Oxygen measurement by multimode diode lasers employing gas correlation spectroscopy.

PubMed

Lou, Xiutao; Somesfalean, Gabriel; Chen, Bin; Zhang, Zhiguo

2009-02-10

Multimode diode laser (MDL)-based correlation spectroscopy (COSPEC) was used to measure oxygen in ambient air, thereby employing a diode laser (DL) having an emission spectrum that overlaps the oxygen absorption lines of the A band. A sensitivity of 700 ppm m was achieved with good accuracy (2%) and linearity (R(2)=0.999). For comparison, measurements of ambient oxygen were also performed by tunable DL absorption spectroscopy (TDLAS) technique employing a vertical cavity surface emitting laser. We demonstrate that, despite slightly degraded sensitivity, the MDL-based COSPEC-based oxygen sensor has the advantages of high stability, low cost, ease-of-use, and relaxed requirements in component selection and instrument buildup compared with the TDLAS-based instrument.

The effect of 7, 8-methylenedioxylycoctonine-type diterpenoid alkaloids on the toxicity of tall larkspur (Delphinium spp.) in cattle.

PubMed

Welch, K D; Green, B T; Gardner, D R; Cook, D; Pfister, J A; Panter, K E

2012-07-01

Delphinium spp. contain numerous norditerpenoid alkaloids which are structurally delineated as 7, 8-methylenedioxylycoctonine (MDL) and N-(methylsuccinimido) anthranoyllycoctonine (MSAL)-type alkaloids. The toxicity of many tall larkspur species has been primarily attributed to their increased concentration of MSAL-type alkaloids, such as methyllycaconitine (MLA), which are typically 20 times more toxic than MDL-type alkaloids. However, the less toxic MDL-type alkaloids are often more abundant than MSAL-type alkaloids in most Delphinium barbeyi and Delphinium occidentale populations. Previous research demonstrated that MDL-type alkaloids increase the acute toxicity of MSAL-type alkaloids. In this study, we examined the role of MDL-type alkaloids on the overall toxicity of tall larkspur plants to cattle while controlling for the exact dose of MSAL-type alkaloids. Cattle were dosed with plant material from 2 different populations of tall larkspur containing either almost exclusively MDL- or MSAL-type alkaloids. These 2 plant populations were combined to create mixtures with ratios of 0.3:1, 1:1, 5:1, and 10:1 MDL- to MSAL-type alkaloids. The dose that elicited similar clinical signs of poisoning in mice and cattle was determined for each mixture on the basis of the MSAL-type alkaloid content. As the ratio of MDL- to MSAL-type alkaloids increased, the amount of MSAL-type alkaloids required to elicit clinical signs decreased. These results indicate that the less toxic MDL-type alkaloids in tall larkspur exacerbate the toxicity of the MSAL-type alkaloids. Consequently, both the amount of MSAL-type alkaloids and the amount of total alkaloids should be fully characterized to determine more accurately the relative toxicity of tall larkspur plant material.

Enzyme immunoassay of two nicergoline metabolites, 10 alpha-methoxy-9, 10-dihydrolysergol (MDL) and 1-methyl-10 alpha-methoxy-9, 10-dihydrolysergol (MMDL).

PubMed

Chen, P; Tian, Z; Digenis, G A; Tai, H H

1996-06-01

Specific and sensitive enzyme immunoassays for two nicergoline metabolites, 10 alpha-methoxy-9, 10-dihydrolysergol (MDL) and 1-methyl-10 alpha-methoxy-9, 10-dihydrolysergol (MMDL) have been developed. The hydroxyl group of hydroxymethyl at position 8 of either MDL or MMDL was carboxymethylated to introduce a carboxyl group for protein conjugation. Antibodies generated from O-carboxymethyl MDL or MMDL recognized the spacer arm between the hapten and the carrier protein and the molecular domain near the conjugation site as well. A heterologous bridge strategy was used to improve the affinity of the hapten-enzyme conjugate to the antibodies. The sensitivity of both assays was greatly increased by using such an approach. Both antibodies are specific for their own haptens. Little cross reactivity was observed with nicergoline and other metabolites. Determination of MDL and MMDL from both spiked plasma and urine showed nearly quantitative recovery. Detection of MDL and MMDL can be as sensitive as 10 pg/ml.

40 CFR 721.2582 - Reaction product of alkylene diamine, MDl, substituted carbomonocyclic amine and alkylamine...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Reaction product of alkylene diamine... Reaction product of alkylene diamine, MDl, substituted carbomonocyclic amine and alkylamine (generic). (a... generically as reaction product of alkylene diamine, MDl, substituted carbomonocyclic amine and alkylamine...

40 CFR 721.2582 - Reaction product of alkylene diamine, MDl, substituted carbomonocyclic amine and alkylamine...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Reaction product of alkylene diamine... Reaction product of alkylene diamine, MDl, substituted carbomonocyclic amine and alkylamine (generic). (a... generically as reaction product of alkylene diamine, MDl, substituted carbomonocyclic amine and alkylamine...

Sequential Modelling of Building Rooftops by Integrating Airborne LIDAR Data and Optical Imagery: Preliminary Results

NASA Astrophysics Data System (ADS)

Sohn, G.; Jung, J.; Jwa, Y.; Armenakis, C.

2013-05-01

This paper presents a sequential rooftop modelling method to refine initial rooftop models derived from airborne LiDAR data by integrating it with linear cues retrieved from single imagery. A cue integration between two datasets is facilitated by creating new topological features connecting between the initial model and image lines, with which new model hypotheses (variances to the initial model) are produced. We adopt Minimum Description Length (MDL) principle for competing the model candidates and selecting the optimal model by considering the balanced trade-off between the model closeness and the model complexity. Our preliminary results, combined with the Vaihingen data provided by ISPRS WGIII/4 demonstrate the image-driven modelling cues can compensate the limitations posed by LiDAR data in rooftop modelling.

Patch-Based Generative Shape Model and MDL Model Selection for Statistical Analysis of Archipelagos

NASA Astrophysics Data System (ADS)

Ganz, Melanie; Nielsen, Mads; Brandt, Sami

We propose a statistical generative shape model for archipelago-like structures. These kind of structures occur, for instance, in medical images, where our intention is to model the appearance and shapes of calcifications in x-ray radio graphs. The generative model is constructed by (1) learning a patch-based dictionary for possible shapes, (2) building up a time-homogeneous Markov model to model the neighbourhood correlations between the patches, and (3) automatic selection of the model complexity by the minimum description length principle. The generative shape model is proposed as a probability distribution of a binary image where the model is intended to facilitate sequential simulation. Our results show that a relatively simple model is able to generate structures visually similar to calcifications. Furthermore, we used the shape model as a shape prior in the statistical segmentation of calcifications, where the area overlap with the ground truth shapes improved significantly compared to the case where the prior was not used.

Random forest models to predict aqueous solubility.

PubMed

Palmer, David S; O'Boyle, Noel M; Glen, Robert C; Mitchell, John B O

2007-01-01

Random Forest regression (RF), Partial-Least-Squares (PLS) regression, Support Vector Machines (SVM), and Artificial Neural Networks (ANN) were used to develop QSPR models for the prediction of aqueous solubility, based on experimental data for 988 organic molecules. The Random Forest regression model predicted aqueous solubility more accurately than those created by PLS, SVM, and ANN and offered methods for automatic descriptor selection, an assessment of descriptor importance, and an in-parallel measure of predictive ability, all of which serve to recommend its use. The prediction of log molar solubility for an external test set of 330 molecules that are solid at 25 degrees C gave an r2 = 0.89 and RMSE = 0.69 log S units. For a standard data set selected from the literature, the model performed well with respect to other documented methods. Finally, the diversity of the training and test sets are compared to the chemical space occupied by molecules in the MDL drug data report, on the basis of molecular descriptors selected by the regression analysis.

Assessment of soil-gas contamination at three former fuel-dispensing sites, Fort Gordon, Georgia, 2010—2011

USGS Publications Warehouse

Caldwell, Andral W.; Falls, W. Fred; Guimaraes, Wladmir B.; Ratliff, W. Hagan; Wellborn, John B.; Landmeyer, James E.

2012-01-01

Soil gas was assessed for contaminants at three former fuel-dispensing sites at Fort Gordon, Georgia, from October 2010 to September 2011. The assessment included delineation of organic contaminants using soil-gas samplers collected from the former fuel-dispensing sites at 8th Street, Chamberlain Avenue, and 12th Street. This assessment was conducted to provide environmental contamination data to Fort Gordon personnel pursuant to requirements for the Resource Conservation and Recovery Act Part B Hazardous Waste Permit process. Soil-gas samplers installed and retrieved during June and August 2011 at the 8th Street site had detections above the method detection level (MDL) for the mass of total petroleum hydrocarbons (TPH), benzene, toluene, ortho-xylene, undecane, tridecane, pentadecane, and chloroform. Total petroleum hydrocarbons soil-gas mass exceeded the MDL of 0.02 microgram in 54 of the 55 soil-gas samplers. The highest detection of TPH soil-gas mass was 146.10 micrograms, located in the central part of the site. Benzene mass exceeded the MDL of 0.01 microgram in 23 soil-gas samplers, whereas toluene was detected in only 10 soil-gas samplers. Ortho-xylene was detected above the MDL in only one soil-gas sampler. The highest soil-gas mass detected for undecane, tridecane, and pentadecane was located in the northeastern corner of the 8th Street site. Chloroform mass greater than the MDL of 0.01 microgram was detected in less than one-third of the soil-gas samplers. Soil-gas masses above the MDL were identified for TPH, gasoline-related compounds, diesel-range alkanes, trimethylbenzenes, naphthalene, 2-methyl-napthalene, octane, and tetrachloroethylene for the July 2011 soil-gas survey at the Chamberlain Avenue site. All 30 of the soil-gas samplers contained TPH mass above the MDL. The highest detection of TPH mass, 426.36 micrograms, was for a soil-gas sampler located near the northern boundary of the site. Gasoline-related compounds and diesel-range alkanes were detected in multiple soil-gas samplers, and the highest detections of these compounds were located near the central part of the site near existing, nonoperational, fuel-dispensing pumps. Trimethylbenzenes were detected in less than half of the soil-gas samplers. Naphthalene soil-gas mass was detected above the MDL in 10 soil-gas samplers, whereas 2-methyl-napthalene was detected above the MDL in half of the soil-gas samplers. Octane mass was detected above the MDL in one soil-gas sampler located near the central part of the site. Tetrachloroethylene soil-gas mass was detected above the MDL in more than half of the soil-gas samplers, and the highest tetrachloroethylene soil-gas mass of 0.90 microgram was located in the northeastern part of the site. Soil-gas samplers collected at the 12th Street site during July 2011 contained soil-gas mass above the MDL for TPH, toluene, undecane, tridecane, and pentadecane (diesel-range alkanes), trichloroethylene, 1,4-dichlorobenzene, chloroform, and 1,2,4-trimethylbenzene. The highest detected TPH mass was 24.37 micrograms in a soil-gas sampler located in the northern part of the site. The highest detection of toluene soil-gas mass was from a soil-gas sampler located near the southern boundary of the site. The diesel-range alkanes were detected above the MDL in five soil-gas samplers; the highest detection of soil-gas diesel mass, 0.65 microgram, was located in the southern part of the site. Trichloroethylene and 1,4-dichlorobenzene were detected above the MDL in the northern part of the site in one soil-gas sampler that also had one of the highest detections of TPH. Chloroform was detected above the MDL in three soil-gas samplers, whereas 1,2,4-trimethylbenzene soil-gas mass was detected above the MDL in two soil-gas samplers.

Synthetic musk in seafood products from south Europe using a quick, easy, cheap, effective, rugged and safe extraction method.

PubMed

Saraiva, M; Cavalheiro, J; Lanceleur, L; Monperrus, M

2016-06-01

This study aims at developing a method for the determination of 9 synthetic musk compounds in seafood products by combining the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method and determination by gas chromatography mass spectrometry (GC-EI-MS). Method detection limits (MDL) ranging between 0.001 and 1.94 ng g(-1) were obtained. The linearity is higher than 0.9899 in the range MDL - 100 ng g(-1) with precision below 18% and recoveries between 46% and 120% were obtained. The method was applied to quantify musk compounds in seafood products from the European southwest coast (oysters, mussels, salmon organs, glass eels). Galaxolide and Tonalide exhibited the highest concentration levels ranging between MDL - 96.4 ng g(-1) and MDL - 6.85 ng g(-1), respectively. Contamination levels observed for the two nitro musks (musk xylene and musk ketone) are significantly lower ranging between MDL - 0.6 ng g(-1) and MDL - 0.09 ng g(-1), respectively. Analysis of different organs of salmons showed higher concentrations in liver and gonad than in muscle tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Predictive minimum description length principle approach to inferring gene regulatory networks.

PubMed

Chaitankar, Vijender; Zhang, Chaoyang; Ghosh, Preetam; Gong, Ping; Perkins, Edward J; Deng, Youping

2011-01-01

Reverse engineering of gene regulatory networks using information theory models has received much attention due to its simplicity, low computational cost, and capability of inferring large networks. One of the major problems with information theory models is to determine the threshold that defines the regulatory relationships between genes. The minimum description length (MDL) principle has been implemented to overcome this problem. The description length of the MDL principle is the sum of model length and data encoding length. A user-specified fine tuning parameter is used as control mechanism between model and data encoding, but it is difficult to find the optimal parameter. In this work, we propose a new inference algorithm that incorporates mutual information (MI), conditional mutual information (CMI), and predictive minimum description length (PMDL) principle to infer gene regulatory networks from DNA microarray data. In this algorithm, the information theoretic quantities MI and CMI determine the regulatory relationships between genes and the PMDL principle method attempts to determine the best MI threshold without the need of a user-specified fine tuning parameter. The performance of the proposed algorithm is evaluated using both synthetic time series data sets and a biological time series data set (Saccharomyces cerevisiae). The results show that the proposed algorithm produced fewer false edges and significantly improved the precision when compared to existing MDL algorithm.

Meteorological Development Laboratory Student Career Experience Program

NASA Astrophysics Data System (ADS)

McCalla, C., Sr.

2007-12-01

The National Oceanic and Atmospheric Administration's (NOAA) National Weather Service (NWS) provides weather, hydrologic, and climate forecasts and warnings for the protection of life and property and the enhancement of the national economy. The NWS's Meteorological Development Laboratory (MDL) supports this mission by developing meteorological prediction methods. Given this mission, NOAA, NWS, and MDL all have a need to continually recruit talented scientists. One avenue for recruiting such talented scientist is the Student Career Experience Program (SCEP). Through SCEP, MDL offers undergraduate and graduate students majoring in meteorology, computer science, mathematics, oceanography, physics, and statistics the opportunity to alternate full-time paid employment with periods of full-time study. Using SCEP as a recruiting vehicle, MDL has employed students who possess some of the very latest technical skills and knowledge needed to make meaningful contributions to projects within the lab. MDL has recently expanded its use of SCEP and has increased the number of students (sometimes called co- ops) in its program. As a co-op, a student can expect to develop and implement computer based scientific techniques, participate in the development of statistical algorithms, assist in the analysis of meteorological data, and verify forecasts. This presentation will focus on describing recruitment, projects, and the application process related to MDL's SCEP. In addition, this presentation will also briefly explore the career paths of students who successfully completed the program.

Comparison of the effects of Truview PCD™ video laryngoscopy and Macintosh blade direct laryngoscopy in geriatric patients.

PubMed

Kurnaz, Muhammed M; Sarıtaş, Aykut

2016-12-01

To compare the effects of Truview PCD™ video laryngoscopy (TVL) and Macintosh blade direct laryngoscopy (MDL) on hemodynamic responses observed during laryngoscopy and orotracheal intubation conditions in geriatric patients. Randomized prospective study. Operating room. One hundred patients in the risk group American Society of Anesthesiologists I to III aged 65 years and older underwent elective surgery under general anesthesia. This prospective study was performed between January 2014 and February 2015 after institutional ethics committee approval. Patients were randomly allocated to 2 groups, namely, TVL and MDL. Hemodynamic parameters, modified Cormack-Lehane grade, intubation period, and preoperative examination (age, sex, American Society of Anesthesiologists, modified Mallampati test score, and thyromental and sternomental distances) of patients were evaluated. There were no statistically significant differences in hemodynamic responses (heart rates and mean arterial pressure) between the 2 groups (P>.05). The median intubation period in the TVL group was significantly higher than observed in the MDL group (t=4.594; P<.05). The laryngoscopy views in TVL group were better than the views in MDL group. The Cormack-Lehane grade in the TVL group was lower when compared to the MDL group. The TVL system does not provide significant hemodynamic response sparing or shorten orotracheal intubation times when compared to MDL in geriatric patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Herbicides and nitrates in the Iowa River alluvial aquifer prior to changing land use, Iowa County, Iowa, 1996

USGS Publications Warehouse

Savoca, Mark E.; Tobias, Jennifer L.; Sadorf, Eric M.; Birkenholtz, Trevor L.

1997-01-01

Four herbicides (alachlor, atrazine, cyanazine, and metolachlor) and one nutrient (nitrate) were selected for study on the basis of frequent usage in Iowa and high detection rates in ground water (Detroy and Kuzniar, 1988). Alachlor was not detected at concentrations greater than the method detection limit (MDL). Atrazine was detected at concentrations greater than the MDL in samples from 48 percent of the 23 wells, cyanazine from 13 percent, metolachlor from 26 percent, and nitrate from 91 percent. None of the four herbicides were detected at concentrations greater than the respective U.S. Environmental Protection Agency's (USEPA) Maximum Contaminant Level (MCL) for drinking water. Thirteen percent of the samples had nitrate concentrations above the USEPA's MCL of 10 mg/L (milligrams per liter). Relations between constituent concentration and well depth were observed for specific constituents at individual well nests.

Heterogeneity of NK-2 tachykinin receptors in hamster and rabbit smooth muscles.

PubMed

Maggi, C A; Eglezos, A; Quartara, L; Patacchini, R; Giachetti, A

1992-01-23

The possible existence of NK-2 receptor subtypes in peripheral smooth muscle preparations from rabbit and hamster was investigated by studying the effect of neurokinin A, the selective NK-2 receptor agonist [beta Ala8] neurokinin A (4-10), the selective NK-2 tachykinin receptor antagonists, MEN 10,376, L 659,877 and R 396, and the pseudopeptide derivative of neurokinin A (4-10), MDL 28,564. All experiments were performed in the presence of peptidase inhibitors (captopril, bestatin and thiorphan, 1 microM each). Both neurokinin A and [beta Ala8] neurokinin A (4-10) produced concentration-dependent contractions of the rabbit isolated bronchus and hamster isolated stomach and colon, as well as enhancement of the nerve-mediated twitches of rabbit isolated vas deferens (pars prostatica). MEN 10,376, L 659,877 and R 396 antagonized the effect of the NK-2 receptor selective agonist in all four tissues under study, although marked differences in antagonist potency were evident for the three antagonists. Thus MEN 10,376 was distinctly more potent (about 100 times) in rabbit than in hamster preparations while L 659,877 and R 396 were more potent in hamster than rabbit preparations. MDL 28,564 showed a distinct agonist character in rabbit preparations while it was virtually inactive in hamster preparations, where it antagonized the effect of the NK-2 receptor selective agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of polyamine and spermine oxidases by polyamine analogues.

PubMed

Bianchi, Marzia; Polticelli, Fabio; Ascenzi, Paolo; Botta, Maurizio; Federico, Rodolfo; Mariottini, Paolo; Cona, Alessandra

2006-03-01

Polyamine oxidase (PAO) and spermine oxidase (SMO) are involved in the catabolism of polyamines--basic regulators of cell growth and proliferation. The discovery of selective inhibitors of PAO and SMO represents an important tool in studying the involvement of these enzymes in polyamine homeostasis and a starting point for the development of novel antineoplastic drugs. Here, a comparative study on murine PAO (mPAO) and SMO (mSMO) inhibition by the polyamine analogues 1,8-diaminooctane, 1,12-diaminododecane, N-prenylagmatine (G3), guazatine and N,N1-bis(2,3-butadienyl)-1,4-butanediamine (MDL72527) is reported. Interestingly, 1,12-Diaminododecane and G3 behave as specific inhibitors of mPAO, values of K(i) for mPAO inhibition being lower than those for mSMO inactivation by several orders of magnitude. The analysis of molecular models of mPAO and mSMO indicates a significant reduction of the hydrophobic pocket located in maize PAO (MPAO) at the wider catalytic tunnel opening. This observation provides a rationale to explain the lower affinity displayed by G3, guazatine and MDL72527 for mPAO and mSMO as compared to MPAO. The different behaviour displayed by 1,12-diaminododecane towards mPAO and mSMO reveals the occurrence of basic differences in the ligand binding mode of the two enzymes, the first enzyme interacting mainly with substrate secondary amino groups and the second one with substrate primary amino groups. Thus, the data reported here provide the basis for the development of novel and selective inhibitors able to discriminate between mammalian SMO and PAO activities.

Evolutionary tree reconstruction

NASA Technical Reports Server (NTRS)

Cheeseman, Peter; Kanefsky, Bob

1990-01-01

It is described how Minimum Description Length (MDL) can be applied to the problem of DNA and protein evolutionary tree reconstruction. If there is a set of mutations that transform a common ancestor into a set of the known sequences, and this description is shorter than the information to encode the known sequences directly, then strong evidence for an evolutionary relationship has been found. A heuristic algorithm is described that searches for the simplest tree (smallest MDL) that finds close to optimal trees on the test data. Various ways of extending the MDL theory to more complex evolutionary relationships are discussed.

Fluorescence stopped-flow study of the interaction of tubulin with the antimitotic drug MDL 27048.

PubMed

Silence, K; D'Hoore, A; Engelborghs, Y; Peyrot, V; Briand, C

1992-11-17

The kinetics of the binding of MDL 27048 to tubulin have been studied by fluorescence stopped flow. The binding is accompanied by a fluorescence increase. The time course can be described by a sum of two exponentials, assumed to be due to the presence of two major tubulin isoforms. The observed rate constants depend in a nonlinear way on the concentration of MDL in pseudo-first-order conditions. This concentration dependence can be described by the presence of a fast equilibrium of low affinity, followed by an isomerization of the initial complex. The dissociation kinetics have been studied by displacement experiments, in which MTC was used as a competitive ligand. The reaction enthalpy change for the first binding equilibrium and the activation energies for the forward and reverse steps of the isomerization were determined from the temperature dependence. This was possible for the two tubulin isotype populations. The kinetics of the binding of MDL to tubulin are slowed down in the presence of 3',4',5'-trimethoxyacetophenone, a fast binding analog of the colchicine A-ring, but are not influenced by the binding of tropolone methyl ether, indicating that the binding site of MDL has the A-subsite in common with colchicine, but not the C-subsite.

Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans.

PubMed

Böttiger, Y; Dostert, P; Benedetti, M S; Bani, M; Fiorentini, F; Casati, M; Poggesti, I; Alm, C; Alvan, G; Bertilsson, L

1996-12-01

1. Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia. 2. Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-alpha-methoxy-9,10-dihydrolysergol (MMDL), which is further N-demethylated to form 10-alpha-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms. 3. After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes. 4. The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL Cmax 59 nmol l-1 and AUC (0, th) 144 nmol l-1h, mean MDL Cmax 183 nmol l-1 and AUC 2627 nmol l-1h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL Cmax 356 nmol l-1 and AUC 10512 nmol l-1h, MDL concentrations below limit of quantitation). 5. We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism.

Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans

PubMed Central

BÖTTIGER, Y.; DOSTERT, P.; STROLIN BENEDETTI, M.; BANI, M.; FIORENTINI, F.; CASATI, M.; POGGESTI, I.; ALM, C.; ALVAN, G.; BERTILSSON, L.

1996-01-01

1Nicergoline, an ergot derivative previously used as a vasodilator, has gained a new indication in treating the symptoms of senile dementia. 2Nicergoline is rapidly hydrolysed to an alcohol derivative, 1-methyl-10-α-methoxy-9,10-dihydrolysergol (MMDL), which is further N-demethylated to form 10-α-methoxy-9,10-dihydrolysergol (MDL). A few individuals display aberrant metabolism of this drug, as shown by their diminished capacity to form the MDL metabolite. The aim of this study was to determine whether defective nicergoline metabolism is associated with the debrisoquine and/or the S-mephenytoin hydroxylation polymorphisms. 3After a single, oral 30 mg dose of nicergoline, the plasma concentrations of its two metabolites were studied in 15 subjects, divided into three groups with respect to their debrisoquine and S-mephenytoin hydroxylation phenotypes. 4The pharmacokinetic parameters of MMDL and MDL were similar in the ten subjects who were extensive metabolisers of debrisoquine (five of whom were poor metabolisers of S-mephenytoin) (mean MMDL Cmax 59 nmol l−1 and AUC (0, th) 144 nmol l−1h, mean MDL Cmax 183 nmol l−1 and AUC 2627 nmol l−1h) but were markedly different from the five subjects who were poor metabolisers of debrisoquine (mean MMDL Cmax 356 nmol l−1 and AUC 10512 nmol l−1h, MDL concentrations below limit of quantitation). 5We conclude that the formation of MDL from MMDL in the metabolism of nicergoline is catalysed to a major extent by CYP2D6 and that the observed interindividual variation in the metabolic pattern of the drug is related to the debrisoquine hydroxylation polymorphism. PMID:8971425

Improving Microbial Biogasoline Production in Escherichia coli Using Tolerance Engineering

PubMed Central

Foo, Jee Loon; Jensen, Heather M.; Dahl, Robert H.; George, Kevin; Keasling, Jay D.; Lee, Taek Soon; Leong, Susanna

2014-01-01

ABSTRACT Engineering microbial hosts for the production of fungible fuels requires mitigation of limitations posed on the production capacity. One such limitation arises from the inherent toxicity of solvent-like biofuel compounds to production strains, such as Escherichia coli. Here we show the importance of host engineering for the production of short-chain alcohols by studying the overexpression of genes upregulated in response to exogenous isopentenol. Using systems biology data, we selected 40 genes that were upregulated following isopentenol exposure and subsequently overexpressed them in E. coli. Overexpression of several of these candidates improved tolerance to exogenously added isopentenol. Genes conferring isopentenol tolerance phenotypes belonged to diverse functional groups, such as oxidative stress response (soxS, fpr, and nrdH), general stress response (metR, yqhD, and gidB), heat shock-related response (ibpA), and transport (mdlB). To determine if these genes could also improve isopentenol production, we coexpressed the tolerance-enhancing genes individually with an isopentenol production pathway. Our data show that expression of 6 of the 8 candidates improved the production of isopentenol in E. coli, with the methionine biosynthesis regulator MetR improving the titer for isopentenol production by 55%. Additionally, expression of MdlB, an ABC transporter, facilitated a 12% improvement in isopentenol production. To our knowledge, MdlB is the first example of a transporter that can be used to improve production of a short-chain alcohol and provides a valuable new avenue for host engineering in biogasoline production. PMID:25370492

Acrolein generation stimulates hypercontraction in isolated human blood vessels

PubMed Central

Conklin, D.J.; Bhatnagar, A.; Cowley, H.R.; Johnson, G.H.; Wiechmann, R.J.; Sayre, L.M.; Trent, M.B.; Boor, P.J.

2012-01-01

Increased risk of vasospasm, a spontaneous hyperconstriction, is associated with atherosclerosis, cigarette smoking, and hypertension—all conditions involving oxidative stress, lipid peroxidation, and inflammation. To test the role of the lipid peroxidation- and inflammation-derived aldehyde, acrolein, in human vasospasm, we developed an ex vivo model using human coronary artery bypass graft (CABG) blood vessels and a demonstrated acrolein precursor, allylamine. Allylamine induces hypercontraction in isolated rat coronary artery in a semicarbazide-sensitive amine oxidase activity (SSAO) dependent manner. Isolated human CABG blood vessels (internal mammary artery, radial artery, saphenous vein) were used to determine: (1) vessel responses and sensitivity to acrolein, allylamine, and H2O2 exposure (1 μM–1 mM), (2) SSAO dependence of allylamine-induced effects using SSAO inhibitors (semicarbazide, 1 mM; MDL 72274-E, active isomer; MDL 72274-Z, inactive isomer; 100 μM), (3) the vasoactive effects of two other SSAO amine substrates, benzylamine and methylamine, and (4) the contribution of extracellular Ca2+ to hypercontraction. Acrolein or allylamine but not H2O2, benzylamine, or methylamine stimulated spontaneous and pharmacologically intractable hypercontraction in CABG blood vessels that was similar to clinical vasospasm. Allylamine-induced hypercontraction and blood vessel SSAO activity were abolished by pretreatment with semicarbazide or MDL 72274-E but not by MDL 72274-Z. Allylamine-induced hypercontraction also was significantly attenuated in Ca2+-free buffer. In isolated aorta of spontaneously hypertensive rat, allylamine-induced an SSAO-dependent contraction and enhanced norepinephrine sensitivity but not in Sprague–Dawley rat aorta. We conclude that acrolein generation in the blood vessel wall increases human susceptibility to vasospasm, an event that is enhanced in hypertension. PMID:17095030

Tachykinin receptors in the guinea-pig renal pelvis: activation by exogenous and endogenous tachykinins.

PubMed Central

Maggi, C. A.; Patacchini, R.; Eglezos, A.; Quartara, L.; Giuliani, S.; Giachetti, A.

1992-01-01

1. The contractile response to substance P, neurokinin A, selective agonists for the NK1, NK2 and NK3 tachykinin receptors and the activity of receptor-selective antagonists has been investigated in circular muscle strips of the guinea-pig isolated renal pelvis in the presence of indomethacin (3 microM). 2. Neurokinin A was the most potent agonist tested, being about 32 times more potent than substance P. The action of both substance P and neurokinin A was enhanced by peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each). The selective NK2 receptor agonist [beta Ala8] neurokinin A (4-10), was slightly less potent and effective than neurokinin A itself. The selective NK1 receptor agonist [Sar9] substance P sulphone was effective at low (nM) concentrations but its maximal effect did not exceed 30% of maximal response to substance P or neurokinin A. The NK3-selective agonist [MePhe7] neurokinin B was effective only at high (microM) concentrations. 3. The pseudopeptide derivative of neurokinin A(4-10), MDL 28,564, displayed a clear-cut agonist character, although it was less potent than neurokinin A. 4. The responses to roughly equieffective (25-35% of maximal response) concentrations of [beta Ala8] neurokinin A (4-10), MDL 28,564 and [MePhe7] neurokinin B were antagonized to a similar extent by MEN 10,376 (3 microM), a selective NK2 tachykinin receptor antagonist, while the response to [Sar9] substance P sulphone was unchanged. 5. The response to [Sar9] substance P sulphone was inhibited by the NK1 receptor-selective antagonist, GR 82,334 (3 microM) while the response to [beta Ala8] neurokinin A (4-10) was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1384907

Using the U.S. Geological Survey National Water Quality Laboratory LT-MDL to Evaluate and Analyze Data

USGS Publications Warehouse

Bonn, Bernadine A.

2008-01-01

A long-term method detection level (LT-MDL) and laboratory reporting level (LRL) are used by the U.S. Geological Survey?s National Water Quality Laboratory (NWQL) when reporting results from most chemical analyses of water samples. Changing to this method provided data users with additional information about their data and often resulted in more reported values in the low concentration range. Before this method was implemented, many of these values would have been censored. The use of the LT-MDL and LRL presents some challenges for the data user. Interpreting data in the low concentration range increases the need for adequate quality assurance because even small contamination or recovery problems can be relatively large compared to concentrations near the LT-MDL and LRL. In addition, the definition of the LT-MDL, as well as the inclusion of low values, can result in complex data sets with multiple censoring levels and reported values that are less than a censoring level. Improper interpretation or statistical manipulation of low-range results in these data sets can result in bias and incorrect conclusions. This document is designed to help data users use and interpret data reported with the LTMDL/ LRL method. The calculation and application of the LT-MDL and LRL are described. This document shows how to extract statistical information from the LT-MDL and LRL and how to use that information in USGS investigations, such as assessing the quality of field data, interpreting field data, and planning data collection for new projects. A set of 19 detailed examples are included in this document to help data users think about their data and properly interpret lowrange data without introducing bias. Although this document is not meant to be a comprehensive resource of statistical methods, several useful methods of analyzing censored data are demonstrated, including Regression on Order Statistics and Kaplan-Meier Estimation. These two statistical methods handle complex censored data sets without resorting to substitution, thereby avoiding a common source of bias and inaccuracy.

Susceptibility of Phytomonas serpens to calpain inhibitors in vitro: interference on the proliferation, ultrastructure, cysteine peptidase expression and interaction with the invertebrate host.

PubMed

Oliveira, Simone Santiago Carvalho de; Gonçalves, Diego de Souza; Garcia-Gomes, Aline Dos Santos; Gonçalves, Inês Correa; Seabra, Sergio Henrique; Menna-Barreto, Rubem Figueiredo; Lopes, Angela Hampshire de Carvalho Santos; D'Avila-Levy, Claudia Masini; Santos, André Luis Souza Dos; Branquinha, Marta Helena

2017-01-01

A pleiotropic response to the calpain inhibitor MDL28170 was detected in the tomato parasite Phytomonas serpens. Ultrastructural studies revealed that MDL28170 caused mitochondrial swelling, shortening of flagellum and disruption of trans Golgi network. This effect was correlated to the inhibition in processing of cruzipain-like molecules, which presented an increase in expression paralleled by decreased proteolytic activity. Concomitantly, a calcium-dependent cysteine peptidase was detected in the parasite extract, the activity of which was repressed by pre-incubation of parasites with MDL28170. Flow cytometry and Western blotting analyses revealed the differential expression of calpain-like proteins (CALPs) in response to the pre-incubation of parasites with the MDL28170, and confocal fluorescence microscopy confirmed their surface location. The interaction of promastigotes with explanted salivary glands of the insect Oncopeltus fasciatus was reduced when parasites were pre-treated with MDL28170, which was correlated to reduced levels of surface cruzipain-like and gp63-like molecules. Treatment of parasites with anti-Drosophila melanogaster (Dm) calpain antibody also decreased the adhesion process. Additionally, parasites recovered from the interaction process presented higher levels of surface cruzipain-like and gp63-like molecules, with similar levels of CALPs cross-reactive to anti-Dm-calpain antibody. The results confirm the importance of exploring the use of calpain inhibitors in studying parasites' physiology.

Susceptibility of Phytomonas serpens to calpain inhibitors in vitro: interference on the proliferation, ultrastructure, cysteine peptidase expression and interaction with the invertebrate host

PubMed Central

de Oliveira, Simone Santiago Carvalho; Gonçalves, Diego de Souza; Garcia-Gomes, Aline dos Santos; Gonçalves, Inês Correa; Seabra, Sergio Henrique; Menna-Barreto, Rubem Figueiredo; Lopes, Angela Hampshire de Carvalho Santos; D’Avila-Levy, Claudia Masini; dos Santos, André Luis Souza; Branquinha, Marta Helena

2016-01-01

A pleiotropic response to the calpain inhibitor MDL28170 was detected in the tomato parasite Phytomonas serpens. Ultrastructural studies revealed that MDL28170 caused mitochondrial swelling, shortening of flagellum and disruption of trans Golgi network. This effect was correlated to the inhibition in processing of cruzipain-like molecules, which presented an increase in expression paralleled by decreased proteolytic activity. Concomitantly, a calcium-dependent cysteine peptidase was detected in the parasite extract, the activity of which was repressed by pre-incubation of parasites with MDL28170. Flow cytometry and Western blotting analyses revealed the differential expression of calpain-like proteins (CALPs) in response to the pre-incubation of parasites with the MDL28170, and confocal fluorescence microscopy confirmed their surface location. The interaction of promastigotes with explanted salivary glands of the insect Oncopeltus fasciatus was reduced when parasites were pre-treated with MDL28170, which was correlated to reduced levels of surface cruzipain-like and gp63-like molecules. Treatment of parasites with anti-Drosophila melanogaster (Dm) calpain antibody also decreased the adhesion process. Additionally, parasites recovered from the interaction process presented higher levels of surface cruzipain-like and gp63-like molecules, with similar levels of CALPs cross-reactive to anti-Dm-calpain antibody. The results confirm the importance of exploring the use of calpain inhibitors in studying parasites’ physiology. PMID:27925020

USE OF METHOD DETECTION LIMITS IN ENVIRONMENTAL MEASUREMENTS

EPA Science Inventory

Environmental measurements often produce values below the method detection limit (MDL). Because low or zero values may be used in determining compliance with regulatory limits, in determining emission factors (typical concentrations emitted by a given type of source), or in model...

Complex discriminative stimulus properties of (+)lysergic acid diethylamide (LSD) in C57Bl/6J mice.

PubMed

Benneyworth, Michael A; Smith, Randy L; Barrett, Robert J; Sanders-Bush, Elaine

2005-06-01

The drug discrimination procedure is the most frequently used in vivo model of hallucinogen activity. Historically, most drug discrimination studies have been conducted in the rat. With the development of genetically modified mice, a powerful new tool has become available for investigating the mechanisms of drug-induced behavior. The current paper is part of an ongoing effort to determine the utility of the drug discrimination technique for evaluating hallucinogenic drugs in mice. To establish the training procedures and characterize the stimulus properties of (+)lysergic acid diethylamide (LSD) in mice. Using a two-lever drug discrimination procedure, C57Bl/6J mice were trained to discriminate 0.45 mg/kg LSD vs saline on a VI30 sec schedule of reinforcement, with vanilla-flavored Ensure serving as the reinforcer. As in rats, acquisition was orderly, but the training dose was nearly five-fold higher for mice than rats. LSD lever selection was dose-dependent. Time-course studies revealed a rapid loss of the LSD stimulus effects. The 5-HT(2A/2C) receptor agonist, 2,5-dimethoxy-4-bromoamphetamine [(-)DOB] (1.0 mg/kg), substituted fully for LSD and the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) (1.6 mg/kg), substituted partially for LSD. Pretreatment with the 5-HT(2A) receptor-selective antagonist, MDL 100907, or the 5-HT(1A)-selective antagonist WAY 100635, showed that each antagonist only partially blocked LSD discrimination. Substitution of 1.0 mg/kg (-)DOB for LSD was fully blocked by pretreatment with MDL 100907 but unaltered by WAY 100635 pretreatment. These data suggest that in mice the stimulus effects of LSD have both a 5-HT(2A) receptor and a 5-HT(1A) receptor component.

Energy Systems Integration News | Energy Systems Integration Facility |

Science.gov Websites

Aids Solar Power in Hawaii Inverter load rejection overvoltage tests completed by NREL with partner the report, Inverter Load Rejection Over-Voltage Testing: SolarCity CRADA Task 1a Final Report. Based % of minimum daytime load (MDL) to 250% of MDL. If those increases are implemented, they will represent

QEPAS based ppb-level detection of CO and N2O using a high power CW DFB-QCL.

PubMed

Ma, Yufei; Lewicki, Rafał; Razeghi, Manijeh; Tittel, Frank K

2013-01-14

An ultra-sensitive and selective quartz-enhanced photoacoustic spectroscopy (QEPAS) sensor platform was demonstrated for detection of carbon monoxide (CO) and nitrous oxide (N2O). This sensor used a state-of-the art 4.61 μm high power, continuous wave (CW), distributed feedback quantum cascade laser (DFB-QCL) operating at 10°C as the excitation source. For the R(6) CO absorption line, located at 2169.2 cm(-1), a minimum detection limit (MDL) of 1.5 parts per billion by volume (ppbv) at atmospheric pressure was achieved with a 1 sec acquisition time and the addition of 2.6% water vapor concentration in the analyzed gas mixture. For the N2O detection, a MDL of 23 ppbv was obtained at an optimum gas pressure of 100 Torr and with the same water vapor content of 2.6%. In both cases the presence of water vapor increases the detected CO and N2O QEPAS signal levels as a result of enhancing the vibrational-translational relaxation rate of both target gases. Allan deviation analyses were performed to investigate the long term performance of the CO and N2O QEPAS sensor systems. For the optimum data acquisition time of 500 sec a MDL of 340 pptv and 4 ppbv was obtained for CO and N2O detection, respectively. To demonstrate reliable and robust operation of the QEPAS sensor a continuous monitoring of atmospheric CO and N2O concentration levels for a period of 5 hours were performed.

The effects of administration of monoamine oxidase-B inhibitors on rat striatal neurone responses to dopamine.

PubMed Central

Berry, M D; Scarr, E; Zhu, M Y; Paterson, I A; Juorio, A V

1994-01-01

1. (-)-Deprenyl has been shown to potentiate rat striatal neurone responses to dopamine agonists at doses not altering dopamine metabolism. Since there are a number of effects of (-)-deprenyl which could result in this phenomenon, we have investigated the effects of MDL 72,145 and Ro 19-6327, whose only common effect with (-)-deprenyl is an inhibition of monoamine oxidase-B (MAO-B), on rat striatal neurone responses to dopamine and on striatal dopamine metabolism. 2. Using in vivo electrophysiology, i.p. injection of either MDL 72,145 or Ro 19-6327 was found to produce a dose-dependent potentiation of striatal neurone responses to dopamine but not gamma-aminobutyric acid. 3. Neurochemical investigations revealed that this occurred at doses (0.25-1 mg kg-1) which, while not affecting levels of dopamine or its metabolites, 3,4-dihydroxyphenylacetic acid or homovanillic acid, did cause a significant, dose-dependent, elevation in striatal levels of the putative neuromodulator, 2-phenylethylamine (PE). 4. Inhibition of PE synthesis by i.p. injection of the aromatic L-amino acid decarboxylase inhibitor, NSD 1015, produced a reversal of the effects of MDL 72,145 and Ro 19-6327. 5. Neurochemical analysis revealed this to occur at a dose of NSD 1015 (10 mg kg-1) selective for reduction of elevated PE levels. 6. These results suggest that PE can act as a neuromodulator of dopaminergic responses and that MAO-B inhibitors may potentiate neuronal responses to dopamine via the indirect mechanism of elevation of PE following MAO-B inhibition. PMID:7889269

Diffusion related isotopic fractionation effects with one-dimensional advective-dispersive transport.

PubMed

Xu, Bruce S; Lollar, Barbara Sherwood; Passeport, Elodie; Sleep, Brent E

2016-04-15

Aqueous phase diffusion-related isotope fractionation (DRIF) for carbon isotopes was investigated for common groundwater contaminants in systems in which transport could be considered to be one-dimensional. This paper focuses not only on theoretically observable DRIF effects in these systems but introduces the important concept of constraining "observable" DRIF based on constraints imposed by the scale of measurements in the field, and on standard limits of detection and analytical uncertainty. Specifically, constraints for the detection of DRIF were determined in terms of the diffusive fractionation factor, the initial concentration of contaminants (C0), the method detection limit (MDL) for isotopic analysis, the transport time, and the ratio of the longitudinal mechanical dispersion coefficient to effective molecular diffusion coefficient (Dmech/Deff). The results allow a determination of field conditions under which DRIF may be an important factor in the use of stable carbon isotope measurements for evaluation of contaminant transport and transformation for one-dimensional advective-dispersive transport. This study demonstrates that for diffusion-dominated transport of BTEX, MTBE, and chlorinated ethenes, DRIF effects are only detectable for the smaller molar mass compounds such as vinyl chloride for C0/MDL ratios of 50 or higher. Much larger C0/MDL ratios, corresponding to higher source concentrations or lower detection limits, are necessary for DRIF to be detectable for the higher molar mass compounds. The distance over which DRIF is observable for VC is small (less than 1m) for a relatively young diffusive plume (<100years), and DRIF will not easily be detected by using the conventional sampling approach with "typical" well spacing (at least several meters). With contaminant transport by advection, mechanical dispersion, and molecular diffusion this study suggests that in field sites where Dmech/Deff is larger than 10, DRIF effects will likely not be observable for common groundwater contaminants. Importantly, under most field conditions, Dmech/Deff≥10 is usually satisfied in the longitudinal direction, suggesting that DRIF is not likely to be observable in most groundwater systems in which contaminant transport is predominantly one-dimensional. Given the importance in the MDL it is recommended that MDL should always be explicitly reported in both modeling and field studies. Copyright © 2016. Published by Elsevier B.V.

Final Environmental Assessment for Proposed Multi-Purpose Machine Gun Range at Joint Base McGuire-Dix-Lakehurst (JB MDL), New Jersey

DTIC Science & Technology

2015-09-01

Proposed MPMGR July 2015 JB MDL, New Jersey 2-2 Heating would be accomplished through electrical, geothermal , heat pump, or solar power. No fuel storage...emissions. Further, to the extent feasible, renewable energy (including, but not limited to solar, wind, geothermal 1 biogas, and biomass) and

40 CFR 141.23 - Inorganic chemical sampling and analytical requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Inorganic Contaminants Contaminant MCL (mg/l) Methodology Detection limit (mg/l) Antimony 0.006 Atomic... January 23, 2006. Unit then, the MCL is 0.05 mg/L. 7 The MDL reported for EPA method 200.9 (Atomic... higher. Using multiple depositions, EPA 200.9 is capable of obtaining MDL of 0.0001 mg/L. 8 Using...

Influence of 7,8-methylenedioxylycoctonine-type alkaloids on the toxic effects associated with ingestion of tall larkspur (Delphinium spp) in cattle.

PubMed

Welch, Kevin D; Green, Benedict T; Gardner, Dale R; Cook, Daniel; Pfister, James A; Stegelmeier, Bryan L; Panter, Kip E; Davis, T Zane

2010-04-01

To determine the contribution of 7,8-methylenedioxylycoctonine (MDL)-type alkaloids to the toxic effects of tall larkspur (Delphinium spp) consumption in cattle. Sixteen 2-year-old Angus steers. Plant material from 3 populations of tall larkspur that contained different concentration ratios of MDL-type-to-N-(methylsuccinimido) anthranoyllycoctonine (MSAL)-type alkaloids was collected, dried, and finely ground. For each plant population, a dose of ground plant material that would elicit similar clinical signs of toxicosis in cattle after oral administration was determined on the basis of the plants' MSAL-type alkaloid concentration. Cattle were treated via oral gavage with single doses of ground plant material from each of the 3 populations of tall larkspur; each animal underwent 1 to 3 single-dose treatments (> or = 21-day interval between treatments). Heart rate was recorded immediately before (baseline) and 24 hours after each larkspur treatment. Tall larkspur populations with a lower MDL-type-to-MSAL-type alkaloid concentration ratio required a greater amount of MSAL-type alkaloids to cause the expected clinical signs of toxicosis (including increased heart rate) in cattle. Results indicated that the typically less toxic MDL-type alkaloids contributed in a significant manner to the toxic effects of tall larkspur in steers. Consequently, both the concentration of MSAL-type alkaloids and the total concentration of MSAL- and MDL-type alkaloids should be determined when assessing the relative toxicity of tall larkspur populations. These results provide valuable information to determine the risk of toxicosis in cattle grazing on tall larkspur-infested rangelands.

The influence of distal locking on the need for fibular plating in intramedullary nailing of distal metaphyseal tibiofibular fractures.

PubMed

Attal, R; Maestri, V; Doshi, H K; Onder, U; Smekal, V; Blauth, M; Schmoelz, W

2014-03-01

Using human cadaver specimens, we investigated the role of supplementary fibular plating in the treatment of distal tibial fractures using an intramedullary nail. Fibular plating is thought to improve stability in these situations, but has been reported to have increased soft-tissue complications and to impair union of the fracture. We proposed that multidirectional locking screws provide adequate stability, making additional fibular plating unnecessary. A distal tibiofibular osteotomy model performed on matched fresh-frozen lower limb specimens was stabilised with reamed nails using conventional biplanar distal locking (CDL) or multidirectional distal locking (MDL) options with and without fibular plating. Rotational stiffness was assessed under a constant axial force of 150 N and a superimposed torque of ± 5 Nm. Total movement, and neutral zone and fracture gap movement were analysed. In the CDL group, fibular plating improved stiffness at the tibial fracture site, albeit to a small degree (p = 0.013). In the MDL group additional fibular plating did not increase the stiffness. The MDL nail without fibular plating was significantly more stable than the CDL nail with an additional fibular plate (p = 0.008). These findings suggest that additional fibular plating does not improve stability if a multidirectional distal locking intramedullary nail is used, and is therefore unnecessary if not needed to aid reduction.

Applying Monte-Carlo simulations to optimize an inelastic neutron scattering system for soil carbon analysis

USDA-ARS?s Scientific Manuscript database

Computer Monte-Carlo (MC) simulations (Geant4) of neutron propagation and acquisition of gamma response from soil samples was applied to evaluate INS system performance characteristic [sensitivity, minimal detectable level (MDL)] for soil carbon measurement. The INS system model with best performanc...

In vitro selection of Phytomonas serpens cells resistant to the calpain inhibitor MDL28170: alterations in fitness and expression of the major peptidases and efflux pumps.

PubMed

Oliveira, Simone S C; Gonçalves, Inês C; Ennes-Vidal, Vitor; Lopes, Angela H C S; Menna-Barreto, Rubem F S; D'Ávila-Levy, Claudia M; Santos, André L S; Branquinha, Marta H

2018-03-01

The species Phytomonas serpens is known to express some molecules displaying similarity to those described in trypanosomatids pathogenic to humans, such as peptidases from Trypanosoma cruzi (cruzipain) and Leishmania spp. (gp63). In this work, a population of P. serpens resistant to the calpain inhibitor MDL28170 at 70 µ m (MDLR population) was selected by culturing promastigotes in increasing concentrations of the drug. The only relevant ultrastructural difference between wild-type (WT) and MDLR promastigotes was the presence of microvesicles within the flagellar pocket of the latter. MDLR population also showed an increased reactivity to anti-cruzipain antibody as well as a higher papain-like proteolytic activity, while the expression of calpain-like molecules cross-reactive to anti-Dm-calpain (from Drosophila melanogaster) antibody and calcium-dependent cysteine peptidase activity were decreased. Gp63-like molecules also presented a diminished expression in MDLR population, which is probably correlated to the reduction in the parasite adhesion to the salivary glands of the insect vector Oncopeltus fasciatus. A lower accumulation of Rhodamine 123 was detected in MDLR cells when compared with the WT population, a phenotype that was reversed when MDLR cells were treated with cyclosporin A and verapamil. Collectively, our results may help in the understanding of the roles of calpain inhibitors in trypanosomatids.

Radioligand binding, autoradiographic and functional studies demonstrate tachykinin NK-2 receptors in dog urinary bladder.

PubMed

Mussap, C J; Stamatakos, C; Burcher, E

1996-10-01

Tachykinin receptors in the dog bladder were characterized using radioligand binding, functional and autoradiographic techniques. In detrusor muscle homogenates, specific binding of [125l]iodohistidyl neurokinin A (INKA) and [125l]Bolton Hunter eledoisin was reversible, saturable and, to a single class of sites of Kd, 3,6 and 27 nM, respectively. No specific binding of [125l]Bolton Hunter[Sar9, Met (O2)11] substance P occurred. INKA binding was reduced by the peptidase inhibitor bacitracin. The rank potency order of agonists competing for binding of both radioligands indicated interaction at NK-2 sites. NK-2-selective antagonists also competed for INKA binding, with SR 48968, GR 94800, MDL 29913 and the selective agonist [Lys5, MeLeu9, Nle10]-NKA(4-10) showing biphasic binding profiles. Autoradiographic studies revealed specific binding of INKA and [125l]Bolton Hunter eledoisin over detrusor muscle and small arteries. [125l]Bolton Hunter [Sar9, Met (O2)11] SP labeled the intima of arteries and arterioles, but not the detrusor muscle. Tachykinins contracted detrusor muscle strips, with potency order at the carbachol EC15 NKA = kassinin > [Lys5, MeLeu9, Nle10]-NKA(4-10) = neuropeptide gamma = neuropeptide K = NKB > > MDL 28564, with [Sar9, Met(O2)11]-SP ineffective. Shallow concentration-response curves, variable efficacies and inhibition by atropine and mepyramine suggest that other mechanisms may influence contractile responses. Responses to [Lys5, MeLeu9, Nle10]-NKA(4-10) were inhibited competitively by MDL 29913 and MEN 10207 (pA2 values: 6.4 and 5.3, respectively). Antagonism by SR 48968 and GR 94800 was noncompetitive (both pK8 values 8.9). In summary, NK-2-preferring ligands showed superior potency as both binding competitors and contractile agonists, demonstrating that NK-2 receptors mediate detrusor muscle contraction, similar to the human detrusor. Tachykinins may play important roles in the micturition reflex and in regulating detrusor muscle blood flow in the dog.

Tachykinin receptors in the guinea-pig isolated bronchi.

PubMed

Maggi, C A; Patacchini, R; Quartara, L; Rovero, P; Santicioli, P

1991-05-17

The aim of the study was to assess which tachykinin receptors mediate the contractile response in the guinea-pig isolated bronchi. Experiments with natural tachykinins and receptor-selective tachykinin agonists were performed in the absence or presence of peptidase inhibitors and in bronchi pretreated with phenoxybenzamine. Both NK-1 (substance P, substance P methylester and septide) and NK-2 (neurokinin A, [beta-Ala8]neurokinin A-(4-10) and MDL 28,564) receptor agonists produced concentration-dependent contraction. NK-3 agonists (senktide and [MePhe7]neurokinin B) were active only at high concentrations. Phenoxybenzamine pretreatment reduced the maximal response to NK-1 agonists and produced a rightward shift of the curve to NK-2 agonists, without depression of the maximum. Five tachykinin antagonists selective for the NK-1 (L 668,169) or the NK-2 (MEN 10,207, MEN 10,376, L 659,877 and R 396) receptor were tested against substance P methylester and [beta-Ala8]neurokinin A-(4-10). The results indicated that these receptor-selective antagonists maintain their characteristic even when tested in a multireceptor assay such as the guinea-pig bronchus. The rank order of potency of NK-2 antagonists against [beta-Ala8]neurokinin A-(4-10) was MEN 10,207 = MEN 10,376 greater than L 659,877 much greater than R 396. This pattern, with the observation of the full agonist activity of MDL 28,564, indicates that in addition to NK-1 receptors, NK-2 receptors also are present in the guinea-pig bronchi and belong to the same subtype (NK-2A) as present in the rabbit pulmonary artery.

Peak Power Control with an Energy Management System

DTIC Science & Technology

2013-03-01

Rectifier - Dr. Giovanna Oriti %initial conditions file for model ec3150_software_lab4.mdl ampl=29*sqrt(2); fund=60; ws=2*pi*fund; Ls =200e-6...original % Ls =2e-4; %reduced source inductance Rs=5e-3; Rload=10; Cdc=1100e-6; %-----H-Bridge Model ----- %EC3150 Software lab#5 - H-bridge...using a Simulink model and an experimental laboratory setup. The Simulink model and EMS functionality are validated with the laboratory experiments

Examining the Interrelations among Knowledge, Interests, and Learning Strategies

ERIC Educational Resources Information Center

Shen, Bo; Chen, Ang

2006-01-01

Guided by the Model of Domain Learning (MDL), the study was designed to explore the extent of interrelations among prior knowledge, learning strategies, interests, physical engagement, and learning outcomes in a sixth-grade (N = 91) volleyball unit. Pearson product-moment correlations and a path analysis were conducted for the research purpose.…

78 FR 1883 - Notice of Lodging of Proposed Partial Consent Decree Under the Clean Water Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-09

... lodged in U.S. v. BP Exploration and Production, et al, Civil No. 10-4536 (E.D. La.) (That case is centralized in MDL 2179: In Re: Oil Spill by the Oil Rig ``Deepwater Horizon'' in the Gulf of Mexico, on April... al, Civil No. 10-4536 (E.D. La.) (centralized in MDL 2179: In Re: Oil Spill by the Oil Rig...

Do serotonin(1-7) receptors modulate short and long-term memory?

PubMed

Meneses, A

2007-05-01

Evidence from invertebrates to human studies indicates that serotonin (5-hydroxytryptamine; 5-HT) system modulates short- (STM) and long-term memory (LTM). This work is primarily focused on analyzing the contribution of 5-HT, cholinergic and glutamatergic receptors as well as protein synthesis to STM and LTM of an autoshaping learning task. It was observed that the inhibition of hippocampal protein synthesis or new mRNA did not produce a significant effect on autoshaping STM performance but it did impair LTM. Both non-contingent protein inhibition and 5-HT depletion showed no effects. It was basically the non-selective 5-HT receptor antagonist cyproheptadine, which facilitated STM. However, the blockade of glutamatergic and cholinergic transmission impaired STM. In contrast, the selective 5-HT(1B) receptor antagonist SB-224289 facilitated both STM and LTM. Selective receptor antagonists for the 5-HT(1A) (WAY100635), 5-HT(1D) (GR127935), 5-HT(2A) (MDL100907), 5-HT(2C/2B) (SB-200646), 5-HT(3) (ondansetron) or 5-HT(4) (GR125487), 5-HT(6) (Ro 04-6790, SB-399885 and SB-35713) or 5-HT(7) (SB-269970) did not impact STM. Nevertheless, WAY100635, MDL100907, SB-200646, GR125487, Ro 04-6790, SB-399885 or SB-357134 facilitated LTM. Notably, some of these changes shown to be independent of food-intake. Concomitantly, these data indicate that '5-HT tone via 5-HT(1B) receptors' might function in a serial manner from STM to LTM, whereas working in parallel using 5-HT(1A), 5-HT(2A), 5-HT(2B/2C), 5-HT(4), or 5-HT(6) receptors.

Novel Small Molecules Disabling the IL-6/IL-6R/GP130 Heterohexamer Complex

DTIC Science & Technology

2012-10-01

fluctuations over 20 ns MD simulation. The HFI unit of MDL-A showed instability in the gp130 D1-domain binding pocket, whereas the hydrophobic tail...compound containing only an HFI unit was not capable of inhibiting gp130 homodimerization. Our MDLs MD simulation studies showed consistent results...chain attached to the HFI unit which is designed to take advantage of interactions with the “additional” subpockets surrounding the MDL-A binding site

Emulsion-core and polyelectrolyte-shell nanocapsules: biocompatibility and neuroprotection against SH-SY5Y cells

NASA Astrophysics Data System (ADS)

Piotrowski, Marek; Szczepanowicz, Krzysztof; Jantas, Danuta; Leśkiewicz, Monika; Lasoń, Władysław; Warszyński, Piotr

2013-11-01

The emulsion-core and polyelectrolyte-coated nanocapsules, designed as water-insoluble neuroprotective drug delivery system, were synthesized using layer-by-layer saturation method. The isopropyl myristate was used as oil phase and docusate sodium salt as emulsifier. For the polyelectrolyte shell preparation, synthetic polyelectrolytes, cationic (PDADMAC, PAH, and PLL) and anionic (PGA) were used. The particle size and zeta potential of nanocapsules were characterized by the dynamic light scattering. The average size of synthesized nanocapsules ranged from 80 to 100 nm. Zeta potential values ranged from less than approximately -30 mV for the polyanion layers to greater than approximately +30 mV for the polycation layers. Biocompatibilities of the synthesized nanocarriers were evaluated against SH-SY5Y human neuroblastoma cells using various biochemical assays. The results obtained show that synthesized nanocapsules coated with PLL and PGA were nontoxic to SH-SY5Y cells, and they were used as nanocarriers for model neuroprotective drug (a calpain inhibitor MDL 28170). The neuroprotective action of the encapsulated MDL 28170 against hydrogen peroxide-induced oxidative stress cytotoxicity was evaluated in the same cell line. The results showed that nanoencapsulated form of MDL 28170 were biocompatible and protected SH-SY5Y cells against the H2O2 (0.5 mM/24 h)-induced damage in 20-40 times lower concentrations than those of the same drug added directly to the culture medium. These data suggest that the nanoscale carriers of neuroprotective drugs might serve as novel promising therapeutic agents for oxidative stress-related neurodegenerative processes.

A multi-dielectric-layered triboelectric nanogenerator as energized by corona discharge.

PubMed

Shao, Jia Jia; Tang, Wei; Jiang, Tao; Chen, Xiang Yu; Xu, Liang; Chen, Bao Dong; Zhou, Tao; Deng, Chao Ran; Wang, Zhong Lin

2017-07-13

Triboelectric nanogenerators (TENGs) have been invented recently for meeting the power requirements of small electronics and potentially solving the worldwide energy crisis. Here, we developed a vertical contact-separation mode TENG based on a novel multi-dielectric-layered (MDL) structure, which was comprised of parylene C, polyimide and SiO 2 films. By using the corona discharge approach, the surface charge density was enhanced to as high as 283 μC m -2 , and especially the open-circuit voltage could be increased by a factor of 55 compared with the original value. Furthermore, the theoretical models were built to reveal the output characteristics and store the electrostatic energy of the TENG. The influences of the structural parameters and operation conditions including the effective dielectric thickness, dielectric constant, gap distance and air breakdown voltage were investigated systematically. It was found that the output performances such as the peak voltage and power density are approximately proportional to the thickness of the MDL film, but they would be restricted by the air breakdown voltage. These unique structures and models could be used to deepen the understanding of the fundamental mechanism of TENGs, and serve as an important guide for designing high performance TENGs.

Minimum Description Length Block Finder, a Method to Identify Haplotype Blocks and to Compare the Strength of Block Boundaries

PubMed Central

Mannila, H.; Koivisto, M.; Perola, M.; Varilo, T.; Hennah, W.; Ekelund, J.; Lukk, M.; Peltonen, L.; Ukkonen, E.

2003-01-01

We describe a new probabilistic method for finding haplotype blocks that is based on the use of the minimum description length (MDL) principle. We give a rigorous definition of the quality of a segmentation of a genomic region into blocks and describe a dynamic programming algorithm for finding the optimal segmentation with respect to this measure. We also describe a method for finding the probability of a block boundary for each pair of adjacent markers: this gives a tool for evaluating the significance of each block boundary. We have applied the method to the published data of Daly and colleagues. The results expose some problems that exist in the current methods for the evaluation of the significance of predicted block boundaries. Our method, MDL block finder, can be used to compare block borders in different sample sets, and we demonstrate this by applying the MDL-based method to define the block structure in chromosomes from population isolates. PMID:12761696

Minimum description length block finder, a method to identify haplotype blocks and to compare the strength of block boundaries.

PubMed

Mannila, H; Koivisto, M; Perola, M; Varilo, T; Hennah, W; Ekelund, J; Lukk, M; Peltonen, L; Ukkonen, E

2003-07-01

We describe a new probabilistic method for finding haplotype blocks that is based on the use of the minimum description length (MDL) principle. We give a rigorous definition of the quality of a segmentation of a genomic region into blocks and describe a dynamic programming algorithm for finding the optimal segmentation with respect to this measure. We also describe a method for finding the probability of a block boundary for each pair of adjacent markers: this gives a tool for evaluating the significance of each block boundary. We have applied the method to the published data of Daly and colleagues. The results expose some problems that exist in the current methods for the evaluation of the significance of predicted block boundaries. Our method, MDL block finder, can be used to compare block borders in different sample sets, and we demonstrate this by applying the MDL-based method to define the block structure in chromosomes from population isolates.

Modeling sports highlights using a time-series clustering framework and model interpretation

NASA Astrophysics Data System (ADS)

Radhakrishnan, Regunathan; Otsuka, Isao; Xiong, Ziyou; Divakaran, Ajay

2005-01-01

In our past work on sports highlights extraction, we have shown the utility of detecting audience reaction using an audio classification framework. The audio classes in the framework were chosen based on intuition. In this paper, we present a systematic way of identifying the key audio classes for sports highlights extraction using a time series clustering framework. We treat the low-level audio features as a time series and model the highlight segments as "unusual" events in a background of an "usual" process. The set of audio classes to characterize the sports domain is then identified by analyzing the consistent patterns in each of the clusters output from the time series clustering framework. The distribution of features from the training data so obtained for each of the key audio classes, is parameterized by a Minimum Description Length Gaussian Mixture Model (MDL-GMM). We also interpret the meaning of each of the mixture components of the MDL-GMM for the key audio class (the "highlight" class) that is correlated with highlight moments. Our results show that the "highlight" class is a mixture of audience cheering and commentator's excited speech. Furthermore, we show that the precision-recall performance for highlights extraction based on this "highlight" class is better than that of our previous approach which uses only audience cheering as the key highlight class.

Directly Observable Behavioral Effects of Lorcaserin in Rats.

PubMed

Serafine, Katherine M; Rice, Kenner C; France, Charles P

2015-12-01

(1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (lorcaserin) is approved by the United States Food and Drug Administration for treating obesity, and its therapeutic effects are thought to result from agonist activity at serotonin (5-HT)2C receptors. Lorcaserin has affinity for other 5-HT receptor subtypes, although its activity at those subtypes is not fully described. The current study compared the behavioral effects of lorcaserin (0.0032-32.0 mg/kg) to the effects of other 5-HT receptor selective agonists in rats (n = 8). The 5-HT2C receptor selective agonist 1-(3-chlorophenyl)piperazine (mCPP, 0.032-1.0 mg/kg) and lorcaserin induced yawning which was attenuated by the 5-HT2C receptor selective antagonist 6-chloro-5-methyl-N-(6-[(2-methylpyridin-3-yl)oxy]pydidin-3-yl)indoline-1-carboxamide (1.0 mg/kg). The 5-HT2A receptor selective agonist 2,5-dimethoxy-4-methylamphetamine (0.1-3.2 mg/kg) induced head twitching, which was attenuated by the 5-HT2A receptor selective antagonist R-(+)-2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] (MDL 100907, 0.01 mg/kg), lorcaserin (3.2 mg/kg), and mCPP (3.2 mg/kg). In rats pretreated with MDL 100907 (1.0 mg/kg), lorcaserin also induced head twitching. At larger doses, lorcaserin produced forepaw treading, which was attenuated by the 5-HT1A receptor selective antagonist N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridyl)cyclohexanecarboxamide (0.178 mg/kg). While the behavioral effects of lorcaserin in rats are consistent with it having agonist activity at 5-HT2C receptors, these data suggest that at larger doses it also has agonist activity at 5-HT2A and possibly 5-HT1A receptors. Mounting evidence suggests that 5-HT2C receptor agonists might be effective for treating drug abuse. A more complete description of the activity of lorcaserin at 5-HT receptor subtypes will facilitate a better understanding of the mechanisms that mediate its therapeutic effects. U.S. Government work not protected by U.S. copyright.

Directly Observable Behavioral Effects of Lorcaserin in Rats

PubMed Central

Serafine, Katherine M.; Rice, Kenner C.

2015-01-01

(1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (lorcaserin) is approved by the United States Food and Drug Administration for treating obesity, and its therapeutic effects are thought to result from agonist activity at serotonin (5-HT)2C receptors. Lorcaserin has affinity for other 5-HT receptor subtypes, although its activity at those subtypes is not fully described. The current study compared the behavioral effects of lorcaserin (0.0032–32.0 mg/kg) to the effects of other 5-HT receptor selective agonists in rats (n = 8). The 5-HT2C receptor selective agonist 1-(3-chlorophenyl)piperazine (mCPP, 0.032–1.0 mg/kg) and lorcaserin induced yawning which was attenuated by the 5-HT2C receptor selective antagonist 6-chloro-5-methyl-N-(6-[(2-methylpyridin-3-yl)oxy]pydidin-3-yl)indoline-1-carboxamide (1.0 mg/kg). The 5-HT2A receptor selective agonist 2,5-dimethoxy-4-methylamphetamine (0.1–3.2 mg/kg) induced head twitching, which was attenuated by the 5-HT2A receptor selective antagonist R-(+)-2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] (MDL 100907, 0.01 mg/kg), lorcaserin (3.2 mg/kg), and mCPP (3.2 mg/kg). In rats pretreated with MDL 100907 (1.0 mg/kg), lorcaserin also induced head twitching. At larger doses, lorcaserin produced forepaw treading, which was attenuated by the 5-HT1A receptor selective antagonist N-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridyl)cyclohexanecarboxamide (0.178 mg/kg). While the behavioral effects of lorcaserin in rats are consistent with it having agonist activity at 5-HT2C receptors, these data suggest that at larger doses it also has agonist activity at 5-HT2A and possibly 5-HT1A receptors. Mounting evidence suggests that 5-HT2C receptor agonists might be effective for treating drug abuse. A more complete description of the activity of lorcaserin at 5-HT receptor subtypes will facilitate a better understanding of the mechanisms that mediate its therapeutic effects. PMID:26384326

Collaboration space division in collaborative product development based on a genetic algorithm

NASA Astrophysics Data System (ADS)

Qian, Xueming; Ma, Yanqiao; Feng, Huan

2018-02-01

The advance in the global environment, rapidly changing markets, and information technology has created a new stage for design. In such an environment, one strategy for success is the Collaborative Product Development (CPD). Organizing people effectively is the goal of Collaborative Product Development, and it solves the problem with certain foreseeability. The development group activities are influenced not only by the methods and decisions available, but also by correlation among personnel. Grouping the personnel according to their correlation intensity is defined as collaboration space division (CSD). Upon establishment of a correlation matrix (CM) of personnel and an analysis of the collaboration space, the genetic algorithm (GA) and minimum description length (MDL) principle may be used as tools in optimizing collaboration space. The MDL principle is used in setting up an object function, and the GA is used as a methodology. The algorithm encodes spatial information as a chromosome in binary. After repetitious crossover, mutation, selection and multiplication, a robust chromosome is found, which can be decoded into an optimal collaboration space. This new method can calculate the members in sub-spaces and individual groupings within the staff. Furthermore, the intersection of sub-spaces and public persons belonging to all sub-spaces can be determined simultaneously.

Ca2+ and calpain mediate capsaicin-induced ablation of axonal terminals expressing transient receptor potential vanilloid 1.

PubMed

Wang, Sheng; Wang, Sen; Asgar, Jamila; Joseph, John; Ro, Jin Y; Wei, Feng; Campbell, James N; Chung, Man-Kyo

2017-05-19

Capsaicin is an ingredient in spicy peppers that produces burning pain by activating transient receptor potential vanilloid 1 (TRPV1), a Ca 2+ -permeable ion channel in nociceptors. Capsaicin has also been used as an analgesic, and its topical administration is approved for the treatment of certain pain conditions. The mechanisms underlying capsaicin-induced analgesia likely involve reversible ablation of nociceptor terminals. However, the mechanisms underlying these effects are not well understood. To visualize TRPV1-lineage axons, a genetically engineered mouse model was used in which a fluorophore is expressed under the TRPV1 promoter. Using a combination of these TRPV1-lineage reporter mice and primary afferent cultures, we monitored capsaicin-induced effects on afferent terminals in real time. We found that Ca 2+ influx through TRPV1 is necessary for capsaicin-induced ablation of nociceptive terminals. Although capsaicin-induced mitochondrial Ca 2+ uptake was TRPV1-dependent, dissipation of the mitochondrial membrane potential, inhibition of the mitochondrial transition permeability pore, and scavengers of reactive oxygen species did not attenuate capsaicin-induced ablation. In contrast, MDL28170, an inhibitor of the Ca 2+ -dependent protease calpain, diminished ablation. Furthermore, overexpression of calpastatin, an endogenous inhibitor of calpain, or knockdown of calpain 2 also decreased ablation. Quantitative assessment of TRPV1-lineage afferents in the epidermis of the hind paws of the reporter mice showed that EGTA and MDL28170 diminished capsaicin-induced ablation. Moreover, MDL28170 prevented capsaicin-induced thermal hypoalgesia. These results suggest that TRPV1/Ca 2+ /calpain-dependent signaling plays a dominant role in capsaicin-induced ablation of nociceptive terminals and further our understanding of the molecular mechanisms underlying the effects of capsaicin on nociceptors. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

TH-AB-209-02: Gadolinium Measurements in Human Bone Using in Vivo K X-Ray Fluorescence (KXRF) Technique

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

Mostafaei, F; Nie, L

Purpose: Improvement in an in vivo K x-ray fluorescence system, based on 109Cd source, for the detection of gadolinium (Gd) in bone has been investigated. Series of improvements to the method is described. Gd is of interest because of the extensive use of Gd-based contrast agents in MR imaging and the potential toxicity of Gd exposure. Methods: A set of seven bone equivalent phantoms with different amount of Gd concentrations (from 0–100 ppm) has been developed. Soft tissue equivalent plastic plates were used to simulate the soft tissue overlaying the tibia bone in an in vivo measurement. A new 5more » GBq 109Cd source was used to improve the source activity in comparison to the previous study (0.17 GBq). An improved spectral fitting program was utilized for data analysis. Results: The previous published minimum detection limit (MDL) for Gd doped phantom measurements using KXRF system was 3.3 ppm. In this study the MDL for bare bone phantoms was found to be 0.8 ppm. Our previous study used only three layers of plastic (0.32, 0.64 and 0.96 mm) as soft tissue equivalent materials and obtained the MDL of 4–4.8 ppm. In this study the plastic plates with more realistic thicknesses to simulate the soft tissue covering tibia bone (nine thicknesses ranging from 0.61–6.13 mm) were used. The MDLs for phantoms were determined to be 1.8–3.5 ppm. Conclusion: With the improvements made to the technology (stronger source, improved data analysis algorithm, realistic soft tissue thicknesses), the MDL of the KXRF system to measure Gd in bare bone was improved by a factor of 4.1. The MDL is at the level of the bone Gd concentration reported in literature. Hence, the system is ready to be tested on human subjects to investigate the use of bone Gd as a biomarker for Gd toxicity.« less

Modulation of haloperidol-induced patterns of the transcription factor Nur77 and Nor-1 expression by serotonergic and adrenergic drugs in the mouse brain

PubMed Central

Maheux, Jérôme; Vuillier, Laura; Mahfouz, Mylène; Rouillard, Claude; Lévesque, Daniel

2015-01-01

Different patterns of expression of the transcription factors of Nur77 and Nor-1 are induced following acute administration of typical and atypical antipsychotic drugs. The pharmacological profile of atypical antipsychotics suggests that serotonergic and/or adrenergic receptors might contribute to these reported differences. In order to test this possibility, we examined the abilities of serotonin 5-HT1A and 5-HT2A/2C, and α1- and α2-adrenergic receptor drugs to modify the pattern of Nur77 (NR4A1) and Nor-1 (NR4A3) mRNA expression induced by haloperidol. Various groups of mice were treated with either saline, DOI, a 5-HT2A/2C agonist, MDL11939, a 5-HT2A antagonist, 8-OH-DPAT, a 5-HT1A agonist, prazosin, an α1-adrenergic antagonist and idazoxan, an α2-adrenergic antagonist, alone or in combination with haloperidol. The 5-HT2A/2C agonist DOI alone significantly increased Nur77 expression in the medial striatum and nucleus accumbens. DOI reduced Nor-1 expression, while MDL11939 increased the expression of this transcript in the cortex. Prazosin reduced Nur77 expression in the dorsal striatum and nucleus accumbens. Interestingly, 8-OH-DPAT and MDL11939 partially prevented haloperidol-induced Nur77 up-regulation, while MDL11939 completely abolished Nor-1 expression in the striatum. In addition, MDL11939 decreased haloperidol-induced Nur77 and Nor-1 mRNA levels in the ventral tegmental area. On the contrary, idazoxan (α2 antagonist) consistently potentiated haloperidol-induced Nur77, but not Nor-1 mRNA levels in the striatum, whereas prazosin (α1 antagonist) remained without effect. Taken together, these results show the ability of a 5-HT1A agonist or a 5-HT2A antagonist to reduce haloperidol-induced Nur77 and Nor-1 striatal expression, suggesting that these serotonin receptor subtypes participate in the differential pattern of gene expression induced by typical and atypical antipsychotic drugs. PMID:21524335

The effect of 7,8-methylenedioxylycoctonine-type diterpenoid alkaloids on the toxicity of methyllycaconitine in mice.

PubMed

Welch, K D; Panter, K E; Gardner, D R; Green, B T; Pfister, J A; Cook, D; Stegelmeier, B L

2008-10-01

Larkspur plants contain numerous norditerpenoid alkaloids, which include the 7,8-methylenedioxylycoctonine (MDL)-type alkaloids and the N-(methylsuccinimido)anthranoyllycoctonine (MSAL)-type alkaloids. The MSAL-type alkaloids are generally much more toxic (typically >20 times). Toxicity of many tall larkspurs, such as Delphinium barbeyi, has been attributed to its large concentration of MSAL-type alkaloids, including methyllycaconitine (MLA). However, the norditerpenoid alkaloids found in the greatest concentrations in most D. barbeyi populations are either deltaline or 14-O-acetyldictyocarpine (14-OAD), both less toxic MDL-type alkaloids. Although the individual toxicities of MLA, 14-OAD, and deltaline have been determined, the impact (additive or antagonistic) that large concentrations of deltaline or 14-OAD in the plant have on the toxicity of MLA is unknown. Consequently, the effect of MDL-type alkaloids on the toxicity of MLA was compared by using median lethal dose (LD(50)) and toxicokinetic profiles of the brainand muscle from mice receiving i.v. administration of these alkaloids, individually or in combination, at ratios of 1:1, 1:5, and 1:25 MLA to MDL-type alkaloids. The LD(50) for MLA alone was 4.4 +/- 0.7 mg/kg of BW, whereas the coadministration of MLA and deltaline at 1:1, 1:5, and 1:25 resulted in an LD(50) of 2.7, 2.5, and 1.9 mg/kg of BW, respectively. Similarly, the coadministration of MLA and 14-OAD at 1:1, 1:5, and 1:25 resulted in an LD(50) of 3.1, 2.2, and 1.5 mg/kg of BW, respectively. Coadministration of mixtures did not result in increased MLA bioavailability or alterations in clearance from the brain and muscle. Consequently, the increased toxicity of the mixtures was not a result of increased MLA bioavailability (based on the maximum concentrations observed) or alterations in MLA clearance from the brain and muscle, because these were unchanged. These results demonstrate that MDL-type alkaloids have an additive effect on MLA toxicity in mice and may also play a role in the overall toxicity of tall larkspur plants in cattle.

Lactational exposure to short-chain chlorinated paraffins in China, Korea, and Japan.

PubMed

Cao, Yang; Harada, Kouji H; Hitomi, Toshiaki; Niisoe, Tamon; Wang, Peiyu; Shi, Yuhui; Yang, Hye-Ran; Takasuga, Takumi; Koizumi, Akio

2017-04-01

To investigate short-chain chlorinated paraffin (SCCP) levels in human breast milk, pooled breast milk samples (BMSs) collected between 2007 and 2010 from Chinese (Beijing, n = 17), Korean (Seoul, Busan, n = 16), and Japanese (Kyoto, Sendai, n = 44) women were analyzed. SCCPs found in air samples in Beijing (n = 4, in 2008) were also analyzed and compared with BMSs to estimate the possible source of contamination in Beijing. The electron-capture negative ionization method demonstrated the different sensitivities for SCCPs, and pentachlorinated alkanes had the highest method detection limit (MDL) among congeners. In Beijing, SCCPs were detected in 8 of 17 pooled BMSs at concentrations more than the highest MDL of each homolog. The total SCCP concentration ranged from below the MDL to 54 ng g -1 lipid weight. Among the SCCP homologs, polychlorinated tridecanes were most frequently detected in Beijing. In Korea and Japan, no samples contained detectable total SCCP concentrations at more than the highest MDL. In Seoul, only two samples showed trace levels of polychlorinated undecanes. In Kyoto and Sendai, congeners of polychlorinated dodecanes were most frequently detected. C 10 components were the major contributors to the SCCPs in the atmosphere of Beijing. Congener profiles in breast milk in Beijing provided a clear contrast to the profiles found in food and air. The unique congener profiles necessitate the monitoring of breast milk for exposure of infants to SCCPs. The calculated mean exposure of SCCPs in 1-year-olds in China was 337 ng (kg body weight) -1  d -1 . These results demonstrate the body burden of SCCPs in the study areas and potential lactational exposure to SCCPs in Asian countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Measurement of nitrous acid (HONO) by external-cavity quantum cascade laser based quartz-enhanced photoacoustic absorption spectroscopy

NASA Astrophysics Data System (ADS)

Yi, Hongming; Maamary, Rabih; Gao, Xiaoming; Sigrist, Markus W.; Fertein, Eric; Chen, Weidong

2016-04-01

Spectroscopic detection of short-lived gaseous nitrous acid (HONO) at 1254.85 cm-1 was realized by off-beam coupled quartz-enhanced photoacoustic spectroscopy (QEPAS) in conjunction with an external cavity quantum cascade lasers (EC-QCL). High sensitivity monitoring of HONO was performed within a very small gas-sample volume (of ~40 mm3) allowing a significant reduction (of about 4 orders of magnitude) of air sampling residence time which is highly desired for accurate quantification of chemically reactive short-lived species. Calibration of the developed QEPAS-based HONO sensor was carried out by means of lab-generated HONO samples whose concentrations were determined by simultaneous measurements of direct HONO absorption spectra in a 109.5 m multipass cell using a distributed feedback (DBF) QCL. A minimum detection limit (MDL @ SNR=1) of 66 ppbv HONO was achieved at 70 mbar using a laser output power of 50 mW and 1 s integration time, which corresponded to a normalized noise equivalent absorption coefficient of 3.6×10-8 cm-1.W/Hz1/2. This MDL was down to 7 ppbv at the optimal integration time of 150 s. The corresponding minimum detected absorption coefficient (SNR=1) is ~1.1×10-7 cm-1 (MDL: ~3 ppbv) in 1 s and ~1.1×10-8 cm-1 (MDL~330 pptv) in 150 s, respectively, with 1 W laser power. Acknowledgements The authors acknowledge financial supports from the CaPPA project (ANR-10-LABX-005) and the CPER CLIMIBIO program. References H. Yi, R. Maamary, X. Gao, M. W. Sigrist, E. Fertein, W. Chen, "Short-lived species detection of nitrous acid by external-cavity quantum cascade laser based quartz-enhanced photoacoustic absorption spectroscopy", Appl. Phys. Lett. 106 (2015) 101109

Psychomotor stimulant effects of beta-phenylethylamine in monkeys treated with MAO-B inhibitors.

PubMed

Bergman, J; Yasar, S; Winger, G

2001-12-01

Sufficiently high doses of beta-phenylethylamine (beta-PEA), a trace amine that is rapidly metabolized by monoamine oxidase-type B (MAO-B), can produce effects comparable to those of cocaine or methamphetamine (MA). The present experiments were conducted to study how the discriminative-stimulus (S(D)) and reinforcing-stimulus (S(R)) effects of beta-PEA in monkeys are modified by treatment with inhibitors of MAO-B [R-(-)-deprenyl and MDL 72974]. In studies of its S(D) effects, doses of beta-PEA up to 30 mg/kg engendered only sporadic responding on the drug-associated lever in squirrel monkeys that discriminated intramuscular injections of 0.3 mg/kg MA from vehicle whereas lower doses of 0.3-1.0 mg/kg beta-PEA produced full substitution when administered after either R-(-)-deprenyl or MDL 72974 (0.3 mg/kg). The MA-like S(D) effects of beta-PEA were attenuated by either dopamine D(1) or D(2) receptor blockers. In studies of its S(R) effects, high doses of beta-PEA maintained responding in two of three monkeys under a second-order fixed-interval schedule (3.0 or 10 mg/kg per injection) and two of three monkeys under a simple fixed ratio (FR) schedule (0.3-1.0 mg/kg per injection) of intravenous (i.v.) self-administration. MAO-B inhibition by R-(-)-deprenyl or MDL 72974 enhanced the S(R) effects of beta-PEA in all monkeys and, under the FR schedule, induced a 30-fold or greater leftward shift in the dose-response function for its i.v. self-administration. Based on time-course determinations, the enhanced S(R) effects of beta-PEA under the FR schedule were long-lasting and dissipated gradually over 3-7 days. These results show that inhibition of MAO-B enhances S(D) and S(R) effects of beta-PEA in monkeys, presumably by delaying its inactivation. MAO-B inhibition leading to increased levels of beta-PEA may be useful, alone or in combination with other therapeutic agents, in the pharmacological management of selected aspects of drug dependence.

Displacement sensors using soft magnetostrictive alloys

NASA Astrophysics Data System (ADS)

Hristoforou, E.; Reilly, R. E.

1994-09-01

We report results on the response of a family of displacement sensors, which are based on the magentostrictive delay line (MDL) technique, using current conductors orthogonal to the MDL. Such sensing technique is based on the change of the magnetic circuit at the acoustic stress point of origin due to the displacement of a soft magnetic material above it. Integrated arrays of sensors can be obtained due to the acoustic delay line technique and they can be used as tactile arrays, digitizers or devices for medical applications (gait analysis etc.), while absence of hysteresis and low cost of manufacturing make them competent in this sector of sensor market.

Gas detection by correlation spectroscopy employing a multimode diode laser.

PubMed

Lou, Xiutao; Somesfalean, Gabriel; Zhang, Zhiguo

2008-05-01

A gas sensor based on the gas-correlation technique has been developed using a multimode diode laser (MDL) in a dual-beam detection scheme. Measurement of CO(2) mixed with CO as an interfering gas is successfully demonstrated using a 1570 nm tunable MDL. Despite overlapping absorption spectra and occasional mode hops, the interfering signals can be effectively excluded by a statistical procedure including correlation analysis and outlier identification. The gas concentration is retrieved from several pair-correlated signals by a linear-regression scheme, yielding a reliable and accurate measurement. This demonstrates the utility of the unsophisticated MDLs as novel light sources for gas detection applications.

X-Ray Microanalysis and Electron Energy Loss Spectrometry in the Analytical Electron Microscope: Review and Future Directions

NASA Technical Reports Server (NTRS)

Goldstein, J. I.; Williams, D. B.

1992-01-01

This paper reviews and discusses future directions in analytical electron microscopy for microchemical analysis using X-ray and Electron Energy Loss Spectroscopy (EELS). The technique of X-ray microanalysis, using the ratio method and k(sub AB) factors, is outlined. The X-ray absorption correction is the major barrier to the objective of obtaining I% accuracy and precision in analysis. Spatial resolution and Minimum Detectability Limits (MDL) are considered with present limitations of spatial resolution in the 2 to 3 microns range and of MDL in the 0.1 to 0.2 wt. % range when a Field Emission Gun (FEG) system is used. Future directions of X-ray analysis include improvement in X-ray spatial resolution to the I to 2 microns range and MDL as low as 0.01 wt. %. With these improvements the detection of single atoms in the analysis volume will be possible. Other future improvements include the use of clean room techniques for thin specimen preparation, quantification available at the I% accuracy and precision level with light element analysis quantification available at better than the 10% accuracy and precision level, the incorporation of a compact wavelength dispersive spectrometer to improve X-ray spectral resolution, light element analysis and MDL, and instrument improvements including source stability, on-line probe current measurements, stage stability, and computerized stage control. The paper reviews the EELS technique, recognizing that it has been slow to develop and still remains firmly in research laboratories rather than in applications laboratories. Consideration of microanalysis with core-loss edges is given along with a discussion of the limitations such as specimen thickness. Spatial resolution and MDL are considered, recognizing that single atom detection is already possible. Plasmon loss analysis is discussed as well as fine structure analysis. New techniques for energy-loss imaging are also summarized. Future directions in the EELS technique will be the development of new spectrometers and improvements in thin specimen preparation. The microanalysis technique needs to be simplified and software developed so that the EELS technique approaches the relative simplicity of the X-ray technique. Finally, one can expect major improvements in EELS imaging as data storage and processing improvements occur.

Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms.

PubMed

Jiang, Xi-Ling; Shen, Hong-Wu; Yu, Ai-Ming

2016-06-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are indolealkylamine (IAA) drugs often abused together. Our recent studies have revealed the significant effects of co-administered harmaline, a monoamine oxidase inhibitor (MAOI), on 5-MeO-DMT pharmacokinetics and thermoregulation. This study was to delineate the impact of harmaline and 5-MeO-DMT on home-cage activity in mouse models, as well as the contribution of serotonin (5-HT) receptors. Home-cage activities of individual animals were monitored automatically in the home cages following implantation of telemetry transmitters and administration of various doses of IAA drugs and 5-HT receptor antagonists. Area under the effect curve (AUEC) of mouse activity values were calculated by trapezoidal rule. High dose of harmaline (15mg/kg, ip) alone caused an early-phase (0-45min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45-180min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20mg/kg, ip) alone induced biphasic effects, an early-phase (0-45min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45-180min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2-15mg/kg) with a subthreshold dose of 5-MeO-DMT (2mg/kg) induced excessive hyperactivities at late phase (45-180min) that could be abolished by either WAY-100635 or MDL-100907. Co-administration of MAOI with 5-MeO-DMT provokes excessive late-phase hyperactivity, which involves the activation of both 5-HT1A and 5-HT2A receptors. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms

PubMed Central

Jiang, Xi-Ling; Shen, Hong-Wu; Yu, Ai-Ming

2016-01-01

Background 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are indolealkylamine (IAA) drugs often abused together. Our recent studies have revealed the significant effects of co-administered harmaline, a monoamine oxidase inhibitor (MAOI), on 5-MeO-DMT pharmacokinetics and thermoregulation. This study was to delineate the impact of harmaline and 5-MeO-DMT on home-cage activity in mouse models, as well as the contribution of serotonin (5-HT) receptors. Methods Home-cage activities of individual animals were monitored automatically in the home cages following implantation of telemetry transmitters and administration of various doses of IAA drugs and 5-HT receptor antagonists. Area under the effect curve (AUEC) of mouse activity values were calculated by trapezoidal rule. Results High dose of harmaline (15 mg/kg, ip) alone caused an early-phase (0–45 min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45–180 min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20 mg/kg, ip) alone induced biphasic effects, an early-phase (0–45 min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45–180 min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2–15 mg/kg) with a subthreshold dose of 5-MeO-DMT (2 mg/kg) induced excessive hyperactivities at late phase (45–180 min) that could be abolished by either WAY-100635 or MDL-100907. Conclusions Co-administration of MAOI with 5-MeO-DMT provokes excessive late-phase hyperactivity, which involves the activation of both 5-HT1A and 5-HT2A receptors. PMID:26977821

Displacement sensors using soft magnetostrictive alloys

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

Hristoforou, E.; Reilly, R.E.

1994-09-01

The authors report results on the response of a family of displacement sensors, which are based on the magnetostrictive delay line (MDL) technique, using current conductor orthogonal to the MDL. Such sensing technique is based on the change of the magnetic circuit and the acoustic stress point of origin due to the displacement of a soft magnetic material above it. Integrated arrays of sensors can be obtained due to the acoustic delay line technique and they can be used as tactile arrays, digitizers or devices for medical application (gait analysis etc.), while absence of hysteresis and low cost of manufacturingmore » make them competent in this sector of sensor market.« less

Imaging features of macrodystrophia lipomatosa: an unusual cause of a brawny arm

PubMed Central

Dhanasekaran, Jagadeesan; Reddy, Ajit Kumar; Sarawagi, Radha; Lakshmanan, Prakash Manikka

2014-01-01

Macrodystrophia lipomatosa (MDL), a rare non-hereditary congenital disorder of localised gigantism, is characterised by progressive proliferation of all mesenchymal elements, with a disproportionate increase in fibroadipose tissue. We report a case of a 19-year-old man who presented with a history of painless enlargement of the left upper limb since childhood, which was gradually increasing in size and predominantly involving the radial aspect of the upper limb with relative sparing of the ulnar aspect. The patient was imaged with X-ray and MRI. Imaging and clinical features were classical of MDL. The patient underwent stage 1 reduction plasty of the left forearm; preoperative and histopathological findings confirmed the preoperative diagnosis. PMID:25406225

Implicit Regularization for Reconstructing 3D Building Rooftop Models Using Airborne LiDAR Data

PubMed Central

Jung, Jaewook; Jwa, Yoonseok; Sohn, Gunho

2017-01-01

With rapid urbanization, highly accurate and semantically rich virtualization of building assets in 3D become more critical for supporting various applications, including urban planning, emergency response and location-based services. Many research efforts have been conducted to automatically reconstruct building models at city-scale from remotely sensed data. However, developing a fully-automated photogrammetric computer vision system enabling the massive generation of highly accurate building models still remains a challenging task. One the most challenging task for 3D building model reconstruction is to regularize the noises introduced in the boundary of building object retrieved from a raw data with lack of knowledge on its true shape. This paper proposes a data-driven modeling approach to reconstruct 3D rooftop models at city-scale from airborne laser scanning (ALS) data. The focus of the proposed method is to implicitly derive the shape regularity of 3D building rooftops from given noisy information of building boundary in a progressive manner. This study covers a full chain of 3D building modeling from low level processing to realistic 3D building rooftop modeling. In the element clustering step, building-labeled point clouds are clustered into homogeneous groups by applying height similarity and plane similarity. Based on segmented clusters, linear modeling cues including outer boundaries, intersection lines, and step lines are extracted. Topology elements among the modeling cues are recovered by the Binary Space Partitioning (BSP) technique. The regularity of the building rooftop model is achieved by an implicit regularization process in the framework of Minimum Description Length (MDL) combined with Hypothesize and Test (HAT). The parameters governing the MDL optimization are automatically estimated based on Min-Max optimization and Entropy-based weighting method. The performance of the proposed method is tested over the International Society for Photogrammetry and Remote Sensing (ISPRS) benchmark datasets. The results show that the proposed method can robustly produce accurate regularized 3D building rooftop models. PMID:28335486

Implicit Regularization for Reconstructing 3D Building Rooftop Models Using Airborne LiDAR Data.

PubMed

Jung, Jaewook; Jwa, Yoonseok; Sohn, Gunho

2017-03-19

With rapid urbanization, highly accurate and semantically rich virtualization of building assets in 3D become more critical for supporting various applications, including urban planning, emergency response and location-based services. Many research efforts have been conducted to automatically reconstruct building models at city-scale from remotely sensed data. However, developing a fully-automated photogrammetric computer vision system enabling the massive generation of highly accurate building models still remains a challenging task. One the most challenging task for 3D building model reconstruction is to regularize the noises introduced in the boundary of building object retrieved from a raw data with lack of knowledge on its true shape. This paper proposes a data-driven modeling approach to reconstruct 3D rooftop models at city-scale from airborne laser scanning (ALS) data. The focus of the proposed method is to implicitly derive the shape regularity of 3D building rooftops from given noisy information of building boundary in a progressive manner. This study covers a full chain of 3D building modeling from low level processing to realistic 3D building rooftop modeling. In the element clustering step, building-labeled point clouds are clustered into homogeneous groups by applying height similarity and plane similarity. Based on segmented clusters, linear modeling cues including outer boundaries, intersection lines, and step lines are extracted. Topology elements among the modeling cues are recovered by the Binary Space Partitioning (BSP) technique. The regularity of the building rooftop model is achieved by an implicit regularization process in the framework of Minimum Description Length (MDL) combined with Hypothesize and Test (HAT). The parameters governing the MDL optimization are automatically estimated based on Min-Max optimization and Entropy-based weighting method. The performance of the proposed method is tested over the International Society for Photogrammetry and Remote Sensing (ISPRS) benchmark datasets. The results show that the proposed method can robustly produce accurate regularized 3D building rooftop models.

BACKGROUND TRACK DENSITY REDUCTION OF 50-HZ-HV ECE-PROCESSED THICK POLYCARBONATE DETECTORS TO IMPROVE LOWER DETECTION LIMIT.

PubMed

Sohrabi, M; Hakimi, A; Soltani, Z

2016-12-01

A recent novel development of 50-Hz-HV ECE of 1-mm-thick and 250-µm-thick polycarbonate track detectors (PCTDs) has proved some promising results for some health physics, dosimetry and ion-beam-related applications. The method while proved having some good characteristics for some applications provided a relatively higher background track density (BGTD) in particular when very high voltages are applied to the PCTDs. In order to decrease the minimum detection limit (MDL) of the PCTDs and to further promote its applications for low dose, the BGTD was reduced by applying a layer removal methodology applying ethylendiamine (EDA). The effects of EDA concentrations (50, 60, 65, 70, 75, 80, 85 and 90 %) in water at room temperature (26°C) and soaking durations up to 100 min at different EDA concentration on BGTD reduction were studied. The thickness of the layer removed from the surface of a PCTD highly depends on the soaking time and EDA concentration; it increases as the EDA concentration increases up to for example 700 µm after 2 h of soaking in the EDA solution. After ∼10 min of soaking duration at any of the above-stated concentrations, the BGTD reaches its minimum value, a value which differs from concentration to concentration. An EDA concentration of 85 % in water provided the lowest BGTD of 64.06 ± 3.12 tracks cm - 2 ; ∼6 times lower than that of its original value. It is shown that the layer removal process does not change the registration characteristics of the PCTD and its appearance significantly. The MDL of the PCTDs depends strongly on the BGTD. The MDL values for a desired confidence level were also studied by three calculation methods. The results of the BGTD and the MDL studies under different conditions applied are presented and discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Role of 5-HT2A, 5-HT2C and mGlu2 Receptors in the Behavioral Effects of Tryptamine Hallucinogens N,N-Dimethyltryptamine and N,N-Diisopropyltryptamine in Rats and Mice

PubMed Central

Carbonaro, Theresa M.; Eshleman, Amy J.; Forster, Michael J.; Cheng, Kejun; Rice, Kenner C.; Gatch, Michael B.

2014-01-01

Rationale: Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. Objective: The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Methods: Drug discrimination, head twitch and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084) and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. Results: MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT’s effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low potency full agonist at 5-HT2CR in vitro. Conclusions: The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree. PMID:24985890

The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

PubMed

Carbonaro, Theresa M; Eshleman, Amy J; Forster, Michael J; Cheng, Kejun; Rice, Kenner C; Gatch, Michael B

2015-01-01

Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro. The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.

Few-mode fiber, splice and SDM component characterization by spatially-diverse optical vector network analysis.

PubMed

Rommel, Simon; Mendinueta, José Manuel Delgado; Klaus, Werner; Sakaguchi, Jun; Olmos, Juan José Vegas; Awaji, Yoshinari; Monroy, Idelfonso Tafur; Wada, Naoya

2017-09-18

This paper discusses spatially diverse optical vector network analysis for space division multiplexing (SDM) component and system characterization, which is becoming essential as SDM is widely considered to increase the capacity of optical communication systems. Characterization of a 108-channel photonic lantern spatial multiplexer, coupled to a 36-core 3-mode fiber, is experimentally demonstrated, extracting the full impulse response and complex transfer function matrices as well as insertion loss (IL) and mode-dependent loss (MDL) data. Moreover, the mode-mixing behavior of fiber splices in the few-mode multi-core fiber and their impact on system IL and MDL are analyzed, finding splices to cause significant mode-mixing and to be non-negligible in system capacity analysis.

Imaging features of macrodystrophia lipomatosa: an unusual cause of a brawny arm.

PubMed

Dhanasekaran, Jagadeesan; Reddy, Ajit Kumar; Sarawagi, Radha; Lakshmanan, Prakash Manikka

2014-11-18

Macrodystrophia lipomatosa (MDL), a rare non-hereditary congenital disorder of localised gigantism, is characterised by progressive proliferation of all mesenchymal elements, with a disproportionate increase in fibroadipose tissue. We report a case of a 19-year-old man who presented with a history of painless enlargement of the left upper limb since childhood, which was gradually increasing in size and predominantly involving the radial aspect of the upper limb with relative sparing of the ulnar aspect. The patient was imaged with X-ray and MRI. Imaging and clinical features were classical of MDL. The patient underwent stage 1 reduction plasty of the left forearm; preoperative and histopathological findings confirmed the preoperative diagnosis. 2014 BMJ Publishing Group Ltd.

Calpain-2 Regulates TNF-α Expression Associated with Neuropathic Pain Following Motor Nerve Injury.

PubMed

Chen, Shao-Xia; Liao, Guang-Jie; Yao, Pei-Wen; Wang, Shao-Kun; Li, Yong-Yong; Zeng, Wei-An; Liu, Xian-Guo; Zang, Ying

2018-04-15

Both calpain-2 (CALP2) and tumor necrosis factor-α (TNF-α) contribute to persistent bilateral hypersensitivity in animals subjected to L5 ventral root transection (L5-VRT), a model of selective motor fiber injury without sensory nerve damage. However, specific upstream mechanisms regulating TNF-α overexpression and possible relationships linking CALP2 and TNF-α have not yet been investigated in this model. We examined changes in CALP2 and TNF-α protein levels and alterations in bilateral mechanical threshold within 24 h following L5-VRT model injury. We observed robust elevation of CALP2 and TNF-α in bilateral dorsal root ganglias (DRGs) and bilateral spinal cord neurons. CALP2 and TNF-α protein induction by L5-VRT were significantly inhibited by pretreatment using the calpain inhibitor MDL28170. Administration of CALP2 to rats without nerve injury further supported a role of CALP2 in the regulation of TNF-α expression. Although clinical trials of calpain inhibition therapy for alleviation of neuropathic pain induced by motor nerve injury have not yet shown success, our observations linking CALP2 and TNF-α provide a framework of a systems' approach based perspective for treating neuropathic pain. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Fault Network Reconstruction using Agglomerative Clustering: Applications to South Californian Seismicity

NASA Astrophysics Data System (ADS)

Kamer, Yavor; Ouillon, Guy; Sornette, Didier; Wössner, Jochen

2014-05-01

We present applications of a new clustering method for fault network reconstruction based on the spatial distribution of seismicity. Unlike common approaches that start from the simplest large scale and gradually increase the complexity trying to explain the small scales, our method uses a bottom-up approach, by an initial sampling of the small scales and then reducing the complexity. The new approach also exploits the location uncertainty associated with each event in order to obtain a more accurate representation of the spatial probability distribution of the seismicity. For a given dataset, we first construct an agglomerative hierarchical cluster (AHC) tree based on Ward's minimum variance linkage. Such a tree starts out with one cluster and progressively branches out into an increasing number of clusters. To atomize the structure into its constitutive protoclusters, we initialize a Gaussian Mixture Modeling (GMM) at a given level of the hierarchical clustering tree. We then let the GMM converge using an Expectation Maximization (EM) algorithm. The kernels that become ill defined (less than 4 points) at the end of the EM are discarded. By incrementing the number of initialization clusters (by atomizing at increasingly populated levels of the AHC tree) and repeating the procedure above, we are able to determine the maximum number of Gaussian kernels the structure can hold. The kernels in this configuration constitute our protoclusters. In this setting, merging of any pair will lessen the likelihood (calculated over the pdf of the kernels) but in turn will reduce the model's complexity. The information loss/gain of any possible merging can thus be quantified based on the Minimum Description Length (MDL) principle. Similar to an inter-distance matrix, where the matrix element di,j gives the distance between points i and j, we can construct a MDL gain/loss matrix where mi,j gives the information gain/loss resulting from the merging of kernels i and j. Based on this matrix, merging events resulting in MDL gain are performed in descending order until no gainful merging is possible anymore. We envision that the results of this study could lead to a better understanding of the complex interactions within the Californian fault system and hopefully use the acquired insights for earthquake forecasting.

Improving microbial biogasoline production in Escherichia coli using tolerance engineering.

PubMed

Foo, Jee Loon; Jensen, Heather M; Dahl, Robert H; George, Kevin; Keasling, Jay D; Lee, Taek Soon; Leong, Susanna; Mukhopadhyay, Aindrila

2014-11-04

Engineering microbial hosts for the production of fungible fuels requires mitigation of limitations posed on the production capacity. One such limitation arises from the inherent toxicity of solvent-like biofuel compounds to production strains, such as Escherichia coli. Here we show the importance of host engineering for the production of short-chain alcohols by studying the overexpression of genes upregulated in response to exogenous isopentenol. Using systems biology data, we selected 40 genes that were upregulated following isopentenol exposure and subsequently overexpressed them in E. coli. Overexpression of several of these candidates improved tolerance to exogenously added isopentenol. Genes conferring isopentenol tolerance phenotypes belonged to diverse functional groups, such as oxidative stress response (soxS, fpr, and nrdH), general stress response (metR, yqhD, and gidB), heat shock-related response (ibpA), and transport (mdlB). To determine if these genes could also improve isopentenol production, we coexpressed the tolerance-enhancing genes individually with an isopentenol production pathway. Our data show that expression of 6 of the 8 candidates improved the production of isopentenol in E. coli, with the methionine biosynthesis regulator MetR improving the titer for isopentenol production by 55%. Additionally, expression of MdlB, an ABC transporter, facilitated a 12% improvement in isopentenol production. To our knowledge, MdlB is the first example of a transporter that can be used to improve production of a short-chain alcohol and provides a valuable new avenue for host engineering in biogasoline production. The use of microbial host platforms for the production of bulk commodities, such as chemicals and fuels, is now a focus of many biotechnology efforts. Many of these compounds are inherently toxic to the host microbe, which in turn places a limit on production despite efforts to optimize the bioconversion pathways. In order to achieve economically viable production levels, it is also necessary to engineer production strains with improved tolerance to these compounds. We demonstrate that microbial tolerance engineering using transcriptomics data can also identify targets that improve production. Our results include an exporter and a methionine biosynthesis regulator that improve isopentenol production, providing a starting point to further engineer the host for biogasoline production. Copyright © 2014 Foo et al.

Improving microbial biogasoline production in Escherichia coli using tolerance engineering

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

Foo, Jee Loon; Jensen, Heather M.; Dahl, Robert H.

Engineering microbial hosts for the production of fungible fuels requires mitigation of limitations posed on the production capacity. One such limitation arises from the inherent toxicity of solvent-like biofuel compounds to production strains, such as Escherichia coli. Here we show the importance of host engineering for the production of short-chain alcohols by studying the overexpression of genes upregulated in response to exogenous isopentenol. Using systems biology data, we selected 40 genes that were upregulated following isopentenol exposure and subsequently overexpressed them in E. coli. Overexpression of several of these candidates improved tolerance to exogenously added isopentenol. Genes conferring isopentenol tolerancemore » phenotypes belonged to diverse functional groups, such as oxidative stress response ( soxS, fpr, and nrdH), general stress response ( metR, yqhD, and gidB), heat shock-related response ( ibpA), and transport ( mdlB). To determine if these genes could also improve isopentenol production, we coexpressed the tolerance-enhancing genes individually with an isopentenol production pathway. Our data show that expression of 6 of the 8 candidates improved the production of isopentenol in E. coli, with the methionine biosynthesis regulator MetR improving the titer for isopentenol production by 55%. Additionally, expression of MdlB, an ABC transporter, facilitated a 12% improvement in isopentenol production. To our knowledge, MdlB is the first example of a transporter that can be used to improve production of a short-chain alcohol and provides a valuable new avenue for host engineering in biogasoline production.The use of microbial host platforms for the production of bulk commodities, such as chemicals and fuels, is now a focus of many biotechnology efforts. Many of these compounds are inherently toxic to the host microbe, which in turn places a limit on production despite efforts to optimize the bioconversion pathways. In order to achieve economically viable production levels, it is also necessary to engineer production strains with improved tolerance to these compounds. We demonstrate that microbial tolerance engineering using transcriptomics data can also identify targets that improve production. Our results include an exporter and a methionine biosynthesis regulator that improve isopentenol production, providing a starting point to further engineer the host for biogasoline production.« less

Improving microbial biogasoline production in Escherichia coli using tolerance engineering

DOE PAGES

Foo, Jee Loon; Jensen, Heather M.; Dahl, Robert H.; ...

2014-11-04

Engineering microbial hosts for the production of fungible fuels requires mitigation of limitations posed on the production capacity. One such limitation arises from the inherent toxicity of solvent-like biofuel compounds to production strains, such as Escherichia coli. Here we show the importance of host engineering for the production of short-chain alcohols by studying the overexpression of genes upregulated in response to exogenous isopentenol. Using systems biology data, we selected 40 genes that were upregulated following isopentenol exposure and subsequently overexpressed them in E. coli. Overexpression of several of these candidates improved tolerance to exogenously added isopentenol. Genes conferring isopentenol tolerancemore » phenotypes belonged to diverse functional groups, such as oxidative stress response ( soxS, fpr, and nrdH), general stress response ( metR, yqhD, and gidB), heat shock-related response ( ibpA), and transport ( mdlB). To determine if these genes could also improve isopentenol production, we coexpressed the tolerance-enhancing genes individually with an isopentenol production pathway. Our data show that expression of 6 of the 8 candidates improved the production of isopentenol in E. coli, with the methionine biosynthesis regulator MetR improving the titer for isopentenol production by 55%. Additionally, expression of MdlB, an ABC transporter, facilitated a 12% improvement in isopentenol production. To our knowledge, MdlB is the first example of a transporter that can be used to improve production of a short-chain alcohol and provides a valuable new avenue for host engineering in biogasoline production.The use of microbial host platforms for the production of bulk commodities, such as chemicals and fuels, is now a focus of many biotechnology efforts. Many of these compounds are inherently toxic to the host microbe, which in turn places a limit on production despite efforts to optimize the bioconversion pathways. In order to achieve economically viable production levels, it is also necessary to engineer production strains with improved tolerance to these compounds. We demonstrate that microbial tolerance engineering using transcriptomics data can also identify targets that improve production. Our results include an exporter and a methionine biosynthesis regulator that improve isopentenol production, providing a starting point to further engineer the host for biogasoline production.« less

A quantification method for peroxyacetyl nitrate (PAN) using gas chromatography (GC) with a non-radioactive pulsed discharge detector (PDD)

NASA Astrophysics Data System (ADS)

Zhang, Lei; Jaffe, Daniel A.; Gao, Xin; McClure, Crystal D.

2018-04-01

In this study, we developed a method for continuous PAN measurements by gas chromatography (GC) with a non-radioactive pulsed discharge detector (PDD). Operational parameters were optimized based on the ratio of peak height over baseline noise (P/N ratio). The GC/PDD system was compared with a traditional radioactive electron-capture detector (ECD). In the lab, the method detection limit (MDL) of the new GC/PDD method (9 pptv) was lower than the radioactive GC/ECD method (15 pptv), demonstrating its excellent potential. The MDL of GC/PDD in the field campaign at the Mt. Bachelor Observatory (MBO) was 23 pptv, higher than in the lab. This was caused in part by the decreased slope of the calibration curve resulting from the low air pressure level at MBO. However, the MDL level of GC/PDD at MBO is still low enough for accurate PAN measurements, although special attention should be paid to its application at high-elevation sites. Observations of PAN were conducted at MBO in the summer of 2016 with the GC/PDD system, and provided more evidence of the performance of the system. PAN was found to be highly correlated with CO. The promising performance of GC/PDD which does not require a radioactive source makes it a useful approach for accurate PAN measurements in the field.

Online clustering algorithms for radar emitter classification.

PubMed

Liu, Jun; Lee, Jim P Y; Senior; Li, Lingjie; Luo, Zhi-Quan; Wong, K Max

2005-08-01

Radar emitter classification is a special application of data clustering for classifying unknown radar emitters from received radar pulse samples. The main challenges of this task are the high dimensionality of radar pulse samples, small sample group size, and closely located radar pulse clusters. In this paper, two new online clustering algorithms are developed for radar emitter classification: One is model-based using the Minimum Description Length (MDL) criterion and the other is based on competitive learning. Computational complexity is analyzed for each algorithm and then compared. Simulation results show the superior performance of the model-based algorithm over competitive learning in terms of better classification accuracy, flexibility, and stability.

Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors

PubMed Central

Halberstadt, Adam L.; Buell, Mahalah R.; Masten, Virginia L.; Risbrough, Victoria B.; Geyer, Mark A.

2010-01-01

RATIONALE The hallucinogenic tea known as ayahuasca is made from a combination of psychoactive plants that contribute the active components N,N-dimethyltryptamine (DMT) and 5-methoxy-DMT (5-MeO-DMT), as well as the monoamine oxidase (MAO) inhibitors (MAOIs) harmine and harmaline for oral activity. OBJECTIVE The present study examined the effects of 5-MeO-DMT in combination with MAOIs in rats using the Behavioral Pattern Monitor (BPM), which enables analyses of patterns of locomotor activity and exploration. Interaction studies using the serotonin (5-HT)1A antagonist WAY-100635 (1.0 mg/kg) and the 5-HT2A antagonist MDL 11,939 (1.0 mg/kg) were also performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in MAOI-treated animals. RESULTS 5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg) decreased locomotor activity and investigatory behavior. In rats pretreated with a behaviorally inactive dose of harmaline (0.1 mg/kg), 1.0 mg/kg 5-MeO-DMT had biphasic effects on locomotor activity, initially reducing locomotion and then increasing activity as time progressed. The ability of harmaline to shift 5-MeO-DMT to a biphasic locomotor pattern was shared by the selective MAOA inhibitor clorgyline, whereas the selective MAOB inhibitor (−)-deprenyl was ineffective. The late hyperactivity induced by the combination of 1.0 mg/kg 5-MeO-DMT and 0.3 mg/kg clorgyline was blocked by pretreatment with MDL 11,939. Pretreatment with WAY-100635 failed to attenuate either the early hypoactivity or the late hyperactivity. CONCLUSIONS The ability of harmaline to modify the behavioral effects of 5-MeO-DMT is mediated by inhibition of MAOA. Further, 5-HT2A receptors are responsible for the late hyperactivity induced by 5-MeO-DMT in the presence of MAOA inhibitors. PMID:18604652

Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors.

PubMed

Halberstadt, Adam L; Buell, Mahalah R; Masten, Virginia L; Risbrough, Victoria B; Geyer, Mark A

2008-11-01

The hallucinogenic tea known as ayahuasca is made from a combination of psychoactive plants that contribute the active components N,N-dimethyltryptamine (DMT) and 5-methoxy-DMT (5-MeO-DMT), as well as the monoamine oxidase (MAO) inhibitors (MAOIs) harmine and harmaline for oral activity. The present study examined the effects of 5-MeO-DMT in combination with MAOIs in rats using the behavioral pattern monitor, which enables analyses of patterns of locomotor activity and exploration. Interaction studies using the serotonin (5-HT)(1A) antagonist WAY-100635 (1.0 mg/kg) and the 5-HT(2A) antagonist MDL 11,939 (1.0 mg/kg) were also performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in MAOI-treated animals. 5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg) decreased locomotor activity and investigatory behavior. In rats pretreated with a behaviorally inactive dose of harmaline (0.1 mg/kg), 1.0 mg/kg 5-MeO-DMT had biphasic effects on locomotor activity, initially reducing locomotion and then increasing activity as time progressed. The ability of harmaline to shift 5-MeO-DMT to a biphasic locomotor pattern was shared by the selective MAO(A) inhibitor clorgyline, whereas the selective MAO(B) inhibitor (-)-deprenyl was ineffective. The late hyperactivity induced by the combination of 1.0 mg/kg 5-MeO-DMT and 0.3 mg/kg clorgyline was blocked by pretreatment with MDL 11,939. Pretreatment with WAY-100635 failed to attenuate either the early hypoactivity or the late hyperactivity. The ability of harmaline to modify the behavioral effects of 5-MeO-DMT is mediated by the inhibition of MAO(A). Furthermore, 5-HT(2A) receptors are responsible for the late hyperactivity induced by 5-MeO-DMT in the presence of MAO(A) inhibitors.

Blockade of 5-hydroxytryptamine(3) receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat

NASA Technical Reports Server (NTRS)

Lucot, James B.

1989-01-01

The effects of the 5-hydroxytryptamine(3) (5-HT-3) antagonists ICS 205-930 and MDL 72222 on the emesis induced by motion or by emetic doses of xylazine (0.66 mg/kg administered SC) or cisplatin (7.5 mg/kg infused over a period of 4-5 min) were investigated in cats. It was found that neither the low (0.1 mg/kg) or the high (1.0 mg.kg) doses of ICS 205-930 or MDL 72222 prevented emesis elicited by screening motion challenges or xylazine. On the other hand, treatment cats by 1.0 mg/kg of ICS 205-930 was effective against cisplatin-induced motion sickness, in agreement with earlier results obtained on other mammals.

Evidence for a role of 5-HT2C receptors in the motor aspects of performance, but not the efficacy of food reinforcers, in a progressive ratio schedule.

PubMed

Bezzina, G; Body, S; Cheung, T H C; Hampson, C L; Bradshaw, C M; Glennon, J C; Szabadi, E

2015-02-01

5-Hydroxytryptamine2C (5-HT2C) receptor agonists reduce the breakpoint in progressive ratio schedules of reinforcement, an effect that has been attributed to a decrease of the efficacy of positive reinforcers. However, a reduction of the breakpoint may also reflect motor impairment. Mathematical models can help to differentiate between these processes. The effects of the 5-HT2C receptor agonist Ro-600175 ((αS)-6-chloro-5-fluoro-α-methyl-1H-indole-1-ethanamine) and the non-selective 5-HT receptor agonist 1-(m-chlorophenyl)piperazine (mCPP) on rats' performance on a progressive ratio schedule maintained by food pellet reinforcers were assessed using a model derived from Killeen's Behav Brain Sci 17:105-172, 1994 general theory of schedule-controlled behaviour, 'mathematical principles of reinforcement'. Rats were trained under the progressive ratio schedule, and running and overall response rates in successive ratios were analysed using the model. The effects of the agonists on estimates of the model's parameters, and the sensitivity of these effects to selective antagonists, were examined. Ro-600175 and mCPP reduced the breakpoint. Neither agonist significantly affected a (the parameter expressing incentive value), but both agonists increased δ (the parameter expressing minimum response time). The effects of both agonists could be attenuated by the selective 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-N-{6-[(2-methylpyridin-3-yl)oxy]pyridin-3-yl}indoline-1-carboxamide). The effect of mCPP was not altered by isamoltane, a selective 5-HT1B receptor antagonist, or MDL-100907 ((±)2,3-dimethoxyphenyl-1-(2-(4-piperidine)methanol)), a selective 5-HT2A receptor antagonist. The results are consistent with the hypothesis that the effect of the 5-HT2C receptor agonists on progressive ratio schedule performance is mediated by an impairment of motor capacity rather than by a reduction of the incentive value of the food reinforcer.

N1-Nonyl-1,4-diaminobutane ameliorates brain infarction size in photochemically induced thrombosis model mice.

PubMed

Masuko, Takashi; Takao, Koichi; Samejima, Keijiro; Shirahata, Akira; Igarashi, Kazuei; Casero, Robert A; Kizawa, Yasuo; Sugita, Yoshiaki

2018-04-13

Inhibitors for polyamine oxidizing enzymes, spermine oxidase (SMOX) and N 1 -acetylpolyamine oxidase (PAOX), were designed and evaluated for their effectiveness in a photochemically induced thrombosis (PIT) mouse model. N 1 -Nonyl-1,4-diaminobutane (C9-4) and N 1 -tridecyl-1,4-diaminobutane (C13-4) competitively inhibited the activity of PAOX and SMOX in a manner comparable to N 1 ,N 4 -bis(2,3-butadienyl)-1,4-butanediamine (MDL72527), an irreversible inhibitor of both enzymes. The two compounds were then tested for their effects in the PIT model. Both intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of C9-4 decreased infarct volumes significantly. By contrast, C13-4 reduced the volume of brain infarction by i.c.v. administration, but no reduction was observed after i.p. administration. C9-4 administered by i.p. injection reduced the volume of brain infarction significantly at doses of more than 3 mg/kg, and the dosage of 5 mg/kg or 10 mg/kg demonstrated the most potent effect and were more effective than equivalent doses of the other inhibitors such as MDL72527 and N-benzylhydroxylamine. I.P. injection of 5 mg/kg of C9-4 provided a therapeutic time window of longer than 12 h. This report demonstrates that C9-4 is a potent inhibitor of the polyamine oxidizing enzymes and is useful lead compound for candidate drugs with a long therapeutic time window, to be used in the treatment of ischemic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Methodology using a portable X-ray fluorescence device for on-site and rapid evaluation of heavy-atom contamination in wounds: a model study for application to plutonium contamination.

PubMed

Yoshii, Hiroshi; Yanagihara, Kouta; Imaseki, Hitoshi; Hamano, Tsuyoshi; Yamanishi, Hirokuni; Inagaki, Masayo; Sakai, Yasuhiro; Sugiura, Nobuyuki; Kurihara, Osamu; Sakai, Kazuo

2014-01-01

Workers decommissioning the Fukushima-Daiichi nuclear power plant damaged from the Great East Japan Earthquake and resulting tsunami are at risk of injury with possible contamination from radioactive heavy atoms including actinides, such as plutonium. We propose a new methodology for on-site and rapid evaluation of heavy-atom contamination in wounds using a portable X-ray fluorescence (XRF) device. In the present study, stable lead was used as the model contaminant substitute for radioactive heavy atoms. First, the wound model was developed by placing a liquid blood phantom on an epoxy resin wound phantom contaminated with lead. Next, the correlation between the concentration of contaminant and the XRF peak intensity was formulated considering the thickness of blood exiting the wound. Methods to determine the minimum detection limit (MDL) of contaminants at any maximal equivalent dose to the wound by XRF measurement were also established. For example, in this system, at a maximal equivalent dose of 16.5 mSv to the wound and blood thickness of 0.5 mm, the MDL value for lead was 1.2 ppm (3.1 nmol). The radioactivity of 239Pu corresponding to 3.1 nmol is 1.7 kBq, which is lower than the radioactivity of 239Pu contaminating puncture wounds in previous severe accidents. In conclusion, the established methodology could be beneficial for future development of a method to evaluate plutonium contamination in wounds. Highlights: Methodology for evaluation of heavy-atom contamination in a wound was established. A portable X-ray fluorescence device enables on-site, rapid and direct evaluation. This method is expected to be used for evaluation of plutonium contamination in wounds.

Cultured rat vascular smooth muscle cells are resistant to methylamine toxicity: no correlation to semicarbazide-sensitive amine oxidase

NASA Technical Reports Server (NTRS)

Langford, S. D.; Trent, M. B.; Boor, P. J.

2001-01-01

Methylamine (MA), a component of serum and a metabolite of nicotine and certain insecticides and herbicides, is metabolized by semicarbazide-sensitive amine oxidase (SSAO). MA is toxic to cultured human umbilical vein and calf pulmonary artery endothelial cells. Endothelial cells, which do not exhibit endogenous SSAO activity, are exposed to SSAO circulating in serum. In contrast, vascular smooth muscle cells (VSMC) do exhibit innate SSAO activity both in vivo and in vitro. This property, together with the critical localization of VSMC within the arterial wall, led us to investigate the potential toxicity of MA to VSMC. Cultured rat VSMC were treated with MA (10-5 to 1 M). In some cultures, SSAO was selectively inhibited with semicarbazide or MDL-72145 [(E)-2-(3,4-dimethoxyphenyl)-3-fluoroallylamine]. Cytotoxicity was measured via MTT, vital dye exclusion, and clonogenic assays. MA proved to be toxic to VSMC only at relatively high concentrations (LC(50) of 0.1 M). The inhibition of SSAO with semicarbazide or MDL-72145 did not increase MA toxicity, suggesting that the production of formaldehyde via tissue-bound, SSAO-mediated MA metabolism does not play a role in the minimal toxicity observed in isolated rat VSMC. The omission of fetal calf serum (FCS), which contains high SSAO activity, from media similarly showed little effect on cytotoxicity. We conclude that VSMC--in contrast to previous results in endothelial cells--are relatively resistant to MA toxicity, and SSAO does not play a role in VSMC injury by MA.

Estrogenic effects in the influents and effluents of the drinking water treatment plants.

PubMed

Gou, Yan-You; Lin, Susana; Que, Danielle E; Tayo, Lemmuel L; Lin, Ding-Yan; Chen, Kuan-Chung; Chen, Fu-An; Chiang, Pen-Chi; Wang, Gen-Shuh; Hsu, Yi-Chyuan; Chuang, Kuo Pin; Chuang, Chun-Yu; Tsou, Tsui-Chun; Chao, How-Ran

2016-05-01

Estrogen-like endocrine disrupting compounds (EEDC) such as bisphenol A, nonylphenol, and phthalic acid esters are toxic compounds that may occur in both raw- and drinking water. The aim of this study was to combine chemical- and bioassay to evaluate the risk of EEDCs in the drinking water treatment plants (DWTPs). Fifty-six samples were collected from seven DWTPs located in northern-, central-, and southern Taiwan from 2011 to 2012 and subjected to chemical analyses and two bioassay methods for total estrogenic activity (E-Screen and T47D-KBluc assay). Among of the considered EEDCs, only dibutyl phthalate (DBP) and di (2-ethylhexyl) phthalate (DEHP) were detected in both drinking and raw water samples. DBP levels in drinking water ranged from

An Ultra-Trace Analysis Technique for SF6 Using Gas Chromatography with Negative Ion Chemical Ionization Mass Spectrometry.

PubMed

Jong, Edmund C; Macek, Paul V; Perera, Inoka E; Luxbacher, Kray D; McNair, Harold M

2015-07-01

Sulfur hexafluoride (SF6) is widely used as a tracer gas because of its detectability at low concentrations. This attribute of SF6 allows the quantification of both small-scale flows, such as leakage, and large-scale flows, such as atmospheric currents. SF6's high detection sensitivity also facilitates greater usage efficiency and lower operating cost for tracer deployments by reducing quantity requirements. The detectability of SF6 is produced by its high molecular electronegativity. This property provides a high potential for negative ion formation through electron capture thus naturally translating to selective detection using negative ion chemical ionization mass spectrometry (NCI-MS). This paper investigates the potential of using gas chromatography (GC) with NCI-MS for the detection of SF6. The experimental parameters for an ultra-trace SF6 detection method utilizing minimal customizations of the analytical instrument are detailed. A method for the detection of parts per trillion (ppt) level concentrations of SF6 for the purpose of underground ventilation tracer gas analysis was successfully developed in this study. The method utilized a Shimadzu gas chromatography with negative ion chemical ionization mass spectrometry system equipped with an Agilent J&W HP-porous layer open tubular column coated with an alumina oxide (Al2O3) S column. The method detection limit (MDL) analysis as defined by the Environmental Protection Agency of the tracer data showed the method MDL to be 5.2 ppt. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Methods of Analysis by the U.S. Geological Survey Organic Geochemistry Research Group-Update and Additions to the Determination of Chloroacetanilide Herbicide Degradation Compounds in Water Using High-Performance Liquid Chromatography/Mass Spectrometry

USGS Publications Warehouse

Lee, E.A.; Kish, J.L.; Zimmerman, L.R.; Thurman, E.

2001-01-01

An analytical method using high-performance liquid chromatography/mass spectrometry (HPLC/MS) was developed by the U.S. Geological Survey in 1999 for the analysis of selected chloroacetanilide herbicide degradation compounds in water. These compounds were acetochlor ethane sulfonic acid (ESA), acetochlor oxanilic acid (OXA), alachlor ESA, alachlor OXA, metolachlor ESA, and metolachlor OXA. The HPLC/MS method was updated in 2000, and the method detection limits were modified accordingly. Four other degradation compounds also were added to the list of compounds that can be analyzed using HPLC/MS; these compounds were dimethenamid ESA, dimethenamid OXA, flufenacet ESA, and flufenacet OXA. Except for flufenacet OXA, good precision and accuracy were demonstrated for the updated HPLC/MS method in buffered reagent water, surface water, and ground water. The mean HPLC/MS recoveries of the degradation compounds from water samples spiked at 0.20 and 1.0 ?g/L (microgram per liter) ranged from 75 to 114 percent, with relative standard deviations of 15.8 percent or less for all compounds except flufenacet OXA, which had relative standard deviations ranging from 11.3 to 48.9 percent. Method detection levels (MDL's) using the updated HPLC/MS method varied from 0.009 to 0.045 ?g/L, with the flufenacet OXA MDL at 0.072 ?g/L. The updated HPLC/MS method is valuable for acquiring information about the fate and transport of the parent chloroacetanilide herbicides in water.

Blood Lead Levels in Captive Giant Pandas.

PubMed

Wintle, Nathan J P; Martin-Wintle, Meghan S; Zhou, Xiaoping; Zhang, Hemin

2018-01-01

Fifteen giant pandas (Ailuropoda melanoleuca) from the Chinese Conservation and Research Center for the Giant Panda (CCRCGP) in Bifengxia, Sichuan, China were analyzed for blood lead concentrations (Pb-B) during the 2017 breeding season. Thirteen of the 15 bears showed Pb-B below the method detection limit (MDL) of 3.3 µg/dL. The two remaining bears, although above the MDL, contained very low concentrations of lead of 3.9 and 4.5 µg/dL. All 15 giant pandas in this analysis had Pb-B concentrations that were within normal background concentrations for mammals in uncontaminated environments. For a threatened species, whose native country is plagued by reports of extremely high air pollution, our findings suggest that giant pandas at the CCRCGP are not absorbing lead at concentrations that would adversely affect their health.

Changepoint detection in base-resolution methylome data reveals a robust signature of methylated domain landscape.

PubMed

Yokoyama, Takao; Miura, Fumihito; Araki, Hiromitsu; Okamura, Kohji; Ito, Takashi

2015-08-12

Base-resolution methylome data generated by whole-genome bisulfite sequencing (WGBS) is often used to segment the genome into domains with distinct methylation levels. However, most segmentation methods include many parameters to be carefully tuned and/or fail to exploit the unsurpassed resolution of the data. Furthermore, there is no simple method that displays the composition of the domains to grasp global trends in each methylome. We propose to use changepoint detection for domain demarcation based on base-resolution methylome data. While the proposed method segments the methylome in a largely comparable manner to conventional approaches, it has only a single parameter to be tuned. Furthermore, it fully exploits the base-resolution of the data to enable simultaneous detection of methylation changes in even contrasting size ranges, such as focal hypermethylation and global hypomethylation in cancer methylomes. We also propose a simple plot termed methylated domain landscape (MDL) that globally displays the size, the methylation level and the number of the domains thus defined, thereby enabling one to intuitively grasp trends in each methylome. Since the pattern of MDL often reflects cell lineages and is largely unaffected by data size, it can serve as a novel signature of methylome. Changepoint detection in base-resolution methylome data followed by MDL plotting provides a novel method for methylome characterization and will facilitate global comparison among various WGBS data differing in size and even species origin.

[Future Regulatory Science through a Global Product Development Strategy to Overcome the Device Lag].

PubMed

Tsuchii, Isao

2016-01-01

Environment that created "medical device lag (MDL)" has changed dramatically, and currently that term is not heard often. This was mainly achieved through the leadership of three groups: government, which determined to overcome MDL and took steps to do so; medical societies, which exhibited accountability in trial participation; and MD companies, which underwent a change in mindset that allowed comprehensive tripartite cooperation to reach the current stage. In particular, the global product development strategy (GPDS) of companies in a changing social environment has taken a new-turn with international harmonization trends, like Global Harmonization Task Force and International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. As a result, this evolution has created opportunities for treatment with cutting-edge MDs in Japanese society. Simultaneously, it has had a major impact on the planning process of GPDS of companies. At the same time, the interest of global companies has shifted to emerging economies for future potential profit since Japan no longer faces MDL issue. This economic trend makes MDLs a greater problem for manufacturers. From the regulatory science viewpoint, this new environment has not made it easy to plan a global strategy that will be adaptable to local societies. Without taking hasty action, flexible thinking from the global point of view is necessary to enable the adjustment of local strategies to fit the situation on the ground so that the innovative Japanese medical technology can be exported to a broad range of societies.

Stimulation of the young poor responder: comparison of the luteal estradiol/gonadotropin-releasing hormone antagonist priming protocol versus oral contraceptive microdose leuprolide.

PubMed

Shastri, Shefali M; Barbieri, Elizabeth; Kligman, Isaac; Schoyer, Katherine D; Davis, Owen K; Rosenwaks, Zev

2011-02-01

To evaluate in vitro fertilization (IVF) cycle outcomes in young poor responders treated with a luteal estradiol/gonadotropin-releasing hormone antagonist (E(2)/ANT) protocol versus an oral contraceptive pill microdose leuprolide protocol (OCP-MDL). Retrospective cohort. Academic practice. Poor responders: 186 women, aged <35 years undergoing IVF with either E(2)/ANT or OCP-MDL protocols. None. Clinical pregnancies, oocytes retrieved, cancellation rate. Patients in the E(2)/ANT group had a greater gonadotropin requirement (71.9 ± 22.2 vs. 57.6 ± 25.7) and lower E(2) level (1,178.6 ± 668 vs. 1,627 ± 889), yet achieved similar numbers of oocytes retrieved and fertilized, and a greater number of embryos transferred (2.3 ± 0.9 vs. 2.0 ± 1.1) with a better mean grade (2.14 ± .06 vs. 2.7 ± 1.8) compared with the OCP/MDL group. The E2/ANT group exhibited a trend toward improved implantation rates (30.5% vs. 21.1%) and ongoing pregnancy rates per started cycle: 44 out of 117 (37%) versus 17 out of 69 (25%). Poor responders aged <35 years may be treated with the aggressive E(2)/ANT protocol to improve cycle outcomes. Both protocols remain viable options for this group. Adequately powered, randomized clinical comparison appears justified. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Biogenic unmodified gold nanoparticles for selective and quantitative detection of cerium using UV-vis spectroscopy and photon correlation spectroscopy (DLS).

PubMed

Priyadarshini, E; Pradhan, N; Panda, P K; Mishra, B K

2015-06-15

The ability of self-functionalized biogenic GNPs towards highly selective colorimetric detection of rare earth element cerium is being reported for the first time. GNPs underwent rapid aggregation on addition of cerium indicated by red shift of SPR peak followed by complete precipitation. Hereby, this concept of co-ordination of cerium ions onto the GNP surface has been utilized for detection of cerium. The remarkable capacity of GNPs to sensitively detect Ce without proves beneficial compared to previous reports of colorimetric sensing. MDL was 15 and 35 ppm by DLS and UV-vis spectroscopy respectively, suggesting DLS to be highly sensitive and a practical alternative in ultrasensitive detection studies. The sensing system showed a good linear fit favouring feasible detection of cerium in range of 2-50 ppm. Similar studies further showed the superior selectivity of biogenic GNPs compared to chemically synthesized counterparts. The sensing system favours on-site analysis as it overcomes need of complex instrumentation, lengthy protocols and surface modification of GNP. Copyright © 2015 Elsevier B.V. All rights reserved.

New public QSAR model for carcinogenicity

PubMed Central

2010-01-01

Background One of the main goals of the new chemical regulation REACH (Registration, Evaluation and Authorization of Chemicals) is to fulfill the gaps in data concerned with properties of chemicals affecting the human health. (Q)SAR models are accepted as a suitable source of information. The EU funded CAESAR project aimed to develop models for prediction of 5 endpoints for regulatory purposes. Carcinogenicity is one of the endpoints under consideration. Results Models for prediction of carcinogenic potency according to specific requirements of Chemical regulation were developed. The dataset of 805 non-congeneric chemicals extracted from Carcinogenic Potency Database (CPDBAS) was used. Counter Propagation Artificial Neural Network (CP ANN) algorithm was implemented. In the article two alternative models for prediction carcinogenicity are described. The first model employed eight MDL descriptors (model A) and the second one twelve Dragon descriptors (model B). CAESAR's models have been assessed according to the OECD principles for the validation of QSAR. For the model validity we used a wide series of statistical checks. Models A and B yielded accuracy of training set (644 compounds) equal to 91% and 89% correspondingly; the accuracy of the test set (161 compounds) was 73% and 69%, while the specificity was 69% and 61%, respectively. Sensitivity in both cases was equal to 75%. The accuracy of the leave 20% out cross validation for the training set of models A and B was equal to 66% and 62% respectively. To verify if the models perform correctly on new compounds the external validation was carried out. The external test set was composed of 738 compounds. We obtained accuracy of external validation equal to 61.4% and 60.0%, sensitivity 64.0% and 61.8% and specificity equal to 58.9% and 58.4% respectively for models A and B. Conclusion Carcinogenicity is a particularly important endpoint and it is expected that QSAR models will not replace the human experts opinions and conventional methods. However, we believe that combination of several methods will provide useful support to the overall evaluation of carcinogenicity. In present paper models for classification of carcinogenic compounds using MDL and Dragon descriptors were developed. Models could be used to set priorities among chemicals for further testing. The models at the CAESAR site were implemented in java and are publicly accessible. PMID:20678182

Orbital

NASA Astrophysics Data System (ADS)

Hanson, Robert M.

2003-06-01

ORBITAL requires the following software, which is available for free download from the Internet: Netscape Navigator, version 4.75 or higher, or Microsoft Internet Explorer, version 5.0 or higher; Chime Plug-in, version compatible with your OS and browser (available from MDL).

The study of in vivo quantification of aluminum (Al) in human bone with a compact DD generator-based neutron activation analysis (NAA) system.

PubMed

Byrne, Patrick; Mostafaei, Farshad; Liu, Yingzi; Blake, Scott P; Koltick, David; Nie, Linda H

2016-05-01

The feasibility and methodology of using a compact DD generator-based neutron activation analysis system to measure aluminum in hand bone has been investigated. Monte Carlo simulations were used to simulate the moderator, reflector, and shielding assembly and to estimate the radiation dose. A high purity germanium (HPGe) detector was used to detect the Al gamma ray signals. The minimum detectable limit (MDL) was found to be 11.13 μg g(-1) dry bone (ppm). An additional HPGe detector would improve the MDL by a factor of 1.4, to 7.9 ppm. The equivalent dose delivered to the irradiated hand was calculated by Monte Carlo to be 11.9 mSv. In vivo bone aluminum measurement with the DD generator was found to be feasible among general population with an acceptable dose to the subject.

Investigation of adaptive filtering and MDL mitigation based on space-time block-coding for spatial division multiplexed coherent receivers

NASA Astrophysics Data System (ADS)

Weng, Yi; He, Xuan; Yao, Wang; Pacheco, Michelle C.; Wang, Junyi; Pan, Zhongqi

2017-07-01

In this paper, we explored the performance of space-time block-coding (STBC) assisted multiple-input multiple-output (MIMO) scheme for modal dispersion and mode-dependent loss (MDL) mitigation in spatial-division multiplexed optical communication systems, whereas the weight matrices of frequency-domain equalization (FDE) were updated heuristically using decision-directed recursive least squares (RLS) algorithm for convergence and channel estimation. The proposed STBC-RLS algorithm can achieve 43.6% enhancement on convergence rate over conventional least mean squares (LMS) for quadrature phase-shift keying (QPSK) signals with merely 16.2% increase in hardware complexity. The overall optical signal to noise ratio (OSNR) tolerance can be improved via STBC by approximately 3.1, 4.9, 7.8 dB for QPSK, 16-quadrature amplitude modulation (QAM) and 64-QAM with respective bit-error-rates (BER) and minimum-mean-square-error (MMSE).

Spinal 5-HT2 and 5-HT3 receptors mediate low, but not high, frequency TENS-induced antihyperalgesia in rats

PubMed Central

Radhakrishnan, Rajan; King, Ellen W.; Dickman, Janelle K.; Herold, Carli A.; Johnston, Natalie F.; Spurgin, Megan L.; Sluka, Kathleen A.

2009-01-01

Transcutaneous electrical nerve stimulation (TENS) is a form of non-pharmacological treatment for pain. Involvement of descending inhibitory systems is implicated in TENS-induced analgesia. In the present study, the roles of spinal 5-HT and α2-adrenoceptors in TENS analgesia were investigated in rats. Hyperalgesia was induced by inflaming the knee joint with 3% kaolin—carrageenan mixture and assessed by measuring paw withdrawal latency (PWL) to heat before and 4 h after injection. The (1) α2-adrenergic antagonist yohimbine (30 μg), (2) 5-HT antagonist methysergide (5-HT1 and 5-HT2,30 μg), one of the 5-HT receptor subtype antagonists, (3) NAN-190 (5-HT1A, 15 μg), (4) ketanserin (5-HT2A, 30 μg), (5) MDL-72222 (5-HT3, 12 μg), or (6) vehicle was administered intrathecally prior to TENS treatment. Low (4 Hz) or high (100 Hz) frequency TENS at sensory intensity was then applied to the inflamed knee for 20 min and PWL was determined. Selectivity of the antagonists used was confirmed using respective agonists administered intrathecally. Yohimbine had no effect on the antihyperalgesia produced by low or high frequency TENS. Methysergide and MDL-72222 prevented the antihyperalgesia produced by low, but not high, frequency TENS. Ketanserin attenuated the antihyperalgesic effects of low frequency TENS whereas NAN-190 had no effect. The results from the present study show that spinal 5-HT receptors mediate low, but not high, frequency TENS-induced antihyperalgesia through activation of 5-HT2A and 5-HT3 receptors in rats. Furthermore, spinal noradrenergic receptors are not involved in either low or high frequency TENS antihyperalgesia. PMID:14499437

Analysis of carbohydrates by anion exchange chromatography and mass spectrometry.

PubMed

Bruggink, Cees; Maurer, Rolf; Herrmann, Heiko; Cavalli, Silvano; Hoefler, Frank

2005-08-26

A versatile liquid chromatographic platform has been developed for analysing underivatized carbohydrates using high performance anion exchange chromatography (HPAEC) followed by an inert PEEK splitter that splits the effluent to the integrated pulsed amperometric detector (IPAD) and to an on-line single quadrupole mass spectrometer (MS). Common eluents for HPAEC such as sodium hydroxide and sodium acetate are beneficial for the amperometric detection but not compatible with electrospray ionisation (ESI). Therefore a membrane-desalting device was installed after the splitter and prior to the ESI interface converting sodium hydroxide into water and sodium acetate into acetic acid. To enhance the sensitivity for the MS detection, 0.5 mmol/l lithium chloride was added after the membrane desalter to form lithium adducts of the carbohydrates. To compare sensitivity of IPAD and MS detection glucose, fructose, and sucrose were used as analytes. A calibration with external standards from 2.5 to 1000 pmole was performed showing a linear range over three orders of magnitude. Minimum detection limits (MDL) with IPAD were determined at 5 pmole levels for glucose to be 0.12 pmole, fructose 0.22 pmole and sucrose 0.11 pmole. With MS detection in the selected ion mode (SIM) the lithium adducts of the carbohydrates were detected obtaining MDL's for glucose of 1.49 pmole, fructose 1.19 pmole, and sucrose 0.36 pmole showing that under these conditions IPAD is 3-10 times more sensitive for those carbohydrates. The applicability of the method was demonstrated analysing carbohydrates in real world samples such as chicory inulin where polyfructans up to a molecular mass of 7000 g/mol were detected as quadrupoly charged lithium adducts. Furthermore mono-, di-, tri-, and oligosaccharides were detected in chicory coffee, honey and beer samples.

Detection of actinides and rare earths in natural matrices with the AGLAE new, high sensitivity detection set-up

NASA Astrophysics Data System (ADS)

Zucchiatti, Alessandro; Alonso, Ursula; Lemasson, Quentin; Missana, Tiziana; Moignard, Brice; Pacheco, Claire; Pichon, Laurent; Camarena de la Mora, Sandra

2014-08-01

A series of granite samples (Grimsel and Äspö) enriched by sorption with natU (10-3 M, 10-4 M, 10-5 M in solution) and La (10-3 M, 10-4 M in solution) has been scanned by PIXE over a surface of 1920 × 1920 mm2 together with non-enriched Grimsel and Äspö granites and a glass standard. An assessment of minimum detection limits, MDL's, for several elements has been performed with the use of standard materials. Due to mapping and the high sensitivity of the new AGLAE detection system, U levels around 30 ppm can be detected from the whole PIXE spectrum (one low energy detector and four summed filtered detectors) while U reach grains, inhomogeneously distributed over the surface can be clearly identified through the multi elemental maps and analyzed separately. Even the nominally enriched samples have La levels below the MDL, probably because precipitation of the element (and not adsorption) mostly took place, and precipitates were eliminated after surface cleaning carried out before PIXE analyses. A multi detector system that implies a PIXE detection solid angle much wider than in any other similar set-up (a factor of 2-5); a higher events selectivity, given by the possibility of filtering individually up to 4 PIXE detectors; a double RBS detector, the new Ion Beam Induced Luminescence (IBIL) spectrometry and gamma spectrometry. Full mapping capability in air, assisted by a powerful event by event reconstruction software. These features allow lower Minimum Detection Limits (MDL) which are highly beneficial to the analysis of cultural heritage objects, meaning generally a reduction of irradiation time. Paintings will then be studied without any damage to the pigments that have color change tendencies which is a major drawback of the previous system. Alternatively they could allow an increase in information collected at equal time, particularly considering the detector's fast response and therefore the potential for high beam currents when sample damage can be tolerated.This kind of set-up should be advantageous for the detection of elements that are present in a geological, archaeological or artistic samples to the level of a few tens ppm. This is true in particular for the rare earths which are relevant to the provenance attribution of various classes of cultural heritage objects (clays, glasses, …) and the actinides which are relevant in very specific and highly impacting dating problems and, more generally, critical environmental elements with special reference to the radionuclide mobility in deep geological formations hosting radioactive waste [2]. Geological materials are highly heterogeneous and consequently their retention of contaminants is heterogeneous as well. In this frame, the capabilities of the AGLAE set-up would allow an improved characterization of natural heterogeneous rock, detecting the presence of the elements of interest (actinides and rare earth) at concentration levels of tens of ppm. This provides a better definition of the initial system, avoiding biased interpretation of the retention properties of the material for the analysis of possible contamination. Additionally, if lower detection limits were achieved, new perspectives to evaluate retention of low solubility contaminants in a wider range of geochemical conditions would be opened.A glass standard and a series of reference granite samples (Grimsel and Äspö), either enriched by sorption with natU and La or kept natural, have been scanned by PIXE at the New-AGLAE detection system, to test measurement protocols and assess the MDL's allowed by the five detectors system.

Nicergoline, a drug used for age-dependent cognitive impairment, protects cultured neurons against beta-amyloid toxicity.

PubMed

Caraci, Filippo; Chisari, Mariangela; Frasca, Giuseppina; Canonico, Pier Luigi; Battaglia, Angelo; Calafiore, Marco; Battaglia, Giuseppe; Bosco, Paolo; Nicoletti, Ferdinando; Copani, Agata; Sortino, Maria Angela

2005-06-14

Nicergoline, a drug used for the treatment of Alzheimer's disease and other types of dementia, was tested for its ability to protect neurons against beta-amyloid toxicity. Pure cultures of rat cortical neurons were challenged with a toxic fragment of beta-amyloid peptide (betaAP(25-35)) and toxicity was assessed after 24 h. Micromolar concentrations of nicergoline or its metabolite, MDL, attenuated betaAP(25-35)-induced neuronal death, whereas MMDL (another metabolite of nicergoline), the alpha1-adrenergic receptor antagonist, prazosin, or the serotonin 5HT-2 receptor antagonist, methysergide, were inactive. Nicergoline increased the basal levels of Bcl-2 and reduced the increase in Bax levels induced by beta-amyloid, indicating that the drug inhibits the execution of an apoptotic program in cortical neurons. In mixed cultures of rat cortical cells containing both neurons and astrocytes, nicergoline and MDL were more efficacious than in pure neuronal cultures in reducing beta-amyloid neurotoxicity. Experiments carried out in pure cultures of astrocytes showed that a component of neuroprotection was mediated by a mechanism of glial-neuronal interaction. The conditioned medium of cultured astrocytes treated with nicergoline or MDL for 72-96 h (collected 24 h after drug withdrawal) was neuroprotective when transferred to pure neuronal cultures challenged with beta-amyloid. In cultured astrocytes, nicergoline increased the intracellular levels of transforming-growth factor-beta and glial-derived neurotrophic factor, two trophic factors that are known to protect neurons against beta-amyloid toxicity. These results raise the possibility that nicergoline reduces neurodegeneration in the Alzheimer's brain.

Estimation of the individual slaughterhouse surveillance sensitivity for bovine tuberculosis in Catalonia (North-Eastern Spain).

PubMed

Garcia-Saenz, A; Napp, S; Lopez, S; Casal, J; Allepuz, A

2015-10-01

The achievement of the Officially Tuberculosis Free (OTF) status in regions with low bovine Tuberculosis (bTB) herd prevalence, as is the case of North-Eastern Spain (Catalonia), might be a likely option in the medium term. In this context, risk-based approaches could be an alternative surveillance strategy to the costly current strategy. However, before any change in the system may be contemplated, a reliable estimate of the sensitivity of the different surveillance components is needed. In this study, we focused on the slaughterhouse component. The probability of detection of a bTB-infected cattle by the slaughterhouses in Catalonia was estimated as the product of three consecutive probabilities: (P1) the probability that a bTB-infected animal arrived at the slaughterhouse presenting Macroscopically Detectable Lesions (MDL); (P2) the probability that MDL were detected by the routine meat inspection process and (P3) the probability that the veterinary officer suspected bTB and sent the sample for laboratory confirmation. The first probability was obtained from data collected through the bTB eradication program carried out in Catalonia between 2005 and 2008, while the last two were obtained through the expert opinion of the veterinary officers working at the slaughterhouses who fulfilled a questionnaire administered during 2014. The bTB surveillance sensitivity of the different cattle slaughterhouses in Catalonia obtained in this study was 31.4% (CI 95%: 28.6-36.2), and there were important differences among them. The low bTB surveillance sensitivity was mainly related with the low probability that a bTB-infected animal arrived at the slaughterhouse presenting MDL (around 44.8%). The variability of the sensitivity among the different slaughterhouses could be explained by significant associations between some variables included in the survey and P2. For instance, factors like attendance to training courses, number of meat technicians and speed of the slaughter chain were significantly related with the probabilities that a MDL was detected by the meat inspection procedure carried out in the slaughterhouse. Technical and policy efforts should be focused on the improvement of these factors in order to maximize the slaughterhouse sensitivity. Copyright © 2015 Elsevier B.V. All rights reserved.

Current-use pesticides in seawater and their bioaccumulation in polar bear-ringed seal food chains of the Canadian Arctic.

PubMed

Morris, Adam D; Muir, Derek C G; Solomon, Keith R; Letcher, Robert J; McKinney, Melissa A; Fisk, Aaron T; McMeans, Bailey C; Tomy, Gregg T; Teixeira, Camilla; Wang, Xiaowa; Duric, Mark

2016-07-01

The distribution of current-use pesticides (CUPs) in seawater and their trophodynamics were investigated in 3 Canadian Arctic marine food chains. The greatest ranges of dissolved-phase concentrations in seawater for each CUP were endosulfan sulfate (less than method detection limit (MDL) to 19 pg L(-1) ) > dacthal (0.76-15 pg L(-1) ) > chlorpyrifos (less than MDL to 8.1 pg L(-1) ) > pentachloronitrobenzene (less than MDL to 2.6 pg L(-1) ) > α-endosulfan (0.20-2.3 pg L(-1) ). Bioaccumulation factors (BAFs, water-respiring organisms) were greatest in plankton, including chlorothalonil (log BAF = 7.4 ± 7.1 L kg(-1) , mean ± standard error), chlorpyrifos (log BAF = 6.9 ± 6.7 L kg(-1) ), and α-endosulfan (log BAF = 6.5 ± 6.0 L kg(-1) ). The largest biomagnification factors (BMFs) were found for dacthal in the capelin:plankton trophic relationship (BMF = 13 ± 5.0) at Cumberland Sound (Nunvavut), and for β-endosulfan (BMF = 16 ± 4.9) and α-endosulfan (BMF = 9.3 ± 2.8) in the polar bear-ringed seal relationship at Barrow and Rae Strait (NU), respectively. Concentrations of endosulfan sulfate exhibited trophic magnification (increasing concentrations with increasing trophic level) in the poikilothermic portion of the food web (trophic magnification factor = 1.4), but all of the CUPs underwent trophic dilution in the marine mammal food web, despite some trophic level-specific biomagnification. Together, these observations are most likely indicative of metabolism of these CUPs in mammals. Environ Toxicol Chem 2016;35:1695-1707. © 2016 SETAC. © 2016 SETAC.

Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

PubMed

Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

2017-01-01

The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Compact TDLAS based optical sensor for ppb-level ethane detection by use of a 3.34 μm room-temperature CW interband cascade laser

DOE PAGES

Li, Chunguang; Dong, Lei; Zheng, Chuantao; ...

2016-03-26

A mid-infrared ethane (C 2H 6) sensor based on a wavelength modulation spectroscopy (WMS) technique was developed using a thermoelectrically cooled (TEC), continuous-wave (CW) interband cascade laser (ICL) emitting at 3.34 μm and a dense multi-pass gas cell (MPGC, 17 × 6.5 × 5.5 cm 3) with a 54.6 m optical path length. A compact optical sensor system with a physical size of 35.5 × 18 × 12.5 cm 3 was designed and constructed. An ICL was employed for targeting a strong C 2H 6 line at 2996.88 cm -1 at <100 Torr gas pressure in the fundamental absorption bandmore » of C 2H 6. The sensor performance, including the minimum detection limit (MDL) and the stability were improved by reducing the effect of laser power drift by means of the 2f/1f-WMS technique. A MDL of ~1.2 parts per billion (ppbv) for 2f-WMS and ~1.0 ppbv for 2f/1f-WMS were achieved, respectively, with a measurement time of 4 s. The MDL was further improved from 299 pptv (@108 s for 2f-WMS) to 239 pptv (@208 s for 2f/1f-WMS), based on an Allan deviation analysis.The rise time (@0 → 100 ppbv) and fall time (@100 → 0 ppbv) were determined to be ~64 s and ~48 s,respectively, at a gas pressure of <100 Torr for the C 2H 6 sensor operation.« less

Compact TDLAS based optical sensor for ppb-level ethane detection by use of a 3.34 μm room-temperature CW interband cascade laser

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

Li, Chunguang; Dong, Lei; Zheng, Chuantao

A mid-infrared ethane (C 2H 6) sensor based on a wavelength modulation spectroscopy (WMS) technique was developed using a thermoelectrically cooled (TEC), continuous-wave (CW) interband cascade laser (ICL) emitting at 3.34 μm and a dense multi-pass gas cell (MPGC, 17 × 6.5 × 5.5 cm 3) with a 54.6 m optical path length. A compact optical sensor system with a physical size of 35.5 × 18 × 12.5 cm 3 was designed and constructed. An ICL was employed for targeting a strong C 2H 6 line at 2996.88 cm -1 at <100 Torr gas pressure in the fundamental absorption bandmore » of C 2H 6. The sensor performance, including the minimum detection limit (MDL) and the stability were improved by reducing the effect of laser power drift by means of the 2f/1f-WMS technique. A MDL of ~1.2 parts per billion (ppbv) for 2f-WMS and ~1.0 ppbv for 2f/1f-WMS were achieved, respectively, with a measurement time of 4 s. The MDL was further improved from 299 pptv (@108 s for 2f-WMS) to 239 pptv (@208 s for 2f/1f-WMS), based on an Allan deviation analysis.The rise time (@0 → 100 ppbv) and fall time (@100 → 0 ppbv) were determined to be ~64 s and ~48 s,respectively, at a gas pressure of <100 Torr for the C 2H 6 sensor operation.« less

Motion perception and driving: predicting performance through testing and shortening braking reaction times through training.

PubMed

Wilkins, Luke; Gray, Rob; Gaska, James; Winterbottom, Marc

2013-12-30

A driving simulator was used to examine the relationship between motion perception and driving performance. Although motion perception test scores have been shown to be related to driving safety, it is not clear which combination of tests are the best predictors and whether motion perception training can improve driving performance. In experiment 1, 60 younger drivers (22.4 ± 2.5 years) completed three motion perception tests (2-dimensional [2D] motion-defined letter [MDL] identification, 3D motion in depth sensitivity [MID], and dynamic visual acuity [DVA]) followed by two driving tests (emergency braking [EB] and hazard perception [HP]). In experiment 2, 20 drivers (21.6 ± 2.1 years) completed 6 weeks of motion perception training (using the MDL, MID, and DVA tests), while 20 control drivers (22.0 ± 2.7 years) completed an online driving safety course. The EB performance was measured before and after training. In experiment 1, MDL (r = 0.34) and MID (r = 0.46) significantly correlated with EB score. The change in DVA score as a function of target speed (i.e., "velocity susceptibility") was correlated most strongly with HP score (r = -0.61). In experiment 2, the motion perception training group had a significant decrease in brake reaction time on the EB test from pre- to posttreatment, while there was no significant change for the control group: t(38) = 2.24, P = 0.03. Tests of 3D motion perception are the best predictor of EB, while DVA velocity susceptibility is the best predictor of hazard perception. Motion perception training appears to result in faster braking responses.

Variational learning and bits-back coding: an information-theoretic view to Bayesian learning.

PubMed

Honkela, Antti; Valpola, Harri

2004-07-01

The bits-back coding first introduced by Wallace in 1990 and later by Hinton and van Camp in 1993 provides an interesting link between Bayesian learning and information-theoretic minimum-description-length (MDL) learning approaches. The bits-back coding allows interpreting the cost function used in the variational Bayesian method called ensemble learning as a code length in addition to the Bayesian view of misfit of the posterior approximation and a lower bound of model evidence. Combining these two viewpoints provides interesting insights to the learning process and the functions of different parts of the model. In this paper, the problem of variational Bayesian learning of hierarchical latent variable models is used to demonstrate the benefits of the two views. The code-length interpretation provides new views to many parts of the problem such as model comparison and pruning and helps explain many phenomena occurring in learning.

Trace-Level Automated Mercury Speciation Analysis

PubMed Central

Taylor, Vivien F.; Carter, Annie; Davies, Colin; Jackson, Brian P.

2011-01-01

An automated system for methyl Hg analysis by purge and trap gas chromatography (GC) was evaluated, with comparison of several different instrument configurations including chromatography columns (packed column or capillary), detector (atomic fluorescence, AFS, or inductively coupled plasma mass spectrometry, ICP-MS, using quadrupole and sector field ICP- MS instruments). Method detection limits (MDL) of 0.042 pg and 0.030 pg for CH3Hg+ were achieved with the automated Hg analysis system configured with AFS and ICPMS detection, respectively. Capillary GC with temperature programming was effective in improving resolution and decreasing retention times of heavier Hg species (in this case C3H7Hg+) although carryover between samples was increased. With capillary GC, the MDL for CH3Hg+ was 0.25 pg for AFS detection and 0.060 pg for ICP-MS detection. The automated system was demonstrated to have high throughput (72 samples analyzed in 8 hours) requiring considerably less analyst time than the manual method for methyl mercury analysis described in EPA 1630. PMID:21572543

Spatial and Temporal Distribution of Current-Use Pesticides in Atmospheric Particulate Matter in Houston, Texas.

PubMed

Clark, Adelaide E; Yoon, Subin; Sheesley, Rebecca J; Usenko, Sascha

2016-12-01

The atmospheric concentrations of seven current-use pesticides in particulate matter were determined at four locations throughout the Houston metropolitan area in TSP and PM 2.5 samples from September 2013. Atmospheric concentrations in both TSP and PM 2.5 ranged from below method detection limits (MDLs) to nearly 1100 pg m -3 . The three compounds most frequently detected above MDLs were chlorothalonil, bifenthrin, and λ-cyhalothrin. Atmospheric chlorothalonil concentrations were above 800 pg m -3 in several TSP samples, but

Testing the ecotoxicology of vegetable versus mineral based lubricating oils: 1. Degradation rates using tropical marine microbes.

PubMed

Mercurio, Philip; Burns, Kathryn A; Negri, Andrew

2004-05-01

Vegetable-derived lubricants (VDL) might be more biodegradable than mineral-derived lubricants (MDL) due to the absence of high molecular weight aromatics, but this remains largely untested in tropical conditions. In this laboratory study, the degradation rates of 2-stroke, 4-stroke and hydraulic VDLs were compared with their MDL counterparts in the presence of mangrove and coral reef microbial communities. While MDLs were comprised largely of unresolved saturated and some aromatic hydrocarbons, their VDL counterparts contained, potentially more degradable, fatty acid methyl esters. Degradation of some VDL was observed by day 7, with the 2-stroke VDL markedly consumed by mangrove microorganisms and the hydraulic VDL degraded by both microorganism communities after this short period. All of the VDL groups were significantly more degraded than the comparable MDLs mineral oil lubricants over 14 days in the presence of either mangrove or coral reef microbial communities. In general the mangrove-sourced microorganisms more efficiently degraded the lubricants than reef-sourced microorganisms.

Simulation Control Graphical User Interface Logging Report

NASA Technical Reports Server (NTRS)

Hewling, Karl B., Jr.

2012-01-01

One of the many tasks of my project was to revise the code of the Simulation Control Graphical User Interface (SIM GUI) to enable logging functionality to a file. I was also tasked with developing a script that directed the startup and initialization flow of the various LCS software components. This makes sure that a software component will not spin up until all the appropriate dependencies have been configured properly. Also I was able to assist hardware modelers in verifying the configuration of models after they have been upgraded to a new software version. I developed some code that analyzes the MDL files to determine if any error were generated due to the upgrade process. Another one of the projects assigned to me was supporting the End-to-End Hardware/Software Daily Tag-up meeting.

Crater-lake Santa Maria del Oro as a Pristine Reference for Persistent Organic Pollutants (POP' s) and Heavy Metals Content in Environmental Investigations in Western Mexico (Project Conacyt-Semarnat 2002-C01-0463, in Progress).

NASA Astrophysics Data System (ADS)

Zarate-Del Valle, P. F.; Gomez-Hermosillo, C. M.; Venegas-Garcia, D. J.

2007-12-01

Santa Maria del Oro Lake ( SMO) (21.37° N, 104.57° W; 750 m a.s.l.) is a quaternary crater-lake located at western Mexico in the natural border between two geological provinces: the plio-quaternary Trans-Mexican Volcanic Belt and the oligo-miocenic silicic volcanic province Sierra Madre Occidental. SMO, a tropical freshwater lake, is a warm-monomictic lake having a diameter of ca. 2 km and a mean depth at the depocenter of ca. 60 m, where three benthos cores were recovered. Contents of POP' s, total inorganic carbon (TIC), total organic carbon (TOC) and heavy metals were analyzed. Geochemistry and mineralogy also were studied in shallow sediments which corresponded to the decade of 50-60's, otherwise the beginning of industrial development of central Mexico; which is considered the possible source of emission of POP' s and heavy metals. Dioxin, furan, plaguicides and PCB' s contents were analyzed by a GC-MS applying USEPA methods. In the first 40 cm (n= 20) of the sedimentary column ( SC) the absence of POP' s was evidenced, applying a method detection limit ( MDL) of 5 μ g/ml for dioxin, furan and PCB' s. For plaguicides like chlordane and toxaphene the MDL was 0.5 μ g/ml and for plaguicides like DDT, aldrin, endrin, dieldrin, heptachlore and mirex the MDL was 5 μ g/ml. The MDL for HCB was 1 μ g/ml. The average (n= 30) for TIC, TOC and total carbon (TC) for the first 40 cm of the SC is as follows: TIC 2.4 %, TOC 3.7 % and TC 6.12 %. The average (n= 20) content (in ppm) of heavy metals for the first 20 cm of the SC is as follows: As 5.97, Cr 27.54, Cu 16.31, Ni 12.29, Pb 21.35 and Zn 82.46. These contents are roughly similar to the clarke of these metals in volcanic rocks. After the criteria of severe effect level ( SEL) of heavy metal in sediments, the content of these metals is below SEL levels. These results permit us to conclude that the sediments of SMO can be considered in unaffected state with respect to antropogenic contamination like POP' s and heavy metals. Consequently, Santa Maria del Oro Lake can be considered as a pristine reference in paleo-ecological and environmental investigations in western Mexico.

Simultaneous determination of sulfonamides, tetracyclines and tiamulin in swine wastewater by solid-phase extraction and liquid chromatography-mass spectrometry.

PubMed

Ben, Weiwei; Qiang, Zhimin; Adams, Craig; Zhang, Heqing; Chen, Liping

2008-08-22

Little is known about the contamination level of antibiotics in swine wastewater in China. The highly complex matrix of swine wastewater, which generally has a chemical oxygen demand (COD) concentration as high as 15,000 mg/L, makes it difficult to detect antibiotics at trace levels. In this work, a highly selective and sensitive analytical method was developed for simultaneous determination of three classes of commonly used veterinary antibiotics including five sulfonamides, three tetracyclines and one macrolide in swine wastewater using solid-phase extraction (SPE) and liquid chromatography-mass spectrometry (LC-MS). The method detection limits (MDL) in the swine wastewater were determined to be between 5 and 91 ng/L, depending on specific antibiotics. Except sulfamethizole, all the other eight antibiotics were detected in the swine wastewaters collected from three concentrated swine feeding plants located in the Beijing (China) area, showing a concentration range of 0.62-32.67 microg/L. These results reveal the representative concentration levels of selected antibiotics in the swine wastewaters of Beijing area.

Neuropharmacology of light-induced locomotor activation.

PubMed

Amato, Davide; Pum, Martin E; Groos, Dominik; Lauber, Andrea C; Huston, Joseph P; Carey, Robert J; de Souza Silva, Maria A; Müller, Christian P

2015-08-01

Presentation of non-aversive light stimuli for several seconds was found to reliably induce locomotor activation and exploratory-like activity. Light-induced locomotor activity (LIA) can be considered a convenient simple model to study sensory-motor activation. LIA was previously shown to coincide with serotonergic and dopaminergic activation in specific cortical areas in freely moving and anesthetized animals. In the present study we explore the neuropharmacology of LIA using a receptor antagonist/agonist approach in rats. The non-selective 5-HT2-receptor antagonist ritanserin (1.5-6 mg/kg, i.p.) dose-dependently reduced LIA. Selective antagonism of either the 5-HT2A-receptor by MDL 11,939 (0.1-0.4 mg/kg, i.p.), or the 5-HT2C-receptor by SDZ SER 082 (0.125-0.5 mg/kg, i.p.), alone or in combination, had no significant influence on LIA. Also the selective 5-HT1A-receptor antagonist, WAY 100635 (0.4 mg/kg, i.p.) did not affect LIA. Neither did the preferential dopamine D2-receptor antagonist, haloperidol (0.025-0.1 mg/kg, i.p.) nor the D2/D3-receptor agonist, quinpirole (0.025-0.5 mg/kg, i.p.) affect the expression of LIA. However, blocking the glutamatergic NMDA-receptor with phencyclidine (PCP, 1.5-6 mg/kg, i.p.) dose-dependently reduced LIA. This effect was also observed with ketamine (10 mg/kg, i.p.). These findings suggest that serotonin and dopamine receptors abundantly expressed in the cortex do not mediate light-stimulus triggered locomotor activity. PCP and ketamine effects, however, suggest an important role of NMDA receptors in LIA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment with polyamine oxidase inhibitor reduces microglial activation and limits vascular injury in ischemic retinopathy

PubMed Central

Patel, C.; Xu, Z.; Shosha, E.; Xing, J.; Lucas, R.; Caldwell, R.W.; Caldwell, R.B.; Narayanan, S.P.

2016-01-01

Retinal vascular injury is a major cause of vision impairment in ischemic retinopathies. Insults such as hyperoxia, oxidative stress and inflammation contribute to this pathology. Previously, we showed that hyperoxia-induced retinal neurodegeneration is associated with increased polyamine oxidation. Here, we are studying the involvement of polyamine oxidases in hyperoxia-induced injury and death of retinal vascular endothelial cells. Newborn C57BL6/J mice were exposed to hyperoxia (70% O2) from postnatal day (P) 7 to 12 and were treated with the polyamine oxidase inhibitor MDL 72527 or vehicle starting at P6. Mice were sacrificed after different durations of hyperoxia and their retinas were analyzed to determine the effects on vascular injury, microglial cell activation, and inflammatory cytokine profiling. The results of this analysis showed that MDL 72527 treatment significantly reduced hyperoxia-induced retinal vascular injury and enhanced vascular sprouting as compared with the vehicle controls. These protective effects were correlated with significant decreases in microglial activation as well as levels of inflammatory cytokines and chemokines. In order to model the effects of polyamine oxidation in causing microglial activation in vitro, studies were performed using rat brain microvascular endothelial cells treated with conditioned-medium from rat retinal microglia stimulated with hydrogen peroxide. Conditioned-medium from activated microglial cultures induced cell stress signals and cell death in microvascular endothelial cells. These studies demonstrate the involvement of polyamine oxidases in hyperoxia-induced retinal vascular injury and retinal inflammation in ischemic retinopathy, through mechanisms involving cross-talk between endothelial cells and resident retinal microglia. PMID:27239699

A novel gene network inference algorithm using predictive minimum description length approach.

PubMed

Chaitankar, Vijender; Ghosh, Preetam; Perkins, Edward J; Gong, Ping; Deng, Youping; Zhang, Chaoyang

2010-05-28

Reverse engineering of gene regulatory networks using information theory models has received much attention due to its simplicity, low computational cost, and capability of inferring large networks. One of the major problems with information theory models is to determine the threshold which defines the regulatory relationships between genes. The minimum description length (MDL) principle has been implemented to overcome this problem. The description length of the MDL principle is the sum of model length and data encoding length. A user-specified fine tuning parameter is used as control mechanism between model and data encoding, but it is difficult to find the optimal parameter. In this work, we proposed a new inference algorithm which incorporated mutual information (MI), conditional mutual information (CMI) and predictive minimum description length (PMDL) principle to infer gene regulatory networks from DNA microarray data. In this algorithm, the information theoretic quantities MI and CMI determine the regulatory relationships between genes and the PMDL principle method attempts to determine the best MI threshold without the need of a user-specified fine tuning parameter. The performance of the proposed algorithm was evaluated using both synthetic time series data sets and a biological time series data set for the yeast Saccharomyces cerevisiae. The benchmark quantities precision and recall were used as performance measures. The results show that the proposed algorithm produced less false edges and significantly improved the precision, as compared to the existing algorithm. For further analysis the performance of the algorithms was observed over different sizes of data. We have proposed a new algorithm that implements the PMDL principle for inferring gene regulatory networks from time series DNA microarray data that eliminates the need of a fine tuning parameter. The evaluation results obtained from both synthetic and actual biological data sets show that the PMDL principle is effective in determining the MI threshold and the developed algorithm improves precision of gene regulatory network inference. Based on the sensitivity analysis of all tested cases, an optimal CMI threshold value has been identified. Finally it was observed that the performance of the algorithms saturates at a certain threshold of data size.

106-17 Telemetry Standards Metadata Configuration Chapter 23

DTIC Science & Technology

2017-07-01

23-1 23.2 Metadata Description Language ...Chapter 23, July 2017 iii Acronyms HTML Hypertext Markup Language MDL Metadata Description Language PCM pulse code modulation TMATS Telemetry...Attributes Transfer Standard W3C World Wide Web Consortium XML eXtensible Markup Language XSD XML schema document Telemetry Network Standard

Accuracy of the One-Stage and Two-Stage Impression Techniques: A Comparative Analysis

PubMed Central

Jamshidy, Ladan; Faraji, Payam; Sharifi, Roohollah

2016-01-01

Introduction. One of the main steps of impression is the selection and preparation of an appropriate tray. Hence, the present study aimed to analyze and compare the accuracy of one- and two-stage impression techniques. Materials and Methods. A resin laboratory-made model, as the first molar, was prepared by standard method for full crowns with processed preparation finish line of 1 mm depth and convergence angle of 3-4°. Impression was made 20 times with one-stage technique and 20 times with two-stage technique using an appropriate tray. To measure the marginal gap, the distance between the restoration margin and preparation finish line of plaster dies was vertically determined in mid mesial, distal, buccal, and lingual (MDBL) regions by a stereomicroscope using a standard method. Results. The results of independent test showed that the mean value of the marginal gap obtained by one-stage impression technique was higher than that of two-stage impression technique. Further, there was no significant difference between one- and two-stage impression techniques in mid buccal region, but a significant difference was reported between the two impression techniques in MDL regions and in general. Conclusion. The findings of the present study indicated higher accuracy for two-stage impression technique than for the one-stage impression technique. PMID:28003824

Accuracy of the One-Stage and Two-Stage Impression Techniques: A Comparative Analysis.

PubMed

Jamshidy, Ladan; Mozaffari, Hamid Reza; Faraji, Payam; Sharifi, Roohollah

2016-01-01

Introduction . One of the main steps of impression is the selection and preparation of an appropriate tray. Hence, the present study aimed to analyze and compare the accuracy of one- and two-stage impression techniques. Materials and Methods . A resin laboratory-made model, as the first molar, was prepared by standard method for full crowns with processed preparation finish line of 1 mm depth and convergence angle of 3-4°. Impression was made 20 times with one-stage technique and 20 times with two-stage technique using an appropriate tray. To measure the marginal gap, the distance between the restoration margin and preparation finish line of plaster dies was vertically determined in mid mesial, distal, buccal, and lingual (MDBL) regions by a stereomicroscope using a standard method. Results . The results of independent test showed that the mean value of the marginal gap obtained by one-stage impression technique was higher than that of two-stage impression technique. Further, there was no significant difference between one- and two-stage impression techniques in mid buccal region, but a significant difference was reported between the two impression techniques in MDL regions and in general. Conclusion . The findings of the present study indicated higher accuracy for two-stage impression technique than for the one-stage impression technique.

Demonstration and Validation of a Regenerated Cellulose Dialysis Membrane Diffusion Sampler for Monitoring Ground Water Quality and Remediation Progress at DoD Sites

DTIC Science & Technology

2007-08-30

ITRC Interstate Technology Regulatory Council LRL Laboratory reporting level LDPE Low-density polyethylene MDL Minimum detection limit MNA...diameter of the well. Another diffusion membrane sampler design consists of a tubular-shaped bag made of flexible low-density polyethylene ( LDPE ...

76 FR 72507 - National Emissions Standards for Hazardous Air Pollutants: Ferroalloys Production

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-23

... MDL method detection limit mg/dscm milligrams per dry standard cubic meter MIR maximum individual risk... pounds per hour per megawatt (lb/hr/ MW) or 35 milligrams per dry standard cubic meter (mg/ dscm) (0.015... stacks) producing ferromanganese. New, reconstructed, or Metal oxygen refining process... 69 mg/dscm (0...

METHOD TO-15 SUPPLEMENT-ANALYSIS OF 1,1-DCE AT PPTV CONCENTRATIONS

EPA Science Inventory

The Supplement to EPA Compendium Method TO-15 provides guidance for reducing the method detection limit (MDL) for the compound 1,1-dichloroethene (1,1-DCE) and for other volatile organic compounds (VOCs) from 0.5 ppbv, as cited in Method TO-15, to much lower concentrations. Revis...

An information theory criteria based blind method for enumerating active users in DS-CDMA system

NASA Astrophysics Data System (ADS)

Samsami Khodadad, Farid; Abed Hodtani, Ghosheh

2014-11-01

In this paper, a new and blind algorithm for active user enumeration in asynchronous direct sequence code division multiple access (DS-CDMA) in multipath channel scenario is proposed. The proposed method is based on information theory criteria. There are two main categories of information criteria which are widely used in active user enumeration, Akaike Information Criterion (AIC) and Minimum Description Length (MDL) information theory criteria. The main difference between these two criteria is their penalty functions. Due to this difference, MDL is a consistent enumerator which has better performance in higher signal-to-noise ratios (SNR) but AIC is preferred in lower SNRs. In sequel, we propose a SNR compliance method based on subspace and training genetic algorithm to have the performance of both of them. Moreover, our method uses only a single antenna, in difference to the previous methods which decrease hardware complexity. Simulation results show that the proposed method is capable of estimating the number of active users without any prior knowledge and the efficiency of the method.

Human dopamine receptor nanovesicles for gate-potential modulators in high-performance field-effect transistor biosensors

NASA Astrophysics Data System (ADS)

Park, Seon Joo; Song, Hyun Seok; Kwon, Oh Seok; Chung, Ji Hyun; Lee, Seung Hwan; An, Ji Hyun; Ahn, Sae Ryun; Lee, Ji Eun; Yoon, Hyeonseok; Park, Tai Hyun; Jang, Jyongsik

2014-03-01

The development of molecular detection that allows rapid responses with high sensitivity and selectivity remains challenging. Herein, we demonstrate the strategy of novel bio-nanotechnology to successfully fabricate high-performance dopamine (DA) biosensor using DA Receptor-containing uniform-particle-shaped Nanovesicles-immobilized Carboxylated poly(3,4-ethylenedioxythiophene) (CPEDOT) NTs (DRNCNs). DA molecules are commonly associated with serious diseases, such as Parkinson's and Alzheimer's diseases. For the first time, nanovesicles containing a human DA receptor D1 (hDRD1) were successfully constructed from HEK-293 cells, stably expressing hDRD1. The nanovesicles containing hDRD1 as gate-potential modulator on the conducting polymer (CP) nanomaterial transistors provided high-performance responses to DA molecule owing to their uniform, monodispersive morphologies and outstanding discrimination ability. Specifically, the DRNCNs were integrated into a liquid-ion gated field-effect transistor (FET) system via immobilization and attachment processes, leading to high sensitivity and excellent selectivity toward DA in liquid state. Unprecedentedly, the minimum detectable level (MDL) from the field-induced DA responses was as low as 10 pM in real- time, which is 10 times more sensitive than that of previously reported CP based-DA biosensors. Moreover, the FET-type DRNCN biosensor had a rapid response time (<1 s) and showed excellent selectivity in human serum.

Bioconcentration of triclosan, methyl-triclosan, and triclocarban in the plants and sediments of a constructed wetland.

PubMed

Zarate, Frederick M; Schulwitz, Sarah E; Stevens, Kevin J; Venables, Barney J

2012-07-01

Constructed wetlands are a potential method for the removal of two pharmaceutical and personal care products from wastewater effluent. Triclosan (TCS; 5-chloro-2-[2,4-dichlorophenoxy]phenol) and triclocarban (TCC; 3,4,4'-trichlorocarbanillide) are antimicrobial agents added to a variety of consumer products whose accumulation patterns in constructed wetlands are poorly understood. Here, we report the accumulation of TCS, its metabolite methyl-triclosan (MTCS; 5-chloro-2-[2,4-dichlorophenoxy]), and TCC in wetland plant tissues and sediments. Three wetland macrophytes: Typha latifolia, Pontederia cordata, and Sagittaria graminea were sampled from a constructed wetland in Denton, Texas, USA. MTCS concentrations were below the method detection limit (MDL) for all species. TCS root tissue concentrations in T. latifolia were significantly greater than root concentrations in P. cordata (mean±SE in ng g(-1): 40.3±11.3 vs. 15.0±1.9, respectively), while for TCC, shoot tissue concentrations in S. graminea were significantly greater than in T. latifolia (22.8±9.3 vs. 9.0 (MDL), respectively). For both TCS and TCC, T. latifolia root tissue concentrations were significantly greater than shoot concentrations (TCS: 40.3±11.3 vs. 17.2±0.2, TCC: 26.0±3.6 vs. 9.0, (MDL)). TCC concentrations in P. cordata roots were significantly greater than in shoots (34.4±5.3 vs. 15.4±2.8, respectively). TCS concentrations in T. latifolia roots and sediments and TCC concentrations in sediments generally decreased from wetland inflow to outflow. To our knowledge, this is the first study documenting species and tissue specific differences in the accumulation of TCS and TCC in plants from an operational constructed wetland. The species specific differences in bioaccumulation suggest TCS and TCC removal from constructed wetlands could be enhanced through targeted plantings. Copyright © 2012 Elsevier Ltd. All rights reserved.

NK2 tachykinin receptors and contraction of circular muscle of the human colon: characterization of the NK2 receptor subtype.

PubMed

Giuliani, S; Barbanti, G; Turini, D; Quartara, L; Rovero, P; Giachetti, A; Maggi, C A

1991-10-22

The contractile effect of substance P, neurokinin A, receptor selective agonists for tachykinin receptors and NK2 tachykinin receptor antagonists was investigated in mucosa-free circular strips of the human isolated colon. Neurokinin A and substance P produced concentration-dependent contractions which approached 80-90% of the maximal response to carbachol. Neurokinin A was about 370 times more potent than substance P. The action of neurokinin A and substance P was not modified by peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each). The NK2 receptor selective agonist, [beta-Ala8]neurokinin A-(4-10) closely mimicked the response to neurokinin A while NK1 and NK3 receptor selective agonists were active only at microM concentrations. The pseudopeptide, MDL 28,564, which is one of the most selective NK2 ligands available, behaved as a full agonist. Responses to [beta-Ala8]neurokinin A were antagonized by NK2 receptor selective antagonists, with the rank order of potency MEN 10,376 greater than L 659,877 much greater than R 396. These data indicate that NK2 tachykinin receptors play a dominant role in determining the contraction of the circular muscle of the human colon to peptides of this family. The NK2 receptor subtype responsible for this effect belongs to the same subtype (NK2A) previously identified in the rabbit pulmonary artery and guinea-pig bronchi.

SUPPLEMENT TO EPA COMPENDIUM METHOD TO-15 - REDUCTION OF METHOD DETECTION LIMITS TO MEET VAPOR INTRUSION MONITORING NEEDS

EPA Science Inventory

The Supplement to EPA Compendium Method TO-15 provides guidance for reducing the method detection limit (MDL) for the compound 1,1- dichloroethene (1,1-DCE) and for other volatile organic compounds (VOCs) from 0.5 ppbv, as cited in Method TO-15, to much lower concentrations. R...

SUPPLEMENT TO EPA COMPENDIUM METHOD TO-15 - REDUCTION OF METHOD DETECTION LIMITS TO MEET VAPOR INTRUSION MONITORING NEEDS

EPA Science Inventory

The Supplement to EPA Compendium Method TO-15 provides guidance for reducing the method detection limit (MDL) for the compound 1,1-dichloroethene (1,1-DCE) and for other volatile organic compounds (VOCs) from 0.5 parts per billion by volume (ppbv), as cited in Method TO-15, to ...

Microgravity

NASA Image and Video Library

1999-04-01

The Equiaxed Dendritic Solidification Experiment (EDSE) is a material sciences investigation under the Formation of Microstructures/pattern formation discipline. The objective is to study the microstructural evolution of and thermal interactions between several equiaxed crystals growing dendritically in a supercooled melt of a pure and transparent substance under diffusion controlled conditions. This image shows the overview for the EDSE in the Microgravity Development Lab (MDL).

Microgravity

NASA Image and Video Library

1999-04-01

The Equiaxed Dendritic Solidification Experiment (EDSE) is a material sciences investigation under the Formation of Microstructures/pattern formation discipline. The objective is to study the microstructural evolution of and thermal interactions between several equiaxed crystals growing dendritically in a supercooled melt of a pure and transparent substance under diffusion controlled conditions. Video and power rack for the EDSE in the Microgravity Development Lab (MDL).

Microgravity

NASA Image and Video Library

1999-04-01

The Equiaxed Dendritic Solidification Experiment (EDSE) is a material sciences investigation under the Formation of Microstructures/pattern formation discipline. The objective is to study the microstructural evolution of and thermal interactions between several equiaxed crystals growing dendritically in a supercooled melt of a pure and transparent substance under diffusion controlled conditions. Dendrite irritator control for the EDSE in the Microgravity Development Lab (MDL).

Sparse Coding and Dictionary Learning Based on the MDL Principle

DTIC Science & Technology

2010-10-01

average bits per pixel obtained was 4.08 bits per pixel ( bpp ), with p = 250 atoms in the final dictionary. We repeated this using `2 instead of Huber...loss, obtaining 4.12 bpp and p = 245. We now show example results obtained with our framework in two very different applications. In both cases we

Separation of Acids, Bases, and Neutral Compounds

NASA Astrophysics Data System (ADS)

Fujita, Megumi; Mah, Helen M.; Sgarbi, Paulo W. M.; Lall, Manjinder S.; Ly, Tai Wei; Browne, Lois M.

2003-01-01

Separation of Acids, Bases, and Neutral Compounds requires the following software, which is available for free download from the Internet: Netscape Navigator, version 4.75 or higher, or Microsoft Internet Explorer, version 5.0 or higher; Chime plug-in, version compatible with your OS and browser (available from MDL); and Flash player, version 5 or higher (available from Macromedia).

77 FR 4492 - Endangered and Threatened Wildlife and Plants; Reissuance of Interim Special Rule for the Polar Bear

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-30

... order in regard to Misc. No. 08- 764 (EGS) MDL Docket No. 1993 IN RE: POLAR BEAR ENDANGERED SPECIES ACT... (Service), published a final rule listing the polar bear (Ursus maritimus) as a threatened species... Special Rule for the Polar Bear AGENCY: Fish and Wildlife Service, Interior. ACTION: Final rule. SUMMARY...

Microgravity

NASA Image and Video Library

1999-04-01

The Equiaxed Dendritic Solidification Experiment (EDSE) is a material sciences investigation under the Formation of Microstructures/pattern formation discipline. The objective is to study the microstructural evolution of and thermal interactions between several equiaxed crystals growing dendritically in a supercooled melt of a pure and transparent substance under diffusion controlled conditions. This image shows the isothermal bath and video system for the EDSE in the Microgravity Development Lab (MDL).

Optimization of 18 F-syntheses using 19 F-reagents at tracer-level concentrations and liquid chromatography/tandem mass spectrometry analysis: Improved synthesis of [18 F]MDL100907.

PubMed

Zhang, Xiang; Dunlow, Ryan; Blackman, Burchelle N; Swenson, Rolf E

2018-05-15

Traditional radiosynthetic optimization faces the challenges of high radiation exposure, cost, and inability to perform serial reactions due to tracer decay. To accelerate tracer development, we have developed a strategy to simulate radioactive 18 F-syntheses by using tracer-level (nanomolar) non-radioactive 19 F-reagents and LC-MS/MS analysis. The methodology was validated with fallypride synthesis under tracer-level 19 F-conditions, which showed reproducible and comparable results with radiosynthesis, and proved the feasibility of this process. Using this approach, the synthesis of [ 18 F]MDL100907 was optimized under 19 F-conditions with greatly improved yield. The best conditions were successfully transferred to radiosynthesis. A radiochemical yield of 19% to 22% was achieved with the radiochemical purity >99% and the molar activity 38.8 to 53.6 GBq/ μmol (n = 3). The tracer-level 19 F-approach provides a high-throughput and cost-effective process to optimize radiosynthesis with reduced radiation exposure. This new method allows medicinal and synthetic chemists to optimize radiolabeling conditions without the need to use radioactivity. Copyright © 2018 John Wiley & Sons, Ltd.

Channel estimation in few mode fiber mode division multiplexing transmission system

NASA Astrophysics Data System (ADS)

Hei, Yongqiang; Li, Li; Li, Wentao; Li, Xiaohui; Shi, Guangming

2018-03-01

It is abundantly clear that obtaining the channel state information (CSI) is of great importance for the equalization and detection in coherence receivers. However, to the best of the authors' knowledge, in most of the existing literatures, CSI is assumed to be perfectly known at the receiver. So far, few literature discusses the effects of imperfect CSI on MDM system performance caused by channel estimation. Motivated by that, in this paper, the channel estimation in few mode fiber (FMF) mode division multiplexing (MDM) system is investigated, in which two classical channel estimation methods, i.e., least square (LS) method and minimum mean square error (MMSE) method, are discussed with the assumption of the spatially white noise lumped at the receiver side of MDM system. Both the capacity and BER performance of MDM system affected by mode-dependent gain or loss (MDL) with different channel estimation errors have been studied. Simulation results show that the capacity and BER performance can be further deteriorated in MDM system by the channel estimation, and an 1e-3 variance of channel estimation error is acceptable in MDM system with 0-6 dB MDL values.

PRESEE: An MDL/MML Algorithm to Time-Series Stream Segmenting

PubMed Central

Jiang, Yexi; Tang, Mingjie; Yuan, Changan; Tang, Changjie

2013-01-01

Time-series stream is one of the most common data types in data mining field. It is prevalent in fields such as stock market, ecology, and medical care. Segmentation is a key step to accelerate the processing speed of time-series stream mining. Previous algorithms for segmenting mainly focused on the issue of ameliorating precision instead of paying much attention to the efficiency. Moreover, the performance of these algorithms depends heavily on parameters, which are hard for the users to set. In this paper, we propose PRESEE (parameter-free, real-time, and scalable time-series stream segmenting algorithm), which greatly improves the efficiency of time-series stream segmenting. PRESEE is based on both MDL (minimum description length) and MML (minimum message length) methods, which could segment the data automatically. To evaluate the performance of PRESEE, we conduct several experiments on time-series streams of different types and compare it with the state-of-art algorithm. The empirical results show that PRESEE is very efficient for real-time stream datasets by improving segmenting speed nearly ten times. The novelty of this algorithm is further demonstrated by the application of PRESEE in segmenting real-time stream datasets from ChinaFLUX sensor networks data stream. PMID:23956693

PRESEE: an MDL/MML algorithm to time-series stream segmenting.

PubMed

Xu, Kaikuo; Jiang, Yexi; Tang, Mingjie; Yuan, Changan; Tang, Changjie

2013-01-01

Time-series stream is one of the most common data types in data mining field. It is prevalent in fields such as stock market, ecology, and medical care. Segmentation is a key step to accelerate the processing speed of time-series stream mining. Previous algorithms for segmenting mainly focused on the issue of ameliorating precision instead of paying much attention to the efficiency. Moreover, the performance of these algorithms depends heavily on parameters, which are hard for the users to set. In this paper, we propose PRESEE (parameter-free, real-time, and scalable time-series stream segmenting algorithm), which greatly improves the efficiency of time-series stream segmenting. PRESEE is based on both MDL (minimum description length) and MML (minimum message length) methods, which could segment the data automatically. To evaluate the performance of PRESEE, we conduct several experiments on time-series streams of different types and compare it with the state-of-art algorithm. The empirical results show that PRESEE is very efficient for real-time stream datasets by improving segmenting speed nearly ten times. The novelty of this algorithm is further demonstrated by the application of PRESEE in segmenting real-time stream datasets from ChinaFLUX sensor networks data stream.

Tachykinin-mediated respiratory effects in conscious guinea pigs: modulation by NK1 and NK2 receptor antagonists.

PubMed

Kudlacz, E M; Logan, D E; Shatzer, S A; Farrell, A M; Baugh, L E

1993-09-07

Tachykinins, in particular neurokinin A and substance P, produce a number of airway effects which may contribute to respiratory diseases such as asthma. We examined the ability of aerosolized substance P, neurokinin A or capsaicin to produce respiratory alterations in conscious guinea pigs using modified whole body plethysmography. Substance P-mediated dyspnea and significant respiratory events were inhibited by the NK1 receptor antagonist, CP-96,345. Neurokinin A-mediated respiratory effects were ablated by the NK2 receptor antagonists: MEN 10207, MDL 29,913 and SR 48,968, the latter being the most potent. The peptide-based antagonist, MEN 10207, produced respiratory effects itself suggesting partial agonist activity. The cyclic hexapeptide, MDL 29,913, relaxed airway smooth muscle via mechanisms other than tachykinin antagonism. NK2 but not NK1 receptor antagonists were able to delay the onset of capsaicin-induced dyspnea, although alone they did not usually (in approximately 10% of the animals) eliminate the response. However, when NK2 receptor antagonists were combined with CP-96,345, the incidence of dyspnea induced by capsaicin decreased significantly (40%) suggesting that both tachykinins contribute to dyspnea in this system.

Effects of Antipsychotic Drugs Haloperidol and Clozapine on Visual Responses of Retinal Ganglion Cells in a Rat Model of Retinitis Pigmentosa.

PubMed

Jensen, Ralph J

2016-12-01

In the P23H rat model of retinitis pigmentosa, the dopamine D2 receptor antagonists sulpiride and eticlopride appear to improve visual responses of retinal ganglion cells (RGCs) by increasing light sensitivity of RGCs and transforming abnormal, long-latency ON-center RGCs into OFF-center cells. Antipsychotic drugs are believed to mediate their therapeutic benefits by blocking D2 receptors. This investigation was conducted to test whether haloperidol (a typical antipsychotic drug) and clozapine (an atypical antipsychotic drug) could similarly alter the light responses of RGCs in the P23H rat retina. Extracellular recordings were made from RGCs in isolated P23H rat retinas. Responses of RGCs to flashes of light were evaluated before and during bath application of a drug. Both haloperidol and clozapine increased light sensitivity of RGCs on average by ∼0.3 log unit. For those ON-center RGCs that exhibit an abnormally long-latency response to the onset of a small spot of light, both haloperidol and clozapine brought out a short-latency OFF response and markedly reduced the long-latency ON response. The selective serotonin 5-HT2A antagonist MDL 100907 had similar effects on RGCs. The effects of haloperidol on light responses of RGCs can be explained by its D2 receptor antagonism. The effects of clozapine on light responses of RGCs on the other hand may largely be due to its 5-HT2A receptor antagonism. Overall, the results suggest that antipsychotic drugs may be useful in improving vision in patients with retinitis pigmentosa.

Identification of spinal 5-HT sub 3 receptors and their role in the modulation of nociceptive responses in the rat

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

Glaum, S.R.

1988-01-01

The project consisted of two related studies: (1) the characterization of serotonin binding sites in crude and purified synaptic membranes prepared from the rat spinal cord, and (2) the association of serotonin binding sites with functional 5-HT receptor responses in the modulation of nociceptive information at the level of the spinal cord. The first series of experiments involved the preparation of membranes from the dorsal and ventral halves of the rat spinal cord and the demonstration of specific ({sup 3}H)serotonin binding to these membranes. High affinity binding sites which conformed to the 5-HT{sub 3} subtype were identified in dorsal, butmore » not ventral spinal cord synaptic membranes. These experiments also confirmed the presence of high affinity ({sup 3}H)5-HT binding sites in dorsal spinal cord synaptic membranes of the 5-HT{sub 1} subtype. The second group of studies demonstrated the ability of selective 5-HT{sub 3} antagonists to inhibit the antinociceptive response to intrathecally administered 5-HT, as measured by a change in tail flick and hot plate latencies. Intrathecal pretreatment with the selective 5-HT{sub 3} antagonists ICS 205-930 or MDL 72222 abolished the antinociceptive effects of 5-HT. Furthermore, the selective 5-HT{sub 3} agonist 2-methyl-5-HT mimicked the antinociceptive effects of 5-HT.« less

Automated Test Methods for XML Metadata

DTIC Science & Technology

2017-12-28

Group under RCC Task TG-147. This document (Volume VI of the RCC Document 118 series) describes procedures used for evaluating XML metadata documents...including TMATS, MDL, IHAL, and DDML documents. These documents contain specifications or descriptions of artifacts and systems of importance to...the collection and management of telemetry data. The methods defined in this report provide a means of evaluating the suitability of such a metadata

Ultra-Violet/Electron Beam Detoxification of Nitroglycerin/Propylene Glycol Dinrate Waste Water, Phase 1

DTIC Science & Technology

1994-03-16

University of Vienna’s Institute for Theoretical and Radiation Chemistry provided assistance in the development of chemical theory. Z. Liu, Associate...Professor of Applied Chemistry at the University of Science and Technology, Hefei, Peoples Republic of China provided support with physical measurements. The...include Glyocollic acid " Inogani Nitates> 90 nitroglycerine, propylene glycol dinitrate Inorganic Nitrates (PGDN), trimethylolethane trinitrate MDL

Microgravity

NASA Image and Video Library

1999-04-01

The Equiaxed Dendritic Solidification Experiment (EDSE) is a material sciences investigation under the Formation of Microstructures/pattern formation discipline. The objective is to study the microstructural evolution of and thermal interactions between several equiaxed crystals growing dendritically in a supercooled melt of a pure and transparent substance under diffusion controlled conditions. Dendrites growing at .4 supercooling from a 2 stinger growth chamber for the EDSE in the Microgravity Development Lab (MDL).

Microgravity

NASA Image and Video Library

1999-04-01

The Equiaxed Dendritic Solidification Experiment (EDSE) is a material sciences investigation under the Formation of Microstructures/pattern formation discipline. The objective is to study the microstructural evolution of and thermal interactions between several quiaxed crystals growing dendritically in a supercooled melt of a pure and transparent substance under diffusion controlled conditions. George Myers, controls engineer, monitors the thermal environment of a ground test for the EDSE located in the Microgravity Development Laboratory (MDL).

Microgravity

NASA Image and Video Library

1999-04-01

The Equiaxed Dendritic Solidification Experiment (EDSE) is a material sciences investigation under the Formation of Microstructures/pattern formation discipline. The objective is to study the microstructural evolution of and thermal interactions between several equiaxed crystals growing dendritically in a supercooled melt of a pure and transparent substance under diffusion controlled conditions. EDSE/TDSE project engineer, Zena Hester, monitors a test run of the EDSE located in the Microgravity Development Laboratory (MDL).

77 FR 11158 - Notice of Lodging of Proposed Consent Decree Under the Clean Water Act

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... Notice is hereby given that on February 17, 2012, a proposed Consent Decree in In Re: Oil Spill by the Oil Rig ``Deepwater Horizon'' in the Gulf of Mexico, on April 20, 2010, MDL 2179, was lodged with the... discharge of oil into the Gulf of Mexico resulting from the April 20, 2010 blowout of the Macondo well and...

Compact DD generator-based neutron activation analysis (NAA) system to determine fluorine in human bone in vivo: a feasibility study.

PubMed

Mostafaei, Farshad; Blake, Scott P; Liu, Yingzi; Sowers, Daniel A; Nie, Linda H

2015-10-01

The subject of whether fluorine (F) is detrimental to human health has been controversial for many years. Much of the discussion focuses on the known benefits and detriments to dental care and problems that F causes in bone structure at high doses. It is therefore advantageous to have the means to monitor F concentrations in the human body as a method to directly assess exposure. F accumulates in the skeleton making bone a useful biomarker to assess long term cumulative exposure to F. This study presents work in the development of a non-invasive method for the monitoring of F in human bone. The work was based on the technique of in vivo neutron activation analysis (IVNAA). A compact deuterium-deuterium (DD) generator was used to produce neutrons. A moderator/reflector/shielding assembly was designed and built for human hand irradiation. The gamma rays emitted through the (19)F(n,γ)(20)F reaction were measured using a HPGe detector. This study was undertaken to (i) find the feasibility of using DD system to determine F in human bone, (ii) estimate the F minimum detection limit (MDL), and (iii) optimize the system using the Monte Carlo N-Particle eXtended (MCNPX) code in order to improve the MDL of the system. The F MDL was found to be 0.54 g experimentally with a neutron flux of 7   ×   10(8) n s(-1) and an optimized irradiation, decay, and measurement time scheme. The numbers of F counts from the experiment were found to be close to the (MCNPX) simulation results with the same irradiation and detection parameters. The equivalent dose to the irradiated hand and the effective dose to the whole body were found to be 0.9 mSv and 0.33 μSv, respectively. Based on these results, it is feasible to develop a compact DD generator based IVNAA system to measure bone F in a population with moderate to high F exposure.

Earth-Affecting Solar Causes Observatory (EASCO): Results of the Mission Concept Study

NASA Technical Reports Server (NTRS)

Gopalswamy, Natchimuthuk

2011-01-01

Coronal mass ejections (CMEs) corotating interaction regions (CIRs) are two large-scale structures that originate from the Sun and affect the heliosphere in general and Earth in particular. While CIRs are generally detected by in-situ plasma signatures, CMEs are remote-sensed when they are still close to the Sun. The current understanding of CMEs primarily come from the SOHO and STEREO missions. In spite of the enormous progress made, there are some serious deficiencies in these missions. For example, these missions did not carry all the necessary instruments (STEREO did not have a magnetograph; SOHO did not have in-situ magnetometer). From the Sun-Earth line, SOHO was not well-suited for observing Earth-directed CMEs because of the occulting disk. STEREO's angle with the Sun-Earth line is changing constantly, so only a limited number of Earth-directed CMEs were observed in profile. In order to overcome these difficulties, we proposed a news L5 mission concept known as the Earth-Affecting Solar Causes Observatory (EASCO). The mission concept was recently studied at the Mission Design Laboratory (MDL), NASA Goddard Space Flight Center. The aim of the MDL study was to see how the scientific payload consisting of ten instruments can be accommodated in the spacecraft bus, what propulsion system can transfer the payload to the Sun-Earth L5, and what launch vehicles are appropriate. The study found that all the ten instruments can be readily accommodated and can be launched using an intermediate size vehicle such as Taurus II with enhanced faring. The study also found that a hybrid propulsion system consisting of an ion thruster (using approximately 55 kg of Xenon) and hydrazine (approximately 10 kg) is adequate to place the payload at L5. The transfer will take about 2 years and the science mission will last for 4 years around the next solar maximum in 2025. The mission can be readily extended for another solar cycle to get a solar-cycle worth of data on Earth-affecting CMEs and CIRs. This paper provides a highlight of the MDL study results.

Pharmacological characterization of the 5-HT receptor-mediated contraction in the mouse isolated ileum

PubMed Central

Tuladhar, B R; Womack, M D; Naylor, R J

2000-01-01

The pharmacological characterization of a 5-HT receptor-mediated contractile response in the mouse isolated ileum is described. In the presence of methysergide (1 μM), 5-hydroxytryptamine (5-HT, 0.3–100 μM) produced phasic concentration-dependent contractions of segments of the mouse isolated ileum with a pEC50 value of 5.47±0.09. The 5-HT3 receptor selective agonists m-chlorophenylbiguanide (0.3–100 μM, pEC50 5.81±0.04), 1-phenylbiguanide (3–100 μM, pEC50 5.05±0.06) and 2-methyl-5-HT (3–100 μM, pEC50 5.00±0.07) acted as full agonists to induce contractile responses. 5-methoxytryptamine (0.1–100 μM), RS 67506 (0.1–100 μM) and α-methyl-5-HT (0.1–100 μM) failed to mimic the 5-HT responses. The contractile response to 5-HT was not antagonized by either 5-HT2 receptor antagonists ritanserin (0.1 μM) or ketanserin (1 μM) nor the 5-HT4 receptor antagonist SB 204070 (0.1 μM). The 5-HT3 receptor selective antagonists granisetron (0.3–1 nM), tropisetron (1–10 nM), ondansetron (10 nM–1 μM) and MDL 72222 (10 nM–1 μM) caused rightward displacement of the concentration-response curves to 5-HT. The lower concentrations of the antagonists caused approximate parallel rightward shifts of the concentration-response curves to 5-HT with apparent pKB values for granisetron (9.70±0.39), tropisetron (9.18±0.20), ondansetron (8.84±0.24) and MDL 72222 (8.65±0.35). But higher concentrations of antagonists resulted in a progressive reduction in the maximum responses. The contractile response to 5-HT was abolished by tetrodotoxin (0.3 μM); atropine (0.1 and 1 μM) decreased the maximum response of the 5-HT concentration-response curve by approximately 65%. It is concluded that a neuronally located 5-HT3 receptor mediates a contractile response to 5-HT in the mouse ileum. The 5-HT3 receptor in the mouse ileum has a different pharmacological profile to that reported for the guinea-pig ileum. PMID:11139451

Actions of 5-hydroxytryptamine and 5-HT1A receptor ligands on rat dorso-lateral septal neurones in vitro.

PubMed

Van den Hooff, P; Galvan, M

1992-08-01

1. The actions of 5-hydroxytryptamine (5-HT) and some 5-HT1A receptor ligands on neurones in the rat dorso-lateral septal nucleus were recorded in vitro by intracellular recording techniques. 2. In the presence of tetrodotoxin (1 microM) to block any indirect effects, bath application of 5-HT (0.3-30 microM) hyperpolarized the neurones in a concentration-dependent manner and reduced membrane resistance. The hyperpolarization did not exhibit desensitization and was sometimes followed by a small depolarization. 3. The 5-HT1A receptor ligands, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT) and buspirone but not the non-selective 5-HT1 receptor agonist, 1-m-trifluoromethylphenylpiperazine (TFMPP), also hyperpolarized the neurones. 4. 5-HT, 8-OH-DPAT and DP-5-CT appeared to act as full agonists whereas buspirone behaved as a partial agonist. The estimated EC50S were: DP-5-CT 15 nM, 8-OH-DPAT 110 nM, 5-HT 3 microM and buspirone 110 nM. 5. At a concentration of 3 microM, the putative 5-HT1A receptor antagonists, spiperone, methiothepin, NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine) and MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl-methylamino)ethyl]-8- azaspiro[4,5]decane-7,9-dione methyl sulphonate), produced a parallel rightward shift in the concentration-response curve to 5-HT with no significant reduction in the maximum response. The estimated pA2 values were: NAN-190 6.79, MDL 73005EF 6.59, spiperone 6.54 and methiothepin 6.17.6. The 5-HT2/5-HTlc receptor antagonist, ketanserin (3 microM) and the 5HT3 receptor antagonist, tropisetron (3 microM) did not antagonize the 5-HT-induced hyperpolarizations; however, ketanserin blocked the depolarization which sometimes followed the hyperpolarization.7. It is concluded that the 5-HT-induced membrane hyperpolarization of rat dorso-lateral septal neurones is mediated by 5-HTA receptors.

Different Roles for Contracture and Calpain in Calcium Paradox-Induced Heart Injury

PubMed Central

Zhang, Jian-Ying; Bi, Sheng-Hui; Xu, Ming; Jin, Zhen-Xiao; Yang, Yang; Jiang, Xiao-Fan; Zhou, Jing-Jun

2012-01-01

The Ca2+ paradox represents a good model to study Ca2+ overload injury in ischemic heart diseases. We and others have demonstrated that contracture and calpain are involved in the Ca2+ paradox-induced injury. This study aimed to elucidate their roles in this model. The Ca2+ paradox was elicited by perfusing isolated rat hearts with Ca2+-free KH media for 3 min or 5 min followed by 30 min of Ca2+ repletion. The LVDP was measured to reflect contractile function, and the LVEDP was measured to indicate contracture. TTC staining and the quantification of LDH release were used to define cell death. Calpain activity and troponin I release were measured after Ca2+ repletion. Ca2+ repletion of the once 3-min Ca2+ depleted hearts resulted in almost no viable tissues and the disappearance of contractile function. Compared to the effects of the calpain inhibitor MDL28170, KB-R7943, an inhibitor of the Na+/Ca2+ exchanger, reduced the LVEDP level to a greater extent, which was well correlated with improved contractile function recovery and tissue survival. The depletion of Ca2+ for 5 min had the same effects on injury as the 3-min Ca2+ depletion, except that the LVEDP in the 5-min Ca2+ depletion group was lower than the level in the 3-min Ca2+ depletion group. KB-R7943 failed to reduce the level of LVEDP, with no improvement in the LVDP recovery in the hearts subjected to the 5-min Ca2+ depletion treatment; however, KB-R7943 preserved its protective effects in surviving tissue. Both KB-R7943 and MDL28170 attenuated the Ca2+ repletion-induced increase in calpain activity in 3 min or 5 min Ca2+ depleted hearts. However, only KB-R7943 reduced the release of troponin I from the Ca2+ paradoxic heart. These results provide evidence suggesting that contracture is the main cause for contractile dysfunction, while activation of calpain mediates cell death in the Ca2+ paradox. PMID:23284963

Detection of hydrogen peroxide based on long-path absorption spectroscopy using a CW EC-QCL

NASA Astrophysics Data System (ADS)

Sanchez, N. P.; Yu, Y.; Dong, L.; Griffin, R.; Tittel, F. K.

2016-02-01

A sensor system based on a CW EC-QCL (mode-hop-free range 1225-1285 cm-1) coupled with long-path absorption spectroscopy was developed for the monitoring of gas-phase hydrogen peroxide (H2O2) using an interference-free absorption line located at 1234.055 cm-1. Wavelength modulation spectroscopy (WMS) with second harmonic detection was implemented for data processing. Optimum levels of pressure and modulation amplitude of the sensor system led to a minimum detection limit (MDL) of 25 ppb using an integration time of 280 sec. The selected absorption line for H2O2, which exhibits no interference from H2O, makes this sensor system suitable for sensitive and selective monitoring of H2O2 levels in decontamination and sterilization processes based on Vapor Phase Hydrogen Peroxide (VPHP) units, in which a mixture of H2O and H2O2 is generated. Furthermore, continuous realtime monitoring of H2O2 concentrations in industrial facilities employing this species can be achieved with this sensing system in order to evaluate average permissible exposure levels (PELs) and potential exceedances of guidelines established by the US Occupational Safety and Health Administration for H2O2.

40 CFR Appendix B to Part 136 - Definition and Procedure for the Determination of the Method Detection Limit-Revision 1.11

Code of Federal Regulations, 2010 CFR

2010-07-01

... calculated method detection limit. To insure that the estimate of the method detection limit is a good...) where: MDL = the method detection limit t(n-1,1- α=.99) = the students' t value appropriate for a 99... Determination of the Method Detection Limit-Revision 1.11 B Appendix B to Part 136 Protection of Environment...

Oxidative Damage in Parkinson’s Disease.

DTIC Science & Technology

1999-10-01

with a monoclonal antibody column. Proc. Natl. Acad. Sei. USA 89:3375-3379; 1992. [34] Deegan , P.; Shigenaga, M. K.; Park, E. M.; Alperin, P. E...Malonate and MPTP Neurotoxicity Russell T Matthews,* Peter Klivenyi,* Gerald Mueller,* Lichuan Yang,* Marike Wermer,* Craig E. Thomas,t and M. Flint...Biochemicals (Wayland, MA). MDL 101,002 was generously supplied by Dr. Craig Thomas of Hoechst Marion Roussell. Male Sprague-Dawley rats (Charles River

Environmental Assessment: Radio Receiving and Transmission Site (RRATS) at Joint Base McGuire-Dix-Lakehurst, New Jersey

DTIC Science & Technology

2012-08-01

with the Proposed Action Based on the analysis in the EA, which is herewith incorporated by reference, I determine that no significant adverse effects ...would proceed with the implementation of the RRATS. I conclude that the environmental effects of the proposed action at JB MDL are not significant...THE AREA OF POTENTIAL EFFECT ............................................................ 3-5 TABLE 5-1. SUMMARY OF IMPACTS

Multimodal Signal Processing for Personnel Detection and Activity Classification for Indoor Surveillance

DTIC Science & Technology

2013-11-15

features and designed a classifier that achieves up to 95% classification accuracy on classifying the occupancy with indoor footstep data. MDL-based...information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and...maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other

Computer Based Behavioral Biometric Authentication via Multi-Modal Fusion

DTIC Science & Technology

2013-03-01

the decisions made by each individual modality. Fusion of features is the simple concatenation of feature vectors from multiple modalities to be...of Features BayesNet MDL 330 LibSVM PCA 80 J48 Wrapper Evaluator 11 3.5.3 Ensemble Based Decision Level Fusion. In ensemble learning multiple ...The high fusion percentages validate our hypothesis that by combining features from multiple modalities, classification accuracy can be improved. As

Implementing Effective Mission Systems Engineering Practices During Early Project Formulation Phases

NASA Technical Reports Server (NTRS)

Moton, Tryshanda

2016-01-01

Developing and implementing a plan for a NASA space mission can be a complicated process. The needs, goals, and objectives of any proposed mission or technology must be assessed early in the Project Life Cycle. The key to successful development of a space mission or flight project is the inclusion of systems engineering in early project formulation, namely during Pre-phase A, Phase A, and Phase B of the NASA Project Life Cycle. When a space mission or new technology is in pre-development, or "pre-Formulation", feasibility must be determined based on cost, schedule, and risk. Inclusion of system engineering during project formulation is key because in addition to assessing feasibility, design concepts are developed and alternatives to design concepts are evaluated. Lack of systems engineering involvement early in the project formulation can result in increased risks later in the implementation and operations phases of the project. One proven method for effective systems engineering practice during the pre-Formulation Phase is the use of a mission conceptual design or technology development laboratory, such as the Mission Design Lab (MDL) at NASA's Goddard Space Flight Center (GSFC). This paper will review the engineering process practiced routinely in the MDL for successful mission or project development during the pre-Formulation Phase.

Tachykinin receptors in the guinea-pig renal pelvis: activation by exogenous and endogenous tachykinins.

PubMed

Maggi, C A; Patacchini, R; Eglezos, A; Quartara, L; Giuliani, S; Giachetti, A

1992-09-01

1. The contractile response to substance P, neurokinin A, selective agonists for the NK1, NK2 and NK3 tachykinin receptors and the activity of receptor-selective antagonists has been investigated in circular muscle strips of the guinea-pig isolated renal pelvis in the presence of indomethacin (3 microM). 2. Neurokinin A was the most potent agonist tested, being about 32 times more potent than substance P. The action of both substance P and neurokinin A was enhanced by peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each). The selective NK2 receptor agonist [beta Ala8] neurokinin A (4-10), was slightly less potent and effective than neurokinin A itself. The selective NK1 receptor agonist [Sar9] substance P sulphone was effective at low (nM) concentrations but its maximal effect did not exceed 30% of maximal response to substance P or neurokinin A. The NK3-selective agonist [MePhe7] neurokinin B was effective only at high (microM) concentrations. 3. The pseudopeptide derivative of neurokinin A(4-10), MDL 28,564, displayed a clear-cut agonist character, although it was less potent than neurokinin A. 4. The responses to roughly equieffective (25-35% of maximal response) concentrations of [beta Ala8] neurokinin A (4-10), MDL 28,564 and [MePhe7] neurokinin B were antagonized to a similar extent by MEN 10,376 (3 microM), a selective NK2 tachykinin receptor antagonist, while the response to [Sar9] substance P sulphone was unchanged. 5. The response to [Sar9] substance P sulphone was inhibited by the NK1 receptor-selective antagonist, GR 82,334 (3 microM) while the response to [beta Ala8] neurokinin A (4-10) was unchanged. 6. The selective NK2 receptor antagonists MEN 10,376, L 659,877 and R 396 antagonized competitively the response to [PAla8] neurokinin A (4-10) with the following rank order of potency (pA2 values in parentheses): MEN 10,376 (7.41)>L 659,877 (7.15)>R 396 (6.43). MEN 10,376 and L 659,877 also competitively antagonized the response to neurokinin A, although with lower potency as compared to the selective NK2 receptor agonist.7. MEN 10,376, L 659,877 and R 396 reduced in a concentration-dependent manner the contractile response produced by electrical field stimulation (1 Hz, 100 V, 0.25 ms pulse width, trains of 10 s). The rank order of potency of NK2 receptor antagonists in blocking the response to electrical stimulation (MEN 10,376> L 659,877> R 396) closely mimicked their potency in antagonizing exogenous tachykinins.8. The inhibitory effect of MEN 10,376 toward responses produced by electrical field stimulation was significantly reduced when tested in the presence of peptidase inhibitors, which increased significantly the response to nerve stimulation.9. GR 82,334 (3 pM) did not significantly affect the response to nerve stimulation in untreated preparations and slightly reduced it in the presence of peptidase inhibitors.10. We conclude that both NK, and NK2 receptors mediate the contractile effect of tachykinins in the circular muscle of the guinea-pig renal pelvis and that the response ascribable to NK2 receptor stimulation is larger than that ascribed to NK, receptor stimulation. The NK2 receptor in the guinea-pig renal pelvis belongs to the same subtype previously identified in the rabbit pulmonary artery. NK2 receptors play a dominant role in the physiological response determined by the release of endogenous tachykinins and a contribution of NKI receptors becomes evident after inhibition of peptide degradation.

Interactive object modelling based on piecewise planar surface patches.

PubMed

Prankl, Johann; Zillich, Michael; Vincze, Markus

2013-06-01

Detecting elements such as planes in 3D is essential to describe objects for applications such as robotics and augmented reality. While plane estimation is well studied, table-top scenes exhibit a large number of planes and methods often lock onto a dominant plane or do not estimate 3D object structure but only homographies of individual planes. In this paper we introduce MDL to the problem of incrementally detecting multiple planar patches in a scene using tracked interest points in image sequences. Planar patches are reconstructed and stored in a keyframe-based graph structure. In case different motions occur, separate object hypotheses are modelled from currently visible patches and patches seen in previous frames. We evaluate our approach on a standard data set published by the Visual Geometry Group at the University of Oxford [24] and on our own data set containing table-top scenes. Results indicate that our approach significantly improves over the state-of-the-art algorithms.

Interactive object modelling based on piecewise planar surface patches☆

PubMed Central

Prankl, Johann; Zillich, Michael; Vincze, Markus

2013-01-01

Detecting elements such as planes in 3D is essential to describe objects for applications such as robotics and augmented reality. While plane estimation is well studied, table-top scenes exhibit a large number of planes and methods often lock onto a dominant plane or do not estimate 3D object structure but only homographies of individual planes. In this paper we introduce MDL to the problem of incrementally detecting multiple planar patches in a scene using tracked interest points in image sequences. Planar patches are reconstructed and stored in a keyframe-based graph structure. In case different motions occur, separate object hypotheses are modelled from currently visible patches and patches seen in previous frames. We evaluate our approach on a standard data set published by the Visual Geometry Group at the University of Oxford [24] and on our own data set containing table-top scenes. Results indicate that our approach significantly improves over the state-of-the-art algorithms. PMID:24511219

Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

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

Valerio, Luis G.; Arvidson, Kirk B.; Chanderbhan, Ronald F.

2007-07-01

Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest ismore » MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals, comprised primarily of pharmaceutical, industrial and some natural products developed under an FDA-MDL cooperative research and development agreement (CRADA). The predictive performance for this group of dietary natural products and the control group was 97% sensitivity and 80% concordance. Specificity was marginal at 53%. This study finds that the in silico QSAR analysis employing this software's rodent carcinogenicity database is capable of identifying the rodent carcinogenic potential of naturally occurring organic molecules found in the human diet with a high degree of sensitivity. It is the first study to demonstrate successful QSAR predictive modeling of naturally occurring carcinogens found in the human diet using an external validation test. Further test validation of this software and expansion of the training data set for dietary chemicals will help to support the future use of such QSAR methods for screening and prioritizing the risk of dietary chemicals when actual animal data are inadequate, equivocal, or absent.« less

Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress

PubMed Central

Jiang, De-guo; Jin, Shi-li; Li, Gong-ying; Li, Qing-qing; Li, Zhi-ruo; Ma, Hong-xia; Zhuo, Chuan-jun; Jiang, Rong-huan; Ye, Min-jie

2016-01-01

Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress. PMID:27857753

Bayesian outcome-based strategy classification.

PubMed

Lee, Michael D

2016-03-01

Hilbig and Moshagen (Psychonomic Bulletin & Review, 21, 1431-1443, 2014) recently developed a method for making inferences about the decision processes people use in multi-attribute forced choice tasks. Their paper makes a number of worthwhile theoretical and methodological contributions. Theoretically, they provide an insightful psychological motivation for a probabilistic extension of the widely-used "weighted additive" (WADD) model, and show how this model, as well as other important models like "take-the-best" (TTB), can and should be expressed in terms of meaningful priors. Methodologically, they develop an inference approach based on the Minimum Description Length (MDL) principles that balances both the goodness-of-fit and complexity of the decision models they consider. This paper aims to preserve these useful contributions, but provide a complementary Bayesian approach with some theoretical and methodological advantages. We develop a simple graphical model, implemented in JAGS, that allows for fully Bayesian inferences about which models people use to make decisions. To demonstrate the Bayesian approach, we apply it to the models and data considered by Hilbig and Moshagen (Psychonomic Bulletin & Review, 21, 1431-1443, 2014), showing how a prior predictive analysis of the models, and posterior inferences about which models people use and the parameter settings at which they use them, can contribute to our understanding of human decision making.

Predicting human skin absorption of chemicals: development of a novel quantitative structure activity relationship.

PubMed

Luo, Wen; Medrek, Sarah; Misra, Jatin; Nohynek, Gerhard J

2007-02-01

The objective of this study was to construct and validate a quantitative structure-activity relationship model for skin absorption. Such models are valuable tools for screening and prioritization in safety and efficacy evaluation, and risk assessment of drugs and chemicals. A database of 340 chemicals with percutaneous absorption was assembled. Two models were derived from the training set consisting 306 chemicals (90/10 random split). In addition to the experimental K(ow) values, over 300 2D and 3D atomic and molecular descriptors were analyzed using MDL's QsarIS computer program. Subsequently, the models were validated using both internal (leave-one-out) and external validation (test set) procedures. Using the stepwise regression analysis, three molecular descriptors were determined to have significant statistical correlation with K(p) (R2 = 0.8225): logK(ow), X0 (quantification of both molecular size and the degree of skeletal branching), and SsssCH (count of aromatic carbon groups). In conclusion, two models to estimate skin absorption were developed. When compared to other skin absorption QSAR models in the literature, our model incorporated more chemicals and explored a large number of descriptors. Additionally, our models are reasonably predictive and have met both internal and external statistical validations.

Determination of a wide range of volatile organic compounds in ambient air using multisorbent adsorption/thermal desorption and gas chromatography/mass spectrometry

USGS Publications Warehouse

Pankow, J.F.; Luo, W.; Isabelle, L.M.; Bender, D.A.; Baker, R.J.

1998-01-01

Adsorption/thermal desorption with multisorbent air-sampling cartridges was developed for the determination of 87 method analytes including halogenated alkanes, halogenated alkenes, ethers, alcohols, nitriles, esters, ketones, aromatics, a disulfide, and a furan. The volatilities of the compounds ranged from that of dichlorofluoromethane (CFC12) to that of 1,2,3- trichlorobenzene. The eight most volatile compounds were determined using a 1.5-L air sample and a sample cartridge containing 50 mg of Carbotrap B and 280 mg of Carboxen 1000; the remaining 79 compounds were determined using a 5-L air sample and a cartridge containing 180 mg of Carbotrap B and 70 mg of Carboxen 1000. Analysis and detection were by gas chromatography/mass spectrometry. The minimum detectable level (MDL) concentration values ranged from 0.01 parts per billion by volume (ppbv) for chlorobenzene to 0.4 ppbv for bromomethane; most of the MDL values were in the range 0.02-0.06 ppbv. No breakthrough was detected with the prescribed sample volumes. Analyte stability on the cartridges was very good. Excellent recoveries were obtained with independent check standards. Travel spike recoveries ranged from 90 to 110% for 72 of the 87 compounds. The recoveries were less than 70% for bromomethane and chloroethene and for a few compounds such as methyl acetate that are subject to losses by hydrolysis; the lowest travel spike recovery was obtained for bromomethane (62%). Blank values for all compounds were either below detection or very low. Ambient atmospheric sampling was conducted in New Jersey from April to December, 1997. Three sites characterized by low, moderate, and high densities of urbanization/traffic were sampled. The median detected concentrations of the compounds were either similar at all three sites (as with the chlorofluorocarbon compounds) or increased with the density of urbanization/traffic (as with dichloromethane, MTBE, benzene, and toluene). For toluene, the median detected concentrations were 0.23, 0.42, and 0.70 ppbv at the three sites. Analytical precision was measured using duplicate sampling. As expected, the precision deteriorated with decreasing concentration. At concentrations greater than 0.2 ppbv, most duplicates differed by less than 20%; below the MDL values, the differences between the duplicates were larger, but they were still typically less than 40%.

Interactive Visualization of Infrared Spectral Data: Synergy of Computation, Visualization, and Experiment for Learning Spectroscopy

NASA Astrophysics Data System (ADS)

Lahti, Paul M.; Motyka, Eric J.; Lancashire, Robert J.

2000-05-01

A straightforward procedure is described to combine computation of molecular vibrational modes using commonly available molecular modeling programs with visualization of the modes using advanced features of the MDL Information Systems Inc. Chime World Wide Web browser plug-in. Minor editing of experimental spectra that are stored in the JCAMP-DX format allows linkage of IR spectral frequency ranges to Chime molecular display windows. The spectra and animation files can be combined by Hypertext Markup Language programming to allow interactive linkage between experimental spectra and computationally generated vibrational displays. Both the spectra and the molecular displays can be interactively manipulated to allow the user maximum control of the objects being viewed. This procedure should be very valuable not only for aiding students through visual linkage of spectra and various vibrational animations, but also by assisting them in learning the advantages and limitations of computational chemistry by comparison to experiment.

Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A

DTIC Science & Technology

2012-04-02

Ashish G. Soman,§ Biren K. Joshi,§ Sara M. Hein,§ Donald T. Wicklow,∥ and Leonard A. Smith*,⊥ †Division of Integrated Toxicology , U.S. Army Medical...of chemicals for bacterial mutagenicity using electrotopological E-state indices and MDL QSAR software. Regul. Toxicol. Pharmacol. 2005, 43, 313−323...12) Feng, J.; Lurati, L.; Ouyang, H.; Robinson, T.; Wang, Y.; Yuan, S.; Young, S. S. Predictive toxicology : Benchmarking molecular descriptors and

Demonstration of a portable near-infrared CH4 detection sensor based on tunable diode laser absorption spectroscopy

NASA Astrophysics Data System (ADS)

Zheng, Chuan-Tao; Huang, Jian-Qiang; Ye, Wei-Lin; Lv, Mo; Dang, Jing-Min; Cao, Tian-Shu; Chen, Chen; Wang, Yi-Ding

2013-11-01

A portable near-infrared (NIR) CH4 detection sensor based on a distributed feedback (DFB) laser modulated at 1.654 μm is experimentally demonstrated. Intelligent temperature controller with an accuracy of -0.07 to +0.09 °C as well as a scan and modulation module generating saw-wave and cosine-wave signals are developed to drive the DFB laser, and a cost effective lock-in amplifier used to extract the second harmonic signal is integrated. Thorough experiments are carried out to obtain detection performances, including detection range, accuracy, stability and the minimum detection limit (MDL). Measurement results show that the absolute detection error relative to the standard value is less than 7% within the range of 0-100%, and the MDL is estimated to be about 11 ppm under an absorption length of 0.2 m and a noise level of 2 mVpp. Twenty-four hours monitoring on two gas samples (0.1% and 20%) indicates that the absolute errors are less than 7% and 2.5%, respectively, suggesting good long term stability. The sensor reveals competitive characteristics compared with other reported portable or handheld sensors. The developed sensor can also be used for the detection of other gases by adopting other DFB lasers with different center-wavelength using the same hardware and slightly modified software.

MIMO capacities and outage probabilities in spatially multiplexed optical transport systems.

PubMed

Winzer, Peter J; Foschini, Gerard J

2011-08-15

With wavelength-division multiplexing (WDM) rapidly nearing its scalability limits, space-division multiplexing (SDM) seems the only option to further scale the capacity of optical transport networks. In order for SDM systems to continue the WDM trend of reducing energy and cost per bit with system capacity, integration will be key to SDM. Since integration is likely to introduce non-negligible crosstalk between multiple parallel transmission paths, multiple-input multiple output (MIMO) signal processing techniques will have to be used. In this paper, we discuss MIMO capacities in optical SDM systems, including related outage considerations which are an important part in the design of such systems. In order to achieve the low-outage standards required for optical transport networks, SDM transponders should be capable of individually addressing, and preferably MIMO processing all modes supported by the optical SDM waveguide. We then discuss the effect of distributed optical noise in MIMO SDM systems and focus on the impact of mode-dependent loss (MDL) on system capacity and system outage. Through extensive numerical simulations, we extract scaling rules for mode-average and mode-dependent loss and show that MIMO SDM systems composed of up to 128 segments and supporting up to 128 modes can tolerate up to 1 dB of per-segment MDL at 90% of the system's full capacity at an outage probability of 10(-4). © 2011 Optical Society of America

Brainstorming: weighted voting prediction of inhibitors for protein targets.

PubMed

Plewczynski, Dariusz

2011-09-01

The "Brainstorming" approach presented in this paper is a weighted voting method that can improve the quality of predictions generated by several machine learning (ML) methods. First, an ensemble of heterogeneous ML algorithms is trained on available experimental data, then all solutions are gathered and a consensus is built between them. The final prediction is performed using a voting procedure, whereby the vote of each method is weighted according to a quality coefficient calculated using multivariable linear regression (MLR). The MLR optimization procedure is very fast, therefore no additional computational cost is introduced by using this jury approach. Here, brainstorming is applied to selecting actives from large collections of compounds relating to five diverse biological targets of medicinal interest, namely HIV-reverse transcriptase, cyclooxygenase-2, dihydrofolate reductase, estrogen receptor, and thrombin. The MDL Drug Data Report (MDDR) database was used for selecting known inhibitors for these protein targets, and experimental data was then used to train a set of machine learning methods. The benchmark dataset (available at http://bio.icm.edu.pl/∼darman/chemoinfo/benchmark.tar.gz ) can be used for further testing of various clustering and machine learning methods when predicting the biological activity of compounds. Depending on the protein target, the overall recall value is raised by at least 20% in comparison to any single machine learning method (including ensemble methods like random forest) and unweighted simple majority voting procedures.

Tachykinin receptors in rabbit airways--characterization by functional, autoradiographic and binding studies.

PubMed Central

Black, J. L.; Diment, L. M.; Alouan, L. A.; Johnson, P. R.; Armour, C. L.; Badgery-Parker, T.; Burcher, E.

1992-01-01

1. In many species, both NK1 and NK2 tachykinin receptors appear to be important in mediating the contraction of airway smooth muscle. We have examined the distribution and characterization of receptors for tachykinins in rabbit airways using functional length tension studies, autoradiography and radioligand binding studies. 2. Contractile responses to tachykinins were elicited in four different areas of the respiratory tree--trachea, and three progressively more distal areas of the right bronchus. The NK2 receptor-preferring agonists, neurokinin A (NKA), neuropeptide gamma (NP gamma) and the NK2-selective [Lys5 MeLeu9, Nle10]-NKA(4-10) [NKA (4-10) analogue] produced similar contraction in all four areas. Substance P (SP) and the NK1-selective [Sar9,Met(O2)11]-SP (Sar-SP) exhibited a marked location-dependence in the magnitude of contraction, producing minimal contraction in the trachea and more proximal bronchi with contractions becoming progressively larger in the more distal airways. Senktide (which is selective for the NK3 receptor) produced negligible contraction in all areas. 3. The NK2-selective antagonist, MDL29,913, was a weak antagonist of NKA and NKA(4-10) analogue. At a concentration of 2 microM, it produced a small but significant shift in the response curve to NKA and a greater shift (8 fold) in the curve to NKA(4-10) analogue, but it had no effect on responses to Sar-SP. The non peptide NK1 receptor antagonist, CP-96,345, was also unexpectedly weak in this preparation. The pD2 value for Sar-SP was decreased 27 fold by CP-96,345 at a concentration of 1 microM, without alteration in the maximum response.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 4 PMID:1384914

Trace level determination of selected organophosphorus pesticides and their degradation products in environmental air samples by liquid chromatography-positive ion electrospray tandem mass spectrometry.

PubMed

Raina, Renata; Sun, Lina

2008-05-01

This paper describes a new analytical method for determination of organophosphorus pesticides (OPs) along with their degradation products involving liquid chromatography (LC) positive ion electrospray (ESI+) tandem mass spectrometry (MS-MS) with selective reaction monitoring (SRM). Chromatography was performed on a Gemini C6-Phenyl (150 mmx2.0 mm, 3 microm) with a gradient elution using water-methanol with 0.1% formic acid, 2 mM ammonium acetate mobile phase at a flow rate of 0.2 mL min(-1). The LC separation and MS/MS operating conditions were optimized with a total analysis time less than 40 minutes. Method detection limits of 0.1-5 microg L(-1) for selected organophosphorus pesticides (OP), OP oxon degradation products, and other degradation products: 3,5,6-trichloro-2-pyridinol (TCP); 2-isopropyl-6-methyl-4-pyrimidol (IMP); and diethyl phosphate (DEP). Some OPs such as fenchlorphos are less sensitive (MDL 30 microg L(-1)). Calibration curves were linear with coefficients of correlation better than 0.995. A three-point identification approach was adopted with area from first selective reaction monitoring (SRM) transition used for quantitative analysis, while a second SRM transition along with the ratio of areas obtained from the first to second transition are used for confirmation with sample tolerance established by the relative standard deviation of the ratio obtained from standards. This new method permitted the first known detection of OP oxon degradation products including chlorpyrifos oxon at Bratt's Lake, SK and diazinon oxon and malathion oxon at Abbotsford, BC in atmospheric samples. Atmospheric detection limits typically ranged from 0.2-10 pg m(-3).

Assessment of dietary intake and nutritional status (MNA) in Polish free-living elderly people from rural environments.

PubMed

Wyka, Joanna; Biernat, Jadwiga; Mikołajczak, Jolanta; Piotrowska, Ewa

2012-01-01

The proportion of elderly people in the global population is rapidly increasing. Their nutritional status indicates many deficiencies that are risky to health. The aim of this paper was to assess the nutrition and nutritional status in elderly individuals above 60 years old living in their family houses in rural areas. Dietary intake and nutritional status were measured in 174 elderly women and 64 men living in the rural areas of Oleśnica (near Wrocław, SW Poland). Energy intake, consumption of nutrients, selected anthropometric and biochemical indicators, were measured in two groups: one at risk of malnutrition and one with adequate nutrition. Using the mini nutritional assessment (MNA) questionnaire, 238 persons over 60 years of age were qualified according to their nutritional status. Anthropometric and biochemical parameters were measured. The group of women at risk of malnutrition (n=30) showed a statistically significantly lower energy intake in their diet (1,127 kcal) compared to women with adequate nutrition (1,351 kcal). The entire group of examined individuals showed a too low consumption of fiber, calcium, vitamins C and D, and folates. Most of the examined women had a too high body mass index (BMI) (on average 28.8), waist circumference was 96.3 cm, and the triceps skinfold (TSF) was 25.2mm thick. Women at a risk of malnutrition had statistically significantly lower lipid parameters than those with adequate nutrition (respectively: TC 191.1 vs. 219.1m/dl, p<0.001, LDL-cholesterol 107.1 vs. 125.1m/dl, p<0.008, TG 129 vs. 143 mg/dl). Men with a risk of malnutrition had a statistically significantly lower BMI (26.0 vs. 28.7, p<0.04), and also lower waist and arm perimeters compared to men with correct nutrition. According to the Charlson comorbidity index (CCI), 8.2% of person with adequate nutrition had poor prognostic indicator for overall survival. All the examined individuals showed many significant nutritional deficiencies. The group with nutritional risk had more pronounced nutritional deficiencies. Despite a too low energy value of foods among individuals with correct nutrition, their anthropometric parameters paradoxically showed the presence of excessive fatty tissue. The most frequent diseases existed in examined group were coronary artery disease and congestive heart failure. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Behavioral and Pharmacokinetic Interactions Between Monoamine Oxidase Inhibitors and the Hallucinogen 5-Methoxy-N,N-dimethyltryptamine

PubMed Central

Halberstadt, Adam L.

2016-01-01

Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. We have shown previously that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The goal of the present studies was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation. The present studies examined whether an MAOI can alter the respective contributions of 5-HT1A and 5-HT2A receptors to the effects of 5-MeO-DMT on PPI. A series of interaction studies using the 5-HT1A antagonist WAY-100635 and the 5-HT2A antagonist MDL 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in rats pretreated with an MAOI. The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using liquid chromatography–electrospray ionization–selective reaction monitoring–tandem mass spectrometry (LC-ESI-SRM-MS/MS). 5-MeO-DMT (1 mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. The present results confirm that 5-MeO-DMT can disrupt PPI by activating 5-HT2A, and indicate that MAOIs alter 5-MeO-DMT pharmacodynamics by increasing its accumulation in the central nervous system. PMID:26780349

Introduction in IND and recursive partitioning

NASA Technical Reports Server (NTRS)

Buntine, Wray; Caruana, Rich

1991-01-01

This manual describes the IND package for learning tree classifiers from data. The package is an integrated C and C shell re-implementation of tree learning routines such as CART, C4, and various MDL and Bayesian variations. The package includes routines for experiment control, interactive operation, and analysis of tree building. The manual introduces the system and its many options, gives a basic review of tree learning, contains a guide to the literature and a glossary, and lists the manual pages for the routines and instructions on installation.

Demonstration and Validation of a Regenerated Cellulose Dialysis Membrane Diffusion Sampler for Monitoring Ground Water Quality and Remediation Progress at DoD Sites for Perchlorate and Explosives Compounds

DTIC Science & Technology

2010-09-01

Regulatory Council LRL Laboratory reporting level LDPE Low-density polyethylene MDL Minimum detection limit MNA Monitored natural attenuation...consists of a tubular-shaped bag made of flexible low-density polyethylene ( LDPE ) (Vroblesky, 2001a, 2001b). The LDPE tube is heat-sealed on one end...be constructed from small- diameter LDPE tubing that fits into small-diameter wells. These polyethylene diffusion bag (PDB) samplers have been

Demonstration and Validation of a Regenerated Cellulose Dialysis Membrane Diffusion Sampler for Monitoring Ground-Water Quality and Remediation Progress at DoD Site: Perchlorate and Ordnance Compounds

DTIC Science & Technology

2011-10-01

Regulatory Council LDPE low-density polyethylene MDL minimum detection limit NAVFAC ESC Naval Facilities Engineering Command Engineering Service...membrane sampler design consists of a tubular-shaped bag made of flexible low-density polyethylene ( LDPE ) (Vroblesky, 2001a, 2001b). The LDPE tube is...requirements, and can be constructed from small-diameter LDPE tubing that fits into small- 4 diameter wells. These polyethylene diffusion bag

Demonstration and Validation of a Regenerated Cellulose Dialysis Membrane Diffusion Sampler for Monitoring Ground-Water Quality and Remediation Progress at DoD Sites

DTIC Science & Technology

2010-04-01

LDPE low-density polyethylene LF low-flow purging LRL laboratory reporting level MDL minimum detection limit MNA monitored natural attenuation...shaped bag made of flexible low-density polyethylene ( LDPE ) (Vroblesky, 2001a, 2001b). The LDPE tube is heat-sealed on one end, filled with high...from small- diameter LDPE tubing that fits into small-diameter wells. These PDB samplers have been shown to be useful only for collection of VOCs

Macrodystrophia Lipomatosa: An Unusual Cause of Localized Gigantism.

PubMed

Maheswari, S Uma; Sampath, V; Ramesh, A; Manoharan, K

2016-01-01

Macrodystrophia lipomatosa (MDL) is a rare congenital form of localized gigantism characterized by progressive overgrowth of all mesenchymal elements with a disproportionate increase in fibro adipose tissue. Here we report a case of 20 years old male who presented with history of painless gradual enlargement of entire left upper limb since childhood. Magnetic resonance imaging and histopathology confirmed the diagnosis of macrodystrophia lipomatosa. This condition has to be differentiated from other causes of localized gigantism, since these conditions differ in their course, prognosis, complications and treatment.

Sources and preparation of data for assessing trends in concentrations of pesticides in streams of the United States, 1992–2010

USGS Publications Warehouse

Martin, Jeffrey D.; Eberle, Michael; Nakagaki, Naomi

2011-01-01

This report updates a previously published water-quality dataset of 44 commonly used pesticides and 8 pesticide degradates suitable for a national assessment of trends in pesticide concentrations in streams of the United States. Water-quality samples collected from January 1992 through September 2010 at stream-water sites of the U.S. Geological Survey (USGS) National Water-Quality Assessment (NAWQA) Program and the National Stream Quality Accounting Network (NASQAN) were compiled, reviewed, selected, and prepared for trend analysis. The principal steps in data review for trend analysis were to (1) identify analytical schedule, (2) verify sample-level coding, (3) exclude inappropriate samples or results, (4) review pesticide detections per sample, (5) review high pesticide concentrations, and (6) review the spatial and temporal extent of NAWQA pesticide data and selection of analytical methods for trend analysis. The principal steps in data preparation for trend analysis were to (1) select stream-water sites for trend analysis, (2) round concentrations to a consistent level of precision for the concentration range, (3) identify routine reporting levels used to report nondetections unaffected by matrix interference, (4) reassign the concentration value for routine nondetections to the maximum value of the long-term method detection level (maxLT-MDL), (5) adjust concentrations to compensate for temporal changes in bias of recovery of the gas chromatography/mass spectrometry (GCMS) analytical method, and (6) identify samples considered inappropriate for trend analysis. Samples analyzed at the USGS National Water Quality Laboratory (NWQL) by the GCMS analytical method were the most extensive in time and space and, consequently, were selected for trend analysis. Stream-water sites with 3 or more water years of data with six or more samples per year were selected for pesticide trend analysis. The selection criteria described in the report produced a dataset of 21,988 pesticide samples at 212 stream-water sites. Only 21,144 pesticide samples, however, are considered appropriate for trend analysis.

Statistical modeling, detection, and segmentation of stains in digitized fabric images

NASA Astrophysics Data System (ADS)

Gururajan, Arunkumar; Sari-Sarraf, Hamed; Hequet, Eric F.

2007-02-01

This paper will describe a novel and automated system based on a computer vision approach, for objective evaluation of stain release on cotton fabrics. Digitized color images of the stained fabrics are obtained, and the pixel values in the color and intensity planes of these images are probabilistically modeled as a Gaussian Mixture Model (GMM). Stain detection is posed as a decision theoretic problem, where the null hypothesis corresponds to absence of a stain. The null hypothesis and the alternate hypothesis mathematically translate into a first order GMM and a second order GMM respectively. The parameters of the GMM are estimated using a modified Expectation-Maximization (EM) algorithm. Minimum Description Length (MDL) is then used as the test statistic to decide the verity of the null hypothesis. The stain is then segmented by a decision rule based on the probability map generated by the EM algorithm. The proposed approach was tested on a dataset of 48 fabric images soiled with stains of ketchup, corn oil, mustard, ragu sauce, revlon makeup and grape juice. The decision theoretic part of the algorithm produced a correct detection rate (true positive) of 93% and a false alarm rate of 5% on these set of images.

The MEMS Knudsen Compressor as a Vacuum Pump for Space Exploration Applications

NASA Technical Reports Server (NTRS)

Vargo, S. E.; Muntz, E. P.; Tang, W. C.

2000-01-01

Several lander, probe and rover missions currently under study at the Jet Propulsion Laboratory (JPL) and especially in the Microdevices Laboratory (MDL) Center for Space Microelectronics Technology, focus on utilizing microelectromechanical systems (MEMS) based instruments for science data gathering. These small instruments and NASA's commitment to "faster, better, cheaper" type missions has brought about the need for novel approaches to satisfying mission requirements. Existing in-situ instrument systems clearly lack novel and integrated methods for satisfying their vacuum needs. One attractive candidate for a MEMS vacuum pump is the Knudsen Compressor, which operates based on thermal transpiration. Thermal transpiration describes gas flows induced by temperature differences maintained across orifices, porous membranes or capillary tubes under rarefied conditions. This device has two overwhelmingly attractive features as a MEMS vacuum pump - no moving parts and no fluids. An initial estimate of a Knudsen Compressor's pumping power requirements for a surface atmospheric sampling task on Mars is less than 80 mW, significantly below than alternative pumps. Due to the relatively low energy use for this task and the applicability of the Knudsen Compressor to other applications, the development of a Knudsen Compressor utilizing MEMS fabrication techniques has been initiated. This paper discusses the initial fabrication of a single-stage MEMS Knudsen Compressor vacuum pump, provides performance criteria such as pumping speed, size, energy use and ultimate pressure and details vacuum pump applications in several MDL related in-situ instruments.

Conceptual Design of a Flight Validation Mission for a Hypervelocity Asteroid Intercept Vehicle

NASA Technical Reports Server (NTRS)

Barbee, Brent W.; Wie, Bong; Steiner, Mark; Getzandanner, Kenneth

2013-01-01

Near-Earth Objects (NEOs) are asteroids and comets whose orbits approach or cross Earth s orbit. NEOs have collided with our planet in the past, sometimes to devastating effect, and continue to do so today. Collisions with NEOs large enough to do significant damage to the ground are fortunately infrequent, but such events can occur at any time and we therefore need to develop and validate the techniques and technologies necessary to prevent the Earth impact of an incoming NEO. In this paper we provide background on the hazard posed to Earth by NEOs and present the results of a recent study performed by the NASA/Goddard Space Flight Center s Mission Design Lab (MDL) in collaboration with Iowa State University s Asteroid Deflection Research Center (ADRC) to design a flight validation mission for a Hypervelocity Asteroid Intercept Vehicle (HAIV) as part of a Phase 2 NASA Innovative Advanced Concepts (NIAC) research project. The HAIV is a two-body vehicle consisting of a leading kinetic impactor and trailing follower carrying a Nuclear Explosive Device (NED) payload. The HAIV detonates the NED inside the crater in the NEO s surface created by the lead kinetic impactor portion of the vehicle, effecting a powerful subsurface detonation to disrupt the NEO. For the flight validation mission, only a simple mass proxy for the NED is carried in the HAIV. Ongoing and future research topics are discussed following the presentation of the detailed flight validation mission design results produced in the MDL.

Seasonal Abundance of Culicoides (Diptera: Ceratopogonidae) Collected by Mosquito Magnet® in Northern Gyeonggi-do (Province), Korea

PubMed Central

Kim, Heung Chul; Bellis, Glenn A.; Kim, Myung-Soon; Klein, Terry A.; Chong, Sung-Tae

2014-01-01

Biting midges (Culicoides: Ceratopogonidae) were collected by Mosquito Magnet® traps at the Neutral Nations Supervisory Commission (NNSC) camp and Daeseongdong village inside the demilitarized zone (DMZ) and near the military demarcation line (MDL) separating North and South Korea and at Warrior Base (US Army training site) and Tongilchon 3 km south of the DMZ in northern Gyeonggi Province, Republic of Korea (ROK), from May-October 2010-2012, to determine their seasonal distributions. A total of 18,647 Culicoides females (18,399; 98.7%) and males (248; 1.3%) comprising 16 species were collected. Overall, the most commonly collected species was Culicoides nipponensis (42.9%), followed by C. erairai (29.2%), C. punctatus (20.3%), C. arakawae (3.3%), C. pallidulus (1.8%), and C. circumscriptus (1.4%), while the remaining 10 species accounted for only 1.1% of all Culicoides spp. collected. The seasonal distribution of C. nipponensis was bimodal, with high numbers collected during May-June and again during September. C. erairai was more frequently collected during June-July, followed by sharply decreased populations from August-October. C. punctatus was collected in low numbers from May-September with high numbers collected during October. C. erairai was predominantly collected from the NNSC camp (85.1% of all C. erairai collected) located adjacent to the MDL at Panmunjeom in the northernmost part of Gyeonggi-do (Province), while other sites yielded low numbers of specimens. PMID:24623883

First light of an external occulter testbed at flight Fresnel numbers

NASA Astrophysics Data System (ADS)

Kim, Yunjong; Sirbu, Dan; Hu, Mia; Kasdin, Jeremy; Vanderbei, Robert J.; Harness, Anthony; Shaklan, Stuart

2017-01-01

Many approaches have been suggested over the last couple of decades for imaging Earth-like planets. One of the main candidates for creating high-contrast for future Earth-like planets detection is an external occulter. The external occulter is a spacecraft flown along the line-of-sight of a space telescope to suppress starlight and enable high-contrast direct imaging of exoplanets. The occulter is typically tens of meters in diameter and the separation from the telescope is of the order of tens of thousands of kilometers. Optical testing of a full-scale external occulter on the ground is impossible because of the long separations. Therefore, laboratory verification of occulter designs is necessary to validate the optical models used to design and predict occulter performance. At Princeton, we have designed and built a testbed that allows verification of scaled occulter designs whose suppressed shadow is mathematically identical to that of space occulters. The goal of this experiment is to demonstrate a pupil plane suppression of better than 1e-9 with a corresponding image plane contrast of better than 1e-11. The occulter testbed uses a 77.2 m optical propagation distance to realize the flight Fresnel number of 14.5. The scaled mask is placed at 27.2 m from the artificial source and the camera is located 50.0 m from the scaled mask. We will use an etched silicon mask, manufactured by the Microdevices Lab(MDL) of the Jet Propulsion Laboratory(JPL), as the occulter. Based on conversations with MDL, we expect that 0.5 μm feature size is an achievable resolution in the mask manufacturing process and is therefore likely the indicator of the best possible performance. The occulter is illuminated by a diverging laser beam to reduce the aberrations from the optics before the occulter. Here, we present first light result of a sample design operating at a flight Fresnel number and the experimental setup of the testbed. We compare the experimental results with simulations that predict the ultimate contrast performance.

Evaluation of the QuEChERS method for the extraction of pharmaceuticals and personal care products from drinking-water treatment sludge with determination by UPLC-ESI-MS/MS.

PubMed

Cerqueira, Maristela B R; Guilherme, Juliana R; Caldas, Sergiane S; Martins, Manoel L; Zanella, Renato; Primel, Ednei G

2014-07-01

A modified version of the QuEChERS method has been evaluated for the determination of 21 pharmaceuticals and 6 personal care products (PPCPs) in drinking-water sludge samples by employing ultra high liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The performance of the method was evaluated through linearity, recovery, precision (intra-day), method detection and quantification limits (MDL and MQL) and matrix effect. The calibration curves prepared in acetonitrile and in the matrix extract showed a correlation coefficient ranging from 0.98 to 0.99. MQLs values were on the ng g(-1) order of magnitude for most compounds. Recoveries between 50% and 93% were reached with RSDs lower than 10% for most compounds. Matrix effect was almost absent with values lower than 16% for 93% of the compounds. By coupling a quick and simple extraction called QuEChERS with the UPLC-MS/MS analysis, a method that is both selective and sensitive was obtained. This methodology was successfully applied to real samples and caffeine and benzophenone-3 were detected in ng g(-1) levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

Determination of metabolite of nicergoline in human plasma by high-performance liquid chromatography and its application in pharmacokinetic studies.

PubMed

Zheng, Rong; Wu, Yi-Hong; Jiang, De-Xi; Zhang, Dan

2012-02-01

A fast, simple and sensitive high performance liquid chromatographic (HPLC) method has been developed for determination of 10 α -methoxy-6-methyl ergoline-8 β -methanol (MDL, a main metabolite of nicergoline) in human plasma. One-step liquid-liquid extraction (LLE) with diethyl ether was employed as the sample preparation method. Tizanidine hydrochloride was selected as the internal standard (IS). Analysis was carried out on a Diamonsil ODS column (150 mm×4.6 mm, 5 μm) using acetonitrile-ammonium acetate (0.1 mol/L) (15/85, v/v) as mobile phase at detection wavelength of 224 nm. The calibration curves were linear over the range of 2.288-73.2 ng/mL with a lower limit of quantitation (LLOQ) of 2.288 ng/mL. The intra- and inter-day precision values were below 13% and the recoveries were from 74.47% to 83.20% at three quality control levels. The method herein described was successfully applied in a randomized crossover bioequivalence study of two different nicergoline preparations after administration of 30 mg in 20 healthy volunteers.

Determination of metabolite of nicergoline in human plasma by high-performance liquid chromatography and its application in pharmacokinetic studies

PubMed Central

Zheng, Rong; Wu, Yi-Hong; Jiang, De-Xi; Zhang, Dan

2012-01-01

A fast, simple and sensitive high performance liquid chromatographic (HPLC) method has been developed for determination of 10α-methoxy-6-methyl ergoline-8β-methanol (MDL, a main metabolite of nicergoline) in human plasma. One-step liquid–liquid extraction (LLE) with diethyl ether was employed as the sample preparation method. Tizanidine hydrochloride was selected as the internal standard (IS). Analysis was carried out on a Diamonsil ODS column (150 mm×4.6 mm, 5 μm) using acetonitrile–ammonium acetate (0.1 mol/L) (15/85, v/v) as mobile phase at detection wavelength of 224 nm. The calibration curves were linear over the range of 2.288–73.2 ng/mL with a lower limit of quantitation (LLOQ) of 2.288 ng/mL. The intra- and inter-day precision values were below 13% and the recoveries were from 74.47% to 83.20% at three quality control levels. The method herein described was successfully applied in a randomized crossover bioequivalence study of two different nicergoline preparations after administration of 30 mg in 20 healthy volunteers. PMID:29403722

Introduction to IND and recursive partitioning, version 1.0

NASA Technical Reports Server (NTRS)

Buntine, Wray; Caruana, Rich

1991-01-01

This manual describes the IND package for learning tree classifiers from data. The package is an integrated C and C shell re-implementation of tree learning routines such as CART, C4, and various MDL and Bayesian variations. The package includes routines for experiment control, interactive operation, and analysis of tree building. The manual introduces the system and its many options, gives a basic review of tree learning, contains a guide to the literature and a glossary, lists the manual pages for the routines, and instructions on installation.

Macrodystrophia Lipomatosa: An Unusual Cause of Localized Gigantism

PubMed Central

Maheswari, S Uma; Sampath, V; Ramesh, A; Manoharan, K

2016-01-01

Macrodystrophia lipomatosa (MDL) is a rare congenital form of localized gigantism characterized by progressive overgrowth of all mesenchymal elements with a disproportionate increase in fibro adipose tissue. Here we report a case of 20 years old male who presented with history of painless gradual enlargement of entire left upper limb since childhood. Magnetic resonance imaging and histopathology confirmed the diagnosis of macrodystrophia lipomatosa. This condition has to be differentiated from other causes of localized gigantism, since these conditions differ in their course, prognosis, complications and treatment. PMID:27293271

CHARACTERIZATION OF THE DISCRIMINATIVE STIMULUS EFFECTS OF LORCASERIN IN RATS

PubMed Central

Serafine, Katherine M.; Rice, Kenner C.; France, Charles P.

2016-01-01

Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0.178–1.0 mg/kg) dose-dependently increased lorcaserin-lever responding. The 5-HT2C receptor agonist mCPP and the 5-HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin-lever responding in seven of eight rats. The 5-HT1A receptor agonist 8-OH-DPAT occasioned greater than 90% lorcaserin-lever responding in four of seven rats. The 5-HT2C receptor selective antagonist SB 242084 attenuated lorcaserin-lever responding in all eight rats and the 5-HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin-lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5-HT2C receptors, lorcaserin also has agonist properties at 5-HT2A and 5-HT1A receptors. Because some drugs with 5-HT2A receptor agonist properties are abused, it is important to fully understand the behavioral effects of lorcaserin while considering its potential for treating substance use disorders. PMID:27640338

Boundary-to-Marker Evidence-Controlled Segmentation and MDL-Based Contour Inference for Overlapping Nuclei.

PubMed

Song, Jie; Xiao, Liang; Lian, Zhichao

2017-03-01

This paper presents a novel method for automated morphology delineation and analysis of cell nuclei in histopathology images. Combining the initial segmentation information and concavity measurement, the proposed method first segments clusters of nuclei into individual pieces, avoiding segmentation errors introduced by the scale-constrained Laplacian-of-Gaussian filtering. After that a nuclear boundary-to-marker evidence computing is introduced to delineate individual objects after the refined segmentation process. The obtained evidence set is then modeled by the periodic B-splines with the minimum description length principle, which achieves a practical compromise between the complexity of the nuclear structure and its coverage of the fluorescence signal to avoid the underfitting and overfitting results. The algorithm is computationally efficient and has been tested on the synthetic database as well as 45 real histopathology images. By comparing the proposed method with several state-of-the-art methods, experimental results show the superior recognition performance of our method and indicate the potential applications of analyzing the intrinsic features of nuclei morphology.

System Testing of Ground Cooling System Components

NASA Technical Reports Server (NTRS)

Ensey, Tyler Steven

2014-01-01

This internship focused primarily upon software unit testing of Ground Cooling System (GCS) components, one of the three types of tests (unit, integrated, and COTS/regression) utilized in software verification. Unit tests are used to test the software of necessary components before it is implemented into the hardware. A unit test determines that the control data, usage procedures, and operating procedures of a particular component are tested to determine if the program is fit for use. Three different files are used to make and complete an efficient unit test. These files include the following: Model Test file (.mdl), Simulink SystemTest (.test), and autotest (.m). The Model Test file includes the component that is being tested with the appropriate Discrete Physical Interface (DPI) for testing. The Simulink SystemTest is a program used to test all of the requirements of the component. The autotest tests that the component passes Model Advisor and System Testing, and puts the results into proper files. Once unit testing is completed on the GCS components they can then be implemented into the GCS Schematic and the software of the GCS model as a whole can be tested using integrated testing. Unit testing is a critical part of software verification; it allows for the testing of more basic components before a model of higher fidelity is tested, making the process of testing flow in an orderly manner.

Development of a UPLC-MS/MS method for the determination of ten anticancer drugs in hospital and urban wastewaters, and its application for the screening of human metabolites assisted by information-dependent acquisition tool (IDA) in sewage samples.

PubMed

Ferrando-Climent, L; Rodriguez-Mozaz, S; Barceló, D

2013-07-01

In the present work, the development, optimization, and validation (including a whole stability study) of a fast, reliable, and comprehensive method for the analysis of ten anticancer drugs in hospital and urban wastewater is described. Extraction of these pharmaceutical compounds was performed using automated off-line solid-phase extraction followed by their determination by ultra-performance liquid chromatography coupled to a triple quadrupole-linear ion trap mass spectrometer. Target compounds include nine cytotoxic agents: cyclophosphamide, ifosfamide, docetaxel, paclitaxel, etoposide, vincristine, tamoxifen, methotrexate, and azathioprine; and the cytotoxic quinolone, ciprofloxacin. Method detection limits (MDL) ranged from 0.8 to 24 ng/L. Levels found of cytostatic agents in the hospital and wastewater influents did not differ significantly, and therefore, hospitals cannot be considered as the primary source of this type of contaminants. All the target compounds were detected in at least one of the influent samples analyzed: Ciprofloxacin, cyclophosphamide, tamoxifen, and azathioprine were found in most of them and achieving maximum levels of 14.725, 0.201, 0.133, and 0.188 μg/L, respectively. The rest of target cancer drugs were less frequently detected and at values ranging between MDL and 0.406 μg/L. Furthermore, a feasible, useful, and advantageous approach based on information acquisition tool (information-dependent acquisition) was used for the screening of human metabolites in hospital effluents, where the hydroxy tamoxifen, endoxifen, and carboxyphosphamide were detected.

Effect of entacapone on colon motility and ion transport in a rat model of Parkinson's disease.

PubMed

Li, Li-Sheng; Liu, Chen-Zhe; Xu, Jing-Dong; Zheng, Li-Fei; Feng, Xiao-Yan; Zhang, Yue; Zhu, Jin-Xia

2015-03-28

To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson's disease (PD) rats. Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC ) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing. COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P < 0.01). Entacapone increased mucosal ISC in the colon of rats with PD. This induction was significantly inhibited by apical application of Cl(-) channel blocker diphenylamine-2, 2'-dicarboxylic acid, basolateral application of Na(+)-K(+)-2Cl(-)co-transporter antagonist bumetanide, elimination of Cl(-) from the extracellular fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl(-) flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin. COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl(-) secretion in the PD rat.

Toward automated biochemotype annotation for large compound libraries.

PubMed

Chen, Xian; Liang, Yizeng; Xu, Jun

2006-08-01

Combinatorial chemistry allows scientists to probe large synthetically accessible chemical space. However, identifying the sub-space which is selectively associated with an interested biological target, is crucial to drug discovery and life sciences. This paper describes a process to automatically annotate biochemotypes of compounds in a library and thus to identify bioactivity related chemotypes (biochemotypes) from a large library of compounds. The process consists of two steps: (1) predicting all possible bioactivities for each compound in a library, and (2) deriving possible biochemotypes based on predictions. The Prediction of Activity Spectra for Substances program (PASS) was used in the first step. In second step, structural similarity and scaffold-hopping technologies are employed. These technologies are used to derive biochemotypes from bioactivity predictions and the corresponding annotated biochemotypes from MDL Drug Data Report (MDDR) database. About a one million (982,889) commercially available compound library (CACL) has been tested using this process. This paper demonstrates the feasibility of automatically annotating biochemotypes for large libraries of compounds. Nevertheless, some issues need to be considered in order to improve the process. First, the prediction accuracy of PASS program has no significant correlation with the number of compounds in a training set. Larger training sets do not necessarily increase the maximal error of prediction (MEP), nor do they increase the hit structural diversity. Smaller training sets do not necessarily decrease MEP, nor do they decrease the hit structural diversity. Second, the success of systematic bioactivity prediction relies on modeling, training data, and the definition of bioactivities (biochemotype ontology). Unfortunately, the biochemotype ontology was not well developed in the PASS program. Consequently, "ill-defined" bioactivities can reduce the quality of predictions. This paper suggests the ways in which the systematic bioactivities prediction program should be improved.

Atmospheric particulate mercury at the urban and forest sites in central Poland.

PubMed

Siudek, Patrycja; Frankowski, Marcin; Siepak, Jerzy

2016-02-01

Particulate mercury concentrations were investigated during intensive field campaigns at the urban and forest sites in central Poland, between April 2013 and October 2014. For the first time, quantitative determination of total particulate mercury in coarse (PHg2.2) and fine (PHg0.7) aerosol samples was conducted in Poznań and Jeziory. The concentrations in urban fine and coarse aerosol fractions amounted to < MDL ± 77.1 pg m(-3) and < MDL ± 604.9 pg m(-3), respectively. Aerosol samples collected during the whole study period showed statistically significant differences for particulate mercury concentrations. A strong impact of meteorological conditions (wind velocity, air mass direction, air temperature, and precipitation amount) on particulate mercury concentrations was also observed. In particular, higher variation and concentration range of PHg0.7 and PHg2.2 was reported for wintertime measurements. An increase in atmospheric particulate mercury during the cold season in the study region indicated that coal combustion, i.e., residential and industrial heating, is the main contribution factor for the selected particle size modes. Coarse particulate Hg at the urban site during summer was mainly attributed to anthropogenic sources, with significant contribution from resuspension processes and long-range transport. The highest values of PHg0.7 and PHg2.2 were found during westerly and southerly wind events, reflecting local emission from highly polluted areas. The period from late fall to spring showed that advection from the southern part of Poland was the main factor responsible for elevated Hg concentrations in fine and coarse particles in the investigated region. Moreover, September 2013 could be given as an example of the influence of additional urban activities which occurred approx. 10 m from the sampling site-construction works connected with replacement of the road surface, asphalting, etc. The concentrations of particulate Hg (>600.0 pg m(-3)) were much higher than during the following months when any similar situation did not occur. Our investigations confirmed that Hg in urban aerosol samples was predominantly related to local industrial and commercial emissions, whereas the main source of Hg in particulate matter collected at the forest site was connected with regional anthropogenic processes. This paper provides the results of the first long-term measurements of size-fractionated particulate mercury conducted in central Poland, which could be an important insight into atmospheric Hg processes within such a scarcely investigated part of Europe.

Behavioral and pharmacokinetic interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine.

PubMed

Halberstadt, Adam L

2016-04-01

Monoamine oxidase inhibitors (MAOIs) are often ingested together with tryptamine hallucinogens, but relatively little is known about the consequences of their combined use. We have shown previously that monoamine oxidase-A (MAO-A) inhibitors alter the locomotor profile of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in rats, and enhance its interaction with 5-HT2A receptors. The goal of the present studies was to investigate the mechanism for the interaction between 5-MeO-DMT and MAOIs, and to determine whether other behavioral responses to 5-MeO-DMT are similarly affected. Hallucinogens disrupt prepulse inhibition (PPI) in rats, an effect typically mediated by 5-HT2A activation. 5-MeO-DMT also disrupts PPI but the effect is primarily attributable to 5-HT1A activation. The present studies examined whether an MAOI can alter the respective contributions of 5-HT1A and 5-HT2A receptors to the effects of 5-MeO-DMT on PPI. A series of interaction studies using the 5-HT1A antagonist WAY-100,635 and the 5-HT2A antagonist MDL 11,939 were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in rats pretreated with an MAOI. The effects of MAO-A inhibition on the pharmacokinetics of 5-MeO-DMT and its metabolism to bufotenine were assessed using liquid chromatography-electrospray ionization-selective reaction monitoring-tandem mass spectrometry (LC-ESI-SRM-MS/MS). 5-MeO-DMT (1mg/kg) had no effect on PPI when tested 45-min post-injection but disrupted PPI in animals pretreated with the MAO-A inhibitor clorgyline or the MAO-A/B inhibitor pargyline. The combined effect of 5-MeO-DMT and pargyline on PPI was antagonized by pretreatment with either WAY-100,635 or MDL 11,939. Inhibition of MAO-A increased the level of 5-MeO-DMT in plasma and whole brain, but had no effect on the conversion of 5-MeO-DMT to bufotenine, which was found to be negligible. The present results confirm that 5-MeO-DMT can disrupt PPI by activating 5-HT2A, and indicate that MAOIs alter 5-MeO-DMT pharmacodynamics by increasing its accumulation in the central nervous system. Copyright © 2016 Elsevier Inc. All rights reserved.

Analytical methodology using ion-pair liquid chromatography-tandem mass spectrometry for the determination of four di-ester metabolites of organophosphate flame retardants in California human urine.

PubMed

Petropoulou, Syrago-Styliani E; Petreas, Myrto; Park, June-Soo

2016-02-19

Alkyl- and aryl-esters of phosphoric acid (both halogenated and non-halogenated) are mainly used as flame retardants (FRs), among other applications, in furniture and consumer products and they are collectively known as organophosphate flame retardants (OPFRs). The absorption, biotransformation or elimination of many of these chemicals in humans and their possible health effects are not yet well known. A major reason for the limited information is the nature of these compounds, which causes several technical difficulties in their isolation and sensitive determination. A novel analytical liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the accurate and sensitive determination of four urinary OPFR metabolites: bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCIPP), and diphenyl phosphate (DPhP), using mixed-mode solid phase extraction and isotope. For the first time all four analytes can be identified in one chromatographic run. An extensive investigation of method development parameters (enzymatic hydrolysis, matrix effects, process efficiency, sources of background interferences, linearity, accuracy, precision, stabilities and limits of detection and quantification) was performed in order to address previously reported method inconsistencies and select a process with the highest accuracy and sensitivity. Chromatographic separation was achieved on a Luna C18 (2) (2.00 mm × 150 mm, 3 μm) with mobile phase 80:20 v/v water: MeOH and MeOH: water 95:5 v/v, both containing 1mM tributylamine and 1mM acetic acid. Limits of detection were 0.025 ng mL(-1) for BDCIPP and BCIPP and 0.1 ng mL(-1) for DPhP and BCEP. Absolute recoveries of all four analytes and their labeled compounds were in the range of 88-107%. The method was tested on 13 adult California urine samples. BCEP was detected at 0.4-15 ng mL(-1) with a geometric mean (GM): 1.9 ng mL(-1); BDCIPP at 0.5-7.3 ng mL(-1), (GM: 2.5 ng mL(-1)) and DPhP at

Determination of thyroid hormones in placenta using isotope-dilution liquid chromatography quadrupole time-of-flight mass spectrometry.

PubMed

Li, Zhong-Min; Giesert, Florian; Vogt-Weisenhorn, Daniela; Main, Katharina Maria; Skakkebæk, Niels Erik; Kiviranta, Hannu; Toppari, Jorma; Feldt-Rasmussen, Ulla; Shen, Heqing; Schramm, Karl-Werner; De Angelis, Meri

2018-01-26

The transplacental passage of thyroid hormones (THs) is of great significance since the maternal THs are vitally important in ensuring the normal fetal development. In this paper, we determined the concentrations of seven THs, viz. L-thyroxine (T 4 ), 3,3',5-triiodo-l-thyronine (T 3 ), 3,3',5'-triiodo-l-thyronine (rT 3 ), 3,3'-diiodo-l-thyronine (T 2 ), 3,5-diiodo-l-thyronine (rT 2 ), 3-iodo-l-thyronine (T 1 ) and 3-iodothyronamine (T 1 AM), in placenta using isotope dilution liquid chromatography quadrupole time-of-flight mass spectrometry. We optimized the method using isotopically labeled quantification standards ( 13 C 6 -T 4 , 13 C 6 -T 3 , 13 C 6 -rT 3 and 13 C 6 -T 2 ) and recovery standard ( 13 C 12 -T 4 ) in combination with solid-liquid extraction, liquid-liquid extraction and solid phase extraction. The linearity was obtained in the range of 0.5-150 pg uL -1 with R 2 values >0.99. The method detection limits (MDLs) ranged from 0.01 ng g -1 to 0.2 ng g -1 , while the method quantification limits (MQLs) were between 0.04 ng g -1 and 0.7 ng g -1 . The spike-recoveries for THs (except for T 1 and T 1 AM) were in the range of 81.0%-112%, with a coefficient of variation (CV) of 0.5-6.2%. The intra-day CVs and inter-day CVs were 0.5%-10.3% and 1.19%-8.88%, respectively. Concentrations of the THs were 22.9-35.0 ng g -1  T 4 , 0.32-0.46 ng g -1  T 3 , 2.86-3.69 ng g -1 rT 3 , 0.16-0.26 ng g -1  T 2 , and < MDL for other THs in five human placentas, and 2.05-3.51 ng g -1  T 4 , 0.37-0.62 ng g -1  T 3 , 0.96-1.3 ng g -1 rT 3 , 0.07-0.13 ng g -1  T 2 and < MDL for other THs in five mouse placentas. The presence of T 2 was tracked in placenta for the first time. This method with improved selectivity and sensitivity allows comprehensive evaluation of TH homeostasis in research of metabolism and effects of environmental contaminant exposures. Copyright © 2017 Elsevier B.V. All rights reserved.

Sleep Homeostatic and Waking Behavioral Phenotypes in Egr3-Deficient Mice Associated with Serotonin Receptor 5-HT2 Deficits.

PubMed

Grønli, Janne; Clegern, William C; Schmidt, Michelle A; Nemri, Rahmi S; Rempe, Michael J; Gallitano, Amelia L; Wisor, Jonathan P

2016-12-01

The expression of the immediate early gene early growth response 3 ( Egr3 ) is a functional marker of brain activity including responses to novelty, sustained wakefulness, and sleep. We examined the role of this gene in regulating wakefulness and sleep. Electroencephalogram/electromyogram (EEG/EMG) were recorded in Egr3 -/- and wild-type (WT) mice during 24 h baseline, 6 h sleep disruption and 6 h recovery. Serotonergic signaling was assessed with 6 h EEG/EMG recordings after injections of nonselective 5-HT2 antagonist (clozapine), selective 5-HT2 antagonists (5-HT2A; MDL100907 and 5-HT2BC; SB206553) and a cocktail of both selective antagonists, administered in a randomized order to each animal. Egr3 -/- mice did not exhibit abnormalities in the timing of wakefulness and slow wave sleep (SWS); however, EEG dynamics in SWS (suppressed 1-3 Hz power) and in quiet wakefulness (elevated 3-8 Hz and 15-35 Hz power) differed in comparison to WT-mice. Egr3 -/- mice showed an exaggerated response to sleep disruption as measured by active wakefulness, but with a blunted increase in homeostatic sleep drive (elevated 1-4 Hz power) relative to WT-mice. Egr3 -/-mice exhibit greatly reduced sedative effects of clozapine at the electroencephalographic level. In addition, clozapine induced a previously undescribed dissociated state (low amplitude, low frequency EEG and a stable, low muscle tone) lasting up to 2 h in WT-mice. Egr3 -/- mice did not exhibit this phenomenon. Selective 5-HT2A antagonist, alone or in combination with selective 5-HT2BC antagonist, caused EEG slowing coincident with behavioral quiescence in WT-mice but not in Egr3 -/- mice. Egr3 has an essential role in regulating cortical arousal, wakefulness, and sleep, presumably by its regulation of 5-HT2 receptors. © 2016 Associated Professional Sleep Societies, LLC.

Black carbon emissions in gasoline vehicle exhaust: a measurement and instrument comparison.

PubMed

Kamboures, Michael A; Hu, Shishan; Yu, Yong; Sandoval, Julia; Rieger, Paul; Huang, Shiou-Mei; Zhang, Sherry; Dzhema, Inna; Huo, Darey; Ayala, Alberto; Chang, M C Oliver

2013-08-01

A pilot study was conducted to evaluate the performance and agreement of several commercially available black carbon (BC) measurement instruments, when applied to the quantification of BC in light-duty vehicle (LDV) exhaust. Samples from six vehicles, three fuels, and three driving cycles were used. The pilot study included determinations of the method detection limit (MDL) and repeatability. With respect to the MDL, the real-time instruments outperformed the time-integrated instruments, with MDL = 0.12 mg/mi for the AE51 Aethalometer, and 0.15 mg/mi for the Micro Soot Sensor (MSS), versus 0.38 mg/mi for the IMPROVE_A thermal/ optical method, and 0.35 mg/mi for the OT21_T Optical Transmissometer. The real-time instruments had repeatability values ranging from 30% to 35%, which are somewhat better than those of the time-integrated instruments (40-41%). These results suggest that, despite being less resource intensive, real-time methods can be equivalent or superior to time-integrated methods in terms of sensitivity and repeatability. BC mass data, from the photoacoustic and light attenuation instruments, were compared against same-test EC data, determined using the IMPROVE_A method. The MSS BC data was well correlated with EC, with R2 = 0.85 for the composite results and R2 = 0.86 for the phase-by-phase (PBP) results. The correlation of BC, by the AE51, AE22, and OT21_T with EC was moderate to weak. The weaker correlation was driven by the inclusion of US06 test data in the linear regression analysis. We hypothesize that test-cycle-dependent BC:EC ratios are due to the different physicochemical properties of particulate matter (PM) in US06 and Federal Test Procedure (FTP) tests. Correlation amongst the real-time MSS, PASS-1, AE51, and AE22 instruments was excellent (R2 = 0.83-0.95), below 1 mg/mi levels. In the process of investigating these BC instruments, we learned that BC emissions at sub-1 mg/mi levels can be measured and are achievable by current-generation gasoline engines. Most comparison studies of black carbon (BC) measurement methods were carried out in the ambient air. This study assesses the agreement among various BC measurement instrument in emissions from light-duty gasoline vehicles (LDGVs) on standard test cycles, and evaluates applicability of these methods under various fuel types, driving cycles, and engine combustion technologies. This research helps to fill in the knowledge gap of BC method standardization as stated in the U.S. Environmental Protection Agency (EPA) 2011 Report to Congress on Black Carbon, and these results demonstrate the feasibility of quantification of BC at the 1 mg/mi PM standard in California Low Emission Vehicle III regulations.

MDMA-induced loss of parvalbumin interneurons within the dentate gyrus is mediated by 5HT2A and NMDA receptors

PubMed Central

Collins, Stuart A.; Gudelsky, Gary A.; Yamamoto, Bryan K.

2015-01-01

MDMA is a widely abused psychostimulant which causes a rapid and robust release of the monoaminergic neurotransmitters dopamine and serotonin. Recently, it was shown that MDMA increases extracellular glutamate concentrations in the dorsal hippocampus, which is dependent on serotonin release and 5HT2A/2C receptor activation. The increased extracellular glutamate concentration coincides with a loss of parvalbumin-immunoreactive (PV-IR) interneurons of the dentate gyrus region. Given the known susceptibility of PV interneurons to excitotoxicity, we examined whether MDMA-induced increases in extracellular glutamate in the dentate gyrus are necessary for the loss of PV cells in rats. Extracellular glutamate concentrations increased in the dentate gyrus during systemic and local administration of MDMA. Administration of the NMDA receptor antagonist, MK-801, during systemic injections of MDMA, prevented the loss of PV-IR interneurons seen 10 days after MDMA exposure. Local administration of MDL100907, a selective 5HT2A receptor antagonist, prevented the increases in glutamate caused by reverse dialysis of MDMA directly into the dentate gyrus and prevented the reduction of PV-IR. These findings provide evidence that MDMA causes decreases in PV within the dentate gyrus through a 5HT2A receptor-mediated increase in glutamate and subsequent NMDA receptor activation. PMID:25936514

Pharmacological Properties and Discriminative Stimulus Effects of a Novel and Selective 5-HT2 Receptor Agonist AL-38022A [(S)-2-(8,9-dihydro-7H-pyrano[2,3-g]indazol-1-yl)-1-methylethylamine

PubMed Central

May, Jesse A.; Sharif, Najam A.; Chen, Hwang-Hsing; Liao, John C.; Kelly, Curtis R.; Glennon, Richard A.; Young, Richard; Li, Jun-Xu; Rice, Kenner C.; France, Charles P.

2013-01-01

AL-38022A is a novel synthetic serotonergic (5-HT) ligand that exhibited high affinity for each of the 5-HT2 receptor subtypes (Ki ≤ 2.2 nM), but a significantly lower (>100-fold less) affinity for other 5-HT receptors. In addition, AL-38022A displayed a very low affinity for a broad array of other receptors, neurotransmitter transport sites, ion channels, and second messenger elements, making it a relatively selective agent. AL-38022A potently stimulated functional responses via native and cloned rat (EC50 range: 1.9 – 22.5 nM) and human (EC50 range: 0.5 – 2.2 nM) 5-HT2 receptor subtypes including [Ca2+]i mobilization and tissue contractions with apparently similar potencies and intrinsic activities and was a full agonist at all 5-HT2 receptor subtypes. The CNS activity of AL-38022A was assessed by evaluating its discriminative stimulus effects in both a rat and a monkey drug discrimination paradigm using DOM as the training drug. AL-38022A fully generalized to the DOM stimulus in each of these studies; in monkeys MDL 100907 antagonized both DOM and AL-38022A. The pharmacological profile of AL-38022A suggests that it could be a useful tool in defining 5-HT2 receptor signaling and receptor characterization where 5-HT may function as a neurotransmitter. PMID:18718483

Characterization of the discriminative stimulus effects of lorcaserin in rats.

PubMed

Serafine, Katherine M; Rice, Kenner C; France, Charles P

2016-09-01

Lorcaserin is approved by the Food and Drug Administration for treating obesity and is under consideration for treating substance use disorders; it has agonist properties at serotonin (5-HT)2C receptors and might also have agonist properties at other 5-HT receptor subtypes. This study used drug discrimination to investigate the mechanism(s) of action of lorcaserin. Male Sprague-Dawley rats discriminated 0.56 mg/kg i.p. lorcaserin from saline while responding under a fixed-ratio 5 schedule for food. Lorcaserin (0.178-1.0 mg/kg) dose-dependently increased lorcaserin-lever responding. The 5-HT2C receptor agonist mCPP and the 5-HT2A receptor agonist DOM each occasioned greater than 90% lorcaserin-lever responding in seven of eight rats. The 5-HT1A receptor agonist 8-OH-DPAT occasioned greater than 90% lorcaserin-lever responding in four of seven rats. The 5-HT2C receptor selective antagonist SB 242084 attenuated lorcaserin-lever responding in all eight rats and the 5-HT2A receptor selective antagonist MDL 100907 attenuated lorcaserin-lever responding in six of seven rats. These results suggest that, in addition to agonist properties at 5-HT2C receptors, lorcaserin also has agonist properties at 5-HT2A and 5-HT1A receptors. Because some drugs with 5-HT2A receptor agonist properties are abused, it is important to fully characterize the behavioral effects of lorcaserin while considering its potential for treating substance use disorders. © 2016 Society for the Experimental Analysis of Behavior.

Behavioral tolerance to lysergic acid diethylamide is associated with reduced serotonin-2A receptor signaling in rat cortex.

PubMed

Gresch, Paul J; Smith, Randy L; Barrett, Robert J; Sanders-Bush, Elaine

2005-09-01

Tolerance is defined as a decrease in responsiveness to a drug after repeated administration. Tolerance to the behavioral effects of hallucinogens occurs in humans and animals. In this study, we used drug discrimination to establish a behavioral model of lysergic acid diethylamide (LSD) tolerance and examined whether tolerance to the stimulus properties of LSD is related to altered serotonin receptor signaling. Rats were trained to discriminate 60 microg/kg LSD from saline in a two-lever drug discrimination paradigm. Two groups of animals were assigned to either chronic saline treatment or chronic LSD treatment. For chronic treatment, rats from each group were injected once per day with either 130 microg/kg LSD or saline for 5 days. Rats were tested for their ability to discriminate either saline or 60 microg/kg LSD, 24 h after the last chronic injection. Rats receiving chronic LSD showed a 44% reduction in LSD lever selection, while rats receiving chronic vehicle showed no change in percent choice on the LSD lever. In another group of rats receiving the identical chronic LSD treatment, LSD-stimulated [35S]GTPgammaS binding, an index of G-protein coupling, was measured in the rat brain by autoradiography. After chronic LSD, a significant reduction in LSD-stimulated [35S]GTPgammaS binding was observed in the medial prefrontal cortex and anterior cingulate cortex. Furthermore, chronic LSD produced a significant reduction in 2,5-dimethoxy-4-iodoamphetamine-stimulated [35S]GTPgammaS binding in medial prefrontal cortex and anterior cingulate cortex, which was blocked by MDL 100907, a selective 5-HT2A receptor antagonist, but not SB206553, a 5-HT2C receptor antagonist, indicating a reduction in 5-HT2A receptor signaling. 125I-LSD binding to 5-HT2A receptors was reduced in cortical regions, demonstrating a reduction in 5-HT2A receptor density. Taken together, these results indicate that adaptive changes in LSD-stimulated serotonin receptor signaling may mediate tolerance to the discriminative stimulus effects of LSD.

Further investigation of the effects of 5-hydroxytryptamine, 8-OH-DPAT and DOI to mediate contraction and relaxation responses in the intestine and emesis in Suncus murinus.

PubMed

Javid, Farideh A; Afshin-Javid, Saeed; Horn, Charles C

2018-02-15

5-HT receptors are implicated in many gastrointestinal disorders. However, the precise role of 5-HT in mediating GI responses in Suncus murnius is still unclear. Therefore in this study, the effects of 5-HT and its agonists were investigated in Suncus. The involvement of 5-HT 2C receptors in mediating emesis was also investigated. The ability of 5-HT and its agonists/antagonists at 5-HT 1A and 5-HT 2 to modify GI motility was investigated in vitro and in vivo. WAY100635 (a 5-HT 1A antagonist) inhibited the contraction response to 5-HT in the proximal segments without affecting the maximum response; whilst enhancing the contraction to 5-HT (>30.0nM) in the distal intestine. The selective 5-HT 2A and 5-HT 2B receptor antagonists MDL-100907 and RS-127445 attenuated 5-HT-induced contractions (<10.0µM) in the distal segments. RS-127445 also attenuated 5-HT-induced contractions in the central segments. The selective 5-HT 2C receptor antagonist SB-242084, attenuated the responses to 5-HT (> 3.0nM) in the proximal and central but not the distal regions. 8-OH-DPAT-induced relaxation was resistant to the antagonism by 5-HT 1A/7 antagonists. DOI in the presence of 5-HT 1A/2A/2B/2C antagonists induced greater contraction responses (>1.0µM) in most tissues, whilst RS-127445, or SB-242084, reduced the responses to DOI (< 1.0µM) in some tissues. SB-242084 also suppressed emesis-induced by motion and intragastric CuSO 4 . In conclusion, within different regions of intestine, 5-HT 2 receptors are differently involved in contraction and emetic responses and that 8-OH-DPAT induces relaxation via non-5-HT 1A/7 receptors. Suncus could provide a model to investigate these diverse actions of 5-HT. Copyright © 2018 Elsevier B.V. All rights reserved.

Geomorphic and Fish Genetics Constraints on Late Cenozoic Long Wavelength Topographic Evolution of the Hangay Mountains, Central Mongolia

NASA Astrophysics Data System (ADS)

Wegmann, K. W.; Tamra, M.; Sabaj Pérez, M.; Lopresti, M.; Cole, M. B.; Gosse, J. C.; Smith, S. G.; Bayasgalan, G.; Ancuta, L. D.; McDannell, K. T.; Gallen, S. F.

2014-12-01

The Hangay Mountains stand 1.5 - 2 km above adjacent lowlands and the timing and cause of their high elevation is debated. As part of a broad collaborative project, we synthesize several data sets that collectively suggest the Hangay increased in elevation during the mid-to-late Miocene, while topographic relief, one metric commonly associated with active mountain ranges, remained largely unchanged. The topographic crest of the Hangay forms the drainage divide between the Selenga River and internal drainage of the Mongolian Depression of Lakes (MDL) and northern Gobi. Synthetic drainage divides for the Hangay were created by filtering digital topography in the spectral domain (50 - 200 km wavelengths) using a 2D-FFT function. The co-location of the synthetic and modern divides suggests that the Hangay divide is in a stable, equilibrium configuration. This assumption is corroborated by chi-maps of steady-state river channel elevations that exhibit nearly equal values across water divides. An exception to both of these metrics occurs in the northwest Hangay where the Bulnay fault crosses a low divide between the western Selenga basin and the MDL. Recent basalt vesicle paleoaltimetry results allow for ~1 km of surface uplift of the central Hangay in the past ~ 10 Ma. These same basalt flows in-filled late Miocene valleys cut into basement with a minimum of 800 m of local relief; similar to the amount of modern, post-glacial relief along the drainage divide. mtDNA analyses from > 250 combined Stone Loaches (Barbatula), Grayling (Thymallus), and Eurasian Dace (Leuciscus) samples from both sides of the continental drainage divide are supportive of Miocene surface uplift. Molecular genetic differences between the loach populations across the divide suggest that they separated from a common ancestor between 20 and 11 Ma. This date is consistent with the timing of surface uplift and valley incision preserved in the Miocene basalt flows. The dace and grayling populations on either side of the divide separated more recently, at ~ 2 Ma and < 1 Ma, respectively. We speculate that either (1) Quaternary climate change via glacial drainage reorganization or (2) drainage capture in response to slip along the Bulnay fault forced these more recent separations. These topo-genetic constrains are needed inputs for regional geodynamic models.

Lysergic acid diethylamide-induced Fos expression in rat brain: role of serotonin-2A receptors.

PubMed

Gresch, P J; Strickland, L V; Sanders-Bush, E

2002-01-01

Lysergic acid diethylamide (LSD) produces altered mood and hallucinations in humans and binds with high affinity to serotonin-2A (5-HT(2A)) receptors. Although LSD interacts with other receptors, the activation of 5-HT(2A) receptors is thought to mediate the hallucinogenic properties of LSD. The goal of this study was to identify the brain sites activated by LSD and to determine the influence of 5-HT(2A) receptors in this activation. Rats were pretreated with the 5-HT(2A) receptor antagonist MDL 100907 (0.3 mg/kg, i.p.) or vehicle 30 min prior to LSD (500 microg/kg, i.p.) administration and killed 3 h later. Brain tissue was examined for Fos protein expression by immunohistochemistry. LSD administration produced a five- to eight-fold increase in Fos-like immunoreactivity in medial prefrontal cortex, anterior cingulate cortex, and central nucleus of amygdala. However, in dorsal striatum and nucleus accumbens no increase in Fos-like immunoreactivity was observed. Pretreatment with MDL 100907 completely blocked LSD-induced Fos-like immunoreactivity in medial prefrontal cortex and anterior cingulate cortex, but only partially blocked LSD-induced Fos-like immunoreactivity in amygdala. Double-labeled immunohistochemistry revealed that LSD did not induce Fos-like immunoreactivity in cortical cells expressing 5-HT(2A) receptors, suggesting an indirect activation of cortical neurons. These results indicate that the LSD activation of medial prefrontal cortex and anterior cingulate cortex is mediated by 5-HT(2A) receptors, whereas in amygdala 5-HT(2A) receptor activation is a component of the response. These findings support the hypothesis that the medial prefrontal cortex, anterior cingulate cortex, and perhaps the amygdala, are important regions involved in the production of hallucinations. Copyright 2002 IBRO

Severe Acute Respiratory Syndrome Coronavirus Replication Is Severely Impaired by MG132 due to Proteasome-Independent Inhibition of M-Calpain

PubMed Central

Schneider, Martha; Ackermann, Kerstin; Stuart, Melissa; Wex, Claudia; Protzer, Ulrike; Schätzl, Hermann M.

2012-01-01

The ubiquitin-proteasome system (UPS) is involved in the replication of a broad range of viruses. Since replication of the murine hepatitis virus (MHV) is impaired upon proteasomal inhibition, the relevance of the UPS for the replication of the severe acute respiratory syndrome coronavirus (SARS-CoV) was investigated in this study. We demonstrate that the proteasomal inhibitor MG132 strongly inhibits SARS-CoV replication by interfering with early steps of the viral life cycle. Surprisingly, other proteasomal inhibitors (e.g., lactacystin and bortezomib) only marginally affected viral replication, indicating that the effect of MG132 is independent of proteasomal impairment. Induction of autophagy by MG132 treatment was excluded from playing a role, and no changes in SARS-CoV titers were observed during infection of wild-type or autophagy-deficient ATG5−/− mouse embryonic fibroblasts overexpressing the human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2). Since MG132 also inhibits the cysteine protease m-calpain, we addressed the role of calpains in the early SARS-CoV life cycle using calpain inhibitors III (MDL28170) and VI (SJA6017). In fact, m-calpain inhibition with MDL28170 resulted in an even more pronounced inhibition of SARS-CoV replication (>7 orders of magnitude) than did MG132. Additional m-calpain knockdown experiments confirmed the dependence of SARS-CoV replication on the activity of the cysteine protease m-calpain. Taken together, we provide strong experimental evidence that SARS-CoV has unique replication requirements which are independent of functional UPS or autophagy pathways compared to other coronaviruses. Additionally, this work highlights an important role for m-calpain during early steps of the SARS-CoV life cycle. PMID:22787216

Short-lived species detection of nitrous acid by external-cavity quantum cascade laser based quartz-enhanced photoacoustic absorption spectroscopy

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

Yi, Hongming; Laboratory of Atmospheric Physico-Chemistry, Anhui Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, P.O. Box 1125, 350 Shushanhu Road, Hefei, Anhui 230031; Maamary, Rabih

2015-03-09

Spectroscopic detection of short-lived gaseous nitrous acid (HONO) at 1254.85 cm{sup −1} was realized by off-beam coupled quartz-enhanced photoacoustic spectroscopy (QEPAS) in conjunction with an external cavity quantum cascade lasers (EC-QCL). High sensitivity monitoring of HONO was performed within a very small gas-sample volume (of ∼40 mm{sup 3}) allowing a significant reduction (of about 4 orders of magnitude) of air sampling residence time which is highly desired for accurate quantification of chemically reactive short-lived species. Calibration of the developed QEPAS-based HONO sensor was carried out by means of lab-generated HONO samples whose concentrations were determined by direct absorption spectroscopy involving a ∼109.5 mmore » multipass cell and a distributed feedback QCL. A minimum detection limit (MDL) of 66 ppbv (1 σ) HONO was achieved at 70 mbar using a laser output power of 50 mW and 1 s integration time, which corresponded to a normalized noise equivalent absorption coefficient of 3.6 × 10{sup −8 }cm{sup −1} W/Hz{sup 1/2}. This MDL was down to 7 ppbv at the optimal integration time of 150 s. The corresponding 1σ minimum detected absorption coefficient is ∼1.1 × 10{sup −7 }cm{sup −1} (MDL ∼ 3 ppbv) in 1 s and ∼1.1 × 10{sup −8 }cm{sup −1} (MDL ∼ 330 pptv) in 150 s, respectively, with 1 W laser power.« less

Determination of endogenous concentrations of nitrites and nitrates in different types of cheese in the United States: method development and validation using ion chromatography.

PubMed

Genualdi, Susan; Jeong, Nahyun; DeJager, Lowri

2018-04-01

Nitrites and nitrates can be present in dairy products from both endogenous and exogenous sources. In the European Union (EU), 150 mg kg - 1 of nitrates are allowed to be added to the cheese milk during the manufacturing process. The CODEX General Standard for Food Additives has a maximum permitted level of 50 mg kg - 1 residue in cheese, while in the United States (U.S.) nitrates are unapproved for use as food additives in cheese. In order to be able to investigate imported cheeses for nitrates intentionally added as preservatives and the endogenous concentrations of nitrates and nitrites present in cheeses in the U.S. marketplace, a method was developed and validated using ion chromatography with conductivity detection. A market sampling of cheese samples purchased in the Washington DC metro area was performed. In 64 samples of cheese, concentrations ranged from below the method detection limit (MDL) to 26 mg kg - 1 for nitrates and no concentrations of nitrites were found in any of the cheese samples above the MDL of 0.1 mg kg - 1 . A majority of the samples (93%) had concentrations below 10 mg kg - 1 , which indicate the presence of endogenous nitrates. The samples with concentrations above 10 mg kg - 1 were mainly processed cheese spread, which can contain additional ingredients often of plant-based origin. These ingredients are likely the cause of the elevated nitrate concentrations. The analysis of 12 additional cheese samples that are liable to the intentional addition of nitrates, 9 of which were imported, indicated that in this limited study, concentrations of nitrate in the U.S.-produced cheeses did not differ from those in imported samples.

A Small Molecule Polyamine Oxidase Inhibitor Blocks Androgen-Induced Oxidative Stress and Delays Prostate Cancer Progression in the TRAMP Mouse Model

PubMed Central

Basu, Hirak S.; Thompson, Todd A.; Church, Dawn R.; Clower, Cynthia C.; Mehraein-Ghomi, Farideh; Amlong, Corey A.; Martin, Christopher T.; Woster, Patrick M.; Lindstrom, Mary J.; Wilding, George

2009-01-01

High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiological factor in prostate cancer (CaP) occurrence, recurrence and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase (SSAT), the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data demonstrate that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays prostate cancer progression. PMID:19773450

Structure-based virtual screening and characterization of a novel IL-6 antagonistic compound from synthetic compound database.

PubMed

Wang, Jing; Qiao, Chunxia; Xiao, He; Lin, Zhou; Li, Yan; Zhang, Jiyan; Shen, Beifen; Fu, Tinghuan; Feng, Jiannan

2016-01-01

According to the three-dimensional (3D) complex structure of (hIL-6⋅hIL-6R⋅gp 130) 2 and the binding orientation of hIL-6, three compounds with high affinity to hIL-6R and bioactivity to block hIL-6 in vitro were screened theoretically from the chemical databases, including 3D-Available Chemicals Directory (ACD) and MDL Drug Data Report (MDDR), by means of the computer-guided virtual screening method. Using distance geometry, molecular modeling and molecular dynamics trajectory analysis methods, the binding mode and binding energy of the three compounds were evaluated theoretically. Enzyme-linked immunosorbent assay analysis demonstrated that all the three compounds could block IL-6 binding to IL-6R specifically. However, only compound 1 could effectively antagonize the function of hIL-6 and inhibit the proliferation of XG-7 cells in a dose-dependent manner, whereas it showed no cytotoxicity to SP2/0 or L929 cells. These data demonstrated that the compound 1 could be a promising candidate of hIL-6 antagonist.

Fibrolipomatous Hamartoma of the Median Nerve with Macrodystrophia Lipomatosa.

PubMed

Azeemuddin, Muhammad; Waheed, Adeel A; Khan, Noman; Sayani, Raza; Ahmed, Anwar

2018-03-09

Fibrolipomatous hamartoma (FLH) is a rare congenital condition that presents with a benign overgrowth of the bone and fibroadipose tissue termed as macrodystrophia lipomatosa (MDL). Although commonly seen in the median nerve, other peripheral nerves can be involved. Diagnosis can be made on magnetic resonance imaging (MRI) due to the characteristic coaxial cable appearance on axial images and the spaghetti appearance on sagittal images. Histology shows mature adipose and fibrous tissue infiltrating the epineural and perineural compartments. Multiple or debulking surgeries are often needed, with an emphasis on cosmetic aspects. We present one such case in which wide margin excision and sural nerve graft were carried out.

An LQG Up-and Away Flight Control Design for the STOL F-15 Aircraft.

DTIC Science & Technology

1985-12-01

bmat ɜ,8) dimension dirmatC5,5),dirbmnat(5,9) character*3 Key, Keyl, datal, data2, data3, run characterti...write( *,*) now we’ll get the input matrix -b bmat (1,1) = xdl b rat ( 1,2) = xd2 bmat ( 1,3) = xd3 bmat <l,4) = xd4 bmat ( 1,5) = xd5 bmatc 1,6) = xd6 bmat ...1,7) = xd7 * bmat ( 1,8) = xd8 bmat (2,1) = mdl bmat (2,2) = md2 bmat (2,3) = md3 bmatc2,4) = md4 bmat ( 2,5) = md 5 bmatc2,6) = md6 bmat (2,7) =

Target specific compound identification using a support vector machine.

PubMed

Plewczynski, Dariusz; von Grotthuss, Marcin; Spieser, Stephane A H; Rychlewski, Leszek; Wyrwicz, Lucjan S; Ginalski, Krzysztof; Koch, Uwe

2007-03-01

In many cases at the beginning of an HTS-campaign, some information about active molecules is already available. Often known active compounds (such as substrate analogues, natural products, inhibitors of a related protein or ligands published by a pharmaceutical company) are identified in low-throughput validation studies of the biochemical target. In this study we evaluate the effectiveness of a support vector machine applied for those compounds and used to classify a collection with unknown activity. This approach was aimed at reducing the number of compounds to be tested against the given target. Our method predicts the biological activity of chemical compounds based on only the atom pairs (AP) two dimensional topological descriptors. The supervised support vector machine (SVM) method herein is trained on compounds from the MDL drug data report (MDDR) known to be active for specific protein target. For detailed analysis, five different biological targets were selected including cyclooxygenase-2, dihydrofolate reductase, thrombin, HIV-reverse transcriptase and antagonists of the estrogen receptor. The accuracy of compound identification was estimated using the recall and precision values. The sensitivities for all protein targets exceeded 80% and the classification performance reached 100% for selected targets. In another application of the method, we addressed the absence of an initial set of active compounds for a selected protein target at the beginning of an HTS-campaign. In such a case, virtual high-throughput screening (vHTS) is usually applied by using a flexible docking procedure. However, the vHTS experiment typically contains a large percentage of false positives that should be verified by costly and time-consuming experimental follow-up assays. The subsequent use of our machine learning method was found to improve the speed (since the docking procedure was not required for all compounds from the database) and also the accuracy of the HTS hit lists (the enrichment factor).

Characterization of the tachykinin neurokinin-2 receptor in the human urinary bladder by means of selective receptor antagonists and peptidase inhibitors.

PubMed

Giuliani, S; Patacchini, R; Barbanti, G; Turini, D; Rovero, P; Quartara, L; Giachetti, A; Maggi, C A

1993-11-01

The tachykinin (NK2) receptor-mediating contraction of the human isolated bladder to NKA was investigated by studying the affinities of eight structurally different receptor-selective antagonists (linear peptides, cyclic peptides and pseudopeptides, nonpeptide NK2 receptor antagonists). The affinities of the antagonists were compared to those measured for the same ligands at the NK2 receptors previously characterized in the rabbit pulmonary artery and hamster trachea. In the presence of a cocktail of peptidase inhibitors (bestatin captopril and thiorphan, 1 microM each) no significant correlation was found between pA2 values measured in the human bladder vs. those measured in the other two NK2 receptor-bearing preparation. In the presence of the aminopeptidase inhibitor amastatin, however, pA2 values of linear antagonists bearing an N-terminal Asp residue MEN 10,207 and MEN 10,376 were significantly enhanced and these pA2 values were used for analysis; a significant correlation was found between pA2 values measured in the human urinary bladder and rabbit pulmonary artery. The pseudopeptide analog of NKA (4-10), MDL 28,564 which also bears a N-terminal Asp residue behaved as an agonist and its action was enhanced by amastatin. We conclude that the NK2 receptor-mediating contraction of the human urinary bladder smooth muscle is similar to that previously characterized in the rabbit pulmonary artery (NK2A receptor category); in the human bladder smooth muscle an amastatin-sensitive peptidase (possibly aminopeptidase A) limits biological activity of linear peptide derivatives of NKA bearing a N-terminal Asp residue.

Experimental, theoretical, and device application development of nanoscale focused electron-beam-induced deposition

NASA Astrophysics Data System (ADS)

Randolph, Steven Jeffrey

Electron-beam-induced deposition (EBID) is a highly versatile nanofabrication technique that allows for growth of a variety of materials with nanoscale precision and resolution. While several applications and studies of EBID have been reported and published, there is still a significant lack of understanding of the complex mechanisms involved in the process. Consequently, EBID process control is, in general, limited and certain common experimental results regarding nanofiber growth have yet to be fully explained. Such anomalous results have been addressed in this work both experimentally and by computer simulation. Specifically, a correlation between SiOx nanofiber deposition observations and the phenomenon of electron beam heating (EBH) was shown by comparison of thermal computer models and experimental results. Depending on the beam energy, beam current, and nanostructure geometry, the heat generated can be substantial and may influence the deposition rate. Temperature dependent EBID growth experiments qualitatively verified the results of the EBH model. Additionally, EBID was used to produce surface image layers for maskless, direct-write lithography (MDL). A single layer process used directly written SiOx features as a masking layer for amorphous silicon thin films. A bilayer process implemented a secondary masking layer consisting of standard photoresist into which a pattern---directly written by EBID tungsten---was transferred. The single layer process was found to be extremely sensitive to the etch selectivity of the plasma etch. In the bilayer process, EBID tungsten was written onto photoresist and the pattern transferred by means of oxygen plasma dry development following a brief refractory descum. Conditions were developed to reduce the spatial spread of electrons in the photoresist layer and obtain ˜ 35 nm lines. Finally, an EBID-based technique for field emitter repair was applied to the Digital Electrostatically focused e-beam Array Lithography (DEAL) parallel electron beam lithography configuration to repair damaged or missing carbon nanofiber cathodes. The I-V response and lithography results from EBID tungsten-based devices were comparable to CNF-based DEAL devices indicating a successful repair technique.

Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization.

PubMed

Thomsen, William J; Grottick, Andrew J; Menzaghi, Frederique; Reyes-Saldana, Hazel; Espitia, Stephen; Yuskin, Diane; Whelan, Kevin; Martin, Michael; Morgan, Michael; Chen, Weichao; Al-Shamma, Hussien; Smith, Brian; Chalmers, Derek; Behan, Dominic

2008-05-01

5-Hydroxytryptamine (5-HT)(2C) receptor agonists hold promise for the treatment of obesity. In this study, we describe the in vitro and in vivo characteristics of lorcaserin [(1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3 benzazepine], a selective, high affinity 5-HT(2C) full agonist. Lorcaserin bound to human and rat 5-HT(2C) receptors with high affinity (K(i) = 15 +/- 1 nM, 29 +/- 7 nM, respectively), and it was a full agonist for the human 5-HT(2C) receptor in a functional inositol phosphate accumulation assay, with 18- and 104-fold selectivity over 5-HT(2A) and 5-HT(2B) receptors, respectively. Lorcaserin was also highly selective for human 5-HT(2C) over other human 5-HT receptors (5-HT(1A), 5-HT(3), 5-HT(4C), 5-HT5(5A), 5-HT(6), and 5-HT(7)), in addition to a panel of 67 other G protein-coupled receptors and ion channels. Lorcaserin did not compete for binding of ligands to serotonin, dopamine, and norepinephrine transporters, and it did not alter their function in vitro. Behavioral observations indicated that unlike the 5-HT(2A) agonist (+/-)-1-(2,5-dimethoxy-4-phenyl)-2-aminopropane, lorcaserin did not induce behavioral changes indicative of functional 5-HT(2A) agonist activity. Acutely, lorcaserin reduced food intake in rats, an effect that was reversed by pretreatment with the 5-HT(2C)-selective antagonist 6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy)pyridin-3-yl-carbamoyl]indoline (SB242,084) but not the 5-HT(2A) antagonist (R)-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (MDL 100,907), demonstrating mediation by the 5-HT(2C) receptor. Chronic daily treatment with lorcaserin to rats maintained on a high fat diet produced dose-dependent reductions in food intake and body weight gain that were maintained during the 4-week study. Upon discontinuation, body weight returned to control levels. These data demonstrate lorcaserin to be a potent, selective, and efficacious agonist of the 5-HT(2C) receptor, with potential for the treatment of obesity.

MDMA-induced loss of parvalbumin interneurons within the dentate gyrus is mediated by 5HT2A and NMDA receptors.

PubMed

Collins, Stuart A; Gudelsky, Gary A; Yamamoto, Bryan K

2015-08-15

MDMA is a widely abused psychostimulant which causes a rapid and robust release of the monoaminergic neurotransmitters dopamine and serotonin. Recently, it was shown that MDMA increases extracellular glutamate concentrations in the dorsal hippocampus, which is dependent on serotonin release and 5HT2A/2C receptor activation. The increased extracellular glutamate concentration coincides with a loss of parvalbumin-immunoreactive (PV-IR) interneurons of the dentate gyrus region. Given the known susceptibility of PV interneurons to excitotoxicity, we examined whether MDMA-induced increases in extracellular glutamate in the dentate gyrus are necessary for the loss of PV cells in rats. Extracellular glutamate concentrations increased in the dentate gyrus during systemic and local administration of MDMA. Administration of the NMDA receptor antagonist, MK-801, during systemic injections of MDMA, prevented the loss of PV-IR interneurons seen 10 days after MDMA exposure. Local administration of MDL100907, a selective 5HT2A receptor antagonist, prevented the increases in glutamate caused by reverse dialysis of MDMA directly into the dentate gyrus and prevented the reduction of PV-IR. These findings provide evidence that MDMA causes decreases in PV within the dentate gyrus through a 5HT2A receptor-mediated increase in glutamate and subsequent NMDA receptor activation. Copyright © 2015 Elsevier B.V. All rights reserved.

Sleep Homeostatic and Waking Behavioral Phenotypes in Egr3-Deficient Mice Associated with Serotonin Receptor 5-HT2 Deficits

PubMed Central

Grønli, Janne; Clegern, William C.; Schmidt, Michelle A.; Nemri, Rahmi S.; Rempe, Michael J.; Gallitano, Amelia L.; Wisor, Jonathan P.

2016-01-01

Study Objective: The expression of the immediate early gene early growth response 3 (Egr3) is a functional marker of brain activity including responses to novelty, sustained wakefulness, and sleep. We examined the role of this gene in regulating wakefulness and sleep. Methods: Electroencephalogram/electromyogram (EEG/EMG) were recorded in Egr3-/- and wild-type (WT) mice during 24 h baseline, 6 h sleep disruption and 6 h recovery. Serotonergic signaling was assessed with 6 h EEG/EMG recordings after injections of nonselective 5-HT2 antagonist (clozapine), selective 5-HT2 antagonists (5-HT2A; MDL100907 and 5-HT2BC; SB206553) and a cocktail of both selective antagonists, administered in a randomized order to each animal. Results: Egr3-/- mice did not exhibit abnormalities in the timing of wakefulness and slow wave sleep (SWS); however, EEG dynamics in SWS (suppressed 1–3 Hz power) and in quiet wakefulness (elevated 3–8 Hz and 15–35 Hz power) differed in comparison to WT-mice. Egr3-/- mice showed an exaggerated response to sleep disruption as measured by active wakefulness, but with a blunted increase in homeostatic sleep drive (elevated 1–4 Hz power) relative to WT-mice. Egr3-/-mice exhibit greatly reduced sedative effects of clozapine at the electroencephalographic level. In addition, clozapine induced a previously undescribed dissociated state (low amplitude, low frequency EEG and a stable, low muscle tone) lasting up to 2 h in WT-mice. Egr3-/- mice did not exhibit this phenomenon. Selective 5-HT2A antagonist, alone or in combination with selective 5-HT2BC antagonist, caused EEG slowing coincident with behavioral quiescence in WT-mice but not in Egr3-/- mice. Conclusion: Egr3 has an essential role in regulating cortical arousal, wakefulness, and sleep, presumably by its regulation of 5-HT2 receptors. Citation: Grønli J, Clegern WC, Schmidt MA, Nemri RS, Rempe MJ, Gallitano AL, Wisor JP. Sleep homeostatic and waking behavioral phenotypes in Egr3-deficient mice associated with serotonin receptor 5-HT2 deficits. SLEEP 2016;39(12):2189–2199. PMID:28057087

Multi-Organization Multi-Discipline Effort Developing a Mitigation Concept for Planetary Defense

NASA Technical Reports Server (NTRS)

Leung, Ronald Y.; Barbee, Brent W.; Seery, Bernard D.; Bambacus, Myra; Finewood, Lee; Greenaugh, Kevin C.; Lewis, Anthony; Dearborn, David; Miller, Paul L.; Weaver, Robert P.;

Effect of entacapone on colon motility and ion transport in a rat model of Parkinson’s disease

PubMed Central

Li, Li-Sheng; Liu, Chen-Zhe; Xu, Jing-Dong; Zheng, Li-Fei; Feng, Xiao-Yan; Zhang, Yue; Zhu, Jin-Xia

2015-01-01

AIM: To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson’s disease (PD) rats. METHODS: Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing. RESULTS: COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P < 0.01). Entacapone increased mucosal ISC in the colon of rats with PD. This induction was significantly inhibited by apical application of Cl- channel blocker diphenylamine-2, 2’-dicarboxylic acid, basolateral application of Na+-K+-2Cl-co-transporter antagonist bumetanide, elimination of Cl- from the extracellular fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl- flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin. CONCLUSION: COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl- secretion in the PD rat. PMID:25834315

Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: evidence for the involvement of the monoaminergic system.

PubMed

Machado, Daniele G; Kaster, Manuella P; Binfaré, Ricardo W; Dias, Munique; Santos, Adair R S; Pizzolatti, Moacir G; Brighente, Inês M C; Rodrigues, Ana Lúcia S

2007-03-30

Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the treatment of depression. In this study, the antidepressant-like effect of the hexanic extract from leaves of S. molle was investigated in the mouse tail suspension test (TST), a predictive model of depression. The immobility time in the TST was significantly reduced by the extract (dose range 30-600 mg/kg, p.o.), without accompanying changes in ambulation when assessed in an open-field test. The efficacy of extract was found to be comparable to that of fluoxetine (10 mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a D(2) receptor antagonist). It may be concluded that the hexanic extract of S. molle produces an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. These results provide evidence that the extract from S. molle shares with established antidepressants some pharmacological effects, at least at a preclinical level.

A small molecule polyamine oxidase inhibitor blocks androgen-induced oxidative stress and delays prostate cancer progression in the transgenic adenocarcinoma of the mouse prostate model.

PubMed

Basu, Hirak S; Thompson, Todd A; Church, Dawn R; Clower, Cynthia C; Mehraein-Ghomi, Farideh; Amlong, Corey A; Martin, Christopher T; Woster, Patrick M; Lindstrom, Mary J; Wilding, George

2009-10-01

High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiologic factor in prostate cancer (CaP) occurrence, recurrence, and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells, as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data show that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays CaP progression.

Quantum probability ranking principle for ligand-based virtual screening.

PubMed

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

Quantum probability ranking principle for ligand-based virtual screening

NASA Astrophysics Data System (ADS)

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2017-04-01

Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.

A Novel Model of Traumatic Brain Injury in Adult Zebrafish Demonstrates Response to Injury and Treatment Comparable with Mammalian Models.

PubMed

McCutcheon, Victoria; Park, Eugene; Liu, Elaine; Sobhebidari, Pooya; Tavakkoli, Jahan; Wen, Xiao-Yan; Baker, Andrew J

2017-04-01

Traumatic brain injury (TBI) is a leading cause of death and morbidity in industrialized countries with considerable associated health care costs. The cost and time associated with pre-clinical development of TBI therapeutics is lengthy and expensive with a poor track record of successful translation to the clinic. The zebrafish is an emerging model organism in research with unique technical and genomic strengths in the study of disease and development. Its high degree of genetic homology and cell signaling pathways relative to mammalian species and amenability to high and medium throughput assays has potential to accelerate the rate of therapeutic drug identification. Accordingly, we developed a novel closed-head model of TBI in adult zebrafish using a targeted, pulsed, high-intensity focused ultrasound (pHIFU) to induce mechanical injury of the brain. Western blot results indicated altered microtubule and neurofilament expression as well as increased expression of cleaved caspase-3 and beta APP (β-APP; p < 0.05). We used automated behavioral tracking software to evaluate locomotor deficits 24 and 48 h post-injury. Significant behavioral impairment included decreased swim distance and velocity (p < 0.05), as well as heightened anxiety and altered group social dynamics. Responses to injury were pHIFU dose-dependent and modifiable with MK-801, MDL-28170, or temperature modulation. Together, results indicate that the zebrafish exhibits responses to injury and intervention similar to mammalian TBI pathophysiology and suggest the potential for use to rapidly evaluate therapeutic compounds with high efficiency.

Independent Review of Simulation of Net Infiltration for Present-Day and Potential Future Climates

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

Review Panel: Soroosh Sorooshian, Ph.D., Panel Chairperson, University of California, Irvine; Jan M. H. Hendrickx, Ph.D., New Mexico Institute of Mining and Technology; Binayak P. Mohanty, Ph.D., Texas A&M University

The DOE Office of Civilian Radioactive Waste Management (OCRWM) tasked Oak Ridge Institute for Science and Education (ORISE) with providing an independent expert review of the documented model and prediction results for net infiltration of water into the unsaturated zone at Yucca Mountain. The specific purpose of the model, as documented in the report MDL-NBS-HS-000023, Rev. 01, is “to provide a spatial representation, including epistemic and aleatory uncertainty, of the predicted mean annual net infiltration at the Yucca Mountain site ...” (p. 1-1) The expert review panel assembled by ORISE concluded that the model report does not provide a technicallymore » credible spatial representation of net infiltration at Yucca Mountain. Specifically, the ORISE Review Panel found that: • A critical lack of site-specific meteorological, surface, and subsurface information prevents verification of (i) the net infiltration estimates, (ii) the uncertainty estimates of parameters caused by their spatial variability, and (iii) the assumptions used by the modelers (ranges and distributions) for the characterization of parameters. The paucity of site-specific data used by the modeling team for model implementation and validation is a major deficiency in this effort. • The model does not incorporate at least one potentially important hydrologic process. Subsurface lateral flow is not accounted for by the model, and the assumption that the effect of subsurface lateral flow is negligible is not adequately justified. This issue is especially critical for the wetter climate periods. This omission may be one reason the model results appear to underestimate net infiltration beneath wash environments and therefore imprecisely represent the spatial variability of net infiltration. • While the model uses assumptions consistently, such as uniform soil depths and a constant vegetation rooting depth, such assumptions may not be appropriate for this net infiltration simulation because they oversimplify a complex landscape and associated hydrologic processes, especially since the model assumptions have not been adequately corroborated by field and laboratory observations at Yucca Mountain.« less

Optimized liquid chromatography tandem mass spectrometry approach for the determination of diquat and paraquat herbicides.

PubMed

Hao, Chunyan; Zhao, Xiaoming; Morse, David; Yang, Paul; Taguchi, Vince; Morra, Franca

2013-08-23

Liquid chromatography tandem mass spectrometry (LC-MS/MS) determination of quaternary ammonium herbicides diquat (DQ) and paraquat (PQ) can be very challenging due to their complicated chromatographic and mass spectrometric behaviors. Various multiple reaction monitoring (MRM) transitions from radical cations M(+) and singly charged cations [M-H](+), have been reported for LC-MS/MS quantitation under different chromatographic and mass spectrometric conditions. However, interference peaks were observed for certain previously reported MRM transitions in our study. Using a Dionex Acclaim(®) reversed-phase and HILIC mixed-mode LC column, we evaluated the most sensitive MRM transitions from three types of quasi-molecular ions of DQ and PQ, elucidated the cross-interference phenomena, and demonstrated that the rarely mentioned MRM transitions from dications M(2+) offered the best selectivity for LC-MS/MS analysis. Experimental parameters, such as IonSpray (IS) voltage, source temperature, declustering potential (DP), column oven temperature, collision energy (CE), acid and salt concentrations in the mobile phases were also optimized and an uncommon electrospray ionization (ESI) capillary voltage of 1000V achieved the highest sensitivity. Employing the proposed dication transitions 92/84.5 for DQ and 93/171 for PQ, the direct aqueous injection LC-MS/MS method developed was able to provide a method detection limit (MDL) of 0.1μg/L for the determination of these two herbicides in drinking water. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

5-HT2A serotonin receptor agonist DOI alleviates cytotoxicity in neuroblastoma cells: role of the ERK pathway.

PubMed

Marinova, Zoya; Walitza, Susanne; Grünblatt, Edna

2013-07-01

Disturbances of serotonergic signaling, including the serotonin 2A (5-HT2A) receptor, have been implicated in neuropsychiatric and neurodegenerative disorders. The aim of the present study was to characterize the effect of a 5-HT2A receptor agonist on cytotoxicity in a neuronal cell line and address the involved mechanism. HTR2A mRNA and protein expression in human neuroblastoma SK-N-SH cells was confirmed. Cells were subjected to serum deprivation and cell viability was monitored continuously with xCELLigence. In a dose-response study the 5-HT2A agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) (25 nM to 5 μM) protected against serum deprivation cytotoxicity. The selective 5-HT2A receptor antagonist MDL 11,939, the general protein tyrosine kinase inhibitor genistein, and the extracellular signal-regulated kinase (ERK) pathway MEK inhibitor U0126, all attenuated DOI's protective effect. An antibody array suggested that 1 μM DOI affected phosphorylation of several tyrosine kinases. Western blot further confirmed that DOI transiently increased ERK phosphorylation, indicating its activation. Finally, protective concentrations of DOI increased cellular mitochondrial mass, an effect prevented by pretreatment with U0126. In conclusion, our results suggest that DOI protects SK-N-SH cells against serum deprivation through ERK pathway activation. They imply 5-HT2A receptor modulation as a potential target for neuroprotection. Copyright © 2013 Elsevier Inc. All rights reserved.

Assessment of the quality of water from hand-dug wells in ghana.

PubMed

Nkansah, Marian Asantewah; Boadi, Nathaniel Owusu; Badu, Mercy

2010-04-26

This study focused upon the determination of physicochemical and microbial properties, including metals, selected anions and coliform bacteria in drinking water samples from hand-dug wells in the Kumasi metropolis of the Republic of Ghana. The purpose was to assess the quality of water from these sources. Ten different water samples were taken from different parts of Kumasi, the capital of the Ashanti region of Ghana and analyzed for physicochemical parameters including pH, electrical conductivity, total dissolved solids, alkalinity total hardness and coliform bacteria. Metals and anions analyzed were Ca, Mg, Fe, Mn, NO(3) (-), NO(2) (-), SO(4) (2-), PO(4) (2-), F(-) and Cl(-). Bacteria analysed were total coliform and Escherichia coli.THE DATA SHOWED VARIATION OF THE INVESTIGATED PARAMETERS IN SAMPLES AS FOLLOWS: pH, 6.30-0.70; conductivity (EC), 46-682 muS/cm; PO(4) (3-), 0.67-76.00 mg/L; F(-), 0.20-0.80 mg/L; NO(3) (-), 0-0.968 mg/L; NO(2) (-), 0-0.063 mg/L; SO(4) (2-), 3.0-07.0 mg/L; Fe, 0-1.2 mg/L; Mn, 0-0.018 mg/L. Total coliform and Escherichia coli were below the minimum detection limit (MDL) of 20 MPN per 100 ml in all the samples. The concentrations of most of the investigated parameters in the drinking water samples from Ashanti region were within the permissible limits of the World Health Organization drinking water quality guidelines.

AN ANIMAL MODEL OF SCHIZOPHRENIA BASED ON CHRONIC LSD ADMINISTRATION: OLD IDEA, NEW RESULTS

PubMed Central

Marona-Lewicka, Danuta; Nichols, Charles D.; Nichols, David E.

2011-01-01

Many people who take LSD experience a second temporal phase of LSD intoxication that is qualitatively different, and was described by Daniel Freedman as “clearly a paranoid state.” We have previously shown that the discriminative stimulus effects of LSD in rats also occur in two temporal phases, with initial effects mediated by activation of 5-HT2A receptors (LSD30), and the later temporal phase mediated by dopamine D2-like receptors (LSD90). Surprisingly, we have now found that non-competitive NMDA antagonists produced full substitution in LSD90 rats, but only in older animals, whereas in LSD30, or in younger animals, these drugs did not mimic LSD. Chronic administration of low doses of LSD (>3 months, 0.16 mg/kg every other day) induces a behavioral state characterized by hyperactivity and hyperirritability, increased locomotor activity, anhedonia, and impairment in social interaction that persists at the same magnitude for at least three months after cessation of LSD treatment. These behaviors, which closely resemble those associated with psychosis in humans, are not induced by withdrawal from LSD; rather, they are the result of neuroadaptive changes occurring in the brain during the chronic administration of LSD. These persistent behaviors are transiently reversed by haloperidol and olanzapine, but are insensitive to MDL-100907. Gene expression analysis data show that chronic LSD treatment produced significant changes in multiple neurotransmitter system-related genes, including those for serotonin and dopamine. Thus, we propose that chronic treatment of rats with low doses of LSD can serve as a new animal model of psychosis that may mimic the development and progression of schizophrenia, as well as model the established disease better than current acute drug administration models utilizing amphetamine or NMDA antagonists such as PCP. PMID:21352832

Comparison of Digestion Methods for the Determination of Trace Elements and Heavy Metals in Human Hair and Nails

PubMed Central

Ishak, Ismarulyusda; Rosli, Farah Dayana; Mohamed, Jamaludin; Mohd Ismail, Muhammad Faiz

2015-01-01

Background Microwave is the most reliable sample digestion method. However, it requires expensive microwave digester automation and has relatively low productivity. In this study, three non-automated digestion methods, i.e. wet acid digestion using nitric acid (HNO3) and hydrogen peroxide (H2O2), wet acid digestion using HNO3, and dry washing, are compared in order to determine the best approach. Methods Certified reference material IAEA-086 (International Atomic Energy Agency, Austria) and hair and nail samples from 20 female students of Universiti Kebangsaan Malaysia, aged 19 to 30 years, were collected and analysed using the three digestion methods. Results For hair samples, analysis of variance of repeated measures showed significant differences in the level of all elements (P < 0.001) between the three methods. For nail samples, only the copper (Cu) level showed no significant difference (P = 0.100) between methods. Wet acid digestion using HNO3 and H2O2 showed the best within- and between-run relative standard deviation (RSD) values, with within-run RSD for all elements, except for selenium (Se), < 5%. The between-run precision ranges from 6.14% to 17.96% for hair and from 3.53% to 11.52% for nail samples. Wet acid digestion using HNO3 and H2O2 showed both good accuracy and precision for manganese (Mn) and magnesium (Mg), with percentage recoveries of 110% and 96.9%, respectively. All elements show higher method detection limit (MDL) values than the previous study: 0.05 μg/g Mg for wet acid digestion using HNO3, 0.02 μg/g Se for wet acid digestion using HNO3 and H2O2, and 0.2 μg/g Mg for dry ash method. Conclusion Wet acid digestion using HNO3 and H2O2 proved to be the best method in terms of precision, accuracy, recovery, and MDL. However, only Mn and Mg showed adequate precision, accuracy, and percentage of recovery. PMID:28223880

Patient satisfaction and uptake of private-sector run malaria diagnosis clinics in a post-conflict district in Sri Lanka.

PubMed

Fernando, Deepika; de Silva, Nipun Lakshitha; Ackers, Isabella; Abeyasinghe, Rabindra; Wijeyaratne, Pandu; Rajapakse, Senaka

2014-06-23

With the incidence of malaria in Sri Lanka declining, intensive parasitological surveillance has been identified as a key strategy to achieve elimination by end 2014. Tropical and Environmental Diseases and Health Associates Private Limited (TEDHA) in collaboration with the Anti-Malaria Campaign established 43 malaria diagnostic laboratories (MDL) in four post-conflict districts of the Northern and Eastern Provinces. This study assesses the patterns of referral of patients with fever for malaria diagnosis by health care providers (HCPs) in four government hospitals in one of the districts of the Northern Province, and patient satisfaction with the laboratory services offered. In this prospective descriptive study, data was collected on the proportion of fever patients being referred by the HCP in hospitals for malaria screening, and the proportion thereof who underwent screening. An interviewer-administered questionnaire was also used to assess patient satisfaction among those attending MDL, which was graded on a scale of 0-4. Of patients presenting to the hospitals with fever, only 44.3% were referred for malaria screening; 81.7% of them underwent screening. Referral depended largely on the presence of a permanent staff HCP. Satisfaction levels were high, with 86.55% giving an overall rating of 4. Comfort within the laboratory was rated satisfactory in three of the four hospitals. This study demonstrates the success of a public-private partnership in the malaria control programme in Sri Lanka. Malaria is considered low on the differential diagnosis in patients with fever even in previously malaria-endemic areas, due to the declining incidence of malaria and the increase in other febrile illnesses in these areas during the recent past. Private sector run malaria diagnostic services provided free of charge within government hospitals are viable and effective, and had good patient satisfaction ratings. In a country on the brink of eliminating malaria, there should be further emphasis on ensuring that HCPs refer patients for malaria diagnosis, in order to prevent a resurgence of the disease.

Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors.

PubMed

Jiang, Xi-Ling; Shen, Hong-Wu; Yu, Ai-Ming

2015-02-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are serotonin (5-HT) analogs often abused together, which alters thermoregulation that may indicate the severity of serotonin toxicity. Our recent studies have revealed that co-administration of monoamine oxidase inhibitor harmaline leads to greater and prolonged exposure to 5-HT agonist 5-MeO-DMT that might be influenced by cytochrome P450 2D6 (CYP2D6) status. This study was to define the effects of harmaline and 5-MeO-DMT on thermoregulation in wild-type and CYP2D6-humanized (Tg-CYP2D6) mice, as well as the involvement of 5-HT receptors. Animal core body temperatures were monitored noninvasively in the home cages after implantation of telemetry transmitters and administration of drugs. Harmaline (5 and 15 mg/kg, i.p.) alone was shown to induce hypothermia that was significantly affected by CYP2D6 status. In contrast, higher doses of 5-MeO-DMT (10 and 20 mg/kg) alone caused hyperthermia. Co-administration of harmaline (2, 5 or 15 mg/kg) remarkably potentiated the hyperthermia elicited by 5-MeO-DMT (2 or 10 mg/kg), which might be influenced by CYP2D6 status at certain dose combination. Interestingly, harmaline-induced hypothermia was only attenuated by 5-HT1A receptor antagonist WAY-100635, whereas 5-MeO-DMT- and harmaline-5-MeO-DMT-induced hyperthermia could be suppressed by either WAY-100635 or 5-HT2A receptor antagonists (MDL-100907 and ketanserin). Moreover, stress-induced hyperthermia under home cage conditions was not affected by WAY-100635 but surprisingly attenuated by MDL-100907 and ketanserin. Our results indicate that co-administration of monoamine oxidase inhibitor largely potentiates 5-MeO-DMT-induced hyperthermia that involves the activation of both 5-HT1A and 5-HT2A receptors. These findings shall provide insights into development of anxiolytic drugs and new strategies to relieve the lethal hyperthermia in serotonin toxicity.

Simultaneous Analysis of 3-MCPD and 1,3-DCP in Asian Style Sauces Using QuEChERS Extraction and Gas Chromatography-Triple Quadrupole Mass Spectrometry.

PubMed

Genualdi, Susan; Nyman, Patricia; DeJager, Lowri

2017-02-01

Acid hydrolyzed vegetable protein (aHVP) is used for flavoring a wide variety of foods and also in the production of nonfermented soy sauce. During the production of aHVP, chloropropanols including 3-monochloropropane-1,2-diol (3-MCPD) and 1,3 dichloropropane-2-ol (1,3-DCP) can be formed through the reaction of the hydrochloric acid catalyst and residual fat and the reaction of 3-MCPD with acetic acid, respectively. 3-MCPD is a carcinogen, and 1,3-DCP has been classified as a genotoxic carcinogen. The European Union (EU) has set a maximum concentration of 0.02 mg/kg of 3-MCPD in aHVP, and the Food and Drug Administration (FDA) set a guidance limit of 1 mg/kg of 3-MCPD in aHVP. 1,3-DCP is not an approved food additive, and the Joint FAO/WHO Expert Committee on Food Additives (JEFCA) has set a limit at 0.005 mg/kg, which is close to the estimated method detection limit. Currently there are few analytical methods for the simultaneous determination of 3-MCPD and 1,3-DCP without derivatization due to differences in their physical chemical properties and reactivity. A new method was developed using QuEChERS (quick, easy, cheap, effective, rugged, and safe) with direct analysis of the extract without derivatization using gas chromatography-triple quadrupole mass spectrometry (GC-QQQ). Additionally, a market sampling of 60 soy sauce samples was performed in 2015 to determine if concentrations have changed since the FDA limit was set in 2008. The sampling results were compared between the new QuEChERS method and a method using phenylboronic acid (PBA) as a derivatizing agent for 3-MCPD analysis. The concentrations of 3-MCPD detected in soy sauce samples collected in 2015 (

Simultaneous Analysis of 3-MCPD and 1,3-DCP in Asian Style Sauces Using QuEChERS Extraction and Gas Chromatography–Triple Quadrupole Mass Spectrometry

PubMed Central

Genualdi, Susan; Nyman, Patricia; DeJager, Lowri

2017-01-01

Acid hydrolyzed vegetable protein (aHVP) is used for flavoring a wide variety of foods and also in the production of nonfermented soy sauce. During the production of aHVP, chloropropanols including 3-monochloropropane-1,2-diol (3-MCPD) and 1,3 dichloropropane-2-ol (1,3-DCP) can be formed through the reaction of the hydrochloric acid catalyst and residual fat and the reaction of 3-MCPD with acetic acid, respectively. 3-MCPD is a carcinogen, and 1,3-DCP has been classified as a genotoxic carcinogen. The European Union (EU) has set a maximum concentration of 0.02 mg/kg of 3-MCPD in aHVP, and the Food and Drug Administration (FDA) set a guidance limit of 1 mg/kg of 3-MCPD in aHVP. 1,3-DCP is not an approved food additive, and the Joint FAO/WHO Expert Committee on Food Additives (JEFCA) has set a limit at 0.005 mg/kg, which is close to the estimated method detection limit. Currently there are few analytical methods for the simultaneous determination of 3-MCPD and 1,3-DCP without derivatization due to differences in their physical chemical properties and reactivity. A new method was developed using QuEChERS (quick, easy, cheap, effective, rugged, and safe) with direct analysis of the extract without derivatization using gas chromatography–triple quadrupole mass spectrometry (GC-QQQ). Additionally, a market sampling of 60 soy sauce samples was performed in 2015 to determine if concentrations have changed since the FDA limit was set in 2008. The sampling results were compared between the new QuEChERS method and a method using phenylboronic acid (PBA) as a derivatizing agent for 3-MCPD analysis. The concentrations of 3-MCPD detected in soy sauce samples collected in 2015 (

Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors

PubMed Central

Jiang, Xi-Ling; Shen, Hong-Wu; Yu, Ai-Ming

2014-01-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are serotonin (5-HT) analogs often abused together, which alters thermoregulation that may indicate the severity of serotonin toxicity. Our recent studies have revealed that co-administration of monoamine oxidase inhibitor harmaline leads to greater and prolonged exposure to 5-HT agonist 5-MeO-DMT that might be influenced by cytochrome P450 2D6 (CYP2D6) status. This study was to define the effects of harmaline and 5-MeO-DMT on thermoregulation in wild-type and CYP2D6-humanized (Tg-CYP2D6) mice, as well as the involvement of 5-HT receptors. Animal core body temperatures were monitored noninvasively in the home cages after implantation of telemetry transmitters and administration of drugs. Harmaline (5 and 15 mg/kg, i.p.) alone was shown to induce hypothermia that was significantly affected by CYP2D6 status. In contrast, higher doses of 5-MeO-DMT (10 and 20 mg/kg) alone caused hyperthermia. Co-administration of harmaline (2, 5 or 15 mg/kg) remarkably potentiated the hyperthermia elicited by 5-MeO-DMT (2 or 10 mg/kg), which might be influenced by CYP2D6 status at certain dose combination. Interestingly, harmaline-induced hypothermia was only attenuated by 5-HT1A receptor antagonist WAY-100635, whereas 5-MeO-DMT- and harmaline-5-MeO-DMT-induced hyperthermia could be suppressed by either WAY-100635 or 5-HT2A receptor antagonists (MDL-100907 and ketanserin). Moreover, stress-induced hyperthermia under home cage conditions was not affected by WAY-100635 but surprisingly attenuated by MDL-100907 and ketanserin. Our results indicate that co-administration of monoamine oxidase inhibitor largely potentiates 5-MeO-DMT-induced hyperthermia that involves the activation of both 5-HT1A and 5-HT2A receptors. These findings shall provide insights into development of anxiolytic drugs and new strategies to relieve the lethal hyperthermia in serotonin toxicity. PMID:25446678

Scutellarin Suppresses NLRP3 Inflammasome Activation in Macrophages and Protects Mice against Bacterial Sepsis

PubMed Central

Liu, Yi; Jing, Yan-Yun; Zeng, Chen-Ying; Li, Chen-Guang; Xu, Li-Hui; Yan, Liang; Bai, Wen-Jing; Zha, Qing-Bing; Ouyang, Dong-Yun; He, Xian-Hui

2018-01-01

The NLRP3 inflammasome plays a critical role in mediating the innate immune defense against pathogenic infections, but aberrant activation of NLRP3 inflammasome has been linked to a variety of inflammatory diseases. Thus targeting the NLRP3 inflammasome represents a promising therapeutic for the treatment of such diseases. Scutellarin is a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz. and has been reported to exhibit potent anti-inflammatory activities, but the underlying mechanism is only partly understood. In this study, we aimed to investigate whether scutellarin could affect the activation of NLRP3 inflammasome in macrophages. The results showed that scutellarin dose-dependently reduced caspase-1 activation and decreased mature interleukin-1β (IL-1β) release in lipopolysaccharide (LPS)-primed macrophages upon ATP or nigericin stimulation, indicating that scutellarin inhibited NLRP3 inflammasome activation in macrophages. Consistent with this, scutellarin also suppressed pyroptotic cell death in LPS-primed macrophages treated with ATP or nigericin. ATP or nigericin-induced ASC speck formation and its oligomerization were blocked by scutellarin pre-treatment. Intriguingly, scutellarin augmented PKA-specific phosphorylation of NLRP3 in LPS-primed macrophages, which was completely blocked by selective PKA inhibitor H89, suggesting that PKA signaling had been involved in the action of scutellarin to suppress NLRP3 inflammasome activation. Supporting this, the inhibitory effect of scutellarin on NLRP3 inflammasome activation was completely counteracted by H89 or adenyl cyclase inhibitor MDL12330A. As NLRP3-dependent release of IL-1β has a critical role in sepsis, the in vivo activity of scutellarin was assayed in a mouse model of bacterial sepsis, which was established by intraperitoneally injection of a lethal dose of viable Escherichia coli. Oral administration of scutellarin significantly improved the survival of mice with bacterial sepsis. In line with this, scutellarin treatment significantly reduced serum IL-1β levels and attenuated the infiltration of inflammatory cells in the liver of E. coli-infected mice. These data indicated that scutellarin suppressed NLRP3 inflammasome activation in macrophages by augmenting PKA signaling, highlighting its potential therapeutic application for treating NLRP3-related inflammatory diseases. PMID:29375379

Scutellarin Suppresses NLRP3 Inflammasome Activation in Macrophages and Protects Mice against Bacterial Sepsis.

PubMed

Liu, Yi; Jing, Yan-Yun; Zeng, Chen-Ying; Li, Chen-Guang; Xu, Li-Hui; Yan, Liang; Bai, Wen-Jing; Zha, Qing-Bing; Ouyang, Dong-Yun; He, Xian-Hui

2017-01-01

The NLRP3 inflammasome plays a critical role in mediating the innate immune defense against pathogenic infections, but aberrant activation of NLRP3 inflammasome has been linked to a variety of inflammatory diseases. Thus targeting the NLRP3 inflammasome represents a promising therapeutic for the treatment of such diseases. Scutellarin is a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz. and has been reported to exhibit potent anti-inflammatory activities, but the underlying mechanism is only partly understood. In this study, we aimed to investigate whether scutellarin could affect the activation of NLRP3 inflammasome in macrophages. The results showed that scutellarin dose-dependently reduced caspase-1 activation and decreased mature interleukin-1β (IL-1β) release in lipopolysaccharide (LPS)-primed macrophages upon ATP or nigericin stimulation, indicating that scutellarin inhibited NLRP3 inflammasome activation in macrophages. Consistent with this, scutellarin also suppressed pyroptotic cell death in LPS-primed macrophages treated with ATP or nigericin. ATP or nigericin-induced ASC speck formation and its oligomerization were blocked by scutellarin pre-treatment. Intriguingly, scutellarin augmented PKA-specific phosphorylation of NLRP3 in LPS-primed macrophages, which was completely blocked by selective PKA inhibitor H89, suggesting that PKA signaling had been involved in the action of scutellarin to suppress NLRP3 inflammasome activation. Supporting this, the inhibitory effect of scutellarin on NLRP3 inflammasome activation was completely counteracted by H89 or adenyl cyclase inhibitor MDL12330A. As NLRP3-dependent release of IL-1β has a critical role in sepsis, the in vivo activity of scutellarin was assayed in a mouse model of bacterial sepsis, which was established by intraperitoneally injection of a lethal dose of viable Escherichia coli . Oral administration of scutellarin significantly improved the survival of mice with bacterial sepsis. In line with this, scutellarin treatment significantly reduced serum IL-1β levels and attenuated the infiltration of inflammatory cells in the liver of E. coli -infected mice. These data indicated that scutellarin suppressed NLRP3 inflammasome activation in macrophages by augmenting PKA signaling, highlighting its potential therapeutic application for treating NLRP3-related inflammatory diseases.

Identification and characterization of a novel flavin-containing spermine oxidase of mammalian cell origin.

PubMed Central

Vujcic, Slavoljub; Diegelman, Paula; Bacchi, Cyrus J; Kramer, Debora L; Porter, Carl W

2002-01-01

During polyamine catabolism, spermine and spermidine are first acetylated by spermidine/spermine N(1)-acetyltransferase (SSAT) and subsequently oxidized by polyamine oxidase (PAO) to produce spermidine and putrescine, respectively. In attempting to clone the PAO involved in this back-conversion pathway, we encountered an oxidase that preferentially cleaves spermine in the absence of prior acetylation by SSAT. A BLAST search using maize PAO sequences identified homologous mammalian cDNAs derived from human hepatoma and mouse mammary carcinoma: the encoded proteins differed by 20 amino acids. When either cDNA was transiently transfected into HEK-293 cells, intracellular spermine pools decreased by 75% while spermidine and N (1)-acetylspermidine pools increased, suggesting that spermine was selectively and directly oxidized by the enzyme. Substrate specificity using lysates of oxidase-transfected HEK-293 cells revealed that the newly identified oxidase strongly favoured spermine over N (1)-acetylspermine and that it failed to act on N (1)-acetylspermidine, spermidine or the preferred PAO substrate, N (1), N (12)-diacetylspermine. The PAO inhibitor, MDL-72,527, only partially blocked oxidation of spermine while a previously reported PAO substrate, N (1)-( n -octanesulphonyl)spermine, potently inhibited the reaction. Overall, the data indicate that the enzyme represents a novel mammalian oxidase which, on the basis of substrate specificity, we have designated spermine oxidase in order to distinguish it from the PAO involved in polyamine back-conversion. The identification of an enzyme capable of directly oxidizing spermine to spermidine has important implications for understanding polyamine homoeostasis and for interpreting metabolic and cellular responses to clinically relevant polyamine analogues and inhibitors. PMID:12141946

A comparison study on the use of Dowex 1 and TEVA-resin in determination of 99Tc in environmental and nuclear coolant samples in a SIA system with ICP-MS detection.

PubMed

Kołacińska, Kamila; Samczyński, Zbigniew; Dudek, Jakub; Bojanowska-Czajka, Anna; Trojanowicz, Marek

2018-07-01

This work refers to a comparative study of sorbents widely used in determinations of 99 Tc such as TEVA resin and Dowex 1. Despite having a similar functional group of quaternary amines, both materials represent different chromatographic methods-extraction (TEVA resin) and anion exchange (Dowex 1)-which provides a diverse range of their properties significant in determination of 99 Tc in flow conditions. The comparative tests, carried out in a SIA-LOV (Sequential Injection Analysis-Lab-on-Valve) system combined with mass spectrometric (ICP-MS) detection, considered several factors that are crucial from the standpoint of resin´s utility such as sorption capacity, durability, or selectivity, critical in 99 Tc separation from interferences. The developed and optimized analytical procedure based on the application of the TEVA resin provided determinations of 99 Tc at minimum detectable limit (MDL) 6.00 mBq L -1 in 50 min and has been successfully employed in analyses of samples from nuclear industrial and research units (reactor coolant and sewage) as well as from the river surrounding the nuclear reactor. The method proved to be sufficient for routine analysis of water samples in accordance with EPA standards. The reliability of the method was confirmed in the analysis of the BH standard provided by the NPL for inter-laboratory proficiency tests. The 99 Tc recovery for all real samples was evaluated as 80-100%. Copyright © 2018 Elsevier B.V. All rights reserved.

Sex differences and serotonergic mechanisms in the behavioural effects of psilocin.

PubMed

Tylš, Filip; Páleníček, Tomáš; Kadeřábek, Lukáš; Lipski, Michaela; Kubešová, Anna; Horáček, Jiří

2016-06-01

Psilocybin has recently attracted a great deal of attention as a clinical research and therapeutic tool. The aim of this paper is to bridge two major knowledge gaps regarding its behavioural pharmacology - sex differences and the underlying receptor mechanisms. We used psilocin (0.25, 1 and 4 mg/kg), an active metabolite of psilocybin, in two behavioural paradigms - the open-field test and prepulse inhibition (PPI) of the acoustic startle reaction. Sex differences were evaluated with respect to the phase of the female cycle. The contribution of serotonin receptors in the behavioural action was tested in male rats with selective serotonin receptor antagonists: 5-HT1A receptor antagonist (WAY100635 1 mg/kg), 5-HT2A receptor antagonist (MDL100907 0.5 mg/kg), 5-HT2B receptor antagonist (SB215505 1 mg/kg) and 5-HT2C receptor antagonist (SB242084 1 mg/kg). Psilocin induced dose-dependent inhibition of locomotion and suppression of normal behaviour in rats (behavioural serotonin syndrome, impaired PPI). The effects were more pronounced in male rats than in females. The inhibition of locomotion was normalized by 5-HT1A and 5-HT2B/C antagonists; however, PPI was not affected significantly by these antagonists. Our findings highlight an important issue of sex-specific reactions to psilocin and that apart from 5-HT2A-mediated effects 5-HT1A and 5-HT2C/B receptors also play an important role. These findings have implications for recent clinical trials.

Segmentation of tumor ultrasound image in HIFU therapy based on texture and boundary encoding

NASA Astrophysics Data System (ADS)

Zhang, Dong; Xu, Menglong; Quan, Long; Yang, Yan; Qin, Qianqing; Zhu, Wenbin

2015-02-01

It is crucial in high intensity focused ultrasound (HIFU) therapy to detect the tumor precisely with less manual intervention for enhancing the therapy efficiency. Ultrasound image segmentation becomes a difficult task due to signal attenuation, speckle effect and shadows. This paper presents an unsupervised approach based on texture and boundary encoding customized for ultrasound image segmentation in HIFU therapy. The approach oversegments the ultrasound image into some small regions, which are merged by using the principle of minimum description length (MDL) afterwards. Small regions belonging to the same tumor are clustered as they preserve similar texture features. The mergence is completed by obtaining the shortest coding length from encoding textures and boundaries of these regions in the clustering process. The tumor region is finally selected from merged regions by a proposed algorithm without manual interaction. The performance of the method is tested on 50 uterine fibroid ultrasound images from HIFU guiding transducers. The segmentations are compared with manual delineations to verify its feasibility. The quantitative evaluation with HIFU images shows that the mean true positive of the approach is 93.53%, the mean false positive is 4.06%, the mean similarity is 89.92%, the mean norm Hausdorff distance is 3.62% and the mean norm maximum average distance is 0.57%. The experiments validate that the proposed method can achieve favorable segmentation without manual initialization and effectively handle the poor quality of the ultrasound guidance image in HIFU therapy, which indicates that the approach is applicable in HIFU therapy.

Minimal Polynomial Method for Estimating Parameters of Signals Received by an Antenna Array

NASA Astrophysics Data System (ADS)

Ermolaev, V. T.; Flaksman, A. G.; Elokhin, A. V.; Kuptsov, V. V.

2018-01-01

The effectiveness of the projection minimal polynomial method for solving the problem of determining the number of sources of signals acting on an antenna array (AA) with an arbitrary configuration and their angular directions has been studied. The method proposes estimating the degree of the minimal polynomial of the correlation matrix (CM) of the input process in the AA on the basis of a statistically validated root-mean-square criterion. Special attention is paid to the case of the ultrashort sample of the input process when the number of samples is considerably smaller than the number of AA elements, which is important for multielement AAs. It is shown that the proposed method is more effective in this case than methods based on the AIC (Akaike's Information Criterion) or minimum description length (MDL) criterion.

Reconfigurable Flight Control System for a STOL (Short Take-Off and Landing) Aircraft Using Quantitative Feedback Theory.

DTIC Science & Technology

1984-12-01

XD2, XD3, XD4, XD5, XD6, XD7, XDS, 7M1, MA, MH, M0,MU, MDl,MD2, MD3, MD4, M5, MOS, MD7, MDS REAL CNB, CYB, CL, L, N DIMENSION AMAT(4,4), BMAT (4,S...NO, MU, ND1, MD2, ND3, MD4,ND5, MD6, ND7, NO REAL CNB, CYB, CL, L, N DIMENSION AMAT(4,4), BMAT (4,S)V DIMENSION DIRMAT(5, 5) ,DIRBMAT(5, SJ CHARACTER*3...INPUT MATRIX 8 C BMAT (l,1) - XO1 BMAT (1,2) - X02 BMAT (1,3) = XD3 BMAT (1,4) -XO4 SMAT(1,5) -XD5 BMAT (1,&) - XDG BMQT(1,7) = XD7 EMAT(I,8) - XDB BMAT (,1

Teaching Introductory Mineralogy With the GeoWall

NASA Astrophysics Data System (ADS)

Anderson, C. D.; Haymon, R. M.

2003-12-01

Mineralogy, like many topics in Earth Sciences, contains inherently three-dimensional topics that are difficult to teach. Concepts such as crystal symmetry and forms, Miller indices, the polymerization of silica tetrahedra and resulting structures of silicate mineral groups, and the interaction of light and minerals are particularly difficult. Two-dimensional diagrams are limited in their effectiveness, and physical models, while effective, are expensive and do not work as well in large class settings. The GeoWall system brings the effectiveness of physical models to the large classroom. In Fall 2003, we will integrate the GeoWall into our introductory mineralogy classes at UCSB using a combination of commercial software, atomic structure models available on the web, and custom content created in-house. The commercial software SHAPE (www.shapesoftware.com) allows users to build and display crystal shapes and their symmetry. Though not designed for the GeoWall, the software's stereopair display mode works perfectly on the system. Using the Chime web browser plug-in (www.mdl.com), computer models of silicate minerals available from the Virtual Museum of Minerals and Molecules (www.soils.umn.eduvirtual_museum) provide an interactive display of silicate mineral structure that illustrates the tetrahedral framework. Again, while not developed for the GeoWall, the Chime plug-in works seamlessly with the GeoWall hardware. 3-D GeoWall images that display light paths through minerals, and reveal relationships between crystal symmetry and optical indicatrix properties, have been developed in-house using a combination of SHAPE and 3D modeling software. The 3-D GeoWall images should convey in an instant these difficult concepts that students historically have struggled to visualize. Initial assessment of the GeoWall's effectiveness as a mineralogy teaching aid at UCSB in Fall 2003 will come from the instructor's impressions and by comparing test scores with classes from previous years.

Splice loss requirements in multi-mode fiber mode-division-multiplex transmission links.

PubMed

Warm, Stefan; Petermann, Klaus

2013-01-14

We investigate numerically the influence of fiber splices and fiber connectors to the statistics of mode dependent loss (MDL) and multiple-input multiple-output (MIMO) outage capacity in mode multiplexed multi-mode fiber links. Our results indicate required splice losses much lower than currently feasible to achieve a reasonable outage capacity in long-haul transmission systems. Splice losses as low as 0.03dB may effectively lead to an outage of MIMO channels after only a few hundred kilometers transmission length. In a first approximation, the relative capacity solely depends on the accumulated splice loss and should be less than ≈ 2dB to ensure a relative capacity of 90%. We also show that discrete mode permutation (mixing) within the transmission line may effectively increase the maximum transmission distance by a factor of 5 for conventional splice losses.

High-Power DFB Diode Laser-Based CO-QEPAS Sensor: Optimization and Performance.

PubMed

Ma, Yufei; Tong, Yao; He, Ying; Yu, Xin; Tittel, Frank K

2018-01-04

A highly sensitive carbon monoxide (CO) trace gas sensor based on quartz-enhanced photoacoustic spectroscopy (QEPAS) was demonstrated. A high-power distributed feedback (DFB), continuous wave (CW) 2.33 μm diode laser with an 8.8 mW output power was used as the QEPAS excitation source. By optimizing the modulation depth and adding an optimum micro-resonator, compared to a bare quartz tuning fork (QTF), a 10-fold enhancement of the CO-QEPAS signal amplitude was achieved. When water vapor acting as a vibrational transfer catalyst was added to the target gas, the signal was further increased by a factor of ~7. A minimum detection limit (MDL) of 11.2 ppm and a calculated normalized noise equivalent absorption (NNEA) coefficient of 1.8 × 10 -5 cm -1 W/√Hz were obtained for the reported CO-QEPAS sensor.

High-Power DFB Diode Laser-Based CO-QEPAS Sensor: Optimization and Performance

PubMed Central

Ma, Yufei; Tong, Yao; He, Ying; Yu, Xin

2018-01-01

A highly sensitive carbon monoxide (CO) trace gas sensor based on quartz-enhanced photoacoustic spectroscopy (QEPAS) was demonstrated. A high-power distributed feedback (DFB), continuous wave (CW) 2.33 μm diode laser with an 8.8 mW output power was used as the QEPAS excitation source. By optimizing the modulation depth and adding an optimum micro-resonator, compared to a bare quartz tuning fork (QTF), a 10-fold enhancement of the CO-QEPAS signal amplitude was achieved. When water vapor acting as a vibrational transfer catalyst was added to the target gas, the signal was further increased by a factor of ~7. A minimum detection limit (MDL) of 11.2 ppm and a calculated normalized noise equivalent absorption (NNEA) coefficient of 1.8 × 10−5 cm−1W/√Hz were obtained for the reported CO-QEPAS sensor. PMID:29300310

Strategy for determination of LOD and LOQ values--some basic aspects.

PubMed

Uhrovčík, Jozef

2014-02-01

The paper is devoted to the evaluation of limit of detection (LOD) and limit of quantification (LOQ) values in concentration domain by using 4 different approaches; namely 3σ and 10σ approaches, ULA2 approach, PBA approach and MDL approach. Brief theoretical analyses of all above mentioned approaches are given together with directions for their practical use. Calculations and correct calibration design are exemplified by using of electrothermal atomic absorption spectrometry for determination of lead in drinking water sample. These validation parameters reached 1.6 μg L(-1) (LOD) and 5.4 μg L(-1) (LOQ) by using 3σ and 10σ approaches. For obtaining relevant values of analyte concentration the influence of calibration design and measurement methodology were examined. The most preferred technique has proven to be a method of preconcentration of the analyte on the surface of the graphite cuvette (boost cycle). © 2013 Elsevier B.V. All rights reserved.

Philanthro-metrics: Mining multi-million-dollar gifts

PubMed Central

2017-01-01

The Million Dollar List (MDL, online at http://www.milliondollarlist.org) is a compilation of publicly announced charitable donations of $1 million or more from across the United States since 2000; as of December 2016, the database contains close to 80,000 gifts made by U.S. individuals, corporations, foundations, and other grant-making nonprofit organizations. This paper discusses the unique value of the Million Dollar List and provides unique insights to key questions such as: How does distance affect giving? How do networks impact million-dollar-plus gifts? Understanding the geospatial and temporal dimensions of philanthropy can assist researchers and policymakers to better understand the role of private funding in innovation and discovery. Moreover, the results from the paper emphasize the importance of philanthropy for fueling research and development in science, the arts, environment, and health. The paper also includes the limitations of the presented analyses and promising future work. PMID:28552937

Optimization experiments on a pixe system and its application to the analysis of trace elements in shaji

NASA Astrophysics Data System (ADS)

Yin, Zhongli; Zhang, Shunun; Jiang, Xinzhou; Ma, Changjun; Li, Zhenkun; Hao, Jifang; Zheng, Zhihao; Liu, Zhaoyuan; Liu, Zhengmin; Ma, Shuxun; Yang, Kunshan

1989-04-01

This paper describes briefly the optimization of a PIXE setup. Three proton energies 1.5, 2.0 and 2.5 MeV and four kinds of absorbers BE (132 μm), Be (460 μm), Al (28 μm) and Be plus Mylar (460 μm+600 μm) were used. The minimum detection limits (MDL) of PIXE for these various combinations were computed and compared. PIXE analysis of Shaji was performed as an application. The result shows that the stack absorber of 460 μm Be and 600 μm Mylar films and a 2.0 MeV proton energy are most suitable for PIXE analysis of Shaji. Results of the Shaji analysis are presented. Shaji is one of the common seabuckthoms. The Shaji referred to here belongs to Hippophae rhamnoides L. Subsp. Sinensis Rousi.

Functional feature embedded space mapping of fMRI data.

PubMed

Hu, Jin; Tian, Jie; Yang, Lei

2006-01-01

We have proposed a new method for fMRI data analysis which is called Functional Feature Embedded Space Mapping (FFESM). Our work mainly focuses on the experimental design with periodic stimuli which can be described by a number of Fourier coefficients in the frequency domain. A nonlinear dimension reduction technique Isomap is applied to the high dimensional features obtained from frequency domain of the fMRI data for the first time. Finally, the presence of activated time series is identified by the clustering method in which the information theoretic criterion of minimum description length (MDL) is used to estimate the number of clusters. The feasibility of our algorithm is demonstrated by real human experiments. Although we focus on analyzing periodic fMRI data, the approach can be extended to analyze non-periodic fMRI data (event-related fMRI) by replacing the Fourier analysis with a wavelet analysis.

Philanthro-metrics: Mining multi-million-dollar gifts.

PubMed

Osili, Una O; Ackerman, Jacqueline; Kong, Chin Hua; Light, Robert P; Börner, Katy

2017-01-01

The Million Dollar List (MDL, online at http://www.milliondollarlist.org) is a compilation of publicly announced charitable donations of $1 million or more from across the United States since 2000; as of December 2016, the database contains close to 80,000 gifts made by U.S. individuals, corporations, foundations, and other grant-making nonprofit organizations. This paper discusses the unique value of the Million Dollar List and provides unique insights to key questions such as: How does distance affect giving? How do networks impact million-dollar-plus gifts? Understanding the geospatial and temporal dimensions of philanthropy can assist researchers and policymakers to better understand the role of private funding in innovation and discovery. Moreover, the results from the paper emphasize the importance of philanthropy for fueling research and development in science, the arts, environment, and health. The paper also includes the limitations of the presented analyses and promising future work.

Information Theory and Voting Based Consensus Clustering for Combining Multiple Clusterings of Chemical Structures.

PubMed

Saeed, Faisal; Salim, Naomie; Abdo, Ammar

2013-07-01

Many consensus clustering methods have been applied in different areas such as pattern recognition, machine learning, information theory and bioinformatics. However, few methods have been used for chemical compounds clustering. In this paper, an information theory and voting based algorithm (Adaptive Cumulative Voting-based Aggregation Algorithm A-CVAA) was examined for combining multiple clusterings of chemical structures. The effectiveness of clusterings was evaluated based on the ability of the clustering method to separate active from inactive molecules in each cluster, and the results were compared with Ward's method. The chemical dataset MDL Drug Data Report (MDDR) and the Maximum Unbiased Validation (MUV) dataset were used. Experiments suggest that the adaptive cumulative voting-based consensus method can improve the effectiveness of combining multiple clusterings of chemical structures. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An animal model of schizophrenia based on chronic LSD administration: old idea, new results.

PubMed

Marona-Lewicka, Danuta; Nichols, Charles D; Nichols, David E

2011-09-01

Many people who take LSD experience a second temporal phase of LSD intoxication that is qualitatively different, and was described by Daniel Freedman as "clearly a paranoid state." We have previously shown that the discriminative stimulus effects of LSD in rats also occur in two temporal phases, with initial effects mediated by activation of 5-HT(2A) receptors (LSD30), and the later temporal phase mediated by dopamine D2-like receptors (LSD90). Surprisingly, we have now found that non-competitive NMDA antagonists produced full substitution in LSD90 rats, but only in older animals, whereas in LSD30, or in younger animals, these drugs did not mimic LSD. Chronic administration of low doses of LSD (>3 months, 0.16 mg/kg every other day) induces a behavioral state characterized by hyperactivity and hyperirritability, increased locomotor activity, anhedonia, and impairment in social interaction that persists at the same magnitude for at least three months after cessation of LSD treatment. These behaviors, which closely resemble those associated with psychosis in humans, are not induced by withdrawal from LSD; rather, they are the result of neuroadaptive changes occurring in the brain during the chronic administration of LSD. These persistent behaviors are transiently reversed by haloperidol and olanzapine, but are insensitive to MDL-100907. Gene expression analysis data show that chronic LSD treatment produced significant changes in multiple neurotransmitter system-related genes, including those for serotonin and dopamine. Thus, we propose that chronic treatment of rats with low doses of LSD can serve as a new animal model of psychosis that may mimic the development and progression of schizophrenia, as well as model the established disease better than current acute drug administration models utilizing amphetamine or NMDA antagonists such as PCP. Copyright © 2011 Elsevier Ltd. All rights reserved.

Blockade of serotonin 5-HT2A receptors potentiates dopamine D2 activation-induced disruption of pup retrieval on an elevated plus maze, but has no effect on D2 blockade-induced one.

PubMed

Nie, Lina; Di, Tianqi; Li, Yu; Cheng, Peng; Li, Ming; Gao, Jun

2018-06-23

Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D 2 receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT 2A receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT 2A on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT 2A receptors on dopamine D 2 -mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole (a D 2 agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D 2 antagonist, 0.1 or 0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT 2A receptor antagonist, 1.0 mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and tested at 30, 90 and 240 min after quinpirole or haloperidol injection on postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup retrieved (an index of maternal motivation) and sequential retrieval score (an index of executive function), prolonged the pup retrieval latencies, reduced the percentage of time spent on the open arms (an index of maternal anxiety), and decreased the distance travelled on the maze in a dose-dependent and time-dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval, but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no effect on the haloperidol-induced one. These findings suggest a complex interactive effect between 5-HT 2A and D 2 receptors on one or several maternal processes (maternal motivation, anxiety and executive function), and support the idea that one molecular mechanism by which 5-HT 2A receptors mediate maternal behavior is through its modulation of D 2 receptors. Copyright © 2018. Published by Elsevier Inc.

Sulfur speciation and sulfide oxidation in the water column of the Black Sea

NASA Astrophysics Data System (ADS)

Luther, George W., III; Church, Thomas M.; Powell, David

We have applied sulfur speciation techniques to understand the chemistry and cycling of sulfur in Black Sea waters. The only reduced dissolved inorganic sulfur species detected (above the low minimum detection limits of the voltammetric methods employed) in the water column was hydrogen sulfide. The maximum concentration of sulfide (423 μM) is similar to previous reports. Using a cathodic stripping square wave voltammetry (CSSWV) method for nanomolar levels of sulfide, we determined the precise boundary between the "free" hydrogen sulfide (sulfidic) zone and the upper (oxic/suboxic) water column at the two stations studied. This boundary has apparently moved up by about 50 m in the past 20 years. Our results help demonstrate three chemically distinct zones of water in the central basin of the Black Sea: (1) the oxic [0-65 m], (2) the anoxic/nonsulfidic [65-100 m] and (3) the sulfidic [>100 m]. Sulfide bound to metals ("complexed" sulfide) is observed in both the oxic and anoxic/nonsulfidic zones of the water column. This supports previous studies on metal sulfide forms. From the electrochemical data, it is possible to estimate the strength of the complexation of sulfide to metals (log K = 10 to 11). Thiosulfate and sulfite were below our minimum detectable limit (MDL) of 50 nM using CSSWV. Elemental sulfur (MDL 5 nM) was detected below the onset of the hydrogen sulfide zone (90-100 m) with a maximum of 30-60 nM near 120 m. The sulfur speciation results for the Black Sea are lower by one order of magnitude or more than other marine systems such as the Cariaco Trench and salt marshes. New HPLC techniques were applied to detect thiols at submicromolar levels. The presence of thiols (2-mercaptoethylamine, 2-mercaptoethanol, N-acetylcysteine and glutathione) is correlated with the remineralization of organic matter at the oxic and anoxic/nonsulfidic interface. Water samples collected from the upper 50 m of the sulfidic zone showed significant sulfide oxidation on storage onboard ship even though they were filtered (0.2 μm) and handled to exclude oxygen contamination. Chemical additives such as formaldehyde, glutaraldehyde, hydroxylamine and ascorbic acid prevented or retarded the sulfide loss. Thiosulfate and azide did not inhibit sulfide loss. These studies suggest an anaerobic chemical oxidation of sulfide rather than a biological oxidation on stored and filtered samples.

Feasibility of measuring selenium in humans using in vivo neutron activation analysis.

PubMed

Tahir, S N A; Chettle, D R; Byun, S H; Prestwich, W V

2015-11-01

Selenium (Se) is an element that, in trace quantities, plays an important role in the normal function of a number of biological processes in humans. Many studies have demonstrated that selenium deficiency in the body may contribute to an increased risk for certain neoplastic, cardiovascular, osseous, and nervous system diseases including retardation of bone formation. However, at higher concentrations Se is cytotoxic. For these reasons it is desirable to have a means of monitoring selenium concentration in humans.This paper presents the outcome of a feasibility study carried out for measuring selenium in humans using in vivo neutron activation analysis (IVNAA). In this technique a small dose of neutrons is delivered to the organ of interest, the neutrons are readily captured by the target nuclei, and the γ-rays given off are detected outside of the body. For the present study, human hand (bone) tissue equivalent phantoms were prepared with varying amounts of Se. These were irradiated by a low energy fast neutron beam produced by the (7)Li(p,n)(7)Be reaction employing the high beam current Tandetron accelerator. The counting data saved using a 4π NaI(TI) detection system were analyzed. The selenium was detected via the neutron capture reaction, (76)Se(n,γ)(77 m)Se, whereas calcium was detected through the (48)Ca(n,γ)(49)Ca reaction for the purpose of normalization of the Se signals to the calcium signals. From the calibration lines drawn between Se/Ca concentrations and Se/Ca counts ratio, the minimum detection limits (MDLs) were computed for two sets of phantoms irradiated under different irradiation parameters.In this study the optimized MDL value was determined to be 81 ng g(-1) (Se/phantom mass) for an equivalent dose of 188 mSv to the phantom. This MDL was found at least 10 times lower than the reported data on Se concentration measured in bone tissues. It was concluded that the NAA technique would be a feasible means of performing in vivo measurements of selenium in humans. Currently the data on in vivo measurement of selenium in humans are limited; the results of the present study would greatly contribute to the present data.

Expression of calpain-like proteins and effects of calpain inhibitors on the growth rate of Angomonas deanei wild type and aposymbiotic strains.

PubMed

de Oliveira, Simone Santiago Carvalho; Garcia-Gomes, Aline dos Santos; d'Avila-Levy, Claudia Masini; dos Santos, André Luis Souza; Branquinha, Marta Helena

2015-09-29

Angomonas deanei is a trypanosomatid parasite of insects that has a bacterial endosymbiont, which supplies amino acids and other nutrients to its host. Bacterium loss induced by antibiotic treatment of the protozoan leads to an aposymbiotic strain with increased need for amino acids and results in increased production of extracellular peptidases. In this work, a more detailed examination of A. deanei was conducted to determine the effects of endosymbiont loss on the host calpain-like proteins (CALPs), followed by testing of different calpain inhibitors on parasite proliferation. Western blotting showed the presence of different protein bands reactive to antibodies against calpain from Drosophila melanogaster (anti-Dm-calpain), lobster calpain (anti-CDPIIb) and cytoskeleton-associated calpain from Trypanosoma brucei (anti-CAP5.5), suggesting a possible modulation of CALPs influenced by the endosymbiont. In the cell-free culture supernatant of A. deanei wild type and aposymbiotic strains, a protein of 80 kDa cross-reacted with the anti-Dm-calpain antibody; however, no cross-reactivity was found with anti-CAP5.5 and anti-CDPIIb antibodies. A search in A. deanei genome for homologues of D. melanogaster calpain, T. brucei CAP5.5 and lobster CDPIIb calpain revealed the presence of hits with at least one calpain conserved domain and also with theoretical molecular mass consistent with the recognition by each antibody. No significant hit was observed in the endosymbiont genome, indicating that calpain molecules might be absent from the symbiont. Flow cytometry analysis of cells treated with the anti-calpain antibodies showed that a larger amount of reactive epitopes was located intracellularly. The reversible calpain inhibitor MDL28170 displayed a much higher efficacy in diminishing the growth of both strains compared to the non-competitive calpain inhibitor PD150606, while the irreversible calpain inhibitor V only marginally diminished the proliferation. Altogether, these results indicate that distinct calpain-like molecules are expressed by A. deanei, with a possible modulation in the expression influenced by the endosymbiont. In addition, treatment with MDL28170 affects the growth rate of both strains, as previously determined in the human pathogenic species Leishmania amazonensis and Trypanosoma cruzi, with whom A. deanei shares immunological and biochemical relationships.

A method for direct, semi-quantitative analysis of gas phase samples using gas chromatography-inductively coupled plasma-mass spectrometry

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

Carter, Kimberly E; Gerdes, Kirk

2013-07-01

A new and complete GC–ICP-MS method is described for direct analysis of trace metals in a gas phase process stream. The proposed method is derived from standard analytical procedures developed for ICP-MS, which are regularly exercised in standard ICP-MS laboratories. In order to implement the method, a series of empirical factors were generated to calibrate detector response with respect to a known concentration of an internal standard analyte. Calibrated responses are ultimately used to determine the concentration of metal analytes in a gas stream using a semi-quantitative algorithm. The method was verified using a traditional gas injection from a GCmore » sampling valve and a standard gas mixture containing either a 1 ppm Xe + Kr mix with helium balance or 100 ppm Xe with helium balance. Data collected for Xe and Kr gas analytes revealed that agreement of 6–20% with the actual concentration can be expected for various experimental conditions. To demonstrate the method using a relevant “unknown” gas mixture, experiments were performed for continuous 4 and 7 hour periods using a Hg-containing sample gas that was co-introduced into the GC sample loop with the xenon gas standard. System performance and detector response to the dilute concentration of the internal standard were pre-determined, which allowed semi-quantitative evaluation of the analyte. The calculated analyte concentrations varied during the course of the 4 hour experiment, particularly during the first hour of the analysis where the actual Hg concentration was under predicted by up to 72%. Calculated concentration improved to within 30–60% for data collected after the first hour of the experiment. Similar results were seen during the 7 hour test with the deviation from the actual concentration being 11–81% during the first hour and then decreasing for the remaining period. The method detection limit (MDL) was determined for the mercury by injecting the sample gas into the system following a period of equilibration. The MDL for Hg was calculated as 6.8 μg · m -3. This work describes the first complete GC–ICP-MS method to directly analyze gas phase samples, and detailed sample calculations and comparisons to conventional ICP-MS methods are provided.« less

Discriminative stimulus effects of the imidazoline I2 receptor ligands BU224 and phenyzoline in rats.

PubMed

Qiu, Yanyan; Zhang, Yanan; Li, Jun-Xu

2015-02-15

Although imidazoline I2 receptor ligands have been used as discriminative stimuli, the role of efficacy of I2 receptor ligands as a critical determinant in drug discrimination has not been explored. This study characterized the discriminative stimulus effects of selective imidazoline I2 receptor ligands BU224 (a low-efficacy I2 receptor ligand) and phenyzoline (a higher efficacy I2 receptor ligand) in rats. Two groups of male Sprague-Dawley rats were trained to discriminate 5.6mg/kg BU224 or 32mg/kg phenyzoline (i.p.) from their vehicle in a two-lever food-reinforced drug discrimination procedure, respectively. All rats acquired the discriminations after an average of 18 (BU224) and 56 (phenyzoline) training sessions, respectively. BU224 and phenyzoline completely substituted for one another symmetrically. Several I2 receptor ligands (tracizoline, CR4056, RS45041, and idazoxan) all occasioned>80% drug-associated lever responding in both discriminations. The I2 receptor ligand 2-BFI and a monoamine oxidase inhibitor harmane occasioned>80% drug-associated lever responding in rats discriminating BU224. Other drugs that occasioned partial or less substitution to BU224 cue included clonidine, methamphetamine, ketamine, morphine, methadone and agmatine. Clonidine, methamphetamine and morphine also only produced partial substitution to phenyzoline cue. Naltrexone, dopamine D2 receptor antagonist haloperidol and serotonin (5-HT)2A receptor antagonist MDL100907 failed to alter the discriminative stimulus effects of BU224 or phenyzoline. Combined, these results are the first to demonstrate that BU224 and phenyzoline can serve as discriminative stimuli and that the low-efficacy I2 receptor ligand BU224 shares similar discriminative stimulus effects with higher-efficacy I2 receptor ligands such as phenyzoline and 2-BFI. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of the tachykinin NK2 receptor in the human bronchus: influence of amastatin-sensitive metabolic pathways.

PubMed Central

Astolfi, M.; Treggiari, S.; Giachetti, A.; Meini, S.; Maggi, C. A.; Manzini, S.

1994-01-01

1. The aim of this study was to characterize the tachykinin NK2 receptor subtype mediating the spasmogenic response in the human isolated bronchus. The motor response to neurokinin A (NKA) and the selective NK2 agonist [beta Ala8]NKA(4-10), as well as the antagonistic effects of cyclic (L659,877) and linear (MEN 10376) peptide NK2 antagonists were assessed in the presence or absence of amastatin (an inhibitor of aminopeptidases A and M). 2. NKA was more potent than [beta Ala8]NKA(4-10) in eliciting bronchoconstriction (pD2 being 7,43 and 6,87 respectively). In the presence of amastatin (1 microM), the estimated affinity of [beta Ala8]NKA(4-10), but not that of NKA, was significantly increased to yield a pD2 of 7,44. 3. L659,877 and MEN 10376 inhibited [beta Ala8]NKA(4-10)-induced contraction with similar affinities; pA2 values were 5.7 +/- 0.22 and 6.3 +/- 0.32, respectively. Amastatin (1 microM) increased the potency of MEN 10376 to 7.28 +/- 0.46, whereas that of L659,877 was unaffected. 4. In the presence of amastatin the pseudopeptide MDL 28,564 behaved as a partial agonist. 5. We conclude that the NK2 receptor subtype present in the human bronchus has properties similar to those described for the circular muscle of the human colon and thus may be classified as a 'NK2A' subtype. We show that the apparent potency of peptides, bearing N-terminal acidic residues, is influenced by an amastatin-sensitive peptidase, possibly aminopeptidase A. PMID:8004400

Characterization of the tachykinin NK2 receptor in the human bronchus: influence of amastatin-sensitive metabolic pathways.

PubMed

Astolfi, M; Treggiari, S; Giachetti, A; Meini, S; Maggi, C A; Manzini, S

1994-02-01

1. The aim of this study was to characterize the tachykinin NK2 receptor subtype mediating the spasmogenic response in the human isolated bronchus. The motor response to neurokinin A (NKA) and the selective NK2 agonist [beta Ala8]NKA(4-10), as well as the antagonistic effects of cyclic (L659,877) and linear (MEN 10376) peptide NK2 antagonists were assessed in the presence or absence of amastatin (an inhibitor of aminopeptidases A and M). 2. NKA was more potent than [beta Ala8]NKA(4-10) in eliciting bronchoconstriction (pD2 being 7,43 and 6,87 respectively). In the presence of amastatin (1 microM), the estimated affinity of [beta Ala8]NKA(4-10), but not that of NKA, was significantly increased to yield a pD2 of 7,44. 3. L659,877 and MEN 10376 inhibited [beta Ala8]NKA(4-10)-induced contraction with similar affinities; pA2 values were 5.7 +/- 0.22 and 6.3 +/- 0.32, respectively. Amastatin (1 microM) increased the potency of MEN 10376 to 7.28 +/- 0.46, whereas that of L659,877 was unaffected. 4. In the presence of amastatin the pseudopeptide MDL 28,564 behaved as a partial agonist. 5. We conclude that the NK2 receptor subtype present in the human bronchus has properties similar to those described for the circular muscle of the human colon and thus may be classified as a 'NK2A' subtype. We show that the apparent potency of peptides, bearing N-terminal acidic residues, is influenced by an amastatin-sensitive peptidase, possibly aminopeptidase A.

Development of matrix solid-phase dispersion method for the extraction of short-chain chlorinated paraffins in human placenta.

PubMed

Wang, Ying; Gao, Wei; Wu, Jing; Liu, Huijin; Wang, Yingjun; Wang, Yawei; Jiang, Guibin

2017-12-01

Chlorinated paraffins (SCCPs) are widely used worldwide, and they can be released into the environment during their production, transport, usage and disposal, which pose potential risks for human health. In this work, an efficient, reliable and rapid pretreatment method based on matrix solid-phase dispersion (MSPD) was developed for the analysis of short-chain CPs (SCCPs) in human placenta by gas chromatograph-electron capture negative ion low-resolution mass spectrometry (GC-ECNI-LRMS) and gas chromatography-quadrupole time-of-flight mass spectrometry (GC-QTOF-HRMS). The MSPD-relevant parameters including dispersing sorbent, sample-to-sorbent mass ratio, and elution solvent were optimized using the orthogonal test. Silica gel was found to be the optimal dispersing sorbent among the selected matrices. Under the optimal conditions, 44% acidic silica gel can be used as the co-sorbent to remove lipid and eluted by the mixture of hexane and dichloromethane (7:3, V/V). The spiked recoveries of the optimized method were 77.4% and 91.4% for analyzing SCCPs in human placenta by GC-ECNI-LRMS and GC-QTOF-HRMS, and the corresponding relative standard deviations were 10.2% and 5.6%, respectively. The method detection limit for the total SCCPs was 36.8ng/g (dry weight, dw) and 19.2ng/g (dw) as measured by GC-ECNI-LRMS and GC-QTOF-HRMS, respectively. The concentrations of SCCPs in four human placentas were in the range of

Sensitive, accurate and rapid detection of trace aliphatic amines in environmental samples with ultrasonic-assisted derivatization microextraction using a new fluorescent reagent for high performance liquid chromatography.

PubMed

Chen, Guang; Liu, Jianjun; Liu, Mengge; Li, Guoliang; Sun, Zhiwei; Zhang, Shijuan; Song, Cuihua; Wang, Hua; Suo, Yourui; You, Jinmao

2014-07-25

A new fluorescent reagent, 1-(1H-imidazol-1-yl)-2-(2-phenyl-1H-phenanthro[9,10-d]imidazol-1-yl)ethanone (IPPIE), is synthesized, and a simple pretreatment based on ultrasonic-assisted derivatization microextraction (UDME) with IPPIE is proposed for the selective derivatization of 12 aliphatic amines (C1: methylamine-C12: dodecylamine) in complex matrix samples (irrigation water, river water, waste water, cultivated soil, riverbank soil and riverbed soil). Under the optimal experimental conditions (solvent: ACN-HCl, catalyst: none, molar ratio: 4.3, time: 8 min and temperature: 80°C), micro amount of sample (40 μL; 5mg) can be pretreated in only 10 min, with no preconcentration, evaporation or other additional manual operations required. The interfering substances (aromatic amines, aliphatic alcohols and phenols) get the derivatization yields of <5%, causing insignificant matrix effects (<4%). IPPIE-analyte derivatives are separated by high performance liquid chromatography (HPLC) and quantified by fluorescence detection (FD). The very low instrumental detection limits (IDL: 0.66-4.02 ng/L) and method detection limits (MDL: 0.04-0.33 ng/g; 5.96-45.61 ng/L) are achieved. Analytes are further identified from adjacent peaks by on-line ion trap mass spectrometry (MS), thereby avoiding additional operations for impurities. With this UDME-HPLC-FD-MS method, the accuracy (-0.73-2.12%), precision (intra-day: 0.87-3.39%; inter-day: 0.16-4.12%), recovery (97.01-104.10%) and sensitivity were significantly improved. Successful applications in environmental samples demonstrate the superiority of this method in the sensitive, accurate and rapid determination of trace aliphatic amines in micro amount of complex samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Opportunities to improve the in vivo measurement of manganese in human hands.

PubMed

Aslam; Chettle, D R; Pejović-Milić, A; Waker, A J

2009-01-07

Manganese (Mn) is an element which is both essential for regulating neurological and skeletal functions in the human body and also toxic when humans are exposed to excessive levels. Its excessive inhalation as a result of exposure through industrial and environmental emissions can cause neurological damage, which may manifest as memory deficit, loss of motor control and reduction in the refinement of certain body motions. A number of clinical studies demonstrate that biological monitoring of Mn exposure using body fluids, particularly blood, plasma/serum and urine is of very limited use and reflect only the most recent exposure and rapidly return to within normal ranges. In this context, a non-invasive neutron activation technique has been developed at the McMaster University accelerator laboratory that could provide an alternative to measure manganese stored in the bones of exposed subjects. In a first pilot study we conducted recently on non-exposed human subjects to measure the ratio of Mn to Ca in hand bones, it was determined that the technique needed further development to improve the precision of the measurements. It could be achieved by improving the minimum detection limit (MDL) of the system from 2.1 microg Mn/g Ca to the reference value of 0.6 microg g(-1) Ca (range: 0.16-0.78 microg Mn/g Ca) for the non-exposed population. However, the developed procedure might still be a suitable means of screening patients and people exposed to excessive amounts of Mn, who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. To improve the MDL of the technique to the expected levels of Mn in a reference population, the present study investigates further optimization of irradiation conditions, which includes the optimal selection of proton beam energy, beam current and irradiation time and the effect of upgrading the 4pi detection system. The maximum local dose equivalent that could be given to the hand as a result of irradiation was constrained to be less than 150 mSv as opposed to the previously imposed dose equivalent limit of 20 mSv. A maximum beam current, which could be delivered on the lithium target to produce neutrons, was restricted to 500 microA. The length of irradiation intervals larger than 10 min, was considered inconvenient and impractical to implement with Mn measurements in humans. To fulfil the requirements for developing a protocol for in vivo bone Mn measurements, a revised estimate of the dose equivalent has been presented here. Beam energy of 1.98 MeV was determined to be optimal to complete the irradiation procedure within 10 min using 500 microA beam current. The local dose equivalent given to hand was estimated as 118 mSv, which is lower by a factor of 1.5 compared to that of 2.00 MeV. The optimized beam parameters are expected to improve the currently obtained detection limit of 2.1 microg Mn/g Ca to 0.6 microg Mn/g Ca. Using this dose equivalent delivered to the central location of the hand, the average dose equivalent to the hand of 74 mSv and an effective dose of approximately 70 microSv will be accompanying the non-invasive, in vivo measurements of bone Mn, which is little over the chest radiograph examination dose.

Opportunities to improve the in vivo measurement of manganese in human hands

NASA Astrophysics Data System (ADS)

Aslam; Chettle, D. R.; Pejović-Milić, A.; Waker, A. J.

2009-01-01

Manganese (Mn) is an element which is both essential for regulating neurological and skeletal functions in the human body and also toxic when humans are exposed to excessive levels. Its excessive inhalation as a result of exposure through industrial and environmental emissions can cause neurological damage, which may manifest as memory deficit, loss of motor control and reduction in the refinement of certain body motions. A number of clinical studies demonstrate that biological monitoring of Mn exposure using body fluids, particularly blood, plasma/serum and urine is of very limited use and reflect only the most recent exposure and rapidly return to within normal ranges. In this context, a non-invasive neutron activation technique has been developed at the McMaster University accelerator laboratory that could provide an alternative to measure manganese stored in the bones of exposed subjects. In a first pilot study we conducted recently on non-exposed human subjects to measure the ratio of Mn to Ca in hand bones, it was determined that the technique needed further development to improve the precision of the measurements. It could be achieved by improving the minimum detection limit (MDL) of the system from 2.1 µg Mn/g Ca to the reference value of 0.6 µg g-1 Ca (range: 0.16-0.78 µg Mn/g Ca) for the non-exposed population. However, the developed procedure might still be a suitable means of screening patients and people exposed to excessive amounts of Mn, who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. To improve the MDL of the technique to the expected levels of Mn in a reference population, the present study investigates further optimization of irradiation conditions, which includes the optimal selection of proton beam energy, beam current and irradiation time and the effect of upgrading the 4π detection system. The maximum local dose equivalent that could be given to the hand as a result of irradiation was constrained to be less than 150 mSv as opposed to the previously imposed dose equivalent limit of 20 mSv. A maximum beam current, which could be delivered on the lithium target to produce neutrons, was restricted to 500 µA. The length of irradiation intervals larger than 10 min, was considered inconvenient and impractical to implement with Mn measurements in humans. To fulfil the requirements for developing a protocol for in vivo bone Mn measurements, a revised estimate of the dose equivalent has been presented here. Beam energy of 1.98 MeV was determined to be optimal to complete the irradiation procedure within 10 min using 500 µA beam current. The local dose equivalent given to hand was estimated as 118 mSv, which is lower by a factor of 1.5 compared to that of 2.00 MeV. The optimized beam parameters are expected to improve the currently obtained detection limit of 2.1 µg Mn/g Ca to 0.6 µg Mn/g Ca. Using this dose equivalent delivered to the central location of the hand, the average dose equivalent to the hand of 74 mSv and an effective dose of approximately 70 µSv will be accompanying the non-invasive, in vivo measurements of bone Mn, which is little over the chest radiograph examination dose.

Determination of the occurrence of gold in an unoxidized Carlin-type ore sample using synchrotron radiation

USGS Publications Warehouse

Chen, J.R.; Chao, E.C.T.; Minkin, J.A.; Back, J.M.; Bagby, W.C.; Rivers, M.L.; Sutton, S.R.; Gordon, B.M.; Hanson, A.L.; Jones, K.W.

1987-01-01

The occurrence of the so-called invisible gold in two unoxidized Carlin-type gold samples from Nevada has been determined using synchrotron X-ray fluorescence (SXRF) analysis at the National Synchrotron Light Source, Brookhaven National Laboratory. A bedded sample from the East ore zone of the Carlin deposit and a breccia sample from Horse Canyon were analyzed. Preliminary results show that gold is found only in the Horse Canyon breccia sample. Experimental details including other X-ray line and diffraction peak interferences, standards used, and minimum detection limits (MDLs) are discussed. Gold, with a MDL range of 0.8 to 3 ppm, was not detected in euhedral pyrite crystals except in the interior porous portion of one grain. Gold was detected in some parts of the matrix. The phase which contains gold has not yet been identified. The highest content of gold so far analyzed is about 40 ppm. There are interesting implications of these new findings. ?? 1987.

Comparison of ion chromatographic methods based on conductivity detection, post-column-reaction and on-line-coupling IC-ICP-MS for the determination of bromate.

PubMed

Schminke, G; Seubert, A

2000-02-01

An established method for the determination of the disinfection by-product bromate is ion chromatography (IC). This paper presents a comparison of three IC methods based on either conductivity detection (IC-CD), a post-column-reaction (IC-PCR-VIS) or the on-line-coupling with inductively coupled plasma mass spectrometry (IC-ICP-MS). Main characteristics of the methods such as method detection limits (MDL), time of analysis and sample pretreatment are compared and applicability for routine analysis is critically discussed. The most sensitive and rugged method is IC-ICP-MS, followed by IC-PCR-VIS. The photometric detection is subject to a minor interference in real world samples, presumably caused by carbonate. The lowest sensitivity is shown by the IC-CD method as slowest method compared, which, in addition, requires a sample pretreatment. The highest amount of information is delivered by IC-PCR-VIS, which allows the simultaneous determination of the seven standard anions and bromate.

OCT for industrial applications

NASA Astrophysics Data System (ADS)

Song, Guiju; Harding, Kevin

2012-11-01

Optical coherence tomography (OCT), as an interferometric method, has been studied as a distance ranger. As a technology capable of producing high-resolution, depth-resolved images of biological tissue, OCT had been widely used for the application of ophthalmology and has been commercialized in the market today. Enlightened by the emerging research interest in biomedical domain, the applications of OCT in industrial inspection were rejuvenated by a few groups to explore its potential for characterizing new materials, imaging or inspecting industrial parts as a service solution[3]. Benefiting from novel photonics components and devices, the industrial application of the older concepts in OCT can be re-visited with respect to the unique performance and availability. Commercial OCT developers such as Michelson Diagnostics (MDL; Orpington, U.K.) and Thorlabs (Newton, NJ) are actively exploring the application of OCT to industrial applications and they have outlined meaningful path toward the metrology application in emerging industry[3]. In this chapter, we will introduce the fundamental concepts of OCT and discuss its current and potential industrial applications.

Verification of spectrophotometric method for nitrate analysis in water samples

NASA Astrophysics Data System (ADS)

Kurniawati, Puji; Gusrianti, Reny; Dwisiwi, Bledug Bernanti; Purbaningtias, Tri Esti; Wiyantoko, Bayu

2017-12-01

The aim of this research was to verify the spectrophotometric method to analyze nitrate in water samples using APHA 2012 Section 4500 NO3-B method. The verification parameters used were: linearity, method detection limit, level of quantitation, level of linearity, accuracy and precision. Linearity was obtained by using 0 to 50 mg/L nitrate standard solution and the correlation coefficient of standard calibration linear regression equation was 0.9981. The method detection limit (MDL) was defined as 0,1294 mg/L and limit of quantitation (LOQ) was 0,4117 mg/L. The result of a level of linearity (LOL) was 50 mg/L and nitrate concentration 10 to 50 mg/L was linear with a level of confidence was 99%. The accuracy was determined through recovery value was 109.1907%. The precision value was observed using % relative standard deviation (%RSD) from repeatability and its result was 1.0886%. The tested performance criteria showed that the methodology was verified under the laboratory conditions.

In vivo measurement of bone aluminum in population living in southern Ontario, Canada

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

Davis, K.; Aslam,; Pejovic-Milic, A.

The harmful biological effect of excessive aluminum (Al) load in humans has been well documented in the literature. Al stored in bone, for instance due to dialysis treatment or occupational exposure, can interfere with normal bone remodeling leading to osteodystrophy, osteoarthritis, or osteomalacia. On the other hand, the relationship between chronic Al exposure and the risk of Alzheimer's disease remains controversial. In this work, the feasibility of in vivo neutron activation analysis (IVNAA) for measuring Al levels in the human hand bone, using the thermal neutron capture reaction {sup 27}Al(n,{gamma}){sup 28}Al, is reported. This noninvasive diagnostic technique employs a highmore » beam current Tandetron accelerator based neutron source, an irradiation/shielding cavity, a 4{pi} NaI(Tl) detector system, and a new set of hand bone phantoms. The photon spectra of the irradiated phantom closely resemble those collected from the hands of nonexposed healthy subjects. A protocol was developed using the newly developed hand phantoms, which resulted in a minimum detectable limit (MDL) of 0.29 mg Al in the human hand. Using the ratio of Al to Ca as an index of Al levels per unit bone mass, the MDL was determined as 19.5{+-}1.5 {mu}g Al/g Ca, which is within the range of the measured levels of 20-27 {mu}g Al/g Ca[ICRP, Report of the Task Group on Reference Man, Publication 23 (Pergamon, Oxford, 1975)] found in other in vivo and in vitro studies. Following the feasibility studies conducted with phantoms, the diagnostic technique was used to measure Al levels in the hand bones of 20 healthy human subjects. The mean hand bone Al concentration was determined as 27.1{+-}16.1 ({+-}1 SD) {mu}g Al/g Ca. The average standard error (1{sigma}) in the Al/Ca is 14.0 {mu}g Al/g Ca, which corresponds to an average relative error of 50% in the measured levels of Al/Ca. These results were achieved with a dose equivalent of 17.6 mSv to a hand and an effective dose of 14.4 {mu}Sv. This effective dose is approximately half of that received in a chest radiograph examination. It is recommended to investigate the use of the bone Al IVNAA diagnostic technique for in vivo measurements of patients with documented overload of Al in bone.« less

[Low-molecular-weight regulators of biogenic polyamine metabolism affect cytokine production and expression of hepatitis С virus proteins in Huh7.5 human hepatocarcinoma cells].

PubMed

Masalova, O V; Lesnova, E I; Samokhvalov, E I; Permyakova, K Yu; Ivanov, A V; Kochetkov, S N; Kushch, A A

2017-01-01

Hepatitis C virus (HCV) induces the expression of the genes of proinflammatory cytokines, the excessive production of which may cause cell death, and contribute to development of liver fibrosis and hepatocarcinoma. The relationship between cytokine production and metabolic disorders in HCV-infected cells remains obscure. The levels of biogenic polyamines, spermine, spermidine, and their precursor putrescine, may be a potential regulator of these processes. The purpose of the present work was to study the effects of the compounds which modulate biogenic polyamines metabolism on cytokine production and HCV proteins expression. Human hepatocarcinoma Huh7.5 cells have been transfected with the plasmids that encode HCV proteins and further incubated with the following low-molecular compounds that affect different stages of polyamine metabolism: (1) difluoromethylornithine (DFMO), the inhibitor of ornithine decarboxylase, the enzyme that catalyzes the biosynthesis of polyamines; (2) N,N'-bis(2,3-butane dienyl)-1,4-diaminobutane (MDL72.527), the inhibitor of proteins involved in polyamine degradation; and (3) synthetic polyamine analog N^(I),N^(II)-diethylnorspermine (DENSpm), an inducer of polyamine degradation enzyme. The intracellular accumulation and secretion of cytokines (IL-6, IL-1β, TNF-α, and TGF-β) was assessed by immunocytochemistry and in the immunoenzyme assay, while the cytokine gene expression was studied using reverse transcription and PCR. The effects of the compounds under analysis on the expression of HCV proteins were analyzed using the indirect immunofluorescence with anti-HCV monoclonal antibodies. It has been demonstrated that, in cells transfected with HCV genes, DFMO reduces the production of three out of four tested cytokines, namely, TNF-α and TGF-β in cells that express HCV core, Е1Е2, NS3, NS5A, and NS5B proteins, and IL-1β in the cells that express HCV core, Е1Е2, and NS3 proteins. MDL72527 and DENSpm decreased cytokine production to a lesser extent. Incubation with DFMO led to a 28-32% decrease in the number of cells expressing NS5B or NS5A, both of which are key components of the HCV replication complex. The results obtained in the work indicate that a further detailed study of the antiviral activity of DFMO is required in order to assess its potential as an anti-hepatitis C therapeutic agent.

Phyllosilicate analysis capabilities of the CheMin mineralogical instrument on the Mars Science Laboratory (MSL '11) Curiosity Rover

NASA Astrophysics Data System (ADS)

Blake, D. F.; Bish, D. L.; Vaniman, D. T.; Chipera, S.; Bristow, T. F.; Sarrazin, P.

2011-12-01

The CheMin mineralogical instrument on the MSL '11 Curiosity rover will return quantitative X-ray diffraction data (XRD) from scooped soil samples and drilled rock powders collected from the Mars surface. Samples of 45-65 mm3 from material sieved to <150 μm will be delivered through a funnel to one of 27 reuseable sample cells (five additional cells on the sample wheel contain diffraction or fluorescence standards). Sample cells are 8-mm diameter discs with 7-μm thick Mylar or Kapton windows spaced 170 μm apart. Within this volume, the sample is shaken by piezoelectric vibration at sonic frequencies, causing the powder to flow past a narrow, collimated X-ray beam in random orientations over the course of an analysis. In this way, diffraction patterns exhibiting little to no preferred orientation can be obtained even from minerals normally exhibiting strong preferred orientation such as phyllosilicates. Individual analyses will require several hours over one or more Mars sols. For typical well-ordered minerals, CheMin has a Minimum Detection Limit (MDL) of <3% by mass, an accuracy of better than 15% and a precision of better than 10% for phases present in concentrations >4X MDL (12%). The resolution of the diffraction patterns is 0.30 degrees 2θ, and the angular measurement range is 4-55 degrees 2θ. With this performance, CheMin can identify and distinguish a number of clay minerals. For example, discrimination between 1:1 phyllosilicates (such as the kaolin minerals), with repeat distances of ~7Å, and smectites (e.g., montmorillonite, nontronite, saponite), with repeat distances from 10-15Å, is straightforward. However, it is important to note that the variety of treatments used in terrestrial laboratories to aid in discrimination of clay minerals will not be accessible on Mars (e.g., saturation with ethylene glycol vapor, heat treatments). Although these treatments will not be available on Mars, dehydration within the CheMin instrument could be used to advantage in discriminating between phyllosilicate minerals that exhibit different dehydration behavior, such as chlorite vs. smectite. In addition, it should be possible to identify the hydrated kaolin mineral, halloysite. The lowest-angle diffraction peak from 10.1Å hydrated halloysite occurs at ~10.2 degrees 2θ with Co radiation and is easily detectable; the mineral may readily dehydrate to ~7Å, making its identification possible based on this transition. Examples will be shown of clay mineral analysis using CheMin IV, a prototype of the CheMin flight instrument.

A basin on an unstable ground: Correlation of the Middle Archaean Moodies Basin, Barberton Greenstone Belt, South Africa

NASA Astrophysics Data System (ADS)

Ohnemueller, Frank; Heubeck, Christoph; Kirstein, Jens; Gamper, Antonia

2010-05-01

The 3.22 Ga-old Moodies Group, representing the uppermost part of the Barberton Supergroup of the Barberton Greenstone Belt (BGB), is the oldest well-exposed, relatively unmetamorphosed, quartz-rich sedimentary unit on Earth. Moodies facies (north of the Inyoka Fault) were thought to be largely of alluvial, fluvial, deltaic or shallow-marine origin (Anhaeusser, 1976; Eriksson, 1980; Heubeck and Lowe, 1994) and in its upper part syndeformational. However, units can only locally be correlated, and the understanding of the interplay between Moodies sedimentation and deformation is thus limited. We mapped and measured Moodies units in the northern BGB. They partly consist of extensive turbiditic deepwater deposits, including graded bedding, flame structures, and slumped beds, interbedded with jaspilites. These contrast with shallow-water environments, south-facing progressive unconformities and overlying alluvial-fan conglomerates along the northern margin of the Saddleback Syncline further south. The palaeogeographic setting in which late BGB deformation was initiated therefore appears complex and cannot be readily explained by a simple southward-directed shortening event. In order to constrain Moodies basin setting before and during late-Moodies basin collapse, we correlated ~15 measured sections in the northern and central BGB. Most units below the Moodies Lava (MdL, ca. 3230.6+-6 Ma) can be correlated throughout although facies variations are apparent. Above the Moodies Lava, coarse-grained units can only be correlated through the Eureka Syncline and the Moodies Hills Block but not with the Saddleback Syncline. Fine-grained and jaspilitic units can be correlated throughout the northern BGB. Moodies below-wavebase deposition occurred largely north of the Saddleback Fault. The observations are consistent with a pronounced basin compartmentalization event following the eruption of the MdL which appeared to have blanketed most of the Moodies basin(s) in middle Moodies time and immediately predates the initiation of basin shortening. Basin compartmentalization was likely due to the movement along a group of major faults (Sheba, Haki, Barbrook, Saddleback Faults) between the present Saddleback and Eureka Synclines, creating at least two subbasins in late Moodies time. Even though sediment provenance thus became localized, intensive Archaean weathering likely contributed to generate petrographically similar quartz-rich sandstones in fault-bounded minibasins. The late-Moodies minibasins may have become connected occasionally, allowing concurrent deposition of thin BIFs. A similar phase of movement along the major transcurrent Inyoka Fault may be responsible for the distinct petrographic character of Moodies sandstones south of that fault.

Serotonergic mechanism of the relieving effect of bee venom acupuncture on oxaliplatin-induced neuropathic cold allodynia in rats.

PubMed

Lee, Ji-Hye; Li, Dong Xing; Yoon, Heera; Go, Donghyun; Quan, Fu Shi; Min, Byung-Il; Kim, Sun Kwang

2014-12-06

Oxaliplatin, an important chemotherapy drug for advanced colorectal cancer, often induces peripheral neuropathy, especially cold allodynia. Our previous study showed that bee venom acupuncture (BVA), which has been traditionally used in Korea to treat various pain symptoms, potently relieves oxaliplatin-induced cold allodynia in rats. However, the mechanism for this anti-allodynic effect of BVA remains poorly understood. We investigated whether and how the central serotonergic system, a well-known pathway for acupuncture analgesia, mediates the relieving effect of BVA on cold allodynia in oxaliplatin-injected rats. The behavioral signs of cold allodynia in Sprague-Dawley (SD) rats were induced by a single injection of oxaliplatin (6 mg/kg, i.p.). Before and after BVA treatment, the cold allodynia signs were evaluated by immersing the rat's tail into cold water (4°C) and measuring the withdrawal latency. For BVA treatment, a diluted BV (0.25 mg/kg) was subcutaneously administered into Yaoyangguan (GV3) acupoint, which is located between the spinous processes of the fourth and the fifth lumbar vertebra. Serotonin was depleted by a daily injection of DL-p-chlorophenylalanine (PCPA, 150 mg/kg, i.p.) for 3 days. The amount of serotonin in the spinal cord was measured by ELISA. Serotonergic receptor antagonists were administered intraperitoneally or intrathecally before BVA treatment. The serotonin levels in the spinal cord were significantly increased by BVA treatment and such increase was significantly reduced by PCPA. This PCPA pretreatment abolished the relieving effect of BVA on oxaliplatin-induced cold allodynia. Either of methysergide (mixed 5-HT1/5-HT2 receptor antagonist, 1 mg/kg, i.p.) or MDL-72222 (5-HT3 receptor antagonist, 1 mg/kg, i.p) blocked the anti-allodynic effect of BVA. Further, an intrathecal injection of MDL-72222 (12 μg) completely blocked the BVA-induced anti-allodynic action, whereas NAN-190 (5-HT1A receptor antagonist, 15 μg, i.t.) or ketanserin (5-HT2A receptor antagonist, 30 μg, i.t.) did not. These results suggest that BVA treatment alleviates oxaliplatin-induced acute cold allodynia in rats via activation of the serotonergic system, especially spinal 5-HT3 receptors. Thus, our findings may provide a clinically useful evidence for the application of BVA as an alternative therapeutic option for the management of peripheral neuropathy, a dose-limiting side effect that occurs after an administration of oxaliplatin.

A Comparison of Aerosol Optical Property Measurements Made During the DOE Aerosol Intensive Operating Period and Their Effects on Regional Climate

NASA Technical Reports Server (NTRS)

Strawa, Anthony W.; Hallar, A. G.; Arnott, W. P.; Covert, D.; Elleman, R.; Ogren, J.; Schmid, B.; Luu, A.

2004-01-01

The amount of radiant energy an aerosol absorbs has profound effects on climate and air quality. It is ironic that aerosol absorption coefficient is one of the most difficult to measure aerosol properties. One of the main purposes of the DOE Aerosol Intensive Operating Period (IOP) flown in May, 2003 was to assess our ability to measure absorption coefficient in situ. This paper compares measurements of aerosol optical properties made during the IOP. Measurements of aerosol absorption coefficient were made by Particle Soot Absorption Photometer (PSAP) aboard the CIRPAS Twin-Otter (U. Washington) and on the DOE Cessna 172 (NOAA-C,MDL). Aerosol absorption coefficient was also measured by a photoacoustic instrument (DRI) that was operated on an aircraft for the first time during the IOP. A new cavity ring-down (CRD) instrument, called Cadenza (NASA-AkC), measures the aerosol extinction coefficient for 675 nm and 1550 nm light, and simultaneously measures the scattering coefficient at 675 nm. Absorption coefficient is obtained from the difference of measured extinction and scattering within the instrument. Measurements of absorption coefficient from all of these instruments during appropriate periods are compared. During the IOP, several significant aerosol layers were sampled aloft. These layers are identified in the remote (AATS-14) as well as in situ measurements. Extinction profiles measured by Cadenza are compared to those derived from the Ames Airborne Tracking Sunphotometer (AATS-14, NASA-ARC). The regional radiative impact of these layers is assessed by using the measured aerosol optical properties in a radiative transfer model.

Development of a modified QuEChERS method for the determination of veterinary antibiotics in swine manure by liquid chromatography tandem mass spectrometry.

PubMed

Guo, Chunna; Wang, Mingru; Xiao, Hui; Huai, Binbin; Wang, Feng; Pan, Guangfang; Liao, Xiaoping; Liu, Yahong

2016-08-01

A QuEChERS (quick, easy, cheap, effective, rugged and safe) based methodology was developed for the rapid, simultaneous quantification and identification of 26 veterinary drugs in swine manure by liquid chromatography tandem mass spectrometry. The selected antibiotics included tetracyclines, sulfonamides, macrolides, fluoroquinolones, lincosamides and pleuromutilins. This is the first study to determine pleuromutilin levels in manure. The QuEChERS process involved two simple steps. First, sample extraction with methanol: acetonitrile: 0.1M EDTA-McIlvaine buffer followed by phase separation with MgSO4: NaCl addition. The supernatant was then extracted and cleaned by dispersive solid-phase extraction using a primary-secondary amine (PSA) and octadecylsilane (C18) support. The proposed method provides a linearity in the range of 1-500ngmL-1 and linear regression coefficients (r) were greater than 0.996. MDL and MQL ranged between 0.01-1.86μgkg(-1) and 0.05-5.91μgkg(-1), respectively. Recoveries ranged from 61.39 to 105.65% with the exception of sulfaquinoxaline (55.7-56.8%) and valnemulin (33.7-37.7%). This method resulted in good precision (repeatability and reproducibility) and relative standard deviations less than 17% within the same day, and lower than 20% between days. The method was then applied to study the swine manure samples collected from Guangdong, China. Chlortetracycline, tetracycline, doxycycline, sulfadimidine and tilmicosin were detected in all samples indicating high residuals in manure. In fact tilmicosin was detected at 14400μgkg(-1) suggesting that prudent treatment of manure should be conducted to prevent environmental contamination. In conclusion, this workflow can provide a simpler and more cost-effective alternative to conventional methods and is compatible with processing large sample numbers over a short time period. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a multi-residue analytical methodology based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for screening and trace level determination of pharmaceuticals in surface and wastewaters.

PubMed

Gros, Meritxell; Petrović, Mira; Barceló, Damiá

2006-11-15

This paper describes development, optimization and validation of a method for the simultaneous determination of 29 multi-class pharmaceuticals using off line solid phase extraction (SPE) followed by liquid chromatography-triple quadrupole mass spectrometry (LC-MS-MS). Target compounds include analgesics and non-steroidal anti-inflammatories (NSAIDs), lipid regulators, psychiatric drugs, anti-histaminics, anti-ulcer agent, antibiotics and beta-blockers. Recoveries obtained were generally higher than 60% for both surface and wastewaters, with exception of several compounds that yielded lower, but still acceptable recoveries: ranitidine (50%), sotalol (50%), famotidine (50%) and mevastatin (34%). The overall variability of the method was below 15%, for all compounds and all tested matrices. Method detection limits (MDL) varied between 1 and 30ng/L and from 3 to 160ng/L for surface and wastewaters, respectively. The precision of the method, calculated as relative standard deviation (R.S.D.), ranged from 0.2 to 6% and from 1 to 11% for inter and intra-day analysis, respectively. A detailed study of matrix effects was performed in order to evaluate the suitability of different calibration approaches (matrix-matched external calibration, internal calibration, extract dilution) to reduce analyte suppression or enhancement during instrumental analysis. The main advantages and drawbacks of each approach are demonstrated, justifying the selection of internal standard calibration as the most suitable approach for our study. The developed analytical method was successfully applied to the analysis of pharmaceutical residues in WWTP influents and effluents, as well as in river water. For both, river and wastewaters, the most ubiquitous compounds belonged to the group of anti-inflammatories and analgesics, antibiotics, the lipid regulators being acetaminophen, trimethoprim, ibuprofen, ketoprofen, atenolol, propranolol, mevastatin, carbamazepine and ranitidine the most frequently detected compounds.

Fe3O4@p-Naphtholbenzein as a novel nano-sorbent for highly effective removal and recovery of Berberine: Response surface methodology for optimization of ultrasound assisted dispersive magnetic solid phase extraction.

PubMed

Aghaie, Ali B G; Hadjmohammadi, Mohammad Reza

2016-08-15

A hydrophobic surface modified iron oxide magnetic nano-sorbent was successfully synthesized, characterized and utilized for highly effective removal and recovery of Berberine (Brb) by Ultrasound Assisted Dispersive Magnetic Solid Phase Extraction (UADM-SPE). Fabrication of p-Naphtholbenzein-coated magnetic nanoparticles (PNB-MNPs) was certified by characteristic analyses such as: Fourier transform infrared spectroscopy (FT-IR), X-ray Diffraction (XRD), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The characterized PNB-MNPs were utilized to develop a UADM-SPE method for Brb, a well-known isoquinoline alkaloid with a highlighted chemical skeleton for designing selective and powerful bioactive molecules. Affecting parameters on the extraction of Brb were optimized through an orthogonal rotatable central composite design (CCD). The optimum condition is obtained when the variables are set to: pH=4, amount of MNPs=20mg, sample volume=30ml, sonication time=1min at room temperature, and desorbing solvent=500µL of methanol. Under the mentioned condition, an extraction recovery of 98.2%, with relative standard deviation of 3.7%, was obtained via five replicated measurements on a 0.1mgL(-1) Brb standard solution. Finally, the method was successfully applied for determination of Brb in human plasma and urine samples. Regarding the method calibration graphs in plasma and urine matrices, spiked in the range of 0.01-200.00µgL(-1), pre-concentration factors of 134 and 122, method detection limit (MDL) of 0.17 and 0.19µgL(-1), and lower limit of quantification of 0.57 and 0.63µgL(-1) were obtained for plasma and urine samples, respectively. The method exhibits good potentials to be a fast, efficient and reliable method for determination of Brb in human biological samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals

PubMed Central

Nakamura, Shuhei; Karalay, Özlem; Jäger, Philipp S.; Horikawa, Makoto; Klein, Corinna; Nakamura, Kayo; Latza, Christian; Templer, Sven E.; Dieterich, Christoph; Antebi, Adam

2016-01-01

Germline removal provokes longevity in several species and shifts resources towards survival and repair. Several Caenorhabditis elegans transcription factors regulate longevity arising from germline removal; yet, how they work together is unknown. Here we identify a Myc-like HLH transcription factor network comprised of Mondo/Max-like complex (MML-1/MXL-2) to be required for longevity induced by germline removal, as well as by reduced TOR, insulin/IGF signalling and mitochondrial function. Germline removal increases MML-1 nuclear accumulation and activity. Surprisingly, MML-1 regulates nuclear localization and activity of HLH-30/TFEB, a convergent regulator of autophagy, lysosome biogenesis and longevity, by downregulating TOR signalling via LARS-1/leucyl-transfer RNA synthase. HLH-30 also upregulates MML-1 upon germline removal. Mammalian MondoA/B and TFEB show similar mutual regulation. MML-1/MXL-2 and HLH-30 transcriptomes show both shared and preferential outputs including MDL-1/MAD-like HLH factor required for longevity. These studies reveal how an extensive interdependent HLH transcription factor network distributes responsibility and mutually enforces states geared towards reproduction or survival. PMID:27001890

Automation of sample processing for ICP-MS determination of 90Sr radionuclide at ppq level for nuclear technology and environmental purposes.

PubMed

Kołacińska, Kamila; Chajduk, Ewelina; Dudek, Jakub; Samczyński, Zbigniew; Łokas, Edyta; Bojanowska-Czajka, Anna; Trojanowicz, Marek

2017-07-01

90 Sr is a widely determined radionuclide for environmental purposes, nuclear waste control, and can be also monitored in coolants in nuclear reactor plants. In the developed method, the ICP-MS detection was employed together with sample processing in sequential injection analysis (SIA) setup, equipped with a lab-on-valve with mechanized renewal of sorbent bed for solid-phase extraction. The optimized conditions of determination included preconcentration of 90 Sr on cation-exchange column and removal of different type of interferences using extraction Sr-resin. The limit of detection of the developed procedure depends essentially on the configuration of the employed ICP-MS spectrometer and on the available volume of the sample to be analyzed. For 1L initial sample volume, the method detection limit (MDL) value was evaluated as 2.9ppq (14.5BqL -1 ). The developed method was applied to analyze spiked river water samples, water reference materials, and also simulated and real samples of the nuclear reactor coolant. Copyright © 2016 Elsevier B.V. All rights reserved.

Motion tracking to enable pre-surgical margin mapping in basal cell carcinoma using optical imaging modalities: initial feasibility study using optical coherence tomography

NASA Astrophysics Data System (ADS)

Duffy, M.; Richardson, T. J.; Craythorne, E.; Mallipeddi, R.; Coleman, A. J.

2014-02-01

A system has been developed to assess the feasibility of using motion tracking to enable pre-surgical margin mapping of basal cell carcinoma (BCC) in the clinic using optical coherence tomography (OCT). This system consists of a commercial OCT imaging system (the VivoSight 1500, MDL Ltd., Orpington, UK), which has been adapted to incorporate a webcam and a single-sensor electromagnetic positional tracking module (the Flock of Birds, Ascension Technology Corp, Vermont, USA). A supporting software interface has also been developed which allows positional data to be captured and projected onto a 2D dermoscopic image in real-time. Initial results using a stationary test phantom are encouraging, with maximum errors in the projected map in the order of 1-2mm. Initial clinical results were poor due to motion artefact, despite attempts to stabilise the patient. However, the authors present several suggested modifications that are expected to reduce the effects of motion artefact and improve the overall accuracy and clinical usability of the system.

SuperNatural: a searchable database of available natural compounds

PubMed Central

Dunkel, Mathias; Fullbeck, Melanie; Neumann, Stefanie; Preissner, Robert

2006-01-01

Although tremendous effort has been put into synthetic libraries, most drugs on the market are still natural compounds or derivatives thereof. There are encyclopaedias of natural compounds, but the availability of these compounds is often unclear and catalogues from numerous suppliers have to be checked. To overcome these problems we have compiled a database of ∼50 000 natural compounds from different suppliers. To enable efficient identification of the desired compounds, we have implemented substructure searches with typical templates. Starting points for in silico screenings are about 2500 well-known and classified natural compounds from a compendium that we have added. Possible medical applications can be ascertained via automatic searches for similar drugs in a free conformational drug database containing WHO indications. Furthermore, we have computed about three million conformers, which are deployed to account for the flexibilities of the compounds when the 3D superposition algorithm that we have developed is used. The SuperNatural Database is publicly available at . Viewing requires the free Chime-plugin from MDL (Chime) or Java2 Runtime Environment (MView), which is also necessary for using Marvin application for chemical drawing. PMID:16381957

Role of the serotonin 5-HT(2A) receptor in learning.

PubMed

Harvey, John A

2003-01-01

This study reviews the role of the serotonin 5-HT2A receptor in learning as measured by the acquisition of the rabbit's classically conditioning nictitating membrane response, a component of the eyeblink response. Agonists at the 5-HT2A receptor including LSD (d-lysergic acid diethylamide) enhanced associative learning at doses that produce cognitive effects in humans. Some antagonists such as BOL (d-bromolysergic acid diethylamide), LY53,857, and ketanserin acted as neutral antagonists in that they had no effect on learning, whereas others (MDL11,939, ritanserin, and mianserin) acted as inverse agonists in that they retarded learning through an action at the 5-HT2A receptor. These results were placed in the context of what is known concerning the anatomical distribution and electrophysiological effects of 5-HT2A receptor activation in frontal cortex and hippocampus, as well as the role of cortical 5-HT2A receptors in schizophrenia. It was concluded that the 5-HT2A receptor demonstrates constitutive activity, and that variations in this activity can produce profound alterations in cognitive states.

Gravimetric Analysis of Particulate Matter using Air Samplers Housing Internal Filtration Capsules.

PubMed

O'Connor, Sean; O'Connor, Paula Fey; Feng, H Amy; Ashley, Kevin

2014-10-01

An evaluation was carried out to investigate the suitability of polyvinyl chloride (PVC) internal capsules, housed within air sampling devices, for gravimetric analysis of airborne particles collected in workplaces. Experiments were carried out using blank PVC capsules and PVC capsules spiked with 0,1 - 4 mg of National Institute of Standards and Technology Standard Reference Material ® (NIST SRM) 1648 (Urban Particulate Matter) and Arizona Road Dust (Air Cleaner Test Dust). The capsules were housed within plastic closed-face cassette samplers (CFCs). A method detection limit (MDL) of 0,075 mg per sample was estimated. Precision S r at 0,5 - 4 mg per sample was 0,031 and the estimated bias was 0,058. Weight stability over 28 days was verified for both blanks and spiked capsules. Independent laboratory testing on blanks and field samples verified long-term weight stability as well as sampling and analysis precision and bias estimates. An overall precision estimate Ŝ rt of 0,059 was obtained. An accuracy measure of ±15,5% was found for the gravimetric method using PVC internal capsules.

Gravimetric Analysis of Particulate Matter using Air Samplers Housing Internal Filtration Capsules

PubMed Central

O'Connor, Sean; O'Connor, Paula Fey; Feng, H. Amy

2015-01-01

Summary An evaluation was carried out to investigate the suitability of polyvinyl chloride (PVC) internal capsules, housed within air sampling devices, for gravimetric analysis of airborne particles collected in workplaces. Experiments were carried out using blank PVC capsules and PVC capsules spiked with 0,1 – 4 mg of National Institute of Standards and Technology Standard Reference Material® (NIST SRM) 1648 (Urban Particulate Matter) and Arizona Road Dust (Air Cleaner Test Dust). The capsules were housed within plastic closed-face cassette samplers (CFCs). A method detection limit (MDL) of 0,075 mg per sample was estimated. Precision Sr at 0,5 - 4 mg per sample was 0,031 and the estimated bias was 0,058. Weight stability over 28 days was verified for both blanks and spiked capsules. Independent laboratory testing on blanks and field samples verified long-term weight stability as well as sampling and analysis precision and bias estimates. An overall precision estimate Ŝrt of 0,059 was obtained. An accuracy measure of ±15,5% was found for the gravimetric method using PVC internal capsules. PMID:26435581

[Determination of short-chain chlorinated paraffins in ambient air using high-volume sampling combined with high resolutimi gas chromatography-electron capture negative ion-low resolution mass spectrometry].

PubMed

Shi, Loimeng; Gao, Yuan; Hou, Xiaohong; Zhang, Haijun; Zhang, Yichi; Chen, Jiping

2016-02-01

An analytical method for quantifying short-chain chlorinated paraffins (SCCPs) in ambient air using high-volume sampling combined with high resolution gas chromatography-electron capture negative ion-low resolution mass spectrometry ( HRGC-ECNI-LRMS) was developed. An acidified silica gel column and a basic alumina column were used to optimize the cleanup procedures. The results showed a good linearity (R2>0. 99) between the total response factors and the degree of chlorination of SCCPs in the content range of 58. 1%-63. 3%. The limits of detection (S/N ≥3) and the limits of quantification (S/N ≥ 10) were 4. 2 and 12 µg, respectively. The method detection limit (MDL) for SCCPs was 0. 34 ng/m3 (n = 7). The recoveries of SCCPs in air samples were in the range of 81. 9% to 94. 2%. It is demonstrated that the method is suitable for the quantitative analysis of SCCPs in air samples.

[Mutual Effect on Determination of Gibberellins and Glyphosate in Groundwater by Spectrophotometry].

PubMed

Zhang, Li; Chen, Liang; Liu, Fei

2015-04-01

In the present study, a spectrophotometry method for the simultaneous determination of gibberellins (GA3) and glyphosate in groundwater was established and optimized. In addition, the mutual effect on simultaneous determination of GA3 and glyphosate was studied. Based on the experiment, good linearity (R2 > 0.99) was obtained for GA3 in the range of 0-20 and 0-100 µg and for glyphosate in the range of 0-8 and 5-15 µg. The method's detection limit (MDL) of GA3 and glyphosate was 0.48 and 0.82 µg, respectively; and the recovery rates of 15 to 150 µg GA3 and 3 to 10 µg glyphosate in all samples at a spiked level were 71.3% ± 1.9% and 98.4% ± 8.1%, respectively. No obvious influence of glyphosate (0-100 mg · L(-1)) on the recovery rates of GA3 was observed, but the presence of glyphosate could cause slight determination precision decrease of GA3. Meanwhile, adding 2 mg · L(-1) GA3 can increase the recovery rate of glyphosate.

The Orphan G Protein-coupled Receptor GPR17 Negatively Regulates Oligodendrocyte Differentiation via Gαi/o and Its Downstream Effector Molecules.

PubMed

Simon, Katharina; Hennen, Stephanie; Merten, Nicole; Blättermann, Stefanie; Gillard, Michel; Kostenis, Evi; Gomeza, Jesus

2016-01-08

Recent studies have recognized G protein-coupled receptors as important regulators of oligodendrocyte development. GPR17, in particular, is an orphan G protein-coupled receptor that has been identified as oligodendroglial maturation inhibitor because its stimulation arrests primary mouse oligodendrocytes at a less differentiated stage. However, the intracellular signaling effectors transducing its activation remain poorly understood. Here, we use Oli-neu cells, an immortalized cell line derived from primary murine oligodendrocytes, and primary rat oligodendrocyte cultures as model systems to identify molecular targets that link cell surface GPR17 to oligodendrocyte maturation blockade. We demonstrate that stimulation of GPR17 by the small molecule agonist MDL29,951 (2-carboxy-4,6-dichloro-1H-indole-3-propionic acid) decreases myelin basic protein expression levels mainly by triggering the Gαi/o signaling pathway, which in turn leads to reduced activity of the downstream cascade adenylyl cyclase-cAMP-PKA-cAMP response element-binding protein (CREB). In addition, we show that GPR17 activation also diminishes myelin basic protein abundance by lessening stimulation of the exchange protein directly activated by cAMP (EPAC), thus uncovering a previously unrecognized role for EPAC to regulate oligodendrocyte differentiation. Together, our data establish PKA and EPAC as key downstream effectors of GPR17 that inhibit oligodendrocyte maturation. We envisage that treatments augmenting PKA and/or EPAC activity represent a beneficial approach for therapeutic enhancement of remyelination in those demyelinating diseases where GPR17 is highly expressed, such as multiple sclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Distribution, bioaccumulation and trophic transfer of chlorinated polyfluoroalkyl ether sulfonic acids in the marine food web of Bohai, China.

PubMed

Chen, Hong; Han, Jianbo; Cheng, Jiayi; Sun, Ruijun; Wang, Xiaomeng; Han, Gengchen; Yang, Wenchao; He, Xin

2018-06-04

Chlorinated polyfluoroalkyl ether sulfonic acids (Cl-PFESAs) caused great concerns recently as novel fluorinated alternatives. However, information on their bioconcentration, bioaccumulation and biomagnification in marine ecosystems is limited. In this study, 152 biological samples including invertebrates, fishes, seabirds and mammals collected from Bohai Sea of China were analyzed to investigate the residual level, spatial distribution, bioaccumulation and biomagnification of Cl-PFESAs. 6:2 Cl-PFESA was found in concentrations ranging from

In Situ Resource-Based Lunar and Martian Habitat Structures Development at NASA/MSFC

NASA Technical Reports Server (NTRS)

Bodiford, Melanie P.; Fiske, Michael R.; McGregory, Walter; Pope, Regina D.

2005-01-01

As the nation prepares to return to the Moon and subsequently to Mars, it is apparent that the viability of long duration visits with appropriate radiation shielding/crew protection, hinges on the development of habitat structures, preferably in advance of a manned landing, and preferably utilizing in-situ resources. A relatively large number of habitat structure configurations can be developed from a relatively small set of in-situ resource-based construction products, including, blocks, raw regolith, reinforced concrete, and glass products. A much larger group of habitat designs can be developed when "imported" material are brought from Earth, including thin films and liners, and foldable, or expandable metal structures. These, and other technologies have been identified, and subjected to a rigorous trade study evaluation with respect to exploration and other performance criteria. In this paper, results of this trade study will be presented, as well as various habitat structure design concepts and concepts for construction automation. Results of initial tests aimed at concrete, block and glass production using Lunar regolith simulants will also be presented. Key issues and concerns will be discussed, as well as design concepts for a Lunar environment testbed to be developed at MSFC's Microgravity Development Laboratory. (MDL).

In-situ Resource-based Lunar and Martian Habitat Structures Development at NASA/MSFC

NASA Technical Reports Server (NTRS)

Bodiford, Melanie P.; Burks, Kevin H.; Fiske, Michael R.; Strong, Janet D.; McGregor, Walter

2005-01-01

As the nation prepares to return to the Moon and subsequently to Mars, it is apparent that the viability of long duration visits with appropriate radiation shielding/crew protection, hinges on the development of habitat structures, preferably in advance of a manned landing, and preferably utilizing in-situ resources. A relatively large number of habitat structure configurations can be developed from a relatively small set of in-situ resource-based construction products, including, blocks, raw regolith, reinforced concrete, and glass products. A much larger group of habitat designs can be developed when "imported" material are brought from Earth, including thin films and liners, and foldable, or expandable metal structures. These, and other technologies have been identified, and subjected to a rigorous trade study evaluation with respect to exploration and other performance criteria. In this paper, results of this trade study will be presented, as well as various habitat structure design concepts and concepts for construction automation. Results of initial tests aimed at concrete, block and glass production using Lunar regolith simulants will also be presented. Key issues and concerns will be discussed, as well as design concepts for a Lunar environment testbed to be developed at MSFC's Microgravity Development Laboratory (MDL).

On the role of adenylate cyclase, tyrosine kinase, and tyrosine phosphatase in the response of nerve and glial cells to photodynamic impact

NASA Astrophysics Data System (ADS)

Kolosov, Mikhail S.; Bragin, D. E.; Dergacheva, Olga Y.; Vanzha, O.; Oparina, L.; Uzdensky, Anatoly B.

2004-08-01

The role of different intercellular signaling pathways involving adenylate cyclase (AC), receptor tyrosine kinase (RTK), tyrosine and serine/threonine protein phosphatases (PTP or PP, respectively) in the response of crayfish mechanoreceptor neuron (MRN) and surrounding glial cells to photodynamic effect of aluminum phthalocyanine Photosens have been studied. AC inhibition by MDL-12330A decreased neuron lifetime, whereas AC activation by forskolin increase it. Thus, increase in cAMP produced by activated AC protects SRN against photodynamic inactivation. Similarly, RTK inhibition by genistein decreased neuron lifetime, while inhibition of PTP or PP that remove phosphate groups from proteins, prolonged neuronal activity. AC inhibition reduced photoinduced damage of the plasma membrane, and, therefore, necrosis in neuronal and glial cells. RTK inhibition protected only neurons against PDT-induced membrane permeabilization while glial cells became lesser permeable under ortovanadate-mediated PTP inhibition. AC activation also prevented PDT-induced apoptosis in glial cells. PP inhibition enhanced apoptotic processes in photosensitized glial cells. Therefore, both intercellular signaling pathways involving AC and TRK are involved in the maintenance of neuronal activity, integrity of the neuronal and glial plasma membranes and in apoptotic processes in glia under photosensitization.

SuperNatural: a searchable database of available natural compounds.

PubMed

Dunkel, Mathias; Fullbeck, Melanie; Neumann, Stefanie; Preissner, Robert

2006-01-01

Although tremendous effort has been put into synthetic libraries, most drugs on the market are still natural compounds or derivatives thereof. There are encyclopaedias of natural compounds, but the availability of these compounds is often unclear and catalogues from numerous suppliers have to be checked. To overcome these problems we have compiled a database of approximately 50,000 natural compounds from different suppliers. To enable efficient identification of the desired compounds, we have implemented substructure searches with typical templates. Starting points for in silico screenings are about 2500 well-known and classified natural compounds from a compendium that we have added. Possible medical applications can be ascertained via automatic searches for similar drugs in a free conformational drug database containing WHO indications. Furthermore, we have computed about three million conformers, which are deployed to account for the flexibilities of the compounds when the 3D superposition algorithm that we have developed is used. The SuperNatural Database is publicly available at http://bioinformatics.charite.de/supernatural. Viewing requires the free Chime-plugin from MDL (Chime) or Java2 Runtime Environment (MView), which is also necessary for using Marvin application for chemical drawing.

Comparison of two derivatization methods for the analysis of short chain fatty acids in the ambient aerosol using GC-MS

NASA Astrophysics Data System (ADS)

Kim, G.; Jeon, S.

2016-12-01

Fatty acids are one of the important compound classes in the polar organic fraction of ambient aerosols. Among them, short chain fatty acids play a significant role in the atmospheric transformation processes. For short-chain acids, the bottleneck of analysis has been the difficulty of sample preparation due to the high solubility and volatility. To overcome this problem, derivatization of polar organic fraction is widely used with silylation reagents to increase the resolution and sensitivity. Two different derivatization procedures; (1) using the tertbutyldimethylsilyl (TBDMS) derivatization and (2) the headspace-solid phase microextraction (HS-SPME) with in-fiber derivatization are compared using gas chromatography-mass spectrometry (GC-MS). At the second method, simultaneous derivatization and extraction were performed by a poly acrylate (PA) coated fiber doped with pyrenyldiazomethane (PDAM). We investigated the chromatographic property and relative sensitivities of each individual short chain acids according to two different derivatization procedures. For the method validation, the linearity, recovery and method detection limit (MDL) were compared. Also, two derivatization methods were applied to the ambient aerosol samples and evaluated with respect to the effectiveness.

Low level determination of (226)Ra in water using a micro-precipitate track method for large-scale environmental monitoring.

PubMed

Taheri, M; Sohrabi, M; Jaleh, B; Hosseini, T; Montazer Rahmati, M M

2009-12-01

In the present paper a method has been developed for the determination of (226)Ra in water by the detection, using a solid-state nuclear track detector (SSNTD), of alpha particles from (226)Ra in equilibrium with (222)Rn in micro-precipitates collected on a filter. The micro-precipitates were prepared from environmental water samples by collection of radium with lead as Pb/RaSO(4). Several factors affect the (226)Ra precipitation on the filter and its recovery, in particular the filter pore size. Therefore in this experiment Whatman #42 and Millipore filters with different pore sizes were used. Using a 0.45 microm Millipore filter, the recovery efficiency was increased up to 96%, and the alpha self-absorption and scattering decreased remarkably. For efficient detection of alphas from (226)Ra/(222)Rn in equilibrium, three types of SSNTD were used-polycarbonate (PC) electrochemically etched (ECE), CR-39 and LR-115 chemically etched (CE). By preparing a standard micro-precipitate on a filter with known (226)Ra/(222)Rn characteristics, the calibration response of each detector and its minimum detection limit (MDL) were determined.

A Quantum-Based Similarity Method in Virtual Screening.

PubMed

Al-Dabbagh, Mohammed Mumtaz; Salim, Naomie; Himmat, Mubarak; Ahmed, Ali; Saeed, Faisal

2015-10-02

One of the most widely-used techniques for ligand-based virtual screening is similarity searching. This study adopted the concepts of quantum mechanics to present as state-of-the-art similarity method of molecules inspired from quantum theory. The representation of molecular compounds in mathematical quantum space plays a vital role in the development of quantum-based similarity approach. One of the key concepts of quantum theory is the use of complex numbers. Hence, this study proposed three various techniques to embed and to re-represent the molecular compounds to correspond with complex numbers format. The quantum-based similarity method that developed in this study depending on complex pure Hilbert space of molecules called Standard Quantum-Based (SQB). The recall of retrieved active molecules were at top 1% and top 5%, and significant test is used to evaluate our proposed methods. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints. Simulated virtual screening experiment show that the effectiveness of SQB method was significantly increased due to the role of representational power of molecular compounds in complex numbers forms compared to Tanimoto benchmark similarity measure.

Taurine activates delayed rectifier KV channels via a metabotropic pathway in retinal neurons

PubMed Central

Bulley, Simon; Liu, Yufei; Ripps, Harris; Shen, Wen

2013-01-01

Taurine is one of the most abundant amino acids in the retina, throughout the CNS, and in heart and muscle cells. In keeping with its broad tissue distribution, taurine serves as a modulator of numerous basic processes, such as enzyme activity, cell development, myocardial function and cytoprotection. Despite this multitude of functional roles, the precise mechanism underlying taurine's actions has not yet been identified. In this study we report findings that indicate a novel role for taurine in the regulation of voltage-gated delayed rectifier potassium (KV) channels in retinal neurons by means of a metabotropic receptor pathway. The metabotropic taurine response was insensitive to the Cl− channel blockers, picrotoxin and strychnine, but it was inhibited by a specific serotonin 5-HT2A receptor antagonist, MDL11939. Moreover, we found that taurine enhanced KV channels via intracellular protein kinase C-mediated pathways. When 5-HT2A receptors were expressed in human embryonic kidney cells, taurine and AL34662, a non-specific 5-HT2 receptor activator, produced a similar regulation of KIR channels. In sum, this study provides new evidence that taurine activates a serotonin system, apparently via 5-HT2A receptors and related intracellular pathways. PMID:23045337

Cisplatin-induced apoptosis inhibits autophagy, which acts as a pro-survival mechanism in human melanoma cells.

PubMed

Del Bello, Barbara; Toscano, Marzia; Moretti, Daniele; Maellaro, Emilia

2013-01-01

The interplay between a non-lethal autophagic response and apoptotic cell death is still a matter of debate in cancer cell biology. In the present study performed on human melanoma cells, we investigate the role of basal or stimulated autophagy in cisplatin-induced cytotoxicity, as well as the contribution of cisplatin-induced activation of caspases 3/7 and conventional calpains. The results show that, while down-regulating Beclin-1, Atg14 and LC3-II, cisplatin treatment inhibits the basal autophagic response, impairing a physiological pro-survival response. Consistently, exogenously stimulated autophagy, obtained with trehalose or calpains inhibitors (MDL-28170 and calpeptin), protects from cisplatin-induced apoptosis, and such a protection is reverted by inhibiting autophagy with 3-methyladenine or ATG5 silencing. In addition, during trehalose-stimulated autophagy, the cisplatin-induced activation of calpains is abrogated, suggesting the existence of a feedback loop between the autophagic process and calpains. On the whole, our results demonstrate that in human melanoma cells autophagy may function as a beneficial stress response, hindered by cisplatin-induced death mechanisms. In a therapeutic perspective, these findings suggest that the efficacy of cisplatin-based polychemotherapies for melanoma could be potentiated by inhibitors of autophagy.

Investigation of the superconducting proximity effect (SPE) and magnetic dead layers (MDL) in thin film double layers

NASA Astrophysics Data System (ADS)

Tateishi, Go

When a thin superconducting film (S film) is condensed onto a thin normal conducting film (N film), the first layers of the S film loose their superconductivity. This phenomenon is generally called the "superconducting proximity effect (SPE)". As an investigation of SPE we focus on the transition temperature of extremely thin NS double layers in the thin regime. Normal metal is condensed on top of insulating Sb, then Pb is deposited on it in small steps. The transition temperature is plotted in an inverse Tc-reduction 1/Delta T c =1/(Ts - Tc) versus Pb thickness graph. To compare our experimental results with the theoretical prediction, a numerical calculation of the SN double layer is performed by our group using the linear gap equation. As a result, there are large discrepancies between the experimental and theoretical results generally. The results of the NS double layers can be divided into three groups in terms of their discrepancies between experiment and theory.(1) Non-coupling (Tc = 0 K): N= Mg, Ag, Cu, Au. There are large deviations between experiment and theory by a factor to the order of 2.5. (2) Weak coupling (Tc is low (< 2.5 K)) : N=Cd, Zn, Al. Deviation is present, but only by a factor of 1.5. (3) Intermediate coupling (T c is around half of Pb's (≈ 4.5 K)) : N=In, Sn. The experimental results agree with the theory. Next, we examine the detection of the magnetic dead layer (MDL) of Ni thin films in terms of the anomalous Hall effect (AHE) with several non-magnetic metal substrates. In our results, when Ni film is contact with a polyvalent metal substrate film, the sandwich film has around 2 to 3.5 at.lay. of magnetic dead layers. However we have not observed the magnetic dead Ni layers with the alkali and noble metal substrate film. Finally, we revisit the Pb/Ni system to measure the magnetic scattering of Ni with the method of Weak Localization (WL) to compare with the dephasing rate due to the Tc-reduction. In this series, we use only very thin Pb films between 1.3 and 5 at.lay. deposited on top of the Ag substrate with about 37 at.lay. thickness, because we make the Ag substrate suppress the superconductivity of the extremely thin Pb film with the SPE and avoid the Azlamazov-Larkin fluctuations. After comparison, it becomes clear that the dephasing rate from the Tc-reduction method is much larger than that measured by the weak localization (the factor is around 120). We consider not only "pair breaking" but also "pair weakening", and conclude that the reduction of the superconducting transition temperature is not due to dephasing by magnetic scattering but due to the resonance scattering of Cooper pairs by non-magnetic d-states.

Predicting ambient aerosol thermal-optical reflectance measurements from infrared spectra: elemental carbon

NASA Astrophysics Data System (ADS)

Dillner, A. M.; Takahama, S.

2015-10-01

Elemental carbon (EC) is an important constituent of atmospheric particulate matter because it absorbs solar radiation influencing climate and visibility and it adversely affects human health. The EC measured by thermal methods such as thermal-optical reflectance (TOR) is operationally defined as the carbon that volatilizes from quartz filter samples at elevated temperatures in the presence of oxygen. Here, methods are presented to accurately predict TOR EC using Fourier transform infrared (FT-IR) absorbance spectra from atmospheric particulate matter collected on polytetrafluoroethylene (PTFE or Teflon) filters. This method is similar to the procedure developed for OC in prior work (Dillner and Takahama, 2015). Transmittance FT-IR analysis is rapid, inexpensive and nondestructive to the PTFE filter samples which are routinely collected for mass and elemental analysis in monitoring networks. FT-IR absorbance spectra are obtained from 794 filter samples from seven Interagency Monitoring of PROtected Visual Environment (IMPROVE) sites collected during 2011. Partial least squares regression is used to calibrate sample FT-IR absorbance spectra to collocated TOR EC measurements. The FT-IR spectra are divided into calibration and test sets. Two calibrations are developed: one developed from uniform distribution of samples across the EC mass range (Uniform EC) and one developed from a uniform distribution of Low EC mass samples (EC < 2.4 μg, Low Uniform EC). A hybrid approach which applies the Low EC calibration to Low EC samples and the Uniform EC calibration to all other samples is used to produce predictions for Low EC samples that have mean error on par with parallel TOR EC samples in the same mass range and an estimate of the minimum detection limit (MDL) that is on par with TOR EC MDL. For all samples, this hybrid approach leads to precise and accurate TOR EC predictions by FT-IR as indicated by high coefficient of determination (R2; 0.96), no bias (0.00 μg m-3, a concentration value based on the nominal IMPROVE sample volume of 32.8 m3), low error (0.03 μg m-3) and reasonable normalized error (21 %). These performance metrics can be achieved with various degrees of spectral pretreatment (e.g., including or excluding substrate contributions to the absorbances) and are comparable in precision and accuracy to collocated TOR measurements. Only the normalized error is higher for the FT-IR EC measurements than for collocated TOR. FT-IR spectra are also divided into calibration and test sets by the ratios OC/EC and ammonium/EC to determine the impact of OC and ammonium on EC prediction. We conclude that FT-IR analysis with partial least squares regression is a robust method for accurately predicting TOR EC in IMPROVE network samples, providing complementary information to TOR OC predictions (Dillner and Takahama, 2015) and the organic functional group composition and organic matter estimated previously from the same set of sample spectra (Ruthenburg et al., 2014).

Predicting ambient aerosol Thermal Optical Reflectance (TOR) measurements from infrared spectra: elemental carbon

NASA Astrophysics Data System (ADS)

Dillner, A. M.; Takahama, S.

2015-06-01

Elemental carbon (EC) is an important constituent of atmospheric particulate matter because it absorbs solar radiation influencing climate and visibility and it adversely affects human health. The EC measured by thermal methods such as Thermal-Optical Reflectance (TOR) is operationally defined as the carbon that volatilizes from quartz filter samples at elevated temperatures in the presence of oxygen. Here, methods are presented to accurately predict TOR EC using Fourier Transform Infrared (FT-IR) absorbance spectra from atmospheric particulate matter collected on polytetrafluoroethylene (PTFE or Teflon) filters. This method is similar to the procedure tested and developed for OC in prior work (Dillner and Takahama, 2015). Transmittance FT-IR analysis is rapid, inexpensive, and non-destructive to the PTFE filter samples which are routinely collected for mass and elemental analysis in monitoring networks. FT-IR absorbance spectra are obtained from 794 filter samples from seven Interagency Monitoring of PROtected Visual Environment (IMPROVE) sites collected during 2011. Partial least squares regression is used to calibrate sample FT-IR absorbance spectra to collocated TOR EC measurements. The FTIR spectra are divided into calibration and test sets. Two calibrations are developed, one which is developed from uniform distribution of samples across the EC mass range (Uniform EC) and one developed from a~uniform distribution of low EC mass samples (EC < 2.4 μg, Low Uniform EC). A hybrid approach which applies the low EC calibration to low EC samples and the Uniform EC calibration to all other samples is used to produces predictions for low EC samples that have mean error on par with parallel TOR EC samples in the same mass range and an estimate of the minimum detection limit (MDL) that is on par with TOR EC MDL. For all samples, this hybrid approach leads to precise and accurate TOR EC predictions by FT-IR as indicated by high coefficient of variation (R2; 0.96), no bias (0.00 μg m-3, concentration value based on the nominal IMPROVE sample volume of 32.8 m-3), low error (0.03 μg m-3) and reasonable normalized error (21 %). These performance metrics can be achieved with various degrees of spectral pretreatment (e.g., including or excluding substrate contributions to the absorbances) and are comparable in precision and accuracy to collocated TOR measurements. Only the normalized error is higher for the FT-IR EC measurements than for collocated TOR. FT-IR spectra are also divided into calibration and test sets by the ratios OC/EC and ammonium/EC to determine the impact of OC and ammonium on EC prediction. We conclude that FT-IR analysis with partial least squares regression is a robust method for accurately predicting TOR EC in IMPROVE network samples; providing complementary information to TOR OC predictions (Dillner and Takahama, 2015) and the organic functional group composition and organic matter (OM) estimated previously from the same set of sample spectra (Ruthenburg et al., 2014).

Serotonin gating of cortical and thalamic glutamate inputs onto principal neurons of the basolateral amygdala.

PubMed

Guo, Ji-Dong; O'Flaherty, Brendan M; Rainnie, Donald G

2017-11-01

The basolateral amygdala (BLA) is a key site for crossmodal association of sensory stimuli and an important relay in the neural circuitry of emotion. Indeed, the BLA receives substantial glutamatergic inputs from multiple brain regions including the prefrontal cortex and thalamic nuclei. Modulation of glutamatergic transmission in the BLA regulates stress- and anxiety-related behaviors. Serotonin (5-HT) also plays an important role in regulating stress-related behavior through activation of both pre- and postsynaptic 5-HT receptors. Multiple 5-HT receptors are expressed in the BLA, where 5-HT has been reported to modulate glutamatergic transmission. However, the 5-HT receptor subtype mediating this effect is not yet clear. The aim of this study was to use patch-clamp recordings from BLA neurons in an ex vivo slice preparation to examine 1) the effect of 5-HT on extrinsic sensory inputs, and 2) to determine if any pathway specificity exists in 5-HT regulation of glutamatergic transmission. Two independent input pathways into the BLA were stimulated: the external capsule to mimic cortical input, and the internal capsule to mimic thalamic input. Bath application of 5-HT reversibly reduced the amplitude of evoked excitatory postsynaptic currents (eEPSCs) induced by stimulation of both pathways. The decrease was associated with an increase in the paired-pulse ratio and coefficient of variation of eEPSC amplitude, suggesting 5-HT acts presynaptically. Moreover, the effect of 5-HT in both pathways was mimicked by the selective 5-HT 1B receptor agonist CP93129, but not by the 5-HT 1A receptor agonist 8-OH DPAT. Similarly the effect of exogenous 5-HT was blocked by the 5-HT 1B receptor antagonist GR55562, but not affected by the 5-HT 1A receptor antagonist WAY 100635 or the 5-HT 2 receptor antagonists pirenperone and MDL 100907. Together these data suggest 5-HT gates cortical and thalamic glutamatergic inputs into the BLA by activating presynaptic 5-HT 1B receptors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.

PubMed

Newman-Tancredi, Adrian; Cussac, Didier; Quentric, Yann; Touzard, Manuelle; Verrièle, Laurence; Carpentier, Nathalie; Millan, Mark J

2002-11-01

Although certain antiparkinson agents interact with serotonin (5-HT) receptors, little information is available concerning functional actions. Herein, we characterized efficacies of apomorphine, bromocriptine, cabergoline, lisuride, piribedil, pergolide, roxindole, and terguride at human (h)5-HT(1A), h5-HT(1B), and h5-HT(1D) receptors [guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding], and at h5-HT(2A), h5-HT(2B), and h5-HT(2C) receptors (depletion of membrane-bound [(3)H]phosphatydilinositol). All drugs stimulated h5-HT(1A) receptors with efficacies (compared with 5-HT, 100%) ranging from modest (apomorphine, 35%) to high (cabergoline, 93%). At h5-HT(1B) receptors, efficacies varied from mild (terguride, 37%) to marked (cabergoline, 102%) and potencies were modest (pEC(50) values of 5.8-7.6): h5-HT(1D) sites were activated with a similar range of efficacies and greater potency (7.1-8.5). Piribedil and apomorphine were inactive at h5-HT(1B) and h5-HT(1D) receptors. At h5-HT(2A) receptors, terguride, lisuride, bromocriptine, cabergoline, and pergolide displayed potent (7.6-8.8) agonist properties (49-103%), whereas apomorphine and roxindole were antagonists and piribedil was inactive. Only pergolide (113%/8.2) and cabergoline (123%/8.6) displayed pronounced agonist properties at h5-HT(2B) receptors. At 5-HT(2C) receptors, lisuride, bromocriptine, pergolide, and cabergoline were efficacious (75-96%) agonists, apomorphine and terguride were antagonists, and piribedil was inactive. MDL100,907 and SB242,084, selective antagonists at 5-HT(2A) and 5-HT(2C) receptors, respectively, abolished these actions of pergolide, cabergoline, and bromocriptine. In conclusion, antiparkinson agents display markedly different patterns of agonist and antagonist properties at multiple 5-HT receptor subtypes. Although all show modest (agonist) activity at 5-HT(1A) sites, their contrasting actions at 5-HT(2A) and 5-HT(2C) sites may be of particular significance to their functional profiles in vivo.

Input variable selection and calibration data selection for storm water quality regression models.

PubMed

Sun, Siao; Bertrand-Krajewski, Jean-Luc

2013-01-01

Storm water quality models are useful tools in storm water management. Interest has been growing in analyzing existing data for developing models for urban storm water quality evaluations. It is important to select appropriate model inputs when many candidate explanatory variables are available. Model calibration and verification are essential steps in any storm water quality modeling. This study investigates input variable selection and calibration data selection in storm water quality regression models. The two selection problems are mutually interacted. A procedure is developed in order to fulfil the two selection tasks in order. The procedure firstly selects model input variables using a cross validation method. An appropriate number of variables are identified as model inputs to ensure that a model is neither overfitted nor underfitted. Based on the model input selection results, calibration data selection is studied. Uncertainty of model performances due to calibration data selection is investigated with a random selection method. An approach using the cluster method is applied in order to enhance model calibration practice based on the principle of selecting representative data for calibration. The comparison between results from the cluster selection method and random selection shows that the former can significantly improve performances of calibrated models. It is found that the information content in calibration data is important in addition to the size of calibration data.

Improving membrane protein expression and function using genomic edits

DOE PAGES

Jensen, Heather M.; Eng, Thomas; Chubukov, Victor; ...

2017-10-12

Expression of membrane proteins often leads to growth inhibition and perturbs central metabolism and this burden varies with the protein being overexpressed. There are also known strain backgrounds that allow greater expression of membrane proteins but that differ in efficacy across proteins. Here, we hypothesized that for any membrane protein, it may be possible to identify a modified strain background where its expression can be accommodated with less burden. To directly test this hypothesis, we used a bar-coded transposon insertion library in tandem with cell sorting to assess genome-wide impact of gene deletions on membrane protein expression. The expression ofmore » five membrane proteins (CyoB, CydB, MdlB, YidC, and LepI) and one soluble protein (GST), each fused to GFP, was examined. We identified Escherichia coli mutants that demonstrated increased membrane protein expression relative to that in wild type. For two of the proteins (CyoB and CydB), we conducted functional assays to confirm that the increase in protein expression also led to phenotypic improvement in function. This study represents a systematic approach to broadly identify genetic loci that can be used to improve membrane protein expression, and our method can be used to improve expression of any protein that poses a cellular burden.« less

ASD: a comprehensive database of allosteric proteins and modulators

PubMed Central

Huang, Zhimin; Zhu, Liang; Cao, Yan; Wu, Geng; Liu, Xinyi; Chen, Yingyi; Wang, Qi; Shi, Ting; Zhao, Yaxue; Wang, Yuefei; Li, Weihua; Li, Yixue; Chen, Haifeng; Chen, Guoqiang; Zhang, Jian

2011-01-01

Allostery is the most direct, rapid and efficient way of regulating protein function, ranging from the control of metabolic mechanisms to signal-transduction pathways. However, an enormous amount of unsystematic allostery information has deterred scientists who could benefit from this field. Here, we present the AlloSteric Database (ASD), the first online database that provides a central resource for the display, search and analysis of structure, function and related annotation for allosteric molecules. Currently, ASD contains 336 allosteric proteins from 101 species and 8095 modulators in three categories (activators, inhibitors and regulators). Proteins are annotated with a detailed description of allostery, biological process and related diseases, and modulators with binding affinity, physicochemical properties and therapeutic area. Integrating the information of allosteric proteins in ASD should allow for the identification of specific allosteric sites of a given subtype among proteins of the same family that can potentially serve as ideal targets for experimental validation. In addition, modulators curated in ASD can be used to investigate potent allosteric targets for the query compound, and also help chemists to implement structure modifications for novel allosteric drug design. Therefore, ASD could be a platform and a starting point for biologists and medicinal chemists for furthering allosteric research. ASD is freely available at http://mdl.shsmu.edu.cn/ASD/. PMID:21051350

Estimating the dose response relationship for occupational radiation exposure measured with minimum detection level.

PubMed

Xue, Xiaonan; Shore, Roy E; Ye, Xiangyang; Kim, Mimi Y

2004-10-01

Occupational exposures are often recorded as zero when the exposure is below the minimum detection level (BMDL). This can lead to an underestimation of the doses received by individuals and can lead to biased estimates of risk in occupational epidemiologic studies. The extent of the exposure underestimation is increased with the magnitude of the minimum detection level (MDL) and the frequency of monitoring. This paper uses multiple imputation methods to impute values for the missing doses due to BMDL. A Gibbs sampling algorithm is developed to implement the method, which is applied to two distinct scenarios: when dose information is available for each measurement (but BMDL is recorded as zero or some other arbitrary value), or when the dose information available represents the summation of a series of measurements (e.g., only yearly cumulative exposure is available but based on, say, weekly measurements). Then the average of the multiple imputed exposure realizations for each individual is used to obtain an unbiased estimate of the relative risk associated with exposure. Simulation studies are used to evaluate the performance of the estimators. As an illustration, the method is applied to a sample of historical occupational radiation exposure data from the Oak Ridge National Laboratory.

Applications of XRF, NAA and low-kV radiographic techniques in the study of body composition and diseased tissue

NASA Astrophysics Data System (ADS)

Bradley, D. A.; Ng, K. H.; Green, S.; Mountford, P. J.; Shukri, A.; Evans, J.

1996-05-01

Members of this group have responded to a number of challenging health issues by attempting to devise sensitive XRF, NAA and low-kV radiographic measurement systems foboth in vivo and in vitro applications. These studies are generally either of toxicological importance, examine potential for diagnosing the presence of disease, or offer effective means for monitoring potentially harmful side-effects of therapy. Particular examples include the in vivo XRF investigation of human skeletal uptake of Pb in working and living environments, in vivo XRF monitoring of elevated levels of Fe in skin (indicating the presence of an undesirable side-effect of the treatment of thalassaemia), in vivo NAA monitoring of elevated levels of Al in bone (indicating an undesirable side-effect of the treatment of chronic renal failure) and in vitro characterization, by means of low-kV imaging, of a range of calcification parameters in healthy and diseased breast tissue. The latter investigation has been conducted in association with an in vitro NAA study of concentrations of trace elements in the same types of tissue. Figures of merit for the various measurement systems have been obtained in terms of minimum detectable levels and concentrations (MDL's and MDC's) and where applicable, image related parameters.

TECHNOLOGIES FOR MONITORING AND MEASUREMENT ...

EPA Pesticide Factsheets

A demonstration of technologies for determining the presence of dioxin and dioxin-like compounds in soil and sediment was conducted under EPA's Superfund Innovative Technology Evaluation Program in Saginaw, Michigan in April 2004. This report describes the performance evaluation of CAPE Technologies DF-1 Dioxin/Furan and PCB TEQ Immunoassay Kits. The kits are immunoassay techniques that report the total toxicity equivalents (TEQ) of dioxin/furans and polychlorinated biphenyls (PCBs. The technology results were compared to high resolution mass spectrometry TEQ results generated using EPA Methods 1613B and 1668A.The CAPE Technologies kits generally reported data higher than the certified PE and reference laboratory values. The technologys estimated MDL was 12 to 33 pg/g TEQ. Results from this demonstration suggest that the CAPE Technologies kits could be an effective screening tool for determining sample results above and below 20 pg/g TEQ and even more effective as a screen for sample above and below 50 pg/g TEQ, particularly considering that both the cost ($59,234 vs. $398,029) and the time (3 weeks vs. 8 months) to analyze the 209 demonstration samples were significantly less than those of the reference laboratory. The objective of this program is to promote the acceptance and use of innovative field technologies by providing well-documented performance and cost data obtained from field demonstrations.

Improving membrane protein expression and function using genomic edits

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

Jensen, Heather M.; Eng, Thomas; Chubukov, Victor

Expression of membrane proteins often leads to growth inhibition and perturbs central metabolism and this burden varies with the protein being overexpressed. There are also known strain backgrounds that allow greater expression of membrane proteins but that differ in efficacy across proteins. Here, we hypothesized that for any membrane protein, it may be possible to identify a modified strain background where its expression can be accommodated with less burden. To directly test this hypothesis, we used a bar-coded transposon insertion library in tandem with cell sorting to assess genome-wide impact of gene deletions on membrane protein expression. The expression ofmore » five membrane proteins (CyoB, CydB, MdlB, YidC, and LepI) and one soluble protein (GST), each fused to GFP, was examined. We identified Escherichia coli mutants that demonstrated increased membrane protein expression relative to that in wild type. For two of the proteins (CyoB and CydB), we conducted functional assays to confirm that the increase in protein expression also led to phenotypic improvement in function. This study represents a systematic approach to broadly identify genetic loci that can be used to improve membrane protein expression, and our method can be used to improve expression of any protein that poses a cellular burden.« less

TECHNOLOGIES FOR MONITORING AND MEASUREMENT ...

EPA Pesticide Factsheets

A demonstration of technologies for determining the presence of dioxin and dioxin-like compounds in soil and sediment was conducted under EPA's Superfund Innovative Technology Evaluation Program in Saginaw, Michigan in April 2004. This report describes the performance evaluation of the Abraxis LLC Coplanar PCB Enzyme-Linked Immunosorbent Assay (ELISA) kit. The kit is an immunoassay technique that reports the total toxicity equivalents (TEQ) of polychlorinated biphenyls (PCBs). The technology results were compared to high resolution mass spectrometry TEQ results generated using EPA Method 1668A.Abraxis generally reported data that were higher than the reference laboratory TEQPCB values, with the exception of ultra-high level PCB samples [> 10,000 picogram/gram (pg/g) TEQ] where Abraxis reported values lower than the reference method. The technologys estimated MDL was 6 to 31 pg/g TEQPCB. Results from this demonstration suggest that the Abraxis kit could be an effective screening tool for screening sample concentrations above and below 50 pg/g TEQPCB, particularly considering that the cost ($22,668 vs. $184,449) and the time to analyze the 209 demonstration samples were significantly less than those of the reference laboratory. The objective of this program is to promote the acceptance and use of innovative field technologies by providing well-documented performance and cost data obtained from field demonstrations.

Improvement in QEPAS system utilizing a second harmonic based wavelength calibration technique

NASA Astrophysics Data System (ADS)

Zhang, Qinduan; Chang, Jun; Wang, Fupeng; Wang, Zongliang; Xie, Yulei; Gong, Weihua

2018-05-01

A simple laser wavelength calibration technique, based on second harmonic signal, is demonstrated in this paper to improve the performance of quartz enhanced photoacoustic spectroscopy (QEPAS) gas sensing system, e.g. improving the signal to noise ratio (SNR), detection limit and long-term stability. Constant current, corresponding to the gas absorption line, combining f/2 frequency sinusoidal signal are used to drive the laser (constant driving mode), a software based real-time wavelength calibration technique is developed to eliminate the wavelength drift due to ambient fluctuations. Compared to conventional wavelength modulation spectroscopy (WMS), this method allows lower filtering bandwidth and averaging algorithm applied to QEPAS system, improving SNR and detection limit. In addition, the real-time wavelength calibration technique guarantees the laser output is modulated steadily at gas absorption line. Water vapor is chosen as an objective gas to evaluate its performance compared to constant driving mode and conventional WMS system. The water vapor sensor was designed insensitive to the incoherent external acoustic noise by the numerical averaging technique. As a result, the SNR increases 12.87 times in wavelength calibration technique based system compared to conventional WMS system. The new system achieved a better linear response (R2 = 0 . 9995) in concentration range from 300 to 2000 ppmv, and achieved a minimum detection limit (MDL) of 630 ppbv.

Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat

NASA Technical Reports Server (NTRS)

Lucot, J. B.

1989-01-01

5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.

Adapting Document Similarity Measures for Ligand-Based Virtual Screening.

PubMed

Himmat, Mubarak; Salim, Naomie; Al-Dabbagh, Mohammed Mumtaz; Saeed, Faisal; Ahmed, Ali

2016-04-13

Quantifying the similarity of molecules is considered one of the major tasks in virtual screening. There are many similarity measures that have been proposed for this purpose, some of which have been derived from document and text retrieving areas as most often these similarity methods give good results in document retrieval and can achieve good results in virtual screening. In this work, we propose a similarity measure for ligand-based virtual screening, which has been derived from a text processing similarity measure. It has been adopted to be suitable for virtual screening; we called this proposed measure the Adapted Similarity Measure of Text Processing (ASMTP). For evaluating and testing the proposed ASMTP we conducted several experiments on two different benchmark datasets: the Maximum Unbiased Validation (MUV) and the MDL Drug Data Report (MDDR). The experiments have been conducted by choosing 10 reference structures from each class randomly as queries and evaluate them in the recall of cut-offs at 1% and 5%. The overall obtained results are compared with some similarity methods including the Tanimoto coefficient, which are considered to be the conventional and standard similarity coefficients for fingerprint-based similarity calculations. The achieved results show that the performance of ligand-based virtual screening is better and outperforms the Tanimoto coefficients and other methods.

[Comparative studies on the bioavailability of nicergoline from two different steady-state preparations].

PubMed

Kohlenberg-Müller, K; Meier, D H; Kunz, K; Wauschkuhn, C H; Schaffler, K

1991-07-01

Comparative Studies on the Bioavailability of Nicergoline from Two Different Preparations in Steady State The bioavailability of nicergoline (CAS 27848-84-6) in a new 30 mg tablet and a 10 mg dragee formulation (Sermion) was evaluated under steady state conditions in 18 healthy male volunteers between the age of 21 and 37 years. During the run-in phase, the volunteers received on 7 consecutive days 30 mg nicergoline either 1 x 30 mg/d tablet (test substance) or 3 x 10 mg dragees (reference). On day 8, after intake of 1 x 30 mg in a 24 h interval or 1 x 10 mg in a 8 h interval respectively, the plasma concentrations of the nicergoline metabolite 10-methoxy-6-methyl-ergoline-8 beta-methanol (MDL) were measured. The area under the plasma concentrations in the 24 h interval after administering the 30 mg tablet was not 3 times greater as to be expected; it was by a factor of 4 significantly greater than the area under the curve of the 10 mg dragee in the 8 h interval. Therefore, nicergoline has a higher availability in the 30 mg tablet than in the 10 mg dragee form. Both formulations were equally well tolerated.

A Primer for Model Selection: The Decisive Role of Model Complexity

NASA Astrophysics Data System (ADS)

Höge, Marvin; Wöhling, Thomas; Nowak, Wolfgang

2018-03-01

Selecting a "best" model among several competing candidate models poses an often encountered problem in water resources modeling (and other disciplines which employ models). For a modeler, the best model fulfills a certain purpose best (e.g., flood prediction), which is typically assessed by comparing model simulations to data (e.g., stream flow). Model selection methods find the "best" trade-off between good fit with data and model complexity. In this context, the interpretations of model complexity implied by different model selection methods are crucial, because they represent different underlying goals of modeling. Over the last decades, numerous model selection criteria have been proposed, but modelers who primarily want to apply a model selection criterion often face a lack of guidance for choosing the right criterion that matches their goal. We propose a classification scheme for model selection criteria that helps to find the right criterion for a specific goal, i.e., which employs the correct complexity interpretation. We identify four model selection classes which seek to achieve high predictive density, low predictive error, high model probability, or shortest compression of data. These goals can be achieved by following either nonconsistent or consistent model selection and by either incorporating a Bayesian parameter prior or not. We allocate commonly used criteria to these four classes, analyze how they represent model complexity and what this means for the model selection task. Finally, we provide guidance on choosing the right type of criteria for specific model selection tasks. (A quick guide through all key points is given at the end of the introduction.)

Frequentist Model Averaging in Structural Equation Modelling.

PubMed

Jin, Shaobo; Ankargren, Sebastian

2018-06-04

Model selection from a set of candidate models plays an important role in many structural equation modelling applications. However, traditional model selection methods introduce extra randomness that is not accounted for by post-model selection inference. In the current study, we propose a model averaging technique within the frequentist statistical framework. Instead of selecting an optimal model, the contributions of all candidate models are acknowledged. Valid confidence intervals and a [Formula: see text] test statistic are proposed. A simulation study shows that the proposed method is able to produce a robust mean-squared error, a better coverage probability, and a better goodness-of-fit test compared to model selection. It is an interesting compromise between model selection and the full model.

A Bayesian random effects discrete-choice model for resource selection: Population-level selection inference

USGS Publications Warehouse

Thomas, D.L.; Johnson, D.; Griffith, B.

2006-01-01

Modeling the probability of use of land units characterized by discrete and continuous measures, we present a Bayesian random-effects model to assess resource selection. This model provides simultaneous estimation of both individual- and population-level selection. Deviance information criterion (DIC), a Bayesian alternative to AIC that is sample-size specific, is used for model selection. Aerial radiolocation data from 76 adult female caribou (Rangifer tarandus) and calf pairs during 1 year on an Arctic coastal plain calving ground were used to illustrate models and assess population-level selection of landscape attributes, as well as individual heterogeneity of selection. Landscape attributes included elevation, NDVI (a measure of forage greenness), and land cover-type classification. Results from the first of a 2-stage model-selection procedure indicated that there is substantial heterogeneity among cow-calf pairs with respect to selection of the landscape attributes. In the second stage, selection of models with heterogeneity included indicated that at the population-level, NDVI and land cover class were significant attributes for selection of different landscapes by pairs on the calving ground. Population-level selection coefficients indicate that the pairs generally select landscapes with higher levels of NDVI, but the relationship is quadratic. The highest rate of selection occurs at values of NDVI less than the maximum observed. Results for land cover-class selections coefficients indicate that wet sedge, moist sedge, herbaceous tussock tundra, and shrub tussock tundra are selected at approximately the same rate, while alpine and sparsely vegetated landscapes are selected at a lower rate. Furthermore, the variability in selection by individual caribou for moist sedge and sparsely vegetated landscapes is large relative to the variability in selection of other land cover types. The example analysis illustrates that, while sometimes computationally intense, a Bayesian hierarchical discrete-choice model for resource selection can provide managers with 2 components of population-level inference: average population selection and variability of selection. Both components are necessary to make sound management decisions based on animal selection.

The Impact of Varied Discrimination Parameters on Mixed-Format Item Response Theory Model Selection

ERIC Educational Resources Information Center

Whittaker, Tiffany A.; Chang, Wanchen; Dodd, Barbara G.

2013-01-01

Whittaker, Chang, and Dodd compared the performance of model selection criteria when selecting among mixed-format IRT models and found that the criteria did not perform adequately when selecting the more parameterized models. It was suggested by M. S. Johnson that the problems when selecting the more parameterized models may be because of the low…

IT vendor selection model by using structural equation model & analytical hierarchy process

NASA Astrophysics Data System (ADS)

Maitra, Sarit; Dominic, P. D. D.

2012-11-01

Selecting and evaluating the right vendors is imperative for an organization's global marketplace competitiveness. Improper selection and evaluation of potential vendors can dwarf an organization's supply chain performance. Numerous studies have demonstrated that firms consider multiple criteria when selecting key vendors. This research intends to develop a new hybrid model for vendor selection process with better decision making. The new proposed model provides a suitable tool for assisting decision makers and managers to make the right decisions and select the most suitable vendor. This paper proposes a Hybrid model based on Structural Equation Model (SEM) and Analytical Hierarchy Process (AHP) for long-term strategic vendor selection problems. The five steps framework of the model has been designed after the thorough literature study. The proposed hybrid model will be applied using a real life case study to assess its effectiveness. In addition, What-if analysis technique will be used for model validation purpose.

Exposure and food web transfer of pharmaceuticals in ospreys (Pandion haliaetus): Predictive model and empirical data

USGS Publications Warehouse

Lazarus, Rebecca S.; Rattner, Barnett A.; Du, Bowen; McGowan, Peter C.; Blazer, Vicki S.; Ottinger, Mary Ann

2015-01-01

The osprey (Pandion haliaetus) is a well-known sentinel of environmental contamination, yet no studies have traced pharmaceuticals through the water–fish–osprey food web. A screening-level exposure assessment was used to evaluate the bioaccumulation potential of 113 pharmaceuticals and metabolites, and an artificial sweetener in this food web. Hypothetical concentrations in water reflecting “wastewater effluent dominated” or “dilution dominated” scenarios were combined with pH-specific bioconcentration factors (BCFs) to predict uptake in fish. Residues in fish and osprey food intake rate were used to calculate the daily intake (DI) of compounds by an adult female osprey. Fourteen pharmaceuticals and a drug metabolite with a BCF greater than 100 and a DI greater than 20 µg/kg were identified as being most likely to exceed the adult human therapeutic dose (HTD). These 15 compounds were also evaluated in a 40 day cumulative dose exposure scenario using first-order kinetics to account for uptake and elimination. Assuming comparable absorption to humans, the half-lives (t1/2) for an adult osprey to reach the HTD within 40 days were calculated. For 3 of these pharmaceuticals, the estimated t1/2 in ospreys was less than that for humans, and thus an osprey might theoretically reach or exceed the HTD in 3 to 7 days. To complement the exposure model, 24 compounds were quantified in water, fish plasma, and osprey nestling plasma from 7 potentially impaired locations in Chesapeake Bay. Of the 18 analytes detected in water, 8 were found in fish plasma, but only 1 in osprey plasma (the antihypertensive diltiazem). Compared to diltiazem detection rate and concentrations in water (10/12 detects,

The genealogy of samples in models with selection.

PubMed

Neuhauser, C; Krone, S M

1997-02-01

We introduce the genealogy of a random sample of genes taken from a large haploid population that evolves according to random reproduction with selection and mutation. Without selection, the genealogy is described by Kingman's well-known coalescent process. In the selective case, the genealogy of the sample is embedded in a graph with a coalescing and branching structure. We describe this graph, called the ancestral selection graph, and point out differences and similarities with Kingman's coalescent. We present simulations for a two-allele model with symmetric mutation in which one of the alleles has a selective advantage over the other. We find that when the allele frequencies in the population are already in equilibrium, then the genealogy does not differ much from the neutral case. This is supported by rigorous results. Furthermore, we describe the ancestral selection graph for other selective models with finitely many selection classes, such as the K-allele models, infinitely-many-alleles models. DNA sequence models, and infinitely-many-sites models, and briefly discuss the diploid case.

The Genealogy of Samples in Models with Selection

PubMed Central

Neuhauser, C.; Krone, S. M.

1997-01-01

We introduce the genealogy of a random sample of genes taken from a large haploid population that evolves according to random reproduction with selection and mutation. Without selection, the genealogy is described by Kingman's well-known coalescent process. In the selective case, the genealogy of the sample is embedded in a graph with a coalescing and branching structure. We describe this graph, called the ancestral selection graph, and point out differences and similarities with Kingman's coalescent. We present simulations for a two-allele model with symmetric mutation in which one of the alleles has a selective advantage over the other. We find that when the allele frequencies in the population are already in equilibrium, then the genealogy does not differ much from the neutral case. This is supported by rigorous results. Furthermore, we describe the ancestral selection graph for other selective models with finitely many selection classes, such as the K-allele models, infinitely-many-alleles models, DNA sequence models, and infinitely-many-sites models, and briefly discuss the diploid case. PMID:9071604

Could the 5-HT1B receptor inverse agonism affect learning consolidation?

PubMed

Meneses, A

2001-03-01

Diverse evidence indicates that, the 5-HT system might play a role in learning and memory, since it occurs in brain areas mediating such processes and 5-HT drugs modulate them. Hence in this work, in order to explore further 5-HT involvement on learning and memory 5-HT1B receptors' role is investigated. Evidence indicates that SB-224289 (a 5-HT1B receptor inverse agonist) post-training injection facilitated learning consolidation in an associative autoshaping learning task, this effect was partially reversed by GR 127935 (a 5-HT1B/1D receptor antagonist), but unaffected by MDL 100907 (a 5-HT2A receptor antagonist) or ketanserin (a 5-HT1D/2A/7 receptor antagonist) at low doses. Moreover, SB-224289 antagonized the learning deficit produced by TFMPP (a 5-HT1A/1B/1D/2A/2C receptor agonist), GR 46611 (a 5-HT1A/1B/1D receptor agonist), mCPP (a 5-HT2A/2C/3/7 receptor agonist/antagonist) or GR 127935 (at low dose). SB-224289 did not alter the 8-OH-DPAT (a 5-HT1A/7 receptor agonist) learning facilitatory effect. SB-224289 eliminated the deficit learning produced by the anticholinergic muscarinic scopolamine or the glutamatergic antagonist dizocilpine. Administration of both, GR 127935 (5mg/kg) plus ketanserin (0.01 mg/kg) did not modify learning consolidation; nevertheless, when ketanserin dose was increased (0.1-1.0mg/kg) and SB-224289 dose was maintained constant, a learning facilitation effect was observed. Notably, SB-224289 at 1.0mg/kg potentiated a subeffective dose of the 5-HT1B/1D receptor agonist/antagonist mixed GR 127935, which facilitated learning consolidation and this effect was abolished by ketanserin at a higher dose. Collectively, the data confirm and extend the earlier findings with GR 127935 and the effects of non-selective 5-HT(1B) receptor agonists. Clearly 5-HT1B agonists induced a learning deficit which can be reversed with SB-224289. Perhaps more importantly, SB-224289 enhances learning consolidation when given alone and can reverse the deficits induced by both cholinergic and glutamatergic antagonist. Hence, 5-HT1B receptor inverse agonists or antagonists could represent drugs for the treatment of learning and memory dysfunctions.

Liquid Chromatography with Post-Column Reagent Addition of Ammonia in Methanol Coupled to Negative Ion Electrospray Ionization Tandem Mass Spectrometry for Determination of Phenoxyacid Herbicides and their Degradation Products in Surface Water

PubMed Central

Raina, Renata; Etter, Michele L.

2010-01-01

A new liquid chromatography (LC)-negative ion electrospray ionization (ESI−)–tandem mass spectrometry (MS/MS) method with post-column addition of ammonia in methanol has been developed for the analysis of acid herbicides: 2,4-dichlorophenoxy acetic acid, 4-chloro-o-tolyloxyacetic acid, 2-(2-methyl-4-chlorophenoxy)butyric acid, mecoprop, dichlorprop, 4-(2,4-dichlorophenoxy) butyric acid, 2,4,5-trichlorophenoxy propionic acid, dicamba and bromoxynil, along with their degradation products: 4-chloro-2-methylphenol, 2,4-dichlorophenol, 2,4,5-trichlorophenol and 3,5-dibromo-4-hydroxybenzoic acid. The samples were extracted from the surface water matrix using solid-phase extraction (SPE) with a polymeric sorbent and analyzed with LC ESI− with selected reaction monitoring (SRM) using a three-point confirmation approach. Chromatography was performed on a Zorbax Eclipse XDB-C18 (50 × 4.6 mm i.d., 1.8 μm) with a gradient elution using water-methanol with 2 mM ammonium acetate mobile phase at a flow rate of 0.15 mL/min. Ammonia in methanol (0.8 M) was added post-column at a flow rate of 0.05 mL/min to enhance ionization of the degradation products in the MS source. One SRM transition was used for quantitative analysis while the second SRM along with the ratio of SRM1/SRM2 within the relative standard deviation determined by standards for each individual pesticide and retention time match were used for confirmation. The standard deviation of ratio of SRM1/SRM2 obtained from standards run on the day of analysis for different phenoxyacid herbicides ranged from 3.9 to 18.5%. Limits of detection (LOD) were between 1 and 15 ng L−1 and method detection limits (MDL) with strict criteria requiring <25% deviation of peak area from best-fit line for both SRM1 and SRM2 ranged from 5 to 10 ng L−1 for acid ingredients (except dicamba at 30 ng L−1) and from 2 to 30 ng L−1 for degradation products. The SPE-LC-ESI− MS/MS method permitted low nanogram-per-liter determination of pesticides and degradation products for surface water samples. PMID:20212919

Measurement of pyrethroids and their environmental degradation products in fresh fruits and vegetables using a modification of the quick easy cheap effective rugged safe (QuEChERS) method.

PubMed

Li, Weiwei; Morgan, Marsha K; Graham, Stephen E; Starr, James M

2016-05-01

Pyrethroid insecticides are used extensively in agriculture, and they, as well as their environmental degradates, may remain as residues on foods such as fruits and vegetables. Since pyrethroid degradates can be identical to the urinary markers used in human biomonitoring, it is important to understand the contribution of these degradates when studying sources of human pyrethroid exposure. We modified the widely used Quick Easy Cheap Effective Rugged Safe (QuEChERS) method to measure several current-use pyrethroids (cis/trans-permethrin, cypermethrin, deltamethrin, esfenvalerate, bifenthrin, cyfluthrin, and cyhalothrin) and their environmental degradation products (3-PBA, cis/trans-DCCA, 4-F-3-PBA, DBCA, and MPA) in selected fresh fruits and vegetables. Using fortified samples, we determined extraction efficiencies from: tomatoes, oranges (whole, peeled, and rind), grapes, apples, bananas (peeled and rind only), onions, lettuce, green peppers, carrots and broccoli. For a subset of these food items (apples, grapes, tomatoes, lettuce and banana peel), we also established limits of detection (MDLs) and quantitation (MQLs). Each sample was homogenized (1kg) then spiked with the target pyrethroids and their degradation products. Sub-samples (15g) were extracted with acetonitrile, then salted out and partitioned with NaCl and MgSO4. The extract was divided and further cleaned using solid phase extraction (SPE) cartridges containing either graphitized non-porous carbon (pyrethroids) or C18 (degradation products). Sample analysis was via liquid chromatography/tandem mass spectrometry (LC-MS/MS). Considering the mean recoveries each of the 14 analytes in all 13 matrices: 42% of the recoveries were ≥90%, 70% were ≥80%, and 90% were ≥70%. All MDL's were less than 100ng/kg, except 3-PBA (132ng/kg, tomato), MPA (129ng/kg, tomato), and trans-permethrin (141ng/kg, banana peel). We then applied the method to non-spiked samples (subset of 5 for which the MDLs/MQLs had been determined) collected weekly for four weeks from local supermarkets. At least one pyrethroid was present in measureable concentrations in all matrices except banana peels. In contrast, the only degradation products detected were cis/trans-DCCA, in one lettuce sample. Published by Elsevier B.V.

Origin of 5-hydroxytryptamine-induced hyperpolarization of the rat superior cervical ganglion and vagus nerve.

PubMed Central

Ireland, S. J.

1987-01-01

1 5-Hydroxytryptamine (5-HT)-induced membrane potential changes were recorded extracellularly from rat superior cervical ganglia (SCG) and cervical vagus nerves in vitro. 2 On the SCG, low concentrations of 5-HT (1 X 10(-8)-3 X 10(-7) M) induced concentration-related hyperpolarization responses. Higher concentrations of 5-HT (1 X 10(-6) 1 X 10(-4) M) induced complex responses which typically consisted of an initial hyperpolarization, followed by a depolarization and subsequent after-hyperpolarization. The depolarization, but not the initial hyperpolarization, was blocked by metoclopramide (3 X 10(-5) M), quipazine (1 X 10(-6) M) or MDL 72222 (1 X 10(-5) M). 3 5-HT-induced hyperpolarization of the SCG was potentiated when the amount of calcium chloride added to the superfusion medium was reduced from 2.5 to 0.15 mmol l-1. Hyperpolarization responses recorded from SCG preparations superfused with this low-calcium medium were unaffected by the substitution of lithium chloride for sodium chloride and were potentiated by the omission of potassium ions. Ouabain (1 X 10(-3) M) abolished both the hyperpolarization and the depolarization induced by 5-HT. 4 On the vagus nerve, 5-HT (1 X 10(-7) - 3 X 10(-5)M) did not induce initial hyperpolarization in either normal or low-calcium Krebs-Henseleit medium. However, in the latter solution only, depolarization responses induced by 5-HT at concentrations of 1 X 10(-6)M or greater were followed by hyperpolarization. Both the depolarization and the post-5-HT hyperpolarization were blocked by metoclopramide (3 X 10(-5)M) but were unaffected by spiperone (1 X 10(-7)M). 5 On the vagus nerve, post-5-HT hyperpolarization responses were selectively and reversibly inhibited by ouabain, and by superfusion with Krebs-Henseleit medium that was either potassium-free or contained lithium chloride in place of sodium chloride. 7 These results demonstrate the generation in the rat SCG of a 5-HT-induced hyperpolarization response that is not mediated through 5-HT3 receptors and is unlikely to be a consequence of depolarization. In contrast, on the rat vagus nerve, the post-5-HT hyperpolarization observed in the present study had the characteristics expected of depolarization-dependent activation of a sodium ion pump. PMID:3676601

Actions of general anaesthetics on 5-HT3 receptors in N1E-115 neuroblastoma cells.

PubMed Central

Jenkins, A.; Franks, N. P.; Lieb, W. R.

1996-01-01

1. NIE-115 mouse neuroblastoma cells were studied under voltage clamp in the whole-cell patch-clamp configuration. Peak currents induced by bath application of 5-hydroxytryptamine (5-HT) were inwardly rectifying, reversed at 0.4 +/- 0.2 mV (mean +/- s.e.mean), and were approximately half-inhibited (at 1 microM 5-HT) by 2 nM of the 5-HT3 selective antagonist MDL-72222 (3-tropanyl-3,5-dichlorobenzoate). 2. Peak inward currents activated by a low concentration of 5-HT at a holding potential of -50 mV were potentiated by volatile general anaesthetics. At their human minimum alveolar concentrations (MACs), the degree of potentiation increased in the order isoflurane < halothane < enflurane < methoxyflurane. Potentiation by methoxyflurane was independent of membrane potential in the range -70 mV to +40 mV. The reversal potential was the same in the presence and absence of methoxyflurane. 3. Methoxyflurane shifted the 5-HT dose-response curve to lower 5-HT concentrations, without significantly changing the Hill coefficient or maximum response. The EC50 concentration for 5-HT decreased from 1.86 +/- 0.02 microM to 1.07 +/- 0.11 microM (means +/- s.e.mean) due to the presence of 1 MAC (270 microM) methoxyflurane. 4. In contrast to the volatile anaesthetics, the barbiturate anaesthetic, thiopentone, inhibited the 5-HT3 receptor. Hill analysis of thiopentone dose-response data gave an average IC50 = 117 +/- 8 microM thiopentone and Hill coefficient = 1.6 +/- 0.2 (means +/- s.e.mean). These parameters were not significantly different for data obtained at 5-HT concentrations above and below the control EC50 concentration for 5-HT, consistent with non-competitive inhibition. 5. The n-alcohols occupied an intermediate position between the volatile and barbiturate anaesthetics. The lower alcohols (butanol and hexanol) potentiated 5-HT responses at low alcohol concentrations but inhibited them at high concentrations. In contrast, the higher alcohols (octanol, decanol, dodecanol, tridecanol, tetradecanol and pentadecanol) produced no potentiation, but only inhibition, at all alcohol concentrations. 6. Inhibition of the 5-HT3 receptor by the n-alcohols exhibited a cutoff in potency similar to those previously found for tadpoles, luciferase enzymes and a neuronal nicotinic acetylcholine receptor channel. PMID:8730747

An immunocapture/scintillation proximity analysis of G alpha q/11 activation by native serotonin (5-HT)2A receptors in rat cortex: blockade by clozapine and mirtazapine.

PubMed

Mannoury La Cour, C; Chaput, C; Touzard, M; Millan, M J

2009-02-01

Though transduction mechanisms recruited by heterologously expressed 5-HT(2A) receptors have been extensively studied, their interaction with specific subtypes of G-protein remains to be directly evaluated in cerebral tissue. Herein, as shown by an immunocapture/scintillation proximity analysis, 5-HT, the prototypical 5-HT(2A) agonist, DOI, and Ro60,0175 all enhanced [(35)S]GTPgammaS binding to G alpha q/11 in rat cortex with pEC(50) values of 6.22, 7.24 and 6.35, respectively. No activation of G o or G s/olf was seen at equivalent concentrations of DOI. Stimulation of G alpha q/11 by 5-HT (30 microM) and DOI (30 microM) was abolished by the selective 5-HT(2A) vs. 5-HT(2C)/5-HT(2B) antagonists, ketanserin (pK(B) values of 9.11 and 8.88, respectively) and MDL100,907 (9.82 and 9.68). By contrast, 5-HT-induced [(35)S]GTPgammaS binding to G alpha q/11 was only weakly inhibited by the preferential 5-HT(2C) receptor antagonists, RS102,221 (6.94) and SB242,084 (7.39), and the preferential 5-HT(2B) receptor antagonist, LY266,097 (6.66). The antipsychotic, clozapine, which had marked affinity for 5-HT(2A) receptors, blocked the recruitment of G alpha q/11 by 5-HT and DOI with pK(B) values of 8.54 and 8.14, respectively. Its actions were mimicked by the "atypical" antidepressant and 5-HT(2A) receptor antagonist, mirtazapine, which likewise blocked 5-HT and DOI-induced G alpha q/11 protein activation with pK(B) values of 7.90 and 7.76, respectively. In conclusion, by use of an immunocapture/scintillation proximity strategy, this study shows that native 5-HT(2A) receptors in rat frontal cortex specifically recruit G alpha q/11 and that this action is blocked by clozapine and mirtazapine. Quantification of 5-HT(2A) receptor-mediated G alpha q/11 activation in frontal cortex should prove instructive in characterizing the actions of diverse classes of psychotropic agent. 2008 Wiley-Liss, Inc.

A Dual-Stage Two-Phase Model of Selective Attention

ERIC Educational Resources Information Center

Hubner, Ronald; Steinhauser, Marco; Lehle, Carola

2010-01-01

The dual-stage two-phase (DSTP) model is introduced as a formal and general model of selective attention that includes both an early and a late stage of stimulus selection. Whereas at the early stage information is selected by perceptual filters whose selectivity is relatively limited, at the late stage stimuli are selected more efficiently on a…

Development of an ATP measurement method suitable for xenobiotic treatment activated sludge biomass.

PubMed

Nguyen, Lan Huong; Chong, Nyuk-Min

2015-09-01

Activated sludge consumes a large amount of energy to degrade a xenobiotic organic compound. By tracking the energy inventory of activated sludge biomass during the sludge's degradation of a xenobiotic, any disadvantageous effect on the sludge's performance caused by energy deficiency can be observed. The purpose of this study was to develop a reliable and accurate method for measuring the ATP contents of activated sludge cells that were to degrade a xenobiotic organic. Cell disruption and cellular ATP extraction were performed by a protocol with which xenobiotic degrading activated sludge biomass was washed with SDS, treated by Tris and TCA, and followed by bead blasting. The suspension of disrupted cells was filtered before the filtrate was injected into HPLC that was set at optimal conditions to measure the ATP concentration therein. This extraction protocol and HPLC measurement of ATP was evaluated for its linearity, limits of detection, and reproducibility. Evaluation test results reported a R(2) of 0.999 of linear fit of ATP concentration versus activated sludge concentration, a LOD=0.00045mg/L, a LOQ=0.0015mg/L for HPLC measurement of ATP, a MDL=0.46mg/g SS for ATP extraction protocol, and a recovery efficiency of 96.4±2%. This method of ATP measurement was simple, rapid, reliable, and was unburdened of some limitations other methods may have. Copyright © 2015 Elsevier B.V. All rights reserved.

3D molecular descriptors important for clinical success.

PubMed

Kombo, David C; Tallapragada, Kartik; Jain, Rachit; Chewning, Joseph; Mazurov, Anatoly A; Speake, Jason D; Hauser, Terry A; Toler, Steve

2013-02-25

The pharmacokinetic and safety profiles of clinical drug candidates are greatly influenced by their requisite physicochemical properties. In particular, it has been shown that 2D molecular descriptors such as fraction of Sp3 carbon atoms (Fsp3) and number of stereo centers correlate with clinical success. Using the proteomic off-target hit rate of nicotinic ligands, we found that shape-based 3D descriptors such as the radius of gyration and shadow indices discriminate off-target promiscuity better than do Fsp3 and the number of stereo centers. We have deduced the relevant descriptor values required for a ligand to be nonpromiscuous. Investigating the MDL Drug Data Report (MDDR) database as compounds move from the preclinical stage toward the market, we have found that these shape-based 3D descriptors predict clinical success of compounds at preclinical and phase1 stages vs compounds withdrawn from the market better than do Fsp3 and LogD. Further, these computed 3D molecular descriptors correlate well with experimentally observed solubility, which is among well-known physicochemical properties that drive clinical success. We also found that about 84% of launched drugs satisfy either Shadow index or Fsp3 criteria, whereas withdrawn and discontinued compounds fail to meet the same criteria. Our studies suggest that spherical compounds (rather than their elongated counterparts) with a minimal number of aromatic rings may exhibit a high propensity to advance from clinical trials to market.

Blocking adenylyl cyclase inhibits olfactory generator currents induced by "IP(3)-odors".

PubMed

Chen, S; Lane, A P; Bock, R; Leinders-Zufall, T; Zufall, F

2000-07-01

Vertebrate olfactory receptor neurons (ORNs) transduce odor stimuli into electrical signals by means of an adenylyl cyclase/cAMP second messenger cascade, but it remains widely debated whether this cAMP cascade mediates transduction for all odorants or only certain odor classes. To address this problem, we have analyzed the generator currents induced by odors that failed to produce cAMP in previous biochemical assays but instead produced IP(3) ("IP(3)-odors"). We show that in single salamander ORNs, sensory responses to "cAMP-odors" and IP(3)-odors are not mutually exclusive but coexist in the same cells. The currents induced by IP(3)-odors exhibit identical biophysical properties as those induced by cAMP odors or direct activation of the cAMP cascade. By disrupting adenylyl cyclase to block cAMP formation using two potent antagonists of adenylyl cyclase, SQ22536 and MDL12330A, we show that this molecular step is necessary for the transduction of both odor classes. To assess whether these results are also applicable to mammals, we examine the electrophysiological responses to IP(3)-odors in intact mouse main olfactory epithelium (MOE) by recording field potentials. The results show that inhibition of adenylyl cyclase prevents EOG responses to both odor classes in mouse MOE, even when "hot spots" with heightened sensitivity to IP(3)-odors are examined.

An Exploration on the Suitability of Airborne Carbonyl Compounds Analysis in relation to Differences in Instrumentation (GC-MS versus HPLC-UV) and Standard Phases (Gas versus Liquid)

PubMed Central

Kim, Ki-Hyun; Szulejko, Jan E.; Kim, Yong-Hyun; Lee, Min-Hee

2014-01-01

The relative performance figure of merits was investigated for the two most common analytical methods employed for carbonyl compounds (CC), for example, between high performance liquid chromatography (HPLC)-UV detector (with 2,4-dinitrophenylhydrazine (DNPH) derivatization) and thermal desorption (TD)-gas chromatography (GC)-mass spectrometry (MS) (without derivatization). To this end, the suitability of each method is assessed by computing the relative recovery (RR) between the gas- and liquid-phase standards containing a suite of CC such as formaldehyde (FA), acetaldehyde (AA), propionaldehyde (PA), butyraldehyde (BA), isovaleraldehyde (IA), and valeraldehyde (VA) along with benzene (B) as a recovery reference for the GC method. The results confirm that a TD-GC-MS is advantageous to attain the maximum recovery for the heavier CCs (i.e., with molecular weights (MW) above BA−MW ≥ 74). On the other hand, the HPLC-UV is favorable for the lighter CCs (like FA and AA) with the least bias. Such compound-specific responses for each platform are validated by relative ordering of CCs as a function of response factor (RF), method detection limit (MDL), and recovery pattern. It is thus desirable to understand the advantages and limitations of each method to attain the CC data with the least experimental bias. PMID:24719571

Determination of polychlorinated biphenyls in transformer oil using various adsorbents for solid phase extraction.

PubMed

Na, Yun-Cheol; Kim, Kang-Jin; Hong, Jongki; Seo, Jung-Ju

2008-08-01

Various adsorbents for a solid phase extraction (SPE) method were used to study their ability to separate PCBs from transformer oil to rapidly determine their sub-ppm concentration in the transformer oil. Approximately 90% of the transformer oil could be removed from the PCBs by using a hydrophilic-lipophilic balanced copolymer (HLB) adsorbent, but the recovery of deca-chlorobiphenyl (deca-CB) used as a surrogate was only 24.5% due to lose during this cleanup process. The use of a silica adsorbent gave good results with 89.9% recovery of the deca-CB. The recovery of Aroclor 1242 and 1260 were 95.4 and 90.3% on silica, and 98.9 and 83.5% on HLB, respectively. Acid treatment was an essential step in removing the ambiguous interference peaks to help identify the PCBs. A decreased sensitivity of the electron capture detection (ECD) for PCBs was observed due to the presence of the remaining trace oil after the workup procedure. This loss in sensitivity was allowed for by using tetrachloroxylene as an internal standard, and this was found to be reliable for the criteria of quality control by employing an experiment in which LCS was spiked with 2mg/l of Aroclor 1260 and analyzed each day over a 25 day period. The MDL for the analytical method established in this study is 0.05 mg/l.

Determination of pesticides associated with suspended sediments in the San Joaquin River, California, USA, using gas chromatography-ion trap mass spectrometry

USGS Publications Warehouse

Bergamaschi, B.A.; Baston, D.S.; Crepeau, K.L.; Kuivila, K.M.

1999-01-01

An analytical method useful for the quantification of a range of pesticides and pesticide degradation products associated with suspended sediments was developed by testing a variety of extraction and cleanup schemes. The final extraction and cleanup methods chosen for use are suitable for the quantification of the listed pesticides using gas chromatography-ion trap mass spectrometry and the removal of interfering coextractable organic material found in suspended sediments. Methylene chloride extraction followed by Florisil cleanup proved most effective for separation of coextractives from the pesticide analytes. Removal of elemental sulfur was accomplished with tetrabutylammonium hydrogen sulfite. The suitability of the method for the analysis of a variety of pesticides was evaluated, and the method detection limits (MDLs) were determined (0.1-6.0 ng/g dry weight of sediment) for 21 compounds. Recovery of pesticides dried onto natural sediments averaged 63%. Analysis of duplicate San Joaquin River suspended-sediment samples demonstrated the utility of the method for environmental samples with variability between replicate analyses lower than between environmental samples. Eight of 21 pesticides measured were observed at concentrations ranging from the MDL to more than 80 ng/g dry weight of sediment and exhibited significant temporal variability. Sediment-associated pesticides, therefore, may contribute to the transport of pesticides through aquatic systems and should be studied separately from dissolved pesticides.

Determination of arsenic in ambient water at sub-part-per-trillion levels by hydride generation Pd coated platform collection and GFAAS detection.

PubMed

Liang, L; Lazoff, S; Chan, C; Horvat, M; Woods, J S

1998-11-01

A method for trace determination of total arsenic in ambient waters is described. Arsenic is separated on-line from a large volume water sample by hydride generation and purging, pre-collected on a Pd coated pyrolytic platform cuvette using a simple and inexpensive system, and finally detected by GFAAS. Instrument parameters, hydride generation, transportation, and collection were optimized. The analytical behavior for major species including As(3+), As(5+), monomethyl As (MMA), and dimethyl As (DMA) were investigated individually. Problems arising from use of the system were discussed and eliminated. The necessity of sample digestion and an efficient digestion method were studied. Sample digestion for water with low organic content such as tap water and clean ground water and some clean surface water can be omitted. The method detection limit (MDL) is 0.3 ng l(-1) for a 25 ml water sample. Recoveries close to 100% with R.S.D.<5% can be easily achieved. Typical aqueous samples including tap, ground, lake, river, rain, sewage effluent, and saline water from different origins in the US, China, and Canada were collected and analyzed using ultra clean sampling and analysis techniques. The background levels of As in most water analyzed were established for the first time, and found to be far above the EPA's health effect criteria, 18 ng l(-1).

Improved in silico prediction of carcinogenic potency (TD50) and the risk specific dose (RSD) adjusted Threshold of Toxicological Concern (TTC) for genotoxic chemicals and pharmaceutical impurities.

PubMed

Contrera, Joseph F

2011-02-01

The Threshold of Toxicological Concern (TTC) is a level of exposure to a genotoxic impurity that is considered to represent a negligible risk to humans. The TTC was derived from the results of rodent carcinogenicity TD50 values that are a measure of carcinogenic potency. The TTC currently sets a default limit of 1.5 μg/day in food contact substances and pharmaceuticals for all genotoxic impurities without carcinogenicity data. Bercu et al. (2010) used the QSAR predicted TD50 to calculate a risk specific dose (RSD) which is a carcinogenic potency adjusted TTC for genotoxic impurities. This promising approach is currently limited by the software used, a combination of MC4PC (www.multicase.com) and a Lilly Inc. in-house software (VISDOM) that is not available to the public. In this report the TD50 and RSD were predicted using a commercially available software, SciQSAR (formally MDL-QSAR, www.scimatics.com) employing the same TD50 training data set and external validation test set that was used by Bercu et al. (2010). The results demonstrate the general applicability of QSAR predicted TD50 values to determine the RSDs for genotoxic impurities and the improved performance of SciQSAR for predicting TD50 values. Copyright © 2010 Elsevier Inc. All rights reserved.

Trace element distribution in the rat cerebellum

NASA Astrophysics Data System (ADS)

Kwiatek, W. M.; Long, G. J.; Pounds, J. G.; Reuhl, K. R.; Hanson, A. L.; Jones, K. W.

1990-04-01

Spatial distributions and concentrations of trace elements (TE) in the brain are important because TE perform catalytic and structural functions in enzymes which regulate brain function and development. We have investigated the distributions of TE in rat cerebellum. Structures were sectioned and analyzed by the Synchrotron Radiation Induced X-ray Emission (SRIXE) method using the NSLS X-26 white-light microprobe facility. Advantages important for TE analysis of biological specimens with X-ray microscopy include short time of measurement, high brightness and flux, good spatial resolution, multielemental detection, good sensitivity, and nondestructive irradiation. Trace elements were measured in thin rat brain sections of 20 μm thickness. The analyses were performed on sample volumes as small as 0.2 nl with Minimum Detectable Limits (MDL) of 50 ppb wet weight for Fe, 100 ppb wet weight for Cu, and Zn, and 1 ppm wet weight for Pb. The distribution of TE in the molecular cell layer, granule cell layer and fiber tract of rat cerebella was investigated. Both point analyses and two-dimensional semiquantitative mapping of the TE distribution in a section were used. All analyzed elements were observed in each structure of the cerebellum except mercury which was not observed in granule cell layer or fiber tract. This approach permits an exacting correlation of the TE distribution in complex structure with the diet, toxic elements, and functional status of the animal.

The Tracking Meteogram, an AWIPS II Tool for Time-Series Analysis

NASA Technical Reports Server (NTRS)

Burks, Jason Eric; Sperow, Ken

2015-01-01

A new tool has been developed for the National Weather Service (NWS) Advanced Weather Interactive Processing System (AWIPS) II through collaboration between NASA's Short-term Prediction Research and Transition (SPoRT) and the NWS Meteorological Development Laboratory (MDL). Referred to as the "Tracking Meteogram", the tool aids NWS forecasters in assessing meteorological parameters associated with moving phenomena. The tool aids forecasters in severe weather situations by providing valuable satellite and radar derived trends such as cloud top cooling rates, radial velocity couplets, reflectivity, and information from ground-based lightning networks. The Tracking Meteogram tool also aids in synoptic and mesoscale analysis by tracking parameters such as the deepening of surface low pressure systems, changes in surface or upper air temperature, and other properties. The tool provides a valuable new functionality and demonstrates the flexibility and extensibility of the NWS AWIPS II architecture. In 2014, the operational impact of the tool was formally evaluated through participation in the NOAA/NWS Operations Proving Ground (OPG), a risk reduction activity to assess performance and operational impact of new forecasting concepts, tools, and applications. Performance of the Tracking Meteogram Tool during the OPG assessment confirmed that it will be a valuable asset to the operational forecasters. This presentation reviews development of the Tracking Meteogram tool, performance and feedback acquired during the OPG activity, and future goals for continued support and extension to other application areas.

Detection of a cyclic perfluorinated acid, perfluoroethylcyclohexane sulfonate, in the Great Lakes of North America.

PubMed

De Silva, Amila O; Spencer, Christine; Scott, Brian F; Backus, Sean; Muir, Derek C G

2011-10-01

Perfluoroethylcyclohexanesulfonate (PFECHS) is a cyclic perfluorinated acid (PFA) mainly used as an erosion inhibitor in aircraft hydraulic fluids. It is expected to be as recalcitrant to environmental degradation as aliphatic PFAs including perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS). For the first time, PFECHS is reported in top predator fish (

Simultaneous detection of nine cyanotoxins in drinking water using dual solid-phase extraction and liquid chromatography-mass spectrometry.

PubMed

Yen, Hung-Kai; Lin, Tsair-Fuh; Liao, Pao-Chi

2011-08-01

A solid-phase extraction (SPE)-liquid chromatography (LC)-mass spectrometry (MS) method was developed to concentrate and detect nine cyanotoxins simultaneously, including six microcystins (MCs) congeners, nodularin (NOD), anatoxin-a (ATX) and cylindrospermopsin (CYN), in pure and natural waters. A dual cartridge SPE assembly was tested for the operating parameters of cyanotoxin extraction. A surrogate standard (SS), 1,9-diaminononane, was spiked in all the samples before the SPE extraction, and an internal standard (IS), 2,3,5-trimethylphenyl methyl carbamate, was spiked before LC/MS analysis. The method detection limit (MDL) was 2-100 ng/L for nine cyanotoxins in pure water and was increased by a factor of three to ten in a more complicated water matrix. The recoveries based on SS were between 83 and 104%, while those based on IS were 80-120%. The developed method was successfully employed in analyzing 33 water samples collected from eutrophic lakes, water treatment plants and distribution taps. MCs, NOD, and CYN were detected in the reservoir water, with concentrations as high as 36 μg/L. In addition, for the first time in Taiwan's tap water, CYN was detected at concentrations as high as 8.6 μg/L. Quality control data for the field samples shows that the analytical scheme developed is appropriate for monitoring cyanotoxins. Copyright © 2011 Elsevier Ltd. All rights reserved.

Attentional Selection in Object Recognition

DTIC Science & Technology

1993-02-01

order. It also affects the choice of strategies in both the 24 A Computational Model of Attentional Selection filtering and arbiter stages. The set...such processing. In Treisman’s model this was hidden in the concept of the selection filter . Later computational models of attention tried to...This thesis presents a novel approach to the selection problem by propos. ing a computational model of visual attentional selection as a paradigm for

Model selection bias and Freedman's paradox

USGS Publications Warehouse

Lukacs, P.M.; Burnham, K.P.; Anderson, D.R.

2010-01-01

In situations where limited knowledge of a system exists and the ratio of data points to variables is small, variable selection methods can often be misleading. Freedman (Am Stat 37:152-155, 1983) demonstrated how common it is to select completely unrelated variables as highly "significant" when the number of data points is similar in magnitude to the number of variables. A new type of model averaging estimator based on model selection with Akaike's AIC is used with linear regression to investigate the problems of likely inclusion of spurious effects and model selection bias, the bias introduced while using the data to select a single seemingly "best" model from a (often large) set of models employing many predictor variables. The new model averaging estimator helps reduce these problems and provides confidence interval coverage at the nominal level while traditional stepwise selection has poor inferential properties. ?? The Institute of Statistical Mathematics, Tokyo 2009.

Input variable selection for data-driven models of Coriolis flowmeters for two-phase flow measurement

NASA Astrophysics Data System (ADS)

Wang, Lijuan; Yan, Yong; Wang, Xue; Wang, Tao

2017-03-01

Input variable selection is an essential step in the development of data-driven models for environmental, biological and industrial applications. Through input variable selection to eliminate the irrelevant or redundant variables, a suitable subset of variables is identified as the input of a model. Meanwhile, through input variable selection the complexity of the model structure is simplified and the computational efficiency is improved. This paper describes the procedures of the input variable selection for the data-driven models for the measurement of liquid mass flowrate and gas volume fraction under two-phase flow conditions using Coriolis flowmeters. Three advanced input variable selection methods, including partial mutual information (PMI), genetic algorithm-artificial neural network (GA-ANN) and tree-based iterative input selection (IIS) are applied in this study. Typical data-driven models incorporating support vector machine (SVM) are established individually based on the input candidates resulting from the selection methods. The validity of the selection outcomes is assessed through an output performance comparison of the SVM based data-driven models and sensitivity analysis. The validation and analysis results suggest that the input variables selected from the PMI algorithm provide more effective information for the models to measure liquid mass flowrate while the IIS algorithm provides a fewer but more effective variables for the models to predict gas volume fraction.

A quantitative model of optimal data selection in Wason's selection task.

PubMed

Hattori, Masasi

2002-10-01

The optimal data selection model proposed by Oaksford and Chater (1994) successfully formalized Wason's selection task (Wason, 1966). The model, however, involved some questionable assumptions and was also not sufficient as a model of the task because it could not provide quantitative predictions of the card selection frequencies. In this paper, the model was revised to provide quantitative fits to the data. The model can predict the selection frequencies of cards based on a selection tendency function (STF), or conversely, it enables the estimation of subjective probabilities from data. Past experimental data were first re-analysed based on the model. In Experiment 1, the superiority of the revised model was shown. However, when the relationship between antecedent and consequent was forced to deviate from the biconditional form, the model was not supported. In Experiment 2, it was shown that sufficient emphasis on probabilistic information can affect participants' performance. A detailed experimental method to sort participants by probabilistic strategies was introduced. Here, the model was supported by a subgroup of participants who used the probabilistic strategy. Finally, the results were discussed from the viewpoint of adaptive rationality.

A Parameter Subset Selection Algorithm for Mixed-Effects Models

DOE PAGES

Schmidt, Kathleen L.; Smith, Ralph C.

2016-01-01

Mixed-effects models are commonly used to statistically model phenomena that include attributes associated with a population or general underlying mechanism as well as effects specific to individuals or components of the general mechanism. This can include individual effects associated with data from multiple experiments. However, the parameterizations used to incorporate the population and individual effects are often unidentifiable in the sense that parameters are not uniquely specified by the data. As a result, the current literature focuses on model selection, by which insensitive parameters are fixed or removed from the model. Model selection methods that employ information criteria are applicablemore » to both linear and nonlinear mixed-effects models, but such techniques are limited in that they are computationally prohibitive for large problems due to the number of possible models that must be tested. To limit the scope of possible models for model selection via information criteria, we introduce a parameter subset selection (PSS) algorithm for mixed-effects models, which orders the parameters by their significance. In conclusion, we provide examples to verify the effectiveness of the PSS algorithm and to test the performance of mixed-effects model selection that makes use of parameter subset selection.« less

Comparison of three models to estimate breeding values for percentage of loin intramuscular fat in Duroc swine.

PubMed

Newcom, D W; Baas, T J; Stalder, K J; Schwab, C R

2005-04-01

Three selection models were evaluated to compare selection candidate rankings based on EBV and to evaluate subsequent effects of model-derived EBV on the selection differential and expected genetic response in the population. Data were collected from carcass- and ultrasound-derived estimates of loin i.m. fat percent (IMF) in a population of Duroc swine under selection to increase IMF. The models compared were Model 1, a two-trait animal model used in the selection experiment that included ultrasound IMF from all pigs scanned and carcass IMF from pigs slaughtered to estimate breeding values for both carcass (C1) and ultrasound IMF (U1); Model 2, a single-trait animal model that included ultrasound IMF values on all pigs scanned to estimate breeding values for ultrasound IMF (U2); and Model 3, a multiple-trait animal model including carcass IMF from slaughtered pigs and the first three principal components from a total of 10 image parameters averaged across four longitudinal ultrasound images to estimate breeding values for carcass IMF (C3). Rank correlations between breeding value estimates for U1 and C1, U1 and U2, and C1 and C3 were 0.95, 0.97, and 0.92, respectively. Other rank correlations were 0.86 or less. In the selection experiment, approximately the top 10% of boars and 50% of gilts were selected. Selection differentials for pigs in Generation 3 were greatest when ranking pigs based on C1, followed by U1, U2, and C3. In addition, selection differential and estimated response were evaluated when simulating selection of the top 1, 5, and 10% of sires and 50% of dams. Results of this analysis indicated the greatest selection differential was for selection based on C1. The greatest loss in selection differential was found for selection based on C3 when selecting the top 10 and 1% of boars and 50% of gilts. The loss in estimated response when selecting varying percentages of boars and the top 50% of gilts was greatest when selection was based on C3 (16.0 to 25.8%) and least for selection based on U1 (1.3 to 10.9%). Estimated genetic change from selection based on carcass IMF was greater than selection based on ultrasound IMF. Results show that selection based on a combination of ultrasonically predicted IMF and sib carcass IMF produced the greatest selection differentials and should lead to the greatest genetic change.

ModelTest Server: a web-based tool for the statistical selection of models of nucleotide substitution online

PubMed Central

Posada, David

2006-01-01

ModelTest server is a web-based application for the selection of models of nucleotide substitution using the program ModelTest. The server takes as input a text file with likelihood scores for the set of candidate models. Models can be selected with hierarchical likelihood ratio tests, or with the Akaike or Bayesian information criteria. The output includes several statistics for the assessment of model selection uncertainty, for model averaging or to estimate the relative importance of model parameters. The server can be accessed at . PMID:16845102

Selecting Single Model in Combination Forecasting Based on Cointegration Test and Encompassing Test

PubMed Central

Jiang, Chuanjin; Zhang, Jing; Song, Fugen

2014-01-01

Combination forecasting takes all characters of each single forecasting method into consideration, and combines them to form a composite, which increases forecasting accuracy. The existing researches on combination forecasting select single model randomly, neglecting the internal characters of the forecasting object. After discussing the function of cointegration test and encompassing test in the selection of single model, supplemented by empirical analysis, the paper gives the single model selection guidance: no more than five suitable single models can be selected from many alternative single models for a certain forecasting target, which increases accuracy and stability. PMID:24892061

Selecting single model in combination forecasting based on cointegration test and encompassing test.

PubMed

Jiang, Chuanjin; Zhang, Jing; Song, Fugen

2014-01-01

Combination forecasting takes all characters of each single forecasting method into consideration, and combines them to form a composite, which increases forecasting accuracy. The existing researches on combination forecasting select single model randomly, neglecting the internal characters of the forecasting object. After discussing the function of cointegration test and encompassing test in the selection of single model, supplemented by empirical analysis, the paper gives the single model selection guidance: no more than five suitable single models can be selected from many alternative single models for a certain forecasting target, which increases accuracy and stability.

Model selection and model averaging in phylogenetics: advantages of akaike information criterion and bayesian approaches over likelihood ratio tests.

PubMed

Posada, David; Buckley, Thomas R

2004-10-01

Model selection is a topic of special relevance in molecular phylogenetics that affects many, if not all, stages of phylogenetic inference. Here we discuss some fundamental concepts and techniques of model selection in the context of phylogenetics. We start by reviewing different aspects of the selection of substitution models in phylogenetics from a theoretical, philosophical and practical point of view, and summarize this comparison in table format. We argue that the most commonly implemented model selection approach, the hierarchical likelihood ratio test, is not the optimal strategy for model selection in phylogenetics, and that approaches like the Akaike Information Criterion (AIC) and Bayesian methods offer important advantages. In particular, the latter two methods are able to simultaneously compare multiple nested or nonnested models, assess model selection uncertainty, and allow for the estimation of phylogenies and model parameters using all available models (model-averaged inference or multimodel inference). We also describe how the relative importance of the different parameters included in substitution models can be depicted. To illustrate some of these points, we have applied AIC-based model averaging to 37 mitochondrial DNA sequences from the subgenus Ohomopterus(genus Carabus) ground beetles described by Sota and Vogler (2001).

Detecting consistent patterns of directional adaptation using differential selection codon models.

PubMed

Parto, Sahar; Lartillot, Nicolas

2017-06-23

Phylogenetic codon models are often used to characterize the selective regimes acting on protein-coding sequences. Recent methodological developments have led to models explicitly accounting for the interplay between mutation and selection, by modeling the amino acid fitness landscape along the sequence. However, thus far, most of these models have assumed that the fitness landscape is constant over time. Fluctuations of the fitness landscape may often be random or depend on complex and unknown factors. However, some organisms may be subject to systematic changes in selective pressure, resulting in reproducible molecular adaptations across independent lineages subject to similar conditions. Here, we introduce a codon-based differential selection model, which aims to detect and quantify the fine-grained consistent patterns of adaptation at the protein-coding level, as a function of external conditions experienced by the organism under investigation. The model parameterizes the global mutational pressure, as well as the site- and condition-specific amino acid selective preferences. This phylogenetic model is implemented in a Bayesian MCMC framework. After validation with simulations, we applied our method to a dataset of HIV sequences from patients with known HLA genetic background. Our differential selection model detects and characterizes differentially selected coding positions specifically associated with two different HLA alleles. Our differential selection model is able to identify consistent molecular adaptations as a function of repeated changes in the environment of the organism. These models can be applied to many other problems, ranging from viral adaptation to evolution of life-history strategies in plants or animals.

Using multilevel models to quantify heterogeneity in resource selection

USGS Publications Warehouse

Wagner, Tyler; Diefenbach, Duane R.; Christensen, Sonja; Norton, Andrew S.

2011-01-01

Models of resource selection are being used increasingly to predict or model the effects of management actions rather than simply quantifying habitat selection. Multilevel, or hierarchical, models are an increasingly popular method to analyze animal resource selection because they impose a relatively weak stochastic constraint to model heterogeneity in habitat use and also account for unequal sample sizes among individuals. However, few studies have used multilevel models to model coefficients as a function of predictors that may influence habitat use at different scales or quantify differences in resource selection among groups. We used an example with white-tailed deer (Odocoileus virginianus) to illustrate how to model resource use as a function of distance to road that varies among deer by road density at the home range scale. We found that deer avoidance of roads decreased as road density increased. Also, we used multilevel models with sika deer (Cervus nippon) and white-tailed deer to examine whether resource selection differed between species. We failed to detect differences in resource use between these two species and showed how information-theoretic and graphical measures can be used to assess how resource use may have differed. Multilevel models can improve our understanding of how resource selection varies among individuals and provides an objective, quantifiable approach to assess differences or changes in resource selection.

Nonmathematical models for evolution of altruism, and for group selection (peck order-territoriality-ant colony-dual-determinant model-tri-determinant model).

PubMed

Darlington, P J

1972-02-01

Mathematical biologists have failed to produce a satisfactory general model for evolution of altruism, i.e., of behaviors by which "altruists" benefit other individuals but not themselves; kin selection does not seem to be a sufficient explanation of nonreciprocal altruism. Nonmathematical (but mathematically acceptable) models are now proposed for evolution of negative altruism in dual-determinant and of positive altruism in tri-determinant systems. Peck orders, territorial systems, and an ant society are analyzed as examples. In all models, evolution is primarily by individual selection, probably supplemented by group selection. Group selection is differential extinction of populations. It can act only on populations preformed by selection at the individual level, but can either cancel individual selective trends (effecting evolutionary homeostasis) or supplement them; its supplementary effect is probably increasingly important in the evolution of increasingly organized populations.

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

Portone, Teresa; Niederhaus, John Henry; Sanchez, Jason James

This report introduces the concepts of Bayesian model selection, which provides a systematic means of calibrating and selecting an optimal model to represent a phenomenon. This has many potential applications, including for comparing constitutive models. The ideas described herein are applied to a model selection problem between different yield models for hardened steel under extreme loading conditions.

Spatio-temporal Bayesian model selection for disease mapping

PubMed Central

Carroll, R; Lawson, AB; Faes, C; Kirby, RS; Aregay, M; Watjou, K

2016-01-01

Spatio-temporal analysis of small area health data often involves choosing a fixed set of predictors prior to the final model fit. In this paper, we propose a spatio-temporal approach of Bayesian model selection to implement model selection for certain areas of the study region as well as certain years in the study time line. Here, we examine the usefulness of this approach by way of a large-scale simulation study accompanied by a case study. Our results suggest that a special case of the model selection methods, a mixture model allowing a weight parameter to indicate if the appropriate linear predictor is spatial, spatio-temporal, or a mixture of the two, offers the best option to fitting these spatio-temporal models. In addition, the case study illustrates the effectiveness of this mixture model within the model selection setting by easily accommodating lifestyle, socio-economic, and physical environmental variables to select a predominantly spatio-temporal linear predictor. PMID:28070156

Multi-Criteria Decision Making For Determining A Simple Model of Supplier Selection

NASA Astrophysics Data System (ADS)

Harwati

2017-06-01

Supplier selection is a decision with many criteria. Supplier selection model usually involves more than five main criteria and more than 10 sub-criteria. In fact many model includes more than 20 criteria. Too many criteria involved in supplier selection models sometimes make it difficult to apply in many companies. This research focuses on designing supplier selection that easy and simple to be applied in the company. Analytical Hierarchy Process (AHP) is used to weighting criteria. The analysis results there are four criteria that are easy and simple can be used to select suppliers: Price (weight 0.4) shipment (weight 0.3), quality (weight 0.2) and services (weight 0.1). A real case simulation shows that simple model provides the same decision with a more complex model.

Exploring Several Methods of Groundwater Model Selection

NASA Astrophysics Data System (ADS)

Samani, Saeideh; Ye, Ming; Asghari Moghaddam, Asghar

2017-04-01

Selecting reliable models for simulating groundwater flow and solute transport is essential to groundwater resources management and protection. This work is to explore several model selection methods for avoiding over-complex and/or over-parameterized groundwater models. We consider six groundwater flow models with different numbers (6, 10, 10, 13, 13 and 15) of model parameters. These models represent alternative geological interpretations, recharge estimates, and boundary conditions at a study site in Iran. The models were developed with Model Muse, and calibrated against observations of hydraulic head using UCODE. Model selection was conducted by using the following four approaches: (1) Rank the models using their root mean square error (RMSE) obtained after UCODE-based model calibration, (2) Calculate model probability using GLUE method, (3) Evaluate model probability using model selection criteria (AIC, AICc, BIC, and KIC), and (4) Evaluate model weights using the Fuzzy Multi-Criteria-Decision-Making (MCDM) approach. MCDM is based on the fuzzy analytical hierarchy process (AHP) and fuzzy technique for order performance, which is to identify the ideal solution by a gradual expansion from the local to the global scale of model parameters. The KIC and MCDM methods are superior to other methods, as they consider not only the fit between observed and simulated data and the number of parameter, but also uncertainty in model parameters. Considering these factors can prevent from occurring over-complexity and over-parameterization, when selecting the appropriate groundwater flow models. These methods selected, as the best model, one with average complexity (10 parameters) and the best parameter estimation (model 3).

A Selective Review of Group Selection in High-Dimensional Models

PubMed Central

Huang, Jian; Breheny, Patrick; Ma, Shuangge

2013-01-01

Grouping structures arise naturally in many statistical modeling problems. Several methods have been proposed for variable selection that respect grouping structure in variables. Examples include the group LASSO and several concave group selection methods. In this article, we give a selective review of group selection concerning methodological developments, theoretical properties and computational algorithms. We pay particular attention to group selection methods involving concave penalties. We address both group selection and bi-level selection methods. We describe several applications of these methods in nonparametric additive models, semiparametric regression, seemingly unrelated regressions, genomic data analysis and genome wide association studies. We also highlight some issues that require further study. PMID:24174707

A genetic algorithm based global search strategy for population pharmacokinetic/pharmacodynamic model selection

PubMed Central

Sale, Mark; Sherer, Eric A

2015-01-01

The current algorithm for selecting a population pharmacokinetic/pharmacodynamic model is based on the well-established forward addition/backward elimination method. A central strength of this approach is the opportunity for a modeller to continuously examine the data and postulate new hypotheses to explain observed biases. This algorithm has served the modelling community well, but the model selection process has essentially remained unchanged for the last 30 years. During this time, more robust approaches to model selection have been made feasible by new technology and dramatic increases in computation speed. We review these methods, with emphasis on genetic algorithm approaches and discuss the role these methods may play in population pharmacokinetic/pharmacodynamic model selection. PMID:23772792

Modeling HIV-1 Drug Resistance as Episodic Directional Selection

PubMed Central

Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L.; Scheffler, Konrad

2012-01-01

The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance. PMID:22589711

Modeling HIV-1 drug resistance as episodic directional selection.

PubMed

Murrell, Ben; de Oliveira, Tulio; Seebregts, Chris; Kosakovsky Pond, Sergei L; Scheffler, Konrad

2012-01-01

The evolution of substitutions conferring drug resistance to HIV-1 is both episodic, occurring when patients are on antiretroviral therapy, and strongly directional, with site-specific resistant residues increasing in frequency over time. While methods exist to detect episodic diversifying selection and continuous directional selection, no evolutionary model combining these two properties has been proposed. We present two models of episodic directional selection (MEDS and EDEPS) which allow the a priori specification of lineages expected to have undergone directional selection. The models infer the sites and target residues that were likely subject to directional selection, using either codon or protein sequences. Compared to its null model of episodic diversifying selection, MEDS provides a superior fit to most sites known to be involved in drug resistance, and neither one test for episodic diversifying selection nor another for constant directional selection are able to detect as many true positives as MEDS and EDEPS while maintaining acceptable levels of false positives. This suggests that episodic directional selection is a better description of the process driving the evolution of drug resistance.

3D-QSAR and molecular docking study on bisarylmaleimide series as glycogen synthase kinase 3, cyclin dependent kinase 2 and cyclin dependent kinase 4 inhibitors: an insight into the criteria for selectivity.

PubMed

Dessalew, Nigus; Bharatam, Prasad V

2007-07-01

Selective glycogen synthase kinase 3 (GSK3) inhibition over cyclin dependent kinases such as cyclin dependent kinase 2 (CDK2) and cyclin dependent kinase 4 (CDK4) is an important requirement for improved therapeutic profile of GSK3 inhibitors. The concepts of selectivity and additivity fields have been employed in developing selective CoMFA models for these related kinases. Initially, sets of three individual CoMFA models were developed, using 36 compounds of bisarylmaleimide series to correlate with the GSK3, CDK2 and CDK4 inhibitory potencies. These models showed a satisfactory statistical significance: CoMFA-GSK3 (r(2)(con), r(2)(cv): 0.931, 0.519), CoMFA-CDK2 (0.937, 0.563), and CoMFA-CDK4 (0.892, 0.725). Three different selective CoMFA models were then developed using differences in pIC(50) values. These three models showed a superior statistical significance: (i) CoMFA-Selective1 (r(2)(con), r(2)(cv): 0.969, 0.768), (ii) CoMFA-Selective 2 (0.974, 0.835) and (iii) CoMFA-Selective3 (0.963, 0.776). The selective models were found to outperform the individual models in terms of the quality of correlation and were found to be more informative in pinpointing the structural basis for the observed quantitative differences of kinase inhibition. An in-depth comparative investigation was carried out between the individual and selective models to gain an insight into the selectivity criterion. To further validate this approach, a set of new compounds were designed which show selectivity and were docked into the active site of GSK3, using FlexX based incremental construction algorithm.

Model Selection with the Linear Mixed Model for Longitudinal Data

ERIC Educational Resources Information Center

Ryoo, Ji Hoon

2011-01-01

Model building or model selection with linear mixed models (LMMs) is complicated by the presence of both fixed effects and random effects. The fixed effects structure and random effects structure are codependent, so selection of one influences the other. Most presentations of LMM in psychology and education are based on a multilevel or…

Comparison of tachykinin NK1 and NK2 receptors in the circular muscle of the guinea-pig ileum and proximal colon.

PubMed Central

Maggi, C. A.; Patacchini, R.; Meini, S.; Quartara, L.; Sisto, A.; Potier, E.; Giuliani, S.; Giachetti, A.

1994-01-01

1. The aim of this study was the pharmacological characterization of tachykinin NK1 and NK2 receptors mediating contraction in the circular muscle of the guinea-pig ileum and proximal colon. The action of substance P (SP), neurokinin A (NKA) and of the synthetic agonists [Sar9]SP sulphone, [Glp6,Pro9]SP(6-11) (septide) and [beta Ala8]NKA(4-10) was investigated. The affinities of various peptide and nonpeptide antagonists for the NK1 and NK2 receptor was estimated by use of receptor selective agonists. 2. The natural agonists, SP and NKA, produced concentration-dependent contraction in both preparations. EC50 values were 100 pM and 5 nM for SP, 1.2 nM and 19 nM for NKA in the ileum and colon, respectively. The action of SP and NKA was not significantly modified by peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each). 3. Synthetic NK1 and NK2 receptor agonists produced concentration-dependent contraction of the circular muscle of the ileum and proximal colon. EC50 values were 83 pM, 36 pM and 10 nM in the ileum, 8 nM, 0.7 nM and 12 nM in the colon for [Sar9]SP sulphone, septide and [beta Ala8]NKA-(4-10), respectively. The pseudopeptide derivative of NKA(4-10), MDL 28,564 behaved as a full or near-to-full agonist in both preparations, its EC50s being 474 nM and 55 nM in the ileum and colon, respectively. 4. Nifedipine (1 microM) abolished the response to septide and [Sar9]SP sulphone in the ileum and produced a rightward shift and large depression of the response in the colon. The response to [beta Ala8]NKA(4-10) was abolished in the ileum and largely unaffected in the colon. 5. The NK1 receptor antagonists, (+/-)-CP 96,34, FK 888 and GR 82,334 competitively antagonized the response to septide and [Sar9]SP sulphone in both preparations without affecting that to [beta Ala8]NKA(4-10). In general, the NK1 receptor antagonists were significantly more potent toward septide than [Sar9]SP sulphone in both preparations. 6. The NK2 receptor antagonists, GR 94,800 and SR 48,968 selectively antagonized the response to [beta Ala8]NKA(4-10) without affecting that to [Sar9]SP sulphone or septide in the ileum and colon. SR 48,968 produced noncompetitive antagonism of the response to the NK2 receptor agonist in the ileum and competitive antagonism in the colon. 7. MEN 10,376 and the cyclic pseudopeptide MEN 10,573 antagonized in a competitive manner the response to [beta Ala8]NKA(4-10) in the ileum and colon.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7518302

Robust check loss-based variable selection of high-dimensional single-index varying-coefficient model

NASA Astrophysics Data System (ADS)

Song, Yunquan; Lin, Lu; Jian, Ling

2016-07-01

Single-index varying-coefficient model is an important mathematical modeling method to model nonlinear phenomena in science and engineering. In this paper, we develop a variable selection method for high-dimensional single-index varying-coefficient models using a shrinkage idea. The proposed procedure can simultaneously select significant nonparametric components and parametric components. Under defined regularity conditions, with appropriate selection of tuning parameters, the consistency of the variable selection procedure and the oracle property of the estimators are established. Moreover, due to the robustness of the check loss function to outliers in the finite samples, our proposed variable selection method is more robust than the ones based on the least squares criterion. Finally, the method is illustrated with numerical simulations.

[Effect of algorithms for calibration set selection on quantitatively determining asiaticoside content in Centella total glucosides by near infrared spectroscopy].

PubMed

Zhan, Xue-yan; Zhao, Na; Lin, Zhao-zhou; Wu, Zhi-sheng; Yuan, Rui-juan; Qiao, Yan-jiang

2014-12-01

The appropriate algorithm for calibration set selection was one of the key technologies for a good NIR quantitative model. There are different algorithms for calibration set selection, such as Random Sampling (RS) algorithm, Conventional Selection (CS) algorithm, Kennard-Stone(KS) algorithm and Sample set Portioning based on joint x-y distance (SPXY) algorithm, et al. However, there lack systematic comparisons between two algorithms of the above algorithms. The NIR quantitative models to determine the asiaticoside content in Centella total glucosides were established in the present paper, of which 7 indexes were classified and selected, and the effects of CS algorithm, KS algorithm and SPXY algorithm for calibration set selection on the accuracy and robustness of NIR quantitative models were investigated. The accuracy indexes of NIR quantitative models with calibration set selected by SPXY algorithm were significantly different from that with calibration set selected by CS algorithm or KS algorithm, while the robustness indexes, such as RMSECV and |RMSEP-RMSEC|, were not significantly different. Therefore, SPXY algorithm for calibration set selection could improve the predicative accuracy of NIR quantitative models to determine asiaticoside content in Centella total glucosides, and have no significant effect on the robustness of the models, which provides a reference to determine the appropriate algorithm for calibration set selection when NIR quantitative models are established for the solid system of traditional Chinese medcine.

Methodological development for selection of significant predictors explaining fatal road accidents.

PubMed

Dadashova, Bahar; Arenas-Ramírez, Blanca; Mira-McWilliams, José; Aparicio-Izquierdo, Francisco

2016-05-01

Identification of the most relevant factors for explaining road accident occurrence is an important issue in road safety research, particularly for future decision-making processes in transport policy. However model selection for this particular purpose is still an ongoing research. In this paper we propose a methodological development for model selection which addresses both explanatory variable and adequate model selection issues. A variable selection procedure, TIM (two-input model) method is carried out by combining neural network design and statistical approaches. The error structure of the fitted model is assumed to follow an autoregressive process. All models are estimated using Markov Chain Monte Carlo method where the model parameters are assigned non-informative prior distributions. The final model is built using the results of the variable selection. For the application of the proposed methodology the number of fatal accidents in Spain during 2000-2011 was used. This indicator has experienced the maximum reduction internationally during the indicated years thus making it an interesting time series from a road safety policy perspective. Hence the identification of the variables that have affected this reduction is of particular interest for future decision making. The results of the variable selection process show that the selected variables are main subjects of road safety policy measures. Published by Elsevier Ltd.

A model of directional selection applied to the evolution of drug resistance in HIV-1.

PubMed

Seoighe, Cathal; Ketwaroo, Farahnaz; Pillay, Visva; Scheffler, Konrad; Wood, Natasha; Duffet, Rodger; Zvelebil, Marketa; Martinson, Neil; McIntyre, James; Morris, Lynn; Hide, Winston

2007-04-01

Understanding how pathogens acquire resistance to drugs is important for the design of treatment strategies, particularly for rapidly evolving viruses such as HIV-1. Drug treatment can exert strong selective pressures and sites within targeted genes that confer resistance frequently evolve far more rapidly than the neutral rate. Rapid evolution at sites that confer resistance to drugs can be used to help elucidate the mechanisms of evolution of drug resistance and to discover or corroborate novel resistance mutations. We have implemented standard maximum likelihood methods that are used to detect diversifying selection and adapted them for use with serially sampled reverse transcriptase (RT) coding sequences isolated from a group of 300 HIV-1 subtype C-infected women before and after single-dose nevirapine (sdNVP) to prevent mother-to-child transmission. We have also extended the standard models of codon evolution for application to the detection of directional selection. Through simulation, we show that the directional selection model can provide a substantial improvement in sensitivity over models of diversifying selection. Five of the sites within the RT gene that are known to harbor mutations that confer resistance to nevirapine (NVP) strongly supported the directional selection model. There was no evidence that other mutations that are known to confer NVP resistance were selected in this cohort. The directional selection model, applied to serially sampled sequences, also had more power than the diversifying selection model to detect selection resulting from factors other than drug resistance. Because inference of selection from serial samples is unlikely to be adversely affected by recombination, the methods we describe may have general applicability to the analysis of positive selection affecting recombining coding sequences when serially sampled data are available.

Cross-validation to select Bayesian hierarchical models in phylogenetics.

PubMed

Duchêne, Sebastián; Duchêne, David A; Di Giallonardo, Francesca; Eden, John-Sebastian; Geoghegan, Jemma L; Holt, Kathryn E; Ho, Simon Y W; Holmes, Edward C

2016-05-26

Recent developments in Bayesian phylogenetic models have increased the range of inferences that can be drawn from molecular sequence data. Accordingly, model selection has become an important component of phylogenetic analysis. Methods of model selection generally consider the likelihood of the data under the model in question. In the context of Bayesian phylogenetics, the most common approach involves estimating the marginal likelihood, which is typically done by integrating the likelihood across model parameters, weighted by the prior. Although this method is accurate, it is sensitive to the presence of improper priors. We explored an alternative approach based on cross-validation that is widely used in evolutionary analysis. This involves comparing models according to their predictive performance. We analysed simulated data and a range of viral and bacterial data sets using a cross-validation approach to compare a variety of molecular clock and demographic models. Our results show that cross-validation can be effective in distinguishing between strict- and relaxed-clock models and in identifying demographic models that allow growth in population size over time. In most of our empirical data analyses, the model selected using cross-validation was able to match that selected using marginal-likelihood estimation. The accuracy of cross-validation appears to improve with longer sequence data, particularly when distinguishing between relaxed-clock models. Cross-validation is a useful method for Bayesian phylogenetic model selection. This method can be readily implemented even when considering complex models where selecting an appropriate prior for all parameters may be difficult.

Equilibrium and nonequilibrium attractors for a discrete, selection-migration model

Treesearch

James F. Selgrade; James H. Roberds

2003-01-01

This study presents a discrete-time model for the effects of selection and immigration on the demographic and genetic compositions of a population. Under biologically reasonable conditions, it is shown that the model always has an equilibrium. Although equilibria for similar models without migration must have real eigenvalues, for this selection-migration model we...

Pleiotropic Models of Polygenic Variation, Stabilizing Selection, and Epistasis

PubMed Central

Gavrilets, S.; de-Jong, G.

1993-01-01

We show that in polymorphic populations many polygenic traits pleiotropically related to fitness are expected to be under apparent ``stabilizing selection'' independently of the real selection acting on the population. This occurs, for example, if the genetic system is at a stable polymorphic equilibrium determined by selection and the nonadditive contributions of the loci to the trait value either are absent, or are random and independent of those to fitness. Stabilizing selection is also observed if the polygenic system is at an equilibrium determined by a balance between selection and mutation (or migration) when both additive and nonadditive contributions of the loci to the trait value are random and independent of those to fitness. We also compare different viability models that can maintain genetic variability at many loci with respect to their ability to account for the strong stabilizing selection on an additive trait. Let V(m) be the genetic variance supplied by mutation (or migration) each generation, V(g) be the genotypic variance maintained in the population, and n be the number of the loci influencing fitness. We demonstrate that in mutation (migration)-selection balance models the strength of apparent stabilizing selection is order V(m)/V(g). In the overdominant model and in the symmetric viability model the strength of apparent stabilizing selection is approximately 1/(2n) that of total selection on the whole phenotype. We show that a selection system that involves pairwise additive by additive epistasis in maintaining variability can lead to a lower genetic load and genetic variance in fitness (approximately 1/(2n) times) than an equivalent selection system that involves overdominance. We show that, in the epistatic model, the apparent stabilizing selection on an additive trait can be as strong as the total selection on the whole phenotype. PMID:8325491

It Takes Three: Selection, Influence, and De-Selection Processes of Depression in Adolescent Friendship Networks

ERIC Educational Resources Information Center

Van Zalk, Maarten Herman Walter; Kerr, Margaret; Branje, Susan J. T.; Stattin, Hakan; Meeus, Wim H. J.

2010-01-01

The authors of this study tested a selection-influence-de-selection model of depression. This model explains friendship influence processes (i.e., friends' depressive symptoms increase adolescents' depressive symptoms) while controlling for two processes: friendship selection (i.e., selection of friends with similar levels of depressive symptoms)…

The Coalescent Process in Models with Selection

PubMed Central

Kaplan, N. L.; Darden, T.; Hudson, R. R.

1988-01-01

Statistical properties of the process describing the genealogical history of a random sample of genes are obtained for a class of population genetics models with selection. For models with selection, in contrast to models without selection, the distribution of this process, the coalescent process, depends on the distribution of the frequencies of alleles in the ancestral generations. If the ancestral frequency process can be approximated by a diffusion, then the mean and the variance of the number of segregating sites due to selectively neutral mutations in random samples can be numerically calculated. The calculations are greatly simplified if the frequencies of the alleles are tightly regulated. If the mutation rates between alleles maintained by balancing selection are low, then the number of selectively neutral segregating sites in a random sample of genes is expected to substantially exceed the number predicted under a neutral model. PMID:3066685

Using variable rate models to identify genes under selection in sequence pairs: their validity and limitations for EST sequences.

PubMed

Church, Sheri A; Livingstone, Kevin; Lai, Zhao; Kozik, Alexander; Knapp, Steven J; Michelmore, Richard W; Rieseberg, Loren H

2007-02-01

Using likelihood-based variable selection models, we determined if positive selection was acting on 523 EST sequence pairs from two lineages of sunflower and lettuce. Variable rate models are generally not used for comparisons of sequence pairs due to the limited information and the inaccuracy of estimates of specific substitution rates. However, previous studies have shown that the likelihood ratio test (LRT) is reliable for detecting positive selection, even with low numbers of sequences. These analyses identified 56 genes that show a signature of selection, of which 75% were not identified by simpler models that average selection across codons. Subsequent mapping studies in sunflower show four of five of the positively selected genes identified by these methods mapped to domestication QTLs. We discuss the validity and limitations of using variable rate models for comparisons of sequence pairs, as well as the limitations of using ESTs for identification of positively selected genes.

SU-F-R-10: Selecting the Optimal Solution for Multi-Objective Radiomics Model

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

Zhou, Z; Folkert, M; Wang, J

2016-06-15

Purpose: To develop an evidential reasoning approach for selecting the optimal solution from a Pareto solution set obtained by a multi-objective radiomics model for predicting distant failure in lung SBRT. Methods: In the multi-objective radiomics model, both sensitivity and specificity are considered as the objective functions simultaneously. A Pareto solution set with many feasible solutions will be resulted from the multi-objective optimization. In this work, an optimal solution Selection methodology for Multi-Objective radiomics Learning model using the Evidential Reasoning approach (SMOLER) was proposed to select the optimal solution from the Pareto solution set. The proposed SMOLER method used the evidentialmore » reasoning approach to calculate the utility of each solution based on pre-set optimal solution selection rules. The solution with the highest utility was chosen as the optimal solution. In SMOLER, an optimal learning model coupled with clonal selection algorithm was used to optimize model parameters. In this study, PET, CT image features and clinical parameters were utilized for predicting distant failure in lung SBRT. Results: Total 126 solution sets were generated by adjusting predictive model parameters. Each Pareto set contains 100 feasible solutions. The solution selected by SMOLER within each Pareto set was compared to the manually selected optimal solution. Five-cross-validation was used to evaluate the optimal solution selection accuracy of SMOLER. The selection accuracies for five folds were 80.00%, 69.23%, 84.00%, 84.00%, 80.00%, respectively. Conclusion: An optimal solution selection methodology for multi-objective radiomics learning model using the evidential reasoning approach (SMOLER) was proposed. Experimental results show that the optimal solution can be found in approximately 80% cases.« less

Increased prediction accuracy in wheat breeding trials using a marker x environment interaction genomic selection model

USDA-ARS?s Scientific Manuscript database

Genomic selection (GS) models use genome-wide genetic information to predict genetic values of candidates for selection. Originally these models were developed without considering genotype ' environment interaction (GE). Several authors have proposed extensions of the cannonical GS model that accomm...

The genealogy of sequences containing multiple sites subject to strong selection in a subdivided population.

PubMed Central

Nordborg, Magnus; Innan, Hideki

2003-01-01

A stochastic model for the genealogy of a sample of recombining sequences containing one or more sites subject to selection in a subdivided population is described. Selection is incorporated by dividing the population into allelic classes and then conditioning on the past sizes of these classes. The past allele frequencies at the selected sites are thus treated as parameters rather than as random variables. The purpose of the model is not to investigate the dynamics of selection, but to investigate effects of linkage to the selected sites on the genealogy of the surrounding chromosomal region. This approach is useful for modeling strong selection, when it is natural to parameterize the past allele frequencies at the selected sites. Several models of strong balancing selection are used as examples, and the effects on the pattern of neutral polymorphism in the chromosomal region are discussed. We focus in particular on the statistical power to detect balancing selection when it is present. PMID:12663556

The genealogy of sequences containing multiple sites subject to strong selection in a subdivided population.

PubMed

Nordborg, Magnus; Innan, Hideki

2003-03-01

A stochastic model for the genealogy of a sample of recombining sequences containing one or more sites subject to selection in a subdivided population is described. Selection is incorporated by dividing the population into allelic classes and then conditioning on the past sizes of these classes. The past allele frequencies at the selected sites are thus treated as parameters rather than as random variables. The purpose of the model is not to investigate the dynamics of selection, but to investigate effects of linkage to the selected sites on the genealogy of the surrounding chromosomal region. This approach is useful for modeling strong selection, when it is natural to parameterize the past allele frequencies at the selected sites. Several models of strong balancing selection are used as examples, and the effects on the pattern of neutral polymorphism in the chromosomal region are discussed. We focus in particular on the statistical power to detect balancing selection when it is present.

Signatures of positive selection: from selective sweeps at individual loci to subtle allele frequency changes in polygenic adaptation.

PubMed

Stephan, Wolfgang

2016-01-01

In the past 15 years, numerous methods have been developed to detect selective sweeps underlying adaptations. These methods are based on relatively simple population genetic models, including one or two loci at which positive directional selection occurs, and one or two marker loci at which the impact of selection on linked neutral variation is quantified. Information about the phenotype under selection is not included in these models (except for fitness). In contrast, in the quantitative genetic models of adaptation, selection acts on one or more phenotypic traits, such that a genotype-phenotype map is required to bridge the gap to population genetics theory. Here I describe the range of population genetic models from selective sweeps in a panmictic population of constant size to evolutionary traffic when simultaneous sweeps at multiple loci interfere, and I also consider the case of polygenic selection characterized by subtle allele frequency shifts at many loci. Furthermore, I present an overview of the statistical tests that have been proposed based on these population genetics models to detect evidence for positive selection in the genome. © 2015 John Wiley & Sons Ltd.

Adaptive Greedy Dictionary Selection for Web Media Summarization.

PubMed

Cong, Yang; Liu, Ji; Sun, Gan; You, Quanzeng; Li, Yuncheng; Luo, Jiebo

2017-01-01

Initializing an effective dictionary is an indispensable step for sparse representation. In this paper, we focus on the dictionary selection problem with the objective to select a compact subset of basis from original training data instead of learning a new dictionary matrix as dictionary learning models do. We first design a new dictionary selection model via l 2,0 norm. For model optimization, we propose two methods: one is the standard forward-backward greedy algorithm, which is not suitable for large-scale problems; the other is based on the gradient cues at each forward iteration and speeds up the process dramatically. In comparison with the state-of-the-art dictionary selection models, our model is not only more effective and efficient, but also can control the sparsity. To evaluate the performance of our new model, we select two practical web media summarization problems: 1) we build a new data set consisting of around 500 users, 3000 albums, and 1 million images, and achieve effective assisted albuming based on our model and 2) by formulating the video summarization problem as a dictionary selection issue, we employ our model to extract keyframes from a video sequence in a more flexible way. Generally, our model outperforms the state-of-the-art methods in both these two tasks.

Network models of frequency modulated sweep detection.

PubMed

Skorheim, Steven; Razak, Khaleel; Bazhenov, Maxim

2014-01-01

Frequency modulated (FM) sweeps are common in species-specific vocalizations, including human speech. Auditory neurons selective for the direction and rate of frequency change in FM sweeps are present across species, but the synaptic mechanisms underlying such selectivity are only beginning to be understood. Even less is known about mechanisms of experience-dependent changes in FM sweep selectivity. We present three network models of synaptic mechanisms of FM sweep direction and rate selectivity that explains experimental data: (1) The 'facilitation' model contains frequency selective cells operating as coincidence detectors, summing up multiple excitatory inputs with different time delays. (2) The 'duration tuned' model depends on interactions between delayed excitation and early inhibition. The strength of delayed excitation determines the preferred duration. Inhibitory rebound can reinforce the delayed excitation. (3) The 'inhibitory sideband' model uses frequency selective inputs to a network of excitatory and inhibitory cells. The strength and asymmetry of these connections results in neurons responsive to sweeps in a single direction of sufficient sweep rate. Variations of these properties, can explain the diversity of rate-dependent direction selectivity seen across species. We show that the inhibitory sideband model can be trained using spike timing dependent plasticity (STDP) to develop direction selectivity from a non-selective network. These models provide a means to compare the proposed synaptic and spectrotemporal mechanisms of FM sweep processing and can be utilized to explore cellular mechanisms underlying experience- or training-dependent changes in spectrotemporal processing across animal models. Given the analogy between FM sweeps and visual motion, these models can serve a broader function in studying stimulus movement across sensory epithelia.

Response to Selection in Finite Locus Models with Nonadditive Effects.

PubMed

Esfandyari, Hadi; Henryon, Mark; Berg, Peer; Thomasen, Jørn Rind; Bijma, Piter; Sørensen, Anders Christian

2017-05-01

Under the finite-locus model in the absence of mutation, the additive genetic variation is expected to decrease when directional selection is acting on a population, according to quantitative-genetic theory. However, some theoretical studies of selection suggest that the level of additive variance can be sustained or even increased when nonadditive genetic effects are present. We tested the hypothesis that finite-locus models with both additive and nonadditive genetic effects maintain more additive genetic variance (VA) and realize larger medium- to long-term genetic gains than models with only additive effects when the trait under selection is subject to truncation selection. Four genetic models that included additive, dominance, and additive-by-additive epistatic effects were simulated. The simulated genome for individuals consisted of 25 chromosomes, each with a length of 1 M. One hundred bi-allelic QTL, 4 on each chromosome, were considered. In each generation, 100 sires and 100 dams were mated, producing 5 progeny per mating. The population was selected for a single trait (h2 = 0.1) for 100 discrete generations with selection on phenotype or BLUP-EBV. VA decreased with directional truncation selection even in presence of nonadditive genetic effects. Nonadditive effects influenced long-term response to selection and among genetic models additive gene action had highest response to selection. In addition, in all genetic models, BLUP-EBV resulted in a greater fixation of favorable and unfavorable alleles and higher response than phenotypic selection. In conclusion, for the schemes we simulated, the presence of nonadditive genetic effects had little effect in changes of additive variance and VA decreased by directional selection. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adaptive Modeling Procedure Selection by Data Perturbation.

PubMed

Zhang, Yongli; Shen, Xiaotong

2015-10-01

Many procedures have been developed to deal with the high-dimensional problem that is emerging in various business and economics areas. To evaluate and compare these procedures, modeling uncertainty caused by model selection and parameter estimation has to be assessed and integrated into a modeling process. To do this, a data perturbation method estimates the modeling uncertainty inherited in a selection process by perturbing the data. Critical to data perturbation is the size of perturbation, as the perturbed data should resemble the original dataset. To account for the modeling uncertainty, we derive the optimal size of perturbation, which adapts to the data, the model space, and other relevant factors in the context of linear regression. On this basis, we develop an adaptive data-perturbation method that, unlike its nonadaptive counterpart, performs well in different situations. This leads to a data-adaptive model selection method. Both theoretical and numerical analysis suggest that the data-adaptive model selection method adapts to distinct situations in that it yields consistent model selection and optimal prediction, without knowing which situation exists a priori. The proposed method is applied to real data from the commodity market and outperforms its competitors in terms of price forecasting accuracy.

Estimation of selection intensity under overdominance by Bayesian methods.

PubMed

Buzbas, Erkan Ozge; Joyce, Paul; Abdo, Zaid

2009-01-01

A balanced pattern in the allele frequencies of polymorphic loci is a potential sign of selection, particularly of overdominance. Although this type of selection is of some interest in population genetics, there exists no likelihood based approaches specifically tailored to make inference on selection intensity. To fill this gap, we present Bayesian methods to estimate selection intensity under k-allele models with overdominance. Our model allows for an arbitrary number of loci and alleles within a locus. The neutral and selected variability within each locus are modeled with corresponding k-allele models. To estimate the posterior distribution of the mean selection intensity in a multilocus region, a hierarchical setup between loci is used. The methods are demonstrated with data at the Human Leukocyte Antigen loci from world-wide populations.

IRT Model Selection Methods for Dichotomous Items

ERIC Educational Resources Information Center

Kang, Taehoon; Cohen, Allan S.

2007-01-01

Fit of the model to the data is important if the benefits of item response theory (IRT) are to be obtained. In this study, the authors compared model selection results using the likelihood ratio test, two information-based criteria, and two Bayesian methods. An example illustrated the potential for inconsistency in model selection depending on…

On the selection of ordinary differential equation models with application to predator-prey dynamical models.

PubMed

Zhang, Xinyu; Cao, Jiguo; Carroll, Raymond J

2015-03-01

We consider model selection and estimation in a context where there are competing ordinary differential equation (ODE) models, and all the models are special cases of a "full" model. We propose a computationally inexpensive approach that employs statistical estimation of the full model, followed by a combination of a least squares approximation (LSA) and the adaptive Lasso. We show the resulting method, here called the LSA method, to be an (asymptotically) oracle model selection method. The finite sample performance of the proposed LSA method is investigated with Monte Carlo simulations, in which we examine the percentage of selecting true ODE models, the efficiency of the parameter estimation compared to simply using the full and true models, and coverage probabilities of the estimated confidence intervals for ODE parameters, all of which have satisfactory performances. Our method is also demonstrated by selecting the best predator-prey ODE to model a lynx and hare population dynamical system among some well-known and biologically interpretable ODE models. © 2014, The International Biometric Society.

Mixed conditional logistic regression for habitat selection studies.

PubMed

Duchesne, Thierry; Fortin, Daniel; Courbin, Nicolas

2010-05-01

1. Resource selection functions (RSFs) are becoming a dominant tool in habitat selection studies. RSF coefficients can be estimated with unconditional (standard) and conditional logistic regressions. While the advantage of mixed-effects models is recognized for standard logistic regression, mixed conditional logistic regression remains largely overlooked in ecological studies. 2. We demonstrate the significance of mixed conditional logistic regression for habitat selection studies. First, we use spatially explicit models to illustrate how mixed-effects RSFs can be useful in the presence of inter-individual heterogeneity in selection and when the assumption of independence from irrelevant alternatives (IIA) is violated. The IIA hypothesis states that the strength of preference for habitat type A over habitat type B does not depend on the other habitat types also available. Secondly, we demonstrate the significance of mixed-effects models to evaluate habitat selection of free-ranging bison Bison bison. 3. When movement rules were homogeneous among individuals and the IIA assumption was respected, fixed-effects RSFs adequately described habitat selection by simulated animals. In situations violating the inter-individual homogeneity and IIA assumptions, however, RSFs were best estimated with mixed-effects regressions, and fixed-effects models could even provide faulty conclusions. 4. Mixed-effects models indicate that bison did not select farmlands, but exhibited strong inter-individual variations in their response to farmlands. Less than half of the bison preferred farmlands over forests. Conversely, the fixed-effect model simply suggested an overall selection for farmlands. 5. Conditional logistic regression is recognized as a powerful approach to evaluate habitat selection when resource availability changes. This regression is increasingly used in ecological studies, but almost exclusively in the context of fixed-effects models. Fitness maximization can imply differences in trade-offs among individuals, which can yield inter-individual differences in selection and lead to departure from IIA. These situations are best modelled with mixed-effects models. Mixed-effects conditional logistic regression should become a valuable tool for ecological research.

A Technical Guide to Ground-Water Model Selection at Sites Contaminated with Radioactive Substances

EPA Pesticide Factsheets

This report addresses the selection of ground-water flow and contaminant transport models and is intended to be used by hydrogeologists and geoscientists responsible for selecting transport models for use at sites containing radioactive materials.

Quantification of model uncertainty in aerosol optical thickness retrieval from Ozone Monitoring Instrument (OMI) measurements

NASA Astrophysics Data System (ADS)

Määttä, A.; Laine, M.; Tamminen, J.; Veefkind, J. P.

2013-09-01

We study uncertainty quantification in remote sensing of aerosols in the atmosphere with top of the atmosphere reflectance measurements from the nadir-viewing Ozone Monitoring Instrument (OMI). Focus is on the uncertainty in aerosol model selection of pre-calculated aerosol models and on the statistical modelling of the model inadequacies. The aim is to apply statistical methodologies that improve the uncertainty estimates of the aerosol optical thickness (AOT) retrieval by propagating model selection and model error related uncertainties more realistically. We utilise Bayesian model selection and model averaging methods for the model selection problem and use Gaussian processes to model the smooth systematic discrepancies from the modelled to observed reflectance. The systematic model error is learned from an ensemble of operational retrievals. The operational OMI multi-wavelength aerosol retrieval algorithm OMAERO is used for cloud free, over land pixels of the OMI instrument with the additional Bayesian model selection and model discrepancy techniques. The method is demonstrated with four examples with different aerosol properties: weakly absorbing aerosols, forest fires over Greece and Russia, and Sahara dessert dust. The presented statistical methodology is general; it is not restricted to this particular satellite retrieval application.

Model Selection in Systems Biology Depends on Experimental Design

PubMed Central

Silk, Daniel; Kirk, Paul D. W.; Barnes, Chris P.; Toni, Tina; Stumpf, Michael P. H.

2014-01-01

Experimental design attempts to maximise the information available for modelling tasks. An optimal experiment allows the inferred models or parameters to be chosen with the highest expected degree of confidence. If the true system is faithfully reproduced by one of the models, the merit of this approach is clear - we simply wish to identify it and the true parameters with the most certainty. However, in the more realistic situation where all models are incorrect or incomplete, the interpretation of model selection outcomes and the role of experimental design needs to be examined more carefully. Using a novel experimental design and model selection framework for stochastic state-space models, we perform high-throughput in-silico analyses on families of gene regulatory cascade models, to show that the selected model can depend on the experiment performed. We observe that experimental design thus makes confidence a criterion for model choice, but that this does not necessarily correlate with a model's predictive power or correctness. Finally, in the special case of linear ordinary differential equation (ODE) models, we explore how wrong a model has to be before it influences the conclusions of a model selection analysis. PMID:24922483

Model selection in systems biology depends on experimental design.

PubMed

Silk, Daniel; Kirk, Paul D W; Barnes, Chris P; Toni, Tina; Stumpf, Michael P H

2014-06-01

Experimental design attempts to maximise the information available for modelling tasks. An optimal experiment allows the inferred models or parameters to be chosen with the highest expected degree of confidence. If the true system is faithfully reproduced by one of the models, the merit of this approach is clear - we simply wish to identify it and the true parameters with the most certainty. However, in the more realistic situation where all models are incorrect or incomplete, the interpretation of model selection outcomes and the role of experimental design needs to be examined more carefully. Using a novel experimental design and model selection framework for stochastic state-space models, we perform high-throughput in-silico analyses on families of gene regulatory cascade models, to show that the selected model can depend on the experiment performed. We observe that experimental design thus makes confidence a criterion for model choice, but that this does not necessarily correlate with a model's predictive power or correctness. Finally, in the special case of linear ordinary differential equation (ODE) models, we explore how wrong a model has to be before it influences the conclusions of a model selection analysis.

Analysis of antibiotic fungicide kasugamycin in irrigation water by high performance liquid chromatography.

PubMed

Sheu, Ceshing; Chen, Shu-Chuan; Lo, Chi-Chu

2010-07-01

A high performance liquid chromatographic (HPLC) analysis method with an ultraviolet (UV) detector and an Aqua C18 (250 x 4.6 mm, Phenomenex) column were applied to analyze the antibiotic fungicide kasugamycin in water. An aromatic sulfonic acid spe column (Backerbond, J. T. Backer) was used to remove the interfering materials from irrigation water. A good linear relation existed between the concentration of the fungicide and the peak area, and correlation coefficient of linearity from 0.1 to 10.2 microg/mL was 0.998. The accuracies expressed as the recoveries of kasugamycin from irrigation water ranged from 112.2 to 111.7 %. The precisions expressed as relative standard deviations (RSD) were found to be below 7.0 %. The quantitative detection limit (LOQ) of kasugamycin in irrigation water was set at 2.2 microg/mL which was 2-times higher than the method detection limit (MDL) 1.03 microg/mL. Electrospray ionization-mass (ESI-MS) and fast-atom bombardment-mass (FAB-MS) were applied to compare the ability of identifying the component of the eluent peak from HPLC, and the result indicated that electrospray ionization-mass (ESI-MS) was more sensitive than fast-atom bombardment-mass (FAB-MS) in the detection of kasugamycin. There was no kasugamycin residue detected in irrigation water samples collected from paddyfields at Wufong, indicated that the residues of kasugamycin in water were less than 2.2 microg/mL, and the risk of water contamination was very low.

Applications of open-path Fourier transform infrared for identification of volatile organic compound pollution sources and characterization of source emission behaviors.

PubMed

Lin, Chitsan; Liou, Naiwei; Sun, Endy

2008-06-01

An open-path Fourier transform infrared spectroscopy (OP-FTIR) system was set up for 3-day continuous line-averaged volatile organic compound (VOC) monitoring in a paint manufacturing plant. Seven VOCs (toluene, m-xylene, p-xylene, styrene, methanol, acetone, and 2-butanone) were identified in the ambient environment. Daytime-only batch operation mode was well explained by the time-series concentration plots. Major sources of methanol, m-xylene, acetone, and 2-butanone were identified in the southeast direction where paint solvent manufacturing processes are located. However, an attempt to uncover sources of styrene was not successful because the method detection limit (MDL) of the OP-FTIR system was not sensitive enough to produce conclusive data. In the second scenario, the OP-FTIR system was set up in an industrial complex to distinguish the origins of several VOCs. Eight major VOCs were identified in the ambient environment. The pollutant detected wind-rose percentage plots that clearly showed that ethylene, propylene, 2-butanone, and toluene mainly originated from the tank storage area, whereas the source of n-butane was mainly from the butadiene manufacturing processes of the refinery plant, and ammonia was identified as an accompanying reduction product in the gasoline desulfuration process. Advantages of OP-FTIR include its ability to simultaneously and continuously analyze many compounds, and its long path length monitoring has also shown advantages in obtaining more comprehensive data than the traditional multiple, single-point monitoring methods.

Occurrence and exposure assessment of organophosphate flame retardants (OPFRs) through the consumption of drinking water in Korea.

PubMed

Lee, Sunggyu; Jeong, Woochang; Kannan, Kurunthachalam; Moon, Hyo-Bang

2016-10-15

Organophosphate flame retardants (OPFRs) have been widely used as flame retardants and plasticizers in commercial products. Limited data are available on the occurrence and exposure of OPFRs via drinking water consumption. In this study, 127 drinking water samples were collected from tap water, purified water (tap water that is passed through in-house filters) and bottled water from major cities in Korea in 2014. The total concentrations of OPFRs (ΣOPFR) in all of the samples ranged from below the method detection limit (MDL) to 1660 (median: 48.7) ng/L. The predominant OPFR compounds in drinking water were tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroethyl) phosphate (TCPP), and tris(2-butoxyethyl) phosphate (TBEP). Significant differences were observed in the levels of TCPP, TBEP and ΣOPFR among various types of drinking water. TCPP is introduced in the drinking water during the water purification process. Regional differences existed in the levels and patterns of OPFRs in water samples, which indicated the existence of diverse sources of these contaminants. Purified water was a significant contributor to the total OPFR intake by humans. The estimated daily intake of OPFRs was lower than the tentative oral reference dose (RfD) values. In comparison with exposure of OPFRs via dust ingestion, water consumption was a significant source of chlorinated PFRs (99% for TCEP and 34% for TCPP to the total intakes) for Koreans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dosimetry study for a new in vivo X-ray fluorescence (XRF) bone lead measurement system

NASA Astrophysics Data System (ADS)

Nie, Huiling; Chettle, David; Luo, Liqiang; O'Meara, Joanne

2007-10-01

A new 109Cd γ-ray induced bone lead measurement system has been developed to reduce the minimum detectable limit (MDL) of the system. The system consists of four 16 mm diameter detectors. It requires a stronger source compared to the "conventional" system. A dosimetry study has been performed to estimate the dose delivered by this system. The study was carried out by using human-equivalent phantoms. Three sets of phantoms were made to estimate the dose delivered to three age groups: 5-year old, 10-year old and adults. Three approaches have been applied to evaluate the dose: calculations, Monte Carlo (MC) simulations, and experiments. Experimental results and analytical calculations were used to validate MC simulation. The experiments were performed by placing Panasonic UD-803AS TLDs at different places in phantoms that representing different organs. Due to the difficulty of obtaining the organ dose and the whole body dose solely by experiments and traditional calculations, the equivalent dose and effective dose were calculated by MC simulations. The result showed that the doses delivered to the organs other than the targeted lower leg are negligibly small. The total effective doses to the three age groups are 8.45/9.37 μSv (female/male), 4.20 μSv, and 0.26 μSv for 5-year old, 10-year old and adult, respectively. An approval to conduct human measurements on this system has been received from the Research Ethics Board based on this research.

Activation of proteolytic enzymes and depression of the sarcolemmal Na+/K+-ATPase in ischemia-reperfused heart may be mediated through oxidative stress.

PubMed

Singh, Raja B; Hryshko, Larry; Freed, Darren; Dhalla, Naranjan S

2012-02-01

We tested whether the activation of proteolytic enzymes, calpain, and matrix metalloproteinases (MMPs) during ischemia-reperfusion (I/R) is mediated through oxidative stress. For this purpose, isolated rat hearts were subjected to a 30 min global ischemia followed by a 30 min reperfusion. Cardiac function was monitored and the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, calpain, and MMP were measured. Depression of cardiac function and Na(+)/K(+)-ATPase activity in I/R hearts was associated with increased calpain and MMP activities. These alterations owing to I/R were similar to those observed in hearts perfused with hypoxic medium, H(2)O(2) and xanthine plus xanthine oxidase. The I/R-induced changes were attenuated by ischemic preconditioning as well as by perfusing the hearts with N-acetylcysteine or mercaptopropionylglycine. Inhibition of MMP activity in hearts treated with doxycycline depressed the I/R-induced changes in cardiac function and Na(+)/K(+)-ATPase activity without affecting the calpain activation. On the other hand, inhibition of calpain activity upon treatment with leupeptin or MDL 28170 significantly reduced the MMP activity in addition to attenuating the I/R-induced alterations in cardiac function and Na(+)/K(+)-ATPase activity. These results suggest that the I/R-induced depression in Na(+)/K(+)-ATPase and cardiac function may be a consequence of the increased activities of both calpain and MMP because of oxidative stress in the heart.

Differential role of calpain-dependent protein cleavage in intermediate and long-term operant memory in Aplysia.

PubMed

Lyons, Lisa C; Gardner, Jacob S; Lentsch, Cassidy T; Gandour, Catherine E; Krishnan, Harini C; Noakes, Eric J

2017-01-01

In addition to protein synthesis, protein degradation or protein cleavage may be necessary for intermediate (ITM) and long-term memory (LTM) to remove molecular constraints, facilitate persistent kinase activity and modulate synaptic plasticity. Calpains, a family of conserved calcium dependent cysteine proteases, modulate synaptic function through protein cleavage. We used the marine mollusk Aplysia californica to investigate the in vivo role of calpains during intermediate and long-term operant memory formation using the learning that food is inedible (LFI) paradigm. A single LFI training session, in which the animal associates a specific netted seaweed with the failure to swallow, generates short (30min), intermediate (4-6h) and long-term (24h) memory. Using the calpain inhibitors calpeptin and MDL-28170, we found that ITM requires calpain activity for induction and consolidation similar to the previously reported requirements for persistent protein kinase C activity in intermediate-term LFI memory. The induction of LTM also required calpain activity. In contrast to ITM, calpain activity was not necessary for the molecular consolidation of LTM. Surprisingly, six hours after LFI training we found that calpain activity was necessary for LTM, although this is a time at which neither persistent PKC activity nor protein synthesis is required for the maintenance of long-term LFI memory. These results demonstrate that calpains function in multiple roles in vivo during associative memory formation. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Physical Methods of Lymphatic Drainage on Postexercise Recovery of Mixed Martial Arts Athletes.

PubMed

Zebrowska, Aleksandra; Trybulski, Robert; Roczniok, Robert; Marcol, Wieslaw

2017-08-16

Physical methods are reported to be important for accelerating skeletal muscle regeneration, decreasing muscle soreness, and shortening of the recovery time. The aim of the study was to assess the effect of the physical methods of lymphatic drainage (PMLD) such as manual lymphatic drainage (MLD), the Bodyflow (BF) therapy, and lymphatic drainage by deep oscillation (DO) on postexercise regeneration of the forearm muscles of mixed martial arts (MMA) athletes. Eighty MMA athletes aged 27.5 ± 6.4 years were allocated to 4 groups: MLD, the BF device, DO therapy, and the control group. Blood flow velocity in the cephalic vein was measured with the ultrasound Doppler velocity meter. Maximal strength of the forearm muscles (Fmax), muscle tissue tension, pain threshold, blood lactate concentration (LA), and activity of creatine kinase were measured in all groups at rest, after the muscle fatigue test (post-ex) and then 20 minutes, 24, and 48 hours after the application of PMLD. The muscle fatigue test reduced Fmax in all subjects, but in the groups receiving MLD, DO, and BF significantly higher Fmax was observed at recovery compared with post-ex values. The application of MDL reduced the postexercise blood LA and postexercise muscle tension. The lymphatic drainage methods, whether manual or using electro-stimulation and DO, improve postexercise regeneration of the forearm muscles of MMA athletes. The methods can be an important element of therapeutic management focused on optimizing training effects and reducing the risk of injuries of the combat sports athletes.

Comparison of the NCI open database with seven large chemical structural databases.

PubMed

Voigt, J H; Bienfait, B; Wang, S; Nicklaus, M C

2001-01-01

Eight large chemical databases have been analyzed and compared to each other. Central to this comparison is the open National Cancer Institute (NCI) database, consisting of approximately 250 000 structures. The other databases analyzed are the Available Chemicals Directory ("ACD," from MDL, release 1.99, 3D-version); the ChemACX ("ACX," from CamSoft, Version 4.5); the Maybridge Catalog and the Asinex database (both as distributed by CamSoft as part of ChemInfo 4.5); the Sigma-Aldrich Catalog (CD-ROM, 1999 Version); the World Drug Index ("WDI," Derwent, version 1999.03); and the organic part of the Cambridge Crystallographic Database ("CSD," from Cambridge Crystallographic Data Center, 1999 Version 5.18). The database properties analyzed are internal duplication rates; compounds unique to each database; cumulative occurrence of compounds in an increasing number of databases; overlap of identical compounds between two databases; similarity overlap; diversity; and others. The crystallographic database CSD and the WDI show somewhat less overlap with the other databases than those with each other. In particular the collections of commercial compounds and compilations of vendor catalogs have a substantial degree of overlap among each other. Still, no database is completely a subset of any other, and each appears to have its own niche and thus "raison d'être". The NCI database has by far the highest number of compounds that are unique to it. Approximately 200 000 of the NCI structures were not found in any of the other analyzed databases.

Condorcet and borda count fusion method for ligand-based virtual screening.

PubMed

Ahmed, Ali; Saeed, Faisal; Salim, Naomie; Abdo, Ammar

2014-01-01

It is known that any individual similarity measure will not always give the best recall of active molecule structure for all types of activity classes. Recently, the effectiveness of ligand-based virtual screening approaches can be enhanced by using data fusion. Data fusion can be implemented using two different approaches: group fusion and similarity fusion. Similarity fusion involves searching using multiple similarity measures. The similarity scores, or ranking, for each similarity measure are combined to obtain the final ranking of the compounds in the database. The Condorcet fusion method was examined. This approach combines the outputs of similarity searches from eleven association and distance similarity coefficients, and then the winner measure for each class of molecules, based on Condorcet fusion, was chosen to be the best method of searching. The recall of retrieved active molecules at top 5% and significant test are used to evaluate our proposed method. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints. Simulated virtual screening experiments with the standard two data sets show that the use of Condorcet fusion provides a very simple way of improving the ligand-based virtual screening, especially when the active molecules being sought have a lowest degree of structural heterogeneity. However, the effectiveness of the Condorcet fusion was increased slightly when structural sets of high diversity activities were being sought.

Condorcet and borda count fusion method for ligand-based virtual screening

PubMed Central

2014-01-01

Background It is known that any individual similarity measure will not always give the best recall of active molecule structure for all types of activity classes. Recently, the effectiveness of ligand-based virtual screening approaches can be enhanced by using data fusion. Data fusion can be implemented using two different approaches: group fusion and similarity fusion. Similarity fusion involves searching using multiple similarity measures. The similarity scores, or ranking, for each similarity measure are combined to obtain the final ranking of the compounds in the database. Results The Condorcet fusion method was examined. This approach combines the outputs of similarity searches from eleven association and distance similarity coefficients, and then the winner measure for each class of molecules, based on Condorcet fusion, was chosen to be the best method of searching. The recall of retrieved active molecules at top 5% and significant test are used to evaluate our proposed method. The MDL drug data report (MDDR), maximum unbiased validation (MUV) and Directory of Useful Decoys (DUD) data sets were used for experiments and were represented by 2D fingerprints. Conclusions Simulated virtual screening experiments with the standard two data sets show that the use of Condorcet fusion provides a very simple way of improving the ligand-based virtual screening, especially when the active molecules being sought have a lowest degree of structural heterogeneity. However, the effectiveness of the Condorcet fusion was increased slightly when structural sets of high diversity activities were being sought. PMID:24883114

Model Selection for Monitoring CO2 Plume during Sequestration

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

2014-12-31

The model selection method developed as part of this project mainly includes four steps: (1) assessing the connectivity/dynamic characteristics of a large prior ensemble of models, (2) model clustering using multidimensional scaling coupled with k-mean clustering, (3) model selection using the Bayes' rule in the reduced model space, (4) model expansion using iterative resampling of the posterior models. The fourth step expresses one of the advantages of the method: it provides a built-in means of quantifying the uncertainty in predictions made with the selected models. In our application to plume monitoring, by expanding the posterior space of models, the finalmore » ensemble of representations of geological model can be used to assess the uncertainty in predicting the future displacement of the CO2 plume. The software implementation of this approach is attached here.« less

Genomic selection of purebred animals for crossbred performance in the presence of dominant gene action

PubMed Central

2013-01-01

Background Genomic selection is an appealing method to select purebreds for crossbred performance. In the case of crossbred records, single nucleotide polymorphism (SNP) effects can be estimated using an additive model or a breed-specific allele model. In most studies, additive gene action is assumed. However, dominance is the likely genetic basis of heterosis. Advantages of incorporating dominance in genomic selection were investigated in a two-way crossbreeding program for a trait with different magnitudes of dominance. Training was carried out only once in the simulation. Results When the dominance variance and heterosis were large and overdominance was present, a dominance model including both additive and dominance SNP effects gave substantially greater cumulative response to selection than the additive model. Extra response was the result of an increase in heterosis but at a cost of reduced purebred performance. When the dominance variance and heterosis were realistic but with overdominance, the advantage of the dominance model decreased but was still significant. When overdominance was absent, the dominance model was slightly favored over the additive model, but the difference in response between the models increased as the number of quantitative trait loci increased. This reveals the importance of exploiting dominance even in the absence of overdominance. When there was no dominance, response to selection for the dominance model was as high as for the additive model, indicating robustness of the dominance model. The breed-specific allele model was inferior to the dominance model in all cases and to the additive model except when the dominance variance and heterosis were large and with overdominance. However, the advantage of the dominance model over the breed-specific allele model may decrease as differences in linkage disequilibrium between the breeds increase. Retraining is expected to reduce the advantage of the dominance model over the alternatives, because in general, the advantage becomes important only after five or six generations post-training. Conclusion Under dominance and without retraining, genomic selection based on the dominance model is superior to the additive model and the breed-specific allele model to maximize crossbred performance through purebred selection. PMID:23621868

Bayesian cross-validation for model evaluation and selection, with application to the North American Breeding Bird Survey

USGS Publications Warehouse

Link, William; Sauer, John R.

2016-01-01

The analysis of ecological data has changed in two important ways over the last 15 years. The development and easy availability of Bayesian computational methods has allowed and encouraged the fitting of complex hierarchical models. At the same time, there has been increasing emphasis on acknowledging and accounting for model uncertainty. Unfortunately, the ability to fit complex models has outstripped the development of tools for model selection and model evaluation: familiar model selection tools such as Akaike's information criterion and the deviance information criterion are widely known to be inadequate for hierarchical models. In addition, little attention has been paid to the evaluation of model adequacy in context of hierarchical modeling, i.e., to the evaluation of fit for a single model. In this paper, we describe Bayesian cross-validation, which provides tools for model selection and evaluation. We describe the Bayesian predictive information criterion and a Bayesian approximation to the BPIC known as the Watanabe-Akaike information criterion. We illustrate the use of these tools for model selection, and the use of Bayesian cross-validation as a tool for model evaluation, using three large data sets from the North American Breeding Bird Survey.

VARIABLE SELECTION FOR REGRESSION MODELS WITH MISSING DATA

PubMed Central

Garcia, Ramon I.; Ibrahim, Joseph G.; Zhu, Hongtu

2009-01-01

We consider the variable selection problem for a class of statistical models with missing data, including missing covariate and/or response data. We investigate the smoothly clipped absolute deviation penalty (SCAD) and adaptive LASSO and propose a unified model selection and estimation procedure for use in the presence of missing data. We develop a computationally attractive algorithm for simultaneously optimizing the penalized likelihood function and estimating the penalty parameters. Particularly, we propose to use a model selection criterion, called the ICQ statistic, for selecting the penalty parameters. We show that the variable selection procedure based on ICQ automatically and consistently selects the important covariates and leads to efficient estimates with oracle properties. The methodology is very general and can be applied to numerous situations involving missing data, from covariates missing at random in arbitrary regression models to nonignorably missing longitudinal responses and/or covariates. Simulations are given to demonstrate the methodology and examine the finite sample performance of the variable selection procedures. Melanoma data from a cancer clinical trial is presented to illustrate the proposed methodology. PMID:20336190

Hebbian Learning in a Random Network Captures Selectivity Properties of the Prefrontal Cortex.

PubMed

Lindsay, Grace W; Rigotti, Mattia; Warden, Melissa R; Miller, Earl K; Fusi, Stefano

2017-11-08

Complex cognitive behaviors, such as context-switching and rule-following, are thought to be supported by the prefrontal cortex (PFC). Neural activity in the PFC must thus be specialized to specific tasks while retaining flexibility. Nonlinear "mixed" selectivity is an important neurophysiological trait for enabling complex and context-dependent behaviors. Here we investigate (1) the extent to which the PFC exhibits computationally relevant properties, such as mixed selectivity, and (2) how such properties could arise via circuit mechanisms. We show that PFC cells recorded from male and female rhesus macaques during a complex task show a moderate level of specialization and structure that is not replicated by a model wherein cells receive random feedforward inputs. While random connectivity can be effective at generating mixed selectivity, the data show significantly more mixed selectivity than predicted by a model with otherwise matched parameters. A simple Hebbian learning rule applied to the random connectivity, however, increases mixed selectivity and enables the model to match the data more accurately. To explain how learning achieves this, we provide analysis along with a clear geometric interpretation of the impact of learning on selectivity. After learning, the model also matches the data on measures of noise, response density, clustering, and the distribution of selectivities. Of two styles of Hebbian learning tested, the simpler and more biologically plausible option better matches the data. These modeling results provide clues about how neural properties important for cognition can arise in a circuit and make clear experimental predictions regarding how various measures of selectivity would evolve during animal training. SIGNIFICANCE STATEMENT The prefrontal cortex is a brain region believed to support the ability of animals to engage in complex behavior. How neurons in this area respond to stimuli-and in particular, to combinations of stimuli ("mixed selectivity")-is a topic of interest. Even though models with random feedforward connectivity are capable of creating computationally relevant mixed selectivity, such a model does not match the levels of mixed selectivity seen in the data analyzed in this study. Adding simple Hebbian learning to the model increases mixed selectivity to the correct level and makes the model match the data on several other relevant measures. This study thus offers predictions on how mixed selectivity and other properties evolve with training. Copyright © 2017 the authors 0270-6474/17/3711021-16$15.00/0.

Selecting climate change scenarios for regional hydrologic impact studies based on climate extremes indices

NASA Astrophysics Data System (ADS)

Seo, Seung Beom; Kim, Young-Oh; Kim, Youngil; Eum, Hyung-Il

2018-04-01

When selecting a subset of climate change scenarios (GCM models), the priority is to ensure that the subset reflects the comprehensive range of possible model results for all variables concerned. Though many studies have attempted to improve the scenario selection, there is a lack of studies that discuss methods to ensure that the results from a subset of climate models contain the same range of uncertainty in hydrologic variables as when all models are considered. We applied the Katsavounidis-Kuo-Zhang (KKZ) algorithm to select a subset of climate change scenarios and demonstrated its ability to reduce the number of GCM models in an ensemble, while the ranges of multiple climate extremes indices were preserved. First, we analyzed the role of 27 ETCCDI climate extremes indices for scenario selection and selected the representative climate extreme indices. Before the selection of a subset, we excluded a few deficient GCM models that could not represent the observed climate regime. Subsequently, we discovered that a subset of GCM models selected by the KKZ algorithm with the representative climate extreme indices could not capture the full potential range of changes in hydrologic extremes (e.g., 3-day peak flow and 7-day low flow) in some regional case studies. However, the application of the KKZ algorithm with a different set of climate indices, which are correlated to the hydrologic extremes, enabled the overcoming of this limitation. Key climate indices, dependent on the hydrologic extremes to be projected, must therefore be determined prior to the selection of a subset of GCM models.

One- and two-objective approaches to an area-constrained habitat reserve site selection problem

Treesearch

Stephanie Snyder; Charles ReVelle; Robert Haight

2004-01-01

We compare several ways to model a habitat reserve site selection problem in which an upper bound on the total area of the selected sites is included. The models are cast as optimization coverage models drawn from the location science literature. Classic covering problems typically include a constraint on the number of sites that can be selected. If potential reserve...

Selective Cooperation in Early Childhood – How to Choose Models and Partners

PubMed Central

Hermes, Jonas; Behne, Tanya; Studte, Kristin; Zeyen, Anna-Maria; Gräfenhain, Maria; Rakoczy, Hannes

2016-01-01

Cooperation is essential for human society, and children engage in cooperation from early on. It is unclear, however, how children select their partners for cooperation. We know that children choose selectively whom to learn from (e.g. preferring reliable over unreliable models) on a rational basis. The present study investigated whether children (and adults) also choose their cooperative partners selectively and what model characteristics they regard as important for cooperative partners and for informants about novel words. Three- and four-year-old children (N = 64) and adults (N = 14) saw contrasting pairs of models differing either in physical strength or in accuracy (in labeling known objects). Participants then performed different tasks (cooperative problem solving and word learning) requiring the choice of a partner or informant. Both children and adults chose their cooperative partners selectively. Moreover they showed the same pattern of selective model choice, regarding a wide range of model characteristics as important for cooperation (preferring both the strong and the accurate model for a strength-requiring cooperation tasks), but only prior knowledge as important for word learning (preferring the knowledgeable but not the strong model for word learning tasks). Young children’s selective model choice thus reveals an early rational competence: They infer characteristics from past behavior and flexibly consider what characteristics are relevant for certain tasks. PMID:27505043

Population genetics of polymorphism and divergence for diploid selection models with arbitrary dominance.

PubMed

Williamson, Scott; Fledel-Alon, Adi; Bustamante, Carlos D

2004-09-01

We develop a Poisson random-field model of polymorphism and divergence that allows arbitrary dominance relations in a diploid context. This model provides a maximum-likelihood framework for estimating both selection and dominance parameters of new mutations using information on the frequency spectrum of sequence polymorphisms. This is the first DNA sequence-based estimator of the dominance parameter. Our model also leads to a likelihood-ratio test for distinguishing nongenic from genic selection; simulations indicate that this test is quite powerful when a large number of segregating sites are available. We also use simulations to explore the bias in selection parameter estimates caused by unacknowledged dominance relations. When inference is based on the frequency spectrum of polymorphisms, genic selection estimates of the selection parameter can be very strongly biased even for minor deviations from the genic selection model. Surprisingly, however, when inference is based on polymorphism and divergence (McDonald-Kreitman) data, genic selection estimates of the selection parameter are nearly unbiased, even for completely dominant or recessive mutations. Further, we find that weak overdominant selection can increase, rather than decrease, the substitution rate relative to levels of polymorphism. This nonintuitive result has major implications for the interpretation of several popular tests of neutrality.

Dendrites Enable a Robust Mechanism for Neuronal Stimulus Selectivity.

PubMed

Cazé, Romain D; Jarvis, Sarah; Foust, Amanda J; Schultz, Simon R

2017-09-01

Hearing, vision, touch: underlying all of these senses is stimulus selectivity, a robust information processing operation in which cortical neurons respond more to some stimuli than to others. Previous models assume that these neurons receive the highest weighted input from an ensemble encoding the preferred stimulus, but dendrites enable other possibilities. Nonlinear dendritic processing can produce stimulus selectivity based on the spatial distribution of synapses, even if the total preferred stimulus weight does not exceed that of nonpreferred stimuli. Using a multi-subunit nonlinear model, we demonstrate that stimulus selectivity can arise from the spatial distribution of synapses. We propose this as a general mechanism for information processing by neurons possessing dendritic trees. Moreover, we show that this implementation of stimulus selectivity increases the neuron's robustness to synaptic and dendritic failure. Importantly, our model can maintain stimulus selectivity for a larger range of loss of synapses or dendrites than an equivalent linear model. We then use a layer 2/3 biophysical neuron model to show that our implementation is consistent with two recent experimental observations: (1) one can observe a mixture of selectivities in dendrites that can differ from the somatic selectivity, and (2) hyperpolarization can broaden somatic tuning without affecting dendritic tuning. Our model predicts that an initially nonselective neuron can become selective when depolarized. In addition to motivating new experiments, the model's increased robustness to synapses and dendrites loss provides a starting point for fault-resistant neuromorphic chip development.

Variable selection and model choice in geoadditive regression models.

PubMed

Kneib, Thomas; Hothorn, Torsten; Tutz, Gerhard

2009-06-01

Model choice and variable selection are issues of major concern in practical regression analyses, arising in many biometric applications such as habitat suitability analyses, where the aim is to identify the influence of potentially many environmental conditions on certain species. We describe regression models for breeding bird communities that facilitate both model choice and variable selection, by a boosting algorithm that works within a class of geoadditive regression models comprising spatial effects, nonparametric effects of continuous covariates, interaction surfaces, and varying coefficients. The major modeling components are penalized splines and their bivariate tensor product extensions. All smooth model terms are represented as the sum of a parametric component and a smooth component with one degree of freedom to obtain a fair comparison between the model terms. A generic representation of the geoadditive model allows us to devise a general boosting algorithm that automatically performs model choice and variable selection.

Selective complexation of K+ and Na+ in simple polarizable ion-ligating systems.

PubMed

Bostick, David L; Brooks, Charles L

2010-09-29

An influx of experimental and theoretical studies of ion transport protein structure has inspired efforts to understand underlying determinants of ionic selectivity. Design principles for selective ion binding can be effectively isolated and interrogated using simplified models composed of a single ion surrounded by a set of ion-ligating molecular species. While quantum mechanical treatments of such systems naturally incorporate electronic degrees of freedom, their computational overhead typically prohibits thorough dynamic sampling of configurational space and, thus, requires approximations when determining ion-selective free energy. As an alternative, we employ dynamical simulations with a polarizable force field to probe the structure and K(+)/Na(+) selectivity in simple models composed of one central K(+)/Na(+) ion surrounded by 0-8 identical model compounds: N-methylacetamide, formamide, or water. In the absence of external restraints, these models represent gas-phase clusters displaying relaxed coordination structures with low coordination number. Such systems display Na(+) selectivity when composed of more than ∼3 organic carbonyl-containing compounds and always display K(+) selectivity when composed of water molecules. Upon imposing restraints that solely enforce specific coordination numbers, we find all models are K(+)-selective when ∼7-8-fold ion coordination is achieved. However, when models composed of the organic compounds provide ∼4-6-fold coordination, they retain their Na(+) selectivity. From these trends, design principles emerge that are of basic importance in the behavior of K(+) channel selectivity filters and suggest a basis not only for K(+) selectivity but also for modulation of block and closure by smaller ions.

Assessing the accuracy and stability of variable selection methods for random forest modeling in ecology.

PubMed

Fox, Eric W; Hill, Ryan A; Leibowitz, Scott G; Olsen, Anthony R; Thornbrugh, Darren J; Weber, Marc H

2017-07-01

Random forest (RF) modeling has emerged as an important statistical learning method in ecology due to its exceptional predictive performance. However, for large and complex ecological data sets, there is limited guidance on variable selection methods for RF modeling. Typically, either a preselected set of predictor variables are used or stepwise procedures are employed which iteratively remove variables according to their importance measures. This paper investigates the application of variable selection methods to RF models for predicting probable biological stream condition. Our motivating data set consists of the good/poor condition of n = 1365 stream survey sites from the 2008/2009 National Rivers and Stream Assessment, and a large set (p = 212) of landscape features from the StreamCat data set as potential predictors. We compare two types of RF models: a full variable set model with all 212 predictors and a reduced variable set model selected using a backward elimination approach. We assess model accuracy using RF's internal out-of-bag estimate, and a cross-validation procedure with validation folds external to the variable selection process. We also assess the stability of the spatial predictions generated by the RF models to changes in the number of predictors and argue that model selection needs to consider both accuracy and stability. The results suggest that RF modeling is robust to the inclusion of many variables of moderate to low importance. We found no substantial improvement in cross-validated accuracy as a result of variable reduction. Moreover, the backward elimination procedure tended to select too few variables and exhibited numerous issues such as upwardly biased out-of-bag accuracy estimates and instabilities in the spatial predictions. We use simulations to further support and generalize results from the analysis of real data. A main purpose of this work is to elucidate issues of model selection bias and instability to ecologists interested in using RF to develop predictive models with large environmental data sets.

A guide to Bayesian model selection for ecologists

USGS Publications Warehouse

Hooten, Mevin B.; Hobbs, N.T.

2015-01-01

The steady upward trend in the use of model selection and Bayesian methods in ecological research has made it clear that both approaches to inference are important for modern analysis of models and data. However, in teaching Bayesian methods and in working with our research colleagues, we have noticed a general dissatisfaction with the available literature on Bayesian model selection and multimodel inference. Students and researchers new to Bayesian methods quickly find that the published advice on model selection is often preferential in its treatment of options for analysis, frequently advocating one particular method above others. The recent appearance of many articles and textbooks on Bayesian modeling has provided welcome background on relevant approaches to model selection in the Bayesian framework, but most of these are either very narrowly focused in scope or inaccessible to ecologists. Moreover, the methodological details of Bayesian model selection approaches are spread thinly throughout the literature, appearing in journals from many different fields. Our aim with this guide is to condense the large body of literature on Bayesian approaches to model selection and multimodel inference and present it specifically for quantitative ecologists as neutrally as possible. We also bring to light a few important and fundamental concepts relating directly to model selection that seem to have gone unnoticed in the ecological literature. Throughout, we provide only a minimal discussion of philosophy, preferring instead to examine the breadth of approaches as well as their practical advantages and disadvantages. This guide serves as a reference for ecologists using Bayesian methods, so that they can better understand their options and can make an informed choice that is best aligned with their goals for inference.

Procedure for the Selection and Validation of a Calibration Model I-Description and Application.

PubMed

Desharnais, Brigitte; Camirand-Lemyre, Félix; Mireault, Pascal; Skinner, Cameron D

2017-05-01

Calibration model selection is required for all quantitative methods in toxicology and more broadly in bioanalysis. This typically involves selecting the equation order (quadratic or linear) and weighting factor correctly modelizing the data. A mis-selection of the calibration model will generate lower quality control (QC) accuracy, with an error up to 154%. Unfortunately, simple tools to perform this selection and tests to validate the resulting model are lacking. We present a stepwise, analyst-independent scheme for selection and validation of calibration models. The success rate of this scheme is on average 40% higher than a traditional "fit and check the QCs accuracy" method of selecting the calibration model. Moreover, the process was completely automated through a script (available in Supplemental Data 3) running in RStudio (free, open-source software). The need for weighting was assessed through an F-test using the variances of the upper limit of quantification and lower limit of quantification replicate measurements. When weighting was required, the choice between 1/x and 1/x2 was determined by calculating which option generated the smallest spread of weighted normalized variances. Finally, model order was selected through a partial F-test. The chosen calibration model was validated through Cramer-von Mises or Kolmogorov-Smirnov normality testing of the standardized residuals. Performance of the different tests was assessed using 50 simulated data sets per possible calibration model (e.g., linear-no weight, quadratic-no weight, linear-1/x, etc.). This first of two papers describes the tests, procedures and outcomes of the developed procedure using real LC-MS-MS results for the quantification of cocaine and naltrexone. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Lande-Kirkpatrick mechanism is the null model of evolution by intersexual selection: implications for meaning, honesty, and design in intersexual signals.

PubMed

Prum, Richard O

2010-11-01

The Fisher-inspired, arbitrary intersexual selection models of Lande (1981) and Kirkpatrick (1982), including both stable and unstable equilibrium conditions, provide the appropriate null model for the evolution of traits and preferences by intersexual selection. Like the Hardy–Weinberg equilibrium, the Lande–Kirkpatrick (LK) mechanism arises as an intrinsic consequence of genetic variation in trait and preference in the absence of other evolutionary forces. The LK mechanism is equivalent to other intersexual selection mechanisms in the absence of additional selection on preference and with additional trait-viability and preference-viability correlations equal to zero. The LK null model predicts the evolution of arbitrary display traits that are neither honest nor dishonest, indicate nothing other than mating availability, and lack any meaning or design other than their potential to correspond to mating preferences. The current standard for demonstrating an arbitrary trait is impossible to meet because it requires proof of the null hypothesis. The LK null model makes distinct predictions about the evolvability of traits and preferences. Examples of recent intersexual selection research document the confirmationist pitfalls of lacking a null model. Incorporation of the LK null into intersexual selection will contribute to serious examination of the extent to which natural selection on preferences shapes signals.

Hebbian Learning in a Random Network Captures Selectivity Properties of the Prefrontal Cortex

PubMed Central

Lindsay, Grace W.

2017-01-01

Complex cognitive behaviors, such as context-switching and rule-following, are thought to be supported by the prefrontal cortex (PFC). Neural activity in the PFC must thus be specialized to specific tasks while retaining flexibility. Nonlinear “mixed” selectivity is an important neurophysiological trait for enabling complex and context-dependent behaviors. Here we investigate (1) the extent to which the PFC exhibits computationally relevant properties, such as mixed selectivity, and (2) how such properties could arise via circuit mechanisms. We show that PFC cells recorded from male and female rhesus macaques during a complex task show a moderate level of specialization and structure that is not replicated by a model wherein cells receive random feedforward inputs. While random connectivity can be effective at generating mixed selectivity, the data show significantly more mixed selectivity than predicted by a model with otherwise matched parameters. A simple Hebbian learning rule applied to the random connectivity, however, increases mixed selectivity and enables the model to match the data more accurately. To explain how learning achieves this, we provide analysis along with a clear geometric interpretation of the impact of learning on selectivity. After learning, the model also matches the data on measures of noise, response density, clustering, and the distribution of selectivities. Of two styles of Hebbian learning tested, the simpler and more biologically plausible option better matches the data. These modeling results provide clues about how neural properties important for cognition can arise in a circuit and make clear experimental predictions regarding how various measures of selectivity would evolve during animal training. SIGNIFICANCE STATEMENT The prefrontal cortex is a brain region believed to support the ability of animals to engage in complex behavior. How neurons in this area respond to stimuli—and in particular, to combinations of stimuli (“mixed selectivity”)—is a topic of interest. Even though models with random feedforward connectivity are capable of creating computationally relevant mixed selectivity, such a model does not match the levels of mixed selectivity seen in the data analyzed in this study. Adding simple Hebbian learning to the model increases mixed selectivity to the correct level and makes the model match the data on several other relevant measures. This study thus offers predictions on how mixed selectivity and other properties evolve with training. PMID:28986463

Bayesian model selection applied to artificial neural networks used for water resources modeling

NASA Astrophysics Data System (ADS)

Kingston, Greer B.; Maier, Holger R.; Lambert, Martin F.

2008-04-01

Artificial neural networks (ANNs) have proven to be extremely valuable tools in the field of water resources engineering. However, one of the most difficult tasks in developing an ANN is determining the optimum level of complexity required to model a given problem, as there is no formal systematic model selection method. This paper presents a Bayesian model selection (BMS) method for ANNs that provides an objective approach for comparing models of varying complexity in order to select the most appropriate ANN structure. The approach uses Markov Chain Monte Carlo posterior simulations to estimate the evidence in favor of competing models and, in this study, three known methods for doing this are compared in terms of their suitability for being incorporated into the proposed BMS framework for ANNs. However, it is acknowledged that it can be particularly difficult to accurately estimate the evidence of ANN models. Therefore, the proposed BMS approach for ANNs incorporates a further check of the evidence results by inspecting the marginal posterior distributions of the hidden-to-output layer weights, which unambiguously indicate any redundancies in the hidden layer nodes. The fact that this check is available is one of the greatest advantages of the proposed approach over conventional model selection methods, which do not provide such a test and instead rely on the modeler's subjective choice of selection criterion. The advantages of a total Bayesian approach to ANN development, including training and model selection, are demonstrated on two synthetic and one real world water resources case study.

A Computational Model of Selection by Consequences

ERIC Educational Resources Information Center

McDowell, J. J.

2004-01-01

Darwinian selection by consequences was instantiated in a computational model that consisted of a repertoire of behaviors undergoing selection, reproduction, and mutation over many generations. The model in effect created a digital organism that emitted behavior continuously. The behavior of this digital organism was studied in three series of…

Division of Attention Relative to Response Between Attended and Unattended Stimuli.

ERIC Educational Resources Information Center

Kantowitz, Barry H.

Research was conducted to investigate two general classes of human attention models, early-selection models which claim that attentional selecting precedes memory and meaning extraction mechanisms, and late-selection models which posit the reverse. This research involved two components: (1) the development of simple, efficient, computer-oriented…

Compromise Approach-Based Genetic Algorithm for Constrained Multiobjective Portfolio Selection Model

NASA Astrophysics Data System (ADS)

Li, Jun

In this paper, fuzzy set theory is incorporated into a multiobjective portfolio selection model for investors’ taking into three criteria: return, risk and liquidity. The cardinality constraint, the buy-in threshold constraint and the round-lots constraints are considered in the proposed model. To overcome the difficulty of evaluation a large set of efficient solutions and selection of the best one on non-dominated surface, a compromise approach-based genetic algorithm is presented to obtain a compromised solution for the proposed constrained multiobjective portfolio selection model.

Targeted versus statistical approaches to selecting parameters for modelling sediment provenance

NASA Astrophysics Data System (ADS)

Laceby, J. Patrick

2017-04-01

One effective field-based approach to modelling sediment provenance is the source fingerprinting technique. Arguably, one of the most important steps for this approach is selecting the appropriate suite of parameters or fingerprints used to model source contributions. Accordingly, approaches to selecting parameters for sediment source fingerprinting will be reviewed. Thereafter, opportunities and limitations of these approaches and some future research directions will be presented. For properties to be effective tracers of sediment, they must discriminate between sources whilst behaving conservatively. Conservative behavior is characterized by constancy in sediment properties, where the properties of sediment sources remain constant, or at the very least, any variation in these properties should occur in a predictable and measurable way. Therefore, properties selected for sediment source fingerprinting should remain constant through sediment detachment, transportation and deposition processes, or vary in a predictable and measurable way. One approach to select conservative properties for sediment source fingerprinting is to identify targeted tracers, such as caesium-137, that provide specific source information (e.g. surface versus subsurface origins). A second approach is to use statistical tests to select an optimal suite of conservative properties capable of modelling sediment provenance. In general, statistical approaches use a combination of a discrimination (e.g. Kruskal Wallis H-test, Mann-Whitney U-test) and parameter selection statistics (e.g. Discriminant Function Analysis or Principle Component Analysis). The challenge is that modelling sediment provenance is often not straightforward and there is increasing debate in the literature surrounding the most appropriate approach to selecting elements for modelling. Moving forward, it would be beneficial if researchers test their results with multiple modelling approaches, artificial mixtures, and multiple lines of evidence to provide secondary support to their initial modelling results. Indeed, element selection can greatly impact modelling results and having multiple lines of evidence will help provide confidence when modelling sediment provenance.

Elementary Teachers' Selection and Use of Visual Models

NASA Astrophysics Data System (ADS)

Lee, Tammy D.; Gail Jones, M.

2018-02-01

As science grows in complexity, science teachers face an increasing challenge of helping students interpret models that represent complex science systems. Little is known about how teachers select and use models when planning lessons. This mixed methods study investigated the pedagogical approaches and visual models used by elementary in-service and preservice teachers in the development of a science lesson about a complex system (e.g., water cycle). Sixty-seven elementary in-service and 69 elementary preservice teachers completed a card sort task designed to document the types of visual models (e.g., images) that teachers choose when planning science instruction. Quantitative and qualitative analyses were conducted to analyze the card sort task. Semistructured interviews were conducted with a subsample of teachers to elicit the rationale for image selection. Results from this study showed that both experienced in-service teachers and novice preservice teachers tended to select similar models and use similar rationales for images to be used in lessons. Teachers tended to select models that were aesthetically pleasing and simple in design and illustrated specific elements of the water cycle. The results also showed that teachers were not likely to select images that represented the less obvious dimensions of the water cycle. Furthermore, teachers selected visual models more as a pedagogical tool to illustrate specific elements of the water cycle and less often as a tool to promote student learning related to complex systems.

Genetic improvement in mastitis resistance: comparison of selection criteria from cross-sectional and random regression sire models for somatic cell score.

PubMed

Odegård, J; Klemetsdal, G; Heringstad, B

2005-04-01

Several selection criteria for reducing incidence of mastitis were developed from a random regression sire model for test-day somatic cell score (SCS). For comparison, sire transmitting abilities were also predicted based on a cross-sectional model for lactation mean SCS. Only first-crop daughters were used in genetic evaluation of SCS, and the different selection criteria were compared based on their correlation with incidence of clinical mastitis in second-crop daughters (measured as mean daughter deviations). Selection criteria were predicted based on both complete and reduced first-crop daughter groups (261 or 65 daughters per sire, respectively). For complete daughter groups, predicted transmitting abilities at around 30 d in milk showed the best predictive ability for incidence of clinical mastitis, closely followed by average predicted transmitting abilities over the entire lactation. Both of these criteria were derived from the random regression model. These selection criteria improved accuracy of selection by approximately 2% relative to a cross-sectional model. However, for reduced daughter groups, the cross-sectional model yielded increased predictive ability compared with the selection criteria based on the random regression model. This result may be explained by the cross-sectional model being more robust, i.e., less sensitive to precision of (co)variance components estimates and effects of data structure.

A Bayesian framework for adaptive selection, calibration, and validation of coarse-grained models of atomistic systems

NASA Astrophysics Data System (ADS)

Farrell, Kathryn; Oden, J. Tinsley; Faghihi, Danial

2015-08-01

A general adaptive modeling algorithm for selection and validation of coarse-grained models of atomistic systems is presented. A Bayesian framework is developed to address uncertainties in parameters, data, and model selection. Algorithms for computing output sensitivities to parameter variances, model evidence and posterior model plausibilities for given data, and for computing what are referred to as Occam Categories in reference to a rough measure of model simplicity, make up components of the overall approach. Computational results are provided for representative applications.

Quantitative Rheological Model Selection

NASA Astrophysics Data System (ADS)

Freund, Jonathan; Ewoldt, Randy

2014-11-01

The more parameters in a rheological the better it will reproduce available data, though this does not mean that it is necessarily a better justified model. Good fits are only part of model selection. We employ a Bayesian inference approach that quantifies model suitability by balancing closeness to data against both the number of model parameters and their a priori uncertainty. The penalty depends upon prior-to-calibration expectation of the viable range of values that model parameters might take, which we discuss as an essential aspect of the selection criterion. Models that are physically grounded are usually accompanied by tighter physical constraints on their respective parameters. The analysis reflects a basic principle: models grounded in physics can be expected to enjoy greater generality and perform better away from where they are calibrated. In contrast, purely empirical models can provide comparable fits, but the model selection framework penalizes their a priori uncertainty. We demonstrate the approach by selecting the best-justified number of modes in a Multi-mode Maxwell description of PVA-Borax. We also quantify relative merits of the Maxwell model relative to powerlaw fits and purely empirical fits for PVA-Borax, a viscoelastic liquid, and gluten.

Identification of solid state fermentation degree with FT-NIR spectroscopy: Comparison of wavelength variable selection methods of CARS and SCARS.

PubMed

Jiang, Hui; Zhang, Hang; Chen, Quansheng; Mei, Congli; Liu, Guohai

2015-01-01

The use of wavelength variable selection before partial least squares discriminant analysis (PLS-DA) for qualitative identification of solid state fermentation degree by FT-NIR spectroscopy technique was investigated in this study. Two wavelength variable selection methods including competitive adaptive reweighted sampling (CARS) and stability competitive adaptive reweighted sampling (SCARS) were employed to select the important wavelengths. PLS-DA was applied to calibrate identified model using selected wavelength variables by CARS and SCARS for identification of solid state fermentation degree. Experimental results showed that the number of selected wavelength variables by CARS and SCARS were 58 and 47, respectively, from the 1557 original wavelength variables. Compared with the results of full-spectrum PLS-DA, the two wavelength variable selection methods both could enhance the performance of identified models. Meanwhile, compared with CARS-PLS-DA model, the SCARS-PLS-DA model achieved better results with the identification rate of 91.43% in the validation process. The overall results sufficiently demonstrate the PLS-DA model constructed using selected wavelength variables by a proper wavelength variable method can be more accurate identification of solid state fermentation degree. Copyright © 2015 Elsevier B.V. All rights reserved.

Gene flow from domesticated species to wild relatives: migration load in a model of multivariate selection.

PubMed

Tufto, Jarle

2010-01-01

Domesticated species frequently spread their genes into populations of wild relatives through interbreeding. The domestication process often involves artificial selection for economically desirable traits. This can lead to an indirect response in unknown correlated traits and a reduction in fitness of domesticated individuals in the wild. Previous models for the effect of gene flow from domesticated species to wild relatives have assumed that evolution occurs in one dimension. Here, I develop a quantitative genetic model for the balance between migration and multivariate stabilizing selection. Different forms of correlational selection consistent with a given observed ratio between average fitness of domesticated and wild individuals offsets the phenotypic means at migration-selection balance away from predictions based on simpler one-dimensional models. For almost all parameter values, correlational selection leads to a reduction in the migration load. For ridge selection, this reduction arises because the distance the immigrants deviates from the local optimum in effect is reduced. For realistic parameter values, however, the effect of correlational selection on the load is small, suggesting that simpler one-dimensional models may still be adequate in terms of predicting mean population fitness and viability.

Identification of solid state fermentation degree with FT-NIR spectroscopy: Comparison of wavelength variable selection methods of CARS and SCARS

NASA Astrophysics Data System (ADS)

Jiang, Hui; Zhang, Hang; Chen, Quansheng; Mei, Congli; Liu, Guohai

2015-10-01

The use of wavelength variable selection before partial least squares discriminant analysis (PLS-DA) for qualitative identification of solid state fermentation degree by FT-NIR spectroscopy technique was investigated in this study. Two wavelength variable selection methods including competitive adaptive reweighted sampling (CARS) and stability competitive adaptive reweighted sampling (SCARS) were employed to select the important wavelengths. PLS-DA was applied to calibrate identified model using selected wavelength variables by CARS and SCARS for identification of solid state fermentation degree. Experimental results showed that the number of selected wavelength variables by CARS and SCARS were 58 and 47, respectively, from the 1557 original wavelength variables. Compared with the results of full-spectrum PLS-DA, the two wavelength variable selection methods both could enhance the performance of identified models. Meanwhile, compared with CARS-PLS-DA model, the SCARS-PLS-DA model achieved better results with the identification rate of 91.43% in the validation process. The overall results sufficiently demonstrate the PLS-DA model constructed using selected wavelength variables by a proper wavelength variable method can be more accurate identification of solid state fermentation degree.

Fitness consequences of sex-specific selection.

PubMed

Connallon, Tim; Cox, Robert M; Calsbeek, Ryan

2010-06-01

Theory suggests that sex-specific selection can facilitate adaptation in sexually reproducing populations. However, sexual conflict theory and recent experiments indicate that sex-specific selection is potentially costly due to sexual antagonism: alleles harmful to one sex can accumulate within a population because they are favored in the other sex. Whether sex-specific selection provides a net fitness benefit or cost depends, in part, on the relative frequency and strength of sexually concordant versus sexually antagonistic selection throughout a species' genome. Here, we model the net fitness consequences of sex-specific selection while explicitly considering both sexually concordant and sexually antagonistic selection. The model shows that, even when sexual antagonism is rare, the fitness costs that it imposes will generally overwhelm fitness benefits of sexually concordant selection. Furthermore, the cost of sexual antagonism is, at best, only partially resolved by the evolution of sex-limited gene expression. To evaluate the key parameters of the model, we analyze an extensive dataset of sex-specific selection gradients from wild populations, along with data from the experimental evolution literature. The model and data imply that sex-specific selection may likely impose a net cost on sexually reproducing species, although additional research will be required to confirm this conclusion.

Methods for selecting fixed-effect models for heterogeneous codon evolution, with comments on their application to gene and genome data.

PubMed

Bao, Le; Gu, Hong; Dunn, Katherine A; Bielawski, Joseph P

2007-02-08

Models of codon evolution have proven useful for investigating the strength and direction of natural selection. In some cases, a priori biological knowledge has been used successfully to model heterogeneous evolutionary dynamics among codon sites. These are called fixed-effect models, and they require that all codon sites are assigned to one of several partitions which are permitted to have independent parameters for selection pressure, evolutionary rate, transition to transversion ratio or codon frequencies. For single gene analysis, partitions might be defined according to protein tertiary structure, and for multiple gene analysis partitions might be defined according to a gene's functional category. Given a set of related fixed-effect models, the task of selecting the model that best fits the data is not trivial. In this study, we implement a set of fixed-effect codon models which allow for different levels of heterogeneity among partitions in the substitution process. We describe strategies for selecting among these models by a backward elimination procedure, Akaike information criterion (AIC) or a corrected Akaike information criterion (AICc). We evaluate the performance of these model selection methods via a simulation study, and make several recommendations for real data analysis. Our simulation study indicates that the backward elimination procedure can provide a reliable method for model selection in this setting. We also demonstrate the utility of these models by application to a single-gene dataset partitioned according to tertiary structure (abalone sperm lysin), and a multi-gene dataset partitioned according to the functional category of the gene (flagellar-related proteins of Listeria). Fixed-effect models have advantages and disadvantages. Fixed-effect models are desirable when data partitions are known to exhibit significant heterogeneity or when a statistical test of such heterogeneity is desired. They have the disadvantage of requiring a priori knowledge for partitioning sites. We recommend: (i) selection of models by using backward elimination rather than AIC or AICc, (ii) use a stringent cut-off, e.g., p = 0.0001, and (iii) conduct sensitivity analysis of results. With thoughtful application, fixed-effect codon models should provide a useful tool for large scale multi-gene analyses.

Effects of the Ordering of Natural Selection and Population Regulation Mechanisms on Wright-Fisher Models

PubMed Central

He, Zhangyi; Beaumont, Mark; Yu, Feng

2017-01-01

We explore the effect of different mechanisms of natural selection on the evolution of populations for one- and two-locus systems. We compare the effect of viability and fecundity selection in the context of the Wright-Fisher model with selection under the assumption of multiplicative fitness. We show that these two modes of natural selection correspond to different orderings of the processes of population regulation and natural selection in the Wright-Fisher model. We find that under the Wright-Fisher model these two different orderings can affect the distribution of trajectories of haplotype frequencies evolving with genetic recombination. However, the difference in the distribution of trajectories is only appreciable when the population is in significant linkage disequilibrium. We find that as linkage disequilibrium decays the trajectories for the two different models rapidly become indistinguishable. We discuss the significance of these findings in terms of biological examples of viability and fecundity selection, and speculate that the effect may be significant when factors such as gene migration maintain a degree of linkage disequilibrium. PMID:28500051

Real-world datasets for portfolio selection and solutions of some stochastic dominance portfolio models.

PubMed

Bruni, Renato; Cesarone, Francesco; Scozzari, Andrea; Tardella, Fabio

2016-09-01

A large number of portfolio selection models have appeared in the literature since the pioneering work of Markowitz. However, even when computational and empirical results are described, they are often hard to replicate and compare due to the unavailability of the datasets used in the experiments. We provide here several datasets for portfolio selection generated using real-world price values from several major stock markets. The datasets contain weekly return values, adjusted for dividends and for stock splits, which are cleaned from errors as much as possible. The datasets are available in different formats, and can be used as benchmarks for testing the performances of portfolio selection models and for comparing the efficiency of the algorithms used to solve them. We also provide, for these datasets, the portfolios obtained by several selection strategies based on Stochastic Dominance models (see "On Exact and Approximate Stochastic Dominance Strategies for Portfolio Selection" (Bruni et al. [2])). We believe that testing portfolio models on publicly available datasets greatly simplifies the comparison of the different portfolio selection strategies.

Generative model selection using a scalable and size-independent complex network classifier

NASA Astrophysics Data System (ADS)

Motallebi, Sadegh; Aliakbary, Sadegh; Habibi, Jafar

2013-12-01

Real networks exhibit nontrivial topological features, such as heavy-tailed degree distribution, high clustering, and small-worldness. Researchers have developed several generative models for synthesizing artificial networks that are structurally similar to real networks. An important research problem is to identify the generative model that best fits to a target network. In this paper, we investigate this problem and our goal is to select the model that is able to generate graphs similar to a given network instance. By the means of generating synthetic networks with seven outstanding generative models, we have utilized machine learning methods to develop a decision tree for model selection. Our proposed method, which is named "Generative Model Selection for Complex Networks," outperforms existing methods with respect to accuracy, scalability, and size-independence.

Assessing the accuracy and stability of variable selection ...

EPA Pesticide Factsheets

Random forest (RF) modeling has emerged as an important statistical learning method in ecology due to its exceptional predictive performance. However, for large and complex ecological datasets there is limited guidance on variable selection methods for RF modeling. Typically, either a preselected set of predictor variables are used, or stepwise procedures are employed which iteratively add/remove variables according to their importance measures. This paper investigates the application of variable selection methods to RF models for predicting probable biological stream condition. Our motivating dataset consists of the good/poor condition of n=1365 stream survey sites from the 2008/2009 National Rivers and Stream Assessment, and a large set (p=212) of landscape features from the StreamCat dataset. Two types of RF models are compared: a full variable set model with all 212 predictors, and a reduced variable set model selected using a backwards elimination approach. We assess model accuracy using RF's internal out-of-bag estimate, and a cross-validation procedure with validation folds external to the variable selection process. We also assess the stability of the spatial predictions generated by the RF models to changes in the number of predictors, and argue that model selection needs to consider both accuracy and stability. The results suggest that RF modeling is robust to the inclusion of many variables of moderate to low importance. We found no substanti

Automated Predictive Big Data Analytics Using Ontology Based Semantics.

PubMed

Nural, Mustafa V; Cotterell, Michael E; Peng, Hao; Xie, Rui; Ma, Ping; Miller, John A

2015-10-01

Predictive analytics in the big data era is taking on an ever increasingly important role. Issues related to choice on modeling technique, estimation procedure (or algorithm) and efficient execution can present significant challenges. For example, selection of appropriate and optimal models for big data analytics often requires careful investigation and considerable expertise which might not always be readily available. In this paper, we propose to use semantic technology to assist data analysts and data scientists in selecting appropriate modeling techniques and building specific models as well as the rationale for the techniques and models selected. To formally describe the modeling techniques, models and results, we developed the Analytics Ontology that supports inferencing for semi-automated model selection. The SCALATION framework, which currently supports over thirty modeling techniques for predictive big data analytics is used as a testbed for evaluating the use of semantic technology.

Automated Predictive Big Data Analytics Using Ontology Based Semantics

PubMed Central

Nural, Mustafa V.; Cotterell, Michael E.; Peng, Hao; Xie, Rui; Ma, Ping; Miller, John A.

2017-01-01

Predictive analytics in the big data era is taking on an ever increasingly important role. Issues related to choice on modeling technique, estimation procedure (or algorithm) and efficient execution can present significant challenges. For example, selection of appropriate and optimal models for big data analytics often requires careful investigation and considerable expertise which might not always be readily available. In this paper, we propose to use semantic technology to assist data analysts and data scientists in selecting appropriate modeling techniques and building specific models as well as the rationale for the techniques and models selected. To formally describe the modeling techniques, models and results, we developed the Analytics Ontology that supports inferencing for semi-automated model selection. The SCALATION framework, which currently supports over thirty modeling techniques for predictive big data analytics is used as a testbed for evaluating the use of semantic technology. PMID:29657954

Optimizing selective cutting strategies for maximum carbon stocks and yield of Moso bamboo forest using BIOME-BGC model.

PubMed

Mao, Fangjie; Zhou, Guomo; Li, Pingheng; Du, Huaqiang; Xu, Xiaojun; Shi, Yongjun; Mo, Lufeng; Zhou, Yufeng; Tu, Guoqing

2017-04-15

The selective cutting method currently used in Moso bamboo forests has resulted in a reduction of stand productivity and carbon sequestration capacity. Given the time and labor expense involved in addressing this problem manually, simulation using an ecosystem model is the most suitable approach. The BIOME-BGC model was improved to suit managed Moso bamboo forests, which was adapted to include age structure, specific ecological processes and management measures of Moso bamboo forest. A field selective cutting experiment was done in nine plots with three cutting intensities (high-intensity, moderate-intensity and low-intensity) during 2010-2013, and biomass of these plots was measured for model validation. Then four selective cutting scenarios were simulated by the improved BIOME-BGC model to optimize the selective cutting timings, intervals, retained ages and intensities. The improved model matched the observed aboveground carbon density and yield of different plots, with a range of relative error from 9.83% to 15.74%. The results of different selective cutting scenarios suggested that the optimal selective cutting measure should be cutting 30% culms of age 6, 80% culms of age 7, and all culms thereafter (above age 8) in winter every other year. The vegetation carbon density and harvested carbon density of this selective cutting method can increase by 74.63% and 21.5%, respectively, compared with the current selective cutting measure. The optimized selective cutting measure developed in this study can significantly promote carbon density, yield, and carbon sink capacity in Moso bamboo forests. Copyright © 2017 Elsevier Ltd. All rights reserved.

Accuracy of travel time distribution (TTD) models as affected by TTD complexity, observation errors, and model and tracer selection

USGS Publications Warehouse

Green, Christopher T.; Zhang, Yong; Jurgens, Bryant C.; Starn, J. Jeffrey; Landon, Matthew K.

2014-01-01

Analytical models of the travel time distribution (TTD) from a source area to a sample location are often used to estimate groundwater ages and solute concentration trends. The accuracies of these models are not well known for geologically complex aquifers. In this study, synthetic datasets were used to quantify the accuracy of four analytical TTD models as affected by TTD complexity, observation errors, model selection, and tracer selection. Synthetic TTDs and tracer data were generated from existing numerical models with complex hydrofacies distributions for one public-supply well and 14 monitoring wells in the Central Valley, California. Analytical TTD models were calibrated to synthetic tracer data, and prediction errors were determined for estimates of TTDs and conservative tracer (NO3−) concentrations. Analytical models included a new, scale-dependent dispersivity model (SDM) for two-dimensional transport from the watertable to a well, and three other established analytical models. The relative influence of the error sources (TTD complexity, observation error, model selection, and tracer selection) depended on the type of prediction. Geological complexity gave rise to complex TTDs in monitoring wells that strongly affected errors of the estimated TTDs. However, prediction errors for NO3− and median age depended more on tracer concentration errors. The SDM tended to give the most accurate estimates of the vertical velocity and other predictions, although TTD model selection had minor effects overall. Adding tracers improved predictions if the new tracers had different input histories. Studies using TTD models should focus on the factors that most strongly affect the desired predictions.

Cognitive Niches: An Ecological Model of Strategy Selection

ERIC Educational Resources Information Center

Marewski, Julian N.; Schooler, Lael J.

2011-01-01

How do people select among different strategies to accomplish a given task? Across disciplines, the strategy selection problem represents a major challenge. We propose a quantitative model that predicts how selection emerges through the interplay among strategies, cognitive capacities, and the environment. This interplay carves out for each…

Fantasy-Testing-Assessment: A Proposed Model for the Investigation of Mate Selection.

ERIC Educational Resources Information Center

Nofz, Michael P.

1984-01-01

Proposes a model for mate selection which outlines three modes of interpersonal relating--fantasy, testing, and assessment (FTA). The model is viewed as a more accurate representation of mate selection processes than suggested by earlier theories, and can be used to clarify couples' understandings of their own relationships. (JAC)

Identification of landscape features influencing gene flow: How useful are habitat selection models?

Treesearch

Gretchen H. Roffler; Michael K. Schwartz; Kristine Pilgrim; Sandra L. Talbot; George K. Sage; Layne G. Adams; Gordon Luikart

2016-01-01

Understanding how dispersal patterns are influenced by landscape heterogeneity is critical for modeling species connectivity. Resource selection function (RSF) models are increasingly used in landscape genetics approaches. However, because the ecological factors that drive habitat selection may be different from those influencing dispersal and gene flow, it is...

Adaptive selection and validation of models of complex systems in the presence of uncertainty

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

Farrell-Maupin, Kathryn; Oden, J. T.

This study describes versions of OPAL, the Occam-Plausibility Algorithm in which the use of Bayesian model plausibilities is replaced with information theoretic methods, such as the Akaike Information Criterion and the Bayes Information Criterion. Applications to complex systems of coarse-grained molecular models approximating atomistic models of polyethylene materials are described. All of these model selection methods take into account uncertainties in the model, the observational data, the model parameters, and the predicted quantities of interest. A comparison of the models chosen by Bayesian model selection criteria and those chosen by the information-theoretic criteria is given.

Adaptive selection and validation of models of complex systems in the presence of uncertainty

DOE PAGES

Farrell-Maupin, Kathryn; Oden, J. T.

2017-08-01

This study describes versions of OPAL, the Occam-Plausibility Algorithm in which the use of Bayesian model plausibilities is replaced with information theoretic methods, such as the Akaike Information Criterion and the Bayes Information Criterion. Applications to complex systems of coarse-grained molecular models approximating atomistic models of polyethylene materials are described. All of these model selection methods take into account uncertainties in the model, the observational data, the model parameters, and the predicted quantities of interest. A comparison of the models chosen by Bayesian model selection criteria and those chosen by the information-theoretic criteria is given.

Bayesian selection of misspecified models is overconfident and may cause spurious posterior probabilities for phylogenetic trees.

PubMed

Yang, Ziheng; Zhu, Tianqi

2018-02-20

The Bayesian method is noted to produce spuriously high posterior probabilities for phylogenetic trees in analysis of large datasets, but the precise reasons for this overconfidence are unknown. In general, the performance of Bayesian selection of misspecified models is poorly understood, even though this is of great scientific interest since models are never true in real data analysis. Here we characterize the asymptotic behavior of Bayesian model selection and show that when the competing models are equally wrong, Bayesian model selection exhibits surprising and polarized behaviors in large datasets, supporting one model with full force while rejecting the others. If one model is slightly less wrong than the other, the less wrong model will eventually win when the amount of data increases, but the method may become overconfident before it becomes reliable. We suggest that this extreme behavior may be a major factor for the spuriously high posterior probabilities for evolutionary trees. The philosophical implications of our results to the application of Bayesian model selection to evaluate opposing scientific hypotheses are yet to be explored, as are the behaviors of non-Bayesian methods in similar situations.

Multicriteria framework for selecting a process modelling language

NASA Astrophysics Data System (ADS)

Scanavachi Moreira Campos, Ana Carolina; Teixeira de Almeida, Adiel

2016-01-01

The choice of process modelling language can affect business process management (BPM) since each modelling language shows different features of a given process and may limit the ways in which a process can be described and analysed. However, choosing the appropriate modelling language for process modelling has become a difficult task because of the availability of a large number modelling languages and also due to the lack of guidelines on evaluating, and comparing languages so as to assist in selecting the most appropriate one. This paper proposes a framework for selecting a modelling language in accordance with the purposes of modelling. This framework is based on the semiotic quality framework (SEQUAL) for evaluating process modelling languages and a multicriteria decision aid (MCDA) approach in order to select the most appropriate language for BPM. This study does not attempt to set out new forms of assessment and evaluation criteria, but does attempt to demonstrate how two existing approaches can be combined so as to solve the problem of selection of modelling language. The framework is described in this paper and then demonstrated by means of an example. Finally, the advantages and disadvantages of using SEQUAL and MCDA in an integrated manner are discussed.

Polynomial order selection in random regression models via penalizing adaptively the likelihood.

PubMed

Corrales, J D; Munilla, S; Cantet, R J C

2015-08-01

Orthogonal Legendre polynomials (LP) are used to model the shape of additive genetic and permanent environmental effects in random regression models (RRM). Frequently, the Akaike (AIC) and the Bayesian (BIC) information criteria are employed to select LP order. However, it has been theoretically shown that neither AIC nor BIC is simultaneously optimal in terms of consistency and efficiency. Thus, the goal was to introduce a method, 'penalizing adaptively the likelihood' (PAL), as a criterion to select LP order in RRM. Four simulated data sets and real data (60,513 records, 6675 Colombian Holstein cows) were employed. Nested models were fitted to the data, and AIC, BIC and PAL were calculated for all of them. Results showed that PAL and BIC identified with probability of one the true LP order for the additive genetic and permanent environmental effects, but AIC tended to favour over parameterized models. Conversely, when the true model was unknown, PAL selected the best model with higher probability than AIC. In the latter case, BIC never favoured the best model. To summarize, PAL selected a correct model order regardless of whether the 'true' model was within the set of candidates. © 2015 Blackwell Verlag GmbH.

A new methodology based on sensitivity analysis to simplify the recalibration of functional-structural plant models in new conditions.

PubMed

Mathieu, Amélie; Vidal, Tiphaine; Jullien, Alexandra; Wu, QiongLi; Chambon, Camille; Bayol, Benoit; Cournède, Paul-Henry

2018-06-19

Functional-structural plant models (FSPMs) describe explicitly the interactions between plants and their environment at organ to plant scale. However, the high level of description of the structure or model mechanisms makes this type of model very complex and hard to calibrate. A two-step methodology to facilitate the calibration process is proposed here. First, a global sensitivity analysis method was applied to the calibration loss function. It provided first-order and total-order sensitivity indexes that allow parameters to be ranked by importance in order to select the most influential ones. Second, the Akaike information criterion (AIC) was used to quantify the model's quality of fit after calibration with different combinations of selected parameters. The model with the lowest AIC gives the best combination of parameters to select. This methodology was validated by calibrating the model on an independent data set (same cultivar, another year) with the parameters selected in the second step. All the parameters were set to their nominal value; only the most influential ones were re-estimated. Sensitivity analysis applied to the calibration loss function is a relevant method to underline the most significant parameters in the estimation process. For the studied winter oilseed rape model, 11 out of 26 estimated parameters were selected. Then, the model could be recalibrated for a different data set by re-estimating only three parameters selected with the model selection method. Fitting only a small number of parameters dramatically increases the efficiency of recalibration, increases the robustness of the model and helps identify the principal sources of variation in varying environmental conditions. This innovative method still needs to be more widely validated but already gives interesting avenues to improve the calibration of FSPMs.

Emotional Bookkeeping and High Partner Selectivity Are Necessary for the Emergence of Partner-Specific Reciprocal Affiliation in an Agent-Based Model of Primate Groups

PubMed Central

Evers, Ellen; de Vries, Han; Spruijt, Berry M.; Sterck, Elisabeth H. M.

2015-01-01

Primate affiliative relationships are differentiated, individual-specific and often reciprocal. However, the required cognitive abilities are still under debate. Recently, we introduced the EMO-model, in which two emotional dimensions regulate social behaviour: anxiety-FEAR and satisfaction-LIKE. Emotional bookkeeping is modelled by providing each individual with partner-specific LIKE attitudes in which the emotional experiences of earlier affiliations with others are accumulated. Individuals also possess fixed partner-specific FEAR attitudes, reflecting the stable dominance hierarchy. In this paper, we focus on one key parameter of the model, namely the degree of partner selectivity, i.e. the extent to which individuals rely on their LIKE attitudes when choosing affiliation partners. Studying the effect of partner selectivity on the emergent affiliative relationships, we found that at high selectivity, individuals restricted their affiliative behaviours more to similar-ranking individuals and that reciprocity of affiliation was enhanced. We compared the emotional bookkeeping model with a control model, in which individuals had fixed LIKE attitudes simply based on the (fixed) rank-distance, instead of dynamic LIKE attitudes based on earlier events. Results from the control model were very similar to the emotional bookkeeping model: high selectivity resulted in preference of similar-ranking partners and enhanced reciprocity. However, only in the emotional bookkeeping model did high selectivity result in the emergence of reciprocal affiliative relationships that were highly partner-specific. Moreover, in the emotional bookkeeping model, LIKE attitude predicted affiliative behaviour better than rank-distance, especially at high selectivity. Our model suggests that emotional bookkeeping is a likely candidate mechanism to underlie partner-specific reciprocal affiliation. PMID:25785601

Potential roles of the interaction between model V1 neurons with orientation-selective and non-selective surround inhibition in contour detection

PubMed Central

Yang, Kai-Fu; Li, Chao-Yi; Li, Yong-Jie

2015-01-01

Both the neurons with orientation-selective and with non-selective surround inhibition have been observed in the primary visual cortex (V1) of primates and cats. Though the inhibition coming from the surround region (named as non-classical receptive field, nCRF) has been considered playing critical role in visual perception, the specific role of orientation-selective and non-selective inhibition in the task of contour detection is less known. To clarify above question, we first carried out computational analysis of the contour detection performance of V1 neurons with different types of surround inhibition, on the basis of which we then proposed two integrated models to evaluate their role in this specific perceptual task by combining the two types of surround inhibition with two different ways. The two models were evaluated with synthetic images and a set of challenging natural images, and the results show that both of the integrated models outperform the typical models with orientation-selective or non-selective inhibition alone. The findings of this study suggest that V1 neurons with different types of center–surround interaction work in cooperative and adaptive ways at least when extracting organized structures from cluttered natural scenes. This work is expected to inspire efficient phenomenological models for engineering applications in field of computational machine-vision. PMID:26136664

Potential roles of the interaction between model V1 neurons with orientation-selective and non-selective surround inhibition in contour detection.

PubMed

Yang, Kai-Fu; Li, Chao-Yi; Li, Yong-Jie

2015-01-01

Both the neurons with orientation-selective and with non-selective surround inhibition have been observed in the primary visual cortex (V1) of primates and cats. Though the inhibition coming from the surround region (named as non-classical receptive field, nCRF) has been considered playing critical role in visual perception, the specific role of orientation-selective and non-selective inhibition in the task of contour detection is less known. To clarify above question, we first carried out computational analysis of the contour detection performance of V1 neurons with different types of surround inhibition, on the basis of which we then proposed two integrated models to evaluate their role in this specific perceptual task by combining the two types of surround inhibition with two different ways. The two models were evaluated with synthetic images and a set of challenging natural images, and the results show that both of the integrated models outperform the typical models with orientation-selective or non-selective inhibition alone. The findings of this study suggest that V1 neurons with different types of center-surround interaction work in cooperative and adaptive ways at least when extracting organized structures from cluttered natural scenes. This work is expected to inspire efficient phenomenological models for engineering applications in field of computational machine-vision.

On Large Time Behavior and Selection Principle for a Diffusive Carr-Penrose Model

NASA Astrophysics Data System (ADS)

Conlon, Joseph G.; Dabkowski, Michael; Wu, Jingchen

2016-04-01

This paper is concerned with the study of a diffusive perturbation of the linear LSW model introduced by Carr and Penrose. A main subject of interest is to understand how the presence of diffusion acts as a selection principle, which singles out a particular self-similar solution of the linear LSW model as determining the large time behavior of the diffusive model. A selection principle is rigorously proven for a model which is a semiclassical approximation to the diffusive model. Upper bounds on the rate of coarsening are also obtained for the full diffusive model.

Neural Underpinnings of Decision Strategy Selection: A Review and a Theoretical Model.

PubMed

Wichary, Szymon; Smolen, Tomasz

2016-01-01

In multi-attribute choice, decision makers use decision strategies to arrive at the final choice. What are the neural mechanisms underlying decision strategy selection? The first goal of this paper is to provide a literature review on the neural underpinnings and cognitive models of decision strategy selection and thus set the stage for a neurocognitive model of this process. The second goal is to outline such a unifying, mechanistic model that can explain the impact of noncognitive factors (e.g., affect, stress) on strategy selection. To this end, we review the evidence for the factors influencing strategy selection, the neural basis of strategy use and the cognitive models of this process. We also present the Bottom-Up Model of Strategy Selection (BUMSS). The model assumes that the use of the rational Weighted Additive strategy and the boundedly rational heuristic Take The Best can be explained by one unifying, neurophysiologically plausible mechanism, based on the interaction of the frontoparietal network, orbitofrontal cortex, anterior cingulate cortex and the brainstem nucleus locus coeruleus. According to BUMSS, there are three processes that form the bottom-up mechanism of decision strategy selection and lead to the final choice: (1) cue weight computation, (2) gain modulation, and (3) weighted additive evaluation of alternatives. We discuss how these processes might be implemented in the brain, and how this knowledge allows us to formulate novel predictions linking strategy use and neural signals.

Mapping of the stochastic Lotka-Volterra model to models of population genetics and game theory

NASA Astrophysics Data System (ADS)

Constable, George W. A.; McKane, Alan J.

2017-08-01

The relationship between the M -species stochastic Lotka-Volterra competition (SLVC) model and the M -allele Moran model of population genetics is explored via timescale separation arguments. When selection for species is weak and the population size is large but finite, precise conditions are determined for the stochastic dynamics of the SLVC model to be mappable to the neutral Moran model, the Moran model with frequency-independent selection, and the Moran model with frequency-dependent selection (equivalently a game-theoretic formulation of the Moran model). We demonstrate how these mappings can be used to calculate extinction probabilities and the times until a species' extinction in the SLVC model.

Selection of relevant input variables in storm water quality modeling by multiobjective evolutionary polynomial regression paradigm

NASA Astrophysics Data System (ADS)

Creaco, E.; Berardi, L.; Sun, Siao; Giustolisi, O.; Savic, D.

2016-04-01

The growing availability of field data, from information and communication technologies (ICTs) in "smart" urban infrastructures, allows data modeling to understand complex phenomena and to support management decisions. Among the analyzed phenomena, those related to storm water quality modeling have recently been gaining interest in the scientific literature. Nonetheless, the large amount of available data poses the problem of selecting relevant variables to describe a phenomenon and enable robust data modeling. This paper presents a procedure for the selection of relevant input variables using the multiobjective evolutionary polynomial regression (EPR-MOGA) paradigm. The procedure is based on scrutinizing the explanatory variables that appear inside the set of EPR-MOGA symbolic model expressions of increasing complexity and goodness of fit to target output. The strategy also enables the selection to be validated by engineering judgement. In such context, the multiple case study extension of EPR-MOGA, called MCS-EPR-MOGA, is adopted. The application of the proposed procedure to modeling storm water quality parameters in two French catchments shows that it was able to significantly reduce the number of explanatory variables for successive analyses. Finally, the EPR-MOGA models obtained after the input selection are compared with those obtained by using the same technique without benefitting from input selection and with those obtained in previous works where other data-modeling techniques were used on the same data. The comparison highlights the effectiveness of both EPR-MOGA and the input selection procedure.

Model Selection Indices for Polytomous Items

ERIC Educational Resources Information Center

Kang, Taehoon; Cohen, Allan S.; Sung, Hyun-Jung

2009-01-01

This study examines the utility of four indices for use in model selection with nested and nonnested polytomous item response theory (IRT) models: a cross-validation index and three information-based indices. Four commonly used polytomous IRT models are considered: the graded response model, the generalized partial credit model, the partial credit…

The long-term evolution of multilocus traits under frequency-dependent disruptive selection.

PubMed

van Doorn, G Sander; Dieckmann, Ulf

2006-11-01

Frequency-dependent disruptive selection is widely recognized as an important source of genetic variation. Its evolutionary consequences have been extensively studied using phenotypic evolutionary models, based on quantitative genetics, game theory, or adaptive dynamics. However, the genetic assumptions underlying these approaches are highly idealized and, even worse, predict different consequences of frequency-dependent disruptive selection. Population genetic models, by contrast, enable genotypic evolutionary models, but traditionally assume constant fitness values. Only a minority of these models thus addresses frequency-dependent selection, and only a few of these do so in a multilocus context. An inherent limitation of these remaining studies is that they only investigate the short-term maintenance of genetic variation. Consequently, the long-term evolution of multilocus characters under frequency-dependent disruptive selection remains poorly understood. We aim to bridge this gap between phenotypic and genotypic models by studying a multilocus version of Levene's soft-selection model. Individual-based simulations and deterministic approximations based on adaptive dynamics theory provide insights into the underlying evolutionary dynamics. Our analysis uncovers a general pattern of polymorphism formation and collapse, likely to apply to a wide variety of genetic systems: after convergence to a fitness minimum and the subsequent establishment of genetic polymorphism at multiple loci, genetic variation becomes increasingly concentrated on a few loci, until eventually only a single polymorphic locus remains. This evolutionary process combines features observed in quantitative genetics and adaptive dynamics models, and it can be explained as a consequence of changes in the selection regime that are inherent to frequency-dependent disruptive selection. Our findings demonstrate that the potential of frequency-dependent disruptive selection to maintain polygenic variation is considerably smaller than previously expected.

A Feature and Algorithm Selection Method for Improving the Prediction of Protein Structural Class.

PubMed

Ni, Qianwu; Chen, Lei

2017-01-01

Correct prediction of protein structural class is beneficial to investigation on protein functions, regulations and interactions. In recent years, several computational methods have been proposed in this regard. However, based on various features, it is still a great challenge to select proper classification algorithm and extract essential features to participate in classification. In this study, a feature and algorithm selection method was presented for improving the accuracy of protein structural class prediction. The amino acid compositions and physiochemical features were adopted to represent features and thirty-eight machine learning algorithms collected in Weka were employed. All features were first analyzed by a feature selection method, minimum redundancy maximum relevance (mRMR), producing a feature list. Then, several feature sets were constructed by adding features in the list one by one. For each feature set, thirtyeight algorithms were executed on a dataset, in which proteins were represented by features in the set. The predicted classes yielded by these algorithms and true class of each protein were collected to construct a dataset, which were analyzed by mRMR method, yielding an algorithm list. From the algorithm list, the algorithm was taken one by one to build an ensemble prediction model. Finally, we selected the ensemble prediction model with the best performance as the optimal ensemble prediction model. Experimental results indicate that the constructed model is much superior to models using single algorithm and other models that only adopt feature selection procedure or algorithm selection procedure. The feature selection procedure or algorithm selection procedure are really helpful for building an ensemble prediction model that can yield a better performance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

How Darwinian is cultural evolution?

PubMed Central

Claidière, Nicolas; Scott-Phillips, Thomas C.; Sperber, Dan

2014-01-01

Darwin-inspired population thinking suggests approaching culture as a population of items of different types, whose relative frequencies may change over time. Three nested subtypes of populational models can be distinguished: evolutionary, selectional and replicative. Substantial progress has been made in the study of cultural evolution by modelling it within the selectional frame. This progress has involved idealizing away from phenomena that may be critical to an adequate understanding of culture and cultural evolution, particularly the constructive aspect of the mechanisms of cultural transmission. Taking these aspects into account, we describe cultural evolution in terms of cultural attraction, which is populational and evolutionary, but only selectional under certain circumstances. As such, in order to model cultural evolution, we must not simply adjust existing replicative or selectional models but we should rather generalize them, so that, just as replicator-based selection is one form that Darwinian selection can take, selection itself is one of several different forms that attraction can take. We present an elementary formalization of the idea of cultural attraction. PMID:24686939

How Darwinian is cultural evolution?

PubMed

Claidière, Nicolas; Scott-Phillips, Thomas C; Sperber, Dan

2014-05-19

Darwin-inspired population thinking suggests approaching culture as a population of items of different types, whose relative frequencies may change over time. Three nested subtypes of populational models can be distinguished: evolutionary, selectional and replicative. Substantial progress has been made in the study of cultural evolution by modelling it within the selectional frame. This progress has involved idealizing away from phenomena that may be critical to an adequate understanding of culture and cultural evolution, particularly the constructive aspect of the mechanisms of cultural transmission. Taking these aspects into account, we describe cultural evolution in terms of cultural attraction, which is populational and evolutionary, but only selectional under certain circumstances. As such, in order to model cultural evolution, we must not simply adjust existing replicative or selectional models but we should rather generalize them, so that, just as replicator-based selection is one form that Darwinian selection can take, selection itself is one of several different forms that attraction can take. We present an elementary formalization of the idea of cultural attraction.

An Optimization Model For Strategy Decision Support to Select Kind of CPO’s Ship

NASA Astrophysics Data System (ADS)

Suaibah Nst, Siti; Nababan, Esther; Mawengkang, Herman

2018-01-01

The selection of marine transport for the distribution of crude palm oil (CPO) is one of strategy that can be considered in reducing cost of transport. The cost of CPO’s transport from one area to CPO’s factory located at the port of destination may affect the level of CPO’s prices and the number of demands. In order to maintain the availability of CPO a strategy is required to minimize the cost of transporting. In this study, the strategy used to select kind of charter ships as barge or chemical tanker. This study aims to determine an optimization model for strategy decision support in selecting kind of CPO’s ship by minimizing costs of transport. The select of ship was done randomly, so that two-stage stochastic programming model was used to select the kind of ship. Model can help decision makers to select either barge or chemical tanker to distribute CPO.

Sage-grouse habitat selection during winter in Alberta

USGS Publications Warehouse

Carpenter, Jennifer L.; Aldridge, Cameron L.; Boyce, Mark S.

2010-01-01

Greater sage-grouse (Centrocercus urophasianus) are dependent on sagebrush (Artemisia spp.) for food and shelter during winter, yet few studies have assessed winter habitat selection, particularly at scales applicable to conservation planning. Small changes to availability of winter habitats have caused drastic reductions in some sage-grouse populations. We modeled winter habitat selection by sage-grouse in Alberta, Canada, by using a resource selection function. Our purpose was to 1) generate a robust winter habitat-selection model for Alberta sage-grouse; 2) spatially depict habitat suitability in a Geographic Information System to identify areas with a high probability of selection and thus, conservation importance; and 3) assess the relative influence of human development, including oil and gas wells, in landscape models of winter habitat selection. Terrain and vegetation characteristics, sagebrush cover, anthropogenic landscape features, and energy development were important in top Akaike's Information Criterionselected models. During winter, sage-grouse selected dense sagebrush cover and homogenous less rugged areas, and avoided energy development and 2-track truck trails. Sage-grouse avoidance of energy development highlights the need for comprehensive management strategies that maintain suitable habitats across all seasons. ?? 2010 The Wildlife Society.

Generative model selection using a scalable and size-independent complex network classifier

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

Motallebi, Sadegh, E-mail: motallebi@ce.sharif.edu; Aliakbary, Sadegh, E-mail: aliakbary@ce.sharif.edu; Habibi, Jafar, E-mail: jhabibi@sharif.edu

2013-12-15

Real networks exhibit nontrivial topological features, such as heavy-tailed degree distribution, high clustering, and small-worldness. Researchers have developed several generative models for synthesizing artificial networks that are structurally similar to real networks. An important research problem is to identify the generative model that best fits to a target network. In this paper, we investigate this problem and our goal is to select the model that is able to generate graphs similar to a given network instance. By the means of generating synthetic networks with seven outstanding generative models, we have utilized machine learning methods to develop a decision tree formore » model selection. Our proposed method, which is named “Generative Model Selection for Complex Networks,” outperforms existing methods with respect to accuracy, scalability, and size-independence.« less

Female mating preferences determine system-level evolution in a gene network model.

PubMed

Fierst, Janna L

2013-06-01

Environmental patterns of directional, stabilizing and fluctuating selection can influence the evolution of system-level properties like evolvability and mutational robustness. Intersexual selection produces strong phenotypic selection and these dynamics may also affect the response to mutation and the potential for future adaptation. In order to to assess the influence of mating preferences on these evolutionary properties, I modeled a male trait and female preference determined by separate gene regulatory networks. I studied three sexual selection scenarios: sexual conflict, a Gaussian model of the Fisher process described in Lande (in Proc Natl Acad Sci 78(6):3721-3725, 1981) and a good genes model in which the male trait signalled his mutational condition. I measured the effects these mating preferences had on the potential for traits and preferences to evolve towards new states, and mutational robustness of both the phenotype and the individual's overall viability. All types of sexual selection increased male phenotypic robustness relative to a randomly mating population. The Fisher model also reduced male evolvability and mutational robustness for viability. Under good genes sexual selection, males evolved an increased mutational robustness for viability. Females choosing their mates is a scenario that is sufficient to create selective forces that impact genetic evolution and shape the evolutionary response to mutation and environmental selection. These dynamics will inevitably develop in any population where sexual selection is operating, and affect the potential for future adaptation.