Integrated molecular analysis of Tamoxifen-resistant invasive lobular breast cancer cells identifies MAPK and GRM/mGluR signaling as therapeutic vulnerabilities.

PubMed

Stires, Hillary; Heckler, Mary M; Fu, Xiaoyong; Li, Zhao; Grasso, Catherine S; Quist, Michael J; Lewis, Joseph A; Klimach, Uwe; Zwart, Alan; Mahajan, Akanksha; Győrffy, Balázs; Cavalli, Luciane R; Riggins, Rebecca B

2018-08-15

Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Impact of GRM: New evidence from the Soviet Union

NASA Technical Reports Server (NTRS)

Mcnutt, M.

1985-01-01

Gravity information released by the Soviet Union allows the quantitative assessment of how the geopotential research mission (GRM) mission might effect the ability to use global gravity data for continental tectonic interpretation. The information is of an isostatic response spectra for eight individual tectonic units in the USSR. The regions examined include the Caroathians, Caucasus, Urals, Pamirs, Tien-Shan, Altal, Chersky Ridge, and East Siberian Platform. The 1 deg x 1 deg gravity data are used to calculate the admittances are used in two different sorts of tectonic studies of mountain belts in the USSR: (1) interpretation of isostatic responses in terms of plate models of compensation for mountainous terrain. Using geologic information concerning time of the orogeny, lithospheric plates involved, and polarity of subduction in collision zones, they convert the best-fitting flexural rigidity to an elastic plate thickness for the lithospheric plate inferred to underlie the mountains; the isostatic admittance functions is an attempt to directly model gravity and topography data for a few select regions in the Soviet Union. By knowing the value of the expected correlation between topography and gravity from the admittances, the Artemjev's map in mountainous areas can be calibrated, and the maps are converted back to Bouguer gravity. This procedure is applied to the Caucasus and southern Urals.

The role of rs2237781 within GRM8 in eating behavior.

PubMed

Gast, Marie-Therese; Tönjes, Anke; Keller, Maria; Horstmann, Annette; Steinle, Nanette; Scholz, Markus; Müller, Ines; Villringer, Arno; Stumvoll, Michael; Kovacs, Peter; Böttcher, Yvonne

2013-09-01

The glutamate receptor, metabotropic 8 gene (GRM8) encodes a G-protein-coupled glutamate receptor and has been associated with smoking behavior and liability to alcoholism implying a role in addiction vulnerability. Data from animal studies suggest that GRM8 may be involved in the regulation of the neuropeptide Y and melanocortin pathways and might influence food intake and metabolism. This study aimed to investigate the effects of the genetic variant rs2237781 within GRM8 on human eating behavior. The initial analysis included 548 Sorbs from Germany who have been extensively phenotyped for metabolic traits and who completed the German version of the three-factor eating questionnaire. In addition, we analyzed two independent sample sets comprising 293 subjects from another German cohort and 430 Old Order Amish individuals. Genetic associations with restraint, disinhibition, and hunger were assessed in an additive linear regression model. Among the Sorbs the major G allele of rs2237781 was significantly associated with increased restraint scores in eating behavior (P = 1.9 × 10(-4); β = +1.936). The German cohort and the Old Order Amish population revealed a trend in the same direction for restraint (P = 0.242; β = +0.874; P = 0.908; β = +0.096; respectively). A meta-analysis resulted in a combined P = 3.1 × 10(-3) (Z-score 2.948). Our data suggest that rs2237781 within GRM8 may influence human eating behavior factors probably via pathways involved in addictive behavior.

Fall risk factors analysis based on sample entropy of plantar kinematic signal during stance phase.

PubMed

Shengyun Liang; Huiyu Jia; Zilong Li; Huiqi Li; Xing Gao; Zuchang Ma; Yingnan Ma; Guoru Zhao

2016-08-01

Falls are a multi-causal phenomenon with a complex interaction. The aim of our research is to study the effect of multiple variables for potential risk of falls and construct an elderly fall risk assessment model based on demographics data and gait characteristics. A total of 101 subjects, whom belong to Malianwa Street, aged above 50 years old and participated in questionnaire survey. Participants were classified into three groups (high, medium and low risk group) according to the score of elderly fall risk assessment scale. In addition, the data of ground reaction force (GRF) and ground reaction moment (GRM) was record when they performed walking at comfortable state. The demographic variables, sample entropy of GRF and GRM, and impulse difference of bilateral foot were considered as potential explanatory variables of risk assessment model. Firstly, we investigated whether different groups could present difference in every variable. Statistical differences were found for the following variables: age (p=2.28e-05); impulse difference (p=0.02036); sample entropy of GRF in vertical direction (p=0.0144); sample entropy of GRM in anterior-posterior direction (p=0.0387). Finally, the multiple regression analysis results indicated that age, impulse difference and sample entropy of resultant GRM could identify individuals who had different levels of fall risk. Therefore, those results could potentially be useful in the fall risk assessment and monitor the state of physical function in elderly population.

Calibration and Validation of the Dutch-Flemish PROMIS Pain Interference Item Bank in Patients with Chronic Pain

PubMed Central

Crins, Martine H. P.; Roorda, Leo D.; Smits, Niels; de Vet, Henrica C. W.; Westhovens, Rene; Cella, David; Cook, Karon F.; Revicki, Dennis; van Leeuwen, Jaap; Boers, Maarten; Dekker, Joost; Terwee, Caroline B.

2015-01-01

The Dutch-Flemish PROMIS Group translated the adult PROMIS Pain Interference item bank into Dutch-Flemish. The aims of the current study were to calibrate the parameters of these items using an item response theory (IRT) model, to evaluate the cross-cultural validity of the Dutch-Flemish translations compared to the original English items, and to evaluate their reliability and construct validity. The 40 items in the bank were completed by 1085 Dutch chronic pain patients. Before calibrating the items, IRT model assumptions were evaluated using confirmatory factor analysis (CFA). Items were calibrated using the graded response model (GRM), an IRT model appropriate for items with more than two response options. To evaluate cross-cultural validity, differential item functioning (DIF) for language (Dutch vs. English) was examined. Reliability was evaluated based on standard errors and Cronbach’s alpha. To evaluate construct validity correlations with scores on legacy instruments (e.g., the Disabilities of the Arm, Shoulder and Hand Questionnaire) were calculated. Unidimensionality of the Dutch-Flemish PROMIS Pain Interference item bank was supported by CFA tests of model fit (CFI = 0.986, TLI = 0.986). Furthermore, the data fit the GRM and showed good coverage across the pain interference continuum (threshold-parameters range: -3.04 to 3.44). The Dutch-Flemish PROMIS Pain Interference item bank has good cross-cultural validity (only two out of 40 items showing DIF), good reliability (Cronbach’s alpha = 0.98), and good construct validity (Pearson correlations between 0.62 and 0.75). A computer adaptive test (CAT) and Dutch-Flemish PROMIS short forms of the Dutch-Flemish PROMIS Pain Interference item bank can now be developed. PMID:26214178

Calibration and Validation of the Dutch-Flemish PROMIS Pain Interference Item Bank in Patients with Chronic Pain.

PubMed

Crins, Martine H P; Roorda, Leo D; Smits, Niels; de Vet, Henrica C W; Westhovens, Rene; Cella, David; Cook, Karon F; Revicki, Dennis; van Leeuwen, Jaap; Boers, Maarten; Dekker, Joost; Terwee, Caroline B

2015-01-01

The Dutch-Flemish PROMIS Group translated the adult PROMIS Pain Interference item bank into Dutch-Flemish. The aims of the current study were to calibrate the parameters of these items using an item response theory (IRT) model, to evaluate the cross-cultural validity of the Dutch-Flemish translations compared to the original English items, and to evaluate their reliability and construct validity. The 40 items in the bank were completed by 1085 Dutch chronic pain patients. Before calibrating the items, IRT model assumptions were evaluated using confirmatory factor analysis (CFA). Items were calibrated using the graded response model (GRM), an IRT model appropriate for items with more than two response options. To evaluate cross-cultural validity, differential item functioning (DIF) for language (Dutch vs. English) was examined. Reliability was evaluated based on standard errors and Cronbach's alpha. To evaluate construct validity correlations with scores on legacy instruments (e.g., the Disabilities of the Arm, Shoulder and Hand Questionnaire) were calculated. Unidimensionality of the Dutch-Flemish PROMIS Pain Interference item bank was supported by CFA tests of model fit (CFI = 0.986, TLI = 0.986). Furthermore, the data fit the GRM and showed good coverage across the pain interference continuum (threshold-parameters range: -3.04 to 3.44). The Dutch-Flemish PROMIS Pain Interference item bank has good cross-cultural validity (only two out of 40 items showing DIF), good reliability (Cronbach's alpha = 0.98), and good construct validity (Pearson correlations between 0.62 and 0.75). A computer adaptive test (CAT) and Dutch-Flemish PROMIS short forms of the Dutch-Flemish PROMIS Pain Interference item bank can now be developed.

Using phenomenological models for forecasting the 2015 Ebola challenge.

PubMed

Pell, Bruce; Kuang, Yang; Viboud, Cecile; Chowell, Gerardo

2018-03-01

The rising number of novel pathogens threatening the human population has motivated the application of mathematical modeling for forecasting the trajectory and size of epidemics. We summarize the real-time forecasting results of the logistic equation during the 2015 Ebola challenge focused on predicting synthetic data derived from a detailed individual-based model of Ebola transmission dynamics and control. We also carry out a post-challenge comparison of two simple phenomenological models. In particular, we systematically compare the logistic growth model and a recently introduced generalized Richards model (GRM) that captures a range of early epidemic growth profiles ranging from sub-exponential to exponential growth. Specifically, we assess the performance of each model for estimating the reproduction number, generate short-term forecasts of the epidemic trajectory, and predict the final epidemic size. During the challenge the logistic equation consistently underestimated the final epidemic size, peak timing and the number of cases at peak timing with an average mean absolute percentage error (MAPE) of 0.49, 0.36 and 0.40, respectively. Post-challenge, the GRM which has the flexibility to reproduce a range of epidemic growth profiles ranging from early sub-exponential to exponential growth dynamics outperformed the logistic growth model in ascertaining the final epidemic size as more incidence data was made available, while the logistic model underestimated the final epidemic even with an increasing amount of data of the evolving epidemic. Incidence forecasts provided by the generalized Richards model performed better across all scenarios and time points than the logistic growth model with mean RMS decreasing from 78.00 (logistic) to 60.80 (GRM). Both models provided reasonable predictions of the effective reproduction number, but the GRM slightly outperformed the logistic growth model with a MAPE of 0.08 compared to 0.10, averaged across all scenarios and time points. Our findings further support the consideration of transmission models that incorporate flexible early epidemic growth profiles in the forecasting toolkit. Such models are particularly useful for quickly evaluating a developing infectious disease outbreak using only case incidence time series of the early phase of an infectious disease outbreak. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Direct mapping of symbolic DNA sequence into frequency domain in global repeat map algorithm

PubMed Central

Glunčić, Matko; Paar, Vladimir

2013-01-01

The main feature of global repeat map (GRM) algorithm (www.hazu.hr/grm/software/win/grm2012.exe) is its ability to identify a broad variety of repeats of unbounded length that can be arbitrarily distant in sequences as large as human chromosomes. The efficacy is due to the use of complete set of a K-string ensemble which enables a new method of direct mapping of symbolic DNA sequence into frequency domain, with straightforward identification of repeats as peaks in GRM diagram. In this way, we obtain very fast, efficient and highly automatized repeat finding tool. The method is robust to substitutions and insertions/deletions, as well as to various complexities of the sequence pattern. We present several case studies of GRM use, in order to illustrate its capabilities: identification of α-satellite tandem repeats and higher order repeats (HORs), identification of Alu dispersed repeats and of Alu tandems, identification of Period 3 pattern in exons, implementation of ‘magnifying glass’ effect, identification of complex HOR pattern, identification of inter-tandem transitional dispersed repeat sequences and identification of long segmental duplications. GRM algorithm is convenient for use, in particular, in cases of large repeat units, of highly mutated and/or complex repeats, and of global repeat maps for large genomic sequences (chromosomes and genomes). PMID:22977183

The Effects of Ultrasound on Biological Systems: Site

NASA Astrophysics Data System (ADS)

El-Karmi, Anan M.

Earlier studies (Dinno et al., Ultrasound Med. Biol. 15:461 -470; 1989) demonstrated that ultrasound at therapeutic intensities causes large increases in total conductance (G_{rm t}) of frog skin. These changes were attributed to non-thermal mechanisms, primarily, cavitation. In this study, the site(s) and mechanism(s) of action of ultrasound for the increase in G_{rm t} were examined. The reversible changes in G_{rm t } and sodium current were monitored in real time as a function of ultrasound exposure. Amiloride, a sodium channel blocker, was used to differentiate between cellular (G_{rm c}) and paracellular (G_{rm s}) pathways in the presence and absence of ultrasound. No significant changes were detected in G_ {rm c}. However, changes in G _{rm s} were significant. These results demonstrate that most of the increase in G _{rm t} due to ultrasound is taking place in the paracellular pathways. Sodium channels were not significantly affected by ultrasound. Thus, the changes in G_{rm c} are not specific. The effects of ultrasound were examined in the presence of radical scavengers and antioxidants. The increase in G_{rm t} due to ultrasound was significantly minimized in the presence of cystamine, cysteamine, and sodium ascorbate. This demonstrates that free radicals and other reactive species generated by cavitation are causing the increase in G_ {rm t}, possibly by acting from inside the cells. Radical scavengers and antioxidants are providing protection from oxidative damage but are not involved in the recovery of G_{ rm t} towards steady state values after sonication. The role of Ca^{2+} in the effects of ultrasound was examined since many of the cellular reactions involved in tissue recovery are dependent on the intracellular availability of free Ca^{2+}. The percentage increase in G_{rm t} in the presence of Ca^{2+} was larger than in its absence (140% vs. 27%). The time constant for G_{rm t} to return to steady state was longer in calcium-free solutions (122 vs. 18 minutes). This demonstrates that the biological effects of ultrasound are influenced by Ca^ {2+}. The larger increases in G _{rm t} and the time constants confirm other studies addressing the role of Ca ^{2+} in potentiating lipid peroxidation by free radicals, and the role of calcium ions in the formation of tight junctions.

Frequency of alcohol consumption in humans; the role of metabotropic glutamate receptors and downstream signaling pathways.

PubMed

Meyers, J L; Salling, M C; Almli, L M; Ratanatharathorn, A; Uddin, M; Galea, S; Wildman, D E; Aiello, A E; Bradley, B; Ressler, K; Koenen, K C

2015-06-23

Rodent models implicate metabotropic glutamate receptors (mGluRs) and downstream signaling pathways in addictive behaviors through metaplasticity. One way mGluRs can influence synaptic plasticity is by regulating the local translation of AMPA receptor trafficking proteins via eukaryotic elongation factor 2 (eEF2). However, genetic variation in this pathway has not been examined with human alcohol use phenotypes. Among a sample of adults living in Detroit, Michigan (Detroit Neighborhood Health Study; n = 788; 83% African American), 206 genetic variants across the mGluR-eEF2-AMPAR pathway (including GRM1, GRM5, HOMER1, HOMER2, EEF2K, MTOR, EIF4E, EEF2, CAMK2A, ARC, GRIA1 and GRIA4) were found to predict number of drinking days per month (corrected P-value < 0.01) when considered as a set (set-based linear regression conducted in PLINK). In addition, a CpG site located in the 3'-untranslated region on the north shore of EEF2 (cg12255298) was hypermethylated in those who drank more frequently (P < 0.05). Importantly, the association between several genetic variants within the mGluR-eEF2-AMPAR pathway and alcohol use behavior (i.e., consumption and alcohol-related problems) replicated in the Grady Trauma Project (GTP), an independent sample of adults living in Atlanta, Georgia (n = 1034; 95% African American), including individual variants in GRM1, GRM5, EEF2, MTOR, GRIA1, GRIA4 and HOMER2 (P < 0.05). Gene-based analyses conducted in the GTP indicated that GRM1 (empirical P < 0.05) and EEF2 (empirical P < 0.01) withstood multiple test corrections and predicted increased alcohol consumption and related problems. In conclusion, insights from rodent studies enabled the identification of novel human alcohol candidate genes within the mGluR-eEF2-AMPAR pathway.

Variation in umami perception and in candidate genes for the umami receptor in mice and humans1234

PubMed Central

Shirosaki, Shinya; Ohkuri, Tadahiro; Sanematsu, Keisuke; Islam, AA Shahidul; Ogiwara, Yoko; Kawai, Misako; Yoshida, Ryusuke; Ninomiya, Yuzo

2009-01-01

The unique taste induced by monosodium glutamate is referred to as umami taste. The umami taste is also elicited by the purine nucleotides inosine 5′-monophosphate and guanosine 5′-monophosphate. There is evidence that a heterodimeric G protein–coupled receptor, which consists of the T1R1 (taste receptor type 1, member 1, Tas1r1) and the T1R3 (taste receptor type 1, member 3, Tas1r3) proteins, functions as an umami taste receptor for rodents and humans. Splice variants of metabotropic glutamate receptors, mGluR1 (glutamate receptor, metabotropic 1, Grm1) and mGluR4 (glutamate receptor, metabotropic 4, Grm4), also have been proposed as taste receptors for glutamate. The taste sensitivity to umami substances varies in inbred mouse strains and in individual humans. However, little is known about the relation of umami taste sensitivity to variations in candidate umami receptor genes in rodents or in humans. In this article, we summarize current knowledge of the diversity of umami perception in mice and humans. Furthermore, we combine previously published data and new information from the single nucleotide polymorphism databases regarding variation in the mouse and human candidate umami receptor genes: mouse Tas1r1 (TAS1R1 for human), mouse Tas1r3 (TAS1R3 for human), mouse Grm1 (GRM1 for human), and mouse Grm4 (GRM4 for human). Finally, we discuss prospective associations between variation of these genes and umami taste perception in both species. PMID:19625681

Application of flood-intensity-duration curve, rainfall-intensity-duration curve and time of concentration to analyze the pattern of storms and their corresponding floods for the natural flood events

NASA Astrophysics Data System (ADS)

Kim, Nam Won; Shin, Mun-Ju; Lee, Jeong Eun

2016-04-01

The analysis of storm effects on floods is essential step for designing hydraulic structure and flood plain. There are previous studies for analyzing the relationship between the storm patterns and peak flow, flood volume and durations for various sizes of the catchments, but they are not enough to analyze the natural storm effects on flood responses quantitatively. This study suggests a novel method of quantitative analysis using unique factors extracted from the time series of storms and floods to investigate the relationship between natural storms and their corresponding flood responses. We used a distributed rainfall-runoff model of Grid based Rainfall-runoff Model (GRM) to generate the simulated flow and areal rainfall for 50 catchments in Republic of Korea size from 5.6 km2 to 1584.2 km2, which are including overlapped dependent catchments and non-overlapped independent catchments. The parameters of the GRM model were calibrated to get the good model performances of Nash-Sutcliffe efficiency. Then Flood-Intensity-Duration Curve (FIDC) and Rainfall-Intensity-Duration Curve (RIDC) were generated by Flood-Duration-Frequency and Intensity-Duration-Frequency methods respectively using the time series of hydrographs and hyetographs. Time of concentration developed for the Korea catchments was used as a consistent measure to extract the unique factors from the FIDC and RIDC over the different size of catchments. These unique factors for the storms and floods were analyzed against the different size of catchments to investigate the natural storm effects on floods. This method can be easily used to get the intuition of the natural storm effects with various patterns on flood responses. Acknowledgement This research was supported by a grant (11-TI-C06) from Advanced Water Management Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government.

Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder

PubMed Central

Elia, Josephine; Glessner, Joseph T; Wang, Kai; Takahashi, Nagahide; Shtir, Corina J; Hadley, Dexter; Sleiman, Patrick M A; Zhang, Haitao; Kim, Cecilia E; Robison, Reid; Lyon, Gholson J; Flory, James H; Bradfield, Jonathan P; Imielinski, Marcin; Hou, Cuiping; Frackelton, Edward C; Chiavacci, Rosetta M; Sakurai, Takeshi; Rabin, Cara; Middleton, Frank A; Thomas, Kelly A; Garris, Maria; Mentch, Frank; Freitag, Christine M; Steinhausen, Hans-Christoph; Todorov, Alexandre A; Reif, Andreas; Rothenberger, Aribert; Franke, Barbara; Mick, Eric O; Roeyers, Herbert; Buitelaar, Jan; Lesch, Klaus-Peter; Banaschewski, Tobias; Ebstein, Richard P; Mulas, Fernando; Oades, Robert D; Sergeant, Joseph; Sonuga-Barke, Edmund; Renner, Tobias J; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Walitza, Susanne; Meyer, Jobst; Pálmason, Haukur; Seitz, Christiane; Loo, Sandra K; Smalley, Susan L; Biederman, Joseph; Kent, Lindsey; Asherson, Philip; Anney, Richard J L; Gaynor, J William; Shaw, Philip; Devoto, Marcella; White, Peter S; Grant, Struan F A; Buxbaum, Joseph D; Rapoport, Judith L; Williams, Nigel M; Nelson, Stanley F; Faraone, Stephen V; Hakonarson, Hakon

2014-01-01

Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 × 10−9). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 × 10−6). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in ~10% of the cases (P = 4.38 × 10−10) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts. PMID:22138692

Compensatory molecular and functional mechanisms in nervous system of the Grm1(crv4) mouse lacking the mGlu1 receptor: a model for motor coordination deficits.

PubMed

Rossi, Pia Irene Anna; Musante, Ilaria; Summa, Maria; Pittaluga, Anna; Emionite, Laura; Ikehata, Masami; Rastaldi, Maria Pia; Ravazzolo, Roberto; Puliti, Aldamaria

2013-09-01

The metabotropic glutamate type 1 (mGlu1) and type 5 (mGlu5) receptors, the only members of group I mGlu receptors, are implicated in synaptic plasticity and mechanisms of feedback control of glutamate release. They exhibit nearly complementary distributions throughout the central nervous system, well evident in the cerebellum, where mGlu1 receptor is most intensely expressed while mGlu5 receptor is not. Despite their different distribution, they show a similar subcellular localization and use common transducing pathways. We recently described the Grm1(crv4) mouse with motor coordination deficits and renal anomalies caused by a spontaneous mutation inactivating the mGlu1 receptor. To define the neuropathological mechanisms in these mice, we evaluated expression and function of the mGlu5 receptor in cerebral and cerebellar cortices. Western blot and immunofluorescence analyses showed mGlu5 receptor overexpression. Quantitative reverse transcriptase-polymerase chain reaction results indicated that the up-regulation is already evident at RNA level. Functional studies confirmed an enhanced glutamate release from cortical cerebral and cerebellar synaptosomes when compared with wild-type that is abolished by the mGlu5 receptor-specific inhibitor, 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP). Finally, acute MPEP treatment of Grm1(crv4/crv4) mice induced an evident although incomplete improvement of motor coordination, suggesting that mGlu5 receptors enhanced activity worsens, instead of improving, the motor-coordination defects in the Grm1(crv4/crv4) mice.

Intracellular Serine Protease Inhibitor SERPINB4 Inhibits Granzyme M-Induced Cell Death

PubMed Central

de Koning, Pieter J. A.; Kummer, J. Alain; de Poot, Stefanie A. H.; Quadir, Razi; Broekhuizen, Roel; McGettrick, Anne F.; Higgins, Wayne J.; Devreese, Bart; Worrall, D. Margaret; Bovenschen, Niels

2011-01-01

Granzyme-mediated cell death is the major pathway for cytotoxic lymphocytes to kill virus-infected and tumor cells. In humans, five different granzymes (i.e. GrA, GrB, GrH, GrK, and GrM) are known that all induce cell death. Expression of intracellular serine protease inhibitors (serpins) is one of the mechanisms by which tumor cells evade cytotoxic lymphocyte-mediated killing. Intracellular expression of SERPINB9 by tumor cells renders them resistant to GrB-induced apoptosis. In contrast to GrB, however, no physiological intracellular inhibitors are known for the other four human granzymes. In the present study, we show that SERPINB4 formed a typical serpin-protease SDS-stable complex with both recombinant and native human GrM. Mutation of the P2-P1-P1′ triplet in the SERPINB4 reactive center loop completely abolished complex formation with GrM and N-terminal sequencing revealed that GrM cleaves SERPINB4 after P1-Leu. SERPINB4 inhibited GrM activity with a stoichiometry of inhibition of 1.6 and an apparent second order rate constant of 1.3×104 M−1s−1. SERPINB4 abolished cleavage of the macromolecular GrM substrates α-tubulin and nucleophosmin. Overexpression of SERPINB4 in tumor cells inhibited recombinant GrM-induced as well as NK cell-mediated cell death and this inhibition depended on the reactive center loop of the serpin. As SERPINB4 is highly expressed by squamous cell carcinomas, our results may represent a novel mechanism by which these tumor cells evade cytotoxic lymphocyte-induced GrM-mediated cell death. PMID:21857942

Computerized Adaptive Testing Provides Reliable and Efficient Depression Measurement Using the CES-D Scale

PubMed Central

2017-01-01

Background The Center for Epidemiologic Studies Depression Scale (CES-D) is a measure of depressive symptomatology which is widely used internationally. Though previous attempts were made to shorten the CES-D scale, few have attempted to develop a Computerized Adaptive Test (CAT) version for the CES-D. Objective The aim of this study was to provide evidence on the efficiency and accuracy of the CES-D when administered using CAT using an American sample group. Methods We obtained a sample of 2060 responses to the CESD-D from US participants using the myPersonality application. The average age of participants was 26 years (range 19-77). We randomly split the sample into two groups to evaluate and validate the psychometric models. We used evaluation group data (n=1018) to assess dimensionality with both confirmatory factor and Mokken analysis. We conducted further psychometric assessments using item response theory (IRT), including assessments of item and scale fit to Samejima’s graded response model (GRM), local dependency and differential item functioning. We subsequently conducted two CAT simulations to evaluate the CES-D CAT using the validation group (n=1042). Results Initial CFA results indicated a poor fit to the model and Mokken analysis revealed 3 items which did not conform to the same dimension as the rest of the items. We removed the 3 items and fit the remaining 17 items to GRM. We found no evidence of differential item functioning (DIF) between age and gender groups. Estimates of the level of CES-D trait score provided by the simulated CAT algorithm and the original CES-D trait score derived from original scale were correlated highly. The second CAT simulation conducted using real participant data demonstrated higher precision at the higher levels of depression spectrum. Conclusions Depression assessments using the CES-D CAT can be more accurate and efficient than those made using the fixed-length assessment. PMID:28931496

A Risk Assessment Comparison of Breast Cancer and Factors Affected to Risk Perception of Women in Turkey: A Cross-sectional Study

PubMed Central

YÜKSEL, Serpil; ALTUN UĞRAŞ, Gülay; ÇAVDAR, İkbal; BOZDOĞAN, Atilla; ÖZKAN GÜRDAL, Sibel; AKYOLCU, Neriman; ESENCAN, Ecem; VAROL SARAÇOĞLU, Gamze; ÖZMEN, Vahit

2017-01-01

Background: The increase in breast cancer incidence has enhanced attention towards breast cancer risk. The aim of this study was to determine the risk of breast cancer and risk perception of women, factors that affect risk perception, and to determine differences between absolute risk and the perception of risk. Methods: This cross-sectional study was carried out among 346 women whose score in the Gail Risk Model (GRM) was ≥ 1.67% and/or had a 1st degree relative with breast cancer in Bahçeşehir town in Istanbul, Turkey between Jul 2012 and Dec 2012. Data were collected through face-to-face interviews. The level of risk for breast cancer has been calculated using GRM and the Breast Cancer Risk Assessment Form (BCRAF). Breast cancer risk perception (BCRP), has been evaluated by visual analogue 100-cm-long scale. Results: Even though 39.6% of the women considered themselves as high-risk carriers, according to the GRM and the BCRAF, only 11.6% and 9.8% of women were in the “high risk” category, respectively. There was a positive significant correlation between the GRM and the BCRAF scores (P<0.001), and the BCRAF and BCRP scores (P<0.001). Factors related to high-risk perception were age (40–59 yr), post-menopausal phase, high-very high economic income level, existence of breast cancer in the family, having regular breast self-examination and clinical breast examination (P<0.05). Conclusion: In women with high risk of breast, cancer there is a significant difference between the women’s risk perception and their absolute risk level. PMID:28435816

U1 Adaptor Oligonucleotides Targeting BCL2 and GRM1 Suppress Growth of Human Melanoma Xenografts In Vivo

PubMed Central

Goraczniak, Rafal; Wall, Brian A; Behlke, Mark A; Lennox, Kim A; Ho, Eric S; Zaphiros, Nikolas H; Jakubowski, Christopher; Patel, Neil R; Zhao, Steven; Magaway, Carlo; Subbie, Stacey A; Jenny Yu, Lumeng; LaCava, Stephanie; Reuhl, Kenneth R; Chen, Suzie; Gunderson, Samuel I

2013-01-01

U1 Adaptor is a recently discovered oligonucleotide-based gene-silencing technology with a unique mechanism of action that targets nuclear pre-mRNA processing. U1 Adaptors have two distinct functional domains, both of which must be present on the same oligonucleotide to exert their gene-silencing function. Here, we present the first in vivo use of U1 Adaptors by targeting two different human genes implicated in melanomagenesis, B-cell lymphoma 2 (BCL2) and metabotropic glutamate receptor 1 (GRM1), in a human melanoma cell xenograft mouse model system. Using a newly developed dendrimer delivery system, anti-BCL2 U1 Adaptors were very potent and suppressed tumor growth at doses as low as 34 µg/kg with twice weekly intravenous (iv) administration. Anti-GRM1 U1 Adaptors suppressed tumor xenograft growth with similar potency. Mechanism of action was demonstrated by showing target gene suppression in tumors and by observing that negative control U1 Adaptors with just one functional domain show no tumor suppression activity. The anti-BCL2 and anti-GRM1 treatments were equally effective against cell lines harboring either wild-type or a mutant V600E B-RAF allele, the most common mutation in melanoma. Treatment of normal immune-competent mice (C57BL6) indicated no organ toxicity or immune stimulation. These proof-of-concept studies represent an in-depth (over 800 mice in ~108 treatment groups) validation that U1 Adaptors are a highly potent gene-silencing therapeutic and open the way for their further development to treat other human diseases. PMID:23673539

An orbit simulation study of a geopotential research mission including satellite-to-satellite tracking and disturbance compensation systems

NASA Technical Reports Server (NTRS)

Antreasian, Peter G.

1988-01-01

Two orbit simulations, one representing the actual Geopotential Research Mission (GRM) orbit and the other representing the orbit estimated from orbit determination techniques, are presented. A computer algorithm was created to simulate GRM's drag compensation mechanism so the fuel expenditure and proof mass trajectories relative to the spacecraft centroid could be calculated for the mission. The results of the GRM DISCOS simulation demonstrated that the spacecraft can essentially be drag-free. The results showed that the centroid of the spacecraft can be controlled so that it will not deviate more than 1.0 mm in any direction from the centroid of the proof mass.

Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer’s disease

PubMed Central

Haas, Laura T.; Salazar, Santiago V.; Kostylev, Mikhail A.; Um, Ji Won; Kaufman, Adam C.

2016-01-01

Alzheimer’s disease-related phenotypes in mice can be rescued by blockade of either cellular prion protein or metabotropic glutamate receptor 5. We sought genetic and biochemical evidence that these proteins function cooperatively as an obligate complex in the brain. We show that cellular prion protein associates via transmembrane metabotropic glutamate receptor 5 with the intracellular protein mediators Homer1b/c, calcium/calmodulin-dependent protein kinase II, and the Alzheimer’s disease risk gene product protein tyrosine kinase 2 beta. Coupling of cellular prion protein to these intracellular proteins is modified by soluble amyloid-β oligomers, by mouse brain Alzheimer’s disease transgenes or by human Alzheimer’s disease pathology. Amyloid-β oligomer-triggered phosphorylation of intracellular protein mediators and impairment of synaptic plasticity in vitro requires Prnp–Grm5 genetic interaction, being absent in transheterozygous loss-of-function, but present in either single heterozygote. Importantly, genetic coupling between Prnp and Grm5 is also responsible for signalling, for survival and for synapse loss in Alzheimer’s disease transgenic model mice. Thus, the interaction between metabotropic glutamate receptor 5 and cellular prion protein has a central role in Alzheimer’s disease pathogenesis, and the complex is a potential target for disease-modifying intervention. PMID:26667279

Some anticipated contributions to core fluid dynamics from the GRM

NASA Technical Reports Server (NTRS)

Vanvorhies, C.

1985-01-01

It is broadly maintained that the secular variation (SV) of the large scale geomagnetic field contains information on the fluid dynamics of Earth's electrically conducting outer core. The electromagnetic theory appropriate to a simple Earth model has recently been combined with reduced geomagnetic data in order to extract some of this information and ascertain its significance. The simple Earth model consists of a rigid, electrically insulating mantle surrounding a spherical, inviscid, and perfectly conducting liquid outer core. This model was tested against seismology by using truncated spherical harmonic models of the observed geomagnetic field to locate Earth's core-mantle boundary, CMB. Further electromagnetic theory has been developed and applied to the problem of estimating the horizontal fluid motion just beneath CMB. Of particular geophysical interest are the hypotheses that these motions: (1) include appreciable surface divergence indicative of vertical motion at depth, and (2) are steady for time intervals of a decade or more. In addition to the extended testing of the basic Earth model, the proposed GRM provides a unique opportunity to test these dynamical hypotheses.

mGluR7 genetics and alcohol: intersection yields clues for addiction.

PubMed

Gyetvai, Beatrix; Simonyi, Agnes; Oros, Melinda; Saito, Mariko; Smiley, John; Vadász, Csaba

2011-06-01

Development of addiction to alcohol or other substances can be attributed in part to exposure-dependent modifications at synaptic efficacy leading to an organism which functions at an altered homeostatic setpoint. Genetic factors may also influence setpoints and the stability of the homeostatic system of an organism. Quantitative genetic analysis of voluntary alcohol drinking, and mapping of the involved genes in the quasi-congenic Recombinant QTL Introgression strain system, identified Eac2 as a Quantitative Trait Locus (QTL) on mouse chromosome 6 which explained 18% of the variance with an effect size of 2.09 g/kg/day alcohol consumption, and Grm7 as a quantitative trait gene underlying Eac2 [Vadasz et al. in Neurochem Res 32:1099-1112, 100, Genomics 90:690-702, 102]. In earlier studies, the product of Grm7 mGluR7, a G protein-coupled receptor, has been implicated in stress systems [Mitsukawa et al. in Proc Natl Acad Sci USA 102:18712-18717, 63], anxiety-like behaviors [Cryan et al. in Eur J Neurosci 17:2409-2417, 14], memory [Holscher et al. in Learn Mem 12:450-455, 26], and psychiatric disorders (e.g., [Mick et al. in Am J Med Genet B Neuropsychiatr Genet 147B:1412-1418, 61; Ohtsuki et al. in Schizophr Res 101:9-16, 72; Pergadia et al. in Paper presented at the 38th Annual Meeting of the Behavior Genetics Association, Louisville, Kentucky, USA, 76]. Here, in experiments with mice, we show that (1) Grm7 knockout mice express increased alcohol consumption, (2) sub-congenic, and congenic mice carrying a Grm7 variant characterized by higher Grm7 mRNA drink less alcohol, and show a tendency for higher circadian dark phase motor activity in a wheel running paradigm, respectively, and (3) there are significant genetic differences in Grm7 mRNA abundance in the mouse brain between congenic and background mice identifying brain areas whose function is implicated in addiction related processes. We hypothesize that metabotropic glutamate receptors may function as regulators of homeostasis, and Grm7 (mGluR7) is involved in multiple processes (including stress, circadian activity, reward control, memory, etc.) which interact with substance use and the development of addiction. In conclusion, we suggest that mGluR7 is a significant new therapeutic target in addiction and related neurobehavioral disorders.

Fast group matching for MR fingerprinting reconstruction.

PubMed

Cauley, Stephen F; Setsompop, Kawin; Ma, Dan; Jiang, Yun; Ye, Huihui; Adalsteinsson, Elfar; Griswold, Mark A; Wald, Lawrence L

2015-08-01

MR fingerprinting (MRF) is a technique for quantitative tissue mapping using pseudorandom measurements. To estimate tissue properties such as T1 , T2 , proton density, and B0 , the rapidly acquired data are compared against a large dictionary of Bloch simulations. This matching process can be a very computationally demanding portion of MRF reconstruction. We introduce a fast group matching algorithm (GRM) that exploits inherent correlation within MRF dictionaries to create highly clustered groupings of the elements. During matching, a group specific signature is first used to remove poor matching possibilities. Group principal component analysis (PCA) is used to evaluate all remaining tissue types. In vivo 3 Tesla brain data were used to validate the accuracy of our approach. For a trueFISP sequence with over 196,000 dictionary elements, 1000 MRF samples, and image matrix of 128 × 128, GRM was able to map MR parameters within 2s using standard vendor computational resources. This is an order of magnitude faster than global PCA and nearly two orders of magnitude faster than direct matching, with comparable accuracy (1-2% relative error). The proposed GRM method is a highly efficient model reduction technique for MRF matching and should enable clinically relevant reconstruction accuracy and time on standard vendor computational resources. © 2014 Wiley Periodicals, Inc.

Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6

PubMed Central

Dryja, Thaddeus P.; McGee, Terri L.; Berson, Eliot L.; Fishman, Gerald A.; Sandberg, Michael A.; Alexander, Kenneth R.; Derlacki, Deborah J.; Rajagopalan, Aruna S.

2005-01-01

We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20/15 to 20/40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform. PMID:15781871

Knocking down metabotropic glutamate receptor 1 improves survival and disease progression in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.

PubMed

Milanese, Marco; Giribaldi, Francesco; Melone, Marcello; Bonifacino, Tiziana; Musante, Ilaria; Carminati, Enrico; Rossi, Pia I A; Vergani, Laura; Voci, Adriana; Conti, Fiorenzo; Puliti, Aldamaria; Bonanno, Giambattista

2014-04-01

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease reflecting degeneration of upper and lower motoneurons (MNs). The cause of ALS and the mechanisms of neuronal death are still largely obscure, thus impairing the establishment of efficacious therapies. Glutamate (Glu)-mediated excitotoxicity plays a major role in MN degeneration in ALS. We recently demonstrated that the activation of Group I metabotropic Glu autoreceptors, belonging to both type 1 and type 5 receptors (mGluR1 and mGluR5), at glutamatergic spinal cord nerve terminals, produces excessive Glu release in mice over-expressing human superoxide-dismutase carrying the G93A point mutation (SOD1(G93A)), a widely used animal model of human ALS. To establish whether these receptors are implicated in ALS, we generated mice expressing half dosage of mGluR1 in the SOD1(G93A) background (SOD1(G93A)Grm1(crv4/+)), by crossing the SOD1(G93A) mutant mouse with the Grm1(crv4/+) mouse, lacking mGluR1 because of a spontaneous recessive mutation. SOD1(G93A)Grm1(crv4/+) mice showed prolonged survival probability, delayed pathology onset, slower disease progression and improved motor performances compared to SOD1(G93A) mice. These effects were associated to reduction of mGluR5 expression, enhanced number of MNs, decreased astrocyte and microglia activation, normalization of metallothionein and catalase mRNA expression, reduced mitochondrial damage, and decrease of abnormal Glu release in spinal cord of SOD1(G93A)Grm1(crv4/+)compared to SOD1(G93A) mice. These results demonstrate that a lower constitutive level of mGluR1 has a significant positive impact on mice with experimental ALS, thus providing the rationale for future pharmacological approaches to ALS by selectively blocking Group I metabotropic Glu receptors. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Gene recovery microdissection (GRM) a process for producing chromosome region-specific libraries of expressed genes

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

Christian, A T; Coleman, M A; Tucker, J D

2001-02-08

Gene Recovery Microdissection (GRM) is a unique and cost-effective process for producing chromosome region-specific libraries of expressed genes. It accelerates the pace, reduces the cost, and extends the capabilities of functional genomic research, the means by which scientists will put to life-saving, life-enhancing use their knowledge of any plant or animal genome.

Simulation and analysis of a geopotential research mission

NASA Technical Reports Server (NTRS)

White, Lisa K.

1987-01-01

Methods for the determination of the initial conditions for the two satellites that will satisfy Geopotential Research Mission (GRM) requirements are investigated. For certain gravitational recovery techniques, the satellites must remain close to a specified separation distance and their groundtracks must repeat after a specified interval of time. Since the objective of the GRM mission is to improve the gravity model, any pre-mission orbit predicted using existing gravity models will be in error. A technique has been developed to eliminate the drift between the two satellites caused by gravitational modeling errors and return them to repeating groundtracks. The concept of frozen orbits, which minimize altitude variations over given latitudes, was investigated. Finally, the effects of temporal perturbations on the relative range-rate signal were studied. At the proposed altitude of 160 km, the range-rate signal produced by perturbations other than the static geopotential field are dominated by the luni-solar effect. This study demonstrates that the combined effects of all the temporal perturbations does not prevent the orbit from being frozen or the satellites from obtaining a repeating groundtrack to within a specified closure distance.

Geopotential Research Mission (GRM)

NASA Technical Reports Server (NTRS)

1985-01-01

The Geopotential Research Mission (GRM) is a satellite system proposed to determine variations in the gravitational and magnetic fields to a resolution of about 100 kilometers. Knowledge and interpretations of the potential fields on scales of 100 kilometers and greater, to clarify the needs for better data in this range of wavelengths were reviewed. The potential contribution of these data to the determination, by satellite altimetry, of a more accurate geoidal reference was discussed.

Effect of metabotropic glutamate receptor-3 variants on prefrontal brain activity in schizophrenia: An imaging genetics study using multi-channel near-infrared spectroscopy.

PubMed

Kinoshita, Akihide; Takizawa, Ryu; Koike, Shinsuke; Satomura, Yoshihiro; Kawasaki, Shingo; Kawakubo, Yuki; Marumo, Kohei; Tochigi, Mamoru; Sasaki, Tsukasa; Nishimura, Yukika; Kasai, Kiyoto

2015-10-01

The glutamatergic system is essential for learning and memory through its crucial role in neural development and synaptic plasticity. Genes associated with the glutamatergic system, including metabotropic glutamate receptor (mGluR or GRM) genes, have been implicated in the pathophysiology of schizophrenia. Few studies, however, have investigated a relationship between polymorphism of glutamate-related genes and cortical function in vivo in patients with schizophrenia. We thus explored an association between genetic variations in GRM3 and brain activation driven by a cognitive task in the prefrontal cortex in patients with schizophrenia. Thirty-one outpatients with schizophrenia and 48 healthy controls participated in this study. We measured four candidate single nucleotide polymorphisms (rs274622, rs2299225, rs1468412, and rs6465084) of GRM3, and activity in the prefrontal and temporal cortices during a category version of a verbal fluency task, using a 52-channel near-infrared spectroscopy instrument. The rs274622 C carriers with schizophrenia were associated with significantly smaller prefrontal activation than patients with TT genotype. This between-genotype difference tended to be confined to the patient group. GRM3 polymorphisms are associated with prefrontal activation during cognitive task in schizophrenia. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-Wide Supported Risk Variants in MIR137, CACNA1C, CSMD1, DRD2, and GRM3 Contribute to Schizophrenia Susceptibility in Pakistani Population.

PubMed

Fatima, Ambrin; Farooq, Muhammad; Abdullah, Uzma; Tariq, Muhammad; Mustafa, Tanveer; Iqbal, Muhammad; Tommerup, Niels; Mahmood Baig, Shahid

2017-09-01

Schizophrenia is a chronic neuropsychiatric disease afflicting around 1.1% of the population worldwide. Recently, MIR137 , CACNA1C , CSMD1 , DRD2 , and GRM3 have been reported as the most robustly emerging candidates involved in the etiology of schizophrenia. In this case control study, we performed an association analysis of rs1625579 ( MIR137 ), rs1006737, rs4765905 ( CACNA1C ), rs10503253 ( CSMD1 ), rs1076560 ( DRD2 ), rs12704290, rs6465084, and rs148754219 ( GRM3 ) in Pakistani population. Schizophrenia was diagnosed on the basis of the Diagnostic and Statistical Manual of Mental Disorders 4th ed (DSM-IV). Detailed clinical information, family history of all patients and healthy controls were collected. RFLP based case control association study was performed in a Pakistani cohort of 508 schizophrenia patients and 300 healthy control subjects. Alleles and genotype frequencies were calculated using SPSS. A significant difference in the genotype and allele frequencies for rs4765905, rs1076560 and rs6465084 were found between the patients and controls (p=0.000). This study provides substantial evidence supporting the role of CACNA1C , GRM3 and DRD2 as schizophrenia susceptibility genes in Pakistani population.

Research activities of the Geodynamics Branch

NASA Technical Reports Server (NTRS)

Kahn, W. D. (Editor); Cohen, S. C. (Editor)

1984-01-01

A broad spectrum of geoscience disciplines including space geodesy, geopotential field modeling, tectonophysics, and dynamic oceanography are discussed. The NASA programs, include the Geodynamics and Ocean Programs, the Crustal Dynamics Project, the proposed Ocean Topography Experiment (TOPEX), and the Geopotential Research Mission (GRM). The papers are grouped into chapters on Crustal Movements, Global Earth Dynamics, Gravity Field Model Development, Sea Surface Topography, and Advanced Studies.

Incorporation of causative quantitative trait nucleotides in single-step GBLUP.

PubMed

Fragomeni, Breno O; Lourenco, Daniela A L; Masuda, Yutaka; Legarra, Andres; Misztal, Ignacy

2017-07-26

Much effort is put into identifying causative quantitative trait nucleotides (QTN) in animal breeding, empowered by the availability of dense single nucleotide polymorphism (SNP) information. Genomic selection using traditional SNP information is easily implemented for any number of genotyped individuals using single-step genomic best linear unbiased predictor (ssGBLUP) with the algorithm for proven and young (APY). Our aim was to investigate whether ssGBLUP is useful for genomic prediction when some or all QTN are known. Simulations included 180,000 animals across 11 generations. Phenotypes were available for all animals in generations 6 to 10. Genotypes for 60,000 SNPs across 10 chromosomes were available for 29,000 individuals. The genetic variance was fully accounted for by 100 or 1000 biallelic QTN. Raw genomic relationship matrices (GRM) were computed from (a) unweighted SNPs, (b) unweighted SNPs and causative QTN, (c) SNPs and causative QTN weighted with results obtained with genome-wide association studies, (d) unweighted SNPs and causative QTN with simulated weights, (e) only unweighted causative QTN, (f-h) as in (b-d) but using only the top 10% causative QTN, and (i) using only causative QTN with simulated weight. Predictions were computed by pedigree-based BLUP (PBLUP) and ssGBLUP. Raw GRM were blended with 1 or 5% of the numerator relationship matrix, or 1% of the identity matrix. Inverses of GRM were obtained directly or with APY. Accuracy of breeding values for 5000 genotyped animals in the last generation with PBLUP was 0.32, and for ssGBLUP it increased to 0.49 with an unweighted GRM, 0.53 after adding unweighted QTN, 0.63 when QTN weights were estimated, and 0.89 when QTN weights were based on true effects known from the simulation. When the GRM was constructed from causative QTN only, accuracy was 0.95 and 0.99 with blending at 5 and 1%, respectively. Accuracies simulating 1000 QTN were generally lower, with a similar trend. Accuracies using the APY inverse were equal or higher than those with a regular inverse. Single-step GBLUP can account for causative QTN via a weighted GRM. Accuracy gains are maximum when variances of causative QTN are known and blending is at 1%.

Dimensionality of genomic information and performance of the Algorithm for Proven and Young for different livestock species.

PubMed

Pocrnic, Ivan; Lourenco, Daniela A L; Masuda, Yutaka; Misztal, Ignacy

2016-10-31

A genomic relationship matrix (GRM) can be inverted efficiently with the Algorithm for Proven and Young (APY) through recursion on a small number of core animals. The number of core animals is theoretically linked to effective population size (N e ). In a simulation study, the optimal number of core animals was equal to the number of largest eigenvalues of GRM that explained 98% of its variation. The purpose of this study was to find the optimal number of core animals and estimate N e for different species. Datasets included phenotypes, pedigrees, and genotypes for populations of Holstein, Jersey, and Angus cattle, pigs, and broiler chickens. The number of genotyped animals varied from 15,000 for broiler chickens to 77,000 for Holsteins, and the number of single-nucleotide polymorphisms used for genomic prediction varied from 37,000 to 61,000. Eigenvalue decomposition of the GRM for each population determined numbers of largest eigenvalues corresponding to 90, 95, 98, and 99% of variation. The number of eigenvalues corresponding to 90% (98%) of variation was 4527 (14,026) for Holstein, 3325 (11,500) for Jersey, 3654 (10,605) for Angus, 1239 (4103) for pig, and 1655 (4171) for broiler chicken. Each trait in each species was analyzed using the APY inverse of the GRM with randomly selected core animals, and their number was equal to the number of largest eigenvalues. Realized accuracies peaked with the number of core animals corresponding to 98% of variation for Holstein and Jersey and closer to 99% for other breed/species. N e was estimated based on comparisons of eigenvalue decomposition in a simulation study. Assuming a genome length of 30 Morgan, N e was equal to 149 for Holsteins, 101 for Jerseys, 113 for Angus, 32 for pigs, and 44 for broilers. Eigenvalue profiles of GRM for common species are similar to those in simulation studies although they are affected by number of genotyped animals and genotyping quality. For all investigated species, the APY required less than 15,000 core animals. Realized accuracies were equal or greater with the APY inverse than with regular inversion. Eigenvalue analysis of GRM can provide a realistic estimate of N e .

43.1 GENETIC INSIGHTS LEAD TO DISCOVERY OF SELECTIVE ACTIVATORS OF MGLU1 AND MGLU3 METABOTROPIC GLUTAMATE RECEPTORS AS POTENTIAL TREATMENTS FOR SCHIZOPHRENIA

PubMed Central

Conn, P Jeffrey; Yohn, Samantha; Stansley, Branden; Foster, Dan; Plumley, Hyekyung; Lindsley, Craig

2018-01-01

Abstract Background A large number of clinical and preclinical studies suggest that dysfunction at synapses for the excitatory neurotransmitter glutamate may play a critical role in the pathophysiological changes that underlie each of the major symptom clusters observed in schizophrenia patients. Interestingly, recent genetic studies identified multiple nonsynonymous single nucleotide polymorphisms (SNPs) in the human genes encoding two specific subtypes of metabotropic glutamate (mGlu) receptors that are associated with schizophrenia. These include GRM1 and GRM3, the genes encoding for the mGlu1 and mGlu3 receptor subtypes respectively. Furthermore, postmortem studies suggest that expression of these mGlu receptor subtypes is altered brains of schizophrenia patients compared to controls. Mutations in GRM1 were identified a range of schizophrenia patients, whereas SNPs in the human gene encoding mGlu3 (GRM3) are selectively associated with poor performance on cognitive tests that are dependent on function of the prefrontal cortex (PFC) and hippocampus. These studies raise the possibility that disrupted signaling of mGlu1 and/or mGlu3 could contribute to the symptoms of schizophrenia and that selective modulators of these receptors could provide a novel approach to treatment of this disorder. Methods Wild-type and mutant forms of mGlu receptors were expressed in cell lines and used for discovery and optimization of highly selective positive allosteric modulators (PAMs) of mGlu1 and mGlu3. Optimized mGlu1 and mGlu3 PAMs were then used along with mouse genetic studies to evaluate the roles of these receptors in specific basal ganglia and forebrain circuits that have been implicated in schizophrenia. Finally, these compounds were used in animal models to assess potential efficacy in rodent models that are relevant for reducing positive, negative, and cognitive symptoms that are observed in schizophrenia patients. Results GRM1 mutations associated with schizophrenia were found to reduce mGlu1 signaling, suggesting that loss of function of this receptor could contribute to symptoms associated with schizophrenia. Furthermore, we found that highly selective mGlu1 PAMs reverse deficits in mGlu1 signaling observed in these mutant receptors, induced a profound reduction in dopamine release in striatal areas implicated in schizophrenia, and have robust antipsychotic-like effects that are mediated by localized inhibition of dopamine release in striatum. In contrast to existing antipsychotic medications, selective mGlu1 PAMs also improve motivation and reduce anhedonia in animal models. Interestingly, selective mGlu3 PAMs have multiple effects in the prefrontal cortex and hippocampus that would be expected to improve cognitive function. Consistent with this, highly selective mGlu3 PAMs have robust cognition-enhancing effects in rodent models that are relevant for the cognitive deficits observed in schizophrenia patients. Discussion These studies provide exciting new evidence that highly selective activators of two glutamate receptors identified in human genetic studies have potential utility in treatment of positive (mGLu1), negative (mGlu1), and cognitive (mGlu3) symptoms of schizophrenia patients. Furthermore, the novel mGlu1 and mGlu3 PAMs discovered in these studies provide excellent drug leads for further optimization and ultimate clinical testing.

Carrion odor and cattle grazing

PubMed Central

Lev-Yadun, Simcha; Gutman, Mario

2013-01-01

Recently, it has been proposed on theoretical grounds that carrion odor from flowers may not only attract pollinators, but also repel mammalian herbivores. Two grazing experiments involving 16 to 26 cattle heads per year, one for eight years (1982–1989) and the other for seven (1994–2000), in a region with no large carnivores that could influence cattle behavior, show that cattle avoid areas where dead cattle have recently been dumped. They grazed much less in these unfenced plots that were used to dump dead cattle each year. In the first experiment, with an area of ca. 20,000 m2 per head, the average grass biomass at the end of the season was 124.6 gr/m2 for the regular grazing area, whereas it was 236.5 gr/m2 for the carcass dumping area. In the second experiment, with a higher stocking level, with ca. 9,000 m2 per head, the average grass biomass at the end of the season was 61.7 gr/m2 for the regular grazing area, and 153.7 gr/m2 for the carcass dumping area. These significant differences existed throughout the 15 y of the experiments. We propose that these results are clear evidence of necrophobia in cattle, a character that might defend them from both pathogenic microbes and predators. This in turn demonstrates that carrion odor, primarily used by plants to attract pollinators, can simultaneously defend plants from herbivory by mammals as proposed. PMID:25210579

Chemical-Genetic Screen Identifies Riluzole as an Enhancer of Wnt/β-catenin signaling in Melanoma

PubMed Central

Biechele, Travis L.; Camp, Nathan D.; Fass, Daniel M.; Kulikauskas, Rima M.; Robin, Nick C.; White, Bryan D.; Taraska, Corinne M.; Moore, Erin C.; Muster, Jeanot; Karmacharya, Rakesh; Haggarty, Stephen J.; Chien, Andy J.; Moon, Randall T.

2010-01-01

SUMMARY To identify new protein and pharmacological regulators of Wnt/β-catenin signaling we used a cell-based reporter assay to screen a collection of 1857 human-experienced compounds for their ability to enhance activation of the β-catenin reporter by a low concentration of WNT3A. This identified 44 unique compounds, including the FDA-approved drug riluzole, which is presently in clinical trials for treating melanoma. We found that treating melanoma cells with riluzole in vitro enhances the ability of WNT3A to regulate gene expression, to promote pigmentation, and to decrease cell proliferation. Furthermore riluzole, like WNT3A, decreases metastases in a mouse melanoma model. Interestingly, siRNAs targeting the metabotropic glutamate receptor, GRM1, a reported indirect target of riluzole, enhance β-catenin signaling. The unexpected regulation of β-catenin signaling by both riluzole and GRM1 has implications for the future uses of this drug. PMID:21095567

Prevalence and influence of cys407* Grm2 mutation in Hannover-derived Wistar rats: mGlu2 receptor loss links to alcohol intake, risk taking and emotional behaviour.

PubMed

Wood, Christian M; Nicolas, Celine S; Choi, Sun-Lim; Roman, Erika; Nylander, Ingrid; Fernandez-Teruel, Alberto; Kiianmaa, Kalervo; Bienkowski, Przemyslaw; de Jong, Trynke R; Colombo, Giancarlo; Chastagnier, Denis; Wafford, Keith A; Collingridge, Graham L; Wildt, Sheryl J; Conway-Campbell, Becky L; Robinson, Emma S J; Lodge, David

2017-03-15

Modulation of metabotropic glutamate 2 (mGlu2) receptor function has huge potential for treating psychiatric and neurological diseases. Development of drugs acting on mGlu2 receptors depends on the development and use of translatable animal models of disease. We report here a stop codon mutation at cysteine 407 in Grm2 (cys407*) that is common in some Wistar rats. Therefore, researchers in this field need to be aware of strains with this mutation. Our genotypic survey found widespread prevalence of the mutation in commercial Wistar strains, particularly those known as Han Wistar. Such Han Wistar rats are ideal for research into the separate roles of mGlu2 and mGlu3 receptors in CNS function. Previous investigations, unknowingly using such mGlu2 receptor-lacking rats, provide insights into the role of mGlu2 receptors in behaviour. The Grm2 mutant rats, which dominate some selectively bred lines, display characteristics of altered emotionality, impulsivity and risk-related behaviours and increased voluntary alcohol intake compared with their mGlu2 receptor-competent counterparts. In addition, the data further emphasize the potential therapeutic role of mGlu2 receptors in psychiatric and neurological disease, and indicate novel methods of studying the role of mGlu2 and mGlu3 receptors. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Improvement of the Earth's gravity field from terrestrial and satellite data

NASA Technical Reports Server (NTRS)

1987-01-01

The terrestrial gravity data base was updated. Studies related to the Geopotential Research Mission (GRM) have primarily considered the local recovery of gravity anomalies on the surface of the Earth based on satellite to satellite tracking or gradiometer data. A simulation study was used to estimate the accuracy of 1 degree-mean anomalies which could be recovered from the GRM data. Numerous procedures were developed for the intent of performing computations at the laser stations in the SL6 system to improve geoid undulation calculations.

Optical models of MXT using Zemax

NASA Astrophysics Data System (ADS)

Le Duigou, J. M.; Mercier, K.; Gonzalez, F.; Götz, D.; Meuris, A.

2017-09-01

The Microchannel X-ray Telescope (MXT) is a soft X-rays instrument on board SVOM, a Sino French mission. The launch is planned in 2021 by a LM-2C rocket. The main SVOM general objective is the survey of Gamma Ray Bursts, in coordination with ground telescopes. The other main on board instruments are ECLAIR (gamma, french), GRM (gamma, Chinese) and VT (visible, chinese).

A module located at a chromosomal integration hot spot is responsible for the multidrug resistance of a reference strain from Escherichia coli clonal group A.

PubMed

Lescat, Mathilde; Calteau, Alexandra; Hoede, Claire; Barbe, Valérie; Touchon, Marie; Rocha, Eduardo; Tenaillon, Olivier; Médigue, Claudine; Johnson, James R; Denamur, Erick

2009-06-01

Escherichia coli clonal group A (CGA) commonly exhibits a distinctive multidrug antimicrobial resistance phenotype-i.e., resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, tetracycline, and trimethoprim (ACSSuTTp)-and has accounted for up to 50% of trimethoprim-sulfamethoxazole-resistant E. coli urinary tract infections in some locales. Annotation of the whole-genome sequencing of UMN026, a reference CGA strain, clarified the genetic basis for this strain's ACSSuTTp antimicrobial resistance phenotype. Most of the responsible genes were clustered in a unique 23-kbp chromosomal region, designated the genomic resistance module (GRM), which occurred within a 105-kbp genomic island situated at the leuX tRNA. The GRM is characterized by numerous remnants of mobilization and rearrangement events suggesting multiple horizontal transfers. Additionally, comparative genomic analysis of the leuX tRNA genomic island in 14 sequenced E. coli genomes showed that this region is a hot spot of integration, with the presence/absence of specific subregions being uncorrelated with either the phylogenetic group or the pathotype. Our data illustrate the importance of whole-genome sequencing in the detection of genetic elements involved in antimicrobial resistance. Additionally, this is the first documentation of the bla(TEM) and dhfrVII genes in a chromosomal location in E. coli strains.

Calibration of the Dutch-Flemish PROMIS Pain Behavior item bank in patients with chronic pain.

PubMed

Crins, M H P; Roorda, L D; Smits, N; de Vet, H C W; Westhovens, R; Cella, D; Cook, K F; Revicki, D; van Leeuwen, J; Boers, M; Dekker, J; Terwee, C B

2016-02-01

The aims of the current study were to calibrate the item parameters of the Dutch-Flemish PROMIS Pain Behavior item bank using a sample of Dutch patients with chronic pain and to evaluate cross-cultural validity between the Dutch-Flemish and the US PROMIS Pain Behavior item banks. Furthermore, reliability and construct validity of the Dutch-Flemish PROMIS Pain Behavior item bank were evaluated. The 39 items in the bank were completed by 1042 Dutch patients with chronic pain. To evaluate unidimensionality, a one-factor confirmatory factor analysis (CFA) was performed. A graded response model (GRM) was used to calibrate the items. To evaluate cross-cultural validity, Differential item functioning (DIF) for language (Dutch vs. English) was evaluated. Reliability of the item bank was also examined and construct validity was studied using several legacy instruments, e.g. the Roland Morris Disability Questionnaire. CFA supported the unidimensionality of the Dutch-Flemish PROMIS Pain Behavior item bank (CFI = 0.960, TLI = 0.958), the data also fit the GRM, and demonstrated good coverage across the pain behavior construct (threshold parameters range: -3.42 to 3.54). Analysis showed good cross-cultural validity (only six DIF items), reliability (Cronbach's α = 0.95) and construct validity (all correlations ≥0.53). The Dutch-Flemish PROMIS Pain Behavior item bank was found to have good cross-cultural validity, reliability and construct validity. The development of the Dutch-Flemish PROMIS Pain Behavior item bank will serve as the basis for Dutch-Flemish PROMIS short forms and computer adaptive testing (CAT). © 2015 European Pain Federation - EFIC®

Scientific prospects for spectroscopy of the gamma-ray burst prompt emission with SVOM

NASA Astrophysics Data System (ADS)

Bernardini, M. G.; Xie, F.; Sizun, P.; Piron, F.; Dong, Y.; Atteia, J.-L.; Antier, S.; Daigne, F.; Godet, O.; Cordier, B.; Wei, J.

2017-10-01

SVOM (Space-based multi-band astronomical Variable Objects Monitor) is a Sino-French space mission dedicated to the study of Gamma-Ray Bursts (GRBs) in the next decade, capable to detect and localise the GRB emission, and to follow its evolution in the high-energy and X-ray domains, and in the visible and NIR bands. The satellite carries two wide-field high-energy instruments: a coded-mask gamma-ray imager (ECLAIRs; 4-150 keV), and a gamma-ray spectrometer (GRM; 15-5500 keV) that, together, will characterise the GRB prompt emission spectrum over a wide energy range. In this paper we describe the performances of the ECLAIRs and GRM system with different populations of GRBs from existing catalogues, from the classical ones to those with a possible thermal component superimposed to their non-thermal emission. The combination of ECLAIRs and the GRM will provide new insights also on other GRB properties, as for example the spectral characterisation of the subclass of short GRBs showing an extended emission after the initial spike.

Genomic prediction using preselected DNA variants from a GWAS with whole-genome sequence data in Holstein-Friesian cattle.

PubMed

Veerkamp, Roel F; Bouwman, Aniek C; Schrooten, Chris; Calus, Mario P L

2016-12-01

Whole-genome sequence data is expected to capture genetic variation more completely than common genotyping panels. Our objective was to compare the proportion of variance explained and the accuracy of genomic prediction by using imputed sequence data or preselected SNPs from a genome-wide association study (GWAS) with imputed whole-genome sequence data. Phenotypes were available for 5503 Holstein-Friesian bulls. Genotypes were imputed up to whole-genome sequence (13,789,029 segregating DNA variants) by using run 4 of the 1000 bull genomes project. The program GCTA was used to perform GWAS for protein yield (PY), somatic cell score (SCS) and interval from first to last insemination (IFL). From the GWAS, subsets of variants were selected and genomic relationship matrices (GRM) were used to estimate the variance explained in 2087 validation animals and to evaluate the genomic prediction ability. Finally, two GRM were fitted together in several models to evaluate the effect of selected variants that were in competition with all the other variants. The GRM based on full sequence data explained only marginally more genetic variation than that based on common SNP panels: for PY, SCS and IFL, genomic heritability improved from 0.81 to 0.83, 0.83 to 0.87 and 0.69 to 0.72, respectively. Sequence data also helped to identify more variants linked to quantitative trait loci and resulted in clearer GWAS peaks across the genome. The proportion of total variance explained by the selected variants combined in a GRM was considerably smaller than that explained by all variants (less than 0.31 for all traits). When selected variants were used, accuracy of genomic predictions decreased and bias increased. Although 35 to 42 variants were detected that together explained 13 to 19% of the total variance (18 to 23% of the genetic variance) when fitted alone, there was no advantage in using dense sequence information for genomic prediction in the Holstein data used in our study. Detection and selection of variants within a single breed are difficult due to long-range linkage disequilibrium. Stringent selection of variants resulted in more biased genomic predictions, although this might be due to the training population being the same dataset from which the selected variants were identified.

Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence.

PubMed

Chen, Andrew C H; Tang, Yongqiang; Rangaswamy, Madhavi; Wang, Jen C; Almasy, Laura; Foroud, Tatiana; Edenberg, Howard J; Hesselbrock, Victor; Nurnberger, John; Kuperman, Samuel; O'Connor, Sean J; Schuckit, Marc A; Bauer, Lance O; Tischfield, Jay; Rice, John P; Bierut, Laura; Goate, Alison; Porjesz, Bernice

2009-04-05

Evidence suggests the P3 amplitude of the event-related potential and its underlying superimposed event-related oscillations (EROs), primarily in the theta (4-5 Hz) and delta (1-3 Hz) frequencies, as endophenotypes for the risk of alcoholism and other disinhibitory disorders. Major neurochemical substrates contributing to theta and delta rhythms and P3 involve strong GABAergic, cholinergic and glutamatergic system interactions. The aim of this study was to test the potential associations between single nucleotide polymorphisms (SNPs) in glutamate receptor genes and ERO quantitative traits. GRM8 was selected because it maps at chromosome 7q31.3-q32.1 under the peak region where we previously identified significant linkage (peak LOD = 3.5) using a genome-wide linkage scan of the same phenotype (event-related theta band for the target visual stimuli). Neural activities recorded from scalp electrodes during a visual oddball task in which rare target elicited P3s were analyzed in a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) sample comprising 1,049 Caucasian subjects from 209 families (with 472 DSM-IV alcohol dependent individuals). The family-based association test (FBAT) detected significant association (P < 0.05) with multiple SNPs in the GRM8 gene and event-related theta power to target visual stimuli, and also with alcohol dependence, even after correction for multiple comparisons by false discovery rate (FDR). Our results suggest that variation in GRM8 may be involved in modulating event-related theta oscillations during information processing and also in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders. (c) 2008 Wiley-Liss, Inc.

Phenotypic characterization of Grm1crv4 mice reveals a functional role for the type 1 metabotropic glutamate receptor in bone mineralization.

PubMed

Musante, Ilaria; Mattinzoli, Deborah; Otescu, Lavinia Alexandra; Bossi, Simone; Ikehata, Masami; Gentili, Chiara; Cangemi, Giuliana; Gatti, Cinzia; Emionite, Laura; Messa, Piergiorgio; Ravazzolo, Roberto; Rastaldi, Maria Pia; Riccardi, Daniela; Puliti, Aldamaria

2017-01-01

Recent increasing evidence supports a role for neuronal type signaling in bone. Specifically glutamate receptors have been found in cells responsible for bone remodeling, namely the osteoblasts and the osteoclasts. While most studies have focused on ionotropic glutamate receptors, the relevance of the metabotropic glutamate signaling in bone is poorly understood. Specifically type 1 metabotropic glutamate (mGlu1) receptors are expressed in bone, but the effect of its ablation on skeletal development has never been investigated. Here we report that Grm1 crv4/crv4 mice, homozygous for an inactivating mutation of the mGlu1 receptor, and mainly characterized by ataxia and renal dysfunction, exhibit decreased body weight, bone length and bone mineral density compared to wild type (WT) animals. Blood analyses of the affected mice demonstrate the absence of changes in circulating factors, such as vitamin D and PTH, suggesting renal damage is not the main culprit of the skeletal phenotype. Cultures of osteoblasts lacking functional mGlu1 receptors exhibit less homogeneous collagen deposition than WT cells, and present increased expression of osteocalcin, a marker of osteoblast maturation. These data suggest that the skeletal damage is directly linked to the absence of the receptor, which in turn leads to osteoblasts dysfunction and earlier maturation. Accordingly, skeletal histomorphology suggests that Grm1 crv4/crv4 mice exhibit enhanced bone maturation, resulting in premature fusion of the growth plate and shortened long bones, and further slowdown of bone apposition rate compared to the WT animals. In summary, this work reveals novel functions of mGlu1 receptors in the bone and indicates that in osteoblasts mGlu1 receptors are necessary for production of normal bone matrix, longitudinal bone growth, and normal skeletal development. Copyright © 2016 Elsevier Inc. All rights reserved.

The e-MSWS-12: improving the multiple sclerosis walking scale using item response theory.

PubMed

Engelhard, Matthew M; Schmidt, Karen M; Engel, Casey E; Brenton, J Nicholas; Patek, Stephen D; Goldman, Myla D

2016-12-01

The Multiple Sclerosis Walking Scale (MSWS-12) is the predominant patient-reported measure of multiple sclerosis (MS) -elated walking ability, yet it had not been analyzed using item response theory (IRT), the emerging standard for patient-reported outcome (PRO) validation. This study aims to reduce MSWS-12 measurement error and facilitate computerized adaptive testing by creating an IRT model of the MSWS-12 and distributing it online. MSWS-12 responses from 284 subjects with MS were collected by mail and used to fit and compare several IRT models. Following model selection and assessment, subpopulations based on age and sex were tested for differential item functioning (DIF). Model comparison favored a one-dimensional graded response model (GRM). This model met fit criteria and explained 87 % of response variance. The performance of each MSWS-12 item was characterized using category response curves (CRCs) and item information. IRT-based MSWS-12 scores correlated with traditional MSWS-12 scores (r = 0.99) and timed 25-foot walk (T25FW) speed (r =  -0.70). Item 2 showed DIF based on age (χ 2  = 19.02, df = 5, p < 0.01), and Item 11 showed DIF based on sex (χ 2  = 13.76, df = 5, p = 0.02). MSWS-12 measurement error depends on walking ability, but could be lowered by improving or replacing items with low information or DIF. The e-MSWS-12 includes IRT-based scoring, error checking, and an estimated T25FW derived from MSWS-12 responses. It is available at https://ms-irt.shinyapps.io/e-MSWS-12 .

Metoprolol Increases Uric Acid and Risk of Gout in African Americans With Chronic Kidney Disease Attributed to Hypertension.

PubMed

Juraschek, Stephen P; Appel, Lawrence J; Miller, Edgar R

2017-09-01

There is little evidence guiding selection of nondiuretic, antihypertensive agents with a goal of lowering uric acid (SUA) and minimizing gout risk. In the African American Study of Kidney Disease and Hypertension (AASK) trial, African Americans with chronic kidney disease were randomly assigned to metoprolol (a beta-blocker), ramipril (an angiotensin-converting enzyme inhibitors [ACEi]), or amlodipine (a dihydropyridine calcium-channel blocker). SUA was measured at baseline and 12 months. Gout-related hospitalizations were based on ICD9 codes. Gout-related medication use (GRMs) was based on active prescriptions of allopurinol, colchicine, or probenecid during the baseline visit of the AASK cohort phase. We examined the effect of drug assignment on 12-month SUA (linear regression), gout-related hospitalization (Cox regression), and GRM (logistic regression). Of the 630 participants, 40% were female with a mean age of 55 years (SD, 10), mean SUA of 8.2 mg/dl (2.0), and mean serum creatinine of 1.8 mg/dl (0.6). After 12 months, metoprolol increased SUA by 0.3 mg/dl, while ramipril or amlodipine had no effect on SUA. Compared to ramipril, metoprolol significantly increased 12-month SUA (0.40; 0.10, 0.70 mg/dl; P = 0.009), nonsignificantly increased risk of gout-related hospitalization (hazard ratio: 3.87; 0.82, 18.26; P = 0.09), and significantly increased the odds of GRM (odds ratio: 1.62; 1.03, 2.54; P = 0.04). While metoprolol was associated with a higher 12-month SUA compared with amlodipine (0.57; 0.18, 0.95; P = 0.004), there was no difference in gout-related hospitalizations or GRM. Metoprolol increased SUA and GRM in African American adults. Health professionals treating patients with kidney disease at risk for gout should avoid metoprolol and possibly consider an ACEi. Trial Number NCT00582777. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Two Ganoderma species: profiling of phenolic compounds by HPLC-DAD, antioxidant, antimicrobial and inhibitory activities on key enzymes linked to diabetes mellitus, Alzheimer's disease and skin disorders.

PubMed

Zengin, Gokhan; Sarikurkcu, Cengiz; Gunes, Erdogan; Uysal, Ahmet; Ceylan, Ramazan; Uysal, Sengul; Gungor, Halil; Aktumsek, Abdurrahman

2015-08-01

This work reports the antioxidant, antimicrobial, and inhibitory effects of methanol and water extracts from Ganoderma applanatum (GAM: methanol extract and GAW: water extract) and G. resinaceum (GRM: methanol extract and GRW: water extract) against cholinesterase, tyrosinase, α-amylase and α-glucosidase. The total phenolics, flavonoids contents, and HPLC profile of phenolic components present in the extracts, were also determined. Antioxidant activities were investigated by using different assays, including DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum and metal chelating assays. Antimicrobial activity of the tested Ganoderma extracts was also studied by the broth microdilution method. Generally, the highest antioxidant (59.24 mg TEs per g extract for DPPH, 41.32 mg TEs per g extract for ABTS, 41.35 mg TEs per g extract for CUPRAC, 49.68 mg TEs per g extract for FRAP, 130.57 mg AAEs per g extract for phosphomolybdenum and 26.92 mg EDTAEs per g extract) and enzyme inhibitory effects (1.47 mg GALAEs per g extract for AChE, 1.51 mg GALAEs per g extract for BChE, 13.40 mg KAEs per g extract for tyrosinase, 1.13 mmol ACEs per g extract for α-amylase and 2.20 mmol ACEs per g extract for α-glucosidase) were observed in GRM, which had the highest concentrations of phenolics (37.32 mg GAEs g(-1) extract). Again, Ganoderma extracts possess weak antibacterial and antifungal activities. Apigenin and protocatechuic acid were determined as the main components in GRM (1761 μg per g extract) and GAM (165 μg per g extract), respectively. The results suggest that the Ganoderma species may be considered as a candidate for preparing new food supplements and can represent a good model for the development of new drug formulations.

Sorting out co-occurrence of rare monogenic retinopathies: Stargardt disease co-existing with congenital stationary night blindness.

PubMed

Huynh, Nancy; Jeffrey, Brett G; Turriff, Amy; Sieving, Paul A; Cukras, Catherine A

2014-03-01

Inherited retinal diseases are uncommon, and the likelihood of having more than one hereditary disorder is rare. Here, we report a case of Stargardt disease and congenital stationary night blindness (CSNB) in the same patient, and the identification of two novel in-frame deletions in the GRM6 gene. The patient underwent an ophthalmic exam and visual function testing including: visual acuity, color vision, Goldmann visual field, and electroretinography (ERG). Imaging of the retina included fundus photography, spectral-domain optical coherence tomography (OCT), and fundus autofluorescence. Genomic DNA was PCR-amplified for analysis of all coding exons and flanking splice sites of both the ABCA4 and GRM6 genes. A 46-year-old woman presented with recently reduced central vision and clinical findings of characteristic yellow flecks consistent with Stargardt disease. However, ERG testing revealed an ERG phenotype unusual for Stargardt disease but consistent with CSNB1. Genetic testing revealed two previously reported mutations in the ABCA4 gene and two novel deletions in the GRM6 gene. Diagnosis of concurrent Stargardt disease and CSNB was made on the ophthalmic history, clinical examination, ERG, and genetic testing. This case highlights that clinical tests need to be taken in context, and that co-existing retinal dystrophies and degenerations should be considered when clinical impressions and objective data do not correlate.

In Vitro Characterization and Concerted Function of Three Core Enzymes of a Glycyl Radical Enzyme - Associated Bacterial Microcompartment.

PubMed

Zarzycki, Jan; Sutter, Markus; Cortina, Niña Socorro; Erb, Tobias J; Kerfeld, Cheryl A

2017-02-16

Many bacteria encode proteinaceous bacterial microcompartments (BMCs) that encapsulate sequential enzymatic reactions of diverse metabolic pathways. Well-characterized BMCs include carboxysomes for CO 2 -fixation, and propanediol- and ethanolamine-utilizing microcompartments that contain B 12 -dependent enzymes. Genes required to form BMCs are typically organized in gene clusters, which promoted their distribution across phyla by horizontal gene transfer. Recently, BMCs associated with glycyl radical enzymes (GREs) were discovered; these are widespread and comprise at least three functionally distinct types. Previously, we predicted one type of these GRE-associated microcompartments (GRMs) represents a B 12 -independent propanediol-utilizing BMC. Here we functionally and structurally characterize enzymes of the GRM of Rhodopseudomonas palustris BisB18 and demonstrate their concerted function in vitro. The GRM signature enzyme, the GRE, is a dedicated 1,2-propanediol dehydratase with a new type of intramolecular encapsulation peptide. It forms a complex with its activating enzyme and, in conjunction with an aldehyde dehydrogenase, converts 1,2-propanediol to propionyl-CoA. Notably, homologous GRMs are also encoded in pathogenic Escherichia coli strains. Our high-resolution crystal structures of the aldehyde dehydrogenase lead to a revised reaction mechanism. The successful in vitro reconstitution of a part of the GRM metabolism provides insights into the metabolic function and steps in the assembly of this BMC.

Expression of group III metabotropic glutamate receptors in the reproductive system of male mice.

PubMed

Marciniak, Marcin; Chruścicka, Barbara; Lech, Tomasz; Burnat, Grzegorz; Pilc, Andrzej

2016-03-01

Although the presence of metabotropic glutamate (mGlu) receptors in the central nervous system is well documented, they have recently been found in peripheral and non-neuronal tissues. In the present study we investigated the expression of group III mGlu receptors in the reproductive system of male mice. Reverse transcription-polymerase chain reaction analysis revealed the presence of mGlu6, mGlu7 and mGlu8 (but not mGlu4) receptor transcripts in testes and epididymides from adult mice. In addition, expression of mGlu6 (Grm6) and mGlu8 receptor (Grm8) mRNA was detected in spermatozoa isolated from the vas deferens. The vas deferens was found to contain only mGlu7 receptor (Grm7) mRNA, which was particularly intense in 21-day-old male mice. In penile homogenates, only the mGlu7 receptor signal was detected. Genetic ablation of the mGlu7 receptor in males led to fertility disorders manifested by decreased insemination capability as well as deterioration of sperm parameters, particularly sperm motility, vitality, sperm membrane integrity and morphology, with a simultaneous increase in sperm concentration. These results indicate that constitutively expressed mGlu receptors in the male reproductive system may play an important role in ejaculation and/or erection processes, as well as in the formation and maturation of spermatozoa.

In Vitro Characterization and Concerted Function of Three Core Enzymes of a Glycyl Radical Enzyme - Associated Bacterial Microcompartment

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

Zarzycki, Jan; Sutter, Markus; Cortina, Niña Socorro

Many bacteria encode proteinaceous bacterial microcompartments (BMCs) that encapsulate sequential enzymatic reactions of diverse metabolic pathways. Well-characterized BMCs include carboxysomes for CO 2-fixation, and propanediol- and ethanolamine-utilizing microcompartments that contain B 12-dependent enzymes. Genes thus required to form BMCs are typically organized in gene clusters, which promoted their distribution across phyla by horizontal gene transfer. Recently, BMCs associated with glycyl radical enzymes (GREs) were discovered; these are widespread and comprise at least three functionally distinct types. Previously, we predicted one type of these GRE-associated microcompartments (GRMs) represents a B 12-independent propanediol-utilizing BMC. We functionally and structurally characterize enzymes of themore » GRM of Rhodopseudomonas palustris BisB18 and demonstrate their concerted function in vitro. The GRM signature enzyme, the GRE, is a dedicated 1,2-propanediol dehydratase with a new type of intramolecular encapsulation peptide. It forms a complex with its activating enzyme and, in conjunction with an aldehyde dehydrogenase, converts 1,2-propanediol to propionyl-CoA. Notably, homologous GRMs are also encoded in pathogenic Escherichia coli strains. Our high-resolution crystal structures of the aldehyde dehydrogenase lead to a revised reaction mechanism. The successful in vitro reconstitution of a part of the GRM metabolism provides insights into the metabolic function and steps in the assembly of this BMC.« less

In Vitro Characterization and Concerted Function of Three Core Enzymes of a Glycyl Radical Enzyme - Associated Bacterial Microcompartment

DOE PAGES

Zarzycki, Jan; Sutter, Markus; Cortina, Niña Socorro; ...

2017-02-16

Many bacteria encode proteinaceous bacterial microcompartments (BMCs) that encapsulate sequential enzymatic reactions of diverse metabolic pathways. Well-characterized BMCs include carboxysomes for CO 2-fixation, and propanediol- and ethanolamine-utilizing microcompartments that contain B 12-dependent enzymes. Genes thus required to form BMCs are typically organized in gene clusters, which promoted their distribution across phyla by horizontal gene transfer. Recently, BMCs associated with glycyl radical enzymes (GREs) were discovered; these are widespread and comprise at least three functionally distinct types. Previously, we predicted one type of these GRE-associated microcompartments (GRMs) represents a B 12-independent propanediol-utilizing BMC. We functionally and structurally characterize enzymes of themore » GRM of Rhodopseudomonas palustris BisB18 and demonstrate their concerted function in vitro. The GRM signature enzyme, the GRE, is a dedicated 1,2-propanediol dehydratase with a new type of intramolecular encapsulation peptide. It forms a complex with its activating enzyme and, in conjunction with an aldehyde dehydrogenase, converts 1,2-propanediol to propionyl-CoA. Notably, homologous GRMs are also encoded in pathogenic Escherichia coli strains. Our high-resolution crystal structures of the aldehyde dehydrogenase lead to a revised reaction mechanism. The successful in vitro reconstitution of a part of the GRM metabolism provides insights into the metabolic function and steps in the assembly of this BMC.« less

A genome wide association study links glutamate receptor pathway to sporadic Creutzfeldt-Jakob disease risk.

PubMed

Sanchez-Juan, Pascual; Bishop, Matthew T; Kovacs, Gabor G; Calero, Miguel; Aulchenko, Yurii S; Ladogana, Anna; Boyd, Alison; Lewis, Victoria; Ponto, Claudia; Calero, Olga; Poleggi, Anna; Carracedo, Ángel; van der Lee, Sven J; Ströbel, Thomas; Rivadeneira, Fernando; Hofman, Albert; Haïk, Stéphane; Combarros, Onofre; Berciano, José; Uitterlinden, Andre G; Collins, Steven J; Budka, Herbert; Brandel, Jean-Philippe; Laplanche, Jean Louis; Pocchiari, Maurizio; Zerr, Inga; Knight, Richard S G; Will, Robert G; van Duijn, Cornelia M

2014-01-01

We performed a genome-wide association (GWA) study in 434 sporadic Creutzfeldt-Jakob disease (sCJD) patients and 1939 controls from the United Kingdom, Germany and The Netherlands. The findings were replicated in an independent sample of 1109 sCJD and 2264 controls provided by a multinational consortium. From the initial GWA analysis we selected 23 SNPs for further genotyping in 1109 sCJD cases from seven different countries. Five SNPs were significantly associated with sCJD after correction for multiple testing. Subsequently these five SNPs were genotyped in 2264 controls. The pooled analysis, including 1543 sCJD cases and 4203 controls, yielded two genome wide significant results: rs6107516 (p-value=7.62x10-9) a variant tagging the prion protein gene (PRNP); and rs6951643 (p-value=1.66x10-8) tagging the Glutamate Receptor Metabotropic 8 gene (GRM8). Next we analysed the data stratifying by country of origin combining samples from the pooled analysis with genotypes from the 1000 Genomes Project and imputed genotypes from the Rotterdam Study (Total n=12967). The meta-analysis of the results showed that rs6107516 (p-value=3.00x10-8) and rs6951643 (p-value=3.91x10-5) remained as the two most significantly associated SNPs. Rs6951643 is located in an intronic region of GRM8, a gene that was additionally tagged by a cluster of 12 SNPs within our top100 ranked results. GRM8 encodes for mGluR8, a protein which belongs to the metabotropic glutamate receptor family, recently shown to be involved in the transduction of cellular signals triggered by the prion protein. Pathway enrichment analyses performed with both Ingenuity Pathway Analysis and ALIGATOR postulates glutamate receptor signalling as one of the main pathways associated with sCJD. In summary, we have detected GRM8 as a novel, non-PRNP, genome-wide significant marker associated with heightened disease risk, providing additional evidence supporting a role of glutamate receptors in sCJD pathogenesis.

The Geopotential Research Mission - Mapping the near earth gravity and magnetic fields

NASA Technical Reports Server (NTRS)

Taylor, P. T.; Keating, T.; Smith, D. E.; Langel, R. A.; Schnetzler, C. C.; Kahn, W. D.

1983-01-01

The Geopotential Research Mission (GRM), NASA's low-level satellite system designed to measure the gravity and magnetic fields of the earth, and its objectives are described. The GRM will consist of two, Shuttle launched, satellite systems (300 km apart) that will operate simultaneously at a 160 km circular-polar orbit for six months. Current mission goals include mapping the global geoid to 10 cm, measuring gravity-field anomalies to 2 mgal with a spatial resolution of 100 km, detecting crustal magnetic anomalies of 100 km wavelength with 1 nT accuracy, measuring the vectors components to + or - 5 arc sec and 5 nT, and computing the main dipole or core field to 5 nT with a 2 nT/year secular variation detection. Resource analysis and exploration geology are additional applications considered.

Mapping magnetized geologic structures from space: The effect of orbital and body parameters

NASA Technical Reports Server (NTRS)

Schnetzler, C. C.; Taylor, P. T.; Langel, R. A.

1984-01-01

When comparing previous satellite magnetometer missions (such as MAGSAT) with proposed new programs (for example, Geopotential Research Mission, GRM) it is important to quantify the difference in scientific information obtained. The ability to resolve separate magnetic blocks (simulating geological units) is used as a parameter for evaluating the expected geologic information from each mission. The effect of satellite orbital altitude on the ability to resolve two magnetic blocks with varying separations is evaluated and quantified. A systematic, nonlinear, relationship exists between resolution and distance between magnetic blocks as a function of orbital altitude. The proposed GRM would provide an order-of-magnitude greater anomaly resolution than the earlier MAGSAT mission for widely separated bodies. The resolution achieved at any particular altitude varies depending on the location of the bodies and orientation.

Response of consumer and research grade indoor air quality monitors to residential sources of fine particles.

PubMed

Singer, B C; Delp, W W

2018-04-23

The ability to inexpensively monitor PM 2.5 to identify sources and enable controls would advance residential indoor air quality (IAQ) management. Consumer IAQ monitors incorporating low-cost optical particle sensors and connections with smart home platforms could provide this service if they reliably detect PM 2.5 in homes. In this study, particles from typical residential sources were generated in a 120 m 3 laboratory and time-concentration profiles were measured with 7 consumer monitors (2-3 units each), 2 research monitors (Thermo pDR-1500, MetOne BT-645), a Grimm Mini Wide-Range Aerosol Spectrometer (GRM), and a Tapered Element Oscillating Microbalance with Filter Dynamic Measurement System (FDMS), a Federal Equivalent Method for PM 2.5 . Sources included recreational combustion (candles, cigarettes, incense), cooking activities, an unfiltered ultrasonic humidifier, and dust. FDMS measurements, filter samples, and known densities were used to adjust the GRM to obtain time-resolved mass concentrations. Data from the research monitors and 4 of the consumer monitors-AirBeam, AirVisual, Foobot, Purple Air-were time correlated and within a factor of 2 of the estimated mass concentrations for most sources. All 7 of the consumer and both research monitors substantially under-reported or missed events for which the emitted mass was comprised of particles smaller than 0.3 μm diameter. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Local gravity disturbance estimation from multiple-high-single-low satellite-to-satellite tracking

NASA Technical Reports Server (NTRS)

Jekeli, Christopher

1989-01-01

The idea of satellite-to-satellite tracking in the high-low mode has received renewed attention in light of the uncertain future of NASA's proposed low-low mission, Geopotential Research Mission (GRM). The principal disadvantage with a high-low system is the increased time interval required to obtain global coverage since the intersatellite visibility is often obscured by Earth. The U.S. Air Force has begun to investigate high-low satellite-to-satellite tracking between the Global Positioning System (GPS) of satellites (high component) and NASA's Space Transportation System (STS), the shuttle (low component). Because the GPS satellites form, or will form, a constellation enabling continuous three-dimensional tracking of a low-altitude orbiter, there will be no data gaps due to lack of intervisibility. Furthermore, all three components of the gravitation vector are estimable at altitude, a given grid of which gives a stronger estimate of gravity on Earth's surface than a similar grid of line-of-sight gravitation components. The proposed Air Force mission is STAGE (Shuttle-GPS Tracking for Anomalous Gravitation Estimation) and is designed for local gravity field determinations since the shuttle will likely not achieve polar orbits. The motivation for STAGE was the feasibility to obtain reasonable accuracies with absolutely minimal cost. Instead of simulating drag-free orbits, STAGE uses direct measurements of the nongravitational forces obtained by an inertial package onboard the shuttle. The sort of accuracies that would be achievable from STAGE vis-a-vis other satellite tracking missions such as GRM and European Space Agency's POPSAT-GRM are analyzed.

Extensive Gene Amplification as a Mechanism for Piperacillin-Tazobactam Resistance in Escherichia coli.

PubMed

Schechter, Lisa M; Creely, David P; Garner, Cherilyn D; Shortridge, Dee; Nguyen, Hoan; Chen, Lei; Hanson, Blake M; Sodergren, Erica; Weinstock, George M; Dunne, W Michael; van Belkum, Alex; Leopold, Shana R

2018-04-24

Although the TEM-1 β-lactamase (Bla TEM-1 ) hydrolyzes penicillins and narrow-spectrum cephalosporins, organisms expressing this enzyme are typically susceptible to β-lactam/β-lactamase inhibitor combinations such as piperacillin-tazobactam (TZP). However, our previous work led to the discovery of 28 clinical isolates of Escherichia coli resistant to TZP that contained only bla TEM-1 One of these isolates, E. coli 907355, was investigated further in this study. E. coli 907355 exhibited significantly higher β-lactamase activity and Bla TEM-1 protein levels when grown in the presence of subinhibitory concentrations of TZP. A corresponding TZP-dependent increase in bla TEM-1 copy number was also observed, with as many as 113 copies of the gene detected per cell. These results suggest that TZP treatment promotes an increase in bla TEM-1 gene dosage, allowing Bla TEM-1 to reach high enough levels to overcome inactivation by the available tazobactam in the culture. To better understand the nature of the bla TEM-1 copy number proliferation, whole-genome sequence (WGS) analysis was performed on E. coli 907355 in the absence and presence of TZP. The WGS data revealed that the bla TEM-1 gene is located in a 10-kb genomic resistance module (GRM) that contains multiple resistance genes and mobile genetic elements. The GRM was found to be tandemly repeated at least 5 times within a p1ESCUM/p1ECUMN-like plasmid when bacteria were grown in the presence of TZP. IMPORTANCE Understanding how bacteria acquire resistance to antibiotics is essential for treating infected patients effectively, as well as preventing the spread of resistant organisms. In this study, a clinical isolate of E. coli was identified that dedicated more than 15% of its genome toward tandem amplification of a ~10-kb resistance module, allowing it to escape antibiotic-mediated killing. Our research is significant in that it provides one possible explanation for clinical isolates that exhibit discordant behavior when tested for antibiotic resistance by different phenotypic methods. Our research also shows that GRM amplification is difficult to detect by short-read WGS technologies. Analysis of raw long-read sequence data was required to confirm GRM amplification as a mechanism of antibiotic resistance. Copyright © 2018 Schechter et al.

The Role of a Novel TRMT1 Gene Mutation and Rare GRM1 Gene Defect in Intellectual Disability in Two Azeri Families

PubMed Central

Kahrizi, Kimia; Musante, Luciana; Fattahi, Zohreh; Hosseini, Masoumeh; Maqsoud, Fariba; Farajollahi, Reza; Wienker, Thomas F.; Ropers, H. Hilger; Najmabadi, Hossein

2015-01-01

Cognitive impairment or intellectual disability (ID) is a widespread neurodevelopmental disorder characterized by low IQ (below 70). ID is genetically heterogeneous and is estimated to affect 1–3% of the world’s population. In affected children from consanguineous families, autosomal recessive inheritance is common, and identifying the underlying genetic cause is an important issue in clinical genetics. In the framework of a larger project, aimed at identifying candidate genes for autosomal recessive intellectual disorder (ARID), we recently carried out single nucleotide polymorphism-based genome-wide linkage analysis in several families from Ardabil province in Iran. The identification of homozygosity-by-descent loci in these families, in combination with whole exome sequencing, led us to identify possible causative homozygous changes in two families. In the first family, a missense variant was found in GRM1 gene, while in the second family, a frameshift alteration was identified in TRMT1, both of which were found to co-segregate with the disease. GRM1, a known causal gene for autosomal recessive spinocerebellar ataxia (SCAR13, MIM#614831), encodes the metabotropic glutamate receptor1 (mGluR1). This gene plays an important role in synaptic plasticity and cerebellar development. Conversely, the TRMT1 gene encodes a tRNA methyltransferase that dimethylates a single guanine residue at position 26 of most tRNAs using S-adenosyl methionine as the methyl group donor. We recently presented TRMT1 as a candidate gene for ARID in a consanguineous Iranian family (Najmabadi et al., 2011). We believe that this second Iranian family with a biallelic loss-of-function mutation in TRMT1 gene supports the idea that this gene likely has function in development of the disorder. PMID:26308914

The Role of a Novel TRMT1 Gene Mutation and Rare GRM1 Gene Defect in Intellectual Disability in Two Azeri Families.

PubMed

Davarniya, Behzad; Hu, Hao; Kahrizi, Kimia; Musante, Luciana; Fattahi, Zohreh; Hosseini, Masoumeh; Maqsoud, Fariba; Farajollahi, Reza; Wienker, Thomas F; Ropers, H Hilger; Najmabadi, Hossein

2015-01-01

Cognitive impairment or intellectual disability (ID) is a widespread neurodevelopmental disorder characterized by low IQ (below 70). ID is genetically heterogeneous and is estimated to affect 1-3% of the world's population. In affected children from consanguineous families, autosomal recessive inheritance is common, and identifying the underlying genetic cause is an important issue in clinical genetics. In the framework of a larger project, aimed at identifying candidate genes for autosomal recessive intellectual disorder (ARID), we recently carried out single nucleotide polymorphism-based genome-wide linkage analysis in several families from Ardabil province in Iran. The identification of homozygosity-by-descent loci in these families, in combination with whole exome sequencing, led us to identify possible causative homozygous changes in two families. In the first family, a missense variant was found in GRM1 gene, while in the second family, a frameshift alteration was identified in TRMT1, both of which were found to co-segregate with the disease. GRM1, a known causal gene for autosomal recessive spinocerebellar ataxia (SCAR13, MIM#614831), encodes the metabotropic glutamate receptor1 (mGluR1). This gene plays an important role in synaptic plasticity and cerebellar development. Conversely, the TRMT1 gene encodes a tRNA methyltransferase that dimethylates a single guanine residue at position 26 of most tRNAs using S-adenosyl methionine as the methyl group donor. We recently presented TRMT1 as a candidate gene for ARID in a consanguineous Iranian family (Najmabadi et al., 2011). We believe that this second Iranian family with a biallelic loss-of-function mutation in TRMT1 gene supports the idea that this gene likely has function in development of the disorder.

A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci.

PubMed

Low, Joyce Siew Yong; Chin, Yoon Ming; Mushiroda, Taisei; Kubo, Michiaki; Govindasamy, Gopala Krishnan; Pua, Kin Choo; Yap, Yoke Yeow; Yap, Lee Fah; Subramaniam, Selva Kumar; Ong, Cheng Ai; Tan, Tee Yong; Khoo, Alan Soo Beng; Ng, Ching Ching

2016-01-01

Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition. A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124). Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96-17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11) overlapping MICA/HCP5/HCG26 genes. Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

Comprehensive gene- and pathway-based analysis of depressive symptoms in older adults.

PubMed

Nho, Kwangsik; Ramanan, Vijay K; Horgusluoglu, Emrin; Kim, Sungeun; Inlow, Mark H; Risacher, Shannon L; McDonald, Brenna C; Farlow, Martin R; Foroud, Tatiana M; Gao, Sujuan; Callahan, Christopher M; Hendrie, Hugh C; Niculescu, Alexander B; Saykin, Andrew J

2015-01-01

Depressive symptoms are common in older adults and are particularly prevalent in those with or at elevated risk for dementia. Although the heritability of depression is estimated to be substantial, single nucleotide polymorphism-based genome-wide association studies of depressive symptoms have had limited success. In this study, we performed genome-wide gene- and pathway-based analyses of depressive symptom burden. Study participants included non-Hispanic Caucasian subjects (n = 6,884) from three independent cohorts, the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Health and Retirement Study (HRS), and the Indiana Memory and Aging Study (IMAS). Gene-based meta-analysis identified genome-wide significant associations (ANGPT4 and FAM110A, q-value = 0.026; GRM7-AS3 and LRFN5, q-value = 0.042). Pathway analysis revealed enrichment of association in 105 pathways, including multiple pathways related to ERK/MAPK signaling, GSK3 signaling in bipolar disorder, cell development, and immune activation and inflammation. GRM7, ANGPT4, and LRFN5 have been previously implicated in psychiatric disorders, including the GRM7 region displaying association with major depressive disorder. The ERK/MAPK signaling pathway is a known target of antidepressant drugs and has important roles in neuronal plasticity, and GSK3 signaling has been previously implicated in Alzheimer's disease and as a promising therapeutic target for depression. Our results warrant further investigation in independent and larger cohorts and add to the growing understanding of the genetics and pathobiology of depressive symptoms in aging and neurodegenerative disorders. In particular, the genes and pathways demonstrating association with depressive symptoms may be potential therapeutic targets for these symptoms in older adults.

Impacts of spatial resolution and representation of flow connectivity on large-scale simulation of floods

NASA Astrophysics Data System (ADS)

Mateo, Cherry May R.; Yamazaki, Dai; Kim, Hyungjun; Champathong, Adisorn; Vaze, Jai; Oki, Taikan

2017-10-01

Global-scale river models (GRMs) are core tools for providing consistent estimates of global flood hazard, especially in data-scarce regions. Due to former limitations in computational power and input datasets, most GRMs have been developed to use simplified representations of flow physics and run at coarse spatial resolutions. With increasing computational power and improved datasets, the application of GRMs to finer resolutions is becoming a reality. To support development in this direction, the suitability of GRMs for application to finer resolutions needs to be assessed. This study investigates the impacts of spatial resolution and flow connectivity representation on the predictive capability of a GRM, CaMa-Flood, in simulating the 2011 extreme flood in Thailand. Analyses show that when single downstream connectivity (SDC) is assumed, simulation results deteriorate with finer spatial resolution; Nash-Sutcliffe efficiency coefficients decreased by more than 50 % between simulation results at 10 km resolution and 1 km resolution. When multiple downstream connectivity (MDC) is represented, simulation results slightly improve with finer spatial resolution. The SDC simulations result in excessive backflows on very flat floodplains due to the restrictive flow directions at finer resolutions. MDC channels attenuated these effects by maintaining flow connectivity and flow capacity between floodplains in varying spatial resolutions. While a regional-scale flood was chosen as a test case, these findings should be universal and may have significant impacts on large- to global-scale simulations, especially in regions where mega deltas exist.These results demonstrate that a GRM can be used for higher resolution simulations of large-scale floods, provided that MDC in rivers and floodplains is adequately represented in the model structure.

Bioinformatic Characterization of Glycyl Radical Enzyme-Associated Bacterial Microcompartments

PubMed Central

Zarzycki, Jan; Erbilgin, Onur

2015-01-01

Bacterial microcompartments (BMCs) are proteinaceous organelles encapsulating enzymes that catalyze sequential reactions of metabolic pathways. BMCs are phylogenetically widespread; however, only a few BMCs have been experimentally characterized. Among them are the carboxysomes and the propanediol- and ethanolamine-utilizing microcompartments, which play diverse metabolic and ecological roles. The substrate of a BMC is defined by its signature enzyme. In catabolic BMCs, this enzyme typically generates an aldehyde. Recently, it was shown that the most prevalent signature enzymes encoded by BMC loci are glycyl radical enzymes, yet little is known about the function of these BMCs. Here we characterize the glycyl radical enzyme-associated microcompartment (GRM) loci using a combination of bioinformatic analyses and active-site and structural modeling to show that the GRMs comprise five subtypes. We predict distinct functions for the GRMs, including the degradation of choline, propanediol, and fuculose phosphate. This is the first family of BMCs for which identification of the signature enzyme is insufficient for predicting function. The distinct GRM functions are also reflected in differences in shell composition and apparently different assembly pathways. The GRMs are the counterparts of the vitamin B12-dependent propanediol- and ethanolamine-utilizing BMCs, which are frequently associated with virulence. This study provides a comprehensive foundation for experimental investigations of the diverse roles of GRMs. Understanding this plasticity of function within a single BMC family, including characterization of differences in permeability and assembly, can inform approaches to BMC bioengineering and the design of therapeutics. PMID:26407889

Ground Truth in Building Human Security

DTIC Science & Technology

2012-11-01

Peace, Charles Call and Vanessa Wyeth, Editors, International Peace Institute, 2008, pp. 164-5. 9. Sandra F. Joireman, Where There is No...that company. http://grm.thomsonreuters.com/news/july-2011/thomson-reuters- completes-acquisition-of-manatron/ 73. P.J.M. van Oosterom, C.H.J

Enzymatic extract containing lignin peroxidase immobilized on carbon nanotubes: Potential biocatalyst in dye decolourization.

PubMed

Oliveira, Sabrina Feliciano; da Luz, José Maria Rodrigues; Kasuya, Maria Catarina Megumi; Ladeira, Luiz Orlando; Correa Junior, Ary

2018-05-01

The majority of the textile dyes are harmful to the environment and potentially carcinogenic. Among strategies for their exclusion, the treatment of dye contaminated wastewater with fungal extract, containing lignin peroxidase (LiP), may be useful. Two fungi isolates, Pleurotus ostreatus (PLO9) and Ganoderma lucidum (GRM117), produced the enzymatic extract by fermentation in the lignocellulosic residue, Jatropha curcas seed cake. The extracts from PLO9 and GRM117 were immobilized on carbon nanotubes and showed an increase of 18 and 27-fold of LiP specific activity compared to the free enzyme. Also, LiP from both fungi extracts showed higher Vmax and lower Km values. Only the immobilized extracts could be efficiently reused in the dye decolourization, contrary, the carbon nanotubes became saturated and they should be discarded over time. This device may offer a final biocatalyst with higher catalytic efficiency and capability to be reused in the dye decolourization process.

BMPR1B mutation causes Pierre Robin sequence

PubMed Central

Yao, Xu; Zhang, Rong; Yang, Hui; Zhao, Rui; Guo, Jihong; Jin, Ke; Mei, Haibo; Luo, Yongqi; Zhao, Liu; Tu, Ming; Zhu, Yimin

2017-01-01

Background We investigated a large family with Pierre Robin sequence (PRS). Aim of the study This study aims to determine the genetic cause of PRS. Results The reciprocal translocation t(4;6)(q22;p21) was identified to be segregated with PRS in a three-generation family. Whole-genome sequencing and Sanger sequencing successfully detected breakpoints in the intragenic regions of BMRP1B and GRM4. We hypothesized that PRS in this family was caused by (i) haploinsufficiency for BMPR1B or (ii) a gain of function mechanism mediated by the BMPR1B-GRM4 fusion gene. In an unrelated family, we identified another BMPR1B-splicing mutation that co-segregated with PRS. Conclusion We detected two BMPR1B mutations in two unrelated PRS families, suggesting that BMPR1B disruption is probably a cause of human PRS. Methods GTG banding, comparative genomic hybridization, whole-genome sequencing, and Sanger sequencing were performed to identify the gene causing PRS. PMID:28418932

The Communicative Participation Item Bank (CPIB): Item bank calibration and development of a disorder-generic short form

PubMed Central

Baylor, Carolyn; Yorkston, Kathryn; Eadie, Tanya; Kim, Jiseon; Chung, Hyewon; Amtmann, Dagmar

2015-01-01

Purpose The purpose of this study was to calibrate the items for the Communicative Participation Item Bank (CPIB) using Item Response Theory (IRT). One overriding objective was to examine if the IRT item parameters would be consistent across different diagnostic groups, thereby allowing creation of a disorder-generic instrument. The intended outcomes were the final item bank and a short form ready for clinical and research applications. Methods Self-report data were collected from 701 individuals representing four diagnoses: multiple sclerosis, Parkinson’s disease, amyotrophic lateral sclerosis and head and neck cancer. Participants completed the CPIB and additional self-report questionnaires. CPIB data were analyzed using the IRT Graded Response Model (GRM). Results The initial set of 94 candidate CPIB items were reduced to an item bank of 46 items demonstrating unidimensionality, local independence, good item fit, and good measurement precision. Differential item function (DIF) analyses detected no meaningful differences across diagnostic groups. A 10-item, disorder-generic short form was generated. Conclusions The CPIB provides speech-language pathologists with a unidimensional, self-report outcomes measurement instrument dedicated to the construct of communicative participation. This instrument may be useful to clinicians and researchers wanting to implement measures of communicative participation in their work. PMID:23816661

75 FR 5790 - Notice of Receipt of Several Pesticide Petitions Filed for Residues of Pesticide Chemicals in or...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-04

... on banana at 0.05 parts per million (ppm). An adequate, validated method (GRM006.01B) is available... insecticide fluazifop-p-butyl, in or on potato, tuber at 1.1 ppm; potato, peel (wet) at 1.1 ppm; potato, chips...

The biomass, abundance, and distribution pattern of starfish Asterias sp. (Echinodermata: Asteroidea) in East Coast of Surabaya

NASA Astrophysics Data System (ADS)

Dewi, N. N.; Pursetyo, K. T.; Aprilianitasari, L.; Zakaria, M. H.; Ramadhan, M. R.; Triatmaja, R. A.

2018-04-01

This study aims to determine the biomass, density, and distribution patterns of Asterias sp. Samples were collected from three locations such as Wonokromo, Dadapan and Juanda, each divided into 3 zones. In each zone, samples were taken as many as 5 repetitions using swept area method. Temporarily, the highest biomass of starfish was 2.95 gr/m2 in Dadapan Zone on January. Spatially, biomass of starfish was found in Dadapan Zone (3,35 gr/m2). Similarly, the high density was also found in Dadapan Zone on January (9 ind/10 m2). In general, the distributionpattern of starfish in East Coast Surabaya throughspatial and temporal showed that the pattern of starfish was grouping distribution (Id value > 1) for Dadapan and Juanda, and uniform for Wonokromo. Oceanographic condition, antropogenic activity, and water quality in East Cost of Surabaya become important things which is affected the biomass, densityand distribution pattern of starfish. The knowledge of starfish biomass and density is very important given that this biota has ecological value as a balancing ecosystem in the waters.

A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci

PubMed Central

Low, Joyce Siew Yong; Chin, Yoon Ming; Mushiroda, Taisei; Kubo, Michiaki; Govindasamy, Gopala Krishnan; Pua, Kin Choo; Yap, Yoke Yeow; Yap, Lee Fah; Subramaniam, Selva Kumar; Ong, Cheng Ai; Tan, Tee Yong; Khoo, Alan Soo Beng; Ng, Ching Ching

2016-01-01

Background Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition. Methods A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124). Results Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96–17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75–10.11) overlapping MICA/HCP5/HCG26 genes. Conclusion Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development. PMID:26730743

An item response theory evaluation of the young mania rating scale and the montgomery-asberg depression rating scale in the systematic treatment enhancement program for bipolar disorder (STEP-BD).

PubMed

Prisciandaro, James J; Tolliver, Bryan K

2016-11-15

The Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS) are among the most widely used outcome measures for clinical trials of medications for Bipolar Disorder (BD). Nonetheless, very few studies have examined the measurement characteristics of the YMRS and MADRS in individuals with BD using modern psychometric methods. The present study evaluated the YMRS and MADRS in the Systematic Treatment Enhancement Program for BD (STEP-BD) study using Item Response Theory (IRT). Baseline data from 3716 STEP-BD participants were available for the present analysis. The Graded Response Model (GRM) was fit separately to YMRS and MADRS item responses. Differential item functioning (DIF) was examined by regressing a variety of clinically relevant covariates (e.g., sex, substance dependence) on all test items and on the latent symptom severity dimension, within each scale. Both scales: 1) contained several items that provided little or no psychometric information, 2) were inefficient, in that the majority of item response categories did not provide incremental psychometric information, 3) poorly measured participants outside of a narrow band of severity, 4) evidenced DIF for nearly all items, suggesting that item responses were, in part, determined by factors other than symptom severity. Limited to outpatients; DIF analysis only sensitive to certain forms of DIF. The present study provides evidence for significant measurement problems involving the YMRS and MADRS. More work is needed to refine these measures and/or develop suitable alternative measures of BD symptomatology for clinical trials research. Copyright © 2016 Elsevier B.V. All rights reserved.

Adding net growth, removals, and mortality estimates for biomass and carbon in FIADB

Treesearch

Jeffery A. Turner

2015-01-01

Traditional growth, removals, and mortality (GRM) estimates produced from Forest Inventory and Analysis (FIA) periodic inventories were limited to changes in volume on timberland. Estimates on forestland were added in the east as the first installment of annual inventory plots was remeasured. The western FIA units have begun annual remeasurement, precipitating the need...

78 FR 3377 - Notice of Receipt of Several Pesticide Petitions Filed for Residues of Pesticide Chemicals in or...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

... AgroSciences, LLC, 9330 Zionsville Road, Indianapolis, IN 46268, requests to establish a tolerance in... Dow AgroSciences method GRM 02.25 ``Determination of Residues of Methoxyfenozide in High Moisture... cereal grains (group 16), cotton, canola (rapeseed), sunflower and peanut and in animal meat, fat, liver...

Graded Reflectivity Mirror for the Solid State Heat Capacity Laser Final Report CRADA No. TC-2085-04

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

Yamamoto, R.; Davis, J. A.

This was a collaborative effort between The Regents of the University of California, Lawrence Livermore National Laboratory (LLNL) and the Boeing Company, to develop a Graded Reflectivity Mirror (GRM) to achieve improved near field fill and higher brightness in the far field output of LLNL’s Solid State Heat Capacity Laser (SSHCL).

Transcriptome comparison in the pituitary-adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure.

PubMed

Luo, Wei; Fang, Meixia; Xu, Haiping; Xing, Huijie; Nie, Qinghua

2015-10-01

Chronic stress can induce a series of maladjustments, and the response to stress is partly regulated by the hypothalamus-pituitary-adrenal axis. The aim of this study was to investigate the genetic mechanisms of this axis regulating stress responsiveness. The pituitary and adrenal cortex of Beagle and Chinese Field Dog (CFD) from a stress exposure group [including Beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), Beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)] and a control group [including Beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), Beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)], selected to perform RNA-seq transcriptome comparisons, showed that 40, 346, 376, 69, 70, 38, 57 and 71 differentially expressed genes were detected in BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1, BP2 vs. CFDP2, BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2 respectively. NPB was a gene common to BAC1 vs. BAC2 and CFDAC1 vs. CFDAC2, indicating it was a potential gene affecting response to chronic stress, regardless of the extent of chronic stress induced. PLP1 was a gene common to BP1 vs. CFDP1 and BP2 vs. CFDP2, suggesting its important roles in affecting the stress-tolerance difference between the two breeds, regardless of whether there was stress exposure or not. Pathway analysis found 12, 4, 11 and 1 enriched pathway in the comparisons of BP1 vs. CFDP1, BP2 vs. CFDP2, CFDP1 vs. CFDP2 and BAC1 vs. BAC2 respectively. Glutamatergic synapse, neuroactive ligand-receptor interaction, retrograde endocannabinoid signaling, GABAergic synapse, calcium signaling pathway and dopaminergic synapse were the most significantly enriched pathways in both CFDP1 vs. CFDP2 and BP1 vs. CFDP1. GO, KEGG pathway and gene network analysis demonstrated that GRIA3, GRIN2A, GRIN2B and NPY were important in regulating the stress response in CFD. Nevertheless, ADORA1, CAMK2A, GRM1, GRM7 and NR4A1 might be critical genes contributing to the stress-tolerance difference between CFD and Beagle when subjected to stress exposure. In addition, RGS4 and SYN1 might play important roles both in regulating the stress response in CFD and in affecting the stress-tolerance difference in different breeds. These observations clearly showed that some genes in the adrenal cortex and pituitary could regulate the stress response in Beagle and CFDs, whereas some others could affect the stress-tolerance difference between these two breeds. Our results can contribute to a more comprehensive understanding of the genetic mechanisms of response to chronic stress. © 2015 Stichting International Foundation for Animal Genetics.

Assessing whether parents and children perceive the meaning of the items in the PedsQLTM 4.0 quality of life instrument consistently: a differential item functioning analysis.

PubMed

Jafari, Peyman; Bagheri, Zahra; Hashemi, Seyyedeh Zahra; Shalileh, Keivan

2013-06-06

Limited studies have examined the effect of differential item functioning (DIF) on comparing health related quality of life (HRQoL) scores across child self-reports and parent proxy-reports. This study aims to determine whether parents and children respond differently to the items in the Persian version of the PedsQoLTM 4.0 measure. The PedsQLTM 4.0 Generic Core Scales was completed by 938 child-parent dyads. The graded response model (GRM) was used to detect DIF between parents and children. The IRT analyses were conducted using IRTPRO 2.1.On the whole, our findings showed that 50% (4 out of 8) of the items in the physical subscale and 40% (2 out of 5) in both emotional and school subscales were flagged with DIF. Among the DIF items, 62.5% (5 out of 8) were uniform and the remaining 37.5% (3 out of 8) were non-uniform. Parents and children interpret certain items of the PedsQLTM 4.0 in a different ways, except for the social subscale. Hence, we should be cautious about using parent proxy-report as a substitute for a child's ratings.

Phase I Study of Cellular Immunotherapy for Recurrent/Refractory Malignant Glioma Using Intratumoral Infusions of GRm13Z40-2, An Allogeneic CD8+ Cytolitic T-Cell Line Genetically Modified to Express the IL 13-Zetakine and HyTK and to be Resistant to Glucocorticoids, in Combination With Interleukin-2

ClinicalTrials.gov

2015-06-03

Anaplastic Astrocytoma; Anaplastic Ependymoma; Anaplastic Meningioma; Anaplastic Oligodendroglioma; Brain Stem Glioma; Ependymoblastoma; Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Grade III Meningioma; Meningeal Hemangiopericytoma; Mixed Glioma; Pineal Gland Astrocytoma; Brain Tumor

A new lead from genetic studies in depressed siblings: assessing studies of chromosome 3.

PubMed

Hamilton, Steven P

2011-08-01

Studies by Breen et al. and Pergadia et al. find evidence for genetic linkage between major depressive disorder and the same region on chromosome 3. The linked region contains the gene GRM7, which encodes a protein for the metabotropic glutamate receptor 7 (mGluR7). Both studies used affected sibling pairs, and neither was able to replicate its finding using association studies in individuals from larger population-based studies. Other family-based studies have also failed to find a signal in this region. Furthermore, there are some differences in how the phenotype was classified, with Breen et al. finding evidence only in the most severely affected patients. Nonetheless, the finding is not without other substantive support. A meta-analysis of 3,957 case subjects with major depressive disorder and 3,428 control subjects from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), Genetics of Recurrent Early-onset Depression (GenRED), and the Genetic Association Information Network-MDD (GAIN-MDD) data sets demonstrated a region of association for major depressive disorder within GRM7. Thus, the significance of this finding remains uncertain, although it points to a gene that might hold significant promise for further developments in studying the pathophysiology and treatment of major depressive disorder.

On the deficit problem of mass and energy of solar coronal mass ejections connected with interplanetary shocks

NASA Technical Reports Server (NTRS)

Ivanchuk, V. I.; Pishkalo, N. I.

1995-01-01

Mean values of a number of parameters of the most powerful coronal mass ejections (CMEs) and interplanetary shocks generated by these ejections are estimated using an analysis of data obtained by the cosmic coronagraphs and spacecrafts, and geomagnetic storm measurements. It was payed attention that the shock mass and mechanical energy, averaging 5 x 10(exp 16) grm and 2 x 10(exp 32) erg respectively, are nearly 10 times larger than corresponding parameters of the ejections. So, the CME energy deficit problem seems to exist really. To solve this problem one can make an assumption that the process of the mass and energy growth of CMEs during their propagation out of the Sun observed in the solar corona is continued in supercorona too up to distances of 10-30 solar radii. This assumption is confirmed by the data analysis of five events observed using zodiacal light photometers of the HELIOS- I and HELIOS-2 spacecrafts. The mass growth rate is estimated to be equal to (1-7) x 10(exp 11) grm/sec. It is concluded that the CME contribution to mass and energy flows in the solar winds probably, is larger enough than the value of 3-5% adopted usually.

Systemic analysis of desertification processes taking place in the Limpopo river basin

NASA Astrophysics Data System (ADS)

Messina, Mario; Attorre, Fabio; Vitale, Marcello

2016-04-01

Desertification and land degradation are phenomena that ranks among the greatest environmental challenges of our time. Desertification is a global issue, with serious implications worldwide for biodiversity, socio-economic stability and sustainable development. Biophysical indicators of land degradation and desertification, like Net Primary Productivity (NPP) and Total Ecosystem Respiration (Reco) were provided by remote sensing technology (MODIS). The study aims to evaluate the dynamical changes of NPP and Reco in the Limpopo river basin, a Southern African region that includes, Botswana, Mozambique, South Africa and Zimbabwe, during the time period 2001-2010. In particular, the relations between NPP, Reco, environmental, physiological and land use parameters have been widely investigated through the application of a new and powerful statistical classifier, the Random Forest Analysis (RFA), and a general non-linear model, the Response Surface Regression Model (GRM). RFA highlighted that Temperature is one of the most important predictors affecting NPP and Reco in the Limpopo river basin. Conversely, other environmental parameters like, Precipitation, Evapotranspiration and Vegetation cover rarely influence NPP and Reco. Our results provide information on desertification and land degradation phenomena and a first step for identifying practices to mitigate their negative impacts. However, it must be taken into account that NPP and Reco depend by a multitude of factors (e.g. human activities, socio-economic policies) and can vary in relation to spatial and temporal scale. In order to achieve a better understanding of land degradation and desertification processes, land use and socio-economic variables should be considered.

Expression quantitative trait loci and genetic regulatory network analysis reveals that Gabra2 is involved in stress responses in the mouse.

PubMed

Dai, Jiajuan; Wang, Xusheng; Chen, Ying; Wang, Xiaodong; Zhu, Jun; Lu, Lu

2009-11-01

Previous studies have revealed that the subunit alpha 2 (Gabra2) of the gamma-aminobutyric acid receptor plays a critical role in the stress response. However, little is known about the gentetic regulatory network for Gabra2 and the stress response. We combined gene expression microarray analysis and quantitative trait loci (QTL) mapping to characterize the genetic regulatory network for Gabra2 expression in the hippocampus of BXD recombinant inbred (RI) mice. Our analysis found that the expression level of Gabra2 exhibited much variation in the hippocampus across the BXD RI strains and between the parental strains, C57BL/6J, and DBA/2J. Expression QTL (eQTL) mapping showed three microarray probe sets of Gabra2 to have highly significant linkage likelihood ratio statistic (LRS) scores. Gene co-regulatory network analysis showed that 10 genes, including Gria3, Chka, Drd3, Homer1, Grik2, Odz4, Prkag2, Grm5, Gabrb1, and Nlgn1 are directly or indirectly associated with stress responses. Eleven genes were implicated as Gabra2 downstream genes through mapping joint modulation. The genetical genomics approach demonstrates the importance and the potential power of the eQTL studies in identifying genetic regulatory networks that contribute to complex traits, such as stress responses.

An endogenous and ectopic expression of metabotropic glutamate receptor 8 (mGluR8) inhibits proliferation and increases chemosensitivity of human neuroblastoma and glioma cells.

PubMed

Jantas, Danuta; Grygier, Beata; Gołda, Sławomir; Chwastek, Jakub; Zatorska, Justyna; Tertil, Magdalena

2018-06-06

The present study aimed to determine the role of metabotropic glutamate receptor 8 (mGluR8) in tumor biology. Using various molecular approaches (RNAi or GRM8 cDNA), cell clones with downregulated (human neuroblastoma SH-SY5Y and human glioma LN229) or overexpressed (human glioma U87-MG and LN18 cell lines) mGluR8 were generated. Next, comparative studies on cell proliferation and migration rates, induction of apoptosis and chemosensitivity were performed among these clones. The mGluR8-downregulated SH-SY5Y clones proliferated faster and were more resistant to cytotoxic action of staurosporine, doxorubicin, irinotecan and cisplatin when compared to control cells. Moreover, these clones were characterized by a lower activity of caspases, calpains and some kinases (GSK-3β, Akt and JNK). The mGluR8-downregulated LN229 clones migrated faster and were less prone to cell-damaging effect of staurosporine and irinotecan when compared with relevant control cells. In contrast, in GRM8-overexpressing U87-MG and LN18 clones, a decreased cell proliferation, increased apoptosis and elevated vulnerability to some cytotoxic agents were found. Altogether, our in vitro data for the first time evidenced a tumor suppressor and chemosensitizing role of mGluR8. Copyright © 2018 Elsevier B.V. All rights reserved.

Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci.

PubMed

Stafford-Smith, Mark; Li, Yi-Ju; Mathew, Joseph P; Li, Yen-Wei; Ji, Yunqi; Phillips-Bute, Barbara G; Milano, Carmelo A; Newman, Mark F; Kraus, William E; Kertai, Miklos D; Shah, Svati H; Podgoreanu, Mihai V

2015-10-01

Acute kidney injury (AKI) is a common, serious complication of cardiac surgery. Since prior studies have supported a genetic basis for postoperative AKI, we conducted a genome-wide association study (GWAS) for AKI following coronary bypass graft (CABG) surgery. The discovery data set consisted of 873 nonemergent CABG surgery patients with cardiopulmonary bypass (PEGASUS), while a replication data set had 380 cardiac surgical patients (CATHGEN). Single-nucleotide polymorphism (SNP) data were based on Illumina Human610-Quad (PEGASUS) and OMNI1-Quad (CATHGEN) BeadChips. We used linear regression with adjustment for a clinical AKI risk score to test SNP associations with the postoperative peak rise relative to preoperative serum creatinine concentration as a quantitative AKI trait. Nine SNPs meeting significance in the discovery set were detected. The rs13317787 in GRM7|LMCD1-AS1 intergenic region (3p21.6) and rs10262995 in BBS9 (7p14.3) were replicated with significance in the CATHGEN data set and exhibited significantly strong overall association following meta-analysis. Additional fine mapping using imputed SNPs across these two regions and meta-analysis found genome-wide significance at the GRM7|LMCD1-AS1 locus and a significantly strong association at BBS9. Thus, through an unbiased GWAS approach, we found two new loci associated with post-CABG AKI providing new insights into the pathogenesis of perioperative AKI.

Potential utility of future satellite magnetic field data

NASA Technical Reports Server (NTRS)

1984-01-01

The requirements for a program of geomagnetic field studies are examined which will satisfy a wide range of user needs in the interim period between now and the time at which data from the Geopotential Research Mission (GRM) becomes available, and the long term needs for NASA's program in this area are considered. An overview of the subject, a justification for the recommended activities in the near term and long term, and a summary of the recommendations reached by the contributors is included.

Satellite techniques for determining the geopotential for sea-surface elevations

NASA Technical Reports Server (NTRS)

Pisacane, V. L.

1984-01-01

Spaceborne altimetry with measurement accuracies of a few centimeters which has the potential to determine sea surface elevations necessary to compute accurate three-dimensonal geostrophic currents from traditional hydrographic observation is discussed. The limitation in this approach is the uncertainties in knowledge of the global and ocean geopotentials which produce satellite and height uncertainties about an order of magnitude larger than the goal of about 10 cm. The quantative effects of geopotential uncertainties on processing altimetry data are described. Potential near term improvements, not requiring additional spacecraft, are discussed. Even though there is substantial improvements at the longer wavelengths, the oceanographic goal will be achieved. The geopotential research mission (GRM) is described which should produce goepotential models that are capable of defining the ocean geid to 10 cm and near-Earth satellite position. The state of the art and the potential of spaceborne gravimetry is described as an alternative approach to improve our knowledge of the geopotential.

Screening key candidate genes and pathways involved in insulinoma by microarray analysis.

PubMed

Zhou, Wuhua; Gong, Li; Li, Xuefeng; Wan, Yunyan; Wang, Xiangfei; Li, Huili; Jiang, Bin

2018-06-01

Insulinoma is a rare type tumor and its genetic features remain largely unknown. This study aimed to search for potential key genes and relevant enriched pathways of insulinoma.The gene expression data from GSE73338 were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified between insulinoma tissues and normal pancreas tissues, followed by pathway enrichment analysis, protein-protein interaction (PPI) network construction, and module analysis. The expressions of candidate key genes were validated by quantitative real-time polymerase chain reaction (RT-PCR) in insulinoma tissues.A total of 1632 DEGs were obtained, including 1117 upregulated genes and 514 downregulated genes. Pathway enrichment results showed that upregulated DEGs were significantly implicated in insulin secretion, and downregulated DEGs were mainly enriched in pancreatic secretion. PPI network analysis revealed 7 hub genes with degrees more than 10, including GCG (glucagon), GCGR (glucagon receptor), PLCB1 (phospholipase C, beta 1), CASR (calcium sensing receptor), F2R (coagulation factor II thrombin receptor), GRM1 (glutamate metabotropic receptor 1), and GRM5 (glutamate metabotropic receptor 5). DEGs involved in the significant modules were enriched in calcium signaling pathway, protein ubiquitination, and platelet degranulation. Quantitative RT-PCR data confirmed that the expression trends of these hub genes were similar to the results of bioinformatic analysis.The present study demonstrated that candidate DEGs and enriched pathways were the potential critical molecule events involved in the development of insulinoma, and these findings were useful for better understanding of insulinoma genesis.

A Bulk Comptonization Model for the Prompt GRM Emission

NASA Technical Reports Server (NTRS)

Kazanas, Demos; Mastichiadis, A.

2010-01-01

The "Supercritical Pile" is a very economical GRB model that provides for the efficient conversion of the energy stored in the protons of a Relativistic Blast Wave (RBW) into radiation and at the same time produces - in the prompt GRB phase, even in the absence of any particle acceleration - a spectral peak at energy approximately 1 MeV. We extend this model to include the evolution of the RBW Lorentz factor F and thus follow its spectral and temporal features into the early GRB afterglow stage. One of the novel features of the present treatment is the inclusion of the feedback of the GRB produced radiation on the evolution of Gamma with radius. This feedback and the presence of kinematic and dynamic thresholds in the model are sources of potentially very rich time evolution which we have began to explore. In particular, one can this way obtain afterglow light curves with steep decays followed by the more conventional flatter afterglow slopes, while at the same time preserving the desirable features of the model, i.e. the well defined relativistic electron source and radiative processes that produce the proper peak in the nu F(sub nu) spectra. In this note we present the results of a specific set of parameters of this model with emphasis on the multiwavelength prompt emission and transition to the early afterglow.

Geopotential research mission, science, engineering and program summary

NASA Technical Reports Server (NTRS)

Keating, T. (Editor); Taylor, P. (Editor); Kahn, W. (Editor); Lerch, F. (Editor)

1986-01-01

This report is based upon the accumulated scientific and engineering studies pertaining to the Geopotential Research Mission (GRM). The scientific need and justification for the measurement of the Earth's gravity and magnetic fields are discussed. Emphasis is placed upon the studies and conclusions of scientific organizations and NASA advisory groups. The engineering design and investigations performed over the last 4 years are described, and a spacecraft design capable of fulfilling all scientific objectives is presented. In addition, critical features of the scientific requirements and state-of-the-art limitations of spacecraft design, mission flight performance, and data processing are discussed.

GWAS-identified risk variants for major depressive disorder: Preliminary support for an association with late-life depressive symptoms and brain structural alterations.

PubMed

Ryan, Joanne; Artero, Sylvaine; Carrière, Isabelle; Maller, Jerome J; Meslin, Chantal; Ritchie, Karen; Ancelin, Marie-Laure

2016-01-01

A number of genome-wide association studies (GWAS) have investigated risk factors for major depressive disorder (MDD), however there has been little attempt to replicate these findings in population-based studies of depressive symptoms. Variants within three genes, BICC1, PCLO and GRM7 were selected for replication in our study based on the following criteria: they were identified in a prior MDD GWAS study; a subsequent study found evidence that they influenced depression risk; and there is a solid biological basis for a role in depression. We firstly investigated whether these variants were associated with depressive symptoms in our population-based cohort of 929 elderly (238 with clinical depressive symptoms and 691 controls), and secondly to investigate associations with structural brain alterations. A number of nominally significant associations were identified, but none reached Bonferroni-corrected significance levels. Common SNPs in BICC1 and PCLO were associated with a 50% and 30% decreased risk of depression, respectively. PCLO rs2522833 was also associated with the volume of grey matter (p=1.6×10(-3)), and to a lesser extent with hippocampal volume and white matter lesions. Among depressed individuals rs9870680 (GRM7) was associated with the volume of grey and white matter (p=10(-4) and 8.3×10(-3), respectively). Our results provide some support for the involvement of BICC1 and PCLO in late-life depressive disorders and preliminary evidence that these genetic variants may also influence brain structural volumes. However effect sizes remain modest and associations did not reach corrected significance levels. Further large imaging studies are needed to confirm our findings. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Comprehensive behavioral study of mGluR3 knockout mice: implication in schizophrenia related endophenotypes

PubMed Central

2014-01-01

Background We previously performed systematic association studies of glutamate receptor gene family members with schizophrenia, and found positive associations of polymorphisms in the GRM3 (a gene of metabotropic glutamate receptor 3: mGluR3) with the disorder. Physiological roles of GRM3 in brain functions and its functional roles in the pathogenesis of schizophrenia remain to be resolved. Results We generated mGluR3 knockout (KO) mice and conducted comprehensive behavioral analyses. KO mice showed hyperactivity in the open field, light/dark transition, and 24-hour home cage monitoring tests, impaired reference memory for stressful events in the Porsolt forced swim test, impaired contextual memory in cued and contextual fear conditioning test, and impaired working memory in the T-Maze forced alternation task test. Hyperactivity and impaired working memory are known as endophenotypes of schizophrenia. We examined long-term synaptic plasticity by assessing long-term potentiation (LTP) in the CA1 region in the hippocampi of KO and wild-type (WT) mice. We observed no differences in the amplitude of LTP between the two genotypes, suggesting that mGluR3 is not essential for LTP in the CA1 region of the mouse hippocampus. As hyperactivity is typically associated with increased dopaminergic transmission, we performed in vivo microdialysis measurements of extracellular dopamine in the nucleus accumbens of KO and WT mice. We observed enhancements in the methamphetamine (MAP)-induced release of dopamine in KO mice. Conclusions These results demonstrate that a disturbance in the glutamate-dopamine interaction may be involved in the pathophysiology of schizophrenia-like behavior, such as hyperactivity in mGluR3 KO mice. PMID:24758191

Altered cortical processing of motor inhibition in schizophrenia.

PubMed

Lindberg, Påvel G; Térémetz, Maxime; Charron, Sylvain; Kebir, Oussama; Saby, Agathe; Bendjemaa, Narjes; Lion, Stéphanie; Crépon, Benoît; Gaillard, Raphaël; Oppenheim, Catherine; Krebs, Marie-Odile; Amado, Isabelle

2016-12-01

Inhibition is considered a key mechanism in schizophrenia. Short-latency intracortical inhibition (SICI) in the motor cortex is reduced in schizophrenia and is considered to reflect locally deficient γ-aminobutyric acid (GABA)-ergic modulation. However, it remains unclear how SICI is modulated during motor inhibition and how it relates to neural processing in other cortical areas. Here we studied motor inhibition Stop signal task (SST) in stabilized patients with schizophrenia (N = 28), healthy siblings (N = 21) and healthy controls (n = 31) matched in general cognitive status and educational level. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were used to investigate neural correlates of motor inhibition. SST performance was similar in patients and controls. SICI was modulated by the task as expected in healthy controls and siblings but was reduced in patients with schizophrenia during inhibition despite equivalent motor inhibition performance. fMRI showed greater prefrontal and premotor activation during motor inhibition in schizophrenia. Task-related modulation of SICI was higher in subjects who showed less inhibition-related activity in pre-supplementary motor area (SMA) and cingulate motor area. An exploratory genetic analysis of selected markers of inhibition (GABRB2, GAD1, GRM1, and GRM3) did not explain task-related differences in SICI or cortical activation. In conclusion, this multimodal study provides direct evidence of a task-related deficiency in SICI modulation in schizophrenia likely reflecting deficient GABA-A related processing in motor cortex. Compensatory activation of premotor areas may explain similar motor inhibition in patients despite local deficits in intracortical processing. Task-related modulation of SICI may serve as a useful non-invasive GABAergic marker in development of therapeutic strategies in schizophrenia. Copyright © 2016 Elsevier Ltd. All rights reserved.

The effect of raloxifene on left ventricular hypertrophy in postmenopausal women: A prospective, randomized, and controlled study

PubMed Central

Bal, Uğur Abbas; Atar, İlyas; Öktem, Mesut; B. Zeyneloğlu, Hulusi; Yıldırır, Aylin; Kuşcu, Esra; Müderrisoğlu, Haldun

2015-01-01

Objective: In healthy women, there is a progressive age-related increase in myocardial mass that is not seen in their male counterparts and occurs primarily in postmenopausal women. Raloxifene is a selective estrogen receptor modulator that has estrogenic actions on bone and the cardiovascular system. The aim of this study was to investigate the effect of raloxifene on myocardial hypertrophy in postmenopausal patients. Methods: A total of 22 postmenopausal osteoporotic women were included in this open-label, randomized, prospective, controlled study. Patients were randomized into two groups: 11 of the patients (group 1) were treated with raloxifene 60 mg/day, and the other 11 patients (group 2) were defined as the control group. Quantitative 2-dimensional and M-mode echocardiographic examination was performed in all patients at the beginning and repeated at the end of the 6-month follow-up period. Left ventricle mass (LVM) and left ventricle mass index (LVMI) were calculated for all patients. Results: The mean age of the patients was 57.2±3.9 years, and baseline clinical characteristics and echocardiographic parameters were similar between the two groups. After 6 months of raloxifene treatment, there was no difference in echocardiographic parameters of LVM and LVMI compared with the control group (201.2±25.9 gr vs. 169.7±46.2 gr, p=0.14 and 120.4±25.9 gr/m2 vs. 105.5±26.3 gr/m2, p=0.195, respectively). There was also no significant difference in LVM and LVMI in the within-group analysis of both groups. Conclusion: Raloxifene therapy does not affect myocardial hypertrophy in postmenopausal women after 6 months of treatment. PMID:25430415

Mutation profiles in early-stage lung squamous cell carcinoma with clinical follow-up and correlation with markers of immune function.

PubMed

Choi, M; Kadara, H; Zhang, J; Parra, E R; Rodriguez-Canales, J; Gaffney, S G; Zhao, Z; Behrens, C; Fujimoto, J; Chow, C; Kim, K; Kalhor, N; Moran, C; Rimm, D; Swisher, S; Gibbons, D L; Heymach, J; Kaftan, E; Townsend, J P; Lynch, T J; Schlessinger, J; Lee, J; Lifton, R P; Herbst, R S; Wistuba, I I

2017-01-01

Lung squamous cell carcinoma (LUSC) accounts for 20–30% of non-small cell lung cancers (NSCLCs). There are limited treatment strategies for LUSC in part due to our inadequate understanding of the molecular underpinnings of the disease. We performed whole-exome sequencing (WES) and comprehensive immune profiling of a unique set of clinically annotated early-stage LUSCs to increase our understanding of the pathobiology of this malignancy. Matched pairs of surgically resected stage I-III LUSCs and normal lung tissues (n = 108) were analyzed by WES. Immunohistochemistry and image analysis-based profiling of 10 immune markers were done on a subset of LUSCs (n = 91). Associations among mutations, immune markers and clinicopathological variables were statistically examined using analysis of variance and Fisher’s exact test. Cox proportional hazards regression models were used for statistical analysis of clinical outcome. This early-stage LUSC cohort displayed an average of 209 exonic mutations per tumor. Fourteen genes exhibited significant enrichment for somatic mutation: TP53, MLL2, PIK3CA, NFE2L2, CDH8, KEAP1, PTEN, ADCY8, PTPRT, CALCR, GRM8, FBXW7, RB1 and CDKN2A. Among mutated genes associated with poor recurrence-free survival, MLL2 mutations predicted poor prognosis in both TP53 mutant and wild-type LUSCs. We also found that in treated patients, FBXW7 and KEAP1 mutations were associated with poor response to adjuvant therapy, particularly in TP53-mutant tumors. Analysis of mutations with immune markers revealed that ADCY8 and PIK3CA mutations were associated with markedly decreased tumoral PD-L1 expression, LUSCs with PIK3CA mutations exhibited elevated CD45ro levels and CDKN2A-mutant tumors displayed an up-regulated immune response. Our findings pinpoint mutated genes that may impact clinical outcome as well as personalized strategies for targeted immunotherapies in early-stage LUSC.

Geodynamics and temporal variations in the gravity field

NASA Technical Reports Server (NTRS)

Mcadoo, D. C.; Wagner, C. A.

1989-01-01

Just as the Earth's surface deforms tectonically, so too does the gravity field evolve with time. Now that precise geodesy is yielding observations of these deformations it is important that concomitant, temporal changes in the gravity field be monitored. Although these temporal changes are minute they are observable: changes in the J2 component of the gravity field were inferred from satellite (LAGEOS) tracking data; changes in other components of the gravity field would likely be detected by Geopotential Research Mission (GRM), a proposed but unapproved NASA gravity field mission. Satellite gradiometers were also proposed for high-precision gravity field mapping. Using simple models of geodynamic processes such as viscous postglacial rebound of the solid Earth, great subduction zone earthquakes and seasonal glacial mass fluctuations, we predict temporal changes in gravity gradients at spacecraft altitudes. It was found that these proposed gravity gradient satellite missions should have sensitivities equal to or better than 10(exp -4) E in order to reliably detect these changes. It was also found that satellite altimetry yields little promise of useful detection of time variations in gravity.

Autosomal-recessive congenital cerebellar ataxia is caused by mutations in metabotropic glutamate receptor 1.

PubMed

Guergueltcheva, Velina; Azmanov, Dimitar N; Angelicheva, Dora; Smith, Katherine R; Chamova, Teodora; Florez, Laura; Bynevelt, Michael; Nguyen, Thai; Cherninkova, Sylvia; Bojinova, Veneta; Kaprelyan, Ara; Angelova, Lyudmila; Morar, Bharti; Chandler, David; Kaneva, Radka; Bahlo, Melanie; Tournev, Ivailo; Kalaydjieva, Luba

2012-09-07

Autosomal-recessive congenital cerebellar ataxia was identified in Roma patients originating from a small subisolate with a known strong founder effect. Patients presented with global developmental delay, moderate to severe stance and gait ataxia, dysarthria, mild dysdiadochokinesia, dysmetria and tremors, intellectual deficit, and mild pyramidal signs. Brain imaging revealed progressive generalized cerebellar atrophy, and inferior vermian hypoplasia and/or a constitutionally small brain were observed in some patients. Exome sequencing, used for linkage analysis on extracted SNP genotypes and for mutation detection, identified two novel (i.e., not found in any database) variants located 7 bp apart within a unique 6q24 linkage region. Both mutations cosegregated with the disease in five affected families, in which all ten patients were homozygous. The mutated gene, GRM1, encodes metabotropic glutamate receptor mGluR1, which is highly expressed in cerebellar Purkinje cells and plays an important role in cerebellar development and synaptic plasticity. The two mutations affect a gene region critical for alternative splicing and the generation of receptor isoforms; they are a 3 bp exon 8 deletion and an intron 8 splicing mutation (c.2652_2654del and c.2660+2T>G, respectively [RefSeq accession number NM_000838.3]). The functional impact of the deletion is unclear and is overshadowed by the splicing defect. Although ataxia lymphoblastoid cell lines expressed GRM1 at levels comparable to those of control cells, the aberrant transcripts skipped exon 8 or ended in intron 8 and encoded various species of nonfunctional receptors either lacking the transmembrane domain and containing abnormal intracellular tails or completely missing the tail. The study implicates mGluR1 in human hereditary ataxia. It also illustrates the potential of the Roma founder populations for mutation identification by exome sequencing. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A conserved BDNF, glutamate- and GABA-enriched gene module related to human depression identified by coexpression meta-analysis and DNA variant genome-wide association studies.

PubMed

Chang, Lun-Ching; Jamain, Stephane; Lin, Chien-Wei; Rujescu, Dan; Tseng, George C; Sibille, Etienne

2014-01-01

Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases. In support of the superior discriminative power of this novel approach, we observed no significant enrichment for GWAS-related genes in coexpression modules extracted from single studies or in meta-modules using gene expression data from non-psychiatric control subjects. Genes in the identified module encode proteins implicated in neuronal signaling and structure, including glutamate metabotropic receptors (GRM1, GRM7), GABA receptors (GABRA2, GABRA4), and neurotrophic and development-related proteins [BDNF, reelin (RELN), Ephrin receptors (EPHA3, EPHA5)]. These results are consistent with the current understanding of molecular mechanisms of MDD and provide a set of putative interacting molecular partners, potentially reflecting components of a functional module across cells and biological pathways that are synchronously recruited in MDD, other brain disorders and MDD-related illnesses. Collectively, this study demonstrates the importance of integrating transcriptome data, gene coexpression modules and GWAS results for providing novel and complementary approaches to investigate the molecular pathology of MDD and other complex brain disorders.

Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-convergence on axonal guidance.

PubMed

Kaalund, Sanne S; Venø, Morten T; Bak, Mads; Møller, Rikke S; Laursen, Henning; Madsen, Flemming; Broholm, Helle; Quistorff, Bjørn; Uldall, Peter; Tommerup, Niels; Kauppinen, Sakari; Sabers, Anne; Fluiter, Kees; Møller, Lisbeth B; Nossent, Anne Y; Silahtaroglu, Asli; Kjems, Jørgen; Aronica, Eleonora; Tümer, Zeynep

2014-12-01

Mesial temporal lobe epilepsy (MTLE) is one of the most common types of the intractable epilepsies and is most often associated with hippocampal sclerosis (HS), which is characterized by pronounced loss of hippocampal pyramidal neurons. microRNAs (miRNAs) have been shown to be dysregulated in epilepsy and neurodegenerative diseases, and we hypothesized that miRNAs could be involved in the pathogenesis of MTLE and HS. miRNA expression was quantified in hippocampal specimens from human patients using miRNA microarray and quantitative real-time polymerase chain reaction RT-PCR, and by RNA-seq on fetal brain specimens from domestic pigs. In situ hybridization was used to show the spatial distribution of miRNAs in the human hippocampus. The potential effect of miRNAs on targets genes was investigated using the dual luciferase reporter gene assay. miRNA expression profiling showed that 25 miRNAs were up-regulated and 5 were down-regulated in hippocampus biopsies of MTLE/HS patients compared to controls. We showed that miR-204 and miR-218 were significantly down-regulated in MTLE and HS, and both were expressed in neurons in all subfields of normal hippocampus. Moreover, miR-204 and miR-218 showed strong changes in expression during fetal development of the hippocampus in pigs, and we identified four target genes, involved in axonal guidance and synaptic plasticity, ROBO1, GRM1, SLC1A2, and GNAI2, as bona fide targets of miR-218. GRM1 was also shown to be a direct target of miR-204. miR-204 and miR-218 are developmentally regulated in the hippocampus and may contribute to the molecular mechanisms underlying the pathogenesis of MTLE and HS. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

[Systemic lupus erythematosus and anaemia].

PubMed

Falcão, S; Barros, R; Mateus, M; Nero, P; de Matos, A Alves; Pimentão, J Bravo; Ribeiro, I; Weigert, A; Branco, J C

2007-01-01

The authors report the case of a 48-years-old Caucasian women, with a previous diagnosis of systemic lupus erythematosus characterized by asthenia, fever, skin rash, alopecia, Raynaud's phenomenon, arthritis, pericardial effusion, interstitial pulmonary involvement, diffuse proliferative glomerulonephritis with crescents and anemia. The presence of severe anemia refractory to high doses of glucocorticoids (1 mg/ /Kg/day), iron therapy and blood transfusions, associated with a low reticulocyte count determined the execution of a bone marrow aspiration, biopsy and immunophenotyping, which were compatible with the diagnosis of Myelodysplastic Syndrome. The treatment with erythropoietin (5.000U 3x/week) and cyclophosphamide pulses (1 gr/m(2) month) induced complete regression of morphologic bone marrow changes and anemia. The main causes of anemia in lupus patients are discussed.

Acute Responses to Resistance and High-Intensity Interval Training in Early Adolescents.

PubMed

Harris, Nigel K; Dulson, Deborah K; Logan, Greig R M; Warbrick, Isaac B; Merien, Fabrice L R; Lubans, David R

2017-05-01

Harris, NK, Dulson, DK, Logan, GRM, Warbrick, IB, Merien, FLR, and Lubans, DR. Acute responses to resistance and high-intensity interval training in early adolescents. J Strength Cond Res 31(5): 1177-1186, 2017-The purpose of this study was to compare the acute physiological responses within and between resistance training (RT) and high-intensity interval training (HIIT) matched for time and with comparable effort, in a school setting. Seventeen early adolescents (12.9 ± 0.3 years) performed both RT (2-5 repetitions perceived short of failure at the end of each set) and HIIT (90% of age-predicted maximum heart rate), equated for total work set and recovery period durations comprising of 12 "sets" of 30-second work followed by 30-second recovery (total session time 12 minutes). Variables of interest included oxygen consumption, set and session heart rate (HR), and rate of perceived exertion, and change in salivary cortisol (SC), salivary alpha amylase, and blood lactate (BL) from presession to postsession. Analyses were conducted to determine responses within and between the 2 different protocols. For both RT and HIIT, there were very large increases pretrial to posttrial for SC and BL, and only BL increased greater in HIIT (9.1 ± 2.6 mmol·L) than RT (6.8 ± 3.3 mmol·L). Mean set HR for both RT (170 ± 9.1 b·min) and HIIT (179 ± 5.6 b·min) was at least 85% of HRmax. V[Combining Dot Above]O2 over all 12 sets was greater for HIIT (33.8 ± 5.21 ml·kg·min) than RT (24.9 ± 3.23 ml·kg·min). Brief, repetitive, intermittent forays into high but not supramaximal intensity exercise using RT or HIIT seemed to be a potent physiological stimulus in adolescents.

Global gravity survey by an orbiting gravity gradiometer

NASA Technical Reports Server (NTRS)

Paik, Ho Jung; Leung, Jurn-Sun; Morgan, Samuel H.; Parker, Joseph

1988-01-01

The scientific aims, design, and mission profile of the Superconducting Gravity Gradiometer Mission (SGGM), a NASA spacecraft mission proposed for the late 1990s, are discussed and illustrated with drawings and diagrams. SGGM would complement the two other planned gravimetry missions, GRM and Aristoteles, and would provide gravitational-field measurements with accuracy 2-3 mGal in 55 x 55-km blocks. The principal instruments are a (1) three-axis superconducting gravity gradiometer with intrinsic sensitivity 100 microeotvos/sq rt Hz, (2) a six-axis superconducting accelerometer with sensitivity 100 fg(E)/sq rt Hz linear and 10 prad/sec squared sq rt Hz angular, and (3) a six-axis shaker for active control of the platform. Consideration is given to the error budget and platform requirements, the orbit selection criteria, and the spacecraft design.

Gamow-Teller Strength for the Mixed Ground State of ARGON-35 via the (proton, Neutron) Reaction.

NASA Astrophysics Data System (ADS)

Wagner, Anthony James

1988-12-01

Early asymmetry measurements of the mixed beta-decay of the ground state of ^{35}Ar to the ground state of ^{35}Cl showed an "anomalous" value of G_{rm V}. This anomalous value surprisingly would infer that unitary symmetry, believed to be spontaneously broken in nature, has been restored in this singular case. From the definition of rho^2, this "anomalous" value also infers a "anomalous" value for B(GT)/B(F). When the half-life data is used instead without the results of the asymmetry experiment, one obtains a different ("normal") value of B(GT)/B(F). The quantity rho^2 derived from the early asymmetry experiments is considered suspect. It has recently been shown that the (p,n) reaction at intermediate energies provides a strong interaction probe of the identical B(GT)/B(F) nuclear strength ratio that can be measured in beta-decay. The value of G_{rm A}/G _{rm V} has been determined very accurately from the beta -decay of the neutron. Thus, (p,n) can be used to determine via a totally independent measurement the value of B(GT)/B(F). The global proportionality constant E _{rm O} = 55 +/- 0.4 MeV is used to analyze the results of a 160 MeV Polarimeter experiment to distinguish between the normal and anomalous value. The results showed more spin-flip probability than was expected. A 120 MeV cross section experiment was required to check whether there was additional spin-flip probability due to a non-negligible DeltaL = 2 component. The results showed a negligible DeltaL = 2 component. The specific proportionality ({ sigma}_{rm GT} (Ground State) = {sigma} _{rm GT} (Excited State)) was then used to reanalyze the results of both experiments. The results showed a B(GT)/B(F) = 0.058 +/- 0.007. The specific proportionality gave a global proportionality constant of E_{rm O} = 32.2 +/- 1.9 MeV. The reason for this deviation in E_{rm O} is not understood.

A Faraday rotation search for magnetic fields in quasar damped Ly alpha absorption systems

NASA Technical Reports Server (NTRS)

Oren, Abraham L.; Wolfe, Arthur M.

1995-01-01

We present the results of a Faraday rotation survey of 61 radio-bright QSOs conducted at the National Radio Astronomy Observatory (NRAO) Very Large Array (VLA). The Galactic contribution to the Faraday rotation is estimated and subtracted to determine the extragalactic rotation measure (RRM) for each source. Eleven of these QSOs are known to exhibit damped Ly alpha absorption. The rate of incidence of significant Faraday rotation of these 11 sources is compared to the remaining 50 and is found to be higher at the 99.8% confidence level. However, as this is based upon only two detections of Faraday rotation in the damped Ly alpha sample, the result is only tentative. If the two detections in the damped Ly alpha sample are dug to the absorbing systems, then the inferred rotation measure induced by these systems is roughly 250 rad/sq m. The two detections were for the two lowest redshift absorbers in the sample. We find that a rotation measure of 250 rad/sq m would have gone undetected for any other absorber in the damped Ly alpha sample due to the 1/(1 + 2) squared dilution of the observed RRM with redshift. Thus the data are consistent with, but do not prove, the hypothesis that Faraday rotation is a generic property of damped Ly alpha absorbers. We do not confirm the suggestion that the amplitude of RRMs increases with redshift. Rather, the data are consistent with no redshift evolution. We find that the uncertainty in the estimation of the Galactic rotation measure (GRM) is a more serious problem than previously realized for extra-galactic Faraday rotation studies of QSO absorbers. A careful analysis of current methods for estimating GRM indicate that it can be determined to an accuracy of about 15 - 20 rad/sq m. Previous studies underestimated this uncertainty by more than a factor of 2. Due to this uncertainty, rotation measures such as we suspect are associated with damped Ly alpha absorption systems can only be detected at redshifts less than z approximately equal 1.

Long-term fluctuations in circalunar Beach aggregations of the box jellyfish Alatina moseri in Hawaii, with links to environmental variability.

PubMed

Chiaverano, Luciano M; Holland, Brenden S; Crow, Gerald L; Blair, Landy; Yanagihara, Angel A

2013-01-01

The box jellyfish Alatina moseri forms monthly aggregations at Waikiki Beach 8-12 days after each full moon, posing a recurrent hazard to swimmers due to painful stings. We present an analysis of long-term (14 years: Jan 1998- Dec 2011) changes in box jellyfish abundance at Waikiki Beach. We tested the relationship of beach counts to climate and biogeochemical variables over time in the North Pacific Sub-tropical Gyre (NPSG). Generalized Additive Models (GAM), Change-Point Analysis (CPA), and General Regression Models (GRM) were used to characterize patterns in box jellyfish arrival at Waikiki Beach 8-12 days following 173 consecutive full moons. Variation in box jellyfish abundance lacked seasonality, but exhibited dramatic differences among months and among years, and followed an oscillating pattern with significant periods of increase (1998-2001; 2006-2011) and decrease (2001-2006). Of three climatic and 12 biogeochemical variables examined, box jellyfish showed a strong, positive relationship with primary production, >2 mm zooplankton biomass, and the North Pacific Gyre Oscillation (NPGO) index. It is clear that that the moon cycle plays a key role in synchronizing timing of the arrival of Alatina moseri medusae to shore. We propose that bottom-up processes, likely initiated by inter-annual regional climatic fluctuations influence primary production, secondary production, and ultimately regulate food availability, and are therefore important in controlling the inter-annual changes in box jellyfish abundance observed at Waikiki Beach.

Long-Term Fluctuations in Circalunar Beach Aggregations of the Box Jellyfish Alatina moseri in Hawaii, with Links to Environmental Variability

PubMed Central

Chiaverano, Luciano M.; Holland, Brenden S.; Crow, Gerald L.; Blair, Landy; Yanagihara, Angel A.

2013-01-01

The box jellyfish Alatina moseri forms monthly aggregations at Waikiki Beach 8–12 days after each full moon, posing a recurrent hazard to swimmers due to painful stings. We present an analysis of long-term (14 years: Jan 1998– Dec 2011) changes in box jellyfish abundance at Waikiki Beach. We tested the relationship of beach counts to climate and biogeochemical variables over time in the North Pacific Sub-tropical Gyre (NPSG). Generalized Additive Models (GAM), Change-Point Analysis (CPA), and General Regression Models (GRM) were used to characterize patterns in box jellyfish arrival at Waikiki Beach 8–12 days following 173 consecutive full moons. Variation in box jellyfish abundance lacked seasonality, but exhibited dramatic differences among months and among years, and followed an oscillating pattern with significant periods of increase (1998–2001; 2006–2011) and decrease (2001–2006). Of three climatic and 12 biogeochemical variables examined, box jellyfish showed a strong, positive relationship with primary production, >2 mm zooplankton biomass, and the North Pacific Gyre Oscillation (NPGO) index. It is clear that that the moon cycle plays a key role in synchronizing timing of the arrival of Alatina moseri medusae to shore. We propose that bottom-up processes, likely initiated by inter-annual regional climatic fluctuations influence primary production, secondary production, and ultimately regulate food availability, and are therefore important in controlling the inter-annual changes in box jellyfish abundance observed at Waikiki Beach. PMID:24194856

Simulation and analysis of a geopotential research mission

NASA Technical Reports Server (NTRS)

Schutz, B. E.

1986-01-01

A computer simulation was performed for a Geopotential Research Mission (GRM) to enable study of the gravitational sensitivity of the range/rate measurement between two satellites and to provide a set of simulated measurements to assist in the evaluation of techniques developed for the determination of the gravity field. The simulation, identified as SGRM 8511, was conducted with two satellites in near circular, frozen orbits at 160 km altitude and separated by 300 km. High precision numerical integration of the polar orbits was used with a gravitational field complete to degree and order 180 coefficients and to degree 300 in orders 0 to 10. The set of simulated data for a mission duration of about 32 days was generated on a Cray X-MP computer. The characteristics of the simulation and the nature of the results are described.

Graphene-like layers as promising chemiresistive sensing material for detection of alcohols at low concentration

NASA Astrophysics Data System (ADS)

Gargiulo, Valentina; Alfano, Brigida; Di Capua, Roberto; Alfé, Michela; Vorokhta, Mykhailo; Polichetti, Tiziana; Massera, Ettore; Miglietta, Maria Lucia; Schiattarella, Chiara; Di Francia, Girolamo

2018-01-01

In the manifold of materials for Volatile Organic Compound (VOC) sensing, graphene related materials (GRMs) gain special attention thanks to their versatility and overall chemico-physical tunability as a function of specific applications. In this work, the sensing performances of graphene-like (GL) layers, a new material belonging to the GRM family, are tested against ethanol and n-butanol. Two typologies of GL samples were produced by employing two different approaches and tested in view of their application as VOC sensors. The experiments were performed under atmospheric pressure, in dry air, and at room temperature and demonstrated that the sensing capabilities are related to the film surface features. The results indicated that GL films are promising candidates for the detection of low concentrations of VOCs at room temperature. The present investigation thus paves the way for VOC sensing optimization using cost-effective and easily scalable materials.

Vertical pillar-superlattice array and graphene hybrid light emitting diodes.

PubMed

Lee, Jung Min; Choung, Jae Woong; Yi, Jaeseok; Lee, Dong Hyun; Samal, Monica; Yi, Dong Kee; Lee, Chul-Ho; Yi, Gyu-Chul; Paik, Ungyu; Rogers, John A; Park, Won Il

2010-08-11

We report a type of device that combines vertical arrays of one-dimensional (1D) pillar-superlattice (PSL) structures with 2D graphene sheets to yield a class of light emitting diode (LED) with interesting mechanical, optical, and electrical characteristics. In this application, graphene sheets coated with very thin metal layers exhibit good mechanical and electrical properties and an ability to mount, in a freely suspended configuration, on the PSL arrays as a top window electrode. Optical characterization demonstrates that graphene exhibits excellent optical transparency even after deposition of the thin metal films. Thermal annealing of the graphene/metal (Gr/M) contact to the GaAs decreases the contact resistance, to provide enhanced carrier injection. The resulting PSL-Gr/M LEDs exhibit bright light emission over large areas. The result suggests the utility of graphene-based materials as electrodes in devices with unusual, nonplanar 3D architectures.

Estimation of Genetic Relationships Between Individuals Across Cohorts and Platforms: Application to Childhood Height.

PubMed

Fedko, Iryna O; Hottenga, Jouke-Jan; Medina-Gomez, Carolina; Pappa, Irene; van Beijsterveldt, Catharina E M; Ehli, Erik A; Davies, Gareth E; Rivadeneira, Fernando; Tiemeier, Henning; Swertz, Morris A; Middeldorp, Christel M; Bartels, Meike; Boomsma, Dorret I

2015-09-01

Combining genotype data across cohorts increases power to estimate the heritability due to common single nucleotide polymorphisms (SNPs), based on analyzing a Genetic Relationship Matrix (GRM). However, the combination of SNP data across multiple cohorts may lead to stratification, when for example, different genotyping platforms are used. In the current study, we address issues of combining SNP data from different cohorts, the Netherlands Twin Register (NTR) and the Generation R (GENR) study. Both cohorts include children of Northern European Dutch background (N = 3102 + 2826, respectively) who were genotyped on different platforms. We explore imputation and phasing as a tool and compare three GRM-building strategies, when data from two cohorts are (1) just combined, (2) pre-combined and cross-platform imputed and (3) cross-platform imputed and post-combined. We test these three strategies with data on childhood height for unrelated individuals (N = 3124, average age 6.7 years) to explore their effect on SNP-heritability estimates and compare results to those obtained from the independent studies. All combination strategies result in SNP-heritability estimates with a standard error smaller than those of the independent studies. We did not observe significant difference in estimates of SNP-heritability based on various cross-platform imputed GRMs. SNP-heritability of childhood height was on average estimated as 0.50 (SE = 0.10). Introducing cohort as a covariate resulted in ≈2 % drop. Principal components (PCs) adjustment resulted in SNP-heritability estimates of about 0.39 (SE = 0.11). Strikingly, we did not find significant difference between cross-platform imputed and combined GRMs. All estimates were significant regardless the use of PCs adjustment. Based on these analyses we conclude that imputation with a reference set helps to increase power to estimate SNP-heritability by combining cohorts of the same ethnicity genotyped on different platforms. However, important factors should be taken into account such as remaining cohort stratification after imputation and/or phenotypic heterogeneity between and within cohorts. Whether one should use imputation, or just combine the genotype data, depends on the number of overlapping SNPs in relation to the total number of genotyped SNPs for both cohorts, and their ability to tag all the genetic variance related to the specific trait of interest.

Predictors of CD34+ cell mobilization and collection in adult men with germ cell tumors: implications for the salvage treatment strategy.

PubMed

Necchi, Andrea; Miceli, Rosalba; Pedrazzoli, Paolo; Giannatempo, Patrizia; Secondino, Simona; Di Nicola, Massimo; Farè, Elena; Raggi, Daniele; Magni, Michele; Matteucci, Paola; Longoni, Paolo; Milanesi, Marco; Paternò, Emanuela; Ravagnani, Fernando; Arienti, Flavio; Nicolai, Nicola; Salvioni, Roberto; Carlo-Stella, Carmelo; Gianni, Alessandro M

2014-06-01

High-dose chemotherapy with tandem or triple carboplatin and etoposide course is currently the first curative choice for relapsing GCT. The collection of an adequate amount of hematopoietic (CD34(+)) stem cells is a priority. We analyzed data of patients who underwent HDCT at 2 referral institutions. Chemotherapy followed by myeloid growth factors was applied in all cases. Uni- and multivariable models were used to evaluate the association between 2 prespecified variables and mobilization parameters. Analyses included only the first mobilizing course of chemotherapy and mobilization failures. A total of 116 consecutive patients underwent a mobilization attempt from December 1995 to November 2012. Mobilizing regimens included cyclophosphamide (CTX) 7 gr/m(2) (n = 39), cisplatin, etoposide, and ifosfamide (PEI) (n = 42), paclitaxel, cisplatin, and gemcitabine (TPG) (n = 11), and mixed regimens (n = 24). Thirty-seven percent were treated in first-line, 50% (n = 58) in second-line, 9.5% (n = 11) and 3.4% (n = 4) in third- and fourth-line settings, respectively. Six patients did not undergo HDCT because they were poor mobilizers, 2 in first- and second-line (1.9%), and 4 beyond the second-line (26.7%). In the multivariable model, third-line or later setting was associated with a lower CD34(+) cell peak/μL (P = .028) and a lower total CD34(+)/kg collected (P = .008). The latter was also influenced by the type of mobilizing regimen (P < .001). A decline in significant mobilization parameters was found, primarily depending on the pretreatment load. Results lend support to the role of CD34(+) cell mobilization in the therapeutic algorithm of relapsing GCT, for whom multiple HDCT courses are still an option, and potentially a cure. Copyright © 2014 Elsevier Inc. All rights reserved.

Shifting towards a model of mGluR5 dysregulation in schizophrenia: Consequences for future schizophrenia treatment.

PubMed

Matosin, Natalie; Fernandez-Enright, Francesca; Lum, Jeremy S; Newell, Kelly A

2017-03-15

Metabotropic glutamate receptor subtype 5 (mGluR5), encoded by the GRM5 gene, represents a compelling novel drug target for the treatment of schizophrenia. mGluR5 is a postsynaptic G-protein coupled glutamate receptor strongly linked with several critical cellular processes that are reported to be disrupted in schizophrenia. Accordingly, mGluR5 positive allosteric modulators show encouraging therapeutic potential in preclinical schizophrenia models, particularly for the treatment of cognitive dysfunctions against which currently available therapeutics are largely ineffective. More work is required to support the progression of mGluR5-targeting drugs into the clinic for schizophrenia treatment, although some obstacles may be overcome by comprehensively understanding how mGluR5 itself is involved in the neurobiology of the disorder. Several processes that are necessary for the regulation of mGluR5 activity have been identified, but not examined, in the context of schizophrenia. These processes include protein-protein interactions, dimerisation, subcellular trafficking, the impact of genetic variability or mutations on protein function, as well as epigenetic, post-transcriptional and post-translational processes. It is essential to understand these aspects of mGluR5 to determine whether they are affected in schizophrenia pathology, and to assess the consequences of mGluR5 dysfunction for the future use of mGluR5-based drugs. Here, we summarise the known processes that regulate mGluR5 and those that have already been studied in schizophrenia, and discuss the consequences of this dysregulation for current mGluR5 pharmacological strategies. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Advanced complex trait analysis.

PubMed

Gray, A; Stewart, I; Tenesa, A

2012-12-01

The Genome-wide Complex Trait Analysis (GCTA) software package can quantify the contribution of genetic variation to phenotypic variation for complex traits. However, as those datasets of interest continue to increase in size, GCTA becomes increasingly computationally prohibitive. We present an adapted version, Advanced Complex Trait Analysis (ACTA), demonstrating dramatically improved performance. We restructure the genetic relationship matrix (GRM) estimation phase of the code and introduce the highly optimized parallel Basic Linear Algebra Subprograms (BLAS) library combined with manual parallelization and optimization. We introduce the Linear Algebra PACKage (LAPACK) library into the restricted maximum likelihood (REML) analysis stage. For a test case with 8999 individuals and 279,435 single nucleotide polymorphisms (SNPs), we reduce the total runtime, using a compute node with two multi-core Intel Nehalem CPUs, from ∼17 h to ∼11 min. The source code is fully available under the GNU Public License, along with Linux binaries. For more information see http://www.epcc.ed.ac.uk/software-products/acta. a.gray@ed.ac.uk Supplementary data are available at Bioinformatics online.

Genetic association studies of glutamate, GABA and related genes in schizophrenia and bipolar disorder: a decade of advance.

PubMed

Cherlyn, Suat Ying Tan; Woon, Puay San; Liu, Jian Jun; Ong, Wei Yi; Tsai, Guo Chuan; Sim, Kang

2010-05-01

Schizophrenia (SZ) and bipolar disorder (BD) are debilitating neurobehavioural disorders likely influenced by genetic and non-genetic factors and which can be seen as complex disorders of synaptic neurotransmission. The glutamatergic and GABAergic neurotransmission systems have been implicated in both diseases and we have reviewed extensive literature over a decade for evidence to support the association of glutamate and GABA genes in SZ and BD. Candidate-gene based population and family association studies have implicated some ionotrophic glutamate receptor genes (GRIN1, GRIN2A, GRIN2B and GRIK3), metabotropic glutamate receptor genes (such as GRM3), the G72/G30 locus and GABAergic genes (e.g. GAD1 and GABRB2) in both illnesses to varying degrees, but further replication studies are needed to validate these results. There is at present no consensus on specific single nucleotide polymorphisms or haplotypes associated with the particular candidate gene loci in these illnesses. The genetic architecture of glutamate systems in bipolar disorder need to be better studied in view of recent data suggesting an overlap in the genetic aetiology of SZ and BD. There is a pressing need to integrate research platforms in genomics, epistatic models, proteomics, metabolomics, neuroimaging technology and translational studies in order to allow a more integrated understanding of glutamate and GABAergic signalling processes and aberrations in SZ and BD as well as their relationships with clinical presentations and treatment progress over time. (c) 2010 Elsevier Ltd. All rights reserved.

Genomic inbreeding estimation in small populations: evaluation of runs of homozygosity in three local dairy cattle breeds.

PubMed

Mastrangelo, S; Tolone, M; Di Gerlando, R; Fontanesi, L; Sardina, M T; Portolano, B

2016-05-01

In the local breeds with small population size, one of the most important problems is the increase of inbreeding coefficient (F). High levels of inbreeding lead to reduced genetic diversity and inbreeding depression. The availability of high-density single nucleotide polymorphism (SNP) arrays has facilitated the quantification of F by genomic markers in farm animals. Runs of homozygosity (ROH) are contiguous lengths of homozygous genotypes and represent an estimate of the degree of autozygosity at genome-wide level. The current study aims to quantify the genomic F derived from ROH (F ROH) in three local dairy cattle breeds. F ROH values were compared with F estimated from the genomic relationship matrix (F GRM), based on the difference between observed v. expected number of homozygous genotypes (F HOM) and the genomic homozygosity of individual i (F MOL i ). The molecular coancestry coefficient (f MOL ij ) between individuals i and j was also estimated. Individuals of Cinisara (71), Modicana (72) and Reggiana (168) were genotyped with the 50K v2 Illumina BeadChip. Genotypes from 96 animals of Italian Holstein cattle breed were also included in the analysis. We used a definition of ROH as tracts of homozygous genotypes that were >4 Mb. Among breeds, 3661 ROH were identified. Modicana showed the highest mean number of ROH per individual and the highest value of F ROH, whereas Reggiana showed the lowest ones. Differences among breeds existed for the ROH lengths. The individuals of Italian Holstein showed high number of short ROH segments, related to ancient consanguinity. Similar results showed the Reggiana with some extreme animals with segments covering 400 Mb and more of genome. Modicana and Cinisara showed similar results between them with the total length of ROH characterized by the presence of large segments. High correlation was found between F HOM and F ROH ranged from 0.83 in Reggiana to 0.95 in Cinisara and Modicana. The correlations among F ROH and other estimated F coefficients were generally lower ranged from 0.45 (F MOL i -F ROH) in Cinisara to 0.17 (F GRM-F ROH) in Modicana. On the basis of our results, recent inbreeding was observed in local breeds, considering that 16 Mb segments are expected to present inbreeding up to three generations ago. Our results showed the necessity of implementing conservation programs to control the rise of inbreeding and coancestry in the three Italian local dairy cattle breeds.

A high-resolution record of the Matuyama-Brunhes transition from the Mediterranean region: The Valle di Manche section (Calabria, Southern Italy)

NASA Astrophysics Data System (ADS)

Macrì, Patrizia; Capraro, Luca; Ferretti, Patrizia; Scarponi, Daniele

2018-05-01

High-resolution palaeomagnetic and rock magnetic investigations on the Valle di Manche section (Crotone Basin, Calabria, Southern Italy) provide a detailed record of the Matuyama-Brunhes (M-B) reversal that, to our best knowledge, is the only available record of the last geomagnetic reversal for the Mediterranean on-land marine stratigraphy. The M-B transition can be pinpointed precisely, as it develops within a 3-cm-thick interval located just above a prominent tephra layer (the "Pitagora ash") where the sedimentation rates are about 27 cm/kyr. Demagnetization analyses indicate a stable palaeomagnetic behaviour throughout the section for both normal and reversed polarity directions, with demagnetization vectors aligned toward the origin of Zijderveld diagrams after the removal of a small viscous low-coercivity remanence component. In the lower part of the studied interval, some samples acquired a spurious gyromagnetic remanent magnetization (GRM) during AF demagnetization in high fields. Rock magnetic analyses confirm that magnetite is the main magnetic carrier for all measured specimens, which also have an abundant paramagnetic fraction. Only the lower part of the record, well below the M-B boundary, is characterized by a downward-increasing presence of iron sulphides (greigite). According to our chronology, which is based on a robust, cross-validated age model, the final reverse-to-normal directional change of the M-B transition occurred at ca. 786.9 ± 5 ka (error includes uncertainty in orbital tuning) and was very rapid, of the order of 100 years or less.

Simulation and analysis of a geopotential research mission

NASA Technical Reports Server (NTRS)

Schutz, B. E.

1987-01-01

Computer simulations were performed for a Geopotential Research Mission (GRM) to enable the study of the gravitational sensitivity of the range rate measurements between the two satellites and to provide a set of simulated measurements to assist in the evaluation of techniques developed for the determination of the gravity field. The simulations were conducted with two satellites in near circular, frozen orbits at 160 km altitudes separated by 300 km. High precision numerical integration of the polar orbits were used with a gravitational field complete to degree and order 360. The set of simulated data for a mission duration of about 32 days was generated on a Cray X-MP computer. The results presented cover the most recent simulation, S8703, and includes a summary of the numerical integration of the simulated trajectories, a summary of the requirements to compute nominal reference trajectories to meet the initial orbit determination requirements for the recovery of the geopotential, an analysis of the nature of the one way integrated Doppler measurements associated with the simulation, and a discussion of the data set to be made available.

Moist Exposed Burn Ointment (MEBO) in partial thickness burns - a randomized, comparative open mono-center study on the efficacy of dermaheal (MEBO) ointment on thermal 2nd degree burns compared to conventional therapy.

PubMed

Hirsch, T; Ashkar, W; Schumacher, O; Steinstraesser, L; Ingianni, G; Cedidi, C C

2008-11-24

Wound healing in burn wounds presents a challenge in healthcare, and there is still a lack of alternatives in topical burn wound treatments. - The purpose of this study was to evaluate the efficacy of a new therapeutic ointment (MEBO) in the treatment of partial thickness burns. 40 patients received either topical treatment with Moist Exposed Burn Ointment (MEBO) or standard Flammazine treatment. All patients suffered from partial-thickness burn injuries (< 20% TBSA). Wounds were evaluated for 60 up to days regarding wound healing, water loss, inflammation, and pain alleviation. For transepidermal water loss, there was a difference of 2.3 gr/m2/h between MEBO, and Flammazine, favoring MEBO. However, this difference was not statistically significant (p=0.78). For all secondary efficacy parameter results were similar. - This study showed that MEBO ointment for topical treatment of burn injuries presents an attractive alternative for the topical treatment of limited partial thickness thermal burns.

The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism

PubMed Central

Hadley, Dexter; Wu, Zhi-liang; Kao, Charlly; Kini, Akshata; Mohamed-Hadley, Alisha; Thomas, Kelly; Vazquez, Lyam; Qiu, Haijun; Mentch, Frank; Pellegrino, Renata; Kim, Cecilia; Connolly, John; Pinto, Dalila; Merikangas, Alison; Klei, Lambertus; Vorstman, Jacob A.S.; Thompson, Ann; Regan, Regina; Pagnamenta, Alistair T.; Oliveira, Bárbara; Magalhaes, Tiago R.; Gilbert, John; Duketis, Eftichia; De Jonge, Maretha V.; Cuccaro, Michael; Correia, Catarina T.; Conroy, Judith; Conceição, Inês C.; Chiocchetti, Andreas G.; Casey, Jillian P.; Bolshakova, Nadia; Bacchelli, Elena; Anney, Richard; Zwaigenbaum, Lonnie; Wittemeyer, Kerstin; Wallace, Simon; Engeland, Herman van; Soorya, Latha; Rogé, Bernadette; Roberts, Wendy; Poustka, Fritz; Mouga, Susana; Minshew, Nancy; McGrew, Susan G.; Lord, Catherine; Leboyer, Marion; Le Couteur, Ann S.; Kolevzon, Alexander; Jacob, Suma; Guter, Stephen; Green, Jonathan; Green, Andrew; Gillberg, Christopher; Fernandez, Bridget A.; Duque, Frederico; Delorme, Richard; Dawson, Geraldine; Café, Cátia; Brennan, Sean; Bourgeron, Thomas; Bolton, Patrick F.; Bölte, Sven; Bernier, Raphael; Baird, Gillian; Bailey, Anthony J.; Anagnostou, Evdokia; Almeida, Joana; Wijsman, Ellen M.; Vieland, Veronica J.; Vicente, Astrid M.; Schellenberg, Gerard D.; Pericak-Vance, Margaret; Paterson, Andrew D.; Parr, Jeremy R.; Oliveira, Guiomar; Almeida, Joana; Café, Cátia; Mouga, Susana; Correia, Catarina; Nurnberger, John I.; Monaco, Anthony P.; Maestrini, Elena; Klauck, Sabine M.; Hakonarson, Hakon; Haines, Jonathan L.; Geschwind, Daniel H.; Freitag, Christine M.; Folstein, Susan E.; Ennis, Sean; Coon, Hilary; Battaglia, Agatino; Szatmari, Peter; Sutcliffe, James S.; Hallmayer, Joachim; Gill, Michael; Cook, Edwin H.; Buxbaum, Joseph D.; Devlin, Bernie; Gallagher, Louise; Betancur, Catalina; Scherer, Stephen W.; Glessner, Joseph; Hakonarson, Hakon

2014-01-01

Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E−09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E−23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E−04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions. PMID:24927284

T227. THE METABOTROPIC GLUTAMATE RECEPTOR SUBTYPE 1 REGULATES STRIATAL DOPAMINE RELEASE VIA AN ENDOCANNABINOID-DEPENDENT MECHANISM: IMPLICATIONS FOR THE TREATMENT OF SCHIZOPHRENIA

PubMed Central

Yohn, Samantha; Covey, Daniel; Foster, Daniel; Moehle, Mark; Galbraith, Jordan; Cheer, Joseph; Lindsley, Craig; Jeffrey Conn, P

2018-01-01

Abstract Background Clinical and preclinical studies suggest that selective activators of the muscarinic M4 receptor have exciting potential as a novel approach for treatment of schizophrenia. M4 reduces striatal dopamine (DA) though release of endocannabinoids (eCB), providing a mechanism for local effects on DA signaling in the striatum. M4 signals through Gαi/o and does not couple to Gαq/11 or induce calcium (Ca++) mobilization. This raises the possibility that M4-induced eCB release and inhibition of DA release may require co-activation of another receptor that activates Gαq/11. If so, this receptor could provide a novel target that may be more proximal to inhibition of DA release. Interestingly, the group 1 metabotropic glutamate (mGlu) receptors (mGlu1 and Glu5), couple to Gαq/11 and activate eCB signaling in multiple brain regions. Methods We tested the hypothesis that M4-induced reductions in DA release and subsequent antipsychotic-effect requires co-activation of group 1 mGlu receptors. The effect of M4 activation on electrically-evoked DA release in striatal slices was assessed using fast-scan cyclic voltammetry (FSCV) in the absence or presence of selective negative allosteric modulators (NAMs) of group 1 mGlu receptor subtypes. To evaluate the potential role of mGlu1, we determined the effects of a selective mGlu1 positive allosteric modulators (PAMs) on striatal DA release and antipsychotic-like activity in rodent models that are dependent on increased DA transmission. Since reductions in DA signaling, including D1 signaling have been implicated in reduced motivation, we also determined the effects of an mGlu1 PAM, M4 PAM, and the typical antipsychotic haloperidol on motivational responding in a progressive ratio (PR) schedule. Results We now present exciting new data in which we found that activation of mGlu1 through application of exogenous agonists or selective stimulation of thalamostriatal afferents induces a reduction of striatal DA release and that selective mGlu1 PAMs have robust antipsychotic-like effects in rodent models. Interestingly, our studies also suggest that mGlu1 activation is required for M4 PAM-induced inhibition of DA release and antipsychotic-like effects. However, in contrast to available antipsychotic agents, the present results and previous studies suggest that mGlu1 and M4 PAMs reduce DA signaling through local release of an eCB from striatal SPNs and activation of CB2 receptors on neighboring DA terminals to reduce DA release. While these studies suggest that the effects of M4 PAMs on DA release require activation of mGlu1, we have also found that these targets have important differences. Most notably, M4 PAMs also directly inhibits D1 signaling in D1-SPN terminals in the substatnia nigra pars reticulata (SNr). Unlike M4, mGlu1 does not directly inhibit DA D1 receptor signaling and does not induce behavioral changes that could be associated with negative symptoms. Discussion Our findings are especially interesting in light of recent findings that multiple loss of function single nucleotide polymorphisms (SNPs) in the human gene encoding mGlu1 (GRM1) are associated with schizophrenia, and points to GRM1/mGlu1 as a gene within the “druggable genome” that could be targeted for treatment of schizophrenia. Recent clinical imaging studies suggesting that symptoms in schizophrenia patients are associated with selective increases in striatal DA signaling and while extrastriatal regions display hypo-dopaminergic function; thus, mGlu1 and M4 PAMs may provide a mechanism for selective inhibition of DA release in striatal regions that are important for antipsychotic efficacy, without further disruptions in extrastriatal DA signaling.

Genotype and phenotype of 101 dutch patients with congenital stationary night blindness.

PubMed

Bijveld, Mieke M C; Florijn, Ralph J; Bergen, Arthur A B; van den Born, L Ingeborgh; Kamermans, Maarten; Prick, Liesbeth; Riemslag, Frans C C; van Schooneveld, Mary J; Kappers, Astrid M L; van Genderen, Maria M

2013-10-01

To investigate the relative frequency of the genetic causes of the Schubert-Bornschein type of congenital stationary night blindness (CSNB) and to determine the genotype-phenotype correlations in CSNB1 and CSNB2. Clinic-based, longitudinal, multicenter study. A total of 39 patients with CSNB1 from 29 families and 62 patients with CSNB2 from 43 families. Patients underwent full ophthalmologic and electrophysiologic examinations. On the basis of standard electroretinograms (ERGs), patients were diagnosed with CSNB1 or CSNB2. Molecular analysis was performed by direct Sanger sequencing of the entire coding regions in NYX, TRPM1, GRM6, and GPR179 in patients with CSNB1 and CACNA1F and CABP4 in patients with CSNB2. Data included genetic cause of CSNB, refractive error, visual acuity, nystagmus, strabismus, night blindness, photophobia, color vision, dark adaptation (DA) curve, and standard ERGs. A diagnosis of CSNB1 or CSNB2 was based on standard ERGs. The photopic ERG was the most specific criterion to distinguish between CSNB1 and CSNB2 because it showed a "square-wave" appearance in CSNB1 and a decreased b-wave in CSNB2. Mutations causing CSNB1 were found in NYX (20 patients, 13 families), TRPM1 (10 patients, 9 families), GRM6 (4 patients, 3 families), and GPR179 (2 patients, 1 family). Congenital stationary night blindness 2 was primarily caused by mutations in CACNA1F (55 patients, 37 families). Only 3 patients had causative mutations in CABP4 (2 families). Patients with CSNB1 mainly had rod-related problems, and patients with CSNB2 had rod- and cone-related problems. The visual acuity on average was better in CSNB1 (0.30 logarithm of the minimum angle of resolution [logMAR]) than in CSNB2 (0.52 logMAR). All patients with CSNB1 and only 54% of the patients with CSNB2 reported night blindness. The dark-adapted threshold was on average more elevated in CSNB1 (3.0 log) than in CSNB2 (1.8 log). The 3 patients with CABP4 had a relative low visual acuity, were hyperopic, had severe nonspecific color vision defects, and had only 1.0 log elevated DA threshold. Congenital stationary night blindness 1, despite different causative mutations, shows 1 unique CSNB1 phenotype. Congenital stationary night blindness 2 caused by mutations in CABP4 merely shows cone-related problems and therefore appears to be distinct from CSNB2 caused by mutations in CACNA1F. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Genomic diversity and population structure of three autochthonous Greek sheep breeds assessed with genome-wide DNA arrays.

PubMed

Michailidou, S; Tsangaris, G; Fthenakis, G C; Tzora, A; Skoufos, I; Karkabounas, S C; Banos, G; Argiriou, A; Arsenos, G

2018-06-01

In the present study, genome-wide genotyping was applied to characterize the genetic diversity and population structure of three autochthonous Greek breeds: Boutsko, Karagouniko and Chios. Dairy sheep are among the most significant livestock species in Greece numbering approximately 9 million animals which are characterized by large phenotypic variation and reared under various farming systems. A total of 96 animals were genotyped with the Illumina's OvineSNP50K microarray beadchip, to study the population structure of the breeds and develop a specialized panel of single-nucleotide polymorphisms (SNPs), which could distinguish one breed from the others. Quality control on the dataset resulted in 46,125 SNPs, which were used to evaluate the genetic structure of the breeds. Population structure was assessed through principal component analysis (PCA) and admixture analysis, whereas inbreeding was estimated based on runs of homozygosity (ROHs) coefficients, genomic relationship matrix inbreeding coefficients (F GRM ) and patterns of linkage disequilibrium (LD). Associations between SNPs and breeds were analyzed with different inheritance models, to identify SNPs that distinguish among the breeds. Results showed high levels of genetic heterogeneity in the three breeds. Genetic distances among breeds were modest, despite their different ancestries. Chios and Karagouniko breeds were more genetically related to each other compared to Boutsko. Analysis revealed 3802 candidate SNPs that can be used to identify two-breed crosses and purebred animals. The present study provides, for the first time, data on the genetic background of three Greek indigenous dairy sheep breeds as well as a specialized marker panel that can be applied for traceability purposes as well as targeted genetic improvement schemes and conservation programs.

Lateralized Feeding Behavior is Associated with Asymmetrical Neuroanatomy and Lateralized Gene Expressions in the Brain in Scale-Eating Cichlid Fish

PubMed Central

Lee, Hyuk Je; Schneider, Ralf F; Manousaki, Tereza; Kang, Ji Hyoun; Lein, Etienne; Franchini, Paolo

2017-01-01

Abstract Lateralized behavior (“handedness”) is unusual, but consistently found across diverse animal lineages, including humans. It is thought to reflect brain anatomical and/or functional asymmetries, but its neuro-molecular mechanisms remain largely unknown. Lake Tanganyika scale-eating cichlid fish, Perissodus microlepis show pronounced asymmetry in their jaw morphology as well as handedness in feeding behavior—biting scales preferentially only from one or the other side of their victims. This makes them an ideal model in which to investigate potential laterality in neuroanatomy and transcription in the brain in relation to behavioral handedness. After determining behavioral handedness in P. microlepis (preferred attack side), we estimated the volume of the hemispheres of brain regions and captured their gene expression profiles. Our analyses revealed that the degree of behavioral handedness is mirrored at the level of neuroanatomical asymmetry, particularly in the tectum opticum. Transcriptome analyses showed that different brain regions (tectum opticum, telencephalon, hypothalamus, and cerebellum) display distinct expression patterns, potentially reflecting their developmental interrelationships. For numerous genes in each brain region, their extent of expression differences between hemispheres was found to be correlated with the degree of behavioral lateralization. Interestingly, the tectum opticum and telencephalon showed divergent biases on the direction of up- or down-regulation of the laterality candidate genes (e.g., grm2) in the hemispheres, highlighting the connection of handedness with gene expression profiles and the different roles of these brain regions. Hence, handedness in predation behavior may be caused by asymmetric size of brain hemispheres and also by lateralized gene expressions in the brain. PMID:29069363

Rare Genome-Wide Copy Number Variation and Expression of Schizophrenia in 22q11.2 Deletion Syndrome.

PubMed

Bassett, Anne S; Lowther, Chelsea; Merico, Daniele; Costain, Gregory; Chow, Eva W C; van Amelsvoort, Therese; McDonald-McGinn, Donna; Gur, Raquel E; Swillen, Ann; Van den Bree, Marianne; Murphy, Kieran; Gothelf, Doron; Bearden, Carrie E; Eliez, Stephan; Kates, Wendy; Philip, Nicole; Sashi, Vandana; Campbell, Linda; Vorstman, Jacob; Cubells, Joseph; Repetto, Gabriela M; Simon, Tony; Boot, Erik; Heung, Tracy; Evers, Rens; Vingerhoets, Claudia; van Duin, Esther; Zackai, Elaine; Vergaelen, Elfi; Devriendt, Koen; Vermeesch, Joris R; Owen, Michael; Murphy, Clodagh; Michaelovosky, Elena; Kushan, Leila; Schneider, Maude; Fremont, Wanda; Busa, Tiffany; Hooper, Stephen; McCabe, Kathryn; Duijff, Sasja; Isaev, Karin; Pellecchia, Giovanna; Wei, John; Gazzellone, Matthew J; Scherer, Stephen W; Emanuel, Beverly S; Guo, Tingwei; Morrow, Bernice E; Marshall, Christian R

2017-11-01

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a more than 20-fold increased risk for developing schizophrenia. The aim of this study was to identify additional genetic factors (i.e., "second hits") that may contribute to schizophrenia expression. Through an international consortium, the authors obtained DNA samples from 329 psychiatrically phenotyped subjects with 22q11.2DS. Using a high-resolution microarray platform and established methods to assess copy number variation (CNV), the authors compared the genome-wide burden of rare autosomal CNV, outside of the 22q11.2 deletion region, between two groups: a schizophrenia group and those with no psychotic disorder at age ≥25 years. The authors assessed whether genes overlapped by rare CNVs were overrepresented in functional pathways relevant to schizophrenia. Rare CNVs overlapping one or more protein-coding genes revealed significant between-group differences. For rare exonic duplications, six of 19 gene sets tested were enriched in the schizophrenia group; genes associated with abnormal nervous system phenotypes remained significant in a stepwise logistic regression model and showed significant interactions with 22q11.2 deletion region genes in a connectivity analysis. For rare exonic deletions, the schizophrenia group had, on average, more genes overlapped. The additional rare CNVs implicated known (e.g., GRM7, 15q13.3, 16p12.2) and novel schizophrenia risk genes and loci. The results suggest that additional rare CNVs overlapping genes outside of the 22q11.2 deletion region contribute to schizophrenia risk in 22q11.2DS, supporting a multigenic hypothesis for schizophrenia. The findings have implications for understanding expression of psychotic illness and herald the importance of whole-genome sequencing to appreciate the overall genomic architecture of schizophrenia.

Lateralized Feeding Behavior is Associated with Asymmetrical Neuroanatomy and Lateralized Gene Expressions in the Brain in Scale-Eating Cichlid Fish.

PubMed

Lee, Hyuk Je; Schneider, Ralf F; Manousaki, Tereza; Kang, Ji Hyoun; Lein, Etienne; Franchini, Paolo; Meyer, Axel

2017-11-01

Lateralized behavior ("handedness") is unusual, but consistently found across diverse animal lineages, including humans. It is thought to reflect brain anatomical and/or functional asymmetries, but its neuro-molecular mechanisms remain largely unknown. Lake Tanganyika scale-eating cichlid fish, Perissodus microlepis show pronounced asymmetry in their jaw morphology as well as handedness in feeding behavior-biting scales preferentially only from one or the other side of their victims. This makes them an ideal model in which to investigate potential laterality in neuroanatomy and transcription in the brain in relation to behavioral handedness. After determining behavioral handedness in P. microlepis (preferred attack side), we estimated the volume of the hemispheres of brain regions and captured their gene expression profiles. Our analyses revealed that the degree of behavioral handedness is mirrored at the level of neuroanatomical asymmetry, particularly in the tectum opticum. Transcriptome analyses showed that different brain regions (tectum opticum, telencephalon, hypothalamus, and cerebellum) display distinct expression patterns, potentially reflecting their developmental interrelationships. For numerous genes in each brain region, their extent of expression differences between hemispheres was found to be correlated with the degree of behavioral lateralization. Interestingly, the tectum opticum and telencephalon showed divergent biases on the direction of up- or down-regulation of the laterality candidate genes (e.g., grm2) in the hemispheres, highlighting the connection of handedness with gene expression profiles and the different roles of these brain regions. Hence, handedness in predation behavior may be caused by asymmetric size of brain hemispheres and also by lateralized gene expressions in the brain. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Lifetime Prediction of IGBT in a STATCOM Using Modified-Graphical Rainflow Counting Algorithm

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

Gopi Reddy, Lakshmi Reddy; Tolbert, Leon M; Ozpineci, Burak

Rainflow algorithms are one of the best counting methods used in fatigue and failure analysis [17]. There have been many approaches to the rainflow algorithm, some proposing modifications. Graphical Rainflow Method (GRM) was proposed recently with a claim of faster execution times [10]. However, the steps of the graphical method of rainflow algorithm, when implemented, do not generate the same output as the four-point or ASTM standard algorithm. A modified graphical method is presented and discussed in this paper to overcome the shortcomings of graphical rainflow algorithm. A fast rainflow algorithm based on four-point algorithm but considering point comparison thanmore » range comparison is also presented. A comparison between the performances of the common rainflow algorithms [6-10], including the proposed methods, in terms of execution time, memory used, and efficiency, complexity, and load sequences is presented. Finally, the rainflow algorithm is applied to temperature data of an IGBT in assessing the lifetime of a STATCOM operating for power factor correction of the load. From 5-minute data load profiles available, the lifetime is estimated to be at 3.4 years.« less

Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies

PubMed Central

Liu, Guangming; Wang, Yiwei; Zhao, Pengyao; Zhu, Yizhun; Yang, Xiaohan; Zheng, Tiezheng; Zhou, Xuezhong; Jin, Weilin; Sun, Changkai

2017-01-01

Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE). Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI) network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., “presynaptic nicotinic acetylcholine receptors”, “signaling by insulin receptor”). Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1) located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy. PMID:28388656

Eccentric LVH healing after starting renal replacement therapy.

PubMed

Vertolli, Ugo; Lupia, Mario; Naso, Agostino

2002-01-01

Hypertension and left ventricular hypertrophy (LVH) are commonly associated in patients with CRF starting RDT. We report a case of eccentric LVH with marked dilatation and subsequent mitral incompetence of +3/4 that disappeared after three months of standard hemodialysis. Mrs SN, 62 years old, starting HD, had an echocardiography because of dyspnoea; the echo showed: dilated left atrium (78 ml/m2), moderately dilated left ventricle with normal systolic function (TDV 81 ml/m2, EF 66%), an increased ventricular mass (120 gr/m2) and a high grade mitral incompetence +3/4. After three months standard RDT and a dry weight only 2 kg less, the patients was normotensive without therapy, a cardiac angiogram with a hemodynamic study was performed as a pre-transplant workout: a normal left ventricle was found with normal systolic function (TDV 66, TSV 17, GS 49, EF 75%), and a perfectly competent mitral valve (reflux disappeared). The coronary angiography did not reveal critical stenosis. A new echocardiography confinned the data of the hemodynamic study: hypertensive cardiomiopathy with normal systolic function. After one year the patient has been transplanted, with a good renal function and the cardiac echo unchanged. Relieving uremic toxicity ameliorated the cardiac performance in this particular patient.

Diffusion Dominant Solute Transport Modelling in Fractured Media Under Deep Geological Environment - 12211

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

Kwong, S.; Jivkov, A.P.

2012-07-01

Deep geologic disposal of high activity and long-lived radioactive waste is gaining increasing support in many countries, where suitable low permeability geological formation in combination with engineered barriers are used to provide long term waste contaminant and minimise the impacts to the environment and risk to the biosphere. This modelling study examines the solute transport in fractured media under low flow velocities that are relevant to a deep geological environment. In particular, reactive solute transport through fractured media is studied using a 2-D model, that considers advection and diffusion, to explore the coupled effects of kinetic and equilibrium chemical processes.more » The effects of water velocity in the fracture, matrix porosity and diffusion on solute transport are investigated and discussed. Some illustrative modelled results are presented to demonstrate the use of the model to examine the effects of media degradation on solute transport, under the influences of hydrogeological (diffusion dominant) and microbially mediated chemical processes. The challenges facing the prediction of long term degradation such as cracks evolution, interaction and coalescence are highlighted. The potential of a novel microstructure informed modelling approach to account for these effects is discussed, particularly with respect to investigating multiple phenomena impact on material performance. The GRM code is used to examine the effects of media degradation for a geological waste disposal package, under the combined hydrogeological (diffusion dominant) and chemical effects in low groundwater flow conditions that are typical of deep geological disposal systems. An illustrative reactive transport modelling application demonstrates the use of the code to examine the interplay of kinetic controlled biogeochemical reactive processes with advective and diffusive transport, under the influence of media degradation. The initial model results are encouraging which show the disposal system to evolve in a physically realistic manner. In the example presented the reactive-transport coupling develops chemically reducing zones, which limit the transport of uranium. This illustrates the potential significance of media degradation and chemical effect on the transport of radionuclides which would need to be taken into account when examining the long-term behaviour and containment properties of the geological disposal system. Microstructure-informed modelling and its potential linkage with continuum flow modelling is a subject of ongoing studies. The approach of microstructure-informed modelling is discussed to provide insight and a mechanistic understanding of macroscopic parameters and their evolution. The proposed theoretical and methodological basis for microstructure-informed modelling of porous quasi-brittle media has the potential to develop into an explanatory and predictive tool for deriving mechanism-based, as opposed to phenomenological, evolution laws for macroscopic properties. These concepts in micro-scale modelling are likely to be applicable to the diffusion process, in addition to advective transport illustrated here for porous media. (authors)« less

The clinical significance of small copy number variants in neurodevelopmental disorders.

PubMed

Asadollahi, Reza; Oneda, Beatrice; Joset, Pascal; Azzarello-Burri, Silvia; Bartholdi, Deborah; Steindl, Katharina; Vincent, Marie; Cobilanschi, Joana; Sticht, Heinrich; Baldinger, Rosa; Reissmann, Regina; Sudholt, Irene; Thiel, Christian T; Ekici, Arif B; Reis, André; Bijlsma, Emilia K; Andrieux, Joris; Dieux, Anne; FitzPatrick, David; Ritter, Susanne; Baumer, Alessandra; Latal, Beatrice; Plecko, Barbara; Jenni, Oskar G; Rauch, Anita

2014-10-01

Despite abundant evidence for pathogenicity of large copy number variants (CNVs) in neurodevelopmental disorders (NDDs), the individual significance of genome-wide rare CNVs <500 kb has not been well elucidated in a clinical context. By high-resolution chromosomal microarray analysis, we investigated the clinical significance of all rare non-polymorphic exonic CNVs sizing 1-500 kb in a cohort of 714 patients with undiagnosed NDDs. We detected 96 rare CNVs <500 kb affecting coding regions, of which 58 (60.4%) were confirmed. 6 of 14 confirmed de novo, one of two homozygous and four heterozygous inherited CNVs affected the known microdeletion regions 17q21.31, 16p11.2 and 2p21 or OMIM morbid genes (CASK, CREBBP, PAFAH1B1, SATB2; AUTS2, NRXN3, GRM8). Two further de novo CNVs affecting single genes (MED13L, CTNND2) were instrumental in delineating novel recurrent conditions. For the first time, we here report exonic deletions of CTNND2 causing low normal IQ with learning difficulties with or without autism spectrum disorder. Additionally, we discovered a homozygous out-of-frame deletion of ACOT7 associated with features comparable to the published mouse model. In total, 24.1% of the confirmed small CNVs were categorised as pathogenic or likely pathogenic (median size 130 kb), 17.2% as likely benign, 3.4% represented incidental findings and 55.2% remained unclear. These results verify the diagnostic relevance of genome-wide rare CNVs <500 kb, which were found pathogenic in ∼2% (14/714) of cases (1.1% de novo, 0.3% homozygous, 0.6% inherited) and highlight their inherent potential for discovery of new conditions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Machine Learning-based Rainfall System for GPM Dual-frequency Radar

NASA Astrophysics Data System (ADS)

Tan, H.; Chandrasekar, V.; Chen, H.

2017-12-01

Precipitation measurement produced by the Global Precipitation Measurement (GPM) Dual-frequency Precipitation Radar (DPR) plays an important role in researching the water circle and forecasting extreme weather event. Compare with its predecessor - Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR), GRM DPR measures precipitation in two different frequencies (i.e., Ku and Ka band), which can provide detailed information on the microphysical properties of precipitation particles, quantify particle size distribution and quantitatively measure light rain and falling snow. This paper presents a novel Machine Learning system for ground-based and space borne radar rainfall estimation. The system first trains ground radar data for rainfall estimation using rainfall measurements from gauges and subsequently uses the ground radar based rainfall estimates to train GPM DPR data in order to get space based rainfall product. Therein, data alignment between space DPR and ground radar is conducted using the methodology proposed by Bolen and Chandrasekar (2013), which can minimize the effects of potential geometric distortion of GPM DPR observations. For demonstration purposes, rainfall measurements from three rain gauge networks near Melbourne, Florida, are used for training and validation purposes. These three gauge networks, which are located in Kennedy Space Center (KSC), South Florida Water Management District (SFL), and St. Johns Water Management District (STJ), include 33, 46, and 99 rain gauge stations, respectively. Collocated ground radar observations from the National Weather Service (NWS) Weather Surveillance Radar - 1988 Doppler (WSR-88D) in Melbourne (i.e., KMLB radar) are trained with the gauge measurements. The trained model is then used to derive KMLB radar based rainfall product, which is used to train GPM DPR data collected from coincident overpasses events. The machine learning based rainfall product is compared against the GPM standard products, which shows great potential of the machine learning concept in radar rainfall estimation.

DNA sequence-level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders.

PubMed

Ryan, Niamh M; Lihm, Jayon; Kramer, Melissa; McCarthy, Shane; Morris, Stewart W; Arnau-Soler, Aleix; Davies, Gail; Duff, Barbara; Ghiban, Elena; Hayward, Caroline; Deary, Ian J; Blackwood, Douglas H R; Lawrie, Stephen M; McIntosh, Andrew M; Evans, Kathryn L; Porteous, David J; McCombie, W Richard; Thomson, Pippa A

2018-06-07

Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes.

Tumour cell dormancy as a contributor to the reduced survival of GBM patients who received standard therapy.

PubMed

Tong, Luqing; Yi, Li; Liu, Peidong; Abeysekera, Iruni Roshanie; Hai, Long; Li, Tao; Tao, Zhennan; Ma, Haiwen; Xie, Yang; Huang, Yubao; Yu, Shengping; Li, Jiabo; Yuan, Feng; Yang, Xuejun

2018-07-01

Glioblastoma multiforme (GBM) is a fatal cancer with varying life expectancy, even for patients undergoing the same standard therapy. Identification of differentially expressed genes in GBM patients with different survival rates may benefit the development of effective therapeutic strategies. In the present study, key pathways and genes correlated with survival in GBM patients were screened with bioinformatic analysis. Included in the study were 136 eligible patients who had undertaken surgical resection of GBM followed by temozolomide (TMZ) chemoradiation and long-term therapy with TMZ. A total of 383 differentially expressed genes (DEGs) related to GBM survival were identified. Gene Ontology and pathway enrichment analysis as well as hub gene screening and module analysis were performed. As expected, angiogenesis and migration of GBM cells were closely correlated with a poor prognosis. Importantly, the results also indicated that cell dormancy was an essential contributor to the reduced survival of GBM patients. Given the lack of specific targeted genes and pathways known to be involved in tumour cell dormancy, we proposed enriched candidate genes related to the negative regulation of cell proliferation, signalling pathways regulating pluripotency of stem cells and neuroactive ligand-receptor interaction, and 3 hub genes (FTH1, GRM1 and DDIT3). Maintaining persistent cell dormancy or preventing tumour cells from entering dormancy during chemoradiation should be a promising therapeutic strategy.

The genetic basis of new treatment modalities in melanoma.

PubMed

Kunz, Manfred

2015-01-01

In recent years, intracellular signal transduction via RAS-RAF-MEK-ERK has been successfully targeted in new treatment approaches for melanoma using small molecule inhibitors against activated BRAF (V600E mutation) and activated MEK1/2. Also mutated c-KIT has been identified as a promising target. Meanwhile, evidence has been provided that combinations between BRAF inhibitors and MEK1/2 inhibitors are more promising than single-agent treatments. Moreover, new treatment algorithms favor sequential treatment using BRAF inhibitors and newly developed immunotherapies targeting common T lymphocyte antigen 4 (CTLA-4) or programmed cell death 1 (PD-1). In depth molecular analyses have uncovered new mechanisms of treatment resistance and recurrence, which may impact on future treatment decisions. Moreover, next-generation sequencing data have shown that recurrent lesions harbor specific genetic aberrations. At the same time, high throughput sequencing studies of melanoma unraveled a series of new treatment candidates for future treatment approaches such as ERBB4, GRIN2A, GRM3, and RAC1. More recent bioinformatic technologies provided genetic evidence for extensive tumor heterogeneity and tumor clonality of solid tumors, which might also be of relevance for melanoma. However, these technologies have not yet been applied to this tumor. In this review, an overview on the genetic basis of current treatment of melanoma, treatment resistance and recurrences including new treatment perspectives based on recent high-throughput sequencing data is provided. Moreover, future aspects of individualized treatment based on each patient's individual mutational landscape are discussed.

Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants

PubMed Central

Flores, Raquel; González, Juan R.; Argente, Jesús; Pérez-Jurado, Luis A.

2017-01-01

Obesity is a multifactorial disorder with high heritability (50–75%), which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs), have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in <1/2000 population controls) in 157 Spanish children with non-syndromic early-onset obesity (EOO: body mass index >3 standard deviations above the mean at <3 years of age) using SNP array molecular karyotypes. We then performed case control studies (480 EOO cases/480 non-obese controls) with the validated CNVs and rare sequence variants (RSVs) detected by targeted resequencing of selected CNV genes (n = 14), and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor (GRPR), all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity. PMID:28489853

Novel genes involved in severe early-onset obesity revealed by rare copy number and sequence variants.

PubMed

Serra-Juhé, Clara; Martos-Moreno, Gabriel Á; Bou de Pieri, Francesc; Flores, Raquel; González, Juan R; Rodríguez-Santiago, Benjamín; Argente, Jesús; Pérez-Jurado, Luis A

2017-05-01

Obesity is a multifactorial disorder with high heritability (50-75%), which is probably higher in early-onset and severe cases. Although rare monogenic forms and several genes and regions of susceptibility, including copy number variants (CNVs), have been described, the genetic causes underlying the disease still remain largely unknown. We searched for rare CNVs (>100kb in size, altering genes and present in <1/2000 population controls) in 157 Spanish children with non-syndromic early-onset obesity (EOO: body mass index >3 standard deviations above the mean at <3 years of age) using SNP array molecular karyotypes. We then performed case control studies (480 EOO cases/480 non-obese controls) with the validated CNVs and rare sequence variants (RSVs) detected by targeted resequencing of selected CNV genes (n = 14), and also studied the inheritance patterns in available first-degree relatives. A higher burden of gain-type CNVs was detected in EOO cases versus controls (OR = 1.71, p-value = 0.0358). In addition to a gain of the NPY gene in a familial case with EOO and attention deficit hyperactivity disorder, likely pathogenic CNVs included gains of glutamate receptors (GRIK1, GRM7) and the X-linked gastrin-peptide receptor (GRPR), all inherited from obese parents. Putatively functional RSVs absent in controls were also identified in EOO cases at NPY, GRIK1 and GRPR. A patient with a heterozygous deletion disrupting two contiguous and related genes, SLCO4C1 and SLCO6A1, also had a missense RSV at SLCO4C1 on the other allele, suggestive of a recessive model. The genes identified showed a clear enrichment of shared co-expression partners with known genes strongly related to obesity, reinforcing their role in the pathophysiology of the disease. Our data reveal a higher burden of rare CNVs and RSVs in several related genes in patients with EOO compared to controls, and implicate NPY, GRPR, two glutamate receptors and SLCO4C1 in highly penetrant forms of familial obesity.

Human amyloid β peptide and tau co-expression impairs behavior and causes specific gene expression changes in Caenorhabditis elegans.

PubMed

Wang, Chenyin; Saar, Valeria; Leung, Ka Lai; Chen, Liang; Wong, Garry

2018-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of extracellular amyloid plaques consisting of Amyloid-β peptide (Aβ) aggregates and neurofibrillary tangles formed by aggregation of hyperphosphorylated microtubule-associated protein tau. We generated a novel invertebrate model of AD by crossing Aβ1-42 (strain CL2355) with either pro-aggregating tau (strain BR5270) or anti-aggregating tau (strain BR5271) pan-neuronal expressing transgenic Caenorhabditis elegans. The lifespan and progeny viability of the double transgenic strains were significantly decreased compared with wild type N2 (P<0.0001). In addition, co-expression of these transgenes interfered with neurotransmitter signaling pathways, caused deficits in chemotaxis associative learning, increased protein aggregation visualized by Congo red staining, and increased neuronal loss. Global transcriptomic RNA-seq analysis revealed 248 up- and 805 down-regulated genes in N2 wild type versus Aβ1-42+pro-aggregating tau animals, compared to 293 up- and 295 down-regulated genes in N2 wild type versus Aβ1-42+anti-aggregating tau animals. Gene set enrichment analysis of Aβ1-42+pro-aggregating tau animals uncovered up-regulated annotation clusters UDP-glucuronosyltransferase (5 genes, P<4.2E-4), protein phosphorylation (5 genes, P<2.60E-02), and aging (5 genes, P<8.1E-2) while the down-regulated clusters included nematode cuticle collagen (36 genes, P<1.5E-21). RNA interference of 13 available top up-regulated genes in Aβ1-42+pro-aggregating tau animals revealed that F-box family genes and nep-4 could enhance life span deficits and chemotaxis deficits while Y39G8C.2 (TTBK2) could suppress these behaviors. Comparing the list of regulated genes from C. elegans to the top 60 genes related to human AD confirmed an overlap of 8 genes: patched homolog 1, PTCH1 (ptc-3), the Rab GTPase activating protein, TBC1D16 (tbc-16), the WD repeat and FYVE domain-containing protein 3, WDFY3 (wdfy-3), ADP-ribosylation factor guanine nucleotide exchange factor 2, ARFGEF2 (agef-1), Early B-cell Factor, EBF1 (unc-3), d-amino-acid oxidase, DAO (daao-1), glutamate receptor, metabotropic 1, GRM1 (mgl-2), prolyl 4-hydroxylase subunit alpha 2, P4HA2 (dpy-18 and phy-2). Taken together, our C. elegans double transgenic model provides insight on the fundamental neurobiologic processes underlying human AD and recapitulates selected transcriptomic changes observed in human AD brains. Copyright © 2017 Elsevier Inc. All rights reserved.

Reflection and refraction seismic on the great Ancona landslide

NASA Astrophysics Data System (ADS)

Stucchi, E.; Mazzotti, A.

2003-04-01

The Adriatic coast in Italy is characterised by the occurrence of several landslide bodies, some of which of huge extension. Here we present the results of seismic refraction and reflection studies recently carried out on the Ancona Landslide, which is located immediately westward of the harbour city of Ancona, and interests an area of about 3.5 km^2 with a landslide front of 2 km. The acquired seismic profile crosses the entire landslide body and was performed employing land and marine sources and receivers. Thus it allows the simultaneous acquisition of marine-marine, marine-land, land-marine and land-land data. The most significant acquisition parameters are: nominal maximum source-receiver offset 600 m, receiver group interval 5 m, single airgun and small explosive charges as energy sources, profile length 1.5 km, average reflection coverage on land 4000% and at sea 20000%. Notwithstanding the significant noise contamination due to intense human activities (road, naval and railway traffic) in the area, the data shows good first breaks and reflections which we use for refraction and reflection processing. The refraction study makes use of GRM and other techniques (Lawton) and it leads to a good definition of the shallower landslide bodies but it is not able to depict the deeper decollement surface. It is also very useful in providing a detailed near surface velocity model that is crucial for the determination of accurate static corrections for the reflection data. High quality subsurface images are achieved by applying different processing sequences to the different sets (marine, land or land-marine) of reflection seismic data. The processing steps that turned out as more effective to the achievement of such a quality were the noise removal by means of FX and SVD filtering, the attenuation of the bubble effect for the marine source data, the ground roll attenuation and the computation of accurate statics. The outcomes of the refraction and reflection investigations are greatly useful in evidencing the geometry of the huge landslide body, its maximum depth and the location, close to the sea shore, of the landslide foot. Moreover, together with other kind of data (a grid of high-resolution marine seismic lines acquired 200 m offshore, several marine and land lines acquired by ENI-AGIP for hydrocarbon exploration), these results clearly evidence the general structural setting of the area which likely plays a role in the landslide dynamic. Ongoing works include the estimation of an optimal velocity model by means of refraction/reflection tomography and pre-post stack depth migration.

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: A review of human brain oscillations as effective endophenotypes

PubMed Central

Rangaswamy, Madhavi; Porjesz, Bernice

2010-01-01

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders. PMID:18634760

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: a review of human brain oscillations as effective endophenotypes.

PubMed

Rangaswamy, Madhavi; Porjesz, Bernice

2008-10-15

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders.

Genetic risk prediction and neurobiological understanding of alcoholism

PubMed Central

Levey, D F; Le-Niculescu, H; Frank, J; Ayalew, M; Jain, N; Kirlin, B; Learman, R; Winiger, E; Rodd, Z; Shekhar, A; Schork, N; Kiefe, F; Wodarz, N; Müller-Myhsok, B; Dahmen, N; Nöthen, M; Sherva, R; Farrer, L; Smith, A H; Kranzler, H R; Rietschel, M; Gelernter, J; Niculescu, A B

2014-01-01

We have used a translational Convergent Functional Genomics (CFG) approach to discover genes involved in alcoholism, by gene-level integration of genome-wide association study (GWAS) data from a German alcohol dependence cohort with other genetic and gene expression data, from human and animal model studies, similar to our previous work in bipolar disorder and schizophrenia. A panel of all the nominally significant P-value SNPs in the top candidate genes discovered by CFG  (n=135 genes, 713 SNPs) was used to generate a genetic  risk prediction score (GRPS), which showed a trend towards significance (P=0.053) in separating  alcohol dependent individuals from controls in an independent German test cohort. We then validated and prioritized our top findings from this discovery work, and subsequently tested them in three independent cohorts, from two continents. In order to validate and prioritize the key genes that drive behavior without some of the pleiotropic environmental confounds present in humans, we used a stress-reactive animal model of alcoholism developed by our group, the D-box binding protein (DBP) knockout mouse, consistent with the surfeit of stress theory of addiction proposed by Koob and colleagues. A much smaller panel (n=11 genes, 66 SNPs) of the top CFG-discovered genes for alcoholism, cross-validated and prioritized by this stress-reactive animal model showed better predictive ability in the independent German test cohort (P=0.041). The top CFG scoring gene for alcoholism from the initial discovery step, synuclein alpha (SNCA) remained the top gene after the stress-reactive animal model cross-validation. We also tested this small panel of genes in two other independent test cohorts from the United States, one with alcohol dependence (P=0.00012) and one with alcohol abuse (a less severe form of alcoholism; P=0.0094). SNCA by itself was able to separate alcoholics from controls in the alcohol-dependent cohort (P=0.000013) and the alcohol abuse cohort (P=0.023). So did eight other genes from the panel of 11 genes taken individually, albeit to a lesser extent and/or less broadly across cohorts. SNCA, GRM3 and MBP survived strict Bonferroni correction for multiple comparisons. Taken together, these results suggest that our stress-reactive DBP animal model helped to validate and prioritize from the CFG-discovered genes some of the key behaviorally relevant genes for alcoholism. These genes fall into a series of biological pathways involved in signal transduction, transmission of nerve impulse (including myelination) and cocaine addiction. Overall, our work provides leads towards a better understanding of illness, diagnostics and therapeutics, including treatment with omega-3 fatty acids. We also examined the overlap between the top candidate genes for alcoholism from this work and the top candidate genes for bipolar disorder, schizophrenia, anxiety from previous CFG analyses conducted by us, as well as cross-tested genetic risk predictions. This revealed the significant genetic overlap with other major psychiatric disorder domains, providing a basis for comorbidity and dual diagnosis, and placing alcohol use in the broader context of modulating the mental landscape. PMID:24844177

Cell-surface markers for colon adenoma and adenocarcinoma

PubMed Central

Sewda, Kamini; Coppola, Domenico; Enkemann, Steven; Yue, Binglin; Kim, Jongphil; Lopez, Alexis S.; Wojtkowiak, Jonathan W.; Stark, Valerie E.; Morse, Brian; Shibata, David; Vignesh, Shivakumar; Morse, David L.

2016-01-01

Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC. PMID:26894861

Cell-surface markers for colon adenoma and adenocarcinoma.

PubMed

Sewda, Kamini; Coppola, Domenico; Enkemann, Steven; Yue, Binglin; Kim, Jongphil; Lopez, Alexis S; Wojtkowiak, Jonathan W; Stark, Valerie E; Morse, Brian; Shibata, David; Vignesh, Shivakumar; Morse, David L

2016-04-05

Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC.

Assessment of Gene-by-Sex Interaction Effect on Bone Mineral Density

PubMed Central

Liu, Ching-Ti; Estrada, Karol; Yerges-Armstrong, Laura M.; Amin, Najaf; Evangelou, Evangelos; Li, Guo; Minster, Ryan L.; Carless, Melanie A.; Kammerer, Candace M.; Oei, Ling; Zhou, Yanhua; Alonso, Nerea; Dailiana, Zoe; Eriksson, Joel; García-Giralt, Natalia; Giroux, Sylvie; Husted, Lise Bjerre; Khusainova, Rita I.; Koromila, Theodora; Kung, Annie WaiChee; Lewis, Joshua R.; Masi, Laura; Mencej-Bedrac, Simona; Nogues, Xavier; Patel, Millan S.; Prezelj, Janez; Richards, J Brent; Sham, Pak Chung; Spector, Timothy; Vandenput, Liesbeth; Xiao, Su-Mei; Zheng, Hou-Feng; Zhu, Kun; Balcells, Susana; Brandi, Maria Luisa; Frost, Morten; Goltzman, David; González-Macías, Jesús; Karlsson, Magnus; Khusnutdinova, Elza K.; Kollia, Panagoula; Langdahl, Bente Lomholt; Ljunggren, Östen; Lorentzon, Mattias; Marc, Janja; Mellström, Dan; Ohlsson, Claes; Olmos, José M.; Ralston, Stuart H.; Riancho, José A.; Rousseau, François; Urreizti, Roser; Van Hul, Wim; Zarrabeitia, María T.; Castano-Betancourt, Martha; Demissie, Serkalem; Grundberg, Elin; Herrera, Lizbeth; Kwan, Tony; Medina-Gómez, Carolina; Pastinen, Tomi; Sigurdsson, Gunnar; Thorleifsson, Gudmar; vanMeurs, Joyce B.J.; Blangero, John; Hofman, Albert; Liu, Yongmei; Mitchell, Braxton D.; O’Connell, Jeffrey R.; Oostra, Ben A.; Rotter, Jerome I; Stefansson, Kari; Streeten, Elizabeth A.; Styrkarsdottir, Unnur; Thorsteinsdottir, Unnur; Tylavsky, Frances A.; Uitterlinden, Andre; Cauley, Jane A.; Harris, Tamara B.; Ioannidis, John P.A.; Psaty, Bruce M.; Robbins, John A; Zillikens, M. Carola; vanDuijn, Cornelia M.; Prince, Richard L.; Karasik, David; Rivadeneira, Fernando; Kiel, Douglas P.; Cupples, L. Adrienne; Hsu, Yi-Hsiang

2012-01-01

Background Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed eQTL analysis and bioinformatics network analysis. Methods We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS-) and femoral neck (FN-) BMD, in 25,353 individuals from eight cohorts. In a second stage, we followed up the 12 top SNPs (P<1×10−5) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. Results We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 & p-value = 3.0×10−5; female effect = −0.007 & p-value=3.3×10−2) and eleven suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (P<5×10−8) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Conclusion Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found influencing BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. PMID:22692763

G-Protein Genomic Association With Normal Variation in Gray Matter Density

PubMed Central

Chen, Jiayu; Calhoun, Vince D.; Arias-Vasquez, Alejandro; Zwiers, Marcel P.; van Hulzen, Kimm; Fernández, Guillén; Fisher, Simon E.; Franke, Barbara; Turner, Jessica A.; Liu, Jingyu

2017-01-01

While detecting genetic variations underlying brain structures helps reveal mechanisms of neural disorders, high data dimensionality poses a major challenge for imaging genomic association studies. In this work, we present the application of a recently proposed approach, parallel independent component analysis with reference (pICA-R), to investigate genomic factors potentially regulating gray matter variation in a healthy population. This approach simultaneously assesses many variables for an aggregate effect and helps to elicit particular features in the data. We applied pICA-R to analyze gray matter density (GMD) images (274,131 voxels) in conjunction with single nucleotide polymorphism (SNP) data (666,019 markers) collected from 1,256 healthy individuals of the Brain Imaging Genetics (BIG) study. Guided by a genetic reference derived from the gene GNA14, pICA-R identified a significant SNP-GMD association (r = −0.16, P = 2.34 × 10−8), implying that subjects with specific genotypes have lower localized GMD. The identified components were then projected to an independent dataset from the Mind Clinical Imaging Consortium (MCIC) including 89 healthy individuals, and the obtained loadings again yielded a significant SNP-GMD association (r = −0.25, P = 0.02). The imaging component reflected GMD variations in frontal, precuneus, and cingulate regions. The SNP component was enriched in genes with neuronal functions, including synaptic plasticity, axon guidance, molecular signal transduction via PKA and CREB, highlighting the GRM1, PRKCH, GNA12, and CAMK2B genes. Collectively, our findings suggest that GNA12 and GNA14 play a key role in the genetic architecture underlying normal GMD variation in frontal and parietal regions. PMID:26248772

Pharmacogenetics of new analgesics

PubMed Central

Lötsch, Jörn; Geisslinger, Gerd

2011-01-01

Patient phenotypes in pharmacological pain treatment varies between individuals, which could be partly assigned to their genotypes regarding the targets of classical analgesics (OPRM1, PTGS2) or associated signalling pathways (KCNJ6). Translational and genetic research have identified new targets, for which new analgesics are being developed. This addresses voltage-gated sodium, calcium and potassium channels, for which SCN9A, CACNA1B, KCNQ2 and KCNQ3, respectively, are primary gene candidates because they code for the subunits of the respective channels targeted by analgesics currently in clinical development. Mutations in voltage gated transient receptor potential (TRPV) channels are known from genetic pain research and may modulate the effects of analgesics under development targeting TRPV1 or TRPV3. To this add ligand-gated ion channels including nicotinic acetylcholine receptors, ionotropic glutamate-gated receptors and ATP-gated purinergic P2X receptors with most important subunits coded by CHRNA4, GRIN2B and P2RX7. Among G protein coupled receptors, δ-opioid receptors (coded by OPRD1), cannabinoid receptors (CNR1 and CNR2), metabotropic glutamate receptors (mGluR5 coded by GRM5), bradykinin B1 (BDKRB1) and 5-HT1A (HTR1A) receptors are targeted by new analgesic substances. Finally, nerve growth factor (NGFB), its tyrosine kinase receptor (NTRK1) and the fatty acid amide hydrolase (FAAH) have become targets of interest. For most of these genes, functional variants have been associated with neuro-psychiatric disorders and not yet with analgesia. However, research on the genetic modulation of pain has already identified variants in these genes, relative to pain, which may facilitate the pharmacogenetic assessments of new analgesics. The increased number of candidate pharmacogenetic modulators of analgesic actions may open opportunities for the broader clinical implementation of genotyping information. PMID:20942817

Histone methylation at gene promoters is associated with developmental regulation and region-specific expression of ionotropic and metabotropic glutamate receptors in human brain.

PubMed

Stadler, Florian; Kolb, Gabriele; Rubusch, Lothar; Baker, Stephen P; Jones, Edward G; Akbarian, Schahram

2005-07-01

Glutamatergic signaling is regulated, in part, through differential expression of NMDA and AMPA/KA channel subunits and G protein-coupled metabotropic receptors. In human brain, region-specific expression patterns of glutamate receptor genes are maintained over the course of decades, suggesting a role for molecular mechanisms involved in long-term regulation of transcription, including methylation of lysine residues at histone N-terminal tails. Using a native chromatin immunoprecipitation assay, we studied histone methylation marks at proximal promoters of 16 ionotropic and metabotropic glutamate receptor genes (GRIN1,2A-D; GRIA1,3,4; GRIK2,4,5; GRM1,3,4,6,7 ) in cerebellar cortex collected across a wide age range from midgestation to 90 years old. Levels of di- and trimethylated histone H3-lysine 4, which are associated with open chromatin and transcription, showed significant differences between promoters and a robust correlation with corresponding mRNA levels in immature and mature cerebellar cortex. In contrast, levels of trimethylated H3-lysine 27 and H4-lysine 20, two histone modifications defining silenced or condensed chromatin, did not correlate with transcription but were up-regulated overall in adult cerebellum. Furthermore, differential gene expression patterns in prefrontal and cerebellar cortex were reflected by similar differences in H3-lysine 4 methylation at promoters. Together, these findings suggest that histone lysine methylation at gene promoters is involved in developmental regulation and maintenance of region-specific expression patterns of ionotropic and metabotropic glutamate receptors. The association of a specific epigenetic mark, H3-(methyl)-lysine 4, with the molecular architecture of glutamatergic signaling in human brain has potential implications for schizophrenia and other disorders with altered glutamate receptor function.

Autoantibodies in melanoma-associated retinopathy target TRPM1 cation channels of retinal ON bipolar cells.

PubMed

Dhingra, Anuradha; Fina, Marie E; Neinstein, Adam; Ramsey, David J; Xu, Ying; Fishman, Gerald A; Alexander, Kenneth R; Qian, Haohua; Peachey, Neal S; Gregg, Ronald G; Vardi, Noga

2011-03-16

Melanoma-associated retinopathy (MAR) is characterized by night blindness, photopsias, and a selective reduction of the electroretinogram b-wave. In certain cases, the serum contains autoantibodies that react with ON bipolar cells, but the target of these autoantibodies has not been identified. Here we show that the primary target of autoantibodies produced in MAR patients with reduced b-wave is the TRPM1 cation channel, the newly identified transduction channel in ON bipolar cells. Sera from two well characterized MAR patients, but not from a control subject, stained human embryonic kidney cells transfected with the TRPM1 gene, and Western blots probed with these MAR sera showed the expected band size (∼180 kDa). Staining of mouse and primate retina with MAR sera revealed immunoreactivity in all types of ON bipolar cells. Similar to staining for TRPM1, staining with the MAR sera was strong in dendritic tips and somas and was weak or absent in axon terminals. This staining colocalized with GFP in Grm6-GFP transgenic mice, where GFP is expressed in all and only ON bipolar cells, and also colocalized with Gα(o), a marker for all types of ON bipolar cells. The staining in ON bipolar cells was confirmed to be specific to TRPM1 because MAR serum did not stain these cells in a Trpm1(-/-) mouse. Evidence suggests that the recognized epitope is likely intracellular, and the sera can be internalized by retinal cells. We conclude that the vision of at least some patients with MAR is compromised due to autoantibody-mediated inactivation of the TRPM1 channel.

A Discovery Resource of Rare Copy Number Variations in Individuals with Autism Spectrum Disorder

PubMed Central

Prasad, Aparna; Merico, Daniele; Thiruvahindrapuram, Bhooma; Wei, John; Lionel, Anath C.; Sato, Daisuke; Rickaby, Jessica; Lu, Chao; Szatmari, Peter; Roberts, Wendy; Fernandez, Bridget A.; Marshall, Christian R.; Hatchwell, Eli; Eis, Peggy S.; Scherer, Stephen W.

2012-01-01

The identification of rare inherited and de novo copy number variations (CNVs) in human subjects has proven a productive approach to highlight risk genes for autism spectrum disorder (ASD). A variety of microarrays are available to detect CNVs, including single-nucleotide polymorphism (SNP) arrays and comparative genomic hybridization (CGH) arrays. Here, we examine a cohort of 696 unrelated ASD cases using a high-resolution one-million feature CGH microarray, the majority of which were previously genotyped with SNP arrays. Our objective was to discover new CNVs in ASD cases that were not detected by SNP microarray analysis and to delineate novel ASD risk loci via combined analysis of CGH and SNP array data sets on the ASD cohort and CGH data on an additional 1000 control samples. Of the 615 ASD cases analyzed on both SNP and CGH arrays, we found that 13,572 of 21,346 (64%) of the CNVs were exclusively detected by the CGH array. Several of the CGH-specific CNVs are rare in population frequency and impact previously reported ASD genes (e.g., NRXN1, GRM8, DPYD), as well as novel ASD candidate genes (e.g., CIB2, DAPP1, SAE1), and all were inherited except for a de novo CNV in the GPHN gene. A functional enrichment test of gene-sets in ASD cases over controls revealed nucleotide metabolism as a potential novel pathway involved in ASD, which includes several candidate genes for follow-up (e.g., DPYD, UPB1, UPP1, TYMP). Finally, this extensively phenotyped and genotyped ASD clinical cohort serves as an invaluable resource for the next step of genome sequencing for complete genetic variation detection. PMID:23275889

Mutation screening of the LRIT3, CABP4, and GPR179 genes in Chinese patients with Schubert-Bornschein congenital stationary night blindness.

PubMed

Dan, Handong; Song, Xiusheng; Li, Jiazhang; Xing, Yiqiao; Li, Tuo

2017-01-01

Schubert-Bornschein congenital stationary night blindness (CSNB) is a rare retinal disorder that may lead to severe visual impairment in patients. The aim of this study was to detect mutations in the LRIT3, CABP4, and GPR179 genes in Chinese patients with Schubert-Bornschein CSNB. A cohort of eight unrelated Chinese probands with Schubert-Bornschein CSNB was recruited for this study. Six of these probands were assessed in our previous study, in which we screened the NYX, CACNA1F, GRM6, and TRPM1 genes for mutations but identified none. The other two patients were newly recruited and had not been screened for mutations in these genes. Genomic DNA and clinical data were collected from the eight recruited families. Variants of the LRIT3, CABP4, and GPR179 genes were identified by Sanger sequencing. All of the identified variants were also assessed in 192 control individuals. In this study, a novel compound heterozygous mutation, c.[1A>G]; [608G>T] (p.[0?]; p.[W203L]), was identified in the LRIT3 gene of a proband. These two mutations were not present in any of the 192 normal control individuals or in the other patients, and the missense mutation c.608G>T was predicted to be pathogenic. No mutations were identified in the CABP4 or GPR179 gene. These results expand the mutational spectrum of LRIT3, thus potentially enriching our understanding of the molecular basis of complete CSNB. Additional genes that potentially contribute to incomplete CSNB remain to be identified in future studies.

Analysis of shared homozygosity regions in Saudi siblings with attention deficit hyperactivity disorder

PubMed Central

Al Yemni, Eman A.A.; Alnaemi, Faten M.; Abebe, Dejene; Al-Abdulaziz, Basma S.; Al Mubarak, Bashayer R.; Ghaziuddin, Mohammad; Al Tassan, Nada A.

2017-01-01

Aim Genetic and clinical complexities are common features of most psychiatric illnesses that pose a major obstacle in risk-gene identification. Attention deficit hyperactivity disorder (ADHD) is the most prevalent child-onset psychiatric illness, with high heritability. Over the past decade, numerous genetic studies utilizing various approaches, such as genome-wide association, candidate-gene association, and linkage analysis, have identified a multitude of candidate loci/genes. However, such studies have yielded diverse findings that are rarely reproduced, indicating that other genetic determinants have not been discovered yet. In this study, we carried out sib-pair analysis on seven multiplex families with ADHD from Saudi Arabia. We aimed to identify the candidate chromosomal regions and genes linked to the disease. Patients and methods A total of 41 individuals from multiplex families were analyzed for shared regions of homozygosity. Genes within these regions were prioritized according to their potential relevance to ADHD. Results We identified multiple genomic regions spanning different chromosomes to be shared among affected members of each family; these included chromosomes 3, 5, 6, 7, 8, 9, 10, 13, 17, and 18. We also found specific regions on chromosomes 8 and 17 to be shared between affected individuals from more than one family. Among the genes present in the regions reported here were involved in neurotransmission (GRM3, SIGMAR1, CHAT, and SLC18A3) and members of the HLA gene family (HLA-A, HLA-DPA1, and MICC). Conclusion The candidate regions identified in this study highlight the genetic diversity of ADHD. Upon further investigation, these loci may reveal candidate genes that enclose variants associated with ADHD. Although most ADHD studies were conducted in other populations, our study provides insight from an understudied, ethnically interesting population. PMID:28452824

Analysis of shared homozygosity regions in Saudi siblings with attention deficit hyperactivity disorder.

PubMed

Shinwari, Jameela M A; Al Yemni, Eman A A; Alnaemi, Faten M; Abebe, Dejene; Al-Abdulaziz, Basma S; Al Mubarak, Bashayer R; Ghaziuddin, Mohammad; Al Tassan, Nada A

2017-08-01

Genetic and clinical complexities are common features of most psychiatric illnesses that pose a major obstacle in risk-gene identification. Attention deficit hyperactivity disorder (ADHD) is the most prevalent child-onset psychiatric illness, with high heritability. Over the past decade, numerous genetic studies utilizing various approaches, such as genome-wide association, candidate-gene association, and linkage analysis, have identified a multitude of candidate loci/genes. However, such studies have yielded diverse findings that are rarely reproduced, indicating that other genetic determinants have not been discovered yet. In this study, we carried out sib-pair analysis on seven multiplex families with ADHD from Saudi Arabia. We aimed to identify the candidate chromosomal regions and genes linked to the disease. A total of 41 individuals from multiplex families were analyzed for shared regions of homozygosity. Genes within these regions were prioritized according to their potential relevance to ADHD. We identified multiple genomic regions spanning different chromosomes to be shared among affected members of each family; these included chromosomes 3, 5, 6, 7, 8, 9, 10, 13, 17, and 18. We also found specific regions on chromosomes 8 and 17 to be shared between affected individuals from more than one family. Among the genes present in the regions reported here were involved in neurotransmission (GRM3, SIGMAR1, CHAT, and SLC18A3) and members of the HLA gene family (HLA-A, HLA-DPA1, and MICC). The candidate regions identified in this study highlight the genetic diversity of ADHD. Upon further investigation, these loci may reveal candidate genes that enclose variants associated with ADHD. Although most ADHD studies were conducted in other populations, our study provides insight from an understudied, ethnically interesting population.

Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses

PubMed Central

Kim, Yoonhee; Zhang, Yinhua; Pang, Kaifang; Kang, Hyojin; Park, Heejoo; Lee, Yeunkum; Lee, Bokyoung; Lee, Heon-Jeong; Kim, Won-Ki; Geum, Dongho

2016-01-01

Bipolar disorder (BD), characterized by recurrent mood swings between depression and mania, is a highly heritable and devastating mental illness with poorly defined pathophysiology. Recent genome-wide molecular genetic studies have identified several protein-coding genes and microRNAs (miRNAs) significantly associated with BD. Notably, some of the proteins expressed from BD-associated genes function in neuronal synapses, suggesting that abnormalities in synaptic function could be one of the key pathogenic mechanisms of BD. In contrast, however, the role of BD-associated miRNAs in disease pathogenesis remains largely unknown, mainly because of a lack of understanding about their target mRNAs and pathways in neurons. To address this problem, in this study, we focused on a recently identified BD-associated but uncharacterized miRNA, miR-1908-5p. We identified and validated its novel target genes including DLGAP4, GRIN1, STX1A, CLSTN1 and GRM4, which all function in neuronal glutamatergic synapses. Moreover, bioinformatic analyses of human brain expression profiles revealed that the expression levels of miR-1908-5p and its synaptic target genes show an inverse-correlation in many brain regions. In our preliminary experiments, the expression of miR-1908-5p was increased after chronic treatment with valproate but not lithium in control human neural progenitor cells. In contrast, it was decreased by valproate in neural progenitor cells derived from dermal fibroblasts of a BD subject. Together, our results provide new insights into the potential role of miR-1908-5p in the pathogenesis of BD and also propose a hypothesis that neuronal synapses could be a key converging pathway of some BD-associated protein-coding genes and miRNAs. PMID:28035180

Genetic risk prediction and neurobiological understanding of alcoholism.

PubMed

Levey, D F; Le-Niculescu, H; Frank, J; Ayalew, M; Jain, N; Kirlin, B; Learman, R; Winiger, E; Rodd, Z; Shekhar, A; Schork, N; Kiefer, F; Kiefe, F; Wodarz, N; Müller-Myhsok, B; Dahmen, N; Nöthen, M; Sherva, R; Farrer, L; Smith, A H; Kranzler, H R; Rietschel, M; Gelernter, J; Niculescu, A B

2014-05-20

We have used a translational Convergent Functional Genomics (CFG) approach to discover genes involved in alcoholism, by gene-level integration of genome-wide association study (GWAS) data from a German alcohol dependence cohort with other genetic and gene expression data, from human and animal model studies, similar to our previous work in bipolar disorder and schizophrenia. A panel of all the nominally significant P-value SNPs in the top candidate genes discovered by CFG  (n=135 genes, 713 SNPs) was used to generate a genetic  risk prediction score (GRPS), which showed a trend towards significance (P=0.053) in separating  alcohol dependent individuals from controls in an independent German test cohort. We then validated and prioritized our top findings from this discovery work, and subsequently tested them in three independent cohorts, from two continents. A panel of all the nominally significant P-value single-nucleotide length polymorphisms (SNPs) in the top candidate genes discovered by CFG (n=135 genes, 713 SNPs) were used to generate a Genetic Risk Prediction Score (GRPS), which showed a trend towards significance (P=0.053) in separating alcohol-dependent individuals from controls in an independent German test cohort. In order to validate and prioritize the key genes that drive behavior without some of the pleiotropic environmental confounds present in humans, we used a stress-reactive animal model of alcoholism developed by our group, the D-box binding protein (DBP) knockout mouse, consistent with the surfeit of stress theory of addiction proposed by Koob and colleagues. A much smaller panel (n=11 genes, 66 SNPs) of the top CFG-discovered genes for alcoholism, cross-validated and prioritized by this stress-reactive animal model showed better predictive ability in the independent German test cohort (P=0.041). The top CFG scoring gene for alcoholism from the initial discovery step, synuclein alpha (SNCA) remained the top gene after the stress-reactive animal model cross-validation. We also tested this small panel of genes in two other independent test cohorts from the United States, one with alcohol dependence (P=0.00012) and one with alcohol abuse (a less severe form of alcoholism; P=0.0094). SNCA by itself was able to separate alcoholics from controls in the alcohol-dependent cohort (P=0.000013) and the alcohol abuse cohort (P=0.023). So did eight other genes from the panel of 11 genes taken individually, albeit to a lesser extent and/or less broadly across cohorts. SNCA, GRM3 and MBP survived strict Bonferroni correction for multiple comparisons. Taken together, these results suggest that our stress-reactive DBP animal model helped to validate and prioritize from the CFG-discovered genes some of the key behaviorally relevant genes for alcoholism. These genes fall into a series of biological pathways involved in signal transduction, transmission of nerve impulse (including myelination) and cocaine addiction. Overall, our work provides leads towards a better understanding of illness, diagnostics and therapeutics, including treatment with omega-3 fatty acids. We also examined the overlap between the top candidate genes for alcoholism from this work and the top candidate genes for bipolar disorder, schizophrenia, anxiety from previous CFG analyses conducted by us, as well as cross-tested genetic risk predictions. This revealed the significant genetic overlap with other major psychiatric disorder domains, providing a basis for comorbidity and dual diagnosis, and placing alcohol use in the broader context of modulating the mental landscape.

Multicolour CCD surface photometry for E and S0 galaxies in 10 clusters

NASA Astrophysics Data System (ADS)

Jorgensen, Inger; Franx, Marijn; Kjaergaard, Per

1995-04-01

CCD surface photometry for 232 E and S0 galaxies is presented. The galaxies are observed in Gunn r and Johnson B, or Gunn r and g. For 48 of the galaxies surface photometry in Johnson U is also presented. Aperture magnitudes in Gunn nu are derived for half of the galaxies. Galaxies in the following clusters have been observed: Abell 194, Abell 539, Abell 3381, Abell 3574, Abell S639, Abell S753, HydraI (Abell 1060), DC2345-28, Doradus and Grm15. The data are part of our ongoing study of the large-scale motions in the Universe and the physical background for the fundamental plane. We use a full model fitting technique for analysing the CCD images. This gives radial profiles of local surface brightness, colour, ellipticity and position angle. The residuals relative to the elliptical isophotes are described quantitatively by Fourier expansions. Effective radius, mean surface brightness and total magnitude are derived by fitting a de Vaucouleurs r^¼ growth curve. We have derived a characteristic radius r_n similar to the diameter D_n introduced by Dressler et al. The derivation of the effective parameters and of r_n takes the seeing into account. We confirm the results by Saglia et al. that the effects of the seeing can be substantial. Seeing-corrected values of the effective parameters and r_n are also presented for 147 E and S0 galaxies in the Coma cluster. Colours, colour gradients and geometrical parameters are derived. The photometry is internally consistent within 0.016 mag. Comparison with the photoelectric aperture photometry from Burstein et al. shows a mean offset of 0.010 mag with an rms scatter of 0.034 mag. The global photometric parameters are compared with data from Faber et al., Lucey et al. and Lucey & Carter. These comparisons imply that the typical rms errors are as follows - log r_n:+/-0.015 log r_e:+/-0.045 m_T:+/-0.09 mag; _e:+/-0.16 mag. The rms error on the combination log r_e-0.35_e which enters the fundamental plane is +/-0.020. Also, comparisons with data from Saglia et al. are presented. The accuracy of the absolute photometry, as well as the derived parameters, makes the data suitable for our investigations of the fundamental plane and of the large-scale motions in the Universe.

Huntington's Disease and its therapeutic target genes: a global functional profile based on the HD Research Crossroads database

PubMed Central

2012-01-01

Background Huntington’s disease (HD) is a fatal progressive neurodegenerative disorder caused by the expansion of the polyglutamine repeat region in the huntingtin gene. Although the disease is triggered by the mutation of a single gene, intensive research has linked numerous other genes to its pathogenesis. To obtain a systematic overview of these genes, which may serve as therapeutic targets, CHDI Foundation has recently established the HD Research Crossroads database. With currently over 800 cataloged genes, this web-based resource constitutes the most extensive curation of genes relevant to HD. It provides us with an unprecedented opportunity to survey molecular mechanisms involved in HD in a holistic manner. Methods To gain a synoptic view of therapeutic targets for HD, we have carried out a variety of bioinformatical and statistical analyses to scrutinize the functional association of genes curated in the HD Research Crossroads database. In particular, enrichment analyses were performed with respect to Gene Ontology categories, KEGG signaling pathways, and Pfam protein families. For selected processes, we also analyzed differential expression, using published microarray data. Additionally, we generated a candidate set of novel genetic modifiers of HD by combining information from the HD Research Crossroads database with previous genome-wide linkage studies. Results Our analyses led to a comprehensive identification of molecular mechanisms associated with HD. Remarkably, we not only recovered processes and pathways, which have frequently been linked to HD (such as cytotoxicity, apoptosis, and calcium signaling), but also found strong indications for other potentially disease-relevant mechanisms that have been less intensively studied in the context of HD (such as the cell cycle and RNA splicing, as well as Wnt and ErbB signaling). For follow-up studies, we provide a regularly updated compendium of molecular mechanism, that are associated with HD, at http://hdtt.sysbiolab.eu Additionally, we derived a candidate set of 24 novel genetic modifiers, including histone deacetylase 3 (HDAC3), metabotropic glutamate receptor 1 (GRM1), CDK5 regulatory subunit 2 (CDK5R2), and coactivator 1ß of the peroxisome proliferator-activated receptor gamma (PPARGC1B). Conclusions The results of our study give us an intriguing picture of the molecular complexity of HD. Our analyses can be seen as a first step towards a comprehensive list of biological processes, molecular functions, and pathways involved in HD, and may provide a basis for the development of more holistic disease models and new therapeutics. PMID:22741533

Regional Earthquake Shaking and Loss Estimation

NASA Astrophysics Data System (ADS)

Sesetyan, K.; Demircioglu, M. B.; Zulfikar, C.; Durukal, E.; Erdik, M.

2009-04-01

This study, conducted under the JRA-3 component of the EU NERIES Project, develops a methodology and software (ELER) for the rapid estimation of earthquake shaking and losses in the Euro-Mediterranean region. This multi-level methodology developed together with researchers from Imperial College, NORSAR and ETH-Zurich is capable of incorporating regional variability and sources of uncertainty stemming from ground motion predictions, fault finiteness, site modifications, inventory of physical and social elements subjected to earthquake hazard and the associated vulnerability relationships. GRM Risk Management, Inc. of Istanbul serves as sub-contractor tor the coding of the ELER software. The methodology encompasses the following general steps: 1. Finding of the most likely location of the source of the earthquake using regional seismotectonic data base and basic source parameters, and if and when possible, by the estimation of fault rupture parameters from rapid inversion of data from on-line stations. 2. Estimation of the spatial distribution of selected ground motion parameters through region specific ground motion attenuation relationships and using shear wave velocity distributions.(Shake Mapping) 4. Incorporation of strong ground motion and other empirical macroseismic data for the improvement of Shake Map 5. Estimation of the losses (damage, casualty and economic) at different levels of sophistication (0, 1 and 2) that commensurate with the availability of inventory of human built environment (Loss Mapping) Both Level 0 (similar to PAGER system of USGS) and Level 1 analyses of the ELER routine are based on obtaining intensity distributions analytically and estimating total number of casualties and their geographic distribution either using regionally adjusted intensity-casualty or magnitude-casualty correlations (Level 0) of using regional building inventory data bases (Level 1). Level 0 analysis is similar to the PAGER system being developed by USGS. For given basis source parameters the intensity distributions can be computed using: a)Regional intensity attenuation relationships, b)Intensity correlations with attenuation relationship based PGV, PGA, and Spectral Amplitudes and, c)Intensity correlations with synthetic Fourier Amplitude Spectrum. In Level 1 analysis EMS98 based building vulnerability relationships are used for regional estimates of building damage and the casualty distributions. Results obtained from pilot applications of the Level 0 and Level 1 analysis modes of the ELER software to the 1999 M 7.4 Kocaeli, 1995 M 6.1 Dinar, and 2007 M 5.4 Bingol earthquakes in terms of ground shaking and losses are presented and comparisons with the observed losses are made. The regional earthquake shaking and loss information is intented for dissemination in a timely manner to related agencies for the planning and coordination of the post-earthquake emergency response. However the same software can also be used for scenario earthquake loss estimation and related Monte-Carlo type simulations.

Non-canonical Smads phosphorylation induced by the glutamate release inhibitor, riluzole, through GSK3 activation in melanoma.

PubMed

Abushahba, Walid; Olabisi, Oyenike O; Jeong, Byeong-Seon; Boregowda, Rajeev K; Wen, Yu; Liu, Fang; Goydos, James S; Lasfar, Ahmed; Cohen-Solal, Karine A

2012-01-01

Riluzole, an inhibitor of glutamate release, has shown the ability to inhibit melanoma cell xenograft growth. A phase 0 clinical trial of riluzole as a single agent in patients with melanoma resulted in involution of tumors associated with inhibition of both the mitogen-activated protein kinase (MAPK) and phophoinositide-3-kinase/AKT (PI3K/AKT) pathways in 34% of patients. In the present study, we demonstrate that riluzole inhibits AKT-mediated glycogen synthase kinase 3 (GSK3) phosphorylation in melanoma cell lines. Because we have demonstrated that GSK3 is involved in the phosphorylation of two downstream effectors of transforming growth factor beta (TGFβ), Smad2 and Smad3, at their linker domain, our aim was to determine whether riluzole could induce GSK3β-mediated linker phosphorylation of Smad2 and Smad3. We present evidence that riluzole increases Smad2 and Smad3 linker phosphorylation at the cluster of serines 245/250/255 and serine 204 respectively. Using GSK3 inhibitors and siRNA knock-down, we demonstrate that the mechanism of riluzole-induced Smad phosphorylation involved GSK3β. In addition, GSK3β could phosphorylate the same linker sites in vitro. The riluzole-induced Smad linker phosphorylation is mechanistically different from the Smad linker phosphorylation induced by TGFβ. We also demonstrate that riluzole-induced Smad linker phosphorylation is independent of the expression of the metabotropic glutamate receptor 1 (GRM1), which is one of the glutamate receptors whose involvement in human melanoma has been documented. We further show that riluzole upregulates the expression of INHBB and PLAU, two genes associated with the TGFβ signaling pathway. The non-canonical increase in Smad linker phosphorylation induced by riluzole could contribute to the modulation of the pro-oncogenic functions of Smads in late stage melanomas.

Non-Canonical Smads Phosphorylation Induced by the Glutamate Release Inhibitor, Riluzole, through GSK3 Activation in Melanoma

PubMed Central

Jeong, Byeong-Seon; Boregowda, Rajeev K.; Wen, Yu; Liu, Fang; Goydos, James S.; Lasfar, Ahmed; Cohen-Solal, Karine A.

2012-01-01

Riluzole, an inhibitor of glutamate release, has shown the ability to inhibit melanoma cell xenograft growth. A phase 0 clinical trial of riluzole as a single agent in patients with melanoma resulted in involution of tumors associated with inhibition of both the mitogen-activated protein kinase (MAPK) and phophoinositide-3-kinase/AKT (PI3K/AKT) pathways in 34% of patients. In the present study, we demonstrate that riluzole inhibits AKT-mediated glycogen synthase kinase 3 (GSK3) phosphorylation in melanoma cell lines. Because we have demonstrated that GSK3 is involved in the phosphorylation of two downstream effectors of transforming growth factor beta (TGFβ), Smad2 and Smad3, at their linker domain, our aim was to determine whether riluzole could induce GSK3β-mediated linker phosphorylation of Smad2 and Smad3. We present evidence that riluzole increases Smad2 and Smad3 linker phosphorylation at the cluster of serines 245/250/255 and serine 204 respectively. Using GSK3 inhibitors and siRNA knock-down, we demonstrate that the mechanism of riluzole-induced Smad phosphorylation involved GSK3β. In addition, GSK3β could phosphorylate the same linker sites in vitro. The riluzole-induced Smad linker phosphorylation is mechanistically different from the Smad linker phosphorylation induced by TGFβ. We also demonstrate that riluzole-induced Smad linker phosphorylation is independent of the expression of the metabotropic glutamate receptor 1 (GRM1), which is one of the glutamate receptors whose involvement in human melanoma has been documented. We further show that riluzole upregulates the expression of INHBB and PLAU, two genes associated with the TGFβ signaling pathway. The non-canonical increase in Smad linker phosphorylation induced by riluzole could contribute to the modulation of the pro-oncogenic functions of Smads in late stage melanomas. PMID:23077590

Reconstruction of an Integrated Genome-Scale Co-Expression Network Reveals Key Modules Involved in Lung Adenocarcinoma

PubMed Central

Hosseini Ashtiani, Saman; Moeini, Ali; Nowzari-Dalini, Abbas; Masoudi-Nejad, Ali

2013-01-01

Our goal of this study was to reconstruct a “genome-scale co-expression network” and find important modules in lung adenocarcinoma so that we could identify the genes involved in lung adenocarcinoma. We integrated gene mutation, GWAS, CGH, array-CGH and SNP array data in order to identify important genes and loci in genome-scale. Afterwards, on the basis of the identified genes a co-expression network was reconstructed from the co-expression data. The reconstructed network was named “genome-scale co-expression network”. As the next step, 23 key modules were disclosed through clustering. In this study a number of genes have been identified for the first time to be implicated in lung adenocarcinoma by analyzing the modules. The genes EGFR, PIK3CA, TAF15, XIAP, VAPB, Appl1, Rab5a, ARF4, CLPTM1L, SP4, ZNF124, LPP, FOXP1, SOX18, MSX2, NFE2L2, SMARCC1, TRA2B, CBX3, PRPF6, ATP6V1C1, MYBBP1A, MACF1, GRM2, TBXA2R, PRKAR2A, PTK2, PGF and MYO10 are among the genes that belong to modules 1 and 22. All these genes, being implicated in at least one of the phenomena, namely cell survival, proliferation and metastasis, have an over-expression pattern similar to that of EGFR. In few modules, the genes such as CCNA2 (Cyclin A2), CCNB2 (Cyclin B2), CDK1, CDK5, CDC27, CDCA5, CDCA8, ASPM, BUB1, KIF15, KIF2C, NEK2, NUSAP1, PRC1, SMC4, SYCE2, TFDP1, CDC42 and ARHGEF9 are present that play a crucial role in cell cycle progression. In addition to the mentioned genes, there are some other genes (i.e. DLGAP5, BIRC5, PSMD2, Src, TTK, SENP2, PSMD2, DOK2, FUS and etc.) in the modules. PMID:23874428

Reconstruction of an integrated genome-scale co-expression network reveals key modules involved in lung adenocarcinoma.

PubMed

Bidkhori, Gholamreza; Narimani, Zahra; Hosseini Ashtiani, Saman; Moeini, Ali; Nowzari-Dalini, Abbas; Masoudi-Nejad, Ali

2013-01-01

Our goal of this study was to reconstruct a "genome-scale co-expression network" and find important modules in lung adenocarcinoma so that we could identify the genes involved in lung adenocarcinoma. We integrated gene mutation, GWAS, CGH, array-CGH and SNP array data in order to identify important genes and loci in genome-scale. Afterwards, on the basis of the identified genes a co-expression network was reconstructed from the co-expression data. The reconstructed network was named "genome-scale co-expression network". As the next step, 23 key modules were disclosed through clustering. In this study a number of genes have been identified for the first time to be implicated in lung adenocarcinoma by analyzing the modules. The genes EGFR, PIK3CA, TAF15, XIAP, VAPB, Appl1, Rab5a, ARF4, CLPTM1L, SP4, ZNF124, LPP, FOXP1, SOX18, MSX2, NFE2L2, SMARCC1, TRA2B, CBX3, PRPF6, ATP6V1C1, MYBBP1A, MACF1, GRM2, TBXA2R, PRKAR2A, PTK2, PGF and MYO10 are among the genes that belong to modules 1 and 22. All these genes, being implicated in at least one of the phenomena, namely cell survival, proliferation and metastasis, have an over-expression pattern similar to that of EGFR. In few modules, the genes such as CCNA2 (Cyclin A2), CCNB2 (Cyclin B2), CDK1, CDK5, CDC27, CDCA5, CDCA8, ASPM, BUB1, KIF15, KIF2C, NEK2, NUSAP1, PRC1, SMC4, SYCE2, TFDP1, CDC42 and ARHGEF9 are present that play a crucial role in cell cycle progression. In addition to the mentioned genes, there are some other genes (i.e. DLGAP5, BIRC5, PSMD2, Src, TTK, SENP2, PSMD2, DOK2, FUS and etc.) in the modules.

Assessment of gene-by-sex interaction effect on bone mineral density.

PubMed

Liu, Ching-Ti; Estrada, Karol; Yerges-Armstrong, Laura M; Amin, Najaf; Evangelou, Evangelos; Li, Guo; Minster, Ryan L; Carless, Melanie A; Kammerer, Candace M; Oei, Ling; Zhou, Yanhua; Alonso, Nerea; Dailiana, Zoe; Eriksson, Joel; García-Giralt, Natalia; Giroux, Sylvie; Husted, Lise Bjerre; Khusainova, Rita I; Koromila, Theodora; Kung, Annie Waichee; Lewis, Joshua R; Masi, Laura; Mencej-Bedrac, Simona; Nogues, Xavier; Patel, Millan S; Prezelj, Janez; Richards, J Brent; Sham, Pak Chung; Spector, Timothy; Vandenput, Liesbeth; Xiao, Su-Mei; Zheng, Hou-Feng; Zhu, Kun; Balcells, Susana; Brandi, Maria Luisa; Frost, Morten; Goltzman, David; González-Macías, Jesús; Karlsson, Magnus; Khusnutdinova, Elza K; Kollia, Panagoula; Langdahl, Bente Lomholt; Ljunggren, Osten; Lorentzon, Mattias; Marc, Janja; Mellström, Dan; Ohlsson, Claes; Olmos, José M; Ralston, Stuart H; Riancho, José A; Rousseau, François; Urreizti, Roser; Van Hul, Wim; Zarrabeitia, María T; Castano-Betancourt, Martha; Demissie, Serkalem; Grundberg, Elin; Herrera, Lizbeth; Kwan, Tony; Medina-Gómez, Carolina; Pastinen, Tomi; Sigurdsson, Gunnar; Thorleifsson, Gudmar; Vanmeurs, Joyce Bj; Blangero, John; Hofman, Albert; Liu, Yongmei; Mitchell, Braxton D; O'Connell, Jeffrey R; Oostra, Ben A; Rotter, Jerome I; Stefansson, Kari; Streeten, Elizabeth A; Styrkarsdottir, Unnur; Thorsteinsdottir, Unnur; Tylavsky, Frances A; Uitterlinden, Andre; Cauley, Jane A; Harris, Tamara B; Ioannidis, John Pa; Psaty, Bruce M; Robbins, John A; Zillikens, M Carola; Vanduijn, Cornelia M; Prince, Richard L; Karasik, David; Rivadeneira, Fernando; Kiel, Douglas P; Cupples, L Adrienne; Hsu, Yi-Hsiang

2012-10-01

Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research. Copyright © 2012 American Society for Bone and Mineral Research.

Potential Impact of miR-137 and Its Targets in Schizophrenia

PubMed Central

Wright, Carrie; Turner, Jessica A.; Calhoun, Vince D.; Perrone-Bizzozero, Nora

2013-01-01

The significant impact of microRNAs (miRNAs) on disease pathology is becoming increasingly evident. These small non-coding RNAs have the ability to post-transcriptionally silence the expression of thousands of genes. Therefore, dysregulation of even a single miRNA could confer a large polygenic effect. Schizophrenia is a genetically complex illness thought to involve multiple genes each contributing a small risk. Large genome-wide association studies identified miR-137, a miRNA shown to be involved in neuronal maturation, as one of the top risk genes. To assess the potential mechanism of impact of miR-137 in this disorder and identify its targets, we used a combination of literature searches, ingenuity pathway analysis (IPA), and freely accessible bioinformatics resources. Using TargetScan and the schizophrenia gene resource (SZGR) database, we found that in addition to CSMD1, C10orf26, CACNA1C, TCF4, and ZNF804A, five schizophrenia risk genes whose transcripts are also validated miR-137 targets, there are other schizophrenia-associated genes that may be targets of miR-137, including ERBB4, GABRA1, GRIN2A, GRM5, GSK3B, NRG2, and HTR2C. IPA analyses of all the potential targets identified several nervous system (NS) functions as the top canonical pathways including synaptic long-term potentiation, a process implicated in learning and memory mechanisms and recently shown to be altered in patients with schizophrenia. Among the subset of targets involved in NS development and function, the top scoring pathways were ephrin receptor signaling and axonal guidance, processes that are critical for proper circuitry formation and were shown to be disrupted in schizophrenia. These results suggest that miR-137 may indeed play a substantial role in the genetic etiology of schizophrenia by regulating networks involved in neural development and brain function. PMID:23637704

Tissue Doppler Imaging can be useful to distinguish pathological from physiological left ventricular hypertrophy: a study in master athletes and mild hypertensive subjects

PubMed Central

Galanti, Giorgio; Toncelli, Loira; Del Furia, Francesca; Stefani, Laura; Cappelli, Brunello; De Luca, Alessio; Vono, Maria Concetta Roberta

2009-01-01

Background Transthoracic echocardiography left ventricular wall thickness is often increased in master athletes and it results by intense physical training. Left Ventricular Hypertrophy can also be due to a constant pressure overload. Conventional Pulsed Wave (PW) Doppler analysis of diastolic function sometimes fails to distinguish physiological from pathological LVH. The aim of this study is to evaluate the role of Pulsed Wave Tissue Doppler Imaging in differentiating pathological from physiological LVH in the middle-aged population. Methods we selected a group of 80 master athletes, a group of 80 sedentary subjects with essential hypertension and an apparent normal diastolic function at standard PW Doppler analysis. The two groups were comparable for increased left ventricular wall thickness and mass index (134.4 ± 19.7 vs 134.5 ± 22.1 gr/m2; p > .05). Diastolic function indexes using the PW technique were in the normal range for both. Results Pulsed Wave TDI study of diastolic function immediately distinguished the two groups. While in master athletes the diastolic TDI-derived parameters remained within normal range (E' 9.4 ± 3.1 cm/sec; E/E' 7.8 ± 2.1), in the hypertensive group these parameters were found to be constantly altered, with mean values and variation ranges always outside normal validated limits (E' 7.2 ± 2.4 cm/sec; E/E' 10.6 ± 3.2), and with E' and E/E' statistically different in the two groups (p < .001). Conclusion Our study showed that the TDI technique can be an easy and validated method to assess diastolic function in differentiating normal from pseudonormal diastolic patterns and it can distinguish physiological from pathological LVH emphasizing the eligibility certification required by legal medical legislation as in Italy. PMID:19845938

Recommendations for Modeling Disaster Responses in Public Health and Medicine: A Position Paper of The Society for Medical Decision Making

PubMed Central

Brandeau, Margaret L.; McCoy, Jessica H.; Hupert, Nathaniel; Holty, Jon-Erik; Bravata, Dena M.

2013-01-01

Purpose Mathematical and simulation models are increasingly used to plan for and evaluate health sector responses to disasters, yet no clear consensus exists regarding best practices for the design, conduct, and reporting of such models. We examined a large selection of published health sector disaster response models to generate a set of best practice guidelines for such models. Methods We reviewed a spectrum of published disaster response models addressing public health or healthcare delivery, focusing in particular on the type of disaster and response decisions considered, decision makers targeted, choice of outcomes evaluated, modeling methodology, and reporting format. We developed initial recommendations for best practices for creating and reporting such models and refined these guidelines after soliciting feedback from response modeling experts and from members of the Society for Medical Decision Making. Results We propose six recommendations for model construction and reporting, inspired by the most exemplary models: Health sector disaster response models should address real-world problems; be designed for maximum usability by response planners; strike the appropriate balance between simplicity and complexity; include appropriate outcomes, which extend beyond those considered in traditional cost-effectiveness analyses; and be designed to evaluate the many uncertainties inherent in disaster response. Finally, good model reporting is particularly critical for disaster response models. Conclusions Quantitative models are critical tools for planning effective health sector responses to disasters. The recommendations we propose can increase the applicability and interpretability of future models, thereby improving strategic, tactical, and operational aspects of preparedness planning and response. PMID:19605887

Recommendations for modeling disaster responses in public health and medicine: a position paper of the society for medical decision making.

PubMed

Brandeau, Margaret L; McCoy, Jessica H; Hupert, Nathaniel; Holty, Jon-Erik; Bravata, Dena M

2009-01-01

Mathematical and simulation models are increasingly used to plan for and evaluate health sector responses to disasters, yet no clear consensus exists regarding best practices for the design, conduct, and reporting of such models. The authors examined a large selection of published health sector disaster response models to generate a set of best practice guidelines for such models. . The authors reviewed a spectrum of published disaster response models addressing public health or health care delivery, focusing in particular on the type of disaster and response decisions considered, decision makers targeted, choice of outcomes evaluated, modeling methodology, and reporting format. They developed initial recommendations for best practices for creating and reporting such models and refined these guidelines after soliciting feedback from response modeling experts and from members of the Society for Medical Decision Making. . The authors propose 6 recommendations for model construction and reporting, inspired by the most exemplary models: health sector disaster response models should address real-world problems, be designed for maximum usability by response planners, strike the appropriate balance between simplicity and complexity, include appropriate outcomes that extend beyond those considered in traditional cost-effectiveness analyses, and be designed to evaluate the many uncertainties inherent in disaster response. Finally, good model reporting is particularly critical for disaster response models. . Quantitative models are critical tools for planning effective health sector responses to disasters. The proposed recommendations can increase the applicability and interpretability of future models, thereby improving strategic, tactical, and operational aspects of preparedness planning and response.

Response Mixture Modeling: Accounting for Heterogeneity in Item Characteristics across Response Times.

PubMed

Molenaar, Dylan; de Boeck, Paul

2018-06-01

In item response theory modeling of responses and response times, it is commonly assumed that the item responses have the same characteristics across the response times. However, heterogeneity might arise in the data if subjects resort to different response processes when solving the test items. These differences may be within-subject effects, that is, a subject might use a certain process on some of the items and a different process with different item characteristics on the other items. If the probability of using one process over the other process depends on the subject's response time, within-subject heterogeneity of the item characteristics across the response times arises. In this paper, the method of response mixture modeling is presented to account for such heterogeneity. Contrary to traditional mixture modeling where the full response vectors are classified, response mixture modeling involves classification of the individual elements in the response vector. In a simulation study, the response mixture model is shown to be viable in terms of parameter recovery. In addition, the response mixture model is applied to a real dataset to illustrate its use in investigating within-subject heterogeneity in the item characteristics across response times.

A Two-Decision Model for Responses to Likert-Type Items

ERIC Educational Resources Information Center

Thissen-Roe, Anne; Thissen, David

2013-01-01

Extreme response set, the tendency to prefer the lowest or highest response option when confronted with a Likert-type response scale, can lead to misfit of item response models such as the generalized partial credit model. Recently, a series of intrinsically multidimensional item response models have been hypothesized, wherein tendency toward…

Modeling Rabbit Responses to Single and Multiple Aerosol ...

EPA Pesticide Factsheets

Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

A Measurement Model for Likert Responses that Incorporates Response Time

ERIC Educational Resources Information Center

Ferrando, Pere J.; Lorenzo-Seva, Urbano

2007-01-01

This article describes a model for response times that is proposed as a supplement to the usual factor-analytic model for responses to graded or more continuous typical-response items. The use of the proposed model together with the factor model provides additional information about the respondent and can potentially increase the accuracy of the…

A Flexible Latent Trait Model for Response Times in Tests

ERIC Educational Resources Information Center

Ranger, Jochen; Kuhn, Jorg-Tobias

2012-01-01

Latent trait models for response times in tests have become popular recently. One challenge for response time modeling is the fact that the distribution of response times can differ considerably even in similar tests. In order to reduce the need for tailor-made models, a model is proposed that unifies two popular approaches to response time…

Using Data Augmentation and Markov Chain Monte Carlo for the Estimation of Unfolding Response Models

ERIC Educational Resources Information Center

Johnson, Matthew S.; Junker, Brian W.

2003-01-01

Unfolding response models, a class of item response theory (IRT) models that assume a unimodal item response function (IRF), are often used for the measurement of attitudes. Verhelst and Verstralen (1993)and Andrich and Luo (1993) independently developed unfolding response models by relating the observed responses to a more common monotone IRT…

A Primer on the 2- and 3-Parameter Item Response Theory Models.

ERIC Educational Resources Information Center

Thornton, Artist

Item response theory (IRT) is a useful and effective tool for item response measurement if used in the proper context. This paper discusses the sets of assumptions under which responses can be modeled while exploring the framework of the IRT models relative to response testing. The one parameter model, or one parameter logistic model, is perhaps…

Modelling climate change responses in tropical forests: similar productivity estimates across five models, but different mechanisms and responses

NASA Astrophysics Data System (ADS)

Rowland, L.; Harper, A.; Christoffersen, B. O.; Galbraith, D. R.; Imbuzeiro, H. M. A.; Powell, T. L.; Doughty, C.; Levine, N. M.; Malhi, Y.; Saleska, S. R.; Moorcroft, P. R.; Meir, P.; Williams, M.

2014-11-01

Accurately predicting the response of Amazonia to climate change is important for predicting changes across the globe. However, changes in multiple climatic factors simultaneously may result in complex non-linear responses, which are difficult to predict using vegetation models. Using leaf and canopy scale observations, this study evaluated the capability of five vegetation models (CLM3.5, ED2, JULES, SiB3, and SPA) to simulate the responses of canopy and leaf scale productivity to changes in temperature and drought in an Amazonian forest. The models did not agree as to whether gross primary productivity (GPP) was more sensitive to changes in temperature or precipitation. There was greater model-data consistency in the response of net ecosystem exchange to changes in temperature, than in the response to temperature of leaf area index (LAI), net photosynthesis (An) and stomatal conductance (gs). Modelled canopy scale fluxes are calculated by scaling leaf scale fluxes to LAI, and therefore in this study similarities in modelled ecosystem scale responses to drought and temperature were the result of inconsistent leaf scale and LAI responses among models. Across the models, the response of An to temperature was more closely linked to stomatal behaviour than biochemical processes. Consequently all the models predicted that GPP would be higher if tropical forests were 5 °C colder, closer to the model optima for gs. There was however no model consistency in the response of the An-gs relationship when temperature changes and drought were introduced simultaneously. The inconsistencies in the An-gs relationships amongst models were caused by to non-linear model responses induced by simultaneous drought and temperature change. To improve the reliability of simulations of the response of Amazonian rainforest to climate change the mechanistic underpinnings of vegetation models need more complete validation to improve accuracy and consistency in the scaling of processes from leaf to canopy.

Urban Earthquake Shaking and Loss Assessment

NASA Astrophysics Data System (ADS)

Hancilar, U.; Tuzun, C.; Yenidogan, C.; Zulfikar, C.; Durukal, E.; Erdik, M.

2009-04-01

This study, conducted under the JRA-3 component of the EU NERIES Project, develops a methodology and software (ELER) for the rapid estimation of earthquake shaking and losses the Euro-Mediterranean region. This multi-level methodology developed together with researchers from Imperial College, NORSAR and ETH-Zurich is capable of incorporating regional variability and sources of uncertainty stemming from ground motion predictions, fault finiteness, site modifications, inventory of physical and social elements subjected to earthquake hazard and the associated vulnerability relationships. GRM Risk Management, Inc. of Istanbul serves as sub-contractor tor the coding of the ELER software. The methodology encompasses the following general steps: 1. Finding of the most likely location of the source of the earthquake using regional seismotectonic data base and basic source parameters, and if and when possible, by the estimation of fault rupture parameters from rapid inversion of data from on-line stations. 2. Estimation of the spatial distribution of selected ground motion parameters through region specific ground motion attenuation relationships and using shear wave velocity distributions.(Shake Mapping) 4. Incorporation of strong ground motion and other empirical macroseismic data for the improvement of Shake Map 5. Estimation of the losses (damage, casualty and economic) at different levels of sophistication (0, 1 and 2) that commensurate with the availability of inventory of human built environment (Loss Mapping) Level 2 analysis of the ELER Software (similar to HAZUS and SELENA) is essentially intended for earthquake risk assessment (building damage, consequential human casualties and macro economic loss quantifiers) in urban areas. The basic Shake Mapping is similar to the Level 0 and Level 1 analysis however, options are available for more sophisticated treatment of site response through externally entered data and improvement of the shake map through incorporation of accelerometric and other macroseismic data (similar to the USGS ShakeMap System). The building inventory data for the Level 2 analysis will consist of grid (geo-cell) based urban building and demographic inventories. For building grouping the European building typology developed within the EU-FP5 RISK-EU project is used. The building vulnerability/fragility relationships to be used can be user selected from a list of applicable relationships developed on the basis of a comprehensive study, Both empirical and analytical relationships (based on the Coefficient Method, Equivalent Linearization Method and the Reduction Factor Method of analysis) can be employed. Casualties in Level 2 analysis are estimated based on the number of buildings in different damaged states and the casualty rates for each building type and damage level. Modifications to the casualty rates can be used if necessary. ELER Level 2 analysis will include calculation of direct monetary losses as a result building damage that will allow for repair-cost estimations and specific investigations associated with earthquake insurance applications (PML and AAL estimations). ELER Level 2 analysis loss results obtained for Istanbul for a scenario earthquake using different techniques will be presented with comparisons using different earthquake damage assessment software. The urban earthquake shaking and loss information is intented for dissemination in a timely manner to related agencies for the planning and coordination of the post-earthquake emergency response. However the same software can also be used for scenario earthquake loss estimation, related Monte-Carlo type simulations and eathquake insurance applications.

Response moderation models for conditional dependence between response time and response accuracy.

PubMed

Bolsinova, Maria; Tijmstra, Jesper; Molenaar, Dylan

2017-05-01

It is becoming more feasible and common to register response times in the application of psychometric tests. Researchers thus have the opportunity to jointly model response accuracy and response time, which provides users with more relevant information. The most common choice is to use the hierarchical model (van der Linden, 2007, Psychometrika, 72, 287), which assumes conditional independence between response time and accuracy, given a person's speed and ability. However, this assumption may be violated in practice if, for example, persons vary their speed or differ in their response strategies, leading to conditional dependence between response time and accuracy and confounding measurement. We propose six nested hierarchical models for response time and accuracy that allow for conditional dependence, and discuss their relationship to existing models. Unlike existing approaches, the proposed hierarchical models allow for various forms of conditional dependence in the model and allow the effect of continuous residual response time on response accuracy to be item-specific, person-specific, or both. Estimation procedures for the models are proposed, as well as two information criteria that can be used for model selection. Parameter recovery and usefulness of the information criteria are investigated using simulation, indicating that the procedure works well and is likely to select the appropriate model. Two empirical applications are discussed to illustrate the different types of conditional dependence that may occur in practice and how these can be captured using the proposed hierarchical models. © 2016 The British Psychological Society.

Modelling Mathematics Problem Solving Item Responses Using a Multidimensional IRT Model

ERIC Educational Resources Information Center

Wu, Margaret; Adams, Raymond

2006-01-01

This research examined students' responses to mathematics problem-solving tasks and applied a general multidimensional IRT model at the response category level. In doing so, cognitive processes were identified and modelled through item response modelling to extract more information than would be provided using conventional practices in scoring…

A heteroscedastic generalized linear model with a non-normal speed factor for responses and response times.

PubMed

Molenaar, Dylan; Bolsinova, Maria

2017-05-01

In generalized linear modelling of responses and response times, the observed response time variables are commonly transformed to make their distribution approximately normal. A normal distribution for the transformed response times is desirable as it justifies the linearity and homoscedasticity assumptions in the underlying linear model. Past research has, however, shown that the transformed response times are not always normal. Models have been developed to accommodate this violation. In the present study, we propose a modelling approach for responses and response times to test and model non-normality in the transformed response times. Most importantly, we distinguish between non-normality due to heteroscedastic residual variances, and non-normality due to a skewed speed factor. In a simulation study, we establish parameter recovery and the power to separate both effects. In addition, we apply the model to a real data set. © 2017 The Authors. British Journal of Mathematical and Statistical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Temperature Responses to Spectral Solar Variability on Decadal Time Scales

NASA Technical Reports Server (NTRS)

Cahalan, Robert F.; Wen, Guoyong; Harder, Jerald W.; Pilewskie, Peter

2010-01-01

Two scenarios of spectral solar forcing, namely Spectral Irradiance Monitor (SIM)-based out-of-phase variations and conventional in-phase variations, are input to a time-dependent radiative-convective model (RCM), and to the GISS modelE. Both scenarios and models give maximum temperature responses in the upper stratosphere, decreasing to the surface. Upper stratospheric peak-to-peak responses to out-of-phase forcing are approx.0.6 K and approx.0.9 K in RCM and modelE, approx.5 times larger than responses to in-phase forcing. Stratospheric responses are in-phase with TSI and UV variations, and resemble HALOE observed 11-year temperature variations. For in-phase forcing, ocean mixed layer response lags surface air response by approx.2 years, and is approx.0.06 K compared to approx.0.14 K for atmosphere. For out-of-phase forcing, lags are similar, but surface responses are significantly smaller. For both scenarios, modelE surface responses are less than 0.1 K in the tropics, and display similar patterns over oceanic regions, but complex responses over land.

Effects of prompting and reinforcement of one response pattern upon imitation of a different modeled pattern

PubMed Central

Bondy, Andrew S.

1982-01-01

Twelve preschool children participated in a study of the effects of explicit training on the imitation of modeled behavior. The responses trained involved a marble-dropping pattern that differed from the modeled pattern. Training consisted of physical prompts and verbal praise during a single session. No prompts or praise were used during test periods. After operant levels of the experimental responses were measured, training either preceded or was interposed within a series of exposures to modeled behavior that differed from the trained behavior. Children who were initially exposed to a modeling session immediately imitated, whereas those children who were initially trained immediately performed the appropriate response. Children initially trained on one pattern generally continued to exhibit that pattern even after many modeling sessions. Children who first viewed the modeled response and then were exposed to explicit training of a different response reversed their response pattern from the trained response to the modeled response within a few sessions. The results suggest that under certain conditions explicit training will exert greater control over responding than immediate modeling stimuli. PMID:16812260

Hidden Markov Item Response Theory Models for Responses and Response Times.

PubMed

Molenaar, Dylan; Oberski, Daniel; Vermunt, Jeroen; De Boeck, Paul

2016-01-01

Current approaches to model responses and response times to psychometric tests solely focus on between-subject differences in speed and ability. Within subjects, speed and ability are assumed to be constants. Violations of this assumption are generally absorbed in the residual of the model. As a result, within-subject departures from the between-subject speed and ability level remain undetected. These departures may be of interest to the researcher as they reflect differences in the response processes adopted on the items of a test. In this article, we propose a dynamic approach for responses and response times based on hidden Markov modeling to account for within-subject differences in responses and response times. A simulation study is conducted to demonstrate acceptable parameter recovery and acceptable performance of various fit indices in distinguishing between different models. In addition, both a confirmatory and an exploratory application are presented to demonstrate the practical value of the modeling approach.

Dynamic Alignment Models for Neural Coding

PubMed Central

Kollmorgen, Sepp; Hahnloser, Richard H. R.

2014-01-01

Recently, there have been remarkable advances in modeling the relationships between the sensory environment, neuronal responses, and behavior. However, most models cannot encompass variable stimulus-response relationships such as varying response latencies and state or context dependence of the neural code. Here, we consider response modeling as a dynamic alignment problem and model stimulus and response jointly by a mixed pair hidden Markov model (MPH). In MPHs, multiple stimulus-response relationships (e.g., receptive fields) are represented by different states or groups of states in a Markov chain. Each stimulus-response relationship features temporal flexibility, allowing modeling of variable response latencies, including noisy ones. We derive algorithms for learning of MPH parameters and for inference of spike response probabilities. We show that some linear-nonlinear Poisson cascade (LNP) models are a special case of MPHs. We demonstrate the efficiency and usefulness of MPHs in simulations of both jittered and switching spike responses to white noise and natural stimuli. Furthermore, we apply MPHs to extracellular single and multi-unit data recorded in cortical brain areas of singing birds to showcase a novel method for estimating response lag distributions. MPHs allow simultaneous estimation of receptive fields, latency statistics, and hidden state dynamics and so can help to uncover complex stimulus response relationships that are subject to variable timing and involve diverse neural codes. PMID:24625448

Women's Endorsement of Models of Sexual Response: Correlates and Predictors.

PubMed

Nowosielski, Krzysztof; Wróbel, Beata; Kowalczyk, Robert

2016-02-01

Few studies have investigated endorsement of female sexual response models, and no single model has been accepted as a normative description of women's sexual response. The aim of the study was to establish how women from a population-based sample endorse current theoretical models of the female sexual response--the linear models and circular model (partial and composite Basson models)--as well as predictors of endorsement. Accordingly, 174 heterosexual women aged 18-55 years were included in a cross-sectional study: 74 women diagnosed with female sexual dysfunction (FSD) based on DSM-5 criteria and 100 non-dysfunctional women. The description of sexual response models was used to divide subjects into four subgroups: linear (Masters-Johnson and Kaplan models), circular (partial Basson model), mixed (linear and circular models in similar proportions, reflective of the composite Basson model), and a different model. Women were asked to choose which of the models best described their pattern of sexual response and how frequently they engaged in each model. Results showed that 28.7% of women endorsed the linear models, 19.5% the partial Basson model, 40.8% the composite Basson model, and 10.9% a different model. Women with FSD endorsed the partial Basson model and a different model more frequently than did non-dysfunctional controls. Individuals who were dissatisfied with a partner as a lover were more likely to endorse a different model. Based on the results, we concluded that the majority of women endorsed a mixed model combining the circular response with the possibility of an innate desire triggering a linear response. Further, relationship difficulties, not FSD, predicted model endorsement.

A Unidimensional Item Response Model for Unfolding Responses from a Graded Disagree-Agree Response Scale.

ERIC Educational Resources Information Center

Roberts, James S.; Laughlin, James E.

1996-01-01

A parametric item response theory model for unfolding binary or graded responses is developed. The graded unfolding model (GUM) is a generalization of the hyperbolic cosine model for binary data of D. Andrich and G. Luo (1993). Applicability of the GUM to attitude testing is illustrated with real data. (SLD)

Theoretical and Empirical Comparisons between Two Models for Continuous Item Responses.

ERIC Educational Resources Information Center

Ferrando, Pere J.

2002-01-01

Analyzed the relations between two continuous response models intended for typical response items: the linear congeneric model and Samejima's continuous response model (CRM). Illustrated the relations described using an empirical example and assessed the relations through a simulation study. (SLD)

Graded Response Model Based on the Logistic Positive Exponent Family of Models for Dichotomous Responses

ERIC Educational Resources Information Center

Samejima, Fumiko

2008-01-01

Samejima ("Psychometrika "65:319--335, 2000) proposed the logistic positive exponent family of models (LPEF) for dichotomous responses in the unidimensional latent space. The objective of the present paper is to propose and discuss a graded response model that is expanded from the LPEF, in the context of item response theory (IRT). This…

Forced-Choice Assessment of Work-Related Maladaptive Personality Traits: Preliminary Evidence From an Application of Thurstonian Item Response Modeling.

PubMed

Guenole, Nigel; Brown, Anna A; Cooper, Andrew J

2018-06-01

This article describes an investigation of whether Thurstonian item response modeling is a viable method for assessment of maladaptive traits. Forced-choice responses from 420 working adults to a broad-range personality inventory assessing six maladaptive traits were considered. The Thurstonian item response model's fit to the forced-choice data was adequate, while the fit of a counterpart item response model to responses to the same items but arranged in a single-stimulus design was poor. Monotrait heteromethod correlations indicated corresponding traits in the two formats overlapped substantially, although they did not measure equivalent constructs. A better goodness of fit and higher factor loadings for the Thurstonian item response model, coupled with a clearer conceptual alignment to the theoretical trait definitions, suggested that the single-stimulus item responses were influenced by biases that the independent clusters measurement model did not account for. Researchers may wish to consider forced-choice designs and appropriate item response modeling techniques such as Thurstonian item response modeling for personality questionnaire applications in industrial psychology, especially when assessing maladaptive traits. We recommend further investigation of this approach in actual selection situations and with different assessment instruments.

Simple Climate Model Evaluation Using Impulse Response Tests

NASA Astrophysics Data System (ADS)

Schwarber, A.; Hartin, C.; Smith, S. J.

2017-12-01

Simple climate models (SCMs) are central tools used to incorporate climate responses into human-Earth system modeling. SCMs are computationally inexpensive, making them an ideal tool for a variety of analyses, including consideration of uncertainty. Despite their wide use, many SCMs lack rigorous testing of their fundamental responses to perturbations. Here, following recommendations of a recent National Academy of Sciences report, we compare several SCMs (Hector-deoclim, MAGICC 5.3, MAGICC 6.0, and the IPCC AR5 impulse response function) to diagnose model behavior and understand the fundamental system responses within each model. We conduct stylized perturbations (emissions and forcing/concentration) of three different chemical species: CO2, CH4, and BC. We find that all 4 models respond similarly in terms of overall shape, however, there are important differences in the timing and magnitude of the responses. For example, the response to a BC pulse differs over the first 20 years after the pulse among the models, a finding that is due to differences in model structure. Such perturbation experiments are difficult to conduct in complex models due to internal model noise, making a direct comparison with simple models challenging. We can, however, compare the simplified model response from a 4xCO2 step experiment to the same stylized experiment carried out by CMIP5 models, thereby testing the ability of SCMs to emulate complex model results. This work allows an assessment of how well current understanding of Earth system responses are incorporated into multi-model frameworks by way of simple climate models.

A note on monotonicity of item response functions for ordered polytomous item response theory models.

PubMed

Kang, Hyeon-Ah; Su, Ya-Hui; Chang, Hua-Hua

2018-03-08

A monotone relationship between a true score (τ) and a latent trait level (θ) has been a key assumption for many psychometric applications. The monotonicity property in dichotomous response models is evident as a result of a transformation via a test characteristic curve. Monotonicity in polytomous models, in contrast, is not immediately obvious because item response functions are determined by a set of response category curves, which are conceivably non-monotonic in θ. The purpose of the present note is to demonstrate strict monotonicity in ordered polytomous item response models. Five models that are widely used in operational assessments are considered for proof: the generalized partial credit model (Muraki, 1992, Applied Psychological Measurement, 16, 159), the nominal model (Bock, 1972, Psychometrika, 37, 29), the partial credit model (Masters, 1982, Psychometrika, 47, 147), the rating scale model (Andrich, 1978, Psychometrika, 43, 561), and the graded response model (Samejima, 1972, A general model for free-response data (Psychometric Monograph no. 18). Psychometric Society, Richmond). The study asserts that the item response functions in these models strictly increase in θ and thus there exists strict monotonicity between τ and θ under certain specified conditions. This conclusion validates the practice of customarily using τ in place of θ in applied settings and provides theoretical grounds for one-to-one transformations between the two scales. © 2018 The British Psychological Society.

Estimating multivariate response surface model with data outliers, case study in enhancing surface layer properties of an aircraft aluminium alloy

NASA Astrophysics Data System (ADS)

Widodo, Edy; Kariyam

2017-03-01

To determine the input variable settings that create the optimal compromise in response variable used Response Surface Methodology (RSM). There are three primary steps in the RSM problem, namely data collection, modelling, and optimization. In this study focused on the establishment of response surface models, using the assumption that the data produced is correct. Usually the response surface model parameters are estimated by OLS. However, this method is highly sensitive to outliers. Outliers can generate substantial residual and often affect the estimator models. Estimator models produced can be biased and could lead to errors in the determination of the optimal point of fact, that the main purpose of RSM is not reached. Meanwhile, in real life, the collected data often contain some response variable and a set of independent variables. Treat each response separately and apply a single response procedures can result in the wrong interpretation. So we need a development model for the multi-response case. Therefore, it takes a multivariate model of the response surface that is resistant to outliers. As an alternative, in this study discussed on M-estimation as a parameter estimator in multivariate response surface models containing outliers. As an illustration presented a case study on the experimental results to the enhancement of the surface layer of aluminium alloy air by shot peening.

Multilevel and Latent Variable Modeling with Composite Links and Exploded Likelihoods

ERIC Educational Resources Information Center

Rabe-Hesketh, Sophia; Skrondal, Anders

2007-01-01

Composite links and exploded likelihoods are powerful yet simple tools for specifying a wide range of latent variable models. Applications considered include survival or duration models, models for rankings, small area estimation with census information, models for ordinal responses, item response models with guessing, randomized response models,…

A Box-Cox normal model for response times.

PubMed

Klein Entink, R H; van der Linden, W J; Fox, J-P

2009-11-01

The log-transform has been a convenient choice in response time modelling on test items. However, motivated by a dataset of the Medical College Admission Test where the lognormal model violated the normality assumption, the possibilities of the broader class of Box-Cox transformations for response time modelling are investigated. After an introduction and an outline of a broader framework for analysing responses and response times simultaneously, the performance of a Box-Cox normal model for describing response times is investigated using simulation studies and a real data example. A transformation-invariant implementation of the deviance information criterium (DIC) is developed that allows for comparing model fit between models with different transformation parameters. Showing an enhanced description of the shape of the response time distributions, its application in an educational measurement context is discussed at length.

On the effect of acoustic coupling on random and harmonic plate vibrations

NASA Technical Reports Server (NTRS)

Frendi, A.; Robinson, J. H.

1993-01-01

The effect of acoustic coupling on random and harmonic plate vibrations is studied using two numerical models. In the coupled model, the plate response is obtained by integration of the nonlinear plate equation coupled with the nonlinear Euler equations for the surrounding acoustic fluid. In the uncoupled model, the nonlinear plate equation with an equivalent linear viscous damping term is integrated to obtain the response of the plate subject to the same excitation field. For a low-level, narrow-band excitation, the two models predict the same plate response spectra. As the excitation level is increased, the response power spectrum predicted by the uncoupled model becomes broader and more shifted towards the high frequencies than that obtained by the coupled model. In addition, the difference in response between the coupled and uncoupled models at high frequencies becomes larger. When a high intensity harmonic excitation is used, causing a nonlinear plate response, both models predict the same frequency content of the response. However, the level of the harmonics and subharmonics are higher for the uncoupled model. Comparisons to earlier experimental and numerical results show that acoustic coupling has a significant effect on the plate response at high excitation levels. Its absence in previous models may explain the discrepancy between predicted and measured responses.

Some Statistics for Assessing Person-Fit Based on Continuous-Response Models

ERIC Educational Resources Information Center

Ferrando, Pere Joan

2010-01-01

This article proposes several statistics for assessing individual fit based on two unidimensional models for continuous responses: linear factor analysis and Samejima's continuous response model. Both models are approached using a common framework based on underlying response variables and are formulated at the individual level as fixed regression…

Stochastic Approximation Methods for Latent Regression Item Response Models

ERIC Educational Resources Information Center

von Davier, Matthias; Sinharay, Sandip

2010-01-01

This article presents an application of a stochastic approximation expectation maximization (EM) algorithm using a Metropolis-Hastings (MH) sampler to estimate the parameters of an item response latent regression model. Latent regression item response models are extensions of item response theory (IRT) to a latent variable model with covariates…

Influence of tyre-road contact model on vehicle vibration response

NASA Astrophysics Data System (ADS)

Múčka, Peter; Gagnon, Louis

2015-09-01

The influence of the tyre-road contact model on the simulated vertical vibration response was analysed. Three contact models were compared: tyre-road point contact model, moving averaged profile and tyre-enveloping model. In total, 1600 real asphalt concrete and Portland cement concrete longitudinal road profiles were processed. The linear planar model of automobile with 12 degrees of freedom (DOF) was used. Five vibration responses as the measures of ride comfort, ride safety and dynamic load of cargo were investigated. The results were calculated as a function of vibration response, vehicle velocity, road quality and road surface type. The marked differences in the dynamic tyre forces and the negligible differences in the ride comfort quantities were observed among the tyre-road contact models. The seat acceleration response for three contact models and 331 DOF multibody model of the truck semi-trailer was compared with the measured response for a known profile of test section.

COBRA ATD multispectral camera response model

NASA Astrophysics Data System (ADS)

Holmes, V. Todd; Kenton, Arthur C.; Hilton, Russell J.; Witherspoon, Ned H.; Holloway, John H., Jr.

2000-08-01

A new multispectral camera response model has been developed in support of the US Marine Corps (USMC) Coastal Battlefield Reconnaissance and Analysis (COBRA) Advanced Technology Demonstration (ATD) Program. This analytical model accurately estimates response form five Xybion intensified IMC 201 multispectral cameras used for COBRA ATD airborne minefield detection. The camera model design is based on a series of camera response curves which were generated through optical laboratory test performed by the Naval Surface Warfare Center, Dahlgren Division, Coastal Systems Station (CSS). Data fitting techniques were applied to these measured response curves to obtain nonlinear expressions which estimates digitized camera output as a function of irradiance, intensifier gain, and exposure. This COBRA Camera Response Model was proven to be very accurate, stable over a wide range of parameters, analytically invertible, and relatively simple. This practical camera model was subsequently incorporated into the COBRA sensor performance evaluation and computational tools for research analysis modeling toolbox in order to enhance COBRA modeling and simulation capabilities. Details of the camera model design and comparisons of modeled response to measured experimental data are presented.

Comparison of Response Surface and Kriging Models for Multidisciplinary Design Optimization

NASA Technical Reports Server (NTRS)

Simpson, Timothy W.; Korte, John J.; Mauery, Timothy M.; Mistree, Farrokh

1998-01-01

In this paper, we compare and contrast the use of second-order response surface models and kriging models for approximating non-random, deterministic computer analyses. After reviewing the response surface method for constructing polynomial approximations, kriging is presented as an alternative approximation method for the design and analysis of computer experiments. Both methods are applied to the multidisciplinary design of an aerospike nozzle which consists of a computational fluid dynamics model and a finite-element model. Error analysis of the response surface and kriging models is performed along with a graphical comparison of the approximations, and four optimization problems m formulated and solved using both sets of approximation models. The second-order response surface models and kriging models-using a constant underlying global model and a Gaussian correlation function-yield comparable results.

A Riparian Vegetation Ecophysiological Response Model

Treesearch

Jeffrey P. Leighton; Roland J. Risser

1989-01-01

A mathematical model is described that relates mature riparian vegetation ecophysiological response to changes in stream level. This model was developed to estimate the physiological response of riparian vegetation to reductions in streamflow. Field data from two sites on the North Fork of the Kings River were used in the model development. The physiological response...

A Linear Variable-[theta] Model for Measuring Individual Differences in Response Precision

ERIC Educational Resources Information Center

Ferrando, Pere J.

2011-01-01

Models for measuring individual response precision have been proposed for binary and graded responses. However, more continuous formats are quite common in personality measurement and are usually analyzed with the linear factor analysis model. This study extends the general Gaussian person-fluctuation model to the continuous-response case and…

Distinguishing Fast and Slow Processes in Accuracy - Response Time Data.

PubMed

Coomans, Frederik; Hofman, Abe; Brinkhuis, Matthieu; van der Maas, Han L J; Maris, Gunter

2016-01-01

We investigate the relation between speed and accuracy within problem solving in its simplest non-trivial form. We consider tests with only two items and code the item responses in two binary variables: one indicating the response accuracy, and one indicating the response speed. Despite being a very basic setup, it enables us to study item pairs stemming from a broad range of domains such as basic arithmetic, first language learning, intelligence-related problems, and chess, with large numbers of observations for every pair of problems under consideration. We carry out a survey over a large number of such item pairs and compare three types of psychometric accuracy-response time models present in the literature: two 'one-process' models, the first of which models accuracy and response time as conditionally independent and the second of which models accuracy and response time as conditionally dependent, and a 'two-process' model which models accuracy contingent on response time. We find that the data clearly violates the restrictions imposed by both one-process models and requires additional complexity which is parsimoniously provided by the two-process model. We supplement our survey with an analysis of the erroneous responses for an example item pair and demonstrate that there are very significant differences between the types of errors in fast and slow responses.

The SGI/Cray T3E: Experiences and Insights

NASA Technical Reports Server (NTRS)

Bernard, Lisa Hamet

1998-01-01

The NASA Goddard Space Flight Center is home to the fifth most powerful supercomputer in the world, a 1024 processor SGI/Cray T3E-600. The original 512 processor system was placed at Goddard in March, 1997 as part of a cooperative agreement between the High Performance Computing and Communications Program's Earth and Space Sciences Project (ESS) and SGI/Cray Research. The goal of this system is to facilitate achievement of the Project milestones of 10, 50 and 100 GFLOPS sustained performance on selected Earth and space science application codes. The additional 512 processors were purchased in March, 1998 by the NASA Earth Science Enterprise for the NASA Seasonal to Interannual Prediction Project (NSIPP). These two "halves" still operate as a single system, and must satisfy the unique requirements of both aforementioned groups, as well as guest researchers from the Earth, space, microgravity, manned space flight and aeronautics communities. Few large scalable parallel systems are configured for capability computing, so models are hard to find. This unique environment has created a challenging system administration task, and has yielded some insights into the supercomputing needs of the various NASA Enterprises, as well as insights into the strengths and weaknesses of the T3E architecture and software. The T3E is a distributed memory system in which the processing elements (PE's) are connected by a low latency, high bandwidth bidirectional 3-D torus. Due to the focus on high speed communication between PE's, the T3E requires PE's to be allocated contiguously per job. Further, jobs will only execute on the user specified number of PE's and PE timesharing is possible but impractical. With a highly varied job mix in both size and runtime of jobs, the resulting scenario is PE fragmentation and an inability to achieve near 100% utilization. SGI/Cray has provided several scheduling and configuration tools to minimize the impact of fragmentation. These tools include PScheD (the political scheduler), GRM (the global resource manager) and NQE (the Network Queuing Environment). Features and impact of these tools will be discussed, as will resulting performance and utilization data. As a distributed memory system, the T3E is designed to be programmed through explicit message passing. Consequently, certain assumptions related to code design are made by the operating system (UNICOS/mk) and its scheduling tools. With the exception of HPF, which does run on the T3E, however poorly, alternative programming styles have the potential to impact the T3E in unexpected and undesirable ways. Several examples will be presented (preceeded with the disclaimer, "Don't try this at home! Violators will be prosecuted!")

Conceptualization of the Sexual Response Models in Men: Are there Differences Between Sexually Functional and Dysfunctional Men?

PubMed

Connaughton, Catherine; McCabe, Marita; Karantzas, Gery

2016-03-01

Research to validate models of sexual response empirically in men with and without sexual dysfunction (MSD), as currently defined, is limited. To explore the extent to which the traditional linear or the Basson circular model best represents male sexual response for men with MSD and sexually functional men. In total, 573 men completed an online questionnaire to assess sexual function and aspects of the models of sexual response. In total, 42.2% of men (242) were sexually functional, and 57.8% (331) had at least one MSD. Models were built and tested using bootstrapping and structural equation modeling. Fit of models for men with and without MSD. The linear model and the initial circular model were a poor fit for men with and without MSD. A modified version of the circular model demonstrated adequate fit for the two groups and showed important interactions between psychological factors and sexual response for men with and without MSD. Male sexual response was not represented by the linear model for men with or without MSD, excluding possible healthy responsive desire. The circular model provided a better fit for the two groups of men but demonstrated that the relations between psychological factors and phases of sexual response were different for men with and without MSD as currently defined. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Response Surface Methodology Using a Fullest Balanced Model: A Re-Analysis of a Dataset in the Korean Journal for Food Science of Animal Resources.

PubMed

Rheem, Sungsue; Rheem, Insoo; Oh, Sejong

2017-01-01

Response surface methodology (RSM) is a useful set of statistical techniques for modeling and optimizing responses in research studies of food science. In the analysis of response surface data, a second-order polynomial regression model is usually used. However, sometimes we encounter situations where the fit of the second-order model is poor. If the model fitted to the data has a poor fit including a lack of fit, the modeling and optimization results might not be accurate. In such a case, using a fullest balanced model, which has no lack of fit, can fix such problem, enhancing the accuracy of the response surface modeling and optimization. This article presents how to develop and use such a model for the better modeling and optimizing of the response through an illustrative re-analysis of a dataset in Park et al. (2014) published in the Korean Journal for Food Science of Animal Resources .

Modeling Response Signal and Response Time Data

ERIC Educational Resources Information Center

Ratcliff, Roger

2006-01-01

The diffusion model (Ratcliff, 1978) and the leaky competing accumulator model (LCA, Usher & McClelland, 2001) were tested against two-choice data collected from the same subjects with the standard response time procedure and the response signal procedure. In the response signal procedure, a stimulus is presented and then, at one of a number of…

Analysis and test evaluation of the dynamic response and stability of three advanced turboprop models

NASA Technical Reports Server (NTRS)

Bansal, P. N.; Arseneaux, P. J.; Smith, A. F.; Turnberg, J. E.; Brooks, B. M.

1985-01-01

Results of dynamic response and stability wind tunnel tests of three 62.2 cm (24.5 in) diameter models of the Prop-Fan, advanced turboprop, are presented. Measurements of dynamic response were made with the rotors mounted on an isolated nacelle, with varying tilt for nonuniform inflow. One model was also tested using a semi-span wing and fuselage configuration for response to realistic aircraft inflow. Stability tests were performed using tunnel turbulence or a nitrogen jet for excitation. Measurements are compared with predictions made using beam analysis methods for the model with straight blades, and finite element analysis methods for the models with swept blades. Correlations between measured and predicted rotating blade natural frequencies for all the models are very good. The IP dynamic response of the straight blade model is reasonably well predicted. The IP response of the swept blades is underpredicted and the wing induced response of the straight blade is overpredicted. Two models did not flutter, as predicted. One swept blade model encountered an instability at a higher RPM than predicted, showing predictions to be conservative.

Regional and Global Climate Response to Anthropogenic SO2 Emissions from China in Three Climate Models

NASA Technical Reports Server (NTRS)

Kasoar, M.; Voulgarakis, Apostolos; Lamarque, Jean-Francois; Shindell, Drew T.; Bellouin, Nicholas; Collins, William J.; Faluvegi, Greg; Tsigaridis, Kostas

2016-01-01

We use the HadGEM3-GA4, CESM1, and GISS ModelE2 climate models to investigate the global and regional aerosol burden, radiative flux, and surface temperature responses to removing anthropogenic sulfur dioxide (SO2) emissions from China. We find that the models differ by up to a factor of 6 in the simulated change in aerosol optical depth (AOD) and shortwave radiative flux over China that results from reduced sulfate aerosol, leading to a large range of magnitudes in the regional and global temperature responses. Two of the three models simulate a near-ubiquitous hemispheric warming due to the regional SO2 removal, with similarities in the local and remote pattern of response, but overall with a substantially different magnitude. The third model simulates almost no significant temperature response. We attribute the discrepancies in the response to a combination of substantial differences in the chemical conversion of SO2 to sulfate, translation of sulfate mass into AOD, cloud radiative interactions, and differences in the radiative forcing efficiency of sulfate aerosol in the models. The model with the strongest response (HadGEM3-GA4) compares best with observations of AOD regionally, however the other two models compare similarly (albeit poorly) and still disagree substantially in their simulated climate response, indicating that total AOD observations are far from sufficient to determine which model response is more plausible. Our results highlight that there remains a large uncertainty in the representation of both aerosol chemistry as well as direct and indirect aerosol radiative effects in current climate models, and reinforces that caution must be applied when interpreting the results of modelling studies of aerosol influences on climate. Model studies that implicate aerosols in climate responses should ideally explore a range of radiative forcing strengths representative of this uncertainty, in addition to thoroughly evaluating the models used against observations.

Ramsay-Curve Item Response Theory for the Three-Parameter Logistic Item Response Model

ERIC Educational Resources Information Center

Woods, Carol M.

2008-01-01

In Ramsay-curve item response theory (RC-IRT), the latent variable distribution is estimated simultaneously with the item parameters of a unidimensional item response model using marginal maximum likelihood estimation. This study evaluates RC-IRT for the three-parameter logistic (3PL) model with comparisons to the normal model and to the empirical…

Using Response Times for Item Selection in Adaptive Testing

ERIC Educational Resources Information Center

van der Linden, Wim J.

2008-01-01

Response times on items can be used to improve item selection in adaptive testing provided that a probabilistic model for their distribution is available. In this research, the author used a hierarchical modeling framework with separate first-level models for the responses and response times and a second-level model for the distribution of the…

Comparison of Response Surface and Kriging Models in the Multidisciplinary Design of an Aerospike Nozzle

NASA Technical Reports Server (NTRS)

Simpson, Timothy W.

1998-01-01

The use of response surface models and kriging models are compared for approximating non-random, deterministic computer analyses. After discussing the traditional response surface approach for constructing polynomial models for approximation, kriging is presented as an alternative statistical-based approximation method for the design and analysis of computer experiments. Both approximation methods are applied to the multidisciplinary design and analysis of an aerospike nozzle which consists of a computational fluid dynamics model and a finite element analysis model. Error analysis of the response surface and kriging models is performed along with a graphical comparison of the approximations. Four optimization problems are formulated and solved using both approximation models. While neither approximation technique consistently outperforms the other in this example, the kriging models using only a constant for the underlying global model and a Gaussian correlation function perform as well as the second order polynomial response surface models.

The Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD) Tool

EPA Pesticide Factsheets

Providing quantal response models, which are also used in the U.S. EPA benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates.

Application for managing model-based material properties for simulation-based engineering

DOEpatents

Hoffman, Edward L [Alameda, CA

2009-03-03

An application for generating a property set associated with a constitutive model of a material includes a first program module adapted to receive test data associated with the material and to extract loading conditions from the test data. A material model driver is adapted to receive the loading conditions and a property set and operable in response to the loading conditions and the property set to generate a model response for the material. A numerical optimization module is adapted to receive the test data and the model response and operable in response to the test data and the model response to generate the property set.

A Mixed Effects Randomized Item Response Model

ERIC Educational Resources Information Center

Fox, J.-P.; Wyrick, Cheryl

2008-01-01

The randomized response technique ensures that individual item responses, denoted as true item responses, are randomized before observing them and so-called randomized item responses are observed. A relationship is specified between randomized item response data and true item response data. True item response data are modeled with a (non)linear…

Nested Logit Models for Multiple-Choice Item Response Data

ERIC Educational Resources Information Center

Suh, Youngsuk; Bolt, Daniel M.

2010-01-01

Nested logit item response models for multiple-choice data are presented. Relative to previous models, the new models are suggested to provide a better approximation to multiple-choice items where the application of a solution strategy precedes consideration of response options. In practice, the models also accommodate collapsibility across all…

Discrete Latent Markov Models for Normally Distributed Response Data

ERIC Educational Resources Information Center

Schmittmann, Verena D.; Dolan, Conor V.; van der Maas, Han L. J.; Neale, Michael C.

2005-01-01

Van de Pol and Langeheine (1990) presented a general framework for Markov modeling of repeatedly measured discrete data. We discuss analogical single indicator models for normally distributed responses. In contrast to discrete models, which have been studied extensively, analogical continuous response models have hardly been considered. These…

Distinguishing Fast and Slow Processes in Accuracy - Response Time Data

PubMed Central

Coomans, Frederik; Hofman, Abe; Brinkhuis, Matthieu; van der Maas, Han L. J.; Maris, Gunter

2016-01-01

We investigate the relation between speed and accuracy within problem solving in its simplest non-trivial form. We consider tests with only two items and code the item responses in two binary variables: one indicating the response accuracy, and one indicating the response speed. Despite being a very basic setup, it enables us to study item pairs stemming from a broad range of domains such as basic arithmetic, first language learning, intelligence-related problems, and chess, with large numbers of observations for every pair of problems under consideration. We carry out a survey over a large number of such item pairs and compare three types of psychometric accuracy-response time models present in the literature: two ‘one-process’ models, the first of which models accuracy and response time as conditionally independent and the second of which models accuracy and response time as conditionally dependent, and a ‘two-process’ model which models accuracy contingent on response time. We find that the data clearly violates the restrictions imposed by both one-process models and requires additional complexity which is parsimoniously provided by the two-process model. We supplement our survey with an analysis of the erroneous responses for an example item pair and demonstrate that there are very significant differences between the types of errors in fast and slow responses. PMID:27167518

Cognitive psychology meets psychometric theory: on the relation between process models for decision making and latent variable models for individual differences.

PubMed

van der Maas, Han L J; Molenaar, Dylan; Maris, Gunter; Kievit, Rogier A; Borsboom, Denny

2011-04-01

This article analyzes latent variable models from a cognitive psychology perspective. We start by discussing work by Tuerlinckx and De Boeck (2005), who proved that a diffusion model for 2-choice response processes entails a 2-parameter logistic item response theory (IRT) model for individual differences in the response data. Following this line of reasoning, we discuss the appropriateness of IRT for measuring abilities and bipolar traits, such as pro versus contra attitudes. Surprisingly, if a diffusion model underlies the response processes, IRT models are appropriate for bipolar traits but not for ability tests. A reconsideration of the concept of ability that is appropriate for such situations leads to a new item response model for accuracy and speed based on the idea that ability has a natural zero point. The model implies fundamentally new ways to think about guessing, response speed, and person fit in IRT. We discuss the relation between this model and existing models as well as implications for psychology and psychometrics. 2011 APA, all rights reserved

Model of the transient neurovascular response based on prompt arterial dilation

PubMed Central

Kim, Jung Hwan; Khan, Reswanul; Thompson, Jeffrey K; Ress, David

2013-01-01

Brief neural stimulation results in a stereotypical pattern of vascular and metabolic response that is the basis for popular brain-imaging methods such as functional magnetic resonance imagine. However, the mechanisms of transient oxygen transport and its coupling to cerebral blood flow (CBF) and oxygen metabolism (CMRO2) are poorly understood. Recent experiments show that brief stimulation produces prompt arterial vasodilation rather than venous vasodilation. This work provides a neurovascular response model for brief stimulation based on transient arterial effects using one-dimensional convection–diffusion transport. Hemoglobin oxygen dissociation is included to enable predictions of absolute oxygen concentrations. Arterial CBF response is modeled using a lumped linear flow model, and CMRO2 response is modeled using a gamma function. Using six parameters, the model successfully fit 161/166 measured extravascular oxygen time courses obtained for brief visual stimulation in cat cerebral cortex. Results show how CBF and CMRO2 responses compete to produce the observed features of the hemodynamic response: initial dip, hyperoxic peak, undershoot, and ringing. Predicted CBF and CMRO2 response amplitudes are consistent with experimental measurements. This model provides a powerful framework to quantitatively interpret oxygen transport in the brain; in particular, its intravascular oxygen concentration predictions provide a new model for fMRI responses. PMID:23756690

A distributed lag approach to fitting non-linear dose-response models in particulate matter air pollution time series investigations.

PubMed

Roberts, Steven; Martin, Michael A

2007-06-01

The majority of studies that have investigated the relationship between particulate matter (PM) air pollution and mortality have assumed a linear dose-response relationship and have used either a single-day's PM or a 2- or 3-day moving average of PM as the measure of PM exposure. Both of these modeling choices have come under scrutiny in the literature, the linear assumption because it does not allow for non-linearities in the dose-response relationship, and the use of the single- or multi-day moving average PM measure because it does not allow for differential PM-mortality effects spread over time. These two problems have been dealt with on a piecemeal basis with non-linear dose-response models used in some studies and distributed lag models (DLMs) used in others. In this paper, we propose a method for investigating the shape of the PM-mortality dose-response relationship that combines a non-linear dose-response model with a DLM. This combined model will be shown to produce satisfactory estimates of the PM-mortality dose-response relationship in situations where non-linear dose response models and DLMs alone do not; that is, the combined model did not systemically underestimate or overestimate the effect of PM on mortality. The combined model is applied to ten cities in the US and a pooled dose-response model formed. When fitted with a change-point value of 60 microg/m(3), the pooled model provides evidence for a positive association between PM and mortality. The combined model produced larger estimates for the effect of PM on mortality than when using a non-linear dose-response model or a DLM in isolation. For the combined model, the estimated percentage increase in mortality for PM concentrations of 25 and 75 microg/m(3) were 3.3% and 5.4%, respectively. In contrast, the corresponding values from a DLM used in isolation were 1.2% and 3.5%, respectively.

A Comparison of Graded Response and Rasch Partial Credit Models with Subjective Well-Being.

ERIC Educational Resources Information Center

Baker, John G.; Rounds, James B.; Zevon, Michael A.

2000-01-01

Compared two multiple category item response theory models using a data set of 52 mood terms with 713 undergraduate psychology students. Comparative model fit for the Samejima (F. Samejima, 1966) logistic model for graded responses and the Masters (G. Masters, 1982) partial credit model favored the former model for this data set. (SLD)

Modeling winter wheat phenological responses to water deficits in the Unified Plant Growth Model (UPGM) component of the spatially distributed Agricultural Ecosystem Services (AgES) model

USDA-ARS?s Scientific Manuscript database

Accurately predicting phenology in crop simulation models is critical for correctly simulating crop production. While extensive work in modeling phenology has focused on the temperature response function (resulting in robust phenology models), limited work on quantifying the phenological responses t...

Bayesian Analysis of Multidimensional Item Response Theory Models: A Discussion and Illustration of Three Response Style Models

ERIC Educational Resources Information Center

Leventhal, Brian C.; Stone, Clement A.

2018-01-01

Interest in Bayesian analysis of item response theory (IRT) models has grown tremendously due to the appeal of the paradigm among psychometricians, advantages of these methods when analyzing complex models, and availability of general-purpose software. Possible models include models which reflect multidimensionality due to designed test structure,…

Sample Invariance of the Structural Equation Model and the Item Response Model: A Case Study.

ERIC Educational Resources Information Center

Breithaupt, Krista; Zumbo, Bruno D.

2002-01-01

Evaluated the sample invariance of item discrimination statistics in a case study using real data, responses of 10 random samples of 500 people to a depression scale. Results lend some support to the hypothesized superiority of a two-parameter item response model over the common form of structural equation modeling, at least when responses are…

Evaluating a Computational Model of Social Causality and Responsibility

DTIC Science & Technology

2006-01-01

Evaluating a Computational Model of Social Causality and Responsibility Wenji Mao University of Southern California Institute for Creative...empirically evaluate a computa- tional model of social causality and responsibility against human social judgments. Results from our experimental...developed a general computational model of social cau- sality and responsibility [10, 11] that formalizes the factors people use in reasoning about

Modelling the isometric force response to multiple pulse stimuli in locust skeletal muscle.

PubMed

Wilson, Emma; Rustighi, Emiliano; Mace, Brian R; Newland, Philip L

2011-02-01

An improved model of locust skeletal muscle will inform on the general behaviour of invertebrate and mammalian muscle with the eventual aim of improving biomedical models of human muscles, embracing prosthetic construction and muscle therapy. In this article, the isometric response of the locust hind leg extensor muscle to input pulse trains is investigated. Experimental data was collected by stimulating the muscle directly and measuring the force at the tibia. The responses to constant frequency stimulus trains of various frequencies and number of pulses were decomposed into the response to each individual stimulus. Each individual pulse response was then fitted to a model, it being assumed that the response to each pulse could be approximated as an impulse response and was linear, no assumption were made about the model order. When the interpulse frequency (IPF) was low and the number of pulses in the train small, a second-order model provided a good fit to each pulse. For moderate IPF or for long pulse trains a linear third-order model provided a better fit to the response to each pulse. The fit using a second-order model deteriorated with increasing IPF. When the input comprised higher IPFs with a large number of pulses the assumptions that the response was linear could not be confirmed. A generalised model is also presented. This model is second-order, and contains two nonlinear terms. The model is able to capture the force response to a range of inputs. This includes cases where the input comprised of higher frequency pulse trains and the assumption of quasi-linear behaviour could not be confirmed.

Multivariate longitudinal data analysis with mixed effects hidden Markov models.

PubMed

Raffa, Jesse D; Dubin, Joel A

2015-09-01

Multiple longitudinal responses are often collected as a means to capture relevant features of the true outcome of interest, which is often hidden and not directly measurable. We outline an approach which models these multivariate longitudinal responses as generated from a hidden disease process. We propose a class of models which uses a hidden Markov model with separate but correlated random effects between multiple longitudinal responses. This approach was motivated by a smoking cessation clinical trial, where a bivariate longitudinal response involving both a continuous and a binomial response was collected for each participant to monitor smoking behavior. A Bayesian method using Markov chain Monte Carlo is used. Comparison of separate univariate response models to the bivariate response models was undertaken. Our methods are demonstrated on the smoking cessation clinical trial dataset, and properties of our approach are examined through extensive simulation studies. © 2015, The International Biometric Society.

A Bivariate Generalized Linear Item Response Theory Modeling Framework to the Analysis of Responses and Response Times.

PubMed

Molenaar, Dylan; Tuerlinckx, Francis; van der Maas, Han L J

2015-01-01

A generalized linear modeling framework to the analysis of responses and response times is outlined. In this framework, referred to as bivariate generalized linear item response theory (B-GLIRT), separate generalized linear measurement models are specified for the responses and the response times that are subsequently linked by cross-relations. The cross-relations can take various forms. Here, we focus on cross-relations with a linear or interaction term for ability tests, and cross-relations with a curvilinear term for personality tests. In addition, we discuss how popular existing models from the psychometric literature are special cases in the B-GLIRT framework depending on restrictions in the cross-relation. This allows us to compare existing models conceptually and empirically. We discuss various extensions of the traditional models motivated by practical problems. We also illustrate the applicability of our approach using various real data examples, including data on personality and cognitive ability.

Multi-Wheat-Model Ensemble Responses to Interannual Climate Variability

NASA Technical Reports Server (NTRS)

Ruane, Alex C.; Hudson, Nicholas I.; Asseng, Senthold; Camarrano, Davide; Ewert, Frank; Martre, Pierre; Boote, Kenneth J.; Thorburn, Peter J.; Aggarwal, Pramod K.; Angulo, Carlos

2016-01-01

We compare 27 wheat models' yield responses to interannual climate variability, analyzed at locations in Argentina, Australia, India, and The Netherlands as part of the Agricultural Model Intercomparison and Improvement Project (AgMIP) Wheat Pilot. Each model simulated 1981e2010 grain yield, and we evaluate results against the interannual variability of growing season temperature, precipitation, and solar radiation. The amount of information used for calibration has only a minor effect on most models' climate response, and even small multi-model ensembles prove beneficial. Wheat model clusters reveal common characteristics of yield response to climate; however models rarely share the same cluster at all four sites indicating substantial independence. Only a weak relationship (R2 0.24) was found between the models' sensitivities to interannual temperature variability and their response to long-termwarming, suggesting that additional processes differentiate climate change impacts from observed climate variability analogs and motivating continuing analysis and model development efforts.

Modeling non-linear growth responses to temperature and hydrology in wetland trees

NASA Astrophysics Data System (ADS)

Keim, R.; Allen, S. T.

2016-12-01

Growth responses of wetland trees to flooding and climate variations are difficult to model because they depend on multiple, apparently interacting factors, but are a critical link in hydrological control of wetland carbon budgets. To more generally understand tree growth to hydrological forcing, we modeled non-linear responses of tree ring growth to flooding and climate at sub-annual time steps, using Vaganov-Shashkin response functions. We calibrated the model to six baldcypress tree-ring chronologies from two hydrologically distinct sites in southern Louisiana, and tested several hypotheses of plasticity in wetlands tree responses to interacting environmental variables. The model outperformed traditional multiple linear regression. More importantly, optimized response parameters were generally similar among sites with varying hydrological conditions, suggesting generality to the functions. Model forms that included interacting responses to multiple forcing factors were more effective than were single response functions, indicating the principle of a single limiting factor is not correct in wetlands and both climatic and hydrological variables must be considered in predicting responses to hydrological or climate change.

On the Relationship Between Classical Test Theory and Item Response Theory: From One to the Other and Back.

PubMed

Raykov, Tenko; Marcoulides, George A

2016-04-01

The frequently neglected and often misunderstood relationship between classical test theory and item response theory is discussed for the unidimensional case with binary measures and no guessing. It is pointed out that popular item response models can be directly obtained from classical test theory-based models by accounting for the discrete nature of the observed items. Two distinct observational equivalence approaches are outlined that render the item response models from corresponding classical test theory-based models, and can each be used to obtain the former from the latter models. Similarly, classical test theory models can be furnished using the reverse application of either of those approaches from corresponding item response models.

Item response theory - A first approach

NASA Astrophysics Data System (ADS)

Nunes, Sandra; Oliveira, Teresa; Oliveira, Amílcar

2017-07-01

The Item Response Theory (IRT) has become one of the most popular scoring frameworks for measurement data, frequently used in computerized adaptive testing, cognitively diagnostic assessment and test equating. According to Andrade et al. (2000), IRT can be defined as a set of mathematical models (Item Response Models - IRM) constructed to represent the probability of an individual giving the right answer to an item of a particular test. The number of Item Responsible Models available to measurement analysis has increased considerably in the last fifteen years due to increasing computer power and due to a demand for accuracy and more meaningful inferences grounded in complex data. The developments in modeling with Item Response Theory were related with developments in estimation theory, most remarkably Bayesian estimation with Markov chain Monte Carlo algorithms (Patz & Junker, 1999). The popularity of Item Response Theory has also implied numerous overviews in books and journals, and many connections between IRT and other statistical estimation procedures, such as factor analysis and structural equation modeling, have been made repeatedly (Van der Lindem & Hambleton, 1997). As stated before the Item Response Theory covers a variety of measurement models, ranging from basic one-dimensional models for dichotomously and polytomously scored items and their multidimensional analogues to models that incorporate information about cognitive sub-processes which influence the overall item response process. The aim of this work is to introduce the main concepts associated with one-dimensional models of Item Response Theory, to specify the logistic models with one, two and three parameters, to discuss some properties of these models and to present the main estimation procedures.

Extreme Response Style: Which Model Is Best?

ERIC Educational Resources Information Center

Leventhal, Brian

2017-01-01

More robust and rigorous psychometric models, such as multidimensional Item Response Theory models, have been advocated for survey applications. However, item responses may be influenced by construct-irrelevant variance factors such as preferences for extreme response options. Through empirical and simulation methods, this study evaluates the use…

Driver Vision Based Perception-Response Time Prediction and Assistance Model on Mountain Highway Curve.

PubMed

Li, Yi; Chen, Yuren

2016-12-30

To make driving assistance system more humanized, this study focused on the prediction and assistance of drivers' perception-response time on mountain highway curves. Field tests were conducted to collect real-time driving data and driver vision information. A driver-vision lane model quantified curve elements in drivers' vision. A multinomial log-linear model was established to predict perception-response time with traffic/road environment information, driver-vision lane model, and mechanical status (last second). A corresponding assistance model showed a positive impact on drivers' perception-response times on mountain highway curves. Model results revealed that the driver-vision lane model and visual elements did have important influence on drivers' perception-response time. Compared with roadside passive road safety infrastructure, proper visual geometry design, timely visual guidance, and visual information integrality of a curve are significant factors for drivers' perception-response time.

A Conditional Joint Modeling Approach for Locally Dependent Item Responses and Response Times

ERIC Educational Resources Information Center

Meng, Xiang-Bin; Tao, Jian; Chang, Hua-Hua

2015-01-01

The assumption of conditional independence between the responses and the response times (RTs) for a given person is common in RT modeling. However, when the speed of a test taker is not constant, this assumption will be violated. In this article we propose a conditional joint model for item responses and RTs, which incorporates a covariance…

A competitive binding model predicts the response of mammalian olfactory receptors to mixtures

NASA Astrophysics Data System (ADS)

Singh, Vijay; Murphy, Nicolle; Mainland, Joel; Balasubramanian, Vijay

Most natural odors are complex mixtures of many odorants, but due to the large number of possible mixtures only a small fraction can be studied experimentally. To get a realistic understanding of the olfactory system we need methods to predict responses to complex mixtures from single odorant responses. Focusing on mammalian olfactory receptors (ORs in mouse and human), we propose a simple biophysical model for odor-receptor interactions where only one odor molecule can bind to a receptor at a time. The resulting competition for occupancy of the receptor accounts for the experimentally observed nonlinear mixture responses. We first fit a dose-response relationship to individual odor responses and then use those parameters in a competitive binding model to predict mixture responses. With no additional parameters, the model predicts responses of 15 (of 18 tested) receptors to within 10 - 30 % of the observed values, for mixtures with 2, 3 and 12 odorants chosen from a panel of 30. Extensions of our basic model with odorant interactions lead to additional nonlinearities observed in mixture response like suppression, cooperativity, and overshadowing. Our model provides a systematic framework for characterizing and parameterizing such mixing nonlinearities from mixture response data.

Pain and the defense response: structural equation modeling reveals a coordinated psychophysiological response to increasing painful stimulation.

PubMed

Donaldson, Gary W; Chapman, C Richard; Nakamura, Yoshi; Bradshaw, David H; Jacobson, Robert C; Chapman, Christopher N

2003-03-01

The defense response theory implies that individuals should respond to increasing levels of painful stimulation with correlated increases in affectively mediated psychophysiological responses. This paper employs structural equation modeling to infer the latent processes responsible for correlated growth in the pain report, evoked potential amplitudes, pupil dilation, and skin conductance of 92 normal volunteers who experienced 144 trials of three levels of increasingly painful electrical stimulation. The analysis assumed a two-level model of latent growth as a function of stimulus level. The first level of analysis formulated a nonlinear growth model for each response measure, and allowed intercorrelations among the parameters of these models across individuals. The second level of analysis posited latent process factors to account for these intercorrelations. The best-fitting parsimonious model suggests that two latent processes account for the correlations. One of these latent factors, the activation threshold, determines the initial threshold response, while the other, the response gradient, indicates the magnitude of the coherent increase in response with stimulus level. Collectively, these two second-order factors define the defense response, a broad construct comprising both subjective pain evaluation and physiological mechanisms.

A mathematical function for the description of nutrient-response curve

PubMed Central

Ahmadi, Hamed

2017-01-01

Several mathematical equations have been proposed to modeling nutrient-response curve for animal and human justified on the goodness of fit and/or on the biological mechanism. In this paper, a functional form of a generalized quantitative model based on Rayleigh distribution principle for description of nutrient-response phenomena is derived. The three parameters governing the curve a) has biological interpretation, b) may be used to calculate reliable estimates of nutrient response relationships, and c) provide the basis for deriving relationships between nutrient and physiological responses. The new function was successfully applied to fit the nutritional data obtained from 6 experiments including a wide range of nutrients and responses. An evaluation and comparison were also done based simulated data sets to check the suitability of new model and four-parameter logistic model for describing nutrient responses. This study indicates the usefulness and wide applicability of the new introduced, simple and flexible model when applied as a quantitative approach to characterizing nutrient-response curve. This new mathematical way to describe nutritional-response data, with some useful biological interpretations, has potential to be used as an alternative approach in modeling nutritional responses curve to estimate nutrient efficiency and requirements. PMID:29161271

A New Model for Acquiescence at the Interface of Psychometrics and Cognitive Psychology.

PubMed

Plieninger, Hansjörg; Heck, Daniel W

2018-05-29

When measuring psychological traits, one has to consider that respondents often show content-unrelated response behavior in answering questionnaires. To disentangle the target trait and two such response styles, extreme responding and midpoint responding, Böckenholt ( 2012a ) developed an item response model based on a latent processing tree structure. We propose a theoretically motivated extension of this model to also measure acquiescence, the tendency to agree with both regular and reversed items. Substantively, our approach builds on multinomial processing tree (MPT) models that are used in cognitive psychology to disentangle qualitatively distinct processes. Accordingly, the new model for response styles assumes a mixture distribution of affirmative responses, which are either determined by the underlying target trait or by acquiescence. In order to estimate the model parameters, we rely on Bayesian hierarchical estimation of MPT models. In simulations, we show that the model provides unbiased estimates of response styles and the target trait, and we compare the new model and Böckenholt's model in a recovery study. An empirical example from personality psychology is used for illustrative purposes.

Understanding the Asian summer monsoon response to greenhouse warming: the relative roles of direct radiative forcing and sea surface temperature change

NASA Astrophysics Data System (ADS)

Li, Xiaoqiong; Ting, Mingfang

2017-10-01

Future hydroclimate projections from state-of-the-art climate models show large uncertainty and model spread, particularly in the tropics and over the monsoon regions. The precipitation and circulation responses to rising greenhouse gases involve a fast component associated with direct radiative forcing and a slow component associated with sea surface temperature (SST) warming; the relative importance of the two may contribute to model discrepancies. In this study, regional hydroclimate responses to greenhouse warming are assessed using output from coupled general circulation models in the Coupled Model Intercomparison Project-Phase 5 (CMIP5) and idealized atmospheric general circulation model experiments from the Atmosphere Model Intercomparison Project. The thermodynamic and dynamic mechanisms causing the rainfall changes are examined using moisture budget analysis. Results show that direct radiative forcing and SST change exert significantly different responses both over land and ocean. For most part of the Asian monsoon region, the summertime rainfall changes are dominated by the direct CO2 radiative effect through enhanced monsoon circulation. The response to SST warming shows a larger model spread compared to direct radiative forcing, possibly due to the cancellation between the thermodynamical and dynamical components. While the thermodynamical response of the Asian monsoon is robust across the models, there is a lack of consensus for the dynamical response among the models and weak multi-model mean responses in the CMIP5 ensemble, which may be related to the multiple physical processes evolving on different time scales.

Impact of the time scale of model sensitivity response on coupled model parameter estimation

NASA Astrophysics Data System (ADS)

Liu, Chang; Zhang, Shaoqing; Li, Shan; Liu, Zhengyu

2017-11-01

That a model has sensitivity responses to parameter uncertainties is a key concept in implementing model parameter estimation using filtering theory and methodology. Depending on the nature of associated physics and characteristic variability of the fluid in a coupled system, the response time scales of a model to parameters can be different, from hourly to decadal. Unlike state estimation, where the update frequency is usually linked with observational frequency, the update frequency for parameter estimation must be associated with the time scale of the model sensitivity response to the parameter being estimated. Here, with a simple coupled model, the impact of model sensitivity response time scales on coupled model parameter estimation is studied. The model includes characteristic synoptic to decadal scales by coupling a long-term varying deep ocean with a slow-varying upper ocean forced by a chaotic atmosphere. Results show that, using the update frequency determined by the model sensitivity response time scale, both the reliability and quality of parameter estimation can be improved significantly, and thus the estimated parameters make the model more consistent with the observation. These simple model results provide a guideline for when real observations are used to optimize the parameters in a coupled general circulation model for improving climate analysis and prediction initialization.

Generalizability in Item Response Modeling

ERIC Educational Resources Information Center

Briggs, Derek C.; Wilson, Mark

2007-01-01

An approach called generalizability in item response modeling (GIRM) is introduced in this article. The GIRM approach essentially incorporates the sampling model of generalizability theory (GT) into the scaling model of item response theory (IRT) by making distributional assumptions about the relevant measurement facets. By specifying a random…

An Immuno-epidemiological Model of Paratuberculosis

NASA Astrophysics Data System (ADS)

Martcheva, M.

2011-11-01

The primary objective of this article is to introduce an immuno-epidemiological model of paratuberculosis (Johne's disease). To develop the immuno-epidemiological model, we first develop an immunological model and an epidemiological model. Then, we link the two models through time-since-infection structure and parameters of the epidemiological model. We use the nested approach to compose the immuno-epidemiological model. Our immunological model captures the switch between the T-cell immune response and the antibody response in Johne's disease. The epidemiological model is a time-since-infection model and captures the variability of transmission rate and the vertical transmission of the disease. We compute the immune-response-dependent epidemiological reproduction number. Our immuno-epidemiological model can be used for investigation of the impact of the immune response on the epidemiology of Johne's disease.

Cognitive diagnosis modelling incorporating item response times.

PubMed

Zhan, Peida; Jiao, Hong; Liao, Dandan

2018-05-01

To provide more refined diagnostic feedback with collateral information in item response times (RTs), this study proposed joint modelling of attributes and response speed using item responses and RTs simultaneously for cognitive diagnosis. For illustration, an extended deterministic input, noisy 'and' gate (DINA) model was proposed for joint modelling of responses and RTs. Model parameter estimation was explored using the Bayesian Markov chain Monte Carlo (MCMC) method. The PISA 2012 computer-based mathematics data were analysed first. These real data estimates were treated as true values in a subsequent simulation study. A follow-up simulation study with ideal testing conditions was conducted as well to further evaluate model parameter recovery. The results indicated that model parameters could be well recovered using the MCMC approach. Further, incorporating RTs into the DINA model would improve attribute and profile correct classification rates and result in more accurate and precise estimation of the model parameters. © 2017 The British Psychological Society.

Toward a unified approach to dose-response modeling in ecotoxicology.

PubMed

Ritz, Christian

2010-01-01

This study reviews dose-response models that are used in ecotoxicology. The focus lies on clarification of differences and similarities between models, and as a side effect, their different guises in ecotoxicology are unravelled. A look at frequently used dose-response models reveals major discrepancies, among other things in naming conventions. Therefore, there is a need for a unified view on dose-response modeling in order to improve the understanding of it and to facilitate communication and comparison of findings across studies, thus realizing its full potential. This study attempts to establish a general framework that encompasses most dose-response models that are of interest to ecotoxicologists in practice. The framework includes commonly used models such as the log-logistic and Weibull models, but also features entire suites of models as found in various guidance documents. An outline on how the proposed framework can be implemented in statistical software systems is also provided.

Simple nonlinear modelling of earthquake response in torsionally coupled R/C structures: A preliminary study

NASA Astrophysics Data System (ADS)

Saiidi, M.

1982-07-01

The equivalent of a single degree of freedom (SDOF) nonlinear model, the Q-model-13, was examined. The study intended to: (1) determine the seismic response of a torsionally coupled building based on the multidegree of freedom (MDOF) and (SDOF) nonlinear models; and (2) develop a simple SDOF nonlinear model to calculate displacement history of structures with eccentric centers of mass and stiffness. It is shown that planar models are able to yield qualitative estimates of the response of the building. The model is used to estimate the response of a hypothetical six-story frame wall reinforced concrete building with torsional coupling, using two different earthquake intensities. It is shown that the Q-Model-13 can lead to a satisfactory estimate of the response of the structure in both cases.

Can a Mathematical Model Predict an Individual’s Trait-like Response to Both Total and Partial Sleep Loss?

DTIC Science & Technology

2015-01-01

Can a mathematical model predict an individual’s trait-like response to both total and partial sleep loss? SR IDHAR RAMAKR I SHNAN 1 , WE I LU 1 , SR...biomathematical model, psychomotor vigilance task, sleep -loss phenotype, trait preservation, two-process model Correspondence Jaques Reifman, PhD...trait-like response to sleep loss. However, it is not known whether this trait-like response can be captured by a mathemat- ical model from only one

A Bifactor Multidimensional Item Response Theory Model for Differential Item Functioning Analysis on Testlet-Based Items

ERIC Educational Resources Information Center

Fukuhara, Hirotaka; Kamata, Akihito

2011-01-01

A differential item functioning (DIF) detection method for testlet-based data was proposed and evaluated in this study. The proposed DIF model is an extension of a bifactor multidimensional item response theory (MIRT) model for testlets. Unlike traditional item response theory (IRT) DIF models, the proposed model takes testlet effects into…

Estimating the Nominal Response Model under Nonnormal Conditions

ERIC Educational Resources Information Center

Preston, Kathleen Suzanne Johnson; Reise, Steven Paul

2014-01-01

The nominal response model (NRM), a much understudied polytomous item response theory (IRT) model, provides researchers the unique opportunity to evaluate within-item category distinctions. Polytomous IRT models, such as the NRM, are frequently applied to psychological assessments representing constructs that are unlikely to be normally…

The Development of a Model of Culturally Responsive Science and Mathematics Teaching

ERIC Educational Resources Information Center

Hernandez, Cecilia M.; Morales, Amanda R.; Shroyer, M. Gail

2013-01-01

This qualitative theoretical study was conducted in response to the current need for an inclusive and comprehensive model to guide the preparation and assessment of teacher candidates for culturally responsive teaching. The process of developing a model of culturally responsive teaching involved three steps: a comprehensive review of the…

Randomized Item Response Theory Models

ERIC Educational Resources Information Center

Fox, Jean-Paul

2005-01-01

The randomized response (RR) technique is often used to obtain answers on sensitive questions. A new method is developed to measure latent variables using the RR technique because direct questioning leads to biased results. Within the RR technique is the probability of the true response modeled by an item response theory (IRT) model. The RR…

Descriptive Linear modeling of steady-state visual evoked response

NASA Technical Reports Server (NTRS)

Levison, W. H.; Junker, A. M.; Kenner, K.

1986-01-01

A study is being conducted to explore use of the steady state visual-evoke electrocortical response as an indicator of cognitive task loading. Application of linear descriptive modeling to steady state Visual Evoked Response (VER) data is summarized. Two aspects of linear modeling are reviewed: (1) unwrapping the phase-shift portion of the frequency response, and (2) parsimonious characterization of task-loading effects in terms of changes in model parameters. Model-based phase unwrapping appears to be most reliable in applications, such as manual control, where theoretical models are available. Linear descriptive modeling of the VER has not yet been shown to provide consistent and readily interpretable results.

An evidence accumulation model for conflict detection performance in a simulated air traffic control task.

PubMed

Neal, Andrew; Kwantes, Peter J

2009-04-01

The aim of this article is to develop a formal model of conflict detection performance. Our model assumes that participants iteratively sample evidence regarding the state of the world and accumulate it over time. A decision is made when the evidence reaches a threshold that changes over time in response to the increasing urgency of the task. Two experiments were conducted to examine the effects of conflict geometry and timing on response proportions and response time. The model is able to predict the observed pattern of response times, including a nonmonotonic relationship between distance at point of closest approach and response time, as well as effects of angle of approach and relative velocity. The results demonstrate that evidence accumulation models provide a good account of performance on a conflict detection task. Evidence accumulation models are a form of dynamic signal detection theory, allowing for the analysis of response times as well as response proportions, and can be used for simulating human performance on dynamic decision tasks.

Handbook of Polytomous Item Response Theory Models

ERIC Educational Resources Information Center

Nering, Michael L., Ed.; Ostini, Remo, Ed.

2010-01-01

This comprehensive "Handbook" focuses on the most used polytomous item response theory (IRT) models. These models help us understand the interaction between examinees and test questions where the questions have various response categories. The book reviews all of the major models and includes discussions about how and where the models…

The Gradual Increase of Responsibility Model: Coaching for Teacher Change

ERIC Educational Resources Information Center

Collet, Vicki S.

2012-01-01

This study examines the gradual increase of responsibility (GIR) model for teacher coaching (Collet, 2008), an adaptation of Pearson and Gallagher's (1983) Gradual Release of Responsibility model. In GIR, instructional coaches model, make recommendations, ask probing questions, affirm teachers' appropriate decisions, and praise in order to provide…

Design considerations and analysis planning of a phase 2a proof of concept study in rheumatoid arthritis in the presence of possible non-monotonicity.

PubMed

Liu, Feng; Walters, Stephen J; Julious, Steven A

2017-10-02

It is important to quantify the dose response for a drug in phase 2a clinical trials so the optimal doses can then be selected for subsequent late phase trials. In a phase 2a clinical trial of new lead drug being developed for the treatment of rheumatoid arthritis (RA), a U-shaped dose response curve was observed. In the light of this result further research was undertaken to design an efficient phase 2a proof of concept (PoC) trial for a follow-on compound using the lessons learnt from the lead compound. The planned analysis for the Phase 2a trial for GSK123456 was a Bayesian Emax model which assumes the dose-response relationship follows a monotonic sigmoid "S" shaped curve. This model was found to be suboptimal to model the U-shaped dose response observed in the data from this trial and alternatives approaches were needed to be considered for the next compound for which a Normal dynamic linear model (NDLM) is proposed. This paper compares the statistical properties of the Bayesian Emax model and NDLM model and both models are evaluated using simulation in the context of adaptive Phase 2a PoC design under a variety of assumed dose response curves: linear, Emax model, U-shaped model, and flat response. It is shown that the NDLM method is flexible and can handle a wide variety of dose-responses, including monotonic and non-monotonic relationships. In comparison to the NDLM model the Emax model excelled with higher probability of selecting ED90 and smaller average sample size, when the true dose response followed Emax like curve. In addition, the type I error, probability of incorrectly concluding a drug may work when it does not, is inflated with the Bayesian NDLM model in all scenarios which would represent a development risk to pharmaceutical company. The bias, which is the difference between the estimated effect from the Emax and NDLM models and the simulated value, is comparable if the true dose response follows a placebo like curve, an Emax like curve, or log linear shape curve under fixed dose allocation, no adaptive allocation, half adaptive and adaptive scenarios. The bias though is significantly increased for the Emax model if the true dose response follows a U-shaped curve. In most cases the Bayesian Emax model works effectively and efficiently, with low bias and good probability of success in case of monotonic dose response. However, if there is a belief that the dose response could be non-monotonic then the NDLM is the superior model to assess the dose response.

Mathematical modeling of human cardiovascular system for simulation of orthostatic response

NASA Technical Reports Server (NTRS)

Melchior, F. M.; Srinivasan, R. S.; Charles, J. B.

1992-01-01

This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.

Overview of the SVOM Gamma-Ray Burst mission under development with a focus on its Trigger system

NASA Astrophysics Data System (ADS)

Schanne, Stephane

2017-08-01

The SVOM mission (Space-based Variable Objects Monitor) is a Chinese-French satellite mission under development, devoted to collecting a complete sample of Gamma-Ray Bursts (GRBs) observed at multi-wavelengths with a high fraction of redshift determinations. In January 2017 the mission entered Phase C, starting officially construction, and the launch is foreseen in 2021. The SVOM satellite is equipped with 4 instruments, 2 of which cover the prompt GRB phase. The ECLAIRs coded-mask imager surveys a 2-sr large portion of the sky in the 4-150 keV energy range, well suited for the detection of X-ray rich and highly redshifted GRBs. The ECLAIRs trigger system continuously searches for GRBs using two algorithms, a count-rate trigger for short time scales and an image trigger for long time scales. In case of a localized new GRB candidate or a bright outburst of a known source, it promptly requests a satellite slew and sends an alert to ground. The onboard GRM (Gamma-Ray Monitor) extends the prompt energy coverage up to 5 MeV. After slew, 2 more onboard instruments study the GRB afterglow and refine the GRB localization: the MXT (Multi-pore optics X-ray Telescope) and the VT (Visible Telescope). Two types of ground telescopes are dedicated to SVOM. The GFTs (Ground Follow-up Telescopes) repoint autonomously to GRB alerts, refine their localization and provide photometric redshift. The SVOM observing strategy with roughly antisolar pointing combined with Galactic plane avoidance, ensures that most GRBs are quickly visible by the GFTs and large spectroscopic telescopes. The GWAC (Ground Wide Angle Camera) will observe the sky simultaneously with ECLAIRs to detect prompt optical GRB emissions. Today part of the GWAC is already operational. The SVOM GRB program is complemented by pre-planned target observations and ground-commanded targets of opportunity, e.g. to search for electromagnetic counterparts of gravity-wave events. On behalf of the SVOM and ECLAIRs teams, this paper presents an overview of SVOM with a focus on its GRB trigger system.

On the deterministic and stochastic use of hydrologic models

USGS Publications Warehouse

Farmer, William H.; Vogel, Richard M.

2016-01-01

Environmental simulation models, such as precipitation-runoff watershed models, are increasingly used in a deterministic manner for environmental and water resources design, planning, and management. In operational hydrology, simulated responses are now routinely used to plan, design, and manage a very wide class of water resource systems. However, all such models are calibrated to existing data sets and retain some residual error. This residual, typically unknown in practice, is often ignored, implicitly trusting simulated responses as if they are deterministic quantities. In general, ignoring the residuals will result in simulated responses with distributional properties that do not mimic those of the observed responses. This discrepancy has major implications for the operational use of environmental simulation models as is shown here. Both a simple linear model and a distributed-parameter precipitation-runoff model are used to document the expected bias in the distributional properties of simulated responses when the residuals are ignored. The systematic reintroduction of residuals into simulated responses in a manner that produces stochastic output is shown to improve the distributional properties of the simulated responses. Every effort should be made to understand the distributional behavior of simulation residuals and to use environmental simulation models in a stochastic manner.

Fast and Slow Precipitation Responses to Individual Climate Forcers: A PDRMIP Multimodel Study

NASA Technical Reports Server (NTRS)

Samset, B. H.; Myhre, G.; Forster, P.M.; Hodnebrog, O.; Andrews, T.; Faluvegi, G.; Flaschner, D.; Kasoar, M.; Kharin, V.; Kirkevag, A.;

Limits on Log Cross-Product Ratios for Item Response Models. Research Report. ETS RR-06-10

ERIC Educational Resources Information Center

Haberman, Shelby J.; Holland, Paul W.; Sinharay, Sandip

2006-01-01

Bounds are established for log cross-product ratios (log odds ratios) involving pairs of items for item response models. First, expressions for bounds on log cross-product ratios are provided for unidimensional item response models in general. Then, explicit bounds are obtained for the Rasch model and the two-parameter logistic (2PL) model.…

Fitting a Mixture Item Response Theory Model to Personality Questionnaire Data: Characterizing Latent Classes and Investigating Possibilities for Improving Prediction

ERIC Educational Resources Information Center

Maij-de Meij, Annette M.; Kelderman, Henk; van der Flier, Henk

2008-01-01

Mixture item response theory (IRT) models aid the interpretation of response behavior on personality tests and may provide possibilities for improving prediction. Heterogeneity in the population is modeled by identifying homogeneous subgroups that conform to different measurement models. In this study, mixture IRT models were applied to the…

Grade of Membership Response Time Model for Detecting Guessing Behaviors

ERIC Educational Resources Information Center

Pokropek, Artur

2016-01-01

A response model that is able to detect guessing behaviors and produce unbiased estimates in low-stake conditions using timing information is proposed. The model is a special case of the grade of membership model in which responses are modeled as partial members of a class that is affected by motivation and a class that responds only according to…

Linking an ecosystem model and a landscape model to study forest species response to climate warming

Treesearch

Hong S. He; David J. Mladenoff; Thomas R. Crow

1999-01-01

No single model can address forest change from single tree to regional scales. We discuss a framework linking an ecosystem process model {LINKAGES) with a spatial landscape model (LANDIS) to examine forest species responses to climate warming for a large, heterogeneous landscape in northern Wisconsin, USA. Individual species response at the ecosystem scale was...

Modeling Answer Change Behavior: An Application of a Generalized Item Response Tree Model

ERIC Educational Resources Information Center

Jeon, Minjeong; De Boeck, Paul; van der Linden, Wim

2017-01-01

We present a novel application of a generalized item response tree model to investigate test takers' answer change behavior. The model allows us to simultaneously model the observed patterns of the initial and final responses after an answer change as a function of a set of latent traits and item parameters. The proposed application is illustrated…

Development of Aeroservoelastic Analytical Models and Gust Load Alleviation Control Laws of a SensorCraft Wind-Tunnel Model Using Measured Data

NASA Technical Reports Server (NTRS)

Silva, Walter A.; Vartio, Eric; Shimko, Anthony; Kvaternik, Raymond G.; Eure, Kenneth W.; Scott,Robert C.

2007-01-01

Aeroservoelastic (ASE) analytical models of a SensorCraft wind-tunnel model are generated using measured data. The data was acquired during the ASE wind-tunnel test of the HiLDA (High Lift-to-Drag Active) Wing model, tested in the NASA Langley Transonic Dynamics Tunnel (TDT) in late 2004. Two time-domain system identification techniques are applied to the development of the ASE analytical models: impulse response (IR) method and the Generalized Predictive Control (GPC) method. Using measured control surface inputs (frequency sweeps) and associated sensor responses, the IR method is used to extract corresponding input/output impulse response pairs. These impulse responses are then transformed into state-space models for use in ASE analyses. Similarly, the GPC method transforms measured random control surface inputs and associated sensor responses into an AutoRegressive with eXogenous input (ARX) model. The ARX model is then used to develop the gust load alleviation (GLA) control law. For the IR method, comparison of measured with simulated responses are presented to investigate the accuracy of the ASE analytical models developed. For the GPC method, comparison of simulated open-loop and closed-loop (GLA) time histories are presented.

Development of Aeroservoelastic Analytical Models and Gust Load Alleviation Control Laws of a SensorCraft Wind-Tunnel Model Using Measured Data

NASA Technical Reports Server (NTRS)

Silva, Walter A.; Shimko, Anthony; Kvaternik, Raymond G.; Eure, Kenneth W.; Scott, Robert C.

2006-01-01

Aeroservoelastic (ASE) analytical models of a SensorCraft wind-tunnel model are generated using measured data. The data was acquired during the ASE wind-tunnel test of the HiLDA (High Lift-to-Drag Active) Wing model, tested in the NASA Langley Transonic Dynamics Tunnel (TDT) in late 2004. Two time-domain system identification techniques are applied to the development of the ASE analytical models: impulse response (IR) method and the Generalized Predictive Control (GPC) method. Using measured control surface inputs (frequency sweeps) and associated sensor responses, the IR method is used to extract corresponding input/output impulse response pairs. These impulse responses are then transformed into state-space models for use in ASE analyses. Similarly, the GPC method transforms measured random control surface inputs and associated sensor responses into an AutoRegressive with eXogenous input (ARX) model. The ARX model is then used to develop the gust load alleviation (GLA) control law. For the IR method, comparison of measured with simulated responses are presented to investigate the accuracy of the ASE analytical models developed. For the GPC method, comparison of simulated open-loop and closed-loop (GLA) time histories are presented.

Predicting multi-level drug response with gene expression profile in multiple myeloma using hierarchical ordinal regression.

PubMed

Zhang, Xinyan; Li, Bingzong; Han, Huiying; Song, Sha; Xu, Hongxia; Hong, Yating; Yi, Nengjun; Zhuang, Wenzhuo

2018-05-10

Multiple myeloma (MM), like other cancers, is caused by the accumulation of genetic abnormalities. Heterogeneity exists in the patients' response to treatments, for example, bortezomib. This urges efforts to identify biomarkers from numerous molecular features and build predictive models for identifying patients that can benefit from a certain treatment scheme. However, previous studies treated the multi-level ordinal drug response as a binary response where only responsive and non-responsive groups are considered. It is desirable to directly analyze the multi-level drug response, rather than combining the response to two groups. In this study, we present a novel method to identify significantly associated biomarkers and then develop ordinal genomic classifier using the hierarchical ordinal logistic model. The proposed hierarchical ordinal logistic model employs the heavy-tailed Cauchy prior on the coefficients and is fitted by an efficient quasi-Newton algorithm. We apply our hierarchical ordinal regression approach to analyze two publicly available datasets for MM with five-level drug response and numerous gene expression measures. Our results show that our method is able to identify genes associated with the multi-level drug response and to generate powerful predictive models for predicting the multi-level response. The proposed method allows us to jointly fit numerous correlated predictors and thus build efficient models for predicting the multi-level drug response. The predictive model for the multi-level drug response can be more informative than the previous approaches. Thus, the proposed approach provides a powerful tool for predicting multi-level drug response and has important impact on cancer studies.

Humanitarian response: improving logistics to save lives.

PubMed

McCoy, Jessica

2008-01-01

Each year, millions of people worldwide are affected by disasters, underscoring the importance of effective relief efforts. Many highly visible disaster responses have been inefficient and ineffective. Humanitarian agencies typically play a key role in disaster response (eg, procuring and distributing relief items to an affected population, assisting with evacuation, providing healthcare, assisting in the development of long-term shelter), and thus their efficiency is critical for a successful disaster response. The field of disaster and emergency response modeling is well established, but the application of such techniques to humanitarian logistics is relatively recent. This article surveys models of humanitarian response logistics and identifies promising opportunities for future work. Existing models analyze a variety of preparation and response decisions (eg, warehouse location and the distribution of relief supplies), consider both natural and manmade disasters, and typically seek to minimize cost or unmet demand. Opportunities to enhance the logistics of humanitarian response include the adaptation of models developed for general disaster response; the use of existing models, techniques, and insights from the literature on commercial supply chain management; the development of working partnerships between humanitarian aid organizations and private companies with expertise in logistics; and the consideration of behavioral factors relevant to a response. Implementable, realistic models that support the logistics of humanitarian relief can improve the preparation for and the response to disasters, which in turn can save lives.

Population activity statistics dissect subthreshold and spiking variability in V1.

PubMed

Bányai, Mihály; Koman, Zsombor; Orbán, Gergő

2017-07-01

Response variability, as measured by fluctuating responses upon repeated performance of trials, is a major component of neural responses, and its characterization is key to interpret high dimensional population recordings. Response variability and covariability display predictable changes upon changes in stimulus and cognitive or behavioral state, providing an opportunity to test the predictive power of models of neural variability. Still, there is little agreement on which model to use as a building block for population-level analyses, and models of variability are often treated as a subject of choice. We investigate two competing models, the doubly stochastic Poisson (DSP) model assuming stochasticity at spike generation, and the rectified Gaussian (RG) model tracing variability back to membrane potential variance, to analyze stimulus-dependent modulation of both single-neuron and pairwise response statistics. Using a pair of model neurons, we demonstrate that the two models predict similar single-cell statistics. However, DSP and RG models have contradicting predictions on the joint statistics of spiking responses. To test the models against data, we build a population model to simulate stimulus change-related modulations in pairwise response statistics. We use single-unit data from the primary visual cortex (V1) of monkeys to show that while model predictions for variance are qualitatively similar to experimental data, only the RG model's predictions are compatible with joint statistics. These results suggest that models using Poisson-like variability might fail to capture important properties of response statistics. We argue that membrane potential-level modeling of stochasticity provides an efficient strategy to model correlations. NEW & NOTEWORTHY Neural variability and covariability are puzzling aspects of cortical computations. For efficient decoding and prediction, models of information encoding in neural populations hinge on an appropriate model of variability. Our work shows that stimulus-dependent changes in pairwise but not in single-cell statistics can differentiate between two widely used models of neuronal variability. Contrasting model predictions with neuronal data provides hints on the noise sources in spiking and provides constraints on statistical models of population activity. Copyright © 2017 the American Physiological Society.

The development of a model of culturally responsive science and mathematics teaching

NASA Astrophysics Data System (ADS)

Hernandez, Cecilia M.; Morales, Amanda R.; Shroyer, M. Gail

2013-12-01

This qualitative theoretical study was conducted in response to the current need for an inclusive and comprehensive model to guide the preparation and assessment of teacher candidates for culturally responsive teaching. The process of developing a model of culturally responsive teaching involved three steps: a comprehensive review of the literature; a synthesis of the literature into thematic categories to capture the dispositions and behaviors of culturally responsive teaching; and the piloting of these thematic categories with teacher candidates to validate the usefulness of the categories and to generate specific exemplars of behavior to represent each category. The model of culturally responsive teaching contains five thematic categories: (1) content integration, (2) facilitating knowledge construction, (3) prejudice reduction, (4) social justice, and (5) academic development. The current model is a promising tool for comprehensively defining culturally responsive teaching in the context of teacher education as well as to guide curriculum and assessment changes aimed to increase candidates' culturally responsive knowledge and skills in science and mathematics teaching.

Modelling the firing pattern of bullfrog vestibular neurons responding to naturalistic stimuli

NASA Technical Reports Server (NTRS)

Paulin, M. G.; Hoffman, L. F.

1999-01-01

We have developed a neural system identification method for fitting models to stimulus-response data, where the response is a spike train. The method involves using a general nonlinear optimisation procedure to fit models in the time domain. We have applied the method to model bullfrog semicircular canal afferent neuron responses during naturalistic, broad-band head rotations. These neurons respond in diverse ways, but a simple four parameter class of models elegantly accounts for the various types of responses observed. c1999 Elsevier Science B.V. All rights reserved.

Prediction of chemo-response in serous ovarian cancer.

PubMed

Gonzalez Bosquet, Jesus; Newtson, Andreea M; Chung, Rebecca K; Thiel, Kristina W; Ginader, Timothy; Goodheart, Michael J; Leslie, Kimberly K; Smith, Brian J

2016-10-19

Nearly one-third of serous ovarian cancer (OVCA) patients will not respond to initial treatment with surgery and chemotherapy and die within one year of diagnosis. If patients who are unlikely to respond to current standard therapy can be identified up front, enhanced tumor analyses and treatment regimens could potentially be offered. Using the Cancer Genome Atlas (TCGA) serous OVCA database, we previously identified a robust molecular signature of 422-genes associated with chemo-response. Our objective was to test whether this signature is an accurate and sensitive predictor of chemo-response in serous OVCA. We first constructed prediction models to predict chemo-response using our previously described 422-gene signature that was associated with response to treatment in serous OVCA. Performance of all prediction models were measured with area under the curves (AUCs, a measure of the model's accuracy) and their respective confidence intervals (CIs). To optimize the prediction process, we determined which elements of the signature most contributed to chemo-response prediction. All prediction models were replicated and validated using six publicly available independent gene expression datasets. The 422-gene signature prediction models predicted chemo-response with AUCs of ~70 %. Optimization of prediction models identified the 34 most important genes in chemo-response prediction. These 34-gene models had improved performance, with AUCs approaching 80 %. Both 422-gene and 34-gene prediction models were replicated and validated in six independent datasets. These prediction models serve as the foundation for the future development and implementation of a diagnostic tool to predict response to chemotherapy for serous OVCA patients.

Optimal plant nitrogen use improves model representation of vegetation response to elevated CO2

NASA Astrophysics Data System (ADS)

Caldararu, Silvia; Kern, Melanie; Engel, Jan; Zaehle, Sönke

2017-04-01

Existing global vegetation models often cannot accurately represent observed ecosystem behaviour under transient conditions such as elevated atmospheric CO2, a problem that can be attributed to an inflexibility in model representation of plant responses. Plant optimality concepts have been proposed as a solution to this problem as they offer a way to represent plastic plant responses in complex models. Here we present a novel, next generation vegetation model which includes optimal nitrogen allocation to and within the canopy as well as optimal biomass allocation between above- and belowground components in response to nutrient and water availability. The underlying hypothesis is that plants adjust their use of nitrogen in response to environmental conditions and nutrient availability in order to maximise biomass growth. We show that for two FACE (Free Air CO2 enrichment) experiments, the Duke forest and Oak Ridge forest sites, the model can better predict vegetation responses over the duration of the experiment when optimal processes are included. Specifically, under elevated CO2 conditions, the model predicts a lower optimal leaf N concentration as well as increased biomass allocation to fine roots, which, combined with a redistribution of leaf N between the Rubisco and chlorophyll components, leads to a continued NPP response under high CO2, where models with a fixed canopy stoichiometry predict a quick onset of N limitation.Existing global vegetation models often cannot accurately represent observed ecosystem behaviour under transient conditions such as elevated atmospheric CO2, a problem that can be attributed to an inflexibility in model representation of plant responses. Plant optimality concepts have been proposed as a solution to this problem as they offer a way to represent plastic plant responses in complex models. Here we present a novel, next generation vegetation model which includes optimal nitrogen allocation to and within the canopy as well as optimal biomass allocation between above- and belowground components in response to nutrient and water availability. The underlying hypothesis is that plants adjust their use of nitrogen in response to environmental conditions and nutrient availability in order to maximise biomass growth. We show that for two FACE (Free Air CO2 enrichment) experiments, the Duke forest and Oak Ridge forest sites, the model can better predict vegetation responses over the duration of the experiment when optimal processes are included. Specifically, under elevated CO2 conditions, the model predicts a lower optimal leaf N concentration as well as increased biomass allocation to fine roots, which, combined with a redistribution of leaf N between the Rubisco and chlorophyll components, leads to a continued NPP response under high CO2, where models with a fixed canopy stoichiometry predict a quick onset of N limitation.

Incorporating Response Times in Item Response Theory Models of Reading Comprehension Fluency

ERIC Educational Resources Information Center

Su, Shiyang

2017-01-01

With the online assessment becoming mainstream and the recording of response times becoming straightforward, the importance of response times as a measure of psychological constructs has been recognized and the literature of modeling times has been growing during the last few decades. Previous studies have tried to formulate models and theories to…

Quantifying Local, Response Dependence between Two Polytomous Items Using the Rasch Model

ERIC Educational Resources Information Center

Andrich, David; Humphry, Stephen M.; Marais, Ida

2012-01-01

Models of modern test theory imply statistical independence among responses, generally referred to as "local independence." One violation of local independence occurs when the response to one item governs the response to a subsequent item. Expanding on a formulation of this kind of violation as a process in the dichotomous Rasch model,…

Person-Fit Statistics for Joint Models for Accuracy and Speed

ERIC Educational Resources Information Center

Fox, Jean-Paul; Marianti, Sukaesi

2017-01-01

Response accuracy and response time data can be analyzed with a joint model to measure ability and speed of working, while accounting for relationships between item and person characteristics. In this study, person-fit statistics are proposed for joint models to detect aberrant response accuracy and/or response time patterns. The person-fit tests…

Speed-Accuracy Response Models: Scoring Rules Based on Response Time and Accuracy

ERIC Educational Resources Information Center

Maris, Gunter; van der Maas, Han

2012-01-01

Starting from an explicit scoring rule for time limit tasks incorporating both response time and accuracy, and a definite trade-off between speed and accuracy, a response model is derived. Since the scoring rule is interpreted as a sufficient statistic, the model belongs to the exponential family. The various marginal and conditional distributions…

Evaluating Social Causality and Responsibility Models: An Initial Report

DTIC Science & Technology

2005-01-01

ICT Technical Report ICT-TR-03-2005 Evaluating Social Causality and Responsibility ... social intelligent agents. In this report, we present a general computational model of social causality and responsibility , and empirical results of...2005 to 00-00-2005 4. TITLE AND SUBTITLE Evaluating Social Causality and Responsibility Models: An Initial Report 5a. CONTRACT NUMBER 5b. GRANT

Spectral response model for a multibin photon-counting spectral computed tomography detector and its applications.

PubMed

Liu, Xuejin; Persson, Mats; Bornefalk, Hans; Karlsson, Staffan; Xu, Cheng; Danielsson, Mats; Huber, Ben

2015-07-01

Variations among detector channels in computed tomography can lead to ring artifacts in the reconstructed images and biased estimates in projection-based material decomposition. Typically, the ring artifacts are corrected by compensation methods based on flat fielding, where transmission measurements are required for a number of material-thickness combinations. Phantoms used in these methods can be rather complex and require an extensive number of transmission measurements. Moreover, material decomposition needs knowledge of the individual response of each detector channel to account for the detector inhomogeneities. For this purpose, we have developed a spectral response model that binwise predicts the response of a multibin photon-counting detector individually for each detector channel. The spectral response model is performed in two steps. The first step employs a forward model to predict the expected numbers of photon counts, taking into account parameters such as the incident x-ray spectrum, absorption efficiency, and energy response of the detector. The second step utilizes a limited number of transmission measurements with a set of flat slabs of two absorber materials to fine-tune the model predictions, resulting in a good correspondence with the physical measurements. To verify the response model, we apply the model in two cases. First, the model is used in combination with a compensation method which requires an extensive number of transmission measurements to determine the necessary parameters. Our spectral response model successfully replaces these measurements by simulations, saving a significant amount of measurement time. Second, the spectral response model is used as the basis of the maximum likelihood approach for projection-based material decomposition. The reconstructed basis images show a good separation between the calcium-like material and the contrast agents, iodine and gadolinium. The contrast agent concentrations are reconstructed with more than 94% accuracy.

Spectral response model for a multibin photon-counting spectral computed tomography detector and its applications

PubMed Central

Liu, Xuejin; Persson, Mats; Bornefalk, Hans; Karlsson, Staffan; Xu, Cheng; Danielsson, Mats; Huber, Ben

2015-01-01

Abstract. Variations among detector channels in computed tomography can lead to ring artifacts in the reconstructed images and biased estimates in projection-based material decomposition. Typically, the ring artifacts are corrected by compensation methods based on flat fielding, where transmission measurements are required for a number of material-thickness combinations. Phantoms used in these methods can be rather complex and require an extensive number of transmission measurements. Moreover, material decomposition needs knowledge of the individual response of each detector channel to account for the detector inhomogeneities. For this purpose, we have developed a spectral response model that binwise predicts the response of a multibin photon-counting detector individually for each detector channel. The spectral response model is performed in two steps. The first step employs a forward model to predict the expected numbers of photon counts, taking into account parameters such as the incident x-ray spectrum, absorption efficiency, and energy response of the detector. The second step utilizes a limited number of transmission measurements with a set of flat slabs of two absorber materials to fine-tune the model predictions, resulting in a good correspondence with the physical measurements. To verify the response model, we apply the model in two cases. First, the model is used in combination with a compensation method which requires an extensive number of transmission measurements to determine the necessary parameters. Our spectral response model successfully replaces these measurements by simulations, saving a significant amount of measurement time. Second, the spectral response model is used as the basis of the maximum likelihood approach for projection-based material decomposition. The reconstructed basis images show a good separation between the calcium-like material and the contrast agents, iodine and gadolinium. The contrast agent concentrations are reconstructed with more than 94% accuracy. PMID:26839904

SiSeRHMap v1.0: a simulator for mapped seismic response using a hybrid model

NASA Astrophysics Data System (ADS)

Grelle, Gerardo; Bonito, Laura; Lampasi, Alessandro; Revellino, Paola; Guerriero, Luigi; Sappa, Giuseppe; Guadagno, Francesco Maria

2016-04-01

The SiSeRHMap (simulator for mapped seismic response using a hybrid model) is a computerized methodology capable of elaborating prediction maps of seismic response in terms of acceleration spectra. It was realized on the basis of a hybrid model which combines different approaches and models in a new and non-conventional way. These approaches and models are organized in a code architecture composed of five interdependent modules. A GIS (geographic information system) cubic model (GCM), which is a layered computational structure based on the concept of lithodynamic units and zones, aims at reproducing a parameterized layered subsoil model. A meta-modelling process confers a hybrid nature to the methodology. In this process, the one-dimensional (1-D) linear equivalent analysis produces acceleration response spectra for a specified number of site profiles using one or more input motions. The shear wave velocity-thickness profiles, defined as trainers, are randomly selected in each zone. Subsequently, a numerical adaptive simulation model (Emul-spectra) is optimized on the above trainer acceleration response spectra by means of a dedicated evolutionary algorithm (EA) and the Levenberg-Marquardt algorithm (LMA) as the final optimizer. In the final step, the GCM maps executor module produces a serial map set of a stratigraphic seismic response at different periods, grid solving the calibrated Emul-spectra model. In addition, the spectra topographic amplification is also computed by means of a 3-D validated numerical prediction model. This model is built to match the results of the numerical simulations related to isolate reliefs using GIS morphometric data. In this way, different sets of seismic response maps are developed on which maps of design acceleration response spectra are also defined by means of an enveloping technique.

The Simplest Complete Model of Choice Response Time: Linear Ballistic Accumulation

ERIC Educational Resources Information Center

Brown, Scott D.; Heathcote, Andrew

2008-01-01

We propose a linear ballistic accumulator (LBA) model of decision making and reaction time. The LBA is simpler than other models of choice response time, with independent accumulators that race towards a common response threshold. Activity in the accumulators increases in a linear and deterministic manner. The simplicity of the model allows…

Hierarchical Diffusion Models for Two-Choice Response Times

ERIC Educational Resources Information Center

Vandekerckhove, Joachim; Tuerlinckx, Francis; Lee, Michael D.

2011-01-01

Two-choice response times are a common type of data, and much research has been devoted to the development of process models for such data. However, the practical application of these models is notoriously complicated, and flexible methods are largely nonexistent. We combine a popular model for choice response times--the Wiener diffusion…

Applying the age-shift approach to model responses to midrotation fertilization

Treesearch

Colleen A. Carlson; Thomas R. Fox; H. Lee Allen; Timothy J. Albaugh

2010-01-01

Growth and yield models used to evaluate midrotation fertilization economics require adjustments to account for the typically observed responses. This study investigated the use of age-shift models to predict midrotation fertilizer responses. Age-shift prediction models were constructed from a regional study consisting of 43 installations of a nitrogen (N) by...

The Impact of Truth Surrogate Variance on Quality Assessment/Assurance in Wind Tunnel Testing

NASA Technical Reports Server (NTRS)

DeLoach, Richard

2016-01-01

Minimum data volume requirements for wind tunnel testing are reviewed and shown to depend on error tolerance, response model complexity, random error variance in the measurement environment, and maximum acceptable levels of inference error risk. Distinctions are made between such related concepts as quality assurance and quality assessment in response surface modeling, as well as between precision and accuracy. Earlier research on the scaling of wind tunnel tests is extended to account for variance in the truth surrogates used at confirmation sites in the design space to validate proposed response models. A model adequacy metric is presented that represents the fraction of the design space within which model predictions can be expected to satisfy prescribed quality specifications. The impact of inference error on the assessment of response model residuals is reviewed. The number of sites where reasonably well-fitted response models actually predict inadequately is shown to be considerably less than the number of sites where residuals are out of tolerance. The significance of such inference error effects on common response model assessment strategies is examined.

Model-experiment synthesis at two FACE sites in the southeastern US. Forest ecosystem responses to elevated CO[2]. (Invited)

NASA Astrophysics Data System (ADS)

Walker, A. P.; Zaehle, S.; De Kauwe, M. G.; Medlyn, B. E.; Dietze, M.; Hickler, T.; Iversen, C. M.; Jain, A. K.; Luo, Y.; McCarthy, H. R.; Parton, W. J.; Prentice, C.; Thornton, P. E.; Wang, S.; Wang, Y.; Warlind, D.; Warren, J.; Weng, E.; Hanson, P. J.; Oren, R.; Norby, R. J.

2013-12-01

Ecosystem observations from two long-term Free-Air CO[2] Enrichment (FACE) experiments (Duke forest and Oak Ridge forest) were used to evaluate the assumptions of 11 terrestrial ecosystem models and the consequences of those assumptions for the responses of ecosystem water, carbon (C) and nitrogen (N) fluxes to elevated CO[2] (eCO[2]). Nitrogen dynamics were the main constraint on simulated productivity responses to eCO[2]. At Oak Ridge some models reproduced the declining response of C and N fluxes, while at Duke none of the models were able to maintain the observed sustained responses. C and N cycles are coupled through a number of complex interactions, which causes uncertainty in model simulations in multiple ways. Nonetheless, the major difference between models and experiments was a larger than observed increase in N-use efficiency and lower than observed response of N uptake. The results indicate that at Duke there were mechanisms by which trees accessed additional N in response to eCO[2] that were not represented in the ecosystem models, and which did not operate with the same efficiency at Oak Ridge. Sequestration of the additional productivity under eCO[2] into forest biomass depended largely on C allocation. Allocation assumptions were classified into three main categories--fixed partitioning coefficients, functional relationships and a partial (leaf allocation only) optimisation. The assumption which best constrained model results was a functional relationship between leaf area and sapwood area (pipe-model) and increased root allocation when nitrogen or water were limiting. Both, productivity and allocation responses to eCO[2] determined the ecosystem-level response of LAI, which together with the response of stomatal conductance (and hence water-use efficiency; WUE) determined the ecosystem response of transpiration. Differences in the WUE response across models were related to the representation of the relationship of stomatal conductance to CO[2] and the relative importance of the combined boundary and aerodynamic resistances in the total resistance to leaf-atmosphere water transport.

Modeling in Real Time During the Ebola Response.

PubMed

Meltzer, Martin I; Santibanez, Scott; Fischer, Leah S; Merlin, Toby L; Adhikari, Bishwa B; Atkins, Charisma Y; Campbell, Caresse; Fung, Isaac Chun-Hai; Gambhir, Manoj; Gift, Thomas; Greening, Bradford; Gu, Weidong; Jacobson, Evin U; Kahn, Emily B; Carias, Cristina; Nerlander, Lina; Rainisch, Gabriel; Shankar, Manjunath; Wong, Karen; Washington, Michael L

2016-07-08

To aid decision-making during CDC's response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC activated a Modeling Task Force to generate estimates on various topics related to the response in West Africa and the risk for importation of cases into the United States. Analysis of eight Ebola response modeling projects conducted during August 2014-July 2015 provided insight into the types of questions addressed by modeling, the impact of the estimates generated, and the difficulties encountered during the modeling. This time frame was selected to cover the three phases of the West African epidemic curve. Questions posed to the Modeling Task Force changed as the epidemic progressed. Initially, the task force was asked to estimate the number of cases that might occur if no interventions were implemented compared with cases that might occur if interventions were implemented; however, at the peak of the epidemic, the focus shifted to estimating resource needs for Ebola treatment units. Then, as the epidemic decelerated, requests for modeling changed to generating estimates of the potential number of sexually transmitted Ebola cases. Modeling to provide information for decision-making during the CDC Ebola response involved limited data, a short turnaround time, and difficulty communicating the modeling process, including assumptions and interpretation of results. Despite these challenges, modeling yielded estimates and projections that public health officials used to make key decisions regarding response strategy and resources required. The impact of modeling during the Ebola response demonstrates the usefulness of modeling in future responses, particularly in the early stages and when data are scarce. Future modeling can be enhanced by planning ahead for data needs and data sharing, and by open communication among modelers, scientists, and others to ensure that modeling and its limitations are more clearly understood. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

Response Surface Modeling Using Multivariate Orthogonal Functions

NASA Technical Reports Server (NTRS)

Morelli, Eugene A.; DeLoach, Richard

2001-01-01

A nonlinear modeling technique was used to characterize response surfaces for non-dimensional longitudinal aerodynamic force and moment coefficients, based on wind tunnel data from a commercial jet transport model. Data were collected using two experimental procedures - one based on modem design of experiments (MDOE), and one using a classical one factor at a time (OFAT) approach. The nonlinear modeling technique used multivariate orthogonal functions generated from the independent variable data as modeling functions in a least squares context to characterize the response surfaces. Model terms were selected automatically using a prediction error metric. Prediction error bounds computed from the modeling data alone were found to be- a good measure of actual prediction error for prediction points within the inference space. Root-mean-square model fit error and prediction error were less than 4 percent of the mean response value in all cases. Efficacy and prediction performance of the response surface models identified from both MDOE and OFAT experiments were investigated.

Item response theory and structural equation modelling for ordinal data: Describing the relationship between KIDSCREEN and Life-H.

PubMed

Titman, Andrew C; Lancaster, Gillian A; Colver, Allan F

2016-10-01

Both item response theory and structural equation models are useful in the analysis of ordered categorical responses from health assessment questionnaires. We highlight the advantages and disadvantages of the item response theory and structural equation modelling approaches to modelling ordinal data, from within a community health setting. Using data from the SPARCLE project focussing on children with cerebral palsy, this paper investigates the relationship between two ordinal rating scales, the KIDSCREEN, which measures quality-of-life, and Life-H, which measures participation. Practical issues relating to fitting models, such as non-positive definite observed or fitted correlation matrices, and approaches to assessing model fit are discussed. item response theory models allow properties such as the conditional independence of particular domains of a measurement instrument to be assessed. When, as with the SPARCLE data, the latent traits are multidimensional, structural equation models generally provide a much more convenient modelling framework. © The Author(s) 2013.

Modeled responses of terrestrial ecosystems to elevated atmospheric CO2: a comparison of simulations by the biogeochemistry models of the Vegetation/Ecosystem Modeling and Analysis Project (VEMAP).

PubMed

Pan, Yude; Melillo, Jerry M; McGuire, A David; Kicklighter, David W; Pitelka, Louis F; Hibbard, Kathy; Pierce, Lars L; Running, Steven W; Ojima, Dennis S; Parton, William J; Schimel, David S

1998-04-01

Although there is a great deal of information concerning responses to increases in atmospheric CO 2 at the tissue and plant levels, there are substantially fewer studies that have investigated ecosystem-level responses in the context of integrated carbon, water, and nutrient cycles. Because our understanding of ecosystem responses to elevated CO 2 is incomplete, modeling is a tool that can be used to investigate the role of plant and soil interactions in the response of terrestrial ecosystems to elevated CO 2 . In this study, we analyze the responses of net primary production (NPP) to doubled CO 2 from 355 to 710 ppmv among three biogeochemistry models in the Vegetation/Ecosystem Modeling and Analysis Project (VEMAP): BIOME-BGC (BioGeochemical Cycles), Century, and the Terrestrial Ecosystem Model (TEM). For the conterminous United States, doubled atmospheric CO 2 causes NPP to increase by 5% in Century, 8% in TEM, and 11% in BIOME-BGC. Multiple regression analyses between the NPP response to doubled CO 2 and the mean annual temperature and annual precipitation of biomes or grid cells indicate that there are negative relationships between precipitation and the response of NPP to doubled CO 2 for all three models. In contrast, there are different relationships between temperature and the response of NPP to doubled CO 2 for the three models: there is a negative relationship in the responses of BIOME-BGC, no relationship in the responses of Century, and a positive relationship in the responses of TEM. In BIOME-BGC, the NPP response to doubled CO 2 is controlled by the change in transpiration associated with reduced leaf conductance to water vapor. This change affects soil water, then leaf area development and, finally, NPP. In Century, the response of NPP to doubled CO 2 is controlled by changes in decomposition rates associated with increased soil moisture that results from reduced evapotranspiration. This change affects nitrogen availability for plants, which influences NPP. In TEM, the NPP response to doubled CO 2 is controlled by increased carboxylation which is modified by canopy conductance and the degree to which nitrogen constraints cause down-regulation of photosynthesis. The implementation of these different mechanisms has consequences for the spatial pattern of NPP responses, and represents, in part, conceptual uncertainty about controls over NPP responses. Progress in reducing these uncertainties requires research focused at the ecosystem level to understand how interactions between the carbon, nitrogen, and water cycles influence the response of NPP to elevated atmospheric CO 2 .

Modeled responses of terrestrial ecosystems to elevated atmospheric CO2: A comparison of simulations by the biogeochemistry models of the Vegetation/Ecosystem Modeling and Analysis Project (VEMAP)

USGS Publications Warehouse

Pan, Y.; Melillo, J.M.; McGuire, A.D.; Kicklighter, D.W.; Pitelka, Louis F.; Hibbard, K.; Pierce, L.L.; Running, S.W.; Ojima, D.S.; Parton, W.J.; Schimel, D.S.; Borchers, J.; Neilson, R.; Fisher, H.H.; Kittel, T.G.F.; Rossenbloom, N.A.; Fox, S.; Haxeltine, A.; Prentice, I.C.; Sitch, S.; Janetos, A.; McKeown, R.; Nemani, R.; Painter, T.; Rizzo, B.; Smith, T.; Woodward, F.I.

1998-01-01

Although there is a great deal of information concerning responses to increases in atmospheric CO2 at the tissue and plant levels, there are substantially fewer studies that have investigated ecosystem-level responses in the context of integrated carbon, water, and nutrient cycles. Because our understanding of ecosystem responses to elevated CO2 is incomplete, modeling is a tool that can be used to investigate the role of plant and soil interactions in the response of terrestrial ecosystems to elevated CO2. In this study, we analyze the responses of net primary production (NPP) to doubled CO2 from 355 to 710 ppmv among three biogeochemistry models in the Vegetation/Ecosystem Modeling and Analysis Project (VEMAP): BIOME-BGC (BioGeochemical Cycles), Century, and the Terrestrial Ecosystem Model (TEM). For the conterminous United States, doubled atmospheric CO2 causes NPP to increase by 5% in Century, 8% in TEM, and 11% in BIOME-BGC. Multiple regression analyses between the NPP response to doubled CO2 and the mean annual temperature and annual precipitation of biomes or grid cells indicate that there are negative relationships between precipitation and the response of NPP to doubled CO2 for all three models. In contrast, there are different relationships between temperature and the response of NPP to doubled CO2 for the three models: there is a negative relationship in the responses of BIOME-BGC, no relationship in the responses of Century, and a positive relationship in the responses of TEM. In BIOME-BGC, the NPP response to doubled CO2 is controlled by the change in transpiration associated with reduced leaf conductance to water vapor. This change affects soil water, then leaf area development and, finally, NPP. In Century, the response of NPP to doubled CO2 is controlled by changes in decomposition rates associated with increased soil moisture that results from reduced evapotranspiration. This change affects nitrogen availability for plants, which influences NPP. In TEM, the NPP response to doubled CO2 is controlled by increased carboxylation which is modified by canopy conductance and the degree to which nitrogen constraints cause down-regulation of photosynthesis. The implementation of these different mechanisms has consequences for the spatial pattern of NPP responses, and represents, in part, conceptual uncertainty about controls over NPP responses. Progress in reducing these uncertainties requires research focused at the ecosystem level to understand how interactions between the carbon, nitrogen, and water cycles influence the response of NPP to elevated atmospheric CO2.

Sensitivity of Antarctic sea ice to the Southern Annular Mode in coupled climate models

NASA Astrophysics Data System (ADS)

Holland, Marika M.; Landrum, Laura; Kostov, Yavor; Marshall, John

2017-09-01

We assess the sea ice response to Southern Annular Mode (SAM) anomalies for pre-industrial control simulations from the Coupled Model Intercomparison Project (CMIP5). Consistent with work by Ferreira et al. (J Clim 28:1206-1226, 2015. doi: 10.1175/JCLI-D-14-00313.1), the models generally simulate a two-timescale response to positive SAM anomalies, with an initial increase in ice followed by an eventual sea ice decline. However, the models differ in the cross-over time at which the change in ice response occurs, in the overall magnitude of the response, and in the spatial distribution of the response. Late twentieth century Antarctic sea ice trends in CMIP5 simulations are related in part to different modeled responses to SAM variability acting on different time-varying transient SAM conditions. This explains a significant fraction of the spread in simulated late twentieth century southern hemisphere sea ice extent trends across the model simulations. Applying the modeled sea ice response to SAM variability but driven by the observed record of SAM suggests that variations in the austral summer SAM, which has exhibited a significant positive trend, have driven a modest sea ice decrease. However, additional work is needed to narrow the considerable model uncertainty in the climate response to SAM variability and its implications for 20th-21st century trends.

Bayesian multimodel inference for dose-response studies

USGS Publications Warehouse

Link, W.A.; Albers, P.H.

2007-01-01

Statistical inference in dose?response studies is model-based: The analyst posits a mathematical model of the relation between exposure and response, estimates parameters of the model, and reports conclusions conditional on the model. Such analyses rarely include any accounting for the uncertainties associated with model selection. The Bayesian inferential system provides a convenient framework for model selection and multimodel inference. In this paper we briefly describe the Bayesian paradigm and Bayesian multimodel inference. We then present a family of models for multinomial dose?response data and apply Bayesian multimodel inferential methods to the analysis of data on the reproductive success of American kestrels (Falco sparveriuss) exposed to various sublethal dietary concentrations of methylmercury.

Cognitive Psychology Meets Psychometric Theory: On the Relation between Process Models for Decision Making and Latent Variable Models for Individual Differences

ERIC Educational Resources Information Center

van der Maas, Han L. J.; Molenaar, Dylan; Maris, Gunter; Kievit, Rogier A.; Borsboom, Denny

2011-01-01

This article analyzes latent variable models from a cognitive psychology perspective. We start by discussing work by Tuerlinckx and De Boeck (2005), who proved that a diffusion model for 2-choice response processes entails a 2-parameter logistic item response theory (IRT) model for individual differences in the response data. Following this line…

Selecting an Informative/Discriminating Multivariate Response for Inverse Prediction

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

Thomas, Edward V.; Lewis, John. R.; Anderson-Cook, Christine Michaela

The inverse prediction is important in a variety of scientific and engineering applications, such as to predict properties/characteristics of an object by using multiple measurements obtained from it. Inverse prediction can be accomplished by inverting parameterized forward models that relate the measurements (responses) to the properties/characteristics of interest. Sometimes forward models are computational/science based; but often, forward models are empirically based response surface models, obtained by using the results of controlled experimentation. For empirical models, it is important that the experiments provide a sound basis to develop accurate forward models in terms of the properties/characteristics (factors). And while nature dictatesmore » the causal relationships between factors and responses, experimenters can control the complexity, accuracy, and precision of forward models constructed via selection of factors, factor levels, and the set of trials that are performed. Recognition of the uncertainty in the estimated forward models leads to an errors-in-variables approach for inverse prediction. The forward models (estimated by experiments or science based) can also be used to analyze how well candidate responses complement one another for inverse prediction over the range of the factor space of interest. Furthermore, one may find that some responses are complementary, redundant, or noninformative. Simple analysis and examples illustrate how an informative and discriminating subset of responses could be selected among candidates in cases where the number of responses that can be acquired during inverse prediction is limited by difficulty, expense, and/or availability of material.« less

Mathematical modeling improves EC50 estimations from classical dose-response curves.

PubMed

Nyman, Elin; Lindgren, Isa; Lövfors, William; Lundengård, Karin; Cervin, Ida; Sjöström, Theresia Arbring; Altimiras, Jordi; Cedersund, Gunnar

2015-03-01

The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50 . Instead, we have applied a mathematical modeling approach to interpret the full dose-response curve in a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose-response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time-resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm). Mathematical modeling thus makes it possible to re-interpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible. The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman. © 2015 FEBS.

Selecting an Informative/Discriminating Multivariate Response for Inverse Prediction

DOE PAGES

Thomas, Edward V.; Lewis, John. R.; Anderson-Cook, Christine Michaela; ...

2017-07-01

The inverse prediction is important in a variety of scientific and engineering applications, such as to predict properties/characteristics of an object by using multiple measurements obtained from it. Inverse prediction can be accomplished by inverting parameterized forward models that relate the measurements (responses) to the properties/characteristics of interest. Sometimes forward models are computational/science based; but often, forward models are empirically based response surface models, obtained by using the results of controlled experimentation. For empirical models, it is important that the experiments provide a sound basis to develop accurate forward models in terms of the properties/characteristics (factors). And while nature dictatesmore » the causal relationships between factors and responses, experimenters can control the complexity, accuracy, and precision of forward models constructed via selection of factors, factor levels, and the set of trials that are performed. Recognition of the uncertainty in the estimated forward models leads to an errors-in-variables approach for inverse prediction. The forward models (estimated by experiments or science based) can also be used to analyze how well candidate responses complement one another for inverse prediction over the range of the factor space of interest. Furthermore, one may find that some responses are complementary, redundant, or noninformative. Simple analysis and examples illustrate how an informative and discriminating subset of responses could be selected among candidates in cases where the number of responses that can be acquired during inverse prediction is limited by difficulty, expense, and/or availability of material.« less

Impact of Future Climate on Radial Growth of Four Major Boreal Tree Species in the Eastern Canadian Boreal Forest

PubMed Central

Huang, Jian-Guo; Bergeron, Yves; Berninger, Frank; Zhai, Lihong; Tardif, Jacques C.; Denneler, Bernhard

2013-01-01

Immediate phenotypic variation and the lagged effect of evolutionary adaptation to climate change appear to be two key processes in tree responses to climate warming. This study examines these components in two types of growth models for predicting the 2010–2099 diameter growth change of four major boreal species Betula papyrifera, Pinus banksiana, Picea mariana, and Populus tremuloides along a broad latitudinal gradient in eastern Canada under future climate projections. Climate-growth response models for 34 stands over nine latitudes were calibrated and cross-validated. An adaptive response model (A-model), in which the climate-growth relationship varies over time, and a fixed response model (F-model), in which the relationship is constant over time, were constructed to predict future growth. For the former, we examined how future growth of stands in northern latitudes could be forecasted using growth-climate equations derived from stands currently growing in southern latitudes assuming that current climate in southern locations provide an analogue for future conditions in the north. For the latter, we tested if future growth of stands would be maximally predicted using the growth-climate equation obtained from the given local stand assuming a lagged response to climate due to genetic constraints. Both models predicted a large growth increase in northern stands due to more benign temperatures, whereas there was a minimal growth change in southern stands due to potentially warm-temperature induced drought-stress. The A-model demonstrates a changing environment whereas the F-model highlights a constant growth response to future warming. As time elapses we can predict a gradual transition between a response to climate associated with the current conditions (F-model) to a more adapted response to future climate (A-model). Our modeling approach provides a template to predict tree growth response to climate warming at mid-high latitudes of the Northern Hemisphere. PMID:23468879

Impact of future climate on radial growth of four major boreal tree species in the Eastern Canadian boreal forest.

PubMed

Huang, Jian-Guo; Bergeron, Yves; Berninger, Frank; Zhai, Lihong; Tardif, Jacques C; Denneler, Bernhard

2013-01-01

Immediate phenotypic variation and the lagged effect of evolutionary adaptation to climate change appear to be two key processes in tree responses to climate warming. This study examines these components in two types of growth models for predicting the 2010-2099 diameter growth change of four major boreal species Betula papyrifera, Pinus banksiana, Picea mariana, and Populus tremuloides along a broad latitudinal gradient in eastern Canada under future climate projections. Climate-growth response models for 34 stands over nine latitudes were calibrated and cross-validated. An adaptive response model (A-model), in which the climate-growth relationship varies over time, and a fixed response model (F-model), in which the relationship is constant over time, were constructed to predict future growth. For the former, we examined how future growth of stands in northern latitudes could be forecasted using growth-climate equations derived from stands currently growing in southern latitudes assuming that current climate in southern locations provide an analogue for future conditions in the north. For the latter, we tested if future growth of stands would be maximally predicted using the growth-climate equation obtained from the given local stand assuming a lagged response to climate due to genetic constraints. Both models predicted a large growth increase in northern stands due to more benign temperatures, whereas there was a minimal growth change in southern stands due to potentially warm-temperature induced drought-stress. The A-model demonstrates a changing environment whereas the F-model highlights a constant growth response to future warming. As time elapses we can predict a gradual transition between a response to climate associated with the current conditions (F-model) to a more adapted response to future climate (A-model). Our modeling approach provides a template to predict tree growth response to climate warming at mid-high latitudes of the Northern Hemisphere.

The development of a fully-integrated immune response model (FIRM) simulator of the immune response through integration of multiple subset models

PubMed Central

2013-01-01

Background The complexity and multiscale nature of the mammalian immune response provides an excellent test bed for the potential of mathematical modeling and simulation to facilitate mechanistic understanding. Historically, mathematical models of the immune response focused on subsets of the immune system and/or specific aspects of the response. Mathematical models have been developed for the humoral side of the immune response, or for the cellular side, or for cytokine kinetics, but rarely have they been proposed to encompass the overall system complexity. We propose here a framework for integration of subset models, based on a system biology approach. Results A dynamic simulator, the Fully-integrated Immune Response Model (FIRM), was built in a stepwise fashion by integrating published subset models and adding novel features. The approach used to build the model includes the formulation of the network of interacting species and the subsequent introduction of rate laws to describe each biological process. The resulting model represents a multi-organ structure, comprised of the target organ where the immune response takes place, circulating blood, lymphoid T, and lymphoid B tissue. The cell types accounted for include macrophages, a few T-cell lineages (cytotoxic, regulatory, helper 1, and helper 2), and B-cell activation to plasma cells. Four different cytokines were accounted for: IFN-γ, IL-4, IL-10 and IL-12. In addition, generic inflammatory signals are used to represent the kinetics of IL-1, IL-2, and TGF-β. Cell recruitment, differentiation, replication, apoptosis and migration are described as appropriate for the different cell types. The model is a hybrid structure containing information from several mammalian species. The structure of the network was built to be physiologically and biochemically consistent. Rate laws for all the cellular fate processes, growth factor production rates and half-lives, together with antibody production rates and half-lives, are provided. The results demonstrate how this framework can be used to integrate mathematical models of the immune response from several published sources and describe qualitative predictions of global immune system response arising from the integrated, hybrid model. In addition, we show how the model can be expanded to include novel biological findings. Case studies were carried out to simulate TB infection, tumor rejection, response to a blood borne pathogen and the consequences of accounting for regulatory T-cells. Conclusions The final result of this work is a postulated and increasingly comprehensive representation of the mammalian immune system, based on physiological knowledge and susceptible to further experimental testing and validation. We believe that the integrated nature of FIRM has the potential to simulate a range of responses under a variety of conditions, from modeling of immune responses after tuberculosis (TB) infection to tumor formation in tissues. FIRM also has the flexibility to be expanded to include both complex and novel immunological response features as our knowledge of the immune system advances. PMID:24074340

Comparison between a typical and a simplified model for blast load-induced structural response

NASA Astrophysics Data System (ADS)

Abd-Elhamed, A.; Mahmoud, S.

2017-02-01

As explosive blasts continue to cause severe damage as well as victims in both civil and military environments. There is a bad need for understanding the behavior of structural elements to such extremely short duration dynamic loads where it is of great concern nowadays. Due to the complexity of the typical blast pressure profile model and in order to reduce the modelling and computational efforts, the simplified triangle model for blast loads profile is used to analyze structural response. This simplified model considers only the positive phase and ignores the suction phase which characterizes the typical one in simulating blast loads. The closed from solution for the equation of motion under blast load as a forcing term modelled either typical or simplified models has been derived. The considered herein two approaches have been compared using the obtained results from simulation response analysis of a building structure under an applied blast load. The computed error in simulating response using the simplified model with respect to the typical one has been computed. In general, both simplified and typical models can perform the dynamic blast-load induced response of building structures. However, the simplified one shows a remarkably different response behavior as compared to the typical one despite its simplicity and the use of only positive phase for simulating the explosive loads. The prediction of the dynamic system responses using the simplified model is not satisfactory due to the obtained larger errors as compared to the system responses obtained using the typical one.

Responses to atmospheric CO2 concentrations in crop simulation models: a review of current simple and semicomplex representations and options for model development.

PubMed

Vanuytrecht, Eline; Thorburn, Peter J

2017-05-01

Elevated atmospheric CO 2 concentrations ([CO 2 ]) cause direct changes in crop physiological processes (e.g. photosynthesis and stomatal conductance). To represent these CO 2 responses, commonly used crop simulation models have been amended, using simple and semicomplex representations of the processes involved. Yet, there is no standard approach to and often poor documentation of these developments. This study used a bottom-up approach (starting with the APSIM framework as case study) to evaluate modelled responses in a consortium of commonly used crop models and illuminate whether variation in responses reflects true uncertainty in our understanding compared to arbitrary choices of model developers. Diversity in simulated CO 2 responses and limited validation were common among models, both within the APSIM framework and more generally. Whereas production responses show some consistency up to moderately high [CO 2 ] (around 700 ppm), transpiration and stomatal responses vary more widely in nature and magnitude (e.g. a decrease in stomatal conductance varying between 35% and 90% among models was found for [CO 2 ] doubling to 700 ppm). Most notably, nitrogen responses were found to be included in few crop models despite being commonly observed and critical for the simulation of photosynthetic acclimation, crop nutritional quality and carbon allocation. We suggest harmonization and consideration of more mechanistic concepts in particular subroutines, for example, for the simulation of N dynamics, as a way to improve our predictive understanding of CO 2 responses and capture secondary processes. Intercomparison studies could assist in this aim, provided that they go beyond simple output comparison and explicitly identify the representations and assumptions that are causal for intermodel differences. Additionally, validation and proper documentation of the representation of CO 2 responses within models should be prioritized. © 2017 John Wiley & Sons Ltd.

A sequential sampling account of response bias and speed-accuracy tradeoffs in a conflict detection task.

PubMed

Vuckovic, Anita; Kwantes, Peter J; Humphreys, Michael; Neal, Andrew

2014-03-01

Signal Detection Theory (SDT; Green & Swets, 1966) is a popular tool for understanding decision making. However, it does not account for the time taken to make a decision, nor why response bias might change over time. Sequential sampling models provide a way of accounting for speed-accuracy trade-offs and response bias shifts. In this study, we test the validity of a sequential sampling model of conflict detection in a simulated air traffic control task by assessing whether two of its key parameters respond to experimental manipulations in a theoretically consistent way. Through experimental instructions, we manipulated participants' response bias and the relative speed or accuracy of their responses. The sequential sampling model was able to replicate the trends in the conflict responses as well as response time across all conditions. Consistent with our predictions, manipulating response bias was associated primarily with changes in the model's Criterion parameter, whereas manipulating speed-accuracy instructions was associated with changes in the Threshold parameter. The success of the model in replicating the human data suggests we can use the parameters of the model to gain an insight into the underlying response bias and speed-accuracy preferences common to dynamic decision-making tasks. © 2013 American Psychological Association

A Multidimensional Ideal Point Item Response Theory Model for Binary Data

ERIC Educational Resources Information Center

Maydeu-Olivares, Albert; Hernandez, Adolfo; McDonald, Roderick P.

2006-01-01

We introduce a multidimensional item response theory (IRT) model for binary data based on a proximity response mechanism. Under the model, a respondent at the mode of the item response function (IRF) endorses the item with probability one. The mode of the IRF is the ideal point, or in the multidimensional case, an ideal hyperplane. The model…

Analytical approach to calculation of response spectra from seismological models of ground motion

USGS Publications Warehouse

Safak, Erdal

1988-01-01

An analytical approach to calculate response spectra from seismological models of ground motion is presented. Seismological models have three major advantages over empirical models: (1) they help in an understanding of the physics of earthquake mechanisms, (2) they can be used to predict ground motions for future earthquakes and (3) they can be extrapolated to cases where there are no data available. As shown with this study, these models also present a convenient form for the calculation of response spectra, by using the methods of random vibration theory, for a given magnitude and site conditions. The first part of the paper reviews the past models for ground motion description, and introduces the available seismological models. Then, the random vibration equations for the spectral response are presented. The nonstationarity, spectral bandwidth and the correlation of the peaks are considered in the calculation of the peak response.

Development of structural and material clavicle response corridors under axial compression and three point bending loading for clavicle finite element model validation.

PubMed

Zhang, Qi; Kindig, Matthew; Li, Zuoping; Crandall, Jeff R; Kerrigan, Jason R

2014-08-22

Clavicle injuries were frequently observed in automotive side and frontal crashes. Finite element (FE) models have been developed to understand the injury mechanism, although no clavicle loading response corridors yet exist in the literature to ensure the model response biofidelity. Moreover, the typically developed structural level (e.g., force-deflection) response corridors were shown to be insufficient for verifying the injury prediction capacity of FE model, which usually is based on strain related injury criteria. Therefore, the purpose of this study is to develop both the structural (force vs deflection) and material level (strain vs force) clavicle response corridors for validating FE models for injury risk modeling. 20 Clavicles were loaded to failure under loading conditions representative of side and frontal crashes respectively, half of which in axial compression, and the other half in three point bending. Both structural and material response corridors were developed for each loading condition. FE model that can accurately predict structural response and strain level provides a more useful tool in injury risk modeling and prediction. The corridor development method in this study could also be extended to develop corridors for other components of the human body. Copyright © 2014 Elsevier Ltd. All rights reserved.

Solar Signals in CMIP-5 Simulations: The Stratospheric Pathway

NASA Technical Reports Server (NTRS)

Mitchell, D.M.; Misios, S.; Gray, L. J.; Tourpali, K.; Matthes, K.; Hood, L.; Schmidt, H.; Chiodo, G.; Thieblemont, R.; Rozanov, E.;

The Graded Unfolding Model: A Unidimensional Item Response Model for Unfolding Graded Responses.

ERIC Educational Resources Information Center

Roberts, James S.; Laughlin, James E.

Binary or graded disagree-agree responses to attitude items are often collected for the purpose of attitude measurement. Although such data are sometimes analyzed with cumulative measurement models, recent investigations suggest that unfolding models are more appropriate (J. S. Roberts, 1995; W. H. Van Schuur and H. A. L. Kiers, 1994). Advances in…

Stochastic Approximation Methods for Latent Regression Item Response Models. Research Report. ETS RR-09-09

ERIC Educational Resources Information Center

von Davier, Matthias; Sinharay, Sandip

2009-01-01

This paper presents an application of a stochastic approximation EM-algorithm using a Metropolis-Hastings sampler to estimate the parameters of an item response latent regression model. Latent regression models are extensions of item response theory (IRT) to a 2-level latent variable model in which covariates serve as predictors of the…

An Estimation Procedure for the Structural Parameters of the Unified Cognitive/IRT Model.

ERIC Educational Resources Information Center

Jiang, Hai; And Others

L. V. DiBello, W. F. Stout, and L. A. Roussos (1993) have developed a new item response model, the Unified Model, which brings together the discrete, deterministic aspects of cognition favored by cognitive scientists, and the continuous, stochastic aspects of test response behavior that underlie item response theory (IRT). The Unified Model blends…

Response Errors Explain the Failure of Independent-Channels Models of Perception of Temporal Order

PubMed Central

García-Pérez, Miguel A.; Alcalá-Quintana, Rocío

2012-01-01

Independent-channels models of perception of temporal order (also referred to as threshold models or perceptual latency models) have been ruled out because two formal properties of these models (monotonicity and parallelism) are not borne out by data from ternary tasks in which observers must judge whether stimulus A was presented before, after, or simultaneously with stimulus B. These models generally assume that observed responses are authentic indicators of unobservable judgments, but blinks, lapses of attention, or errors in pressing the response keys (maybe, but not only, motivated by time pressure when reaction times are being recorded) may make observers misreport their judgments or simply guess a response. We present an extension of independent-channels models that considers response errors and we show that the model produces psychometric functions that do not satisfy monotonicity and parallelism. The model is illustrated by fitting it to data from a published study in which the ternary task was used. The fitted functions describe very accurately the absence of monotonicity and parallelism shown by the data. These characteristics of empirical data are thus consistent with independent-channels models when response errors are taken into consideration. The implications of these results for the analysis and interpretation of temporal order judgment data are discussed. PMID:22493586

Equilibrium Atmospheric Response to North Atlantic SST Anomalies.

NASA Astrophysics Data System (ADS)

Kushnir, Yochanan; Held, Isaac M.

1996-06-01

The equilibrium general circulation model (GCM) response to sea surface temperature (SST) anomalies in the western North Atlantic region is studied. A coarse resolution GCM, with realistic lower boundary conditions including topography and climatological SST distribution, is integrated in perpetual January and perpetual October modes, distinguished from one another by the strength of the midlatitude westerlies. An SST anomaly with a maximum of 4°C is added to the climatological SST distribution of the model with both positive and negative polarity. These anomaly runs are compared to one another, and to a control integration, to determine the atmospheric response. In all cases warming (cooling) of the midlatitude ocean surface yields a warming (cooling) of the atmosphere over and to the east of the SST anomaly center. The atmospheric temperature change is largest near the surface and decreases upward. Consistent with this simple thermal response, the geopotential height field displays a baroclinic response with a shallow anomalous low somewhat downstream from the warm SST anomaly. The equivalent barotropic, downstream response is weak and not robust. To help interpret the results, the realistic GCM integrations are compared with parallel idealized model runs. The idealized model has full physics and a similar horizontal and vertical resolution, but an all-ocean surface with a single, permanent zonal asymmetry. The idealized and realistic versions of the GCM display compatible response patterns that are qualitatively consistent with stationary, linear, quasigeostrophic theory. However, the idealized model response is stronger and more coherent. The differences between the two model response patterns can be reconciled based on the size of the anomaly, the model treatment of cloud-radiation interaction, and the static stability of the model atmosphere in the vicinity of the SST anomaly. Model results are contrasted with other GCM studies and observations.

Calibration Designs for Non-Monolithic Wind Tunnel Force Balances

NASA Technical Reports Server (NTRS)

Johnson, Thomas H.; Parker, Peter A.; Landman, Drew

2010-01-01

This research paper investigates current experimental designs and regression models for calibrating internal wind tunnel force balances of non-monolithic design. Such calibration methods are necessary for this class of balance because it has an electrical response that is dependent upon the sign of the applied forces and moments. This dependency gives rise to discontinuities in the response surfaces that are not easily modeled using traditional response surface methodologies. An analysis of current recommended calibration models is shown to lead to correlated response model terms. Alternative modeling methods are explored which feature orthogonal or near-orthogonal terms.

Modelling climate change responses in tropical forests: similar productivity estimates across five models, but different mechanisms and responses

NASA Astrophysics Data System (ADS)

Rowland, L.; Harper, A.; Christoffersen, B. O.; Galbraith, D. R.; Imbuzeiro, H. M. A.; Powell, T. L.; Doughty, C.; Levine, N. M.; Malhi, Y.; Saleska, S. R.; Moorcroft, P. R.; Meir, P.; Williams, M.

2015-04-01

Accurately predicting the response of Amazonia to climate change is important for predicting climate change across the globe. Changes in multiple climatic factors simultaneously result in complex non-linear ecosystem responses, which are difficult to predict using vegetation models. Using leaf- and canopy-scale observations, this study evaluated the capability of five vegetation models (Community Land Model version 3.5 coupled to the Dynamic Global Vegetation model - CLM3.5-DGVM; Ecosystem Demography model version 2 - ED2; the Joint UK Land Environment Simulator version 2.1 - JULES; Simple Biosphere model version 3 - SiB3; and the soil-plant-atmosphere model - SPA) to simulate the responses of leaf- and canopy-scale productivity to changes in temperature and drought in an Amazonian forest. The models did not agree as to whether gross primary productivity (GPP) was more sensitive to changes in temperature or precipitation, but all the models were consistent with the prediction that GPP would be higher if tropical forests were 5 °C cooler than current ambient temperatures. There was greater model-data consistency in the response of net ecosystem exchange (NEE) to changes in temperature than in the response to temperature by net photosynthesis (An), stomatal conductance (gs) and leaf area index (LAI). Modelled canopy-scale fluxes are calculated by scaling leaf-scale fluxes using LAI. At the leaf-scale, the models did not agree on the temperature or magnitude of the optimum points of An, Vcmax or gs, and model variation in these parameters was compensated for by variations in the absolute magnitude of simulated LAI and how it altered with temperature. Across the models, there was, however, consistency in two leaf-scale responses: (1) change in An with temperature was more closely linked to stomatal behaviour than biochemical processes; and (2) intrinsic water use efficiency (IWUE) increased with temperature, especially when combined with drought. These results suggest that even up to fairly extreme temperature increases from ambient levels (+6 °C), simulated photosynthesis becomes increasingly sensitive to gs and remains less sensitive to biochemical changes. To improve the reliability of simulations of the response of Amazonian rainforest to climate change, the mechanistic underpinnings of vegetation models need to be validated at both leaf- and canopy-scales to improve accuracy and consistency in the quantification of processes within and across an ecosystem.

Predictive Ensemble Decoding of Acoustical Features Explains Context-Dependent Receptive Fields.

PubMed

Yildiz, Izzet B; Mesgarani, Nima; Deneve, Sophie

2016-12-07

A primary goal of auditory neuroscience is to identify the sound features extracted and represented by auditory neurons. Linear encoding models, which describe neural responses as a function of the stimulus, have been primarily used for this purpose. Here, we provide theoretical arguments and experimental evidence in support of an alternative approach, based on decoding the stimulus from the neural response. We used a Bayesian normative approach to predict the responses of neurons detecting relevant auditory features, despite ambiguities and noise. We compared the model predictions to recordings from the primary auditory cortex of ferrets and found that: (1) the decoding filters of auditory neurons resemble the filters learned from the statistics of speech sounds; (2) the decoding model captures the dynamics of responses better than a linear encoding model of similar complexity; and (3) the decoding model accounts for the accuracy with which the stimulus is represented in neural activity, whereas linear encoding model performs very poorly. Most importantly, our model predicts that neuronal responses are fundamentally shaped by "explaining away," a divisive competition between alternative interpretations of the auditory scene. Neural responses in the auditory cortex are dynamic, nonlinear, and hard to predict. Traditionally, encoding models have been used to describe neural responses as a function of the stimulus. However, in addition to external stimulation, neural activity is strongly modulated by the responses of other neurons in the network. We hypothesized that auditory neurons aim to collectively decode their stimulus. In particular, a stimulus feature that is decoded (or explained away) by one neuron is not explained by another. We demonstrated that this novel Bayesian decoding model is better at capturing the dynamic responses of cortical neurons in ferrets. Whereas the linear encoding model poorly reflects selectivity of neurons, the decoding model can account for the strong nonlinearities observed in neural data. Copyright © 2016 Yildiz et al.

Robust Estimation of Latent Ability in Item Response Models

ERIC Educational Resources Information Center

Schuster, Christof; Yuan, Ke-Hai

2011-01-01

Because of response disturbances such as guessing, cheating, or carelessness, item response models often can only approximate the "true" individual response probabilities. As a consequence, maximum-likelihood estimates of ability will be biased. Typically, the nature and extent to which response disturbances are present is unknown, and, therefore,…

Optimal Linking Design for Response Model Parameters

ERIC Educational Resources Information Center

Barrett, Michelle D.; van der Linden, Wim J.

2017-01-01

Linking functions adjust for differences between identifiability restrictions used in different instances of the estimation of item response model parameters. These adjustments are necessary when results from those instances are to be compared. As linking functions are derived from estimated item response model parameters, parameter estimation…

Prediction and control of neural responses to pulsatile electrical stimulation

NASA Astrophysics Data System (ADS)

Campbell, Luke J.; Sly, David James; O'Leary, Stephen John

2012-04-01

This paper aims to predict and control the probability of firing of a neuron in response to pulsatile electrical stimulation of the type delivered by neural prostheses such as the cochlear implant, bionic eye or in deep brain stimulation. Using the cochlear implant as a model, we developed an efficient computational model that predicts the responses of auditory nerve fibers to electrical stimulation and evaluated the model's accuracy by comparing the model output with pooled responses from a group of guinea pig auditory nerve fibers. It was found that the model accurately predicted the changes in neural firing probability over time to constant and variable amplitude electrical pulse trains, including speech-derived signals, delivered at rates up to 889 pulses s-1. A simplified version of the model that did not incorporate adaptation was used to adaptively predict, within its limitations, the pulsatile electrical stimulus required to cause a desired response from neurons up to 250 pulses s-1. Future stimulation strategies for cochlear implants and other neural prostheses may be enhanced using similar models that account for the way that neural responses are altered by previous stimulation.

A meta-analysis of response-time tests of the sequential two-systems model of moral judgment.

PubMed

Baron, Jonathan; Gürçay, Burcu

2017-05-01

The (generalized) sequential two-system ("default interventionist") model of utilitarian moral judgment predicts that utilitarian responses often arise from a system-two correction of system-one deontological intuitions. Response-time (RT) results that seem to support this model are usually explained by the fact that low-probability responses have longer RTs. Following earlier results, we predicted response probability from each subject's tendency to make utilitarian responses (A, "Ability") and each dilemma's tendency to elicit deontological responses (D, "Difficulty"), estimated from a Rasch model. At the point where A = D, the two responses are equally likely, so probability effects cannot account for any RT differences between them. The sequential two-system model still predicts that many of the utilitarian responses made at this point will result from system-two corrections of system-one intuitions, hence should take longer. However, when A = D, RT for the two responses was the same, contradicting the sequential model. Here we report a meta-analysis of 26 data sets, which replicated the earlier results of no RT difference overall at the point where A = D. The data sets used three different kinds of moral judgment items, and the RT equality at the point where A = D held for all three. In addition, we found that RT increased with A-D. This result holds for subjects (characterized by Ability) but not for items (characterized by Difficulty). We explain the main features of this unanticipated effect, and of the main results, with a drift-diffusion model.

A linear model fails to predict orientation selectivity of cells in the cat visual cortex.

PubMed Central

Volgushev, M; Vidyasagar, T R; Pei, X

1996-01-01

1. Postsynaptic potentials (PSPs) evoked by visual stimulation in simple cells in the cat visual cortex were recorded using in vivo whole-cell technique. Responses to small spots of light presented at different positions over the receptive field and responses to elongated bars of different orientations centred on the receptive field were recorded. 2. To test whether a linear model can account for orientation selectivity of cortical neurones, responses to elongated bars were compared with responses predicted by a linear model from the receptive field map obtained from flashing spots. 3. The linear model faithfully predicted the preferred orientation, but not the degree of orientation selectivity or the sharpness of orientation tuning. The ratio of optimal to non-optimal responses was always underestimated by the model. 4. Thus non-linear mechanisms, which can include suppression of non-optimal responses and/or amplification of optimal responses, are involved in the generation of orientation selectivity in the primary visual cortex. PMID:8930828

A Generalized QMRA Beta-Poisson Dose-Response Model.

PubMed

Xie, Gang; Roiko, Anne; Stratton, Helen; Lemckert, Charles; Dunn, Peter K; Mengersen, Kerrie

2016-10-01

Quantitative microbial risk assessment (QMRA) is widely accepted for characterizing the microbial risks associated with food, water, and wastewater. Single-hit dose-response models are the most commonly used dose-response models in QMRA. Denoting PI(d) as the probability of infection at a given mean dose d, a three-parameter generalized QMRA beta-Poisson dose-response model, PI(d|α,β,r*), is proposed in which the minimum number of organisms required for causing infection, K min , is not fixed, but a random variable following a geometric distribution with parameter 0

An Empirical Correction Method for Improving off-Axes Response Prediction in Component Type Flight Mechanics Helicopter Models

NASA Technical Reports Server (NTRS)

Mansur, M. Hossein; Tischler, Mark B.

1997-01-01

Historically, component-type flight mechanics simulation models of helicopters have been unable to satisfactorily predict the roll response to pitch stick input and the pitch response to roll stick input off-axes responses. In the study presented here, simple first-order low-pass filtering of the elemental lift and drag forces was considered as a means of improving the correlation. The method was applied to a blade-element model of the AH-64 APache, and responses of the modified model were compared with flight data in hover and forward flight. Results indicate that significant improvement in the off-axes responses can be achieved in hover. In forward flight, however, the best correlation in the longitudinal and lateral off-axes responses required different values of the filter time constant for each axis. A compromise value was selected and was shown to result in good overall improvement in the off-axes responses. The paper describes both the method and the model used for its implementation, and presents results obtained at hover and in forward flight.

Improved system identification using artificial neural networks and analysis of individual differences in responses of an identified neuron.

PubMed

Costalago Meruelo, Alicia; Simpson, David M; Veres, Sandor M; Newland, Philip L

2016-03-01

Mathematical modelling is used routinely to understand the coding properties and dynamics of responses of neurons and neural networks. Here we analyse the effectiveness of Artificial Neural Networks (ANNs) as a modelling tool for motor neuron responses. We used ANNs to model the synaptic responses of an identified motor neuron, the fast extensor motor neuron, of the desert locust in response to displacement of a sensory organ, the femoral chordotonal organ, which monitors movements of the tibia relative to the femur of the leg. The aim of the study was threefold: first to determine the potential value of ANNs as tools to model and investigate neural networks, second to understand the generalisation properties of ANNs across individuals and to different input signals and third, to understand individual differences in responses of an identified neuron. A metaheuristic algorithm was developed to design the ANN architectures. The performance of the models generated by the ANNs was compared with those generated through previous mathematical models of the same neuron. The results suggest that ANNs are significantly better than LNL and Wiener models in predicting specific neural responses to Gaussian White Noise, but not significantly different when tested with sinusoidal inputs. They are also able to predict responses of the same neuron in different individuals irrespective of which animal was used to develop the model, although notable differences between some individuals were evident. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Development of Web-based Graphical User Interface for Unified Modeling Data with Multi (Correlated) Responses

NASA Astrophysics Data System (ADS)

Made Tirta, I.; Anggraeni, Dian

2018-04-01

Statistical models have been developed rapidly into various directions to accommodate various types of data. Data collected from longitudinal, repeated measured, clustered data (either continuous, binary, count, or ordinal), are more likely to be correlated. Therefore statistical model for independent responses, such as Generalized Linear Model (GLM), Generalized Additive Model (GAM) are not appropriate. There are several models available to apply for correlated responses including GEEs (Generalized Estimating Equations), for marginal model and various mixed effect model such as GLMM (Generalized Linear Mixed Models) and HGLM (Hierarchical Generalized Linear Models) for subject spesific models. These models are available on free open source software R, but they can only be accessed through command line interface (using scrit). On the othe hand, most practical researchers very much rely on menu based or Graphical User Interface (GUI). We develop, using Shiny framework, standard pull down menu Web-GUI that unifies most models for correlated responses. The Web-GUI has accomodated almost all needed features. It enables users to do and compare various modeling for repeated measure data (GEE, GLMM, HGLM, GEE for nominal responses) much more easily trough online menus. This paper discusses the features of the Web-GUI and illustrates the use of them. In General we find that GEE, GLMM, HGLM gave very closed results.

A comparison of item response models for accuracy and speed of item responses with applications to adaptive testing.

PubMed

van Rijn, Peter W; Ali, Usama S

2017-05-01

We compare three modelling frameworks for accuracy and speed of item responses in the context of adaptive testing. The first framework is based on modelling scores that result from a scoring rule that incorporates both accuracy and speed. The second framework is the hierarchical modelling approach developed by van der Linden (2007, Psychometrika, 72, 287) in which a regular item response model is specified for accuracy and a log-normal model for speed. The third framework is the diffusion framework in which the response is assumed to be the result of a Wiener process. Although the three frameworks differ in the relation between accuracy and speed, one commonality is that the marginal model for accuracy can be simplified to the two-parameter logistic model. We discuss both conditional and marginal estimation of model parameters. Models from all three frameworks were fitted to data from a mathematics and spelling test. Furthermore, we applied a linear and adaptive testing mode to the data off-line in order to determine differences between modelling frameworks. It was found that a model from the scoring rule framework outperformed a hierarchical model in terms of model-based reliability, but the results were mixed with respect to correlations with external measures. © 2017 The British Psychological Society.

Climate Change: Modeling the Human Response

NASA Astrophysics Data System (ADS)

Oppenheimer, M.; Hsiang, S. M.; Kopp, R. E.

2012-12-01

Integrated assessment models have historically relied on forward modeling including, where possible, process-based representations to project climate change impacts. Some recent impact studies incorporate the effects of human responses to initial physical impacts, such as adaptation in agricultural systems, migration in response to drought, and climate-related changes in worker productivity. Sometimes the human response ameliorates the initial physical impacts, sometimes it aggravates it, and sometimes it displaces it onto others. In these arenas, understanding of underlying socioeconomic mechanisms is extremely limited. Consequently, for some sectors where sufficient data has accumulated, empirically based statistical models of human responses to past climate variability and change have been used to infer response sensitivities which may apply under certain conditions to future impacts, allowing a broad extension of integrated assessment into the realm of human adaptation. We discuss the insights gained from and limitations of such modeling for benefit-cost analysis of climate change.

System level analysis and control of manufacturing process variation

DOEpatents

Hamada, Michael S.; Martz, Harry F.; Eleswarpu, Jay K.; Preissler, Michael J.

2005-05-31

A computer-implemented method is implemented for determining the variability of a manufacturing system having a plurality of subsystems. Each subsystem of the plurality of subsystems is characterized by signal factors, noise factors, control factors, and an output response, all having mean and variance values. Response models are then fitted to each subsystem to determine unknown coefficients for use in the response models that characterize the relationship between the signal factors, noise factors, control factors, and the corresponding output response having mean and variance values that are related to the signal factors, noise factors, and control factors. The response models for each subsystem are coupled to model the output of the manufacturing system as a whole. The coefficients of the fitted response models are randomly varied to propagate variances through the plurality of subsystems and values of signal factors and control factors are found to optimize the output of the manufacturing system to meet a specified criterion.

The temporal representation of speech in a nonlinear model of the guinea pig cochlea

NASA Astrophysics Data System (ADS)

Holmes, Stephen D.; Sumner, Christian J.; O'Mard, Lowel P.; Meddis, Ray

2004-12-01

The temporal representation of speechlike stimuli in the auditory-nerve output of a guinea pig cochlea model is described. The model consists of a bank of dual resonance nonlinear filters that simulate the vibratory response of the basilar membrane followed by a model of the inner hair cell/auditory nerve complex. The model is evaluated by comparing its output with published physiological auditory nerve data in response to single and double vowels. The evaluation includes analyses of individual fibers, as well as ensemble responses over a wide range of best frequencies. In all cases the model response closely follows the patterns in the physiological data, particularly the tendency for the temporal firing pattern of each fiber to represent the frequency of a nearby formant of the speech sound. In the model this behavior is largely a consequence of filter shapes; nonlinear filtering has only a small contribution at low frequencies. The guinea pig cochlear model produces a useful simulation of the measured physiological response to simple speech sounds and is therefore suitable for use in more advanced applications including attempts to generalize these principles to the response of human auditory system, both normal and impaired. .

Meeting national response time targets for priority 1 incidents in an urban emergency medical services system in South Africa: More ambulances won't help.

PubMed

Stein, Christopher; Wallis, Lee; Adetunji, Olufemi

2015-09-19

Response time is viewed as a key performance indicator in most emergency medical services (EMS) systems. To determine the effect of increased emergency vehicle numbers on response time performance for priority 1 incidents in an urban EMS system in Cape Town, South Africa, using discrete-event computer simulation. A simulation model was created, based on input data from part of the EMS operations. Two different versions of the model were used, one with primary response vehicles and ambulances and one with only ambulances. In both cases the models were run in seven different scenarios. The first scenario used the actual number of emergency vehicles in the real system, and in each subsequent scenario vehicle numbers were increased by adding the baseline number to the cumulative total. The model using only ambulances had shorter response times and a greater number of responses meeting national response time targets than models using primary response vehicles and ambulances. In both cases an improvement in response times and the number of responses meeting national response time targets was observed with the first incremental addition of vehicles. After this the improvements rapidly diminished and eventually became negligible with each successive increase in vehicle numbers. The national response time target for urban areas was never met, even with a seven-fold increase in vehicle numbers. The addition of emergency vehicles to an urban EMS system improves response times in priority 1 incidents, but alone is not capable of the magnitude of response time improvement needed to meet the national response time targets.

TThe role of nitrogen availability in land-atmosphere interactions: a systematic evaluation of carbon-nitrogen coupling in a global land surface model using plot-level nitrogen fertilization experiments

NASA Astrophysics Data System (ADS)

Thomas, R. Q.; Goodale, C. L.; Bonan, G. B.; Mahowald, N. M.; Ricciuto, D. M.; Thornton, P. E.

2010-12-01

Recent research from global land surface models emphasizes the important role of nitrogen cycling on global climate, via its control on the terrestrial carbon balance. Despite the implications of nitrogen cycling on global climate predictions, the research community has not performed a systematic evaluation of nitrogen cycling in global models. Here, we present such an evaluation for one global land model, CLM-CN. In the evaluation we simulated 45 plot-scale nitrogen-fertilization experiments distributed across 33 temperate and boreal forest sites. Model predictions were evaluated against field observations by comparing the vegetation and soil carbon responses to the additional nitrogen. Aggregated across all experiments, the model predicted a larger vegetation carbon response and a smaller soil carbon response than observed; the responses partially offset each other, leading to a slightly larger total ecosystem carbon response than observed. However, the model-observation agreement improved for vegetation carbon when the sites with observed negative carbon responses to nitrogen were excluded, which may be because the model lacks mechanisms whereby nitrogen additions increase tree mortality. Among experiments, younger forests and boreal forests’ vegetation carbon responses were less than predicted and mature forests (> 40 years old) were greater than predicted. Specific to the CLM-CN, this study used a systematic evaluation to identify key areas to focus model development, especially soil carbon- nitrogen interactions and boreal forest nitrogen cycling. Applicable to the modeling community, this study demonstrates a standardized protocol for comparing carbon-nitrogen interactions among global land models.

A review: Development of a microdose model for analysis of adaptive response and bystander dose response behavior.

PubMed

Leonard, Bobby E

2008-02-27

Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type (125)I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1. Single Specific Energy Hits initiate Adaptive Response. 2. Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3. For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4. The dose range of the AR protection depends on the value of the Specific Energy per Hit, 1 >. 5. Alpha particle induced deleterious Bystander damage is modulated by low LET radiation.

Estimation and Identifiability of Model Parameters in Human Nociceptive Processing Using Yes-No Detection Responses to Electrocutaneous Stimulation.

PubMed

Yang, Huan; Meijer, Hil G E; Buitenweg, Jan R; van Gils, Stephan A

2016-01-01

Healthy or pathological states of nociceptive subsystems determine different stimulus-response relations measured from quantitative sensory testing. In turn, stimulus-response measurements may be used to assess these states. In a recently developed computational model, six model parameters characterize activation of nerve endings and spinal neurons. However, both model nonlinearity and limited information in yes-no detection responses to electrocutaneous stimuli challenge to estimate model parameters. Here, we address the question whether and how one can overcome these difficulties for reliable parameter estimation. First, we fit the computational model to experimental stimulus-response pairs by maximizing the likelihood. To evaluate the balance between model fit and complexity, i.e., the number of model parameters, we evaluate the Bayesian Information Criterion. We find that the computational model is better than a conventional logistic model regarding the balance. Second, our theoretical analysis suggests to vary the pulse width among applied stimuli as a necessary condition to prevent structural non-identifiability. In addition, the numerically implemented profile likelihood approach reveals structural and practical non-identifiability. Our model-based approach with integration of psychophysical measurements can be useful for a reliable assessment of states of the nociceptive system.

An empirical propellant response function for combustion stability predictions

NASA Technical Reports Server (NTRS)

Hessler, R. O.

1980-01-01

An empirical response function model was developed for ammonium perchlorate propellants to supplant T-burner testing at the preliminary design stage. The model was developed by fitting a limited T-burner data base, in terms of oxidizer size and concentration, to an analytical two parameter response function expression. Multiple peaks are predicted, but the primary effect is of a single peak for most formulations, with notable bulges for the various AP size fractions. The model was extended to velocity coupling with the assumption that dynamic response was controlled primarily by the solid phase described by the two parameter model. The magnitude of velocity coupling was then scaled using an erosive burning law. Routine use of the model for stability predictions on a number of propulsion units indicates that the model tends to overpredict propellant response. It is concluded that the model represents a generally conservative prediction tool, suited especially for the preliminary design stage when T-burner data may not be readily available. The model work included development of a rigorous summation technique for pseudopropellant properties and of a concept for modeling ordered packing of particulates.

Emergent climate and CO2 sensitivities of net primary productivity in ecosystem models do not agree with empirical data in temperate forests of eastern North America.

PubMed

Rollinson, Christine R; Liu, Yao; Raiho, Ann; Moore, David J P; McLachlan, Jason; Bishop, Daniel A; Dye, Alex; Matthes, Jaclyn H; Hessl, Amy; Hickler, Thomas; Pederson, Neil; Poulter, Benjamin; Quaife, Tristan; Schaefer, Kevin; Steinkamp, Jörg; Dietze, Michael C

2017-07-01

Ecosystem models show divergent responses of the terrestrial carbon cycle to global change over the next century. Individual model evaluation and multimodel comparisons with data have largely focused on individual processes at subannual to decadal scales. Thus far, data-based evaluations of emergent ecosystem responses to climate and CO 2 at multidecadal and centennial timescales have been rare. We compared the sensitivity of net primary productivity (NPP) to temperature, precipitation, and CO 2 in ten ecosystem models with the sensitivities found in tree-ring reconstructions of NPP and raw ring-width series at six temperate forest sites. These model-data comparisons were evaluated at three temporal extents to determine whether the rapid, directional changes in temperature and CO 2 in the recent past skew our observed responses to multiple drivers of change. All models tested here were more sensitive to low growing season precipitation than tree-ring NPP and ring widths in the past 30 years, although some model precipitation responses were more consistent with tree rings when evaluated over a full century. Similarly, all models had negative or no response to warm-growing season temperatures, while tree-ring data showed consistently positive effects of temperature. Although precipitation responses were least consistent among models, differences among models to CO 2 drive divergence and ensemble uncertainty in relative change in NPP over the past century. Changes in forest composition within models had no effect on climate or CO 2 sensitivity. Fire in model simulations reduced model sensitivity to climate and CO 2 , but only over the course of multiple centuries. Formal evaluation of emergent model behavior at multidecadal and multicentennial timescales is essential to reconciling model projections with observed ecosystem responses to past climate change. Future evaluation should focus on improved representation of disturbance and biomass change as well as the feedbacks with moisture balance and CO 2 in individual models. © 2017 John Wiley & Sons Ltd.

RRAWFLOW: Rainfall-Response Aquifer and Watershed Flow Model (v1.11)

NASA Astrophysics Data System (ADS)

Long, A. J.

2014-09-01

The Rainfall-Response Aquifer and Watershed Flow Model (RRAWFLOW) is a lumped-parameter model that simulates streamflow, springflow, groundwater level, solute transport, or cave drip for a measurement point in response to a system input of precipitation, recharge, or solute injection. The RRAWFLOW open-source code is written in the R language and is included in the Supplement to this article along with an example model of springflow. RRAWFLOW includes a time-series process to estimate recharge from precipitation and simulates the response to recharge by convolution; i.e., the unit hydrograph approach. Gamma functions are used for estimation of parametric impulse-response functions (IRFs); a combination of two gamma functions results in a double-peaked IRF. A spline fit to a set of control points is introduced as a new method for estimation of nonparametric IRFs. Other options include the use of user-defined IRFs and different methods to simulate time-variant systems. For many applications, lumped models simulate the system response with equal accuracy to that of distributed models, but moreover, the ease of model construction and calibration of lumped models makes them a good choice for many applications. RRAWFLOW provides professional hydrologists and students with an accessible and versatile tool for lumped-parameter modeling.

Modeling and Identification for Vector Propulsion of an Unmanned Surface Vehicle: Three Degrees of Freedom Model and Response Model.

PubMed

Mu, Dongdong; Wang, Guofeng; Fan, Yunsheng; Sun, Xiaojie; Qiu, Bingbing

2018-06-08

This paper presents a complete scheme for research on the three degrees of freedom model and response model of the vector propulsion of an unmanned surface vehicle. The object of this paper is “Lanxin”, an unmanned surface vehicle (7.02 m × 2.6 m), which is equipped with a single vector propulsion device. First, the “Lanxin” unmanned surface vehicle and the related field experiments (turning test and zig-zag test) are introduced and experimental data are collected through various sensors. Then, the thrust of the vector thruster is estimated by the empirical formula method. Third, using the hypothesis and simplification, the three degrees of freedom model and the response model of USV are deduced and established, respectively. Fourth, the parameters of the models (three degrees of freedom model, response model and thruster servo model) are obtained by system identification, and we compare the simulated turning test and zig-zag test with the actual data to verify the accuracy of the identification results. Finally, the biggest advantage of this paper is that it combines theory with practice. Based on identified response model, simulation and practical course keeping experiments are carried out to further verify feasibility and correctness of modeling and identification.

Crossfit analysis: a novel method to characterize the dynamics of induced plant responses.

PubMed

Jansen, Jeroen J; van Dam, Nicole M; Hoefsloot, Huub C J; Smilde, Age K

2009-12-16

Many plant species show induced responses that protect them against exogenous attacks. These responses involve the production of many different bioactive compounds. Plant species belonging to the Brassicaceae family produce defensive glucosinolates, which may greatly influence their favorable nutritional properties for humans. Each responding compound may have its own dynamic profile and metabolic relationships with other compounds. The chemical background of the induced response is therefore highly complex and may therefore not reveal all the properties of the response in any single model. This study therefore aims to describe the dynamics of the glucosinolate response, measured at three time points after induction in a feral Brassica, by a three-faceted approach, based on Principal Component Analysis. First the large-scale aspects of the response are described in a 'global model' and then each time-point in the experiment is individually described in 'local models' that focus on phenomena that occur at specific moments in time. Although each local model describes the variation among the plants at one time-point as well as possible, the response dynamics are lost. Therefore a novel method called the 'Crossfit' is described that links the local models of different time-points to each other. Each element of the described analysis approach reveals different aspects of the response. The crossfit shows that smaller dynamic changes may occur in the response that are overlooked by global models, as illustrated by the analysis of a metabolic profiling dataset of the same samples.

Crossfit analysis: a novel method to characterize the dynamics of induced plant responses

PubMed Central

2009-01-01

Background Many plant species show induced responses that protect them against exogenous attacks. These responses involve the production of many different bioactive compounds. Plant species belonging to the Brassicaceae family produce defensive glucosinolates, which may greatly influence their favorable nutritional properties for humans. Each responding compound may have its own dynamic profile and metabolic relationships with other compounds. The chemical background of the induced response is therefore highly complex and may therefore not reveal all the properties of the response in any single model. Results This study therefore aims to describe the dynamics of the glucosinolate response, measured at three time points after induction in a feral Brassica, by a three-faceted approach, based on Principal Component Analysis. First the large-scale aspects of the response are described in a 'global model' and then each time-point in the experiment is individually described in 'local models' that focus on phenomena that occur at specific moments in time. Although each local model describes the variation among the plants at one time-point as well as possible, the response dynamics are lost. Therefore a novel method called the 'Crossfit' is described that links the local models of different time-points to each other. Conclusions Each element of the described analysis approach reveals different aspects of the response. The crossfit shows that smaller dynamic changes may occur in the response that are overlooked by global models, as illustrated by the analysis of a metabolic profiling dataset of the same samples. PMID:20015363

Modelling the spatio-temporal modulation response of ganglion cells with difference-of-Gaussians receptive fields: relation to photoreceptor response kinetics.

PubMed

Donner, K; Hemilä, S

1996-01-01

Difference-of-Gaussians (DOG) models for the receptive fields of retinal ganglion cells accurately predict linear responses to both periodic stimuli (typically moving sinusoidal gratings) and aperiodic stimuli (typically circular fields presented as square-wave pulses). While the relation of spatial organization to retinal anatomy has received considerable attention, temporal characteristics have been only loosely connected to retinal physiology. Here we integrate realistic photoreceptor response waveforms into the DOG model to clarify how far a single set of physiological parameters predict temporal aspects of linear responses to both periodic and aperiodic stimuli. Traditional filter-cascade models provide a useful first-order approximation of the single-photon response in photoreceptors. The absolute time scale of these, plus a time for retinal transmission, here construed as a fixed delay, are obtained from flash/step data. Using these values, we find that the DOG model predicts the main features of both the amplitude and phase response of linear cat ganglion cells to sinusoidal flicker. Where the simplest model formulation fails, it serves to reveal additional mechanisms. Unforeseen facts are the attenuation of low temporal frequencies even in pure center-type responses, and the phase advance of the response relative to the stimulus at low frequencies. Neither can be explained by any experimentally documented cone response waveform, but both would be explained by signal differentiation, e.g. in the retinal transmission pathway, as demonstrated at least in turtle retina.

Adaptation of non-linear mixed amount with zero amount response surface model for analysis of concentration-dependent synergism and safety with midazolam, alfentanil, and propofol sedation.

PubMed

Liou, J-Y; Ting, C-K; Teng, W-N; Mandell, M S; Tsou, M-Y

2018-06-01

The non-linear mixed amount with zero amounts response surface model can be used to describe drug interactions and predict loss of response to noxious stimuli and respiratory depression. We aimed to determine whether this response surface model could be used to model sedation with the triple drug combination of midazolam, alfentanil and propofol. Sedation was monitored in 56 patients undergoing gastrointestinal endoscopy (modelling group) using modified alertness/sedation scores. A total of 227 combinations of effect-site concentrations were derived from pharmacokinetic models. Accuracy and the area under the receiver operating characteristic curve were calculated. Accuracy was defined as an absolute difference <0.5 between the binary patient responses and the predicted probability of loss of responsiveness. Validation was performed with a separate group (validation group) of 47 patients. Effect-site concentration ranged from 0 to 108 ng ml -1 for midazolam, 0-156 ng ml -1 for alfentanil, and 0-2.6 μg ml -1 for propofol in both groups. Synergy was strongest with midazolam and alfentanil (24.3% decrease in U 50 , concentration for half maximal drug effect). Adding propofol, a third drug, offered little additional synergy (25.8% decrease in U 50 ). Two patients (3%) experienced respiratory depression. Model accuracy was 83% and 76%, area under the curve was 0.87 and 0.80 for the modelling and validation group, respectively. The non-linear mixed amount with zero amounts triple interaction response surface model predicts patient sedation responses during endoscopy with combinations of midazolam, alfentanil, or propofol that fall within clinical use. Our model also suggests a safety margin of alfentanil fraction <0.12 that avoids respiratory depression after loss of responsiveness. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Parametric design and analysis on the landing gear of a planet lander using the response surface method

NASA Astrophysics Data System (ADS)

Zheng, Guang; Nie, Hong; Luo, Min; Chen, Jinbao; Man, Jianfeng; Chen, Chuanzhi; Lee, Heow Pueh

2018-07-01

The purpose of this paper is to obtain the design parameter-landing response relation for designing the configuration of the landing gear in a planet lander quickly. To achieve this, parametric studies on the landing gear are carried out using the response surface method (RSM), based on a single landing gear landing model validated by experimental results. According to the design of experiment (DOE) results of the landing model, the RS (response surface)-functions of the three crucial landing responses are obtained, and the sensitivity analysis (SA) of the corresponding parameters is performed. Also, two multi-objective optimizations designs on the landing gear are carried out. The analysis results show that the RS (response surface)-model performs well for the landing response design process, with a minimum fitting accuracy of 98.99%. The most sensitive parameters for the three landing response are the design size of the buffers, struts friction and the diameter of the bending beam. Moreover, the good agreement between the simulated model and RS-model results are obtained in two optimized designs, which show that the RS-model coupled with the FE (finite element)-method is an efficient method to obtain the design configuration of the landing gear.

COMPUTATIONAL MODELING OF SIGNALING PATHWAYS MEDIATING CELL CYCLE AND APOPTOTIC RESPONSES TO IONIZING RADIATION MEDIATED DNA DAMAGE

EPA Science Inventory

Demonstrated of the use of a computational systems biology approach to model dose response relationships. Also discussed how the biologically motivated dose response models have only limited reference to the underlying molecular level. Discussed the integration of Computational S...

Investigating the LGBTQ Responsive Model for Supervision of Group Work

ERIC Educational Resources Information Center

Luke, Melissa; Goodrich, Kristopher M.

2013-01-01

This article reports an investigation of the LGBTQ Responsive Model for Supervision of Group Work, a trans-theoretical supervisory framework to address the needs of lesbian, gay, bisexual, transgender, and questioning (LGBTQ) persons (Goodrich & Luke, 2011). Findings partially supported applicability of the LGBTQ Responsive Model for Supervision…

Ethical Leaders Resist: A Feminist Response to ACCEL

ERIC Educational Resources Information Center

Brimager, Ashley

2017-01-01

This response to Sternberg's ACCEL (Active Concerned Citizenship and Ethical Leadership) model aims to provide a feminist perspective on the rationale and relevance of the model in mitigating harmful patriarchal gender expectations. Additionally, this response investigates potential barriers to the implementation of ACCEL as a model for gifted…

Projective Item Response Model for Test-Independent Measurement

ERIC Educational Resources Information Center

Ip, Edward Hak-Sing; Chen, Shyh-Huei

2012-01-01

The problem of fitting unidimensional item-response models to potentially multidimensional data has been extensively studied. The focus of this article is on response data that contains a major dimension of interest but that may also contain minor nuisance dimensions. Because fitting a unidimensional model to multidimensional data results in…

Climate model diversity in the Northern Hemisphere Polar vortex response to climate change.

NASA Astrophysics Data System (ADS)

Simpson, I.; Seager, R.; Hitchcock, P.; Cohen, N.

2017-12-01

Global climate models vary widely in their predictions of the future of the Northern Hemisphere stratospheric polar vortex, with some showing a significant strengthening of the vortex, some showing a significant weakening and others displaying a response that is not outside of the range expected from internal variability alone. This inter-model spread in stratospheric predictions may account for some inter-model spread in tropospheric predictions with important implications for the storm tracks and regional climate change, particularly for the North Atlantic sector. Here, our current state of understanding of this model spread and its tropospheric impacts will be reviewed. Previous studies have proposed relationships between a models polar vortex response to climate change and its present day vortex climatology while others have demonstrated links between a models polar vortex response and changing wave activity coming up from the troposphere below under a warming climate. The extent to which these mechanisms can account for the spread in polar vortex changes exhibited by the Coupled Model Intercomparison Project, phase 5 models will be assessed. In addition, preliminary results from a series of idealized experiments with the Community Atmosphere Model will be presented. In these experiments, nudging of the stratospheric zonal mean state has been imposed to mimic the inter-model spread in the polar vortex response to climate change so that the downward influence of the spread in zonal mean stratospheric responses on the tropospheric circulation can be assessed within one model.

Model updating strategy for structures with localised nonlinearities using frequency response measurements

NASA Astrophysics Data System (ADS)

Wang, Xing; Hill, Thomas L.; Neild, Simon A.; Shaw, Alexander D.; Haddad Khodaparast, Hamed; Friswell, Michael I.

2018-02-01

This paper proposes a model updating strategy for localised nonlinear structures. It utilises an initial finite-element (FE) model of the structure and primary harmonic response data taken from low and high amplitude excitations. The underlying linear part of the FE model is first updated using low-amplitude test data with established techniques. Then, using this linear FE model, the nonlinear elements are localised, characterised, and quantified with primary harmonic response data measured under stepped-sine or swept-sine excitations. Finally, the resulting model is validated by comparing the analytical predictions with both the measured responses used in the updating and with additional test data. The proposed strategy is applied to a clamped beam with a nonlinear mechanism and good agreements between the analytical predictions and measured responses are achieved. Discussions on issues of damping estimation and dealing with data from amplitude-varying force input in the updating process are also provided.

Carotene Degradation and Isomerization during Thermal Processing: A Review on the Kinetic Aspects.

PubMed

Colle, Ines J P; Lemmens, Lien; Knockaert, Griet; Van Loey, Ann; Hendrickx, Marc

2016-08-17

Kinetic models are important tools for process design and optimization to balance desired and undesired reactions taking place in complex food systems during food processing and preservation. This review covers the state of the art on kinetic models available to describe heat-induced conversion of carotenoids, in particular lycopene and β-carotene. First, relevant properties of these carotenoids are discussed. Second, some general aspects of kinetic modeling are introduced, including both empirical single-response modeling and mechanism-based multi-response modeling. The merits of multi-response modeling to simultaneously describe carotene degradation and isomerization are demonstrated. The future challenge in this research field lies in the extension of the current multi-response models to better approach the real reaction pathway and in the integration of kinetic models with mass transfer models in case of reaction in multi-phase food systems.

Effect of space flight on interferon production - mechanistic studies

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald

1991-01-01

Ground-based models were studied for the effects of space flight on immune responses. Most time was spent on the model for the antiorthostatic, hypokinetic, hypodynamic suspension model for rats. Results indicate that suspension is useful for modeling the effects of spaceflight on functional immune responses, such as interferon and interleukin production. It does not appear to be useful for modeling shifts in leukocyte sub-populations. Calcium and 1,25-dihydroxyvitamin D sub 3 appear to play a pivitol role in regulating shifts in immune responses due to suspension. The macrophage appears to be an important target cell for the effects of suspension on immune responses.

Testing simulations of intra- and inter-annual variation in the plant production response to elevated CO(2) against measurements from an 11-year FACE experiment on grazed pasture.

PubMed

Li, Frank Yonghong; Newton, Paul C D; Lieffering, Mark

2014-01-01

Ecosystem models play a crucial role in understanding and evaluating the combined impacts of rising atmospheric CO2 concentration and changing climate on terrestrial ecosystems. However, we are not aware of any studies where the capacity of models to simulate intra- and inter-annual variation in responses to elevated CO2 has been tested against long-term experimental data. Here we tested how well the ecosystem model APSIM/AgPasture was able to simulate the results from a free air carbon dioxide enrichment (FACE) experiment on grazed pasture. At this FACE site, during 11 years of CO2 enrichment, a wide range in annual plant production response to CO2 (-6 to +28%) was observed. As well as running the full model, which includes three plant CO2 response functions (plant photosynthesis, nitrogen (N) demand and stomatal conductance), we also tested the influence of these three functions on model predictions. Model/data comparisons showed that: (i) overall the model over-predicted the mean annual plant production response to CO2 (18.5% cf 13.1%) largely because years with small or negative responses to CO2 were not well simulated; (ii) in general seasonal and inter-annual variation in plant production responses to elevated CO2 were well represented by the model; (iii) the observed CO2 enhancement in overall mean legume content was well simulated but year-to-year variation in legume content was poorly captured by the model; (iv) the best fit of the model to the data required all three CO2 response functions to be invoked; (v) using actual legume content and reduced N fixation rate under elevated CO2 in the model provided the best fit to the experimental data. We conclude that in temperate grasslands the N dynamics (particularly the legume content and N fixation activity) play a critical role in pasture production responses to elevated CO2 , and are processes for model improvement. © 2013 John Wiley & Sons Ltd.

Process-Response Modeling and the Scientific Process.

ERIC Educational Resources Information Center

Fichter, Lynn S.

1988-01-01

Discusses the process-response model (PRM) in its theoretical and practical forms. Describes how geologists attempt to reconstruct the process from the response (the geologic phenomenon) being studied. (TW)

STRESS RESPONSE STUDIES USING ANIMAL MODELS

EPA Science Inventory

This presentation will provide the evidence that ozone exposure in animal models induce neuroendocrine stress response and this stress response modulates lung injury and inflammation through adrenergic and glucocorticoid receptors.

Classifying Multi-Model Wheat Yield Impact Response Surfaces Showing Sensitivity to Temperature and Precipitation Change

NASA Technical Reports Server (NTRS)

Fronzek, Stefan; Pirttioja, Nina; Carter, Timothy R.; Bindi, Marco; Hoffmann, Holger; Palosuo, Taru; Ruiz-Ramos, Margarita; Tao, Fulu; Trnka, Miroslav; Acutis, Marco;

Chemical Sensor Array Response Modeling Using Quantitative Structure-Activity Relationships Technique

NASA Astrophysics Data System (ADS)

Shevade, Abhijit V.; Ryan, Margaret A.; Homer, Margie L.; Zhou, Hanying; Manfreda, Allison M.; Lara, Liana M.; Yen, Shiao-Pin S.; Jewell, April D.; Manatt, Kenneth S.; Kisor, Adam K.

We have developed a Quantitative Structure-Activity Relationships (QSAR) based approach to correlate the response of chemical sensors in an array with molecular descriptors. A novel molecular descriptor set has been developed; this set combines descriptors of sensing film-analyte interactions, representing sensor response, with a basic analyte descriptor set commonly used in QSAR studies. The descriptors are obtained using a combination of molecular modeling tools and empirical and semi-empirical Quantitative Structure-Property Relationships (QSPR) methods. The sensors under investigation are polymer-carbon sensing films which have been exposed to analyte vapors at parts-per-million (ppm) concentrations; response is measured as change in film resistance. Statistically validated QSAR models have been developed using Genetic Function Approximations (GFA) for a sensor array for a given training data set. The applicability of the sensor response models has been tested by using it to predict the sensor activities for test analytes not considered in the training set for the model development. The validated QSAR sensor response models show good predictive ability. The QSAR approach is a promising computational tool for sensing materials evaluation and selection. It can also be used to predict response of an existing sensing film to new target analytes.

A multi-agent safety response model in the construction industry.

PubMed

Meliá, José L

2015-01-01

The construction industry is one of the sectors with the highest accident rates and the most serious accidents. A multi-agent safety response approach allows a useful diagnostic tool in order to understand factors affecting risk and accidents. The special features of the construction sector can influence the relationships among safety responses along the model of safety influences. The purpose of this paper is to test a model explaining risk and work-related accidents in the construction industry as a result of the safety responses of the organization, the supervisors, the co-workers and the worker. 374 construction employees belonging to 64 small Spanish construction companies working for two main companies participated in the study. Safety responses were measured using a 45-item Likert-type questionnaire. The structure of the measure was analyzed using factor analysis and the model of effects was tested using a structural equation model. Factor analysis clearly identifies the multi-agent safety dimensions hypothesized. The proposed safety response model of work-related accidents, involving construction specific results, showed a good fit. The multi-agent safety response approach to safety climate is a useful framework for the assessment of organizational and behavioral risks in construction.

Solar irradiance reduction to counteract radiative forcing from a quadrupling of CO2: climate responses simulated by four earth system models

NASA Astrophysics Data System (ADS)

Schmidt, H.; Alterskjær, K.; Karam, D. Bou; Boucher, O.; Jones, A.; Kristjánsson, J. E.; Niemeier, U.; Schulz, M.; Aaheim, A.; Benduhn, F.; Lawrence, M.; Timmreck, C.

2012-06-01

In this study we compare the response of four state-of-the-art Earth system models to climate engineering under scenario G1 of two model intercomparison projects: GeoMIP (Geoengineering Model Intercomparison Project) and IMPLICC (EU project "Implications and risks of engineering solar radiation to limit climate change"). In G1, the radiative forcing from an instantaneous quadrupling of the CO2 concentration, starting from the preindustrial level, is balanced by a reduction of the solar constant. Model responses to the two counteracting forcings in G1 are compared to the preindustrial climate in terms of global means and regional patterns and their robustness. While the global mean surface air temperature in G1 remains almost unchanged compared to the control simulation, the meridional temperature gradient is reduced in all models. Another robust response is the global reduction of precipitation with strong effects in particular over North and South America and northern Eurasia. In comparison to the climate response to a quadrupling of CO2 alone, the temperature responses are small in experiment G1. Precipitation responses are, however, in many regions of comparable magnitude but globally of opposite sign.

Analysis of Mars Pathfinder Entry Data, Aerothermal Heating, and Heat Shield Material Response

NASA Technical Reports Server (NTRS)

Milos, Frank; Chen, Y. K.; Tran, H. K.; Rasky, Daniel J. (Technical Monitor)

1997-01-01

The Mars Pathfinder heatshield contained several thermocouples and resistance thermometers. A description of the experiment, the entry data, and analysis of the entry environment and material response is presented. In particular, the analysis addresses uncertainties of the data and the fluid dynamics and material response models. The calculations use the latest trajectory and atmosphere reconstructions for the Pathfinder entry. A modified version of the GIANTS code is used for CFD (computational fluid dynamics) analyses, and FIAT is used for material response. The material response and flowfield are coupled appropriately. Three different material response models are considered. The analysis of Pathfinder entry data for validation of aerothermal heating and material response models is complicated by model uncertainties and unanticipated data-acquisition and processing problems. We will discuss these issues as well as ramifications of the data and analysis for future Mars missions.

Modal identification of structures from the responses and random decrement signatures

NASA Technical Reports Server (NTRS)

Brahim, S. R.; Goglia, G. L.

1977-01-01

The theory and application of a method which utilizes the free response of a structure to determine its vibration parameters is described. The time-domain free response is digitized and used in a digital computer program to determine the number of modes excited, the natural frequencies, the damping factors, and the modal vectors. The technique is applied to a complex generalized payload model previously tested using sine sweep method and analyzed by NASTRAN. Ten modes of the payload model are identified. In case free decay response is not readily available, an algorithm is developed to obtain the free responses of a structure from its random responses, due to some unknown or known random input or inputs, using the random decrement technique without changing time correlation between signals. The algorithm is tested using random responses from a generalized payload model and from the space shuttle model.

Mixed-effects Gaussian process functional regression models with application to dose-response curve prediction.

PubMed

Shi, J Q; Wang, B; Will, E J; West, R M

2012-11-20

We propose a new semiparametric model for functional regression analysis, combining a parametric mixed-effects model with a nonparametric Gaussian process regression model, namely a mixed-effects Gaussian process functional regression model. The parametric component can provide explanatory information between the response and the covariates, whereas the nonparametric component can add nonlinearity. We can model the mean and covariance structures simultaneously, combining the information borrowed from other subjects with the information collected from each individual subject. We apply the model to dose-response curves that describe changes in the responses of subjects for differing levels of the dose of a drug or agent and have a wide application in many areas. We illustrate the method for the management of renal anaemia. An individual dose-response curve is improved when more information is included by this mechanism from the subject/patient over time, enabling a patient-specific treatment regime. Copyright © 2012 John Wiley & Sons, Ltd.

A comparison of models of the isometric force of locust skeletal muscle in response to pulse train inputs.

PubMed

Wilson, Emma; Rustighi, Emiliano; Newland, Philip L; Mace, Brian R

2012-03-01

Muscle models are an important tool in the development of new rehabilitation and diagnostic techniques. Many models have been proposed in the past, but little work has been done on comparing the performance of models. In this paper, seven models that describe the isometric force response to pulse train inputs are investigated. Five of the models are from the literature while two new models are also presented. Models are compared in terms of their ability to fit to isometric force data, using Akaike's and Bayesian information criteria and by examining the ability of each model to describe the underlying behaviour in response to individual pulses. Experimental data were collected by stimulating the locust extensor tibia muscle and measuring the force generated at the tibia. Parameters in each model were estimated by minimising the error between the modelled and actual force response for a set of training data. A separate set of test data, which included physiological kick-type data, was used to assess the models. It was found that a linear model performed the worst whereas a new model was found to perform the best. The parameter sensitivity of this new model was investigated using a one-at-a-time approach, and it found that the force response is not particularly sensitive to changes in any parameter.

A comparison of methods of fitting several models to nutritional response data.

PubMed

Vedenov, D; Pesti, G M

2008-02-01

A variety of models have been proposed to fit nutritional input-output response data. The models are typically nonlinear; therefore, fitting the models usually requires sophisticated statistical software and training to use it. An alternative tool for fitting nutritional response models was developed by using widely available and easier-to-use Microsoft Excel software. The tool, implemented as an Excel workbook (NRM.xls), allows simultaneous fitting and side-by-side comparisons of several popular models. This study compared the results produced by the tool we developed and PROC NLIN of SAS. The models compared were the broken line (ascending linear and quadratic segments), saturation kinetics, 4-parameter logistics, sigmoidal, and exponential models. The NRM.xls workbook provided results nearly identical to those of PROC NLIN. Furthermore, the workbook successfully fit several models that failed to converge in PROC NLIN. Two data sets were used as examples to compare fits by the different models. The results suggest that no particular nonlinear model is necessarily best for all nutritional response data.

Modeling human vestibular responses during eccentric rotation and off vertical axis rotation

NASA Technical Reports Server (NTRS)

Merfeld, D. M.; Paloski, W. H. (Principal Investigator)

1995-01-01

A mathematical model has been developed to help explain human multi-sensory interactions. The most important constituent of the model is the hypothesis that the nervous system incorporates knowledge of sensory dynamics into an "internal model" of these dynamics. This internal model allows the nervous system to integrate the sensory information from many different sensors into a coherent estimate of self-motion. The essence of the model is unchanged from a previously published model of monkey eye movement responses; only a few variables have been adjusted to yield the prediction of human responses. During eccentric rotation, the model predicts that the axis of eye rotation shifts slightly toward alignment with gravito-inertial force. The model also predicts that the time course of the perception of tilt following the acceleration phase of eccentric rotation is much slower than that during deceleration. During off vertical axis rotation (OVAR) the model predicts a small horizontal bias along with small horizontal, vertical, and torsional oscillations. Following OVAR stimulation, when stopped right- or left-side down, a small vertical component is predicted that decays with the horizontal post-rotatory response. All of the predictions are consistent with measurements of human responses.

Comparing the GPR responses of real experiment and simulation of cavity

NASA Astrophysics Data System (ADS)

Yu, H.; Nam, M. J.; Kim, C.; Lee, D. K.

2017-12-01

Seoul, capital city of South Korea, has been suffering from ground subsidence mainly caused by cavities beneath the road. Urban subsidence usually brings serious social problems such as damages of human life, properties and so on. To prevent ground subsidence, Korea government embark much money in developing techniques to detect cavities in advance. Ground penetrating radar (GPR) is known as the most effective method among geophysical surveys in exploring underground cavitied but shallow ones only. For the study of GPR responses for underground cavities, real scale physical models have been made and GPR surveys are conducted. In simulating cavities with various sizes at various depths, spheres of polystyrene have been used since the electric permittivity of polystyrene has a similar value to that of the air. However, the real scale experiments only used simple shapes of cavities due to its expensive construction cost and further changing in shapes of cavities is limited once they are built. For not only comparison between field responses for the physical model and numerical responses but also for analyzing GPR responses for more various cavity shapes in numerous environments, we conducted numerical simulation of GPR responses using three-dimensional (3D) finite difference time domain (FDTD) GPR modeling algorithm employing staggered grid. We first construct numerical modeling for models similar to the physical models to confirm considering radiation pattern in numerical modeling of GPR responses which is critical to generate similar responses to field GPR data. Further, GPR responses computed for various shapes of cavities in several different environments determine not only additional construction of the physical cavities but also analyze the characteristics of GPR responses.

On the dimension of complex responses in nonlinear structural vibrations

NASA Astrophysics Data System (ADS)

Wiebe, R.; Spottswood, S. M.

2016-07-01

The ability to accurately model engineering systems under extreme dynamic loads would prove a major breakthrough in many aspects of aerospace, mechanical, and civil engineering. Extreme loads frequently induce both nonlinearities and coupling which increase the complexity of the response and the computational cost of finite element models. Dimension reduction has recently gained traction and promises the ability to distill dynamic responses down to a minimal dimension without sacrificing accuracy. In this context, the dimensionality of a response is related to the number of modes needed in a reduced order model to accurately simulate the response. Thus, an important step is characterizing the dimensionality of complex nonlinear responses of structures. In this work, the dimensionality of the nonlinear response of a post-buckled beam is investigated. Significant detail is dedicated to carefully introducing the experiment, the verification of a finite element model, and the dimensionality estimation algorithm as it is hoped that this system may help serve as a benchmark test case. It is shown that with minor modifications, the method of false nearest neighbors can quantitatively distinguish between the response dimension of various snap-through, non-snap-through, random, and deterministic loads. The state-space dimension of the nonlinear system in question increased from 2-to-10 as the system response moved from simple, low-level harmonic to chaotic snap-through. Beyond the problem studied herein, the techniques developed will serve as a prescriptive guide in developing fast and accurate dimensionally reduced models of nonlinear systems, and eventually as a tool for adaptive dimension-reduction in numerical modeling. The results are especially relevant in the aerospace industry for the design of thin structures such as beams, panels, and shells, which are all capable of spatio-temporally complex dynamic responses that are difficult and computationally expensive to model.

Test-Anchored Vibration Response Predictions for an Acoustically Energized Curved Orthogrid Panel with Mounted Components

NASA Technical Reports Server (NTRS)

Frady, Gregory P.; Duvall, Lowery D.; Fulcher, Clay W. G.; Laverde, Bruce T.; Hunt, Ronald A.

2011-01-01

rich body of vibroacoustic test data was recently generated at Marshall Space Flight Center for component-loaded curved orthogrid panels typical of launch vehicle skin structures. The test data were used to anchor computational predictions of a variety of spatially distributed responses including acceleration, strain and component interface force. Transfer functions relating the responses to the input pressure field were generated from finite element based modal solutions and test-derived damping estimates. A diffuse acoustic field model was applied to correlate the measured input sound pressures across the energized panel. This application quantifies the ability to quickly and accurately predict a variety of responses to acoustically energized skin panels with mounted components. Favorable comparisons between the measured and predicted responses were established. The validated models were used to examine vibration response sensitivities to relevant modeling parameters such as pressure patch density, mesh density, weight of the mounted component and model form. Convergence metrics include spectral densities and cumulative root-mean squared (RMS) functions for acceleration, velocity, displacement, strain and interface force. Minimum frequencies for response convergence were established as well as recommendations for modeling techniques, particularly in the early stages of a component design when accurate structural vibration requirements are needed relatively quickly. The results were compared with long-established guidelines for modeling accuracy of component-loaded panels. A theoretical basis for the Response/Pressure Transfer Function (RPTF) approach provides insight into trends observed in the response predictions and confirmed in the test data. The software developed for the RPTF method allows easy replacement of the diffuse acoustic field with other pressure fields such as a turbulent boundary layer (TBL) model suitable for vehicle ascent. Structural responses using a TBL model were demonstrated, and wind tunnel tests have been proposed to anchor the predictions and provide new insight into modeling approaches for this environment. Finally, design load factors were developed from the measured and predicted responses and compared with those derived from traditional techniques such as historical Mass Acceleration Curves and Barrett scaling methods for acreage and component-loaded panels.

General mixture item response models with different item response structures: Exposition with an application to Likert scales.

PubMed

Tijmstra, Jesper; Bolsinova, Maria; Jeon, Minjeong

2018-01-10

This article proposes a general mixture item response theory (IRT) framework that allows for classes of persons to differ with respect to the type of processes underlying the item responses. Through the use of mixture models, nonnested IRT models with different structures can be estimated for different classes, and class membership can be estimated for each person in the sample. If researchers are able to provide competing measurement models, this mixture IRT framework may help them deal with some violations of measurement invariance. To illustrate this approach, we consider a two-class mixture model, where a person's responses to Likert-scale items containing a neutral middle category are either modeled using a generalized partial credit model, or through an IRTree model. In the first model, the middle category ("neither agree nor disagree") is taken to be qualitatively similar to the other categories, and is taken to provide information about the person's endorsement. In the second model, the middle category is taken to be qualitatively different and to reflect a nonresponse choice, which is modeled using an additional latent variable that captures a person's willingness to respond. The mixture model is studied using simulation studies and is applied to an empirical example.

Shift-variant linear system modeling for multispectral scanners

NASA Astrophysics Data System (ADS)

Amini, Abolfazl M.; Ioup, George E.; Ioup, Juliette W.

1995-07-01

Multispectral scanner data are affected both by the spatial impulse response of the sensor and the spectral response of each channel. To achieve a realistic representation for the output data for a given scene spectral input, both of these effects must be incorporated into a forward model. Each channel can have a different spatial response and each has its characteristic spectral response. A forward model is built which includes the shift invariant spatial broadening of the input for the channels and the shift variant spectral response across channels. The model is applied to the calibrated airborne multispectral scanner as well as the airborne terrestrial applications sensor developed at NASA Stennis Space Center.

Modeling Information Accumulation in Psychological Tests Using Item Response Times

ERIC Educational Resources Information Center

Ranger, Jochen; Kuhn, Jörg-Tobias

2015-01-01

In this article, a latent trait model is proposed for the response times in psychological tests. The latent trait model is based on the linear transformation model and subsumes popular models from survival analysis, like the proportional hazards model and the proportional odds model. Core of the model is the assumption that an unspecified monotone…

A discourse on sensitivity analysis for discretely-modeled structures

NASA Technical Reports Server (NTRS)

Adelman, Howard M.; Haftka, Raphael T.

1991-01-01

A descriptive review is presented of the most recent methods for performing sensitivity analysis of the structural behavior of discretely-modeled systems. The methods are generally but not exclusively aimed at finite element modeled structures. Topics included are: selections of finite difference step sizes; special consideration for finite difference sensitivity of iteratively-solved response problems; first and second derivatives of static structural response; sensitivity of stresses; nonlinear static response sensitivity; eigenvalue and eigenvector sensitivities for both distinct and repeated eigenvalues; and sensitivity of transient response for both linear and nonlinear structural response.

User-experience surveys with maternity services: a randomized comparison of two data collection models.

PubMed

Bjertnaes, Oyvind Andresen; Iversen, Hilde Hestad

2012-08-01

To compare two ways of combining postal and electronic data collection for a maternity services user-experience survey. Cross-sectional survey. Maternity services in Norway. All women who gave birth at a university hospital in Norway between 1 June and 27 July 2010. Patients were randomized into the following groups (n= 752): Group A, who were posted questionnaires with both electronic and paper response options for both the initial and reminder postal requests; and Group B, who were posted questionnaires with an electronic response option for the initial request, and both electronic and paper response options for the reminder postal request. Response rate, the amount of difference in background variables between respondents and non-respondents, main study results and estimated cost-effectiveness. The final response rate was significantly higher in Group A (51.9%) than Group B (41.1%). None of the background variables differed significantly between the respondents and non-respondents in Group A, while two variables differed significantly between the respondents and non-respondents in Group B. None of the 11 user-experience scales differed significantly between Groups A and B. The estimated costs per response for the forthcoming national survey was €11.7 for data collection Model A and €9.0 for Model B. The model with electronic-only response option in the first request had lowest response rate. However, this model performed equal to the other model on non-response bias and better on estimated cost-effectiveness, and is the better of the two models in large-scale user experiences surveys with maternity services.

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…

Development of a multi-body nonlinear model for a seat-occupant system

NASA Astrophysics Data System (ADS)

Azizi, Yousof

A car seat is an important component of today's cars, which directly affects ride comfort experienced by occupants. Currently, the process of ride comfort evaluation is subjective. Alternatively, the ride comfort can be evaluated by a series of objective metrics in the dynamic response of the occupant. From previous studies it is well known that the dynamic behavior of a seat-occupant system is greatly affected by soft nonlinear viscoelastic materials used in the seat cushion. Therefore, in this research, especial attention was given to efficiently modeling the behavior of seat cushion. In the first part of this research, a phenomenological nonlinear viscoelastic foam model was proposed and its ability to capture uniaxial behavior of foam was investigated. The model is based on the assumption that the total stress can be decomposed into the sum of a nonlinear elastic component, modeled by a higher order polynomial of strain, and a nonlinear hereditary type viscoelastic component. System identification procedures were developed to estimate the model parameters using uniaxial cyclic compression data from experiments conducted at different rates on two types of low density polyurethane foams and three types of high density CONFOR foams. The performance of the proposed model was compared to that of other traditional continuum models. For each foam type, it was observed that lower order models are sufficient to describe the uniaxial behavior of the foam compressed at different rates. Although, the estimated model parameters were functions of the input strain rate. Alternatively, higher order comprehensive models, with strain independent parameters, were estimated as well. The estimated comprehensive model predicts foam responses under different compression rates. Also, a methodology was proposed to predict the stress-response of a layered foam system using the estimated models of each foam in the layers. Next, the estimated foam model was incorporated into a single-degree of freedom foam-mass model which is also the simplest model of seat-occupant systems. The steady-state response of the system when it is subjected to harmonic base excitation was studied using the incremental harmonic balance method. The incremental harmonic balance method was used to reduce the time required to generate the steady-state response of the system. The incremental harmonic balance method was used to reduce the time required to generate the steady-state response of the system. Experiments are conducted on a single-degree of freedom foam-mass system subjected to harmonic base excitation. Initially, the simulated response predictions were found to deviate from the experimental results. The foam-mass model was then modified to incorporate rate dependency of foam parameters resulting in response predictions that were in good agreement with experimental results. In the second part of this research, the dynamic response of a seat-occupant system was examined through a more realistic planar multi-body seat-occupant model. A constraint Lagrangian formulation was used to derive the governing equations for the seat-occupant model. First, the governing equations were solved numerically to obtain the occupant transient response, the occupant's H-Point location and the interfacial pressure distribution. Variations in the H-Point location and the seat-occupant pressure distribution with changes in the seat-occupant parameters, including the seat geometry and the occupant's characteristics, were studied. The estimated pressure was also investigated experimentally and was found to match with the results obtained using the seat-occupant model. Next, the incremental harmonic balance method was modified and used to obtain the occupant's steady-state response when the seat-occupant system was subjected to harmonic base excitation at different frequencies. The system frequency response and mode shapes at different frequencies were also obtained and compared to the previously measured experimental frequency responses. Finally, variations in the estimated frequency response with changes in the seat-occupant parameters, including the seat geometry and the occupant characteristics, were studied.

Improved partition equilibrium model for predicting analyte response in electrospray ionization mass spectrometry.

PubMed

Du, Lihong; White, Robert L

2009-02-01

A previously proposed partition equilibrium model for quantitative prediction of analyte response in electrospray ionization mass spectrometry is modified to yield an improved linear relationship. Analyte mass spectrometer response is modeled by a competition mechanism between analyte and background electrolytes that is based on partition equilibrium considerations. The correlation between analyte response and solution composition is described by the linear model over a wide concentration range and the improved model is shown to be valid for a wide range of experimental conditions. The behavior of an analyte in a salt solution, which could not be explained by the original model, is correctly predicted. The ion suppression effects of 16:0 lysophosphatidylcholine (LPC) on analyte signals are attributed to a combination of competition for excess charge and reduction of total charge due to surface tension effects. In contrast to the complicated mathematical forms that comprise the original model, the simplified model described here can more easily be employed to predict analyte mass spectrometer responses for solutions containing multiple components. Copyright (c) 2008 John Wiley & Sons, Ltd.

An Improved Dynamic Model for the Respiratory Response to Exercise

PubMed Central

Serna, Leidy Y.; Mañanas, Miguel A.; Hernández, Alher M.; Rabinovich, Roberto A.

2018-01-01

Respiratory system modeling has been extensively studied in steady-state conditions to simulate sleep disorders, to predict its behavior under ventilatory diseases or stimuli and to simulate its interaction with mechanical ventilation. Nevertheless, the studies focused on the instantaneous response are limited, which restricts its application in clinical practice. The aim of this study is double: firstly, to analyze both dynamic and static responses of two known respiratory models under exercise stimuli by using an incremental exercise stimulus sequence (to analyze the model responses when step inputs are applied) and experimental data (to assess prediction capability of each model). Secondly, to propose changes in the models' structures to improve their transient and stationary responses. The versatility of the resulting model vs. the other two is shown according to the ability to simulate ventilatory stimuli, like exercise, with a proper regulation of the arterial blood gases, suitable constant times and a better adjustment to experimental data. The proposed model adjusts the breathing pattern every respiratory cycle using an optimization criterion based on minimization of work of breathing through regulation of respiratory frequency. PMID:29467674

Harnessing the theoretical foundations of the exponential and beta-Poisson dose-response models to quantify parameter uncertainty using Markov Chain Monte Carlo.

PubMed

Schmidt, Philip J; Pintar, Katarina D M; Fazil, Aamir M; Topp, Edward

2013-09-01

Dose-response models are the essential link between exposure assessment and computed risk values in quantitative microbial risk assessment, yet the uncertainty that is inherent to computed risks because the dose-response model parameters are estimated using limited epidemiological data is rarely quantified. Second-order risk characterization approaches incorporating uncertainty in dose-response model parameters can provide more complete information to decisionmakers by separating variability and uncertainty to quantify the uncertainty in computed risks. Therefore, the objective of this work is to develop procedures to sample from posterior distributions describing uncertainty in the parameters of exponential and beta-Poisson dose-response models using Bayes's theorem and Markov Chain Monte Carlo (in OpenBUGS). The theoretical origins of the beta-Poisson dose-response model are used to identify a decomposed version of the model that enables Bayesian analysis without the need to evaluate Kummer confluent hypergeometric functions. Herein, it is also established that the beta distribution in the beta-Poisson dose-response model cannot address variation among individual pathogens, criteria to validate use of the conventional approximation to the beta-Poisson model are proposed, and simple algorithms to evaluate actual beta-Poisson probabilities of infection are investigated. The developed MCMC procedures are applied to analysis of a case study data set, and it is demonstrated that an important region of the posterior distribution of the beta-Poisson dose-response model parameters is attributable to the absence of low-dose data. This region includes beta-Poisson models for which the conventional approximation is especially invalid and in which many beta distributions have an extreme shape with questionable plausibility. © Her Majesty the Queen in Right of Canada 2013. Reproduced with the permission of the Minister of the Public Health Agency of Canada.

Asymmetric responses of primary productivity to altered precipitation simulated by ecosystem models across three long-term grassland sites

NASA Astrophysics Data System (ADS)

Wu, Donghai; Ciais, Philippe; Viovy, Nicolas; Knapp, Alan K.; Wilcox, Kevin; Bahn, Michael; Smith, Melinda D.; Vicca, Sara; Fatichi, Simone; Zscheischler, Jakob; He, Yue; Li, Xiangyi; Ito, Akihiko; Arneth, Almut; Harper, Anna; Ukkola, Anna; Paschalis, Athanasios; Poulter, Benjamin; Peng, Changhui; Ricciuto, Daniel; Reinthaler, David; Chen, Guangsheng; Tian, Hanqin; Genet, Hélène; Mao, Jiafu; Ingrisch, Johannes; Nabel, Julia E. S. M.; Pongratz, Julia; Boysen, Lena R.; Kautz, Markus; Schmitt, Michael; Meir, Patrick; Zhu, Qiuan; Hasibeder, Roland; Sippel, Sebastian; Dangal, Shree R. S.; Sitch, Stephen; Shi, Xiaoying; Wang, Yingping; Luo, Yiqi; Liu, Yongwen; Piao, Shilong

2018-06-01

Field measurements of aboveground net primary productivity (ANPP) in temperate grasslands suggest that both positive and negative asymmetric responses to changes in precipitation (P) may occur. Under normal range of precipitation variability, wet years typically result in ANPP gains being larger than ANPP declines in dry years (positive asymmetry), whereas increases in ANPP are lower in magnitude in extreme wet years compared to reductions during extreme drought (negative asymmetry). Whether the current generation of ecosystem models with a coupled carbon-water system in grasslands are capable of simulating these asymmetric ANPP responses is an unresolved question. In this study, we evaluated the simulated responses of temperate grassland primary productivity to scenarios of altered precipitation with 14 ecosystem models at three sites: Shortgrass steppe (SGS), Konza Prairie (KNZ) and Stubai Valley meadow (STU), spanning a rainfall gradient from dry to moist. We found that (1) the spatial slopes derived from modeled primary productivity and precipitation across sites were steeper than the temporal slopes obtained from inter-annual variations, which was consistent with empirical data; (2) the asymmetry of the responses of modeled primary productivity under normal inter-annual precipitation variability differed among models, and the mean of the model ensemble suggested a negative asymmetry across the three sites, which was contrary to empirical evidence based on filed observations; (3) the mean sensitivity of modeled productivity to rainfall suggested greater negative response with reduced precipitation than positive response to an increased precipitation under extreme conditions at the three sites; and (4) gross primary productivity (GPP), net primary productivity (NPP), aboveground NPP (ANPP) and belowground NPP (BNPP) all showed concave-down nonlinear responses to altered precipitation in all the models, but with different curvatures and mean values. Our results indicated that most models overestimate the negative drought effects and/or underestimate the positive effects of increased precipitation on primary productivity under normal climate conditions, highlighting the need for improving eco-hydrological processes in those models in the future.

A bivariate model for analyzing recurrent multi-type automobile failures

NASA Astrophysics Data System (ADS)

Sunethra, A. A.; Sooriyarachchi, M. R.

2017-09-01

The failure mechanism in an automobile can be defined as a system of multi-type recurrent failures where failures can occur due to various multi-type failure modes and these failures are repetitive such that more than one failure can occur from each failure mode. In analysing such automobile failures, both the time and type of the failure serve as response variables. However, these two response variables are highly correlated with each other since the timing of failures has an association with the mode of the failure. When there are more than one correlated response variables, the fitting of a multivariate model is more preferable than separate univariate models. Therefore, a bivariate model of time and type of failure becomes appealing for such automobile failure data. When there are multiple failure observations pertaining to a single automobile, such data cannot be treated as independent data because failure instances of a single automobile are correlated with each other while failures among different automobiles can be treated as independent. Therefore, this study proposes a bivariate model consisting time and type of failure as responses adjusted for correlated data. The proposed model was formulated following the approaches of shared parameter models and random effects models for joining the responses and for representing the correlated data respectively. The proposed model is applied to a sample of automobile failures with three types of failure modes and up to five failure recurrences. The parametric distributions that were suitable for the two responses of time to failure and type of failure were Weibull distribution and multinomial distribution respectively. The proposed bivariate model was programmed in SAS Procedure Proc NLMIXED by user programming appropriate likelihood functions. The performance of the bivariate model was compared with separate univariate models fitted for the two responses and it was identified that better performance is secured by the bivariate model. The proposed model can be used to determine the time and type of failure that would occur in the automobiles considered here.

Computerized Adaptive Test (CAT) Applications and Item Response Theory Models for Polytomous Items

ERIC Educational Resources Information Center

Aybek, Eren Can; Demirtasli, R. Nukhet

2017-01-01

This article aims to provide a theoretical framework for computerized adaptive tests (CAT) and item response theory models for polytomous items. Besides that, it aims to introduce the simulation and live CAT software to the related researchers. Computerized adaptive test algorithm, assumptions of item response theory models, nominal response…

Introduction to Multilevel Item Response Theory Analysis: Descriptive and Explanatory Models

ERIC Educational Resources Information Center

Sulis, Isabella; Toland, Michael D.

2017-01-01

Item response theory (IRT) models are the main psychometric approach for the development, evaluation, and refinement of multi-item instruments and scaling of latent traits, whereas multilevel models are the primary statistical method when considering the dependence between person responses when primary units (e.g., students) are nested within…

The Cognitive-Miser Response Model: Testing for Intuitive and Deliberate Reasoning

ERIC Educational Resources Information Center

Bockenholt, Ulf

2012-01-01

In a number of psychological studies, answers to reasoning vignettes have been shown to result from both intuitive and deliberate response processes. This paper utilizes a psychometric model to separate these two response tendencies. An experimental application shows that the proposed model facilitates the analysis of dual-process item responses…

Stressor-response modeling using the 2D water quality model and regression trees to predict chlorophyll-a in a reservoir system

USDA-ARS?s Scientific Manuscript database

In order to control algal blooms, stressor-response relationships between water quality metrics, environmental variables, and algal growth should be understood and modeled. Machine-learning methods were suggested to express stressor-response relationships found by application of mechanistic water qu...

IRTPRO 2.1 for Windows (Item Response Theory for Patient-Reported Outcomes)

ERIC Educational Resources Information Center

Paek, Insu; Han, Kyung T.

2013-01-01

This article reviews a new item response theory (IRT) model estimation program, IRTPRO 2.1, for Windows that is capable of unidimensional and multidimensional IRT model estimation for existing and user-specified constrained IRT models for dichotomously and polytomously scored item response data. (Contains 1 figure and 2 notes.)

The Role of Assessment in a Response to Intervention Model

ERIC Educational Resources Information Center

Crawford, Lindy

2014-01-01

This article discusses the role of assessment in a response-to-intervention model. Although assessment represents only 1 component in a response-to-intervention model, a well-articulated assessment system is critical in providing teachers with reliable data that are easily interpreted and used to make instructional decisions. Three components of…

KERIS: kaleidoscope of gene responses to inflammation between species

PubMed Central

Li, Peng; Tompkins, Ronald G; Xiao, Wenzhong

2017-01-01

A cornerstone of modern biomedical research is the use of animal models to study disease mechanisms and to develop new therapeutic approaches. In order to help the research community to better explore the similarities and differences of genomic response between human inflammatory diseases and murine models, we developed KERIS: kaleidoscope of gene responses to inflammation between species (available at http://www.igenomed.org/keris/). As of June 2016, KERIS includes comparisons of the genomic response of six human inflammatory diseases (burns, trauma, infection, sepsis, endotoxin and acute respiratory distress syndrome) and matched mouse models, using 2257 curated samples from the Inflammation and the Host Response to Injury Glue Grant studies and other representative studies in Gene Expression Omnibus. A researcher can browse, query, visualize and compare the response patterns of genes, pathways and functional modules across different diseases and corresponding murine models. The database is expected to help biologists choosing models when studying the mechanisms of particular genes and pathways in a disease and prioritizing the translation of findings from disease models into clinical studies. PMID:27789704

Do Responses to Different Anthropogenic Forcings Add Linearly in Climate Models?

NASA Technical Reports Server (NTRS)

Marvel, Kate; Schmidt, Gavin A.; Shindell, Drew; Bonfils, Celine; LeGrande, Allegra N.; Nazarenko, Larissa; Tsigaridis, Kostas

2015-01-01

Many detection and attribution and pattern scaling studies assume that the global climate response to multiple forcings is additive: that the response over the historical period is statistically indistinguishable from the sum of the responses to individual forcings. Here, we use the NASA Goddard Institute for Space Studies (GISS) and National Center for Atmospheric Research Community Climate System Model (CCSM) simulations from the CMIP5 archive to test this assumption for multi-year trends in global-average, annual-average temperature and precipitation at multiple timescales. We find that responses in models forced by pre-computed aerosol and ozone concentrations are generally additive across forcings; however, we demonstrate that there are significant nonlinearities in precipitation responses to di?erent forcings in a configuration of the GISS model that interactively computes these concentrations from precursor emissions. We attribute these to di?erences in ozone forcing arising from interactions between forcing agents. Our results suggest that attribution to specific forcings may be complicated in a model with fully interactive chemistry and may provide motivation for other modeling groups to conduct further single-forcing experiments.

Do responses to different anthropogenic forcings add linearly in climate models?

DOE PAGES

Marvel, Kate; Schmidt, Gavin A.; Shindell, Drew; ...

2015-10-14

Many detection and attribution and pattern scaling studies assume that the global climate response to multiple forcings is additive: that the response over the historical period is statistically indistinguishable from the sum of the responses to individual forcings. Here, we use the NASA Goddard Institute for Space Studies (GISS) and National Center for Atmospheric Research Community Climate System Model (CCSM4) simulations from the CMIP5 archive to test this assumption for multi-year trends in global-average, annual-average temperature and precipitation at multiple timescales. We find that responses in models forced by pre-computed aerosol and ozone concentrations are generally additive across forcings. However,more » we demonstrate that there are significant nonlinearities in precipitation responses to different forcings in a configuration of the GISS model that interactively computes these concentrations from precursor emissions. We attribute these to differences in ozone forcing arising from interactions between forcing agents. Lastly, our results suggest that attribution to specific forcings may be complicated in a model with fully interactive chemistry and may provide motivation for other modeling groups to conduct further single-forcing experiments.« less

Hierarchical dose response of E. coli O157:H7 from human outbreaks incorporating heterogeneity in exposure.

PubMed

Teunis, P F M; Ogden, I D; Strachan, N J C

2008-06-01

The infectivity of pathogenic microorganisms is a key factor in the transmission of an infectious disease in a susceptible population. Microbial infectivity is generally estimated from dose-response studies in human volunteers. This can only be done with mildly pathogenic organisms. Here a hierarchical Beta-Poisson dose-response model is developed utilizing data from human outbreaks. On the lowest level each outbreak is modelled separately and these are then combined at a second level to produce a group dose-response relation. The distribution of foodborne pathogens often shows strong heterogeneity and this is incorporated by introducing an additional parameter to the dose-response model, accounting for the degree of overdispersion relative to Poisson distribution. It was found that heterogeneity considerably influences the shape of the dose-response relationship and increases uncertainty in predicted risk. This uncertainty is greater than previously reported surrogate and outbreak models using a single level of analysis. Monte Carlo parameter samples (alpha, beta of the Beta-Poisson model) can be readily incorporated in risk assessment models built using tools such as S-plus and @ Risk.

Dose- and time-dependence of the host-mediated response to paclitaxel therapy: a mathematical modeling approach.

PubMed

Benguigui, Madeleine; Alishekevitz, Dror; Timaner, Michael; Shechter, Dvir; Raviv, Ziv; Benzekry, Sebastien; Shaked, Yuval

2018-01-05

It has recently been suggested that pro-tumorigenic host-mediated processes induced in response to chemotherapy counteract the anti-tumor activity of therapy, and thereby decrease net therapeutic outcome. Here we use experimental data to formulate a mathematical model describing the host response to different doses of paclitaxel (PTX) chemotherapy as well as the duration of the response. Three previously described host-mediated effects are used as readouts for the host response to therapy. These include the levels of circulating endothelial progenitor cells in peripheral blood and the effect of plasma derived from PTX-treated mice on migratory and invasive properties of tumor cells in vitro . A first set of mathematical models, based on basic principles of pharmacokinetics/pharmacodynamics, did not appropriately describe the dose-dependence and duration of the host response regarding the effects on invasion. We therefore provide an alternative mathematical model with a dose-dependent threshold, instead of a concentration-dependent one, that describes better the data. This model is integrated into a global model defining all three host-mediated effects. It not only precisely describes the data, but also correctly predicts host-mediated effects at different doses as well as the duration of the host response. This mathematical model may serve as a tool to predict the host response to chemotherapy in cancer patients, and therefore may be used to design chemotherapy regimens with improved therapeutic outcome by minimizing host mediated effects.

Modeling the interactions between pathogenic bacteria, bacteriophage and immune response

NASA Astrophysics Data System (ADS)

Leung, Chung Yin (Joey); Weitz, Joshua S.

The prevalence of antibiotic-resistant strains of pathogenic bacteria has led to renewed interest in the use of bacteriophage (phage), or virus that infects bacteria, as a therapeutic agent against bacterial infections. However, little is known about the theoretical mechanism by which phage therapy may work. In particular, interactions between the bacteria, the phage and the host immune response crucially influences the outcome of the therapy. Few models of phage therapy have incorporated all these three components, and existing models suffer from unrealistic assumptions such as unbounded growth of the immune response. We propose a model of phage therapy with an emphasis on nonlinear feedback arising from interactions with bacteria and the immune response. Our model shows a synergistic effect between the phage and the immune response which underlies a possible mechanism for phage to catalyze the elimination of bacteria even when neither the immune response nor phage could do so alone. We study the significance of this effect for different parameters of infection and immune response, and discuss its implications for phage therapy.

Causal Responsibility and Counterfactuals

PubMed Central

Lagnado, David A; Gerstenberg, Tobias; Zultan, Ro'i

2013-01-01

How do people attribute responsibility in situations where the contributions of multiple agents combine to produce a joint outcome? The prevalence of over-determination in such cases makes this a difficult problem for counterfactual theories of causal responsibility. In this article, we explore a general framework for assigning responsibility in multiple agent contexts. We draw on the structural model account of actual causation (e.g., Halpern & Pearl, 2005) and its extension to responsibility judgments (Chockler & Halpern, 2004). We review the main theoretical and empirical issues that arise from this literature and propose a novel model of intuitive judgments of responsibility. This model is a function of both pivotality (whether an agent made a difference to the outcome) and criticality (how important the agent is perceived to be for the outcome, before any actions are taken). The model explains empirical results from previous studies and is supported by a new experiment that manipulates both pivotality and criticality. We also discuss possible extensions of this model to deal with a broader range of causal situations. Overall, our approach emphasizes the close interrelations between causality, counterfactuals, and responsibility attributions. PMID:23855451

Assessment of health surveys: fitting a multidimensional graded response model.

PubMed

Depaoli, Sarah; Tiemensma, Jitske; Felt, John M

The multidimensional graded response model, an item response theory (IRT) model, can be used to improve the assessment of surveys, even when sample sizes are restricted. Typically, health-based survey development utilizes classical statistical techniques (e.g. reliability and factor analysis). In a review of four prominent journals within the field of Health Psychology, we found that IRT-based models were used in less than 10% of the studies examining scale development or assessment. However, implementing IRT-based methods can provide more details about individual survey items, which is useful when determining the final item content of surveys. An example using a quality of life survey for Cushing's syndrome (CushingQoL) highlights the main components for implementing the multidimensional graded response model. Patients with Cushing's syndrome (n = 397) completed the CushingQoL. Results from the multidimensional graded response model supported a 2-subscale scoring process for the survey. All items were deemed as worthy contributors to the survey. The graded response model can accommodate unidimensional or multidimensional scales, be used with relatively lower sample sizes, and is implemented in free software (example code provided in online Appendix). Use of this model can help to improve the quality of health-based scales being developed within the Health Sciences.

Chlorine truck attack consequences and mitigation.

PubMed

Barrett, Anthony Michael; Adams, Peter J

2011-08-01

We develop and apply an integrated modeling system to estimate fatalities from intentional release of 17 tons of chlorine from a tank truck in a generic urban area. A public response model specifies locations and actions of the populace. A chemical source term model predicts initial characteristics of the chlorine vapor and aerosol cloud. An atmospheric dispersion model predicts cloud spreading and movement. A building air exchange model simulates movement of chlorine from outdoors into buildings at each location. A dose-response model translates chlorine exposures into predicted fatalities. Important parameters outside defender control include wind speed, atmospheric stability class, amount of chlorine released, and dose-response model parameters. Without fast and effective defense response, with 2.5 m/sec wind and stability class F, we estimate approximately 4,000 (half within ∼10 minutes) to 30,000 fatalities (half within ∼20 minutes), depending on dose-response model. Although we assume 7% of the population was outdoors, they represent 60-90% of fatalities. Changing weather conditions result in approximately 50-90% lower total fatalities. Measures such as sheltering in place, evacuation, and use of security barriers and cryogenic storage can reduce fatalities, sometimes by 50% or more, depending on response speed and other factors. © 2011 Society for Risk Analysis.

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

PubMed

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

2016-09-01

An in situ survey was performed in 8 French cities in 2012 to study the annoyance due to combined transportation noises. As the European Commission recommends to use the exposure-response relationships suggested by Miedema and Oudshoorn [Environmental Health Perspective, 2001] to predict annoyance due to single transportation noise, these exposure-response relationships were tested using the annoyance due to each transportation noise measured during the French survey. These relationships only enabled a good prediction in terms of the percentages of people highly annoyed by road traffic noise. For the percentages of people annoyed and a little annoyed by road traffic noise, the quality of prediction is weak. For aircraft and railway noises, prediction of annoyance is not satisfactory either. As a consequence, the annoyance equivalents model of Miedema [The Journal of the Acoustical Society of America, 2004], based on these exposure-response relationships did not enable a good prediction of annoyance due to combined transportation noises. Local exposure-response relationships were derived, following the whole computation suggested by Miedema and Oudshoorn [Environmental Health Perspective, 2001]. They led to a better calculation of annoyance due to each transportation noise in the French cities. A new version of the annoyance equivalents model was proposed using these new exposure-response relationships. This model enabled a better prediction of the total annoyance due to the combined transportation noises. These results encourage therefore to improve the annoyance prediction for noise in isolation with local or revised exposure-response relationships, which will also contribute to improve annoyance modeling for combined noises. With this aim in mind, a methodology is proposed to consider noise sensitivity in exposure-response relationships and in the annoyance equivalents model. The results showed that taking into account such variable did not enable to enhance both exposure-response relationships and the annoyance equivalents model. Copyright © 2016 Elsevier Ltd. All rights reserved.

A simple model for strong ground motions and response spectra

USGS Publications Warehouse

Safak, Erdal; Mueller, Charles; Boatwright, John

1988-01-01

A simple model for the description of strong ground motions is introduced. The model shows that response spectra can be estimated by using only four parameters of the ground motion, the RMS acceleration, effective duration and two corner frequencies that characterize the effective frequency band of the motion. The model is windowed band-limited white noise, and is developed by studying the properties of two functions, cumulative squared acceleration in the time domain, and cumulative squared amplitude spectrum in the frequency domain. Applying the methods of random vibration theory, the model leads to a simple analytical expression for the response spectra. The accuracy of the model is checked by using the ground motion recordings from the aftershock sequences of two different earthquakes and simulated accelerograms. The results show that the model gives a satisfactory estimate of the response spectra.

Models of subjective response to in-flight motion data

NASA Technical Reports Server (NTRS)

Rudrapatna, A. N.; Jacobson, I. D.

1973-01-01

Mathematical relationships between subjective comfort and environmental variables in an air transportation system are investigated. As a first step in model building, only the motion variables are incorporated and sensitivities are obtained using stepwise multiple regression analysis. The data for these models have been collected from commercial passenger flights. Two models are considered. In the first, subjective comfort is assumed to depend on rms values of the six-degrees-of-freedom accelerations. The second assumes a Rustenburg type human response function in obtaining frequency weighted rms accelerations, which are used in a linear model. The form of the human response function is examined and the results yield a human response weighting function for different degrees of freedom.

RRAWFLOW: Rainfall-Response Aquifer and Watershed Flow Model (v1.15)

USGS Publications Warehouse

Long, Andrew J.

2015-01-01

The Rainfall-Response Aquifer and Watershed Flow Model (RRAWFLOW) is a lumped-parameter model that simulates streamflow, spring flow, groundwater level, or solute transport for a measurement point in response to a system input of precipitation, recharge, or solute injection. I introduce the first version of RRAWFLOW available for download and public use and describe additional options. The open-source code is written in the R language and is available at http://sd.water.usgs.gov/projects/RRAWFLOW/RRAWFLOW.html along with an example model of streamflow. RRAWFLOW includes a time-series process to estimate recharge from precipitation and simulates the response to recharge by convolution, i.e., the unit-hydrograph approach. Gamma functions are used for estimation of parametric impulse-response functions (IRFs); a combination of two gamma functions results in a double-peaked IRF. A spline fit to a set of control points is introduced as a new method for estimation of nonparametric IRFs. Several options are included to simulate time-variant systems. For many applications, lumped models simulate the system response with equal accuracy to that of distributed models, but moreover, the ease of model construction and calibration of lumped models makes them a good choice for many applications (e.g., estimating missing periods in a hydrologic record). RRAWFLOW provides professional hydrologists and students with an accessible and versatile tool for lumped-parameter modeling.

TRPM8-Dependent Dynamic Response in a Mathematical Model of Cold Thermoreceptor

PubMed Central

Olivares, Erick; Salgado, Simón; Maidana, Jean Paul; Herrera, Gaspar; Campos, Matías; Madrid, Rodolfo; Orio, Patricio

2015-01-01

Cold-sensitive nerve terminals (CSNTs) encode steady temperatures with regular, rhythmic temperature-dependent firing patterns that range from irregular tonic firing to regular bursting (static response). During abrupt temperature changes, CSNTs show a dynamic response, transiently increasing their firing frequency as temperature decreases and silencing when the temperature increases (dynamic response). To date, mathematical models that simulate the static response are based on two depolarizing/repolarizing pairs of membrane ionic conductance (slow and fast kinetics). However, these models fail to reproduce the dynamic response of CSNTs to rapid changes in temperature and notoriously they lack a specific cold-activated conductance such as the TRPM8 channel. We developed a model that includes TRPM8 as a temperature-dependent conductance with a calcium-dependent desensitization. We show by computer simulations that it appropriately reproduces the dynamic response of CSNTs from mouse cornea, while preserving their static response behavior. In this model, the TRPM8 conductance is essential to display a dynamic response. In agreement with experimental results, TRPM8 is also needed for the ongoing activity in the absence of stimulus (i.e. neutral skin temperature). Free parameters of the model were adjusted by an evolutionary optimization algorithm, allowing us to find different solutions. We present a family of possible parameters that reproduce the behavior of CSNTs under different temperature protocols. The detection of temperature gradients is associated to a homeostatic mechanism supported by the calcium-dependent desensitization. PMID:26426259

Firing-rate response of linear and nonlinear integrate-and-fire neurons to modulated current-based and conductance-based synaptic drive.

PubMed

Richardson, Magnus J E

2007-08-01

Integrate-and-fire models are mainstays of the study of single-neuron response properties and emergent states of recurrent networks of spiking neurons. They also provide an analytical base for perturbative approaches that treat important biological details, such as synaptic filtering, synaptic conductance increase, and voltage-activated currents. Steady-state firing rates of both linear and nonlinear integrate-and-fire models, receiving fluctuating synaptic drive, can be calculated from the time-independent Fokker-Planck equation. The dynamic firing-rate response is less easy to extract, even at the first-order level of a weak modulation of the model parameters, but is an important determinant of neuronal response and network stability. For the linear integrate-and-fire model the response to modulations of current-based synaptic drive can be written in terms of hypergeometric functions. For the nonlinear exponential and quadratic models no such analytical forms for the response are available. Here it is demonstrated that a rather simple numerical method can be used to obtain the steady-state and dynamic response for both linear and nonlinear models to parameter modulation in the presence of current-based or conductance-based synaptic fluctuations. To complement the full numerical solution, generalized analytical forms for the high-frequency response are provided. A special case is also identified--time-constant modulation--for which the response to an arbitrarily strong modulation can be calculated exactly.

Assessing item fit for unidimensional item response theory models using residuals from estimated item response functions.

PubMed

Haberman, Shelby J; Sinharay, Sandip; Chon, Kyong Hee

2013-07-01

Residual analysis (e.g. Hambleton & Swaminathan, Item response theory: principles and applications, Kluwer Academic, Boston, 1985; Hambleton, Swaminathan, & Rogers, Fundamentals of item response theory, Sage, Newbury Park, 1991) is a popular method to assess fit of item response theory (IRT) models. We suggest a form of residual analysis that may be applied to assess item fit for unidimensional IRT models. The residual analysis consists of a comparison of the maximum-likelihood estimate of the item characteristic curve with an alternative ratio estimate of the item characteristic curve. The large sample distribution of the residual is proved to be standardized normal when the IRT model fits the data. We compare the performance of our suggested residual to the standardized residual of Hambleton et al. (Fundamentals of item response theory, Sage, Newbury Park, 1991) in a detailed simulation study. We then calculate our suggested residuals using data from an operational test. The residuals appear to be useful in assessing the item fit for unidimensional IRT models.

Simultaneously Coupled Mechanical-Electrochemical-Thermal Simulation of Lithium-Ion Cells

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

Zhang, C.; Santhanagopalan, S.; Sprague, M. A.

2016-07-28

Understanding the combined electrochemical-thermal and mechanical response of a system has a variety of applications, for example, structural failure from electrochemical fatigue and the potential induced changes of material properties. For lithium-ion batteries, there is an added concern over the safety of the system in the event of mechanical failure of the cell components. In this work, we present a generic multi-scale simultaneously coupled mechanical-electrochemical-thermal model to examine the interaction between mechanical failure and electrochemical-thermal responses. We treat the battery cell as a homogeneous material while locally we explicitly solve for the mechanical response of individual components using a homogenizationmore » model and the electrochemical-thermal responses using an electrochemical model for the battery. A benchmark problem is established to demonstrate the proposed modeling framework. The model shows the capability to capture the gradual evolution of cell electrochemical-thermal responses, and predicts the variation of those responses under different short-circuit conditions.« less

Simultaneously Coupled Mechanical-Electrochemical-Thermal Simulation of Lithium-Ion Cells: Preprint

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

Zhang, Chao; Santhanagopalan, Shriram; Sprague, Michael A.

2016-08-01

Understanding the combined electrochemical-thermal and mechanical response of a system has a variety of applications, for example, structural failure from electrochemical fatigue and the potential induced changes of material properties. For lithium-ion batteries, there is an added concern over the safety of the system in the event of mechanical failure of the cell components. In this work, we present a generic multi-scale simultaneously coupled mechanical-electrochemical-thermal model to examine the interaction between mechanical failure and electrochemical-thermal responses. We treat the battery cell as a homogeneous material while locally we explicitly solve for the mechanical response of individual components using a homogenizationmore » model and the electrochemical-thermal responses using an electrochemical model for the battery. A benchmark problem is established to demonstrate the proposed modeling framework. The model shows the capability to capture the gradual evolution of cell electrochemical-thermal responses, and predicts the variation of those responses under different short-circuit conditions.« less

Unification of color postprocessing techniques for 3-dimensional computational mechanics

NASA Technical Reports Server (NTRS)

Bailey, Bruce Charles

1985-01-01

To facilitate the understanding of complex three-dimensional numerical models, advanced interactive color postprocessing techniques are introduced. These techniques are sufficiently flexible so that postprocessing difficulties arising from model size, geometric complexity, response variation, and analysis type can be adequately overcome. Finite element, finite difference, and boundary element models may be evaluated with the prototype postprocessor. Elements may be removed from parent models to be studied as independent subobjects. Discontinuous responses may be contoured including responses which become singular, and nonlinear color scales may be input by the user for the enhancement of the contouring operation. Hit testing can be performed to extract precise geometric, response, mesh, or material information from the database. In addition, stress intensity factors may be contoured along the crack front of a fracture model. Stepwise analyses can be studied, and the user can recontour responses repeatedly, as if he were paging through the response sets. As a system, these tools allow effective interpretation of complex analysis results.

NLTE steady-state response matrix method.

NASA Astrophysics Data System (ADS)

Faussurier, G.; More, R. M.

2000-05-01

A connection between atomic kinetics and non-equilibrium thermodynamics has been recently established by using a collisional-radiative model modified to include line absorption. The calculated net emission can be expressed as a non-local thermodynamic equilibrium (NLTE) symmetric response matrix. In the paper, this connection is extended to both cases of the average-atom model and the Busquet's model (RAdiative-Dependent IOnization Model, RADIOM). The main properties of the response matrix still remain valid. The RADIOM source function found in the literature leads to a diagonal response matrix, stressing the absence of any frequency redistribution among the frequency groups at this order of calculation.

Modeling of biodynamic responses distributed at the fingers and the palm of the human hand-arm system.

PubMed

Dong, Ren G; Dong, Jennie H; Wu, John Z; Rakheja, Subhash

2007-01-01

The objective of this study is to develop analytical models for simulating driving-point biodynamic responses distributed at the fingers and palm of the hand under vibration along the forearm direction (z(h)-axis). Two different clamp-like model structures are formulated to analyze the distributed responses at the fingers-handle and palm-handle interfaces, as opposed to the single driving point invariably considered in the reported models. The parameters of the proposed four- and five degrees-of-freedom models are identified through minimization of an rms error function of the model and measured responses under different hand actions, namely, fingers pull, push only, grip only, and combined push and grip. The results show that the responses predicted from both models agree reasonably well with the measured data in terms of distributed as well total impedance magnitude and phase. The variations in the identified model parameters under different hand actions are further discussed in view of the biological system behavior. The proposed models are considered to serve as useful tools for design and assessment of vibration isolation methods, and for developing a hand-arm simulator for vibration analysis of power tools.

Mutual information and the fidelity of response of gene regulatory models

NASA Astrophysics Data System (ADS)

Tabbaa, Omar P.; Jayaprakash, C.

2014-08-01

We investigate cellular response to extracellular signals by using information theory techniques motivated by recent experiments. We present results for the steady state of the following gene regulatory models found in both prokaryotic and eukaryotic cells: a linear transcription-translation model and a positive or negative auto-regulatory model. We calculate both the information capacity and the mutual information exactly for simple models and approximately for the full model. We find that (1) small changes in mutual information can lead to potentially important changes in cellular response and (2) there are diminishing returns in the fidelity of response as the mutual information increases. We calculate the information capacity using Gillespie simulations of a model for the TNF-α-NF-κ B network and find good agreement with the measured value for an experimental realization of this network. Our results provide a quantitative understanding of the differences in cellular response when comparing experimentally measured mutual information values of different gene regulatory models. Our calculations demonstrate that Gillespie simulations can be used to compute the mutual information of more complex gene regulatory models, providing a potentially useful tool in synthetic biology.

A Review: Development of a Microdose Model for Analysis of Adaptive Response and Bystander Dose Response Behavior

PubMed Central

Leonard, Bobby E.

2008-01-01

Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type 125I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1.) Single Specific Energy Hits initiate Adaptive Response, 2.) Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3.) For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4.) The dose range of the AR protection depends on the value of the Specific Energy per Hit, . 5.) Alpha particle induced deleterious Bystander damage is modulated by low LET radiation. PMID:18648579

Modeling rate sensitivity of exercise transient responses to limb motion.

PubMed

Yamashiro, Stanley M; Kato, Takahide

2014-10-01

Transient responses of ventilation (V̇e) to limb motion can exhibit predictive characteristics. In response to a change in limb motion, a rapid change in V̇e is commonly observed with characteristics different than during a change in workload. This rapid change has been attributed to a feed-forward or adaptive response. Rate sensitivity was explored as a specific hypothesis to explain predictive V̇e responses to limb motion. A simple model assuming an additive feed-forward summation of V̇e proportional to the rate of change of limb motion was studied. This model was able to successfully account for the adaptive phase correction observed during human sinusoidal changes in limb motion. Adaptation of rate sensitivity might also explain the reduction of the fast component of V̇e responses previously reported following sudden exercise termination. Adaptation of the fast component of V̇e response could occur by reduction of rate sensitivity. Rate sensitivity of limb motion was predicted by the model to reduce the phase delay between limb motion and V̇e response without changing the steady-state response to exercise load. In this way, V̇e can respond more quickly to an exercise change without interfering with overall feedback control. The asymmetry between responses to an incremental and decremental ramp change in exercise can also be accounted for by the proposed model. Rate sensitivity leads to predicted behavior, which resembles responses observed in exercise tied to expiratory reserve volume. Copyright © 2014 the American Physiological Society.

Climate Change Effects on Agriculture: Economic Responses to Biophysical Shocks

NASA Technical Reports Server (NTRS)

Nelson, Gerald C.; Valin, Hugo; Sands, Ronald D.; Havlik, Petr; Ahammad, Helal; Deryng, Delphine; Elliott, Joshua; Fujimori, Shinichiro; Hasegawa, Tomoko; Heyhoe, Edwina

2014-01-01

Agricultural production is sensitive to weather and thus directly affected by climate change. Plausible estimates of these climate change impacts require combined use of climate, crop, and economic models. Results from previous studies vary substantially due to differences in models, scenarios, and data. This paper is part of a collective effort to systematically integrate these three types of models. We focus on the economic component of the assessment, investigating how nine global economic models of agriculture represent endogenous responses to seven standardized climate change scenarios produced by two climate and five crop models. These responses include adjustments in yields, area, consumption, and international trade. We apply biophysical shocks derived from the Intergovernmental Panel on Climate Change's representative concentration pathway with end-of-century radiative forcing of 8.5 W/m(sup 2). The mean biophysical yield effect with no incremental CO2 fertilization is a 17% reduction globally by 2050 relative to a scenario with unchanging climate. Endogenous economic responses reduce yield loss to 11%, increase area of major crops by 11%, and reduce consumption by 3%. Agricultural production, cropland area, trade, and prices show the greatest degree of variability in response to climate change, and consumption the lowest. The sources of these differences include model structure and specification; in particular, model assumptions about ease of land use conversion, intensification, and trade. This study identifies where models disagree on the relative responses to climate shocks and highlights research activities needed to improve the representation of agricultural adaptation responses to climate change.

Climate change effects on agriculture: Economic responses to biophysical shocks

PubMed Central

Nelson, Gerald C.; Valin, Hugo; Sands, Ronald D.; Havlík, Petr; Ahammad, Helal; Deryng, Delphine; Elliott, Joshua; Fujimori, Shinichiro; Hasegawa, Tomoko; Heyhoe, Edwina; Kyle, Page; Von Lampe, Martin; Lotze-Campen, Hermann; Mason d’Croz, Daniel; van Meijl, Hans; van der Mensbrugghe, Dominique; Müller, Christoph; Popp, Alexander; Robertson, Richard; Robinson, Sherman; Schmid, Erwin; Schmitz, Christoph; Tabeau, Andrzej; Willenbockel, Dirk

2014-01-01

Agricultural production is sensitive to weather and thus directly affected by climate change. Plausible estimates of these climate change impacts require combined use of climate, crop, and economic models. Results from previous studies vary substantially due to differences in models, scenarios, and data. This paper is part of a collective effort to systematically integrate these three types of models. We focus on the economic component of the assessment, investigating how nine global economic models of agriculture represent endogenous responses to seven standardized climate change scenarios produced by two climate and five crop models. These responses include adjustments in yields, area, consumption, and international trade. We apply biophysical shocks derived from the Intergovernmental Panel on Climate Change’s representative concentration pathway with end-of-century radiative forcing of 8.5 W/m2. The mean biophysical yield effect with no incremental CO2 fertilization is a 17% reduction globally by 2050 relative to a scenario with unchanging climate. Endogenous economic responses reduce yield loss to 11%, increase area of major crops by 11%, and reduce consumption by 3%. Agricultural production, cropland area, trade, and prices show the greatest degree of variability in response to climate change, and consumption the lowest. The sources of these differences include model structure and specification; in particular, model assumptions about ease of land use conversion, intensification, and trade. This study identifies where models disagree on the relative responses to climate shocks and highlights research activities needed to improve the representation of agricultural adaptation responses to climate change. PMID:24344285

Climate change effects on agriculture: economic responses to biophysical shocks.

PubMed

Nelson, Gerald C; Valin, Hugo; Sands, Ronald D; Havlík, Petr; Ahammad, Helal; Deryng, Delphine; Elliott, Joshua; Fujimori, Shinichiro; Hasegawa, Tomoko; Heyhoe, Edwina; Kyle, Page; Von Lampe, Martin; Lotze-Campen, Hermann; Mason d'Croz, Daniel; van Meijl, Hans; van der Mensbrugghe, Dominique; Müller, Christoph; Popp, Alexander; Robertson, Richard; Robinson, Sherman; Schmid, Erwin; Schmitz, Christoph; Tabeau, Andrzej; Willenbockel, Dirk

2014-03-04

Agricultural production is sensitive to weather and thus directly affected by climate change. Plausible estimates of these climate change impacts require combined use of climate, crop, and economic models. Results from previous studies vary substantially due to differences in models, scenarios, and data. This paper is part of a collective effort to systematically integrate these three types of models. We focus on the economic component of the assessment, investigating how nine global economic models of agriculture represent endogenous responses to seven standardized climate change scenarios produced by two climate and five crop models. These responses include adjustments in yields, area, consumption, and international trade. We apply biophysical shocks derived from the Intergovernmental Panel on Climate Change's representative concentration pathway with end-of-century radiative forcing of 8.5 W/m(2). The mean biophysical yield effect with no incremental CO2 fertilization is a 17% reduction globally by 2050 relative to a scenario with unchanging climate. Endogenous economic responses reduce yield loss to 11%, increase area of major crops by 11%, and reduce consumption by 3%. Agricultural production, cropland area, trade, and prices show the greatest degree of variability in response to climate change, and consumption the lowest. The sources of these differences include model structure and specification; in particular, model assumptions about ease of land use conversion, intensification, and trade. This study identifies where models disagree on the relative responses to climate shocks and highlights research activities needed to improve the representation of agricultural adaptation responses to climate change.

Structural Equation Model Approach to the Use of Response Times for Improving Estimation in Item Response Models

ERIC Educational Resources Information Center

Sen, Rohini

2012-01-01

In the last five decades, research on the uses of response time has extended into the field of psychometrics (Schnikpe & Scrams, 1999; van der Linden, 2006; van der Linden, 2007), where interest has centered around the usefulness of response time information in item calibration and person measurement within an item response theory. framework.…

The Social Responsibility Performance Outcomes Model: Building Socially Responsible Companies through Performance Improvement Outcomes.

ERIC Educational Resources Information Center

Hatcher, Tim

2000-01-01

Considers the role of performance improvement professionals and human resources development professionals in helping organizations realize the ethical and financial power of corporate social responsibility. Explains the social responsibility performance outcomes model, which incorporates the concepts of societal needs and outcomes. (LRW)

Bayesian Estimation of Multi-Unidimensional Graded Response IRT Models

ERIC Educational Resources Information Center

Kuo, Tzu-Chun

2015-01-01

Item response theory (IRT) has gained an increasing popularity in large-scale educational and psychological testing situations because of its theoretical advantages over classical test theory. Unidimensional graded response models (GRMs) are useful when polytomous response items are designed to measure a unified latent trait. They are limited in…

SiSeRHMap v1.0: a simulator for mapped seismic response using a hybrid model

NASA Astrophysics Data System (ADS)

Grelle, G.; Bonito, L.; Lampasi, A.; Revellino, P.; Guerriero, L.; Sappa, G.; Guadagno, F. M.

2015-06-01

SiSeRHMap is a computerized methodology capable of drawing up prediction maps of seismic response. It was realized on the basis of a hybrid model which combines different approaches and models in a new and non-conventional way. These approaches and models are organized in a code-architecture composed of five interdependent modules. A GIS (Geographic Information System) Cubic Model (GCM), which is a layered computational structure based on the concept of lithodynamic units and zones, aims at reproducing a parameterized layered subsoil model. A metamodeling process confers a hybrid nature to the methodology. In this process, the one-dimensional linear equivalent analysis produces acceleration response spectra of shear wave velocity-thickness profiles, defined as trainers, which are randomly selected in each zone. Subsequently, a numerical adaptive simulation model (Spectra) is optimized on the above trainer acceleration response spectra by means of a dedicated Evolutionary Algorithm (EA) and the Levenberg-Marquardt Algorithm (LMA) as the final optimizer. In the final step, the GCM Maps Executor module produces a serial map-set of a stratigraphic seismic response at different periods, grid-solving the calibrated Spectra model. In addition, the spectra topographic amplification is also computed by means of a numerical prediction model. This latter is built to match the results of the numerical simulations related to isolate reliefs using GIS topographic attributes. In this way, different sets of seismic response maps are developed, on which, also maps of seismic design response spectra are defined by means of an enveloping technique.

An Evaluation of Three Approximate Item Response Theory Models for Equating Test Scores.

ERIC Educational Resources Information Center

Marco, Gary L.; And Others

Three item response models were evaluated for estimating item parameters and equating test scores. The models, which approximated the traditional three-parameter model, included: (1) the Rasch one-parameter model, operationalized in the BICAL computer program; (2) an approximate three-parameter logistic model based on coarse group data divided…

Dynamic response tests of inertial and optical wind-tunnel model attitude measurement devices

NASA Technical Reports Server (NTRS)

Buehrle, R. D.; Young, C. P., Jr.; Burner, A. W.; Tripp, J. S.; Tcheng, P.; Finley, T. D.; Popernack, T. G., Jr.

1995-01-01

Results are presented for an experimental study of the response of inertial and optical wind-tunnel model attitude measurement systems in a wind-off simulated dynamic environment. This study is part of an ongoing activity at the NASA Langley Research Center to develop high accuracy, advanced model attitude measurement systems that can be used in a dynamic wind-tunnel environment. This activity was prompted by the inertial model attitude sensor response observed during high levels of model vibration which results in a model attitude measurement bias error. Significant bias errors in model attitude measurement were found for the measurement using the inertial device during wind-off dynamic testing of a model system. The amount of bias present during wind-tunnel tests will depend on the amplitudes of the model dynamic response and the modal characteristics of the model system. Correction models are presented that predict the vibration-induced bias errors to a high degree of accuracy for the vibration modes characterized in the simulated dynamic environment. The optical system results were uncorrupted by model vibration in the laboratory setup.

Frequency Response of Synthetic Vocal Fold Models with Linear and Nonlinear Material Properties

PubMed Central

Shaw, Stephanie M.; Thomson, Scott L.; Dromey, Christopher; Smith, Simeon

2014-01-01

Purpose The purpose of this study was to create synthetic vocal fold models with nonlinear stress-strain properties and to investigate the effect of linear versus nonlinear material properties on fundamental frequency during anterior-posterior stretching. Method Three materially linear and three materially nonlinear models were created and stretched up to 10 mm in 1 mm increments. Phonation onset pressure (Pon) and fundamental frequency (F0) at Pon were recorded for each length. Measurements were repeated as the models were relaxed in 1 mm increments back to their resting lengths, and tensile tests were conducted to determine the stress-strain responses of linear versus nonlinear models. Results Nonlinear models demonstrated a more substantial frequency response than did linear models and a more predictable pattern of F0 increase with respect to increasing length (although range was inconsistent across models). Pon generally increased with increasing vocal fold length for nonlinear models, whereas for linear models, Pon decreased with increasing length. Conclusions Nonlinear synthetic models appear to more accurately represent the human vocal folds than linear models, especially with respect to F0 response. PMID:22271874

Frequency response of synthetic vocal fold models with linear and nonlinear material properties.

PubMed

Shaw, Stephanie M; Thomson, Scott L; Dromey, Christopher; Smith, Simeon

2012-10-01

The purpose of this study was to create synthetic vocal fold models with nonlinear stress-strain properties and to investigate the effect of linear versus nonlinear material properties on fundamental frequency (F0) during anterior-posterior stretching. Three materially linear and 3 materially nonlinear models were created and stretched up to 10 mm in 1-mm increments. Phonation onset pressure (Pon) and F0 at Pon were recorded for each length. Measurements were repeated as the models were relaxed in 1-mm increments back to their resting lengths, and tensile tests were conducted to determine the stress-strain responses of linear versus nonlinear models. Nonlinear models demonstrated a more substantial frequency response than did linear models and a more predictable pattern of F0 increase with respect to increasing length (although range was inconsistent across models). Pon generally increased with increasing vocal fold length for nonlinear models, whereas for linear models, Pon decreased with increasing length. Nonlinear synthetic models appear to more accurately represent the human vocal folds than do linear models, especially with respect to F0 response.

A generalized linear factor model approach to the hierarchical framework for responses and response times.

PubMed

Molenaar, Dylan; Tuerlinckx, Francis; van der Maas, Han L J

2015-05-01

We show how the hierarchical model for responses and response times as developed by van der Linden (2007), Fox, Klein Entink, and van der Linden (2007), Klein Entink, Fox, and van der Linden (2009), and Glas and van der Linden (2010) can be simplified to a generalized linear factor model with only the mild restriction that there is no hierarchical model at the item side. This result is valuable as it enables all well-developed modelling tools and extensions that come with these methods. We show that the restriction we impose on the hierarchical model does not influence parameter recovery under realistic circumstances. In addition, we present two illustrative real data analyses to demonstrate the practical benefits of our approach. © 2014 The British Psychological Society.

ELM control with RMP: plasma response models and the role of edge peeling response

NASA Astrophysics Data System (ADS)

Liu, Yueqiang; Ham, C. J.; Kirk, A.; Li, Li; Loarte, A.; Ryan, D. A.; Sun, Youwen; Suttrop, W.; Yang, Xu; Zhou, Lina

2016-11-01

Resonant magnetic perturbations (RMP) have extensively been demonstrated as a plausible technique for mitigating or suppressing large edge localized modes (ELMs). Associated with this is a substantial amount of theory and modelling efforts during recent years. Various models describing the plasma response to the RMP fields have been proposed in the literature, and are briefly reviewed in this work. Despite their simplicity, linear response models can provide alternative criteria, than the vacuum field based criteria, for guiding the choice of the coil configurations to achieve the best control of ELMs. The role of the edge peeling response to the RMP fields is illustrated as a key indicator for the ELM mitigation in low collisionality plasmas, in various tokamak devices.

An AgMIP framework for improved agricultural representation in integrated assessment models

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

Ruane, Alex C.; Rosenzweig, Cynthia; Asseng, Senthold

Integrated assessment models (IAMs) hold great potential to assess how future agricultural systems will be shaped by socioeconomic development, technological innovation, and changing climate conditions. By coupling with climate and crop model emulators, IAMs have the potential to resolve important agricultural feedback loops and identify unintended consequences of socioeconomic development for agricultural systems. Here we propose a framework to develop robust representation of agricultural system responses within IAMs, linking downstream applications with model development and the coordinated evaluation of key climate responses from local to global scales. We survey the strengths and weaknesses of protocol-based assessments linked to the Agriculturalmore » Model Intercomparison and Improvement Project (AgMIP), each utilizing multiple sites and models to evaluate crop response to core climate changes including shifts in carbon dioxide concentration, temperature, and water availability, with some studies further exploring how climate responses are affected by nitrogen levels and adaptation in farm systems. Site-based studies with carefully calibrated models encompass the largest number of activities; however they are limited in their ability to capture the full range of global agricultural system diversity. Representative site networks provide more targeted response information than broadly-sampled networks, with limitations stemming from difficulties in covering the diversity of farming systems. Global gridded crop models provide comprehensive coverage, although with large challenges for calibration and quality control of inputs. Diversity in climate responses underscores that crop model emulators must distinguish between regions and farming system while recognizing model uncertainty. Finally, to bridge the gap between bottom-up and top-down approaches we recommend the deployment of a hybrid climate response system employing a representative network of sites to bias-correct comprehensive gridded simulations, opening the door to accelerated development and a broad range of applications.« less

An AgMIP framework for improved agricultural representation in integrated assessment models

NASA Astrophysics Data System (ADS)

Ruane, Alex C.; Rosenzweig, Cynthia; Asseng, Senthold; Boote, Kenneth J.; Elliott, Joshua; Ewert, Frank; Jones, James W.; Martre, Pierre; McDermid, Sonali P.; Müller, Christoph; Snyder, Abigail; Thorburn, Peter J.

2017-12-01

Integrated assessment models (IAMs) hold great potential to assess how future agricultural systems will be shaped by socioeconomic development, technological innovation, and changing climate conditions. By coupling with climate and crop model emulators, IAMs have the potential to resolve important agricultural feedback loops and identify unintended consequences of socioeconomic development for agricultural systems. Here we propose a framework to develop robust representation of agricultural system responses within IAMs, linking downstream applications with model development and the coordinated evaluation of key climate responses from local to global scales. We survey the strengths and weaknesses of protocol-based assessments linked to the Agricultural Model Intercomparison and Improvement Project (AgMIP), each utilizing multiple sites and models to evaluate crop response to core climate changes including shifts in carbon dioxide concentration, temperature, and water availability, with some studies further exploring how climate responses are affected by nitrogen levels and adaptation in farm systems. Site-based studies with carefully calibrated models encompass the largest number of activities; however they are limited in their ability to capture the full range of global agricultural system diversity. Representative site networks provide more targeted response information than broadly-sampled networks, with limitations stemming from difficulties in covering the diversity of farming systems. Global gridded crop models provide comprehensive coverage, although with large challenges for calibration and quality control of inputs. Diversity in climate responses underscores that crop model emulators must distinguish between regions and farming system while recognizing model uncertainty. Finally, to bridge the gap between bottom-up and top-down approaches we recommend the deployment of a hybrid climate response system employing a representative network of sites to bias-correct comprehensive gridded simulations, opening the door to accelerated development and a broad range of applications.

Assessment of Response Surface Models using Independent Confirmation Point Analysis

NASA Technical Reports Server (NTRS)

DeLoach, Richard

2010-01-01

This paper highlights various advantages that confirmation-point residuals have over conventional model design-point residuals in assessing the adequacy of a response surface model fitted by regression techniques to a sample of experimental data. Particular advantages are highlighted for the case of design matrices that may be ill-conditioned for a given sample of data. The impact of both aleatory and epistemological uncertainty in response model adequacy assessments is considered.

Teaching Personal and Social Responsibility Model-Based Programmes in Physical Education: A Systematic Review

ERIC Educational Resources Information Center

Pozo, Pablo; Grao-Cruces, Alberto; Pérez-Ordás, Raquel

2018-01-01

The purpose of this study was to conduct a review of research on the Teaching Personal and Social Responsibility model-based programme within physical education. Papers selected for analysis were found through searches of Web of Science, SportDiscus (EBSCO), SCOPUS, and ERIC (ProQuest) databases. The keywords "responsibility model" and…

Bridging Scientific Model Outputs with Emergency Response Needs in Catastrophic Earthquake Responses

ERIC Educational Resources Information Center

Johannes, Tay W.

2010-01-01

In emergency management, scientific models are widely used for running hazard simulations and estimating losses often in support of planning and mitigation efforts. This work expands utility of the scientific model into the response phase of emergency management. The focus is on the common operating picture as it gives context to emergency…

Detecting Aberrant Response Patterns in the Rasch Model. Rapport 87-3.

ERIC Educational Resources Information Center

Kogut, Jan

In this paper, the detection of response patterns aberrant from the Rasch model is considered. For this purpose, a new person fit index, recently developed by I. W. Molenaar (1987) and an iterative estimation procedure are used in a simulation study of Rasch model data mixed with aberrant data. Three kinds of aberrant response behavior are…

Item Response Models for Examinee-Selected Items

ERIC Educational Resources Information Center

Wang, Wen-Chung; Jin, Kuan-Yu; Qiu, Xue-Lan; Wang, Lei

2012-01-01

In some tests, examinees are required to choose a fixed number of items from a set of given items to answer. This practice creates a challenge to standard item response models, because more capable examinees may have an advantage by making wiser choices. In this study, we developed a new class of item response models to account for the choice…

Modeling Nonignorable Missing Data in Speeded Tests

ERIC Educational Resources Information Center

Glas, Cees A. W.; Pimentel, Jonald L.

2008-01-01

In tests with time limits, items at the end are often not reached. Usually, the pattern of missing responses depends on the ability level of the respondents; therefore, missing data are not ignorable in statistical inference. This study models data using a combination of two item response theory (IRT) models: one for the observed response data and…

An NCME Instructional Module on Latent DIF Analysis Using Mixture Item Response Models

ERIC Educational Resources Information Center

Cho, Sun-Joo; Suh, Youngsuk; Lee, Woo-yeol

2016-01-01

The purpose of this ITEMS module is to provide an introduction to differential item functioning (DIF) analysis using mixture item response models. The mixture item response models for DIF analysis involve comparing item profiles across latent groups, instead of manifest groups. First, an overview of DIF analysis based on latent groups, called…

Recovery of Graded Response Model Parameters: A Comparison of Marginal Maximum Likelihood and Markov Chain Monte Carlo Estimation

ERIC Educational Resources Information Center

Kieftenbeld, Vincent; Natesan, Prathiba

2012-01-01

Markov chain Monte Carlo (MCMC) methods enable a fully Bayesian approach to parameter estimation of item response models. In this simulation study, the authors compared the recovery of graded response model parameters using marginal maximum likelihood (MML) and Gibbs sampling (MCMC) under various latent trait distributions, test lengths, and…

A Semiparametric Model for Jointly Analyzing Response Times and Accuracy in Computerized Testing

ERIC Educational Resources Information Center

Wang, Chun; Fan, Zhewen; Chang, Hua-Hua; Douglas, Jeffrey A.

2013-01-01

The item response times (RTs) collected from computerized testing represent an underutilized type of information about items and examinees. In addition to knowing the examinees' responses to each item, we can investigate the amount of time examinees spend on each item. Current models for RTs mainly focus on parametric models, which have the…

White Complicity and Social Justice Education: Can One Be Culpable without Being Liable?

ERIC Educational Resources Information Center

Applebaum, Barbara

2007-01-01

In part of an ongoing study of white complicity, moral responsibility, and moral agency in social justice education, Barbara Applebaum asks in this essay what model or models of moral responsibility can help white students recognize their white complicity and which models of moral responsibility obscure such acknowledgment. To address this…

An Extension of Least Squares Estimation of IRT Linking Coefficients for the Graded Response Model

ERIC Educational Resources Information Center

Kim, Seonghoon

2010-01-01

The three types (generalized, unweighted, and weighted) of least squares methods, proposed by Ogasawara, for estimating item response theory (IRT) linking coefficients under dichotomous models are extended to the graded response model. A simulation study was conducted to confirm the accuracy of the extended formulas, and a real data study was…

Partially Testing a Process Model for Understanding Victim Responses to an Anticipated Worksite Closure

ERIC Educational Resources Information Center

Blau, Gary

2007-01-01

This study partially tested a recent process model for understanding victim responses to worksite/function closure (W/FC) proposed by Blau [Blau, G. (2006). A process model for understanding victim responses to worksite/function closure. "Human Resource Management Review," 16, 12-28], in a pharmaceutical manufacturing site. Central to the model…

Model Choice and Sample Size in Item Response Theory Analysis of Aphasia Tests

ERIC Educational Resources Information Center

Hula, William D.; Fergadiotis, Gerasimos; Martin, Nadine

2012-01-01

Purpose: The purpose of this study was to identify the most appropriate item response theory (IRT) measurement model for aphasia tests requiring 2-choice responses and to determine whether small samples are adequate for estimating such models. Method: Pyramids and Palm Trees (Howard & Patterson, 1992) test data that had been collected from…

Test-Anchored Vibration Response Predictions for an Acoustically Energized Curved Orthogrid Panel with Mounted Components

NASA Technical Reports Server (NTRS)

Frady, Gregory P.; Duvall, Lowery D.; Fulcher, Clay W. G.; Laverde, Bruce T.; Hunt, Ronald A.

2011-01-01

A rich body of vibroacoustic test data was recently generated at Marshall Space Flight Center for a curved orthogrid panel typical of launch vehicle skin structures. Several test article configurations were produced by adding component equipment of differing weights to the flight-like vehicle panel. The test data were used to anchor computational predictions of a variety of spatially distributed responses including acceleration, strain and component interface force. Transfer functions relating the responses to the input pressure field were generated from finite element based modal solutions and test-derived damping estimates. A diffuse acoustic field model was employed to describe the assumed correlation of phased input sound pressures across the energized panel. This application demonstrates the ability to quickly and accurately predict a variety of responses to acoustically energized skin panels with mounted components. Favorable comparisons between the measured and predicted responses were established. The validated models were used to examine vibration response sensitivities to relevant modeling parameters such as pressure patch density, mesh density, weight of the mounted component and model form. Convergence metrics include spectral densities and cumulative root-mean squared (RMS) functions for acceleration, velocity, displacement, strain and interface force. Minimum frequencies for response convergence were established as well as recommendations for modeling techniques, particularly in the early stages of a component design when accurate structural vibration requirements are needed relatively quickly. The results were compared with long-established guidelines for modeling accuracy of component-loaded panels. A theoretical basis for the Response/Pressure Transfer Function (RPTF) approach provides insight into trends observed in the response predictions and confirmed in the test data. The software modules developed for the RPTF method can be easily adapted for quick replacement of the diffuse acoustic field with other pressure field models; for example a turbulent boundary layer (TBL) model suitable for vehicle ascent. Wind tunnel tests have been proposed to anchor the predictions and provide new insight into modeling approaches for this type of environment. Finally, component vibration environments for design were developed from the measured and predicted responses and compared with those derived from traditional techniques such as Barrett scaling methods for unloaded and component-loaded panels.

Implementation of the zooplankton functional response in plankton models: State of the art, recent challenges and future directions

NASA Astrophysics Data System (ADS)

Morozov, Andrew; Poggiale, Jean-Christophe; Cordoleani, Flora

2012-09-01

The conventional way of describing grazing in plankton models is based on a zooplankton functional response framework, according to which the consumption rate is computed as the product of a certain function of food (the functional response) and the density/biomass of herbivorous zooplankton. A large amount of literature on experimental feeding reports the existence of a zooplankton functional response in microcosms and small mesocosms, which goes a long way towards explaining the popularity of this framework both in mean-field (e.g. NPZD models) and spatially resolved models. On the other hand, the complex foraging behaviour of zooplankton (feeding cycles) as well as spatial heterogeneity of food and grazer distributions (plankton patchiness) across time and space scales raise questions as to the existence of a functional response of herbivores in vivo. In the current review, we discuss limitations of the ‘classical’ zooplankton functional response and consider possible ways to amend this framework to cope with the complexity of real planktonic ecosystems. Our general conclusion is that although the functional response of herbivores often does not exist in real ecosystems (especially in the form observed in the laboratory), this framework can be rather useful in modelling - but it does need some amendment which can be made based on various techniques of model reduction. We also show that the shape of the functional response depends on the spatial resolution (‘frame’) of the model. We argue that incorporating foraging behaviour and spatial heterogeneity in plankton models would not necessarily require the use of individual based modelling - an approach which is now becoming dominant in the literature. Finally, we list concrete future directions and challenges and emphasize the importance of a closer collaboration between plankton biologists and modellers in order to make further progress towards better descriptions of zooplankton grazing.

Pattern Adaptation and Normalization Reweighting.

PubMed

Westrick, Zachary M; Heeger, David J; Landy, Michael S

2016-09-21

Adaptation to an oriented stimulus changes both the gain and preferred orientation of neural responses in V1. Neurons tuned near the adapted orientation are suppressed, and their preferred orientations shift away from the adapter. We propose a model in which weights of divisive normalization are dynamically adjusted to homeostatically maintain response products between pairs of neurons. We demonstrate that this adjustment can be performed by a very simple learning rule. Simulations of this model closely match existing data from visual adaptation experiments. We consider several alternative models, including variants based on homeostatic maintenance of response correlations or covariance, as well as feedforward gain-control models with multiple layers, and we demonstrate that homeostatic maintenance of response products provides the best account of the physiological data. Adaptation is a phenomenon throughout the nervous system in which neural tuning properties change in response to changes in environmental statistics. We developed a model of adaptation that combines normalization (in which a neuron's gain is reduced by the summed responses of its neighbors) and Hebbian learning (in which synaptic strength, in this case divisive normalization, is increased by correlated firing). The model is shown to account for several properties of adaptation in primary visual cortex in response to changes in the statistics of contour orientation. Copyright © 2016 the authors 0270-6474/16/369805-12$15.00/0.

Mathematical Modeling of Allelopathy. III. A Model for Curve-Fitting Allelochemical Dose Responses

PubMed Central

Liu, De Li; An, Min; Johnson, Ian R.; Lovett, John V.

2003-01-01

Bioassay techniques are often used to study the effects of allelochemicals on plant processes, and it is generally observed that the processes are stimulated at low allelochemical concentrations and inhibited as the concentrations increase. A simple empirical model is presented to analyze this type of response. The stimulation-inhibition properties of allelochemical-dose responses can be described by the parameters in the model. The indices, p% reductions, are calculated to assess the allelochemical effects. The model is compared with experimental data for the response of lettuce seedling growth to Centaurepensin, the olfactory response of weevil larvae to α-terpineol, and the responses of annual ryegrass (Lolium multiflorum Lam.), creeping red fescue (Festuca rubra L., cv. Ensylva), Kentucky bluegrass (Poa pratensis L., cv. Kenblue), perennial ryegrass (L. perenne L., cv. Manhattan), and Rebel tall fescue (F. arundinacea Schreb) seedling growth to leachates of Rebel and Kentucky 31 tall fescue. The results show that the model gives a good description to observations and can be used to fit a wide range of dose responses. Assessments of the effects of leachates of Rebel and Kentucky 31 tall fescue clearly differentiate the properties of the allelopathic sources and the relative sensitivities of indicators such as the length of root and leaf. PMID:19330111

Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

PubMed

Dong, Xu; Foteinou, Panagiota T; Calvano, Steven E; Lowry, Stephen F; Androulakis, Ioannis P

2010-02-18

Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions. An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades. The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve our understanding of how manipulating the behavior of the molecular species could manifest into emergent behavior of the overall system.

A Multidimensional Ideal Point Item Response Theory Model for Binary Data.

PubMed

Maydeu-Olivares, Albert; Hernández, Adolfo; McDonald, Roderick P

2006-12-01

We introduce a multidimensional item response theory (IRT) model for binary data based on a proximity response mechanism. Under the model, a respondent at the mode of the item response function (IRF) endorses the item with probability one. The mode of the IRF is the ideal point, or in the multidimensional case, an ideal hyperplane. The model yields closed form expressions for the cell probabilities. We estimate and test the goodness of fit of the model using only information contained in the univariate and bivariate moments of the data. Also, we pit the new model against the multidimensional normal ogive model estimated using NOHARM in four applications involving (a) attitudes toward censorship, (b) satisfaction with life, (c) attitudes of morality and equality, and (d) political efficacy. The normal PDF model is not invariant to simple operations such as reverse scoring. Thus, when there is no natural category to be modeled, as in many personality applications, it should be fit separately with and without reverse scoring for comparisons.

Synthesis of a control model for a liquid nitrogen cooled, closed circuit, cryogenic nitrogen wind tunnel and its validation

NASA Technical Reports Server (NTRS)

Balakrishna, S.; Goglia, G. L.

1979-01-01

The details of the efforts to synthesize a control-compatible multivariable model of a liquid nitrogen cooled, gaseous nitrogen operated, closed circuit, cryogenic pressure tunnel are presented. The synthesized model was transformed into a real-time cryogenic tunnel simulator, and this model is validated by comparing the model responses to the actual tunnel responses of the 0.3 m transonic cryogenic tunnel, using the quasi-steady-state and the transient responses of the model and the tunnel. The global nature of the simple, explicit, lumped multivariable model of a closed circuit cryogenic tunnel is demonstrated.

Parental modelling and prompting effects on acceptance of a novel fruit in 2-4-year-old children are dependent on children's food responsiveness.

PubMed

Blissett, Jackie; Bennett, Carmel; Fogel, Anna; Harris, Gillian; Higgs, Suzanne

2016-02-14

Few children consume the recommended portions of fruit or vegetables. This study examined the effects of parental physical prompting and parental modelling in children's acceptance of a novel fruit (NF) and examined the role of children's food-approach and food-avoidance traits on NF engagement and consumption. A total of 120 caregiver-child dyads (fifty-four girls, sixty-six boys) participated in this study. Dyads were allocated to one of the following three conditions: physical prompting but no modelling, physical prompting and modelling or a modelling only control condition. Dyads ate a standardised meal containing a portion of a fruit new to the child. Parents completed measures of children's food approach and avoidance. Willingness to try the NF was observed, and the amount of the NF consumed was measured. Physical prompting but no modelling resulted in greater physical refusal of the NF. There were main effects of enjoyment of food and food fussiness on acceptance. Food responsiveness interacted with condition such that children who were more food responsive had greater NF acceptance in the prompting and modelling conditions in comparison with the modelling only condition. In contrast, children with low food responsiveness had greater acceptance in the modelling control condition than in the prompting but no modelling condition. Physical prompting in the absence of modelling is likely to be detrimental to NF acceptance. Parental use of physical prompting strategies, in combination with modelling of NF intake, may facilitate acceptance of NF, but only in food-responsive children. Modelling consumption best promotes acceptance in children with low food responsiveness.

Attenuation of empennage buffet response through active control of damping using piezoelectric material

NASA Technical Reports Server (NTRS)

Heeg, Jennifer; Miller, Jonathan M.; Doggett, Robert V., Jr.

1993-01-01

Dynamic response and damping data obtained from buffet studies conducted in a low-speed wind tunnel by using a simple, rigid model attached to spring supports are presented. The two parallel leaf spring supports provided a means for the model to respond in a vertical translation mode, thus simulating response in an elastic first bending mode. Wake-induced buffeting flow was created by placing an airfoil upstream of the model of that the wake of the airfoil impinged on the model. Model response was sensed by a strain gage mounted on one of the springs. The output signal from the strain gage was fed back through a control law implemented on a desktop computer. The processed signals were used to 'actuate' a piezoelectric bending actuator bonded to the other spring in such a way as to add damping as the model responded. The results of this 'proof-of-concept' study show that the piezoelectric actuator was effective in attenuating the wake-induced buffet response over the range of parameters investigated.

Climate warming due to increasing atmospheric CO2 - Simulations with a multilayer coupled atmosphere-ocean seasonal energy balance model

NASA Technical Reports Server (NTRS)

Li, Peng; Chou, Ming-Dah; Arking, Albert

1987-01-01

The transient response of the climate to increasing CO2 is studied using a modified version of the multilayer energy balance model of Peng et al. (1982). The main characteristics of the model are described. Latitudinal and seasonal distributions of planetary albedo, latitude-time distributions of zonal mean temperatures, and latitudinal distributions of evaporation, water vapor transport, and snow cover generated from the model and derived from actual observations are analyzed and compared. It is observed that in response to an atmospheric doubling of CO2, the model reaches within 1/e of the equilibrium response of global mean surface temperature in 9-35 years for the probable range of vertical heat diffusivity in the ocean. For CO2 increases projected by the National Research Council (1983), the model's transient response in annually and globally averaged surface temperatures is 60-75 percent of the corresponding equilibrium response, and the disequilibrium increases with increasing heat diffusivity of the ocean.

Constitutive Modeling of a Glass Fiber-Reinforced PTFE Gasketed-Joint Under a Re-torque

NASA Astrophysics Data System (ADS)

Williams, James; Gordon, Ali P.

Joints gasketed with viscoelastic seals often receive an application of a secondary torque, i.e., retorque, in order to ensure joint tightness and proper sealing. The motivation of this study is to characterize and analytically model the load and deflection re-torque response of a single 25% glass-fiber reinforced polytetrafluorethylene (PTFE) gasket-bolted joint with serrated flange detail. The Burger-type viscoelastic modeling constants of the material are obtained through isolating the gasket from the bolt by performing a gasket creep test via a MTS electromechanical test frame. The re-load creep response is also investigated by re-loading the gasket after a period of initial creep to observe the response. The modeling constants obtained from the creep tests are used with a Burger-type viscoelastic model to predict the re-torque response of a single bolt-gasket test fixture in order to validate the ability of the model to simulate the re-torque response under various loading conditions and flange detail.

Development of Response Spectral Ground Motion Prediction Equations from Empirical Models for Fourier Spectra and Duration of Ground Motion

NASA Astrophysics Data System (ADS)

Bora, S. S.; Scherbaum, F.; Kuehn, N. M.; Stafford, P.; Edwards, B.

2014-12-01

In a probabilistic seismic hazard assessment (PSHA) framework, it still remains a challenge to adjust ground motion prediction equations (GMPEs) for application in different seismological environments. In this context, this study presents a complete framework for the development of a response spectral GMPE easily adjustable to different seismological conditions; and which does not suffer from the technical problems associated with the adjustment in response spectral domain. Essentially, the approach consists of an empirical FAS (Fourier Amplitude Spectrum) model and a duration model for ground motion which are combined within the random vibration theory (RVT) framework to obtain the full response spectral ordinates. Additionally, FAS corresponding to individual acceleration records are extrapolated beyond the frequency range defined by the data using the stochastic FAS model, obtained by inversion as described in Edwards & Faeh, (2013). To that end, an empirical model for a duration, which is tuned to optimize the fit between RVT based and observed response spectral ordinate, at each oscillator frequency is derived. Although, the main motive of the presented approach was to address the adjustability issues of response spectral GMPEs; comparison, of median predicted response spectra with the other regional models indicate that presented approach can also be used as a stand-alone model. Besides that, a significantly lower aleatory variability (σ<0.5 in log units) in comparison to other regional models, at shorter periods brands it to a potentially viable alternative to the classical regression (on response spectral ordinates) based GMPEs for seismic hazard studies in the near future. The dataset used for the presented analysis is a subset of the recently compiled database RESORCE-2012 across Europe, Middle East and the Mediterranean region.

Kinetic operational models of agonism for G-protein-coupled receptors.

PubMed

Hoare, Samuel R J; Pierre, Nicolas; Moya, Arturo Gonzalez; Larson, Brad

2018-06-07

The application of kinetics to research and therapeutic development of G-protein-coupled receptors has become increasingly valuable. Pharmacological models provide the foundation of pharmacology, providing concepts and measurable parameters such as efficacy and potency that have underlain decades of successful drug discovery. Currently there are few pharmacological models that incorporate kinetic activity in such a way as to yield experimentally-accessible drug parameters. In this study, a kinetic model of pharmacological response was developed that provides a kinetic descriptor of efficacy (the transduction rate constant, k τ ) and allows measurement of receptor-ligand binding kinetics from functional data. The model assumes: (1) receptor interacts with a precursor of the response ("Transduction potential") and converts it to the response. (2) The response can decay. Familiar response vs time plots emerge, depending on whether transduction potential is depleted and/or response decays. These are the straight line, the "association" exponential curve, and the rise-and-fall curve. Convenient, familiar methods are described for measuring the model parameters and files are provided for the curve-fitting program Prism (GraphPad Software) that can be used as a guide. The efficacy parameter k τ is straightforward to measure and accounts for receptor reserve; all that is required is measurement of response over time at a maximally-stimulating concentration of agonist. The modular nature of the model framework allows it to be extended. Here this is done to incorporate antagonist-receptor binding kinetics and slow agonist-receptor equilibration. In principle, the modular framework can incorporate other cellular processes, such as receptor desensitization. The kinetic response model described here can be applied to measure kinetic pharmacological parameters than can be used to advance the understanding of GPCR pharmacology and optimize new and improved therapeutics. Copyright © 2018 Elsevier Ltd. All rights reserved.

The uses and limitations of the square‐root‐impedance method for computing site amplification

USGS Publications Warehouse

Boore, David

2013-01-01

The square‐root‐impedance (SRI) method is a fast way of computing approximate site amplification that does not depend on the details from velocity models. The SRI method underestimates the peak response of models with large impedance contrasts near their base, but the amplifications for those models is often close to or equal to the root mean square of the theoretical full resonant (FR) response of the higher modes. On the other hand, for velocity models made up of gradients, with no significant impedance changes across small ranges of depth, the SRI method systematically underestimates the theoretical FR response over a wide frequency range. For commonly used gradient models for generic rock sites, the SRI method underestimates the FR response by about 20%–30%. Notwithstanding the persistent underestimation of amplifications from theoretical FR calculations, however, amplifications from the SRI method may often provide more useful estimates of amplifications than the FR method, because the SRI amplifications are not sensitive to details of the models and will not exhibit the many peaks and valleys characteristic of theoretical full resonant amplifications (jaggedness sometimes not seen in amplifications based on averages of site response from multiple recordings at a given site). The lack of sensitivity to details of the velocity models also makes the SRI method useful in comparing the response of various velocity models, in spite of any systematic underestimation of the response. The quarter‐wavelength average velocity, which is fundamental to the SRI method, is useful by itself in site characterization, and as such, is the fundamental parameter used to characterize the site response in a number of recent ground‐motion prediction equations.

New model performance index for engineering design of control systems

NASA Technical Reports Server (NTRS)

1970-01-01

Performance index includes a model representing linear control-system design specifications. Based on a geometric criterion for approximation of the model by the actual system, the index can be interpreted directly in terms of the desired system response model without actually having the model's time response.

Log-Multiplicative Association Models as Item Response Models

ERIC Educational Resources Information Center

Anderson, Carolyn J.; Yu, Hsiu-Ting

2007-01-01

Log-multiplicative association (LMA) models, which are special cases of log-linear models, have interpretations in terms of latent continuous variables. Two theoretical derivations of LMA models based on item response theory (IRT) arguments are presented. First, we show that Anderson and colleagues (Anderson & Vermunt, 2000; Anderson & Bockenholt,…

Air Quality Response Modeling for Decision Support | Science ...

EPA Pesticide Factsheets

Air quality management relies on photochemical models to predict the responses of pollutant concentrations to changes in emissions. Such modeling is especially important for secondary pollutants such as ozone and fine particulate matter which vary nonlinearly with changes in emissions. Numerous techniques for probing pollutant-emission relationships within photochemical models have been developed and deployed for a variety of decision support applications. However, atmospheric response modeling remains complicated by the challenge of validating sensitivity results against observable data. This manuscript reviews the state of the science of atmospheric response modeling as well as efforts to characterize the accuracy and uncertainty of sensitivity results. The National Exposure Research Laboratory′s (NERL′s) Atmospheric Modeling and Analysis Division (AMAD) conducts research in support of EPA′s mission to protect human health and the environment. AMAD′s research program is engaged in developing and evaluating predictive atmospheric models on all spatial and temporal scales for forecasting the Nation′s air quality and for assessing changes in air quality and air pollutant exposures, as affected by changes in ecosystem management and regulatory decisions. AMAD is responsible for providing a sound scientific and technical basis for regulatory policies based on air quality models to improve ambient air quality. The models developed by AMAD are being use

Reconciling the Observed and Modeled Southern Hemisphere Circulation Response to Volcanic Eruptions

NASA Astrophysics Data System (ADS)

McGraw, M. C.; Barnes, E. A.; Deser, C.

2016-12-01

Confusion exists regarding the tropospheric circulation response to volcanic eruptions, with models and observations seeming to disagree on the sign of the response. The forced Southern Hemisphere circulation response to the eruptions of Pinatubo and El Chichon is shown to be a robust positive annular mode, using over 200 ensemble members from 38 climate models. It is demonstrated that the models and observations are not at odds, but rather, internal climate variability is large and can overwhelm the forced response. It is further argued that the state of ENSO can at least partially explain the sign of the observed anomalies, and may account for the perceived discrepancy between model and observational studies. The eruptions of both El Chichon and Pinatubo occurred during El Nino events, and it is demonstrated that the SAM anomalies following volcanic eruptions are weaker during El Nino events compared to La Nina events.

A shock absorber model for structure-borne noise analyses

NASA Astrophysics Data System (ADS)

Benaziz, Marouane; Nacivet, Samuel; Thouverez, Fabrice

2015-08-01

Shock absorbers are often responsible for undesirable structure-borne noise in cars. The early numerical prediction of this noise in the automobile development process can save time and money and yet remains a challenge for industry. In this paper, a new approach to predicting shock absorber structure-borne noise is proposed; it consists in modelling the shock absorber and including the main nonlinear phenomena responsible for discontinuities in the response. The model set forth herein features: compressible fluid behaviour, nonlinear flow rate-pressure relations, valve mechanical equations and rubber mounts. The piston, base valve and complete shock absorber model are compared with experimental results. Sensitivity of the shock absorber response is evaluated and the most important parameters are classified. The response envelope is also computed. This shock absorber model is able to accurately reproduce local nonlinear phenomena and improves our state of knowledge on potential noise sources within the shock absorber.

Low and High Frequency Models of Response Statistics of a Cylindrical Orthogrid Vehicle Panel to Acoustic Excitation

NASA Technical Reports Server (NTRS)

Smith, Andrew; LaVerde, Bruce; Teague, David; Gardner, Bryce; Cotoni, Vincent

2010-01-01

This presentation further develops the orthogrid vehicle panel work. Employed Hybrid Module capabilities to assess both low/mid frequency and high frequency models in the VA One simulation environment. The response estimates from three modeling approaches are compared to ground test measurements. Detailed Finite Element Model of the Test Article -Expect to capture both the global panel modes and the local pocket mode response, but at a considerable analysis expense (time & resources). A Composite Layered Construction equivalent global stiffness approximation using SEA -Expect to capture response of the global panel modes only. An SEA approximation using the Periodic Subsystem Formulation. A finite element model of a single periodic cell is used to derive the vibroacoustic properties of the entire periodic structure (modal density, radiation efficiency, etc. Expect to capture response at various locations on the panel (on the skin and on the ribs) with less analysis expense

A parameters optimization method for planar joint clearance model and its application for dynamics simulation of reciprocating compressor

NASA Astrophysics Data System (ADS)

Hai-yang, Zhao; Min-qiang, Xu; Jin-dong, Wang; Yong-bo, Li

2015-05-01

In order to improve the accuracy of dynamics response simulation for mechanism with joint clearance, a parameter optimization method for planar joint clearance contact force model was presented in this paper, and the optimized parameters were applied to the dynamics response simulation for mechanism with oversized joint clearance fault. By studying the effect of increased clearance on the parameters of joint clearance contact force model, the relation of model parameters between different clearances was concluded. Then the dynamic equation of a two-stage reciprocating compressor with four joint clearances was developed using Lagrange method, and a multi-body dynamic model built in ADAMS software was used to solve this equation. To obtain a simulated dynamic response much closer to that of experimental tests, the parameters of joint clearance model, instead of using the designed values, were optimized by genetic algorithms approach. Finally, the optimized parameters were applied to simulate the dynamics response of model with oversized joint clearance fault according to the concluded parameter relation. The dynamics response of experimental test verified the effectiveness of this application.

Finite Element Aircraft Simulation of Turbulence

NASA Technical Reports Server (NTRS)

McFarland, R. E.

1997-01-01

A turbulence model has been developed for realtime aircraft simulation that accommodates stochastic turbulence and distributed discrete gusts as a function of the terrain. This model is applicable to conventional aircraft, V/STOL aircraft, and disc rotor model helicopter simulations. Vehicle angular activity in response to turbulence is computed from geometrical and temporal relationships rather than by using the conventional continuum approximations that assume uniform gust immersion and low frequency responses. By using techniques similar to those recently developed for blade-element rotor models, the angular-rate filters of conventional turbulence models are not required. The model produces rotational rates as well as air mass translational velocities in response to both stochastic and deterministic disturbances, where the discrete gusts and turbulence magnitudes may be correlated with significant terrain features or ship models. Assuming isotropy, a two-dimensional vertical turbulence field is created. A novel Gaussian interpolation technique is used to distribute vertical turbulence on the wing span or lateral rotor disc, and this distribution is used to compute roll responses. Air mass velocities are applied at significant centers of pressure in the computation of the aircraft's pitch and roll responses.

Suppression of antigen-specific lymphocyte activation in modeled microgravity

NASA Technical Reports Server (NTRS)

Cooper, D.; Pride, M. W.; Brown, E. L.; Risin, D.; Pellis, N. R.; McIntire, L. V. (Principal Investigator)

2001-01-01

Various parameters of immune suppression are observed in lymphocytes from astronauts during and after a space flight. It is difficult to ascribe this suppression to microgravity effects on immune cells in crew specimens, due to the complex physiological response to space flight and the resultant effect on in vitro immune performance. Use of isolated immune cells in true and modeled microgravity in immune performance tests, suggests a direct effect of microgravity on in vitro cellular function. Specifically, polyclonal activation of T-cells is severely suppressed in true and modeled microgravity. These recent findings suggest a potential suppression of oligoclonal antigen-specific lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors as an analog of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction, as a model for a primary immune response, a tetanus toxoid response and a Borrelia burgdorferi response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

Computational modeling of the human auditory periphery: Auditory-nerve responses, evoked potentials and hearing loss.

PubMed

Verhulst, Sarah; Altoè, Alessandro; Vasilkov, Viacheslav

2018-03-01

Models of the human auditory periphery range from very basic functional descriptions of auditory filtering to detailed computational models of cochlear mechanics, inner-hair cell (IHC), auditory-nerve (AN) and brainstem signal processing. It is challenging to include detailed physiological descriptions of cellular components into human auditory models because single-cell data stems from invasive animal recordings while human reference data only exists in the form of population responses (e.g., otoacoustic emissions, auditory evoked potentials). To embed physiological models within a comprehensive human auditory periphery framework, it is important to capitalize on the success of basic functional models of hearing and render their descriptions more biophysical where possible. At the same time, comprehensive models should capture a variety of key auditory features, rather than fitting their parameters to a single reference dataset. In this study, we review and improve existing models of the IHC-AN complex by updating their equations and expressing their fitting parameters into biophysical quantities. The quality of the model framework for human auditory processing is evaluated using recorded auditory brainstem response (ABR) and envelope-following response (EFR) reference data from normal and hearing-impaired listeners. We present a model with 12 fitting parameters from the cochlea to the brainstem that can be rendered hearing impaired to simulate how cochlear gain loss and synaptopathy affect human population responses. The model description forms a compromise between capturing well-described single-unit IHC and AN properties and human population response features. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Nursing resources and responsibilities according to hospital organizational model for management of inflammatory bowel disease in Spain.

PubMed

Marín, Laura; Torrejón, Antonio; Oltra, Lorena; Seoane, Montserrat; Hernández-Sampelayo, Paloma; Vera, María Isabel; Casellas, Francesc; Alfaro, Noelia; Lázaro, Pablo; García-Sánchez, Valle

2011-06-01

Nurses play an important role in the multidisciplinary management of inflammatory bowel disease (IBD), but little is known about this role and the associated resources. To improve knowledge of resource availability for health care activities and the different organizational models in managing IBD in Spain. Cross-sectional study with data obtained by questionnaire directed at Spanish Gastroenterology Services (GS). Five GS models were identified according to whether they have: no specific service for IBD management (Model A); IBD outpatient office for physician consultations (Model B); general outpatient office for nurse consultations (Model C); both, Model B and Model C (Model D); and IBD Unit (Model E) when the hospital has a Comprehensive Care Unit for IBD with telephone helpline, computer, including a Model B. Available resources and activities performed were compared according to GS model (chi-square test and test for linear trend). Responses were received from 107 GS: 33 Model A (31%), 38 Model B (36%), 4 Model C (4%), 16 Model D (15%) and 16 Model E (15%). The model in which nurses have the most resources and responsibilities is the Model E. The more complete the organizational model, the more frequent the availability of nursing resources (educational material, databases, office, and specialized software) and responsibilities (management of walk-in appointments, provision of emotional support, health education, follow-up of drug treatment and treatment adherence) (p<0.05). Nurses have more resources and responsibilities the more complete is the organizational model for IBD management. Development of these areas may improve patient outcomes. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

A Comparison of Dose-Response Models for the Parotid Gland in a Large Group of Head-and-Neck Cancer Patients

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

Houweling, Antonetta C., E-mail: A.Houweling@umcutrecht.n; Philippens, Marielle E.P.; Dijkema, Tim

2010-03-15

Purpose: The dose-response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy. Methods and Materials: A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose-response study. The patients were treated with either conventional radiotherapy or intensity-modulated radiotherapy. Dose-volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulatedmore » salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose-threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaike's information criterion (AIC). Results: None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD{sub 50} in these models was approximately 39 Gy. Conclusions: The mean dose model was preferred for describing the dose-response relationship of the parotid gland.« less

Statistical Comparison of Spike Responses to Natural Stimuli in Monkey Area V1 With Simulated Responses of a Detailed Laminar Network Model for a Patch of V1

PubMed Central

Schuch, Klaus; Logothetis, Nikos K.; Maass, Wolfgang

2011-01-01

A major goal of computational neuroscience is the creation of computer models for cortical areas whose response to sensory stimuli resembles that of cortical areas in vivo in important aspects. It is seldom considered whether the simulated spiking activity is realistic (in a statistical sense) in response to natural stimuli. Because certain statistical properties of spike responses were suggested to facilitate computations in the cortex, acquiring a realistic firing regimen in cortical network models might be a prerequisite for analyzing their computational functions. We present a characterization and comparison of the statistical response properties of the primary visual cortex (V1) in vivo and in silico in response to natural stimuli. We recorded from multiple electrodes in area V1 of 4 macaque monkeys and developed a large state-of-the-art network model for a 5 × 5-mm patch of V1 composed of 35,000 neurons and 3.9 million synapses that integrates previously published anatomical and physiological details. By quantitative comparison of the model response to the “statistical fingerprint” of responses in vivo, we find that our model for a patch of V1 responds to the same movie in a way which matches the statistical structure of the recorded data surprisingly well. The deviation between the firing regimen of the model and the in vivo data are on the same level as deviations among monkeys and sessions. This suggests that, despite strong simplifications and abstractions of cortical network models, they are nevertheless capable of generating realistic spiking activity. To reach a realistic firing state, it was not only necessary to include both N-methyl-d-aspartate and GABAB synaptic conductances in our model, but also to markedly increase the strength of excitatory synapses onto inhibitory neurons (>2-fold) in comparison to literature values, hinting at the importance to carefully adjust the effect of inhibition for achieving realistic dynamics in current network models. PMID:21106898

Large-scale geomorphology: Classical concepts reconciled and integrated with contemporary ideas via a surface processes model

NASA Astrophysics Data System (ADS)

Kooi, Henk; Beaumont, Christopher

1996-02-01

Linear systems analysis is used to investigate the response of a surface processes model (SPM) to tectonic forcing. The SPM calculates subcontinental scale denudational landscape evolution on geological timescales (1 to hundreds of million years) as the result of simultaneous hillslope transport, modeled by diffusion, and fluvial transport, modeled by advection and reaction. The tectonically forced SPM accommodates the large-scale behavior envisaged in classical and contemporary conceptual geomorphic models and provides a framework for their integration and unification. The following three model scales are considered: micro-, meso-, and macroscale. The concepts of dynamic equilibrium and grade are quantified at the microscale for segments of uniform gradient subject to tectonic uplift. At the larger meso- and macroscales (which represent individual interfluves and landscapes including a number of drainage basins, respectively) the system response to tectonic forcing is linear for uplift geometries that are symmetric with respect to baselevel and which impose a fully integrated drainage to baselevel. For these linear models the response time and the transfer function as a function of scale characterize the model behavior. Numerical experiments show that the styles of landscape evolution depend critically on the timescales of the tectonic processes in relation to the response time of the landscape. When tectonic timescales are much longer than the landscape response time, the resulting dynamic equilibrium landscapes correspond to those envisaged by Hack (1960). When tectonic timescales are of the same order as the landscape response time and when tectonic variations take the form of pulses (much shorter than the response time), evolving landscapes conform to the Penck type (1972) and to the Davis (1889, 1899) and King (1953, 1962) type frameworks, respectively. The behavior of the SPM highlights the importance of phase shifts or delays of the landform response and sediment yield in relation to the tectonic forcing. Finally, nonlinear behavior resulting from more general uplift geometries is discussed. A number of model experiments illustrate the importance of "fundamental form," which is an expression of the conformity of antecedent topography with the current tectonic regime. Lack of conformity leads to models that exhibit internal thresholds and a complex response.

The l z ( p ) * Person-Fit Statistic in an Unfolding Model Context.

PubMed

Tendeiro, Jorge N

2017-01-01

Although person-fit analysis has a long-standing tradition within item response theory, it has been applied in combination with dominance response models almost exclusively. In this article, a popular log likelihood-based parametric person-fit statistic under the framework of the generalized graded unfolding model is used. Results from a simulation study indicate that the person-fit statistic performed relatively well in detecting midpoint response style patterns and not so well in detecting extreme response style patterns.

Software life cycle dynamic simulation model: The organizational performance submodel

NASA Technical Reports Server (NTRS)

Tausworthe, Robert C.

1985-01-01

The submodel structure of a software life cycle dynamic simulation model is described. The software process is divided into seven phases, each with product, staff, and funding flows. The model is subdivided into an organizational response submodel, a management submodel, a management influence interface, and a model analyst interface. The concentration here is on the organizational response model, which simulates the performance characteristics of a software development subject to external and internal influences. These influences emanate from two sources: the model analyst interface, which configures the model to simulate the response of an implementing organization subject to its own internal influences, and the management submodel that exerts external dynamic control over the production process. A complete characterization is given of the organizational response submodel in the form of parameterized differential equations governing product, staffing, and funding levels. The parameter values and functions are allocated to the two interfaces.

The non-linear response of a muscle in transverse compression: assessment of geometry influence using a finite element model.

PubMed

Gras, Laure-Lise; Mitton, David; Crevier-Denoix, Nathalie; Laporte, Sébastien

2012-01-01

Most recent finite element models that represent muscles are generic or subject-specific models that use complex, constitutive laws. Identification of the parameters of such complex, constitutive laws could be an important limit for subject-specific approaches. The aim of this study was to assess the possibility of modelling muscle behaviour in compression with a parametric model and a simple, constitutive law. A quasi-static compression test was performed on the muscles of dogs. A parametric finite element model was designed using a linear, elastic, constitutive law. A multi-variate analysis was performed to assess the effects of geometry on muscle response. An inverse method was used to define Young's modulus. The non-linear response of the muscles was obtained using a subject-specific geometry and a linear elastic law. Thus, a simple muscle model can be used to have a bio-faithful, biomechanical response.

Assessment of hemoglobin responsiveness to epoetin alfa in patients on hemodialysis using a population pharmacokinetic pharmacodynamic model.

PubMed

Wu, Liviawati; Mould, Diane R; Perez Ruixo, Juan Jose; Doshi, Sameer

2015-10-01

A population pharmacokinetic pharmacodynamic (PK/PD) model describing the effect of epoetin alfa on hemoglobin (Hb) response in hemodialysis patients was developed. Epoetin alfa pharmacokinetics was described using a linear 2-compartment model. PK parameter estimates were similar to previously reported values. A maturation-structured cytokinetic model consisting of 5 compartments linked in a catenary fashion by first-order cell transfer rates following a zero-order input process described the Hb time course. The PD model described 2 subpopulations, one whose Hb response reflected epoetin alfa dosing and a second whose response was unrelated to epoetin alfa dosing. Parameter estimates from the PK/PD model were physiologically reasonable and consistent with published reports. Numerical and visual predictive checks using data from 2 studies were performed. The PK and PD of epoetin alfa were well described by the model. © 2015, The American College of Clinical Pharmacology.

Paleoclimate diagnostics: consistent large-scale temperature responses in warm and cold climates

NASA Astrophysics Data System (ADS)

Izumi, Kenji; Bartlein, Patrick; Harrison, Sandy

2015-04-01

The CMIP5 model simulations of the large-scale temperature responses to increased raditative forcing include enhanced land-ocean contrast, stronger response at higher latitudes than in the tropics, and differential responses in warm and cool season climates to uniform forcing. Here we show that these patterns are also characteristic of CMIP5 model simulations of past climates. The differences in the responses over land as opposed to over the ocean, between high and low latitudes, and between summer and winter are remarkably consistent (proportional and nearly linear) across simulations of both cold and warm climates. Similar patterns also appear in historical observations and paleoclimatic reconstructions, implying that such responses are characteristic features of the climate system and not simple model artifacts, thereby increasing our confidence in the ability of climate models to correctly simulate different climatic states. We also show the possibility that a small set of common mechanisms control these large-scale responses of the climate system across multiple states.

From reactive to proactive and selective control: developing a richer model for stopping inappropriate responses

PubMed Central

Aron, Adam R

2010-01-01

A better understanding of the neural systems underlying impulse control is important for psychiatry. While most impulses are motivational or emotional rather than motoric per se, it is research into the neural architecture of motor response control that has made the greatest strides. This article reviews recent developments in the cognitive neuroscience of stopping responses. Most research of this kind has focused on reactive control – i.e. how subjects stop a response outright when instructed by a signal. It is argued that reactive paradigms are limited as models of control relevant to psychiatry. Instead, a set of paradigms is advocated that begins to model proactive inhibitory control – i.e. how a subject prepares to stop an upcoming response tendency. Proactive inhibitory control is generated according to the goals of the subject, rather than by an external signal, and it can be selectively targeted at a particular response tendency. This may have wider validity than reactive control as an experimental model for stopping inappropriate responses. PMID:20932513

Locating helicopter emergency medical service bases to optimise population coverage versus average response time.

PubMed

Garner, Alan A; van den Berg, Pieter L

2017-10-16

New South Wales (NSW), Australia has a network of multirole retrieval physician staffed helicopter emergency medical services (HEMS) with seven bases servicing a jurisdiction with population concentrated along the eastern seaboard. The aim of this study was to estimate optimal HEMS base locations within NSW using advanced mathematical modelling techniques. We used high resolution census population data for NSW from 2011 which divides the state into areas containing 200-800 people. Optimal HEMS base locations were estimated using the maximal covering location problem facility location optimization model and the average response time model, exploring the number of bases needed to cover various fractions of the population for a 45 min response time threshold or minimizing the overall average response time to all persons, both in green field scenarios and conditioning on the current base structure. We also developed a hybrid mathematical model where average response time was optimised based on minimum population coverage thresholds. Seven bases could cover 98% of the population within 45mins when optimised for coverage or reach the entire population of the state within an average of 21mins if optimised for response time. Given the existing bases, adding two bases could either increase the 45 min coverage from 91% to 97% or decrease the average response time from 21mins to 19mins. Adding a single specialist prehospital rapid response HEMS to the area of greatest population concentration decreased the average state wide response time by 4mins. The optimum seven base hybrid model that was able to cover 97.75% of the population within 45mins, and all of the population in an average response time of 18 mins included the rapid response HEMS model. HEMS base locations can be optimised based on either percentage of the population covered, or average response time to the entire population. We have also demonstrated a hybrid technique that optimizes response time for a given number of bases and minimum defined threshold of population coverage. Addition of specialized rapid response HEMS services to a system of multirole retrieval HEMS may reduce overall average response times by improving access in large urban areas.

Selecting an Informative/Discriminating Multivariate Response for Inverse Prediction

DOE PAGES

Thomas, Edward V.; Lewis, John R.; Anderson-Cook, Christine M.; ...

2017-11-21

nverse prediction is important in a wide variety of scientific and engineering contexts. One might use inverse prediction to predict fundamental properties/characteristics of an object using measurements obtained from it. This can be accomplished by “inverting” parameterized forward models that relate the measurements (responses) to the properties/characteristics of interest. Sometimes forward models are science based; but often, forward models are empirically based, using the results of experimentation. For empirically-based forward models, it is important that the experiments provide a sound basis to develop accurate forward models in terms of the properties/characteristics (factors). While nature dictates the causal relationship between factorsmore » and responses, experimenters can influence control of the type, accuracy, and precision of forward models that can be constructed via selection of factors, factor levels, and the set of trials that are performed. Whether the forward models are based on science, experiments or both, researchers can influence the ability to perform inverse prediction by selecting informative response variables. By using an errors-in-variables framework for inverse prediction, this paper shows via simple analysis and examples how the capability of a multivariate response (with respect to being informative and discriminating) can vary depending on how well the various responses complement one another over the range of the factor-space of interest. Insights derived from this analysis could be useful for selecting a set of response variables among candidates in cases where the number of response variables that can be acquired is limited by difficulty, expense, and/or availability of material.« less

Selecting an Informative/Discriminating Multivariate Response for Inverse Prediction

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

Thomas, Edward V.; Lewis, John R.; Anderson-Cook, Christine M.

nverse prediction is important in a wide variety of scientific and engineering contexts. One might use inverse prediction to predict fundamental properties/characteristics of an object using measurements obtained from it. This can be accomplished by “inverting” parameterized forward models that relate the measurements (responses) to the properties/characteristics of interest. Sometimes forward models are science based; but often, forward models are empirically based, using the results of experimentation. For empirically-based forward models, it is important that the experiments provide a sound basis to develop accurate forward models in terms of the properties/characteristics (factors). While nature dictates the causal relationship between factorsmore » and responses, experimenters can influence control of the type, accuracy, and precision of forward models that can be constructed via selection of factors, factor levels, and the set of trials that are performed. Whether the forward models are based on science, experiments or both, researchers can influence the ability to perform inverse prediction by selecting informative response variables. By using an errors-in-variables framework for inverse prediction, this paper shows via simple analysis and examples how the capability of a multivariate response (with respect to being informative and discriminating) can vary depending on how well the various responses complement one another over the range of the factor-space of interest. Insights derived from this analysis could be useful for selecting a set of response variables among candidates in cases where the number of response variables that can be acquired is limited by difficulty, expense, and/or availability of material.« less

Modeling of a Surface Acoustic Wave Strain Sensor

NASA Technical Reports Server (NTRS)

Wilson, W. C.; Atkinson, Gary M.

2010-01-01

NASA Langley Research Center is investigating Surface Acoustic Wave (SAW) sensor technology for harsh environments aimed at aerospace applications. To aid in development of sensors a model of a SAW strain sensor has been developed. The new model extends the modified matrix method to include the response of Orthogonal Frequency Coded (OFC) reflectors and the response of SAW devices to strain. These results show that the model accurately captures the strain response of a SAW sensor on a Langasite substrate. The results of the model of a SAW Strain Sensor on Langasite are presented

Validation and upgrading of physically based mathematical models

NASA Technical Reports Server (NTRS)

Duval, Ronald

1992-01-01

The validation of the results of physically-based mathematical models against experimental results was discussed. Systematic techniques are used for: (1) isolating subsets of the simulator mathematical model and comparing the response of each subset to its experimental response for the same input conditions; (2) evaluating the response error to determine whether it is the result of incorrect parameter values, incorrect structure of the model subset, or unmodeled external effects of cross coupling; and (3) modifying and upgrading the model and its parameter values to determine the most physically appropriate combination of changes.

A Comparison of Linking and Concurrent Calibration under the Graded Response Model.

ERIC Educational Resources Information Center

Kim, Seock-Ho; Cohen, Allan S.

Applications of item response theory to practical testing problems including equating, differential item functioning, and computerized adaptive testing, require that item parameter estimates be placed onto a common metric. In this study, two methods for developing a common metric for the graded response model under item response theory were…

Hillslope threshold response to rainfall: (2) development and use of a macroscale model

Treesearch

Chris B. Graham; Jeffrey J. McDonnell

2010-01-01

Hillslope hydrological response to precipitation is extremely complex and poorly modeled. One possible approach for reducing the complexity of hillslope response and its mathematical parameterization is to look for macroscale hydrological behavior. Hillslope threshold response to storm precipitation is one such macroscale behavior observed at field sites across the...

Using SAS PROC MCMC for Item Response Theory Models

PubMed Central

Samonte, Kelli

2014-01-01

Interest in using Bayesian methods for estimating item response theory models has grown at a remarkable rate in recent years. This attentiveness to Bayesian estimation has also inspired a growth in available software such as WinBUGS, R packages, BMIRT, MPLUS, and SAS PROC MCMC. This article intends to provide an accessible overview of Bayesian methods in the context of item response theory to serve as a useful guide for practitioners in estimating and interpreting item response theory (IRT) models. Included is a description of the estimation procedure used by SAS PROC MCMC. Syntax is provided for estimation of both dichotomous and polytomous IRT models, as well as a discussion on how to extend the syntax to accommodate more complex IRT models. PMID:29795834

A computer program for predicting nonlinear uniaxial material responses using viscoplastic models

NASA Technical Reports Server (NTRS)

Chang, T. Y.; Thompson, R. L.

1984-01-01

A computer program was developed for predicting nonlinear uniaxial material responses using viscoplastic constitutive models. Four specific models, i.e., those due to Miller, Walker, Krieg-Swearengen-Rhode, and Robinson, are included. Any other unified model is easily implemented into the program in the form of subroutines. Analysis features include stress-strain cycling, creep response, stress relaxation, thermomechanical fatigue loop, or any combination of these responses. An outline is given on the theoretical background of uniaxial constitutive models, analysis procedure, and numerical integration methods for solving the nonlinear constitutive equations. In addition, a discussion on the computer program implementation is also given. Finally, seven numerical examples are included to demonstrate the versatility of the computer program developed.

Using process algebra to develop predator-prey models of within-host parasite dynamics.

PubMed

McCaig, Chris; Fenton, Andy; Graham, Andrea; Shankland, Carron; Norman, Rachel

2013-07-21

As a first approximation of immune-mediated within-host parasite dynamics we can consider the immune response as a predator, with the parasite as its prey. In the ecological literature of predator-prey interactions there are a number of different functional responses used to describe how a predator reproduces in response to consuming prey. Until recently most of the models of the immune system that have taken a predator-prey approach have used simple mass action dynamics to capture the interaction between the immune response and the parasite. More recently Fenton and Perkins (2010) employed three of the most commonly used prey-dependent functional response terms from the ecological literature. In this paper we make use of a technique from computing science, process algebra, to develop mathematical models. The novelty of the process algebra approach is to allow stochastic models of the population (parasite and immune cells) to be developed from rules of individual cell behaviour. By using this approach in which individual cellular behaviour is captured we have derived a ratio-dependent response similar to that seen in the previous models of immune-mediated parasite dynamics, confirming that, whilst this type of term is controversial in ecological predator-prey models, it is appropriate for models of the immune system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Robust Unit Commitment Considering Uncertain Demand Response

DOE PAGES

Liu, Guodong; Tomsovic, Kevin

2014-09-28

Although price responsive demand response has been widely accepted as playing an important role in the reliable and economic operation of power system, the real response from demand side can be highly uncertain due to limited understanding of consumers' response to pricing signals. To model the behavior of consumers, the price elasticity of demand has been explored and utilized in both research and real practice. However, the price elasticity of demand is not precisely known and may vary greatly with operating conditions and types of customers. To accommodate the uncertainty of demand response, alternative unit commitment methods robust to themore » uncertainty of the demand response require investigation. In this paper, a robust unit commitment model to minimize the generalized social cost is proposed for the optimal unit commitment decision taking into account uncertainty of the price elasticity of demand. By optimizing the worst case under proper robust level, the unit commitment solution of the proposed model is robust against all possible realizations of the modeled uncertain demand response. Numerical simulations on the IEEE Reliability Test System show the e ectiveness of the method. Finally, compared to unit commitment with deterministic price elasticity of demand, the proposed robust model can reduce the average Locational Marginal Prices (LMPs) as well as the price volatility.« less