analytical model, a new iterative algorithm and model are proposed for the calculation of combined bearings preload and stiffness, and the dynamic effects include centrifugal force and gyroscopic moment have to be considered. It is demonstrated that the new method has general applicability, the preload factors of combined bearings are calculated according to the different design preloads, and the static and dynamic stiffness for various arrangements of combined bearings are comparatively studied and analyzed, and the influences of the design preload magnitude, axial load and rotating speed are discussed in detail. Besides, the change rule of dynamic contact angles of combined bearings with respect to the rotating speed is also discussed. The results show that bearing arrangement modes, rotating speed and design preload magnitude have a significant influence on the preload and stiffness of combined bearings. The proposed formulation provides a useful tool in dynamic analysis of the complex bearing-rotor system.

Independent and Combined Associations of Physical Activity and Sedentary Behavior with Depressive Symptoms Among Japanese Adults.

Science.gov (United States)

Liao, Yung; Shibata, Ai; Ishii, Kaori; Oka, Koichiro

2016-08-01

Associations between levels of sedentary behavior and depressive symptoms independently and in combination with different levels of physical activity remain unclear. This study aimed to examine independent and combined associations of physical activity (PA) and sedentary behavior (SB) with depressive symptoms among Japanese adults. An Internet-based survey collected data on depression levels (Center for Epidemiologic Studies Depression Scale), self-reported time spent in PA and SB (Japanese short version of the International Physical Activity Questionnaire), and sociodemographic variables from 2,914 adults in 2009. Binary logistic regression analyses were conducted to examine the odds ratios (ORs) for being depressed (depression scores ≥16) according to independent PA levels (none, insufficient, sufficient), SB levels (low, moderate, high), and nine combinations of PA and SB categories. After adjusting for potential confounders, sufficient PA level was found to be related to lower risk of depressive symptoms independently (OR = 0.61), whereas no significant associations were observed between SB levels and depression. In the combined associations, adults in the sufficient PA/high SB (OR = 0.44), sufficient PA/moderate SB (OR = 0.56), and sufficient PA/low SB (OR = 0.57) categories were significantly less likely to have depressive symptoms in comparison with the no PA/high SB category. Meeting physical activity recommendations is associated with a lower risk of depressive symptoms, regardless of time spent in total sedentary behavior. These results suggest that promoting physical activity may be an effective strategy against depressive symptoms among Japanese adults.

Traditional, Cyber and Combined Bullying Roles: Differences in Risky Online and Offline Activities

NARCIS (Netherlands)

Wachs, Sebastian; Junger, Marianne; Sittichai, Ruthaychonee

2015-01-01

This study (1) reports frequency rates of mutually exclusive traditional, cyber and combined (both traditional and cyber) bullying roles; and (2) investigates whether adolescents belonging to particular bullying roles show higher levels of involvement in risky online activities (Compulsive Internet

Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models.

Science.gov (United States)

Leu, Jyh-Der; Wang, Bo-Shen; Chiu, Shu-Jun; Chang, Chun-Yuan; Chen, Chien-Chih; Chen, Fu-Du; Avirmed, Shiirevnyamba; Lee, Yi-Jang

2016-12-01

Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vivo effects of fisetin on tumor growth remain unclear. In the present study a murine xenograft tumor model was employed to investigate the therapeutic effects of fisetin in combination with radiation on CT-26 colon cancer cells and human HCT116 colorectal cancer cells. This revealed that intratumoral injection of fisetin significantly suppressed the growth of CT-26 tumors compared with the untreated control group, but had little effect on the growth of HCT116 tumors. However, fisetin in combination with 2-Gy radiation enhanced tumor suppressor activity in murine colon and human colorectal xenograft tumors, as compared with 2-Gy fractionated radiation administered alone for 5 days and fisetin alone. Interestingly, fisetin downregulated the expression of the oncoprotein securin in a p53-independent manner. However, securin-null HCT116 tumors showed only moderate sensitivity to fisetin treatment, and the combination of fisetin and radiation did not significantly suppress securin-null HCT116 tumor growth compared with normal HCT116 tumors. Therefore, the role of securin in mediating the effect of fisetin on colorectal cancer growth warrants further investigation. In conclusion, the results of the current study provide important preclinical data for evaluating the efficacy of fisetin and radiation combination treatment as an adjuvant chemoradiotherapy for human colorectal cancers.

Modelling the viability of heat recovery from combined sewers.

Science.gov (United States)

Abdel-Aal, M; Smits, R; Mohamed, M; De Gussem, K; Schellart, A; Tait, S

2014-01-01

Modelling of wastewater temperatures along a sewer pipe using energy balance equations and assuming steady-state conditions was achieved. Modelling error was calculated, by comparing the predicted temperature drop to measured ones in three combined sewers, and was found to have an overall root mean squared error of 0.37 K. Downstream measured wastewater temperature was plotted against modelled values; their line gradients were found to be within the range of 0.9995-1.0012. The ultimate aim of the modelling is to assess the viability of recovering heat from sewer pipes. This is done by evaluating an appropriate location for a heat exchanger within a sewer network that can recover heat without impacting negatively on the downstream wastewater treatment plant (WWTP). Long sewers may prove to be more viable for heat recovery, as heat lost can be reclaimed before wastewater reaching the WWTP.

Modelization of cognition, activity and motivation as indicators for Interactive Learning Environment

Directory of Open Access Journals (Sweden)

Asmaa Darouich

2017-06-01

Full Text Available In Interactive Learning Environment (ILE, the cognitive activity and behavior of learners are the center of the researchers’ concerns. The improvement of learning through combining these axes as a structure of indicators for well-designed learning environment, encloses the measurement of the educational activity as a part of the learning process. In this paper, we propose a mathematical modeling approach based on learners actions to estimate the cognitive activity, learning behavior and motivation, in accordance with a proposed course content structure. This Cognitive indicator includes the study of knowledge, memory and reasoning. While, activity indicator aims to study effort, resistance and intensity. The results recovered on a sample of students with different levels of education, assume that the proposed approach presents a relation among all these indicators which is relatively reliable in the term of cognitive system.

A new semi-supervised learning model combined with Cox and SP-AFT models in cancer survival analysis.

Science.gov (United States)

Chai, Hua; Li, Zi-Na; Meng, De-Yu; Xia, Liang-Yong; Liang, Yong

2017-10-12

Gene selection is an attractive and important task in cancer survival analysis. Most existing supervised learning methods can only use the labeled biological data, while the censored data (weakly labeled data) far more than the labeled data are ignored in model building. Trying to utilize such information in the censored data, a semi-supervised learning framework (Cox-AFT model) combined with Cox proportional hazard (Cox) and accelerated failure time (AFT) model was used in cancer research, which has better performance than the single Cox or AFT model. This method, however, is easily affected by noise. To alleviate this problem, in this paper we combine the Cox-AFT model with self-paced learning (SPL) method to more effectively employ the information in the censored data in a self-learning way. SPL is a kind of reliable and stable learning mechanism, which is recently proposed for simulating the human learning process to help the AFT model automatically identify and include samples of high confidence into training, minimizing interference from high noise. Utilizing the SPL method produces two direct advantages: (1) The utilization of censored data is further promoted; (2) the noise delivered to the model is greatly decreased. The experimental results demonstrate the effectiveness of the proposed model compared to the traditional Cox-AFT model.

Combination therapy of chitosan, gynostemma, and motherwort alleviates the progression of experimental rat chronic renal failure by inhibiting STAT1 activation

Science.gov (United States)

Bai, Wenxia; Wang, Shudong; An, Shanshan; Guo, Mengjie; Gong, Guangming; Liu, Wenya; Ma, Shaoxin; Li, Xin; Fu, Jihua; Yao, Wenbing

2018-01-01

This study aimed to investigate the effect of single and combination therapy using chitosan (K), gynostemma (J), and motherwort (Y) on an experimental rat model of chronic renal failure (CRF) induced by adenine and the underlying mechanisms. CRF rats were treated with individual or combinational therapy with two or three of these agents. Biochemical indicators showed that the levels of blood urea nitrogen, creatinine and uric acid decreased and the levels of albumin and hemoglobin increased by single or combination therapy of these drugs. Drug treatment also decreased oxidative stress damage of renal tissues in CRF rats. Histopathological lesions were attenuated in each drug treatment group by various degrees. Additionally, drug treatment affected the expression of extracellular matrix (ECM) proteins including plasminogen activator inhibitor 1, collagen I, matrix metalloprotease-1, and tissue inhibitor of metalloproteinases 1. In particular, the combination therapy of K, J, and Y was superior to the respective monotherapy, which supported the prescription of KJY combination. We further studied the inhibitory effect of KJY on LPS-induced inflammation in RAW264.7 macrophages. The results showed that KJY inhibited LPS-induced secretion of inflammatory cytokines (Interferon-gamma, Interleukin-1 Beta, chemokine (C-X-C motif) ligand 10, cyclooxygenase-2 and Tumor necrosis factor-α in RAW264.7 macrophages. Combination therapy of KJY suppressed the protein expression of Cyclooxygenase-2 and inducible nitric oxide synthase in vivo and in vitro. Further study indicated that KJY inhibited STAT1 activation by down regulating p-STAT1 to exert anti-inflammatory effect and improve renal function in rats with chronic renal failure. PMID:29643988

Comparison of high-latitude thermospheric meridionalwinds II: combined FPI, radar and model Climatologies

Directory of Open Access Journals (Sweden)

E. M. Griffin

2004-03-01

Full Text Available The climatological behaviour of the thermospheric meridional wind above Kiruna, Sweden (67.4°N, 20.4°E has been investigated for seasonal and solar cycle dependence using six different techniques, comprising both model and experimental sources. Model output from both the empirical Horizontal Wind Model (HWM (Hedin et al., 1988 and the numerical Coupled Thermosphere and Ionosphere Model (CTIM are compared to the measured behaviour at Kiruna, as a single site example. The empirical International Reference Ionosphere (IRI model is used as input to an implementation of servo theory, to provide another climatology combining empirical input with a theoretical framework. The experimental techniques have been introduced in a companion paper in this issue and provide climatologies from direct measurements, using Fabry-Perot Interferometers (FPI, together with 2 separate techniques applied to the European Incoherent Scatter radar (EISCAT database to derive neutral winds. One of these techniques uses the same implementation of servo theory as has been used with the IRI model. Detailed comparisons for each season and solar activity category allow for conclusions to be drawn as to the major influences on the climatological behaviour of the wind at this latitude. Comparison of the incoherent scatter radar (ISR derived neutral winds with FPI, empirical model and numerical model winds is important to our understanding and judgement of the validity of the techniques used to derive thermospheric wind databases. The comparisons also test model performance and indicate possible reasons for differences found between the models. In turn, the conclusions point to possible improvements in their formulation. In particular it is found that the empirical models are over-reliant on mid-latitude data in their formulation, and fail to provide accurate estimates of the winds at high-latitudes.

Key words. Meteorology and atmospheric dynamics (thermospheric dynamics

Comparison of high-latitude thermospheric meridionalwinds II: combined FPI, radar and model Climatologies

Directory of Open Access Journals (Sweden)

E. M. Griffin

2004-03-01

Full Text Available The climatological behaviour of the thermospheric meridional wind above Kiruna, Sweden (67.4°N, 20.4°E has been investigated for seasonal and solar cycle dependence using six different techniques, comprising both model and experimental sources. Model output from both the empirical Horizontal Wind Model (HWM (Hedin et al., 1988 and the numerical Coupled Thermosphere and Ionosphere Model (CTIM are compared to the measured behaviour at Kiruna, as a single site example. The empirical International Reference Ionosphere (IRI model is used as input to an implementation of servo theory, to provide another climatology combining empirical input with a theoretical framework. The experimental techniques have been introduced in a companion paper in this issue and provide climatologies from direct measurements, using Fabry-Perot Interferometers (FPI, together with 2 separate techniques applied to the European Incoherent Scatter radar (EISCAT database to derive neutral winds. One of these techniques uses the same implementation of servo theory as has been used with the IRI model. Detailed comparisons for each season and solar activity category allow for conclusions to be drawn as to the major influences on the climatological behaviour of the wind at this latitude. Comparison of the incoherent scatter radar (ISR derived neutral winds with FPI, empirical model and numerical model winds is important to our understanding and judgement of the validity of the techniques used to derive thermospheric wind databases. The comparisons also test model performance and indicate possible reasons for differences found between the models. In turn, the conclusions point to possible improvements in their formulation. In particular it is found that the empirical models are over-reliant on mid-latitude data in their formulation, and fail to provide accurate estimates of the winds at high-latitudes. Key words. Meteorology and atmospheric dynamics (thermospheric dynamics

Activation of the human immune system by chemotherapeutic or targeted agents combined with the oncolytic parvovirus H-1

International Nuclear Information System (INIS)

Moehler, Markus; Sieben, Maike; Roth, Susanne; Springsguth, Franziska; Leuchs, Barbara; Zeidler, Maja; Dinsart, Christiane; Rommelaere, Jean; Galle, Peter R

2011-01-01

Parvovirus H-1 (H-1PV) infects and lyses human tumor cells including melanoma, hepatoma, gastric, colorectal, cervix and pancreatic cancers. We assessed whether the beneficial effects of chemotherapeutic agents or targeted agents could be combined with the oncolytic and immunostimmulatory properties of H-1PV. Using human ex vivo models we evaluated the biological and immunological effects of H-1PV-induced tumor cell lysis alone or in combination with chemotherapeutic or targeted agents in human melanoma cells +/- characterized human cytotoxic T-cells (CTL) and HLA-A2-restricted dendritic cells (DC). H-1PV-infected MZ7-Mel cells showed a clear reduction in cell viability of >50%, which appeared to occur primarily through apoptosis. This correlated with viral NS1 expression levels and was enhanced by combination with chemotherapeutic agents or sunitinib. Tumor cell preparations were phagocytosed by DC whose maturation was measured according to the treatment administered. Immature DC incubated with H-1PV-induced MZ7-Mel lysates significantly increased DC maturation compared with non-infected or necrotic MZ7-Mel cells. Tumor necrosis factor-α and interleukin-6 release was clearly increased by DC incubated with H-1PV-induced SK29-Mel tumor cell lysates (TCL) and was also high with DC-CTL co-cultures incubated with H-1PV-induced TCL. Similarly, DC co-cultures with TCL incubated with H-1PV combined with cytotoxic agents or sunitinib enhanced DC maturation to a greater extent than cytotoxic agents or sunitinib alone. Again, these combinations increased pro-inflammatory responses in DC-CTL co-cultures compared with chemotherapy or sunitinib alone. In our human models, chemotherapeutic or targeted agents did not only interfere with the pronounced immunomodulatory properties of H-1PV, but also reinforced drug-induced tumor cell killing. H-1PV combined with cisplatin, vincristine or sunitinib induced effective immunostimulation via a pronounced DC maturation, better cytokine

Speech Perception With Combined Electric-Acoustic Stimulation: A Simulation and Model Comparison.

Science.gov (United States)

Rader, Tobias; Adel, Youssef; Fastl, Hugo; Baumann, Uwe

2015-01-01

The aim of this study is to simulate speech perception with combined electric-acoustic stimulation (EAS), verify the advantage of combined stimulation in normal-hearing (NH) subjects, and then compare it with cochlear implant (CI) and EAS user results from the authors' previous study. Furthermore, an automatic speech recognition (ASR) system was built to examine the impact of low-frequency information and is proposed as an applied model to study different hypotheses of the combined-stimulation advantage. Signal-detection-theory (SDT) models were applied to assess predictions of subject performance without the need to assume any synergistic effects. Speech perception was tested using a closed-set matrix test (Oldenburg sentence test), and its speech material was processed to simulate CI and EAS hearing. A total of 43 NH subjects and a customized ASR system were tested. CI hearing was simulated by an aurally adequate signal spectrum analysis and representation, the part-tone-time-pattern, which was vocoded at 12 center frequencies according to the MED-EL DUET speech processor. Residual acoustic hearing was simulated by low-pass (LP)-filtered speech with cutoff frequencies 200 and 500 Hz for NH subjects and in the range from 100 to 500 Hz for the ASR system. Speech reception thresholds were determined in amplitude-modulated noise and in pseudocontinuous noise. Previously proposed SDT models were lastly applied to predict NH subject performance with EAS simulations. NH subjects tested with EAS simulations demonstrated the combined-stimulation advantage. Increasing the LP cutoff frequency from 200 to 500 Hz significantly improved speech reception thresholds in both noise conditions. In continuous noise, CI and EAS users showed generally better performance than NH subjects tested with simulations. In modulated noise, performance was comparable except for the EAS at cutoff frequency 500 Hz where NH subject performance was superior. The ASR system showed similar behavior

Sequence Tree Modeling for Combined Accident and Feed-and-Bleed Operation

International Nuclear Information System (INIS)

Kim, Bo Gyung; Kang Hyun Gook; Yoon, Ho Joon

2016-01-01

In order to address this issue, this study suggests the sequence tree model to analyze accident sequence systematically. Using the sequence tree model, all possible scenarios which need a specific safety action to prevent the core damage can be identified and success conditions of safety action under complicated situation such as combined accident will be also identified. Sequence tree is branch model to divide plant condition considering the plant dynamics. Since sequence tree model can reflect the plant dynamics, arising from interaction of different accident timing and plant condition and from the interaction between the operator action, mitigation system, and the indicators for operation, sequence tree model can be used to develop the dynamic event tree model easily. Target safety action for this study is a feed-and-bleed (F and B) operation. A F and B operation directly cools down the reactor cooling system (RCS) using the primary cooling system when residual heat removal by the secondary cooling system is not available. In this study, a TLOFW accident and a TLOFW accident with LOCA were the target accidents. Based on the conventional PSA model and indicators, the sequence tree model for a TLOFW accident was developed. If sampling analysis is performed, practical accident sequences can be identified based on the sequence analysis. If a realistic distribution for the variables can be obtained for sampling analysis, much more realistic accident sequences can be described. Moreover, if the initiating event frequency under a combined accident can be quantified, the sequence tree model can translate into a dynamic event tree model based on the sampling analysis results

Sequence Tree Modeling for Combined Accident and Feed-and-Bleed Operation

Energy Technology Data Exchange (ETDEWEB)

Kim, Bo Gyung; Kang Hyun Gook [KAIST, Daejeon (Korea, Republic of); Yoon, Ho Joon [Khalifa University of Science, Abu Dhabi (United Arab Emirates)

2016-05-15

In order to address this issue, this study suggests the sequence tree model to analyze accident sequence systematically. Using the sequence tree model, all possible scenarios which need a specific safety action to prevent the core damage can be identified and success conditions of safety action under complicated situation such as combined accident will be also identified. Sequence tree is branch model to divide plant condition considering the plant dynamics. Since sequence tree model can reflect the plant dynamics, arising from interaction of different accident timing and plant condition and from the interaction between the operator action, mitigation system, and the indicators for operation, sequence tree model can be used to develop the dynamic event tree model easily. Target safety action for this study is a feed-and-bleed (F and B) operation. A F and B operation directly cools down the reactor cooling system (RCS) using the primary cooling system when residual heat removal by the secondary cooling system is not available. In this study, a TLOFW accident and a TLOFW accident with LOCA were the target accidents. Based on the conventional PSA model and indicators, the sequence tree model for a TLOFW accident was developed. If sampling analysis is performed, practical accident sequences can be identified based on the sequence analysis. If a realistic distribution for the variables can be obtained for sampling analysis, much more realistic accident sequences can be described. Moreover, if the initiating event frequency under a combined accident can be quantified, the sequence tree model can translate into a dynamic event tree model based on the sampling analysis results.

Effects of Cu, Zn and Pb Combined Pollution on Soil Hydrolase Activities

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FENG Dan

2015-08-01

Full Text Available To study the relations between soil enzyme activities and heavy metal pollution, the combined effects of Cu, Zn and Pb on the three hydrolase activities, including invertase(IN, urease(Uand alkaline phosphatase(ALPwere investigated via an orthogonal experiment. Results showed as the following: When the concentration of Cu was 400 mg·kg-1, the U and ALP activities were decreased 51% and 44%, separately; When Zn was at 500 mg·kg-1, IN and ALP activities were only decreased 3% and 9%, while U activity was increased; When Pb was at 500 mg·kg-1, IN and U activities were increased, while ALP activity was decreased 13%. As a whole, Cu was considered as the most remarkable influence factor for IN, U and ALP activity regardless of interactions among the heavy metals, Zn came second, and Pb mainly showed activation. Considering interactions, Cu×Zn could significantly influence U activity(P<0.05, effects of Cu×Pb and Cu×Zn on ALP activity were remarkable(95% confidence interval. The response of ALP activity was more sensitive than the other two enzymes. Soil ALP activity might be a sensitive tool for assessing the pollution degree of Cu.

Oral Metronomic Topotecan Sensitizes Crizotinib Antitumor Activity in ALKF1174L Drug-Resistant Neuroblastoma Preclinical Models

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Libo Zhang

2017-08-01

Full Text Available BACKGROUND: Anaplastic lymphoma kinase (ALK inhibitor crizotinib has proven to be effective in the treatment of ALK-mutated neuroblastoma, but crizotinib resistance was commonly observed in patients. We aimed to overcome crizotinib resistance by combining with the MEK inhibitor trametinib or low-dose metronomic (LDM topotecan in preclinical neuroblastoma models. METHODS: We selected a panel of neuroblastoma cell lines carrying various ALK genetic aberrations to assess the therapeutic efficacy on cell proliferation in vitro. Downstream signals of ALK activation, including phosphorylation of ERK1/2, Akt as well as HIF-1α expression were evaluated under normoxic and hypoxic conditions. Tumor growth inhibition was further assessed in NOD/SCID xenograft mouse models. RESULTS: All NBL cell lines responded to crizotinib treatment but at variable ED50 levels, ranging from 0.25 to 5.58 μM. ALK-mutated cell lines SH-SY5Y, KELLY, LAN-5, and CHLA-20 are more sensitive than ALK wild-type cell lines. In addition, we demonstrated that under hypoxic conditions, all NBL cell lines showed marked decrease of ED50s when compared to normoxia except for KELLY cells. Taking into consideration the hypoxia sensitivity to crizotinib, combined treatment with crizotinib and LDM topotecan demonstrated a synergistic effect in ALKF1174L-mutated SH-SY5Y cells. In vivo, single-agent crizotinib showed limited antitumor activity in ALKF1174L-mutated SH-SY5Y and KELLY xenograft models; however, when combined with topotecan, significantly delayed tumor development was achieved in both SH-SY5Y and KELLY tumor models. CONCLUSIONS: Oral metronomic topotecan reversed crizotinib drug resistance in the ALKF1174L-mutated neuroblastoma preclinical model.

Combining users' activity survey and simulators to evaluate human activity recognition systems.

Science.gov (United States)

Azkune, Gorka; Almeida, Aitor; López-de-Ipiña, Diego; Chen, Liming

2015-04-08

Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant.

Combining Users’ Activity Survey and Simulators to Evaluate Human Activity Recognition Systems

Directory of Open Access Journals (Sweden)

Gorka Azkune

2015-04-01

Full Text Available Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant.

Combining Users' Activity Survey and Simulators to Evaluate Human Activity Recognition Systems

Science.gov (United States)

Azkune, Gorka; Almeida, Aitor; López-de-Ipiña, Diego; Chen, Liming

2015-01-01

Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant. PMID:25856329

Effects of combination therapy with vildagliptin and valsartan in a mouse model of type 2 diabetes

Science.gov (United States)

2013-01-01

Background Dipeptidyl peptidase-4 (DPP-4) inhibitors modulate incretin hormones and exert anti-diabetic effects in type 2 diabetes mellitus. Treatment with angiotensin II type 1 receptor blockers (ARB) is a proven successful intervention for hypertension with type 2 diabetes. The present study investigated the combined effects of the DPP-4 inhibitor vildagliptin and the ARB valsartan in a mouse model of type 2 diabetes. Methods C57BL/6 J mice fed with high-fat diet (HFD) or db/db mice were treated with placebo, phloridzin (PHZ), vildagliptin alone (ViL), valsartan alone (VaL) or ViL with VaL (ViLVaL) for 8 weeks. Results Glucose metabolism was improved in response to PHZ, ViL and ViLVaL in both HFD and db/db mice. Upon glucose challenge, ViLVaL showed the greatest suppression of blood glucose excursions, with increased insulin secretion, in db/db mice. ViLVaL treatment also showed an improvement of insulin sensitivity in db/db mice. Serum inflammatory cytokines were significantly decreased, and adiponectin was highest, in the ViLVaL group. ViLVaL improved insulin signaling and attenuated stress signaling in liver with amelioration of hepatic steatosis due to activated fatty acid oxidation in db/db mice. Furthermore, immunohistochemical analysis of the pancreas revealed that the combination treatment resulted in an increased expression of insulin and PDX-1, and increased insulin content. Conclusions The combination therapy of ViL and VaL improves both pancreatic beta-cell function and insulin sensitivity, with a reduction of the inflammatory and cell stress milieu in mouse models of T2DM. Our results suggest that this combination therapy exerts additive or even synergistic benefits to treat T2DM. PMID:24188631

Application of Combined Cake Filtration-Complete Blocking Model to Ultrafiltration of Skim Milk

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Mansoor Kazemimoghadam

2017-10-01

Full Text Available Membrane ultrafiltration (UF is widely used in dairy industries like milk concentration and dehydration processes. The limiting factor of UF systems is fouling which is defined as the precipitation of solutes in the form of a cake layer on the surface of the membrane. In this study, the combined cake filtration-complete blocking model was compared to cake filtration mechanism for flux data through ultrafiltration of skim milk at constant flow rate. The resistance data also was modeled using cake filtration model and standard blocking model. The effect of different trans-membrane pressures and temperatures on flux decline was then investigated. Based on the results obtained here, the combined complete blocking-cake formation model was in excellent agreement with experimental data. The cake filtration model also provided good data fits and can be applied to solutions whose solutes tend to accumulate on the surface of the membrane in the form of a cake layer. With increasing pressure, the differences between the model and experimental data increased.

Change in catalase and peroxidase activity in rat blood in case of combined radiation and mechanical injuries

International Nuclear Information System (INIS)

Volkovaya, T.A.

1982-01-01

Changes of catalase and peroxide activity of blood in rats in case of irradiation at 2.0 and 7.0 Gy, mechanical injury of animal chest and combined radiation injury were studied. The given data testify to considerable increase of the above enzymes activity in case of all these effects. The less decrease of catalase and peroxide activity was observed after infliction of mechanical injury alone. Aggravating effect of mechanical injury on the irradiated organism leads to more noticeable decrease of catalase activity (at early periods of observation) in comparison with radiation effect. Peroxide changes in case of combined radiation and mechanical injury of rats differ slightly from similar factors observed in case of irradiation alone

Synergistic activity profile of griffithsin in combination with tenofovir, maraviroc and enfuvirtide against HIV-1 clade C

International Nuclear Information System (INIS)

Ferir, Geoffrey; Palmer, Kenneth E.; Schols, Dominique

2011-01-01

Griffithsin (GRFT) is possibly the most potent anti-HIV peptide found in natural sources. Due to its potent and broad-spectrum antiviral activity and unique safety profile it has great potential as topical microbicide component. Here, we evaluated various combinations of GRFT against HIV-1 clade B and clade C isolates in primary peripheral blood mononuclear cells (PBMCs) and in CD4 + MT-4 cells. In all combinations tested, GRFT showed synergistic activity profile with tenofovir, maraviroc and enfuvirtide based on the median effect principle with combination indices (CI) varying between 0.34 and 0.79 at the calculated EC 95 level. Furthermore, the different glycosylation patterns on the viral envelope of clade B and clade C gp120 had no observable effect on the synergistic interactions. Overall, we can conclude that the evaluated two-drug combination increases their antiviral potency and supports further clinical investigations in pre-exposure prophylaxis for GRFT combinations in the context of HIV-1 clade C infection.

Modeling and simulation of syngas purification and power generation in integrated gasification combined cycle (IGCS)

Energy Technology Data Exchange (ETDEWEB)

Mehmood, N; Zaman, Z U; Mehran, M T [National Development, Islamabad (Pakistan)

2011-07-01

Integrated Gasification Combined Cycle (IGCC) is one of the most promising technologies for power generation; The environmental benefits and the higher energy conversion efficiency distinguish it from traditional coal generation technologies. This work presents a structured and validated conceptual model of purification of coal gas produced during the Underground Coal Gasification (UCG) of coal containing high sulfur contents. Gas cleaning operations for CO/sub 2/, H/sub 2/S and moisture removal have been modeled in steady and dynamic state. The power generation from combined cycle is also modeled. The model has been developed using Aspen HYSYS and Aspen Plus simulation software. Predicted results of clean gas composition and generated power present a good agreement with industrial data and efficiency parameters. This study is aimed at obtaining optimal assessment of an integrated gasification combined cycle (IGCC) power plant configurations. (author)

Modeling and simulation of syngas purification and power generation in integrated gasification combined cycle (IGCS)

International Nuclear Information System (INIS)

Mehmood, N.; Zaman, Z.U.; Mehran, M.T.

2011-01-01

Integrated Gasification Combined Cycle (IGCC) is one of the most promising technologies for power generation; The environmental benefits and the higher energy conversion efficiency distinguish it from traditional coal generation technologies. This work presents a structured and validated conceptual model of purification of coal gas produced during the Underground Coal Gasification (UCG) of coal containing high sulfur contents. Gas cleaning operations for CO/sub 2/, H/sub 2/S and moisture removal have been modeled in steady and dynamic state. The power generation from combined cycle is also modeled. The model has been developed using Aspen HYSYS and Aspen Plus simulation software. Predicted results of clean gas composition and generated power present a good agreement with industrial data and efficiency parameters. This study is aimed at obtaining optimal assessment of an integrated gasification combined cycle (IGCC) power plant configurations. (author)

[Open-field behavioral study in rat hyperlipidemia combined with chronic unpredictable mild stress model].

Science.gov (United States)

Hu, Hua; Zhang, Yingchun; Xu, Yeqing; Liu, Chunfeng; Wang, Liwei

2015-06-16

To investigate behavioral changes in a rat hyperlipidemia model induced by high lipid feed combined with depression by Chronic Unpredictable Mild Stress (CUMS). A total of 40 rats were randomly divided into control (CON), control feed for 9 weeks followed by CUMS for 4 weeks (CON + CUMS), high fat diet (HFD) and high lipid feed for 9 weeks followed by CUMS for 4 weeks (HFD + CUMS) (n = 10 each). Open-field test was individually measured at baseline, week 9 and week 13. (1) Serum lipids: total cholesterol [(2.67 ± 0.04) mmol/L, (2.68 ± 0.02) mmol/L] and low density lipoprotein [(1.08 ± 0.03) mmol/L, (1.06 ± 0.01) mmol/L] of HFD and HFD + CUMS were both significantly higher than those of CON and CON + CUMS [(1.78 ± 0.12) mmol/L, (0.79 ± 0.04) mmol/L; (1.76 ± 0.09) mmol/L, (0.76 ± 0.06) mmol/L, all P Open-field test: at week 13, compared to CON rats, CON + CUMS rats exhibited enhanced locomotor activity during the first minute, reduced activity in the center squares and rearing, and increased the number of grooming and defecation (all P < 0.05). In comparison to the CON rats, a decrease in total squares in 5 min, central squares and peripheral squares was observed in HFD rats at week 13 (all P < 0.05). However, compared with HFD, CON, CON + CUMS rats, when high lipid feed for 9 weeks combined with depression, significant decrease activities in total squares in 5 min, central squares and peripheral squares were observed in HFD + CUMS rats at week 13. Besides these, the number of rearing was reduced, however, locomotor activity during the first minute and the number of grooming and defecation was significantly increased (all P < 0.001). Under uncontrolled hyperlipidemia, severe depressive symptoms will present more early once exposure to a series of chronic stressors followed by significant autonomic nervous dysfunctional symptoms.

Antimicrobial Activity of Individual and Combined Essential Oils against Foodborne Pathogenic Bacteria.

Science.gov (United States)

Reyes-Jurado, Fatima; López-Malo, Aurelio; Palou, Enrique

2016-02-01

The antimicrobial activities of essential oils from Mexican oregano (Lippia berlandieri Schauer), mustard (Brassica nigra), and thyme (Thymus vulgaris) were evaluated alone and in binary combinations against Listeria monocytogenes, Staphylococcus aureus, or Salmonella Enteritidis. Chemical compositions of the essential oils were analyzed by gas chromatography-mass spectrometry. The MICs of the evaluated essential oils ranged from 0.05 to 0.50% (vol/vol). Mustard essential oil was the most effective, likely due to the presence of allyl isothiocyanate, identified as its major component. Furthermore, mustard essential oil exhibited synergistic effects when combined with either Mexican oregano or thyme essential oils (fractional inhibitory concentration indices of 0.75); an additive effect was obtained by combining thyme and Mexican oregano essential oils (fractional inhibitory concentration index = 1.00). These results suggest the potential of studied essential oil mixtures to inhibit microbial growth and preserve foods; however, their effect on sensory quality in selected foods compatible with their flavor needs to be assessed.

Spectral Quantitative Analysis Model with Combining Wavelength Selection and Topology Structure Optimization

Directory of Open Access Journals (Sweden)

Qian Wang

2016-01-01

Full Text Available Spectroscopy is an efficient and widely used quantitative analysis method. In this paper, a spectral quantitative analysis model with combining wavelength selection and topology structure optimization is proposed. For the proposed method, backpropagation neural network is adopted for building the component prediction model, and the simultaneousness optimization of the wavelength selection and the topology structure of neural network is realized by nonlinear adaptive evolutionary programming (NAEP. The hybrid chromosome in binary scheme of NAEP has three parts. The first part represents the topology structure of neural network, the second part represents the selection of wavelengths in the spectral data, and the third part represents the parameters of mutation of NAEP. Two real flue gas datasets are used in the experiments. In order to present the effectiveness of the methods, the partial least squares with full spectrum, the partial least squares combined with genetic algorithm, the uninformative variable elimination method, the backpropagation neural network with full spectrum, the backpropagation neural network combined with genetic algorithm, and the proposed method are performed for building the component prediction model. Experimental results verify that the proposed method has the ability to predict more accurately and robustly as a practical spectral analysis tool.

Electrical properties of alkali-activated slag composite with combined graphite/CNT filler

Science.gov (United States)

Rovnaník, P.; Míková, M.; Kusák, I.

2017-10-01

Alkali-activated industrial by-products such as blast furnace slag are known to possess properties which are comparable to or even better than those observed for ordinary Portland cement. The combination of alkali-activated slag matrix with conductive filler introduces new functionalities which are commonly known for self-sensing or self-heating concrete. The present paper discusses the effect of the mixture of two different conductive fillers, graphite powder and carbon nanotubes (CNTs), on the electrical properties of alkali-activated slag mortars. Prepared samples were also tested for their mechanical properties and microstructure was investigated by means of mercury intrusion porosimetry and scanning electron microscopy. The percolation threshold for the resistance was reached for the mixture containing 0.1% CNTs and 8% graphite powder.

Representing and estimating interactions between activities in a need-based model of activity generation

NARCIS (Netherlands)

Nijland, L.; Arentze, T.; Timmermans, H.

2013-01-01

Although several activity-based models made the transition to practice in recent years, modeling dynamic activity generation and especially, the mechanisms underlying activity generation are not well incorporated in the current activity-based models. For instance, current models assume that

Representing and estimating interactions between activities in a need-based model of activity generation

NARCIS (Netherlands)

Nijland, E.W.L.; Arentze, T.A.; Timmermans, H.J.P.

2011-01-01

Although several activity-based models made the transition to practice in recent years, modelling dynamic activity generation and especially, the mechanisms underlying activity generation are not well incorporated in the current activity-based models. For example, current models assume that

A model for the scattering of high-frequency electromagnetic fields from dielectrics exhibiting thermally-activated electrical losses

Science.gov (United States)

Hann, Raiford E.

1991-01-01

An equivalent circuit model (ECM) approach is used to predict the scattering behavior of temperature-activated, electrically lossy dielectric layers. The total electrical response of the dielectric (relaxation + conductive) is given by the ECM and used in combination with transmission line theory to compute reflectance spectra for a Dallenbach layer configuration. The effects of thermally-activated relaxation processes on the scattering properties is discussed. Also, the effect of relaxation and conduction activation energy on the electrical properties of the dielectric is described.

Combining patient journey modelling and visual multi-agent computer simulation: a framework to improving knowledge translation in a healthcare environment.

Science.gov (United States)

Curry, Joanne; Fitzgerald, Anneke; Prodan, Ante; Dadich, Ann; Sloan, Terry

2014-01-01

This article focuses on a framework that will investigate the integration of two disparate methodologies: patient journey modelling and visual multi-agent simulation, and its impact on the speed and quality of knowledge translation to healthcare stakeholders. Literature describes patient journey modelling and visual simulation as discrete activities. This paper suggests that their combination and their impact on translating knowledge to practitioners are greater than the sum of the two technologies. The test-bed is ambulatory care and the goal is to determine if this approach can improve health services delivery, workflow, and patient outcomes and satisfaction. The multidisciplinary research team is comprised of expertise in patient journey modelling, simulation, and knowledge translation.

Helicobacter pylori eradication by sitafloxacin-lansoprazole combination and sitafloxacin pharmacokinetics in Mongolian gerbils and its in vitro activity and resistance development.

Science.gov (United States)

Yamamoto, Tatsuo; Takano, Tomomi; Higuchi, Wataru; Nishiyama, Akihito; Taneike, Ikue; Yoshida, Kumi; Kanda, Hiroko; Imamura, Yuichiro

2011-09-01

A total of 293 strains of Helicobacter pylori, including strains resistant to levofloxacin, clarithromycin, metronidazole, or amoxicillin, were examined for in vitro susceptibility to 10 antimicrobial agents. Among these agents, sitafloxacin (a fluoroquinolone) showed the greatest activity (MIC(90), 0.06 μg/ml), with high bactericidal activity and synergy in sitafloxacin-lansoprazole (a proton pump inhibitor) combination. In a Mongolian gerbil model with a H. pylori ATCC 43504 challenge, marked eradication effects were observed at ≥1 mg/kg for sitafloxacin, ≥10 mg/kg for levofloxacin, and ≥10 mg/kg for lansoprazole, reflecting MIC levels for each agent (0.008, 0.25, and 2 μg/ml, respectively). The therapeutic rates were 83.3% for the sitafloxacin (0.3 mg/kg)-lansoprazole (2.5 mg/kg) combination and 0% for either sitafloxacin or lansoprazole alone. The maximum serum concentration (C(max)) of sitafloxacin was 0.080 ± 0.054 μg/ml at 30 min, when orally administered at 1 mg/kg. The simultaneous administration of lansoprazole resulted in no difference. In the resistance development assay, MICs of levofloxacin increased 64- to 256-fold with gyrA mutations (Ala88Pro and Asn87Lys), while MICs of sitafloxacin only up to 16-fold with the Asn87Lys mutation. The data suggest that sitafloxacin exhibited superior anti-H. pylori activity with low rates of resistance development in vitro and that, reflecting high in vitro activities, sitafloxacin-lansoprazole combination exhibited strong therapeutic effects in Mongolian gerbils with a C(max) of sitafloxacin that was 10-fold higher than the MIC value at a 1-mg/kg administration.

Combinations of Epoch Durations and Cut-Points to Estimate Sedentary Time and Physical Activity among Adolescents

Science.gov (United States)

Fröberg, Andreas; Berg, Christina; Larsson, Christel; Boldemann, Cecilia; Raustorp, Anders

2017-01-01

The purpose of the current study was to investigate how combinations of different epoch durations and cut-points affect the estimations of sedentary time and physical activity in adolescents. Accelerometer data from 101 adolescents were derived and 30 combinations were used to estimate sedentary time, light, moderate, vigorous, and combined…

Tariff Model for Combined Transport

Directory of Open Access Journals (Sweden)

Velimir Kolar

2002-11-01

Full Text Available By analysing the cwTen.t situation on the Croatian transportationmarket, and considering all parameters needed forthe development of combined transport, measures are suggestedin order to improve and stimulate its development. Oneof the first measures is the standardisation and introduction ofunique tariffs for combined transport, and then government incentivefor the organisation and development of combinedtransport means and equipment. A significant role in thisshould be set on adequately defined transport policy.

Activation of human CD141+ and CD1c+ dendritic cells in vivo with combined TLR3 and TLR7/8 ligation.

Science.gov (United States)

Pearson, Frances E; Chang, Karshing; Minoda, Yoshihito; Rojas, Ingrid M Leal; Haigh, Oscar L; Daraj, Ghazal; Tullett, Kirsteen M; Radford, Kristen J

2018-04-01

Mice reconstituted with human hematopoietic stem cells are valuable models to study aspects of the human immune system in vivo. We describe a humanized mouse model (hu mice) in which fully functional human CD141 + and CD1c + myeloid and CD123 + plasmacytoid dendritic cells (DC) develop from human cord blood CD34 + cells in immunodeficient mice. CD141 + DC are the human equivalents of murine CD8 + /CD103 + DC which are essential for the induction of tumor-inhibitory cytotoxic T lymphocyte responses, making them attractive targets to exploit for the development of new cancer immunotherapies. We used CD34 + -engrafted NSG-A2 mice to investigate activation of DC subsets by synthetic dsRNA or ssRNA analogs polyinosinic-polycytidylic acid/poly I:C and Resiquimod/R848, agonists for TLR3 and TLR8, respectively, both of which are expressed by CD141 + DC. Injection of hu mice with these agonists resulted in upregulation of costimulatory molecules CD80, CD83 and CD86 by CD141 + and CD1c + DC alike, and their combination further enhanced expression of these molecules by both subsets. When combined, poly I:C and R848 enhanced serum levels of key cytokines associated with cross-presentation and the induction of cytotoxic T lymphocyte responses including IFN-α, IFN-β, IL-12 and CXCL10. These data advocate a combination of poly I:C and R848 TLR agonists as means of activating human DC for immunotherapy. © 2018 Australasian Society for Immunology Inc.

Combined electromagnetic and photoreaction modeling of CLD-1 photobleaching in polymer microring resonators

Science.gov (United States)

Huang, Yanyi; Poon, Joyce K. S.; Liang, Wei; Yariv, Amnon; Zhang, Cheng; Dalton, Larry R.

2005-08-01

By combining a solid-state photoreaction model with the modal solutions of an optical waveguide, we simulate the refractive index change due to the photobleaching of CLD-1 chromophores in an amorphous polycarbonate microring resonator. The simulation agrees well with experimental results. The photobleaching quantum efficiency of the CLD-1 chromophores is determined to be 0.65%. The combined modeling of the electromagnetic wave propagation and photoreaction precisely illustrates the spatial and temporal evolution of the optical properties of the polymer material as manifested in the refractive index and their effects on the modal and physical properties of the optical devices.

Activity build-up on the circulation loops of boiling water reactors: Basics for modelling of transport and deposition processes

International Nuclear Information System (INIS)

Covelli, B.; Alder, H.P.

1988-03-01

In the past 20 years the radiation field of nuclear power plant loops outside the core zone was the object of investigations in many countries. In this context test loops were built and basic research done. At our Institute PSI the installation of a LWR-contamination loop is planned for this year. This experimental loop has the purpose to investigate the complex phenomena of activity deposition from the primary fluid of reactor plants and to formulate analytical models. From the literature the following conclusions can be drawn: The principal correlations of the activity build-up outside the core are known. The plant specific single phenomena as corrosion, crud-transport, activation and deposit of cobalt in the oxide layer are complex and only partially understood. The operational experience of particular plants with low contaminated loops (BWR-recirculation loops) show that in principle the problem is manageable. The reduction of the activity build-up in older plants necessitates a combination of measures to modify the crud balance in the primary circuit. In parallel to the experimental work several simulation models in the form of computer programs were developed. These models have the common feature that they are based on mass balances, in which the exchange of materials and the sedimentation processes are described by global empirical transport coefficients. These models yield satisfactory results and allow parameter studies; the application however is restricted to the particular installation. All programs lack models that describe the thermodynamic and hydrodynamic mechanisms on the surface of deposition layers. Analytical investigations on fouling of process equipment led to models that are also applicable to the activity build-up in reactor loops. Therefore it seems appropriate to combine the nuclear simulation models with the fundamental equations for deposition. 10 refs., 18 figs., 3 tabs

Separate and combined sewer systems: a long-term modelling approach.

Science.gov (United States)

Mannina, Giorgio; Viviani, Gaspare

2009-01-01

Sewer systems convey mostly dry weather flow, coming from domestic and industrial sanitary sewage as well as infiltration flow, and stormwater due to meteoric precipitations. Traditionally, in urban drainage two types of sewer systems are adopted: separate and combined sewers. The former convey dry and wet weather flow separately into two different networks, while the latter convey dry and wet weather flow together. Which is the best solution in terms of cost-benefit analysis still remains a controversial subject. The present study was aimed at comparing the pollution loads discharged to receiving bodies by Wastewater Treatment Plant (WWTP) and Combined Sewer Overflow (CSO) for different kinds of sewer systems (combined and separate). To accomplish this objective, a comparison between the two systems was carried out using results from simulations of catchments characterised by different dimensions, population densities and water supply rate. The analysis was based on a parsimonious mathematical model able to simulate the sewer system as well as the WWTP during both dry and wet weather. The rain series employed for the simulations was six years long. Several pollutants, both dissolved and particulate, were modelled. The results confirmed the uncertainties in the choice of one system versus the other, emphasising the concept that case-by-case solutions have to be undertaken. Further, the compared systems showed different responses in terms of effectiveness in reducing the discharged mass to the RWB in relation to the particular pollutant taken into account.

Integrated gasification combined-cycle research development and demonstration activities in the US

Energy Technology Data Exchange (ETDEWEB)

Ness, H.M.; Brdar, R.D.

1996-09-01

The United States Department of Energy (DOE)`s Office of Fossil Energy, Morgantown Energy Technology Center, is managing a research development and demonstration (RD&D) program that supports the commercialization of integrated gasification combined-cycle (IGCC) advanced power systems. This overview briefly describes the supporting RD&D activities and the IGCC projects selected for demonstration in the Clean Coal Technology (CCT) Program.

Combined HQSAR, topomer CoMFA, homology modeling and docking studies on triazole derivatives as SGLT2 inhibitors.

Science.gov (United States)

Yu, Shuling; Yuan, Jintao; Zhang, Yi; Gao, Shufang; Gan, Ying; Han, Meng; Chen, Yuewen; Zhou, Qiaoqiao; Shi, Jiahua

2017-06-01

Sodium-glucose cotransporter 2 (SGLT2) is a promising target for diabetes therapy. We aimed to develop computational approaches to identify structural features for more potential SGLT2 inhibitors. In this work, 46 triazole derivatives as SGLT2 inhibitors were studied using a combination of several approaches, including hologram quantitative structure-activity relationships (HQSAR), topomer comparative molecular field analysis (CoMFA), homology modeling, and molecular docking. HQSAR and topomer CoMFA were used to construct models. Molecular docking was conducted to investigate the interaction of triazole derivatives and homology modeling of SGLT2, as well as to validate the results of the HQSAR and topomer CoMFA models. The most effective HQSAR and topomer CoMFA models exhibited noncross-validated correlation coefficients of 0.928 and 0.891 for the training set, respectively. External predictions were made successfully on a test set and then compared with previously reported models. The graphical results of HQSAR and topomer CoMFA were proven to be consistent with the binding mode of the inhibitors and SGLT2 from molecular docking. The models and docking provided important insights into the design of potent inhibitors for SGLT2.

Effects of Combined High Hydrostatic Pressure and Dense Phase Carbon Dioxide on the Activity, Structure and Size of Polyphenoloxidase.

Science.gov (United States)

Duong, Trang; Balaban, Murat; Perera, Conrad

2015-11-01

High hydrostatic pressure (HHP) may activate undesirable enzymes such as polyphenoloxidase (PPO). Carbon dioxide (CO2 ) addition to HHP could increase enzyme inactivation. We investigated the inactivation of combined HHP and dense phase carbon dioxide process on activity, secondary conformation and size of pure PPO from mushroom. Solutions (2.35μM, in phosphate buffer pH 6.8) were treated with HHP alone (HHP), or 3.6% w/w of CO2 was injected into the package (HHP+CO2). Treatment conditions were 600 MPa, 20 °C, for 1, 3, 5, 7, and 9 min. HHP+CO2 treatment significantly decreased residual enzyme activity (REA) to 30% to 12% after 1 to 9 min, respectively, whereas only HHP had no significant effect. Both HHP and HHP+CO2 treatments caused changes in secondary conformations, however HHP+CO2 changes were more extensive. Alpha-helix fractions were reduced by 32% and 41%, while β sheet, turn and unordered increased by 63% and 213%, 100% and 71%, and 118% and 82% for HHP and HHP+CO2, respectively after 9 min. The protein size in HHP+CO2 samples was 5- to 6-fold larger than that of Control and HHP treatment, and this increase was inversely correlated with REA. The best inactivation kinetics of HHP+CO2 model was the 2-fractional model with 2 simultaneous 1st-order steps, contributing 70% and 30% to original enzyme activity, with k(labile) = 12.15 min(-1) and k(stable) = 0.07 min(-1), respectively. No recovery in activity, secondary conformation and size in all samples were observed after 1-mo storage. Addition of CO2 in HHP treatment can improve enzyme inactivation, and therefore product shelf-life and quality. High hydrostatic pressure (HHP) achieves the safety of foods as a nonthermal method, but it may activate undesirable enzymes resulting in short shelf life due to, for example flavor and color changes. Our study determined that addition of CO2 to HHP has significant effects on enzyme inactivation, secondary conformational and molecular size changes of mushroom PPO

Combined thermo-chemo-sonic disintegration of waste activated sludge for biogas production.

Science.gov (United States)

Kavitha, S; Yukesh Kannah, R; Yeom, Ick Tae; Do, Khac-Uan; Banu, J Rajesh

2015-12-01

In the present study, there was an investigation about the impact of a new combined thermo-chemo-sonic disintegration of waste activated sludge (WAS) on biodegradability. The outcome of sludge disintegration reveals that maximum Suspended Solids (SS) reduction and Chemical Oxygen Demand (COD) solubilization effectuated at a specific energy input of 5290.5kJ/kgTS, and was found to be 20%, 16.4%, 15% and 27%, 22%, and 20%, respectively for the three alkalis (NaOH, KOH, and Ca(OH)2). The conversion coefficient of the Volatile Suspended Solids (VSS) to product Soluble COD (SCOD), calculated by nonlinear regression modeling, was found to be 0.5530gSCOD/gVSS, 0.4587gSCOD/gVSS, and 0.4195gSCOD/gVSS for NaOH, KOH, and Ca(OH)2, respectively. In the biodegradability studies, the parameter evaluation provides an estimate of parameter uncertainty and correlation, and elucidates that there is no significant difference in biodegradability (0.413gCOD/gCOD, 0.367gCOD/gCOD, and 0.342gCOD/gCOD) for three alkalis (NaOH, KOH, and Ca(OH)2). Copyright © 2015 Elsevier Ltd. All rights reserved.

Hierarchical modeling of active materials

International Nuclear Information System (INIS)

Taya, Minoru

2003-01-01

Intelligent (or smart) materials are increasingly becoming key materials for use in actuators and sensors. If an intelligent material is used as a sensor, it can be embedded in a variety of structure functioning as a health monitoring system to make their life longer with high reliability. If an intelligent material is used as an active material in an actuator, it plays a key role of making dynamic movement of the actuator under a set of stimuli. This talk intends to cover two different active materials in actuators, (1) piezoelectric laminate with FGM microstructure, (2) ferromagnetic shape memory alloy (FSMA). The advantage of using the FGM piezo laminate is to enhance its fatigue life while maintaining large bending displacement, while that of use in FSMA is its fast actuation while providing a large force and stroke capability. Use of hierarchical modeling of the above active materials is a key design step in optimizing its microstructure for enhancement of their performance. I will discuss briefly hierarchical modeling of the above two active materials. For FGM piezo laminate, we will use both micromechanical model and laminate theory, while for FSMA, the modeling interfacing nano-structure, microstructure and macro-behavior is discussed. (author)

Theoretical Modeling and Analysis of L- and P-band Radar Backscatter Sensitivity to Soil Active Layer Dielectric Variations

Directory of Open Access Journals (Sweden)

Jinyang Du

2015-07-01

Full Text Available Freeze-thaw (FT and moisture dynamics within the soil active layer are critical elements of boreal, arctic and alpine ecosystems, and environmental change assessments. We evaluated the potential for detecting dielectric changes within different soil layers using combined L- and P-band radar remote sensing as a prerequisite for detecting FT and moisture profile changes within the soil active layer. A two-layer scattering model was developed and validated for simulating radar responses from vertically inhomogeneous soil. The model simulations indicated that inhomogeneity in the soil dielectric profile contributes to both L- and P-band backscatter, but with greater P-band sensitivity at depth. The difference in L- and P-band responses to soil dielectric profile inhomogeneity appears suitable for detecting associated changes in soil active layer conditions. Additional evaluation using collocated airborne radar (AIRSAR observations and in situ soil moisture measurements over alpine tundra indicates that combined L- and P-band SAR observations are sensitive to soil dielectric profile heterogeneity associated with variations in soil moisture and FT conditions.

Synergistic activity of antibiotics combined with ivermectin to kill body lice.

Science.gov (United States)

Sangaré, Abdoul Karim; Rolain, Jean Marc; Gaudart, Jean; Weber, Pascal; Raoult, Didier

2016-03-01

Ivermectin and doxycycline have been found to be independently effective in killing body lice. In this study, 450 body lice were artificially fed on a Parafilm™ membrane with human blood associated with antibiotics (doxycycline, erythromycin, rifampicin and azithromycin) alone and in combination with ivermectin. Fluorescence in situ hybridisation and spectral deconvolution were performed to evaluate bacterial transcriptional activity following antibiotic intake by the lice. In the first series, a lethal effect of antibiotics on lice was observed compared with the control group at 18 days (log-rank test, P≤10(-3)), with a significant difference between groups in the production of nits (P=0.019, Kruskal-Wallis test). A high lethal effect of ivermectin alone (50ng/mL) was observed compared with the control group (log-rank test, P≤10(-3)). Fluorescence of bacteriocytes in lice treated with 20μg/mL doxycycline was lower than in untreated lice (PKruskal-Wallis test). In the second series with antibiotic-ivermectin combinations, a synergistic lethal effect on treated lice (log-rank test, PKruskal-Wallis test). Additionally, survival of lice in the combination treatment groups compared with ivermectin alone was significant (log-rank test, P=0.0008). These data demonstrate that the synergistic effect of combinations of antibiotics and ivermectin could be used to achieve complete eradication of lice and to avoid selection of a resistant louse population. Copyright © 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Establishment of a new murine elastase-induced aneurysm model combined with transplantation.

Directory of Open Access Journals (Sweden)

Zuzanna Rowinska

Full Text Available The aim of our study was to develop a reproducible murine model of elastase-induced aneurysm formation combined with aortic transplantation.Adult male mice (n = 6-9 per group underwent infrarenal, orthotopic transplantation of the aorta treated with elastase or left untreated. Subsequently, both groups of mice were monitored by ultrasound until 7 weeks after grafting.Mice receiving an elastase-pretreated aorta developed aneurysms and exhibited a significantly increased diastolic vessel diameter compared to control grafted mice at 7 week after surgery (1.11 ± 0.10 mm vs. 0.75 ± 0.03 mm; p ≤ 0,001. Histopathological examination revealed disruption of medial elastin, an increase in collagen content and smooth muscle cells, and neointima formation in aneurysm grafts.We developed a reproducible murine model of elastase-induced aneurysm combined with aortic transplantation. This model may be suitable to investigate aneurysm-specific inflammatory processes and for use in gene-targeted animals.

A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation

Energy Technology Data Exchange (ETDEWEB)

John R. Ford

2005-11-01

Existing dosimetric models of the radiation response of tissues are essentially static. Consideration of changes in the cell populations over time has not been addressed realistically. For a single acute dose this is not a concern, but for modeling chronic exposures or fractionated acute exposures, the natural turnover and progression of cells could have a significant impact on a variety of endpoints. This proposal addresses the shortcomings of current methods by combining current dose-based calculation techniques with information on the cell turnover for a model tissue. The proposed model will examine effects at the single-cell level for an exposure of a section of human bronchiole. The cell model will be combined with Monte Carlo calculations of doses to cells and cell nuclei due to varying dose-rates of different radiation qualities. Predictions from the model of effects on survival, apoptosis rates, and changes in the number of cycling and differentiating cells will be tested experimentally. The availability of dynamic dosimetric models of tissues at the single-cell level will be useful for analysis of low-level radiation exposures and in the development of new radiotherapy protocols.

TLR9 played a more important role than TLR2 in the combination of maltose-binding protein and BCG-induced Th1 activation.

Science.gov (United States)

Ni, Weihua; Wang, Fang; Liu, Guomu; Zhang, Nannan; Yuan, Hongyan; Jie, Jing; Tai, Guixiang

2016-11-01

Our previous study demonstrated that maltose-binding protein (MBP) combined with BCG induced synergistic mouse Th1 activation in vivo. Here, to explore the mechanism of MBP combined with BCG on Th1 activation, mouse purified CD4 + T cells were stimulated with MBP and BCG in vitro. The results showed that MBP combined with BCG synergistically increased IFN-γ production, accompanied with the upregulation of TLR2/9 expressions, suggesting that TLR2/9 were involved in the combination-induced Th1 activation. Next, TLR2 antibodies and TLR9 inhibitor were used to further analyze the effects of TLRs in Th1 activation. Results showed TLR2 antibody partly decreased MBP combined with BCG-induced IFN-γ production, MyD88 expression and IκB phosphorylation, indicating that TLR2-mediated MyD88-dependent pathway was involved in the MBP combined with BCG-induced Th1 activation. Moreover, MBP combined with BCG-induced Th1 activation was completely abrogated by TLR9 inhibitor, suggesting that TLR9-mediated MyD88-dependent pathway played a more important role than TLR2 in the combination-induced Th1 activation. Further study showed that TLR9 inhibitor downregulated TLR2 expression, suggesting that TLR9 signaling regulated TLR2 activation to favor Th1 resonse induced by MBP combined with BCG. Collectively, we demonstrated for the first time that the cross-talk of TLR2 and TLR9 triggered Th1 activation collaboratively and our findings provided valuable information about designing more effective adjuvant for cancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Influence of Urban Land-Use and Public Transport Facilities on Active Commuting in Wellington, New Zealand: Active Transport Forecasting Using the WILUTE Model

Directory of Open Access Journals (Sweden)

Joreintje Dingena Mackenbach

2016-03-01

Full Text Available Physical activity has numerous physical and mental health benefits, and active commuting (walking or cycling to work can help meet physical activity recommendations. This study investigated socioeconomic differences in active commuting, and assessed the impact of urban land-use and public transport policies on active commuting in the Wellington region in New Zealand. We combined data from the New Zealand Household Travel Survey and GIS data on land-use and public transport facilities with the Wellington Integrated Land-Use, Transportation and Environment (WILUTE model, and forecasted changes in active commuter trips associated with changes in the built environment. Results indicated high income individuals were more likely to commute actively than individuals on low income. Several land-use and transportation factors were associated with active commuting and results from the modelling showed a potential increase in active commuting following an increase in bus frequency and parking fees. In conclusion, regional level policies stimulating environmental factors that directly or indirectly affect active commuting may be a promising strategy to increase population level physical activity. Access to, and frequency of, public transport in the neighbourhood can act as a facilitator for a more active lifestyle among its residents without negatively affecting disadvantaged groups.

Modeling of active control of external magnetohydrodynamic instabilities

International Nuclear Information System (INIS)

Bialek, James; Boozer, Allen H.; Mauel, M.E.; Navratil, G.A.

2001-01-01

A general circuit formulation of resistive wall mode (RWM) feedback stabilization developed by Boozer [Phys. Plasmas 5, 3350 (1998)] has been used as the basis for the VALEN computer code that calculates the performance of an active control system in arbitrary geometry. The code uses a finite element representation of a thin shell structure in an integral formulation to model arbitrary conducting walls. This is combined with a circuit representation of stable and unstable plasma modes. Benchmark comparisons of VALEN results with large aspect ratio analytic model of the current driven kink mode are in very good agreement. VALEN also models arbitrary sensors, control coils, and the feedback logic connecting these sensors and control coils to provide a complete simulation capability for feedback control of plasma instabilities. VALEN modeling is in good agreement with experimental results on DIII-D [Garofalo et al., Nucl. Fusion 40, 1491 (2000)] and HBT-EP [Cates et al., Phys. Plasmas 7, 3133 (2000)]. VALEN feedback simulations have also been used to evaluate and optimize the sensor/coil configurations for present and planned RWM experiments on DIII-D. These studies have shown a clear advantage for the use of local poloidal field sensors driving a 'mode control' feedback logic control loop and configurations which minimize the control coil coupling to the stabilizing resistive wall

Understanding Catalytic Activity Trends for NO Decomposition and CO Oxidation using Density Functional Theory and Microkinetic Modeling

DEFF Research Database (Denmark)

Falsig, Hanne

-metal surfaces by combining a database of adsorption energies on stepped metal surfaces with known Brønsted–Evans–Polanyi (BEP) relations for the activation barriers of dissociation of diatomic molecules over stepped transition- and noble-metal surfaces. The potential energy diagram directly points to why Pd......The main aim of this thesis is to understand the catalytic activity of transition metals and noble metals for the direct decomposition of NO and the oxidation of CO. The formation of NOx from combustion of fossil and renewable fuels continues to be a dominant environmental issue. We take one step...... towards rationalizing trends in catalytic activity of transition metal catalysts for NO decomposition by combining microkinetic modelling with density functional theory calculations. We establish the full potential energy diagram for the direct NO decomposition reaction over stepped transition...

p-Nitrophenol removal by combination of powdered activated carbon adsorption and ultrafiltration - comparison of different operational modes.

Science.gov (United States)

Ivancev-Tumbas, Ivana; Hobby, Ralph; Küchle, Benjamin; Panglisch, Stefan; Gimbel, Rolf

2008-09-01

Ultrafiltration is classified as a low-pressure membrane technology which effectively removes particulate matter and microorganisms and to a certain extent dissolved organic matter (15-25%) and colour. The technology has been optimized and is becoming competitive compared to conventional processes for larger scale plant capacities. In combination with activated carbon it is an effective barrier regarding the removal of synthetic organic chemicals. Growing interest in ultrafiltration raises the question of better usage of the adsorption capacity of powdered activated carbon (PAC) used in combination with this low-pressure membrane technique. This paper presents a pilot plant study of different PAC dosing procedures within a combined hybrid membrane IN/OUT process for removal of p-nitrophenol (PNP) from water (c(0)=1mg/L) under real case conditions (e.g. usage of the same module for the whole duration of the experiment, backwashing with permeate water, no separate saturation of the membrane with substance without presence of carbon). p-Nitrophenol was chosen as an appropriate test substance to assess the efficiency of different operation modes. Dead-end and cross-flow filtration were compared with respect to different PAC dosing procedures: continuous dosing into a continuously stirred tank reactor (CSTR) in front of the module and direct dosing into the pipe in front of the module (continuous, single-pulse and multi-pulse dosing). There was no advantage in cross-flow mode over dead-end referring to PNP concentration in the permeate. Relating to the carbon dosing procedure, the best results were obtained for continuous PAC addition. The option of dosing directly into the pipe has the advantage of no additional tank being necessary. In the case of single-pulse dosing, the formation of a carbon layer on the membrane surface was assumed and an LDF model applied for a simplified estimation of the "breakthrough behaviour" in the thus formed "PAC filter layer".

Qualitative and quantitative combined nonlinear dynamics model and its application in analysis of price, supply–demand ratio and selling rate

International Nuclear Information System (INIS)

Zhu, Dingju

2016-01-01

The qualitative and quantitative combined nonlinear dynamics model proposed in this paper fill the gap in nonlinear dynamics model in terms of qualitative and quantitative combined methods, allowing the qualitative model and quantitative model to perfectly combine and overcome their weaknesses by learning from each other. These two types of models use their strengths to make up for the other’s deficiencies. The qualitative and quantitative combined models can surmount the weakness that the qualitative model cannot be applied and verified in a quantitative manner, and the high costs and long time of multiple construction as well as verification of the quantitative model. The combined model is more practical and efficient, which is of great significance for nonlinear dynamics. The qualitative and quantitative combined modeling and model analytical method raised in this paper is not only applied to nonlinear dynamics, but can be adopted and drawn on in the modeling and model analysis of other fields. Additionally, the analytical method of qualitative and quantitative combined nonlinear dynamics model proposed in this paper can satisfactorily resolve the problems with the price system’s existing nonlinear dynamics model analytical method. The three-dimensional dynamics model of price, supply–demand ratio and selling rate established in this paper make estimates about the best commodity prices using the model results, thereby providing a theoretical basis for the government’s macro-control of price. Meanwhile, this model also offer theoretical guidance to how to enhance people’s purchasing power and consumption levels through price regulation and hence to improve people’s living standards.

Solar resources estimation combining digital terrain models and satellite images techniques

Energy Technology Data Exchange (ETDEWEB)

Bosch, J.L.; Batlles, F.J. [Universidad de Almeria, Departamento de Fisica Aplicada, Ctra. Sacramento s/n, 04120-Almeria (Spain); Zarzalejo, L.F. [CIEMAT, Departamento de Energia, Madrid (Spain); Lopez, G. [EPS-Universidad de Huelva, Departamento de Ingenieria Electrica y Termica, Huelva (Spain)

2010-12-15

One of the most important steps to make use of any renewable energy is to perform an accurate estimation of the resource that has to be exploited. In the designing process of both active and passive solar energy systems, radiation data is required for the site, with proper spatial resolution. Generally, a radiometric stations network is used in this evaluation, but when they are too dispersed or not available for the study area, satellite images can be utilized as indirect solar radiation measurements. Although satellite images cover wide areas with a good acquisition frequency they usually have a poor spatial resolution limited by the size of the image pixel, and irradiation must be interpolated to evaluate solar irradiation at a sub-pixel scale. When pixels are located in flat and homogeneous areas, correlation of solar irradiation is relatively high, and classic interpolation can provide a good estimation. However, in complex topography zones, data interpolation is not adequate and the use of Digital Terrain Model (DTM) information can be helpful. In this work, daily solar irradiation is estimated for a wide mountainous area using a combination of Meteosat satellite images and a DTM, with the advantage of avoiding the necessity of ground measurements. This methodology utilizes a modified Heliosat-2 model, and applies for all sky conditions; it also introduces a horizon calculation of the DTM points and accounts for the effect of snow covers. Model performance has been evaluated against data measured in 12 radiometric stations, with results in terms of the Root Mean Square Error (RMSE) of 10%, and a Mean Bias Error (MBE) of +2%, both expressed as a percentage of the mean value measured. (author)

SYSTEMATIC SCANNING ELECTRON MICROSCOPY TECHNIQUE FOR EVALUATING COMBINED BIOLOIGCAL/GRANULAR ACTIVATED CARBON TREATMENT PROCESSES

Science.gov (United States)

A systematic scanning election microscope analytical technique has been developed to examine granular activated carbon used a a medium for biomass attachment in liquid waste treatment. The procedure allows for the objective monitoring, comparing, and trouble shooting of combined ...

Activation of the intrinsic-apoptotic pathway in LNCaP prostate cancer cells by genistein- topotecan combination treatments

Directory of Open Access Journals (Sweden)

Vanessa Hörmann

2013-03-01

Full Text Available ABSTRACTBackground: Prostate cancer is the second most common cancer in American men. The development of alternative preventative and/or treatment options utilizing a combination of phytochemicals and chemotherapeutic drugs could be an attractive alternative compared to conventional carcinoma treatments. Genistein isoflavone is the primary dietary phytochemical found in soy and has demonstrated anti-tumor activities in LNCaP prostate cancer cells. Topotecan Hydrochloride (Hycamtin is an FDA-approved chemotherapy for secondary treatment of lung, ovarian and cervical cancers. The purpose of this study was to detail the potential activation of the intrinsic apoptotic pathway in LNCaP prostate cancer cells through genistein-topotecan combination treatments.Methods: LNCaP cells were cultured in complete RPMI medium in a monolayer (70-80% confluency at 37ºC and 5% CO2. Treatment consisted of single and combination groups of genistein and topotecan for 24 hours. The treated cells were assayed for i growth inhibition through trypan blue exclusion assay and microphotography , ii classification of cellular death through acridine/ ethidium bromide fluorescent staining, and iii activation of the intrinsic apoptotic pathway through Jc-1: mitochondrial membrane potential assay, cytochrome c release and Bcl-2 protein expression.Results: The overall data indicated that genistein-topotecan combination was significantly more efficacious in reducing the prostate carcinoma’s viability compared to the single treatment options. In all treatment groups, cell death occurred primarily through the activation of the intrinsic apoptotic pathway.Conclusion: The combination of topotecan and genistein has the potential to lead to treatment options with equal therapeutic efficiency as traditional chemo- and radiation therapies, but lower cell cytotoxicity and fewer side effects in patients.

A grey neural network and input-output combined forecasting model. Primary energy consumption forecasts in Spanish economic sectors

International Nuclear Information System (INIS)

Liu, Xiuli; Moreno, Blanca; García, Ana Salomé

2016-01-01

A combined forecast of Grey forecasting method and neural network back propagation model, which is called Grey Neural Network and Input-Output Combined Forecasting Model (GNF-IO model), is proposed. A real case of energy consumption forecast is used to validate the effectiveness of the proposed model. The GNF-IO model predicts coal, crude oil, natural gas, renewable and nuclear primary energy consumption volumes by Spain's 36 sub-sectors from 2010 to 2015 according to three different GDP growth scenarios (optimistic, baseline and pessimistic). Model test shows that the proposed model has higher simulation and forecasting accuracy on energy consumption than Grey models separately and other combination methods. The forecasts indicate that the primary energies as coal, crude oil and natural gas will represent on average the 83.6% percent of the total of primary energy consumption, raising concerns about security of supply and energy cost and adding risk for some industrial production processes. Thus, Spanish industry must speed up its transition to an energy-efficiency economy, achieving a cost reduction and increase in the level of self-supply. - Highlights: • Forecasting System Using Grey Models combined with Input-Output Models is proposed. • Primary energy consumption in Spain is used to validate the model. • The grey-based combined model has good forecasting performance. • Natural gas will represent the majority of the total of primary energy consumption. • Concerns about security of supply, energy cost and industry competitiveness are raised.

Radiation combined injury models to study the effects of interventions and wound biomechanics.

Science.gov (United States)

Zawaski, Janice A; Yates, Charles R; Miller, Duane D; Kaffes, Caterina C; Sabek, Omaima M; Afshar, Solmaz F; Young, Daniel A; Yang, Yunzhi; Gaber, M Waleed

2014-12-01

In the event of a nuclear detonation, a considerable number of projected casualties will suffer from combined radiation exposure and burn and/or wound injury. Countermeasure assessment in the setting of radiation exposure combined with dermal injury is hampered by a lack of animal models in which the effects of interventions have been characterized. To address this need, we used two separate models to characterize wound closure. The first was an open wound model in mice to study the effect of wound size in combination with whole-body 6 Gy irradiation on the rate of wound closure, animal weight and survival (morbidity). In this model the addition of interventions, wound closure, subcutaneous vehicle injection, topical antiseptic and topical antibiotics were studied to measure their effect on healing and survival. The second was a rat closed wound model to study the biomechanical properties of a healed wound at 10 days postirradiation (irradiated with 6 or 7.5 Gy). In addition, complete blood counts were performed and wound pathology by staining with hematoxylin and eosin, trichrome, CD68 and Ki67. In the mouse open wound model, we found that wound size and morbidity were positively correlated, while wound size and survival were negatively correlated. Regardless of the wound size, the addition of radiation exposure delayed the healing of the wound by approximately 5-6 days. The addition of interventions caused, at a minimum, a 30% increase in survival and improved mean survival by ∼9 days. In the rat closed wound model we found that radiation exposure significantly decreased all wound biomechanical measurements as well as white blood cell, platelet and red blood cell counts at 10 days post wounding. Also, pathological changes showed a loss of dermal structure, thickening of dermis, loss of collagen/epithelial hyperplasia and an increased density of macrophages. In conclusion, we have characterized the effect of a changing wound size in combination with radiation

Comparison of high-latitude thermospheric meridional winds II: combined FPI, radar and model climatologies

Energy Technology Data Exchange (ETDEWEB)

Griffin, E.M.; Aruliah, A.; Mueller-Wodarg, I.C.F.; Aylward, A. [Atmospheric Physics Lab., Univ. Coll. London, London (United Kingdom)

2004-07-01

The climatological behaviour of the thermospheric meridional wind above Kiruna, Sweden (67.4 N, 20.4 E) has been investigated for seasonal and solar cycle dependence using six different techniques, comprising both model and experimental sources. Model output from both the empirical Horizontal Wind Model (HWM) (Hedin et al., 1988) and the numerical coupled thermosphere and ionosphere model (CTIM) are compared to the measured behaviour at kiruna, as a single site example. The empirical International Reference Ionosphere (IRI) model is used as input to an implementation of servo theory, to provide another climatology combining empirical input with a theoretical framework. The experimental techniques have been introduced in a companion paper in this issue and provide climatologies from direct measurements, using fabry-perot interferometers (FPI), together with 2 separate techniques applied to the European incoherent scatter radar (EISCAT) database to derive neutral winds. One of these techniques uses the same implementation of servo theory as has been used with the IRI model. Detailed comparisons for each season and solar activity category allow for conclusions to be drawn as to the major influences on the climatological behaviour of the wind at this latitude. Comparison of the incoherent scatter radar (ISR) derived neutral winds with FPI, empirical model and numerical model winds is important to our understanding and judgement of the validity of the techniques used to derive thermospheric wind databases. The comparisons also test model performance and indicate possible reasons for differences found between the models. In turn, the conclusions point to possible improvements in their formulation. In particular it is found that the empirical models are over-reliant on mid-latitude data in their formulation, and fail to provide accurate estimates of the winds at high-latitudes. (orig.)

Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms: revival of an old drug.

Directory of Open Access Journals (Sweden)

Jennifer Keiser

Full Text Available BACKGROUND: It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. METHODOLOGY: We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. PRINCIPAL FINDINGS: We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI = 2.53. Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively. A highly synergistic effect (CI = 0.15 was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. CONCLUSION/SIGNIFICANCE: Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be

Modeling of Combined Impact and Blast Loading on Reinforced Concrete Slabs

Directory of Open Access Journals (Sweden)

P. Del Linz

Full Text Available Abstract Explosive devices represent a significant threat to military and civilian structures. Specific design procedures have to be followed to account for this and ensure buildings will have the capacity to resist the imposed pressures. Shrapnel can also be produced during explosions and the resulting impacts can weaken the structure, reducing its capacity to resist the blast pressure wave and potentially causing failures to occur. Experiments were performed by the Defence Science and Technology Agency (DSTA of Singapore to study this combined loading phenomenon. Slabs were placed on the ground and loaded with approximately 9 kg TNT charges at a standoff distance of 2.1 m. Spherical steel ball bearings were used to reproduce the shrapnel loading. Loading and damage characteristics were recorded from the experiments. A finite element analysis (FEA model was then created which could simulate the effect of combined shrapnel impacts and blast pressure waves in reinforced concrete slabs, so that its results could be compared to experimental data from the blast tests. Quarter models of the experimental concrete slabs were built using LS-Dyna. Material models available in the software were employed to represent all the main components, taking into account projectile deformations. The penetration depth and damage areas measured were then compared to the experimental data and an analytical solution to validate the models.

The combination of glutamate receptor antagonist MK-801 with tamoxifen and its active metabolites potentiates their antiproliferative activity in mouse melanoma K1735-M2 cells

International Nuclear Information System (INIS)

Ribeiro, Mariana P.C.; Nunes-Correia, Isabel; Santos, Armanda E.; Custódio, José B.A.

2014-01-01

Recent reports suggest that N-methyl-D-aspartate receptor (NMDAR) blockade by MK-801 decreases tumor growth. Thus, we investigated whether other ionotropic glutamate receptor (iGluR) antagonists were also able to modulate the proliferation of melanoma cells. On the other hand, the antiestrogen tamoxifen (TAM) decreases the proliferation of melanoma cells, and is included in combined therapies for melanoma. As the efficacy of TAM is limited by its metabolism, we investigated the effects of the NMDAR antagonist MK-801 in combination with TAM and its active metabolites, 4-hydroxytamoxifen (OHTAM) and endoxifen (EDX). The NMDAR blockers MK-801 and memantine decreased mouse melanoma K1735-M2 cell proliferation. In contrast, the NMDAR competitive antagonist APV and the AMPA and kainate receptor antagonist NBQX did not affect cell proliferation, suggesting that among the iGluR antagonists only the NMDAR channel blockers inhibit melanoma cell proliferation. The combination of antiestrogens with MK-801 potentiated their individual effects on cell biomass due to diminished cell proliferation, since it decreased the cell number and DNA synthesis without increasing cell death. Importantly, TAM metabolites combined with MK-801 promoted cell cycle arrest in G1. Therefore, the data obtained suggest that the activity of MK-801 and antiestrogens in K1735-M2 cells is greatly enhanced when used in combination. - Highlights: • MK-801 and memantine decrease melanoma cell proliferation. • The combination of MK-801 with antiestrogens inhibits melanoma cell proliferation. • These combinations greatly enhance the effects of the compounds individually. • MK-801 combined with tamoxifen active metabolites induces cell cycle arrest in G1. • The combination of MK-801 and antiestrogens is an innovative strategy for melanoma

On hierarchical models for visual recognition and learning of objects, scenes, and activities

CERN Document Server

Spehr, Jens

2015-01-01

In many computer vision applications, objects have to be learned and recognized in images or image sequences. This book presents new probabilistic hierarchical models that allow an efficient representation of multiple objects of different categories, scales, rotations, and views. The idea is to exploit similarities between objects and object parts in order to share calculations and avoid redundant information. Furthermore inference approaches for fast and robust detection are presented. These new approaches combine the idea of compositional and similarity hierarchies and overcome limitations of previous methods. Besides classical object recognition the book shows the use for detection of human poses in a project for gait analysis. The use of activity detection is presented for the design of environments for ageing, to identify activities and behavior patterns in smart homes. In a presented project for parking spot detection using an intelligent vehicle, the proposed approaches are used to hierarchically model...

The combination of Bifidobacterium breve with non-digestible oligosaccharides suppresses airway inflammation in a murine model for chronic asthma.

Science.gov (United States)

Sagar, Seil; Vos, Arjan P; Morgan, Mary E; Garssen, Johan; Georgiou, Niki A; Boon, Louis; Kraneveld, Aletta D; Folkerts, Gert

2014-04-01

Over the last decade, there has been a growing interest in the use of interventions that target the intestinal microbiota as a treatment approach for asthma. This study is aimed at exploring the therapeutic effects of long-term treatment with a combination of Bifidobacterium breve with non-digestible oligosaccharides on airway inflammation and remodeling. A murine ovalbumin-induced chronic asthma model was used. Pulmonary airway inflammation; mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; expression of Foxp3 in blood Th cells; in vitro T cell activation; mast cell degranulation; and airway remodeling were examined. The combination of B. breve with non-digestible oligosaccharides suppressed pulmonary airway inflammation; reduced T cell activation and mast cell degranulation; modulated expression of pattern recognition receptors, cytokines and transcription factors; and reduced airway remodeling. The treatment induced regulatory T cell responses, as shown by increased Il10 and Foxp3 transcription in lung tissue, and augmented Foxp3 protein expression in blood CD4+CD25+Foxp3+ T cells. This specific combination of beneficial bacteria with non-digestible oligosaccharides has strong anti-inflammatory properties, possibly via the induction of a regulatory T cell response, resulting in reduced airway remodeling and, therefore, may be beneficial in the treatment of chronic inflammation in allergic asthma. Copyright © 2014 Elsevier B.V. All rights reserved.

Combination of Deterministic and Probabilistic Meteorological Models to enhance Wind Farm Power Forecasts

International Nuclear Information System (INIS)

Bremen, Lueder von

2007-01-01

Large-scale wind farms will play an important role in the future worldwide energy supply. However, with increasing wind power penetration all stakeholders on the electricity market will ask for more skilful wind power predictions regarding save grid integration and to increase the economic value of wind power. A Neural Network is used to calculate Model Output Statistics (MOS) for each individual forecast model (ECMWF and HIRLAM) and to model the aggregated power curve of the Middelgrunden offshore wind farm. We showed that the combination of two NWP models clearly outperforms the better single model. The normalized day-ahead RMSE forecast error for Middelgrunden can be reduced by 1% compared to single ECMWF. This is a relative improvement of 6%. For lead times >24h it is worthwhile to use a more sophisticated model combination approach than simple linear weighting. The investigated principle component regression is able to extract the uncorrelated information from two NWP forecasts. The spread of Ensemble Predictions is related to the skill of wind power forecasts. Simple contingency diagrams show that low spread corresponds is more often related to low forecast errors and high spread to large forecast errors

Conceptual Combination During Sentence Comprehension

Science.gov (United States)

Swinney, David; Love, Tracy; Walenski, Matthew; Smith, Edward E.

2008-01-01

This experiment examined the time course of integration of modifier-noun (conceptual) combinations during auditory sentence comprehension using cross-modal lexical priming. The study revealed that during ongoing comprehension, there is initial activation of features of the noun prior to activation of (emergent) features of the entire conceptual combination. These results support compositionality in conceptual combination; that is, they indicate that features of the individual words constituting a conceptual combination are activated prior to combination of the words into a new concept. PMID:17576278

Model experiment and numerical simulation of drop impact response of multilayer-combinational container

International Nuclear Information System (INIS)

Xie Ruoze; Zhong Weizhou; Wan Qiang; Huang Xicheng; Zhang Fangju

2015-01-01

The drop impact process of multilayer-combinational container was simulated experimentally using a gas gun, and the normal impact and oblique impact of scaled models were tested. The experiments of scaled models were simulated numerically, and the stress distribution and plastic deformation in the tested structures during collision process were obtained. The results were compared with the experiment data. It was shown that the impact work mainly converted into plastic work due to the plastic deformation of the cushion wood and the plastic hinge in the buckled steel shell. The plastic deformation mainly happened at the collided end of the scaled models, and there was no plastic deformation found far from the collided end. The compressive stress-strain curve of the wood in texture direction can be used to simulate numerically the drop impact process of multilayer-combinational container. (authors)

MCNP modelling of a combined neutron/gamma counter

CERN Document Server

Bourva, L C A; Ottmar, H; Weaver, D R

1999-01-01

A series of Monte Carlo neutron calculations for a combined gamma/passive neutron coincidence counter has been performed. This type of device, part of a suite of non-destructive assay instruments utilised for the enforcement of the Euratom nuclear safeguards within the European Union, is to be used for high accuracy measurements of the plutonium content of small samples of nuclear materials. The multi-purpose Monte Carlo N-particle (MCNP) code version 4B has been used to model in detail the neutron coincidence detector and to investigate the leakage self-multiplication of PuO sub 2 and mixed U-Pu oxide (MOX) reference samples used to calibrate the instrument. The MCNP calculations have been used together with a neutron coincidence counting interpretative model to determine characteristic parameters of the detector. A comparative study to both experimental and previous numerical results has been performed. Sensitivity curves of the variation of the detector's efficiency, epsilon, to, alpha, the ratio of (alpha...

Forward modeling transient brightenings and microflares around an active region observed with Hi-C

Energy Technology Data Exchange (ETDEWEB)

Kobelski, Adam R. [Now at National Radio Astronomy Observatory, P.O. Box 2, Green Bank, WV 24944 (United States); McKenzie, David E., E-mail: kobelski@solar.physics.montana.edu [Department of Physics, P.O. Box 173840, Montana State University, Bozeman, MT 59717-3840 (United States)

2014-10-20

Small-scale flare-like brightenings around active regions are among the smallest and most fundamental of energetic transient events in the corona, providing a testbed for models of heating and active region dynamics. In a previous study, we modeled a large collection of these microflares observed with Hinode/X-Ray Telescope (XRT) using EBTEL and found that they required multiple heating events, but could not distinguish between multiple heating events on a single strand, or multiple strands each experiencing a single heating event. We present here a similar study, but with extreme-ultraviolet data of Active Region 11520 from the High Resolution Coronal Imager (Hi-C) sounding rocket. Hi-C provides an order of magnitude improvement to the spatial resolution of XRT, and a cooler temperature sensitivity, which combine to provide significant improvements to our ability to detect and model microflare activity around active regions. We have found that at the spatial resolution of Hi-C (≈0.''3), the events occur much more frequently than expected (57 events detected, only 1 or 2 expected), and are most likely made from strands of the order of 100 km wide, each of which is impulsively heated with multiple heating events. These findings tend to support bursty reconnection as the cause of the energy release responsible for the brightenings.

Combined paracetamol and amitriptyline adsorption to activated charcoal

DEFF Research Database (Denmark)

Hoegberg, Lotte Christine Groth; Groenlykke, Thor Buch; Abildtrup, Ulla

2010-01-01

Objectives. High-gram drug doses seen in multiple-drug poisonings might be close to the adsorption capacity of activated charcoal (AC). The aim was to determine the maximum adsorption capacities (Q(m)) of amitriptyline and paracetamol, separately and in combination, to AC. Methods. ACs (Carbomix......® and Norit Ready-To-Use) were tested in vitro. At pH 1.2 and pH 7.2, 0.250 g AC and paracetamol and/or amitriptyline were mixed and incubated. The AC: drug ratios were 10:1, 5:1, 3:1, 2:1, and 1:1. The mixed-drug adsorption vials contained the same AC: paracetamol ratios, but amitriptyline was added as fixed...... Ready-To-Use. The tested pH differences had minor effect on the adsorption. The mixed-drug adsorption showed about 40% Q(m) reduction of each drug with increasing amounts of drug/g AC, but the total gram of drug adsorbed to AC was increased compared to one-drug conditions. Conclusion. The adsorption...

A deterministic combination of numerical and physical models for coastal waves

DEFF Research Database (Denmark)

Zhang, Haiwen

2006-01-01

of numerical and physical modelling hence provides an attractive alternative to the use of either tool on it's own. The goal of this project has been to develop a deterministically combined numerical/physical model where the physical wave tank is enclosed in a much larger computational domain, and the two......Numerical and physical modelling are the two main tools available for predicting the influence of water waves on coastlines and structures placed in the near-shore environment. Numerical models can cover large areas at the correct scale, but are limited in their ability to capture strong...... nonlinearities, wave breaking, splash, mixing, and other such complicated physics. Physical models naturally include the real physics (at the model scale), but are limited by the physical size of the facility and must contend with the fact that different physical effects scale differently. An integrated use...

Modeling Aspects Of Activated Sludge Processes Part I: Process Modeling Of Activated Sludge Facilitation And Sedimentation

International Nuclear Information System (INIS)

Ibrahim, H. I.; EI-Ahwany, A.H.; Ibrahim, G.

2004-01-01

Process modeling of activated sludge flocculation and sedimentation reviews consider the activated sludge floc characteristics such as: morphology viable and non-viable cell ratio density and water content, bio flocculation and its kinetics were studied considering the characteristics of bio flocculation and explaining theory of Divalent Cation Bridging which describes the major role of cations in bio flocculation. Activated sludge flocculation process modeling was studied considering mass transfer limitations from Clifft and Andrew, 1981, Benefild and Molz 1983 passing Henze 1987, until Tyagi 1996 and G. Ibrahim et aI. 2002. Models of aggregation and breakage of flocs were studied by Spicer and Pratsinis 1996,and Biggs 2002 Size distribution of floes influences mass transfer and biomass separation in the activated sludge process. Therefore, it is of primary importance to establish the role of specific process operation factors, such as sludge loading dynamic sludge age and dissolved oxygen, on this distribution with special emphasis on the formation of primary particles

Multiplexed profiling of GPCR activities by combining split TEV assays and EXT-based barcoded readouts.

Science.gov (United States)

Galinski, Sabrina; Wichert, Sven P; Rossner, Moritz J; Wehr, Michael C

2018-05-25

G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors and are implicated in the physiological regulation of many biological processes. The high diversity of GPCRs and their physiological functions make them primary targets for therapeutic drugs. For the generation of novel compounds, however, selectivity towards a given target is a critical issue in drug development as structural similarities between members of GPCR subfamilies exist. Therefore, the activities of multiple GPCRs that are both closely and distantly related to assess compound selectivity need to be tested simultaneously. Here, we present a cell-based multiplexed GPCR activity assay, termed GPCRprofiler, which uses a β-arrestin recruitment strategy and combines split TEV protein-protein interaction and EXT-based barcode technologies. This approach enables simultaneous measurements of receptor activities of multiple GPCR-ligand combinations by applying massively parallelized reporter assays. In proof-of-principle experiments covering 19 different GPCRs, both the specificity of endogenous agonists and the polypharmacological effects of two known antipsychotics on GPCR activities were demonstrated. Technically, normalization of barcode reporters across individual assays allows quantitative pharmacological assays in a parallelized manner. In summary, the GPCRprofiler technique constitutes a flexible and scalable approach, which enables simultaneous profiling of compound actions on multiple receptor activities in living cells.

Thermodynamic modelling of alkali-activated slag cements

International Nuclear Information System (INIS)

Myers, Rupert J.; Lothenbach, Barbara; Bernal, Susan A.; Provis, John L.

2015-01-01

Highlights: • A thermodynamic modelling analysis of alkali-activated slag cements is presented. • Thermodynamic database describes zeolites, alkali carbonates, C–(N–)A–S–H gel. • Updated thermodynamic model for Mg–Al layered double hydroxides. • Description of phase assemblages in Na 2 SiO 3 - and Na 2 CO 3 -activated slag cements. • Phase diagrams for NaOH-activated and Na 2 SiO 3 -activated slag cements are simulated. - Abstract: This paper presents a thermodynamic modelling analysis of alkali-activated slag-based cements, which are high performance and potentially low-CO 2 binders relative to Portland cement. The thermodynamic database used here contains a calcium (alkali) aluminosilicate hydrate ideal solid solution model (CNASH-ss), alkali carbonate and zeolite phases, and an ideal solid solution model for a hydrotalcite-like Mg–Al layered double hydroxide phase. Simulated phase diagrams for NaOH- and Na 2 SiO 3 -activated slag-based cements demonstrate the high stability of zeolites and other solid phases in these materials. Thermodynamic modelling provides a good description of the chemical compositions and types of phases formed in Na 2 SiO 3 -activated slag cements over the most relevant bulk chemical composition range for these cements, and the simulated volumetric properties of the cement paste are consistent with previously measured and estimated values. Experimentally determined and simulated solid phase assemblages for Na 2 CO 3 -activated slag cements were also found to be in good agreement. These results can be used to design the chemistry of alkali-activated slag-based cements, to further promote the uptake of this technology and valorisation of metallurgical slags

The Use of Molecular Modeling as "Pseudoexperimental" Data for Teaching VSEPR as a Hands-On General Chemistry Activity

Science.gov (United States)

Martin, Christopher B.; Vandehoef, Crissie; Cook, Allison

2015-01-01

A hands-on activity appropriate for first-semester general chemistry students is presented that combines traditional VSEPR methods of predicting molecular geometries with introductory use of molecular modeling. Students analyze a series of previously calculated output files consisting of several molecules each in various geometries. Each structure…

Modeling Atmospheric Activity of Cool Stars

Science.gov (United States)

Schrijver, C. J.

2003-10-01

This review discusses a set of simple models for cool-star activity with which we compute (1) photospheric field patterns on stars of different activity levels, (2) the associated outer-atmospheric field configurations, and (3) the soft X-ray emission that is expected to result from the ensemble of loop atmospheres in the coronae of these stars. The model is based on empirically-determined properties of solar activity. It allows us to extrapolate to stars of significantly higher and lower activity than seen on the present-day Sun through its cycle. With it, we can, for example, gain insight into stellar field patterns (including a possible formation mechanism for polar starspots), as well as in the properties of coronal heating (helpful in the identification of the quiescent coronal heating mechanism). Lacking comprehensive theoretical understanding, the model's reliance on empirical solar data means that the multitude of processes involved are approximated to be independent of rotation rate, activity level, and fundamental stellar parameters, or -- where unavoidably necessary -- assumed to simply scale with activity. An evaluation of the most important processes involved guides a discussion of the limits of the model, of the limitations in our knowledge, and of future needs. "I propose to adopt such rules as will ensure the testability of scientific statements; which is to say, their falsifiability." Karl Popper (1902-1994)

1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models

Science.gov (United States)

Ma, Yingyu; Yu, Wei-Dong; Trump, Donald L.; Johnson, Candace S.

2010-01-01

Background 1,25 dihydroxyvitamin D3 (1,25D3) potentiates the cytotoxic effects of several common chemotherapeutic agents. The combination of gemcitabine and cisplatin (GC) is a current standard chemotherapy regimen for bladder cancer. We investigated whether 1,25D3 could enhance the antitumor activity of GC in bladder cancer model systems. Methods Human bladder cancer T24 and UMUC3 cells were pretreated with 1,25D3 followed by GC. Apoptosis were assessed by annexin V staining. Caspase activation was examined by immunoblot analysis and substrate-based caspase activity assay. The cytotoxic effects were examined using MTT and in vitro clonogenic assay. p73 protein levels were assessed by immunoblot analysis. Knockdown of p73 was achieved by siRNA. The in vivo antitumor activity was assessed by in vivo excision clonogenic assay and tumor regrowth delay in the T24 xenograft model. Results 1,25D3 pretreatment enhanced GC-induced apoptosis and the activities of caspases- 8, 9 and 3 in T24 and UMUC3 cells. 1,25D3 synergistically reduced GC-suppressed surviving fraction in T24 cells. 1,25D3, gemcitabine, or cisplatin induced p73 accumulation, which was enhanced by GC or 1,25D3 and GC. p73 expression was lower in human primary bladder tumor tissue compared with adjacent normal tissue. Knockdown of p73 increased clonogenic capacity of T24 cells treated with 1,25D3, GC or 1,25D3 and GC. 1,25D3 and GC combination enhanced tumor regression compared with 1,25D3 or GC alone. Conclusions 1,25D3 potentiates GC-mediated growth inhibition in human bladder cancer models in vitro and in vivo, which involves p73 induction and apoptosis. PMID:20564622

A Waterline Extraction Method from Remote Sensing Image Based on Quad-tree and Multiple Active Contour Model

Directory of Open Access Journals (Sweden)

YU Jintao

2016-09-01

Full Text Available After the characteristics of geodesic active contour model (GAC, Chan-Vese model(CV and local binary fitting model(LBF are analyzed, and the active contour model based on regions and edges is combined with image segmentation method based on quad-tree, a waterline extraction method based on quad-tree and multiple active contour model is proposed in this paper. Firstly, the method provides an initial contour according to quad-tree segmentation. Secondly, a new signed pressure force(SPF function based on global image statistics information of CV model and local image statistics information of LBF model has been defined, and then ,the edge stopping function(ESF is replaced by the proposed SPF function, which solves the problem such as evolution stopped in advance and excessive evolution. Finally, the selective binary and Gaussian filtering level set method is used to avoid reinitializing and regularization to improve the evolution efficiency. The experimental results show that this method can effectively extract the weak edges and serious concave edges, and owns some properties such as sub-pixel accuracy, high efficiency and reliability for waterline extraction.

Modelling activity transport behavior in PWR plant

International Nuclear Information System (INIS)

Henshaw, Jim; McGurk, John; Dickinson, Shirley; Burrows, Robert; Hinds, Kelvin; Hussey, Dennis; Deshon, Jeff; Barrios Figueras, Joan Pau; Maldonado Sanchez, Santiago; Fernandez Lillo, Enrique; Garbett, Keith

2012-09-01

The activation and transport of corrosion products around a PWR circuit is a major concern to PWR plant operators as these may give rise to high personnel doses. The understanding of what controls dose rates on ex-core surfaces and shutdown releases has improved over the years but still several questions remain unanswered. For example the relative importance of particle and soluble deposition in the core to activity levels in the plant is not clear. Wide plant to plant and cycle to cycle variations are noted with no apparent explanations why such variations are observed. Over the past few years this group have been developing models to simulate corrosion product transport around a PWR circuit. These models form the basis for the latest version of the BOA code and simulate the movement of Fe and Ni around the primary circuit. Part of this development is to include the activation and subsequent transport of radioactive species around the circuit and this paper describes some initial modelling work in this area. A simple model of activation, release and deposition is described and then applied to explain the plant behaviour at Sizewell B and Vandellos II. This model accounts for activation in the core, soluble and particulate activity movement around the circuit and for activity capture ex-core on both the inner and outer oxides. The model gives a reasonable comparison with plant observations and highlights what controls activity transport in these plants and importantly what factors can be ignored. (authors)

A combined aeroelastic-aeroacoustic model for wind turbine noise: Verification and analysis of field measurements

DEFF Research Database (Denmark)

Bertagnolio, Franck; Aagaard Madsen, Helge; Fischer, Andreas

2017-01-01

In this paper, semi-empirical engineering models for the three main wind turbine aerodynamic noise sources, namely, turbulent inflow, trailing edge and stall noise, are introduced. They are implemented into the in-house aeroelastic code HAWC2 commonly used for wind turbine load calculations...... and design. The results of the combined aeroelastic and aeroacoustic model are compared with field noise measurements of a 500kW wind turbine. Model and experimental data are in fairly good agreement in terms of noise levels and directivity. The combined model allows separating the various noise sources...... and highlights a number of mechanisms that are difficult to differentiate when only the overall noise from a wind turbine is measured....

Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry.

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Shafqat Ahmad

Full Text Available Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2, sex, study center (for multicenter studies, and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction  = 0.015. However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction  = 0.014 vs. n = 71,611, Pinteraction  = 0.275 for Europeans. In secondary analyses, both the FTO rs1121980 (Pinteraction  = 0.003 and the SEC16B rs10913469 (Pinteraction  = 0.025 variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

Combined heat transfer and kinetic models to predict cooking loss during heat treatment of beef meat.

Science.gov (United States)

Kondjoyan, Alain; Oillic, Samuel; Portanguen, Stéphane; Gros, Jean-Bernard

2013-10-01

A heat transfer model was used to simulate the temperature in 3 dimensions inside the meat. This model was combined with a first-order kinetic models to predict cooking losses. Identification of the parameters of the kinetic models and first validations were performed in a water bath. Afterwards, the performance of the combined model was determined in a fan-assisted oven under different air/steam conditions. Accurate knowledge of the heat transfer coefficient values and consideration of the retraction of the meat pieces are needed for the prediction of meat temperature. This is important since the temperature at the center of the product is often used to determine the cooking time. The combined model was also able to predict cooking losses from meat pieces of different sizes and subjected to different air/steam conditions. It was found that under the studied conditions, most of the water loss comes from the juice expelled by protein denaturation and contraction and not from evaporation. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Wavelet Support Vector Machine Combination Model for Singapore Tourist Arrival to Malaysia

Science.gov (United States)

Rafidah, A.; Shabri, Ani; Nurulhuda, A.; Suhaila, Y.

2017-08-01

In this study, wavelet support vector machine model (WSVM) is proposed and applied for monthly data Singapore tourist time series prediction. The WSVM model is combination between wavelet analysis and support vector machine (SVM). In this study, we have two parts, first part we compare between the kernel function and second part we compare between the developed models with single model, SVM. The result showed that kernel function linear better than RBF while WSVM outperform with single model SVM to forecast monthly Singapore tourist arrival to Malaysia.

A combined Importance Sampling and Kriging reliability method for small failure probabilities with time-demanding numerical models

International Nuclear Information System (INIS)

Echard, B.; Gayton, N.; Lemaire, M.; Relun, N.

2013-01-01

Applying reliability methods to a complex structure is often delicate for two main reasons. First, such a structure is fortunately designed with codified rules leading to a large safety margin which means that failure is a small probability event. Such a probability level is difficult to assess efficiently. Second, the structure mechanical behaviour is modelled numerically in an attempt to reproduce the real response and numerical model tends to be more and more time-demanding as its complexity is increased to improve accuracy and to consider particular mechanical behaviour. As a consequence, performing a large number of model computations cannot be considered in order to assess the failure probability. To overcome these issues, this paper proposes an original and easily implementable method called AK-IS for active learning and Kriging-based Importance Sampling. This new method is based on the AK-MCS algorithm previously published by Echard et al. [AK-MCS: an active learning reliability method combining Kriging and Monte Carlo simulation. Structural Safety 2011;33(2):145–54]. It associates the Kriging metamodel and its advantageous stochastic property with the Importance Sampling method to assess small failure probabilities. It enables the correction or validation of the FORM approximation with only a very few mechanical model computations. The efficiency of the method is, first, proved on two academic applications. It is then conducted for assessing the reliability of a challenging aerospace case study submitted to fatigue.

Generic Energy Matching Model and Figure of Matching Algorithm for Combined Renewable Energy Systems

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J.C. Brezet

2009-08-01

Full Text Available In this paper the Energy Matching Model and Figure of Matching Algorithm which originally was dedicated only to photovoltaic (PV systems [1] are extended towards a Model and Algorithm suitable for combined systems which are a result of integration of two or more renewable energy sources into one. The systems under investigation will range from mobile portable devices up to the large renewable energy system conceivably to be applied at the Afsluitdijk (Closure- dike in the north of the Netherlands. This Afsluitdijk is the major dam in the Netherlands, damming off the Zuiderzee, a salt water inlet of the North Sea and turning it into the fresh water lake of the IJsselmeer. The energy chain of power supplies based on a combination of renewable energy sources can be modeled by using one generic Energy Matching Model as starting point.

A comparison of combined heat and power feasibility models

Energy Technology Data Exchange (ETDEWEB)

Hinojosa, L.R.; Day, A.R.; Maidment, G.G. [Department of Engineering Systems, Faculty of Engineering, Science and the Built Environment, London South Bank University, 103 Borough Road, London SE1 0AA (United Kingdom); Dunham, C.; Kirk, P. [SEA/RENUE, 42 Braganza Street, London SE17 3RJ (United Kingdom)

2007-09-15

Carrying out feasibility studies for combined heat and power (CHP) in buildings systems is one of the most important steps in the decision-making process. This paper compares the features of different software packages available in the market and some custom-built models. It also discusses the advantages and disadvantages of building one's own application. The number of variables that need to be considered will depend on the level of accuracy and flexibility sought. Software packages are a good start, but they tend to be either overly simple or extremely complicated, and sometimes not very flexible. On the other hand, building custom-built generic models that include different technologies, unit sizes, control modes, market restrictions and benefits, can be a complex and laborious process, but will be more transparent to the user. (author)

Combined blockade of ADP receptors and PI3-kinase p110β fully prevents platelet and leukocyte activation during hypothermic extracorporeal circulation.

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Stefanie Krajewski

Full Text Available Extracorporeal circulation (ECC and hypothermia are used to maintain stable circulatory parameters and improve the ischemia tolerance of patients in cardiac surgery. However, ECC and hypothermia induce activation mechanisms in platelets and leukocytes, which are mediated by the platelet agonist ADP and the phosphoinositide-3-kinase (PI3K p110β. Under clinical conditions these processes are associated with life-threatening complications including thromboembolism and inflammation. This study analyzes effects of ADP receptor P(2Y(12 and P(2Y(1 blockade and PI3K p110β inhibition on platelets and granulocytes during hypothermic ECC. Human blood was treated with the P(2Y(12 antagonist 2-MeSAMP, the P(2Y(1 antagonist MRS2179, the PI3K p110β inhibitor TGX-221, combinations thereof, or PBS and propylene glycol (controls. Under static in vitro conditions a concentration-dependent effect regarding the inhibition of ADP-induced platelet activation was found using 2-MeSAMP or TGX-221. Further inhibition of ADP-mediated effects was achieved with MRS2179. Next, blood was circulated in an ex vivo ECC model at 28°C for 30 minutes and various platelet and granulocyte markers were investigated using flow cytometry, ELISA and platelet count analysis. GPIIb/IIIa activation induced by hypothermic ECC was inhibited using TGX-221 alone or in combination with P(2Y blockers (p<0.05, while no effect of hypothermic ECC or antiplatelet agents on GPIIb/IIIa and GPIbα expression and von Willebrand factor binding was observed. Sole P(2Y and PI3K blockade or a combination thereof inhibited P-selectin expression on platelets and platelet-derived microparticles during hypothermic ECC (p<0.05. P(2Y blockade alone or combined with TGX-221 prevented ECC-induced platelet-granulocyte aggregate formation (p<0.05. Platelet adhesion to the ECC surface, platelet loss and Mac-1 expression on granulocytes were inhibited by combined P(2Y and PI3K blockade (p<0.05. Combined blockade of P

Progress with modeling activity landscapes in drug discovery.

Science.gov (United States)

Vogt, Martin

2018-04-19

Activity landscapes (ALs) are representations and models of compound data sets annotated with a target-specific activity. In contrast to quantitative structure-activity relationship (QSAR) models, ALs aim at characterizing structure-activity relationships (SARs) on a large-scale level encompassing all active compounds for specific targets. The popularity of AL modeling has grown substantially with the public availability of large activity-annotated compound data sets. AL modeling crucially depends on molecular representations and similarity metrics used to assess structural similarity. Areas covered: The concepts of AL modeling are introduced and its basis in quantitatively assessing molecular similarity is discussed. The different types of AL modeling approaches are introduced. AL designs can broadly be divided into three categories: compound-pair based, dimensionality reduction, and network approaches. Recent developments for each of these categories are discussed focusing on the application of mathematical, statistical, and machine learning tools for AL modeling. AL modeling using chemical space networks is covered in more detail. Expert opinion: AL modeling has remained a largely descriptive approach for the analysis of SARs. Beyond mere visualization, the application of analytical tools from statistics, machine learning and network theory has aided in the sophistication of AL designs and provides a step forward in transforming ALs from descriptive to predictive tools. To this end, optimizing representations that encode activity relevant features of molecules might prove to be a crucial step.

Comparison of activity coefficient models for electrolyte systems

DEFF Research Database (Denmark)

Lin, Yi; ten Kate, Antoon; Mooijer, Miranda

2010-01-01

Three activity coefficient models for electrolyte solutions were evaluated and compared. The activity coefficient models are: The electrolyte NRTL model (ElecNRTL) by Aspentech, the mixed solvent electrolyte model (MSE) by OLI Systems Inc., and the Extended UNIQUAC model from the Technical Univer...

Active control: Wind turbine model

DEFF Research Database (Denmark)

Bindner, H.

1999-01-01

This report is a part of the reporting of the work done in the project 'Active Control of Wind Turbines'. This project aim is to develop a simulation model for design of control systems for turbines with pitch control and to use that model to designcontrollers. This report describes the model...... validation as well as parameter estimation. The model includes a simple model of the structure of the turbine including tower and flapwise blade bending,a detailed model of the gear box and induction generator, a linearized aerodynamic model including modelling of induction lag and actuator and sensor models...

Combined Antimicrobial Activity of Photodynamic Inactivation and Antimicrobials–State of the Art

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Agata Wozniak

2018-05-01

Full Text Available Antimicrobial photodynamic inactivation (aPDI is a promising tool for the eradication of life-threatening pathogens with different profiles of resistance. This study presents the state-of-the-art published studies that have been dedicated to analyzing the bactericidal effects of combining aPDI and routinely applied antibiotics in in vitro (using biofilm and planktonic cultures and in vivo experiments. Furthermore, the current paper reviews the methodology used to obtain the published data that describes the synergy between these antimicrobial approaches. The authors are convinced that even though the combined efficacy of aPDI and antimicrobials could be investigated with the wide range of methods, the use of a unified experimental methodology that is in agreement with antimicrobial susceptibility testing (AST is required to investigate possible synergistic cooperation between aPDI and antimicrobials. Conclusions concerning the possible synergistic activity between the two treatments can be drawn only when appropriate assays are employed. It must be noticed that some of the described papers were just aimed at determination if combined treatments exert enhanced antibacterial outcome, without following the standard methodology to evaluate the synergistic effect, but in most of them (18 out of 27 authors indicated the existence of synergy between described antibacterial approaches. In general, the increase in bacterial inactivation was observed when both therapies were used in combination.

Combining antiangiogenic therapy with adoptive cell immunotherapy exerts better antitumor effects in non-small cell lung cancer models.

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Shujing Shi

Full Text Available INTRODUCTION: Cytokine-induced killer cells (CIK cells are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment. METHODS: We combined recombinant human endostatin (rh-endostatin and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells. RESULTS: Our results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments. CONCLUSIONS: Our results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells

Explorations in combining cognitive models of individuals and system dynamics models of groups.

Energy Technology Data Exchange (ETDEWEB)

Backus, George A.

2008-07-01

This report documents a demonstration model of interacting insurgent leadership, military leadership, government leadership, and societal dynamics under a variety of interventions. The primary focus of the work is the portrayal of a token societal model that responds to leadership activities. The model also includes a linkage between leadership and society that implicitly represents the leadership subordinates as they directly interact with the population. The societal model is meant to demonstrate the efficacy and viability of using System Dynamics (SD) methods to simulate populations and that these can then connect to cognitive models depicting individuals. SD models typically focus on average behavior and thus have limited applicability to describe small groups or individuals. On the other hand, cognitive models readily describe individual behavior but can become cumbersome when used to describe populations. Realistic security situations are invariably a mix of individual and population dynamics. Therefore, the ability to tie SD models to cognitive models provides a critical capability that would be otherwise be unavailable.

[Activity of amphotericin B and anidulafungin, alone and combined, against Candida tropicalis biofilms developed on Teflon® and titanium].

Science.gov (United States)

Fernández-Rivero, Marcelo Ernesto; Del Pozo, José L; Valentín, Amparo; Fornes, Victoria; Molina de Diego, Araceli; Pemán, Javier; Cantón, Emilia

Current therapeutic strategies have a limited efficacy against Candida biofilms that form on the surfaces of biomedical devices. Few studies have evaluated the activity of antifungal agents against Candida tropicalis biofilms. To evaluate the activity of amphotericin B (AMB) and anidulafungin (AND), alone and in combination, against C. tropicalis biofilms developed on polytetrafluoroethylene (teflon -PTFE) and titanium surfaces using time-kill assays. Assays were performed using the CDC Biofilm Reactor equipped with PTFE and titanium disks with C. tropicalis biofilms after 24h of maturation. The concentrations assayed were 40mg/l for AMB and 8mg/l for AND, both alone and combined. After 24, 48 and 72h of exposure to the antifungals, the cfu/cm 2 was determined by a vortexing-sonication procedure. AMB reduced biofilm viable cells attached to PTFE and titanium by ≥99% and AND by 89.3% on PTFE and 96.8% on titanium. The AMB+AND combination was less active than AMB alone, both on PTFE (decrease of cfu/cm 2 3.09 Log 10 vs. 1.08 when combined) and titanium (4.51 vs. 1.53 when combined), being the interaction irrelevant on both surfaces. AMB is more active than AND against C. tropicalis biofilms. Yeast killing rates are higher on titanium than on PTFE surfaces. The combination of AMB plus AND is less effective than AMB alone on both surfaces. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Rate and State Friction Relation for Nanoscale Contacts: Thermally Activated Prandtl-Tomlinson Model with Chemical Aging

Science.gov (United States)

Tian, Kaiwen; Goldsby, David L.; Carpick, Robert W.

2018-05-01

Rate and state friction (RSF) laws are widely used empirical relationships that describe macroscale to microscale frictional behavior. They entail a linear combination of the direct effect (the increase of friction with sliding velocity due to the reduced influence of thermal excitations) and the evolution effect (the change in friction with changes in contact "state," such as the real contact area or the degree of interfacial chemical bonds). Recent atomic force microscope (AFM) experiments and simulations found that nanoscale single-asperity amorphous silica-silica contacts exhibit logarithmic aging (increasing friction with time) over several decades of contact time, due to the formation of interfacial chemical bonds. Here we establish a physically based RSF relation for such contacts by combining the thermally activated Prandtl-Tomlinson (PTT) model with an evolution effect based on the physics of chemical aging. This thermally activated Prandtl-Tomlinson model with chemical aging (PTTCA), like the PTT model, uses the loading point velocity for describing the direct effect, not the tip velocity (as in conventional RSF laws). Also, in the PTTCA model, the combination of the evolution and direct effects may be nonlinear. We present AFM data consistent with the PTTCA model whereby in aging tests, for a given hold time, static friction increases with the logarithm of the loading point velocity. Kinetic friction also increases with the logarithm of the loading point velocity at sufficiently high velocities, but at a different increasing rate. The discrepancy between the rates of increase of static and kinetic friction with velocity arises from the fact that appreciable aging during static contact changes the energy landscape. Our approach extends the PTT model, originally used for crystalline substrates, to amorphous materials. It also establishes how conventional RSF laws can be modified for nanoscale single-asperity contacts to provide a physically based friction

Model Integrating Fuzzy Argument with Neural Network Enhancing the Performance of Active Queue Management

Directory of Open Access Journals (Sweden)

Nguyen Kim Quoc

2015-08-01

Full Text Available The bottleneck control by active queue management mechanisms at network nodes is essential. In recent years, some researchers have used fuzzy argument to improve the active queue management mechanisms to enhance the network performance. However, the projects using the fuzzy controller depend heavily on professionals and their parameters cannot be updated according to changes in the network, so the effectiveness of this mechanism is not high. Therefore, we propose a model combining the fuzzy controller with neural network (FNN to overcome the limitations above. Results of the training of the neural networks will find the optimal parameters for the adaptive fuzzy controller well to changes of the network. This improves the operational efficiency of the active queue management mechanisms at network nodes.

Models of intracellular mechanisms of plant bioelectrical potentials caused by combined stimulation

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D. V. Chernetchenko

2014-10-01

Full Text Available This paper deals with bioelectrical potentials of the plants recorded during different types of stimuli and combined stimulus as well. All registrations were observed on the leaves of the corn. We used different stimuli, such as cold, heat, photo- and electrical stimulation, and certain combination of this stimuli. Hardware and software system for automated recording of bioelectrical potentials has been successfully used in this work. We proposed the universal pattern of bioelectrical potentials’ recording which allowed to detect the response of the biological object to different stimuli and various combinations of these stimuli. This pattern can be used for the deeper understanding of biological mechanisms of electrical potentials’ generation in cells and discovering of processes of accommodation of whole organisms to these stimuli. Integrated system of recording and biometrical processing was used for analysis of corn leaves electrical responses to the thermal stimuli. The dynamics of these potentials was studied, with the quantitative analysis of the potential level stabilization.We calculated the ratio of amplitude of response potentials to the first response amplitude. Mathematical models of the plant cell were used for studying of intracellular mechanisms of biopotentials gereration. As a result of modeling, we revealed that electrical response of the cells was based on selectiveconductivity of cell membrane for Н+ and Ca2+ ions. Therefore, we showed the biophysical relation of plant potentials to underlying intracellular biophysical mechanisms during thermal and combined stimulation.

Combining segmentation and attention: a new foveal attention model

Directory of Open Access Journals (Sweden)

Rebeca eMarfil

2014-08-01

Full Text Available Artificial vision systems cannot process all the information that they receive from the world in real time because it is highly expensive and inefficient in terms of computational cost. Inspired by biological perception systems, articial attention models pursuit to select only the relevant part of the scene. Besides, it is well established that the units of attention on human vision are not merely spatial but closely related to perceptual objects (proto-objects. This implies a strong bidirectional relationship between segmentation and attention processes. Therefore, while the segmentation process is the responsible to extract the proto-objects from the scene, attention can guide segmentation, arising the concept of foveal attention. When the focus of attention is deployed from one visual unit to another, the rest of the scene is perceived but at a lower resolution that the focused object. The result is a multi-resolution visual perception in which the fovea, a dimple on the central retina, provides the highest resolution vision. In this paper, a bottom-up foveal attention model is presented. In this model the input image is a foveal image represented using a Cartesian Foveal Geometry (CFG, which encodes the field of view of the sensor as a fovea (placed in the focus of attention surrounded by a set of concentric rings with decreasing resolution. Then multirresolution perceptual segmentation is performed by building a foveal polygon using the Bounded Irregular Pyramid (BIP. Bottom-up attention is enclosed in the same structure, allowing to set the fovea over the most salient image proto-object. Saliency is computed as a linear combination of multiple low level features such us colour and intensity contrast, symmetry, orientation and roundness. Obtained results from natural images show that the performance of the combination of hierarchical foveal segmentation and saliency estimation is good in terms of accuracy and speed.

Modeling Patterns of Activities using Activity Curves.

Science.gov (United States)

Dawadi, Prafulla N; Cook, Diane J; Schmitter-Edgecombe, Maureen

2016-06-01

Pervasive computing offers an unprecedented opportunity to unobtrusively monitor behavior and use the large amount of collected data to perform analysis of activity-based behavioral patterns. In this paper, we introduce the notion of an activity curve , which represents an abstraction of an individual's normal daily routine based on automatically-recognized activities. We propose methods to detect changes in behavioral routines by comparing activity curves and use these changes to analyze the possibility of changes in cognitive or physical health. We demonstrate our model and evaluate our change detection approach using a longitudinal smart home sensor dataset collected from 18 smart homes with older adult residents. Finally, we demonstrate how big data-based pervasive analytics such as activity curve-based change detection can be used to perform functional health assessment. Our evaluation indicates that correlations do exist between behavior and health changes and that these changes can be automatically detected using smart homes, machine learning, and big data-based pervasive analytics.

Inertial Cavitation Ultrasound with Microbubbles Improves Reperfusion Efficacy When Combined with Tissue Plasminogen Activator in an In Vitro Model of Microvascular Obstruction.

Science.gov (United States)

Goyal, Akash; Yu, Francois T H; Tenwalde, Mathea G; Chen, Xucai; Althouse, Andrew; Villanueva, Flordeliza S; Pacella, John J

2017-07-01

We have previously reported that long-tone-burst, high-mechanical-index ultrasound (US) and microbubble (MB) therapy can restore perfusion in both in vitro and in vivo models of microvascular obstruction (MVO). Addition of MBs to US has been found to potentiate the efficacy of thrombolytics on large venous thrombi; however, the optimal US parameters for achieving microvascular reperfusion of MVO caused by microthrombi, when combined with tissue plasminogen activator (tPA), are unknown. We sought to elucidate the specific effects of US, with and without tPA, for effective reperfusion of MVO in an in vitro model using both venous and arterial microthrombi. Venous- and arterial-type microthrombi were infused onto a mesh with 40-μm pores to simulate MVO. Pulsed US (1 MHz) was delivered with inertial cavitation (IC) (1.0 MPa, 1000 cycles, 0.33 Hz) and stable cavitation (SC) US (0.23 MPa, 20% duty cycle, 0.33 Hz) regimes while MB suspension (2 × 10 6  MBs/mL) was infused. The efficacy of sonoreperfusion with these parameters was tested with and without tPA. Sonoreperfusion efficacy was significantly greater for IC + tPA compared with tPA alone, IC, SC and SC + tPA, suggesting lytic synergism between tPA and US for both venous- and arterial-type microthrombi. In contrast to our previous in vitro studies using 1.5 MPa at 5000 US cycles without tPA, the IC regime employed herein used 90% less US energy. These findings suggest an IC regime can be used with tPA synergistically to achieve a high degree of fibrinolysis for both thrombus types. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Antimicrobial activity of suspensions and nanoemulsions of citral in combination with heat or pulsed electric fields.

Science.gov (United States)

Pagán, E; Berdejo, D; Espina, L; García-Gonzalo, D; Pagán, R

2018-01-01

The application of essential oils in form of nanoemulsions has been proposed as a method to improve their solubility in aqueous solutions, and hence their antimicrobial activity. The objective of this study was to evaluate the antimicrobial activity of citral, applied directly or in combined treatments with heat or pulsed electric fields (PEF), as a function of the inoculation procedure assayed: (i) a simple, vigorous shaking method by vortex agitation (suspension of citral; s-citral) or (ii) the previous preparation of nanoemulsions by the emulsion phase inversion (EPI) method (nanoemulsion of citral; n-citral). n-Citral was more effective in either inhibiting or inactivating Escherichia coli O157:H7 Sakai than s-citral. However, when combined with heat, a greater synergistic effect was observed with s-citral rather than with n-citral, either in lab media (pH 7·0 and 4·0) or apple juice. For instance, while almost 5 log 10 cell cycles were inactivated in apple juice after 15 min at 53°C in the presence of 0·1 μl ml -1 of s-citral, the use of n-citral required 30 min. The use of nanoemulsions did not modify the slight synergism observed when citral and mild PEF were combined (150 μs, 30 kV cm -1 ). The exploration of different delivery systems of antimicrobial compounds such as citral in aqueous food products aids in the establishment of successful combined treatments for food preservation. While at room temperature, citral in form of a nanoemulsion shows a higher antimicrobial activity; its combination with heat would imply a partial loss of the outstanding synergistic lethal effect achieved when added in suspension form. Therefore, the most suitable procedure to magnify the synergism between heat and citral when processing juices would merely require an intense homogenization step prior to the combined treatment. © 2017 The Society for Applied Microbiology.

Forecast Combinations

OpenAIRE

Timmermann, Allan G

2005-01-01

Forecast combinations have frequently been found in empirical studies to produce better forecasts on average than methods based on the ex-ante best individual forecasting model. Moreover, simple combinations that ignore correlations between forecast errors often dominate more refined combination schemes aimed at estimating the theoretically optimal combination weights. In this paper we analyse theoretically the factors that determine the advantages from combining forecasts (for example, the d...

Revisiting Dosing Regimen Using Pharmacokinetic/Pharmacodynamic Mathematical Modeling: Densification and Intensification of Combination Cancer Therapy.

Science.gov (United States)

Meille, Christophe; Barbolosi, Dominique; Ciccolini, Joseph; Freyer, Gilles; Iliadis, Athanassios

2016-08-01

Controlling effects of drugs administered in combination is particularly challenging with a densified regimen because of life-threatening hematological toxicities. We have developed a mathematical model to optimize drug dosing regimens and to redesign the dose intensification-dose escalation process, using densified cycles of combined anticancer drugs. A generic mathematical model was developed to describe the main components of the real process, including pharmacokinetics, safety and efficacy pharmacodynamics, and non-hematological toxicity risk. This model allowed for computing the distribution of the total drug amount of each drug in combination, for each escalation dose level, in order to minimize the average tumor mass for each cycle. This was achieved while complying with absolute neutrophil count clinical constraints and without exceeding a fixed risk of non-hematological dose-limiting toxicity. The innovative part of this work was the development of densifying and intensifying designs in a unified procedure. This model enabled us to determine the appropriate regimen in a pilot phase I/II study in metastatic breast patients for a 2-week-cycle treatment of docetaxel plus epirubicin doublet, and to propose a new dose-ranging process. In addition to the present application, this method can be further used to achieve optimization of any combination therapy, thus improving the efficacy versus toxicity balance of such a regimen.

Combining Metabolite-Based Pharmacophores with Bayesian Machine Learning Models for Mycobacterium tuberculosis Drug Discovery.

Science.gov (United States)

Ekins, Sean; Madrid, Peter B; Sarker, Malabika; Li, Shao-Gang; Mittal, Nisha; Kumar, Pradeep; Wang, Xin; Stratton, Thomas P; Zimmerman, Matthew; Talcott, Carolyn; Bourbon, Pauline; Travers, Mike; Yadav, Maneesh; Freundlich, Joel S

2015-01-01

Integrated computational approaches for Mycobacterium tuberculosis (Mtb) are useful to identify new molecules that could lead to future tuberculosis (TB) drugs. Our approach uses information derived from the TBCyc pathway and genome database, the Collaborative Drug Discovery TB database combined with 3D pharmacophores and dual event Bayesian models of whole-cell activity and lack of cytotoxicity. We have prioritized a large number of molecules that may act as mimics of substrates and metabolites in the TB metabolome. We computationally searched over 200,000 commercial molecules using 66 pharmacophores based on substrates and metabolites from Mtb and further filtering with Bayesian models. We ultimately tested 110 compounds in vitro that resulted in two compounds of interest, BAS 04912643 and BAS 00623753 (MIC of 2.5 and 5 μg/mL, respectively). These molecules were used as a starting point for hit-to-lead optimization. The most promising class proved to be the quinoxaline di-N-oxides, evidenced by transcriptional profiling to induce mRNA level perturbations most closely resembling known protonophores. One of these, SRI58 exhibited an MIC = 1.25 μg/mL versus Mtb and a CC50 in Vero cells of >40 μg/mL, while featuring fair Caco-2 A-B permeability (2.3 x 10-6 cm/s), kinetic solubility (125 μM at pH 7.4 in PBS) and mouse metabolic stability (63.6% remaining after 1 h incubation with mouse liver microsomes). Despite demonstration of how a combined bioinformatics/cheminformatics approach afforded a small molecule with promising in vitro profiles, we found that SRI58 did not exhibit quantifiable blood levels in mice.

Combined MEK and ERK inhibition overcomes therapy-mediated pathway reactivation in RAS mutant tumors.

Directory of Open Access Journals (Sweden)

Mark Merchant

Full Text Available Mitogen-activated protein kinase (MAPK pathway dysregulation is implicated in >30% of all cancers, rationalizing the development of RAF, MEK and ERK inhibitors. While BRAF and MEK inhibitors improve BRAF mutant melanoma patient outcomes, these inhibitors had limited success in other MAPK dysregulated tumors, with insufficient pathway suppression and likely pathway reactivation. In this study we show that inhibition of either MEK or ERK alone only transiently inhibits the MAPK pathway due to feedback reactivation. Simultaneous targeting of both MEK and ERK nodes results in deeper and more durable suppression of MAPK signaling that is not achievable with any dose of single agent, in tumors where feedback reactivation occurs. Strikingly, combined MEK and ERK inhibition is synergistic in RAS mutant models but only additive in BRAF mutant models where the RAF complex is dissociated from RAS and thus feedback productivity is disabled. We discovered that pathway reactivation in RAS mutant models occurs at the level of CRAF with combination treatment resulting in a markedly more active pool of CRAF. However, distinct from single node targeting, combining MEK and ERK inhibitor treatment effectively blocks the downstream signaling as assessed by transcriptional signatures and phospho-p90RSK. Importantly, these data reveal that MAPK pathway inhibitors whose activity is attenuated due to feedback reactivation can be rescued with sufficient inhibition by using a combination of MEK and ERK inhibitors. The MEK and ERK combination significantly suppresses MAPK pathway output and tumor growth in vivo to a greater extent than the maximum tolerated doses of single agents, and results in improved anti-tumor activity in multiple xenografts as well as in two Kras mutant genetically engineered mouse (GEM models. Collectively, these data demonstrate that combined MEK and ERK inhibition is functionally unique, yielding greater than additive anti-tumor effects and