Evaluating a Model of Youth Physical Activity

ERIC Educational Resources Information Center

Heitzler, Carrie D.; Lytle, Leslie A.; Erickson, Darin J.; Barr-Anderson, Daheia; Sirard, John R.; Story, Mary

2010-01-01

Objective: To explore the relationship between social influences, self-efficacy, enjoyment, and barriers and physical activity. Methods: Structural equation modeling examined relationships between parent and peer support, parent physical activity, individual perceptions, and objectively measured physical activity using accelerometers among a…

Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships (MCBIOS)

EPA Science Inventory

Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships Jie Liu1,2, Richard Judson1, Matthew T. Martin1, Huixiao Hong3, Imran Shah1 1National Center for Computational Toxicology (NCCT), US EPA, RTP, NC...

Global structure–activity relationship model for nonmutagenic carcinogens using virtual ligand-protein interactions as model descriptors

PubMed Central

Cunningham, Albert R.; Trent, John O.

2012-01-01

Structure–activity relationship (SAR) models are powerful tools to investigate the mechanisms of action of chemical carcinogens and to predict the potential carcinogenicity of untested compounds. We describe the use of a traditional fragment-based SAR approach along with a new virtual ligand-protein interaction-based approach for modeling of nonmutagenic carcinogens. The ligand-based SAR models used descriptors derived from computationally calculated ligand-binding affinities for learning set agents to 5495 proteins. Two learning sets were developed. One set was from the Carcinogenic Potency Database, where chemicals tested for rat carcinogenesis along with Salmonella mutagenicity data were provided. The second was from Malacarne et al. who developed a learning set of nonalerting compounds based on rodent cancer bioassay data and Ashby’s structural alerts. When the rat cancer models were categorized based on mutagenicity, the traditional fragment model outperformed the ligand-based model. However, when the learning sets were composed solely of nonmutagenic or nonalerting carcinogens and noncarcinogens, the fragment model demonstrated a concordance of near 50%, whereas the ligand-based models demonstrated a concordance of 71% for nonmutagenic carcinogens and 74% for nonalerting carcinogens. Overall, these findings suggest that expert system analysis of virtual chemical protein interactions may be useful for developing predictive SAR models for nonmutagenic carcinogens. Moreover, a more practical approach for developing SAR models for carcinogenesis may include fragment-based models for chemicals testing positive for mutagenicity and ligand-based models for chemicals devoid of DNA reactivity. PMID:22678118

Global structure-activity relationship model for nonmutagenic carcinogens using virtual ligand-protein interactions as model descriptors.

PubMed

Cunningham, Albert R; Carrasquer, C Alex; Qamar, Shahid; Maguire, Jon M; Cunningham, Suzanne L; Trent, John O

2012-10-01

Structure-activity relationship (SAR) models are powerful tools to investigate the mechanisms of action of chemical carcinogens and to predict the potential carcinogenicity of untested compounds. We describe the use of a traditional fragment-based SAR approach along with a new virtual ligand-protein interaction-based approach for modeling of nonmutagenic carcinogens. The ligand-based SAR models used descriptors derived from computationally calculated ligand-binding affinities for learning set agents to 5495 proteins. Two learning sets were developed. One set was from the Carcinogenic Potency Database, where chemicals tested for rat carcinogenesis along with Salmonella mutagenicity data were provided. The second was from Malacarne et al. who developed a learning set of nonalerting compounds based on rodent cancer bioassay data and Ashby's structural alerts. When the rat cancer models were categorized based on mutagenicity, the traditional fragment model outperformed the ligand-based model. However, when the learning sets were composed solely of nonmutagenic or nonalerting carcinogens and noncarcinogens, the fragment model demonstrated a concordance of near 50%, whereas the ligand-based models demonstrated a concordance of 71% for nonmutagenic carcinogens and 74% for nonalerting carcinogens. Overall, these findings suggest that expert system analysis of virtual chemical protein interactions may be useful for developing predictive SAR models for nonmutagenic carcinogens. Moreover, a more practical approach for developing SAR models for carcinogenesis may include fragment-based models for chemicals testing positive for mutagenicity and ligand-based models for chemicals devoid of DNA reactivity.

Novel Uses of In Vitro Data to Develop Quantitative Biological Activity Relationship Models for in Vivo Carcinogenicity Prediction.

PubMed

Pradeep, Prachi; Povinelli, Richard J; Merrill, Stephen J; Bozdag, Serdar; Sem, Daniel S

2015-04-01

The availability of large in vitro datasets enables better insight into the mode of action of chemicals and better identification of potential mechanism(s) of toxicity. Several studies have shown that not all in vitro assays can contribute as equal predictors of in vivo carcinogenicity for development of hybrid Quantitative Structure Activity Relationship (QSAR) models. We propose two novel approaches for the use of mechanistically relevant in vitro assay data in the identification of relevant biological descriptors and development of Quantitative Biological Activity Relationship (QBAR) models for carcinogenicity prediction. We demonstrate that in vitro assay data can be used to develop QBAR models for in vivo carcinogenicity prediction via two case studies corroborated with firm scientific rationale. The case studies demonstrate the similarities between QBAR and QSAR modeling in: (i) the selection of relevant descriptors to be used in the machine learning algorithm, and (ii) the development of a computational model that maps chemical or biological descriptors to a toxic endpoint. The results of both the case studies show: (i) improved accuracy and sensitivity which is especially desirable under regulatory requirements, and (ii) overall adherence with the OECD/REACH guidelines. Such mechanism based models can be used along with QSAR models for prediction of mechanistically complex toxic endpoints. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative structure-activity relationship modeling of rat acute toxicity by oral exposure.

PubMed

Zhu, Hao; Martin, Todd M; Ye, Lin; Sedykh, Alexander; Young, Douglas M; Tropsha, Alexander

2009-12-01

Few quantitative structure-activity relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity end points. In this study, a comprehensive data set of 7385 compounds with their most conservative lethal dose (LD(50)) values has been compiled. A combinatorial QSAR approach has been employed to develop robust and predictive models of acute toxicity in rats caused by oral exposure to chemicals. To enable fair comparison between the predictive power of models generated in this study versus a commercial toxicity predictor, TOPKAT (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the entire data set was selected that included all 3472 compounds used in TOPKAT's training set. The remaining 3913 compounds, which were not present in the TOPKAT training set, were used as the external validation set. QSAR models of five different types were developed for the modeling set. The prediction accuracy for the external validation set was estimated by determination coefficient R(2) of linear regression between actual and predicted LD(50) values. The use of the applicability domain threshold implemented in most models generally improved the external prediction accuracy but expectedly led to the decrease in chemical space coverage; depending on the applicability domain threshold, R(2) ranged from 0.24 to 0.70. Ultimately, several consensus models were developed by averaging the predicted LD(50) for every compound using all five models. The consensus models afforded higher prediction accuracy for the external validation data set with the higher coverage as compared to individual constituent models. The validated consensus LD(50) models developed in this study can be used as reliable computational predictors of in vivo acute toxicity.

Application of quantitative structure activity relationship (QSAR) models to predict ozone toxicity in the lung.

PubMed

Kafoury, Ramzi M; Huang, Ming-Ju

2005-08-01

The sequence of events leading to ozone-induced airway inflammation is not well known. To elucidate the molecular and cellular events underlying ozone toxicity in the lung, we hypothesized that lipid ozonation products (LOPs) generated by the reaction of ozone with unsaturated fatty acids in the epithelial lining fluid and cell membranes play a key role in mediating ozone-induced airway inflammation. To test our hypothesis, we ozonized 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) and generated LOPs. Confluent human bronchial epithelial cells were exposed to the derivatives of ozonized POPC-9-oxononanoyl, 9-hydroxy-9-hydroperoxynonanoyl, and 8-(5-octyl-1,2,4-trioxolan-3-yl-)octanoyl-at a concentration of 10 muM, and the activity of phospholipases A2 (PLA2), C (PLC), and D (PLD) was measured (1, 0.5, and 1 h, respectively). Quantitative structure-activity relationship (QSAR) models were utilized to predict the biological activity of LOPs in airway epithelial cells. The QSAR results showed a strong correlation between experimental and computed activity (r = 0.97, 0.98, 0.99, for PLA2, PLC, and PLD, respectively). The results indicate that QSAR models can be utilized to predict the biological activity of the various ozone-derived LOP species in the lung. Copyright 2005 Wiley Periodicals, Inc.

Quantitative structure-activity relationship modeling on in vitro endocrine effects and metabolic stability involving 26 selected brominated flame retardants.

PubMed

Harju, Mikael; Hamers, Timo; Kamstra, Jorke H; Sonneveld, Edwin; Boon, Jan P; Tysklind, Mats; Andersson, Patrik L

2007-04-01

In this work, quantitative structure-activity relationships (QSARs) were developed to aid human and environmental risk assessment processes for brominated flame retardants (BFRs). Brominated flame retardants, such as the high-production-volume chemicals polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A, and hexabromocyclododecane, have been identified as potential endocrine disruptors. Quantitative structure-activity relationship models were built based on the in vitro potencies of 26 selected BFRs. The in vitro assays included interactions with, for example, androgen, progesterone, estrogen, and dioxin (aryl hydrocarbon) receptor, plus competition with thyroxine for its plasma carrier protein (transthyretin), inhibition of estradiol sulfation via sulfotransferase, and finally, rate of metabolization. The QSAR modeling, a number of physicochemical parameters were calculated describing the electronic, lipophilic, and structural characteristics of the molecules. These include frontier molecular orbitals, molecular charges, polarities, log octanol/water partitioning coefficient, and two- and three-dimensional molecularproperties. Experimental properties were included and measured for PBDEs, such as their individual ultraviolet spectra (200-320 nm) and retention times on three different high-performance liquid chromatography columns and one nonpolar gas chromatography column. Quantitative structure-activity relationship models based on androgen antagonism and metabolic degradation rates generally gave similar results, suggesting that lower-brominated PBDEs with bromine substitutions in ortho positions and bromine-free meta- and para positions had the highest potencies and metabolic degradation rates. Predictions made for the constituents of the technical flame retardant Bromkal 70-5DE found BDE 17 to be a potent androgen antagonist and BDE 66, which is a relevant PBDE in environmental samples, to be only a weak antagonist.

Molecular design and structure--activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664.

PubMed

Das, Jagabandhu; Kimball, S David; Hall, Steven E; Han, Wen Ching; Iwanowicz, Edwin; Lin, James; Moquin, Robert V; Reid, Joyce A; Sack, John S; Malley, Mary F; Chang, Chiehying Y; Chong, Saeho; Wang-Iverson, David B; Roberts, Daniel G M; Seiler, Steven M; Schumacher, William A; Ogletree, Martin L

2002-01-07

A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.

Evaluating a Model of Youth Physical Activity

PubMed Central

Heitzler, Carrie D.; Lytle, Leslie A.; Erickson, Darin J.; Barr-Anderson, Daheia; Sirard, John R.; Story, Mary

2011-01-01

Objective To explore the relationship between social influences, self-efficacy, enjoyment, and barriers and physical activity. Methods Structural equation modeling examined relationships between parent and peer support, parent physical activity, individual perceptions, and objectively measured physical activity using accelerometers among a sample of youth aged 10–17 years (N=720). Results Peer support, parent physical activity, and perceived barriers were directly related to youth activity. The proposed model accounted for 14.7% of the variance in physical activity. Conclusions The results demonstrate a need to further explore additional individual, social, and environmental factors that may influence youth’s regular participation in physical activity. PMID:20524889

Quantitative structure-antifungal activity relationships of some benzohydrazides against Botrytis cinerea.

PubMed

Reino, José L; Saiz-Urra, Liane; Hernandez-Galan, Rosario; Aran, Vicente J; Hitchcock, Peter B; Hanson, James R; Gonzalez, Maykel Perez; Collado, Isidro G

2007-06-27

Fourteen benzohydrazides have been synthesized and evaluated for their in vitro antifungal activity against the phytopathogenic fungus Botrytis cinerea. The best antifungal activity was observed for the N',N'-dibenzylbenzohydrazides 3b-d and for the N-aminoisoindoline-derived benzohydrazide 5. A quantitative structure-activity relationship (QSAR) study has been developed using a topological substructural molecular design (TOPS-MODE) approach to interpret the antifungal activity of these synthetic compounds. The model described 98.3% of the experimental variance, with a standard deviation of 4.02. The influence of an ortho substituent on the conformation of the benzohydrazides was investigated by X-ray crystallography and supported by QSAR study. Several aspects of the structure-activity relationships are discussed in terms of the contribution of different bonds to the antifungal activity, thereby making the relationships between structure and biological activity more transparent.

Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar G.; Swaminathan S.; Kumaran, D.

Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC{sub 50} of 0.9 {micro}M and a K{sub i} ofmore » 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features.« less

Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling.

PubMed

Kumar, Gyanendra; Kumaran, Desigan; Ahmed, S Ashraf; Swaminathan, Subramanyam

2012-05-01

Clostridium botulinum neurotoxins are classified as Category A bioterrorism agents by the Centers for Disease Control and Prevention (CDC). The seven serotypes (A-G) of the botulinum neurotoxin, the causative agent of the disease botulism, block neurotransmitter release by specifically cleaving one of the three SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins and induce flaccid paralysis. Using a structure-based drug-design approach, a number of peptide inhibitors were designed and their inhibitory activity against botulinum serotype A (BoNT/A) protease was determined. The most potent peptide, RRGF, inhibited BoNT/A protease with an IC(50) of 0.9 µM and a K(i) of 358 nM. High-resolution crystal structures of various peptide inhibitors in complex with the BoNT/A protease domain were also determined. Based on the inhibitory activities and the atomic interactions deduced from the cocrystal structures, the structure-activity relationship was analyzed and a pharmacophore model was developed. Unlike the currently available models, this pharmacophore model is based on a number of enzyme-inhibitor peptide cocrystal structures and improved the existing models significantly, incorporating new features. © 2012 International Union of Crystallography

Virulence Factor-activity Relationships: Workshop Summary

EPA Science Inventory

The concept or notion of virulence factor–activity relationships (VFAR) is an approach for identifying an analogous process to the use of qualitative structure–activity relationships (QSAR) for identifying new microbial contaminants. In QSAR, it is hypothesized that, for new chem...

PLS modelling of structure—activity relationships of catechol O-methyltransferase inhibitors

NASA Astrophysics Data System (ADS)

Lotta, Timo; Taskinen, Jyrki; Bäckström, Reijo; Nissinen, Erkki

1992-06-01

Quantitative structure-activity analysis was carried out for in vitro inhibition of rat brain soluble catechol O-methyltransferase by a series (N=99) of 1,5-substituted-3,4-dihydroxybenzenes using computational chemistry and multivariate PLS modelling of data sets. The molecular structural descriptors (N=19) associated with the electronics of the catecholic ring and sizes of substituents were derived theoretically. For the whole set of molecules two separate PLS models have to be used. A PLS model with two significant (crossvalidated) model dimensions describing 82.2% of the variance in inhibition activity data was capable of predicting all molecules except those having the largest R1 substituent or having a large R5 substituent compared to the NO2 group. The other PLS model with three significant (crossvalidated) model dimensions described 83.3% of the variance in inhibition activity data. This model could not handle compounds having a small R5 substituent, compared to the NO2 group, or the largest R1 substituent. The predictive capability of these PLS models was good. The models reveal that inhibition activity is nonlinearly related to the size of the R5 substituent. The analysis of the PLS models also shows that the binding affinity is greatly dependent on the electronic nature of both R1 and R5 substituents. The electron-withdrawing nature of the substituents enhances inhibition activity. In addition, the size of the R1 substituent and its lipophilicity are important in the binding of inhibitors. The size of the R1 substituent has an upper limit. On the other hand, ionized R1 substituents decrease inhibition activity.

Trainable structure-activity relationship model for virtual screening of CYP3A4 inhibition.

PubMed

Didziapetris, Remigijus; Dapkunas, Justas; Sazonovas, Andrius; Japertas, Pranas

2010-11-01

A new structure-activity relationship model predicting the probability for a compound to inhibit human cytochrome P450 3A4 has been developed using data for >800 compounds from various literature sources and tested on PubChem screening data. Novel GALAS (Global, Adjusted Locally According to Similarity) modeling methodology has been used, which is a combination of baseline global QSAR model and local similarity based corrections. GALAS modeling method allows forecasting the reliability of prediction thus defining the model applicability domain. For compounds within this domain the statistical results of the final model approach the data consistency between experimental data from literature and PubChem datasets with the overall accuracy of 89%. However, the original model is applicable only for less than a half of PubChem database. Since the similarity correction procedure of GALAS modeling method allows straightforward model training, the possibility to expand the applicability domain has been investigated. Experimental data from PubChem dataset served as an example of in-house high-throughput screening data. The model successfully adapted itself to both data classified using the same and different IC₅₀ threshold compared with the training set. In addition, adjustment of the CYP3A4 inhibition model to compounds with a novel chemical scaffold has been demonstrated. The reported GALAS model is proposed as a useful tool for virtual screening of compounds for possible drug-drug interactions even prior to the actual synthesis.

Weather and children's physical activity; how and why do relationships vary between countries?

PubMed

Harrison, Flo; Goodman, Anna; van Sluijs, Esther M F; Andersen, Lars Bo; Cardon, Greet; Davey, Rachel; Janz, Kathleen F; Kriemler, Susi; Molloy, Lynn; Page, Angie S; Pate, Russ; Puder, Jardena J; Sardinha, Luis B; Timperio, Anna; Wedderkopp, Niels; Jones, Andy P

2017-05-30

Globally most children do not engage in enough physical activity. Day length and weather conditions have been identified as determinants of physical activity, although how they may be overcome as barriers is not clear. We aim to examine if and how relationships between children's physical activity and weather and day length vary between countries and identify settings in which children were better able to maintain activity levels given the weather conditions they experienced. In this repeated measures study, we used data from 23,451 participants in the International Children's Accelerometry Database (ICAD). Daily accelerometer-measured physical activity (counts per minute; cpm) was matched to local weather conditions and the relationships assessed using multilevel regression models. Multilevel models accounted for clustering of days within occasions within children within study-cities, and allowed us to explore if and how the relationships between weather variables and physical activity differ by setting. Increased precipitation and wind speed were associated with decreased cpm while better visibility and more hours of daylight were associated with increased cpm. Models indicated that increases in these variables resulted in average changes in mean cpm of 7.6/h of day length, -13.2/cm precipitation, 10.3/10 km visibility and -10.3/10kph wind speed (all p < 0.01). Temperature showed a cubic relationship with cpm, although between 0 and 20 degrees C the relationship was broadly linear. Age showed interactions with temperature and precipitation, with the associations larger among younger children. In terms of geographic trends, participants from Northern European countries and Melbourne, Australia were the most active, and also better maintained their activity levels given the weather conditions they experienced compared to those in the US and Western Europe. We found variation in the relationship between weather conditions and physical activity between ICAD

Cookie-Ases: Interactive Models for Teaching Genotype-Phenotype Relationships

ERIC Educational Resources Information Center

Seipelt, Rebecca L.

2006-01-01

Several hands-on and wet laboratory activities have been proposed to model the genetic concepts of genotypes and phenotypes and their relationship. The exercise presented in this article is a novel, time effective, student-centered, role-playing activity in which students learn about the intricate connection between genotype and phenotype by…

Further evaluation of quantitative structure--activity relationship models for the prediction of the skin sensitization potency of selected fragrance allergens.

PubMed

Patlewicz, Grace Y; Basketter, David A; Pease, Camilla K Smith; Wilson, Karen; Wright, Zoe M; Roberts, David W; Bernard, Guillaume; Arnau, Elena Giménez; Lepoittevin, Jean-Pierre

2004-02-01

Fragrance substances represent a very diverse group of chemicals; a proportion of them are associated with the ability to cause allergic reactions in the skin. Efforts to find substitute materials are hindered by the need to undertake animal testing for determining both skin sensitization hazard and potency. One strategy to avoid such testing is through an understanding of the relationships between chemical structure and skin sensitization, so-called structure-activity relationships. In recent work, we evaluated 2 groups of fragrance chemicals -- saturated aldehydes and alpha,beta-unsaturated aldehydes. Simple quantitative structure-activity relationship (QSAR) models relating the EC3 values [derived from the local lymph node assay (LLNA)] to physicochemical properties were developed for both sets of aldehydes. In the current study, we evaluated an additional group of carbonyl-containing compounds to test the predictive power of the developed QSARs and to extend their scope. The QSAR models were used to predict EC3 values of 10 newly selected compounds. Local lymph node assay data generated for these compounds demonstrated that the original QSARs were fairly accurate, but still required improvement. Development of these QSAR models has provided us with a better understanding of the potential mechanisms of action for aldehydes, and hence how to avoid or limit allergy. Knowledge generated from this work is being incorporated into new/improved rules for sensitization in the expert toxicity prediction system, deductive estimation of risk from existing knowledge (DEREK).

Relationship among Phosphorus Circulation Activity, Bacterial Biomass, pH, and Mineral Concentration in Agricultural Soil.

PubMed

Adhikari, Dinesh; Jiang, Tianyi; Kawagoe, Taiki; Kai, Takamitsu; Kubota, Kenzo; Araki, Kiwako S; Kubo, Motoki

2017-12-04

Improvement of phosphorus circulation in the soil is necessary to enhance phosphorus availability to plants. Phosphorus circulation activity is an index of soil's ability to supply soluble phosphorus from organic phosphorus in the soil solution. To understand the relationship among phosphorus circulation activity; bacterial biomass; pH; and Fe, Al, and Ca concentrations (described as mineral concentration in this paper) in agricultural soil, 232 soil samples from various agricultural fields were collected and analyzed. A weak relationship between phosphorus circulation activity and bacterial biomass was observed in all soil samples ( R ² = 0.25), and this relationship became significantly stronger at near-neutral pH (6.0-7.3; R ² = 0.67). No relationship between phosphorus circulation activity and bacterial biomass was observed at acidic (pH < 6.0) or alkaline (pH > 7.3) pH. A negative correlation between Fe and Al concentrations and phosphorus circulation activity was observed at acidic pH ( R ² = 0.72 and 0.73, respectively), as well as for Ca at alkaline pH ( R ² = 0.64). Therefore, bacterial biomass, pH, and mineral concentration should be considered together for activation of phosphorus circulation activity in the soil. A relationship model was proposed based on the effects of bacterial biomass and mineral concentration on phosphorus circulation activity. The suitable conditions of bacterial biomass, pH, and mineral concentration for phosphorus circulation activity could be estimated from the relationship model.

The effect of leverage and/or influential on structure-activity relationships.

PubMed

Bolboacă, Sorana D; Jäntschi, Lorentz

2013-05-01

In the spirit of reporting valid and reliable Quantitative Structure-Activity Relationship (QSAR) models, the aim of our research was to assess how the leverage (analysis with Hat matrix, h(i)) and the influential (analysis with Cook's distance, D(i)) of QSAR models may reflect the models reliability and their characteristics. The datasets included in this research were collected from previously published papers. Seven datasets which accomplished the imposed inclusion criteria were analyzed. Three models were obtained for each dataset (full-model, h(i)-model and D(i)-model) and several statistical validation criteria were applied to the models. In 5 out of 7 sets the correlation coefficient increased when compounds with either h(i) or D(i) higher than the threshold were removed. Withdrawn compounds varied from 2 to 4 for h(i)-models and from 1 to 13 for D(i)-models. Validation statistics showed that D(i)-models possess systematically better agreement than both full-models and h(i)-models. Removal of influential compounds from training set significantly improves the model and is recommended to be conducted in the process of quantitative structure-activity relationships developing. Cook's distance approach should be combined with hat matrix analysis in order to identify the compounds candidates for removal.

Imidazole derivatives as angiotensin II AT1 receptor blockers: Benchmarks, drug-like calculations and quantitative structure-activity relationships modeling

NASA Astrophysics Data System (ADS)

Alloui, Mebarka; Belaidi, Salah; Othmani, Hasna; Jaidane, Nejm-Eddine; Hochlaf, Majdi

2018-03-01

We performed benchmark studies on the molecular geometry, electron properties and vibrational analysis of imidazole using semi-empirical, density functional theory and post Hartree-Fock methods. These studies validated the use of AM1 for the treatment of larger systems. Then, we treated the structural, physical and chemical relationships for a series of imidazole derivatives acting as angiotensin II AT1 receptor blockers using AM1. QSAR studies were done for these imidazole derivatives using a combination of various physicochemical descriptors. A multiple linear regression procedure was used to design the relationships between molecular descriptor and the activity of imidazole derivatives. Results validate the derived QSAR model.

Activism and Leadership Development: Examining the Relationship between College Student Activism Involvement and Socially Responsible Leadership Capacity

ERIC Educational Resources Information Center

Page, Jeremy Dale

2010-01-01

The purpose of this study was to examine the relationship between participation in student activism and leadership development among college students. This study applied the social change model of leadership development (SCM) as the theoretical model used to measure socially responsible leadership capacity in students. The study utilized data…

Quantitative Structure-Antifungal Activity Relationships for cinnamate derivatives.

PubMed

Saavedra, Laura M; Ruiz, Diego; Romanelli, Gustavo P; Duchowicz, Pablo R

2015-12-01

Quantitative Structure-Activity Relationships (QSAR) are established with the aim of analyzing the fungicidal activities of a set of 27 active cinnamate derivatives. The exploration of more than a thousand of constitutional, topological, geometrical and electronic molecular descriptors, which are calculated with Dragon software, leads to predictions of the growth inhibition on Pythium sp and Corticium rolfsii fungi species, in close agreement to the experimental values extracted from the literature. A set containing 21 new structurally related cinnamate compounds is prepared. The developed QSAR models are applied to predict the unknown fungicidal activity of this set, showing that cinnamates like 38, 28 and 42 are expected to be highly active for Pythium sp, while this is also predicted for 28 and 34 in C. rolfsii. Copyright © 2015 Elsevier Inc. All rights reserved.

Progress with modeling activity landscapes in drug discovery.

PubMed

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.

Investigation on Quantitative Structure Activity Relationships and Pharmacophore Modeling of a Series of mGluR2 Antagonists

PubMed Central

Zhang, Meng-Qi; Zhang, Xiao-Le; Li, Yan; Fan, Wen-Jia; Wang, Yong-Hua; Hao, Ming; Zhang, Shu-Wei; Ai, Chun-Zhi

2011-01-01

MGluR2 is G protein-coupled receptor that is targeted for diseases like anxiety, depression, Parkinson’s disease and schizophrenia. Herein, we report the three-dimensional quantitative structure–activity relationship (3D-QSAR) studies of a series of 1,3-dihydrobenzo[ b][1,4]diazepin-2-one derivatives as mGluR2 antagonists. Two series of models using two different activities of the antagonists against rat mGluR2, which has been shown to be very similar to the human mGluR2, (activity I: inhibition of [3H]-LY354740; activity II: mGluR2 (1S,3R)-ACPD inhibition of forskolin stimulated cAMP.) were derived from datasets composed of 137 and 69 molecules respectively. For activity I study, the best predictive model obtained from CoMFA analysis yielded a Q2 of 0.513, R2 ncv of 0.868, R2 pred = 0.876, while the CoMSIA model yielded a Q2 of 0.450, R2 ncv = 0.899, R2 pred = 0.735. For activity II study, CoMFA model yielded statistics of Q2 = 0.5, R2 ncv = 0.715, R2 pred = 0.723. These results prove the high predictability of the models. Furthermore, a combined analysis between the CoMFA, CoMSIA contour maps shows that: (1) Bulky substituents in R7, R3 and position A benefit activity I of the antagonists, but decrease it when projected in R8 and position B; (2) Hydrophilic groups at position A and B increase both antagonistic activity I and II; (3) Electrostatic field plays an essential rule in the variance of activity II. In search for more potent mGluR2 antagonists, two pharmacophore models were developed separately for the two activities. The first model reveals six pharmacophoric features, namely an aromatic center, two hydrophobic centers, an H-donor atom, an H-acceptor atom and an H-donor site. The second model shares all features of the first one and has an additional acceptor site, a positive N and an aromatic center. These models can be used as guidance for the development of new mGluR2 antagonists of high activity and selectivity. This work is the first report on 3

Investigation on quantitative structure activity relationships and pharmacophore modeling of a series of mGluR2 antagonists.

PubMed

Zhang, Meng-Qi; Zhang, Xiao-Le; Li, Yan; Fan, Wen-Jia; Wang, Yong-Hua; Hao, Ming; Zhang, Shu-Wei; Ai, Chun-Zhi

2011-01-01

MGluR2 is G protein-coupled receptor that is targeted for diseases like anxiety, depression, Parkinson's disease and schizophrenia. Herein, we report the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of a series of 1,3-dihydrobenzo[ b][1,4]diazepin-2-one derivatives as mGluR2 antagonists. Two series of models using two different activities of the antagonists against rat mGluR2, which has been shown to be very similar to the human mGluR2, (activity I: inhibition of [(3)H]-LY354740; activity II: mGluR2 (1S,3R)-ACPD inhibition of forskolin stimulated cAMP.) were derived from datasets composed of 137 and 69 molecules respectively. For activity I study, the best predictive model obtained from CoMFA analysis yielded a Q(2) of 0.513, R(2) (ncv) of 0.868, R(2) (pred) = 0.876, while the CoMSIA model yielded a Q(2) of 0.450, R(2) (ncv) = 0.899, R(2) (pred) = 0.735. For activity II study, CoMFA model yielded statistics of Q(2) = 0.5, R(2) (ncv) = 0.715, R(2) (pred) = 0.723. These results prove the high predictability of the models. Furthermore, a combined analysis between the CoMFA, CoMSIA contour maps shows that: (1) Bulky substituents in R(7), R(3) and position A benefit activity I of the antagonists, but decrease it when projected in R(8) and position B; (2) Hydrophilic groups at position A and B increase both antagonistic activity I and II; (3) Electrostatic field plays an essential rule in the variance of activity II. In search for more potent mGluR2 antagonists, two pharmacophore models were developed separately for the two activities. The first model reveals six pharmacophoric features, namely an aromatic center, two hydrophobic centers, an H-donor atom, an H-acceptor atom and an H-donor site. The second model shares all features of the first one and has an additional acceptor site, a positive N and an aromatic center. These models can be used as guidance for the development of new mGluR2 antagonists of high activity and selectivity

Structure-activity relationship of cyanine tau aggregation inhibitors

PubMed Central

Chang, Edward; Congdon, Erin E.; Honson, Nicolette S.; Duff, Karen E.; Kuret, Jeff

2009-01-01

A structure-activity relationship for symmetrical cyanine inhibitors of human tau aggregation was elaborated using a filter trap assay. Antagonist activity depended on cyanine heterocycle, polymethine bridge length, and the nature of meso- and N-substituents. One potent member of the series, 3,3’-diethyl-9-methylthiacarbocyanine iodide (compound 11), retained submicromolar potency and had calculated physical properties consistent with blood-brain barrier and cell membrane penetration. Exposure of organotypic slices prepared from JNPL3 transgenic mice (which express human tau harboring the aggregation prone P301L tauopathy mutation) to compound 11 for one week revealed a biphasic dose response relationship. Low nanomolar concentrations decreased insoluble tau aggregates to half those observed in slices treated with vehicle alone. In contrast, high concentrations (≥300 nM) augmented tau aggregation and produced abnormalities in tissue tubulin levels. These data suggest that certain symmetrical carbocyanine dyes can modulate tau aggregation in the slice biological model at concentrations well below those associated with toxicity. PMID:19432420

3D-quantitative structure-activity relationship study for the design of novel enterovirus A71 3C protease inhibitors.

PubMed

Nie, Quandeng; Xu, Xiaoyi; Zhang, Qi; Ma, Yuying; Yin, Zheng; Shang, Luqing

2018-06-07

A three-dimensional quantitative structure-activity relationships model of enterovirus A71 3C protease inhibitors was constructed in this study. The protein-ligand interaction fingerprint was analyzed to generate a pharmacophore model. A predictive and reliable three-dimensional quantitative structure-activity relationships model was built based on the Flexible Alignment of AutoGPA. Moreover, three novel compounds (I-III) were designed and evaluated for their biochemical activity against 3C protease and anti-enterovirus A71 activity in vitro. III exhibited excellent inhibitory activity (IC 50 =0.031 ± 0.005 μM, EC 50 =0.036 ± 0.007 μM). Thus, this study provides a useful quantitative structure-activity relationships model to develop potent inhibitors for enterovirus A71 3C protease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Relationships Between Modelling and Argumentation from the Perspective of the Model of Modelling Diagram

NASA Astrophysics Data System (ADS)

Cardoso Mendonça, Paula Cristina; Justi, Rosária

2013-09-01

Some studies related to the nature of scientific knowledge demonstrate that modelling is an inherently argumentative process. This study aims at discussing the relationship between modelling and argumentation by analysing data collected during the modelling-based teaching of ionic bonding and intermolecular interactions. The teaching activities were planned from the transposition of the main modelling stages that constitute the 'Model of Modelling Diagram' so that students could experience each of such stages. All the lessons were video recorded and their transcriptions supported the elaboration of case studies for each group of students. From the analysis of the case studies, we identified argumentative situations when students performed all of the modelling stages. Our data show that the argumentative situations were related to sense making, articulating and persuasion purposes, and were closely related to the generation of explanations in the modelling processes. They also show that representations are important resources for argumentation. Our results are consistent with some of those already reported in the literature regarding the relationship between modelling and argumentation, but are also divergent when they show that argumentation is not only related to the model evaluation phase.

A Novel Two-Step Hierarchical Quantitative Structure–Activity Relationship Modeling Work Flow for Predicting Acute Toxicity of Chemicals in Rodents

PubMed Central

Zhu, Hao; Ye, Lin; Richard, Ann; Golbraikh, Alexander; Wright, Fred A.; Rusyn, Ivan; Tropsha, Alexander

2009-01-01

Background Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Objective A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects. Methods and results A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC50) and in vivo rodent median lethal dose (LD50) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure–activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD50 values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC50 and LD50. However, a linear IC50 versus LD50 correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC50 and LD50 values: One group comprises compounds with linear IC50 versus LD50 relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD50 values from chemical descriptors. All models were extensively validated using special protocols. Conclusions The novelty of this modeling approach is that it uses the relationships

A novel two-step hierarchical quantitative structure-activity relationship modeling work flow for predicting acute toxicity of chemicals in rodents.

PubMed

Zhu, Hao; Ye, Lin; Richard, Ann; Golbraikh, Alexander; Wright, Fred A; Rusyn, Ivan; Tropsha, Alexander

2009-08-01

Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public-private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects. A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC(50)) and in vivo rodent median lethal dose (LD(50)) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure-activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD(50) values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC(50) and LD(50). However, a linear IC(50) versus LD(50) correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC(50) and LD(50) values: One group comprises compounds with linear IC(50) versus LD(50) relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD(50) values from chemical descriptors. All models were extensively validated using special protocols. The novelty of this modeling approach is that it uses the relationships between in vivo and in vitro data only

Modeling the relationship between family home environment factors and parental health.

PubMed

Didericksen, Katharine Wickel; Berge, Jerica M

2015-06-01

Understanding parental health is an important part of understanding family health. Previous research suggests that family meals, familial relationship satisfaction, and family physical activity may separately be related to physical health. The current study aims to combine these variables into a structural equation model to determine the collective relationship they have with adult health within a sample of parents (n = 1,435). Most parents were married, White, and highly educated. The relationship between family meals and parental health was significant (β = -.07, t = -2.29, p < .05), with the full model having adequate fit and accounting for some of the overall variance in parental health. Familial relationship satisfaction and family physical activity were not found to be associated with parental health. Exploratory findings of the sample stratified by biological sex are described. Findings from the current study were consistent with a systemic perspective in that parents may have health benefits when they participate in family-level behavior (e.g., family meals). Additional areas for research and limitations to the current study are also discussed. (c) 2015 APA, all rights reserved).

Quantitative studies on structure-DPPH• scavenging activity relationships of food phenolic acids.

PubMed

Jing, Pu; Zhao, Shu-Juan; Jian, Wen-Jie; Qian, Bing-Jun; Dong, Ying; Pang, Jie

2012-11-01

Phenolic acids are potent antioxidants, yet the quantitative structure-activity relationships of phenolic acids remain unclear. The purpose of this study was to establish 3D-QSAR models able to predict phenolic acids with high DPPH• scavenging activity and understand their structure-activity relationships. The model has been established by using a training set of compounds with cross-validated q2 = 0.638/0.855, non-cross-validated r2 = 0.984/0.986, standard error of estimate = 0.236/0.216, and F = 139.126/208.320 for the best CoMFA/CoMSIA models. The predictive ability of the models was validated with the correlation coefficient r2(pred) = 0.971/0.996 (>0.6) for each model. Additionally, the contour map results suggested that structural characteristics of phenolics acids favorable for the high DPPH• scavenging activity might include: (1) bulky and/or electron-donating substituent groups on the phenol ring; (2) electron-donating groups at the meta-position and/or hydrophobic groups at the meta-/ortho-position; (3) hydrogen-bond donor/electron-donating groups at the ortho-position. The results have been confirmed based on structural analyses of phenolic acids and their DPPH• scavenging data from eight recent publications. The findings may provide deeper insight into the antioxidant mechanisms and provide useful information for selecting phenolic acids for free radical scavenging properties.

Investigating the Relationship among Extracurricular Activities, Learning Approach and Academic Outcomes: A Case Study

ERIC Educational Resources Information Center

Chan, Yiu-Kong

2016-01-01

Learning effectiveness requires an understanding of the relationship among extracurricular activities, learning approach and academic performance and, it is argued, this helps educators develop techniques designed to enrich learning effectiveness. Biggs' Presage-Process-Product model on student learning has identified the relationship among…

Testing a Theoretical Model of Immigration Transition and Physical Activity.

PubMed

Chang, Sun Ju; Im, Eun-Ok

2015-01-01

The purposes of the study were to develop a theoretical model to explain the relationships between immigration transition and midlife women's physical activity and test the relationships among the major variables of the model. A theoretical model, which was developed based on transitions theory and the midlife women's attitudes toward physical activity theory, consists of 4 major variables, including length of stay in the United States, country of birth, level of acculturation, and midlife women's physical activity. To test the theoretical model, a secondary analysis with data from 127 Hispanic women and 123 non-Hispanic (NH) Asian women in a national Internet study was used. Among the major variables of the model, length of stay in the United States was negatively associated with physical activity in Hispanic women. Level of acculturation in NH Asian women was positively correlated with women's physical activity. Country of birth and level of acculturation were significant factors that influenced physical activity in both Hispanic and NH Asian women. The findings support the theoretical model that was developed to examine relationships between immigration transition and physical activity; it shows that immigration transition can play an essential role in influencing health behaviors of immigrant populations in the United States. The NH theoretical model can be widely used in nursing practice and research that focus on immigrant women and their health behaviors. Health care providers need to consider the influences of immigration transition to promote immigrant women's physical activity.

Quantitative structure activity relationship studies of mushroom tyrosinase inhibitors

NASA Astrophysics Data System (ADS)

Xue, Chao-Bin; Luo, Wan-Chun; Ding, Qi; Liu, Shou-Zhu; Gao, Xing-Xiang

2008-05-01

Here, we report our results from quantitative structure-activity relationship studies on tyrosinase inhibitors. Interactions between benzoic acid derivatives and tyrosinase active sites were also studied using a molecular docking method. These studies indicated that one possible mechanism for the interaction between benzoic acid derivatives and the tyrosinase active site is the formation of a hydrogen-bond between the hydroxyl (aOH) and carbonyl oxygen atoms of Tyr98, which stabilized the position of Tyr98 and prevented Tyr98 from participating in the interaction between tyrosinase and ORF378. Tyrosinase, also known as phenoloxidase, is a key enzyme in animals, plants and insects that is responsible for catalyzing the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones. In the present study, the bioactivities of 48 derivatives of benzaldehyde, benzoic acid, and cinnamic acid compounds were used to construct three-dimensional quantitative structure-activity relationship (3D-QSAR) models using comparative molecular field (CoMFA) and comparative molecular similarity indices (CoMSIA) analyses. After superimposition using common substructure-based alignments, robust and predictive 3D-QSAR models were obtained from CoMFA ( q 2 = 0.855, r 2 = 0.978) and CoMSIA ( q 2 = 0.841, r 2 = 0.946), with 6 optimum components. Chemical descriptors, including electronic (Hammett σ), hydrophobic (π), and steric (MR) parameters, hydrogen bond acceptor (H-acc), and indicator variable ( I), were used to construct a 2D-QSAR model. The results of this QSAR indicated that π, MR, and H-acc account for 34.9, 31.6, and 26.7% of the calculated biological variance, respectively. The molecular interactions between ligand and target were studied using a flexible docking method (FlexX). The best scored candidates were docked flexibly, and the interaction between the benzoic acid derivatives and the tyrosinase active site was elucidated in detail. We believe

Structure-activity relationships between sterols and their thermal stability in oil matrix.

PubMed

Hu, Yinzhou; Xu, Junli; Huang, Weisu; Zhao, Yajing; Li, Maiquan; Wang, Mengmeng; Zheng, Lufei; Lu, Baiyi

2018-08-30

Structure-activity relationships between 20 sterols and their thermal stabilities were studied in a model oil system. All sterol degradations were found to be consistent with a first-order kinetic model with determination of coefficient (R 2 ) higher than 0.9444. The number of double bonds in the sterol structure was negatively correlated with the thermal stability of sterol, whereas the length of the branch chain was positively correlated with the thermal stability of sterol. A quantitative structure-activity relationship (QSAR) model to predict thermal stability of sterol was developed by using partial least squares regression (PLSR) combined with genetic algorithm (GA). A regression model was built with R 2 of 0.806. Almost all sterol degradation constants can be predicted accurately with R 2 of cross-validation equals to 0.680. Four important variables were selected in optimal QSAR model and the selected variables were observed to be related with information indices, RDF descriptors, and 3D-MoRSE descriptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Antitumor activity of 3,4-ethylenedioxythiophene derivatives and quantitative structure-activity relationship analysis

NASA Astrophysics Data System (ADS)

Jukić, Marijana; Rastija, Vesna; Opačak-Bernardi, Teuta; Stolić, Ivana; Krstulović, Luka; Bajić, Miroslav; Glavaš-Obrovac, Ljubica

2017-04-01

The aim of this study was to evaluate nine newly synthesized amidine derivatives of 3,4- ethylenedioxythiophene (3,4-EDOT) for their cytotoxic activity against a panel of human cancer cell lines and to perform a quantitative structure-activity relationship (QSAR) analysis for the antitumor activity of a total of 27 3,4-ethylenedioxythiophene derivatives. Induction of apoptosis was investigated on the selected compounds, along with delivery options for the optimization of activity. The best obtained QSAR models include the following group of descriptors: BCUT, WHIM, 2D autocorrelations, 3D-MoRSE, GETAWAY descriptors, 2D frequency fingerprint and information indices. Obtained QSAR models should be relieved in elucidation of important physicochemical and structural requirements for this biological activity. Highly potent molecules have a symmetrical arrangement of substituents along the x axis, high frequency of distance between N and O atoms at topological distance 9, as well as between C and N atoms at topological distance 10, and more C atoms located at topological distances 6 and 3. Based on the conclusion given in the QSAR analysis, a new compound with possible great activity was proposed.

Brief Report: Activities in Heterosexual Romantic Relationships--Grade Differences and Associations with Relationship Satisfaction

ERIC Educational Resources Information Center

Carlson, Wendy; Rose, Amanda J.

2012-01-01

Whereas much research addresses relations of youths' heterosexual romantic relationships with sexual and/or delinquent activities, less attention has been paid to youths' more normative, day-to-day activities with romantic partners. This gap in the literature is problematic given that these activities define the substance of the relationships and…

The Importance of Leisure Activities in the Relationship between Physical Health and Well-Being in a Life Span Sample.

PubMed

Paggi, Michelle E; Jopp, Daniela; Hertzog, Christopher

2016-01-01

Previous studies have examined the relationships between physical health and leisure activities and between leisure activities and well-being, but, to our knowledge, none has examined these relationships simultaneously. This study investigated the relationships between leisure activities, health and well-being considering the role of age, and whether leisure activities mediate the relationship between physical health and well-being. Utilizing a cross-sectional database of 259 adults (ages 18-81 years) who completed several questionnaires, linear regression models and mediation models were tested. Regression analyses indicated that physical health was related to leisure activities and leisure activities were related to well-being. When physical health was measured by subjective ratings, age had a stronger relationship with leisure activities. However, when physical health was indicated by health restrictions, physical health had a stronger relationship with leisure activities than did age. Leisure activities were a partial mediator of the relationship between physical health and well-being. The results demonstrated that the reduction in leisure activities with age has more to do with physical health limitations than with older age itself. In addition, regardless of age, the benefits of physical health for well-being are due in part to the level of leisure activity participation. These results highlight the importance of leisure activities for successful aging throughout the adult life span. Interventions designed to improve well-being through increasing leisure activity participation should take physical health into consideration, particularly for older adults. © 2016 S. Karger AG, Basel.

Modelling the maximum voluntary joint torque/angular velocity relationship in human movement.

PubMed

Yeadon, Maurice R; King, Mark A; Wilson, Cassie

2006-01-01

The force exerted by a muscle is a function of the activation level and the maximum (tetanic) muscle force. In "maximum" voluntary knee extensions muscle activation is lower for eccentric muscle velocities than for concentric velocities. The aim of this study was to model this "differential activation" in order to calculate the maximum voluntary knee extensor torque as a function of knee angular velocity. Torque data were collected on two subjects during maximal eccentric-concentric knee extensions using an isovelocity dynamometer with crank angular velocities ranging from 50 to 450 degrees s(-1). The theoretical tetanic torque/angular velocity relationship was modelled using a four parameter function comprising two rectangular hyperbolas while the activation/angular velocity relationship was modelled using a three parameter function that rose from submaximal activation for eccentric velocities to full activation for high concentric velocities. The product of these two functions gave a seven parameter function which was fitted to the joint torque/angular velocity data, giving unbiased root mean square differences of 1.9% and 3.3% of the maximum torques achieved. Differential activation accounts for the non-hyperbolic behaviour of the torque/angular velocity data for low concentric velocities. The maximum voluntary knee extensor torque that can be exerted may be modelled accurately as the product of functions defining the maximum torque and the maximum voluntary activation level. Failure to include differential activation considerations when modelling maximal movements will lead to errors in the estimation of joint torque in the eccentric phase and low velocity concentric phase.

The role of Patient Health Engagement Model (PHE-model) in affecting patient activation and medication adherence: A structural equation model

PubMed Central

Graffigna, Guendalina; Bonanomi, Andrea

2017-01-01

Background Increasing bodies of scientific research today examines the factors and interventions affecting patients’ ability to self-manage and adhere to treatment. Patient activation is considered the most reliable indicator of patients’ ability to manage health autonomously. Only a few studies have tried to assess the role of psychosocial factors in promoting patient activation. A more systematic modeling of the psychosocial factors explaining the variance of patient activation is needed. Objective To test the hypothesized effect of patient activation on medication adherence; to test the the hypothesized effects of positive emotions and of the quality of the patient/doctor relationship on patient activation; and to test the hypothesized mediating effect of Patient Health Engagement (PHE-model) in this pathway. Material and methods This cross-sectional study involved 352 Italian-speaking adult chronic patients. The survey included measures of i) patient activation (Patient Activation Measure 13 –short form); ii) Patient Health Engagement model (Patient Health Engagement Scale); iii) patient adherence (4 item-Morinsky Medication Adherence Scale); iv) the quality of the patients’ emotional feelings (Manikin Self Assessment Scale); v) the quality of the patient/doctor relationship (Health Care Climate Questionnaire). Structural equation modeling was used to test the hypotheses proposed. Results According to the theoretical model we hypothesized, research results confirmed that patients’ activation significantly affects their reported medication adherence. Moreover, psychosocial factors, such as the patients’ quality of the emotional feelings and the quality of the patient/doctor relationship were demonstrated to be factors affecting the level of patient activation. Finally, the mediation effect of the Patient Health Engagement model was confirmed by the analysis. Conclusions Consistently with the results of previous studies, these findings demonstrate

The role of Patient Health Engagement Model (PHE-model) in affecting patient activation and medication adherence: A structural equation model.

PubMed

Graffigna, Guendalina; Barello, Serena; Bonanomi, Andrea

2017-01-01

Increasing bodies of scientific research today examines the factors and interventions affecting patients' ability to self-manage and adhere to treatment. Patient activation is considered the most reliable indicator of patients' ability to manage health autonomously. Only a few studies have tried to assess the role of psychosocial factors in promoting patient activation. A more systematic modeling of the psychosocial factors explaining the variance of patient activation is needed. To test the hypothesized effect of patient activation on medication adherence; to test the the hypothesized effects of positive emotions and of the quality of the patient/doctor relationship on patient activation; and to test the hypothesized mediating effect of Patient Health Engagement (PHE-model) in this pathway. This cross-sectional study involved 352 Italian-speaking adult chronic patients. The survey included measures of i) patient activation (Patient Activation Measure 13 -short form); ii) Patient Health Engagement model (Patient Health Engagement Scale); iii) patient adherence (4 item-Morinsky Medication Adherence Scale); iv) the quality of the patients' emotional feelings (Manikin Self Assessment Scale); v) the quality of the patient/doctor relationship (Health Care Climate Questionnaire). Structural equation modeling was used to test the hypotheses proposed. According to the theoretical model we hypothesized, research results confirmed that patients' activation significantly affects their reported medication adherence. Moreover, psychosocial factors, such as the patients' quality of the emotional feelings and the quality of the patient/doctor relationship were demonstrated to be factors affecting the level of patient activation. Finally, the mediation effect of the Patient Health Engagement model was confirmed by the analysis. Consistently with the results of previous studies, these findings demonstrate that the Patient Health Engagement Model is a critical factor in enhancing

Developing sensor activity relationships for the JPL electronic nose sensors using molecular modeling and QSAR techniques

NASA Technical Reports Server (NTRS)

Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Jewell, A. D.; Zhou, H.; Manatt, K.; Kisor, A. K.

2005-01-01

We report a Quantitative Structure-Activity Relationships (QSAR) study using Genetic Function Approximations (GFA) to describe the polymer-carbon composite sensor activities in the JPL Electronic Nose, when exposed to chemical vapors at parts-per-million concentration levels.

Active and passive characteristics of muscle tone and their relationship to models of subluxation/joint dysfunction

PubMed Central

Knutson, Gary A.; Owens, Edward F.

2003-01-01

The relationship of muscles to the causes and effects of the pathophysiologic entity referred to as chiropractic subluxation or joint dysfunction is critical. Part I of this paper reviewed the complexities of skeletal muscle in regards to anatomy, active and passive tone, detection of muscle tone, neurophysiology, and how muscle function fits into a variety of subluxation/joint dysfunction models. The concluding part of the review culminates in a hypothesis to describe and explain varying degrees of muscle tone that may be encountered clinically. It is hoped that knowledge of the differing levels of muscle tone and their causes will help the clinician to better determine the underlying cause of a neuromusculoskeletal problem allowing application of necessary and proper intervention.

Modeling the relationship between physical activity and quality of life in menopausal-aged women: a cross-sectional study.

PubMed

Javadivala, Zeinab; Kousha, Ahmad; Allahverdipour, Hamid; Asghari Jafarabadi, Mohammad; Tallebian, Hossein

2013-09-17

The purpose of the present study was (a) to assess the relationship between physical activity and the intensity and duration of menopausal symptoms, (b) to investigate the relationship between physical activity and the four domains of health-related quality of life (HRQOL) and (c) to assess the relationship between physical activity and chronic diseases. This descriptive-analytical study that was conducted in Tabriz City, Iran. Data were collected in 2012 by personal home-based interviews, using structured questionnaires. All participants (n= 273), who were middle-aged (age range of 40-60 yr) were recruited from two of the 25 urban health service centers' clients, by clustered random sampling allocation. There was a positive significant relationship between Psychological, Social, and Environmental domains of HRQOL with physical activity (P<0.001). In addition, a negative significant relation was found between somatic complaints including sexual problems (P< 0.017) and vaginal dryness (P<0.030) as well as joint-muscular discomfort (P<0.018), and the level of physical activity. Diabetic (P<0.047) and women with history of heart disease (P<0.040) performed 2.670 and 3.548 hours more than who were not. Regular physical activity would be effective in decreasing menopausal symptoms as well as improving healthy aging and also physical activity promotion as a part of healthy life style promotion programs needs to be improved in communities where women are physically inactive. In addition, women need to be informed about importance of physical activity on their life which it leads to feel healthy aging and pre and post- menopausal stages.

Compound toxicity screening and structure-activity relationship modeling in Escherichia coli.

PubMed

Planson, Anne-Gaëlle; Carbonell, Pablo; Paillard, Elodie; Pollet, Nicolas; Faulon, Jean-Loup

2012-03-01

Synthetic biology and metabolic engineering are used to develop new strategies for producing valuable compounds ranging from therapeutics to biofuels in engineered microorganisms. When developing methods for high-titer production cells, toxicity is an important element to consider. Indeed the production rate can be limited due to toxic intermediates or accumulation of byproducts of the heterologous biosynthetic pathway of interest. Conversely, highly toxic molecules are desired when designing antimicrobials. Compound toxicity in bacteria plays a major role in metabolic engineering as well as in the development of new antibacterial agents. Here, we screened a diversified chemical library of 166 compounds for toxicity in Escherichia coli. The dataset was built using a clustering algorithm maximizing the chemical diversity in the library. The resulting assay data was used to develop a toxicity predictor that we used to assess the toxicity of metabolites throughout the metabolome. This new tool for predicting toxicity can thus be used for fine-tuning heterologous expression and can be integrated in a computational-framework for metabolic pathway design. Many structure-activity relationship tools have been developed for toxicology studies in eukaryotes [Valerio (2009), Toxicol Appl Pharmacol, 241(3): 356-370], however, to the best of our knowledge we present here the first E. coli toxicity prediction web server based on QSAR models (EcoliTox server: http://www.issb.genopole.fr/∼faulon/EcoliTox.php). Copyright © 2011 Wiley Periodicals, Inc.

Chemistry and Structure-Activity Relationships of Psychedelics.

PubMed

Nichols, David E

2018-01-01

This chapter will summarize structure-activity relationships (SAR) that are known for the classic serotonergic hallucinogens (aka psychedelics), focusing on the three chemical types: tryptamines, ergolines, and phenethylamines. In the brain, the serotonin 5-HT 2A receptor plays a key role in regulation of cortical function and cognition, and also appears to be the principal target for hallucinogenic/psychedelic drugs such as LSD. It is one of the most extensively studied of the 14 known types of serotonin receptors. Important structural features will be identified for activity and, where possible, those that the psychedelics have in common will be discussed. Because activation of the 5-HT 2A receptor is the principal mechanism of action for psychedelics, compounds with 5-HT 2A agonist activity generally are quickly discarded by the pharmaceutical industry. Thus, most of the research on psychedelics can be related to activation of 5-HT 2A receptors. Therefore, much of the discussion will include not only clinical or anecdotal studies, but also will consider data from animal models as well as a certain amount of molecular pharmacology where it is known.

Supervisor's Interactive Model of Organizational Relationships

ERIC Educational Resources Information Center

O'Reilly, Frances L.; Matt, John; McCaw, William P.

2014-01-01

The Supervisor's Interactive Model of Organizational Relationships (SIMOR) integrates two models addressed in the leadership literature and then highlights the importance of relationships. The Supervisor's Interactive Model of Organizational Relationships combines the modified Hersey and Blanchard model of situational leadership, the…

Relationship between self-efficacy and physical activity among patients with type 2 diabetes.

PubMed

Dutton, Gareth R; Tan, Fei; Provost, Bridgette C; Sorenson, Jamie L; Allen, Brandon; Smith, Dawn

2009-06-01

While previous studies indicate a significant relationship between self-efficacy and physical activity, less research has focused on this relationship among patients with type 2 diabetes. The purpose of this investigation was to examine whether self-efficacy mediated the relationship between participation in a 1-month, print-based physical activity intervention and improvements in activity levels. Participants (N = 85; mean age = 57; 73% Caucasian; 69% female) were recruited from a community diabetes center. The intervention was individually-tailored based on theoretical constructs, including self-efficacy. After controlling for age, baseline activity, and baseline self-efficacy, the tailored intervention was associated with significant improvements in physical activity, 95% CI [23.01, 271.68] as well as self-efficacy, CI [0.02, 3.48]. There was an indirect effect of treatment on physical activity through self-efficacy, CI [0.77, 73.11], and the direct effect of treatment on physical activity was no longer significant, CI [-7.33, 253.40], after the influences of self-efficacy change were accounted for in the model. Results supported a mediation effect, such that the treatment effect on physical activity was completely mediated by changes in self-efficacy. Although replication is needed, results support the theoretical rationale for targeting self-efficacy to promote physical activity among patients with type 2 diabetes.

Linear and non-linear quantitative structure-activity relationship models on indole substitution patterns as inhibitors of HIV-1 attachment.

PubMed

Nirouei, Mahyar; Ghasemi, Ghasem; Abdolmaleki, Parviz; Tavakoli, Abdolreza; Shariati, Shahab

2012-06-01

The antiviral drugs that inhibit human immunodeficiency virus (HIV) entry to the target cells are already in different phases of clinical trials. They prevent viral entry and have a highly specific mechanism of action with a low toxicity profile. Few QSAR studies have been performed on this group of inhibitors. This study was performed to develop a quantitative structure-activity relationship (QSAR) model of the biological activity of indole glyoxamide derivatives as inhibitors of the interaction between HIV glycoprotein gp120 and host cell CD4 receptors. Forty different indole glyoxamide derivatives were selected as a sample set and geometrically optimized using Gaussian 98W. Different combinations of multiple linear regression (MLR), genetic algorithms (GA) and artificial neural networks (ANN) were then utilized to construct the QSAR models. These models were also utilized to select the most efficient subsets of descriptors in a cross-validation procedure for non-linear log (1/EC50) prediction. The results that were obtained using GA-ANN were compared with MLR-MLR and MLR-ANN models. A high predictive ability was observed for the MLR, MLR-ANN and GA-ANN models, with root mean sum square errors (RMSE) of 0.99, 0.91 and 0.67, respectively (N = 40). In summary, machine learning methods were highly effective in designing QSAR models when compared to statistical method.

Synthetic cannabinoids: In silico prediction of the cannabinoid receptor 1 affinity by a quantitative structure-activity relationship model.

PubMed

Paulke, Alexander; Proschak, Ewgenij; Sommer, Kai; Achenbach, Janosch; Wunder, Cora; Toennes, Stefan W

2016-03-14

The number of new synthetic psychoactive compounds increase steadily. Among the group of these psychoactive compounds, the synthetic cannabinoids (SCBs) are most popular and serve as a substitute of herbal cannabis. More than 600 of these substances already exist. For some SCBs the in vitro cannabinoid receptor 1 (CB1) affinity is known, but for the majority it is unknown. A quantitative structure-activity relationship (QSAR) model was developed, which allows the determination of the SCBs affinity to CB1 (expressed as binding constant (Ki)) without reference substances. The chemically advance template search descriptor was used for vector representation of the compound structures. The similarity between two molecules was calculated using the Feature-Pair Distribution Similarity. The Ki values were calculated using the Inverse Distance Weighting method. The prediction model was validated using a cross validation procedure. The predicted Ki values of some new SCBs were in a range between 20 (considerably higher affinity to CB1 than THC) to 468 (considerably lower affinity to CB1 than THC). The present QSAR model can serve as a simple, fast and cheap tool to get a first hint of the biological activity of new synthetic cannabinoids or of other new psychoactive compounds. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Is Sexual Activity During Adolescence Good for Future Romantic Relationships?

PubMed

Shulman, Shmuel; Seiffge-Krenke, Inge; Walsh, Sophie D

2017-09-01

Past research has consistently shown that romantic experiences during adolescence affect the nature and quality of romantic relationships during emerging adulthood. However, less is known about the role of adolescent sexual experiences in future sexual and romantic relationships. The current study examined the impact of different forms of sexual activity at age 16 (within a romantic relationship or casual encounters) on the nature and quality of sexual experiences in romantic relationships at age 23. One hundred and forty four (59.7% females) 16 year olds reported on their sexual activity within a romantic relationship or sexual encounters. In addition they reported on the quality of relationships they were involved in and their tendency to suppress emotions (included as an aspect of personality). At age 23 they reported on their romantic and sexual experiences during the past 2 years (number of short lived relationships, numbers of friends with benefits, casual sex encounters) and the quality of their romantic relationships (the duration of their longest relationship, partner support and feelings of certainty in the relationships). Findings showed that the tendency to suppress emotions was associated with lower likelihood to engage in casual sex at age 23. However, greater sexual experience in casual encounters during adolescence was consistently longitudinally associated with different forms of casual sexual encounters and short romantic involvements above and beyond the contribution of personality. In contrast, sexual activity within a romantic relationship predicted only a few indices of the quality of romantic involvement at age 23. The distinctive role of casual sexual activity and sexual activity within a romantic relationship for future sexual and romantic activities is discussed.

Spatial heterogeneity of the relationships between environmental characteristics and active commuting: towards a locally varying social ecological model.

PubMed

Feuillet, Thierry; Charreire, Hélène; Menai, Mehdi; Salze, Paul; Simon, Chantal; Dugas, Julien; Hercberg, Serge; Andreeva, Valentina A; Enaux, Christophe; Weber, Christiane; Oppert, Jean-Michel

2015-03-25

According to the social ecological model of health-related behaviors, it is now well accepted that environmental factors influence habitual physical activity. Most previous studies on physical activity determinants have assumed spatial homogeneity across the study area, i.e. that the association between the environment and physical activity is the same whatever the location. The main novelty of our study was to explore geographical variation in the relationships between active commuting (walking and cycling to/from work) and residential environmental characteristics. 4,164 adults from the ongoing Nutrinet-Santé web-cohort, residing in and around Paris, France, were studied using a geographically weighted Poisson regression (GWPR) model. Objective environmental variables, including both the built and the socio-economic characteristics around the place of residence of individuals, were assessed by GIS-based measures. Perceived environmental factors (index including safety, aesthetics, and pollution) were reported by questionnaires. Our results show that the influence of the overall neighborhood environment appeared to be more pronounced in the suburban southern part of the study area (Val-de-Marne) compared to Paris inner city, whereas more complex patterns were found elsewhere. Active commuting was positively associated with the built environment only in the southern and northeastern parts of the study area, whereas positive associations with the socio-economic environment were found only in some specific locations in the southern and northern parts of the study area. Similar local variations were observed for the perceived environmental variables. These results suggest that: (i) when applied to active commuting, the social ecological conceptual framework should be locally nuanced, and (ii) local rather than global targeting of public health policies might be more efficient in promoting active commuting.

Modelers and policymakers : improving the relationships.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karas, Thomas H.

2004-06-01

On April 22 and 23, 2004, a diverse group of 14 policymakers, modelers, analysts, and scholars met with some 22 members of the Sandia National Laboratories staff to explores ways in which the relationships between modelers and policymakers in the energy and environment fields (with an emphasis on energy) could be made more productive for both. This report is not a transcription of that workshop, but draws very heavily on its proceedings. It first describes the concept of modeling, the varying ways in which models are used to support policymaking, and the institutional context for those uses. It then proposesmore » that the goal of modelers and policymakers should be a relationship of mutual trust, built on a foundation of communication, supported by the twin pillars of policy relevance and technical credibility. The report suggests 20 guidelines to help modelers improve the relationship, followed by 10 guidelines to help policymakers toward the same goal.« less

Research data management and libraries: relationships, activities, drivers and influences.

PubMed

Pinfield, Stephen; Cox, Andrew M; Smith, Jen

2014-01-01

The management of research data is now a major challenge for research organisations. Vast quantities of born-digital data are being produced in a wide variety of forms at a rapid rate in universities. This paper analyses the contribution of academic libraries to research data management (RDM) in the wider institutional context. In particular it: examines the roles and relationships involved in RDM, identifies the main components of an RDM programme, evaluates the major drivers for RDM activities, and analyses the key factors influencing the shape of RDM developments. The study is written from the perspective of library professionals, analysing data from 26 semi-structured interviews of library staff from different UK institutions. This is an early qualitative contribution to the topic complementing existing quantitative and case study approaches. Results show that although libraries are playing a significant role in RDM, there is uncertainty and variation in the relationship with other stakeholders such as IT services and research support offices. Current emphases in RDM programmes are on developments of policies and guidelines, with some early work on technology infrastructures and support services. Drivers for developments include storage, security, quality, compliance, preservation, and sharing with libraries associated most closely with the last three. The paper also highlights a 'jurisdictional' driver in which libraries are claiming a role in this space. A wide range of factors, including governance, resourcing and skills, are identified as influencing ongoing developments. From the analysis, a model is constructed designed to capture the main aspects of an institutional RDM programme. This model helps to clarify the different issues involved in RDM, identifying layers of activity, multiple stakeholders and drivers, and a large number of factors influencing the implementation of any initiative. Institutions may usefully benchmark their activities against the

Research Data Management and Libraries: Relationships, Activities, Drivers and Influences

PubMed Central

Pinfield, Stephen; Cox, Andrew M.; Smith, Jen

2014-01-01

The management of research data is now a major challenge for research organisations. Vast quantities of born-digital data are being produced in a wide variety of forms at a rapid rate in universities. This paper analyses the contribution of academic libraries to research data management (RDM) in the wider institutional context. In particular it: examines the roles and relationships involved in RDM, identifies the main components of an RDM programme, evaluates the major drivers for RDM activities, and analyses the key factors influencing the shape of RDM developments. The study is written from the perspective of library professionals, analysing data from 26 semi-structured interviews of library staff from different UK institutions. This is an early qualitative contribution to the topic complementing existing quantitative and case study approaches. Results show that although libraries are playing a significant role in RDM, there is uncertainty and variation in the relationship with other stakeholders such as IT services and research support offices. Current emphases in RDM programmes are on developments of policies and guidelines, with some early work on technology infrastructures and support services. Drivers for developments include storage, security, quality, compliance, preservation, and sharing with libraries associated most closely with the last three. The paper also highlights a ‘jurisdictional’ driver in which libraries are claiming a role in this space. A wide range of factors, including governance, resourcing and skills, are identified as influencing ongoing developments. From the analysis, a model is constructed designed to capture the main aspects of an institutional RDM programme. This model helps to clarify the different issues involved in RDM, identifying layers of activity, multiple stakeholders and drivers, and a large number of factors influencing the implementation of any initiative. Institutions may usefully benchmark their activities against

Comparing estimates of genetic variance across different relationship models.

PubMed

Legarra, Andres

2016-02-01

Use of relationships between individuals to estimate genetic variances and heritabilities via mixed models is standard practice in human, plant and livestock genetics. Different models or information for relationships may give different estimates of genetic variances. However, comparing these estimates across different relationship models is not straightforward as the implied base populations differ between relationship models. In this work, I present a method to compare estimates of variance components across different relationship models. I suggest referring genetic variances obtained using different relationship models to the same reference population, usually a set of individuals in the population. Expected genetic variance of this population is the estimated variance component from the mixed model times a statistic, Dk, which is the average self-relationship minus the average (self- and across-) relationship. For most typical models of relationships, Dk is close to 1. However, this is not true for very deep pedigrees, for identity-by-state relationships, or for non-parametric kernels, which tend to overestimate the genetic variance and the heritability. Using mice data, I show that heritabilities from identity-by-state and kernel-based relationships are overestimated. Weighting these estimates by Dk scales them to a base comparable to genomic or pedigree relationships, avoiding wrong comparisons, for instance, "missing heritabilities". Copyright © 2015 Elsevier Inc. All rights reserved.

Quantitative structure activity relationship (QSAR) of piperine analogs for bacterial NorA efflux pump inhibitors.

PubMed

Nargotra, Amit; Sharma, Sujata; Koul, Jawahir Lal; Sangwan, Pyare Lal; Khan, Inshad Ali; Kumar, Ashwani; Taneja, Subhash Chander; Koul, Surrinder

2009-10-01

Quantitative structure activity relationship (QSAR) analysis of piperine analogs as inhibitors of efflux pump NorA from Staphylococcus aureus has been performed in order to obtain a highly accurate model enabling prediction of inhibition of S. aureus NorA of new chemical entities from natural sources as well as synthetic ones. Algorithm based on genetic function approximation method of variable selection in Cerius2 was used to generate the model. Among several types of descriptors viz., topological, spatial, thermodynamic, information content and E-state indices that were considered in generating the QSAR model, three descriptors such as partial negative surface area of the compounds, area of the molecular shadow in the XZ plane and heat of formation of the molecules resulted in a statistically significant model with r(2)=0.962 and cross-validation parameter q(2)=0.917. The validation of the QSAR models was done by cross-validation, leave-25%-out and external test set prediction. The theoretical approach indicates that the increase in the exposed partial negative surface area increases the inhibitory activity of the compound against NorA whereas the area of the molecular shadow in the XZ plane is inversely proportional to the inhibitory activity. This model also explains the relationship of the heat of formation of the compound with the inhibitory activity. The model is not only able to predict the activity of new compounds but also explains the important regions in the molecules in quantitative manner.

A review of the global relationship among freshwater fish, autotrophic activity, and regional climate

USGS Publications Warehouse

Deines, Andrew M.; Bunnell, David B.; Rogers, Mark W.; Beard, T. Douglas; Taylor, William W.

2015-01-01

The relationship between autotrophic activity and freshwater fish populations is an important consideration for ecologists describing trophic structure in aquatic communities, fisheries managers tasked with increasing sustainable fisheries development, and fish farmers seeking to maximize production. Previous studies of the empirical relationships of autotrophic activity and freshwater fish yield have found positive relationships but were limited by small sample sizes, small geographic scopes, and the inability to compare patterns among many types of measurement techniques. Individual studies and reviews have also lacked consistent consideration of regional climate factors which may inform relationships between fisheries and autotrophic activity. We compiled data from over 700 freshwater systems worldwide and used meta-analysis and linear models to develop a comprehensive global synthesis between multiple metrics of autotrophic activity, fisheries, and climate indicators. Our results demonstrate that multiple metrics of fish (i.e., catch per unit effort, yield, and production) increase with autotrophic activity across a variety of fisheries. At the global scale additional variation in this positive relationship can be ascribed to regional climate differences (i.e., temperature and precipitation) across systems. Our results provide a method and proof-of-concept for assessing inland fisheries production at the global scale, where current estimates are highly uncertain, and may therefore inform the continued sustainable use of global inland fishery resources.

Structure-Activity Relationships for the Antifungal Activity of Selective Estrogen Receptor Antagonists Related to Tamoxifen

PubMed Central

Butts, Arielle; Martin, Jennifer A.; DiDone, Louis; Bradley, Erin K.; Mutz, Mitchell; Krysan, Damian J.

2015-01-01

Cryptococcosis is one of the most important invasive fungal infections and is a significant contributor to the mortality associated with HIV/AIDS. As part of our program to repurpose molecules related to the selective estrogen receptor modulator (SERM) tamoxifen as anti-cryptococcal agents, we have explored the structure-activity relationships of a set of structurally diverse SERMs and tamoxifen derivatives. Our data provide the first insights into the structural requirements for the antifungal activity of this scaffold. Three key molecular characteristics affecting anti-cryptococcal activity emerged from our studies: 1) the presence of an alkylamino group tethered to one of the aromatic rings of the triphenylethylene core; 2) an appropriately sized aliphatic substituent at the 2 position of the ethylene moiety; and 3) electronegative substituents on the aromatic rings modestly improved activity. Using a cell-based assay of calmodulin antagonism, we found that the anti-cryptococcal activity of the scaffold correlates with calmodulin inhibition. Finally, we developed a homology model of C. neoformans calmodulin and used it to rationalize the structural basis for the activity of these molecules. Taken together, these data and models provide a basis for the further optimization of this promising anti-cryptococcal scaffold. PMID:26016941

A prospective examination of the relationship between physical activity and dementia risk in later life.

PubMed

Bowen, Mary Elizabeth

2012-01-01

To examine the relationship between vigorous physical activity and dementia risk. Prospective study design utilizing physical activity data from the Health and Retirement Study and cognitive outcome data from the Aging, Demographics, and Memory Study. Community-based. Adults age 71 and over (N  =  808) with 3 to 7 years of physical activity information prior to dementia/no dementia diagnosis. Physical activity was measured by participation in vigorous activities such as aerobics, sports, running, bicycling, and heavy housework three or more times per week (yes/no). Dementia diagnosis was based on an expert panel (e.g., neuropsychologists, neurologists, geropsychiatrists) who performed and reviewed a battery of neuropsychological tests. Binary logistic regression models were used to account for demographic characteristics, genetic risk factors (one or two apolipoprotein E ε4 alleles), health behaviors (e.g., smoking, drinking alcohol), health indicators (body mass index), and health conditions (e.g., diabetes, heart disease) in a sequential model-building process. The relationship between vigorous physical activity and dementia risk remained robust across models. In the final model, older adults who were physically active were 21% (p ≤ .05) less likely than their counterparts to be diagnosed with dementia. Vigorous physical activity may reduce the risk for dementia independently of the factors examined here. This study's findings are important given that few preventative strategies for dementia have been explored beyond hormonal therapy and anti-inflammatory drugs.

Small molecule non-peptide inhibitors of botulinum neurotoxin serotype E: Structure-activity relationship and a pharmacophore model.

PubMed

Kumar, Gyanendra; Agarwal, Rakhi; Swaminathan, Subramanyam

2016-09-15

Botulinum neurotoxins (BoNTs) are the most poisonous biological substance known to humans. They cause flaccid paralysis by blocking the release of acetylcholine at the neuromuscular junction. Here, we report a number of small molecule non-peptide inhibitors of BoNT serotype E. The structure-activity relationship and a pharmacophore model are presented. Although non-peptidic in nature, these inhibitors mimic key features of the uncleavable substrate peptide Arg-Ile-Met-Glu (RIME) of the SNAP-25 protein. Among the compounds tested, most of the potent inhibitors bear a zinc-chelating moiety connected to a hydrophobic and aromatic moiety through a carboxyl or amide linker. All of them show low micromolar IC50 values. Copyright © 2016 Elsevier Ltd. All rights reserved.

Small molecule non-peptide inhibitors of botulinum neurotoxin serotype E: Structure–activity relationship and a pharmacophore model

DOE PAGES

Kumar, Gyanendra; Agarwal, Rakhi; Swaminathan, Subramanyam

2016-06-18

Botulinum neurotoxins (BoNTs) are the most poisonous biological substance known to humans. They cause flaccid paralysis by blocking the release of acetylcholine at the neuromuscular junction. Here, we report a number of small molecule non-peptide inhibitors of BoNT serotype E. In addition, the structure–activity relationship and a pharmacophore model are presented. Although non-peptidic in nature, these inhibitors mimic key features of the uncleavable substrate peptide Arg-Ile-Met-Glu (RIME) of the SNAP-25 protein. Among the compounds tested, most of the potent inhibitors bear a zinc-chelating moiety connected to a hydrophobic and aromatic moiety through a carboxyl or amide linker. All of themmore » show low micromolar IC 50 values.« less

Discovering Anti-platelet Drug Combinations with an Integrated Model of Activator-Inhibitor Relationships, Activator-Activator Synergies and Inhibitor-Inhibitor Synergies

PubMed Central

Lombardi, Federica; Golla, Kalyan; Fitzpatrick, Darren J.; Casey, Fergal P.; Moran, Niamh; Shields, Denis C.

2015-01-01

Identifying effective therapeutic drug combinations that modulate complex signaling pathways in platelets is central to the advancement of effective anti-thrombotic therapies. However, there is no systems model of the platelet that predicts responses to different inhibitor combinations. We developed an approach which goes beyond current inhibitor-inhibitor combination screening to efficiently consider other signaling aspects that may give insights into the behaviour of the platelet as a system. We investigated combinations of platelet inhibitors and activators. We evaluated three distinct strands of information, namely: activator-inhibitor combination screens (testing a panel of inhibitors against a panel of activators); inhibitor-inhibitor synergy screens; and activator-activator synergy screens. We demonstrated how these analyses may be efficiently performed, both experimentally and computationally, to identify particular combinations of most interest. Robust tests of activator-activator synergy and of inhibitor-inhibitor synergy required combinations to show significant excesses over the double doses of each component. Modeling identified multiple effects of an inhibitor of the P2Y12 ADP receptor, and complementarity between inhibitor-inhibitor synergy effects and activator-inhibitor combination effects. This approach accelerates the mapping of combination effects of compounds to develop combinations that may be therapeutically beneficial. We integrated the three information sources into a unified model that predicted the benefits of a triple drug combination targeting ADP, thromboxane and thrombin signaling. PMID:25875950

The relationship between particulate pollution levels in Australian cities, meteorology, and landscape fire activity detected from MODIS hotspots.

PubMed

Price, Owen F; Williamson, Grant J; Henderson, Sarah B; Johnston, Fay; Bowman, David M J S

2012-01-01

Smoke from bushfires is an emerging issue for fire managers because of increasing evidence for its public health effects. Development of forecasting models to predict future pollution levels based on the relationship between bushfire activity and current pollution levels would be a useful management tool. As a first step, we use daily thermal anomalies detected by the MODIS Active Fire Product (referred to as "hotspots"), pollution concentrations, and meteorological data for the years 2002 to 2008, to examine the statistical relationship between fire activity in the landscapes and pollution levels around Perth and Sydney, two large Australian cities. Resultant models were statistically significant, but differed in their goodness of fit and the distance at which the strength of the relationship was strongest. For Sydney, a univariate model for hotspot activity within 100 km explained 24% of variation in pollution levels, and the best model including atmospheric variables explained 56% of variation. For Perth, the best radius was 400 km, explaining only 7% of variation, while the model including atmospheric variables explained 31% of the variation. Pollution was higher when the atmosphere was more stable and in the presence of on-shore winds, whereas there was no effect of wind blowing from the fires toward the pollution monitors. Our analysis shows there is a good prospect for developing region-specific forecasting tools combining hotspot fire activity with meteorological data.

The Relationship between Particulate Pollution Levels in Australian Cities, Meteorology, and Landscape Fire Activity Detected from MODIS Hotspots

PubMed Central

Price, Owen F.; Williamson, Grant J.; Henderson, Sarah B.; Johnston, Fay; Bowman, David M. J. S.

2012-01-01

Smoke from bushfires is an emerging issue for fire managers because of increasing evidence for its public health effects. Development of forecasting models to predict future pollution levels based on the relationship between bushfire activity and current pollution levels would be a useful management tool. As a first step, we use daily thermal anomalies detected by the MODIS Active Fire Product (referred to as “hotspots”), pollution concentrations, and meteorological data for the years 2002 to 2008, to examine the statistical relationship between fire activity in the landscapes and pollution levels around Perth and Sydney, two large Australian cities. Resultant models were statistically significant, but differed in their goodness of fit and the distance at which the strength of the relationship was strongest. For Sydney, a univariate model for hotspot activity within 100 km explained 24% of variation in pollution levels, and the best model including atmospheric variables explained 56% of variation. For Perth, the best radius was 400 km, explaining only 7% of variation, while the model including atmospheric variables explained 31% of the variation. Pollution was higher when the atmosphere was more stable and in the presence of on-shore winds, whereas there was no effect of wind blowing from the fires toward the pollution monitors. Our analysis shows there is a good prospect for developing region-specific forecasting tools combining hotspot fire activity with meteorological data. PMID:23071788

Passion for an activity and quality of interpersonal relationships: the mediating role of emotions.

PubMed

Philippe, Frederick L; Vallerand, Robert J; Houlfort, Nathalie; Lavigne, Geneviève L; Donahue, Eric G

2010-06-01

Our purpose in this research was to investigate the role of passion (Vallerand et al., 2003) for a given activity in the quality of interpersonal relationships experienced within the context of that activity in 4 studies. Study 1 demonstrated that a harmonious passion was positively associated with the quality of interpersonal relationships within the context of the passionate activity, whereas an obsessive passion was unrelated to it. Furthermore, in line with the broaden-and-build theory (Fredrickson, 2001), results also showed that positive emotions experienced at work fully mediated the relation between harmonious passion and quality of interpersonal relationships. Obsessive passion was not associated with positive emotions. Study 2 replicated the results from Study 1 while controlling for trait extraversion. Also, in Study 2, we examined the negative mediating role of negative emotions between obsessive passion and quality of interpersonal relationships. Finally, Studies 3 and 4 replicated the results of Study 2 with prospective designs and with objective ratings of interpersonal relationships quality. Implications for the dualistic model of passion and the broaden-and-build theory are discussed. (c) 2010 APA, all rights reserved).

Structure-Thermodynamics-Antioxidant Activity Relationships of Selected Natural Phenolic Acids and Derivatives: An Experimental and Theoretical Evaluation

PubMed Central

Zheng, Jie; Liang, Guizhao

2015-01-01

Phenolic acids and derivatives have potential biological functions, however, little is known about the structure-activity relationships and the underlying action mechanisms of these phenolic acids to date. Herein we investigate the structure-thermodynamics-antioxidant relationships of 20 natural phenolic acids and derivatives using DPPH• scavenging assay, density functional theory calculations at the B3LYP/6-311++G(d,p) levels of theory, and quantitative structure-activity relationship (QSAR) modeling. Three main working mechanisms (HAT, SETPT and SPLET) are explored in four micro-environments (gas-phase, benzene, water and ethanol). Computed thermodynamics parameters (BDE, IP, PDE, PA and ETE) are compared with the experimental radical scavenging activities against DPPH•. Available theoretical and experimental investigations have demonstrated that the extended delocalization and intra-molecular hydrogen bonds are the two main contributions to the stability of the radicals. The C = O or C = C in COOH, COOR, C = CCOOH and C = CCOOR groups, and orthodiphenolic functionalities are shown to favorably stabilize the specific radical species to enhance the radical scavenging activities, while the presence of the single OH in the ortho position of the COOH group disfavors the activities. HAT is the thermodynamically preferred mechanism in the gas phase and benzene, whereas SPLET in water and ethanol. Furthermore, our QSAR models robustly represent the structure-activity relationships of these explored compounds in polar media. PMID:25803685

Structure-thermodynamics-antioxidant activity relationships of selected natural phenolic acids and derivatives: an experimental and theoretical evaluation.

PubMed

Chen, Yuzhen; Xiao, Huizhi; Zheng, Jie; Liang, Guizhao

2015-01-01

Phenolic acids and derivatives have potential biological functions, however, little is known about the structure-activity relationships and the underlying action mechanisms of these phenolic acids to date. Herein we investigate the structure-thermodynamics-antioxidant relationships of 20 natural phenolic acids and derivatives using DPPH• scavenging assay, density functional theory calculations at the B3LYP/6-311++G(d,p) levels of theory, and quantitative structure-activity relationship (QSAR) modeling. Three main working mechanisms (HAT, SETPT and SPLET) are explored in four micro-environments (gas-phase, benzene, water and ethanol). Computed thermodynamics parameters (BDE, IP, PDE, PA and ETE) are compared with the experimental radical scavenging activities against DPPH•. Available theoretical and experimental investigations have demonstrated that the extended delocalization and intra-molecular hydrogen bonds are the two main contributions to the stability of the radicals. The C = O or C = C in COOH, COOR, C = CCOOH and C = CCOOR groups, and orthodiphenolic functionalities are shown to favorably stabilize the specific radical species to enhance the radical scavenging activities, while the presence of the single OH in the ortho position of the COOH group disfavors the activities. HAT is the thermodynamically preferred mechanism in the gas phase and benzene, whereas SPLET in water and ethanol. Furthermore, our QSAR models robustly represent the structure-activity relationships of these explored compounds in polar media.

Adolescents' social environment and depression: social networks, extracurricular activity, and family relationship influences.

PubMed

Mason, Michael J; Schmidt, Christopher; Abraham, Anisha; Walker, Leslie; Tercyak, Kenneth

2009-12-01

The present study examined components of adolescents' social environment (social network, extracurricular activities, and family relationships) in association with depression. A total of 332 adolescents presenting for a routine medical check-up were self-assessed for social network risk (i.e., smoking habits of best male and female friends), extracurricular activity level (i.e., participation in organized sports teams, clubs, etc.), family relationship quality (i.e., cohesion and conflict), and symptoms of depression (i.e., minimal, mild, moderate/severe). Results of a forward linear regression modeling indicate that social environment components were associated with a significant proportion of the variance in adolescent depression (Adjusted R (2) = .177, p < or = .05). Specifically, adolescent females (beta = .166, p < .01) and those having more smokers in their social network (beta = .107, p < .05) presented with significantly greater depression symptoms. Conversely, adolescents who engaged in more extracurricular activities (beta = -.118, p < .05) and experienced higher quality family relationships (beta = -.368, p < .001) presented with significantly lower depressive symptoms. These findings highlight the important role that the social environment plays in adolescent depression, as well as yields new insights into socially-based intervention targets that may ameliorate adolescent depression. These intervention targets may be gender-specific, include positive social network skills training, increase adolescents' engagement in organized activities, and attend to the quality of their family relationships.

The effects of physically active leisure on stress-health relationships.

PubMed

Iwasaki, Y; Zuzanek, J; Mannell, R C

2001-01-01

In this article, the effects of physically active leisure on the relationships between stress and health are examined using structural equation modeling (SEM). The analyses are based on data from Canada's 1994 National Population Health Survey (n = 17,626). Overall, physically active leisure was found to directly contribute to higher levels of physical health and wellbeing, and lower levels of mental ill-health among Canadians. When the respondents experienced higher levels of chronic stress, life event stress, and/or work stress, involvement in physically active leisure appeared to help them maintain good health and wellbeing. Also, higher levels of participation in physically active leisure helped paid workers suppress levels of work stress. Agencies involved in health promotion and lifestyle intervention should give greater consideration to physically active leisure. As a significant component of an active lifestyle, physically active leisure can contribute to better health, and provide a valuable resource for coping with stress.

Assessment of quantitative structure-activity relationship of toxicity prediction models for Korean chemical substance control legislation

PubMed Central

Kim, Kwang-Yon; Shin, Seong Eun; No, Kyoung Tai

2015-01-01

Objectives For successful adoption of legislation controlling registration and assessment of chemical substances, it is important to obtain sufficient toxicological experimental evidence and other related information. It is also essential to obtain a sufficient number of predicted risk and toxicity results. Particularly, methods used in predicting toxicities of chemical substances during acquisition of required data, ultimately become an economic method for future dealings with new substances. Although the need for such methods is gradually increasing, the-required information about reliability and applicability range has not been systematically provided. Methods There are various representative environmental and human toxicity models based on quantitative structure-activity relationships (QSAR). Here, we secured the 10 representative QSAR-based prediction models and its information that can make predictions about substances that are expected to be regulated. We used models that predict and confirm usability of the information expected to be collected and submitted according to the legislation. After collecting and evaluating each predictive model and relevant data, we prepared methods quantifying the scientific validity and reliability, which are essential conditions for using predictive models. Results We calculated predicted values for the models. Furthermore, we deduced and compared adequacies of the models using the Alternative non-testing method assessed for Registration, Evaluation, Authorization, and Restriction of Chemicals Substances scoring system, and deduced the applicability domains for each model. Additionally, we calculated and compared inclusion rates of substances expected to be regulated, to confirm the applicability. Conclusions We evaluated and compared the data, adequacy, and applicability of our selected QSAR-based toxicity prediction models, and included them in a database. Based on this data, we aimed to construct a system that can be used

Improving quantitative structure-activity relationship models using Artificial Neural Networks trained with dropout.

PubMed

Mendenhall, Jeffrey; Meiler, Jens

2016-02-01

Dropout is an Artificial Neural Network (ANN) training technique that has been shown to improve ANN performance across canonical machine learning (ML) datasets. Quantitative Structure Activity Relationship (QSAR) datasets used to relate chemical structure to biological activity in Ligand-Based Computer-Aided Drug Discovery pose unique challenges for ML techniques, such as heavily biased dataset composition, and relatively large number of descriptors relative to the number of actives. To test the hypothesis that dropout also improves QSAR ANNs, we conduct a benchmark on nine large QSAR datasets. Use of dropout improved both enrichment false positive rate and log-scaled area under the receiver-operating characteristic curve (logAUC) by 22-46 % over conventional ANN implementations. Optimal dropout rates are found to be a function of the signal-to-noise ratio of the descriptor set, and relatively independent of the dataset. Dropout ANNs with 2D and 3D autocorrelation descriptors outperform conventional ANNs as well as optimized fingerprint similarity search methods.

Improving Quantitative Structure-Activity Relationship Models using Artificial Neural Networks Trained with Dropout

PubMed Central

Mendenhall, Jeffrey; Meiler, Jens

2016-01-01

Dropout is an Artificial Neural Network (ANN) training technique that has been shown to improve ANN performance across canonical machine learning (ML) datasets. Quantitative Structure Activity Relationship (QSAR) datasets used to relate chemical structure to biological activity in Ligand-Based Computer-Aided Drug Discovery (LB-CADD) pose unique challenges for ML techniques, such as heavily biased dataset composition, and relatively large number of descriptors relative to the number of actives. To test the hypothesis that dropout also improves QSAR ANNs, we conduct a benchmark on nine large QSAR datasets. Use of dropout improved both Enrichment false positive rate (FPR) and log-scaled area under the receiver-operating characteristic curve (logAUC) by 22–46% over conventional ANN implementations. Optimal dropout rates are found to be a function of the signal-to-noise ratio of the descriptor set, and relatively independent of the dataset. Dropout ANNs with 2D and 3D autocorrelation descriptors outperform conventional ANNs as well as optimized fingerprint similarity search methods. PMID:26830599

The Relationship Between Approach to Activity Engagement, Specific Aspects of Physical Function, and Pain Duration in Chronic Pain.

PubMed

Andrews, Nicole E; Strong, Jenny; Meredith, Pamela J

2016-01-01

To examine: (1) the relationships between habitual approach to activity engagement and specific aspects of physical functioning in chronic pain; and (2) whether or not these relationships differ according to pain duration. Outpatients (N=169) with generalized chronic pain completed a set of written questionnaires. Categories of "approach to activity engagement" were created using the confronting and avoidance subscales of the Pain and Activity Relations Questionnaire. An interaction term between "approach to activity engagement" categories and pain duration was entered into analysis with age, sex, pain intensity, the categorical "approach to activity engagement" variable, and pain duration, in 9 ordinal regression models investigating functioning in a variety of daily activities. The "approach to activity engagement" category predicted the personal care, lifting, sleeping, social life, and traveling aspects of physical functioning but, interestingly, not the performance skills used during these activities, that is, walking, sitting, and standing. The interaction term was significant in 2 models; however, the effect of pain duration on associations was the inverse of that theorized, with the relationship between variables becoming less pronounced with increasing duration of pain. The results of this study do not support the commonly held notion that avoidance and/or overactivity behavior leads to deconditioning and reduced physical capacity over time. Findings do, however, suggest that a relationship exists between avoidance and/or overactivity behavior and reduced participation in activities. Implications for the clinical management of chronic pain and directions for further research are discussed.

Irreversible Inhibition of EGFR: Modeling the Combined Pharmacokinetic-Pharmacodynamic Relationship of Osimertinib and Its Active Metabolite AZ5104.

PubMed

Yates, James W T; Ashton, Susan; Cross, Darren; Mellor, Martine J; Powell, Steve J; Ballard, Peter

2016-10-01

Osimertinib (AZD9291) is a potent, selective, irreversible inhibitor of EGFR-sensitizing (exon 19 and L858R) and T790M-resistant mutation. In vivo, in the mouse, it is metabolized to an active des-methyl metabolite, AZ5104. To understand the therapeutic potential in patients, this study aimed to assess the relationship between osimertinib pharmacokinetics, the pharmacokinetics of the active metabolite, the pharmacodynamics of phosphorylated EGFR reduction, and efficacy in mouse xenograft models of EGFR-driven cancers, including two NSCLC lines. Osimertinib was dosed in xenografted models of EGFR-driven cancers. In one set of experiments, changes in phosphorylated EGFR were measured to confirm target engagement. In a second set of efficacy studies, the resulting changes in tumor volume over time after repeat dosing of osimertinib were observed. To account for the contributions of both molecules, a mathematical modeling approach was taken to integrate the resulting datasets. The model was able to describe the pharmacokinetics, pharmacodynamics, and efficacy in A431, PC9, and NCI-H1975 xenografts, with the differences in sensitivity described by the varying potency against wild-type, sensitizing, and T790M-mutant EGFR and the phosphorylated EGFR reduction required to reduce tumor volume. It was inferred that recovery of pEGFR is slower after chronic dosing due to reduced resynthesis. It was predicted and further demonstrated that although inhibition is irreversible, the resynthesis of EGFR is such that infrequent intermittent dosing is not as efficacious as once daily dosing. Mol Cancer Ther; 15(10); 2378-87. ©2016 AACR. ©2016 American Association for Cancer Research.

Investigation on Quantitative Structure Activity Relationships of a Series of Inducible Nitric Oxide.

PubMed

Sharma, Mukesh C; Sharma, S

2016-12-01

A series of 2-dihydro-4-quinazolin with potent highly selective inhibitors of inducible nitric oxide synthase activities was subjected to quantitative structure activity relationships (QSAR) analysis. Statistically significant equations with high correlation coefficient (r 2  = 0.8219) were developed. The k-nearest neighbor model has showed good cross-validated correlation coefficient and external validation values of 0.7866 and 0.7133, respectively. The selected electrostatic field descriptors the presence of blue ball around R1 and R4 in the quinazolinamine moiety showed electronegative groups favorable for nitric oxide synthase activity. The QSAR models may lead to the structural requirements of inducible nitric oxide compounds and help in the design of new compounds.

Lacosamide derivatives with anticonvulsant activity as carbonic anhydrase inhibitors. Molecular modeling, docking and QSAR analysis.

PubMed

Garro Martinez, Juan C; Vega-Hissi, Esteban G; Andrada, Matías F; Duchowicz, Pablo R; Torrens, Francisco; Estrada, Mario R

2014-01-01

Lacosamide is an anticonvulsant drug which presents carbonic anhydrase inhibition. In this paper, we analyzed the apparent relationship between both activities performing a molecular modeling, docking and QSAR studies on 18 lacosamide derivatives with known anticonvulsant activity. Docking results suggested the zinc-binding site of carbonic anhydrase is a possible target of lacosamide and lacosamide derivatives making favorable Van der Waals interactions with Asn67, Gln92, Phe131 and Thr200. The mathematical models revealed a poor relationship between the anticonvulsant activity and molecular descriptors obtained from DFT and docking calculations. However, a QSAR model was developed using Dragon software descriptors. The statistic parameters of the model are: correlation coefficient, R=0.957 and standard deviation, S=0.162. Our results provide new valuable information regarding the relationship between both activities and contribute important insights into the essential molecular requirements for the anticonvulsant activity.

3D-quantitative structure-activity relationship studies on benzothiadiazepine hydroxamates as inhibitors of tumor necrosis factor-alpha converting enzyme.

PubMed

Murumkar, Prashant R; Giridhar, Rajani; Yadav, Mange Ram

2008-04-01

A set of 29 benzothiadiazepine hydroxamates having selective tumor necrosis factor-alpha converting enzyme inhibitory activity were used to compare the quality and predictive power of 3D-quantitative structure-activity relationship, comparative molecular field analysis, and comparative molecular similarity indices models for the atom-based, centroid/atom-based, data-based, and docked conformer-based alignment. Removal of two outliers from the initial training set of molecules improved the predictivity of models. Among the 3D-quantitative structure-activity relationship models developed using the above four alignments, the database alignment provided the optimal predictive comparative molecular field analysis model for the training set with cross-validated r(2) (q(2)) = 0.510, non-cross-validated r(2) = 0.972, standard error of estimates (s) = 0.098, and F = 215.44 and the optimal comparative molecular similarity indices model with cross-validated r(2) (q(2)) = 0.556, non-cross-validated r(2) = 0.946, standard error of estimates (s) = 0.163, and F = 99.785. These models also showed the best test set prediction for six compounds with predictive r(2) values of 0.460 and 0.535, respectively. The contour maps obtained from 3D-quantitative structure-activity relationship studies were appraised for activity trends for the molecules analyzed. The comparative molecular similarity indices models exhibited good external predictivity as compared with that of comparative molecular field analysis models. The data generated from the present study helped us to further design and report some novel and potent tumor necrosis factor-alpha converting enzyme inhibitors.

Exploring Third-Grade Student Model-Based Explanations about Plant Relationships within an Ecosystem

NASA Astrophysics Data System (ADS)

Zangori, Laura; Forbes, Cory T.

2015-12-01

Elementary students should have opportunities to develop scientific models to reason and build understanding about how and why plants depend on relationships within an ecosystem for growth and survival. However, scientific modeling practices are rarely included within elementary science learning environments and disciplinary content is often treated as discrete pieces separate from scientific practice. Elementary students have few, if any, opportunities to reason about how individual organisms, such as plants, hold critical relationships with their surrounding environment. The purpose of this design-based research study is to build a learning performance to identify and explore the third-grade students' baseline understanding of and their reasoning about plant-ecosystem relationships when engaged in the practices of modeling. The developed learning performance integrated scientific content and core scientific activity to identify and measure how students build knowledge about the role of plants in ecosystems through the practices of modeling. Our findings indicate that the third-grade students' ideas about plant growth include abiotic and biotic relationships. Further, they used their models to reason about how and why these relationships were necessary to maintain plant stasis. However, while the majority of the third-grade students were able to identify and reason about plant-abiotic relationships, a much smaller group reasoned about plant-abiotic-animal relationships. Implications from the study suggest that modeling serves as a tool to support elementary students in reasoning about system relationships, but they require greater curricular and instructional support in conceptualizing how and why ecosystem relationships are necessary for plant growth and development. This paper is based on data from a doctoral dissertation. An earlier version of this paper was presented at the 2015 international conference for the National Association for Research in Science

Understanding Activity Engagement Across Weekdays and Weekend Days: A Multivariate Multiple Discrete-Continuous Modeling Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garikapati, Venu; Astroza, Sebastian; Bhat, Prerna C.

This paper is motivated by the increasing recognition that modeling activity-travel demand for a single day of the week, as is done in virtually all travel forecasting models, may be inadequate in capturing underlying processes that govern activity-travel scheduling behavior. The considerable variability in daily travel suggests that there are important complementary relationships and competing tradeoffs involved in scheduling and allocating time to various activities across days of the week. Both limited survey data availability and methodological challenges in modeling week-long activity-travel schedules have precluded the development of multi-day activity-travel demand models. With passive and technology-based data collection methods increasinglymore » in vogue, the collection of multi-day travel data may become increasingly commonplace in the years ahead. This paper addresses the methodological challenge associated with modeling multi-day activity-travel demand by formulating a multivariate multiple discrete-continuous probit (MDCP) model system. The comprehensive framework ties together two MDCP model components, one corresponding to weekday time allocation and the other to weekend activity-time allocation. By tying the two MDCP components together, the model system also captures relationships in activity-time allocation between weekdays on the one hand and weekend days on the other. Model estimation on a week-long travel diary data set from the United Kingdom shows that there are significant inter-relationships between weekdays and weekend days in activity-travel scheduling behavior. The model system presented in this paper may serve as a higher-level multi-day activity scheduler in conjunction with existing daily activity-based travel models.« less

Design, synthesis and exploring the quantitative structure-activity relationship of some antioxidant flavonoid analogues.

PubMed

Das, Sreeparna; Mitra, Indrani; Batuta, Shaikh; Niharul Alam, Md; Roy, Kunal; Begum, Naznin Ara

2014-11-01

A series of flavonoid analogues were synthesized and screened for the in vitro antioxidant activity through their ability to quench 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical. The activity of these compounds, measured in comparison to the well-known standard antioxidants (29-32), their precursors (38-42) and other bioactive moieties (38-42) resembling partially the flavone skeleton was analyzed further to develop Quantitative Structure-Activity Relationship (QSAR) models using the Genetic Function Approximation (GFA) technique. Based on the essential structural requirements predicted by the QSAR models, some analogues were designed, synthesized and tested for activity. The predicted and experimental activities of these compounds were well correlated. Flavone analogue 20 was found to be the most potent antioxidant. Copyright © 2014 Elsevier Ltd. All rights reserved.

Possible relationships between solar activity and meteorological phenomena

NASA Technical Reports Server (NTRS)

Bandeen, W. R. (Editor); Maran, S. P. (Editor)

1975-01-01

A symposium was conducted in which the following questions were discussed: (1) the evidence concerning possible relationships between solar activity and meteorological phenomena; (2) plausible physical mechanisms to explain these relationships; and (3) kinds of critical measurements needed to determine the nature of solar/meteorological relationships and/or the mechanisms to explain them, and which of these measurements can be accomplished best from space.

Augmented multivariate image analysis applied to quantitative structure-activity relationship modeling of the phytotoxicities of benzoxazinone herbicides and related compounds on problematic weeds.

PubMed

Freitas, Mirlaine R; Matias, Stella V B G; Macedo, Renato L G; Freitas, Matheus P; Venturin, Nelson

2013-09-11

Two of major weeds affecting cereal crops worldwide are Avena fatua L. (wild oat) and Lolium rigidum Gaud. (rigid ryegrass). Thus, development of new herbicides against these weeds is required; in line with this, benzoxazinones, their degradation products, and analogues have been shown to be important allelochemicals and natural herbicides. Despite earlier structure-activity studies demonstrating that hydrophobicity (log P) of aminophenoxazines correlates to phytotoxicity, our findings for a series of benzoxazinone derivatives do not show any relationship between phytotoxicity and log P nor with other two usual molecular descriptors. On the other hand, a quantitative structure-activity relationship (QSAR) analysis based on molecular graphs representing structural shape, atomic sizes, and colors to encode other atomic properties performed very accurately for the prediction of phytotoxicities of these compounds against wild oat and rigid ryegrass. Therefore, these QSAR models can be used to estimate the phytotoxicity of new congeners of benzoxazinone herbicides toward A. fatua L. and L. rigidum Gaud.

Personality, relationship conflict, and teamwork-related mental models.

PubMed

Vîrgă, Delia; Curşeu, Petru Lucian; CurŞeu, Petru Lucian; Maricuţoiu, Laurenţiu; Sava, Florin A; Macsinga, Irina; Măgurean, Silvia

2014-01-01

This study seeks to explore whether neuroticism, agreeableness, and conscientiousness moderate the influence of relationship conflict experienced in groups on changes in group members' evaluative cognitions related to teamwork quality (teamwork-related mental models). Data from 216 students, nested in 48 groups were analyzed using a multilevel modeling approach. Our results show that the experience of relationship conflict leads to a negative shift from the pre-task to the post-task teamwork-related mental models. Moreover, the results indicate that conscientiousness buffered the negative association between relationship conflict and the change in teamwork-related mental models. Our results did not support the hypothesized moderating effect of agreeableness and show that the detrimental effect of relationship conflict on the shift in teamwork-related mental models is accentuated for group members scoring low rather than high on neuroticism. These findings open new research venues for exploring the association between personality, coping styles and change in teamwork-related mental models.

Personality, Relationship Conflict, and Teamwork-Related Mental Models

PubMed Central

Vîrgă, Delia; CurŞeu, Petru Lucian; Maricuţoiu, Laurenţiu; Sava, Florin A.; Macsinga, Irina; Măgurean, Silvia

2014-01-01

This study seeks to explore whether neuroticism, agreeableness, and conscientiousness moderate the influence of relationship conflict experienced in groups on changes in group members' evaluative cognitions related to teamwork quality (teamwork-related mental models). Data from 216 students, nested in 48 groups were analyzed using a multilevel modeling approach. Our results show that the experience of relationship conflict leads to a negative shift from the pre-task to the post-task teamwork-related mental models. Moreover, the results indicate that conscientiousness buffered the negative association between relationship conflict and the change in teamwork-related mental models. Our results did not support the hypothesized moderating effect of agreeableness and show that the detrimental effect of relationship conflict on the shift in teamwork-related mental models is accentuated for group members scoring low rather than high on neuroticism. These findings open new research venues for exploring the association between personality, coping styles and change in teamwork-related mental models. PMID:25372143

A test of an expert-based bird-habitat relationship model in South Carolina

Treesearch

John C. Kilgo; David L. Gartner; Brian R. Chapman; John B. Dunnin; Kathleen E. Franzreb; Sidney A. Gauthreaux; Cathryn H. Greenberg; Douglas J. Levey; Karl V. Miller; Scott F. Pearson

2002-01-01

Wildlife-habitat relationships models are used widely by land managers to provide information on which species are likely to occur in an area of interest and may be impacted by a proposed management activity. Few such models have been tested. We used recent avian census data from the Savannah River Site, South Carolina to validate BIRDHAB, a geographic information...

Prediction-error in the context of real social relationships modulates reward system activity.

PubMed

Poore, Joshua C; Pfeifer, Jennifer H; Berkman, Elliot T; Inagaki, Tristen K; Welborn, Benjamin L; Lieberman, Matthew D

2012-01-01

The human reward system is sensitive to both social (e.g., validation) and non-social rewards (e.g., money) and is likely integral for relationship development and reputation building. However, data is sparse on the question of whether implicit social reward processing meaningfully contributes to explicit social representations such as trust and attachment security in pre-existing relationships. This event-related fMRI experiment examined reward system prediction-error activity in response to a potent social reward-social validation-and this activity's relation to both attachment security and trust in the context of real romantic relationships. During the experiment, participants' expectations for their romantic partners' positive regard of them were confirmed (validated) or violated, in either positive or negative directions. Primary analyses were conducted using predefined regions of interest, the locations of which were taken from previously published research. Results indicate that activity for mid-brain and striatal reward system regions of interest was modulated by social reward expectation violation in ways consistent with prior research on reward prediction-error. Additionally, activity in the striatum during viewing of disconfirmatory information was associated with both increases in post-scan reports of attachment anxiety and decreases in post-scan trust, a finding that follows directly from representational models of attachment and trust.

In vitro-in vivo activity relationship of substituted benzimidazole cell division inhibitors with activity against Mycobacteria tuberculosis

PubMed Central

Knudson, Susan E.; Kumar, Kunal; Awasthi, Divya; Ojima, Iwao; Slayden, Richard A.

2014-01-01

Structure based drug design was used to develop a compound library of novel 2,5,6- and 2,5,7-trisubstituted benzimidazoles. Three structural analogs, SB-P1G10, SB-P8B2 and SB-P3G2 were selected from this library based on previous studies for advanced study. In vitro studies revealed that SB-P8B2 and SB-P3G2 had sigmoidal kill-curves while in contrast SB-P1G10 showed a narrow zonal susceptibility. The in vitro studies also demonstrated that exposure to SB-P8B2 or SB-P3G2 was bactericidal, while SB-P1G10 treatment never resulted in complete killing. The dose curves for the three compounds against clinical isolates were comparable to their respective dose curves in the laboratory strain of M. tuberculosis. SB-P8B2 and SB-P3G2 exhibited antibacterial activity against non-replicating bacilli under low oxygen conditions. SB-P3G2 and SB-P1G10 were assessed in acute short-term animal models of tuberculosis, which showed that SB-P3G2 treatment demonstrated activity against M. tuberculosis. Together, these studies reveal an in vitro- in vivo relationship of the 2,5,6-trisubstituted benzimidazoles that serves as a criterion for advancing this class of cell division inhibitors into more resource intensive in vivo efficacy models such as the long-term murine model of tuberculosis and Pre-IND PK/PD studies. Specifically, these studies are the first demonstration of efficacy and an in vitro–in vivo activity relationship for 2,5,6-trisubstituted benzimidazoles. The in vivo activity presented in this manuscript substantiates this class of cell division inhibitors as having potency and efficacy against M. tuberculosis. PMID:24746463

Development of a Conceptual Model for Smoking Cessation: Physical Activity, Neurocognition, and Executive Functioning.

PubMed

Loprinzi, Paul D; Herod, Skyla M; Walker, Jerome F; Cardinal, Bradley J; Mahoney, Sara E; Kane, Christy

2015-01-01

Considerable research has shown adverse neurobiological effects of chronic alcohol use, including long-term and potentially permanent changes in the structure and function of the brain; however, much less is known about the neurobiological consequences of chronic smoking, as it has largely been ignored until recently. In this article, we present a conceptual model proposing the effects of smoking on neurocognition and the role that physical activity may play in this relationship as well as its role in smoking cessation. Pertinent published peer-reviewed articles deposited in PubMed delineating the pathways in the proposed model were reviewed. The proposed model, which is supported by emerging research, demonstrates a bidirectional relationship between smoking and executive functioning. In support of our conceptual model, physical activity may moderate this relationship and indirectly influence smoking behavior through physical activity-induced changes in executive functioning. Our model may have implications for aiding smoking cessation efforts through the promotion of physical activity as a mechanism for preventing smoking-induced deficits in neurocognition and executive function.

Modelling the vicious circle between obesity and physical activity in children and adolescents using a bivariate probit model with endogenous regressors.

PubMed

Yeh, C-Y; Chen, L-J; Ku, P-W; Chen, C-M

2015-01-01

The increasing prevalence of obesity in children and adolescents has become one of the most important public health issues around the world. Lack of physical activity is a risk factor for obesity, while being obese could reduce the likelihood of participating in physical activity. Failing to account for the endogeneity between obesity and physical activity would result in biased estimation. This study investigates the relationship between overweight and physical activity by taking endogeneity into consideration. It develops an endogenous bivariate probit model estimated by the maximum likelihood method. The data included 4008 boys and 4197 girls in the 5th-9th grades in Taiwan in 2007-2008. The relationship between overweight and physical activity is significantly negative in the endogenous model, but insignificant in the comparative exogenous model. This endogenous relationship presents a vicious circle in which lower levels of physical activity lead to overweight, while those who are already overweight engage in less physical activity. The results not only reveal the importance of endogenous treatment, but also demonstrate the robust negative relationship between these two factors. An emphasis should be put on overweight and obese children and adolescents in order to break the vicious circle. Promotion of physical activity by appropriate counselling programmes and peer support could be effective in reducing the prevalence of obesity in children and adolescents.

49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Activity-mass relationships for uranium and....434 Activity-mass relationships for uranium and natural thorium. The table of activity-mass relationships for uranium and natural thorium are as follows: Thorium and uranium enrichment 1(Wt% 235 U present...

49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 2 2012-10-01 2012-10-01 false Activity-mass relationships for uranium and....434 Activity-mass relationships for uranium and natural thorium. The table of activity-mass relationships for uranium and natural thorium are as follows: Thorium and uranium enrichment 1(Wt% 235 U present...

49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Activity-mass relationships for uranium and....434 Activity-mass relationships for uranium and natural thorium. The table of activity-mass relationships for uranium and natural thorium are as follows: Thorium and uranium enrichment 1(Wt% 235 U present...

Supplier Relationship Management: Models, Considerations and Implications for DOD

DTIC Science & Technology

2003-01-01

AY 2002-2003 SUPPLIER RELATIONSHIP MANAGEMENT : MODELS, CONSIDERATIONS AND IMPLICATIONS FOR DOD STRATEGIC SUPPLY INDUSTRY STUDY COURSE COLONEL TOM...REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Supplier Relationship Management : Models, Considerations and Implications for DOD...nature of the market or industry drive differences in supplier relationships ? This paper begins by defining supplier relationship management (SRM) and why

Evaluation of analgesic and anti-inflammatory activities of Rubia cordifolia L. by spectrum-effect relationships.

PubMed

Shen, Cai-Hong; Liu, Cui-Ting; Song, Xiao-Juan; Zeng, Wei-Ya; Lu, Xiao-Ying; Zheng, Zuo-Liang; Jie-Pan; Zhan, Ruo-Ting; Ping-Yan

2018-07-15

The objective of the current work was to evaluate the spectrum-effect relationships between high-performance liquid chromatography fingerprints and analgesic and anti-inflammatory effects of Rubia cordifolia L. extract (RCE), and to identify active components of RCE. Chemical fingerprints of ten batches of RC from various sources were obtained by HPLC, and similarity and hierarchical clustering analyses were carried out. Pharmacodynamic assays were performed in adjuvant-induced arthritis rat model to assess the analgesic and anti-inflammatory properties of RCE. The spectrum-effect relationships between chemical fingerprints and the analgesic and anti-inflammatory effects of RCE were established by gray correlation analysis. UPLC-ESI-MS was used to identify the structures of potential active components, by reference standards comparison. The results showed that a close correlation existed between chemical fingerprints with analgesic and anti-inflammatory activities, and alizarin, 6-hydroxyrubiadin, purpurin and rubiadin might be the active constituents of RCE. In addition, RCE attenuated pathological changes in adjuvant-induced arthritis. The current findings provide a strong basis for combining chemical fingerprints with analgesic and anti-inflammatory activities in assessing the spectrum-effect relationships of RCE. Copyright © 2018. Published by Elsevier B.V.

A Generic Model of Dyadic Social Relationships

PubMed Central

Favre, Maroussia; Sornette, Didier

2015-01-01

We introduce a model of dyadic social interactions and establish its correspondence with relational models theory (RMT), a theory of human social relationships. RMT posits four elementary models of relationships governing human interactions, singly or in combination: Communal Sharing, Authority Ranking, Equality Matching, and Market Pricing. To these are added the limiting cases of asocial and null interactions, whereby people do not coordinate with reference to any shared principle. Our model is rooted in the observation that each individual in a dyadic interaction can do either the same thing as the other individual, a different thing or nothing at all. To represent these three possibilities, we consider two individuals that can each act in one out of three ways toward the other: perform a social action X or Y, or alternatively do nothing. We demonstrate that the relationships generated by this model aggregate into six exhaustive and disjoint categories. We propose that four of these categories match the four relational models, while the remaining two correspond to the asocial and null interactions defined in RMT. We generalize our results to the presence of N social actions. We infer that the four relational models form an exhaustive set of all possible dyadic relationships based on social coordination. Hence, we contribute to RMT by offering an answer to the question of why there could exist just four relational models. In addition, we discuss how to use our representation to analyze data sets of dyadic social interactions, and how social actions may be valued and matched by the agents. PMID:25826403

30-year Dynamics of Terrestrial Vegetation Activity and the Relationship with Climatologies

NASA Astrophysics Data System (ADS)

de Jong, R.; Schaepman, M. E.; Furrer, R.; de Bruin, S.; Verburg, P. H.

2013-12-01

The climate governs the seasonal activity of terrestrial vegetation while humankind influences it. The relative role of these drivers in changing vegetation activity is crucial information for accurate modeling of vegetation and climate dynamics and for adaptation and mitigation strategies. Disentangling the two, however, is an ongoing scientific challenge, because of limited data availability, mainly regarding non-climatic drivers, and complex biosphere-atmosphere feedback mechanisms. Here, we contribute to this quest by modeling the spatial relationship between climatologies and changes in global vegetation activity (de Jong et al., 2013a). Vegetation activity is commonly quantified using remotely sensed vegetation indices (VI). Extensive reports on temporal trends over the past decades in time series of such indices can be found in literature, including the detection of shifts (de Jong et al., 2013b), which may be related to climate (e.g. Zhao & Running, 2010). However, little remains known about the exact processes underlying vegetation change at large spatial scales. Depending on eco-region, three climatologies potentially constrain plant growth (Churkina and Running, 1998). In the humid mid-latitudes, for example, temperature is the largest influencing factor; in (semi) arid regions it is the availability of water and in the tropics incident solar radiation. Based on this logic, we developed a mixed-effect model to relate changes in these climatologies to changes in vegetation activity and to quantify the spatial process underlying the other drivers, including human land use. Little over 50% of the spatial variation in vegetation change could be attributed to changes in climatologies; conspicuously, many of the global ';greening' trends and the ';browning' hotspots in Argentina and Australia. Browning hotspots in the non-climatic component were especially located in subequatorial Africa (e.g. parts of Zimbabwe and Tanzania), where human drivers may be

Comparative analysis of predictive models for nongenotoxic hepatocarcinogenicity using both toxicogenomics and quantitative structure-activity relationships.

PubMed

Liu, Zhichao; Kelly, Reagan; Fang, Hong; Ding, Don; Tong, Weida

2011-07-18

The primary testing strategy to identify nongenotoxic carcinogens largely relies on the 2-year rodent bioassay, which is time-consuming and labor-intensive. There is an increasing effort to develop alternative approaches to prioritize the chemicals for, supplement, or even replace the cancer bioassay. In silico approaches based on quantitative structure-activity relationships (QSAR) are rapid and inexpensive and thus have been investigated for such purposes. A slightly more expensive approach based on short-term animal studies with toxicogenomics (TGx) represents another attractive option for this application. Thus, the primary questions are how much better predictive performance using short-term TGx models can be achieved compared to that of QSAR models, and what length of exposure is sufficient for high quality prediction based on TGx. In this study, we developed predictive models for rodent liver carcinogenicity using gene expression data generated from short-term animal models at different time points and QSAR. The study was focused on the prediction of nongenotoxic carcinogenicity since the genotoxic chemicals can be inexpensively removed from further development using various in vitro assays individually or in combination. We identified 62 chemicals whose hepatocarcinogenic potential was available from the National Center for Toxicological Research liver cancer database (NCTRlcdb). The gene expression profiles of liver tissue obtained from rats treated with these chemicals at different time points (1 day, 3 days, and 5 days) are available from the Gene Expression Omnibus (GEO) database. Both TGx and QSAR models were developed on the basis of the same set of chemicals using the same modeling approach, a nearest-centroid method with a minimum redundancy and maximum relevancy-based feature selection with performance assessed using compound-based 5-fold cross-validation. We found that the TGx models outperformed QSAR in every aspect of modeling. For example, the

Applications of genetic algorithms on the structure-activity relationship analysis of some cinnamamides.

PubMed

Hou, T J; Wang, J M; Liao, N; Xu, X J

1999-01-01

Quantitative structure-activity relationships (QSARs) for 35 cinnamamides were studied. By using a genetic algorithm (GA), a group of multiple regression models with high fitness scores was generated. From the statistical analyses of the descriptors used in the evolution procedure, the principal features affecting the anticonvulsant activity were found. The significant descriptors include the partition coefficient, the molar refraction, the Hammet sigma constant of the substituents on the benzene ring, and the formation energy of the molecules. It could be found that the steric complementarity and the hydrophobic interaction between the inhibitors and the receptor were very important to the biological activity, while the contribution of the electronic effect was not so obvious. Moreover, by construction of the spline models for these four principal descriptors, the effective range for each descriptor was identified.

Physical activity and fatigue in breast cancer survivors: a panel model examining the role of self-efficacy and depression.

PubMed

Phillips, Siobhan M; McAuley, Edward

2013-05-01

Physical activity is associated with reductions in fatigue in breast cancer survivors. However, mechanisms underlying this relationship are not well-understood. The purpose of this study was to longitudinally test a model examining the role of self-efficacy and depression as potential mediators of the relationship between physical activity and fatigue in a sample of breast cancer survivors using both self-report and objective measures of physical activity. All participants (N = 1,527) completed self-report measures of physical activity, self-efficacy, depression, and fatigue at baseline and 6 months. A subsample was randomly selected to wear an accelerometer at both time points. It was hypothesized that physical activity indirectly influences fatigue via self-efficacy and depression. Relationships among model constructs were examined over the 6-month period using panel analysis within a covariance modeling framework. The hypothesized model provided a good model-data fit (χ(2) = 599.66, df = 105, P ≤ 0.001; CFI = 0.96; SRMR = 0.02) in the full sample when controlling for covariates. At baseline, physical activity indirectly influenced fatigue via self-efficacy and depression. These relationships were also supported across time. In addition, the majority of the hypothesized relationships were supported in the subsample with accelerometer data (χ(2) = 387.48, df = 147, P ≤ 0.001, CFI = 0.94, SRMR = 0.04). This study provides evidence to suggest the relationship between physical activity and fatigue in breast cancer survivors may be mediated by more proximal, modifiable outcomes of physical activity participation. Recommendations are made relative to future applications and research concerning these relationships.

Relationships between coordination, active drag and propelling efficiency in crawl.

PubMed

Seifert, Ludovic; Schnitzler, Christophe; Bideault, Gautier; Alberty, Morgan; Chollet, Didier; Toussaint, Huub Martin

2015-02-01

This study examines the relationships between the index of coordination (IdC) and active drag (D) assuming that at constant average speed, average drag equals average propulsion. The relationship between IdC and propulsive efficiency (ep) was also investigated at maximal speed. Twenty national swimmers completed two incremental speed tests swimming front crawl with arms only in free condition and using a measurement of active drag system. Each test was composed of eight 25-m bouts from 60% to 100% of maximal intensity whereby each lap was swum at constant speed. Different regression models were tested to analyse IdC-D relationship. Correlation between IdC and ep was calculated. IdC was linked to D by linear regression (IdC=0.246·D-27.06; R(2)=0.88, P<.05); swimmers switched from catch-up to superposition coordination mode at a speed of ∼1.55ms(-1) where average D is ∼110N. No correlation between IdC and ep at maximal speed was found. The intra-individual analysis revealed that coordination plays an important role in scaling propulsive forces with higher speed levels such that these are adapted to aquatic resistance. Inter-individual analysis showed that high IdC did not relate to a high ep suggesting an individual optimization of force and power generation is at play to reach high speeds. Copyright © 2014 Elsevier B.V. All rights reserved.

Dynamic causal modelling of brain-behaviour relationships.

PubMed

Rigoux, L; Daunizeau, J

2015-08-15

In this work, we expose a mathematical treatment of brain-behaviour relationships, which we coin behavioural Dynamic Causal Modelling or bDCM. This approach aims at decomposing the brain's transformation of stimuli into behavioural outcomes, in terms of the relative contribution of brain regions and their connections. In brief, bDCM places the brain at the interplay between stimulus and behaviour: behavioural outcomes arise from coordinated activity in (hidden) neural networks, whose dynamics are driven by experimental inputs. Estimating neural parameters that control network connectivity and plasticity effectively performs a neurobiologically-constrained approximation to the brain's input-outcome transform. In other words, neuroimaging data essentially serves to enforce the realism of bDCM's decomposition of input-output relationships. In addition, post-hoc artificial lesions analyses allow us to predict induced behavioural deficits and quantify the importance of network features for funnelling input-output relationships. This is important, because this enables one to bridge the gap with neuropsychological studies of brain-damaged patients. We demonstrate the face validity of the approach using Monte-Carlo simulations, and its predictive validity using empirical fMRI/behavioural data from an inhibitory control task. Lastly, we discuss promising applications of this work, including the assessment of functional degeneracy (in the healthy brain) and the prediction of functional recovery after lesions (in neurological patients). Copyright © 2015 Elsevier Inc. All rights reserved.

Relationships among measures of physical activity and hearing in African Americans: The Jackson Heart Study.

PubMed

Haas, Patrick J; Bishop, Charles E; Gao, Yan; Griswold, Michael E; Schweinfurth, John M

2016-10-01

To evaluate the relationships among measures of physical activity and hearing in the Jackson Heart Study. Prospective cohort study. We assessed hearing on 1,221 Jackson Heart Study participants who also had validated physical activity questionnaire data on file. Hearing thresholds were measured across frequency octaves from 250 to 8,000 Hz, and various frequency pure-tone averages (PTAs) were constructed, including PTA4 (average of 500, 1,000, 2,000, and 4,000 Hz), PTA-high (average of 4,000 and 8,000 Hz), PTA-mid (average of 1,000 and 2,000 Hz), and PTA-low (average of 250 and 500 Hz). Hearing loss was defined for pure tones and pure-tone averages as >25 dB HL in either ear and averaged between the ears. Associations between physical activity and hearing were estimated using linear regression, reporting changes in decibel hearing level, and logistic regression, reporting odds ratios (OR) of hearing loss. Physical activity exhibited a statistically significant but small inverse relationship with PTA4, -0.20 dB HL per doubling of activity (95% confidence interval [CI]: -0.35, -0.04; P = .016), as well as with PTA-low and pure tones at 250, 2,000, and 4,000 Hz in adjusted models. Multivariable logistic regression modeling supported a decrease in the odds of high-frequency hearing loss among participants who reported at least some moderate weekly physical activity (PTA-high, OR: 0.69 [95% CI: 0.52, 0.92]; P = .011 and 4000 Hz, OR: 0.75 [95% CI: 0.57, 0.99]; P = .044). Our study provides further evidence that physical activity is related to better hearing; however, the clinical significance of this relationship cannot be estimated given the nature of the cross-sectional study design. 2b Laryngoscope, 126:2376-2381, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

PubMed Central

de Araújo, Rodrigo S. A.; Guerra, Felipe Q. S.; de O. Lima, Edeltrudes; de Simone, Carlos A.; Tavares, Josean F.; Scotti, Luciana; Scotti, Marcus T.; de Aquino, Thiago M.; de Moura, Ricardo O.; Mendonça, Francisco J. B.; Barbosa-Filho, José M.

2013-01-01

The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 μg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO2 and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity. PMID:23306152

The emergence of the Activity Reduces Conflict Associated Strain (ARCAS) model: a test of a conditional mediation model of workplace conflict and employee strain.

PubMed

Dijkstra, Maria T M; Beersma, Bianca; Cornelissen, Roosmarijn A W M

2012-07-01

To test and extend the emerging Activity Reduces Conflict-Associated Strain (ARCAS) model, we predicted that the relationship between task conflict and employee strain would be weakened to the extent that people experience high organization-based self-esteem (OBSE). A survey among Dutch employees demonstrated that, consistent with the model, the conflict-employee strain relationship was weaker the higher employees' OBSE and the more they engaged in active problem-solving conflict management. Our data also revealed that higher levels of OBSE were related to more problem-solving conflict management. Moreover, consistent with the ARCAS model, we could confirm a conditional mediation model in which organization-based self-esteem through its relationship with problem-solving conflict management weakened the relationship between task conflict and employee strain. Potential applications of the results are discussed.

A Probabilistic Model of Phonological Relationships from Contrast to Allophony

ERIC Educational Resources Information Center

Hall, Kathleen Currie

2009-01-01

This dissertation proposes a model of phonological relationships, the Probabilistic Phonological Relationship Model (PPRM), that quantifies how predictably distributed two sounds in a relationship are. It builds on a core premise of traditional phonological analysis, that the ability to define phonological relationships such as contrast and…

Structure—activity relationships for insecticidal carbamates*

PubMed Central

Metcalf, Robert L.

1971-01-01

Carbamate insecticides are biologically active because of their structural complementarity to the active site of acetylcholinesterase (AChE) and their consequent action as substrates with very low turnover numbers. Carbamates behave as synthetic neurohormones that produce their toxic action by interrupting the normal action of AChE so that acetylcholine accumulates at synaptic junctions. The necessary properties for a suitable insecticidal carbamate are lipid solubility, suitable structural complementarity to AChE, and sufficient stability to multifunction-oxidase detoxification. The relationships between the structure and the activity of a large number of synthetic carbamates are analysed in detail, with particular attention to the second of these properties. PMID:5315358

Investigating the Relationship between Students' Views of Scientific Models and Their Development of Models

ERIC Educational Resources Information Center

Cheng, Meng-Fei; Lin, Jang-Long

2015-01-01

Understanding the nature of models and engaging in modeling practice have been emphasized in science education. However, few studies discuss the relationships between students' views of scientific models and their ability to develop those models. Hence, this study explores the relationship between students' views of scientific models and their…

A New Structure-Activity Relationship (SAR) Model for Predicting Drug-Induced Liver Injury, Based on Statistical and Expert-Based Structural Alerts

PubMed Central

Pizzo, Fabiola; Lombardo, Anna; Manganaro, Alberto; Benfenati, Emilio

2016-01-01

The prompt identification of chemical molecules with potential effects on liver may help in drug discovery and in raising the levels of protection for human health. Besides in vitro approaches, computational methods in toxicology are drawing attention. We built a structure-activity relationship (SAR) model for evaluating hepatotoxicity. After compiling a data set of 950 compounds using data from the literature, we randomly split it into training (80%) and test sets (20%). We also compiled an external validation set (101 compounds) for evaluating the performance of the model. To extract structural alerts (SAs) related to hepatotoxicity and non-hepatotoxicity we used SARpy, a statistical application that automatically identifies and extracts chemical fragments related to a specific activity. We also applied the chemical grouping approach for manually identifying other SAs. We calculated accuracy, specificity, sensitivity and Matthews correlation coefficient (MCC) on the training, test and external validation sets. Considering the complexity of the endpoint, the model performed well. In the training, test and external validation sets the accuracy was respectively 81, 63, and 68%, specificity 89, 33, and 33%, sensitivity 93, 88, and 80% and MCC 0.63, 0.27, and 0.13. Since it is preferable to overestimate hepatotoxicity rather than not to recognize unsafe compounds, the model's architecture followed a conservative approach. As it was built using human data, it might be applied without any need for extrapolation from other species. This model will be freely available in the VEGA platform. PMID:27920722

Quantitative structure-activity relationship of organosulphur compounds as soybean 15-lipoxygenase inhibitors using CoMFA and CoMSIA.

PubMed

Caballero, Julio; Fernández, Michael; Coll, Deysma

2010-12-01

Three-dimensional quantitative structure-activity relationship studies were carried out on a series of 28 organosulphur compounds as 15-lipoxygenase inhibitors using comparative molecular field analysis and comparative molecular similarity indices analysis. Quantitative information on structure-activity relationships is provided for further rational development and direction of selective synthesis. All models were carried out over a training set including 22 compounds. The best comparative molecular field analysis model only included steric field and had a good Q² = 0.789. Comparative molecular similarity indices analysis overcame the comparative molecular field analysis results: the best comparative molecular similarity indices analysis model also only included steric field and had a Q² = 0.894. In addition, this model predicted adequately the compounds contained in the test set. Furthermore, plots of steric comparative molecular similarity indices analysis field allowed conclusions to be drawn for the choice of suitable inhibitors. In this sense, our model should prove useful in future 15-lipoxygenase inhibitor design studies. © 2010 John Wiley & Sons A/S.

The relationship between physical activity, meaning in life, and subjective vitality in community-dwelling older adults.

PubMed

Ju, Haewon

2017-11-01

The present study examined the potential contribution of meaning in life to the relationship between physical activity and subjective vitality in older adults. Two-hundred and fifty community-dwelling elders completed the instruments assessing physical activity, meaning in life, and subjective vitality. Results from structural equation modeling indicated that physical activity was positively associated with both meaning in life and subjective vitality. Further, the relationship between physical activity and vitality was partially mediated by meaning in life. Although previous studies have consistently found a positive impact of physical activity on vitality, the current study suggested that it is more productive to focus not only on physical activity, but also on meaning in life, in order to vitalize elders. Further, a focus on meaning in life can be a productive way to continue to vitalize older adults who are unable to engage in regular physical activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular design of anticancer drug leads based on three-dimensional quantitative structure-activity relationship.

PubMed

Huang, Xiao Yan; Shan, Zhi Jie; Zhai, Hong Lin; Li, Li Na; Zhang, Xiao Yun

2011-08-22

Heat shock protein 90 (Hsp90) takes part in the developments of several cancers. Novobiocin, a typically C-terminal inhibitor for Hsp90, will probably used as an important anticancer drug in the future. In this work, we explored the valuable information and designed new novobiocin derivatives based on a three-dimensional quantitative structure-activity relationship (3D QSAR). The comparative molecular field analysis and comparative molecular similarity indices analysis models with high predictive capability were established, and their reliabilities are supported by the statistical parameters. Based on the several important influence factors obtained from these models, six new novobiocin derivatives with higher inhibitory activities were designed and confirmed by the molecular simulation with our models, which provide the potential anticancer drug leads for further research.

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure-activity relationship.

PubMed

Wang, Hui; Jiang, Mingyue; Li, Shujun; Hse, Chung-Yun; Jin, Chunde; Sun, Fangli; Li, Zhuo

2017-09-01

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure-activity relationships (QSARs) for CAAS compounds against Aspergillus niger ( A. niger ) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models ( R 2  = 0.9346 for A. niger , R 2  = 0.9590 for P. citrinum, ) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi.

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure–activity relationship

PubMed Central

Wang, Hui; Jiang, Mingyue; Hse, Chung-Yun; Jin, Chunde; Sun, Fangli; Li, Zhuo

2017-01-01

Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure–activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were analysed. The QSAR models (R2 = 0.9346 for A. niger, R2 = 0.9590 for P. citrinum,) were constructed and validated. The models indicated that the molecular polarity and the Max atomic orbital electronic population had a significant effect on antifungal activity. Based on the best QSAR models, two new compounds were designed and synthesized. Antifungal activity tests proved that both of them have great bioactivity against the selected fungi. PMID:28989758

Development of Novel Repellents Using Structure - Activity Modeling of Compounds in the USDA Archival Database

DTIC Science & Technology

2011-01-01

used in efforts to develop QSAR models. Measurement of Repellent Efficacy Screening for Repellency of Compounds with Unknown Toxicology In screening...CPT) were used to develop Quantitative Structure Activity Relationship ( QSAR ) models to predict repellency. Successful prediction of novel...acylpiperidine QSAR models employed 4 descriptors to describe the relationship between structure and repellent duration. The ANN model of the carboxamides did not

Dose-response relationship between sports activity and musculoskeletal pain in adolescents.

PubMed

Kamada, Masamitsu; Abe, Takafumi; Kitayuguchi, Jun; Imamura, Fumiaki; Lee, I-Min; Kadowaki, Masaru; Sawada, Susumu S; Miyachi, Motohiko; Matsui, Yuzuru; Uchio, Yuji

2016-06-01

Physical activity has multiple health benefits but may also increase the risk of developing musculoskeletal pain (MSP). However, the relationship between physical activity and MSP has not been well characterized. This study examined the dose-response relationship between sports activity and MSP among adolescents. Two school-based serial surveys were conducted 1 year apart in adolescents aged 12 to 18 years in Unnan, Japan. Self-administered questionnaires were completed by 2403 students. Associations between time spent in organized sports activity and MSP were analyzed cross-sectionally (n = 2403) and longitudinally (n = 374, students free of pain and in seventh or 10th grade at baseline) with repeated-measures Poisson regression and restricted cubic splines, with adjustment for potential confounders. The prevalence of overall pain, defined as having pain recently at least several times a week in at least one part of the body, was 27.4%. In the cross-sectional analysis, sports activity was significantly associated with pain prevalence. Each additional 1 h/wk of sports activity was associated with a 3% higher probability of having pain (prevalence ratio = 1.03, 95% confidence interval = 1.02-1.04). Similar trends were found across causes (traumatic and nontraumatic pain) and anatomic locations (upper limbs, lower back, and lower limbs). In longitudinal analysis, the risk ratio for developing pain at 1-year follow-up per 1 h/wk increase in baseline sports activity was 1.03 (95% confidence interval = 1.02-1.05). Spline models indicated a linear association (P < 0.001) but not a nonlinear association (P ≥ 0.45). The more the adolescents played sports, the more likely they were to have and develop pain.

Dose–response relationship between sports activity and musculoskeletal pain in adolescents

PubMed Central

Kamada, Masamitsu; Abe, Takafumi; Kitayuguchi, Jun; Imamura, Fumiaki; Lee, I-Min; Kadowaki, Masaru; Sawada, Susumu S.; Miyachi, Motohiko; Matsui, Yuzuru; Uchio, Yuji

2016-01-01

Abstract Physical activity has multiple health benefits but may also increase the risk of developing musculoskeletal pain (MSP). However, the relationship between physical activity and MSP has not been well characterized. This study examined the dose–response relationship between sports activity and MSP among adolescents. Two school-based serial surveys were conducted 1 year apart in adolescents aged 12 to 18 years in Unnan, Japan. Self-administered questionnaires were completed by 2403 students. Associations between time spent in organized sports activity and MSP were analyzed cross-sectionally (n = 2403) and longitudinally (n = 374, students free of pain and in seventh or 10th grade at baseline) with repeated-measures Poisson regression and restricted cubic splines, with adjustment for potential confounders. The prevalence of overall pain, defined as having pain recently at least several times a week in at least one part of the body, was 27.4%. In the cross-sectional analysis, sports activity was significantly associated with pain prevalence. Each additional 1 h/wk of sports activity was associated with a 3% higher probability of having pain (prevalence ratio = 1.03, 95% confidence interval = 1.02-1.04). Similar trends were found across causes (traumatic and nontraumatic pain) and anatomic locations (upper limbs, lower back, and lower limbs). In longitudinal analysis, the risk ratio for developing pain at 1-year follow-up per 1 h/wk increase in baseline sports activity was 1.03 (95% confidence interval = 1.02-1.05). Spline models indicated a linear association (P < 0.001) but not a nonlinear association (P ≥ 0.45). The more the adolescents played sports, the more likely they were to have and develop pain. PMID:26894915

Objective vs. self-reported physical activity and sedentary time: effects of measurement method on relationships with risk biomarkers.

PubMed

Celis-Morales, Carlos A; Perez-Bravo, Francisco; Ibañez, Luis; Salas, Carlos; Bailey, Mark E S; Gill, Jason M R

2012-01-01

Imprecise measurement of physical activity variables might attenuate estimates of the beneficial effects of activity on health-related outcomes. We aimed to compare the cardiometabolic risk factor dose-response relationships for physical activity and sedentary behaviour between accelerometer- and questionnaire-based activity measures. Physical activity and sedentary behaviour were assessed in 317 adults by 7-day accelerometry and International Physical Activity Questionnaire (IPAQ). Fasting blood was taken to determine insulin, glucose, triglyceride and total, LDL and HDL cholesterol concentrations and homeostasis model-estimated insulin resistance (HOMA(IR)). Waist circumference, BMI, body fat percentage and blood pressure were also measured. For both accelerometer-derived sedentary time (<100 counts.min(-1)) and IPAQ-reported sitting time significant positive (negative for HDL cholesterol) relationships were observed with all measured risk factors--i.e. increased sedentary behaviour was associated with increased risk (all p ≤ 0.01). However, for HOMA(IR) and insulin the regression coefficients were >50% lower for the IPAQ-reported compared to the accelerometer-derived measure (p<0.0001 for both interactions). The relationships for moderate-to-vigorous physical activity (MVPA) and risk factors were less strong than those observed for sedentary behaviours, but significant negative relationships were observed for both accelerometer and IPAQ MVPA measures with glucose, and insulin and HOMA(IR) values (all p<0.05). For accelerometer-derived MVPA only, additional negative relationships were seen with triglyceride, total cholesterol and LDL cholesterol concentrations, BMI, waist circumference and percentage body fat, and a positive relationship was evident with HDL cholesterol (p = 0.0002). Regression coefficients for HOMA(IR), insulin and triglyceride were 43-50% lower for the IPAQ-reported compared to the accelerometer-derived MVPA measure (all p≤0.01). Using the

On the Relationship between Variational Level Set-Based and SOM-Based Active Contours

PubMed Central

Abdelsamea, Mohammed M.; Gnecco, Giorgio; Gaber, Mohamed Medhat; Elyan, Eyad

2015-01-01

Most Active Contour Models (ACMs) deal with the image segmentation problem as a functional optimization problem, as they work on dividing an image into several regions by optimizing a suitable functional. Among ACMs, variational level set methods have been used to build an active contour with the aim of modeling arbitrarily complex shapes. Moreover, they can handle also topological changes of the contours. Self-Organizing Maps (SOMs) have attracted the attention of many computer vision scientists, particularly in modeling an active contour based on the idea of utilizing the prototypes (weights) of a SOM to control the evolution of the contour. SOM-based models have been proposed in general with the aim of exploiting the specific ability of SOMs to learn the edge-map information via their topology preservation property and overcoming some drawbacks of other ACMs, such as trapping into local minima of the image energy functional to be minimized in such models. In this survey, we illustrate the main concepts of variational level set-based ACMs, SOM-based ACMs, and their relationship and review in a comprehensive fashion the development of their state-of-the-art models from a machine learning perspective, with a focus on their strengths and weaknesses. PMID:25960736

Relationships between Interlibrary Loan and Research Activity in Canada

ERIC Educational Resources Information Center

Duy, Joanna; Larivière, Vincent

2014-01-01

Interlibrary Loan borrowing rates in academic libraries are influenced by an array of factors. This article explores the relationship between interlibrary loan borrowing activity and research activity at 42 Canadian academic institutions. A significant positive correlation was found between interlibrary loan borrowing activity and measures of…

Does community type moderate the relationship between parent perceptions of the neighborhood and physical activity in children?

PubMed

Durand, Casey P; Dunton, Genevieve F; Spruijt-Metz, Donna; Pentz, Mary Ann

2012-01-01

To examine whether residing in a community designed to promote physical activity moderates the relationship between parent perceptions of the neighborhood and general physical activity or active commuting to school in their children. Cross-sectional. San Bernardino County, California. Three hundred sixty-five families (one parent and one child in grades four through eight). Eighty-five reside in a smart growth community designed to be more conducive to physical activity. Parent perceptions assessed using the Neighborhood Environment Walkability Scale (NEWS). General child physical activity was measured using accelerometers, and active commuting was self-reported by children. Two sets of regressions were performed: one for general physical activity, and one for active commuting. Separate models were run in the two sets for each of the 14 NEWS factors, while controlling for demographics. For general physical activity, walking infrastructure, lack of cul-de-sacs, and social interaction had significant main effect associations (p ≤ .05). No factors were moderated by community. The relationships between active commuting to school and perceived crime, traffic hazards, hilliness, physical barriers, cul-de-sac connectivity, aesthetics, and walking infrastructure were significant for those in the smart growth community only (p ≤ .05). Living in an activity-friendly environment is associated with positive relationships between parent perceptions and active commuting behaviors in children. Future interventions should account for both the perceived neighborhood environment and available physical activity infrastructure.

Young Adolescents' Perceptions of Romantic Relationships and Sexual Activity

ERIC Educational Resources Information Center

Royer, Heather R.; Keller, Mary L.; Heidrich, Susan M.

2009-01-01

The purpose of this article is to describe young adolescents' perceptions of romantic relationships, ratings of important romantic partner characteristics, and acceptability of sexual activity with romantic relationships. Fifty-seven eighth-grade participants (average age = 13.8 years) from one urban US public middle school completed an anonymous…

Nonparametric regression applied to quantitative structure-activity relationships

PubMed

Constans; Hirst

2000-03-01

Several nonparametric regressors have been applied to modeling quantitative structure-activity relationship (QSAR) data. The simplest regressor, the Nadaraya-Watson, was assessed in a genuine multivariate setting. Other regressors, the local linear and the shifted Nadaraya-Watson, were implemented within additive models--a computationally more expedient approach, better suited for low-density designs. Performances were benchmarked against the nonlinear method of smoothing splines. A linear reference point was provided by multilinear regression (MLR). Variable selection was explored using systematic combinations of different variables and combinations of principal components. For the data set examined, 47 inhibitors of dopamine beta-hydroxylase, the additive nonparametric regressors have greater predictive accuracy (as measured by the mean absolute error of the predictions or the Pearson correlation in cross-validation trails) than MLR. The use of principal components did not improve the performance of the nonparametric regressors over use of the original descriptors, since the original descriptors are not strongly correlated. It remains to be seen if the nonparametric regressors can be successfully coupled with better variable selection and dimensionality reduction in the context of high-dimensional QSARs.

Protective activity of (1S,2E,4R,6R,7E,11E)-2,7,11-cembratriene-4,6-diol analogues against diisopropylfluorophosphate neurotoxicity: preliminary structure-activity relationship and pharmacophore modeling.

PubMed

Eterović, Vesna A; Del Valle-Rodriguez, Angelie; Pérez, Dinely; Carrasco, Marimée; Khanfar, Mohammad A; El Sayed, Khalid A; Ferchmin, Pedro A

2013-08-01

Diisopropylfluorophosphate (DFP) is an organophosphorous insecticide used as a surrogate for the more toxic chemical warfare nerve agent sarin. DFP produces neurotoxicity in vivo and irreversibly decreases the area of population spikes recorded from the CA1 region of acute hippocampal slices. (1S,2E,4R,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) is a neuroprotective natural cembranoid that reverses DFP-induced damage both in vivo and in the hippocampal slice. Cembranoid 1 acts by noncompetitive inhibition of the α7 nicotinic acetylcholine receptor. This study aims at establishing a preliminary structure-activity relationship to define the neuroprotective cembranoid pharmacophores using the hippocampal slice assay and pharmacophore modeling. Fourteen natural, semisynthetic, or biocatalytic cembranoid analogues 2-15 related to 1 were tested for their capacity to protect the population spikes from DFP-induced damage and intrinsic toxicity. Twelve cembranoids caused significant reversal of DFP toxicity; only 3 active analogues displayed minor intrinsic toxicity at 10 μM. The C-4 epimer of 1 (2) and the 4-O-methyl ether analogue of 1 (3), were totally devoid of neuroprotective activity. The results suggested a model for cembranoid binding where the hydrophobic ring surface binds to a hydrophobic (Hbic) patch on the receptor molecule and an electronegative atom (oxygen or sulfur) in proper spatial relationship to the ring surface interacts with an electropositive group in the receptor binding site. A pharmacophore model consisting of 1 hydrogen bond acceptor (HBA), 2 Hbic, and 10 exclusion spheres was established using HipHop-REFINE and supported the above mentioned pharmacophoric hypothesis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Structure-Activity Relationships of Nitro-Substituted Aroylhydrazone Iron Chelators with Antioxidant and Antiproliferative Activities.

PubMed

Hrušková, Kateřina; Potůčková, Eliška; Opálka, Lukáš; Hergeselová, Tereza; Hašková, Pavlína; Kovaříková, Petra; Šimůnek, Tomáš; Vávrová, Kateřina

2018-05-23

Aroylhydrazone iron chelators such as salicylaldehyde isonicotinoyl hydrazone (SIH) protect various cells against oxidative injury and display antineoplastic activities. Previous studies have shown that a nitro-substituted hydrazone, namely, NHAPI, displayed markedly improved plasma stability, selective antitumor activity, and moderate antioxidant properties. In this study, we prepared four series of novel NHAPI derivatives and explored their iron chelation activities, anti- or pro-oxidant effects, protection against model oxidative injury in the H9c2 cell line derived from rat embryonic cardiac myoblasts, cytotoxicities to the corresponding noncancerous H9c2 cells, and antiproliferative activities against the MCF-7 human breast adenocarcinoma and HL-60 human promyelocytic leukemia cell lines. Nitro substitution had both negative and positive effects on the examined properties, and we identified new structure-activity relationships. Naphthyl and biphenyl derivatives showed selective antiproliferative action, particularly in the breast adenocarcinoma MCF-7 cell line, where they exceeded the selectivity of the parent compound NHAPI. Of particular interest is a compound prepared from 2-hydroxy-5-methyl-3-nitroacetophenone and biphenyl-4-carbohydrazide, which protected cardiomyoblasts against oxidative injury at 1.8 ± 1.2 μM with 24-fold higher selectivity than SIH. These compounds will serve as leads for further structural optimization and mechanistic studies.

Structure activity relationship modelling of milk protein-derived peptides with dipeptidyl peptidase IV (DPP-IV) inhibitory activity.

PubMed

Nongonierma, Alice B; FitzGerald, Richard J

2016-05-01

Quantitative structure activity type models were developed in an attempt to predict the key features of peptide sequences having dipeptidyl peptidase IV (DPP-IV) inhibitory activity. The models were then employed to help predict the potential of peptides, which are currently reported in the literature to be present in the intestinal tract of humans following milk/dairy product ingestion, to act as inhibitors of DPP-IV. Two models (z- and v-scale) for short (2-5 amino acid residues) bovine milk peptides, behaving as competitive inhibitors of DPP-IV, were developed. The z- and the v-scale models (p<0.05, R(2) of 0.829 and 0.815, respectively) were then applied to 56 milk protein-derived peptides previously reported in the literature to be found in the intestinal tract of humans which possessed a structural feature of DPP-IV inhibitory peptides (P at the N2 position). Ten of these peptides were synthetized and tested for their in vitro DPP-IV inhibitory properties. There was no agreement between the predicted and experimentally determined DPP-IV half maximal inhibitory concentrations (IC50) for the competitive peptide inhibitors. However, the ranking for DPP-IV inhibitory potency of the competitive peptide inhibitors was conserved. Furthermore, potent in vitro DPP-IV inhibitory activity was observed with two peptides, LPVPQ (IC50=43.8±8.8μM) and IPM (IC50=69.5±8.7μM). Peptides present within the gastrointestinal tract of human may have promise for the development of natural DPP-IV inhibitors for the management of serum glucose. Copyright © 2016 Elsevier Inc. All rights reserved.

Inequity in work and intimate relationships: a Spillover-Crossover model.

PubMed

Bakker, Arnold B; Petrou, Paraskevas; Tsaousis, Ioannis

2012-01-01

This study among 267 Greek teachers and their partners tested and expanded the recently proposed Spillover-Crossover model (SCM) of well-being. Accordingly, experiences built up at work spill over to the home domain, and then influence the partner. The authors integrated equity theory in the model by formulating hypotheses about exchange in interpersonal relationships. Structural equation modeling analyses supported the spillover hypothesis that teachers who lose their work engagement as a result of an inequitable relationship with their students invest less in the relationship with their partner. In addition, the results supported the crossover hypothesis that teachers' relationship investments, in turn, show a negative relationship with inequity in the intimate relationship as perceived by the partner; and inequity in the intimate relationship contributed to partner depression. The findings are discussed in light of the SCM of well-being.

Relationship between skin temperature and muscle activation during incremental cycle exercise.

PubMed

Priego Quesada, Jose I; Carpes, Felipe P; Bini, Rodrigo R; Salvador Palmer, Rosario; Pérez-Soriano, Pedro; Cibrián Ortiz de Anda, Rosa M

2015-02-01

While different studies showed that better fitness level adds to the efficiency of the thermoregulatory system, the relationship between muscular effort and skin temperature is still unknown. Therefore, the present study assessed the relationship between neuromuscular activation and skin temperature during cycle exercise. Ten physically active participants performed an incremental workload cycling test to exhaustion while neuromuscular activations were recorded (via surface electromyography - EMG) from rectus femoris, vastus lateralis, biceps femoris and gastrocnemius medialis. Thermographic images were recorded before, immediately after and 10 min after finishing the cycling test, at four body regions of interest corresponding to the muscles where neuromuscular activations were monitored. Frequency band analysis was conducted to assess spectral properties of EMG signals in order to infer on priority in recruitment of motor units. Significant inverse relationship between changes in skin temperature and changes in overall neuromuscular activation for vastus lateralis was observed (r<-0.5 and p<0.04). Significant positive relationship was observed between skin temperature and low frequency components of neuromuscular activation from vastus lateralis (r>0.7 and p<0.01). Participants with larger overall activation and reduced low frequency component for vastus lateralis activation presented a better adaptive response of their thermoregulatory system by showing fewer changes in skin temperature after incremental cycling test. Copyright © 2014 Elsevier Ltd. All rights reserved.

Toxicity of ionic liquids: database and prediction via quantitative structure-activity relationship method.

PubMed

Zhao, Yongsheng; Zhao, Jihong; Huang, Ying; Zhou, Qing; Zhang, Xiangping; Zhang, Suojiang

2014-08-15

A comprehensive database on toxicity of ionic liquids (ILs) is established. The database includes over 4000 pieces of data. Based on the database, the relationship between IL's structure and its toxicity has been analyzed qualitatively. Furthermore, Quantitative Structure-Activity relationships (QSAR) model is conducted to predict the toxicities (EC50 values) of various ILs toward the Leukemia rat cell line IPC-81. Four parameters selected by the heuristic method (HM) are used to perform the studies of multiple linear regression (MLR) and support vector machine (SVM). The squared correlation coefficient (R(2)) and the root mean square error (RMSE) of training sets by two QSAR models are 0.918 and 0.959, 0.258 and 0.179, respectively. The prediction R(2) and RMSE of QSAR test sets by MLR model are 0.892 and 0.329, by SVM model are 0.958 and 0.234, respectively. The nonlinear model developed by SVM algorithm is much outperformed MLR, which indicates that SVM model is more reliable in the prediction of toxicity of ILs. This study shows that increasing the relative number of O atoms of molecules leads to decrease in the toxicity of ILs. Copyright © 2014 Elsevier B.V. All rights reserved.

Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases: Synthesis, Structure–Activity Relationship, and Selective Antitumor Activity

PubMed Central

2015-01-01

Mutations of isocitrate dehydrogenase 1 (IDH1) are frequently found in certain cancers such as glioma. Different from the wild-type (WT) IDH1, the mutant enzymes catalyze the reduction of α-ketoglutaric acid to d-2-hydroxyglutaric acid (D2HG), leading to cancer initiation. Several 1-hydroxypyridin-2-one compounds were identified to be inhibitors of IDH1(R132H). A total of 61 derivatives were synthesized, and their structure–activity relationships were investigated. Potent IDH1(R132H) inhibitors were identified with Ki values as low as 140 nM, while they possess weak or no activity against WT IDH1. Activities of selected compounds against IDH1(R132C) were found to be correlated with their inhibitory activities against IDH1(R132H), as well as cellular production of D2HG, with R2 of 0.83 and 0.73, respectively. Several inhibitors were found to be permeable through the blood–brain barrier in a cell-based model assay and exhibit potent and selective activity (EC50 = 0.26–1.8 μM) against glioma cells with the IDH1 R132H mutation. PMID:25271760

The Relationship between Training and Innovation Activities in Enterprises

ERIC Educational Resources Information Center

Børing, Pål

2017-01-01

We examine the relationship between enterprises' use of employee training (or education) as a method to stimulate new ideas or creativity among their staff and enterprises' innovation activities. A data set of 5204 Norwegian enterprises is used. Based on correlation coefficients, we find a positive relationship between enterprises' use of employee…

Relationships between solar activity and climate change

NASA Technical Reports Server (NTRS)

Roberts, W. O.

1975-01-01

The relationship between recurrent droughts in the High Plains of the United States and the double sunspot cycle is discussed in detail. It is suggested that high solar activity is generally related to an increase in meridional circulation and blocking patterns at high and intermediate latitudes, especially in winter, and the effect is related to the sudden formation of cirrus clouds during strong geomagnetic activity that originates in the solar corpuscular emission.

Comparison of 3D quantitative structure-activity relationship methods: Analysis of the in vitro antimalarial activity of 154 artemisinin analogues by hypothetical active-site lattice and comparative molecular field analysis

NASA Astrophysics Data System (ADS)

Woolfrey, John R.; Avery, Mitchell A.; Doweyko, Arthur M.

1998-03-01

Two three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, comparative molecular field analysis (CoMFA) and hypothetical active site lattice (HASL), were compared with respect to the analysis of a training set of 154 artemisinin analogues. Five models were created, including a complete HASL and two trimmed versions, as well as two CoMFA models (leave-one-out standard CoMFA and the guided-region selection protocol). Similar r2 and q2 values were obtained by each method, although some striking differences existed between CoMFA contour maps and the HASL output. Each of the four predictive models exhibited a similar ability to predict the activity of a test set of 23 artemisinin analogues, although some differences were noted as to which compounds were described well by either model.

Modeling Spatial Relationships within a Fuzzy Framework.

ERIC Educational Resources Information Center

Petry, Frederick E.; Cobb, Maria A.

1998-01-01

Presents a model for representing and storing binary topological and directional relationships between 2-dimensional objects that is used to provide a basis for fuzzy querying capabilities. A data structure called an abstract spatial graph (ASG) is defined for the binary relationships that maintains all necessary information regarding topology and…

QSAR models for anti-malarial activity of 4-aminoquinolines.

PubMed

Masand, Vijay H; Toropov, Andrey A; Toropova, Alla P; Mahajan, Devidas T

2014-03-01

In the present study, predictive quantitative structure - activity relationship (QSAR) models for anti-malarial activity of 4-aminoquinolines have been developed. CORAL, which is freely available on internet (http://www.insilico.eu/coral), has been used as a tool of QSAR analysis to establish statistically robust QSAR model of anti-malarial activity of 4-aminoquinolines. Six random splits into the visible sub-system of the training and invisible subsystem of validation were examined. Statistical qualities for these splits vary, but in all these cases, statistical quality of prediction for anti-malarial activity was quite good. The optimal SMILES-based descriptor was used to derive the single descriptor based QSAR model for a data set of 112 aminoquinolones. All the splits had r(2)> 0.85 and r(2)> 0.78 for subtraining and validation sets, respectively. The three parametric multilinear regression (MLR) QSAR model has Q(2) = 0.83, R(2) = 0.84 and F = 190.39. The anti-malarial activity has strong correlation with presence/absence of nitrogen and oxygen at a topological distance of six.

Spatial and Activities Models of Airport Based on GIS and Dynamic Model

NASA Astrophysics Data System (ADS)

Masri, R. M.; Purwaamijaya, I. M.

2017-02-01

The purpose of research were (1) a conceptual, functional model designed and implementation for spatial airports, (2) a causal, flow diagrams and mathematical equations made for airport activity, (3) obtained information on the conditions of space and activities at airports assessment, (4) the space and activities evaluation at airports based on national and international airport services standards, (5) options provided to improve the spatial and airport activities performance become the international standards airport. Descriptive method is used for the research. Husein Sastranegara Airport in Bandung, West Java, Indonesia was study location. The research was conducted on September 2015 to April 2016. A spatial analysis is used to obtain runway, taxiway and building airport geometric information. A system analysis is used to obtain the relationship between components in airports, dynamic simulation activity at airports and information on the results tables and graphs of dynamic model. Airport national and international standard could not be fulfilled by spatial and activity existing condition of Husein Sastranegara. Idea of re-location program is proposed as problem solving for constructing new airport which could be serving international air transportation.

Quantitative structure-activity relationship study of P2X7 receptor inhibitors using combination of principal component analysis and artificial intelligence methods.

PubMed

Ahmadi, Mehdi; Shahlaei, Mohsen

2015-01-01

P2X7 antagonist activity for a set of 49 molecules of the P2X7 receptor antagonists, derivatives of purine, was modeled with the aid of chemometric and artificial intelligence techniques. The activity of these compounds was estimated by means of combination of principal component analysis (PCA), as a well-known data reduction method, genetic algorithm (GA), as a variable selection technique, and artificial neural network (ANN), as a non-linear modeling method. First, a linear regression, combined with PCA, (principal component regression) was operated to model the structure-activity relationships, and afterwards a combination of PCA and ANN algorithm was employed to accurately predict the biological activity of the P2X7 antagonist. PCA preserves as much of the information as possible contained in the original data set. Seven most important PC's to the studied activity were selected as the inputs of ANN box by an efficient variable selection method, GA. The best computational neural network model was a fully-connected, feed-forward model with 7-7-1 architecture. The developed ANN model was fully evaluated by different validation techniques, including internal and external validation, and chemical applicability domain. All validations showed that the constructed quantitative structure-activity relationship model suggested is robust and satisfactory.

Quantitative structure–activity relationship study of P2X7 receptor inhibitors using combination of principal component analysis and artificial intelligence methods

PubMed Central

Ahmadi, Mehdi; Shahlaei, Mohsen

2015-01-01

P2X7 antagonist activity for a set of 49 molecules of the P2X7 receptor antagonists, derivatives of purine, was modeled with the aid of chemometric and artificial intelligence techniques. The activity of these compounds was estimated by means of combination of principal component analysis (PCA), as a well-known data reduction method, genetic algorithm (GA), as a variable selection technique, and artificial neural network (ANN), as a non-linear modeling method. First, a linear regression, combined with PCA, (principal component regression) was operated to model the structure–activity relationships, and afterwards a combination of PCA and ANN algorithm was employed to accurately predict the biological activity of the P2X7 antagonist. PCA preserves as much of the information as possible contained in the original data set. Seven most important PC's to the studied activity were selected as the inputs of ANN box by an efficient variable selection method, GA. The best computational neural network model was a fully-connected, feed-forward model with 7−7−1 architecture. The developed ANN model was fully evaluated by different validation techniques, including internal and external validation, and chemical applicability domain. All validations showed that the constructed quantitative structure–activity relationship model suggested is robust and satisfactory. PMID:26600858

Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait activity, industriousness, exercise social cognitions, exercise intentions, and physical activity in a representative U.S. sample.

PubMed

Vo, Phuong T; Bogg, Tim

2015-01-01

Prior research identified assorted relations between trait and social cognition models of personality and engagement in physical activity. Using a representative U.S. sample (N = 957), the goal of the present study was to test two alternative structural models of the relationships among the extraversion-related facet of activity, the conscientiousness-related facet of industriousness, social cognitions from the Theory of Planned Behavior (perceived behavioral control, affective attitudes, subjective norms, intentions), Social Cognitive Theory (self-efficacy, outcome expectancies), and the Transtheoretical Model (behavioral processes of change), and engagement in physical activity. Path analyses with bootstrapping procedures were used to model direct and indirect effects of trait and social cognition constructs on physical activity through two distinct frameworks - the Theory of Planned Behavior and Neo-Socioanalytic Theory. While both models showed good internal fit, comparative model information criteria showed the Theory-of-Planned-Behavior-informed model provided a better fit. In the model, social cognitions fully mediated the relationships from the activity facet and industriousness to intentions for and engagement in physical activity, such that the relationships were primarily maintained by positive affective evaluations, positive expected outcomes, and confidence in overcoming barriers related to physical activity engagement. The resultant model - termed the Disposition-Belief-Motivation model- is proposed as a useful framework for organizing and integrating personality trait facets and social cognitions from various theoretical perspectives to investigate the expression of health-related behaviors, such as physical activity. Moreover, the results are discussed in terms of extending the application of the Disposition-Belief-Motivation model to longitudinal and intervention designs for physical activity engagement.

Application of Quantitative Structure–Activity Relationship Models of 5-HT1A Receptor Binding to Virtual Screening Identifies Novel and Potent 5-HT1A Ligands

PubMed Central

2015-01-01

The 5-hydroxytryptamine 1A (5-HT1A) serotonin receptor has been an attractive target for treating mood and anxiety disorders such as schizophrenia. We have developed binary classification quantitative structure–activity relationship (QSAR) models of 5-HT1A receptor binding activity using data retrieved from the PDSP Ki database. The prediction accuracy of these models was estimated by external 5-fold cross-validation as well as using an additional validation set comprising 66 structurally distinct compounds from the World of Molecular Bioactivity database. These validated models were then used to mine three major types of chemical screening libraries, i.e., drug-like libraries, GPCR targeted libraries, and diversity libraries, to identify novel computational hits. The five best hits from each class of libraries were chosen for further experimental testing in radioligand binding assays, and nine of the 15 hits were confirmed to be active experimentally with binding affinity better than 10 μM. The most active compound, Lysergol, from the diversity library showed very high binding affinity (Ki) of 2.3 nM against 5-HT1A receptor. The novel 5-HT1A actives identified with the QSAR-based virtual screening approach could be potentially developed as novel anxiolytics or potential antischizophrenic drugs. PMID:24410373

Using avian radar to examine relationships among avian activity, bird strikes, and meteorological factors

USGS Publications Warehouse

Coates, Peter S.; Casazza, Michael L.; Halstead, Brian J.; Fleskes, Joseph P.; Laughlin, James A.

2011-01-01

Radar systems designed to detect avian activity at airfields are useful in understanding factors that influence the risk of bird and aircraft collisions (bird strikes). We used an avian radar system to measure avian activity at Beale Air Force Base, California, USA, during 2008 and 2009. We conducted a 2-part analysis to examine relationships among avian activity, bird strikes, and meteorological and time-dependent factors. We found that avian activity around the airfield was greater at times when bird strikes occurred than on average using a permutation resampling technique. Second, we developed generalized linear mixed models of an avian activity index (AAI). Variation in AAI was first explained by seasons that were based on average migration dates of birds at the study area. We then modeled AAI by those seasons to further explain variation by meteorological factors and daily light levels within a 24-hour period. In general, avian activity increased with decreased temperature, wind, visibility, precipitation, and increased humidity and cloud cover. These effects differed by season. For example, during the spring bird migration period, most avian activity occurred before sunrise at twilight hours on clear days with low winds, whereas during fall migration, substantial activity occurred after sunrise, and birds generally were more active at lower temperatures. We report parameter estimates (i.e., constants and coefficients) averaged across models and a relatively simple calculation for safety officers and wildlife managers to predict AAI and the relative risk of bird strike based on time, date, and meteorological values. We validated model predictability and assessed model fit. These analyses will be useful for general inference of avian activity and risk assessment efforts. Further investigation and ongoing data collection will refine these inference models and improve our understanding of factors that influence avian activity, which is necessary to inform

Intermittent pair-housing, pair relationship qualities, and HPA activity in adult female rhesus macaques.

PubMed

Hannibal, Darcy L; Cassidy, Lauren C; Vandeleest, Jessica; Semple, Stuart; Barnard, Allison; Chun, Katie; Winkler, Sasha; McCowan, Brenda

2018-05-02

Laboratory rhesus macaques are often housed in pairs and may be temporarily or permanently separated for research, health, or management reasons. While both long-term social separations and introductions can stimulate a stress response that impacts inflammation and immune function, the effects of short-term overnight separations and whether qualities of the pair relationship mediate these effects are unknown. In this study, we investigated the effects of overnight separations on the urinary cortisol concentration of 20 differentially paired adult female rhesus macaques (Macaca mulatta) at the California National Primate Research Center. These females were initially kept in either continuous (no overnight separation) or intermittent (with overnight separation) pair-housing and then switched to the alternate pair-housing condition part way through the study. Each study subject was observed for 5 weeks, during which we collected measures of affiliative, aggressive, anxious, abnormal, and activity-state behaviors in both pair-housing conditions. Additionally, up to three urine samples were collected from each subject per week and assayed for urinary free cortisol and creatinine. Lastly, the behavioral observer scored each pair on four relationship quality attributes ("Anxious," "Tense," "Well-meshed," and "Friendly") using a seven-point scale. Data were analyzed using a generalized linear model with gamma distribution and an information theoretic approach to determine the best model set. An interaction between the intermittent pairing condition and tense pair adjective rating was in the top three models of the best model set. Dominance and rates of affiliation were also important for explaining urinary cortisol variation. Our results suggest that to prevent significant changes in HPA-axis activation in rhesus macaque females, which could have unintended effects on research outcomes, pairs with "Tense" relationships and overnight separations preventing tactile contact

Youth participation in organized and informal sports activities across childhood and adolescence: exploring the relationships of motivational beliefs, developmental stage and gender.

PubMed

Dawes, Nickki Pearce; Vest, Andrea; Simpkins, Sandra

2014-08-01

Involvement in physically active pursuits, such as sports, contributes to achieving and maintaining good emotional and physical health. The central goal of this article was to examine the longitudinal relationships between participation (i.e., time spent in the activities) in organized and informal sports contexts and motivational beliefs, and factors that might impact these relationships, such as developmental stage and gender. The data for the current study were drawn from the childhood and beyond longitudinal study, which utilized a cohort sequential design with data collected on three cohorts across four waves. The current study sample included 986 European American youth (51 % female), who t were mostly from working- and middle-class families. Self-report questionnaires were used to collect data from the youth about their participation in sports and their motivational beliefs (i.e., value and perceptions of competence) about this activity. Structural equation modeling was used to examine the relationships between participation and motivational beliefs across childhood and adolescence. The results provide some support for a model of reciprocal relationships between participation and motivational beliefs in organized and informal sports activities. These relationships between participation and motivational beliefs did not vary significantly based on developmental stage or by gender. Overall, the findings suggest that participation in organized and informal sports contexts may be fostered by supporting the development of positive motivational beliefs about the activities across developmental periods.

STRUCTURE-ACTIVITY RELATIONSHIP STUIDES AND THEIR ROLE IN PREDICTING AND INVESTIGATING CHEMICAL TOXICITY

EPA Science Inventory

Structure-Activity Relationship Studies and their Role in Predicting and Investigating Chemical Toxicity

Structure-activity relationships (SAR) represent attempts to generalize chemical information relative to biological activity for the twin purposes of generating insigh...

Relationship between speed and EEG activity during imagined and executed hand movements

NASA Astrophysics Data System (ADS)

Yuan, Han; Perdoni, Christopher; He, Bin

2010-04-01

The relationship between primary motor cortex and movement kinematics has been shown in nonhuman primate studies of hand reaching or drawing tasks. Studies have demonstrated that the neural activities accompanying or immediately preceding the movement encode the direction, speed and other information. Here we investigated the relationship between the kinematics of imagined and actual hand movement, i.e. the clenching speed, and the EEG activity in ten human subjects. Study participants were asked to perform and imagine clenching of the left hand and right hand at various speeds. The EEG activity in the alpha (8-12 Hz) and beta (18-28 Hz) frequency bands were found to be linearly correlated with the speed of imagery clenching. Similar parametric modulation was also found during the execution of hand movements. A single equation relating the EEG activity to the speed and the hand (left versus right) was developed. This equation, which contained a linear independent combination of the two parameters, described the time-varying neural activity during the tasks. Based on the model, a regression approach was developed to decode the two parameters from the multiple-channel EEG signals. We demonstrated the continuous decoding of dynamic hand and speed information of the imagined clenching. In particular, the time-varying clenching speed was reconstructed in a bell-shaped profile. Our findings suggest an application to providing continuous and complex control of noninvasive brain-computer interface for movement-impaired paralytics.

Structure-activity relationship of indoloquinoline analogs anti-MRSA.

PubMed

Zhao, Min; Kamada, Tomonori; Takeuchi, Aya; Nishioka, Hiromi; Kuroda, Teruo; Takeuchi, Yasuo

2015-12-01

Indolo[3,2-b]quinoline analogs (3a-3s), 4-(acridin-9-ylamino) phenol hydrochloride (4), benzofuro[3,2-b]quinoline (3t), indeno[1,2-b]quinolines (3u and 3v) have been synthesized. Those compounds were found to exhibit anti-bacterial activity towards Methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Structure-activity relationship studies were conducted that indoloquinoline ring, benzofuroquinoline ring and 4-aminophenol group are essential structure for anti-MRSA activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Data Base Design Using Entity-Relationship Models.

ERIC Educational Resources Information Center

Davis, Kathi Hogshead

1983-01-01

The entity-relationship (ER) approach to database design is defined, and a specific example of an ER model (personnel-payroll) is examined. The requirements for converting ER models into specific database management systems are discussed. (Author/MSE)

Quantitative structure property relationships for the adsorption of pharmaceuticals onto activated carbon.

PubMed

Dickenson, E R V; Drewes, J E

2010-01-01

Isotherms were determined for the adsorption of five pharmaceutical residues, primidone, carbamazepine, ibuprofen, naproxen and diclofenac, to Calgon Filtrasorb 300 powdered activated carbon (PAC). The sorption behavior was examined in ultra-pure and wastewater effluent organic matter (EfOM) matrices, where more sorption was observed in the ultra-pure water for PAC doses greater than 10 mg/L suggesting the presence of EfOM hinders the sorption of the pharmaceuticals to the PAC. Adsorption behaviors were described by the Freundlich isotherm model. Quantitative structure property relationships (QSPRs) in the form of polyparameter linear solvation energy relationships were developed for simulating the Freundlich adsorption capacity in both ultra-pure and EfOM matrices. The significant 3D-based descriptors for the QSPRs were the molar volume, polarizability and hydrogen-bond donor parameters.

Synthesis and quantitative structure-antifungal activity relationships of clovane derivatives against Botrytis cinerea.

PubMed

Saiz-Urra, Liane; Racero, Juan C; Macías-Sáchez, Antonio J; Hernández-Galán, Rosario; Hanson, James R; Perez-Gonzalez, Maykel; Collado, Isidro G

2009-03-25

Twenty-three clovane derivatives, nine described here for the first time, bearing substituents on carbon C-2, have been synthesized and evaluated for their in vitro antifungal activity against the phytopathogenic fungus Botrytis cinerea. The results showed that compounds 9, 14, 16, and 18 bearing nitrogen atoms in the chain attached at C-2 displayed potent antifungal activity, whereas mercapto derivatives 13, 19, and 22 displayed low activity. The antifungal activity showed a clear structure-activity relationship (SAR) trend, which confirmed the importance of the nature of the C-2 chain on the antifungal activity. On the basis of these observations, the metabolism of compounds 8 and 14 by the fungus B. cinerea, and the metabolism of other clovanes by this fungus, described previously, a pro-drug action mechanism for 2-alkoxyclovane compounds is proposed. Quantitative structure-activity relationship (QSAR) studies were performed to rationalize the results and to suggest further optimization, using a topological sub-structural molecular design (TOPS-MODE) approach. The model displayed good fit and predictive capability, describing 85.5% of the experimental variance, with a standard deviation of 9.502 and yielding high values of cross-validation determination coefficients (q2CV-LOO = 0.784 and q2boot = 0.673). The most significant variables were the spectral moments weighted by bond dipole moment (Dip), hydrophobicity (Hyd), and the combined dipolarity/polarizability Abraham molecular descriptor (Ab-pi2H).

Do Perceptions of Competence Mediate The Relationship Between Fundamental Motor Skill Proficiency and Physical Activity Levels of Children in Kindergarten?

PubMed

Crane, Jeff R; Naylor, Patti J; Cook, Ryan; Temple, Viviene A

2015-07-01

Perceptions of competence mediate the relationship between motor skill proficiency and physical activity among older children and adolescents. This study examined kindergarten children's perceptions of physical competence as a mediator of the relationship between motor skill proficiency as a predictor variable and physical activity levels as the outcome variable; and also with physical activity as a predictor and motor skill proficiency as the outcome. Participants were 116 children (mean age = 5 years 7 months, 58% boys) from 10 schools. Motor skills were measured using the Test of Gross Motor Development-2 and physical activity was monitored through accelerometry. Perceptions of physical competence were measured using The Pictorial Scale of Perceived Competence and Social Acceptance for Young Children, and the relationships between these variables were examined using a model of mediation. The direct path between object control skills and moderate-vigorous physical activity (MVPA) was significant and object control skills predicted perceived physical competence. However, perceived competence did not mediate the relationship between object control skills and MVPA. The significant relationship between motor proficiency and perceptions of competence did not in turn influence kindergarten children's participation in physical activity. These findings support concepts of developmental differences in the structure of the self-perception system.

Spatial and temporal relationships of electrocorticographic alpha and gamma activity during auditory processing.

PubMed

Potes, Cristhian; Brunner, Peter; Gunduz, Aysegul; Knight, Robert T; Schalk, Gerwin

2014-08-15

relationships reflect direct cortico-cortical connections rather than common driving input from subcortical structures such as the thalamus. In summary, our inter-subject analyses defined the spatial and temporal relationships between music-related brain activity in the alpha and high gamma bands. They provide experimental evidence supporting current theories about the putative mechanisms of alpha and gamma activity, i.e., reflections of thalamo-cortical interactions and local cortical neural activity, respectively, and the results are also in agreement with existing functional models of auditory processing. Copyright © 2014 Elsevier Inc. All rights reserved.

ABO/Rh Blood-Typing Model: A Problem-Solving Activity

ERIC Educational Resources Information Center

Wake, Carol

2005-01-01

An ARO/Rh Blood-Typing kit useful for students to visualize blood-typing activities and practice problem-solving skills with transfusion reactions is presented. The model also enables students to identify relationships between A, B, and Rh antigens and antibodies in blood and to understand molecular mechanisms involved in transfusion agglutination…

Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid Amides.

PubMed

Du, Shijie; Tian, Zaimin; Yang, Dongyan; Li, Xiuyun; Li, Hong; Jia, Changqing; Che, Chuanliang; Wang, Mian; Qin, Zhaohai

2015-05-08

A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

Parent Education within a Relationship-Focused Model.

ERIC Educational Resources Information Center

Kelly, Jean F.; Barnard, Kathryn E.

1999-01-01

This response to Mahoney et al. (EC 623 392) agrees that parent education should be an important component of early intervention programs and proposes that parent education be included in a relationship-focused early-intervention model. This model is illustrated, explained, and compared with the previous child-focused model and the current…

Three-dimensional quantitative structure-activity relationship modeling of cocaine binding by a novel human monoclonal antibody.

PubMed

Paula, Stefan; Tabet, Michael R; Farr, Carol D; Norman, Andrew B; Ball, W James

2004-01-01

Human monoclonal antibodies (mAbs) designed for immunotherapy have a high potential for avoiding the complications that may result from human immune system responses to the introduction of nonhuman mAbs into patients. This study presents a characterization of cocaine/antibody interactions that determine the binding properties of the novel human sequence mAb 2E2 using three-dimensional quantitative structure-activity relationship (3D-QSAR) methodology. We have experimentally determined the binding affinities of mAb 2E2 for cocaine and 38 cocaine analogues. The K(d) of mAb 2E2 for cocaine was 4 nM, indicating a high affinity. Also, mAb 2E2 displayed good cocaine specificity, as reflected in its 10-, 1500-, and 25000-fold lower binding affinities for the three physiologically relevant cocaine metabolites benzoylecgonine, ecgonine methyl ester, and ecgonine, respectively. 3D-QSAR models of cocaine binding were developed by comparative molecular similarity index analysis (CoMSIA). A model of high statistical quality was generated showing that cocaine binds to mAb 2E2 in a sterically restricted binding site that leaves the methyl group attached to the ring nitrogen of cocaine solvent-exposed. The methyl ester group of cocaine appears to engage in attractive van der Waals interactions with mAb 2E2, whereas the phenyl group contributes to the binding primarily via hydrophobic interactions. The model further indicated that an increase in partial positive charge near the nitrogen proton and methyl ester carbonyl group enhances binding affinity and that the ester oxygen likely forms an intermolecular hydrogen bond with mAb 2E2. Overall, the cocaine binding properties of mAb 2E2 support its clinical potential for development as a treatment of cocaine overdose and addiction.

Quantitative structure-activity relationship studies of threo-methylphenidate analogs.

PubMed

Misra, Milind; Shi, Qing; Ye, Xiaocong; Gruszecka-Kowalik, Ewa; Bu, Wei; Liu, Zhanzhu; Schweri, Margaret M; Deutsch, Howard M; Venanzi, Carol A

2010-10-15

Complementary two-dimensional (2D) and three-dimensional (3D) Quantitative Structure-Activity Relationship (QSAR) techniques were used to derive a preliminary model for the dopamine transporter (DAT) binding affinity of 80 racemic threo-methylphenidate (MP) analogs. A novel approach based on using the atom-level E-state indices of the 14 common scaffold atoms in a sphere exclusion protocol was used to identify a test set for 2D- and 3D-QSAR model validation. Comparative Molecular Field Analysis (CoMFA) contour maps based on the structure-activity data of the training set indicate that the 2' position of the phenyl ring cannot tolerate much steric bulk and that addition of electron-withdrawing groups to the 3' or 4' positions of the phenyl ring leads to improved DAT binding affinity. In particular, the optimal substituents were found to be those whose bulk is mainly in the plane of the phenyl ring. Substituents with significant bulk above or below the plane of the ring led to decreased binding affinity. Suggested alterations to be explored in the design of new compounds are the placement at the 3' and 4' position of the phenyl ring of electron-withdrawing groups that lie chiefly in the plane of the ring, for example, halogen substituents on the 3',4'-benzo analog, 79. A complementary 2D-QSAR approach-partial least squares analysis using a reduced set of Molconn-Z descriptors-supports the CoMFA structure-activity interpretation that phenyl ring substitution is a major determinant of DAT binding affinity. The potential usefulness of the CoMFA models was demonstrated by the prediction of the binding affinity of methyl 2-(naphthalen-1-yl)-2-(piperidin-2-yl)acetate, an analog not in the original data set, to be in good agreement with the experimental value. Copyright © 2010 Elsevier Ltd. All rights reserved.

Testing a pharmacist-patient relationship quality model among older persons with diabetes.

PubMed

Worley, Marcia M

2006-03-01

Considering recent changes to the Medicare program, pharmacists will have unique opportunities to be reimbursed for providing Medication Therapy Management Services to older persons with diabetes. A high-quality pharmacist-patient relationship can lay the foundation for effective provision of Medication Therapy Management Services and improved care in this cohort. To test a pharmacist-patient relationship quality model in a group of older persons with diabetes from the patient's perspective. Antecedents to relationship quality were pharmacist participative behavior/patient-centeredness of relationship, patient participative behavior, and pharmacist-patient interpersonal communication. Pharmacist-patient relationship commitment was the outcome of relationship quality studied. Data were collected via mailed questionnaire from a random sample of 600 community-dwelling adults in the United States who (1) were 65 years of age and older, (2) had type 1 or type 2 diabetes, (3) used at least one prescription medication to treat their diabetes, and (4) used some type of nonmail order pharmacy as their primary source of obtaining prescription medications. Model relationships were tested using path analysis. The adjusted response rate was 41.6% (221/531). The models explained 47% and 49% of the variance in relationship quality and relationship commitment, respectively. In the relationship quality model, pharmacist participative behavior/patient-centeredness of relationship (beta=.51, P<.001) and pharmacist-patient interpersonal communication (beta=.17, P=.008) had direct effects on relationship quality. In the relationship commitment model, relationship quality had a direct effect on relationship commitment (beta=.60, P<.001). Pharmacist participative behavior/patient-centeredness and pharmacist-patient interpersonal communication had indirect effects on relationship commitment through their effects on relationship quality, which is a mediator in the model. Results affirm

Structure-activity relationships of rosiglitazone for peroxisome proliferator-activated receptor gamma transrepression.

PubMed

Toyota, Yosuke; Nomura, Sayaka; Makishima, Makoto; Hashimoto, Yuichi; Ishikawa, Minoru

2017-06-15

Anti-inflammatory effects of peroxisome proliferator-activated receptor gamma (PPRAγ) ligands are thought to be largely due to PPARγ-mediated transrepression. Thus, transrepression-selective PPARγ ligands without agonistic activity or with only partial agonistic activity should exhibit anti-inflammatory properties with reduced side effects. Here, we investigated the structure-activity relationships (SARs) of PPARγ agonist rosiglitazone, focusing on transrepression activity. Alkenic analogs showed slightly more potent transrepression with reduced efficacy of transactivating agonistic activity. Removal of the alkyl group on the nitrogen atom improved selectivity for transrepression over transactivation. Among the synthesized compounds, 3l exhibited stronger transrepressional activity (IC 50 : 14μM) and weaker agonistic efficacy (11%) than rosiglitazone or pioglitazone. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibitor-based validation of a homology model of the active-site of tripeptidyl peptidase II.

PubMed

De Winter, Hans; Breslin, Henry; Miskowski, Tamara; Kavash, Robert; Somers, Marijke

2005-04-01

A homology model of the active site region of tripeptidyl peptidase II (TPP II) was constructed based on the crystal structures of four subtilisin-like templates. The resulting model was subsequently validated by judging expectations of the model versus observed activities for a broad set of prepared TPP II inhibitors. The structure-activity relationships observed for the prepared TPP II inhibitors correlated nicely with the structural details of the TPP II active site model, supporting the validity of this model and its usefulness for structure-based drug design and pharmacophore searching experiments.

49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

Code of Federal Regulations, 2011 CFR

2011-10-01

... natural thorium. 173.434 Section 173.434 Transportation Other Regulations Relating to Transportation....434 Activity-mass relationships for uranium and natural thorium. The table of activity-mass relationships for uranium and natural thorium are as follows: Thorium and uranium enrichment 1(Wt% 235 U present...

49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

Code of Federal Regulations, 2010 CFR

2010-10-01

... natural thorium. 173.434 Section 173.434 Transportation Other Regulations Relating to Transportation....434 Activity-mass relationships for uranium and natural thorium. The table of activity-mass relationships for uranium and natural thorium are as follows: Thorium and uranium enrichment 1(Wt% 235 U present...

The relationship between functional magnetic resonance imaging activation, diffusion tensor imaging, and training effects.

PubMed

Farrar, Danielle; Budson, Andrew E

2017-04-01

While the relationship between diffusion tensor imaging (DTI) measurements and training effects is explored by Voelker et al. (this issue), a cursory discussion of functional magnetic resonance imaging (fMRI) measurements categorizes increased activation with findings of greater white matter integrity. Evidence of the relationship between fMRI activation and white matter integrity is conflicting, as is the relationship between fMRI activation and training effects. An examination of the changes in fMRI activation in response to training is helpful, but the relationship between DTI and fMRI activation, particularly in the context of white matter changes, must be examined further before general conclusions can be drawn.

Relationship of physical activity to fundamental movement skills among adolescents.

PubMed

Okely, A D; Booth, M L; Patterson, J W

2001-11-01

To determine the relationship of participation in organized and nonorganized physical activity with fundamental movement skills among adolescents. Male and female children in Grade 8 (mean age, 13.3 yr) and Grade 10 (mean age, 15.3 yr) were assessed on six fundamental movement skills (run, vertical jump, catch, overhand throw, forehand strike, and kick). Physical activity was assessed using a self-report recall measure where students reported the type, duration, and frequency of participation in organized physical activity and nonorganized physical activity during a usual week. Multiple regression analysis indicated that fundamental movement skills significantly predicted time in organized physical activity, although the percentage of variance it could explain was small. This prediction was stronger for girls than for boys. Multiple regression analysis showed no relationship between time in nonorganized physical activity and fundamental movement skills. Fundamental movement skills are significantly associated with adolescents' participation in organized physical activity, but predict only a small portion of it.

The relationship between physical activity levels and pain in children with juvenile idiopathic arthritis.

PubMed

Limenis, Elizaveta; Grosbein, Haddas A; Feldman, Brian M

2014-02-01

Pain and reduced physical activity levels are common in children with juvenile idiopathic arthritis (JIA). Currently, there is no consensus about the role of physical activity in managing pain in JIA. The purpose of our study was to assess the relationship between physical activity level and pain in children ages 11 to 18 years with JIA. A random sample of 50 patients with JIA were approached by mailed questionnaires. Physical activity was determined using the Physical Activity Questionnaire (PAQ). Pain measures included the Numerical Rating Scale (pain severity), SUPER-KIDZ body diagram (number of painful areas), and the Child Activities Limitations Inventory-21 (pain interference). Generalized linear models were used to assess the relationship between physical activity and pain, as well as the roles of sex and age. The response rate was 84%. Thirty-four respondents completed the questionnaire package. The median age was 15 years. The mean PAQ score was 2.16/5. Physical activity declines with increasing age in youth with JIA (r = 0.53, p = 0.0014). Lower physical activity is associated with greater pain interference (r = 0.39, p = 0.0217) and more severe pain (r = 0.35, p = 0.0422). Children with JIA report significantly less activity than healthy children based on PAQ scores, with physical activity declining throughout adolescence. Physical activity is inversely related to pain interference and severity in children with JIA. Our findings suggest that physical activity interventions may play an important role in the management of pain in JIA.

Planetary spacecraft cost modeling utilizing labor estimating relationships

NASA Technical Reports Server (NTRS)

Williams, Raymond

1990-01-01

A basic computerized technology is presented for estimating labor hours and cost of unmanned planetary and lunar programs. The user friendly methodology designated Labor Estimating Relationship/Cost Estimating Relationship (LERCER) organizes the forecasting process according to vehicle subsystem levels. The level of input variables required by the model in predicting cost is consistent with pre-Phase A type mission analysis. Twenty one program categories were used in the modeling. To develop the model, numerous LER and CER studies were surveyed and modified when required. The result of the research along with components of the LERCER program are reported.

Testing Theory of Planned Behavior and Neo-Socioanalytic Theory models of trait activity, industriousness, exercise social cognitions, exercise intentions, and physical activity in a representative U.S. sample

PubMed Central

Vo, Phuong T.; Bogg, Tim

2015-01-01

Prior research identified assorted relations between trait and social cognition models of personality and engagement in physical activity. Using a representative U.S. sample (N = 957), the goal of the present study was to test two alternative structural models of the relationships among the extraversion-related facet of activity, the conscientiousness-related facet of industriousness, social cognitions from the Theory of Planned Behavior (perceived behavioral control, affective attitudes, subjective norms, intentions), Social Cognitive Theory (self-efficacy, outcome expectancies), and the Transtheoretical Model (behavioral processes of change), and engagement in physical activity. Path analyses with bootstrapping procedures were used to model direct and indirect effects of trait and social cognition constructs on physical activity through two distinct frameworks – the Theory of Planned Behavior and Neo-Socioanalytic Theory. While both models showed good internal fit, comparative model information criteria showed the Theory-of-Planned-Behavior-informed model provided a better fit. In the model, social cognitions fully mediated the relationships from the activity facet and industriousness to intentions for and engagement in physical activity, such that the relationships were primarily maintained by positive affective evaluations, positive expected outcomes, and confidence in overcoming barriers related to physical activity engagement. The resultant model – termed the Disposition-Belief-Motivation model– is proposed as a useful framework for organizing and integrating personality trait facets and social cognitions from various theoretical perspectives to investigate the expression of health-related behaviors, such as physical activity. Moreover, the results are discussed in terms of extending the application of the Disposition-Belief-Motivation model to longitudinal and intervention designs for physical activity engagement. PMID:26300811

Electron-density descriptors as predictors in quantitative structure--activity/property relationships and drug design.

PubMed

Matta, Chérif F; Arabi, Alya A

2011-06-01

The use of electron density-based molecular descriptors in drug research, particularly in quantitative structure--activity relationships/quantitative structure--property relationships studies, is reviewed. The exposition starts by a discussion of molecular similarity and transferability in terms of the underlying electron density, which leads to a qualitative introduction to the quantum theory of atoms in molecules (QTAIM). The starting point of QTAIM is the topological analysis of the molecular electron-density distributions to extract atomic and bond properties that characterize every atom and bond in the molecule. These atomic and bond properties have considerable potential as bases for the construction of robust quantitative structure--activity/property relationships models as shown by selected examples in this review. QTAIM is applicable to the electron density calculated from quantum-chemical calculations and/or that obtained from ultra-high resolution x-ray diffraction experiments followed by nonspherical refinement. Atomic and bond properties are introduced followed by examples of application of each of these two families of descriptors. The review ends with a study whereby the molecular electrostatic potential, uniquely determined by the density, is used in conjunction with atomic properties to elucidate the reasons for the biological similarity of bioisosteres.

Quantitative structure-activity relationships for organophosphates binding to acetylcholinesterase.

PubMed

Ruark, Christopher D; Hack, C Eric; Robinson, Peter J; Anderson, Paul E; Gearhart, Jeffery M

2013-02-01

Organophosphates are a group of pesticides and chemical warfare nerve agents that inhibit acetylcholinesterase, the enzyme responsible for hydrolysis of the excitatory neurotransmitter acetylcholine. Numerous structural variants exist for this chemical class, and data regarding their toxicity can be difficult to obtain in a timely fashion. At the same time, their use as pesticides and military weapons is widespread, which presents a major concern and challenge in evaluating human toxicity. To address this concern, a quantitative structure-activity relationship (QSAR) was developed to predict pentavalent organophosphate oxon human acetylcholinesterase bimolecular rate constants. A database of 278 three-dimensional structures and their bimolecular rates was developed from 15 peer-reviewed publications. A database of simplified molecular input line entry notations and their respective acetylcholinesterase bimolecular rate constants are listed in Supplementary Material, Table I. The database was quite diverse, spanning 7 log units of activity. In order to describe their structure, 675 molecular descriptors were calculated using AMPAC 8.0 and CODESSA 2.7.10. Orthogonal projection to latent structures regression, bootstrap leave-random-many-out cross-validation and y-randomization were used to develop an externally validated consensus QSAR model. The domain of applicability was assessed by the William's plot. Six external compounds were outside the warning leverage indicating potential model extrapolation. A number of compounds had residuals >2 or <-2, indicating potential outliers or activity cliffs. The results show that the HOMO-LUMO energy gap contributed most significantly to the binding affinity. A mean training R (2) of 0.80, a mean test set R (2) of 0.76 and a consensus external test set R (2) of 0.66 were achieved using the QSAR. The training and external test set RMSE values were found to be 0.76 and 0.88. The results suggest that this QSAR model can be used in

Biomacromolecular quantitative structure-activity relationship (BioQSAR): a proof-of-concept study on the modeling, prediction and interpretation of protein-protein binding affinity.

PubMed

Zhou, Peng; Wang, Congcong; Tian, Feifei; Ren, Yanrong; Yang, Chao; Huang, Jian

2013-01-01

Quantitative structure-activity relationship (QSAR), a regression modeling methodology that establishes statistical correlation between structure feature and apparent behavior for a series of congeneric molecules quantitatively, has been widely used to evaluate the activity, toxicity and property of various small-molecule compounds such as drugs, toxicants and surfactants. However, it is surprising to see that such useful technique has only very limited applications to biomacromolecules, albeit the solved 3D atom-resolution structures of proteins, nucleic acids and their complexes have accumulated rapidly in past decades. Here, we present a proof-of-concept paradigm for the modeling, prediction and interpretation of the binding affinity of 144 sequence-nonredundant, structure-available and affinity-known protein complexes (Kastritis et al. Protein Sci 20:482-491, 2011) using a biomacromolecular QSAR (BioQSAR) scheme. We demonstrate that the modeling performance and predictive power of BioQSAR are comparable to or even better than that of traditional knowledge-based strategies, mechanism-type methods and empirical scoring algorithms, while BioQSAR possesses certain additional features compared to the traditional methods, such as adaptability, interpretability, deep-validation and high-efficiency. The BioQSAR scheme could be readily modified to infer the biological behavior and functions of other biomacromolecules, if their X-ray crystal structures, NMR conformation assemblies or computationally modeled structures are available.

Physical activity measurement in older adults: relationships with mental health.

PubMed

Parker, Sarah J; Strath, Scott J; Swartz, Ann M

2008-10-01

This study examined the relationship between physical activity (PA) and mental health among older adults as measured by objective and subjective PA-assessment instruments. Pedometers (PED), accelerometers (ACC), and the Physical Activity Scale for the Elderly (PASE) were administered to measure 1 week of PA among 84 adults age 55-87 (mean = 71) years. General mental health was measured using the Positive and Negative Affect Scale (PANAS) and the Satisfaction With Life Scale (SWL). Linear regressions revealed that PA estimated by PED significantly predicted 18.1%, 8.3%, and 12.3% of variance in SWL and positive and negative affect, respectively, whereas PA estimated by the PASE did not predict any mental health variables. Results from ACC data were mixed. Hotelling-William tests between correlation coefficients revealed that the relationship between PED and SWL was significantly stronger than the relationship between PASE and SWL. Relationships between PA and mental health might depend on the PA measure used.

An orientation sensitive approach in biomolecule interaction quantitative structure-activity relationship modeling and its application in ion-exchange chromatography.

PubMed

Kittelmann, Jörg; Lang, Katharina M H; Ottens, Marcel; Hubbuch, Jürgen

2017-01-27

Quantitative structure-activity relationship (QSAR) modeling for prediction of biomolecule parameters has become an established technique in chromatographic purification process design. Unfortunately available descriptor sets fail to describe the orientation of biomolecules and the effects of ionic strength in the mobile phase on the interaction with the stationary phase. The literature describes several special descriptors used for chromatographic retention modeling, all of these do not describe the screening of electrostatic potential by the mobile phase in use. In this work we introduce two new approaches of descriptor calculations, namely surface patches and plane projection, which capture an oriented binding to charged surfaces and steric hindrance of the interaction with chromatographic ligands with regard to electrostatic potential screening by mobile phase ions. We present the use of the developed descriptor sets for predictive modeling of Langmuir isotherms for proteins at different pH values between pH 5 and 10 and varying ionic strength in the range of 10-100mM. The resulting model has a high correlation of calculated descriptors and experimental results, with a coefficient of determination of 0.82 and a predictive coefficient of determination of 0.92 for unknown molecular structures and conditions. The agreement of calculated molecular interaction orientations with both, experimental results as well as molecular dynamic simulations from literature is shown. The developed descriptors provide the means for improved QSAR models of chromatographic processes, as they reflect the complex interactions of biomolecules with chromatographic phases. Copyright © 2016 Elsevier B.V. All rights reserved.

Adolescents' Perception of the Relationship between Movement Skills, Physical Activity and Sport

ERIC Educational Resources Information Center

Barnett, Lisa; Cliff, Ken; Morgan, Philip; van Beurden, Eric

2013-01-01

Movement skill competence is important to organised youth physical activity participation, but it is unclear how adolescents view this relationship. The primary aim of this study was to explore adolescents' perception of the relationship between movement skills, physical activity and sport, and whether their perceptions differed according to…

Explaining the Relationship Between Sexually Explicit Internet Material and Casual Sex: A Two-Step Mediation Model.

PubMed

Vandenbosch, Laura; van Oosten, Johanna M F

2018-07-01

Despite increasing interest in the implications of adolescents' use of sexually explicit Internet material (SEIM), we still know little about the relationship between SEIM use and adolescents' casual sexual activities. Based on a three-wave online panel survey study among Dutch adolescents (N = 1079; 53.1% boys; 93.5% with an exclusively heterosexual orientation; M age  = 15.11; SD = 1.39), we found that watching SEIM predicted engagement in casual sex over time. In turn, casual sexual activities partially predicted adolescents' use of SEIM. A two-step mediation model was tested to explain the relationship between watching SEIM and casual sex. It was partially confirmed. First, watching SEIM predicted adolescents' perceptions of SEIM as a relevant information source from Wave 2 to Wave 3, but not from Wave 1 to Wave 2. Next, such perceived utility of SEIM was positively related to stronger instrumental attitudes toward sex and thus their views about sex as a core instrument for sexual gratification. Lastly, adolescents' instrumental attitudes toward sex predicted adolescents' engagement in casual sex activities consistently across waves. Partial support emerged for a reciprocal relationship between watching SEIM and perceived utility. We did not find a reverse relationship between casual sex activities and instrumental attitudes toward sex. No significant gender differences emerged.

Structure-activity relationship of karrikin germination stimulants.

PubMed

Flematti, Gavin R; Scaffidi, Adrian; Goddard-Borger, Ethan D; Heath, Charles H; Nelson, David C; Commander, Lucy E; Stick, Robert V; Dixon, Kingsley W; Smith, Steven M; Ghisalberti, Emilio L

2010-08-11

Karrikins (2H-furo[2,3-c]pyran-2-ones) are potent smoke-derived germination promoters for a diverse range of plant species but, to date, their mode of action remains unknown. This paper reports the structure-activity relationship of numerous karrikin analogues to increase understanding of the key structural features of the molecule that are required for biological activity. The results demonstrate that modification at the C5 position is preferred over modification at the C3, C4, or C7 positions for retaining the highest bioactivity.

Cause-and-effect relationships in tandem swimmer models using transfer entropy

NASA Astrophysics Data System (ADS)

Peterson, Sean; Rosen, Maxwell; Gementzopoulos, Antonios; Zhang, Peng; Porfiri, Maurizio

2017-11-01

Swimming in a group affords a number of advantages to fish, including an enhanced ability to escape from predators, search for food, and mate. To study coordinated movements of fish, principled approaches are needed to unravel cause-and-effect relationships from raw-time series of multiple bodies moving in an encompassing fluid. In this work, we aim at demonstrating the validity of transfer entropy to elucidate cause-and-effect relationships in a fluid-structure interaction problem. Specifically, we consider two tandem airfoils in a uniform flow, wherein the pitching angle of one airfoil is actively controlled while the other is allowed to passively rotate. The active control alternates the pitch angle based upon an underlying two-state ergodic Markov process. We monitor the pitch angle of both the active and passive airfoils in time and demonstrate that transfer entropy can detect causality independent of which airfoil is actuated. The influence estimated by transfer entropy is found to be modulated by the distance between the two airfoils. The proposed data-driven technique offers a model-free perspective on fluid-structure interactions that can help illuminate the mechanisms of swimming in coordination. This work was supported by the National Science Foundation under Grant Numbers CBET-1332204 and CMMI-1433670.

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.

PubMed

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 (<3 kDa) derived from combinations of thermolysin + alcalase and thermolysin + proteinase K demonstrated high ACE inhibitory activities. Peptide sequences in hydrolysates derived from these two combinations were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). On the basis of the QSAR modeling prediction, a total of 16 peptides were selected for molecular docking analysis. The docking study revealed that four of the peptides (KFPQY, MPFPKYP, MFPPQ, and QWQVL) bound the active site of ACE. These four novel peptides were chemically synthesized, and their IC 50 was determined. Among these peptides, KFPQY showed the highest ACE inhibitory activity (IC 50 = 12.37 ± 0.43 μM). Our study indicated that Qula casein presents an excellent source to produce ACE inhibitory peptides.

Examining the relationships between body image, eating attitudes, BMI, and physical activity in rural and urban South African young adult females using structural equation modeling

PubMed Central

Wrottesley, Stephanie V.; Cohen, Emmanuel; Reddy, Ankita; Said-Mohamed, Rihlat; Twine, Rhian; Tollman, Stephen M.; Kahn, Kathleen; Dunger, David B.; Norris, Shane A.

2017-01-01

The persistence of food insecurity, malnutrition, increasing adiposity, and decreasing physical activity, heightens the need to understand relationships between body image satisfaction, eating attitudes, BMI and physical activity levels in South Africa. Females aged 18–23 years were recruited from rural (n = 509) and urban (n = 510) settings. Body image satisfaction was measured using Stunkard’s silhouettes, and the 26-item Eating Attitudes questionnaire (EAT-26) was used to evaluate participants’ risk of disordered eating. Minutes per week of moderate to vigorous physical activity (MVPA) was assessed using the Global Physical Activity Questionnaire (GPAQ). Significant linear correlates were included in a series of regressions run separately for urban and rural participants. Structural equation modeling (SEM) was used to test the relationships between variables. Urban females were more likely to be overweight and obese than rural females (p = 0.02), and had a greater desire to be thinner (p = 0.02). In both groups, being overweight or obese was positively associated with a desire to be thinner (p<0.01), and negatively associated with a desire to be fatter (p<0.01). Having a disordered eating attitude was associated with body image dissatisfaction in the urban group (β = 1.27, p<0.01, CI: 0.38; 2.16), but only with a desire to be fatter in the rural group (β = 0.63, p = 0.04, CI: 0.03; 1.23). In the SEM model, body image dissatisfaction was associated with disordered eating (β = 0.63), as well as higher MVPA participation (p<0.01). These factors were directly associated with a decreased risk of disordered eating attitude, and with a decreased desire to be thinner. Findings indicate a shift in both settings towards more Westernised ideals. Physical activity may provide a means to promote a healthy body image, while reducing the risk of disordered eating. Given the high prevalence of overweight and obesity in both rural and urban women, this study provides

Examining the relationships between body image, eating attitudes, BMI, and physical activity in rural and urban South African young adult females using structural equation modeling.

PubMed

Prioreschi, Alessandra; Wrottesley, Stephanie V; Cohen, Emmanuel; Reddy, Ankita; Said-Mohamed, Rihlat; Twine, Rhian; Tollman, Stephen M; Kahn, Kathleen; Dunger, David B; Norris, Shane A

2017-01-01

The persistence of food insecurity, malnutrition, increasing adiposity, and decreasing physical activity, heightens the need to understand relationships between body image satisfaction, eating attitudes, BMI and physical activity levels in South Africa. Females aged 18-23 years were recruited from rural (n = 509) and urban (n = 510) settings. Body image satisfaction was measured using Stunkard's silhouettes, and the 26-item Eating Attitudes questionnaire (EAT-26) was used to evaluate participants' risk of disordered eating. Minutes per week of moderate to vigorous physical activity (MVPA) was assessed using the Global Physical Activity Questionnaire (GPAQ). Significant linear correlates were included in a series of regressions run separately for urban and rural participants. Structural equation modeling (SEM) was used to test the relationships between variables. Urban females were more likely to be overweight and obese than rural females (p = 0.02), and had a greater desire to be thinner (p = 0.02). In both groups, being overweight or obese was positively associated with a desire to be thinner (p<0.01), and negatively associated with a desire to be fatter (p<0.01). Having a disordered eating attitude was associated with body image dissatisfaction in the urban group (β = 1.27, p<0.01, CI: 0.38; 2.16), but only with a desire to be fatter in the rural group (β = 0.63, p = 0.04, CI: 0.03; 1.23). In the SEM model, body image dissatisfaction was associated with disordered eating (β = 0.63), as well as higher MVPA participation (p<0.01). These factors were directly associated with a decreased risk of disordered eating attitude, and with a decreased desire to be thinner. Findings indicate a shift in both settings towards more Westernised ideals. Physical activity may provide a means to promote a healthy body image, while reducing the risk of disordered eating. Given the high prevalence of overweight and obesity in both rural and urban women, this study provides insights

Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling.

PubMed

Yost, Erin E; Stanek, John; DeWoskin, Robert S; Burgoon, Lyle D

2016-07-19

The United States Environmental Protection Agency (EPA) identified 1173 chemicals associated with hydraulic fracturing fluids, flowback, or produced water, of which 1026 (87%) lack chronic oral toxicity values for human health assessments. To facilitate the ranking and prioritization of chemicals that lack toxicity values, it may be useful to employ toxicity estimates from quantitative structure-activity relationship (QSAR) models. Here we describe an approach for applying the results of a QSAR model from the TOPKAT program suite, which provides estimates of the rat chronic oral lowest-observed-adverse-effect level (LOAEL). Of the 1173 chemicals, TOPKAT was able to generate LOAEL estimates for 515 (44%). To address the uncertainty associated with these estimates, we assigned qualitative confidence scores (high, medium, or low) to each TOPKAT LOAEL estimate, and found 481 to be high-confidence. For 48 chemicals that had both a high-confidence TOPKAT LOAEL estimate and a chronic oral reference dose from EPA's Integrated Risk Information System (IRIS) database, Spearman rank correlation identified 68% agreement between the two values (permutation p-value =1 × 10(-11)). These results provide support for the use of TOPKAT LOAEL estimates in identifying and prioritizing potentially hazardous chemicals. High-confidence TOPKAT LOAEL estimates were available for 389 of 1026 hydraulic fracturing-related chemicals that lack chronic oral RfVs and OSFs from EPA-identified sources, including a subset of chemicals that are frequently used in hydraulic fracturing fluids.

CONSIDERATION OF REACTION INTERMEDIATES IN STRUCTURE-ACTIVITY RELATIONSHIPS: A KEY TO UNDERSTANDING AND PREDICTION

EPA Science Inventory

Consideration of Reaction Intermediates in Structure- Activity Relationships: A Key to Understanding and Prediction

A structure-activity relationship (SAR) represents an empirical means for generalizing chemical information relative to biological activity, and is frequent...

A Relationship-Building Model for the Web Retail Marketplace.

ERIC Educational Resources Information Center

Wang, Fang; Head, Milena; Archer, Norm

2000-01-01

Discusses the effects of the Web on marketing practices. Introduces the concept and theory of relationship marketing. The relationship network concept, which typically is only applied to the business-to-business market, is discussed within the business-to-consumer market, and a new relationship-building model for the Web marketplace is proposed.…

A Multi-Stage Maturity Model for Long-Term IT Outsourcing Relationship Success

ERIC Educational Resources Information Center

Luong, Ming; Stevens, Jeff

2015-01-01

The Multi-Stage Maturity Model for Long-Term IT Outsourcing Relationship Success, a theoretical stages-of-growth model, explains long-term success in IT outsourcing relationships. Research showed the IT outsourcing relationship life cycle consists of four distinct, sequential stages: contract, transition, support, and partnership. The model was…

Shared social and emotional activities within adolescent romantic and non-romantic sexual relationships.

PubMed

Williams, Lela Rankin; Russell, Stephen T

2013-05-01

Typically, "non-romantic" sexual relationships are assumed to be casual; however, the emotional and social distinctions between romantic and non-romantic contexts are not well understood, particularly in adolescence. Data from the National Longitudinal Study of Adolescent Health (Add Health) was used to compare shared emotional (e.g., telling partner that they love her/him) and social (e.g., going out in a group) activities within romantic and non-romantic sexual relationships. Adolescents who reported exclusively romantic sexual relationships (n = 1,891) shared more emotional, but not social, activities with their partners than adolescents who were in non-romantic sexual relationships (n = 315; small effect size, r = .07-.13), akin to adolescents who experienced both relationship types (n = 519; small-to-medium effect size, r = .18-.38). Girls shared more emotional and social activities with their partners than boys when in romantic relationships (small effect size, r = .06-.10); there were no significant gender differences within non-romantic sexual relationships. Findings suggest that gendered scripts remain for sexual relationships that are romantic but not for those that are non-romantic. Notably, for the majority of adolescents, non-romantic relationships still held many emotional and social dimensions typical of romantic relationships and differences between relationship types were small. Although non-romantic relationships were less intimate than romantic sexual relationships, there was remarkable heterogeneity within this relationship type. Caution is advised when working with adolescents engaged in "casual" sexual relationships. Understanding the complexity of adolescent sexual relationships is critical for the advancement of effective sex education programming.

Cognitive processes and conflict in close relationships: an attribution-efficacy model.

PubMed

Fincham, F D; Bradbury, T N

1987-12-01

A recently proposed model of cognitive processes underlying conflict in close relationships (Doherty, 1978, 1981a, 1981b) is revised and tested in two studies. Central to the original model are the causal attributions made for conflict and the perceived efficacy or ability to resolve conflict. The model is revised to incorporate judgments of responsibility and to provide a closer link to self-efficacy theory. The first study examines attributions and efficacy expectations in mother-child relationships. As anticipated, only weak evidence was obtained for predictions retained from the original model, high-lighting the relationship-specific nature of cognitive processes for conflict in families. A second study examines husband-wife relationships and provides evidence for the usefulness of an attribution-efficacy model for marital conflict. The attributional component of the model received greater support than that pertaining to efficacy expectations. In both studies, support was obtained for the proposal that the relation between conflict dimensions (e.g., blame) and causal dimensions is mediated by judgments of responsibility. The significance of the revisions to Doherty's model for understanding conflict in close relationships is discussed, and several avenues for further research are outlined.

The First Structure–Activity Relationship Studies for Designer Receptors Exclusively Activated by Designer Drugs

PubMed Central

2016-01-01

Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand–receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure–activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3. PMID:25587888

The Relationship between Traits of Creativity and Physical Activity in the Elderly.

ERIC Educational Resources Information Center

Malone, Harry Nevin

The purpose of this study was to determine if a relationship exists between traits of creativity in the elderly and their level of physical activity. Another purpose was to determine if there was a relationship between traits of creativity focusing on arousal, sensation-seeking, and playfulness and activity. The study used an ex post facto…

Demystifying Multitask Deep Neural Networks for Quantitative Structure-Activity Relationships.

PubMed

Xu, Yuting; Ma, Junshui; Liaw, Andy; Sheridan, Robert P; Svetnik, Vladimir

2017-10-23

Deep neural networks (DNNs) are complex computational models that have found great success in many artificial intelligence applications, such as computer vision1,2 and natural language processing.3,4 In the past four years, DNNs have also generated promising results for quantitative structure-activity relationship (QSAR) tasks.5,6 Previous work showed that DNNs can routinely make better predictions than traditional methods, such as random forests, on a diverse collection of QSAR data sets. It was also found that multitask DNN models-those trained on and predicting multiple QSAR properties simultaneously-outperform DNNs trained separately on the individual data sets in many, but not all, tasks. To date there has been no satisfactory explanation of why the QSAR of one task embedded in a multitask DNN can borrow information from other unrelated QSAR tasks. Thus, using multitask DNNs in a way that consistently provides a predictive advantage becomes a challenge. In this work, we explored why multitask DNNs make a difference in predictive performance. Our results show that during prediction a multitask DNN does borrow "signal" from molecules with similar structures in the training sets of the other tasks. However, whether this borrowing leads to better or worse predictive performance depends on whether the activities are correlated. On the basis of this, we have developed a strategy to use multitask DNNs that incorporate prior domain knowledge to select training sets with correlated activities, and we demonstrate its effectiveness on several examples.

Modeling microbial products in activated sludge under feast-famine conditions.

PubMed

Ni, Bing-Jie; Fang, Fang; Rittmann, Bruce E; Yu, Han-Qing

2009-04-01

We develop an expanded unified model that integrates production and consumption of internal storage products (X(STO)) into a unified model for extracellular polymeric substances (EPS), soluble microbial products (SMP), and active and inert biomass in activated sludge. We also conducted independent experiments to find needed parameter values and to test the ability of the expanded unified model to describe all the microbial products, along with original substrate and oxygen uptake. The model simulations match all experimental measurements and provide insights into the dynamics of soluble and solid components in activated sludge exposed to dynamic feast-and-famine conditions in two batch experiments and in one cycle of a sequencing batch reactor. In particular, the model illustrates how X(STO) cycles up and down rapidly during feast and famine periods, while EPS and biomass components are relatively stable despite feast and famine. The agreement between model outputs and experimental EPS, SMP, and X(STO) data from distinctly different experiments supports that the expanded unified model properly captures the relationships among the forms of microbial products.

The activation strain model and molecular orbital theory

PubMed Central

Wolters, Lando P; Bickelhaupt, F Matthias

2015-01-01

The activation strain model is a powerful tool for understanding reactivity, or inertness, of molecular species. This is done by relating the relative energy of a molecular complex along the reaction energy profile to the structural rigidity of the reactants and the strength of their mutual interactions: ΔE(ζ) = ΔEstrain(ζ) + ΔEint(ζ). We provide a detailed discussion of the model, and elaborate on its strong connection with molecular orbital theory. Using these approaches, a causal relationship is revealed between the properties of the reactants and their reactivity, e.g., reaction barriers and plausible reaction mechanisms. This methodology may reveal intriguing parallels between completely different types of chemical transformations. Thus, the activation strain model constitutes a unifying framework that furthers the development of cross-disciplinary concepts throughout various fields of chemistry. We illustrate the activation strain model in action with selected examples from literature. These examples demonstrate how the methodology is applied to different research questions, how results are interpreted, and how insights into one chemical phenomenon can lead to an improved understanding of another, seemingly completely different chemical process. WIREs Comput Mol Sci 2015, 5:324–343. doi: 10.1002/wcms.1221 PMID:26753009

Contraceptive use and pregnancies in adolescents' romantic relationships: role of relationship activities and parental attitudes and communication.

PubMed

Amialchuk, Aliaksandr; Gerhardinger, Laura

2015-01-01

In a unified framework, the authors estimate whether romantic relationship activities and parental attitudes predict contraception use and consistency, and whether contraception use and consistency predict pregnancy risk among male and females adolescents in the United States. Data on 3717 participants of the first 2 waves of the National Longitudinal Study of Adolescent Health (Add Health) who were sexually experienced in their recent romantic relationship were analyzed to examine how presex activities in the romantic relationship and parental attitudes and communication are associated with contraception choices and how contraception choices are associated with pregnancies. In multivariate logistic regression analysis, only some relationship activities and parental communication about contraception were significant predictors of contraception, and their influence differed by gender. Going out with the partner increased contraception consistency among males (odds ratio, 2.04). Discussing contraception with the partner before having first sex increased the odds of ever using contraception for both genders (2.61 for females and 1.59 for males) and increased the odds of consistent contraception for females (1.505). Discussing contraception with parent increased the odds of consistent contraception among females (1.383). Merely, using contraception was not a significant predictor of the risk of pregnancy, whereas using contraception consistently significantly reduced the odds of getting partner pregnant for males (0.413) and the odds of pregnancy of females (0.343). Contraception and pregnancy education programs should take into account qualities of romantic relationship and emphasize consistent use of contraception and communication about contraception between partners and with parents.

Relationship between leptin concentrations and disease activity in patients with rheumatoid arthritis.

PubMed

Batún-Garrido, José Antonio de Jesús; Salas-Magaña, Marisol; Juárez-Rojop, Isela Esther; Hernández-Núñez, Eúfrates; Olán, Francisco

2018-05-11

Multiple studies have found a direct relationship between leptin concentrations and disease activity in rheumatoid arthritis. We studied 77 patients with the diagnosis of rheumatoid arthritis; the leptin determination was through an enzyme immunoassay. Disease activity was assessed by the DAS-28 CRP. A multivariate logistic regression model was used to determine the association between significant variables and leptin concentrations. 40.3% of the patients were in remission, 41.6% were mildly active, 11.7% were moderately active and 6.5% were severely active. The results show an independent association between higher concentrations of leptin and disease activity (OR 1.7; 95% CI 1.4-3.2; p .03), the number of swollen joints (OR 4.6; 95% CI 1.7-8.3; p .000), the number of painful joints (OR 3.4; 95% CI 1.6-4.6; p .000), and the presence of metabolic syndrome (OR 1.3; 95% IC 1.2-1,9; p .045). The data suggest that serum leptin is elevated in patients with active RA. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Is the relationship between the built environment and physical activity moderated by perceptions of crime and safety?

PubMed

Bracy, Nicole L; Millstein, Rachel A; Carlson, Jordan A; Conway, Terry L; Sallis, James F; Saelens, Brian E; Kerr, Jacqueline; Cain, Kelli L; Frank, Lawrence D; King, Abby C

2014-02-24

Direct relationships between safety concerns and physical activity have been inconsistently patterned in the literature. To tease out these relationships, crime, pedestrian, and traffic safety were examined as moderators of built environment associations with physical activity. Exploratory analyses used two cross-sectional studies of 2068 adults ages 20-65 and 718 seniors ages 66+ with similar designs and measures. The studies were conducted in the Baltimore, Maryland-Washington, DC and Seattle-King County, Washington regions during 2001-2005 (adults) and 2005-2008 (seniors). Participants were recruited from areas selected to sample high- and low- income and walkability. Independent variables perceived crime, traffic, and pedestrian safety were measured using scales from validated instruments. A GIS-based walkability index was calculated for a street-network buffer around each participant's home address. Outcomes were total physical activity measured using accelerometers and transportation and leisure walking measured with validated self-reports (IPAQ-long). Mixed effects regression models were conducted separately for each sample. Of 36 interactions evaluated across both studies, only 5 were significant (p< .05). Significant interactions did not consistently support a pattern of highest physical activity when safety was rated high and environments were favorable. There was not consistent evidence that safety concerns reduced the beneficial effects of favorable environments on physical activity. Only pedestrian safety showed evidence of a consistent main effect with physical activity outcomes, possibly because pedestrian safety items (e.g., crosswalks, sidewalks) were not as subjective as those on the crime and traffic safety scales. Clear relationships between crime, pedestrian, and traffic safety with physical activity levels remain elusive. The development of more precise safety variables and the use of neighborhood-specific physical activity outcomes may help

Is the relationship between the built environment and physical activity moderated by perceptions of crime and safety?

PubMed Central

2014-01-01

Background Direct relationships between safety concerns and physical activity have been inconsistently patterned in the literature. To tease out these relationships, crime, pedestrian, and traffic safety were examined as moderators of built environment associations with physical activity. Methods Exploratory analyses used two cross-sectional studies of 2068 adults ages 20–65 and 718 seniors ages 66+ with similar designs and measures. The studies were conducted in the Baltimore, Maryland-Washington, DC and Seattle-King County, Washington regions during 2001–2005 (adults) and 2005–2008 (seniors). Participants were recruited from areas selected to sample high- and low- income and walkability. Independent variables perceived crime, traffic, and pedestrian safety were measured using scales from validated instruments. A GIS-based walkability index was calculated for a street-network buffer around each participant’s home address. Outcomes were total physical activity measured using accelerometers and transportation and leisure walking measured with validated self-reports (IPAQ-long). Mixed effects regression models were conducted separately for each sample. Results Of 36 interactions evaluated across both studies, only 5 were significant (p < .05). Significant interactions did not consistently support a pattern of highest physical activity when safety was rated high and environments were favorable. There was not consistent evidence that safety concerns reduced the beneficial effects of favorable environments on physical activity. Only pedestrian safety showed evidence of a consistent main effect with physical activity outcomes, possibly because pedestrian safety items (e.g., crosswalks, sidewalks) were not as subjective as those on the crime and traffic safety scales. Conclusions Clear relationships between crime, pedestrian, and traffic safety with physical activity levels remain elusive. The development of more precise safety variables and the use of

Team Risk Management: A New Model for Customer-Supplier Relationships

DTIC Science & Technology

1994-07-01

Management : A New Model for Customer - Supplier Relationships Ronald P. Higuera "Audrey J. Dorofee Julie A. Walker Ray C. Williams July 1994 ""•// 94...N/A N/A N/A 11. TITLE (Include Secuity Claaaificatioa) Team Risk Management : A New Model for Customer -Supplier Relationships 12. PERSONAL AUTHOR(S...by block number) FIELD GROUP SUB. GR. Customer - Supplier Relationships Risk Team Risk Management 19. ABSTRACT (cominus on = if necesaryd id’y by block

DEVELOPMENT OF STRUCTURE ACTIVITY RELATIONSHIPS FOR ASSESSING ECOLOGICAL RISKS

EPA Science Inventory

In the field of environmental toxicology, structure activity relationships (SARs) have developed as scientifically-credible tools for predicting the effects of chemicals when little or no empirical data are available.

Relationship between participation in leisure activities and constraints on Taiwanese breastfeeding mothers during leisure activities

PubMed Central

2013-01-01

Background Participation in leisure activities strongly associates with health and well-being. Little research has explored the relationship between participation in leisure activities and constraints on breastfeeding mothers during leisure activities. The purposes of this study are: 1) to investigate constraints on breastfeeding mothers during leisure activities and participation in leisure activities; 2) to investigate the differences between preferences for leisure activities and actual participation by breastfeeding mothers; 3) to segment breastfeeding mothers with similar patterns, using a cluster analysis based on the delineated participation in leisure activities and leisure preferences; 4) to explore any differences between clusters of breastfeeding mothers with respect to socio-demographic characteristics, breastfeeding behaviours and leisure constraints. Methods This study has a cross-sectional design using an online survey conducted among mothers having breastfeeding experiences of more than four months. The questionnaire includes demographic variables, breastfeeding behaviours, preferences for leisure activities participation, and constraints on leisure activities. Collection of data occurred between March and July 2011, producing 415 valid responses for analysis. Results For breastfeeding mothers, this study identifies constraints on breastfeeding related to leisure activities in addition to the three traditional factors for constraints in the model. This study demonstrates that reports of constraints related to children, family, and nursing environments are the most frequent. Breastfeeding mothers in Taiwan participate regularly in family activities or activities related to their children. Cluster analysis classified breastfeeding mothers into Action and Contemplation groups, and found that mothers within the latter group participate less in leisure activities and experienced more constraints related to breastfeeding. Conclusions Implications provide

American time use survey: sleep time and its relationship to waking activities.

PubMed

Basner, Mathias; Fomberstein, Kenneth M; Razavi, Farid M; Banks, Siobhan; William, Jeffrey H; Rosa, Roger R; Dinges, David F

2007-09-01

To gain some insight into how various behavioral (lifestyle) factors influence sleep duration, by investigation of the relationship of sleep time to waking activities using the American Time Use Survey (ATUS). Cross-sectional data from ATUS, an annual telephone survey of a population sample of US citizens who are interviewed regarding how they spent their time during a 24-hour period between 04:00 on the previous day and 04:00 on the interview day. Data were pooled from the 2003, 2004, and 2005 ATUS databases involving N=47,731 respondents older than 14 years of age. N/A. Adjusted multiple linear regression models showed that the largest reciprocal relationship to sleep was found for work time, followed by travel time, which included commute time. Only shorter than average sleepers (<7.5 h) spent more time socializing, relaxing, and engaging in leisure activities, while both short (<5.5 h) and long sleepers (> or =8.5 h) watched more TV than the average sleeper. The extent to which sleep time was exchanged for waking activities was also shown to depend on age and gender. Sleep time was minimal while work time was maximal in the age group 45-54 yr, and sleep time increased both with lower and higher age. Work time, travel time, and time for socializing, relaxing, and leisure are the primary activities reciprocally related to sleep time among Americans. These activities may be confounding the frequently observed association between short and long sleep on one hand and morbidity and mortality on the other hand and should be controlled for in future studies.

Designing a Quantitative Structure-Activity Relationship for the ...

EPA Pesticide Factsheets

Toxicokinetic models serve a vital role in risk assessment by bridging the gap between chemical exposure and potentially toxic endpoints. While intrinsic metabolic clearance rates have a strong impact on toxicokinetics, limited data is available for environmentally relevant chemicals including nearly 8000 chemicals tested for in vitro bioactivity in the Tox21 program. To address this gap, a quantitative structure-activity relationship (QSAR) for intrinsic metabolic clearance rate was developed to offer reliable in silico predictions for a diverse array of chemicals. Models were constructed with curated in vitro assay data for both pharmaceutical-like chemicals (ChEMBL database) and environmentally relevant chemicals (ToxCast screening) from human liver microsomes (2176 from ChEMBL) and human hepatocytes (757 from ChEMBL and 332 from ToxCast). Due to variability in the experimental data, a binned approach was utilized to classify metabolic rates. Machine learning algorithms, such as random forest and k-nearest neighbor, were coupled with open source molecular descriptors and fingerprints to provide reasonable estimates of intrinsic metabolic clearance rates. Applicability domains defined the optimal chemical space for predictions, which covered environmental chemicals well. A reduced set of informative descriptors (including relative charge and lipophilicity) and a mixed training set of pharmaceuticals and environmentally relevant chemicals provided the best intr

Models of physician-patient relationships in pharmaceutical direct-to-consumer advertising and consumer interviews.

PubMed

Arney, Jennifer; Lewin, Benjamin

2013-07-01

The rise of direct-to-consumer advertising (DTCA) has mirrored, if not facilitated, the shift toward more active health care consumers. We used content analysis to identify models of physician-patient interaction in DTCA from the 1997 to 2006 issues of a broad sample of women's, men's, and common readership magazines. We also conducted 36 in-depth interviews to examine the ways consumers receive and regard advertising messages, and to explore their preferences for clinical communication and decision making. We identified four models of physician-patient relationships that vary in their locus of control (physician, patient, or shared) and the form of support sought or obtained in the relationship (emotional or instrumental). Whereas consumer interviews reflected references to all four models of interaction, only two appeared in DTCA. The limited range of interactions seen in these advertisements creates a lack of congruity between interaction styles found in advertisements vs. styles reported by actual consumers.

Three-dimensional quantitative structure-activity relationship studies on c-Src inhibitors based on different docking methods.

PubMed

Bairy, Santhosh Kumar; Suneel Kumar, B V S; Bhalla, Joseph Uday Tej; Pramod, A B; Ravikumar, Muttineni

2009-04-01

c-Src kinase play an important role in cell growth and differentiation and its inhibitors can be useful for the treatment of various diseases, including cancer, osteoporosis, and metastatic bone disease. Three dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on quinazolin derivatives inhibiting c-Src kinase. Molecular field analysis (MFA) models with four different alignment techniques, namely, GLIDE, GOLD, LIGANDFIT and Least squares based methods were developed. glide based MFA model showed better results (Leave one out cross validation correlation coefficient r(2)(cv) = 0.923 and non-cross validation correlation coefficient r(2)= 0.958) when compared with other models. These results help us to understand the nature of descriptors required for activity of these compounds and thereby provide guidelines to design novel and potent c-Src kinase inhibitors.

Quantitative structure-activity relationships of selective antagonists of glucagon receptor using QuaSAR descriptors.

PubMed

Manoj Kumar, Palanivelu; Karthikeyan, Chandrabose; Hari Narayana Moorthy, Narayana Subbiah; Trivedi, Piyush

2006-11-01

In the present paper, quantitative structure activity relationship (QSAR) approach was applied to understand the affinity and selectivity of a novel series of triaryl imidazole derivatives towards glucagon receptor. Statistically significant and highly predictive QSARs were derived for glucagon receptor inhibition by triaryl imidazoles using QuaSAR descriptors of molecular operating environment (MOE) employing computer-assisted multiple regression procedure. The generated QSAR models revealed that factors related to hydrophobicity, molecular shape and geometry predominantly influences glucagon receptor binding affinity of the triaryl imidazoles indicating the relevance of shape specific steric interactions between the molecule and the receptor. Further, QSAR models formulated for selective inhibition of glucagon receptor over p38 mitogen activated protein (MAP) kinase of the compounds in the series highlights that the same structural features, which influence the glucagon receptor affinity, also contribute to their selective inhibition.

Non-linear quantitative structure-activity relationship for adenine derivatives as competitive inhibitors of adenosine deaminase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadat Hayatshahi, Sayyed Hamed; Abdolmaleki, Parviz; Safarian, Shahrokh

2005-12-16

Logistic regression and artificial neural networks have been developed as two non-linear models to establish quantitative structure-activity relationships between structural descriptors and biochemical activity of adenosine based competitive inhibitors, toward adenosine deaminase. The training set included 24 compounds with known k {sub i} values. The models were trained to solve two-class problems. Unlike the previous work in which multiple linear regression was used, the highest of positive charge on the molecules was recognized to be in close relation with their inhibition activity, while the electric charge on atom N1 of adenosine was found to be a poor descriptor. Consequently, themore » previously developed equation was improved and the newly formed one could predict the class of 91.66% of compounds correctly. Also optimized 2-3-1 and 3-4-1 neural networks could increase this rate to 95.83%.« less

The Relationships between Modelling and Argumentation from the Perspective of the Model of Modelling Diagram

ERIC Educational Resources Information Center

Mendonça, Paula Cristina Cardoso; Justi, Rosária

2013-01-01

Some studies related to the nature of scientific knowledge demonstrate that modelling is an inherently argumentative process. This study aims at discussing the relationship between modelling and argumentation by analysing data collected during the modelling-based teaching of ionic bonding and intermolecular interactions. The teaching activities…

Modeling time-lagged reciprocal psychological empowerment-performance relationships.

PubMed

Maynard, M Travis; Luciano, Margaret M; D'Innocenzo, Lauren; Mathieu, John E; Dean, Matthew D

2014-11-01

Employee psychological empowerment is widely accepted as a means for organizations to compete in increasingly dynamic environments. Previous empirical research and meta-analyses have demonstrated that employee psychological empowerment is positively related to several attitudinal and behavioral outcomes including job performance. While this research positions psychological empowerment as an antecedent influencing such outcomes, a close examination of the literature reveals that this relationship is primarily based on cross-sectional research. Notably, evidence supporting the presumed benefits of empowerment has failed to account for potential reciprocal relationships and endogeneity effects. Accordingly, using a multiwave, time-lagged design, we model reciprocal relationships between psychological empowerment and job performance using a sample of 441 nurses from 5 hospitals. Incorporating temporal effects in a staggered research design and using structural equation modeling techniques, our findings provide support for the conventional positive correlation between empowerment and subsequent performance. Moreover, accounting for the temporal stability of variables over time, we found support for empowerment levels as positive influences on subsequent changes in performance. Finally, we also found support for the reciprocal relationship, as performance levels were shown to relate positively to changes in empowerment over time. Theoretical and practical implications of the reciprocal psychological empowerment-performance relationships are discussed. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Modeling process-structure-property relationships for additive manufacturing

NASA Astrophysics Data System (ADS)

Yan, Wentao; Lin, Stephen; Kafka, Orion L.; Yu, Cheng; Liu, Zeliang; Lian, Yanping; Wolff, Sarah; Cao, Jian; Wagner, Gregory J.; Liu, Wing Kam

2018-02-01

This paper presents our latest work on comprehensive modeling of process-structure-property relationships for additive manufacturing (AM) materials, including using data-mining techniques to close the cycle of design-predict-optimize. To illustrate the processstructure relationship, the multi-scale multi-physics process modeling starts from the micro-scale to establish a mechanistic heat source model, to the meso-scale models of individual powder particle evolution, and finally to the macro-scale model to simulate the fabrication process of a complex product. To link structure and properties, a highefficiency mechanistic model, self-consistent clustering analyses, is developed to capture a variety of material response. The model incorporates factors such as voids, phase composition, inclusions, and grain structures, which are the differentiating features of AM metals. Furthermore, we propose data-mining as an effective solution for novel rapid design and optimization, which is motivated by the numerous influencing factors in the AM process. We believe this paper will provide a roadmap to advance AM fundamental understanding and guide the monitoring and advanced diagnostics of AM processing.

The relationship of alcohol use and physical activity from an ecologic perspective.

PubMed

Bigelow, April; Villarruel, Antonia; Ronis, David L

2014-01-01

To determine the predictors of alcohol use (AU) and their relationship to physical activity (PA) among adolescents and to examine differences among groups using an ecologic model. Cross sectional secondary analysis of 11,432 adolescents (51% 8th and 49% 10th graders). Attitude, perception of risk, and academic performance were the strongest predictors of AU. PA did not moderate, but it had a positive influence on AU in 10th graders. Differences were observed among groups. Nurses can address individual and school factors in an effort to decrease AU and guide nurses in creating an individualized plan. © 2013, Wiley Periodicals, Inc.

Couple Infertility: From the Perspective of the Close-Relationship Model.

ERIC Educational Resources Information Center

Higgins, Barbara S.

1990-01-01

Presents Close-Relationship Model as comprehensive framework in which to examine interrelated nature of causes and effects of infertility on marital relationship. Includes these factors: physical and psychological characteristics of both partners; joint, couple characteristics; physical and social environment; and relationship itself. Discusses…

Adaptation of the length-active tension relationship in rabbit detrusor

PubMed Central

Almasri, Atheer M.; Bhatia, Hersch; Klausner, Adam P.; Ratz, Paul H.

2009-01-01

Studies have shown that the length-tension (L-T) relationships in airway and vascular smooth muscles are dynamic and can adapt to length changes over a period of time. Our prior studies have shown that the passive L-T relationship in rabbit detrusor smooth muscle (DSM) is also dynamic and that DSM exhibits adjustable passive stiffness (APS) characterized by a passive L-T curve that can shift along the length axis as a function of strain history and activation history. The present study demonstrates that the active L-T curve for DSM is also dynamic and that the peak active tension produced at a particular muscle length is a function of both strain and activation history. More specifically, this study reveals that the active L-T relationship, or curve, does not have a unique peak tension value with a single ascending and descending limb, but instead reveals that multiple ascending and descending limbs can be exhibited in the same DSM strip. This study also demonstrates that for DSM strips not stretched far enough to reveal a descending limb, the peak active tension produced by a maximal KCl-induced contraction at a short, passively slack muscle length of 3 mm was reduced by 58.6 ± 4.1% (n = 15) following stretches to and contractions at threefold the original muscle length, 9 mm. Moreover, five subsequent contractions at the short muscle length displayed increasingly greater tension; active tension produced by the sixth contraction was 91.5 ± 9.1% of that produced by the prestretch contraction at that length. Together, these findings indicate for the first time that DSM exhibits length adaptation, similar to vascular and airway smooth muscles. In addition, our findings demonstrate that preconditioning, APS and adaptation of the active L-T curve can each impact the maximum total tension observed at a particular DSM length. PMID:19675182

The relationship between vigorous physical activity and juvenile delinquency: a mediating role for self-esteem?

PubMed

Faulkner, Guy E J; Adlaf, Edward M; Irving, Hyacinth M; Allison, Kenneth R; Dwyer, John J M; Goodman, Jack

2007-04-01

Many policy-related reviews of the potential social value of sport and physical activity list the prevention of juvenile delinquency. We examined the relationships among vigorous physical activity, self-esteem, and delinquent behavior among adolescents in a large cross-sectional survey of Ontario adolescents. Data are based on questionnaires from 3,796 students (range 11-20 years) derived from the 2005 Ontario Student Drug Use Survey. Negative binominal regression methods were used to estimate both additive and interactive models predicting delinquent behavior. Vigorous physical activity was positively associated with delinquent behavior; however, this pattern of association was observed only among male adolescents. There was no evidence of a mediating role for self-esteem. Our findings suggest that physical activity is not the solution for reducing juvenile delinquency.

Structure- and ligand-based structure-activity relationships for a series of inhibitors of aldolase.

PubMed

Ferreira, Leonardo G; Andricopulo, Adriano D

2012-12-01

Aldolase has emerged as a promising molecular target for the treatment of human African trypanosomiasis. Over the last years, due to the increasing number of patients infected with Trypanosoma brucei, there is an urgent need for new drugs to treat this neglected disease. In the present study, two-dimensional fragment-based quantitative-structure activity relationship (QSAR) models were generated for a series of inhibitors of aldolase. Through the application of leave-one-out and leave-many-out cross-validation procedures, significant correlation coefficients were obtained (r²=0.98 and q²=0.77) as an indication of the statistical internal and external consistency of the models. The best model was employed to predict pKi values for a series of test set compounds, and the predicted values were in good agreement with the experimental results, showing the power of the model for untested compounds. Moreover, structure-based molecular modeling studies were performed to investigate the binding mode of the inhibitors in the active site of the parasitic target enzyme. The structural and QSAR results provided useful molecular information for the design of new aldolase inhibitors within this structural class.

Physical activity and healthy diet: determinants and implicit relationship.

PubMed

Tavares, Aida Isabel

2014-06-01

People who decide to lose weight by dieting often do so without participating in any associated physical activity. Although some people who participate in sports are unconcerned about their diet, it is generally believed that people who exercise tend to eat a healthy diet and those who do not exercise eat a less healthy diet. There is no clear relationship between the decisions regarding participation in physical activity and eating a healthy diet when choices are taken freely and not influenced by policy factors promoting healthy behaviour. However, these decisions may reveal some common explanatory factors and an implicit link. As such the aim of this study was to identify the common explanatory factors and investigate the existence of an implicit relationship. Econometric estimate - bivariate probit estimation. Using data from the Portuguese National Health Survey, a bivariate probit was undertaken for decisions regarding participation in physical activity and eating a healthy diet. The correlation between the residuals gives information on the implicit relationship between the healthy choices. Common explanatory factors were found between the decisions to eat healthy snacks and participate in physical activity, such as being married. However, holding voluntary private health insurance, smoking, getting older, living alone and unemployment were found to dissuade people from making healthy choices. Positive correlation was found between the residuals of the probit estimations, indicating that other unmeasurable variables have a similar influence on both decisions, such as peer pressure, cultural values, fashion, advertising and risk aversion. Further research is needed to improve understanding of decision making related to participation in physical activity and eating a healthy diet. This will facilitate the design of policies that will make a greater contribution to healthy lifestyles. Copyright © 2014 The Royal Society for Public Health. Published by Elsevier

Assessing the relationship between quality of life and behavioral activation using the Japanese Behavioral Activation for Depression Scale-Short Form.

PubMed

Shudo, Yusuke; Yamamoto, Tatsuya

2017-01-01

Quality of life (QOL) is an important health-related concept. Identifying factors that affect QOL can help develop and improve health-promotion interventions. Previous studies suggest that behavioral activation fosters subjective QOL, including well-being. However, the mechanism by which behavioral activation improves QOL is not clear. Considering that QOL improves when depressive symptoms improve post-treatment and that behavioral activation is an effective treatment for depression, it is possible that behavioral activation affects QOL indirectly rather than directly. To clarify the mechanism of the influence of behavioral activation on QOL, it is necessary to examine the relationships between factors related to behavioral activation, depressive symptoms, and QOL. Therefore, we attempted to examine the relationship between these factors. Participants comprised 221 Japanese undergraduate students who completed questionnaires on behavioral activation, QOL, and depressive symptoms: the Japanese versions of the Behavioral Activation for Depression Scale-Short Form (BADS-SF), WHO Quality of Life-BREF (WHOQOL-26), and Center for Epidemiologic Studies Depression Scale (CES-D). The BADS-SF comprises two subscales, Activation and Avoidance, and the WHOQOL-26 measures overall QOL and four domains, Physical Health, Psychological Health, Social Relationships, and Environment. Mediation analyses were conducted with BADS-SF activation and avoidance as independent variables, CES-D as a mediator variable, and each WHO-QOL as an outcome variable. Results indicated that depression completely mediated the relationship between Avoidance and QOL, and partially mediated the relationship between Activation and QOL. In addition, analyses of each domain of QOL showed that Activation positively affected all aspects of QOL directly and indirectly, but Avoidance had a negative influence on only part of QOL mainly through depression. The present study provides behavioral activation strategies

Prospective Relationships Between Physical Activity and Optimism in Young and Mid-aged Women.

PubMed

Pavey, Toby G; Burton, Nicola W; Brown, Wendy J

2015-07-01

There is growing evidence that regular physical activity (PA) reduces the risk of poor mental health. Less research has focused on the relationship between PA and positive wellbeing. The study aims were to assess the prospective associations between PA and optimism, in both young and mid-aged women. 9688 young women (born 1973-1978) completed self-report surveys in 2000 (age 22 to 27), 2003, 2006, and 2009; and 11,226 mid-aged women (born 1946-1951) completed surveys in 2001 (age 50-55) 2004, 2007, and 2010, as part of the Australian Longitudinal Study on Women's Health. Generalized estimating equation models (with 3-year time lag) were used to examine the relationship between PA and optimism in both cohorts. In both cohorts, women reporting higher levels of PA had greater odds of reporting higher optimism over the 9-year period, (young, OR = 5.04, 95% CI: 3.85-6.59; mid-age, OR = 5.77, 95% CI: 4.76-7.00) than women who reported no PA. Odds were attenuated in adjusted models, with depression accounting for a large amount of this attenuation (young, OR = 2.00, 95% CI: 1.57-2.55; mid-age, OR = 1.64 95% CI: 1.38-1.94). Physical activity can promote optimism in young and mid-aged women over time, even after accounting for the negative effects of other psychosocial indicators such as depression.

Investigating attachment, caregiving, and mental health: a model of maternal-fetal relationships.

PubMed

Walsh, Judi; Hepper, Erica G; Marshall, Benjamin J

2014-11-19

Maternal-fetal relationships have been associated with psychosocial outcomes for women and children, but there has been a lack of conceptual clarity about the nature of the maternal relationship with the unborn child, and inconsistent findings assessing its predictors. We proposed and tested a model whereby maternal-fetal relationship quality was predicted by factors relating to the quality of the couple relationship and psychological health. We hypothesized that the contribution of individual differences in romantic attachment shown in past research would be mediated by romantic caregiving responsiveness, as maternal-fetal relationships reflect the beginnings of the caregiving system. 258 women in pregnancy (13, 23, and 33-weeks gestation) completed online measures of attachment to partner, caregiving responsiveness to partner, mental health, and thoughts about their unborn baby. Structural equation modeling was used to test a model of maternal-fetal relationships. Maternal-fetal relationship quality was higher for women at 23-weeks than 13-weeks gestation. Women in first pregnancies had higher self-reported scores of psychological functioning and quality of maternal-fetal relationships than women in subsequent pregnancies. Structural equation models indicated that the quality of the maternal-fetal relationship was best predicted by romantic caregiving responsiveness to partner and women's own psychological health, and that the association between adult romantic attachment avoidance and maternal-fetal relationships was fully mediated by caregiving responsiveness to partner, even after controlling for other factors. These data support the hypothesis that maternal-fetal relationships better reflect the operation of the caregiving system than the care-seeking (i.e., attachment) system. Models of maternal-fetal relationships and interventions with couples should consider the role of caregiving styles of mothers to partners and the relationship between expectant

Active public Facebook use and adolescents' feelings of loneliness: Evidence for a curvilinear relationship.

PubMed

Wang, Kexin; Frison, Eline; Eggermont, Steven; Vandenbosch, Laura

2018-06-09

Inconsistent results have been reported concerning the relationships between SNS usage and loneliness. The current two-wave panel study with a one year interval examined the possibility of reciprocal and curvilinear relationships between active public Facebook use and adolescents' social/emotional loneliness. Belgian adolescents from fifteen high schools participated (N = 1188, 55% male). The results showed a U-shaped relationship between (1) active Facebook use and social/emotional loneliness and (2) emotional loneliness and active Facebook use. Specifically, active Facebook use predicted decreased social/emotional loneliness among low to moderate users, while among heavy users, increased levels of social/emotional loneliness were predicted by active Facebook use. Emotional loneliness predicted higher active Facebook use among lonely adolescents. At the same time, emotional loneliness predicted decreased active Facebook use among adolescents who did not feel lonely. These findings stress to consider different types of loneliness, and reciprocal and curvilinear relationships in future social media research. Copyright © 2018 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Relationship between Frequency and Intensity of Physical Activity and Health Behaviors of Adolescents

ERIC Educational Resources Information Center

Delisle, Tony T.; Werch, Chudley E.; Wong, Alvin H.; Bian, Hui; Weiler, Robert

2010-01-01

Background: While studies have determined the importance of physical activity in advancing health outcomes, relatively few have explored the relationship between exercise and various health behaviors of adolescents. The purpose of this study is to examine the relationship between frequency and intensity of physical activity and both health risk…

Obscure phenomena in statistical analysis of quantitative structure-activity relationships. Part 1: Multicollinearity of physicochemical descriptors.

PubMed

Mager, P P; Rothe, H

1990-10-01

Multicollinearity of physicochemical descriptors leads to serious consequences in quantitative structure-activity relationship (QSAR) analysis, such as incorrect estimators and test statistics of regression coefficients of the ordinary least-squares (OLS) model applied usually to QSARs. Beside the diagnosis of the known simple collinearity, principal component regression analysis (PCRA) also allows the diagnosis of various types of multicollinearity. Only if the absolute values of PCRA estimators are order statistics that decrease monotonically, the effects of multicollinearity can be circumvented. Otherwise, obscure phenomena may be observed, such as good data recognition but low predictive model power of a QSAR model.

Structure-activity relationships of rationally designed AMACR 1A inhibitors.

PubMed

Yevglevskis, Maksims; Lee, Guat L; Nathubhai, Amit; Petrova, Yoana D; James, Tony D; Threadgill, Michael D; Woodman, Timothy J; Lloyd, Matthew D

2018-04-30

α-Methylacyl-CoA racemase (AMACR; P504S) is a promising novel drug target for prostate and other cancers. Assaying enzyme activity is difficult due to the reversibility of the 'racemisation' reaction and the difficulties in the separation of epimeric products; consequently few inhibitors have been described and no structure-activity relationship study has been performed. This paper describes the first structure-activity relationship study, in which a series of 23 known and potential rational AMACR inhibitors were evaluated. AMACR was potently inhibited (IC 50  = 400-750 nM) by ibuprofenoyl-CoA and derivatives. Potency was positively correlated with inhibitor lipophilicity. AMACR was also inhibited by straight-chain and branched-chain acyl-CoA esters, with potency positively correlating with inhibitor lipophilicity. 2-Methyldecanoyl-CoAs were ca. 3-fold more potent inhibitors than decanoyl-CoA, demonstrating the importance of the 2-methyl group for effective inhibition. Elimination substrates and compounds with modified acyl-CoA cores were also investigated, and shown to be potent inhibitors. These results are the first to demonstrate structure-activity relationships of rational AMACR inhibitors and that potency can be predicted by acyl-CoA lipophilicity. The study also demonstrates the utility of the colorimetric assay for thorough inhibitor characterisation. Copyright © 2018 Elsevier Inc. All rights reserved.

ANXIETY AND ATTACHMENT TO THE MOTHER IN PRESCHOOLERS RECEIVING PSYCHIATRIC CARE: THE FATHER-CHILD ACTIVATION RELATIONSHIP AS A PROTECTIVE FACTOR.

PubMed

Gaumon, Sébastien; Paquette, Daniel; Cyr, Chantal; Émond-Nakamura, Mutsuko; St-André, Martin

2016-07-01

This 49-family study is the first to explore the father-child relationship in a clinical population of preschoolers (at a tertiary care child psychiatry clinic) and to examine its relation to child anxiety and attachment to the mother. A moderation model of the father-child activation relationship on the relation between attachment to the mother and child anxiety was tested and discussed. Analyses confirmed the expected independence between mother-child attachment and father-child activation as well as the association between mother-child attachment and anxiety. The highest levels of anxiety were found in insecure children, and more specifically, in insecure-ambivalent children and insecure disorganized-controlling children of the caregiving subtype. Hypotheses regarding the relation between anxiety and activation were only partially confirmed. Finally, the activation relationship with the father was shown to have a moderating effect on the relation between attachment to the mother and child anxiety; activation by the father may be considered either a protective or a risk factor. Results for this clinical population of young children are discussed in the light of attachment theory and activation relationship theory. The study's findings have the potential to contribute to the development of preventative, diagnostic, and intervention programs that take both parental figures into account. © 2016 Michigan Association for Infant Mental Health.

Parental Modeling and Deidentification in Romantic Relationships Among Mexican-origin Youth.

PubMed

Kuo, Sally I-Chun; Wheeler, Lorey A; Updegraff, Kimberly A; McHale, Susan M; Umaña-Taylor, Adriana J; Perez-Brena, Norma J

2017-10-01

This study investigated youth's modeling of and de-identification from parents in romantic relationships, using two phases of data from adolescent siblings, mothers, and fathers in 246 Mexican-origin families. Each parent reported his/her marital satisfaction and conflict, and youth reported on parent-adolescent warmth and conflict at Time 1. Youth's reports of modeling of and de-identification from their mothers and fathers and three romantic relationship outcomes were assessed at Time 2. Findings revealed that higher parental marital satisfaction, lower marital conflict, and higher warmth and lower conflict in parent-adolescent relationships were associated with more modeling and less de-identification from parents. Moreover, higher de-identification was linked to a greater likelihood of youth being involved in a romantic relationship and cohabitation, whereas more modeling was linked to a lower likelihood of cohabitation and older age of first sex. Discussion underscores the importance of assessing parental modeling and de-identification and understanding correlates of these processes.

Adolescents' working models and styles for relationships with parents, friends, and romantic partners.

PubMed

Furman, Wyndol; Simon, Valerie A; Shaffer, Laura; Bouchey, Heather A

2002-01-01

This study examined the links among adolescents' representations of their relationships with parents, friends, and romantic partners. Sixty-eight adolescents were interviewed three times to assess their working models for each of these types of relationships. Working models of friendships were related to working models of relationships with parents and romantic partners. Working models of relationships with parents and romantic partners were inconsistently related. A similar pattern of results was obtained for self-report measures of relational styles for the three types of relationships. Perceived experiences were also related. Specifically, support in relationships with parents tended to be related to support in romantic relationships and friendships, but the latter two were unrelated. On the other hand, self and other controlling behaviors in friendships were related to corresponding behaviors in romantic relationships. Negative interactions in the three types of relationships also tended to be related. Taken together, the findings indicate that the representations of the three types of relationships are distinct, yet related. Discussion focuses on the nature of the links among the three.

Phosphorus Export Model Development in a Terminal Lake Basin using Concentration-Streamflow Relationship

NASA Astrophysics Data System (ADS)

Jeannotte, T.; Mahmood, T. H.; Matheney, R.; Hou, X.

2017-12-01

Nutrient export to streams and lakes by anthropogenic activities can lead to eutrophication and degradation of surface water quality. In Devils Lake, ND, the only terminal lake in the Northern Great Plains, the algae boom is of great concern due to the recent increase in streamflow and consequent rise in phosphorus (P) export from prairie agricultural fields. However, to date, very few studies explored the concentration (c) -streamflow (q) relationship in the headwater catchments of the Devils Lake basin. A robust watershed-scale quantitative framework would aid understanding of the c-q relationship, simulating P concentration and load. In this study, we utilize c-q relationships to develop a simple model to estimate phosphorus concentration and export from two headwater catchments of different size (Mauvais Coulee: 1032 km2 and Trib 3: 160 km2) draining to Devils Lake. Our goal is to link the phosphorus export model with a physically based hydrologic model to identify major drivers of phosphorus export. USGS provided the streamflow measurements, and we collected water samples (filtered and unfiltered) three times daily during the spring snowmelt season (March 31, 2017- April 12, 2017) at the outlets of both headwater catchments. Our results indicate that most P is dissolved and very little is particulate, suggesting little export of fine-grained sediment from agricultural fields. Our preliminary analyses in the Mauvais Coulee catchment show a chemostatic c-q relationship in the rising limb of the hydrograph, while the recession limb shows a linear and positive c-q relationship. The poor correlation in the rising limb of the hydrograph suggests intense flushing of P by spring snowmelt runoff. Flushing then continues in the recession limb of the hydrograph, but at a more constant rate. The estimated total P load for the Mauvais Coulee basin is 193 kg/km2, consistent with other catchments of similar size across the Red River of the North basin to the east. We expect

Structure-activity relationships for chloro- and nitrophenol toxicity in the pollen tube growth test

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schueuermann, G.; Somashekar, R.K.; Kristen, U.

Acute toxicity of 10 chlorophenols and 10 nitrophenols with identical substitution patterns is analyzed with the pollen tube growth (PTG) test. Concentration values of 50% growth inhibition (IC50) between 0.1 and 300 mg/L indicate that the absolute sensitivity of this alternative biotest is comparable to conventional aquatic test systems. Analysis of quantitative structure-activity relationships using lipophilicity (log K{sub ow}), acidity (pK{sub a}), and quantum chemical parameters to model intrinsic acidity, solvation interactions, and nucleophilicity reveals substantial differences between the intraseries trends of log IC50. With chlorophenols, a narcotic-type relationship is derived, which, however, shows marked differences in slope and interceptmore » when compared to reference regression equations for polar narcosis. Regression analysis of nitrophenol toxicity suggests interpretation in terms of two modes of action: oxidative uncoupling activity is associated with a pK{sub a} window from 3.8 to 8.5, and more acidic congeners with diortho-substitution show a transition from uncoupling to a narcotic mode of action with decreasing pK{sub a} and log K{sub ow}. Model calculations for phenol nucleophilicity suggest that differences in the phenol readiness for glucuronic acid conjugation as a major phase-II detoxication pathway have no direct influence on acute PTG toxicity of the compounds.« less

Structure-activity relationship of crustacean peptide hormones.

PubMed

Katayama, Hidekazu

2016-01-01

In crustaceans, various physiological events, such as molting, vitellogenesis, and sex differentiation, are regulated by peptide hormones. To understanding the functional sites of these hormones, many structure-activity relationship (SAR) studies have been published. In this review, the author focuses the SAR of crustacean hyperglycemic hormone-family peptides and androgenic gland hormone and describes the detailed results of our and other research groups. The future perspectives will be also discussed.

Characteristics of activities that affect the development of women's same-sex relationships.

PubMed

Davis-Delano, Laurel R

2014-01-01

The author utilized semistructured interviews with 56 women to explore how a wide range of activities affected the development of the participants' same-sex attractions and relationships. The researcher was able to identify and describe some aspects of the process by which eight characteristics of activities that are more or less present in various social contexts have the potential to impact whether these contexts are more or less conducive or hindering to the development of women's same-sex attractions and relationships. Activities were more apt to nurture the development of the participants' same-sex attractions and relationships when the activity (a) included lesbians, (b) was composed primarily of women, (c) affirmed women, (d) facilitated bonding, (e) featured a climate of acceptance of lesbians/gays/bisexuals, (f) did not feature a climate that emphasized heteronormativity, (g) was perceived as gender neutral, and (h) generated or drew participants who were similar to each other.

Evaluation of MRI Models in the Measurement of CMRO2 and Its Relationship With CBF

PubMed Central

Lin, Ai-Ling; Fox, Peter T.; Yang, Yihong; Lu, Hanzhang; Tan, Li-Hai; Gao, Jia-Hong

2008-01-01

The aim of this study was to investigate the various MRI biophysical models in the measurements of local cerebral metabolic rate of oxygen (CMRO2) and the corresponding relationship with cerebral blood flow (CBF) during brain activation. This aim was addressed by simultaneously measuring the relative changes in CBF, cerebral blood volume (CBV), and blood oxygen level dependent (BOLD) MRI signals in the human visual cortex during visual stimulation. A radial checkerboard delivered flash stimulation at five different frequencies. Two MRI models, the single-compartment model (SCM) and the multi-compartment model (MCM), were used to determine the relative changes in CMRO2 using three methods: [1] SCM with parameters identical to those used in a prior MRI study (M = 0.22; α = 0.38); [2] SCM with directly measured parameters (M from hypercapnia and α from measured δCBV and δCBF); and [3] MCM. The magnitude of relative changes in CMRO2 and the nonlinear relationship between CBF and CMRO2 obtained with Methods [2] and [3] were not in agreement with those obtained using Method [1]. However, the results of Methods [2] and [3] were aligned with positron emission tomography findings from the literature. Our results indicate that if appropriate parameters are used, the SCM and MCM models are equivalent for quantifying the values of CMRO2 and determining the flow-metabolism relationship. PMID:18666102

Relationship between physical activity and disability in low back pain: a systematic review and meta-analysis.

PubMed

Lin, Chung-Wei Christine; McAuley, James H; Macedo, Luciana; Barnett, Dominique C; Smeets, Rob J; Verbunt, Jeanine A

2011-03-01

It is often assumed that patients with pain-related disability due to low back pain (LBP) will have reduced physical activity levels, but recent studies have provided results that challenge this assumption. The aim of our systematic review was to examine the relationship between physical activity and disability in LBP. The literature search included 6 electronic databases and the reference list of relevant systematic reviews and studies to May 2010. To be included, studies had to measure both disability (eg, with the Roland Morris Disability Questionnaire) and physical activity (eg, by accelerometry) in patients with non-specific LBP. Two independent reviewers screened search results and extracted data, and authors were contacted for additional data. Correlation coefficients were pooled using the random-effects model. The search identified 3213 records and 18 studies were eligible for inclusion. The pooled results showed a weak relationship between physical activity and disability in acute or subacute (<3months) LBP (r=-0.08, 95% confidence interval=-0.17 to 0.002), and a moderate and negative relationship in chronic (>3months) LBP (r=-0.33, 95% confidence interval=-0.51 to -0.15). That is, persons with acute or subacute LBP appear to vary in the levels of physical activity independent of their pain-related disability. Persons with chronic LBP with high levels of disability are also likely to have low levels of physical activity. Persons with acute or subacute back pain appear to vary in the levels of physical activity independent of disability. Persons with chronic back pain with high levels of disability will likely have low levels of physical activity. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Relationship between urban sprawl and physical activity, obesity, and morbidity.

PubMed

Ewing, Reid; Schmid, Tom; Killingsworth, Richard; Zlot, Amy; Raudenbush, Stephen

2003-01-01

To determine the relationship between urban sprawl, health, and health-related behaviors. Cross-sectional analysis using hierarchical modeling to relate characteristics of individuals and places to levels of physical activity, obesity, body mass index (BMI), hypertension, diabetes, and coronary heart disease. U.S. counties (448) and metropolitan areas (83). Adults (n = 206,992) from pooled 1998, 1999, and 2000 Behavioral Risk Factor Surveillance System (BRFSS). Sprawl indices, derived with principal components analysis from census and other data, served as independent variables. Self-reported behavior and health status from BRFSS served as dependent variables. After controlling for demographic and behavioral covariates, the county sprawl index had small but significant associations with minutes walked (p = .004), obesity (p < .001), BMI (p = .005), and hypertension (p = .018). Residents of sprawling counties were likely to walk less during leisure time, weigh more, and have greater prevalence of hypertension than residents of compact counties. At the metropolitan level, sprawl was similarly associated with minutes walked (p = .04) but not with the other variables. This ecologic study reveals that urban form could be significantly associated with some forms of physical activity and some health outcomes. More research is needed to refine measures of urban form, improve measures of physical activity, and control for other individual and environmental influences on physical activity, obesity, and related health outcomes.

Relationship between self-reported and objectively measured physical activity and subjective memory impairment in breast cancer survivors: role of self-efficacy, fatigue and distress.

PubMed

Phillips, Siobhan M; Lloyd, Gillian R; Awick, Elizabeth A; McAuley, Edward

2017-09-01

Many breast cancer survivors report cancer and cancer treatment-associated cognitive change. However, very little is known about the relationship between physical activity and subjective memory impairment (SMI) in this population. The purpose of this study is to examine the relationship between physical activity and SMI and longitudinally test a model examining the role of self-efficacy, fatigue and distress as potential mediators. Post-treatment breast cancer survivors (N = 1477) completed measures of physical activity, self-efficacy, distress (depression, concerns about recurrence, perceived stress, anxiety), fatigue and SMI at baseline and 6-month follow-up. A subsample (n = 362) was randomly selected to wear an accelerometer. It was hypothesized that physical activity indirectly influences SMI via exercise self-efficacy, distress and fatigue. Relationships were examined using panel analysis within a covariance modeling framework. The hypothesized model provided a good fit in the full sample (χ 2  = 1462.5, df = 469, p = <0.001; CFI = 0.96; SRMR = 0.04) and the accelerometer subsample (χ2 = 961.8, df = 535, p = <0.001, CFI = 0.94, SRMR = 0.05) indicating increased physical activity is indirectly associated with reduction in SMI across time, via increased exercise self-efficacy and reduced distress and fatigue. Higher levels of physical activity, lower levels of fatigue and distress and higher exercise self-efficacy may play an important role in understanding SMI in breast cancer survivors across time. Future research is warranted to replicate and explore these relationships further. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Synthesis, activity, and structure--activity relationship studies of novel cationic lipids for DNA transfer.

PubMed

Byk, G; Dubertret, C; Escriou, V; Frederic, M; Jaslin, G; Rangara, R; Pitard, B; Crouzet, J; Wils, P; Schwartz, B; Scherman, D

1998-01-15

We have designed and synthesized original cationic lipids for gene delivery. A synthetic method on solid support allowed easy access to unsymmetrically monofunctionalized polyamine building blocks of variable geometries. These polyamine building blocks were introduced into cationic lipids. To optimize the transfection efficiency in the novel series, we have carried out structure-activity relationship studies by introduction of variable-length lipids, of variable-length linkers between lipid and cationic moiety, and of substituted linkers. We introduce the concept of using the linkers within cationic lipids molecules as carriers of side groups harboring various functionalities (side chain entity), as assessed by the introduction of a library composed of cationic entities, additional lipid chains, targeting groups, and finally the molecular probes rhodamine and biotin for cellular traffic studies. The transfection activity of the products was assayed in vitro on Hela carcinoma, on NIH3T3, and on CV1 fibroblasts and in vivo on the Lewis Lung carcinoma model. Products from the series displayed high transfection activities. Results indicated that the introduction of a targeting side chain moiety into the cationic lipid is permitted. A primary physicochemical characterization of the DNA/lipid complexes was demonstrated with this leading compound. Selected products from the series are currently being developed for preclinical studies, and the labeled lipopolyamines can be used to study the intracellular traffic of DNA/cationic lipid complexes.

Assessing the relationship between alcohol outlets and domestic violence: routine activities and the neighborhood environment.

PubMed

Roman, Caterina G; Reid, Shannon E

2012-01-01

Studies have consistently found a positive relationship between alcohol outlet density and assault, but only a handful of studies have examined whether outlet density has an influence on domestic violence. Using a framework based in crime opportunity theories, this study estimates spatial econometric regression models to test whether the density of alcohol outlets across neighborhoods is positively associated with police calls for service for domestic violence. Models also were developed to test whether the relationships found were consistent across time periods associated with the use of alcohol outlets (weeknights and weekends). The findings indicate that off-premise outlets were associated with a significant increase in domestic violence, but on-premise outlets (specifically restaurants and nightclubs) were associated with a decrease in domestic violence. The risk for domestic violence in areas of high densities of off-premise outlets was found to be high during the weekend but not during the weeknight, suggesting different routine activities for domestic violence offenders during the week.

Identifying and Evaluating the Relationships that Control a Land Surface Model's Hydrological Behavior

NASA Technical Reports Server (NTRS)

Koster, Randal D.; Mahanama, Sarith P.

2012-01-01

The inherent soil moisture-evaporation relationships used in today 's land surface models (LSMs) arguably reflect a lot of guesswork given the lack of contemporaneous evaporation and soil moisture observations at the spatial scales represented by regional and global models. The inherent soil moisture-runoff relationships used in the LSMs are also of uncertain accuracy. Evaluating these relationships is difficult but crucial given that they have a major impact on how the land component contributes to hydrological and meteorological variability within the climate system. The relationships, it turns out, can be examined efficiently and effectively with a simple water balance model framework. The simple water balance model, driven with multi-decadal observations covering the conterminous United States, shows how different prescribed relationships lead to different manifestations of hydrological variability, some of which can be compared directly to observations. Through the testing of a wide suite of relationships, the simple model provides estimates for the underlying relationships that operate in nature and that should be operating in LSMs. We examine the relationships currently used in a number of different LSMs in the context of the simple water balance model results and make recommendations for potential first-order improvements to these LSMs.

Acceptance and relationship context: a model of substance use disorder treatment outcome.

PubMed

Gifford, Elizabeth V; Ritsher, Jennifer B; McKellar, John D; Moos, Rudolf H

2006-08-01

This study presented and tested a model of behavior change in long-term substance use disorder recovery, the acceptance and relationship context (ARC) model. The model specifies that acceptance-based behavior and constructive social relationships lead to recovery, and that treatment programs with supportive, involved relationships facilitate the development of these factors. This study used a prospective longitudinal naturalistic design and controlled for baseline levels of study variables. The model was tested on a sample of 2549 patients in 15 residential substance use disorder treatment programs. Acceptance-based responding (ABR), social relationship quality (SRQ), treatment program alliance (TPA) and substance use-related impairment were assessed using interviews and self-report questionnaires. TPA predicted ABR and SRQ and, in turn, ABR predicted better 2-year and 5-year treatment outcomes. The baseline-controlled model accounted for 41% of the variance in outcome at 2-year follow-up and 28% of the variance in outcome at 5-year follow-up. CONCLUSIONS Patients from treatment programs with an affiliative relationship network are more likely to respond adaptively to internal states associated previously with substance use, develop constructive social relationships and achieve long-term treatment benefits.

Design and prediction of new acetylcholinesterase inhibitor via quantitative structure activity relationship of huprines derivatives.

PubMed

Zhang, Shuqun; Hou, Bo; Yang, Huaiyu; Zuo, Zhili

2016-05-01

Acetylcholinesterase (AChE) is an important enzyme in the pathogenesis of Alzheimer's disease (AD). Comparative quantitative structure-activity relationship (QSAR) analyses on some huprines inhibitors against AChE were carried out using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram QSAR (HQSAR) methods. Three highly predictive QSAR models were constructed successfully based on the training set. The CoMFA, CoMSIA, and HQSAR models have values of r (2) = 0.988, q (2) = 0.757, ONC = 6; r (2) = 0.966, q (2) = 0.645, ONC = 5; and r (2) = 0.957, q (2) = 0.736, ONC = 6. The predictabilities were validated using an external test sets, and the predictive r (2) values obtained by the three models were 0.984, 0.973, and 0.783, respectively. The analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the AChE to further understand the vital interactions between huprines and the protease. On the basis of the QSAR study, 14 new potent molecules have been designed and six of them are predicted to be more active than the best active compound 24 described in the literature. The final QSAR models could be helpful in design and development of novel active AChE inhibitors.

Analysis of the relationship between end-to-end distance and activity of single-chain antibody against colorectal carcinoma.

PubMed

Zhang, Jianhua; Liu, Shanhong; Shang, Zhigang; Shi, Li; Yun, Jun

2012-08-22

We investigated the relationship of End-to-end distance between VH and VL with different peptide linkers and the activity of single-chain antibodies by computer-aided simulation. First, we developed (G4S)n (where n = 1-9) as the linker to connect VH and VL, and estimated the 3D structure of single-chain Fv antibody (scFv) by homologous modeling. After molecular models were evaluated and optimized, the coordinate system of every protein was built and unified into one coordinate system, and End-to-end distances calculated using 3D space coordinates. After expression and purification of scFv-n with (G4S)n as n = 1, 3, 5, 7 or 9, the immunoreactivity of purified ND-1 scFv-n was determined by ELISA. A multi-factorial relationship model was employed to analyze the structural factors affecting scFv: rn=ABn-ABO2+CDn-CDO2+BCn-BCst2. The relationship between immunoreactivity and r-values revealed that fusion protein structure approached the desired state when the r-value = 3. The immunoreactivity declined as the r-value increased, but when the r-value exceeded a certain threshold, it stabilized. We used a linear relationship to analyze structural factors affecting scFv immunoreactivity.

Structure-activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids, and their tricyclic and bicyclic analogues.

PubMed

Van Baelen, Gitte; Hostyn, Steven; Dhooghe, Liene; Tapolcsányi, Pál; Mátyus, Péter; Lemière, Guy; Dommisse, Roger; Kaiser, Marcel; Brun, Reto; Cos, Paul; Maes, Louis; Hajós, György; Riedl, Zsuzsanna; Nagy, Ildikó; Maes, Bert U W; Pieters, Luc

2009-10-15

Based on the indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3) and isoneocryptolepine (4), used as lead compounds for new antimalarial agents, a series of tricyclic and bicyclic analogues, including carbolines, azaindoles, pyrroloquinolines and pyrroloisoquinolines was synthesized and biologically evaluated. None of the bicyclic compounds was significantly active against the chloroquine-resistant strain Plasmodium falciparum K1, in contrast to the tricyclic derivatives. The tricyclic compound 2-methyl-2H-pyrido[3,4-b]indole (9), or 2-methyl-beta-carboline, showed the best in vitro activity, with an IC(50) value of 0.45 microM against P. falciparum K1, without apparent cytotoxicity against L6 cells (SI>1000). However, this compound was not active in the Plasmodium berghei mouse model. Structure-activity relationships are discussed and compared with related naturally occurring compounds.

Development of structure-activity relationship for metal oxide nanoparticles

NASA Astrophysics Data System (ADS)

Liu, Rong; Zhang, Hai Yuan; Ji, Zhao Xia; Rallo, Robert; Xia, Tian; Chang, Chong Hyun; Nel, Andre; Cohen, Yoram

2013-05-01

Nanomaterial structure-activity relationships (nano-SARs) for metal oxide nanoparticles (NPs) toxicity were investigated using metrics based on dose-response analysis and consensus self-organizing map clustering. The NP cellular toxicity dataset included toxicity profiles consisting of seven different assays for human bronchial epithelial (BEAS-2B) and murine myeloid (RAW 264.7) cells, over a concentration range of 0.39-100 mg L-1 and exposure time up to 24 h, for twenty-four different metal oxide NPs. Various nano-SAR building models were evaluated, based on an initial pool of thirty NP descriptors. The conduction band energy and ionic index (often correlated with the hydration enthalpy) were identified as suitable NP descriptors that are consistent with suggested toxicity mechanisms for metal oxide NPs and metal ions. The best performing nano-SAR with the above two descriptors, built with support vector machine (SVM) model and of validated robustness, had a balanced classification accuracy of ~94%. An applicability domain for the present data was established with a reasonable confidence level of 80%. Given the potential role of nano-SARs in decision making, regarding the environmental impact of NPs, the class probabilities provided by the SVM nano-SAR enabled the construction of decision boundaries with respect to toxicity classification under different acceptance levels of false negative relative to false positive predictions.Nanomaterial structure-activity relationships (nano-SARs) for metal oxide nanoparticles (NPs) toxicity were investigated using metrics based on dose-response analysis and consensus self-organizing map clustering. The NP cellular toxicity dataset included toxicity profiles consisting of seven different assays for human bronchial epithelial (BEAS-2B) and murine myeloid (RAW 264.7) cells, over a concentration range of 0.39-100 mg L-1 and exposure time up to 24 h, for twenty-four different metal oxide NPs. Various nano-SAR building models were

Adolescents Online: The Importance of Internet Activity Choices to Salient Relationships

ERIC Educational Resources Information Center

Blais, Julie J.; Craig, Wendy M.; Pepler, Debra; Connolly, Jennifer

2008-01-01

The purpose of this study was to determine whether using the Internet for different activities affects the quality of close adolescent relationships (i.e., best friendships and romantic relationships). In a one-year longitudinal study of 884 adolescents (Mean age = 15, 46% male), we examined whether visiting chat rooms, using ICQ, using the…

Structure-Activity Relationship and Molecular Mechanics Reveal the Importance of Ring Entropy in the Biosynthesis and Activity of a Natural Product.

PubMed

Tran, Hai L; Lexa, Katrina W; Julien, Olivier; Young, Travis S; Walsh, Christopher T; Jacobson, Matthew P; Wells, James A

2017-02-22

Macrocycles are appealing drug candidates due to their high affinity, specificity, and favorable pharmacological properties. In this study, we explored the effects of chemical modifications to a natural product macrocycle upon its activity, 3D geometry, and conformational entropy. We chose thiocillin as a model system, a thiopeptide in the ribosomally encoded family of natural products that exhibits potent antimicrobial effects against Gram-positive bacteria. Since thiocillin is derived from a genetically encoded peptide scaffold, site-directed mutagenesis allows for rapid generation of analogues. To understand thiocillin's structure-activity relationship, we generated a site-saturation mutagenesis library covering each position along thiocillin's macrocyclic ring. We report the identification of eight unique compounds more potent than wild-type thiocillin, the best having an 8-fold improvement in potency. Computational modeling of thiocillin's macrocyclic structure revealed a striking requirement for a low-entropy macrocycle for activity. The populated ensembles of the active mutants showed a rigid structure with few adoptable conformations while inactive mutants showed a more flexible macrocycle which is unfavorable for binding. This finding highlights the importance of macrocyclization in combination with rigidifying post-translational modifications to achieve high-potency binding.

Modeling the Relationship between Prosodic Sensitivity and Early Literacy

ERIC Educational Resources Information Center

Holliman, Andrew; Critten, Sarah; Lawrence, Tony; Harrison, Emily; Wood, Clare; Hughes, David

2014-01-01

A growing literature has demonstrated that prosodic sensitivity is related to early literacy development; however, the precise nature of this relationship remains unclear. It has been speculated in recent theoretical models that the observed relationship between prosodic sensitivity and early literacy might be partially mediated by children's…

Selective CB2 receptor agonists. Part 2: Structure-activity relationship studies and optimization of proline-based compounds.

PubMed

Riether, Doris; Zindell, Renee; Wu, Lifen; Betageri, Raj; Jenkins, James E; Khor, Someina; Berry, Angela K; Hickey, Eugene R; Ermann, Monika; Albrecht, Claudia; Ceci, Angelo; Gemkow, Mark J; Nagaraja, Nelamangala V; Romig, Helmut; Sauer, Achim; Thomson, David S

2015-02-01

Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure-activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparative pharmacodynamic analysis of imidazoline compounds using rat model of ocular mydriasis with a test of quantitative structure-activity relationships.

PubMed

Raczak-Gutknecht, Joanna; Nasal, Antoni; Frąckowiak, Teresa; Kornicka, Anita; Sączewski, Franciszek; Wawrzyniak, Renata; Kubik, Łukasz; Kaliszan, Roman

2017-09-10

Imidazol(in)e derivatives, having the chemical structure similar to clonidine, exert diverse pharmacological activities connected with their interactions with alpha2-adrenergic receptors, e.g. hypotension, bradycardia, sedation as well as antinociceptive, anxiolytic, antiarrhythmic, muscle relaxant and mydriatic effects. The mechanism of pupillary dilation observed after systemic administration of imidazol(in)es to rats, mice and cats depends on the stimulation of postsynaptic alpha2-adrenoceptors within the brain. It was proved that the central nervous system (CNS)-localized I1-imidazoline receptors are not engaged in those effects. It appeared interesting to analyze the CNS-mediated pharmacodynamics of imidazole(in)e agents in terms of their chromatographic and calculation chemistry-derived parameters. In the present study a systematic determination and comparative pharmacometric analysis of mydriatic effects in rats were performed on a series of 20 imidazol(in)e agents, composed of the well-known drugs and of the substances used in experimental pharmacology. The eye pupil dilatory activities of the compounds were assessed in anesthetized Wistar rats according to the established Koss method. Among twenty imidazol(in)e derivatives studied, 18 produced diverse dose-dependent mydriatic effects. In the quantitative structure-activity relationships (QSAR) analysis, the pharmacological data (half maximum mydriatic effect - ED 50 in μmol/kg) were considered along with the structural parameters of the agents from molecular modeling. The theoretically calculated lipophilicity parameters, CLOGP, of imidazol(in)es, as well as their lipophilicity parameters from HPLC, logk w , were also considered. The attempts to derive statistically significant QSAR equations for a full series of the agents under study were unsuccessful. However, for a subgroup of eight apparently structurally related imidazol(in)es a significant relationship between log(1/ED 50 ) and logk w values was

PLS-based quantitative structure-activity relationship for substituted benzamides of clebopride type. Application of experimental design in drug design.

PubMed

Norinder, U; Högberg, T

1992-04-01

The advantageous approach of using an experimentally designed training set as the basis for establishing a quantitative structure-activity relationship with good predictive capability is described. The training set was selected from a fractional factorial design scheme based on a principal component description of physico-chemical parameters of aromatic substituents. The derived model successfully predicts the activities of additional substituted benzamides of 6-methoxy-N-(4-piperidyl)salicylamide type. The major influence on activity of the 3-substituent is demonstrated.

The Soul Mates Model: A Seven-Stage Model for Couple's Long-Term Relationship Development and Flourishing

ERIC Educational Resources Information Center

De La Lama, Luisa Batthyany; De La Lama, Luis; Wittgenstein, Ariana

2012-01-01

This article presents the integrative soul mates relationship development model, which provides the helping professionals with a conceptual map for couples' relationship development from dating, to intimacy, to soul mating, and long-term flourishing. This model is informed by a holistic, a developmental, and a positive psychology conceptualization…

Testing of the European Union exposure-response relationships and annoyance equivalents model for annoyance due to transportation noises: The need of revised exposure-response relationships and annoyance equivalents model.

PubMed

Gille, Laure-Anne; Marquis-Favre, Catherine; Morel, Julien

2016-09-01

An in situ survey was performed in 8 French cities in 2012 to study the annoyance due to combined transportation noises. As the European Commission recommends to use the exposure-response relationships suggested by Miedema and Oudshoorn [Environmental Health Perspective, 2001] to predict annoyance due to single transportation noise, these exposure-response relationships were tested using the annoyance due to each transportation noise measured during the French survey. These relationships only enabled a good prediction in terms of the percentages of people highly annoyed by road traffic noise. For the percentages of people annoyed and a little annoyed by road traffic noise, the quality of prediction is weak. For aircraft and railway noises, prediction of annoyance is not satisfactory either. As a consequence, the annoyance equivalents model of Miedema [The Journal of the Acoustical Society of America, 2004], based on these exposure-response relationships did not enable a good prediction of annoyance due to combined transportation noises. Local exposure-response relationships were derived, following the whole computation suggested by Miedema and Oudshoorn [Environmental Health Perspective, 2001]. They led to a better calculation of annoyance due to each transportation noise in the French cities. A new version of the annoyance equivalents model was proposed using these new exposure-response relationships. This model enabled a better prediction of the total annoyance due to the combined transportation noises. These results encourage therefore to improve the annoyance prediction for noise in isolation with local or revised exposure-response relationships, which will also contribute to improve annoyance modeling for combined noises. With this aim in mind, a methodology is proposed to consider noise sensitivity in exposure-response relationships and in the annoyance equivalents model. The results showed that taking into account such variable did not enable to enhance both

Three-dimensional quantitative structure-activity relationship study on anti-cancer activity of 3,4-dihydroquinazoline derivatives against human lung cancer A549 cells

NASA Astrophysics Data System (ADS)

Cho, Sehyeon; Choi, Min Ji; Kim, Minju; Lee, Sunhoe; Lee, Jinsung; Lee, Seok Joon; Cho, Haelim; Lee, Kyung-Tae; Lee, Jae Yeol

2015-03-01

A series of 3,4-dihydroquinazoline derivatives with anti-cancer activities against human lung cancer A549 cells were subjected to three-dimensional quantitative structure-activity relationship (3D-QSAR) studies using the comparative molecular similarity indices analysis (CoMSIA) approaches. The most potent compound, 1 was used to align the molecules. As a result, the best prediction was obtained with CoMSIA combined the steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor fields (q2 = 0.720, r2 = 0.897). This model was validated by an external test set of 6 compounds giving satisfactory predictive r2 value of 0.923 as well as the scrambling stability test. This model would guide the design of potent 3,4-dihydroquinazoline derivatives as anti-cancer agent for the treatment of human lung cancer.

Antibacterial Activity of Polyphenols: Structure-Activity Relationship and Influence of Hyperglycemic Condition.

PubMed

Xie, Yixi; Chen, Jing; Xiao, Aiping; Liu, Liangliang

2017-11-06

Polyphenols are plant-derived natural products with well-documented health benefits to human beings, such as antibacterial activities. However, the antibacterial activities of polyphenols under hyperglycemic conditions have been rarely studied, which could be relevant to their antibacterial efficacy in disease conditions, such as in diabetic patients. Herein, the antibacterial activities of 38 polyphenols under mimicked hyperglycemic conditions were evaluated. The structure-antibacterial activity relationships of polyphenols were also tested and analyzed. The presence of glucose apparently promoted the growth of the bacterial strains tested in this study. The OD600 values of tested bacteria strains increased from 1.09-fold to 1.49-fold by adding 800 mg/dL glucose. The polyphenols showed structurally dependent antibacterial activities, which were significantly impaired under the hyperglycemic conditions. The results from this study indicated that high blood glucose might promote bacterial infection, and the hyperglycemic conditions resulting from diabetes were likely to suppress the antibacterial benefits of polyphenols.

Using machine learning to model dose-response relationships.

PubMed

Linden, Ariel; Yarnold, Paul R; Nallamothu, Brahmajee K

2016-12-01

Establishing the relationship between various doses of an exposure and a response variable is integral to many studies in health care. Linear parametric models, widely used for estimating dose-response relationships, have several limitations. This paper employs the optimal discriminant analysis (ODA) machine-learning algorithm to determine the degree to which exposure dose can be distinguished based on the distribution of the response variable. By framing the dose-response relationship as a classification problem, machine learning can provide the same functionality as conventional models, but can additionally make individual-level predictions, which may be helpful in practical applications like establishing responsiveness to prescribed drug regimens. Using data from a study measuring the responses of blood flow in the forearm to the intra-arterial administration of isoproterenol (separately for 9 black and 13 white men, and pooled), we compare the results estimated from a generalized estimating equations (GEE) model with those estimated using ODA. Generalized estimating equations and ODA both identified many statistically significant dose-response relationships, separately by race and for pooled data. Post hoc comparisons between doses indicated ODA (based on exact P values) was consistently more conservative than GEE (based on estimated P values). Compared with ODA, GEE produced twice as many instances of paradoxical confounding (findings from analysis of pooled data that are inconsistent with findings from analyses stratified by race). Given its unique advantages and greater analytic flexibility, maximum-accuracy machine-learning methods like ODA should be considered as the primary analytic approach in dose-response applications. © 2016 John Wiley & Sons, Ltd.

Quantitative structure-activity relationship: promising advances in drug discovery platforms.

PubMed

Wang, Tao; Wu, Mian-Bin; Lin, Jian-Ping; Yang, Li-Rong

2015-12-01

Quantitative structure-activity relationship (QSAR) modeling is one of the most popular computer-aided tools employed in medicinal chemistry for drug discovery and lead optimization. It is especially powerful in the absence of 3D structures of specific drug targets. QSAR methods have been shown to draw public attention since they were first introduced. In this review, the authors provide a brief discussion of the basic principles of QSAR, model development and model validation. They also highlight the current applications of QSAR in different fields, particularly in virtual screening, rational drug design and multi-target QSAR. Finally, in view of recent controversies, the authors detail the challenges faced by QSAR modeling and the relevant solutions. The aim of this review is to show how QSAR modeling can be applied in novel drug discovery, design and lead optimization. QSAR should intentionally be used as a powerful tool for fragment-based drug design platforms in the field of drug discovery and design. Although there have been an increasing number of experimentally determined protein structures in recent years, a great number of protein structures cannot be easily obtained (i.e., membrane transport proteins and G-protein coupled receptors). Fragment-based drug discovery, such as QSAR, could be applied further and have a significant role in dealing with these problems. Moreover, along with the development of computer software and hardware, it is believed that QSAR will be increasingly important.

Population Genetic-Based Pharmacokinetic Modeling of Methadone and its Relationship with the QTc Interval in Opioid-Dependent Patients.

PubMed

Csajka, Chantal; Crettol, Séverine; Guidi, Monia; Eap, Chin B

2016-12-01

Methadone is a μ-opioid agonist widely used for the treatment of pain, and for detoxification or maintenance treatment in opioid addiction. It has been shown to exhibit large pharmacokinetic variability and concentration-QTc relationships. In this study we investigated the relative influence of genetic polymorphism and other variables on the dose concentration-QTc relationship. A population model for methadone enantiomers in 251 opioid-dependent patients was developed using non-linear mixed effect modeling (NONMEM ® ). Various models were tested to characterize the pharmacokinetics of (R)- and (S)-methadone and the pharmacokinetic-pharmacodynamic relationship, while including demographics, physiological conditions, co-medications, and genetic variants as covariates. Model-based simulations were performed to assess the relative increase in QTc with dose upon stratification according to genetic polymorphisms involved in methadone disposition. A two-compartment model with first-order absorption and lag time provided the best model fit for (R)- and (S)-methadone pharmacokinetics. (S)-methadone clearance was influenced by cytochrome P450 (CYP) 2B6 activity, ABCB1 3435C>T, and α-1 acid glycoprotein level, while (R)-methadone clearance was influenced by CYP2B6 activity, POR*28, and CYP3A4*22. A linear model described the methadone concentration-QTc relationship, with a mean QTc increase of 9.9 ms and 19.2 ms per 1000 ng/ml of (R)- and (S)-methadone, respectively. Simulations with different methadone doses up to 240 mg/day showed that <8 % of patients presented with a QTc interval above 450 ms; however, this might reach 12 to 18 % for (R)- and (S)-methadone, respectively, in patients with a genetic status associated with a decreased methadone elimination at doses exceeding 240 mg/day. Risk factor assessment, electrocardiogram monitoring, and therapeutic drug monitoring are beneficial to optimize treatment in methadone patients, especially for those who have low

Internet-Related Work Activities and Academic Government Documents Librarians' Professional Relationships.

ERIC Educational Resources Information Center

Roselle, Ann

1999-01-01

Examines specific Internet-related work activities of academic government documents librarians in the United States and how these activities are affecting academic government documents librarians' professional relationships. Results are reported from a national survey of 226 academic government documents librarians that indicate closer…

An investigation into the relationship between age and physiological function in highly active older adults

PubMed Central

Pollock, Ross D; Carter, Scott; Velloso, Cristiana P; Duggal, Niharika A; Lord, Janet M; Lazarus, Norman R; Harridge, Stephen D R

2015-01-01

Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55–79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well-being. Significant associations between age and function were observed for many functions. The maximal rate of oxygen consumption ( showed the closest association with age (r = −0.443 to −0.664; P < 0.001), but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The results of this cross-sectional study suggest that even when many confounding variables are removed the relationship between function and healthy ageing is complex and likely to be highly individualistic and that physical activity levels must be taken into account in ageing studies. Key Points The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual. This could be due to a variety of confounding

An investigation into the relationship between age and physiological function in highly active older adults.

PubMed

Pollock, Ross D; Carter, Scott; Velloso, Cristiana P; Duggal, Niharika A; Lord, Janet M; Lazarus, Norman R; Harridge, Stephen D R

2015-02-01

The relationship between age and physiological function remains poorly defined and there are no physiological markers that can be used to reliably predict the age of an individual. This could be due to a variety of confounding genetic and lifestyle factors, and in particular to ill-defined and low levels of physical activity. This study assessed the relationship between age and a diverse range of physiological functions in a cohort of highly active older individuals (cyclists) aged 55-79 years in whom the effects of lifestyle factors would be ameliorated. Significant associations between age and function were observed for many functions. V̇O2max was most closely associated with age, but even here the variance in age for any given level was high, precluding the clear identification of the age of any individual. The data suggest that the relationship between human ageing and physiological function is highly individualistic and modified by inactivity. Despite extensive research, the relationship between age and physiological function remains poorly characterised and there are currently no reliable markers of human ageing. This is probably due to a number of confounding factors, particularly in studies of a cross-sectional nature. These include inter-subject genetic variation, as well as inter-generational differences in nutrition, healthcare and insufficient levels of physical activity as well as other environmental factors. We have studied a cohort of highly and homogeneously active older male (n = 84) and female (n = 41) cyclists aged 55-79 years who it is proposed represent a model for the study of human ageing free from the majority of confounding factors, especially inactivity. The aim of the study was to identify physiological markers of ageing by assessing the relationship between function and age across a wide range of indices. Each participant underwent a detailed physiological profiling which included measures of cardiovascular, respiratory, neuromuscular

Maturational differences in physical self- perceptions and the relationship with physical activity in early adolescent girls.

PubMed

Niven, Alisa G; Fawkner, Samantha G; Knowles, Anne-Marie; Stephenson, Claire

2007-11-01

This cross-sectional study examined the relationship between physical self-perceptions (PSPs), maturation, and physical activity and compared the strength of the relationships of biological and chronological age with PSPs in early adolescent girls (N = 208; mean age = 11.83 +/- 0.39 years). Participants completed the Physical Activity Questionnaire for Older Children, the Children's Physical Self-Perception Profile, and the Pubertal Development Scale. Results indicated that PSPs were significantly and moderately correlated with physical activity. There were no differences in physical activity between maturation stages. Girls who were in the early stages of maturation had significantly more positive perceptions of body attractiveness and physical self-worth than girls in the mid stages of maturation. There was no evidence of a relationship between PSPs and chronological age. This study provided further support for the relationship between PSPs and physical activity and the relationship between maturation and aspects of PSPs. In this age group, maturation does not appear to be related to physical activity or the PSPs most strongly influential on physical activity behavior.

Relationship between soil erodibility and modeled infiltration rate in different soils

NASA Astrophysics Data System (ADS)

Wang, Guoqiang; Fang, Qingqing; Wu, Binbin; Yang, Huicai; Xu, Zongxue

2015-09-01

The relationship between soil erodibility, which is hard to measure, and modeled infiltration rate were rarely researched. Here, the soil erodibility factors (K and Ke in the USLE, Ki and K1 in the WEPP) were calculated and the infiltration rates were modeled based on the designed laboratory simulation experiments and proposed infiltration model, in order to build their relationship. The impacts of compost amendment on the soil erosion characteristics and relationship were also studied. Two contrasting agricultural soils (bare and cultivated fluvo-aquic soils) were used, and different poultry compost contents (control, low and high) were applied to both soils. The results indicated that the runoff rate, sediment yield rate and soil erodibility of the bare soil treatments were generally higher than those of the corresponding cultivated soil treatments. The application of composts generally decreased sediment yield and soil erodibility but did not always decrease runoff. The comparison of measured and modeled infiltration rates indicated that the model represented the infiltration processes well with an N-S coefficient of 0.84 for overall treatments. Significant negative logarithmic correlations have been found between final infiltration rate (FIR) and the four soil erodibility factors, and the relationship between USLE-K and FIR demonstrated the best correlation. The application of poultry composts would not influence the logarithmic relationship between FIR and soil erodibility. Our study provided a useful tool to estimate soil erodibility.

Modeling the cross-sectional relationships between religion, physical health, social support, and depressive symptoms.

PubMed

Koenig, H G; Hays, J C; George, L K; Blazer, D G; Larson, D B; Landerman, L R

1997-01-01

The authors examined models of the relationships between religious activities, physical health, social support, and depressive symptoms in a sample of 4,000 persons age 65 and over. Religious activity was examined first as a single composite construct and then split into three component variables that were examined individually. Religious activity as a single construct was correlated with both social support and good physical health but was unrelated to depression. Split into the three components, model fit was significantly increased. Frequency of church attendance was positively related to physical health and negatively related to depression, but was surprisingly unrelated to social support. Frequent churchgoers were about half as likely to be depressed. Private prayer/Bible reading was negatively correlated with physical health and positively correlated with social support, but unrelated to depression. Religious TV/radio listening was unrelated to social support, negatively related to good physical health, and, unexpectedly, positively associated with depression.

Self-efficacy and pain acceptance as mediators of the relationship between pain and performance of valued life activities in women and men with rheumatoid arthritis.

PubMed

Ahlstrand, Inger; Vaz, Sharmila; Falkmer, Torbjörn; Thyberg, Ingrid; Björk, Mathilda

2017-06-01

To study whether personal factors (self-efficacy and pain acceptance) mediate the relationship between pain and performance of valued life activities in persons with rheumatoid arthritis. Persons with rheumatoid arthritis for at least four years ( n = 737; 73% women) answered a questionnaire measuring self-efficacy, pain acceptance, performance of valued life activities, and self-rated pain. Relationships among these constructs were explored using univariate and multivariate analyses. Structural equation modelling was then used to examine the mediational role of personal factors on the relationship between pain and performance of valued life activities. A direct negative association between pain and performance of valued life activities was identified ( Beta = .34, P < .001). This suggests that people with rheumatoid arthritis who had higher levels of pain has increased difficulties in performing valued life activities. Self-efficacy and activity engagement component of pain acceptance mediated the relationship between pain and performance of valued life activities, however the pain willingness component of pain acceptance did not influence participation in valued life activities. These findings highlight the importance of considering personal factors, such as pain acceptance and self-efficacy, in facilitating participation in valued life activities.

The Structure-Activity Relationship between Marine Algae Polysaccharides and Anti-Complement Activity

PubMed Central

Jin, Weihua; Zhang, Wenjing; Liang, Hongze; Zhang, Quanbin

2015-01-01

In this study, 33 different polysaccharides were prepared to investigate the structure-activity relationships between the polysaccharides, mainly from marine algae, and anti-complement activity in the classical pathway. Factors considered included extraction methods, fractionations, molecular weight, molar ratio of galactose to fucose, sulfate, uronic acid (UA) content, linkage, branching, and the type of monosaccharide. It was shown that the larger the molecular weights, the better the activities. The molar ratio of galactose (Gal) to fucose (Fuc) was a positive factor at a concentration lower than 10 µg/mL, while it had no effect at a concentration more than 10 µg/mL. In addition, sulfate was necessary; however, the sulfate content, the sulfate pattern, linkage and branching had no effect at a concentration of more than 10 µg/mL. Moreover, the type of monosaccharide had no effect. Laminaran and UA fractions had no activity; however, they could reduce the activity by decreasing the effective concentration of the active composition when they were mixed with the active compositions. The effect of the extraction methods could not be determined. Finally, it was observed that sulfated galactofucan showed good anti-complement activity after separation. PMID:26712768

[RELATIONSHIP BETWEEN JUNIOR AND SENIOR DOCTORS: A BUBERIAN MODEL].

PubMed

Pougnet, Richard; Pougnet, Laurence

2016-01-01

Doctors in training work in services under the supervision of senior doctors. These professional relationships may lead to frustrations, or ill-being at work. Indeed doctors are often very busy with care and can hardly communicate. The purpose of this article is to propose ways to think in its ethical dimension this relationship, by learning from Martin Buber's ideas. He thought a philosophy of relationship in two word pairs: I-Thou and I-It. This thought can be useful in the context of the médical relationship and mentorship. Indeed we can see our colleague as a person or only as a caregiver. We offer a relationship model according to buberian thought, between junior and senior doctor caring about the same patients.

Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships.

PubMed

Sun, Wenlong; Zhuang, Chunlin; Li, Xia; Zhang, Bowei; Lu, Xinhua; Zheng, Zhihui; Dong, Yuesheng

2017-08-01

Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential therapies for diabetes and obesity have attracted much attention in recent years. Six varic acid analogues were isolated from two strains of fungi and evaluated for PTP1B inhibition activities. The structure-activity relationships were also characterized and predicted by molecular modeling. Further kinetic studies indicated the reversible and competitive inhibition manner of varic acid analogues. Trivaric acid showed insulin-sensitizing effect not only in vitro but also in vivo, representing a promising lead compound for further optimization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fragment-based quantitative structure-activity relationship (FB-QSAR) for fragment-based drug design.

PubMed

Du, Qi-Shi; Huang, Ri-Bo; Wei, Yu-Tuo; Pang, Zong-Wen; Du, Li-Qin; Chou, Kuo-Chen

2009-01-30

In cooperation with the fragment-based design a new drug design method, the so-called "fragment-based quantitative structure-activity relationship" (FB-QSAR) is proposed. The essence of the new method is that the molecular framework in a family of drug candidates are divided into several fragments according to their substitutes being investigated. The bioactivities of molecules are correlated with the physicochemical properties of the molecular fragments through two sets of coefficients in the linear free energy equations. One coefficient set is for the physicochemical properties and the other for the weight factors of the molecular fragments. Meanwhile, an iterative double least square (IDLS) technique is developed to solve the two sets of coefficients in a training data set alternately and iteratively. The IDLS technique is a feedback procedure with machine learning ability. The standard Two-dimensional quantitative structure-activity relationship (2D-QSAR) is a special case, in the FB-QSAR, when the whole molecule is treated as one entity. The FB-QSAR approach can remarkably enhance the predictive power and provide more structural insights into rational drug design. As an example, the FB-QSAR is applied to build a predictive model of neuraminidase inhibitors for drug development against H5N1 influenza virus. (c) 2008 Wiley Periodicals, Inc.

Mothers' Perspectives on the Development of Their Preschoolers' Dietary and Physical Activity Behaviors and Parent-Child Relationship: Implications for Pediatric Primary Care Physicians.

PubMed

Pratt, Keeley J; Van Fossen, Catherine; Cotto-Maisonet, Jennifer; Palmer, Elizabeth N; Eneli, Ihuoma

2017-07-01

The study explores female caregivers' reflections on their relationship with their child (2-5 years old) and the development of their child's dietary and physical activity behaviors. Five, 90-minute semistructured focus groups were conducted to inquire about children's growth, eating behaviors and routines, physical activity, personality, and the parent-child relationship. Nineteen female caregivers diverse in race/ethnicity, age, and educational attainment participated. Participants reported that they maintained a schedule, but needed to be flexible to accommodate daily responsibilities. Family, social factors, and day care routines were influences on their children's behaviors. The main physical activity barriers were safety and time constraints. Guidance from pediatric primary care providers aimed at supporting female caregivers to build a positive foundation in their parent-child relationship, and to adopt and model healthy diet and physical activity behaviors that are respectful of schedules and barriers should be a priority for childhood obesity prevention.

Structure-Activity Relationships for in vitro Diuretic Activity of CAP2b in the Housefly

DTIC Science & Technology

2007-01-01

p e p t i d e s 2 8 ( 2 0 0 7 ) 5 7 – 6 1Structure-activity relationships for in vitro diuretic activity of CAP2b in the housefly Ronald J. Nachman a...the peptide Manse-CAP2b (pELYAFPRV-NH2) were assayed for diuretic activity on Malpighian tubules of the housefly Musca domestica (M. domestica). The C...required the C-terminal heptapeptide, which was equipotent with the most active of the native housefly CAP2b peptides. Replacement of Arg7 and Val8 with

Coopetitive Supply Chain Relationship Model: Application to the Smartphone Manufacturing Network.

PubMed

Kwok, Jeremy Jie Ming; Lee, Dong-Yup

2015-01-01

Previous researches for understanding supply chain relationship have mostly focused on its vertical collaboration between buyers and suppliers. However, there have been some instances of volatile and stable collaborative relationships amongst competitors such as Apple-Samsung product manufacturer-component supplier relationship and airline alliances, respectively, which is recognized as coopetition. Even though there have been several qualitative studies and a number of game theory models on coopetition, it is rare to find any attempts on quantitative characterization of such coopetitive dynamic behavior in supply chain relationship. Hence, in this work, we formulated a MINLP model mathematically representing coopetitive relationships in a cost efficient supply chain network. In particular, the coopetition factor was newly introduced to measure the degree of coopetition among supply chain players and determine the optimal level of coopetition to engage in. The utility and practicality of the model were strongly demonstrated using a case study of a hypothetical smartphone supply chain network under different scenarios, thus proposing their strategically viable optimal interactions. Therefore, this exploratory study can herald a new era of global coopetitive business.

Coopetitive Supply Chain Relationship Model: Application to the Smartphone Manufacturing Network

PubMed Central

Kwok, Jeremy Jie Ming; Lee, Dong-Yup

2015-01-01

Previous researches for understanding supply chain relationship have mostly focused on its vertical collaboration between buyers and suppliers. However, there have been some instances of volatile and stable collaborative relationships amongst competitors such as Apple-Samsung product manufacturer-component supplier relationship and airline alliances, respectively, which is recognized as coopetition. Even though there have been several qualitative studies and a number of game theory models on coopetition, it is rare to find any attempts on quantitative characterization of such coopetitive dynamic behavior in supply chain relationship. Hence, in this work, we formulated a MINLP model mathematically representing coopetitive relationships in a cost efficient supply chain network. In particular, the coopetition factor was newly introduced to measure the degree of coopetition among supply chain players and determine the optimal level of coopetition to engage in. The utility and practicality of the model were strongly demonstrated using a case study of a hypothetical smartphone supply chain network under different scenarios, thus proposing their strategically viable optimal interactions. Therefore, this exploratory study can herald a new era of global coopetitive business. PMID:26186227

On the virtues of automated quantitative structure-activity relationship: the new kid on the block.

PubMed

de Oliveira, Marcelo T; Katekawa, Edson

2018-02-01

Quantitative structure-activity relationship (QSAR) has proved to be an invaluable tool in medicinal chemistry. Data availability at unprecedented levels through various databases have collaborated to a resurgence in the interest for QSAR. In this context, rapid generation of quality predictive models is highly desirable for hit identification and lead optimization. We showcase the application of an automated QSAR approach, which randomly selects multiple training/test sets and utilizes machine-learning algorithms to generate predictive models. Results demonstrate that AutoQSAR produces models of improved or similar quality to those generated by practitioners in the field but in just a fraction of the time. Despite the potential of the concept to the benefit of the community, the AutoQSAR opportunity has been largely undervalued.

Relationships between water table and model simulated ET

Treesearch

Prem B. Parajuli; Gretchen F. Sassenrath; Ying Ouyang

2013-01-01

This research was conducted to develop relationships among evapotranspiration (ET), percolation (PERC), groundwater discharge to the stream (GWQ), and water table fluctuations through a modeling approach. The Soil and Water Assessment Tool (SWAT) hydrologic and crop models were applied in the Big Sunflower River watershed (BSRW; 7660 km2) within the Yazoo River Basin...

Synthesis and structure-activity relationship of novel bisindole amidines active against MDR Gram-positive and Gram-negative bacteria.

PubMed

Liu, Yonghua; Hu, Xinxin; Wu, Yanbin; Zhang, Weixing; Chen, Xiaofang; You, Xuefu; Hu, Laixing

2018-04-25

A series of novel diamidines with N-substituents on an amidine N-atom were synthesized and evaluated for their cytotoxicity and in vitro antibacterial activity against a range of Gram-positive and Gram-negative bacterial strains. Based on structure-activity relationship, N-substituents with a branched chain and a shorter carbon chain on the amidine N-atom exhibited more promising activity against Gram-negative and MDR-Gram-positive bacteria; compounds 5c and 5i were the most powerful candidate compounds. Compound 5c showed greater efficacy than levofloxacin against most drug-resistant Gram-positive bacteria and exhibited broad-spectrum antibacterial activity against Gram-negative bacteria, with MIC values in the range of 2-16 μg/mL. Slightly more potent antibacterial activity against Klebsiella pneumoniae, Acinetobacter calcoaceticus, Enterobacter cloacae, and Proteus mirabilis was observed for 5i in comparison with 5c. Compound 5i also showed remarkable antibacterial activity against NDM-1-producing Gram-negative bacteria, with MIC values in the range of 2-4 μg/mL, and was superior to the reference drugs meropenem and levofloxacin. Effective antibacterial activity of 5i was also shown in vivo in a mouse model of Staphylococcus aureus MRSA strain, with an ED 50 values of 2.62 mg/kg. Copyright © 2018. Published by Elsevier Masson SAS.

Analyzing the Validity of Relationship Banking through Agent-based Modeling

NASA Astrophysics Data System (ADS)

Nishikido, Yukihito; Takahashi, Hiroshi

This article analyzes the validity of relationship banking through agent-based modeling. In the analysis, we especially focus on the relationship between economic conditions and both lenders' and borrowers' behaviors. As a result of intensive experiments, we made the following interesting findings: (1) Relationship banking contributes to reducing bad loan; (2) relationship banking is more effective in enhancing the market growth compared to transaction banking, when borrowers' sales scale is large; (3) keener competition among lenders may bring inefficiency to the market.

Multi-Parametric Analysis and Modeling of Relationships between Mitochondrial Morphology and Apoptosis

PubMed Central

Reis, Yara; Wolf, Thomas; Brors, Benedikt; Hamacher-Brady, Anne; Eils, Roland; Brady, Nathan R.

2012-01-01

Mitochondria exist as a network of interconnected organelles undergoing constant fission and fusion. Current approaches to study mitochondrial morphology are limited by low data sampling coupled with manual identification and classification of complex morphological phenotypes. Here we propose an integrated mechanistic and data-driven modeling approach to analyze heterogeneous, quantified datasets and infer relations between mitochondrial morphology and apoptotic events. We initially performed high-content, multi-parametric measurements of mitochondrial morphological, apoptotic, and energetic states by high-resolution imaging of human breast carcinoma MCF-7 cells. Subsequently, decision tree-based analysis was used to automatically classify networked, fragmented, and swollen mitochondrial subpopulations, at the single-cell level and within cell populations. Our results revealed subtle but significant differences in morphology class distributions in response to various apoptotic stimuli. Furthermore, key mitochondrial functional parameters including mitochondrial membrane potential and Bax activation, were measured under matched conditions. Data-driven fuzzy logic modeling was used to explore the non-linear relationships between mitochondrial morphology and apoptotic signaling, combining morphological and functional data as a single model. Modeling results are in accordance with previous studies, where Bax regulates mitochondrial fragmentation, and mitochondrial morphology influences mitochondrial membrane potential. In summary, we established and validated a platform for mitochondrial morphological and functional analysis that can be readily extended with additional datasets. We further discuss the benefits of a flexible systematic approach for elucidating specific and general relationships between mitochondrial morphology and apoptosis. PMID:22272225

On the Scatter in the Radius-Luminosity Relationship for Active Galactic Nuclei

NASA Astrophysics Data System (ADS)

Kilerci Eser, E.; Vestergaard, M.; Peterson, B. M.; Denney, K. D.; Bentz, M. C.

2015-03-01

We investigate and quantify the observed scatter in the empirical relationship between the broad line region size R and the luminosity of the active galactic nucleus, in order to better understand its origin. This study is motivated by the indispensable role of this relationship in the mass estimation of cosmologically distant black holes, but may also be relevant to the recently proposed application of this relationship for measuring cosmic distances. We study six nearby reverberation-mapped active galactic nuclei (AGNs) for which simultaneous UV and optical monitoring data exist. We also examine the long-term optical luminosity variations of the Seyfert 1 galaxy NGC 5548 and employ Monte Carlo simulations to study the effects of the intrinsic variability of individual objects on the scatter in the global relationship for a sample of ~40 AGNs. We find the scatter in this relationship has a correctable dependence on color. For individual AGNs, the size of the Hβ emitting region has a steeper dependence on the nuclear optical luminosity than on the UV luminosity, which can introduce a scatter of ~0.08 dex into the global relationship, due the nonlinear relationship between the variations in the ionizing continuum and those in the optical continuum. Also, our analysis highlights the importance of understanding and minimizing the scatter in the relationship traced by the intrinsic variability of individual AGNs since it propagates directly into the global relationship. We find that using the UV luminosity as a substitute for the ionizing luminosity can reduce a sizable fraction of the current observed scatter of ~0.13 dex.

USE OF TRANS-CONTEXTUAL MODEL-BASED PHYSICAL ACTIVITY COURSE IN DEVELOPING LEISURE-TIME PHYSICAL ACTIVITY BEHAVIOR OF UNIVERSITY STUDENTS.

PubMed

Müftüler, Mine; İnce, Mustafa Levent

2015-08-01

This study examined how a physical activity course based on the Trans-Contextual Model affected the variables of perceived autonomy support, autonomous motivation, determinants of leisure-time physical activity behavior, basic psychological needs satisfaction, and leisure-time physical activity behaviors. The participants were 70 Turkish university students (M age=23.3 yr., SD=3.2). A pre-test-post-test control group design was constructed. Initially, the participants were randomly assigned into an experimental (n=35) and a control (n=35) group. The experimental group followed a 12 wk. trans-contextual model-based intervention. The participants were pre- and post-tested in terms of Trans-Contextual Model constructs and of self-reported leisure-time physical activity behaviors. Multivariate analyses showed significant increases over the 12 wk. period for perceived autonomy support from instructor and peers, autonomous motivation in leisure-time physical activity setting, positive intention and perceived behavioral control over leisure-time physical activity behavior, more fulfillment of psychological needs, and more engagement in leisure-time physical activity behavior in the experimental group. These results indicated that the intervention was effective in developing leisure-time physical activity and indicated that the Trans-Contextual Model is a useful way to conceptualize these relationships.

Modeling the Prospective Relationships of Impairment, Injury Severity, and Participation to Quality of Life Following Traumatic Brain Injury

PubMed Central

Kalpinski, Ryan J.; Williamson, Meredith L. C.; Elliott, Timothy R.; Berry, Jack W.; Underhill, Andrea T.; Fine, Philip R.

2013-01-01

Identifying reliable predictors of positive adjustment following traumatic brain injury (TBI) remains an important area of inquiry. Unfortunately, much of available research examines direct relationships between predictor variables and outcomes without attending to the contextual relationships that can exist between predictor variables. Relying on theoretical models of well-being, we examined a theoretical model of adjustment in which the capacity to engage in intentional activities would be prospectively associated with greater participation, which in turn would predict subsequent life satisfaction and perceived health assessed at a later time. Structural equation modeling of data collected from 312 individuals (226 men, 86 women) with TBI revealed that two elements of participation—mobility and occupational activities—mediated the prospective influence of functional independence and injury severity to optimal adjustment 60 months following medical discharge for TBI. The model accounted for 21% of the variance in life satisfaction and 23% of the variance in self-rated health. Results indicate that the effects of functional independence and injury severity to optimal adjustment over time may be best understood in the context of participation in meaningful, productive activities. Implications for theoretical models of well-being and for clinical interventions that promote adjustmentafter TBI are discussed. PMID:24199186

Phytochemicals from Dodonaea viscosa and their antioxidant and anticholinesterase activities with structure-activity relationships.

PubMed

Muhammad, Akhtar; Tel-Çayan, Gülsen; Öztürk, Mehmet; Duru, Mehmet Emin; Nadeem, Said; Anis, Itrat; Ng, Seik Weng; Shah, Muhammad Raza

2016-09-01

Context Dodonaea viscosa (L.) Jacq (Sapindaceae) has been used in traditional medicine as antimalarial, antidiabetic and antibacterial agent, but further investigations are needed. Objective This study determines the antioxidant and anticholinesterase activities of six compounds (1-6) and two crystals (1A and 3A) isolated from D. viscosa, and discusses their structure-activity relationships. Materials and methods Antioxidant activity was evaluated using six complementary tests, i.e., β-carotene-linoleic acid; DPPH(•), ABTS(•+), superoxide scavenging, CUPRAC and metal chelating assays. Anticholinesterase activity was performed using the Elman method. Results Clerodane diterpenoids (1 and 2) and phenolics (3-6) - together with three crystals (1A, 3A and 7A) - were isolated from the aerial parts of D. viscosa. Compound 3A exhibited good antioxidant activity in DPPH (IC50: 27.44 ± 1.06 μM), superoxide (28.18 ± 1.35% inhibition at 100 μM) and CUPRAC (A0.5: 35.89 ± 0.09 μM) assays. Compound 5 (IC50: 11.02 ± 0.02 μM) indicated best activity in ABTS assay, and 6 (IC50: 14.30 ± 0.18 μM) in β-carotene-linoleic acid assay. Compounds 1 and 3 were also obtained in the crystal (1A and 3A) form. Both crystals showed antioxidant activity. Furthermore, crystal 3A was more active than 3 in all activity tests. Phenol 6 possessed moderate anticholinesterase activity against acetylcholinesterase and butyrylcholinesterase enzymes (IC50 values: 158.14 ± 1.65 and 111.60 ± 1.28 μM, respectively). Discussion and conclusion This is the first report on antioxidant and anticholinesterase activities of compounds 1, 2, 5, 6, 1A and 3A, and characterisation of 7A using XRD. Furthermore, the structure-activity relationships are also discussed in detail for the first time.

[The bidirectional relationship between physical activity and sleep in depressed versus non-depressed individuals].

PubMed

Oude Oosterik, N A M; Bouwmans, M E J; de Groot, I W; Bos, E H; de Jonge, P

Sleep and physical activity are related, but the direction of this relationship is unclear and it is not known whether the direction differs in depressed and non-depressed persons. To study the bidirectional relationship between physical activity and sleep in daily life by making repeated measurements in depressed and non-depressed people. Every day for 30 consecutive days each depressed (N = 27) and non-depressed (N = 27) participant in our study had to complete an electronic questionnaire relating to subjective sleep quality and sleep duration and were required to wear an accelerometer that recorded physical activity. Multi-level analysis showed that an increase in subjective sleep duration resulted in a decrease in physical activity. The differences between individuals with regard to the direction and strength of this relationship were significant. Changes in physical activity did not predict changes in sleep quality or sleep duration. We did not find any differences in the relationships for depressed and non-depressed participants. Change in sleep duration predicts change in physical activity, although there was significant heterogeneity in the results for individuals. Our findings underline the importance of further research and of the development of interventions that are tailored to the precise needs of the individual patient.

Identifying relationships between unrelated pharmaceutical target proteins on the basis of shared active compounds.

PubMed

Miljković, Filip; Kunimoto, Ryo; Bajorath, Jürgen

2017-08-01

Computational exploration of small-molecule-based relationships between target proteins from different families. Target annotations of drugs and other bioactive compounds were systematically analyzed on the basis of high-confidence activity data. A total of 286 novel chemical links were established between distantly related or unrelated target proteins. These relationships involved a total of 1859 bioactive compounds including 147 drugs and 141 targets. Computational analysis of large amounts of compounds and activity data has revealed unexpected relationships between diverse target proteins on the basis of compounds they share. These relationships are relevant for drug discovery efforts. Target pairs that we have identified and associated compound information are made freely available.

Relationship between motivation and learning in physical education and after-school physical activity.

PubMed

Chen, Senlin; Sun, Haichun; Zhu, Xihe; Chen, Ang

2014-12-01

A primary goal of physical education is to develop physically literate individuals with the knowledge, skills, and confidence necessary for a physically active lifestyle. Guided by the expectancy-value and interest motivation theories, the purpose of this study was to identify the relationship between students' motivation and health-related fitness knowledge developed in physical education and their after-school physical activity participation. Third-, 4th-, and 5th-grade students (N = 293) from 6 elementary schools in a large metropolitan school district in the United States provided data on expectancy beliefs and perceived task values, situational interest, health-related fitness knowledge, and after-school physical activity. Data were analyzed using descriptive statistics and a simultaneous multiple regression model. It was found that expectancy beliefs (β = .20, t = 2.16, p = .03) and perceived exploration demand (β = .25, t = 2.58, p = .01), a source for situational interest, were positively related to after-school physical activity. The 2 variables, however, accounted for only 11.2% of the variances for children's after-school physical activity participation. This study demonstrates that students' active exploration and expectancy beliefs for success in physical education have limited influence on leisure-time physical activity participation.

The reciprocal relationship between daily fatigue and catastrophizing following cancer treatment: Affect and physical activity as potential mediators.

PubMed

Müller, Fabiola; Stephenson, Ellen; DeLongis, Anita; Smink, Ans; Van Ginkel, Robert J; Tuinman, Marrit A; Hagedoorn, Mariët

2018-03-01

Fatigue is a distressing symptom many cancer patients experience even after completion of treatment. Although theory and empirical evidence indicate that negative cognitions perpetuate fatigue after completion of treatment, insight into how this process unfolds in daily life is limited. This study used an intensive longitudinal design to investigate the reciprocal relationship between catastrophizing and fatigue in daily life and whether affective and behavioral processes mediate these relationships. Post-treatment colorectal cancer patients (n = 101) completed daily diaries (14 days, 3 times daily) regarding their fatigue, catastrophizing, positive and negative affect, and physical activity. Multilevel modeling was applied to investigate within-person associations within days. Analyses revealed a positive reciprocal relationship between fatigue and catastrophizing throughout the day. That is, high levels of catastrophizing were associated with increases in fatigue within patients. In turn, but to a lesser extent, high levels of fatigue predicted increases in catastrophizing at the next assessment. Low positive affect and high negative affect mediated the effect of catastrophizing on increases in fatigue. Only negative affect mediated the reverse relationship. Physical activity did not mediate either relationship. This study provides evidence for a mutually reinforcing relationship between catastrophizing and fatigue in daily life, which might explain the perpetuation of fatigue after completion of cancer treatment. Fatigue-specific cognitive behavior therapy could be improved by educating patients about this daily reciprocal relationship, train them to quickly replace catastrophizing thoughts in daily life, and help them to cope with affective changes induced by fatigue. Copyright © 2017 John Wiley & Sons, Ltd.

The effects of parental education and family income on mother-child relationships, father-child relationships, and family environments in the People's Republic of China.

PubMed

Zhang, Xiao

2012-12-01

Using a cross-sectional design with 407 Chinese children aged 3-5 years and their parents, this study examined the effects of socioeconomic status, specifically parents' education and family income, on the children's mother-child relationships, father-child relationships, and the social environment in their families. The results indicated that income negatively predicted conflict in father-child relationships and positively predicted family active-recreational environments. Income also positively predicted family cohesion among girls but not boys. Maternal education negatively predicted conflict in mother-child relationships and positively predicted closeness in mother-child and father-child relationships, family cohesion, and the intellectual-cultural and active-recreational environments in the family. Paternal education positively predicted family cohesion and intellectual-cultural and active-recreational environments. Income was found to partially mediate the effects of both maternal and paternal education on family active-recreational environments. Findings are discussed in the frameworks of the family stress model and the family investment model. © FPI, Inc.

Molecular modeling and snake venom phospholipase A2 inhibition by phenolic compounds: Structure-activity relationship.

PubMed

Alam, Md Iqbal; Alam, Mohammed A; Alam, Ozair; Nargotra, Amit; Taneja, Subhash Chandra; Koul, Surrinder

2016-05-23

In our earlier study, we have reported that a phenolic compound 2-hydroxy-4-methoxybenzaldehyde from Janakia arayalpatra root extract was active against Viper and Cobra envenomations. Based on the structure of this natural product, libraries of synthetic structurally variant phenolic compounds were studied through molecular docking on the venom protein. To validate the activity of eight selected compounds, we have tested them in in vivo and in vitro models. The compound 21 (2-hydroxy-3-methoxy benzaldehyde), 22 (2-hydroxy-4-methoxybenzaldehyde) and 35 (2-hydroxy-3-methoxybenzylalcohol) were found to be active against venom-induced pathophysiological changes. The compounds 20, 15 and 35 displayed maximum anti-hemorrhagic, anti-lethal and PLA2 inhibitory activity respectively. In terms of SAR, the presence of a formyl group in conjunction with a phenolic group was seen as a significant contributor towards increasing the antivenom activity. The above observations confirmed the anti-venom activity of the phenolic compounds which needs to be further investigated for the development of new anti-snake venom leads. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Cross-sectional and prospective relationship between physical activity and chronic diseases in European older adults.

PubMed

Marques, Adilson; Peralta, Miguel; Martins, João; de Matos, Margarida Gaspar; Brownson, Ross C

2017-05-01

This study examined the relationship between physical activity (PA) and chronic diseases in European older adults, using a prospective analysis with data from 2011 and 2013. Participants were 37,524 older adults (16,204 men) who responded to the fourth (in 2011) and fifth (in 2013) wave of SHARE project, from 13 European countries. Participants' answers to interview questions about the presence of chronic conditions and PA. The cross-sectional and prospective association between PA and the number of chronic diseases was assessed using general linear models. Among men and women, moderate or vigorous physical activity (MVPA) in 2011 was associated with fewer reported chronic diseases in 2011 and 2013. In prospective analysis, MVPA in 2011 was inversely associated with the number of chronic diseases in 2013 in the unadjusted model. In the adjusted model MVPA more than once a week remained as a significant predictor of fewer chronic diseases. PA should be prescribed to older adults in order to prevent and reduce the number of chronic diseases, and, when possible, vigorous intensity PA should be recommended.

A cross-sectional study of the relationship between parents' and children's physical activity.

PubMed

Stearns, Jodie A; Rhodes, Ryan; Ball, Geoff D C; Boule, Normand; Veugelers, Paul J; Cutumisu, Nicoleta; Spence, John C

2016-10-28

Though parents' physical activity (PA) is thought to be a predictor of children's PA, findings have been mixed. The purpose of this study was to examine the relationship between pedometer-measured steps/day of parents' and their children and potential moderators of this relationship. We also assessed the parent-child PA relationship as measured by questionnaires. Six-hundred and twelve 7-8 year olds and one of their parents wore Steps Count (SC)-T2 pedometers for four consecutive days. Parents reported their PA from the last seven days and their child's usual PA. Hierarchical linear regressions were used to assess the parent-child PA relationships, controlling for covariates. Gender (parent, child), gender homogeneity, weight status (parent, child), weight status homogeneity, and socioeconomic status (SES) variables (parent education, household income, area-level SES) were tested as potential moderators of this relationship. Partial r's were used as an estimate of effect size. Parents' steps was significantly related to children's steps (r partial  = .24). For every 1,000 step increase in parents' steps, the children took 260 additional steps. None of the tested interactions were found to moderate this relationship. Using questionnaires, a relatively smaller parent-child PA relationship was found (r partial  = .14). Physically active parents tend to have physically active children. Interventions designed to get children moving more throughout the day could benefit from including a parent component. Future research should explore the mechanisms by which parents influence their children, and other parent attributes and styles as potential moderators.

A nonlinear dynamical analogue model of geomagnetic activity

NASA Technical Reports Server (NTRS)

Klimas, A. J.; Baker, D. N.; Roberts, D. A.; Fairfield, D. H.; Buechner, J.

1992-01-01

Consideration is given to the solar wind-magnetosphere interaction within the framework of deterministic nonlinear dynamics. An earlier dripping faucet analog model of the low-dimensional solar wind-magnetosphere system is reviewed, and a plasma physical counterpart to that model is constructed. A Faraday loop in the magnetotail is considered, and the relationship of electric potentials on the loop to changes in the magnetic flux threading the loop is developed. This approach leads to a model of geomagnetic activity which is similar to the earlier mechanical model but described in terms of the geometry and plasma contents of the magnetotail. The model is characterized as an elementary time-dependent global convection model. The convection evolves within a magnetotail shape that varies in a prescribed manner in response to the dynamical evolution of the convection. The result is a nonlinear model capable of exhibiting a transition from regular to chaotic loading and unloading. The model's behavior under steady loading and also some elementary forms of time-dependent loading is discussed.

Establishment of quantitative retention-activity model by optimized microemulsion liquid chromatography.

PubMed

Xu, Liyuan; Gao, Haoshi; Li, Liangxing; Li, Yinnong; Wang, Liuyun; Gao, Chongkai; Li, Ning

2016-12-23

The effective permeability coefficient is of theoretical and practical importance in evaluation of the bioavailability of drug candidates. However, most methods currently used to measure this coefficient are expensive and time-consuming. In this paper, we addressed these problems by proposing a new measurement method which is based on the microemulsion liquid chromatography. First, the parallel artificial membrane permeability assays model was used to determine the effective permeability of drug so that quantitative retention-activity relationships could be established, which were used to optimize the microemulsion liquid chromatography. The most effective microemulsion system used a mobile phase of 6.0% (w/w) Brij35, 6.6% (w/w) butanol, 0.8% (w/w) octanol, and 86.6% (w/w) phosphate buffer (pH 7.4). Next, support vector machine and back-propagation neural networks are employed to develop a quantitative retention-activity relationships model associated with the optimal microemulsion system, and used to improve the prediction ability. Finally, an adequate correlation between experimental value and predicted value is computed to verify the performance of the optimal model. The results indicate that the microemulsion liquid chromatography can serve as a possible alternative to the PAMPA method for determination of high-throughput permeability and simulation of biological processes. Copyright © 2016. Published by Elsevier B.V.

Development of a Conceptual Model to Predict Physical Activity Participation in Adults with Brain Injuries

ERIC Educational Resources Information Center

Driver, Simon

2008-01-01

The purpose was to examine psychosocial factors that influence the physical activity behaviors of adults with brain injuries. Two differing models, based on Harter's model of self-worth, were proposed to examine the relationship between perceived competence, social support, physical self-worth, affect, and motivation. Adults numbering 384 with…

Parabolic quantitative structure-activity relationships and photodynamic therapy: application of a three-compartment model with clearance to the in vivo quantitative structure-activity relationships of a congeneric series of pyropheophorbide derivatives used as photosensitizers for photodynamic therapy.

PubMed

Potter, W R; Henderson, B W; Bellnier, D A; Pandey, R K; Vaughan, L A; Weishaupt, K R; Dougherty, T J

1999-11-01

An open three-compartment pharmacokinetic model was applied to the in vivo quantitative structure-activity relationship (QSAR) data of a homologous series of pyropheophorbide photosensitizers for photodynamic therapy (PDT). The physical model was a lipid compartment sandwiched between two identical aqueous compartments. The first compartment was assumed to clear irreversibly at a rate K0. The measured octanol-water partition coefficients, P(i) (where i is the number of carbons in the alkyl chain) and the clearance rate K0 determined the clearance kinetics of the drugs. Solving the coupled differential equations of the three-compartment model produced clearance kinetics for each of the sensitizers in each of the compartments. The third compartment was found to contain the target of PDT. This series of compounds is quite lipophilic. Therefore these drugs are found mainly in the second compartment. The drug level in the third compartment represents a small fraction of the tissue level and is thus not accessible to direct measurement by extraction. The second compartment of the model accurately predicted the clearance from the serum of mice of the hexyl ether of pyropheophorbide a, one member of this series of compounds. The diffusion and clearance rate constants were those found by fitting the pharmacokinetics of the third compartment to the QSAR data. This result validated the magnitude and mechanistic significance of the rate constants used to model the QSAR data. The PDT response to dose theory was applied to the kinetic behavior of the target compartment drug concentration. This produced a pharmacokinetic-based function connecting PDT response to dose as a function of time postinjection. This mechanistic dose-response function was fitted to published, single time point QSAR data for the pheophorbides. As a result, the PDT target threshold dose together with the predicted QSAR as a function of time postinjection was found.

Generalized in vitro-in vivo relationship (IVIVR) model based on artificial neural networks

PubMed Central

Mendyk, Aleksander; Tuszyński, Paweł K; Polak, Sebastian; Jachowicz, Renata

2013-01-01

Background The aim of this study was to develop a generalized in vitro-in vivo relationship (IVIVR) model based on in vitro dissolution profiles together with quantitative and qualitative composition of dosage formulations as covariates. Such a model would be of substantial aid in the early stages of development of a pharmaceutical formulation, when no in vivo results are yet available and it is impossible to create a classical in vitro-in vivo correlation (IVIVC)/IVIVR. Methods Chemoinformatics software was used to compute the molecular descriptors of drug substances (ie, active pharmaceutical ingredients) and excipients. The data were collected from the literature. Artificial neural networks were used as the modeling tool. The training process was carried out using the 10-fold cross-validation technique. Results The database contained 93 formulations with 307 inputs initially, and was later limited to 28 in a course of sensitivity analysis. The four best models were introduced into the artificial neural network ensemble. Complete in vivo profiles were predicted accurately for 37.6% of the formulations. Conclusion It has been shown that artificial neural networks can be an effective predictive tool for constructing IVIVR in an integrated generalized model for various formulations. Because IVIVC/IVIVR is classically conducted for 2–4 formulations and with a single active pharmaceutical ingredient, the approach described here is unique in that it incorporates various active pharmaceutical ingredients and dosage forms into a single model. Thus, preliminary IVIVC/IVIVR can be available without in vivo data, which is impossible using current IVIVC/IVIVR procedures. PMID:23569360

Duration Models to Analyze Dating Relationship: The Controversial Role of Gift Giving.

ERIC Educational Resources Information Center

Huang, Ming-Hui; Yu, Shihti

2000-01-01

Econometric duration models were used to analyze dating relationships of 225 college students. Using gifts to enhance the self, express love, and announce relationships helped ensure the success of relationships. Gifts that were too frequent or rare resulted in self-depreciation and anxiety and harmed relationships. (SK)

Investigating Supervisory Relationships and Therapeutic Alliances Using Structural Equation Modeling

ERIC Educational Resources Information Center

DePue, Mary Kristina; Lambie, Glenn W.; Liu, Ren; Gonzalez, Jessica

2016-01-01

The authors used structural equation modeling to examine the contribution of supervisees' supervisory relationship levels to therapeutic alliance (TA) scores with their clients in practicum. Results showed that supervisory relationship scores positively contributed to the TA. Client and counselor ratings of the TA also differed.

Relationship between peroxisome proliferator-activated receptor alpha activity and cellular concentration of 14 perfluoroalkyl substances in HepG2 cells.

PubMed

Rosenmai, Anna Kjerstine; Ahrens, Lutz; le Godec, Théo; Lundqvist, Johan; Oskarsson, Agneta

2018-02-01

Peroxisome proliferator-activated receptor alpha (PPARα) is a molecular target for perfluoroalkyl substances (PFASs). Little is known about the cellular uptake of PFASs and how it affects the PPARα activity. We investigated the relationship between PPARα activity and cellular concentration in HepG2 cells of 14 PFASs, including perfluoroalkyl carboxylates (PFCAs), perfluoroalkyl sulfonates and perfluorooctane sulfonamide (FOSA). Cellular concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry and PPARα activity was determined in transiently transfected cells by reporter gene assay. Cellular uptake of the PFASs was low (0.04-4.1%) with absolute cellular concentrations in the range 4-2500 ng mg -1 protein. Cellular concentration of PFCAs increased with perfluorocarbon chain length up to perfluorododecanoate. PPARα activity of PFCAs increased with chain length up to perfluorooctanoate. The maximum induction of PPARα activity was similar for short-chain (perfluorobutanoate and perfluoropentanoate) and long-chain PFCAs (perfluorododecanoate and perfluorotetradecanoate) (approximately twofold). However, PPARα activities were induced at lower cellular concentrations for the short-chain homologs compared to the long-chain homologs. Perfluorohexanoate, perfluoroheptanoate, perfluorooctanoate, perfluorononanoate (PFNA) and perfluorodecanoate induced PPARα activities >2.5-fold compared to controls. The concentration-response relationships were positive for all the tested compounds, except perfluorooctane sulfonate PFOS and FOSA, and were compound-specific, as demonstrated by differences in the estimated slopes. The relationships were steeper for PFCAs with chain lengths up to and including PFNA than for the other studied PFASs. To our knowledge, this is the first report establishing relationships between PPARα activity and cellular concentration of a broad range of PFASs. Copyright © 2017 John Wiley & Sons, Ltd.

ON THE SCATTER IN THE RADIUS-LUMINOSITY RELATIONSHIP FOR ACTIVE GALACTIC NUCLEI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kilerci Eser, E.; Vestergaard, M.; Peterson, B. M.

2015-03-01

We investigate and quantify the observed scatter in the empirical relationship between the broad line region size R and the luminosity of the active galactic nucleus, in order to better understand its origin. This study is motivated by the indispensable role of this relationship in the mass estimation of cosmologically distant black holes, but may also be relevant to the recently proposed application of this relationship for measuring cosmic distances. We study six nearby reverberation-mapped active galactic nuclei (AGNs) for which simultaneous UV and optical monitoring data exist. We also examine the long-term optical luminosity variations of the Seyfert 1more » galaxy NGC 5548 and employ Monte Carlo simulations to study the effects of the intrinsic variability of individual objects on the scatter in the global relationship for a sample of ∼40 AGNs. We find the scatter in this relationship has a correctable dependence on color. For individual AGNs, the size of the Hβ emitting region has a steeper dependence on the nuclear optical luminosity than on the UV luminosity, which can introduce a scatter of ∼0.08 dex into the global relationship, due the nonlinear relationship between the variations in the ionizing continuum and those in the optical continuum. Also, our analysis highlights the importance of understanding and minimizing the scatter in the relationship traced by the intrinsic variability of individual AGNs since it propagates directly into the global relationship. We find that using the UV luminosity as a substitute for the ionizing luminosity can reduce a sizable fraction of the current observed scatter of ∼0.13 dex.« less

A phenomenological model of muscle fatigue and the power-endurance relationship.

PubMed

James, A; Green, S

2012-11-01

The relationship between power output and the time that it can be sustained during exercise (i.e., endurance) at high intensities is curvilinear. Although fatigue is implicit in this relationship, there is little evidence pertaining to it. To address this, we developed a phenomenological model that predicts the temporal response of muscle power during submaximal and maximal exercise and which was based on the type, contractile properties (e.g., fatiguability), and recruitment of motor units (MUs) during exercise. The model was first used to predict power outputs during all-out exercise when fatigue is clearly manifest and for several distributions of MU type. The model was then used to predict times that different submaximal power outputs could be sustained for several MU distributions, from which several power-endurance curves were obtained. The model was simultaneously fitted to two sets of human data pertaining to all-out exercise (power-time profile) and submaximal exercise (power-endurance relationship), yielding a high goodness of fit (R(2) = 0.96-0.97). This suggested that this simple model provides an accurate description of human power output during submaximal and maximal exercise and that fatigue-related processes inherent in it account for the curvilinearity of the power-endurance relationship.

Chinese College Students' Physical Activity Correlates and Behavior: A Transtheoretical Model Perspective

ERIC Educational Resources Information Center

Xiong, Shanying; Li, Xianxiong; Tao, Kun; Zeng, Nan; Ayyub, Mohammad; Peng, Qingwen; Yan, Xiaoni; Wang, Junli; Wu, Yizhong; Lei, Mingzhi

2017-01-01

Guided by the Transtheoretical Model (Prochaska & DiClemente, 1982), this study investigated the differences of physical activity levels and correlates (i.e., self-efficacy, decisional balance, process of change) across different stages of change levels among Chinese college students. The relationships between students' physical activity…

Brief Report: Relationships between Physical Activity and Depressive Symptoms in Adolescent Girls

ERIC Educational Resources Information Center

Raudsepp, Lennart; Neissaar, Inga

2012-01-01

This study examined the relationships between changes in physical activity and depressive symptoms in adolescent girls. Participants were 277 urban adolescent girls. Physical activity was measured using the 3-Day Physical Activity Recall and depressive symptoms were assessed using questionnaire. Data were collected on three occasions over a 3-year…

Fish biomarkers for environmental monitoring: An integrated model supporting enzyme activity and histopathological lesions

NASA Astrophysics Data System (ADS)

Neta, Raimunda Nonata Fortes Carvalho; Torres Junior, Audalio Rebelo

2014-10-01

We present a mathematical model describing the association between glutathione-S-transferase activity and brachial lesions in the catfish, Sciades herzbergii (Ariidae) from a polluted port. The catfish were sampled from a port known to be contaminated with heavy metals and organic compounds and from a natural reserve in São Marcos Bay, Brazil. Two biomarkers, hepatic glutathione S-transferase (GST) activity and histopathological lesions, in gills tissue were measured. The values for GST activity were modeled with the occurrence of branchial lesions by fitting a third order polynomial. Results from the mathematical model indicate that GST activity has a strong polynomial relationship with the occurrence of branchial lesions in both the wet and the dry seasons, but only at the polluted port site. The model developed in this study indicates that branchial and hepatic lesions are initiated when GST activity reaches 2.15 μmol min-1 mg protein-1. Beyond this limit, GST activity decreased to very low levels and irreversible histopathological lesions occurred. This mathematical model provides a realistic approach to analyze predictive biomarkers of environmental health status.

Network diffusion accurately models the relationship between structural and functional brain connectivity networks

PubMed Central

Abdelnour, Farras; Voss, Henning U.; Raj, Ashish

2014-01-01

The relationship between anatomic connectivity of large-scale brain networks and their functional connectivity is of immense importance and an area of active research. Previous attempts have required complex simulations which model the dynamics of each cortical region, and explore the coupling between regions as derived by anatomic connections. While much insight is gained from these non-linear simulations, they can be computationally taxing tools for predicting functional from anatomic connectivities. Little attention has been paid to linear models. Here we show that a properly designed linear model appears to be superior to previous non-linear approaches in capturing the brain’s long-range second order correlation structure that governs the relationship between anatomic and functional connectivities. We derive a linear network of brain dynamics based on graph diffusion, whereby the diffusing quantity undergoes a random walk on a graph. We test our model using subjects who underwent diffusion MRI and resting state fMRI. The network diffusion model applied to the structural networks largely predicts the correlation structures derived from their fMRI data, to a greater extent than other approaches. The utility of the proposed approach is that it can routinely be used to infer functional correlation from anatomic connectivity. And since it is linear, anatomic connectivity can also be inferred from functional data. The success of our model confirms the linearity of ensemble average signals in the brain, and implies that their long-range correlation structure may percolate within the brain via purely mechanistic processes enacted on its structural connectivity pathways. PMID:24384152

MOLECULAR INTERACTION POTENTIALS FOR THE DEVELOPMENT OF STRUCTURE-ACTIVITY RELATIONSHIPS

EPA Science Inventory

Abstract
One reasonable approach to the analysis of the relationships between molecular structure and toxic activity is through the investigation of the forces and intermolecular interactions responsible for chemical toxicity. The interaction between the xenobiotic and the bio...

Discovery of imidazo[1,2-b]pyridazine derivatives as IKKbeta inhibitors. Part 1: Hit-to-lead study and structure-activity relationship.

PubMed

Shimizu, Hiroki; Tanaka, Shinji; Toki, Tadashi; Yasumatsu, Isao; Akimoto, Toshihiko; Morishita, Kaoru; Yamasaki, Tomonori; Yasukochi, Takanori; Iimura, Shin

2010-09-01

Imidazo[1,2-b]pyridazine derivatives from high-throughput screening were developed as IKKbeta inhibitors. By the optimization of the 3- and 6-position of imidazo[1,2-b]pyridazine scaffold, cell-free IKKbeta inhibitory activity and TNFalpha inhibitory activity in THP-1 cell increased. Also, these compounds showed high kinase selectivity. The structure-activity relationship was revealed and the interaction model of imidazo[1,2-b]pyridazine compounds with IKKbeta was constructed. Copyright 2010. Published by Elsevier Ltd.

Relationships between fundamental movement skills and objectively measured physical activity in preschool children.

PubMed

Cliff, Dylan P; Okely, Anthony D; Smith, Leif M; McKeen, Kim

2009-11-01

Gender differences in cross-sectional relationships between fundamental movement skill (FMS) subdomains (locomotor skills, object-control skills) and physical activity were examined in preschool children. Forty-six 3- to 5-year-olds (25 boys) had their FMS video assessed (Test of Gross Motor Development II) and their physical activity objectively monitored (Actigraph 7164 accelerometers). Among boys, object-control skills were associated with physical activity and explained 16.9% (p = .024) and 13.7% (p = .049) of the variance in percent of time in moderate-to-vigorous physical activity (MVPA) and total physical activity, respectively, after controlling for age, SES and z-BMI. Locomotor skills were inversely associated with physical activity among girls, and explained 19.2% (p = .023) of the variance in percent of time in MVPA after controlling for confounders. Gender and FMS subdomain may influence the relationship between FMS and physical activity in preschool children.

Exploring the relationship between outdoor recreation activities, community participation, and environmental attitudes

Treesearch

Lindsey Barker; Chad Dawson

2012-01-01

The relationship between environmental attitudes (EA) and environmentally responsible behavior (ERB) has been the focus of several studies in environmental psychology and recreation research. The purpose of this study was to explore the relationship between EAs and ERBs at both a general level and at an activity-specific level using a 2009 survey of motorized...

STRUCTURE-ACTIVITY RELATIONSHIPS (SARS) AMONG MUTAGENS AND CARCINOGENS: A REVIEW

EPA Science Inventory

The review is an introduction to methods for evaluating structure-activity relationships (SARs), and, in particular, to those methods that have been applied to study mutagenicity and carcinogenicity. A brief history and some background material on the earliest attempts to correla...

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS FOR CHEMICAL REDUCTIONS OF ORGANIC CONTAMINANTS

EPA Science Inventory

Sufficient kinetic data on abiotic reduction reactions involving organic contaminants are now available that quantitative structure-activity relationships (QSARs) for these reactions can be developed. Over 50 QSARs have been reported, most in just the last few years, and they ar...

Discovery and structure-activity relationships of a series of pyroglutamic acid amide antagonists of the P2X7 receptor.

PubMed

Abdi, Muna H; Beswick, Paul J; Billinton, Andy; Chambers, Laura J; Charlton, Andrew; Collins, Sue D; Collis, Katharine L; Dean, David K; Fonfria, Elena; Gleave, Robert J; Lejeune, Clarisse L; Livermore, David G; Medhurst, Stephen J; Michel, Anton D; Moses, Andrew P; Page, Lee; Patel, Sadhana; Roman, Shilina A; Senger, Stefan; Slingsby, Brian; Steadman, Jon G A; Stevens, Alexander J; Walter, Daryl S

2010-09-01

A computational lead-hopping exercise identified compound 4 as a structurally distinct P2X(7) receptor antagonist. Structure-activity relationships (SAR) of a series of pyroglutamic acid amide analogues of 4 were investigated and compound 31 was identified as a potent P2X(7) antagonist with excellent in vivo activity in animal models of pain, and a profile suitable for progression to clinical studies. Copyright 2010 Elsevier Ltd. All rights reserved.

Granger Causality Relationships between Local Field Potentials in an Animal Model of Temporal Lobe Epilepsy

PubMed Central

Cadotte, Alex J.; DeMarse, Thomas B.; Mareci, Thomas H.; Parekh, Mansi; Talathi, Sachin S.; Hwang, Dong-Uk; Ditto, William L.; Ding, Mingzhou; Carney, Paul R.

2010-01-01

An understanding of the in vivo spatial emergence of abnormal brain activity during spontaneous seizure onset is critical to future early seizure detection and closed-loop seizure prevention therapies. In this study, we use Granger causality (GC) to determine the strength and direction of relationships between local field potentials (LFPs) recorded from bilateral microelectrode arrays in an intermittent spontaneous seizure model of chronic temporal lobe epilepsy before, during, and after Racine grade partial onset generalized seizures. Our results indicate distinct patterns of directional GC relationships within the hippocampus, specifically from the CA1 subfield to the dentate gryus, prior to and during seizure onset. Our results suggest sequential and hierarchical temporal relationships between the CA1 and dentate gyrus within and across hippocampal hemispheres during seizure. Additionally, our analysis suggests a reversal in the direction of GC relationships during seizure, from an abnormal pattern to more anatomically expected pattern. This reversal correlates well with the observed behavioral transition from tonic to clonic seizure in time-locked video. These findings highlight the utility of GC to reveal dynamic directional temporal relationships between multichannel LFP recordings from multiple brain regions during unprovoked spontaneous seizures. PMID:20304005

Structure-activity relationships of selected phenazines against Mycobacterium leprae in vitro.

PubMed Central

Franzblau, S G; O'Sullivan, J F

1988-01-01

Structure-activity relationships of phenazines against Mycobacterium leprae were investigated by using an in vitro radiorespirometric assay. In general, activity in ascending order was observed in compounds containing no chlorine atoms, a monochlorinated phenazine nucleus, and chlorines in the para positions of both the anilino and phenyl rings. The most active compounds contained a 2,2,6,6-tetramethylpiperidine substitution at the imino nitrogen. Most of these chlorinated phenazines were considerably more active in vitro than clofazimine (B663). PMID:3056241

Negative childhood experiences and adult love relationships: the role of internal working models of attachment.

PubMed

McCarthy, Gerard; Maughan, Barbara

2010-09-01

This study investigated links between internal working models of attachment and the quality of adult love relationships in a high risk sample of women (n = 34), all of whom reported negative parenting in childhood. Half of the sample was identified as having a history of satisfying adult love relationships, while the remainder had experienced ongoing adult relationship problems. Measures of internal working models of attachment were made using the Adult Attachment Interview (AAI). A strong association was found between attachment classifications and the quality of adult love relationships. In addition, women with satisfying love relationships demonstrated significantly higher coherence of mind ratings than those with poor relationship histories. Insecure working models of attachment were associated with problems in adult love relationships. Although secure/autonomous attachment status was linked to optimal adult relationship outcomes, some women with a history of satisfying love relationships had insecure working models of attachment. These results suggest that the ways that adults process early experiences may influence later psychosocial functioning.

The Relationship Between Walking Capacity, Biopsychosocial Factors, Self-Efficacy and Walking Activity in Individuals Post Stroke

PubMed Central

Danks, Kelly A.; Pohlig, Ryan T.; Roos, Margie; Wright, Tamara R.; Reisman, Darcy S.

2016-01-01

Background/Purpose Many factors appear to be related to physical activity after stroke, yet it is unclear how these factors interact and which ones might be the best predictors. Therefore, the purpose of this study was twofold: 1) to examine the relationship between walking capacity and walking activity, and 2) to investigate how biopsychosocial factors and self-efficacy relate to walking activity, above and beyond walking capacity impairment post-stroke. Methods Individuals greater than 3 months post-stroke (n=55) completed the Yesavage Geriatric Depression Scale (GDS), Fatigue Severity Scale (FSS), Modified Cumulative Illness Rating (MCIR) Scale, Walk 12, Activities Specific Balance Confidence (ABC) Scale, Functional Gait Assessment (FGA), and oxygen consumption testing. Walking activity data was collected via a StepWatch Activity Monitor (SAM). Predictors were grouped into 3 constructs: (1) Walking Capacity: oxygen consumption and FGA; (2) Biopsychosocial: GDS, FSS, and MCIR; (3) Self-Efficacy: Walk 12 and ABC. Moderated sequential regression models were used to examine what factors best predicted walking activity. Results Walking capacity explained 35.9% (p<0.001) of the variance in walking activity. Self-efficacy (ΔR2 = 0.15, p<0.001) and the interaction between the FGA*ABC (ΔR2 = 0.047, p<0.001) significantly increased the variability explained. FGA (β=0.37, p=0.01), MCIR (β=−0.26, p=0.01), and Walk 12 (β=−0.45, p=0.00) were each individually significantly associated with walking activity. Discussion/Conclusion While measures of walking capacity and self-efficacy significantly contributed to "real-world" walking activity, balance self-efficacy moderated the relationship between walking capacity and walking activity. Improving low balance self-efficacy may augment walking capacity and translate to improved walking activity post-stroke. PMID:27548750

Treating personality-relationship transactions with respect: narrow facets, advanced models, and extended time frames.

PubMed

Mund, Marcus; Neyer, Franz J

2014-08-01

Contrary to premises of dynamic transactionism, most studies investigating personality-relationship transaction only found personality effects on relationships but failed to find effects of relationship experiences on personality development. The current study reconsiders this issue in 3 ways. First, alongside the broad Big Five characteristics (Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness), specific personality facets were considered to make comparisons with relationships more symmetric. Second, a recent extension of latent change modeling was applied allowing for a theoretically more appropriate model that compensates for the shortcomings of traditionally used cross-lagged panel or growth curve models. Third, personality-relationship transaction was studied from young adulthood to midlife using a 15-year longitudinal study with 654 German adults. Results showed patterns of personality-relationship transaction with the romantic partner, friends, kin, and other interaction partners. Specifically, the development of Neuroticism, Agreeableness, and Conscientiousness and their facets was closely interacting with partner and friend relationships, underlining the importance of these relationships for personality maturation during the adult years. We conclude that relationship effects have often been underestimated in previous studies. They are not bound to specific developmental periods, such as emerging adulthood, but their detection depends on the modeling approach and the analysis level (broad dimensions vs. facets). Relationship effects are most likely to occur in relationships that reflect self-selected life styles and circumstances.

Rational design, synthesis, biologic evaluation, and structure-activity relationship studies of novel 1-indanone alpha(1)-adrenoceptor antagonists.

PubMed

Li, Minyong; Xia, Lin

2007-11-01

In the present report, a novel series of 1-indanone alpha(1)-adrenoceptor antagonists were designed and synthesized based on 3D-pharmacophore model. Their in vitro alpha(1)-adrenoceptor antagonistic assay showed that three compounds (2a, 2m, and 2o) had similar or improved alpha(1)-adrenoceptor antagonistic activities relative to the positive control prazosin. Based on these results, a three-dimensional quantitative structure-activity relationship study was performed using a Self-Organizing Molecular Field Analysis method to provide insight for the future development of alpha(1)-adrenoceptor antagonists.

Building Customer Relationships: A Model for Vocational Education and Training Delivery.

ERIC Educational Resources Information Center

Jarratt, Denise G.; Murphy, Tom; Lowry, Diannah

1997-01-01

Review of the theory of relational marketing and interviews with training providers identified a training delivery model that includes elements of trust and commitment, investment by relationship partners, and knowledge exchange, supporting relationship longevity. (SK)

Use of Cell Viability Assay Data Improves the Prediction Accuracy of Conventional Quantitative Structure–Activity Relationship Models of Animal Carcinogenicity

PubMed Central

Zhu, Hao; Rusyn, Ivan; Richard, Ann; Tropsha, Alexander

2008-01-01

Background To develop efficient approaches for rapid evaluation of chemical toxicity and human health risk of environmental compounds, the National Toxicology Program (NTP) in collaboration with the National Center for Chemical Genomics has initiated a project on high-throughput screening (HTS) of environmental chemicals. The first HTS results for a set of 1,408 compounds tested for their effects on cell viability in six different cell lines have recently become available via PubChem. Objectives We have explored these data in terms of their utility for predicting adverse health effects of the environmental agents. Methods and results Initially, the classification k nearest neighbor (kNN) quantitative structure–activity relationship (QSAR) modeling method was applied to the HTS data only, for a curated data set of 384 compounds. The resulting models had prediction accuracies for training, test (containing 275 compounds together), and external validation (109 compounds) sets as high as 89%, 71%, and 74%, respectively. We then asked if HTS results could be of value in predicting rodent carcinogenicity. We identified 383 compounds for which data were available from both the Berkeley Carcinogenic Potency Database and NTP–HTS studies. We found that compounds classified by HTS as “actives” in at least one cell line were likely to be rodent carcinogens (sensitivity 77%); however, HTS “inactives” were far less informative (specificity 46%). Using chemical descriptors only, kNN QSAR modeling resulted in 62.3% prediction accuracy for rodent carcinogenicity applied to this data set. Importantly, the prediction accuracy of the model was significantly improved (72.7%) when chemical descriptors were augmented by HTS data, which were regarded as biological descriptors. Conclusions Our studies suggest that combining NTP–HTS profiles with conventional chemical descriptors could considerably improve the predictive power of computational approaches in toxicology. PMID

Capillary pressure – saturation relationships for gas shales measured using a water activity meter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donnelly, B.; Perfect, E.; McKay, L. D.

Hydraulic fracturing of gas shale formations involves pumping a large volume of fracking fluid into a hydrocarbon reservoir to fracture the rock and thus increase its permeability. The majority of the fracking fluid introduced is never recovered and the fate of this lost fluid, often called “leak off,” has become the source of much debate. Information on the capillary pressure – saturation relationship for each wetting phase is needed to simulate leak off using numerical reservoir models. The petroleum industry commonly employs air – water capillary pressure – saturation curves to predict these relationships for mixed wet reservoirs. Traditional methodsmore » of measuring this curve are unsuitable for gas shales due to high capillary pressures associated with the small pores present. Still, a possible alternative method is the water activity meter which is used widely in the soil sciences for such measurements. However, its application to lithified material has been limited. Here, this study utilized a water activity meter to measure air – water capillary pressures (ranging from 1.3 to 219.6 MPa) at several water saturation levels in both the wetting and drying directions. Water contents were measured gravimetrically. Seven types of gas producing shale with different porosities (2.5–13.6%) and total organic carbon contents (0.4–13.5%) were investigated. Nonlinear regression was used to fit the resulting capillary pressure – water saturation data pairs for each shale type to the Brooks and Corey equation. Data for six of the seven shale types investigated were successfully fitted (median R 2 = 0.93), indicating this may be a viable method for parameterizing capillary pressure – saturation relationships for inclusion in numerical reservoir models. As expected, the different shale types had statistically different Brooks and Corey parameters. However, there were no significant differences between the Brooks and Corey parameters for the wetting

Capillary pressure – saturation relationships for gas shales measured using a water activity meter

DOE PAGES

Donnelly, B.; Perfect, E.; McKay, L. D.; ...

2016-05-10

Hydraulic fracturing of gas shale formations involves pumping a large volume of fracking fluid into a hydrocarbon reservoir to fracture the rock and thus increase its permeability. The majority of the fracking fluid introduced is never recovered and the fate of this lost fluid, often called “leak off,” has become the source of much debate. Information on the capillary pressure – saturation relationship for each wetting phase is needed to simulate leak off using numerical reservoir models. The petroleum industry commonly employs air – water capillary pressure – saturation curves to predict these relationships for mixed wet reservoirs. Traditional methodsmore » of measuring this curve are unsuitable for gas shales due to high capillary pressures associated with the small pores present. Still, a possible alternative method is the water activity meter which is used widely in the soil sciences for such measurements. However, its application to lithified material has been limited. Here, this study utilized a water activity meter to measure air – water capillary pressures (ranging from 1.3 to 219.6 MPa) at several water saturation levels in both the wetting and drying directions. Water contents were measured gravimetrically. Seven types of gas producing shale with different porosities (2.5–13.6%) and total organic carbon contents (0.4–13.5%) were investigated. Nonlinear regression was used to fit the resulting capillary pressure – water saturation data pairs for each shale type to the Brooks and Corey equation. Data for six of the seven shale types investigated were successfully fitted (median R 2 = 0.93), indicating this may be a viable method for parameterizing capillary pressure – saturation relationships for inclusion in numerical reservoir models. As expected, the different shale types had statistically different Brooks and Corey parameters. However, there were no significant differences between the Brooks and Corey parameters for the wetting

Rapid Scanning Structure-Activity Relationships in Combinatorial Data Sets: Identification of Activity Switches

PubMed Central

Medina-Franco, José L.; Edwards, Bruce S.; Pinilla, Clemencia; Appel, Jon R.; Giulianotti, Marc A.; Santos, Radleigh G.; Yongye, Austin B.; Sklar, Larry A.; Houghten, Richard A.

2013-01-01

We present a general approach to describe the structure-activity relationships (SAR) of combinatorial data sets with activity for two biological endpoints with emphasis on the rapid identification of substitutions that have a large impact on activity and selectivity. The approach uses Dual-Activity Difference (DAD) maps that represent a visual and quantitative analysis of all pairwise comparisons of one, two, or more substitutions around a molecular template. Scanning the SAR of data sets using DAD maps allows the visual and quantitative identification of activity switches defined as specific substitutions that have an opposite effect on the activity of the compounds against two targets. The approach also rapidly identifies single- and double-target R-cliffs, i.e., compounds where a single or double substitution around the central scaffold dramatically modifies the activity for one or two targets, respectively. The approach introduced in this report can be applied to any analogue series with two biological activity endpoints. To illustrate the approach, we discuss the SAR of 106 pyrrolidine bis-diketopiperazines tested against two formylpeptide receptors obtained from positional scanning deconvolution methods of mixture-based libraries. PMID:23705689

A Model of Female Sexual Desire: Internalized Working Models of Parent-Child Relationships and Sexual Body Self-Representations.

PubMed

Cherkasskaya, Eugenia; Rosario, Margaret

2017-11-01

The etiology of low female sexual desire, the most prevalent sexual complaint in women, is multi-determined, implicating biological and psychological factors, including women's early parent-child relationships and bodily self-representations. The current study evaluated a model that hypothesized that sexual body self-representations (sexual subjectivity, self-objectification, genital self-image) explain (i.e., mediate) the relation between internalized working models of parent-child relationships (attachment, separation-individuation, parental identification) and sexual desire in heterosexual women. We recruited 614 young, heterosexual women (M = 25.5 years, SD = 4.63) through social media. The women completed an online survey. Structural equation modeling was used. The hypotheses were supported in that the relation between internalized working models of parent-child relationships (attachment and separation-individuation) and sexual desire was mediated by sexual body self-representations (sexual body esteem, self-objectification, genital self-image). However, parental identification was not related significantly to sexual body self-representations or sexual desire in the model. Current findings demonstrated that understanding female sexual desire necessitates considering women's internalized working models of early parent-child relationships and their experiences of their bodies in a sexual context. Treatment of low or absent desire in women would benefit from modalities that emphasize early parent-child relationships as well as interventions that foster mind-body integration.

Risk models of dating aggression across different adolescent relationships: a developmental psychopathology approach.

PubMed

Williams, Tricia S; Connolly, Jennifer; Pepler, Debra; Craig, Wendy; Laporte, Lise

2008-08-01

The present study examined physical dating aggression in different adolescent relationships and assessed linear, threshold, and moderator risk models for recurrent aggressive relationships. The 621 participants (59% girls, 41% boys) were drawn from a 1-year longitudinal survey of Canadian high school youths ranging from Grade 9 through Grade 12. Approximately 13% of participants reported recurrent dating aggression across 2 different relationships. Using peer and dyadic risk factors from Time 1 of the study, the authors confirmed a linear risk model, such that adolescents in 2 different violent relationships had significantly more contextual risk factors than did adolescents in 1 or no violent relationship. Further, structural equation modeling assessing moderation of contextual risk factors indicated that, for adolescents with high acceptance of dating aggression, peer aggression and delinquency significantly predicted recurrent aggression in a new relationship. In comparison, for adolescents with low acceptance of dating aggression, negative relationship characteristics significantly predicted recurrent aggression. Acceptance did not moderate concurrent associations between risk factors and aggression in 1 relationship. Results support a developmental psychopathological approach to the understanding of recurrent aggression and its associated risk factors. Copyright 2008 APA, all rights reserved.

Moderators, mediators, and bidirectional relationships in the International Classification of Functioning, Disability and Health (ICF) framework: An empirical investigation using a longitudinal design and Structural Equation Modeling (SEM).

PubMed

Rouquette, Alexandra; Badley, Elizabeth M; Falissard, Bruno; Dub, Timothée; Leplege, Alain; Coste, Joël

2015-06-01

The International Classification of Functioning, Disability and Health (ICF) published in 2001 describes the consequences of health conditions with three components of impairments in body structures or functions, activity limitations and participation restrictions. Two of the new features of the conceptual model were the possibility of feedback effects between each ICF component and the introduction of contextual factors conceptualized as moderators of the relationship between the components. The aim of this longitudinal study is to provide empirical evidence of these two kinds of effect. Structural equation modeling was used to analyze data from a French population-based cohort of 548 patients with knee osteoarthritis recruited between April 2007 and March 2009 and followed for three years. Indicators of the body structure and function, activity and participation components of the ICF were derived from self-administered standardized instruments. The measurement model revealed four separate factors for body structures impairments, body functions impairments, activity limitations and participation restrictions. The classic sequence from body impairments to participation restrictions through activity limitations was found at each assessment time. Longitudinal study of the ICF component relationships showed a feedback pathway indicating that the level of participation restrictions at baseline was predictive of activity limitations three years later. Finally, the moderating role of personal (age, sex, mental health, etc.) and environmental factors (family relationships, mobility device use, etc.) was investigated. Three contextual factors (sex, family relationships and walking stick use) were found to be moderators for the relationship between the body impairments and the activity limitations components. Mental health was found to be a mediating factor of the effect of activity limitations on participation restrictions. Copyright © 2015 Elsevier Ltd. All rights

Network Modeling Reveals Prevalent Negative Regulatory Relationships between Signaling Sectors in Arabidopsis Immune Signaling

PubMed Central

Sato, Masanao; Tsuda, Kenichi; Wang, Lin; Coller, John; Watanabe, Yuichiro; Glazebrook, Jane; Katagiri, Fumiaki

2010-01-01

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

Relationship of plasma nonesterified fatty acids and walking activity in postpartum dairy cows.

PubMed

Adewuyi, A A; Roelofs, J B; Gruys, E; Toussaint, M J M; van Eerdenburg, F J C M

2006-08-01

To survive and produce milk, postpartum dairy cows use their reserves through lipolysis. If the negative energy balance is severe, nonesterified fatty acids (NEFA) are formed that can impair several physiological processes. A pilot study suggested that increased walking activity after calving may be related to a reduced serum concentration of NEFA. The objective of this study was to determine the relationship between plasma concentrations of NEFA and walking activity in dairy cattle during the postpartum period. Data were collected from 33 multiparous Holstein-Friesian dairy cows. Walking activities were quantified using pedometry, and blood samples were collected for determination of NEFA. Results of this study indicated that a negative relationship existed between walking activity and plasma NEFA concentrations in postpartum dairy cows.

Structural similarity based kriging for quantitative structure activity and property relationship modeling.

PubMed

Teixeira, Ana L; Falcao, Andre O

2014-07-28

Structurally similar molecules tend to have similar properties, i.e. closer molecules in the molecular space are more likely to yield similar property values while distant molecules are more likely to yield different values. Based on this principle, we propose the use of a new method that takes into account the high dimensionality of the molecular space, predicting chemical, physical, or biological properties based on the most similar compounds with measured properties. This methodology uses ordinary kriging coupled with three different molecular similarity approaches (based on molecular descriptors, fingerprints, and atom matching) which creates an interpolation map over the molecular space that is capable of predicting properties/activities for diverse chemical data sets. The proposed method was tested in two data sets of diverse chemical compounds collected from the literature and preprocessed. One of the data sets contained dihydrofolate reductase inhibition activity data, and the second molecules for which aqueous solubility was known. The overall predictive results using kriging for both data sets comply with the results obtained in the literature using typical QSPR/QSAR approaches. However, the procedure did not involve any type of descriptor selection or even minimal information about each problem, suggesting that this approach is directly applicable to a large spectrum of problems in QSAR/QSPR. Furthermore, the predictive results improve significantly with the similarity threshold between the training and testing compounds, allowing the definition of a confidence threshold of similarity and error estimation for each case inferred. The use of kriging for interpolation over the molecular metric space is independent of the training data set size, and no reparametrizations are necessary when more compounds are added or removed from the set, and increasing the size of the database will consequentially improve the quality of the estimations. Finally it is shown

Do changes in neuromuscular activation contribute to the knee extensor angle-torque relationship?

PubMed

Lanza, Marcel B; Balshaw, Thomas G; Folland, Jonathan P

2017-08-01

What is the central question of the study? Do changes in neuromuscular activation contribute to the knee extensor angle-torque relationship? What is the main finding and its importance? Both agonist (quadriceps) and antagonist coactivation (hamstrings) differed with knee joint angle during maximal isometric knee extensions and thus both are likely to contribute to the angle-torque relationship. Specifically, two independent measurement techniques showed quadriceps activation to be lower at more extended positions. These effects might influence the capacity for neural changes in response to training and rehabilitation at different knee joint angles. The influence of joint angle on knee extensor neuromuscular activation is unclear, owing in part to the diversity of surface electromyography (sEMG) and/or interpolated twitch technique (ITT) methods used. The aim of the study was to compare neuromuscular activation, using rigorous contemporary sEMG and ITT procedures, during isometric maximal voluntary contractions (iMVCs) of the quadriceps femoris at different knee joint angles and examine whether activation contributes to the angle-torque relationship. Sixteen healthy active men completed two familiarization sessions and two experimental sessions of isometric knee extension and knee flexion contractions. The experimental sessions included the following at each of four joint angles (25, 50, 80 and 106 deg): iMVCs (with and without superimposed evoked doublets); submaximal contractions with superimposed doublets; and evoked twitch and doublet contractions whilst voluntarily passive, and knee flexion iMVC at the same knee joint positions. The absolute quadriceps femoris EMG was normalized to the peak-to-peak amplitude of an evoked maximal M-wave, and the doublet-voluntary torque relationship was used to calculate activation with the ITT. Agonist activation, assessed with both normalized EMG and the ITT, was reduced at the more extended compared with the more flexed

Influence of lipophilicity in O-acyl and O-alkyl derivatives of juglone and lawsone: a structure-activity relationship study in the search for natural herbicide models.

PubMed

Durán, Alexandra G; Chinchilla, Nuria; Molinillo, José Mg; Macías, Francisco A

2018-03-01

Naphthoquinones are known for their broad range of biological activities. Given the increasing demands of consumers in relation to food quality and growing concerns about the impact of synthetic herbicides, it is necessary to search for new agrochemicals. Natural products and allelopathy provide new alternatives for the development of pesticides with lower toxicity and greater environmental compatibility. A structure-activity relationship to evaluate the effect of bioavailability was performed. A total of 44 O-acyl and O-alkyl derivatives of juglone and lawsone with different linear chain lengths were prepared. These compounds were tested on etiolated wheat coleoptiles, standard target species (STS) and four weeds, Echinochloa crus-galli L., Lolium rigidum Gaud., Lolium perenne L. and Avena fatua L. The results showed a strong influence of lipophilicity and, in most cases, the data fitted a logP-dependent quadratic mathematical model. The effects produced were mostly stunting and necrosis caused by growth inhibition. The potential structure and activity behaviour is described. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

The Stress-Metabolic Syndrome Relationship in Adolescents: An Examination of the Moderating Potential of Physical Activity.

PubMed

Holmes, Megan E; Pivarnik, Jim; Pfeiffer, Karin; Maier, Kimberly S; Eisenmann, Joey C; Ewing, Martha

2016-10-01

The role of psychosocial stress in the development of obesity and metabolic syndrome is receiving increased attention and has led to examination of whether physical activity may moderate the stress-metabolic syndrome relationship. The current study examined relationships among physical activity, stress, and metabolic syndrome in adolescents. Participants (N = 126; 57 girls, 69 boys) were assessed for anthropometry, psychosocial stress, physical activity, and metabolic syndrome variables; t tests were used to examine sex differences, and regression analysis was used to assess relationships among variables controlling for sex and maturity status. Mean body mass index approached the 75th percentile for both sexes. Typical sex differences were observed for systolic blood pressure, time spent in moderate and vigorous physical activity, and perceived stress. Although stress was not associated with MetS (β = -.001, P = .82), a modest, positive relationship was observed with BMI (β = .20, P = .04). Strong relationships between physical activity and stress with MetS or BMI were not found in this sample. Results may be partially explained by overall good physical health status of the participants. Additional research in groups exhibiting varying degrees of health is needed.

Complementary models of tree species-soil relationships in old-growth temperate forests

USGS Publications Warehouse

Cross, Alison; Perakis, Steven S.

2011-01-01

Ecosystem level studies identify plant soil feed backs as important controls on soil nutrient availability,particularly for nitrogen and phosphorus. Although site and species specific studies of tree species soil relationships are relatively common,comparatively fewer studies consider multiple coexisting speciesin old-growth forests across a range of sites that vary underlying soil fertility. We characterized patterns in forest floor and mineral soil nutrients associated with four common tree species across eight undisturbed old-growth forests in Oregon, USA, and used two complementary conceptual models to assess tree species soil relationships. Plant soil feedbacks that could reinforce sitelevel differences in nutrient availability were assessed using the context dependent relationships model, where by relative species based differences in each soil nutrient divergedorconvergedas nutrient status changed across sites. Tree species soil relationships that did not reflect strong feedbacks were evaluated using a site independent relationships model, where by forest floor and surface mineral soil nutrient tools differed consistently by tree species across sites,without variation in deeper mineral soils. We found that theorganically cycled elements carbon, nitrogen, and phosphorus exhibited context-dependent differences among species in both forest floor and mineral soil, and most of ten followed adivergence model,where by species differences were greatest at high-nutrient sites. These patterns are consistent with the oryemphasizing biotic control of these elements through plant soil feedback mechanisms. Site independent species differences were strongest for pool so if the weather able cations calcium, magnesium, potassium,as well as phosphorus, in mineral soils. Site independent species differences in forest floor nutrients we reattributable too nespecies that displayed significant greater forest floor mass accumulation. Our finding confirmed that site-independent and

A DOUBLE-RING ALGORITHM FOR MODELING SOLAR ACTIVE REGIONS: UNIFYING KINEMATIC DYNAMO MODELS AND SURFACE FLUX-TRANSPORT SIMULATIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Munoz-Jaramillo, Andres; Martens, Petrus C. H.; Nandy, Dibyendu

The emergence of tilted bipolar active regions (ARs) and the dispersal of their flux, mediated via processes such as diffusion, differential rotation, and meridional circulation, is believed to be responsible for the reversal of the Sun's polar field. This process (commonly known as the Babcock-Leighton mechanism) is usually modeled as a near-surface, spatially distributed {alpha}-effect in kinematic mean-field dynamo models. However, this formulation leads to a relationship between polar field strength and meridional flow speed which is opposite to that suggested by physical insight and predicted by surface flux-transport simulations. With this in mind, we present an improved double-ring algorithmmore » for modeling the Babcock-Leighton mechanism based on AR eruption, within the framework of an axisymmetric dynamo model. Using surface flux-transport simulations, we first show that an axisymmetric formulation-which is usually invoked in kinematic dynamo models-can reasonably approximate the surface flux dynamics. Finally, we demonstrate that our treatment of the Babcock-Leighton mechanism through double-ring eruption leads to an inverse relationship between polar field strength and meridional flow speed as expected, reconciling the discrepancy between surface flux-transport simulations and kinematic dynamo models.« less

Prospective relationships of physical activity with quality of life among colorectal cancer survivors

USDA-ARS?s Scientific Manuscript database

Physical activity can enhance quality of life for cancer survivors. However, few longitudinal studies have examined whether physical activity has a sustained effect on improvements in quality of life. The present study aims to examine the relationships between physical activity and quality of life o...

The Relationships between Weather-Related Factors and Daily Outdoor Physical Activity Counts on an Urban Greenway

PubMed Central

Wolff, Dana; Fitzhugh, Eugene C.

2011-01-01

The purpose of this study was to examine relationships between weather and outdoor physical activity (PA). An online weather source was used to obtain daily max temperature [DMT], precipitation, and wind speed. An infra-red trail counter provided data on daily trail use along a greenway, over a 2-year period. Multiple regression analysis was used to examine associations between PA and weather, while controlling for day of the week and month of the year. The overall regression model explained 77.0% of the variance in daily PA (p < 0.001). DMT (b = 10.5), max temp-squared (b = −4.0), precipitation (b = −70.0), and max wind speed (b = 1.9) contributed significantly. Conclusion: Aggregated daily data can detect relationships between weather and outdoor PA. PMID:21556205

[Spectrum-effect Relationship Between Total Antioxidant Activity and HPLC Fingerprint of Arctium lappa Root].

PubMed

Wang, Xiao-juan; Jiang, Lin

2014-12-01

To explore the spectrum-effect relationship between the HPLC fingerprint of Arctium lappa root methanol extract and the total antioxidant activity. The experiment was carried out with Gemini C18 110A (250 mm x 4.6 mm, 5 µm) column using methanol-0.04% phosphoric acid as gradient mobile phase at the flow rate of 1.0 mL/min, detection wavelength of 320 nm. The total antioxidant activity was determined by measuring the absorbance of each sample after being reacted with ammonium molybdate reagent. The spectrum-effect relationship was investigated using canonical correlation analysis (CCA). The spectrum-effect relationship between the HPLC fingerprint of Arctium lappa root methanol extract and the total antioxidant activity were established, the similarity of fingerprint of all samples was above 0.9. Peaks 1, 6, 9, 12 and 14 were principle components of Arctium lappa root for the total antioxidant activity. This method contributes to the fast comprehensive evaluation of quality of Arctium lappa root.

Testing a healthcare provider-patient communicative relationship quality model of pharmaceutical care in hospitals.

PubMed

Wang, Dan; Liu, Chenxi; Zhang, Zinan; Ye, Liping; Zhang, Xinping

2018-06-01

Background Patient-centeredness and participatory care is increasingly regarded as a proxy for high-quality interpersonal care. Considering the development of patient-centeredness and participatory care relationship model in pharmacist-patient domain, it is of great significance to explore the mechanism of how pharmacist and patient participative behaviors influence relationship quality and patient outcomes. Objective To validate pharmacist-patient relationship quality model in Chinese hospitals. Four tertiary hospitals in 2017. Methods The provision of pharmaceutical care was investigated. A cross-sectional questionnaire survey covering different constructs of communicative relationship quality model was conducted and the associations among pairs of the study constructs were explored. Based on the results of confirmatory factor analysis, path analysis was conducted to validate the proposed communicative relationship quality model. Main outcome measure Model fit indicators including Tucker-Lewis index (TLI), comparative fit index (CFI), root mean square error of approximation (RMSEA) and weighted root mean square residual(WRMR). Results There were 589 patients included in our study. The final path model had an excellent fit (TLI = 0.98, CFI = 0.98, RMSEA = 0.05; WRMR = 1.06). HCP participative behavior/patient-centeredness (β = 0.79, p < 0.001) and interpersonal communication (β = 0.13, p < 0.001) directly impact the communicative relationship quality. But patient participative behavior was not a predictor of either communicative relationship quality or patient satisfaction. Conclusion HCP participative behavior/patient-centeredness and interpersonal communication are positively related to relationship quality, and relationship quality is mediator between HCP participative behavior and interpersonal communication with patient satisfaction.

Cytotoxic and antifungal activities of melleolide antibiotics follow dissimilar structure-activity relationships.

PubMed

Bohnert, Markus; Nützmann, Hans-Wilhelm; Schroeckh, Volker; Horn, Fabian; Dahse, Hans-Martin; Brakhage, Axel A; Hoffmeister, Dirk

2014-09-01

The fungal genus Armillaria is unique in that it is the only natural source of melleolide antibiotics, i.e., protoilludene alcohols esterified with orsellinic acid or its derivatives. This class of natural products is known to exert antimicrobial and cytotoxic effects. Here, we present a refined relationship between the structure and the antimicrobial activity of the melleolides. Using both agar diffusion and broth dilution assays, we identified the Δ(2,4)-double bond of the protoilludene moiety as a key structural feature for antifungal activity against Aspergillus nidulans, Aspergillus flavus, and Penicillium notatum. These findings contrast former reports on cytotoxic activities and may indicate a different mode of action towards susceptible fungi. We also report the isolation and structure elucidation of five melleolides (6'-dechloroarnamial, 6'-chloromelleolide F, 10-hydroxy-5'-methoxy-6'-chloroarmillane, and 13-deoxyarmellides A and B), along with the finding that treatment with an antifungal melleolide impacts transcription of A. nidulans natural product genes. Copyright © 2014 Elsevier Ltd. All rights reserved.

2D- and 3D-quantitative structure-activity relationship studies for a series of phenazine N,N'-dioxide as antitumour agents.

PubMed

Cunha, Jonathan Da; Lavaggi, María Laura; Abasolo, María Inés; Cerecetto, Hugo; González, Mercedes

2011-12-01

Hypoxic regions of tumours are associated with increased resistance to radiation and chemotherapy. Nevertheless, hypoxia has been used as a tool for specific activation of some antitumour prodrugs, named bioreductive agents. Phenazine dioxides are an example of such bioreductive prodrugs. Our 2D-quantitative structure activity relationship studies established that phenazine dioxides electronic and lipophilic descriptors are related to survival fraction in oxia or in hypoxia. Additionally, statistically significant models, derived by partial least squares, were obtained between survival fraction in oxia and comparative molecular field analysis standard model (r² = 0.755, q² = 0.505 and F = 26.70) or comparative molecular similarity indices analysis-combined steric and electrostatic fields (r² = 0.757, q² = 0.527 and F = 14.93), and survival fraction in hypoxia and comparative molecular field analysis standard model (r² = 0.736, q² = 0.521 and F = 18.63) or comparative molecular similarity indices analysis-hydrogen bond acceptor field (r² = 0.858, q² = 0.737 and F = 27.19). Categorical classification was used for the biological parameter selective cytotoxicity emerging also good models, derived by soft independent modelling of class analogy, with both comparative molecular field analysis standard model (96% of overall classification accuracy) and comparative molecular similarity indices analysis-steric field (92% of overall classification accuracy). 2D- and 3D-quantitative structure-activity relationships models provided important insights into the chemical and structural basis involved in the molecular recognition process of these phenazines as bioreductive agents and should be useful for the design of new structurally related analogues with improved potency. © 2011 John Wiley & Sons A/S.

Species-environment relationships and potential for distribution modelling in coastal waters

NASA Astrophysics Data System (ADS)

Snickars, M.; Gullström, M.; Sundblad, G.; Bergström, U.; Downie, A.-L.; Lindegarth, M.; Mattila, J.

2014-01-01

Due to increasing pressure on the marine environment there is a growing need to understand species-environment relationships. To provide background for prioritising among variables (predictors) for use in distribution models, the relevance of predictors for benthic species was reviewed using the coastal Baltic Sea as a case-study area. Significant relationships for three response groups (fish, macroinvertebrates, macrovegetation) and six predictor categories (bottom topography, biotic features, hydrography, wave exposure, substrate and spatiotemporal variability) were extracted from 145 queried peer-reviewed field-studies covering three decades and six subregions. In addition, the occurrence of interaction among predictors was analysed. Hydrography was most often found in significant relationships, had low level of interaction with other predictors, but also had the most non-significant relationships. Depth and wave exposure were important in all subregions and are readily available, increasing their applicability for cross-regional modelling efforts. Otherwise, effort to model species distributions may prove challenging at larger scale as the relevance of predictors differed among both response groups and regions. Fish and hard bottom macrovegetation have the largest modelling potential, as they are structured by a set of predictors that at the same time are accurately mapped. A general importance of biotic features implies that these need to be accounted for in distribution modelling, but the mapping of most biotic features is challenging, which currently lowers the applicability. The presence of interactions suggests that predictive methods allowing for interactive effects are preferable. Detailing these complexities is important for future distribution modelling.

Predicting Monoamine Oxidase Inhibitory Activity through Ligand-Based Models

PubMed Central

Vilar, Santiago; Ferino, Giulio; Quezada, Elias; Santana, Lourdes; Friedman, Carol

2013-01-01

The evolution of bio- and cheminformatics associated with the development of specialized software and increasing computer power has produced a great interest in theoretical in silico methods applied in drug rational design. These techniques apply the concept that “similar molecules have similar biological properties” that has been exploited in Medicinal Chemistry for years to design new molecules with desirable pharmacological profiles. Ligand-based methods are not dependent on receptor structural data and take into account two and three-dimensional molecular properties to assess similarity of new compounds in regards to the set of molecules with the biological property under study. Depending on the complexity of the calculation, there are different types of ligand-based methods, such as QSAR (Quantitative Structure-Activity Relationship) with 2D and 3D descriptors, CoMFA (Comparative Molecular Field Analysis) or pharmacophoric approaches. This work provides a description of a series of ligand-based models applied in the prediction of the inhibitory activity of monoamine oxidase (MAO) enzymes. The controlled regulation of the enzymes’ function through the use of MAO inhibitors is used as a treatment in many psychiatric and neurological disorders, such as depression, anxiety, Alzheimer’s and Parkinson’s disease. For this reason, multiple scaffolds, such as substituted coumarins, indolylmethylamine or pyridazine derivatives were synthesized and assayed toward MAO-A and MAO-B inhibition. Our intention is to focus on the description of ligand-based models to provide new insights in the relationship between the MAO inhibitory activity and the molecular structure of the different inhibitors, and further study enzyme selectivity and possible mechanisms of action. PMID:23231398

Inverse relationship between physical activity and arterial stiffness in adults with hypertension.

PubMed

O'Donovan, Cuisle; Lithander, Fiona E; Raftery, Tara; Gormley, John; Mahmud, Azra; Hussey, Juliette

2014-02-01

Physical activity has beneficial effects on arterial stiffness among healthy adults. There is a lack of data on this relationship in adults with hypertension. The majority of studies which have examined physical activity and arterial stiffness have used subjective measures of activity. The aim of this study was to investigate the relationship between objectively measured habitual physical activity and arterial stiffness in individuals with newly diagnosed essential hypertension. Adults attending an outpatient hypertension clinic were recruited into this cross sectional study. Physical activity was measured using a triaxial accelerometer. Pulse wave velocity (PWV) and augmentation index (AIx) were measured using applanation tonometry. Participant's full lipid profile and glucose were determined through the collection of a fasting blood sample. Fifty-three adults [51(14) years, 26 male] participated, 16 of whom had the metabolic syndrome. Inactivity was positively correlated with PWV (r = .53, P < .001) and AIx (r = .48, P < .001). There were significant inverse associations between habitual physical activity of all intensities and both AIx and PWV. In stepwise regression, after adjusting for potential confounders, physical activity was a significant predictor of AIx and PWV. Habitual physical activity of all intensities is associated with reduced arterial stiffness among adults with hypertension.

The relationship between social capital and the way of spending leisure time, based on physical activities

PubMed Central

Karimian, Jahangir; Hosseini, Taghi Agha; Shekarchizadeh, Parivash; Nafchi, Sayed Morteza Mousavi

2015-01-01

Background: Today, social capital is a need in the society. Also, leisure time and physical activities are among the most important productive sources of social capital, which have been realized recently. This study aims to find the relationship between social capital and physical leisure time of the faculty members of Isfahan University of Medical Sciences. Materials and Methods: A descriptive correlation method was used in this study. Two questionnaires were used for data collection. Social capital questionnaire is based on SCAT Model. Also, leisure time questionnaire was made by the researcher for which face and content validity was verified by experts. Reliability coefficients by using Cronbach's alpha coefficients were calculated as 0.92 and 0.82, respectively. Sample population was calculated by Cochran's formula, and 150 people were selected as the sample using multiple cluster sampling by taking the sex and college into consideration as the variables. Findings: According to the findings, there was a direct relationship between a combination of social capital parameters (including commitment, attitude, trust, participation, mutual relationship, social norm, and unity) and the way of spending physical leisure time (R = 0.659, P = 0.000). Among the parameters, “commitment” was significant with a beta coefficient B = 0.293 and P = 0.044 and social norms was significant with a beta coefficient B = 0.196 and P = 0.047, but the rest of the factors were not significant. Conclusion: Playing sport and doing physical activities in the leisure time and also taking part in group activities and their membership provide a situation for people to respect the group interests through communication. Such activities can cause the level of social capital and its factors to be increased. PMID:27462621

Synthesis, antimicrobial activity and advances in structure-activity relationships (SARs) of novel tri-substituted thiazole derivatives.

PubMed

Reddy, Guda Mallikarjuna; Garcia, Jarem Raul; Reddy, Vemulapati Hanuman; de Andrade, Ageo Meier; Camilo, Alexandre; Pontes Ribeiro, Renan Augusto; de Lazaro, Sergio Ricardo

2016-11-10

Trisubstituted thiazoles were synthesized and studied for their antimicrobial activity and supported by theoretical calculations. In addition, MIC, MBC and MFC were also tested. Moreover, the present study was analyzed to scrutinize comprehensive structure-activity relationships. In fact, LUMO orbital energy and orbital orientation was reliable to explain their antibacterial and antifungal assay. Amongst the tested compounds, tri-methyl-substituted thiazole compound showed higher antimicrobial activity and low MIC value due to highest LUMO energy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Physical activity and calorie intake mediate the relationship from depression to body fat mass among female Mexican health workers.

PubMed

Quezada, Amado D; Macías-Waldman, Nayeli; Salmerón, Jorge; Swigart, Tessa; Gallegos-Carrillo, Katia

2017-11-17

Depression is a foremost cause of morbidity throughout the world and the prevalence of depression in women is about twice as high as men. Additionally, overweight and obesity are major global health concerns. We explored the relationship between depression and body fat, and the role of physical activity and diet as mediators of this relationship in a sample of 456 adult female Mexican health workers. Longitudinal and cross-sectional analyses using data from adult women of the Health Workers Cohort Study (HWCS) Measures of body fat mass (kg from DEXA), dietary intake (kcal from FFQ), leisure time activity (METs/wk) and depression (CES-D) were determined in two waves (2004-2006 and 2010-2011). We explored the interrelation between body fat, diet, leisure time, physical activity, and depression using a cross-lagged effects model fitted to longitudinal data. We also fitted a structural equations model to cross-sectional data with body fat as the main outcome, and dietary intake and physical activity from leisure time as mediators between depression and body fat. Baseline depression was significantly related to higher depression, higher calorie intake, and lower leisure time physical activity at follow-up. From our cross-sectional model, each standard deviation increase in the depression score was associated with an average increase of 751 ± 259 g (± standard error) in body fat through the mediating effects of calorie intake and physical activity. The results of this study show how depression may influence energy imbalance between calories consumed and calories expended, resulting in higher body fat among those with a greater depression score. Evaluating the role of mental conditions like depression in dietary and physical activity behaviors should be positioned as a key research goal for better designed and targeted public health interventions. The HealthWorkers Cohort Study (HWCS) has been approved by the Institutional IRB. Number: 2005-785-012.

Relationship between fundamental motor skills and physical activity in 4-year-old preschool children.

PubMed

Iivonen, K S; Sääkslahti, A K; Mehtälä, A; Villberg, J J; Tammelin, T H; Kulmala, J S; Poskiparta, M

2013-10-01

This study evaluated the relationships between objectively measured physical activity and fundamental motor skills in 4-year-old children. Physical activity was monitored in 20 girls and 17 boys over 5 consecutive days (3 days at preschool and 2 days at home) and their fundamental motor skills measured. Multiple linear regressions controlled for sex, age, and body mass index indicated that the total skill score was significantly associated with physical activity, explaining 13%, 16%, and 16% of the variance in total, moderate-to-vigorous, and light-to-vigorous physical activity, respectively. Sliding and galloping were significantly associated with moderate-to-vigorous physical activity, and throwing and catching combination was significantly associated with total, moderate-to-vigorous, and light-to-vigorous physical activity. The findings warrant future investigations with larger samples to examine the relationship between locomotor, manipulative skills, and physical activity behaviors.

Constitutive Relationships and Models in Continuum Theories of Multiphase Flows. [conferences

NASA Technical Reports Server (NTRS)

Decker, Rand (Editor)

1989-01-01

In April, 1989, a workshop on constitutive relationships and models in continuum theories of multiphase flows was held at NASA's Marshall Space Flight Center. Topics of constitutive relationships for the partial or per phase stresses, including the concept of solid phase pressure are discussed. Models used for the exchange of mass, momentum, and energy between the phases in a multiphase flow are also discussed. The program, abstracts, and texts of the presentations from the workshop are included.

A complex speciation–richness relationship in a simple neutral model

PubMed Central

Desjardins-Proulx, Philippe; Gravel, Dominique

2012-01-01

Speciation is the “elephant in the room” of community ecology. As the ultimate source of biodiversity, its integration in ecology's theoretical corpus is necessary to understand community assembly. Yet, speciation is often completely ignored or stripped of its spatial dimension. Recent approaches based on network theory have allowed ecologists to effectively model complex landscapes. In this study, we use this framework to model allopatric and parapatric speciation in networks of communities. We focus on the relationship between speciation, richness, and the spatial structure of communities. We find a strong opposition between speciation and local richness, with speciation being more common in isolated communities and local richness being higher in more connected communities. Unlike previous models, we also find a transition to a positive relationship between speciation and local richness when dispersal is low and the number of communities is small. We use several measures of centrality to characterize the effect of network structure on diversity. The degree, the simplest measure of centrality, is the best predictor of local richness and speciation, although it loses some of its predictive power as connectivity grows. Our framework shows how a simple neutral model can be combined with network theory to reveal complex relationships between speciation, richness, and the spatial organization of populations. PMID:22957181