Dynamic Assessment of Narratives: Efficient, Accurate Identification of Language Impairment in Bilingual Students

ERIC Educational Resources Information Center

Petersen, Douglas B.; Chanthongthip, Helen; Ukrainetz, Teresa A.; Spencer, Trina D.; Steeve, Roger W.

2017-01-01

Purpose: This study investigated the classification accuracy of a concentrated English narrative dynamic assessment (DA) for identifying language impairment (LI). Method: Forty-two Spanish-English bilingual kindergarten to third-grade children (10 LI and 32 with no LI) were administered two 25-min DA test-teach-test sessions. Pre- and posttest…

Planning Intervention Using Dynamic Assessments: A Case Study

ERIC Educational Resources Information Center

Hasson, Natalie; Dodd, Barbara

2014-01-01

Dynamic assessments (DA) of language have been shown to be a useful addition to the battery of tests used to diagnose language impairments in children, and to evaluate their skills. The current article explores the value of the information gained from a DA in planning intervention for a child with language impairment. A single case study was used…

The Development of a New Method of Idiographic Measurement for Dynamic Assessment Intervention

ERIC Educational Resources Information Center

Hurley, Emma; Murphy, Raegan

2015-01-01

This paper proposes a new method of idiographic measurement for dynamic assessment (DA) intervention. There are two main methods of measurement for DA intervention; split-half tests and integrated scoring systems. Split-half tests of ability have proved useful from a research perspective. Integrated scoring systems coupled with case studies are…

Computerized Dynamic Assessment (C-DA): Diagnosing L2 Development According to Learner Responsiveness to Mediation

ERIC Educational Resources Information Center

Poehner, Matthew E.; Zhang, Jie; Lu, Xiaofei

2015-01-01

Dynamic assessment (DA) derives from the sociocultural theory of mind as elaborated by Russian psychologist L. S. Vygotsky. By offering mediation when individuals experience difficulties and carefully tracing their responsiveness, Vygotsky (1998) proposed that diagnoses may uncover abilities that have fully formed as well as those still in the…

The Measurement Paradigm and Role of Mediators in Dynamic Assessment: A Qualitative Meta-Synthesis

ERIC Educational Resources Information Center

Rezaee, Abbas Ali; Ghanbarpour, Mahsa

2016-01-01

As dynamic assessment (DA) continues to come to prominence as a procedure that endeavors to ameliorate learner performance and further development through mediators' assistance with the intent of discerning learning potential, a plethora of research has delved into the applicability of DA in second/foreign language education. This article employed…

Development of First-Graders' Word Reading Skills: For Whom Can Dynamic Assessment Tell Us More?

ERIC Educational Resources Information Center

Cho, Eunsoo; Compton, Donald L.; Gilbert, Jennifer K.; Steacy, Laura M.; Collins, Alyson A.; Lindström, Esther R.

2017-01-01

Dynamic assessment (DA) of word reading measures learning potential for early reading development by documenting the amount of assistance needed to learn how to read words with unfamiliar orthography. We examined the additive value of DA for predicting first-grade decoding and word recognition development while controlling for autoregressive…

Development of First-Graders' Word Reading Skills: For Whom Can Dynamic Assessment Tell Us More?

PubMed

Cho, Eunsoo; Compton, Donald L; Gilbert, Jennifer K; Steacy, Laura M; Collins, Alyson A; Lindström, Esther R

2017-01-01

Dynamic assessment (DA) of word reading measures learning potential for early reading development by documenting the amount of assistance needed to learn how to read words with unfamiliar orthography. We examined the additive value of DA for predicting first-grade decoding and word recognition development while controlling for autoregressive effects. Additionally, we examined whether predictive validity of DA would be higher for students who have poor phonological awareness skills. First-grade students (n = 105) were assessed on measures of word reading, phonological awareness, rapid automatized naming, and DA in the fall and again assessed on word reading measures in the spring. A series of planned, moderated multiple regression analyses indicated that DA made a significant and unique contribution in predicting word recognition development above and beyond the autoregressor, particularly for students with poor phonological awareness skills. For these students, DA explained 3.5% of the unique variance in end-of-first-grade word recognition that was not attributable to autoregressive effect. Results suggest that DA provides an important source of individual differences in the development of word recognition skills that cannot be fully captured by merely assessing the present level of reading skills through traditional static assessment, particularly for students at risk for developing reading disabilities. © Hammill Institute on Disabilities 2015.

Using Dynamic Assessment to Evaluate the Expressive Syntax of Children who use Augmentative and Alternative Communication

PubMed Central

King, Marika R.; Binger, Cathy; Kent-Walsh, Jennifer

2015-01-01

The developmental readiness of four 5-year-old children to produce basic sentences using graphic symbols on an augmentative and alternative communication (AAC) device during a dynamic assessment (DA) task was examined. Additionally, the ability of the DA task to predict performance on a subsequent experimental task was evaluated. A graduated prompting framework was used during DA. Measures included amount of support required to produce the targets, modifiability (change in participant performance) within a DA session, and predictive validity of DA. Participants accurately produced target structures with varying amounts of support. Modifiability within DA sessions was evident for some participants, and partial support was provided for the measures of predictive validity. These initial results indicate that DA may be a viable way to measure young children’s developmental readiness to learn how to sequence simple, rule-based messages via aided AAC. PMID:25621928

Dynamic Assessment: A Case of Unfulfilled Potential?

ERIC Educational Resources Information Center

Elliott, Julian G.; Resing, Wilma C. M.; Beckmann, Jens F.

2018-01-01

This paper updates a review of dynamic assessment in education by the first author, published in this journal in 2003. It notes that the original review failed to examine the important conceptual distinction between dynamic testing (DT) and dynamic assessment (DA). While both approaches seek to link assessment and intervention, the former is of…

The Effect of Dynamic Assessment on Adult Learners of Arabic: A Mixed-Method Study at the Defense Language Institute Foreign Language Center

ERIC Educational Resources Information Center

Fahmy, Mohsen M.

2013-01-01

Dynamic assessment (DA) is based on Vygotsky's (1978) sociocultural theory and his Zone of Proximal Development (ZPD). ZPD is the range of abilities bordered by the learner's assisted and independent performances. Previous studies showed promising results for DA in tutoring settings. However, they did not use proficiency-based rubrics to measure…

Dynamic Assessment for 3- and 4-Year-Old Children Who Use Augmentative and Alternative Communication: Evaluating Expressive Syntax.

PubMed

Binger, Cathy; Kent-Walsh, Jennifer; King, Marika

2017-07-12

The developmental readiness to produce early sentences with an iPad communication application was assessed with ten 3- and 4-year-old children with severe speech disorders using graduated prompting dynamic assessment (DA) techniques. The participants' changes in performance within the DA sessions were evaluated, and DA performance was compared with performance during a subsequent intervention. Descriptive statistics were used to examine patterns of performance at various cueing levels and mean levels of cueing support. The Wilcoxon signed-ranks test was used to measure changes within the DA sessions. Correlational data were calculated to determine how well performance in DA predicted performance during a subsequent intervention. Participants produced targets successfully in DA at various cueing levels, with some targets requiring less cueing than others. Performance improved significantly within the DA sessions-that is, the level of cueing required for accurate productions of the targets decreased during DA sessions. Last, moderate correlations existed between DA scores and performance during the intervention for 3 out of 4 targets, with statistically significant findings for 2 of 4 targets. DA offers promise for examining the developmental readiness of young children who use augmentative and alternative communication to produce early expressive language structures.

Dynamic Assessment for 3- and 4-Year-Old Children Who Use Augmentative and Alternative Communication: Evaluating Expressive Syntax

PubMed Central

Kent-Walsh, Jennifer; King, Marika

2017-01-01

Purpose The developmental readiness to produce early sentences with an iPad communication application was assessed with ten 3- and 4-year-old children with severe speech disorders using graduated prompting dynamic assessment (DA) techniques. The participants' changes in performance within the DA sessions were evaluated, and DA performance was compared with performance during a subsequent intervention. Method Descriptive statistics were used to examine patterns of performance at various cueing levels and mean levels of cueing support. The Wilcoxon signed-ranks test was used to measure changes within the DA sessions. Correlational data were calculated to determine how well performance in DA predicted performance during a subsequent intervention. Results Participants produced targets successfully in DA at various cueing levels, with some targets requiring less cueing than others. Performance improved significantly within the DA sessions—that is, the level of cueing required for accurate productions of the targets decreased during DA sessions. Last, moderate correlations existed between DA scores and performance during the intervention for 3 out of 4 targets, with statistically significant findings for 2 of 4 targets. Conclusion DA offers promise for examining the developmental readiness of young children who use augmentative and alternative communication to produce early expressive language structures. PMID:28614580

Predicting First Graders' Development of Calculation versus Word-Problem Performance: The Role of Dynamic Assessment.

PubMed

Seethaler, Pamela M; Fuchs, Lynn S; Fuchs, Douglas; Compton, Donald L

2012-02-01

The purpose of this study was to assess the value of dynamic assessment (DA; degree of scaffolding required to learn unfamiliar mathematics content) for predicting 1(st)-grade calculations (CA) and word problems (WP) development, while controlling for the role of traditional assessments. Among 184 1(st) graders, predictors (DA, Quantity Discrimination, Test of Mathematics Ability, language, and reasoning) were assessed near the start of 1(st) grade. CA and WP were assessed near the end of 1(st) grade. Planned regression and commonality analyses indicated that for forecasting CA development, Quantity Discrimination, which accounted for 8.84% of explained variance, was the single most powerful predictor, followed by Test of Mathematics Ability and DA; language and reasoning were not uniquely predictive. By contrast, for predicting WP development, DA was the single most powerful predictor, which accounted for 12.01% of explained variance, with Test of Mathematics Ability, Quantity Discrimination, and language also uniquely predictive. Results suggest that different constellations of cognitive resources are required for CA versus WP development and that DA may be useful in predicting 1(st)-grade mathematics development, especially WP.

Predicting First Graders’ Development of Calculation versus Word-Problem Performance: The Role of Dynamic Assessment

PubMed Central

Seethaler, Pamela M.; Fuchs, Lynn S.; Fuchs, Douglas; Compton, Donald L.

2012-01-01

The purpose of this study was to assess the value of dynamic assessment (DA; degree of scaffolding required to learn unfamiliar mathematics content) for predicting 1st-grade calculations (CA) and word problems (WP) development, while controlling for the role of traditional assessments. Among 184 1st graders, predictors (DA, Quantity Discrimination, Test of Mathematics Ability, language, and reasoning) were assessed near the start of 1st grade. CA and WP were assessed near the end of 1st grade. Planned regression and commonality analyses indicated that for forecasting CA development, Quantity Discrimination, which accounted for 8.84% of explained variance, was the single most powerful predictor, followed by Test of Mathematics Ability and DA; language and reasoning were not uniquely predictive. By contrast, for predicting WP development, DA was the single most powerful predictor, which accounted for 12.01% of explained variance, with Test of Mathematics Ability, Quantity Discrimination, and language also uniquely predictive. Results suggest that different constellations of cognitive resources are required for CA versus WP development and that DA may be useful in predicting 1st-grade mathematics development, especially WP. PMID:22347725

Does the Value of Dynamic Assessment in Predicting End-of-First-Grade Mathematics Performance Differ as a Function of English Language Proficiency?

PubMed Central

Seethaler, Pamela M.; Fuchs, Lynn S.; Fuchs, Douglas; Compton, Donald L.

2015-01-01

The purpose of this study was to assess the added value of dynamic assessment (DA) beyond more conventional static measures for predicting individual differences in year-end 1st-grade calculation (CA) and word-problem (WP) performance, as a function of limited English proficiency (LEP) status. At the start of 1st grade, students (129 LEP; 163 non-LEP) were assessed on a brief static mathematics test, an extended static mathematics test, static tests of domain-general abilities associated with CAs and WPs (vocabulary; reasoning), and DA. Near end of 1st grade, they were assessed on CA and WP. Regression analyses indicated that the value of the predictor depends on the predicted outcome and LEP status. In predicting CAs, the extended mathematics test and DA uniquely explained variance for LEP children, with stronger predictive value for the extended mathematics test; for non-LEP children, the extended mathematics test was the only significant predictor. However, in predicting WPs, only DA and vocabulary were uniquely predictive for LEP children, with stronger value for DA; for non-LEP children, the extended mathematics test and DA were comparably uniquely predictive. Neither the brief static mathematics test nor reasoning was significant in predicting either outcome. The potential value of a gated screening process, using an extended mathematics assessment to predict CAs and using DA to predict WPs, is discussed. PMID:26523068

Implications of Vygotsky's Sociocultural Theory for Second Language (L2) Assessment

ERIC Educational Resources Information Center

Shabani, Karim

2016-01-01

Dynamic assessment (DA) research, still in its infancy, takes its roots from Vygotsky's concept of zone of proximal development (ZPD) to account for learner's developmental process. Breaking away from a static, incomplete and, thus, unethical assessment of learner's abilities, DA came to the fore to better crystallize learner's levels of abilities…

The Effect of Dynamic Assessment on Iranian EFL Learners' Reading Comprehension

ERIC Educational Resources Information Center

Amirian, Mohammad Reza; Davoudi, Mohammad; Ramazanian, Mohsen

2014-01-01

Dynamic Assessment (DA), is grounded in Vygotsky's idea on Sociocultural Theory (SCT) of mind, his concept of Zone of Proximal Development (ZPD) and its related metaphor; scaffolding. This study examined the effects of dynamic assessment on improving reading comprehension of Iranian intermediate students who were learning English as a foreign…

Dynamic Assessment of Algebraic Learning in Predicting Third Graders’ Development of Mathematical Problem Solving

PubMed Central

Fuchs, Lynn S.; Compton, Donald L.; Fuchs, Douglas; Hollenbeck, Kurstin N.; Craddock, Caitlin F.; Hamlett, Carol L.

2008-01-01

Dynamic assessment (DA) involves helping students learn a task and indexing responsiveness to that instruction as a measure of learning potential. The purpose of this study was to explore the utility of a DA of algebraic learning in predicting 3rd graders’ development of mathematics problem solving. In the fall, 122 3rd-grade students were assessed on language, nonverbal reasoning, attentive behavior, calculations, word-problem skill, and DA. On the basis of random assignment, students received 16 weeks of validated instruction on word problems or received 16 weeks of conventional instruction on word problems. Then, students were assessed on word-problem measures proximal and distal to instruction. Structural equation measurement models showed that DA measured a distinct dimension of pretreatment ability and that proximal and distal word-problem measures were needed to account for outcome. Structural equation modeling showed that instruction (conventional vs. validated) was sufficient to account for math word-problem outcome proximal to instruction; by contrast, language, pretreatment math skill, and DA were needed to forecast learning on word-problem outcomes more distal to instruction. Findings are discussed in terms of responsiveness-to-intervention models for preventing and identifying learning disabilities. PMID:19884957

A Knowledge-Structure-Based Adaptive Dynamic Assessment System for Calculus Learning

ERIC Educational Resources Information Center

Ting, M.-Y.; Kuo, B.-C.

2016-01-01

The purpose of this study was to investigate the effect of a calculus system that was designed using an adaptive dynamic assessment (DA) framework on performance in the "finding an area using an integral". In this study, adaptive testing and dynamic assessment were combined to provide different test items depending on students'…

Revealing the Effects of Cognitive Education Programmes through Dynamic Assessment

ERIC Educational Resources Information Center

Tzuriel, David

2011-01-01

The major objective of this paper is to demonstrate the effectiveness of dynamic assessment (DA) in revealing outcomes of cognitive education programmes. Three programmes based on "mediated learning experience" theory are reviewed: "Feuerstein's Instrumental Enrichment", "Bright Start", and "Peer Mediation with…

Understanding and Addressing the Challenges of Learning Computer-Mediated Dynamic Assessment: A Teacher Education Study

ERIC Educational Resources Information Center

McNeil, Levi

2018-01-01

Although the second language literature on Dynamic Assessment (DA)--the unity of assessment and instruction into a singular activity to promote cognitive development--shows promising results, very little has been written about how to educate teachers to use it. This two-cycle, exploratory action research study aimed to understand and address the…

Dynamic Assessment of Word Learning Skills: Identifying Language Impairment in Bilingual Children

ERIC Educational Resources Information Center

Kapantzoglou, Maria; Restrepo, M. Adelaida; Thompson, Marilyn S.

2012-01-01

Purpose: Bilingual children are often diagnosed with language impairment, although they may simply have fewer opportunities to learn English than English-speaking monolingual children. This study examined whether dynamic assessment (DA) of word learning skills is an effective method for identifying bilingual children with primary language…

Dynamic Assessment, Tutor Mediation and Academic Writing Development

ERIC Educational Resources Information Center

Shrestha, Prithvi; Coffin, Caroline

2012-01-01

Supporting undergraduate students with their academic literacies has recently been a major focus in higher education in the UK. This paper explores the value of tutor mediation in the context of academic writing development among undergraduate business studies students in open and distance learning, following the dynamic assessment (DA) approach…

The Predictive Validity of Dynamic Assessment: A Review

ERIC Educational Resources Information Center

Caffrey, Erin; Fuchs, Douglas; Fuchs, Lynn S.

2008-01-01

The authors report on a mixed-methods review of 24 studies that explores the predictive validity of dynamic assessment (DA). For 15 of the studies, they conducted quantitative analyses using Pearson's correlation coefficients. They descriptively examined the remaining studies to determine if their results were consistent with findings from the…

Examining the Predictive Validity of a Dynamic Assessment of Decoding to Forecast Response Tier 2 to Intervention

PubMed Central

Cho, Eunsoo; Compton, Donald L.; Fuchs, Doug; Fuchs, Lynn S.; Bouton, Bobette

2013-01-01

The purpose of this study was to examine the role of a dynamic assessment (DA) of decoding in predicting responsiveness to Tier 2 small group tutoring in a response-to-intervention model. First-grade students (n=134) who did not show adequate progress in Tier 1 based on 6 weeks of progress monitoring received Tier 2 small-group tutoring in reading for 14 weeks. Student responsiveness to Tier 2 was assessed weekly with word identification fluency (WIF). A series of conditional individual growth curve analyses were completed that modeled the correlates of WIF growth (final level of performance and growth). Its purpose was to examine the predictive validity of DA in the presence of 3 sets of variables: static decoding measures, Tier 1 responsiveness indicators, and pre-reading variables (phonemic awareness, rapid letter naming, oral vocabulary, and IQ). DA was a significant predictor of final level and growth, uniquely explaining 3% – 13% of the variance in Tier 2 responsiveness depending on the competing predictors in the model and WIF outcome (final level of performance or growth). Although the additional variances explained uniquely by DA were relatively small, results indicate the potential of DA in identifying Tier 2 nonresponders. PMID:23213050

Examining the predictive validity of a dynamic assessment of decoding to forecast response to tier 2 intervention.

PubMed

Cho, Eunsoo; Compton, Donald L; Fuchs, Douglas; Fuchs, Lynn S; Bouton, Bobette

2014-01-01

The purpose of this study was to examine the role of a dynamic assessment (DA) of decoding in predicting responsiveness to Tier 2 small-group tutoring in a response-to-intervention model. First grade students (n = 134) who did not show adequate progress in Tier 1 based on 6 weeks of progress monitoring received Tier 2 small-group tutoring in reading for 14 weeks. Student responsiveness to Tier 2 was assessed weekly with word identification fluency (WIF). A series of conditional individual growth curve analyses were completed that modeled the correlates of WIF growth (final level of performance and growth). Its purpose was to examine the predictive validity of DA in the presence of three sets of variables: static decoding measures, Tier 1 responsiveness indicators, and prereading variables (phonemic awareness, rapid letter naming, oral vocabulary, and IQ). DA was a significant predictor of final level and growth, uniquely explaining 3% to 13% of the variance in Tier 2 responsiveness depending on the competing predictors in the model and WIF outcome (final level of performance or growth). Although the additional variances explained uniquely by DA were relatively small, results indicate the potential of DA in identifying Tier 2 nonresponders. © Hammill Institute on Disabilities 2012.

A pseudoproxy assessment of data assimilation for reconstructing the atmosphere-ocean dynamics of hydroclimate extremes

NASA Astrophysics Data System (ADS)

Steiger, Nathan J.; Smerdon, Jason E.

2017-10-01

Because of the relatively brief observational record, the climate dynamics that drive multiyear to centennial hydroclimate variability are not adequately characterized and understood. Paleoclimate reconstructions based on data assimilation (DA) optimally fuse paleoclimate proxies with the dynamical constraints of climate models, thus providing a coherent dynamical picture of the past. DA is therefore an important new tool for elucidating the mechanisms of hydroclimate variability over the last several millennia. But DA has so far remained untested for global hydroclimate reconstructions. Here we explore whether or not DA can be used to skillfully reconstruct global hydroclimate variability along with the driving climate dynamics. Through a set of idealized pseudoproxy experiments, we find that an established DA reconstruction approach can in principle be used to reconstruct hydroclimate at both annual and seasonal timescales. We find that the skill of such reconstructions is generally highest near the proxy sites. This set of reconstruction experiments is specifically designed to estimate a realistic upper bound for the skill of this DA approach. Importantly, this experimental framework allows us to see where and for what variables the reconstruction approach may never achieve high skill. In particular for tree rings, we find that hydroclimate reconstructions depend critically on moisture-sensitive trees, while temperature reconstructions depend critically on temperature-sensitive trees. Real-world DA-based reconstructions will therefore likely require a spatial mixture of temperature- and moisture-sensitive trees to reconstruct both temperature and hydroclimate variables. Additionally, we illustrate how DA can be used to elucidate the dynamical mechanisms of drought with two examples: tropical drivers of multiyear droughts in the North American Southwest and in equatorial East Africa. This work thus provides a foundation for future DA-based hydroclimate reconstructions using real-proxy networks while also highlighting the utility of this important tool for hydroclimate research.

Dynamic Assessment of Reading Difficulties: Predictive and Incremental Validity on Attitude toward Reading and the Use of Dialogue/Participation Strategies in Classroom Activities.

PubMed

Navarro, Juan-José; Lara, Laura

2017-01-01

Dynamic Assessment (DA) has been shown to have more predictive value than conventional tests for academic performance. However, in relation to reading difficulties, further research is needed to determine the predictive validity of DA for specific aspects of the different processes involved in reading and the differential validity of DA for different subgroups of students with an academic disadvantage. This paper analyzes the implementation of a DA device that evaluates processes involved in reading (EDPL) among 60 students with reading comprehension difficulties between 9 and 16 years of age, of whom 20 have intellectual disabilities, 24 have reading-related learning disabilities, and 16 have socio-cultural disadvantages. We specifically analyze the predictive validity of the EDPL device over attitude toward reading, and the use of dialogue/participation strategies in reading activities in the classroom during the implementation stage. We also analyze if the EDPL device provides additional information to that obtained with a conventionally applied personal-social adjustment scale (APSL). Results showed that dynamic scores, obtained from the implementation of the EDPL device, significantly predict the studied variables. Moreover, dynamic scores showed a significant incremental validity in relation to predictions based on an APSL scale. In relation to differential validity, the results indicated the superior predictive validity for DA for students with intellectual disabilities and reading disabilities than for students with socio-cultural disadvantages. Furthermore, the role of metacognition and its relation to the processes of personal-social adjustment in explaining the results is discussed.

Dynamic Assessment of Reading Difficulties: Predictive and Incremental Validity on Attitude toward Reading and the Use of Dialogue/Participation Strategies in Classroom Activities

PubMed Central

Navarro, Juan-José; Lara, Laura

2017-01-01

Dynamic Assessment (DA) has been shown to have more predictive value than conventional tests for academic performance. However, in relation to reading difficulties, further research is needed to determine the predictive validity of DA for specific aspects of the different processes involved in reading and the differential validity of DA for different subgroups of students with an academic disadvantage. This paper analyzes the implementation of a DA device that evaluates processes involved in reading (EDPL) among 60 students with reading comprehension difficulties between 9 and 16 years of age, of whom 20 have intellectual disabilities, 24 have reading-related learning disabilities, and 16 have socio-cultural disadvantages. We specifically analyze the predictive validity of the EDPL device over attitude toward reading, and the use of dialogue/participation strategies in reading activities in the classroom during the implementation stage. We also analyze if the EDPL device provides additional information to that obtained with a conventionally applied personal-social adjustment scale (APSL). Results showed that dynamic scores, obtained from the implementation of the EDPL device, significantly predict the studied variables. Moreover, dynamic scores showed a significant incremental validity in relation to predictions based on an APSL scale. In relation to differential validity, the results indicated the superior predictive validity for DA for students with intellectual disabilities and reading disabilities than for students with socio-cultural disadvantages. Furthermore, the role of metacognition and its relation to the processes of personal-social adjustment in explaining the results is discussed. PMID:28243215

Dynamic assessment of narrative ability in English accurately identifies language impairment in English language learners.

PubMed

Peña, Elizabeth D; Gillam, Ronald B; Bedore, Lisa M

2014-12-01

To assess the identification accuracy of dynamic assessment (DA) of narrative ability in English for children learning English as a 2nd language. A DA task was administered to 54 children: 18 Spanish-English-speaking children with language impairment (LI); 18 age-, sex-, IQ- and language experience-matched typical control children; and an additional 18 age- and language experience-matched comparison children. A variety of quantitative and qualitative measures were collected in the pretest phase, the mediation phase, and the posttest phase of the study. Exploratory discriminant analysis was used to determine the set of measures that best differentiated among this group of children with and without LI. A combination of examiner ratings of modifiability (compliance, metacognition, and task orientation), DA story scores (setting, dialogue, and complexity of vocabulary), and ungrammaticality (derived from the posttest narrative sample) classified children with 80.6% to 97.2% accuracy. DA conducted in English provides a systematic means for measuring learning processes and learning outcomes, resulting in a clinically useful procedure for identifying LIs in bilingual children who are in the process of learning English as a second language.

Does the Value of Dynamic Assessment in Predicting End-of-First-Grade Mathematics Performance Differ as a Function of English Language Proficiency?

ERIC Educational Resources Information Center

Seethaler, Pamela M.; Fuchs, Lynn S.; Fuchs, Douglas; Compton, Donald L.

2016-01-01

The purpose of this study was to assess the added value of dynamic assessment (DA) for predicting individual differences in year-end first-grade calculation (CA) and word-problem (WP) performance as a function of limited English proficiency (LEP) status. Beginning first graders (129 LEP; 163 non-LEP) were assessed on brief and static mathematics…

Enhancing Learners' Emotions in an L2 Context through Emotionalized Dynamic Assessment

ERIC Educational Resources Information Center

Abdolrezapour, Parisa; Tavakoli, Mansoor; Ketabi, Saeed

2013-01-01

The aim of this study was to gain more in-depth understanding of students' emotions in an EFL context by applying dynamic assessment (DA) procedures to the development of learners' emotional intelligence. The study with 50 intermediate learners aged 12-15 used three modalities: a control group, which was taught under institute's normal procedures;…

Validating Dynamic Assessment of Triadic Gaze for Young Children with Severe Disabilities

ERIC Educational Resources Information Center

Olswang, Lesley B.; Feuerstein, Julie L.; Pinder, Gay Lloyd; Dowden, Patricia

2013-01-01

Purpose: This research investigated the use of a dynamic assessment (DA) to identify differences among young children with severe disabilities, which would predict progress in learning behaviors indicating coordinated joint attention (CJA). Method: Six children 10-24 months of age were enrolled in a 16-week treatment for behaviors indicating CJA,…

A portable device to assess underwater changes of cardio dynamic variables by impedance cardiography

NASA Astrophysics Data System (ADS)

Tocco, F.; Crisafulli, A.; Marongiu, E.; Milia, R.; Kalb, A.; Concu, A.

2012-12-01

Data concerning heart rate (HR), stroke volume (SV), and cardiac output (CO) during dynamic apnoea (DA) were collected from 10 healthy male, elite divers by means of an impedance cardiograph adapted to the underwater environment (C. O. Re., from 2C Technologies Inc, Italy). Three trials were performed by the divers in a 3-m-deep pool with a water temperature of 25°C: 3-minute head-out immersion during normal breathing (A), till exhaustion immersed at the surface (B) and at 3m depth (C). Both B and C conditions did not led to changes in HR, SV and CO compared to A. Data indicate that typical diving response consisting in a reduction of HR, SV and CO was not present during DA, probably due to sympathetic activation induced by exercise during DA, which partially obscured the effects of the diving response. Moreover, this study highlights the innovative role of our portable, impedance cardiography device, i.e. the C. O. Re., in easily assessing cardiodynamic changes in subjects engaged in exercise schedules including phases of underwater, dynamic apnoea.

The Effect of Dynamic Assessment in Synchronous Computer-Mediated Communication on Iranian EFL Learners' Listening Comprehension Ability at Upper-Intermediate Level

ERIC Educational Resources Information Center

Heidar, Davood Mashhadi; Afghari, Akbar

2015-01-01

The present paper concentrates on a web-based inquiry in the synchronous computer-mediated communication (SCMC) via Web 2.0 technologies of Talk and Write and Skype. It investigates EFL learners' socio-cognitive progress through dynamic assessment (DA), which follows Vygotsky's inclination for supportive interchange in the zone of proximal…

The Effect of Dynamic Assessment on L2 Grammar Acquisition by Iranian EFL Learners

ERIC Educational Resources Information Center

Kamali, Mojtaba; Abbasi, Mehdi; Sadighi, Firooz

2018-01-01

This study investigated the effect of dynamic Assessment (DA) on the acquisition of L2 grammar by EFL learners. The focus was on teaching Conditional Type II, or Unreal Conditional, which is a difficult structure for language learners to acquire. To this end, two intact classes of intermediate EFL learners, each consisting of 23 male students were…

Does the Value of Dynamic Assessment in Predicting End-of-First-Grade Mathematics Performance Differ as a Function of English Language Proficiency?

ERIC Educational Resources Information Center

Seethaler, Pamela M.; Fuchs, Lynn S.; Fuchs, Douglas; Compton, Donald L.

2016-01-01

The purpose of this study was to assess the added value of dynamic assessment (DA) beyond more conventional static measures for predicting individual differences in year-end 1st-grade calculation (CA) and word-problem (WP) performance, as a function of limited English proficiency (LEP) status. At the start of 1st grade, students (129 LEP; 163…

Beyond static assessment of children's receptive vocabulary: the dynamic assessment of word learning (DAWL).

PubMed

Camilleri, Bernard; Botting, Nicola

2013-01-01

Children's low scores on vocabulary tests are often erroneously interpreted as reflecting poor cognitive and/or language skills. It may be necessary to incorporate the measurement of word-learning ability in estimating children's lexical abilities. To explore the reliability and validity of the Dynamic Assessment of Word Learning (DAWL), a new dynamic assessment of receptive vocabulary. A dynamic assessment (DA) of word learning ability was developed and adopted within a nursery school setting with 15 children aged between 3;07 and 4;03, ten of whom had been referred to speech and language therapy. A number of quantitative measures were derived from the DA procedure, including measures of children's ability to identify the targeted items and to generalize to a second exemplar, as well as measures of children's ability to retain the targeted items. Internal, inter-rater and test-retest reliability of the DAWL was established as well as correlational measures of concurrent and predictive validity. The DAWL was found to provide both quantitative and qualitative information which could be used to improve the accuracy of differential diagnosis and the understanding of processes underlying the child's performance. The latter can be used for the purpose of designing more individualized interventions. © 2013 Royal College of Speech and Language Therapists.

The Construct and Predictive Validity of a Dynamic Assessment of Young Children Learning to Read: Implications for RTI Frameworks

PubMed Central

Fuchs, Douglas; Compton, Donald L.; Fuchs, Lynn S.; Bouton, Bobette; Caffrey, Erin

2016-01-01

The purpose of this study was to examine the construct and predictive validity of a dynamic assessment (DA) of decoding learning. Students (N = 318) were assessed in the fall of first grade on an array of instruments that were given in hopes of forecasting responsiveness to reading instruction. These instruments included DA as well as one-point-in-time (static) measures of early alphabetic knowledge, rapid automatized naming (RAN), phonemic awareness, oral vocabulary, listening comprehension, attentive behavior, and hyperactive or impulsive behavior. An IQ test was administered in spring of second grade. Measures of reading outcomes administered in spring of first grade were accuracy and fluency of word identification skills and reading comprehension. Factor analysis using principal axis factor extraction indicated that DA loaded on a first factor that also included language abilities and IQ, which the authors refer to as the “language, IQ, and DA” factor. It was relatively distinct from two additional factors: (a) “speeded alphabetic knowledge and RAN” and (b) “task-oriented behavior.” A three-level (children nested within classroom; classrooms nested within school) random intercept model with fixed effects predictors suggested that DA differed from word attack in predicting future reading skill and that DA was a significant predictor of responsiveness to instruction, contributing unique variance to end-of-first-grade word identification and reading comprehension beyond that explained by other well-established predictors of reading development. PMID:21685347

Group Dynamic Assessment of L2 Learners' Writing Abilities

ERIC Educational Resources Information Center

Shabani, Karim

2018-01-01

The present study was designed to test a group-based format of dynamic assessment (G-DA) in the context of writing over a time span of twelve weeks of instruction. A cohort of 60 students took a homogeneity test and based on the results, 44 students were selected to participate forming the two groups of experimental (N = 22) and control (N = 22).…

Load evaluation of the da Vinci surgical system for transoral robotic surgery.

PubMed

Fujiwara, Kazunori; Fukuhara, Takahiro; Niimi, Koji; Sato, Takahiro; Kitano, Hiroya

2015-12-01

Transoral robotic surgery, performed with the da Vinci surgical system (da Vinci), is a surgical approach for benign and malignant lesions of the oral cavity and laryngopharynx. It provides several unique advantages, which include a 3-dimensional magnified view and ability to see and work around curves or angles. However, the current da Vinci surgical system does not provide haptic feedback. This is problematic because the potential risks specific to the transoral use of the da Vinci include tooth injury, mucosal laceration, ocular injury and mandibular fracture. To assess the potential for intraoperative injuries, we measured the load of the endoscope and the instrument of the da Vinci Si surgical system. We pressed the endoscope and instrument of the da Vinci Si against Load cell six times each and measured the dynamic load and the time-to-maximum load. We also struck the da Vinci Si endoscope and instrument against the Load cell six times each and measured the impact load. The maximum dynamic load was 7.27 ± 1.31 kg for the endoscope and 1.90 ± 0.72 for the instrument. The corresponding time-to-maximum loads were 1.72 ± 0.22 and 1.29 ± 0.34 s, but the impact loads were significantly lower than the dynamic load. It remains possible that a major load is exerted on adjacent structures by continuous contact with the endoscope and instrument of da Vinci Si. However, there is a minor delay in reaching the maximum load. Careful monitoring by an on-site assistant may, therefore, help prevent contiguous injury.

Examining the Predictive Validity of a Dynamic Assessment of Decoding to Forecast Response to Tier 2 Intervention

ERIC Educational Resources Information Center

Cho, Eunsoo; Compton, Donald L.; Fuchs, Douglas; Fuchs, Lynn S.; Bouton, Bobette

2014-01-01

The purpose of this study was to examine the role of a dynamic assessment (DA) of decoding in predicting responsiveness to Tier 2 small-group tutoring in a response-to-intervention model. First grade students (n = 134) who did not show adequate progress in Tier 1 based on 6 weeks of progress monitoring received Tier 2 small-group tutoring in…

Diagnosing dry eye with dynamic-area high-speed videokeratoscopy

NASA Astrophysics Data System (ADS)

Alonso-Caneiro, David; Turuwhenua, Jason; Iskander, D. Robert; Collins, Michael J.

2011-07-01

Dry eye syndrome is one of the most commonly reported eye health conditions. Dynamic-area high-speed videokeratoscopy (DA-HSV) represents a promising alternative to the most invasive clinical methods for the assessment of the tear film surface quality (TFSQ), particularly as Placido-disk videokeratoscopy is both relatively inexpensive and widely used for corneal topography assessment. Hence, improving this technique to diagnose dry eye is of clinical significance and the aim of this work. First, a novel ray-tracing model is proposed that simulates the formation of a Placido image. This model shows the relationship between tear film topography changes and the obtained Placido image and serves as a benchmark for the assessment of indicators of the ring's regularity. Further, a novel block-feature TFSQ indicator is proposed for detecting dry eye from a series of DA-HSV measurements. The results of the new indicator evaluated on data from a retrospective clinical study, which contains 22 normal and 12 dry eyes, have shown a substantial improvement of the proposed technique to discriminate dry eye from normal tear film subjects. The best discrimination was obtained under suppressed blinking conditions. In conclusion, this work highlights the potential of the DA-HSV as a clinical tool to diagnose dry eye syndrome.

Study protocol for promoting respectful maternity care initiative to assess, measure and design interventions to reduce disrespect and abuse during childbirth in Kenya

PubMed Central

2013-01-01

Background Increases in the proportion of facility-based deliveries have been marginal in many low-income countries in the African region. Preliminary clinical and anthropological evidence suggests that one major factor inhibiting pregnant women from delivering at facility is disrespectful and abusive treatment by health care providers in maternity units. Despite acknowledgement of this behavior by policy makers, program staff, civil society groups and community members, the problem appears to be widespread but prevalence is not well documented. Formative research will be undertaken to test the reliability and validity of a disrespect and abuse (D&A) construct and to then measure the prevalence of disrespect and abuse suffered by clinic clients and the general population. Methods/design A quasi-experimental design will be followed with surveys at twelve health facilities in four districts and one large maternity hospital in Nairobi and areas before and after the introduction of disrespect and abuse (D&A) interventions. The design is aimed to control for potential time dependent confounding on observed factors. Discussion This study seeks to conduct implementation research aimed at designing, testing, and evaluating an approach to significantly reduce disrespectful and abusive (D&A) care of women during labor and delivery in facilities. Specifically the proposed study aims to: (i) determine the manifestations, types and prevalence of D&A in childbirth (ii) develop and validate tools for assessing D&A (iii) identify and explore the potential drivers of D&A (iv) design, implement, monitor and evaluate the impact of one or more interventions to reduce D&A and (v) document and assess the dynamics of implementing interventions to reduce D&A and generate lessons for replication at scale. PMID:23347548

Influence of aortic valve leaflet calcification on dynamic aortic valve motion assessed by cardiac computed tomography.

PubMed

Minami, Keisuke; Yoneyama, Kihei; Izumo, Masaki; Suzuki, Kengo; Ogawa, Yasuyoshi; Chikaraishi, Kousuke; Ogawa, Yukihisa; Kobayashi, Yasuyuki; Furukawa, Toshiyuki; Tanabe, Yasuhiro; Akashi, Yoshihiro J

Computed tomography is the best noninvasive imaging modality for evaluating valve leaflet calcification. To evaluate the association of aortic valve leaflet calcification with instantaneous valve opening and closing using dynamic multidetector computed tomography (MDCT). We retrospectively evaluated 58 consecutive patients who underwent dynamic MDCT imaging. Aortic valve calcification (AVC) was quantified using the Agatston method. The aortic valve area (AVA) tracking curves were derived by planimetry during the cardiac cycle using all 20 phases (5% reconstruction). da/dt in cm 2 /s was calculated as the rate of change of AVA during opening (positive) or closing (negative). Patients were divided into 3 three groups according to Agatston score quartile: no AVC (Q2, Score 0, n = 18), mild AVC (Q3, Score 1-2254, n = 24), and severe AVC (Q4 Score >2254, n = 14). In multivariable linear regression, compared to the non AVC group, the mild and severe AVC groups had lower maximum AVA (by -1.71 cm 2 and -2.25 cm 2 , respectively), lower peak positive da/dt (by -21.88 cm 2 /s and -26.65 cm 2 /s, respectively), and higher peak negative da/dt (by 13.78 cm 2 /s and 18.11 cm 2 /s, respectively) (p < 0.05 for all comparisons). AVA and its opening and closing were influenced by leaflet calcification. The present study demonstrates the ability of dynamic MDCT imaging to assess quantitative aortic valve motion in a clinical setting. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Isogeometric Collocation for Elastostatics and Explicit Dynamics

DTIC Science & Technology

2012-01-25

ICES REPORT 12-07 January 2012 Isogeometric collocation for elastostatics and explicit dynamics by F. Auricchio, L. Beirao da Veiga , T.J.R. Hughes, A...Auricchio, L. Beirao da Veiga , T.J.R. Hughes, A. Reali, G. Sangalli, Isogeometric collocation for elastostatics and explicit dynamics, ICES REPORT 12-07...Isogeometric collocation for elastostatics and explicit dynamics F. Auricchio a,c, L. Beirão da Veiga b,c, T.J.R. Hughes d, A. Reali a,c,∗, G

Gait dynamics to optimize fall risk assessment in geriatric patients admitted to an outpatient diagnostic clinic

PubMed Central

de Groot, Maartje H.; van Campen, Jos P.; Beijnen, Jos H.; Hortobágyi, Tibor; Vuillerme, Nicolas; Lamoth, Claudine C. J.

2017-01-01

Fall prediction in geriatric patients remains challenging because the increased fall risk involves multiple, interrelated factors caused by natural aging and/or pathology. Therefore, we used a multi-factorial statistical approach to model categories of modifiable fall risk factors among geriatric patients to identify fallers with highest sensitivity and specificity with a focus on gait performance. Patients (n = 61, age = 79; 41% fallers) underwent extensive screening in three categories: (1) patient characteristics (e.g., handgrip strength, medication use, osteoporosis-related factors) (2) cognitive function (global cognition, memory, executive function), and (3) gait performance (speed-related and dynamic outcomes assessed by tri-axial trunk accelerometry). Falls were registered prospectively (mean follow-up 8.6 months) and one year retrospectively. Principal Component Analysis (PCA) on 11 gait variables was performed to determine underlying gait properties. Three fall-classification models were then built using Partial Least Squares–Discriminant Analysis (PLS-DA), with separate and combined analyses of the fall risk factors. PCA identified ‘pace’, ‘variability’, and ‘coordination’ as key properties of gait. The best PLS-DA model produced a fall classification accuracy of AUC = 0.93. The specificity of the model using patient characteristics was 60% but reached 80% when cognitive and gait outcomes were added. The inclusion of cognition and gait dynamics in fall classification models reduced misclassification. We therefore recommend assessing geriatric patients’ fall risk using a multi-factorial approach that incorporates patient characteristics, cognition, and gait dynamics. PMID:28575126

Gait dynamics to optimize fall risk assessment in geriatric patients admitted to an outpatient diagnostic clinic.

PubMed

Kikkert, Lisette H J; de Groot, Maartje H; van Campen, Jos P; Beijnen, Jos H; Hortobágyi, Tibor; Vuillerme, Nicolas; Lamoth, Claudine C J

2017-01-01

Fall prediction in geriatric patients remains challenging because the increased fall risk involves multiple, interrelated factors caused by natural aging and/or pathology. Therefore, we used a multi-factorial statistical approach to model categories of modifiable fall risk factors among geriatric patients to identify fallers with highest sensitivity and specificity with a focus on gait performance. Patients (n = 61, age = 79; 41% fallers) underwent extensive screening in three categories: (1) patient characteristics (e.g., handgrip strength, medication use, osteoporosis-related factors) (2) cognitive function (global cognition, memory, executive function), and (3) gait performance (speed-related and dynamic outcomes assessed by tri-axial trunk accelerometry). Falls were registered prospectively (mean follow-up 8.6 months) and one year retrospectively. Principal Component Analysis (PCA) on 11 gait variables was performed to determine underlying gait properties. Three fall-classification models were then built using Partial Least Squares-Discriminant Analysis (PLS-DA), with separate and combined analyses of the fall risk factors. PCA identified 'pace', 'variability', and 'coordination' as key properties of gait. The best PLS-DA model produced a fall classification accuracy of AUC = 0.93. The specificity of the model using patient characteristics was 60% but reached 80% when cognitive and gait outcomes were added. The inclusion of cognition and gait dynamics in fall classification models reduced misclassification. We therefore recommend assessing geriatric patients' fall risk using a multi-factorial approach that incorporates patient characteristics, cognition, and gait dynamics.

Differential Dopamine Release Dynamics in the Nucleus Accumbens Core and Shell Reveal Complementary Signals for Error Prediction and Incentive Motivation

PubMed Central

Cacciapaglia, Fabio; Wightman, R. Mark; Carelli, Regina M.

2015-01-01

Mesolimbic dopamine (DA) is phasically released during appetitive behaviors, though there is substantive disagreement about the specific purpose of these DA signals. For example, prediction error (PE) models suggest a role of learning, while incentive salience (IS) models argue that the DA signal imbues stimuli with value and thereby stimulates motivated behavior. However, within the nucleus accumbens (NAc) patterns of DA release can strikingly differ between subregions, and as such, it is possible that these patterns differentially contribute to aspects of PE and IS. To assess this, we measured DA release in subregions of the NAc during a behavioral task that spatiotemporally separated sequential goal-directed stimuli. Electrochemical methods were used to measure subsecond NAc dopamine release in the core and shell during a well learned instrumental chain schedule in which rats were trained to press one lever (seeking; SL) to gain access to a second lever (taking; TL) linked with food delivery, and again during extinction. In the core, phasic DA release was greatest following initial SL presentation, but minimal for the subsequent TL and reward events. In contrast, phasic shell DA showed robust release at all task events. Signaling decreased between the beginning and end of sessions in the shell, but not core. During extinction, peak DA release in the core showed a graded decrease for the SL and pauses in release during omitted expected rewards, whereas shell DA release decreased predominantly during the TL. These release dynamics suggest parallel DA signals capable of supporting distinct theories of appetitive behavior. SIGNIFICANCE STATEMENT Dopamine signaling in the brain is important for a variety of cognitive functions, such as learning and motivation. Typically, it is assumed that a single dopamine signal is sufficient to support these cognitive functions, though competing theories disagree on how dopamine contributes to reward-based behaviors. Here, we have found that real-time dopamine release within the nucleus accumbens (a primary target of midbrain dopamine neurons) strikingly varies between core and shell subregions. In the core, dopamine dynamics are consistent with learning-based theories (such as reward prediction error) whereas in the shell, dopamine is consistent with motivation-based theories (e.g., incentive salience). These findings demonstrate that dopamine plays multiple and complementary roles based on discrete circuits that help animals optimize rewarding behaviors. PMID:26290234

Rethinking Traffic Management: Design of Optimizable Networks

DTIC Science & Technology

2008-06-01

Though this paper used optimization theory to design and analyze DaVinci , op- timization theory is one of many possible tools to enable a grounded...dynamically allocate bandwidth shares. The distributed protocols can be implemented using DaVinci : Dynamically Adaptive VIrtual Networks for a Customized...Internet. In DaVinci , each virtual network runs traffic-management protocols optimized for a traffic class, and link bandwidth is dynamically allocated

Mediated Development: A Vygotskian Approach to Transforming Second Language Learner Abilities

ERIC Educational Resources Information Center

Poehner, Matthew E.; Infante, Paolo

2017-01-01

The authors point to systemic-theoretical instruction (STI), which underscores the importance of abstract conceptual knowledge in schooling, and dynamic assessment (DA), in which mediators and learners function cooperatively, as examples of the theory-practice relation envisioned by Vygotsky (1987). This article proposes an interactional framework…

Moving Triadic Gaze Intervention into Practice: Measuring Clinician Attitude and Implementation Fidelity

ERIC Educational Resources Information Center

Feuerstein, Julie; Olswang, Lesley B.; Greenslade, Kathryn; Pinder, Gay Lloyd; Dowden, Patricia; Madden, Jodi

2017-01-01

Purpose: This research investigated a first step in implementing the dynamic assessment (DA) component of Triadic Gaze Intervention (Olswang, Feuerstein, Pinder, & Dowden, 2013; Olswang et al., 2014), an evidence-based protocol for teaching early signals of communication to young children with physical disabilities. Clinician attitudes about…

Modulating dopamine release by optogenetics in transgenic mice reveals terminal dopaminergic dynamics

PubMed Central

Lu, Yao; Driscoll, Nicolette; Ozden, Ilker; Yu, Zeyang; Nurmikko, Arto V.

2015-01-01

Abstract. Dopamine (DA) release and uptake dynamics in the nucleus accumbens (NAc) have important implications for neurological diseases and mammalian animal behaviors. We demonstrate here the use of cell-type-specific optogenetic targeting in conjunction with fast-scan cyclic voltammetry applied to brain slices prepared from specifically tailored transgenic mice, which conditionally express channelrhodopsin-2 (ChR2) through dopamine transporter (DAT)-Cre. Terminal dopaminergic dynamics and the direct manipulation of induced DA release level by controlling light intensity, pulse width, and the shape of stimulation waveforms were studied. Effective cell terminal-targeting optogenetic induction of DA release at physiological levels in NAc is demonstrated and discussed. It was found that delivering more light energy by increasing stimulation intensity and length is not the only way to control DA release; the temporal shape of the stimulus waveform at light onset is also critically related to induced DA concentrations. In addition, DA uptake dynamics as well as the recovery of the presynaptic releasable DA pool are studied and modeled. More broadly, our experimental findings provide important further evidence for effectively applying optogenetics to induce neurotransmitter release in the behaviorally relevant region of the brain in a highly cell-type selective context. PMID:26171413

Multi-objective dynamic aperture optimization for storage rings

DOE PAGES

Li, Yongjun; Yang, Lingyun

2016-11-30

We report an efficient dynamic aperture (DA) optimization approach using multiobjective genetic algorithm (MOGA), which is driven by nonlinear driving terms computation. It was found that having small low order driving terms is a necessary but insufficient condition of having a decent DA. Then direct DA tracking simulation is implemented among the last generation candidates to select the best solutions. The approach was demonstrated successfully in optimizing NSLS-II storage ring DA.

Differential Dopamine Release Dynamics in the Nucleus Accumbens Core and Shell Reveal Complementary Signals for Error Prediction and Incentive Motivation.

PubMed

Saddoris, Michael P; Cacciapaglia, Fabio; Wightman, R Mark; Carelli, Regina M

2015-08-19

Mesolimbic dopamine (DA) is phasically released during appetitive behaviors, though there is substantive disagreement about the specific purpose of these DA signals. For example, prediction error (PE) models suggest a role of learning, while incentive salience (IS) models argue that the DA signal imbues stimuli with value and thereby stimulates motivated behavior. However, within the nucleus accumbens (NAc) patterns of DA release can strikingly differ between subregions, and as such, it is possible that these patterns differentially contribute to aspects of PE and IS. To assess this, we measured DA release in subregions of the NAc during a behavioral task that spatiotemporally separated sequential goal-directed stimuli. Electrochemical methods were used to measure subsecond NAc dopamine release in the core and shell during a well learned instrumental chain schedule in which rats were trained to press one lever (seeking; SL) to gain access to a second lever (taking; TL) linked with food delivery, and again during extinction. In the core, phasic DA release was greatest following initial SL presentation, but minimal for the subsequent TL and reward events. In contrast, phasic shell DA showed robust release at all task events. Signaling decreased between the beginning and end of sessions in the shell, but not core. During extinction, peak DA release in the core showed a graded decrease for the SL and pauses in release during omitted expected rewards, whereas shell DA release decreased predominantly during the TL. These release dynamics suggest parallel DA signals capable of supporting distinct theories of appetitive behavior. Dopamine signaling in the brain is important for a variety of cognitive functions, such as learning and motivation. Typically, it is assumed that a single dopamine signal is sufficient to support these cognitive functions, though competing theories disagree on how dopamine contributes to reward-based behaviors. Here, we have found that real-time dopamine release within the nucleus accumbens (a primary target of midbrain dopamine neurons) strikingly varies between core and shell subregions. In the core, dopamine dynamics are consistent with learning-based theories (such as reward prediction error) whereas in the shell, dopamine is consistent with motivation-based theories (e.g., incentive salience). These findings demonstrate that dopamine plays multiple and complementary roles based on discrete circuits that help animals optimize rewarding behaviors. Copyright © 2015 the authors 0270-6474/15/3511572-11$15.00/0.

Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Torres, Gonzalo E; Wagner, Amy K

2015-03-02

Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can assess real-time in vivo dopamine (DA) concentration changes to study the kinetics of DA neurotransmission. Electrical stimulation of dopaminergic (DAergic) pathways can elicit FSCV DA responses that largely reflect a balance of DA release and reuptake. Interpretation of these evoked DA responses requires a framework to discern the contribution of DA release and reuptake. The current, widely implemented interpretive framework for doing so is the Michaelis-Menten (M-M) model, which is grounded on two assumptions- (1) DA release rate is constant during stimulation, and (2) DA reuptake occurs through dopamine transporters (DAT) in a manner consistent with M-M enzyme kinetics. Though the M-M model can simulate evoked DA responses that rise convexly, response types that predominate in the ventral striatum, the M-M model cannot simulate dorsal striatal responses that rise concavely. Based on current neurotransmission principles and experimental FSCV data, we developed a novel, quantitative, neurobiological framework to interpret DA responses that assumes DA release decreases exponentially during stimulation and continues post-stimulation at a diminishing rate. Our model also incorporates dynamic M-M kinetics to describe DA reuptake as a process of decreasing reuptake efficiency. We demonstrate that this quantitative, neurobiological model is an extension of the traditional M-M model that can simulate heterogeneous regional DA responses following manipulation of stimulation duration, frequency, and DA pharmacology. The proposed model can advance our interpretive framework for future in vivo FSCV studies examining regional DA kinetics and their alteration by disease and DA pharmacology. Copyright © 2015 Elsevier B.V. All rights reserved.

Can color-coded parametric maps improve dynamic enhancement pattern analysis in MR mammography?

PubMed

Baltzer, P A; Dietzel, M; Vag, T; Beger, S; Freiberg, C; Herzog, A B; Gajda, M; Camara, O; Kaiser, W A

2010-03-01

Post-contrast enhancement characteristics (PEC) are a major criterion for differential diagnosis in MR mammography (MRM). Manual placement of regions of interest (ROIs) to obtain time/signal intensity curves (TSIC) is the standard approach to assess dynamic enhancement data. Computers can automatically calculate the TSIC in every lesion voxel and combine this data to form one color-coded parametric map (CCPM). Thus, the TSIC of the whole lesion can be assessed. This investigation was conducted to compare the diagnostic accuracy (DA) of CCPM with TSIC for the assessment of PEC. 329 consecutive patients with 469 histologically verified lesions were examined. MRM was performed according to a standard protocol (1.5 T, 0.1 mmol/kgbw Gd-DTPA). ROIs were drawn manually within any lesion to calculate the TSIC. CCPMs were created in all patients using dedicated software (CAD Sciences). Both methods were rated by 2 observers in consensus on an ordinal scale. Receiver operating characteristics (ROC) analysis was used to compare both methods. The area under the curve (AUC) was significantly (p=0.026) higher for CCPM (0.829) than TSIC (0.749). The sensitivity was 88.5% (CCPM) vs. 82.8% (TSIC), whereas equal specificity levels were found (CCPM: 63.7%, TSIC: 63.0%). The color-coded parametric maps (CCPMs) showed a significantly higher DA compared to TSIC, in particular the sensitivity could be increased. Therefore, the CCPM method is a feasible approach to assessing dynamic data in MRM and condenses several imaging series into one parametric map. © Georg Thieme Verlag KG Stuttgart · New York.

Modeling Fast-scan Cyclic Voltammetry Data from Electrically Stimulated Dopamine Neurotransmission Data Using QNsim1.0.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Wagner, Amy K

2017-06-05

Central dopaminergic (DAergic) pathways have an important role in a wide range of functions, such as attention, motivation, and movement. Dopamine (DA) is implicated in diseases and disorders including attention deficit hyperactivity disorder, Parkinson's disease, and traumatic brain injury. Thus, DA neurotransmission and the methods to study it are of intense scientific interest. In vivo fast-scan cyclic voltammetry (FSCV) is a method that allows for selectively monitoring DA concentration changes with fine temporal and spatial resolution. This technique is commonly used in conjunction with electrical stimulations of ascending DAergic pathways to control the impulse flow of dopamine neurotransmission. Although the stimulated DA neurotransmission paradigm can produce robust DA responses with clear morphologies, making them amenable for kinetic analysis, there is still much debate on how to interpret the responses in terms of their DA release and clearance components. To address this concern, a quantitative neurobiological (QN) framework of stimulated DA neurotransmission was recently developed to realistically model the dynamics of DA release and reuptake over the course of a stimulated DA response. The foundations of this model are based on experimental data from stimulated DA neurotransmission and on principles of neurotransmission adopted from various lines of research. The QN model implements 12 parameters related to stimulated DA release and reuptake dynamics to model DA responses. This work describes how to simulate DA responses using QNsim1.0 and also details principles that have been implemented to systematically discern alterations in the stimulated dopamine release and reuptake dynamics.

Deterministic Role of Collision Cascade Density in Radiation Defect Dynamics in Si

NASA Astrophysics Data System (ADS)

Wallace, J. B.; Aji, L. B. Bayu; Shao, L.; Kucheyev, S. O.

2018-05-01

The formation of stable radiation damage in solids often proceeds via complex dynamic annealing (DA) processes, involving point defect migration and interaction. The dependence of DA on irradiation conditions remains poorly understood even for Si. Here, we use a pulsed ion beam method to study defect interaction dynamics in Si bombarded in the temperature range from ˜-30 ° C to 210 °C with ions in a wide range of masses, from Ne to Xe, creating collision cascades with different densities. We demonstrate that the complexity of the influence of irradiation conditions on defect dynamics can be reduced to a deterministic effect of a single parameter, the average cascade density, calculated by taking into account the fractal nature of collision cascades. For each ion species, the DA rate exhibits two well-defined Arrhenius regions where different DA mechanisms dominate. These two regions intersect at a critical temperature, which depends linearly on the cascade density. The low-temperature DA regime is characterized by an activation energy of ˜0.1 eV , independent of the cascade density. The high-temperature regime, however, exhibits a change in the dominant DA process for cascade densities above ˜0.04 at.%, evidenced by an increase in the activation energy. These results clearly demonstrate a crucial role of the collision cascade density and can be used to predict radiation defect dynamics in Si.

Deterministic Role of Collision Cascade Density in Radiation Defect Dynamics in Si.

PubMed

Wallace, J B; Aji, L B Bayu; Shao, L; Kucheyev, S O

2018-05-25

The formation of stable radiation damage in solids often proceeds via complex dynamic annealing (DA) processes, involving point defect migration and interaction. The dependence of DA on irradiation conditions remains poorly understood even for Si. Here, we use a pulsed ion beam method to study defect interaction dynamics in Si bombarded in the temperature range from ∼-30 °C to 210 °C with ions in a wide range of masses, from Ne to Xe, creating collision cascades with different densities. We demonstrate that the complexity of the influence of irradiation conditions on defect dynamics can be reduced to a deterministic effect of a single parameter, the average cascade density, calculated by taking into account the fractal nature of collision cascades. For each ion species, the DA rate exhibits two well-defined Arrhenius regions where different DA mechanisms dominate. These two regions intersect at a critical temperature, which depends linearly on the cascade density. The low-temperature DA regime is characterized by an activation energy of ∼0.1  eV, independent of the cascade density. The high-temperature regime, however, exhibits a change in the dominant DA process for cascade densities above ∼0.04 at.%, evidenced by an increase in the activation energy. These results clearly demonstrate a crucial role of the collision cascade density and can be used to predict radiation defect dynamics in Si.

Combining Graphical and Analytical Methods with Molecular Simulations To Analyze Time-Resolved FRET Measurements of Labeled Macromolecules Accurately

PubMed Central

2017-01-01

Förster resonance energy transfer (FRET) measurements from a donor, D, to an acceptor, A, fluorophore are frequently used in vitro and in live cells to reveal information on the structure and dynamics of DA labeled macromolecules. Accurate descriptions of FRET measurements by molecular models are complicated because the fluorophores are usually coupled to the macromolecule via flexible long linkers allowing for diffusional exchange between multiple states with different fluorescence properties caused by distinct environmental quenching, dye mobilities, and variable DA distances. It is often assumed for the analysis of fluorescence intensity decays that DA distances and D quenching are uncorrelated (homogeneous quenching by FRET) and that the exchange between distinct fluorophore states is slow (quasistatic). This allows us to introduce the FRET-induced donor decay, εD(t), a function solely depending on the species fraction distribution of the rate constants of energy transfer by FRET, for a convenient joint analysis of fluorescence decays of FRET and reference samples by integrated graphical and analytical procedures. Additionally, we developed a simulation toolkit to model dye diffusion, fluorescence quenching by the protein surface, and FRET. A benchmark study with simulated fluorescence decays of 500 protein structures demonstrates that the quasistatic homogeneous model works very well and recovers for single conformations the average DA distances with an accuracy of < 2%. For more complex cases, where proteins adopt multiple conformations with significantly different dye environments (heterogeneous case), we introduce a general analysis framework and evaluate its power in resolving heterogeneities in DA distances. The developed fast simulation methods, relying on Brownian dynamics of a coarse-grained dye in its sterically accessible volume, allow us to incorporate structural information in the decay analysis for heterogeneous cases by relating dye states with protein conformations to pave the way for fluorescence and FRET-based dynamic structural biology. Finally, we present theories and simulations to assess the accuracy and precision of steady-state and time-resolved FRET measurements in resolving DA distances on the single-molecule and ensemble level and provide a rigorous framework for estimating approximation, systematic, and statistical errors. PMID:28709377

Characteristics of dynamic magnetic resonance image enhancement in prolactinomas resistant to dopamine agonist therapy.

PubMed

Guo, Qinghua; Erickson, Bradley J; Chang, Alice Y; Erickson, Dana

2015-03-01

The objective of this study was to determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, MN). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naive groups, and between the first and follow-up dMRIs. We identified 49 patients with prolactinomas, with 6 (12.2%) showing DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group versus the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P = 0.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P = 0.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% confidence interval, 1.07-3.27; P = 0.02). Dynamic MRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas.

Single-cell full-length total RNA sequencing uncovers dynamics of recursive splicing and enhancer RNAs.

PubMed

Hayashi, Tetsutaro; Ozaki, Haruka; Sasagawa, Yohei; Umeda, Mana; Danno, Hiroki; Nikaido, Itoshi

2018-02-12

Total RNA sequencing has been used to reveal poly(A) and non-poly(A) RNA expression, RNA processing and enhancer activity. To date, no method for full-length total RNA sequencing of single cells has been developed despite the potential of this technology for single-cell biology. Here we describe random displacement amplification sequencing (RamDA-seq), the first full-length total RNA-sequencing method for single cells. Compared with other methods, RamDA-seq shows high sensitivity to non-poly(A) RNA and near-complete full-length transcript coverage. Using RamDA-seq with differentiation time course samples of mouse embryonic stem cells, we reveal hundreds of dynamically regulated non-poly(A) transcripts, including histone transcripts and long noncoding RNA Neat1. Moreover, RamDA-seq profiles recursive splicing in >300-kb introns. RamDA-seq also detects enhancer RNAs and their cell type-specific activity in single cells. Taken together, we demonstrate that RamDA-seq could help investigate the dynamics of gene expression, RNA-processing events and transcriptional regulation in single cells.

Vietnamese children and language-based processing tasks.

PubMed

Hwa-Froelich, Deborah A; Matsuo, Hisako

2005-07-01

Vietnamese children's performance on language-based processing tasks of fast-mapping (FM) word-learning and dynamic assessment (DA) word- and rule-learning tasks were investigated. Twenty-one first- and second-generation Vietnamese preschool children participated in this study. All children were enrolled in 2 Head Start programs in a large city in the Midwest. All children had passed a developmental assessment and routine speech, language, and hearing screenings. All participants were taught 4 invented monosyllabic words in an FM word task, an invented monosyllabic suffix rule (-po) meaning "a part of" in a DA rule task, and 4 invented bisyllabic words in a DA word task. Potential relationships among task performances were investigated. Receptive task performances, expressive task performances, and task totals were added to create receptive total, expressive total, and accumulated performance total (APT) scores. Relationships among receptive total, expressive total, and APT scores were also investigated. Significant correlations were found between FM word, DA rule, and the receptive total. The expressive total correlated with all task total scores, APT, age, and modifiability scores. Modifiability scores correlated with the two DA tasks, expressive total, and the APT. Findings indicate that FM word and the expressive total were positively correlated with most of the other tasks, composite totals, and age. Performance on language-based processing tasks may provide valuable information for separating typically developing Vietnamese preschool children from their peers with language disorders. Practitioners should consider linguistic characteristics of target stimuli. Comparisons should include task, receptive, expressive, and APT.

Dynamics of Structural Phase Transformations Using Molecular Dynamics

DTIC Science & Technology

2013-12-08

Investigator AFOSR Young Investigator ASCE Leonardo Da Vinci Young Investigator Award Eshelby Mechanics Award for Young Faculty 01/06/2011...Investigator Awards • Junior chair from Carnegie Mellon University, 2013-2016 • ASCE Engineering Mechanics Leonardo Da Vinci Early Career Award, 2013

Effects of robotic manipulators on movements of novices and surgeons.

PubMed

Nisky, Ilana; Okamura, Allison M; Hsieh, Michael H

2014-07-01

Robot-assisted surgery is widely adopted for many procedures but has not realized its full potential to date. Based on human motor control theories, the authors hypothesized that the dynamics of the master manipulators impose challenges on the motor system of the user and may impair performance and slow down learning. Although studies have shown that robotic outcomes are correlated with the case experience of the surgeon, the relative contribution of cognitive versus motor skill is unknown. This study quantified the effects of da Vinci Si master manipulator dynamics on movements of novice users and experienced surgeons and suggests possible implications for training and robot design. In the reported study, six experienced robotic surgeons and ten novice nonmedical users performed movements under two conditions: teleoperation of a da Vinci Si Surgical system and freehand. A linear mixed model was applied to nine kinematic metrics (including endpoint error, movement time, peak speed, initial jerk, and deviation from a straight line) to assess the effects of teleoperation and expertise. To assess learning effects, t tests between the first and last movements of each type were used. All the users moved slower during teleoperation than during freehand movements (F(1,9343) = 345; p < 0.001). The experienced surgeons had smaller errors than the novices (F(1,14) = 36.8; p < 0.001). The straightness of movements depended on their direction (F(7,9343) = 117; p < 0.001). Learning effects were observed in all conditions. Novice users first learned the task and then the dynamics of the manipulator. The findings showed differences between the novices and the experienced surgeons for extremely simple point-to-point movements. The study demonstrated that manipulator dynamics affect user movements, suggesting that these dynamics could be improved in future robot designs. The authors showed the partial adaptation of novice users to the dynamics. Future studies are needed to evaluate whether it will be beneficial to include early training sessions dedicated to learning the dynamics of the manipulator.

Improving Ecological Forecasting: Data Assimilation Enhances the Ecological Forecast Horizon of a Complex Food Web

NASA Astrophysics Data System (ADS)

Massoud, E. C.; Huisman, J.; Benincà, E.; Bouten, W.; Vrugt, J. A.

2017-12-01

Species abundances in ecological communities can display chaotic non-equilibrium dynamics. A characteristic feature of chaotic systems is that long-term prediction of the system's trajectory is fundamentally impossible. How then should we make predictions for complex multi-species communities? We explore data assimilation (DA) with the Ensemble Kalman Filter (EnKF) to fuse a two-predator-two-prey model with abundance data from a long term experiment of a plankton community which displays chaotic dynamics. The results show that DA improves substantially the predictability and ecological forecast horizon of complex community dynamics. In addition, we show that DA helps provide guidance on measurement design, for instance on defining the frequency of observations. The study presented here is highly innovative, because DA methods at the current stage are almost unknown in ecology.

Differential permeability of the blood-testis barrier during reinitiation of spermatogenesis in adult male rats.

PubMed

Haverfield, Jenna T; Meachem, Sarah J; Nicholls, Peter K; Rainczuk, Katarzyna E; Simpson, Evan R; Stanton, Peter G

2014-03-01

The blood-testis barrier (BTB) sequesters meiotic spermatocytes and differentiating spermatids away from the vascular environment. We aimed to assess whether meiosis and postmeiotic differentiation could occur when the BTB is permeable. Using a model of meiotic suppression and reinitiation, BTB function was assessed using permeability tracers of small, medium, and large (0.6-, 70-, and 150-kDa) sizes to emulate blood- and lymphatic-borne factors that could cross the BTB. Adult rats (n = 9/group) received the GnRH antagonist acyline (10 wk) to suppress gonadotropins, followed by testosterone (24cm Silastic implant), for 2, 4, 7, 10, 15, and 35 days. In acyline-suppressed testes, all tracers permeated the seminiferous epithelium. As spermatocytes up to diplotene stage XIII reappeared, both the 0.6- and 70-kDa tracers, but not 150 kDa, permeated around these cells. Intriguingly, the 0.6- and 70-kDa tracers were excluded from pachytene spermatocytes at stages VII and VIII but not in subsequent stages. The BTB became progressively impermeable to the 0.6- and 70-kDa tracers as stages IV-VII round spermatids reappeared in the epithelium. This coincided with the appearance of the tight junction protein, claudin-12, in Sertoli cells and at the BTB. We conclude that meiosis can occur when the BTB is permeable to factors up to 70 kDa during the reinitiation of spermatogenesis. Moreover, BTB closure corresponds with the presence of particular pachytene spermatocytes and round spermatids. This research has implications for understanding the effects of BTB dynamics in normal spermatogenesis and also potentially in states where spermatogenesis is suppressed, such as male hormonal contraception or infertility.

Application of fast-scan cyclic voltammetry for the in vivo characterization of optically evoked dopamine in the olfactory tubercle of the rat brain.

PubMed

Wakabayashi, Ken T; Bruno, Michael J; Bass, Caroline E; Park, Jinwoo

2016-06-21

The olfactory tubercle (OT), as a component of the ventral striatum, serves as an important multisensory integration center for reward-related processes in the brain. Recent studies show that dense dopaminergic innervation from the ventral tegmental area (VTA) into the OT may play an outsized role in disorders such as psychostimulant addiction and disorders of motivation, increasing recent scientific interest in this brain region. However, due to its anatomical inaccessibility, relative small size, and proximity to other dopamine-rich structures, neurochemical assessments using conventional methods cannot be readily employed. Here, we investigated dopamine (DA) regulation in the OT of urethane-anesthetized rats using in vivo fast-scan voltammetry (FSCV) coupled with carbon-fiber microelectrodes, following optogenetic stimulation of the VTA. The results were compared with DA regulation in the nucleus accumbens (NAc), a structure located adjacent to the OT and which also receives dense DA innervation from the VTA. FSCV coupled with optically evoked release allowed us to investigate the spatial distribution of DA in the OT and characterize OT DA dynamics (release and clearance) with subsecond temporal and micrometer spatial resolution for the first time. In this study, we demonstrated that DA transporters play an important role in regulating DA in the OT. However, the control of extracellular DA by uptake in the OT was less than in the NAc. The difference in DA transmission in the terminal fields of the OT and NAc may be involved in region-specific responses to drugs of abuse and contrasting roles in mediating reward-related behavior.

PD2P: PanDA Dynamic Data Placement for ATLAS

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

Maeno, T.; De, K.; Panitkin, S.

2012-12-13

The PanDA (Production and Distributed Analysis) system plays a key role in the ATLAS distributed computing infrastructure. PanDA is the ATLAS workload management system for processing all Monte-Carlo (MC) simulation and data reprocessing jobs in addition to user and group analysis jobs. The PanDA Dynamic Data Placement (PD2P) system has been developed to cope with difficulties of data placement for ATLAS. We will describe the design of the new system, its performance during the past year of data taking, dramatic improvements it has brought about in the efficient use of storage and processing resources, and plans for the future.

Loss of mitochondrial fission depletes axonal mitochondria in midbrain dopamine neurons.

PubMed

Berthet, Amandine; Margolis, Elyssa B; Zhang, Jue; Hsieh, Ivy; Zhang, Jiasheng; Hnasko, Thomas S; Ahmad, Jawad; Edwards, Robert H; Sesaki, Hiromi; Huang, Eric J; Nakamura, Ken

2014-10-22

Disruptions in mitochondrial dynamics may contribute to the selective degeneration of dopamine (DA) neurons in Parkinson's disease (PD). However, little is known about the normal functions of mitochondrial dynamics in these neurons, especially in axons where degeneration begins, and this makes it difficult to understand the disease process. To study one aspect of mitochondrial dynamics-mitochondrial fission-in mouse DA neurons, we deleted the central fission protein dynamin-related protein 1 (Drp1). Drp1 loss rapidly eliminates the DA terminals in the caudate-putamen and causes cell bodies in the midbrain to degenerate and lose α-synuclein. Without Drp1, mitochondrial mass dramatically decreases, especially in axons, where the mitochondrial movement becomes uncoordinated. However, in the ventral tegmental area (VTA), a subset of midbrain DA neurons characterized by small hyperpolarization-activated cation currents (Ih) is spared, despite near complete loss of their axonal mitochondria. Drp1 is thus critical for targeting mitochondria to the nerve terminal, and a disruption in mitochondrial fission can contribute to the preferential death of nigrostriatal DA neurons. Copyright © 2014 the authors 0270-6474/14/3414304-14$15.00/0.

Quantitation of Hydrogen Peroxide Fluctuations and Their Modulation of Dopamine Dynamics in the Rat Dorsal Striatum Using Fast-Scan Cyclic Voltammetry

PubMed Central

2013-01-01

The dopaminergic neurons of the nigrostriatal dopamine (DA) projection from the substantia nigra to the dorsal striatum become dysfunctional and slowly degenerate in Parkinson’s disease, a neurodegenerative disorder that afflicts more than one million Americans. There is no specific known cause for idiopathic Parkinson’s disease; however, multiple lines of evidence implicate oxidative stress as an underlying factor in both the initiation and progression of the disease. This involves the enhanced generation of reactive oxygen species, including hydrogen peroxide (H2O2), whose role in complex biological processes is not well understood. Using fast-scan cyclic voltammetry at bare carbon-fiber microelectrodes, we have simultaneously monitored and quantified H2O2 and DA fluctuations in intact striatal tissue under basal conditions and in response to the initiation of oxidative stress. Furthermore, we have assessed the effect of acute increases in local H2O2 concentration on both electrically evoked DA release and basal DA levels. Increases in endogenous H2O2 in the dorsal striatum attenuated electrically evoked DA release, and also decreased basal DA levels in this brain region. These novel results will help to disambiguate the chemical mechanisms underlying the progression of neurodegenerative disease states, such as Parkinson’s disease, that involve oxidative stress. PMID:23556461

The Impact of a Three-Year Teacher Professional Development Course on Quality of Teaching: Strengths and Limitations of the Dynamic Approach

ERIC Educational Resources Information Center

Kyriakides, L.; Christoforidou, M.; Panayiotou, A.; Creemers, B. P. M.

2017-01-01

The dynamic approach (DA) suggests that professional development should be differentiated to meet teachers' individual needs while engaging participants into systematic and guided critical reflection. Previous experimental studies demonstrated that one-year interventions based on the DA have a positive impact on teacher effectiveness. The study…

"Click chemistry" in tailor-made polymethacrylates bearing reactive furfuryl functionality: a new class of self-healing polymeric material.

PubMed

Kavitha, A Amalin; Singha, Nikhil K

2009-07-01

This investigation reports the effective use of the Diels-Alder (DA) reaction, a "click reaction" in the preparation of thermally amendable and self-healing polymeric materials having reactive furfuryl functionality. In this case, the DA and retro-DA (rDA) reactions were carried out between the tailor-made homo- and copolymer of furfuryl methacrylate prepared by atom-transfer radical polymerization and a bismaleimide (BM). The kinetic studies of DA and rDA reactions were carried out using Fourier transform infrared spectroscopy. The DA polymers were insoluble in toluene at room temperature. When the DA polymers were heated at 100 degrees C in toluene, it was soluble. This is because of the cleavage between furfuryl functionality and BM. The chemical cross-link density was determined by the Flory-Rehner equation. The cross-linked polymer showed much greater adhesive strength at room temperature, but the adhesive strength was quite low at higher temperature. The self-healing capability was studied by using scanning electron microscopy analysis. The thermal and dynamic mechanical properties of the thermally amendable cross-linked materials were investigated by thermogravimetric analysis and dynamic mechanical analysis.

Alterations in the Striatal Dopamine System During Intravenous Methamphetamine Exposure: Effects of Contingent and Noncontingent Administration

PubMed Central

Laćan, Goran; Hadamitzky, Martin; Kuczenski, Ronald; Melega, William P.

2014-01-01

The continuing spread of methamphetamine (METH) abuse has stimulated research aimed at understanding consequences of its prolonged exposure. Alterations in nigrostriatal dopamine (DA) system parameters have been characterized in experimental studies after discontinuation of long term METH but fewer studies have included similar assessments during METH exposure. Here, we report METH plasma pharmacokinetics and striatal DA system alterations in rat after noncontingent and contingent METH administration for 7.5 weeks. Escalating METH exposure was delivered by dynamic infusion (DI) that incorporated a ‘humanized’ plasma METH half life, or by intravenous self-administration (IVSA) that included binge intakes. Kinetic modeling of DI and IVSA for 24 h periods during the final week of METH exposure showed that plasma METH levels remained between 0.7–1.5 μM. Animals were sacrificed during their last METH administration for autoradiography assessment using [3H]ligands and D2 agonist-induced [35S]GTPγS binding. DA transporter binding was decreased (DI, 34%; IVSA, 15%) while vesicular monoamine transporter binding and substantia nigra DA cell numbers were unchanged. Decreases were measured for D2 receptor (DI and IVSA, 15–20%) and [35S]GTPγS binding (DI, 35%; IVSA, 18%). These similar patterns of DI and IVSA associated decreases in striatal DA markers reflect consequences of cumulative METH exposure and not the drug delivery method. For METH IVSA, individual differences were observed, yet each animal’s total intake was similar within and across three 24 h binges. IVSA rodent models may be useful for identifying molecular mechanisms that are associated with METH binges in humans. PMID:23417852

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

Li, Yongjun; Yang, Lingyun

We report an efficient dynamic aperture (DA) optimization approach using multiobjective genetic algorithm (MOGA), which is driven by nonlinear driving terms computation. It was found that having small low order driving terms is a necessary but insufficient condition of having a decent DA. Then direct DA tracking simulation is implemented among the last generation candidates to select the best solutions. The approach was demonstrated successfully in optimizing NSLS-II storage ring DA.

A top-down perspective on dopamine, motivation and memory.

PubMed

Phillips, Anthony G; Vacca, Giada; Ahn, Soyon

2008-08-01

Dopamine (DA) activity, in the form of increased neural firing or enhanced release of transmitter from nerve terminals and varicosities, is linked to a number of important psychological processes including: movement; hedonic reactions to positive reward; provision of an error detection signal during the acquisition of new learning; response to novel stimuli; provision of reinforcement signals essential for acquisition of new action patterns; and incentive motivation. This review focuses primarily on our research linking dynamic changes in DA efflux on the timescale of minutes, with incentive motivation, as revealed by brain dialysis experiments in behaving animals. Recent experiments on sensory-specific satiety and successive positive and negative contrast are discussed along with the distinction between preparatory behaviors that precede contact with biologically significant stimuli and subsequent consummatory behaviors. The relationship between DA efflux in the medial prefrontal cortex (mPFC) and foraging for food based on working memory is also discussed in support of the conjecture that DA may serve as a link between motivation and memory functions. Evidence in support of 'top-down' regulation of dopaminergic activity in the mesocorticolimbic DA pathways is reviewed briefly to introduce a mechanism by which activation of ascending DA projections in this manner might optimize dopaminergic modulation of executive function within regions such as the mPFC. Collectively, these processes could ensure coordination between cognitive processes that assess current opportunities and the motivational systems that select and engage patterns of approach behavior that bring organisms into contact with the essentials for survival.

Long timestep dynamics of peptides by the dynamics driver approach.

PubMed

Derreumaux, P; Schlick, T

1995-04-01

Previous experience with the Langevin/implicit-Euler scheme for dynamics ("LI") on model systems (butane, water) has shown that LI is numerically stable for timesteps in the 5-20 fs range but quenches high-frequency modes. To explore applications to polypeptides, we apply LI to model systems (several dipeptides, a tetrapeptide, and a 13-residue oligoalanine) and also develop a new dynamics driver approach ("DA"). The DA scheme, based on LI, addresses the important issue of proper sampling, which is unlikely to be solved by small-timestep integration methods or implicit methods with intrinsic damping at room temperature, such as LI. Equilibrium averages, time-dependent molecular properties, and sampling trends at room temperature are reported for both LI and DA dynamics simulations, which are then compared to those generated by a standard explicit discretization of the Langevin equation with a 1 fs timestep. We find that LI's quenching effects are severe on both the fast and slow (due to vibrational coupling) frequency modes of all-atom polypeptides and lead to more restricted dynamics at moderate timesteps (40 fs). The DA approach empirically counteracts these damping effects by adding random atomic perturbations to the coordinates at each step (before the minimization of a dynamics function). By restricting the energetic fluctuations and controlling the kinetic energy, we are able with a 60 fs timestep to generate continuous trajectories that sample more of the relevant conformational space and also reproduce reasonably Boltzmann statistics. Although the timescale for transition may be accelerated by the DA approach, the transitional information obtained for the alanine dipeptide and the tetrapeptide is consistent with that obtained by several other theoretical approaches that focus specifically on the determination of pathways. While the trajectory for oligoalanine by the explicit scheme over the nanosecond timeframe remains in the vicinity of the full alpha R-helix starting structure, and a high-temperature (600 degrees K) MD trajectory departs slowly from the alpha helical structure, the DA-generated trajectory for the same CPU time exhibits unfolding and refolding and reveals a range of conformations with an intermediate helix content. Significantly, this range of states is more consistent with spectroscopic experiments on small peptides, as well as the cooperative two-state model for helix-coil transition. The good, near-Boltzmann statistics reported for the smaller systems above, in combination with the interesting oligoalanine results, suggest that DA is a promising tool for efficiently exploring conformational spaces of biomolecules and exploring folding/unfolding processes of polypeptides.

Retinal Vascular and Oxygen Temporal Dynamic Responses to Light Flicker in Humans

PubMed Central

Felder, Anthony E.; Wanek, Justin; Blair, Norman P.

2017-01-01

Purpose To mathematically model the temporal dynamic responses of retinal vessel diameter (D), oxygen saturation (SO2), and inner retinal oxygen extraction fraction (OEF) to light flicker and to describe their responses to its cessation in humans. Methods In 16 healthy subjects (age: 60 ± 12 years), retinal oximetry was performed before, during, and after light flicker stimulation. At each time point, five metrics were measured: retinal arterial and venous D (DA, DV) and SO2 (SO2A, SO2V), and OEF. Intra- and intersubject variability of metrics was assessed by coefficient of variation of measurements before flicker within and among subjects, respectively. Metrics during flicker were modeled by exponential functions to determine the flicker-induced steady state metric values and the time constants of changes. Metrics after the cessation of flicker were compared to those before flicker. Results Intra- and intersubject variability for all metrics were less than 6% and 16%, respectively. At the flicker-induced steady state, DA and DV increased by 5%, SO2V increased by 7%, and OEF decreased by 13%. The time constants of DA and DV (14, 15 seconds) were twofold smaller than those of SO2V and OEF (39, 34 seconds). Within 26 seconds after the cessation of flicker, all metrics were not significantly different from before flicker values (P ≥ 0.07). Conclusions Mathematical modeling revealed considerable differences in the time courses of changes among metrics during flicker, indicating flicker duration should be considered separately for each metric. Future application of this method may be useful to elucidate alterations in temporal dynamic responses to light flicker due to retinal diseases. PMID:29098297

Solvent as electron donor: Donor/acceptor electronic coupling is a dynamical variable

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

Castner, E.W. Jr.; Kennedy, D.; Cave, R.J.

2000-04-06

The authors combine analysis of measurements by femtosecond optical spectroscopy, computer simulations, and the generalized Mulliken-Hush (GMH) theory in the study of electron-transfer reactions and electron donor-acceptor interactions. The study focus is on ultrafast photoinduced electron-transfer reactions from aromatic amine solvent donors to excited-state acceptors. The experimental results from femtosecond dynamical measurements fall into three categories: six coumarin acceptors reductively quenched by N,N-dimethylaniline (DMA), eight electron-donating amine solvents reductively quenching coumarin 152 (7-(dimethylamino)-4-(trifluoromethyl)-coumarin), and reductive quenching dynamics of two coumarins by DMA as a function of dilution in the nonreactive solvents toluene and chlorobenzene. Applying a combination of molecular dynamicsmore » trajectories, semiempirical quantum mechanical calculations (of the relevant adiabatic electronic states), and GMH theory to the C152/DMA photoreaction, the authors calculate the electron donor/acceptor interaction parameter H{sub DA} at various time frames, H{sub DA} is strongly modulated by both inner-sphere and outer-sphere nuclear dynamics, leading us to conclude that H{sub DA} must be considered as a dynamical variable.« less

Effects of brain-derived neurotrophic factor on dopaminergic function and motor behavior during aging

PubMed Central

Boger, Heather A.; Mannangatti, Padmanabhan; Samuvel, Devadoss J.; Saylor, Alicia J.; Bender, Tara S.; McGinty, Jacqueline F.; Fortress, Ashley M.; Zaman, Vandana; Huang, Peng; Middaugh, Lawrence D.; Randall, Patrick K.; Jayanthi, Lankupalle D.; Rohrer, Baerbel; Helke, Kristi L.; Granholm, Ann-Charlotte; Ramamoorthy, Sammanda

2010-01-01

Brain-derived neurotrophic factor (BDNF) is critical in synaptic plasticity and in the survival and function of midbrain dopamine neurons. In the present study, we assessed the effects of a partial genetic deletion of BDNF on motor function and dopamine (DA) neurotransmitter measures by comparing (Bdnf+/−) with wildtype mice (WT) at different ages. Bdnf+/ and WT mice had similar body weights until 12 months of age; however, at 21 months, Bdnf+/− mice were significantly heavier than WT mice. Horizontal and vertical motor activity was reduced for Bdnf+/− compared to WT mice; but was not influenced by Age. Performance on an accelerating rotarod declined with age for both genotypes and was exacerbated for Bdnf+/− mice. Body weight did not correlate with any of the three behavioral measures studied. DA neurotransmitter markers indicated no genotypic difference in striatal tyrosine hydroxylase (TH), dopamine transporter (DAT), or vesicular monoamine transporter 2 (VMAT2) immunoreactivity at any age. However, DA transport via DAT (starting at 12 months) and VMAT2 (starting at 3 months) as well as KCl-stimulated DA release were reduced in Bdnf+/− mice and declined with age suggesting an increasingly important role for BDNF in the release and uptake of DA with the aging process. These findings suggest that a BDNF expression deficit becomes more critical to dopaminergic dynamics and related behavioral activities with increasing age. PMID:20860702

Measurement of cardiac output from dynamic pulmonary circulation time CT

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

Yee, Seonghwan, E-mail: Seonghwan.Yee@Beaumont.edu; Scalzetti, Ernest M.

Purpose: To introduce a method of estimating cardiac output from the dynamic pulmonary circulation time CT that is primarily used to determine the optimal time window of CT pulmonary angiography (CTPA). Methods: Dynamic pulmonary circulation time CT series, acquired for eight patients, were retrospectively analyzed. The dynamic CT series was acquired, prior to the main CTPA, in cine mode (1 frame/s) for a single slice at the level of the main pulmonary artery covering the cross sections of ascending aorta (AA) and descending aorta (DA) during the infusion of iodinated contrast. The time series of contrast changes obtained for DA,more » which is the downstream of AA, was assumed to be related to the time series for AA by the convolution with a delay function. The delay time constant in the delay function, representing the average time interval between the cross sections of AA and DA, was determined by least square error fitting between the convoluted AA time series and the DA time series. The cardiac output was then calculated by dividing the volume of the aortic arch between the cross sections of AA and DA (estimated from the single slice CT image) by the average time interval, and multiplying the result by a correction factor. Results: The mean cardiac output value for the six patients was 5.11 (l/min) (with a standard deviation of 1.57 l/min), which is in good agreement with the literature value; the data for the other two patients were too noisy for processing. Conclusions: The dynamic single-slice pulmonary circulation time CT series also can be used to estimate cardiac output.« less

Characteristics of Dynamic Magnetic Resonance Image Enhancement in Prolactinomas Resistant to Dopamine Agonist Therapy

PubMed Central

Guo, Qinghua; Erickson, Bradley J.; Chang, Alice Y.; Erickson, Dana

2015-01-01

Objective To determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas. Methods We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, Minnesota). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naïve groups, and between the first and follow-up dMRIs. Results We identified 49 patients with prolactinomas, with 6 (12.2%) that showed DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group vs the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P=.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P=.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% CI, 1.07-3.27; P=.02). Conclusions dMRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas. PMID:25551412

Bursting as a source of non-linear determinism in the firing patterns of nigral dopamine neurons

PubMed Central

Jeong, Jaeseung; Shi, Wei-Xing; Hoffman, Ralph; Oh, Jihoon; Gore, John C.; Bunney, Benjamin S.; Peterson, Bradley S.

2012-01-01

Nigral dopamine (DA) neurons in vivo exhibit complex firing patterns consisting of tonic single-spikes and phasic bursts that encode information for certain types of reward-related learning and behavior. Non-linear dynamical analysis has previously demonstrated the presence of a non-linear deterministic structure in complex firing patterns of DA neurons, yet the origin of this non-linear determinism remains unknown. In this study, we hypothesized that bursting activity is the primary source of non-linear determinism in the firing patterns of DA neurons. To test this hypothesis, we investigated the dimension complexity of inter-spike interval data recorded in vivo from bursting and non-bursting DA neurons in the chloral hydrate-anesthetized rat substantia nigra. We found that bursting DA neurons exhibited non-linear determinism in their firing patterns, whereas non-bursting DA neurons showed truly stochastic firing patterns. Determinism was also detected in the isolated burst and inter-burst interval data extracted from firing patterns of bursting neurons. Moreover, less bursting DA neurons in halothane-anesthetized rats exhibited higher dimensional spiking dynamics than do more bursting DA neurons in chloral hydrate-anesthetized rats. These results strongly indicate that bursting activity is the main source of low-dimensional, non-linear determinism in the firing patterns of DA neurons. This finding furthermore suggests that bursts are the likely carriers of meaningful information in the firing activities of DA neurons. PMID:22831464

A plastic corticostriatal circuit model of adaptation in perceptual decision making

PubMed Central

Hsiao, Pao-Yueh; Lo, Chung-Chuan

2013-01-01

The ability to optimize decisions and adapt them to changing environments is a crucial brain function that increase survivability. Although much has been learned about the neuronal activity in various brain regions that are associated with decision making, and about how the nervous systems may learn to achieve optimization, the underlying neuronal mechanisms of how the nervous systems optimize decision strategies with preference given to speed or accuracy, and how the systems adapt to changes in the environment, remain unclear. Based on extensive empirical observations, we addressed the question by extending a previously described cortico-basal ganglia circuit model of perceptual decisions with the inclusion of a dynamic dopamine (DA) system that modulates spike-timing dependent plasticity (STDP). We found that, once an optimal model setting that maximized the reward rate was selected, the same setting automatically optimized decisions across different task environments through dynamic balancing between the facilitating and depressing components of the DA dynamics. Interestingly, other model parameters were also optimal if we considered the reward rate that was weighted by the subject's preferences for speed or accuracy. Specifically, the circuit model favored speed if we increased the phasic DA response to the reward prediction error, whereas the model favored accuracy if we reduced the tonic DA activity or the phasic DA responses to the estimated reward probability. The proposed model provides insight into the roles of different components of DA responses in decision adaptation and optimization in a changing environment. PMID:24339814

Dynamic fluctuations in dopamine efflux in the prefrontal cortex and nucleus accumbens during risk-based decision making.

PubMed

St Onge, Jennifer R; Ahn, Soyon; Phillips, Anthony G; Floresco, Stan B

2012-11-21

Mesocorticolimbic dopamine (DA) has been implicated in cost/benefit decision making about risks and rewards. The prefrontal cortex (PFC) and nucleus accumbens (NAc) are two DA terminal regions that contribute to decision making in distinct manners. However, how fluctuations of tonic DA levels may relate to different aspects of decision making remains to be determined. The present study measured DA efflux in the PFC and NAc with microdialysis in well trained rats performing a probabilistic discounting task. Selection of a small/certain option always delivered one pellet, whereas another, large/risky option yielded four pellets, with probabilities that decreased (100-12.5%) or increased (12.5-100%) across four blocks of trials. Yoked-reward groups were also included to control for reward delivery. PFC DA efflux during decision making decreased or increased over a session, corresponding to changes in large/risky reward probabilities. Similar profiles were observed from yoked-rewarded rats, suggesting that fluctuations in PFC DA reflect changes in the relative rate of reward received. NAc DA efflux also showed decreasing/increasing trends over the session during both tasks. However, DA efflux was higher during decision making on free- versus forced-choice trials and during periods of greater reward uncertainty. Moreover, changes in NAc DA closely tracked shifts in choice biases. These data reveal dynamic and dissociable fluctuations in PFC and NAc DA transmission associated with different aspects of risk-based decision making. PFC DA may signal changes in reward availability that facilitates modification of choice biases, whereas NAc DA encodes integrated signals about reward rates, uncertainty, and choice, reflecting implementation of decision policies.

Monte Carlo Bayesian System Reliability and MTBF-Confidence Assessment, II. Volume 2. SPARCS-2 Users Manual

DTIC Science & Technology

1978-03-01

1977 Approved for public release; distribution unlimited. AIR FORCE FLIGHT DYNAMICS LABORATORY AIR FORCE WRIGHT AERONAUTICAL LABORATORIES AIR FORCE...SYSTEMS COMMAND WRIGHT-PATTERSON AIR FORCE BASE, OHIO 45433 NOTI CE When Gove~inme~nt d’tawi~ngz, .6pe~c4Lcatiton, ct o-theAi da~ta cute -6e~d Joit any... AIR FORCE/56780/6 June 1978 -450 Unclassified SECURITY CLASSIFICATION OF THIS PAGE ("hen Date ýntered) READ INSTRUCTIONSREPORT DOCUMENTATION PAGE

Modeling Parkinson's disease falls associated with brainstem cholinergic systems decline.

PubMed

Kucinski, Aaron; Sarter, Martin

2015-04-01

In addition to the primary disease-defining symptoms, approximately half of patients with Parkinson's disease (PD) suffer from postural instability, impairments in gait control and a propensity for falls. Consistent with evidence from patients, we previously demonstrated that combined striatal dopamine (DA) and basal forebrain (BF) cholinergic cell loss causes falls in rats traversing dynamic surfaces. Because evidence suggests that degeneration of brainstem cholinergic neurons arising from the pedunculopontine nucleus (PPN) also contributes to impaired gait and falls, here we assessed the effects of selective cholinergic PPN lesions in combination with striatal DA loss or BF cholinergic cells loss as well as losses in all 3 regions. Results indicate that all combination losses that included the BF cholinergic system slowed traversal and increased slips and falls. However, the performance of rats with losses in all 3 regions (PPN, BF, and DA) was not more severely impaired than following combined BF cholinergic and striatal DA lesions. These results confirm the hypothesis that BF cholinergic-striatal disruption of attentional-motor interactions is a primary source of falls. Additional losses of PPN cholinergic neurons may worsen posture and gait control in situations not captured by the current testing conditions. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Moving Triadic Gaze Intervention Into Practice: Measuring Clinician Attitude and Implementation Fidelity

PubMed Central

Olswang, Lesley B.; Greenslade, Kathryn; Pinder, Gay Lloyd; Dowden, Patricia; Madden, Jodi

2017-01-01

Purpose This research investigated a first step in implementing the dynamic assessment (DA) component of Triadic Gaze Intervention (Olswang, Feuerstein, Pinder, & Dowden, 2013; Olswang et al., 2014), an evidence-based protocol for teaching early signals of communication to young children with physical disabilities. Clinician attitudes about adopting external evidence into practice and implementation fidelity in DA protocol delivery were examined following training. Method Seven early intervention clinicians from multiple disciplines were trained to deliver the four essential elements of the DA protocol: (a) provide communication opportunity, (b) recognize child's potentially communicative signal, (c) shape child's signal toward triadic gaze, and (d) reinforce with play. Clinician attitude regarding adopting evidence into practice was measured at baseline and follow-up, with the Evidence-Based Practice Attitude Scale (Aarons, 2004). Implementation fidelity in delivering the protocol was measured for adherence (accuracy) and competence (quality) during trial implementation. Results Clinicians' attitudes about trying new evidence that at first was perceived as incongruent with their practice improved over the course of the research. Clinicians demonstrated strong adherence to the DA protocol; however, competence varied across clinicians and appeared related to child performance. Conclusions The results provided insight into moving Triadic Gaze Intervention into practice and yielded valuable information regarding the implementation process, with implications for future research. PMID:28525577

Yarkovsky-driven Impact Predictions: Apophis and 1950 DA

NASA Astrophysics Data System (ADS)

Chesley, Steven R.; Farnocchia, D.; Chodas, P. W.; Milani, A.

2013-10-01

Orbit determination for Near-Earth Asteroids presents unique technical challenges due to the imperative of early detection and careful assessment of the risk posed by specific Earth close approaches. The occurrence of an Earth impact can be decisively driven by the Yarkovsky effect, which is the most important nongravitational perturbation as it causes asteroids to undergo a secular variation in semimajor axis resulting in a quadratic effect in anomaly. We discuss the cases of (99942) Apophis and (29075) 1950 DA. The relevance of the Yarkovsky effect for Apophis is due to a scattering close approach in 2029 with minimum geocentric distance ~38000 km. For 1950 DA the influence of the Yarkovsky effect in 2880 is due to the long time interval preceding the impact. We use the available information from the astrometry and the asteroids' physical models and dynamical evolution as a starting point for a Monte Carlo method that allows us to measure how the Yarkovsky effect affects orbital predictions. We also find that 1950 DA has a 98% likelihood of being a retrograde rotator. For Apophis we map onto the 2029 close approach b-plane and analyze the keyholes corresponding to resonant close approaches. For 1950 DA we use the b-plane corresponding to the possible impact in 2880. We finally compute the impact probability from the mapped probability density function on the considered b-plane. For Apophis we have 4 in a million chances of an impact in 2068, while the probability of Earth impact in 2880 for 1950 DA is 0.04%.

Bursting as a source of non-linear determinism in the firing patterns of nigral dopamine neurons.

PubMed

Jeong, Jaeseung; Shi, Wei-Xing; Hoffman, Ralph; Oh, Jihoon; Gore, John C; Bunney, Benjamin S; Peterson, Bradley S

2012-11-01

Nigral dopamine (DA) neurons in vivo exhibit complex firing patterns consisting of tonic single-spikes and phasic bursts that encode information for certain types of reward-related learning and behavior. Non-linear dynamical analysis has previously demonstrated the presence of a non-linear deterministic structure in complex firing patterns of DA neurons, yet the origin of this non-linear determinism remains unknown. In this study, we hypothesized that bursting activity is the primary source of non-linear determinism in the firing patterns of DA neurons. To test this hypothesis, we investigated the dimension complexity of inter-spike interval data recorded in vivo from bursting and non-bursting DA neurons in the chloral hydrate-anesthetized rat substantia nigra. We found that bursting DA neurons exhibited non-linear determinism in their firing patterns, whereas non-bursting DA neurons showed truly stochastic firing patterns. Determinism was also detected in the isolated burst and inter-burst interval data extracted from firing patterns of bursting neurons. Moreover, less bursting DA neurons in halothane-anesthetized rats exhibited higher dimensional spiking dynamics than do more bursting DA neurons in chloral hydrate-anesthetized rats. These results strongly indicate that bursting activity is the main source of low-dimensional, non-linear determinism in the firing patterns of DA neurons. This finding furthermore suggests that bursts are the likely carriers of meaningful information in the firing activities of DA neurons. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

General contrast effects in speech perception: effect of preceding liquid on stop consonant identification.

PubMed

Lotto, A J; Kluender, K R

1998-05-01

When members of a series of synthesized stop consonants varying acoustically in F3 characteristics and varying perceptually from /da/ to /ga/ are preceded by /al/, subjects report hearing more /ga/ syllables relative to when each member is preceded by /ar/ (Mann, 1980). It has been suggested that this result demonstrates the existence of a mechanism that compensates for coarticulation via tacit knowledge of articulatory dynamics and constraints, or through perceptual recovery of vocal-tract dynamics. The present study was designed to assess the degree to which these perceptual effects are specific to qualities of human articulatory sources. In three experiments, series of consonant-vowel (CV) stimuli varying in F3-onset frequency (/da/-/ga/) were preceded by speech versions or nonspeech analogues of /al/ and /ar/. The effect of liquid identity on stop consonant labeling remained when the preceding VC was produced by a female speaker and the CV syllable was modeled after a male speaker's productions. Labeling boundaries also shifted when the CV was preceded by a sine wave glide modeled after F3 characteristics of /al/ and /ar/. Identifications shifted even when the preceding sine wave was of constant frequency equal to the offset frequency of F3 from a natural production. These results suggest an explanation in terms of general auditory processes as opposed to recovery of or knowledge of specific articulatory dynamics.

On the Da Vinci size effect in tensile strengths of nanowires: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Zhao, Ziyu; Liu, Jinxing; Soh, Ai Kah

2018-01-01

In recent decades, size effects caused by grain size, strain gradient, typical defects etc., have been widely investigated. Nevertheless, the dependence of tensile strength on the specimen length, addressed by Da Vinci around 500 hundred years ago, has received rather limited attention, even though it is one unavoidable question to answer if people attempt to bring materials' amazing nano-scale strengths up to macro-level. Therefore, we make efforts to study tensile behaviors of copper nanowires with a common cross-section and various lengths by employing the molecular dynamics simulations. Surprisingly, a strong size effect of Da Vinci type indeed arises. We have shown the influences of lattice orientation, temperature and prescribed notch on such a Da Vinci size effect. Two different theoretical explanations are briefly proposed for a qualitative understanding. Finally, a simple scaling rule is summarized to cover the tendencies observed.

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

Huh, S; Lee, S; Dagan, R

Purpose: To investigate the feasibility of utilizing Dynamic Arc (DA) and IMRT with 5mm MLC leaf of VERO treatment unit for SRS/FSRT brain cancer patients with non-invasive stereotactic treatments. The DA and IMRT plans using the VERO unit (BrainLab Inc, USA) are compared with cone-based planning and proton plans to evaluate their dosimetric advantages. Methods: The Vero treatment has unique features like no rotational or translational movements of the table during treatments, Dynamic Arc/IMRT, tracking of IR markers, limitation of Ring rotation. Accuracies of the image fusions using CBCT, orthogonal x-rays, and CT are evaluated less than ∼ 0.7mm withmore » a custom-made target phantom with 18 hidden targets. 1mm margin is given to GTV to determine PTV for planning constraints considering all the uncertainties of planning computer and mechanical uncertainties of the treatment unit. Also, double-scattering proton plans with 6F to 9F beams and typical clinical parameters, multiple isocenter plans with 6 to 21 isocenters, and DA/IMRT plans are evaluated to investigate the dosimetric advantages of the DA/IMRT for complex shape of targets. Results: 3 Groups of the patients are divided: (1) Group A (complex target shape), CI's are same for IMRT, and DGI of the proton plan are better by 9.5% than that of the IMRT, (2) Group B, CI of the DA plans (1.91+/−0.4) are better than cone-based plan, while DGI of the DA plan is 4.60+/−1.1 is better than cone-based plan (5.32+/−1.4), (3) Group C (small spherical targets), CI of the DA and cone-based plans are almost the same. Conclusion: For small spherical targets, cone-based plans are superior to other 2 plans: DS proton and DA plans. For complex or irregular plans, dynamic and IMRT plans are comparable to cone-based and proton plans for complex targets.« less

ECTA/DaSy Framework Self-Assessment Comparison Tool

ERIC Educational Resources Information Center

Center for IDEA Early Childhood Data Systems (DaSy), 2016

2016-01-01

The Self-Assessment Comparison (SAC) Tool is for state Part C and Section 619/Preschool programs to use to assess changes in the implementation of one or more components of the ECTA System Framework and/or subcomponenets of the DaSy Data System Framework. It is a companion to the ECTA/DaSy Framework Self-Assessment. Key features of the SAC are…

Loss of Mitochondrial Fission Depletes Axonal Mitochondria in Midbrain Dopamine Neurons

PubMed Central

Berthet, Amandine; Margolis, Elyssa B.; Zhang, Jue; Hsieh, Ivy; Zhang, Jiasheng; Hnasko, Thomas S.; Ahmad, Jawad; Edwards, Robert H.; Sesaki, Hiromi; Huang, Eric J.

2014-01-01

Disruptions in mitochondrial dynamics may contribute to the selective degeneration of dopamine (DA) neurons in Parkinson's disease (PD). However, little is known about the normal functions of mitochondrial dynamics in these neurons, especially in axons where degeneration begins, and this makes it difficult to understand the disease process. To study one aspect of mitochondrial dynamics—mitochondrial fission—in mouse DA neurons, we deleted the central fission protein dynamin-related protein 1 (Drp1). Drp1 loss rapidly eliminates the DA terminals in the caudate–putamen and causes cell bodies in the midbrain to degenerate and lose α-synuclein. Without Drp1, mitochondrial mass dramatically decreases, especially in axons, where the mitochondrial movement becomes uncoordinated. However, in the ventral tegmental area (VTA), a subset of midbrain DA neurons characterized by small hyperpolarization-activated cation currents (Ih) is spared, despite near complete loss of their axonal mitochondria. Drp1 is thus critical for targeting mitochondria to the nerve terminal, and a disruption in mitochondrial fission can contribute to the preferential death of nigrostriatal DA neurons. PMID:25339743

Dynamic Loading of Immature Epiphyseal Cartilage Pumps Nutrients out of Vascular Canals

PubMed Central

Albro, Michael B.; Banerjee, Rajan E.; Li, Roland; Oungoulian, Sevan R.; Chen, Bo; del Palomar, Amaya P.; Hung, Clark T.; Ateshian, Gerard A.

2011-01-01

The potential influence of mechanical loading on transvascular transport in vascularized soft tissues has not been explored extensively. This experimental investigation introduced and explored the hypothesis that dynamic mechanical loading can pump solutes out of blood vessels and into the surrounding tissue, leading to faster uptake and higher solute concentrations than could otherwise be achieved under unloaded conditions. Immature epiphyseal cartilage was used as a model tissue system, with fluorescein (332 Da), dextran (3, 10 and 70 kDa) and transferrin (80 kDa) as model solutes. Cartilage disks were either dynamically loaded (±10% compression over a 10% static offset strain, at 0.2 Hz) or maintained unloaded in solution for up to 20 hours. Results demonstrated statistically significant solute uptake in dynamically loaded (DL) explants relative to passive diffusion (PD) controls for all solutes except unbound fluorescein, as evidenced by the DL:PD concentration ratios after 20 hours (1.0 ± 0.2, 2.4 ± 1.1, 6.1 ± 3.3, 9.0 ± 4.0, and 5.5±1.6 for fluorescein, 3, 10, and 70 kDa dextran, and transferrin). Significant uptake enhancements were also observed within the first 30 seconds of loading. Termination of dynamic loading produced dissipation of enhanced solute uptake back to PD control values. Confocal images confirmed that solute uptake occurred from cartilage canals into their surrounding extracellular matrix. The incidence of this loading-induced transvascular solute pumping mechanism may significantly alter our understanding of the interaction of mechanical loading and tissue metabolism. PMID:21481875

The Caenorhabditis elegans DAF-12 nuclear receptor: structure, dynamics, and interaction with ligands.

PubMed

Alvarez, Lautaro D; Mañez, Pau Arroyo; Estrin, Darío A; Burton, Gerardo

2012-07-01

A structure for the ligand binding domain (LBD) of the DAF-12 receptor from Caenorhabditis elegans was obtained from the X-ray crystal structure of the receptor LBD from Strongyloides stercoralis bound to (25R)-Δ(7)-dafachronic acid (DA) (pdb:3GYU). The model was constructed in the presence of the ligand using a combination of Modeller, Autodock, and molecular dynamics (MD) programs, and then its dynamical behavior was studied by MD. A strong ligand binding mode (LBM) was found, with the three arginines in the ligand binding pocket (LBP) contacting the C-26 carboxylate group of the DA. The quality of the ceDAF-12 model was then evaluated by constructing several ligand systems for which the experimental activity is known. Thus, the dynamical behavior of the ceDAF-12 complex with the more active (25S)-Δ(7)-DA showed two distinct binding modes, one of them being energetically more favorable compared with the 25R isomer. Then the effect of the Arg564Cys and Arg598Met mutations on the (25R)-Δ(7)-DA binding was analyzed. The MD simulations showed that in the first case the complex was unstable, consistent with the lack of transactivation activity of (25R)-Δ(7)-DA in this mutant. Instead, in the case of the Arg598Met mutant, known to produce a partial loss of activity, our model predicted smaller effects on the LBM with a more stable MD trajectory. The model also showed that removal of the C-25 methyl does not impede the simultaneous strong interaction of the carboxylate with the three arginines, predicting that 27-nor-DAs are putative ceDAF-12 ligands. Copyright © 2012 Wiley Periodicals, Inc.

Sensitivity analysis of a data assimilation technique for hindcasting and forecasting hydrodynamics of a complex coastal water body

NASA Astrophysics Data System (ADS)

Ren, Lei; Hartnett, Michael

2017-02-01

Accurate forecasting of coastal surface currents is of great economic importance due to marine activities such as marine renewable energy and fish farms in coastal regions in recent twenty years. Advanced oceanographic observation systems such as satellites and radars can provide many parameters of interest, such as surface currents and waves, with fine spatial resolution in near real time. To enhance modelling capability, data assimilation (DA) techniques which combine the available measurements with the hydrodynamic models have been used since the 1990s in oceanography. Assimilating measurements into hydrodynamic models makes the original model background states follow the observation trajectory, then uses it to provide more accurate forecasting information. Galway Bay is an open, wind dominated water body on which two coastal radars are deployed. An efficient and easy to implement sequential DA algorithm named Optimal Interpolation (OI) was used to blend radar surface current data into a three-dimensional Environmental Fluid Dynamics Code (EFDC) model. Two empirical parameters, horizontal correlation length and DA cycle length (CL), are inherent within OI. No guidance has previously been published regarding selection of appropriate values of these parameters or how sensitive OI DA is to variations in their values. Detailed sensitivity analysis has been performed on both of these parameters and results presented. Appropriate value of DA CL was examined and determined on producing the minimum Root-Mean-Square-Error (RMSE) between radar data and model background states. Analysis was performed to evaluate assimilation index (AI) of using an OI DA algorithm in the model. AI of the half-day forecasting mean vectors' directions was over 50% in the best assimilation model. The ability of using OI to improve model forecasts was also assessed and is reported upon.

The proline-rich region of 18.5 kDa myelin basic protein binds to the SH3-domain of Fyn tyrosine kinase with the aid of an upstream segment to form a dynamic complex in vitro

PubMed Central

De Avila, Miguel; Vassall, Kenrick A.; Smith, Graham S. T.; Bamm, Vladimir V.; Harauz, George

2014-01-01

The intrinsically disordered 18.5 kDa classic isoform of MBP (myelin basic protein) interacts with Fyn kinase during oligodendrocyte development and myelination. It does so primarily via a central proline-rich SH3 (Src homology 3) ligand (T92–R104, murine 18.5 kDa MBP sequence numbering) that is part of a molecular switch due to its high degree of conservation and modification by MAP (mitogen-activated protein) and other kinases, especially at residues T92 and T95. Here, we show using co-transfection experiments of an early developmental oligodendroglial cell line (N19) that an MBP segment upstream of the primary ligand is involved in MBP–Fyn–SH3 association in cellula. Using solution NMR spectroscopy in vitro, we define this segment to comprise MBP residues (T62–L68), and demonstrate further that residues (V83–P93) are the predominant SH3-target, assessed by the degree of chemical shift change upon titration. We show by chemical shift index analysis that there is no formation of local poly-proline type II structure in the proline-rich segment upon binding, and by NOE (nuclear Overhauser effect) and relaxation measurements that MBP remains dynamic even while complexed with Fyn–SH3. The association is a new example first of a non-canonical SH3-domain interaction and second of a fuzzy MBP complex. PMID:25343306

The proline-rich region of 18.5 kDa myelin basic protein binds to the SH3-domain of Fyn tyrosine kinase with the aid of an upstream segment to form a dynamic complex in vitro.

PubMed

De Avila, Miguel; Vassall, Kenrick A; Smith, Graham S T; Bamm, Vladimir V; Harauz, George

2014-12-08

The intrinsically disordered 18.5 kDa classic isoform of MBP (myelin basic protein) interacts with Fyn kinase during oligodendrocyte development and myelination. It does so primarily via a central proline-rich SH3 (Src homology 3) ligand (T92-R104, murine 18.5 kDa MBP sequence numbering) that is part of a molecular switch due to its high degree of conservation and modification by MAP (mitogen-activated protein) and other kinases, especially at residues T92 and T95. Here, we show using co-transfection experiments of an early developmental oligodendroglial cell line (N19) that an MBP segment upstream of the primary ligand is involved in MBP-Fyn-SH3 association in cellula. Using solution NMR spectroscopy in vitro, we define this segment to comprise MBP residues (T62-L68), and demonstrate further that residues (V83-P93) are the predominant SH3-target, assessed by the degree of chemical shift change upon titration. We show by chemical shift index analysis that there is no formation of local poly-proline type II structure in the proline-rich segment upon binding, and by NOE (nuclear Overhauser effect) and relaxation measurements that MBP remains dynamic even while complexed with Fyn-SH3. The association is a new example first of a non-canonical SH3-domain interaction and second of a fuzzy MBP complex.

Dynamic analysis of the blood-brain barrier disruption in experimental stroke using time domain in vivo fluorescence imaging.

PubMed

Abulrob, Abedelnasser; Brunette, Eric; Slinn, Jacqueline; Baumann, Ewa; Stanimirovic, Danica

2008-01-01

The blood-brain barrier (BBB) disruption following cerebral ischemia can be exploited to deliver imaging agents and therapeutics into the brain. The aim of this study was (a) to establish novel in vivo optical imaging methods for longitudinal assessment of the BBB disruption and (b) to assess size selectivity and temporal patterns of the BBB disruption after a transient focal ischemia. The BBB permeability was assessed using in vivo time domain near-infrared optical imaging after contrast enhancement with either free Cy5.5 (1 kDa) or Cy5.5 conjugated with bovine serum albumin (BSA) (67 kDa) in mice subjected to either 60- or 20-minute transient middle cerebral artery occlusion (MCAO) and various times of reperfusion (up to 14 days). In vivo imaging observations were corroborated by ex vivo brain imaging and microscopic analyses of fluorescent tracer extravasation. The in vivo optical contrast enhancement with Cy5.5 was spatially larger than that observed with BSA-Cy5.5. Longitudinal studies after a transient 20-minute MCAO suggested a bilateral BBB disruption, more pronounced in the ipsilateral hemisphere, peaking at day 7 and resolving at day 14 after ischemia. The area differential between the BBB disruption for small and large molecules could potentially be useful as a surrogate imaging marker for assessing perinfarct tissues to which neuroprotective therapies of appropriate sizes could be delivered.

Use of electronic dietary assessment tools in primary care: an interdisciplinary perspective.

PubMed

Bonilla, Carolina; Brauer, Paula; Royall, Dawna; Keller, Heather; Hanning, Rhona M; DiCenso, Alba

2015-02-25

Dietary assessment can be challenging for many reasons, including the wide variety of foods, eating patterns and nutrients to be considered. In team-based primary care practice, various disciplines may be involved in assessing diet. Electronic-based dietary assessment (e-DA) instruments available now through mobile apps or websites can potentially facilitate dietary assessment. Providers views of facilitators and barriers related to e-DA instruments and their recommendations for improvement can inform the further development of these tools. The objective of this study was to explore provider perspectives on e-DA tools in mobile apps and websites. The exploratory sequential mixed methods design included interdisciplinary focus groups followed by a web-based survey sent to Family Health Teams throughout Ontario, Canada. Descriptive and bivariate analyses were completed. Focus group transcripts contributed to web-survey content, while interpretive themes added depth and context. 11 focus groups with 50 providers revealed varying perspectives on the use of e-DA for: 1) improving patients' eating habits; 2) improving the quality of dietary assessment; and, 3) integrating e-DA into the care process. In the web-survey 191 respondents from nine disciplines in 73 FHTs completed the survey. Dietitians reported greater use of e-DA than other providers (63% vs.19%; p = .000) respectively. There was strong interest among disciplines in the use of e-DA tools for the management of obesity, diabetes and heart disease, especially for patient self-monitoring. Barriers identified were: patients' lack of comfort with using technology, misinterpretation of e-DA results by patients, time and education for providers to interpret results, and time for providers to offer counselling. e-DA tools in mobile apps and websites may improve dietary counselling over time. Addressing the identified facilitators and barriers can potentially promote the uptake of e-DA into clinical practice.

Synthesis, Protein Levels, Activity and Phosphorylation State of Tyrosine Hydroxylase in Mesoaccumbens and Nigrostriatal Dopamine Pathways of Chronically Food-restricted Rats

PubMed Central

Pan, Yan; Berman, Yemiliya; Haberny, Sandra; Meller, Emanuel; Carr, Kenneth D.

2006-01-01

Chronic food restriction (FR) enhances the rewarding and motor-activating effects of abused drugs, and is accompanied by changes in dopamine (DA) dynamics and increased D-1 DA receptor-mediated cell signaling and transcriptional responses in nucleus accumbens (NAc). However, little is known about effects of FR on DA synthetic activity in the mesoaccumbens and nigrostriatal pathways. In Experiment 1 of the present study, tyrosine hydroxylase (TH) gene expression was measured in ventral tegmental area and substantia nigra, using real time RT-PCR and in situ hybridization; no differences were observed between FR and ad libitum fed (AL) rats. In Experiment 2, TH protein levels, determined by Western blot, were found to be elevated in NAc and caudate-putamen (CPu) of FR relative to AL rats. In the absence of increased transcription, this may reflect a slowing of TH degradation. In Experiments 3 and 4, DA synthetic activity was assessed by Western blot measurement of TH phosphorylation at Ser-40, and HPLC measurement of in vivo tyrosine hydroxylation rate, as reflected by DOPA accumulation following administration of a decarboxylase inhibitor (NSD-1015; 100 mg/kg, i.p.). Basal phospho-Ser(40)-TH levels did not differ between groups but DOPA accumulation was decreased by FR. Decreased DOPA synthesis, despite increased levels of TH protein, may reflect the inhibitory effect of increased DA binding to TH protein or decreased concentrations of cofactor tetrahydrobiopterin. Finally, in response to d-amphetamine (0.5 and 5.0 mg/kg, i.p.), phospho-Ser(40)-TH was selectively decreased in NAc of FR rats. This suggests increased feedback inhibition of DA synthesis - a possible consequence of postsynaptic receptor hypersensitivity, or increased extracellular DA concentration. These results indicate that FR increases TH protein levels, but may decrease the capacity for DA synthesis by decreasing TH activity. According to this scheme, the previously observed upregulation of striatal cell signaling and transcriptional responses to DA receptor agonist administration may include compensatory neuroadaptations. SECTION: 1. Systems Neuroscience (Regulatory Systems) PMID:17010321

Dynamically Cross-linked Elastomer Hybrids with Light-Induced Rapid and Efficient Self-Healing Ability and Reprogrammable Shape Memory Behavior.

PubMed

Bai, Jing; Shi, Zixing

2017-08-16

Pristine carbon nanotubes (CNTs) were activated to exhibit Diels-Alder (DA) reactivity in a polymer matrix, which was modified with monomers containing furan groups. The DA-active polymer matrix was transferred into a dynamic reversible cross-linked inorganic-organic network via a Diels-Alder reaction with CNTs, where pristine CNTs were used as dienophile chemicals and furan-modified SBS acted as the macromolecular diene. In this system, the mechanical properties as well as resilience and solvent resistance were greatly improved even with the presence of only 1 wt % CNTs. Meanwhile, the hybrids retained recyclability and exhibited some smart behaviors, including self-healing and reprogrammable shape memory properties. Furthermore, due to the photothermal effect of CNTs, a retro-Diels-Alder (rDA) reaction was activated under laser irradiation, and healing of a crack on the hybrid surface was demonstrated in approximately 10 s with almost complete recovery of the mechanical properties. Such fast and efficient self-healing performance provides a new concept in designing self-healing nanocomposites with tunable structures and mechanical properties. Furthermore, the DA and rDA reactions could be combined to reprogram the shape memory behavior under laser irradiation or thermal treatment, wherein the temporary shape of the sample could be transferred to a permanent shape via the rDA reaction at high temperature.

Percent Mammographic Density and Dense Area as Risk Factors for Breast Cancer.

PubMed

Rauh, C; Hack, C C; Häberle, L; Hein, A; Engel, A; Schrauder, M G; Fasching, P A; Jud, S M; Ekici, A B; Loehberg, C R; Meier-Meitinger, M; Ozan, S; Schulz-Wendtland, R; Uder, M; Hartmann, A; Wachter, D L; Beckmann, M W; Heusinger, K

2012-08-01

Purpose: Mammographic characteristics are known to be correlated to breast cancer risk. Percent mammographic density (PMD), as assessed by computer-assisted methods, is an established risk factor for breast cancer. Along with this assessment the absolute dense area (DA) of the breast is reported as well. Aim of this study was to assess the predictive value of DA concerning breast cancer risk in addition to other risk factors and in addition to PMD. Methods: We conducted a case control study with hospital-based patients with a diagnosis of invasive breast cancer and healthy women as controls. A total of 561 patients and 376 controls with available mammographic density were included into this study. We describe the differences concerning the common risk factors BMI, parital status, use of hormone replacement therapy (HRT) and menopause between cases and controls and estimate the odds ratios for PMD and DA, adjusted for the mentioned risk factors. Furthermore we compare the prediction models with each other to find out whether the addition of DA improves the model. Results: Mammographic density and DA were highly correlated with each other. Both variables were as well correlated to the commonly known risk factors with an expected direction and strength, however PMD (ρ = -0.56) was stronger correlated to BMI than DA (ρ = -0.11). The group of women within the highest quartil of PMD had an OR of 2.12 (95 % CI: 1.25-3.62). This could not be seen for the fourth quartile concerning DA. However the assessment of breast cancer risk could be improved by including DA in a prediction model in addition to common risk factors and PMD. Conclusions: The inclusion of the parameter DA into a prediction model for breast cancer in addition to established risk factors and PMD could improve the breast cancer risk assessment. As DA is measured together with PMD in the process of computer-assisted assessment of PMD it might be considered to include it as one additional breast cancer risk factor that is obtained from breast imaging.

Understanding the adoption dynamics of medical innovations: affordances of the da Vinci robot in the Netherlands.

PubMed

Abrishami, Payam; Boer, Albert; Horstman, Klasien

2014-09-01

This study explored the rather rapid adoption of a new surgical device - the da Vinci robot - in the Netherlands despite the high costs and its controversial clinical benefits. We used the concept 'affordances' as a conceptual-analytic tool to refer to the perceived promises, symbolic meanings, and utility values of an innovation constructed in the wider social context of use. This concept helps us empirically understand robot adoption. Data from 28 in-depth interviews with diverse purposively-sampled stakeholders, and from medical literature, policy documents, Health Technology Assessment reports, congress websites and patients' weblogs/forums between April 2009 and February 2014 were systematically analysed from the perspective of affordances. We distinguished five interrelated affordances of the robot that accounted for shaping and fulfilling its rapid adoption: 'characteristics-related' affordances such as smart nomenclature and novelty, symbolising high-tech clinical excellence; 'research-related' affordances offering medical-technical scientific excellence; 'entrepreneurship-related' affordances for performing better-than-the-competition; 'policy-related' affordances indicating the robot's liberalised provision and its reduced financial risks; and 'communication-related' affordances of the robot in shaping patients' choices and the public's expectations by resonating promising discourses while pushing uncertainties into the background. These affordances make the take-up and use of the da Vinci robot sound perfectly rational and inevitable. This Dutch case study demonstrates the fruitfulness of the affordances approach to empirically capturing the contextual dynamics of technology adoption in health care: exploring in-depth actors' interaction with the technology while considering the interpretative spaces created in situations of use. This approach can best elicit real-life value of innovations, values as defined through the eyes of (potential) users. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens reveals local modulation of presynaptic release

PubMed Central

Melchior, James R.; Ferris, Mark J.; Stuber, Garret D.; Riddle, David R.; Jones, Sara R.

2015-01-01

The nucleus accumbens is highly heterogeneous, integrating regionally distinct afferent projections and accumbal interneurons, resulting in diverse local microenvironments. Dopamine (DA) neuron terminals similarly express a heterogeneous collection of terminal receptors that modulate DA signaling. Cyclic voltammetry is often used to probe DA terminal dynamics in brain slice preparations; however, this method traditionally requires electrical stimulation to induce DA release. Electrical stimulation excites all of the neuronal processes in the stimulation field, potentially introducing simultaneous, multi-synaptic modulation of DA terminal release. We used optogenetics to selectively stimulate DA terminals and used voltammetry to compare DA responses from electrical and optical stimulation of the same area of tissue around a recording electrode. We found that with multiple pulse stimulation trains, optically stimulated DA release increasingly exceeded that of electrical stimulation. Furthermore, electrical stimulation produced inhibition of DA release across longer duration stimulations. The GABAB antagonist, CGP 55845, increased electrically stimulated DA release significantly more than light stimulated release. The nicotinic acetylcholine receptor antagonist, dihydro-β-erythroidine hydrobromide, inhibited single pulse electrically stimulated DA release while having no effect on optically stimulated DA release. Our results demonstrate that electrical stimulation introduces local multi-synaptic modulation of DA release that is absent with optogenetically targeted stimulation. PMID:26011081

Pathomechanisms of Dopamine Dysregulation in DYT1 Dystonia: Targets for Therapeutics

DTIC Science & Technology

2016-10-01

DA release in DYT1(ΔE) knockin mice by assessing VMAT2 function, vesicle utilization, the ultrastructure of DA terminals, and D2 DA...in slice, the ultrastructure of DA terminals, D2 DA autoreceptor function nicotinic AChR (nAChR) heteroreceptors function. 2) To determine the

Comparing Real-time Versus Delayed Video Assessments for Evaluating ACGME Sub-competency Milestones in Simulated Patient Care Environments

PubMed Central

Stiegler, Marjorie; Hobbs, Gene; Martinelli, Susan M; Zvara, David; Arora, Harendra; Chen, Fei

2018-01-01

Background Simulation is an effective method for creating objective summative assessments of resident trainees. Real-time assessment (RTA) in simulated patient care environments is logistically challenging, especially when evaluating a large group of residents in multiple simulation scenarios. To date, there is very little data comparing RTA with delayed (hours, days, or weeks later) video-based assessment (DA) for simulation-based assessments of Accreditation Council for Graduate Medical Education (ACGME) sub-competency milestones. We hypothesized that sub-competency milestone evaluation scores obtained from DA, via audio-video recordings, are equivalent to the scores obtained from RTA. Methods Forty-one anesthesiology residents were evaluated in three separate simulated scenarios, representing different ACGME sub-competency milestones. All scenarios had one faculty member perform RTA and two additional faculty members perform DA. Subsequently, the scores generated by RTA were compared with the average scores generated by DA. Variance component analysis was conducted to assess the amount of variation in scores attributable to residents and raters. Results Paired t-tests showed no significant difference in scores between RTA and averaged DA for all cases. Cases 1, 2, and 3 showed an intraclass correlation coefficient (ICC) of 0.67, 0.85, and 0.50 for agreement between RTA scores and averaged DA scores, respectively. Analysis of variance of the scores assigned by the three raters showed a small proportion of variance attributable to raters (4% to 15%). Conclusions The results demonstrate that video-based delayed assessment is as reliable as real-time assessment, as both assessment methods yielded comparable scores. Based on a department’s needs or logistical constraints, our findings support the use of either real-time or delayed video evaluation for assessing milestones in a simulated patient care environment. PMID:29736352

Long-term evolution of 1991 DA: A dynamically evolved extinct Halley-type comet

NASA Technical Reports Server (NTRS)

Hahn, Gerhard; Bailey, M. E.

1992-01-01

The long-term dynamical evolution of 21 variational orbits for the intermediate-period asteroid 1991 DA was followed for up to +/-10(exp 5) years from the present. 1991 DA is close to the 2:7 resonance with Jupiter; it has avoided close encounters, within 1 AU, with this planet for at least the past 30,000 years, even at the node crossing. The future evolution typically shows no close encounters with Jupiter within at least 50,000 years. This corresponds to the mean time between node crossings with either Jupiter or Saturn. Close encounters with Saturn and Jupiter lead to a chaotic evolution for the whole ensemble, while secular perturbations cause large-amplitude swings in eccentricity and inclination (the latter covering the range 15 deg approximately less than i approximately less than 85 deg) which correlate with deep excursions of the perihelion distance to values much less than 1 AU. These variations are similar to those found in P/Machholz and a variety of other high-inclination orbits, e.g., P/Hartley-IRAS. We emphasize the connection between the orbital evolution of 1991 DA and that of Halley-type comets. If 1991 DA was once a comet, it is not surprising that it is now extinct.

Through-Space Ultrafast Photoinduced Electron Transfer Dynamics of a C 70 -Encapsulated Bisporphyrin Covalent Organic Polyhedron in a Low-Dielectric Medium

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

Ortiz, Michael; Cho, Sung; Niklas, Jens

Ultrafast photoinduced electron transfer (PIET) dynamics of a C 70-encapsulated bisporphyrin covalent organic polyhedron hybrid (C 70@COP-5) is studied in a nonpolar toluene medium with fluorescence and transient absorption spectroscopies. This structurally rigid donor (D)-acceptor (A) molecular hybrid offers a new platform featuring conformationally predetermined cofacial D-A orientation with a fixed edge-to-edge separation, R EE (2.8 Å), without the aid of covalent bonds. Sub-picosecond PIET (T ET ≤ 0.4 ps) and very slow charge recombination (T CR ≈ 600 ps) dynamics are observed. The origin of these dynamics is discussed in terms of enhanced D-A coupling (V = 675 cmmore » -1) and extremely small reorganization energy (λ ≈ 0.18 eV), induced by the intrinsic structural rigidity of the C 70@COP-5 complex.« less

Through-Space Ultrafast Photoinduced Electron Transfer Dynamics of a C 70 -Encapsulated Bisporphyrin Covalent Organic Polyhedron in a Low-Dielectric Medium

DOE PAGES

Ortiz, Michael; Cho, Sung; Niklas, Jens; ...

2017-03-13

Ultrafast photoinduced electron transfer (PIET) dynamics of a C 70-encapsulated bisporphyrin covalent organic polyhedron hybrid (C 70@COP-5) is studied in a nonpolar toluene medium with fluorescence and transient absorption spectroscopies. This structurally rigid donor (D)-acceptor (A) molecular hybrid offers a new platform featuring conformationally predetermined cofacial D-A orientation with a fixed edge-to-edge separation, R EE (2.8 Å), without the aid of covalent bonds. Sub-picosecond PIET (T ET ≤ 0.4 ps) and very slow charge recombination (T CR ≈ 600 ps) dynamics are observed. The origin of these dynamics is discussed in terms of enhanced D-A coupling (V = 675 cmmore » -1) and extremely small reorganization energy (λ ≈ 0.18 eV), induced by the intrinsic structural rigidity of the C 70@COP-5 complex.« less

Through-Space Ultrafast Photoinduced Electron Transfer Dynamics of a C70-Encapsulated Bisporphyrin Covalent Organic Polyhedron in a Low-Dielectric Medium.

PubMed

Ortiz, Michael; Cho, Sung; Niklas, Jens; Kim, Seonah; Poluektov, Oleg G; Zhang, Wei; Rumbles, Garry; Park, Jaehong

2017-03-29

Ultrafast photoinduced electron transfer (PIET) dynamics of a C 70 -encapsulated bisporphyrin covalent organic polyhedron hybrid (C 70 @COP-5) is studied in a nonpolar toluene medium with fluorescence and transient absorption spectroscopies. This structurally rigid donor (D)-acceptor (A) molecular hybrid offers a new platform featuring conformationally predetermined cofacial D-A orientation with a fixed edge-to-edge separation, R EE (2.8 Å), without the aid of covalent bonds. Sub-picosecond PIET (τ ET ≤ 0.4 ps) and very slow charge recombination (τ CR ≈ 600 ps) dynamics are observed. The origin of these dynamics is discussed in terms of enhanced D-A coupling (V = 675 cm -1 ) and extremely small reorganization energy (λ ≈ 0.18 eV), induced by the intrinsic structural rigidity of the C 70 @COP-5 complex.

Novel codrugs with GABAergic activity for dopamine delivery in the brain.

PubMed

Denora, Nunzio; Cassano, Tommaso; Laquintana, Valentino; Lopalco, Antonio; Trapani, Adriana; Cimmino, Concetta Stefania; Laconca, Leonardo; Giuffrida, Andrea; Trapani, Giuseppe

2012-11-01

This study investigates the use of codrugs of the GABAergic agent 2-phenyl-imidazo[1,2-a]pyridinacetamide and dopamine (DA) or ethyl ester L-Dopa (LD) as a strategy to deliver DA and simultaneously activate GABA-receptors in the brain. For this purpose, both DA and LD ethyl ester were linked by carbamate bond to imidazo[1,2-a]pyridine acetamide moieties to yield two DA- and two LD-imidazopyridine derivatives. These compounds were evaluated in vitro to assess their stability, binding affinities and cell membrane transport, and in vivo to assess their bio-availability via microdialysis studies. The two DA derivatives were adequately stable in buffered solution, but underwent cleavage in diluted human serum. By contrast, the LD derivatives were unstable in buffered solution. Receptor binding studies showed that the DA-imidazopyridine carbamates had binding affinity for benzodiazepine receptors in the nanomolar range. Brain microdialysis experiments indicated that intraperitoneal administration of the DA derivatives sustained DA levels in rat striatum over a 4-h period. These results suggest that DA-imidazopyridine carbamates are new DA codrugs with potential application for DA replacement therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Methamphetamine-induced neurotoxicity disrupts pharmacologically evoked dopamine transients in the dorsomedial and dorsolateral striatum.

PubMed

Robinson, John D; Howard, Christopher D; Pastuzyn, Elissa D; Byers, Diane L; Keefe, Kristen A; Garris, Paul A

2014-08-01

Phasic dopamine (DA) signaling, during which burst firing by DA neurons generates short-lived elevations in extracellular DA in terminal fields called DA transients, is implicated in reinforcement learning. Disrupted phasic DA signaling is proposed to link DA depletions and cognitive-behavioral impairment in methamphetamine (METH)-induced neurotoxicity. Here, we further investigated this disruption by assessing effects of METH pretreatment on DA transients elicited by a drug cocktail of raclopride, a D2 DA receptor antagonist, and nomifensine, an inhibitor of the dopamine transporter (DAT). One advantage of this approach is that pharmacological activation provides a large, high-quality data set of transients elicited by endogenous burst firing of DA neurons for analysis of regional differences and neurotoxicity. These pharmacologically evoked DA transients were measured in the dorsomedial (DM) and dorsolateral (DL) striatum of urethane-anesthetized rats by fast-scan cyclic voltammetry. Electrically evoked DA levels were also recorded to quantify DA release and uptake, and DAT binding was determined by means of autoradiography to index DA denervation. Pharmacologically evoked DA transients in intact animals exhibited a greater amplitude and frequency and shorter duration in the DM compared to the DL striatum, despite similar pre- and post-drug assessments of DA release and uptake in both sub-regions as determined from the electrically evoked DA signals. METH pretreatment reduced transient activity. The most prominent effect of METH pretreatment on transients across striatal sub-region was decreased amplitude, which mirrored decreased DAT binding and was accompanied by decreased DA release. Overall, these results identify marked intrastriatal differences in the activity of DA transients that appear independent of presynaptic mechanisms for DA release and uptake and further support disrupted phasic DA signaling mediated by decreased DA release in rats with METH-induced neurotoxicity.

Managing Risk for Cassini During Mission Operations and Data Analysis (MOandDA)

NASA Technical Reports Server (NTRS)

Witkowski, Mona M.

2002-01-01

A Risk Management Process has been tailored for Cassini that not only satisfies the requirements of NASA and JPL, but also allows the Program to proactively identify and assess risks that threaten mission objectives. Cassini Risk Management is a team effort that involves both management and engineering staff. The process is managed and facilitated by the Mission Assurance Manager (MAM), but requires regular interactions with Program Staff and team members to instill the risk management philosophy into the day to day mission operations. While Risk Management is well defined for projects in the development phase, it is a relatively new concept for Mission Operations. The Cassini team has embraced this process and has begun using it in an effective, proactive manner, to ensure mission success. It is hoped that the Cassini Risk Management Process will form the basis by which risk management is conducted during MO&DA on future projects. proactive in identifying, assessing and mitigating risks before they become problems. Cost ehtiveness is achieved by: Comprehensively identifying risks Rapidly assessing which risks require the expenditure of pruject cewums Taking early actions to mitigate these risks Iterating the process frequently, to be responsive to the dynamic internal and external environments The Cassini Program has successfully implemented a Risk Management Process for mission operations, The initial SRL has been developed and input into he online tool. The Risk Management webbased system has been rolled out for use by the flight team and risk owners we working proactive in identifying, assessing and mitigating risks before they become problems. Cost ehtiveness is achieved by: Comprehensively identifying risks Rapidly assessing which risks require the expenditure of pruject cewums Taking early actions to mitigate these risks Iterating the process frequently, to be responsive to the dynamic internal and external environments The Cassini Program has successfully implemented a Risk Management Process for mission operations, The initial SRL has been developed and input into he online tool. The Risk Management webbased system has been rolled out for use by the flight team and risk owners we working put into place will become visible and will be illusmted in future papers.

METHAMPHETAMINE-INDUCED NEUROTOXICITY DISRUPTS PHARMACOLOGICALLY EVOKED DOPAMINE TRANSIENTS IN THE DORSOMEDIAL AND DORSOLATERAL STRIATUM

PubMed Central

Robinson, John D.; Howard, Christopher D.; Pastuzyn, Elissa D.; Byers, Diane L.; Keefe, Kristen A.; Garris, Paul A.

2014-01-01

Phasic dopamine (DA) signaling, during which burst firing by dopamine neurons generates short-lived elevations in extracellular DA in terminal fields called DA transients, is implicated in reinforcement learning. Disrupted phasic DA signaling is proposed to link DA depletions and cognitive-behavioral impairment in methamphetamine (METH)-induced neurotoxicity. Here we further investigated this disruption by assessing effects of METH pretreatment on DA transients elicited by a drug cocktail of raclopride, a D2 DA receptor antagonist, and nomifensine, an inhibitor of the dopamine transporter (DAT). One advantage of this approach is that pharmacological activation provides a large, high-quality data set of transients elicited by endogenous burst firing of DA neurons for analysis of regional differences and neurotoxicity. These pharmacologically evoked DA transients were measured in the dorsomedial (DM) and dorsolateral (DL) striatum of urethane-anesthetized rats by fast-scan cyclic voltammetry. Electrically evoked DA levels were also recorded to quantify DA release and uptake, and DAT binding was determined by autoradiography to index DA denervation. Pharmacologically evoked DA transients in intact animals exhibited a greater amplitude and frequency and shorter duration in the DM compared to the DL striatum, despite similar pre- and post-drug assessments of DA release and uptake in both sub-regions as determined from the electrically evoked DA signals. METH pretreatment reduced transient activity. The most prominent effect of METH pretreatment on transients across striatal sub-region was decreased amplitude, which mirrored decreased DAT binding and was accompanied by decreased DA release. Overall, these results identify marked intrastriatal differences in the activity of DA transients that appear independent of presynaptic mechanisms for DA release and uptake and further support disrupted phasic DA signaling mediated by decreased DA release in rats with METH-induced neurotoxicity. PMID:24562969

Dopamine Dynamics and Signaling in Drosophila: An Overview of Genes, Drugs and Behavioral Paradigms

PubMed Central

Yamamoto, Shinya; Seto, Elaine S.

2014-01-01

Changes in dopamine (DA) signaling have been implicated in a number of human neurologic and psychiatric disorders. Similarly, defects in DA signaling in the fruit fly, Drosophila melanogaster, have also been associated with several behavioral defects. As most genes involved in DA synthesis, transport, secretion, and signaling are conserved between species, Drosophila is a powerful genetic model organism to study the regulation of DA signaling in vivo. In this review, we will provide an overview of the genes and drugs that regulate DA biology in Drosophila. Furthermore, we will discuss the behavioral paradigms that are regulated by DA signaling in flies. By analyzing the genes and neuronal circuits that govern such behaviors using sophisticated genetic, pharmacologic, electrophysiologic, and imaging approaches in Drosophila, we will likely gain a better understanding about how this neuromodulator regulates motor tasks and cognition in humans. PMID:24770636

Activation of VTA GABA neurons disrupts reward consumption

PubMed Central

van Zessen, Ruud; Phillips, Jana L.; Budygin, Evgeny A.; Stuber, Garret D.

2012-01-01

The activity of Ventral Tegmental Area (VTA) dopamine (DA) neurons promotes behavioral responses to rewards and environmental stimuli that predict them. VTA GABA inputs synapse directly onto DA neurons and may regulate DA neuronal activity to alter reward-related behaviors, however, the functional consequences of selective activation of VTA GABA neurons remains unknown. Here, we show that in vivo optogenetic activation of VTA GABA neurons disrupts reward consummatory behavior, but not conditioned anticipatory behavior in response to reward-predictive cues. In addition, direct activation of VTA GABA projections to the nucleus accumbens (NAc) resulted in detectable GABA release, but did not alter reward consumption. Furthermore, optogenetic stimulation of VTA GABA neurons directly suppressed the activity and excitability of neighboring DA neurons, as well as the release of DA in the NAc, suggesting that the dynamic interplay between VTA DA and GABA neurons can control the initiation and termination of reward-related behaviors. PMID:22445345

Convergent Validity of the Autism Spectrum Disorders-Diagnostic Adult (ASD-DA) with the Pervasive Developmental Disorder/Autism Subscale of the Diagnostic Assessment for the Severely Handicapped-II (DASH-II)

ERIC Educational Resources Information Center

Belva, Brian C.; Matson, Johnny L.; Hattier, Megan A.; Kozlowski, Allison M.; Bamburg, Jay W.

2012-01-01

The "Autism Spectrum Disorders-Diagnosis for Adults" ("ASD-DA") is a standardized assessment used to measure autistic symptomatology in adults with intellectual disabilities (ID). In order to further establish the validity of this measure, convergent validity of the "ASD-DA" was established by comparing…

Endogenous dopamine (DA) modulates (3H)spiperone binding in vivo in rat brain

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

Bischoff, S.; Krauss, J.; Grunenwald, C.

1991-01-01

(3H)spiperone (SPI) binding in vivo, biochemical parameters and behavior were measured after modulating DA levels by various drug treatments. DA releasers and uptake inhibitors increased SPI binding in rat striatum. In other brain areas, the effects were variable, but only the pituitary remained unaffected. Surprisingly, nomifensine decreased SPI binding in frontal cortex. The effects of these drugs were monitored by measuring DA, serotonin (5-HT) and their metabolites in the same rats. The increased SPI binding in striatum was parallel to the locomotor stimulation with the following rank order: amfonelic acid greater than nomifensine greater than D-amphetamine greater than or equalmore » to methylphenidate greater than amineptine greater than bupropion. Decreasing DA levels with reserpine or alpha-methyl-para-tyrosine reduced SPI binding by 45% in striatum only when both drugs were combined. In contrast, reserpine enhanced SPI binding in pituitary. Thus, the amount of releasable DA seems to modulate SPI binding characteristics. It is suggested that in vivo, DA receptors are submitted to dynamic regulation in response to changes in intrasynaptic concentrations of DA.« less

Emotional states of love moderate the association between catecholamines and female sexual responses in the laboratory.

PubMed

Dundon, Carolyn M; Rellini, Alessandra H

2012-10-01

Research suggests that there are three interrelated, yet distinct, emotion-motivation brain systems for human love (lust, romantic love, and attachment), each associated with a unique catecholaminergic and hormonal profile. Of interest for the current study are norepinephrine (NE) and dopamine (DA), which have a hypothesized connection with romantic love. As NE and DA are also known to facilitate sexual arousal, it is plausible that NE and DA may have a greater positive association with the sexual arousal responses of women in romantic love compared with women in lust. This study investigated if the effects of NE and DA activity on sexual arousal responses would differ depending on emotion-motivation state (Lust or Romantic). Physiological sexual arousal was assessed by photoplethysmography and subjective sexual arousal was assessed with a participant-controlled lever. Seventeen women were included in the Lust group and 29 in the Romantic group. All participants provided a urine sample (to assess NE and DA) and completed a psychophysiological assessment. Elevated NE was positively and significantly associated with greater subjective and physiological sexual arousal for the Lust group, but not for the Romantic group. Similarly, elevated DA was positively and significantly associated with greater subjective sexual arousal for the Lust group, but not for the Romantic group. The sexual arousal responses of women in the Lust group, but not in the Romantic group, were positively and significantly associated with elevated NE and DA. It is feasible that, when women are seeking a partner (Lust), NE and DA may facilitate attention toward sexually relevant stimuli. © 2012 International Society for Sexual Medicine.

Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis.

PubMed

Segurado, O G; Sasso, E H

2014-01-01

Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

Monoaminc and metabolite levels in the cerebrospinal fluid of hibernating and euthermic marmots.

PubMed

Reid; Kilduff; Romero; Florant; Dement; Heller

1992-03-01

Cerebrospinal fluid from yellow-bellied marmots, Marmota flaviventris, was analysed for monoamine and monoamine metabolite content during euthermia and deep hibernation. Dopamine (DA) levels were decreased, while DA metabolite levels, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were dramatically increased in hibernating marmots. Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5HIAA) levels were also greatly enhanced during hibernation while norepinephrine (NE) levels were only moderately increased. These findings demonstrate that cerebrospinal monoamine levels are dynamically altered during hibernation, such that DA versus 5-HT and NE levels undergo opposite changes. Therefore, these data indicate that DA, 5-HT and NE neuronal systems are differentially altered during hibernation in mammals.

More Fluorous Surface Modifier Makes it Less Oleophobic: Fluorinated-Siloxane Copolymer/PDMS Coatings

PubMed Central

Zhang, Wei; Zheng, Ying; Orsini, Lorenzo; Morelli, Andrea; Galli, Giancarlo; Chiellini, Emo; Carpenter, Everett E.; Wynne, Kenneth J.

2010-01-01

A copolyacrylate with semifluorinated and polydimethylsiloxane side chains (D5-3) was used as a surface modifier for a condensation cured PDMS coating. The decyl fluorous group is represented by “D”; “5” is a 5 kDa silicone, and “3” the mole ratio of fluorous to silicone side chain. Wetting behavior was assessed by dynamic contact angle (DCA) analysis using isopropanol, which differentiates silicone and fluorous wetting behavior. Interestingly, a maximum in surface oleophobicity was found at low D5-3 concentration (0.4 wt%). Higher concentrations result in decreased oleophobicity reflected in decreased contact angles. To understand this unexpected observation, dynamic light scattering (DLS) studies were initiated on a model system consisting of hydroxyl-terminated PDMS (18 kDa) containing varying amounts of D5-3. DLS revealed D5-3 aggregation as a function of temperature and concentration. A model is proposed by which D5-3 surface concentration is depleted via phase separation favoring D5-3 aggregation at concentrations >0.4 wt%, that is, the CMC. This model suggests increasing aggregate / micelle concentrations at increased D5-3 concentration. Bulk morphologies studied by scanning electron microscopy (SEM) and atomic force microscopy (AFM) support this model by showing increased aggregate concentrations with increased D5-3 >0.4 wt%. PMID:20000339

Indices and Dynamics of Global Hydroclimate Over the Past Millennium from Data Assimilation

NASA Astrophysics Data System (ADS)

Steiger, N. J.; Smerdon, J. E.

2017-12-01

Reconstructions based on data assimilation (DA) are at the forefront of model-data syntheses in that such reconstructions optimally fuse proxy data with climate models. DA-based paleoclimate reconstructions have the benefit of being physically-consistent across the reconstructed climate variables and are capable of providing dynamical information about past climate phenomena. Here we use a new implementation of DA, that includes updated proxy system models and climate model bias correction procedures, to reconstruct global hydroclimate on seasonal and annual timescales over the last millennium. This new global hydroclimate product includes reconstructions of the Palmer Drought Severity Index, the Standardized Precipitation Evapotranspiration Index, and global surface temperature along with dynamical variables including the Nino 3.4 index, the latitudinal location of the intertropical convergence zone, and an index of the Atlantic Multidecadal Oscillation. Here we present a validation of the reconstruction product and also elucidate the causes of severe drought in North America and in equatorial Africa. Specifically, we explore the connection between droughts in North America and modes of ocean variability in the Pacific and Atlantic oceans. We also link drought over equatorial Africa to shifts of the intertropical convergence zone and modes of ocean variability.

Evolution of the ATLAS PanDA workload management system for exascale computational science

NASA Astrophysics Data System (ADS)

Maeno, T.; De, K.; Klimentov, A.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.; Yu, D.; Atlas Collaboration

2014-06-01

An important foundation underlying the impressive success of data processing and analysis in the ATLAS experiment [1] at the LHC [2] is the Production and Distributed Analysis (PanDA) workload management system [3]. PanDA was designed specifically for ATLAS and proved to be highly successful in meeting all the distributed computing needs of the experiment. However, the core design of PanDA is not experiment specific. The PanDA workload management system is capable of meeting the needs of other data intensive scientific applications. Alpha-Magnetic Spectrometer [4], an astro-particle experiment on the International Space Station, and the Compact Muon Solenoid [5], an LHC experiment, have successfully evaluated PanDA and are pursuing its adoption. In this paper, a description of the new program of work to develop a generic version of PanDA will be given, as well as the progress in extending PanDA's capabilities to support supercomputers and clouds and to leverage intelligent networking. PanDA has demonstrated at a very large scale the value of automated dynamic brokering of diverse workloads across distributed computing resources. The next generation of PanDA will allow other data-intensive sciences and a wider exascale community employing a variety of computing platforms to benefit from ATLAS' experience and proven tools.

Trends in the application of dynamic allocation methods in multi-arm cancer clinical trials.

PubMed

Pond, Gregory R; Tang, Patricia A; Welch, Stephen A; Chen, Eric X

2010-06-01

Dynamic allocation (DA) methods which attempt to balance baseline prognostic factors between treatment arms, can be used in multi-arm clinical trials to sequentially allocate patients to treatment. Although some experts express concern regarding the validity of inference from trials using DA, others believe DA methods produce more credible results. A review of published multi-arm cancer clinical trials was conducted to explore the frequency of DA use in oncology. Multi-arm phase III clinical trials of at least 100 patients per arm, published in 13 major oncology journals from 1995-2005 were manually reviewed. Information about reported use of DA methods, or randomization via random permuted blocks (PB), was extracted along with trial characteristics. Of 476 published clinical trials, 112 (23.5%) reported using some form of DA method, while 103 (21.6%) reported using PB methods. Most trials (403 or 84.7%) reported stratifying on at least one baseline factor. The mean number of stratification factors was 2.70 per trial, and 78.6% of DA trials reported 3 or more stratification factors compared with 30.2% of non-DA trials (p < 0.001). The frequency of DA use increased over time, with 20.2%, 21.3%, 25.8%, 28.8% and 38.9% of trials reported use in 1995-2001, 2002, 2003, 2004, and 2005, respectively. Use of DA methods was more frequently reported in trials involving an academic co-operative group (28.4% vs. 13.8%), however, no difference was observed between industry-funded and other-funded trials (24.0% vs. 23.2%) or geographical region (19.7% of North American trials, 26.2% of European trials and 21.7% of multinational/other trials). As a retrospective analysis, the true frequency of DA use is likely underreported. Few trials gave complete details of the allocation method used, thus it is possible some manuscripts reported incorrect allocation methods. Journals were selected which were assumed to publish most large, multi-arm clinical trials in cancer from 1995-2005, however, some trials were likely reported in journals other than what was reviewed. DA methods are frequently used in multi-arm cancer clinical trials. The use of DA appears to becoming more common over time and are used more frequently when an academic cooperative group is involved. No relationship between industry funded trials or geographic region and allocation method was observed. Clinical Trials 2010; 7: 227-234. http://ctj.sagepub.com.

Functional and Structural Characterization of a Thermostable Phospholipase A2 from a Sparidae Fish (Diplodus annularis).

PubMed

Smichi, Nabil; Othman, Houcemeddine; Achouri, Neila; Noiriel, Alexandre; Arondel, Vincent; Srairi-Abid, Najet; Abousalham, Abdelkarim; Gargouri, Youssef; Miled, Nabil; Fendri, Ahmed

2017-03-22

Novel phospholipase (PLA 2 ) genes from the Sparidae family were cloned. The sequenced PLA 2 revealed an identity with pancreatic PLA 2 group IB. To better understand the structure/function relationships of these enzymes and their evolution, the Diplodus annularis PLA 2 (DaPLA 2 ) was overexpressed in E. coli. The refolded enzyme was purified by Ni-affinity chromatography and has a molecular mass of 15 kDa as determined by MALDI-TOF spectrometry. Interestingly, unlike the pancreatic type, the DaPLA 2 was active and stable at higher temperatures, which suggests its great potential in biotechnological applications. The 3D structure of DaPLA 2 was constructed to gain insights into the functional properties of sparidae PLA 2 . Molecular docking and dynamic simulations were performed to explain the higher thermal stability and the substrate specificity of DaPLA 2 . Using the monolayer technique, the purified DaPLA 2 was found to be active on various phospholipids ranging from 10 to 20 mN·m -1 , which explained the absence of the hemolytic activity for DaPLA 2 .

Overview of ATLAS PanDA Workload Management

NASA Astrophysics Data System (ADS)

Maeno, T.; De, K.; Wenaus, T.; Nilsson, P.; Stewart, G. A.; Walker, R.; Stradling, A.; Caballero, J.; Potekhin, M.; Smith, D.; ATLAS Collaboration

2011-12-01

The Production and Distributed Analysis System (PanDA) plays a key role in the ATLAS distributed computing infrastructure. All ATLAS Monte-Carlo simulation and data reprocessing jobs pass through the PanDA system. We will describe how PanDA manages job execution on the grid using dynamic resource estimation and data replication together with intelligent brokerage in order to meet the scaling and automation requirements of ATLAS distributed computing. PanDA is also the primary ATLAS system for processing user and group analysis jobs, bringing further requirements for quick, flexible adaptation to the rapidly evolving analysis use cases of the early datataking phase, in addition to the high reliability, robustness and usability needed to provide efficient and transparent utilization of the grid for analysis users. We will describe how PanDA meets ATLAS requirements, the evolution of the system in light of operational experience, how the system has performed during the first LHC data-taking phase and plans for the future.

Overview of ATLAS PanDA Workload Management

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

Maeno T.; De K.; Wenaus T.

2011-01-01

The Production and Distributed Analysis System (PanDA) plays a key role in the ATLAS distributed computing infrastructure. All ATLAS Monte-Carlo simulation and data reprocessing jobs pass through the PanDA system. We will describe how PanDA manages job execution on the grid using dynamic resource estimation and data replication together with intelligent brokerage in order to meet the scaling and automation requirements of ATLAS distributed computing. PanDA is also the primary ATLAS system for processing user and group analysis jobs, bringing further requirements for quick, flexible adaptation to the rapidly evolving analysis use cases of the early datataking phase, in additionmore » to the high reliability, robustness and usability needed to provide efficient and transparent utilization of the grid for analysis users. We will describe how PanDA meets ATLAS requirements, the evolution of the system in light of operational experience, how the system has performed during the first LHC data-taking phase and plans for the future.« less

Dynamics of rapid dopamine release in the nucleus accumbens during goal-directed behaviors for cocaine versus natural rewards

PubMed Central

Cameron, Courtney M.; Wightman, R. Mark; Carelli, Regina M.

2014-01-01

Electrophysiological studies show that distinct subsets of nucleus accumbens (NAc) neurons differentially encode information about goal-directed behaviors for intravenous cocaine versus natural (food/water) rewards. Further, NAc rapid dopamine signaling occurs on a timescale similar to phasic cell firing during cocaine and natural reward-seeking behaviors. However, it is not known whether dopamine signaling is reinforcer specific (i.e., is released during responding for only one type of reinforcer) within discrete NAc locations, similar to neural firing dynamics. Here, fast-scan cyclic voltammetry (FSCV) was used to measure rapid dopamine release during multiple schedules involving sucrose reward and cocaine self-administration (n=8 rats) and, in a separate group of rats (n = 6), during a sucrose/food multiple schedule. During the sucrose/cocaine multiple schedule, dopamine increased within seconds of operant responding for both reinforcers. Although dopamine release was not reinforcer specific, more subtle differences were observed in peak dopamine concentration [DA] across reinforcer conditions. Specifically, peak [DA] was higher during the first phase of the multiple schedule, regardless of reinforcer type. Further, the time to reach peak [DA] was delayed during cocaine-responding compared to sucrose. During the sucrose/food multiple schedule, increases in dopamine release were also observed relative to operant responding for both natural rewards. However, peak [DA] was higher relative to responding for sucrose than food, regardless of reinforcer order. Overall, the results reveal the dynamics of rapid dopamine signaling in discrete locations in the NAc across reward conditions, and provide novel insight into the functional role of this system in reward-seeking behaviors. PMID:25174553

Assessment of SWE data assimilation for ensemble streamflow predictions

NASA Astrophysics Data System (ADS)

Franz, Kristie J.; Hogue, Terri S.; Barik, Muhammad; He, Minxue

2014-11-01

An assessment of data assimilation (DA) for Ensemble Streamflow Prediction (ESP) using seasonal water supply hindcasting in the North Fork of the American River Basin (NFARB) and the National Weather Service (NWS) hydrologic forecast models is undertaken. Two parameter sets, one from the California Nevada River Forecast Center (RFC) and one from the Differential Evolution Adaptive Metropolis (DREAM) algorithm, are tested. For each parameter set, hindcasts are generated using initial conditions derived with and without the inclusion of a DA scheme that integrates snow water equivalent (SWE) observations. The DREAM-DA scenario uses an Integrated Uncertainty and Ensemble-based data Assimilation (ICEA) framework that also considers model and parameter uncertainty. Hindcasts are evaluated using deterministic and probabilistic forecast verification metrics. In general, the impact of DA on the skill of the seasonal water supply predictions is mixed. For deterministic (ensemble mean) predictions, the Percent Bias (PBias) is improved with integration of the DA. DREAM-DA and the RFC-DA have the lowest biases and the RFC-DA has the lowest Root Mean Squared Error (RMSE). However, the RFC and DREAM-DA have similar RMSE scores. For the probabilistic predictions, the RFC and DREAM have the highest Continuous Ranked Probability Skill Scores (CRPSS) and the RFC has the best discrimination for low flows. Reliability results are similar between the non-DA and DA tests and the DREAM and DREAM-DA have better reliability than the RFC and RFC-DA for forecast dates February 1 and later. Despite producing improved streamflow simulations in previous studies, the hindcast analysis suggests that the DA method tested may not result in obvious improvements in streamflow forecasts. We advocate that integration of hindcasting and probabilistic metrics provides more rigorous insight on model performance for forecasting applications, such as in this study.

Predicting non-stationary algal dynamics following changes in hydrometeorological conditions using data assimilation techniques

NASA Astrophysics Data System (ADS)

Kim, S.; Seo, D. J.

2017-12-01

When water temperature (TW) increases due to changes in hydrometeorological conditions, the overall ecological conditions change in the aquatic system. The changes can be harmful to human health and potentially fatal to fish habitat. Therefore, it is important to assess the impacts of thermal disturbances on in-stream processes of water quality variables and be able to predict effectiveness of possible actions that may be taken for water quality protection. For skillful prediction of in-stream water quality processes, it is necessary for the watershed water quality models to be able to reflect such changes. Most of the currently available models, however, assume static parameters for the biophysiochemical processes and hence are not able to capture nonstationaries seen in water quality observations. In this work, we assess the performance of the Hydrological Simulation Program-Fortran (HSPF) in predicting algal dynamics following TW increase. The study area is located in the Republic of Korea where waterway change due to weir construction and drought concurrently occurred around 2012. In this work we use data assimilation (DA) techniques to update model parameters as well as the initial condition of selected state variables for in-stream processes relevant to algal growth. For assessment of model performance and characterization of temporal variability, various goodness-of-fit measures and wavelet analysis are used.

Combined Application of UHPLC-QTOF/MS, HPLC-ELSD and 1 H-NMR Spectroscopy for Quality Assessment of DA-9801, A Standardised Dioscorea Extract.

PubMed

Kang, Kyo Bin; Ryu, Jayoung; Cho, Youngwoong; Choi, Sang-Zin; Son, Miwon; Sung, Sang Hyun

2017-05-01

DA-9801, a standardised 50% aqueous ethanolic extract of a mixture of Dioscorea japonica and D. nipponica, is a botanical drug candidate for the treatment of diabetic neuropathy, which finished its US phase II clinical trials recently. An advanced quality control method is needed for further development of DA-9801, considering its high contents of both primary and secondary metabolites. Development of a quality assessment strategy for DA-9801, based on the combination of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H-NMR spectroscopy. The method was developed and tested with 15 batch products of DA-9801. The steroidal saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS and were quantified with the validated HPLC-ELSD method. Primary metabolites of DA-9801 were identified and profiled using 1 H-NMR spectrometry. The batch-to-batch equivalence of DA-9801 was tested with the 1 H-NMR spectra using spectral binning, correlation analysis, and principal component analysis. Six major saponins of DA-9801 were tentatively identified by UHPLC-QTOF/MS. Among them, protodioscin and dioscin were quantified by the validated HPLC-ELSD method. Twenty-six metabolites were identified in 1 H-NMR spectra. The similarity between DA-9801 batches could be evaluated with the NMR spectra of DA-9801. The 1 H-NMR method also revealed that two Dioscorea species contributed distinct amino acids to the contents of DA-9801. This study validates the effectiveness of UHPLC-QTOF/MS, HPLC-ELSD, and 1 H NMR-combined method for quality control of DA-9801 and its crude materials. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Army Reserve Capabilities-Based Prioritization Study

DTIC Science & Technology

2008-08-15

regulations and procedural guidance are not sufficient to determine the ‘ground truth’ of Planning, Programming, Budgeting and Execution System (PPBES...list), Department of the Army (DA) and Army Reserve Regulations and DA pamphlets. A-3 c. Why this Study Has Not Yet Been Performed/Funded...Memorandum, Management Decision Packages, 1-N list), Department of the Army (DA) and Army Reserve Regulations and DA pamphlets. b. Initial Assessment

Amphetamine regulation of mesolimbic dopamine/cholecystokinin neurotransmission.

PubMed

Hurd, Y L; Lindefors, N; Brodin, E; Brené, S; Persson, H; Ungerstedt, U; Hökfelt, T

1992-04-24

The effects of acute and repeated amphetamine administration on mesolimbic dopamine (DA) neurons was assessed by studying DA and cholecystokinin (CCK) release in the nucleus accumbens (Acc), as well as effects on mRNA genes regulating DA and CCK synthesis in ventral tegmental area (VTA) cells in rats. Amphetamine (1.5 mg/kg) markedly increased extracellular levels of DA in the medial Acc (assessed by in vivo microdialysis) in drug-naive animals, about twice the amount released in animals repeatedly administered the drug for the previous 7 days (twice daily). CCK overflow was found to mirror the DA responses in that the very transient elevation of CCK monitored in drug-naive animals was attenuated in those with prior amphetamine use. The attenuation of both DA and CCK overflow in the medial Acc was found to be associated with a decrease in the number of CCK mRNA-positive VTA neurons (assessed by in situ hybridization histochemistry). Although the number of cells expressing CCK mRNA were decreased, the gene expression in those positive CCK and tyrosine hydroxylase mRNA cells in the VTA was significantly increased. The CCK mRNA neurons in the VTA were positively identified as those projecting to the medial Acc by the local perfusion of Fluoro-gold retrograde tracer via microdialysis probes located in the Acc.

Epothilone D Prevents Binge Methamphetamine-Mediated Loss of Striatal Dopaminergic Markers

PubMed Central

Killinger, Bryan A.; Moszczynska, Anna

2016-01-01

Exposure to binge methamphetamine (METH) can result in a permanent or transient loss of dopaminergic (DAergic) markers such as dopamine (DA), dopamine transporter (DAT), and tyrosine hydroxylase (TH) in the striatum. We hypothesized that the METH-induced loss of striatal DAergic markers was, in part, due to destabilization of microtubules (MTs) in the nigrostriatal DA pathway that ultimately impedes anterograde axonal transport of these markers. To test this hypothesis, adult male Sprague Dawley rats were treated with binge METH or saline in the presence or absence of epothilone D (EpoD), a MT-stabilizing compound, and assessed for the levels of several DAergic markers as well as for the levels of tubulins and their posttranslational modifications (PMTs) at 3 days after the treatments. Binge METH induced a loss of stable long-lived MTs within the striatum but not within the SNpc. Treatment with a low dose of EpoD increased the levels of markers of stable MTs and prevented METH-mediated deficits in several DAergic markers in the striatum. By contrast, administration of a high dose of EpoD appeared to destabilize MTs and potentiated the METH-induced deficits in several DAergic markers. The low-dose EpoD also prevented the METH-induced increase in striatal DA turnover and increased behavioral stereotypy during METH treatment. Together, these results demonstrate that MT dynamics plays a role in the development of METH-induced losses of several DAergic markers in the striatum and may mediate METH-induced degeneration of terminals in the nigrostriatal DA pathway. Our study also demonstrates that MT-stabilizing drugs, such as EpoD have a potential to serve as useful therapeutic agents to restore function of DAergic nerve terminals following METH exposure when administered at low doses. PMID:26465779

Using iPSC-derived human DA neurons from opioid-dependent subjects to study dopamine dynamics.

PubMed

Sheng, Yang; Filichia, Emily; Shick, Elizabeth; Preston, Kenzie L; Phillips, Karran A; Cooperman, Leslie; Lin, Zhicheng; Tesar, Paul; Hoffer, Barry; Luo, Yu

2016-08-01

The dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug-dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology. In this study, we produced DA neurons differentiated using iPSCs derived from opioid-dependent and control subjects carrying different 3' VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3). In addition, the effects of valproic acid (VPA) exposures on iPSC-derived human DA neurons are also examined. We present the first evidence suggesting that the 3' VNTR polymorphism in the hDAT gene affects DAT expression level in iPSC-derived human DA neurons. In human DA neurons, which provide an appropriate cellular milieu, VPA treatment alters the expression of several genes important for dopaminergic neuron function including DAT, Nurr1, and TH; this might partly explain its action in regulating addictive behaviors. VPA treatment also significantly increased DA D2 receptor (Drd2) expression, especially in the opioid-dependent iPSC cell lines. Our data suggest that human iPSC-derived DA neurons may be useful in in vitro experimental model to examine the effects of genetic variation in gene regulation, to examine the underlying mechanisms in neurological disorders including drug addiction, and to serve as a platform for therapeutic development.

Dynamics of rapid dopamine release in the nucleus accumbens during goal-directed behaviors for cocaine versus natural rewards.

PubMed

Cameron, Courtney M; Wightman, R Mark; Carelli, Regina M

2014-11-01

Electrophysiological studies show that distinct subsets of nucleus accumbens (NAc) neurons differentially encode information about goal-directed behaviors for intravenous cocaine versus natural (food/water) rewards. Further, NAc rapid dopamine signaling occurs on a timescale similar to phasic cell firing during cocaine and natural reward-seeking behaviors. However, it is not known whether dopamine signaling is reinforcer specific (i.e., is released during responding for only one type of reinforcer) within discrete NAc locations, similar to neural firing dynamics. Here, fast-scan cyclic voltammetry (FSCV) was used to measure rapid dopamine release during multiple schedules involving sucrose reward and cocaine self-administration (n = 8 rats) and, in a separate group of rats (n = 6), during a sucrose/food multiple schedule. During the sucrose/cocaine multiple schedule, dopamine increased within seconds of operant responding for both reinforcers. Although dopamine release was not reinforcer specific, more subtle differences were observed in peak dopamine concentration [DA] across reinforcer conditions. Specifically, peak [DA] was higher during the first phase of the multiple schedule, regardless of reinforcer type. Further, the time to reach peak [DA] was delayed during cocaine-responding compared to sucrose. During the sucrose/food multiple schedule, increases in dopamine release were also observed relative to operant responding for both natural rewards. However, peak [DA] was higher relative to responding for sucrose than food, regardless of reinforcer order. Overall, the results reveal the dynamics of rapid dopamine signaling in discrete locations in the NAc across reward conditions, and provide novel insight into the functional role of this system in reward-seeking behaviors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Scientific and technological capabilities in health-related areas: opportunities, challenges, and interactions with the industrial sector.

PubMed

Vargas, Marco Antonio; Britto, Jorge

2016-11-03

Characterization of the scientific and technological infrastructure in health and its interactions with the industrial sector provides key elements for understanding the dynamics of innovation in health. This study conducts an exploratory analysis of the potentialities and limitations associated with scientific and technological capabilities in the health area in Brazil and the different links between the scientific and industrial sectors in health. The analysis points to important growth in internationally indexed research output, especially in certain areas such as pharmaceutics, public health, genetics, morphology, physiology, and microbiology. There has also been important growth in research groups that interact with the industrial sector in selected areas of health. The study highlights the importance of building more solid and permanent bridges between companies, research institutions, and the health system, linking the knowledge developed in research institutions to the dynamics of the industrial sector in health. Resumo: A caracterização da infraestrutura científica e tecnológica na área da saúde e das suas formas de articulação com a base produtiva representam elementos centrais na compreensão da dinâmica de inovação em saúde. Este estudo faz uma análise exploratória sobre as potencialidades e limitações associadas às capacitações científicas e tecnológicas na área da saúde no Brasil e as formas de articulação entre a base científica e a base produtiva em saúde. A análise aponta para o crescimento expressivo da produção bibliográfica com circulação internacional no campo da saúde, particularmente em determinadas áreas como farmácia, saúde coletiva, genética, morfologia, fisiologia e microbiologia. Além disso, observa-se um crescimento expressivo dos grupos de pesquisa com relacionamentos com o setor produtivo em áreas selecionadas da saúde. Destaca-se a importância da construção de pontes mais sólidas e permanentes entre empresas, instituições de pesquisa e sistema de saúde, articulando-se o conhecimento desenvolvido em instituições de pesquisa à dinamização da base produtiva em saúde.

Structure of the 30 kDa HIV-1 RNA Dimerization Signal by a Hybrid Cryo-EM, NMR, and Molecular Dynamics Approach.

PubMed

Zhang, Kaiming; Keane, Sarah C; Su, Zhaoming; Irobalieva, Rossitza N; Chen, Muyuan; Van, Verna; Sciandra, Carly A; Marchant, Jan; Heng, Xiao; Schmid, Michael F; Case, David A; Ludtke, Steven J; Summers, Michael F; Chiu, Wah

2018-03-06

Cryoelectron microscopy (cryo-EM) and nuclear magnetic resonance (NMR) spectroscopy are routinely used to determine structures of macromolecules with molecular weights over 65 and under 25 kDa, respectively. We combined these techniques to study a 30 kDa HIV-1 dimer initiation site RNA ([DIS] 2 ; 47 nt/strand). A 9 Å cryo-EM map clearly shows major groove features of the double helix and a right-handed superhelical twist. Simulated cryo-EM maps generated from time-averaged molecular dynamics trajectories (10 ns) exhibited levels of detail similar to those in the experimental maps, suggesting internal structural flexibility limits the cryo-EM resolution. Simultaneous inclusion of the cryo-EM map and 2 H-edited NMR-derived distance restraints during structure refinement generates a structure consistent with both datasets and supporting a flipped-out base within a conserved purine-rich bulge. Our findings demonstrate the power of combining global and local structural information from these techniques for structure determination of modest-sized RNAs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Convergent evidence from alcohol-dependent humans and rats for a hyperdopaminergic state in protracted abstinence

PubMed Central

Hirth, Natalie; Meinhardt, Marcus W.; Noori, Hamid R.; Salgado, Humberto; Torres-Ramirez, Oswaldo; Uhrig, Stefanie; Broccoli, Laura; Vengeliene, Valentina; Roßmanith, Martin; Perreau-Lenz, Stéphanie; Köhr, Georg; Sommer, Wolfgang H.; Spanagel, Rainer; Hansson, Anita C.

2016-01-01

A major hypothesis in addiction research is that alcohol induces neuroadaptations in the mesolimbic dopamine (DA) system and that these neuroadaptations represent a key neurochemical event in compulsive drug use and relapse. Whether these neuroadaptations lead to a hypo- or hyperdopaminergic state during abstinence is a long-standing, unresolved debate among addiction researchers. The answer is of critical importance for understanding the neurobiological mechanism of addictive behavior. Here we set out to study systematically the neuroadaptive changes in the DA system during the addiction cycle in alcohol-dependent patients and rats. In postmortem brain samples from human alcoholics we found a strong down-regulation of the D1 receptor- and DA transporter (DAT)-binding sites, but D2-like receptor binding was unaffected. To gain insight into the time course of these neuroadaptations, we compared the human data with that from alcohol-dependent rats at several time points during abstinence. We found a dynamic regulation of D1 and DAT during 3 wk of abstinence. After the third week the rat data mirrored our human data. This time point was characterized by elevated extracellular DA levels, lack of synaptic response to D1 stimulation, and augmented motor activity. Further functional evidence is given by a genetic rat model for hyperdopaminergia that resembles a phenocopy of alcohol-dependent rats during protracted abstinence. In summary, we provide a new dynamic model of abstinence-related changes in the striatal DA system; in this model a hyperdopaminergic state during protracted abstinence is associated with vulnerability for relapse. PMID:26903621

Keep focussing: striatal dopamine multiple functions resolved in a single mechanism tested in a simulated humanoid robot

PubMed Central

Fiore, Vincenzo G.; Sperati, Valerio; Mannella, Francesco; Mirolli, Marco; Gurney, Kevin; Friston, Karl; Dolan, Raymond J.; Baldassarre, Gianluca

2014-01-01

The effects of striatal dopamine (DA) on behavior have been widely investigated over the past decades, with “phasic” burst firings considered as the key expression of a reward prediction error responsible for reinforcement learning. Less well studied is “tonic” DA, where putative functions include the idea that it is a regulator of vigor, incentive salience, disposition to exert an effort and a modulator of approach strategies. We present a model combining tonic and phasic DA to show how different outflows triggered by either intrinsically or extrinsically motivating stimuli dynamically affect the basal ganglia by impacting on a selection process this system performs on its cortical input. The model, which has been tested on the simulated humanoid robot iCub interacting with a mechatronic board, shows the putative functions ascribed to DA emerging from the combination of a standard computational mechanism coupled to a differential sensitivity to the presence of DA across the striatum. PMID:24600422

High Doses of Amphetamine Augment, Rather Than Disrupt, Exocytotic Dopamine Release in the Dorsal and Ventral Striatum of the Anesthetized Rat

PubMed Central

Ramsson, Eric S.; Howard, Christopher D.; Covey, Dan P.; Garris, Paul A.

2011-01-01

High doses of amphetamine (AMPH) are thought to disrupt normal patterns of action potential-dependent dopaminergic neurotransmission by depleting vesicular stores of dopamine (DA) and inducing robust non-exocytotic DA release or efflux via dopamine transporter (DAT) reversal. However, these cardinal AMPH actions have been difficult to establish definitively in vivo. Here, we use fast-scan cyclic voltammetry (FSCV) in the urethane-anesthetized rat to evaluate the effects of 10 and 20 mg/kg AMPH on vesicular DA release and DAT function in dorsal and ventral striata. An equivalent high dose of cocaine (40 mg/kg) was also examined for comparison to psychostimulants acting preferentially by DAT inhibition. Parameters describing exocytotic DA release and neuronal DA uptake were determined from dynamic DA signals evoked by mild electrical stimulation previously established to be reinforcing. High-sensitivity FSCV with nanomolar detection was used to monitor changes in the background voltammetric signal as an index of DA efflux. Both doses of AMPH and cocaine markedly elevated evoked DA levels over the entire 2-h time course in the dorsal and ventral striatum. These increases were mediated by augmented vesicular DA release and diminished DA uptake typically acting concurrently. AMPH, but not cocaine, induced a slow, DA-like rise in some baseline recordings. However, this effect was highly variable in amplitude and duration, modest, and generally not present at all. These data thus describe a mechanistically similar activation of action potential-dependent dopaminergic neurotransmission by AMPH and cocaine in vivo. Moreover, DA efflux appears to be a unique, but secondary, AMPH action. PMID:21806614

Molecular modeling and molecular dynamics simulations based structural analysis of the SG2NA protein variants.

PubMed

Soni, Sangeeta; Tyagi, Chetna; Grover, Abhinav; Goswami, Shyamal K

2014-07-11

SG2NA is a member of the striatin sub-family of WD-40 repeat proteins. Striatin family members have been associated with diverse physiological functions. SG2NA has also been shown to have roles in cell cycle progression, signal transduction etc. They have been known to interact with a number of proteins including Caveolin and Calmodulin and also propagate the formation of a multimeric protein unit called striatin-interacting phosphatase and kinase. As a pre-requisite for such interaction ability, these proteins are known to be unstable and primarily disordered in their arrangement. Earlier we had identified that it has multiple isoforms (namely 35, 78, 87 kDa based on its molecular weight) which are generated by alternative splicing. However, detailed structural information of SG2NA is still eluding the researchers. This study was aimed towards three-dimensional molecular modeling and characterization of SG2NA protein and its isoforms. One structure out of five was selected for each variant having the least value for C score. Out of these, m35 kDa with a C score value of -3.21 was the most poorly determined structure in comparison to m78 kDa and m87 kDa variants with C scores of -1.16 and -1.97 respectively. Further evaluation resulted in about 61.6% residues of m35 kDa, 76.6% residues of m78 kDa and 72.1% residues of m87 kDa falling in the favorable regions of Ramchandran Plot. Molecular dynamics simulations were also carried out to obtain biologically relevant structural models and compared with previous atomic coordinates. N-terminal region of all variants was found to be highly disordered. This study provides first-hand detailed information to understand the structural conformation of SG2NA protein variants (m35 kDa, m78 kDa and m87 kDa). The WD-40 repeat domain was found to constitute antiparallel strands of β-sheets arranged circularly. This study elucidates the crucial structural features of SG2NA proteins which are involved in various protein-protein interactions and also reveals the extent of disorder present in the SG2NA structure crucial for excessive interaction and multimeric protein complexes. The study also potentiates the role of computational approaches for preliminary examination of unknown proteins in the absence of experimental information.

Reproducibility of quantitative measures of binding potential in rat striatum: A test re-test study using DTBZ dynamic PET studies

NASA Astrophysics Data System (ADS)

Avendaño-Estrada, A.; Lara-Camacho, V. M.; Ávila-García, M. C.; Ávila-Rodríguez, M. A.

2014-11-01

There is great interest in the study of dopamine (DA) pathways due to the increasing number of patients with illnesses related to the dopaminergic system and molecular imaging based in Positron Emission Tomography (PET) has been proven helpful for this task. Among the different radiopharmaceuticals available to study DA interaction, [11C ]Dihydrotetrabenazine (DTBZ) has a high affinity for the vesicular monoamine transporter type 2 (VMAT2) and its binding potential (BP) is a marker of DA terminal integrity. This paper reports on the intersubject reproducibility of BP measurements in rat striatum with [11C]DTBZ using the Logańs method.

Reproducibility of quantitative measures of binding potential in rat striatum: A test re-test study using DTBZ dynamic PET studies

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

Avendaño-Estrada, A., E-mail: avilarod@uwalumni.com; Lara-Camacho, V. M., E-mail: avilarod@uwalumni.com; Ávila-García, M. C., E-mail: avilarod@uwalumni.com

2014-11-07

There is great interest in the study of dopamine (DA) pathways due to the increasing number of patients with illnesses related to the dopaminergic system and molecular imaging based in Positron Emission Tomography (PET) has been proven helpful for this task. Among the different radiopharmaceuticals available to study DA interaction, [{sup 11}C]Dihydrotetrabenazine (DTBZ) has a high affinity for the vesicular monoamine transporter type 2 (VMAT2) and its binding potential (BP) is a marker of DA terminal integrity. This paper reports on the intersubject reproducibility of BP measurements in rat striatum with [11C]DTBZ using the Logańs method.

Striatal dopamine dynamics in mice following acute and repeated toluene exposure.

PubMed

Apawu, Aaron K; Mathews, Tiffany A; Bowen, Scott E

2015-01-01

The abused inhalant toluene has potent behavioral effects, but only recently has progress been made in understanding the neurochemical actions that mediate the action of toluene in the brain. Available evidence suggests that toluene inhalation alters dopamine (DA) neurotransmission, but toluene's mechanism of action is unknown. The present study evaluated the effect of acute and repeated toluene inhalation (0, 2,000, or 4,000 ppm) on locomotor activity as well as striatal DA release and uptake using slice fast-scan cyclic voltammetry. Acutely, 2,000 and 4,000 ppm toluene increased locomotor activity, while neurochemically only 4,000 ppm toluene potentiated electrically evoked DA release across the caudate-putamen and the nucleus accumbens. Repeated administration of toluene resulted in sensitization to toluene's locomotor activity effects. Brain slices obtained from mice repeatedly exposed to toluene demonstrated no difference in stimulated DA release in the caudate-putamen as compared to control animals. Repeated exposure to 2,000 and 4,000 ppm toluene caused a concentration-dependent decrease of 25-50 % in evoked DA release in the nucleus accumbens core and shell relative to air-exposed mice. These voltammetric neurochemical findings following repeated toluene exposure suggest that there may be a compensatory downregulation of the DA system. Acute or repeated toluene exposure had no effect on the DA uptake kinetics. Taken together, these results demonstrate that acute toluene inhalation potentiates DA release, while repeated toluene exposure attenuates DA release in the nucleus accumbens only.

Intranasal Dopamine Reduces In Vivo [(123)I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response.

PubMed

de Souza Silva, Maria A; Mattern, Claudia; Decheva, Cvetana; Huston, Joseph P; Sadile, Adolfo G; Beu, Markus; Müller, H-W; Nikolaus, Susanne

2016-01-01

Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [(123)I]FP-CIT to the DAT should be decreased due to competition at the receptor. Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [(123)I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand. (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs. (a) demonstrate a direct central action of intranasally applied DA on the DAT in the dorsal striatum, indicating enhanced DA availability; and (b) provide first evidence of a Pavlovian conditioned DA response at the DAT. The latter results have relevance to understanding neurochemical mechanisms that underlie placebo action in the treatment of Parkinsonian patients.

PanDA for ATLAS distributed computing in the next decade

NASA Astrophysics Data System (ADS)

Barreiro Megino, F. H.; De, K.; Klimentov, A.; Maeno, T.; Nilsson, P.; Oleynik, D.; Padolski, S.; Panitkin, S.; Wenaus, T.; ATLAS Collaboration

2017-10-01

The Production and Distributed Analysis (PanDA) system has been developed to meet ATLAS production and analysis requirements for a data-driven workload management system capable of operating at the Large Hadron Collider (LHC) data processing scale. Heterogeneous resources used by the ATLAS experiment are distributed worldwide at hundreds of sites, thousands of physicists analyse the data remotely, the volume of processed data is beyond the exabyte scale, dozens of scientific applications are supported, while data processing requires more than a few billion hours of computing usage per year. PanDA performed very well over the last decade including the LHC Run 1 data taking period. However, it was decided to upgrade the whole system concurrently with the LHC’s first long shutdown in order to cope with rapidly changing computing infrastructure. After two years of reengineering efforts, PanDA has embedded capabilities for fully dynamic and flexible workload management. The static batch job paradigm was discarded in favor of a more automated and scalable model. Workloads are dynamically tailored for optimal usage of resources, with the brokerage taking network traffic and forecasts into account. Computing resources are partitioned based on dynamic knowledge of their status and characteristics. The pilot has been re-factored around a plugin structure for easier development and deployment. Bookkeeping is handled with both coarse and fine granularities for efficient utilization of pledged or opportunistic resources. An in-house security mechanism authenticates the pilot and data management services in off-grid environments such as volunteer computing and private local clusters. The PanDA monitor has been extensively optimized for performance and extended with analytics to provide aggregated summaries of the system as well as drill-down to operational details. There are as well many other challenges planned or recently implemented, and adoption by non-LHC experiments such as bioinformatics groups successfully running Paleomix (microbial genome and metagenomes) payload on supercomputers. In this paper we will focus on the new and planned features that are most important to the next decade of distributed computing workload management.

Vi-da: vitiligo diagnostic assistance mobile application

NASA Astrophysics Data System (ADS)

Nugraha, G. A.; Nurhudatiana, A.; Bahana, R.

2018-03-01

Vitiligo is a skin disorder in which white patches of depigmentation appear on different parts of the body. Usually, patients come to hospitals or clinics to have their vitiligo conditions assessed. This can be very tiring to the patients, as vitiligo treatments usually take a relatively long period of time, which can range from months to years. To address this challenge, we present in this paper a prototype of an Android-based mobile application called Vi-DA, which stands for Vitiligo Diagnostic Assistance. Vi-DA consists of three subsystems, which are user sign-up subsystem, camera and image analysis subsystem, and progress report subsystem. The mobile application was developed in Java programming language and uses MySQL as the database system. Vi-DA adopts a vitiligo segmentation algorithm to segment input image into normal skin area, vitiligo skin area, and non-skin area. Results showed that Vi-DA gave comparable results to the previous system implemented in Matlab. User acceptance testing results also showed that all respondents agreed on the usefulness of the system and agreed to use Vi-DA again in the future. Vi-DA benefits both dermatologists and patients as not only a computer-aided diagnosis (CAD) tool but also as a smart application that can be used for self-assessment at home.

The dynamic of FUS-induced BBB Opening in Mouse Brain assessed by contrast enhanced MRI

NASA Astrophysics Data System (ADS)

Jenne, Jürgen W.; Krafft, Axel J.; Maier, Florian; Krause, Marie N.; Kleber, Susanne; Huber, Peter E.; Martin-Villalba, Ana; Bock, Michael

2010-03-01

Focused ultrasound (FUS) in combination with the administration of gas-filled microbubbles, can induce a localized and reversible opening of the blood brain barrier (BBB). Contrast enhanced magnetic resonance imaging (MRI) has been demonstrated as a precise tool to monitor such a local BBB disruption. However, the opening/closing mechanisms of the BBB with FUS are still largely unknown. In this ongoing project, we study the BBB opening dynamics in mouse brain comparing an interstitial and an intravascular MR contrast agent (CA). FUS in mouse brain was performed with an MRI compatible treatment setup (1.7 MHz fix-focus US transducer, f' = 68 mm, NA = 0.44; focus: 8.1 mm length; O/ = 1.1 mm) in a 1.5 T whole body MRI system. For BBB opening, forty 10 ms-long FUS-pulses were applied at a repetition rate of 1 Hz at 1 MPa. The i.v. administration of the micro bubbles (50 μl SonoVue®) was started simultaneously with FUS exposure. To analyze the BBB opening process, short-term and long-term MRI signal dynamics of the interstitial MR contrast agent Magnevist® and the intravascular CA Vasovist® (Bayer-Schering) were studied. To assess short-term signal dynamics, T1-weighted inversion recovery turbo FLASH images (1s) were repeatedly acquired. Repeated 3D FLASH acquisitions (90 s) were used to assess long-term MRI signal dynamics. The short-term MRI signal enhancements showed comparable time constants for both types of MR contrast agents: 1.1 s (interstitial) vs. 0.8 s (intravascular). This time constant may serve as a time constant of the BBB opening process with the given FUS exposure parameters. For the long-term signal dynamics the intravascular CA (62±10 min) showed a fife times greater time constant as the interstitial contrast agent (12±10 min). This might be explained by the high molecular weight (˜60 kDa) of the intravascular Vasovist due to its reversible binding to blood serum albumin resulting in a prolonged half-life in the blood stream compared to the interstitial CA. As the intravascular CA offers a much longer time window for therapy assessment, FUS-BBB therapy control with an intravascular CA might be favorable.

Ecological Carrying Capacity of Land Use Changes in Da'an City

NASA Astrophysics Data System (ADS)

Wang, H.; Zhang, J.; Li, B.

2018-04-01

Based on GIS and RS technology, this paper analyzed the land use change in Da'an city from 1995 to 2010. land-use ecological evaluation index was constructed to evaluate the land-use ecological risk of Da 'an city dynamically, and the land-use ecological risk level map was made, and then the distribution and change of the land-use ecological carrying capacity pattern of Da'an city were analyzed qualitatively. According to the evaluation results of ecological carrying capacity, the ecological environment of Da'an city has deteriorated in fifteen years. in 1995, the poor ecological environment area is mainly distributed in the northeast area of Da'an city, and the area is small, while the area of the central and southern areas is large; In 2010, the western region also appeared environmental degradation, the northeast environment deterioration is serious, the dominant area is reduced, and a small amount of deterioration in the central and southern regions. According to the study of this paper, in the future, we should strengthen the comprehensive management of this part of the area, strengthen vegetation coverage, reduce soil erosion, ensure the effective improvement of ecological environment.

Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States

PubMed Central

Orio, Patricio; Soudry, Daniel

2012-01-01

Background The phenomena that emerge from the interaction of the stochastic opening and closing of ion channels (channel noise) with the non-linear neural dynamics are essential to our understanding of the operation of the nervous system. The effects that channel noise can have on neural dynamics are generally studied using numerical simulations of stochastic models. Algorithms based on discrete Markov Chains (MC) seem to be the most reliable and trustworthy, but even optimized algorithms come with a non-negligible computational cost. Diffusion Approximation (DA) methods use Stochastic Differential Equations (SDE) to approximate the behavior of a number of MCs, considerably speeding up simulation times. However, model comparisons have suggested that DA methods did not lead to the same results as in MC modeling in terms of channel noise statistics and effects on excitability. Recently, it was shown that the difference arose because MCs were modeled with coupled gating particles, while the DA was modeled using uncoupled gating particles. Implementations of DA with coupled particles, in the context of a specific kinetic scheme, yielded similar results to MC. However, it remained unclear how to generalize these implementations to different kinetic schemes, or whether they were faster than MC algorithms. Additionally, a steady state approximation was used for the stochastic terms, which, as we show here, can introduce significant inaccuracies. Main Contributions We derived the SDE explicitly for any given ion channel kinetic scheme. The resulting generic equations were surprisingly simple and interpretable – allowing an easy, transparent and efficient DA implementation, avoiding unnecessary approximations. The algorithm was tested in a voltage clamp simulation and in two different current clamp simulations, yielding the same results as MC modeling. Also, the simulation efficiency of this DA method demonstrated considerable superiority over MC methods, except when short time steps or low channel numbers were used. PMID:22629320

Assimilation of the AVISO Altimetry Data into the Ocean Dynamics Model with a High Spatial Resolution Using Ensemble Optimal Interpolation (EnOI)

NASA Astrophysics Data System (ADS)

Kaurkin, M. N.; Ibrayev, R. A.; Belyaev, K. P.

2018-01-01

A parallel realization of the Ensemble Optimal Interpolation (EnOI) data assimilation (DA) method in conjunction with the eddy-resolving global circulation model is implemented. The results of DA experiments in the North Atlantic with the assimilation of the Archiving, Validation and Interpretation of Satellite Oceanographic (AVISO) data from the Jason-1 satellite are analyzed. The results of simulation are compared with the independent temperature and salinity data from the ARGO drifters.

FoxO regulates microtubule dynamics and polarity to promote dendrite branching in Drosophila sensory neurons

PubMed Central

Sears, James C.; Broihier, Heather T.

2016-01-01

The size and shape of dendrite arbors are defining features of neurons and critical determinants of neuronal function. The molecular mechanisms establishing arborization patterns during development are not well understood, though properly regulated microtubule (MT) dynamics and polarity are essential. We previously found that FoxO regulates axonal MTs, raising the question of whether it also regulates dendritic MTs and morphology. Here we demonstrate that FoxO promotes dendrite branching in all classes of Drosophila dendritic arborization (da) neurons. FoxO is required both for initiating growth of new branches and for maintaining existing branches. To elucidate FoxO function, we characterized MT organization in both foxO null and overexpressing neurons. We find that FoxO directs MT organization and dynamics in dendrites. Moreover, it is both necessary and sufficient for anterograde MT polymerization, which is known to promote dendrite branching. Lastly, FoxO promotes proper larval nociception, indicating a functional consequence of impaired da neuron morphology in foxO mutants. Together, our results indicate that FoxO regulates dendrite structure and function and suggest that FoxO-mediated pathways control MT dynamics and polarity. PMID:27546375

PKC phosphorylates residues in the N-terminal of the DA transporter to regulate amphetamine-induced DA efflux.

PubMed

Wang, Qiang; Bubula, Nancy; Brown, Jason; Wang, Yunliang; Kondev, Veronika; Vezina, Paul

2016-05-27

The DA transporter (DAT), a phosphoprotein, controls extracellular dopamine (DA) levels in the central nervous system through transport or reverse transport (efflux). Multiple lines of evidence support the claim that PKC significantly contributes to amphetamine-induced DA efflux. Other signaling pathways, involving CaMKII and ERK, have also been shown to regulate DAT mediated efflux. Here we assessed the contribution of putative PKC residues (S4, S7, S13) in the N-terminal of the DAT to amphetamine-induced DA efflux by transfecting DATs containing different serine to alanine (S-A) point mutations into DA pre-loaded HEK-293 cells and incubating these cells in amphetamine (2μM). The effects of a S-A mutation at the non-PKC residue S12 and a threonine to alanine (T-A) mutation at the ERK T53 residue were also assessed for comparison. WT-DATs were used as controls. In an initial experiment, we confirmed that inhibiting PKC with Go6976 (130nM) significantly reduced amphetamine-induced DA efflux. In subsequent experiments, cells transfected with the S4A, S12A, S13A, T53A and S4,7,13A mutants showed a reduction in amphetamine-induced DA efflux similar to that observed with Go6976. Interestingly, cells transfected with the S7A mutant, identified by some as a PKC-PKA residue, showed unperturbed WT-DAT levels of amphetamine-induced DA efflux. These results indicate that phosphorylation by PKC of select residues in the DAT N-terminal can regulate amphetamine-induced efflux. PKC can act either independently or in concert with other kinases such as ERK to produce this effect. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Face, content and concurrent validity of the Mimic® dV-Trainer for robot-assisted endoscopic surgery: a prospective study.

PubMed

Egi, H; Hattori, M; Tokunaga, M; Suzuki, T; Kawaguchi, K; Sawada, H; Ohdan, H

2013-01-01

The aim of this study was to determine whether any correlation exists between the performance of the Mimic® dV-Trainer (Mimic Technologies, Seattle, Wash., USA) and the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif., USA). Twelve participants were recruited, ranging from residents to consultants. We used four training tasks, consisting of 'Pick and Place', 'Peg Board', 'Thread the Rings' and 'Suture Sponge', from the software program of the Mimic dV-Trainer. The performance of the participants was recorded and measured. Additionally, we prepared the same tasks for the da Vinci Surgical System. All participants completed the tasks using the da Vinci Surgical System and were assessed according to time, the Objective Structured Assessment of Technical Skill checklist and the global rating score for endoscopic suturing assessed by two independent blinded observers. After performing these tasks, the participants completed a questionnaire that evaluated the Mimic dV-Trainer's face and content validity. The final results for each participant for the Mimic dV-Trainer and the da Vinci Surgical System were compared. All participants ranked the Mimic dV-Trainer as a realistic training platform that is useful for residency training. There was a significant relationship between the Mimic dV-Trainer and the da Vinci Surgical System in all four tasks. We verified the reliability of the assessment of the checklist and the global rating scores for endoscopic suturing assessed by the two blinded observers using Cronbach's alpha test (r = 0.803, 0.891). We evaluated the concurrent validity of the Mimic dV-Trainer and the da Vinci Surgical System. Our results suggest the possibility that training using the Mimic dV-Trainer may therefore be able to improve the operator's performance during live robot-assisted surgery. © 2013 S. Karger AG, Basel.

A Novel Decision Aid to Support Informed Decision-Making Process in Patients with a Symptomatic Nonlower Pole Renal Stone <20 mm in Diameter.

PubMed

Gökce, Mehmet İlker; Esen, Barış; Sancı, Adem; Akpınar, Cağrı; Süer, Evren; Gülpınar, Ömer

2017-07-01

Stone disease is an important health problem, and patients have different treatment choices. Shared decision making is recommended for deciding the treatment type, but patient education is necessary. Decision aids (DAs) are used for this aim, and herein, we developed a novel DA for patients with symptomatic nonlower pole renal stones <20 mm in diameter. The DA development process was established based on the recommended guides. General characteristics of the stone disease and details of the shockwave lithotripsy and retrograde intrarenal surgery were included in the content of the DA. The DA was further revised based on the suggestions of different physician groups and patients. The DA was evaluated by three physicians (Delphi assessment-International Patient Decision Aid Standards [IPDAS] Collaboration standards) and 25 patients (questionnaire of six questions with five-point Likert scale). The DA was designed as a booklet, and Delphi group assessment resulted in a total score of 50/54. Patient evaluation of the DA resulted in favorable outcomes, and patients generally recommended its use by other patients. This novel DA for patients with a symptomatic nonlower pole renal stone <20 mm showed promising results and was well accepted by the patients. We believe that this DA will have a positive impact on patients' level of knowledge. Increased level of knowledge will also improve the patients' contribution to the shared decision-making process. A further prospective randomized trial to compare with the standard patient informing process is also planned.

Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia.

PubMed

Choi, Myung-Gyu; Rhee, Poong-Lyul; Park, Hyojin; Lee, Oh Young; Lee, Kwang Jae; Choi, Suck Chei; Seol, Sang Young; Chun, Hoon Jai; Rew, Jong-Sun; Lee, Dong Ho; Song, Geun Am; Jung, Hwoon Yong; Jeong, Hyung Yong; Sung, In Kyung; Lee, Joon Seong; Lee, Soo Teik; Kim, Sung Kook; Shin, Yong Woon

2015-07-30

Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspep-tic symptoms and the overall treatment effect. Impact on patients' quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as ≥ 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with com-parable safety.

Activation of mesocorticolimbic reward circuits for assessment of relief of ongoing pain: a potential biomarker of efficacy.

PubMed

Xie, Jennifer Y; Qu, Chaoling; Patwardhan, Amol; Ossipov, Michael H; Navratilova, Edita; Becerra, Lino; Borsook, David; Porreca, Frank

2014-08-01

Preclinical assessment of pain has increasingly explored operant methods that may allow behavioral assessment of ongoing pain. In animals with incisional injury, peripheral nerve block produces conditioned place preference (CPP) and activates the mesolimbic dopaminergic reward pathway. We hypothesized that activation of this circuit could serve as a neurochemical output measure of relief of ongoing pain. Medications commonly used clinically, including gabapentin and nonsteroidal anti-inflammatory drugs (NSAIDs), were evaluated in models of post-surgical (1 day after incision) or neuropathic (14 days after spinal nerve ligation [SNL]) pain to determine whether the clinical efficacy profile of these drugs in these pain conditions was reflected by extracellular dopamine (DA) release in the nucleus accumbens (NAc) shell. Microdialysis was performed in awake rats. Basal DA levels were not significantly different between experimental groups, and no significant treatment effects were seen in sham-operated animals. Consistent with clinical observation, spinal clonidine produced CPP and produced a dose-related increase in net NAc DA release in SNL rats. Gabapentin, commonly used to treat neuropathic pain, produced increased NAc DA in rats with SNL but not in animals with incisional, injury. In contrast, ketorolac or naproxen produced increased NAc DA in animals with incisional but not neuropathic pain. Increased extracellular NAc DA release was consistent with CPP and was observed selectively with treatments commonly used clinically for post-surgical or neuropathic pain. Evaluation of NAc DA efflux in animal pain models may represent an objective neurochemical assay that may serve as a biomarker of efficacy for novel pain-relieving mechanisms. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Comparison of two simulation systems to support robotic-assisted surgical training: a pilot study (Swine model).

PubMed

Whitehurst, Sabrina V; Lockrow, Ernest G; Lendvay, Thomas S; Propst, Anthony M; Dunlow, Susan G; Rosemeyer, Christopher J; Gobern, Joseph M; White, Lee W; Skinner, Anna; Buller, Jerome L

2015-01-01

To compare the efficacy of simulation-based training between the Mimic dV- Trainer and traditional dry lab da Vinci robot training. A prospective randomized study analyzing the performance of 20 robotics-naive participants. Participants were enrolled in an online da Vinci Intuitive Surgical didactic training module, followed by training in use of the da Vinci standard surgical robot. Spatial ability tests were performed as well. Participants were randomly assigned to 1 of 2 training conditions: performance of 3 Fundamentals of Laparoscopic Surgery dry lab tasks using the da Vinci or performance of 4 dV-Trainer tasks. Participants in both groups performed all tasks to empirically establish proficiency criterion. Participants then performed the transfer task, a cystotomy closure using the daVinci robot on a live animal (swine) model. The performance of robotic tasks was blindly assessed by a panel of experienced surgeons using objective tracking data and using the validated Global Evaluative Assessment of Robotic Surgery (GEARS), a structured assessment tool. No statistically significant difference in surgeon performance was found between the 2 training conditions, dV-Trainer and da Vinci robot. Analysis of a 95% confidence interval for the difference in means (-0.803 to 0.543) indicated that the 2 methods are unlikely to differ to an extent that would be clinically meaningful. Based on the results of this study, a curriculum on the dV- Trainer was shown to be comparable to traditional da Vinci robot training. Therefore, we have identified that training on a virtual reality system may be an alternative to live animal training for future robotic surgeons. Published by Elsevier Inc.

Graphene-loaded nanofiber-modified electrodes for the ultrasensitive determination of dopamine.

PubMed

Rodthongkum, Nadnudda; Ruecha, Nipapan; Rangkupan, Ratthapol; Vachet, Richard W; Chailapakul, Orawon

2013-12-04

A novel and highly sensitive electrochemical system based on electrospun graphene/polyaniline/polystyrene (G/PANI/PS) nanofiber-modified screen-printed carbon electrodes has been developed for dopamine (DA) determination. A dramatic increase (9 times) in the current signal for the redox reaction of a standard, ferri/ferrocyanide [Fe(CN)6](3-/4-) couple was found when compared to an unmodified electrode. This modified electrode also exhibited favorable electron transfer kinetics and excellent electrocatalytic activity toward the oxidation of DA. When used together with square wave voltammetry (SWV), DA can be selectively determined in the presence of the common interferents (i.e. ascorbic acid and uric acid). Under optimal conditions, a very low limit of detection (0.05 nM) and limit of quantification (0.30 nM) were achieved for DA. In addition, a wide dynamic range of 0.1 nM to 100 μM was found for this electrode system. Finally, the system can be successfully applied to determine DA in complex biological environment (e.g. human serum, urine) with excellent reproducibility. Copyright © 2013 Elsevier B.V. All rights reserved.

Nuclear localization signal-dependent and -independent movements of Drosophila melanogaster dUTPase isoforms during nuclear cleavage

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

Muha, Villo; Zagyva, Imre; Venkei, Zsolt

2009-04-03

Two dUTPase isoforms (23 kDa and 21 kDa) are present in the fruitfly with the sole difference of an N-terminal extension. In Drosophila embryo, both isoforms are detected inside the nucleus. Here, we investigated the function of the N-terminal segment using eYFP-dUTPase constructs. In Schneider 2 cells, only the 23 kDa construct showed nuclear localization arguing that it may contain a nuclear localization signal (NLS). Sequence comparisons identified a lysine-rich nonapeptide with similarity to the human c-myc NLS. In Drosophila embryos during nuclear cleavages, the 23 kDa isoform showed the expected localization shifts. Contrariwise, although the 21 kDa isoform wasmore » excluded from the nuclei during interphase, it was shifted to the nucleus during prophase and forthcoming mitotic steps. The observed dynamic localization character showed strict timing to the nuclear cleavage phases and explained how both isoforms can be present within the nuclear microenvironment, although at different stages of cell cycle.« less

Synthesis of concentric circular antenna arrays using dragonfly algorithm

NASA Astrophysics Data System (ADS)

Babayigit, B.

2018-05-01

Due to the strong non-linear relationship between the array factor and the array elements, concentric circular antenna array (CCAA) synthesis problem is challenging. Nature-inspired optimisation techniques have been playing an important role in solving array synthesis problems. Dragonfly algorithm (DA) is a novel nature-inspired optimisation technique which is based on the static and dynamic swarming behaviours of dragonflies in nature. This paper presents the design of CCAAs to get low sidelobes using DA. The effectiveness of the proposed DA is investigated in two different (with and without centre element) cases of two three-ring (having 4-, 6-, 8-element or 8-, 10-, 12-element) CCAA design. The radiation pattern of each design cases is obtained by finding optimal excitation weights of the array elements using DA. Simulation results show that the proposed algorithm outperforms the other state-of-the-art techniques (symbiotic organisms search, biogeography-based optimisation, sequential quadratic programming, opposition-based gravitational search algorithm, cat swarm optimisation, firefly algorithm, evolutionary programming) for all design cases. DA can be a promising technique for electromagnetic problems.

A new anisotropy index on trabecular bone radiographic images using the fast Fourier transform

PubMed Central

Brunet-Imbault, Barbara; Lemineur, Gerald; Chappard, Christine; Harba, Rachid; Benhamou, Claude-Laurent

2005-01-01

Background The degree of anisotropy (DA) on radiographs is related to bone structure, we present a new index to assess DA. Methods In a region of interest from calcaneus radiographs, we applied a Fast Fourier Transform (FFT). All the FFT spectra involve the horizontal and vertical components corresponding respectively to longitudinal and transversal trabeculae. By visual inspection, we measured the spreading angles: Dispersion Longitudinal Index (DLI) and Dispersion Transverse Index (DTI) and calculated DA = 180/(DLI+DTI). To test the reliability of DA assessment, we synthesized images simulating radiological projections of periodic structures with elements more or less disoriented. Results Firstly, we tested synthetic images which comprised a large variety of structures from highly anisotropic structure to the almost isotropic, DA was ranging from 1.3 to 3.8 respectively. The analysis of the FFT spectra was performed by two observers, the Coefficients of Variation were 1.5% and 3.1 % for intra-and inter-observer reproducibility, respectively. In 22 post-menopausal women with osteoporotic fracture cases and 44 age-matched controls, DA values were respectively 1.87 ± 0.15 versus 1.72 ± 0.18 (p = 0.001). From the ROC analysis, the Area Under Curve (AUC) were respectively 0.65, 0.62, 0.64, 0.77 for lumbar spine, femoral neck, total femoral BMD and DA. Conclusion The highest DA values in fracture cases suggest that the structure is more anisotropic in osteoporosis due to preferential deletion of trabeculae in some directions. PMID:15927072

Aversive Stimuli Differentially Modulate Real-Time Dopamine Transmission Dynamics within the Nucleus Accumbens Core and Shell

PubMed Central

Badrinarayan, Aneesha; Wescott, Seth A.; Vander Weele, Caitlin M.; Saunders, Benjamin T.; Couturier, Brenann E.; Maren, Stephen

2012-01-01

Although fear directs adaptive behavioral responses, how aversive cues recruit motivational neural circuitry is poorly understood. Specifically, while it is known that dopamine (DA) transmission within the nucleus accumbens (NAc) is imperative for mediating appetitive motivated behaviors, its role in aversive behavior is controversial. It has been proposed that divergent phasic DA transmission following aversive events may correspond to segregated mesolimbic dopamine pathways; however, this prediction has never been tested. Here, we used fast-scan cyclic voltammetry to examine real-time DA transmission within NAc core and shell projection systems in response to a fear-evoking cue. In male Sprague Dawley rats, we first demonstrate that a fear cue results in decreased DA transmission within the NAc core, but increased transmission within the NAc shell. We examined whether these changes in DA transmission could be attributed to modulation of phasic transmission evoked by cue presentation. We found that cue presentation decreased the probability of phasic DA release in the core, while the same cue enhanced the amplitude of release events in the NAc shell. We further characterized the relationship between freezing and both changes in DA as well as local pH. Although we found that both analytes were significantly correlated with freezing in the NAc across the session, changes in DA were not strictly associated with freezing while basic pH shifts in the core more consistently followed behavioral expression. Together, these results provide the first real-time neurochemical evidence that aversive cues differentially modulate distinct DA projection systems. PMID:23136417

Phosphatidylcholine Coatings Deliver Local Antimicrobials and Reduce Infection in a Murine Model: A Preliminary Study.

PubMed

Harris, Michael A; Beenken, Karen E; Smeltzer, Mark S; Haggard, Warren O; Jennings, J Amber

2017-07-01

Phosphatidylcholine coatings have been shown to elute antibiotics for several days. A recently developed biofilm inhibitor, cis-2-decenoic acid (C2DA), has been shown to exhibit synergistic activity with several common antibiotics. This study aims to evaluate the effectiveness of C2DA and amikacin dual drug delivery from a phosphatidylcholine coating. (1) What are the in vitro elution profiles of amikacin and C2DA from phosphatidylcholine-coated coupons in incubated phosphate-buffered saline? (2) Does the presence of C2DA in eluate samples lower the amount of amikacin needed for bacterial inhibition in overnight bacterial turbidity assays? (3) Does addition of amikacin and C2DA result in decreased colony-forming units (CFUs) on wire implants and bone when compared with phosphatidylcholine coatings alone in a mouse model of periprosthetic joint infection? Effects of loading concentrations were assessed during 7-day in vitro elution studies for coatings containing all mixtures of 0%, 5%, 15%, and 25% wt of amikacin and C2DA (n = 4) through quantitative high-performance liquid chromatography concentration determination and plotting concentration eluted over time. Antimicrobial activity was assessed by overnight turbidity testing of elution study samples against Staphylococcus aureus or Pseudomonas aeruginosa. In vivo efficacy was assessed using phosphatidylcholine-coated wire implants in a murine (mouse) model of infection (n = 3). Wire implants were coated with phosphatidylcholine containing no antimicrobials, amikacin alone, C2DA alone, or amikacin and C2DA and then inserted into the intramedullary femur of each mouse and inoculated with S aureus. The number of viable bacterial colonies on the implant surface and in the surrounding bone was determined after 1 week with the goal of achieving complete bacterial clearance. Total viable CFU count and proportion of samples achieving complete clearance were compared between groups. Elution samples showed a burst response of amikacin and C2DA for 1 to 2 days with C2DA release continuing at low levels through Day 4. All tested eluate samples inhibited P aeruginosa. Samples from coatings containing 25% amikacin or 15% amikacin and any amount of C2DA were able to inhibit S aureus formation, but all coatings with 5% amikacin or 15% amikacin but no C2DA were not inhibitory. All in vivo treatment groups achieved complete bacterial clearance on the wire implant, and the C2DA alone and amikacin alone coatings cleared all CFUs in bone (pin: phosphatidylcholine only one of three; amikacin three of three, C2DA three of three, amikacin + C2DA three of three, p = 0.04 [Fisher's exact test]; bone: coating only: zero of three; amikacin: three of three; C2DA; three of three; C2DA + amikacin: one of three; p = 0.03 [Fisher's exact test]). Phosphatidylcholine coatings elute antimicrobials in vitro under infinite sink conditions for up to 4 days in phosphate-buffered saline and were able to reduce bacterial colonies in a preliminary in vivo model. Turbidity testing with eluate samples containing varying amounts of C2DA and amikacin agrees with previous studies showing synergy between them. Used as an adjunctive to systemic therapy, C2DA-loaded phosphatidylcholine coatings have potential value as a prophylactic infection prevention measure. Future studies may include different antibiotics, animal studies with larger sample sizes and more controls, and advanced coating delivery methods.

Post Fire Vegetation Recovery in Greece after the large Drought event of 2007

NASA Astrophysics Data System (ADS)

Gouveia, Célia M.; Bastos, Ana; DaCamara, Carlos; Trigo, Ricardo

2013-04-01

Fire is a natural factor of Mediterranean ecosystems. However, fire regimes in the European Mediterranean areas have been changing in the last decades, mainly due to land-use changes and climate driven factors possibly associated with climatic warming (e.g. decline of precipitation, increasing temperatures but also higher frequency of heatwaves). In Greece, the fire season of 2007 was particularly devastating, achieving the new all-time record of estimated burnt area (225 734 ha), since 1980. Additionally, we must stress that prior to the summer fire season in 2007, Greece suffered an exceptional drought event. This severe drought had a strong negative impact in vegetation dynamics. Since water availability is a crucial factor in post-fire vegetation recovery, it is desirable to assess the impact that such water-stress conditions had on fire sensitivity and post-fire vegetation recovery. Based on monthly values of NDVI, at the 1km×1km spatial scale, as obtained from the VEGETATION-SPOT5 instrument, from 1999 to 2010, large burnt scars are identified in Greece, during 2007 fire season. Vegetation recovery is then assessed based on a mono parametric regression model originally developed by Gouveia et al. (2010) to identify large burnt scars in Portugal during the 2003 fire season and after applied to 2005 fire season (Bastos et al., 2012). Some large burnt areas are selected and the respective NDVI behaviour is monitored throughout the pre and the post fire period. The vegetation dynamics during the pre-fire period is analysed and related to the extreme climatic events that characterised the considered period. An analysis is made of the dependence of recovery rates on land cover types and fire damage. Finally results are compared to results already obtained for Portugal (Gouveia et al. 2010). This work emphasises the use of a simple methodology, when applied to low resolution satellite imagery in order to monitor vegetation recovery after large fires events over distinct regions of Mediterranean Europe. Gouveia C., DaCamara C.C, Trigo R.M. (2010). "Post-fire vegetation dynamics in Portugal". Natural Hazards and Earth System Sciences, 10, 4, 673-684. Bastos A., Gouveia C., DaCamara C.C., and Trigo R.M.: Modelling post-fire vegetation recovery in Portugal.Biogeosciences, 8, 4559-4601, 2011.

Orofacial esthetics and dental anxiety: associations with oral and psychological health.

PubMed

Carlsson, Viktor; Hakeberg, Magnus; Blomkvist, Klas; Wide Boman, Ulla

2014-11-01

Severe dental anxiety (DA) is associated with both oral health and psychosocial consequences in what has been described as a vicious circle of DA. The aim of this study was to investigate self-rated orofacial esthetics in patients with DA and its relationship to psychological and oral health. A consecutive sample of 152 adult patients who were referred or self-referred to a specialized dental anxiety clinic filled out the Orofacial Esthetic Scale (OES) as well as measurements on DA, self-rated oral health and general anxiety and depression. Clinical measures of dental status were also obtained. Compared with the general population, patients with DA had lower ratings of satisfaction on all aspects of their orofacial esthetics, which included the teeth, gingiva, mouth and face, as well as a global orofacial assessment. Furthermore, the perception of the orofacial appearance was related both to dental status and self-rated oral health, as well as to general anxiety and depression. The level of dissatisfaction with the orofacial appearance was similar for both genders, but women reported more regular dental care and better dental status. The results of this study clearly show less satisfaction with dental and facial appearance in patients with DA, and that the self-rating of orofacial esthetics is related to both oral and psychological health. The OES can be used to assess orofacial esthetics in patients with DA.

Determining rotational dynamics of the guanidino group of arginine side chains in proteins by carbon-detected NMR.

PubMed

Gerecht, Karola; Figueiredo, Angelo Miguel; Hansen, D Flemming

2017-09-16

Arginine residues are imperative for many active sites and protein-interaction interfaces. A new NMR-based method is presented to determine the rotational dynamics around the N ε -C ζ bond of arginine side chains. An application to a 19 kDa protein shows that the strengths of interactions involving arginine side chains can be characterised.

Prevalence of and factors associated with dental anxiety among medical and dental students of the Northern State Medical University, Arkhangelsk, North-West Russia.

PubMed

Drachev, Sergei N; Brenn, Tormod; Trovik, Tordis A

2018-12-01

The objective was to assess the prevalence of and factors associated with dental anxiety (DA) in medical and dental students in North-West Russia. This cross-sectional study included 422 medical and 285 dental undergraduate Russian students aged 18-25 years from the Northern State Medical University in Arkhangelsk. Corah's Dental Anxiety Scale (DAS) was applied to measure DA. Information on socio-demographic and socioeconomic factors, oral health behaviour and general and oral health was obtained from a structured, self-administered questionnaire. A clinical examination was performed to assess caries experience, Simplified Oral Hygiene Index, and Gingival Index. DAS score ≥13 was found in 13.7% and 2.2% of medical and dental students, respectively. Female sex (incidence rate ratio [IRR] = 1.11, p = 0.013), lower education of mother (IRR = 1.13, p = 0.001), and poor self-assessed oral health (IRR = 1.15, p < 0.001) were associated with DA in medical students. Corresponding factors in dental students were female sex (IRR = 1.16, p = 0.001), irregular dental visits (IRR = 1.19, p = 0.001), infrequent tooth-brushing (IRR = 1.17, p = 0.007), pain in mouth (IRR = 1.09, p = 0.031) and number of missing teeth (IRR = 1.13, p = 0.007). The prevalence of high DA was lower in dental students than in medical students. DA was associated with sex, mother's education, poor oral health behaviour and self-assessed and clinically assessed oral health.

Evaluation of the accuracy of Demirjian method for estimation of dental age among 6-12 years of children in Navi Mumbai: A radiographic study.

PubMed

Hegde, Rahul J; Khare, Sumedh Suhas; Saraf, Tanvi A; Trivedi, Sonal; Naidu, Sonal

2015-01-01

Dental formation is superior to eruption as a method of dental age (DA) assessment. Eruption is only a brief occurrence, whereas formation may be related at different chronologic age levels, thereby providing a precise index for determining DA. The study was designed to determine the nature of inter-relationship between chronologic and DA. Age estimation depending upon tooth formation was done by Demirjian method and accuracy of Demirjian method was also evaluated. The sample for the study consisted of 197 children of Navi Mumbai. Significant positive correlation was found between chronologic age and DA that is, (r = 0.995), (P < 0.0001) for boys and (r = 0.995), (P < 0.0001) for girls. When age estimation was done by Demirjian method, mean the difference between true age (chronologic age) and assessed (DA) was 2 days for boys and 37 days for girls. Demirjian method showed high accuracy when applied to Navi Mumbai (Maharashtra - India) population. Demirjian method showed high accuracy when applied to Navi Mumbai (Maharashtra - India) population.

Concurrent Exposure of Bottlenose Dolphins (Tursiops truncatus) to Multiple Algal Toxins in Sarasota Bay, Florida, USA

PubMed Central

Twiner, Michael J.; Fire, Spencer; Schwacke, Lori; Davidson, Leigh; Wang, Zhihong; Morton, Steve; Roth, Stephen; Balmer, Brian; Rowles, Teresa K.; Wells, Randall S.

2011-01-01

Sentinel species such as bottlenose dolphins (Tursiops truncatus) can be impacted by large-scale mortality events due to exposure to marine algal toxins. In the Sarasota Bay region (Gulf of Mexico, Florida, USA), the bottlenose dolphin population is frequently exposed to harmful algal blooms (HABs) of Karenia brevis and the neurotoxic brevetoxins (PbTx; BTX) produced by this dinoflagellate. Live dolphins sampled during capture-release health assessments performed in this region tested positive for two HAB toxins; brevetoxin and domoic acid (DA). Over a ten-year study period (2000–2009) we have determined that bottlenose dolphins are exposed to brevetoxin and/or DA on a nearly annual basis (i.e., DA: 2004, 2005, 2006, 2008, 2009; brevetoxin: 2000, 2004, 2005, 2008, 2009) with 36% of all animals testing positive for brevetoxin (n = 118) and 53% positive for DA (n = 83) with several individuals (14%) testing positive for both neurotoxins in at least one tissue/fluid. To date there have been no previously published reports of DA in southwestern Florida marine mammals, however the May 2008 health assessment coincided with a Pseudo-nitzschia pseudodelicatissima bloom that was the likely source of DA observed in seawater and live dolphin samples. Concurrently, both DA and brevetoxin were observed in common prey fish. Although no Pseudo-nitzschia bloom was identified the following year, DA was identified in seawater, fish, sediment, snails, and dolphins. DA concentrations in feces were positively correlated with hematologic parameters including an increase in total white blood cell (p = 0.001) and eosinophil (p<0.001) counts. Our findings demonstrate that dolphins within Sarasota Bay are commonly exposed to two algal toxins, and provide the impetus to further explore the potential long-term impacts on bottlenose dolphin health. PMID:21423740

Randomized, Controlled, Multi-center Trial: Comparing the Safety and Efficacy of DA-9701 and Itopride Hydrochloride in Patients With Functional Dyspepsia

PubMed Central

Choi, Myung-Gyu; Rhee, Poong-Lyul; Park, Hyojin; Lee, Oh Young; Lee, Kwang Jae; Choi, Suck Chei; Seol, Sang Young; Chun, Hoon Jai; Rew, Jong-Sun; Lee, Dong Ho; Song, Geun Am; Jung, Hwoon Yong; Jeong, Hyung Yong; Sung, In Kyung; Lee, Joon Seong; Lee, Soo Teik; Kim, Sung Kook; Shin, Yong Woon

2015-01-01

Background/Aims Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients. Methods Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspeptic symptoms and the overall treatment effect. Impact on patients’ quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire. Results We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as ≥ 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable. Conclusions DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with comparable safety. PMID:26130637

m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.

PubMed

Consolato, Francesco; Maltecca, Francesca; Tulli, Susanna; Sambri, Irene; Casari, Giorgio

2018-04-09

The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation of mitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and auto-proteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 [matrix (m) - AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m - AAA and i - AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

The ATLAS PanDA Monitoring System and its Evolution

NASA Astrophysics Data System (ADS)

Klimentov, A.; Nevski, P.; Potekhin, M.; Wenaus, T.

2011-12-01

The PanDA (Production and Distributed Analysis) Workload Management System is used for ATLAS distributed production and analysis worldwide. The needs of ATLAS global computing imposed challenging requirements on the design of PanDA in areas such as scalability, robustness, automation, diagnostics, and usability for both production shifters and analysis users. Through a system-wide job database, the PanDA monitor provides a comprehensive and coherent view of the system and job execution, from high level summaries to detailed drill-down job diagnostics. It is (like the rest of PanDA) an Apache-based Python application backed by Oracle. The presentation layer is HTML code generated on the fly in the Python application which is also responsible for managing database queries. However, this approach is lacking in user interface flexibility, simplicity of communication with external systems, and ease of maintenance. A decision was therefore made to migrate the PanDA monitor server to Django Web Application Framework and apply JSON/AJAX technology in the browser front end. This allows us to greatly reduce the amount of application code, separate data preparation from presentation, leverage open source for tools such as authentication and authorization mechanisms, and provide a richer and more dynamic user experience. We describe our approach, design and initial experience with the migration process.

Performances on simulator and da Vinci robot on subjects with and without surgical background.

PubMed

Moglia, Andrea; Ferrari, Vincenzo; Melfi, Franca; Ferrari, Mauro; Mosca, Franco; Cuschieri, Alfred; Morelli, Luca

2017-08-17

To assess whether previous training in surgery influences performance on da Vinci Skills Simulator and da Vinci robot. In this prospective study, thirty-seven participants (11 medical students, 17 residents, and 9 attending surgeons) without previous experience in laparoscopy and robotic surgery performed 26 exercises at da Vinci Skills Simulator. Thirty-five then executed a suture using a da Vinci robot. The overall scores on the exercises at the da Vinci Skills Simulator show a similar performance among the groups with no statistically significant pair-wise differences (p < .05). The quality of the suturing based on the unedited videos of the test run was similar for the intermediate (7 (4, 10)) and expert group (6.5 (4.5, 10)), and poor for the untrained groups (5 (3.5, 9)), without statistically significant difference (p < .05). This study showed, for subjects new to laparoscopy and robotic surgery, insignificant differences in the scores at the da Vinci Skills Simulator and at the da Vinci robot on inanimate models.

Exposure to Domestic Violence and Abuse: Evidence of Distinct Physical and Psychological Dimensions.

PubMed

Naughton, Catherine M; O'Donnell, Aisling T; Muldoon, Orla T

2017-05-01

Recent literature on exposure to domestic violence (DV) highlights the need for increased understanding of the dynamics of domestic violence and abuse (DVA). The current aims were to explore whether two separate dimensions, physical and psychological DVA, were evident in adult children's reports of their exposure to DVA in their family of origin, and whether these dimensions affected psychological well-being and perceived satisfaction with emotional support (hereafter referred to as social support satisfaction). Young adults ( N = 465, aged 17-25, 70% female) reported their experiences of DVA as perpetrated by their parents/caregivers, as well as psychological well-being and social support satisfaction, in an online survey. Using confirmatory factor analysis (CFA), we verified the presence of a two-factor model (physical and psychological DVA). Hierarchical linear regression analysis demonstrated the differing impact of these two factors: Specifically, although exposure to psychological DVA (domestic abuse [DA]) was related to reduced psychological well-being, there was no significant effect of exposure to physical DVA (DV). However, mediation analysis suggested the presence of a suppression effect; there was a magnification of the negative relationship between exposure to psychological DA and social support satisfaction when exposure to physical DV was accounted for. Although findings are preliminary, they provide strong evidence to support theoretical arguments regarding the need for future research to conceptualize exposure to DVA in terms of both physical and psychological dimensions. Our findings also highlight that to improve service response and provide effective interventions, it is essential to include exposure to psychological DA in risk assessments of such young adults.

Effect of DA-9701 on gastric emptying in a mouse model: assessment by ¹³C-octanoic acid breath test.

PubMed

Lim, Chul-Hyun; Choi, Myung-Gyu; Park, Hyeyeon; Baeg, Myong Ki; Park, Jae Myung

2013-07-21

To evaluate the effects of DA-9701 on the gastric emptying of a solid meal using the ¹³C-octanoic acid breath test in a mouse model. Male C57BL/6 mice aged > 8 wk and with body weights of 20-25 g were used in this study. The solid test meal consisted of 200 mg of egg yolk labeled with 1.5 L/g ¹³C-octanoic acid. The mice were placed in a 130 mL chamber flushed with air at a flow speed of 200 mL/min. Breath samples were collected for 6 h. The half-emptying time and lag phase were calculated using a modified power exponential model. To assess the reproducibility of the ¹³C-octanoic acid breath test, the breath test was performed two times at intervals of one week in ten mice without drug treatment. To assess the gastrokinetic effects of DA-9701, the breath test was performed three times in another twelve mice, with a randomized crossover sequence of three drug treatments: DA-9701 3 mg/kg, erythromycin 6 mg/kg, or saline. Each breath test was performed at an interval of one week. Repeatedly measured half gastric emptying time of ten mice without drug treatment showed 0.856 of the intraclass correlation coefficient for the half gastric emptying time (P = 0.004). The mean cumulative excretion curve for the ¹³C-octanoic acid breath test showed accelerated gastric emptying after DA-9701 treatment compared with the saline control (P = 0.028). The median half gastric emptying time after the DA-9701 treatment was significantly shorter than after the saline treatment [122.4 min (109.0-137.9 min) vs 134.5 min (128.4-167.0 min), respectively; P = 0.028] and similar to that after the erythromycin treatment [123.3 min (112.9-138.2 min)]. The lag phase, which was defined as the period taken to empty 15% of a meal, was significantly shorter after the DA-9701 treatment than after the saline treatment [48.1 min (44.6-57.1 min) vs 52.6 min (49.45-57.4 min), respectively; P = 0.049]. The novel prokinetic agent DA-9701 accelerated gastric emptying, assessed with repeated measurements in the same mouse using the ¹³C-octanoic acid breath test. Our findings suggest that DA-9701 has therapeutic potential for the treatment of functional dyspepsia.

Decreased dopamine activity predicts relapse in methamphetamine abusers

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

Wang G. J.; Wang, G.-J.; Smith, L.

2011-01-20

Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested withinmore » 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.« less

Decreased dopamine activity predicts relapse in methamphetamine abusers.

PubMed

Wang, G J; Smith, L; Volkow, N D; Telang, F; Logan, J; Tomasi, D; Wong, C T; Hoffman, W; Jayne, M; Alia-Klein, N; Thanos, P; Fowler, J S

2012-09-01

Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [(11)C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

Prior Methamphetamine Self-Administration Attenuates the Dopaminergic Deficits Caused by a Subsequent Methamphetamine Exposure

PubMed Central

McFadden, Lisa M.; Vieira-Brock, Paula L.; Hanson, Glen R.; Fleckenstein, Annette E.

2015-01-01

Others and we have reported that prior methamphetamine (METH) exposure attenuates the persistent striatal dopaminergic deficits caused by a subsequent high-dose “binge” METH exposure. The current study investigated intermediate neurochemical changes that may contribute to, or serve to predict, this resistance. Rats self-administered METH or saline for 7 d. On the following day (specifically, 16 h after the conclusion of the final METH self-administration session), rats received a binge exposure of METH or saline (so as to assess the impact of prior METH self-administration), or were sacrificed without a subsequent METH exposure (i.e., to assess the status of the rats at what would have been the initiation of the binge METH treatment). Results revealed that METH self-administration per se decreased striatal dopamine (DA) transporter (DAT) function and DA content, as assessed 16 h after the last self-administration session. Exposure to a binge METH treatment beginning at this 16-h time point decreased DAT function and DA content as assessed 1 h after the binge METH exposure: this effect on DA content (but not DAT function) was attenuated if rats previously self-administered METH. In contrast, 24 h after the binge METH treatment prior METH self-administration: 1) attenuated deficits in DA content, DAT function and vesicular monoamine transporter-2 function; and 2) prevented increases in glial fibrillary acidic protein and DAT complex immunoreactivity. These data suggest that changes 24 h, but not 1 h, after binge METH exposure are predictive of tolerance against the persistence of neurotoxic changes following binge METH exposures. PMID:25645392

DaMoScope and its internet graphics for the visual control of adjusting mathematical models describing experimental data

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

Belousov, V. I.; Ezhela, V. V.; Kuyanov, Yu. V., E-mail: Yu.Kuyanov@gmail.com

The experience of using the dynamic atlas of the experimental data and mathematical models of their description in the problems of adjusting parametric models of observable values depending on kinematic variables is presented. The functional possibilities of an image of a large number of experimental data and the models describing them are shown by examples of data and models of observable values determined by the amplitudes of elastic scattering of hadrons. The Internet implementation of an interactive tool DaMoScope and its interface with the experimental data and codes of adjusted parametric models with the parameters of the best description ofmore » data are schematically shown. The DaMoScope codes are freely available.« less

Ferritins: dynamic management of biological iron and oxygen chemistry.

PubMed

Liu, Xiaofeng; Theil, Elizabeth C

2005-03-01

Ferritins are spherical, cage-like proteins with nanocavities formed by multiple polypeptide subunits (four-helix bundles) that manage iron/oxygen chemistry. Catalytic coupling yields diferric oxo/hydroxo complexes at ferroxidase sites in maxi-ferritin subunits (24 subunits, 480 kDa; plants, animals, microorganisms). Oxidation occurs at the cavity surface of mini-ferritins/Dps proteins (12 subunits, 240 kDa; bacteria). Oxidation products are concentrated as minerals in the nanocavity for iron-protein cofactor synthesis (maxi-ferritins) or DNA protection (mini-ferritins). The protein cage and nanocavity characterize all ferritins, although amino acid sequences diverge, especially in bacteria. Catalytic oxidation/di-iron coupling in the protein cage (maxi-ferritins, 480 kDa; plants, bacteria and animal cell-specific isoforms) or on the cavity surface (mini-ferritins/Dps proteins, 280 kDa; bacteria) initiates mineralization. Gated pores (eight or four), symmetrically arranged, control iron flow. The multiple ferritin functions combine pore, channel, and catalytic functions in compact protein structures required for life and disease response.

Multiple-scale neuroendocrine signals connect brain and pituitary hormone rhythms

PubMed Central

Romanò, Nicola; Guillou, Anne; Martin, Agnès O; Mollard, Patrice

2017-01-01

Small assemblies of hypothalamic “parvocellular” neurons release their neuroendocrine signals at the median eminence (ME) to control long-lasting pituitary hormone rhythms essential for homeostasis. How such rapid hypothalamic neurotransmission leads to slowly evolving hormonal signals remains unknown. Here, we show that the temporal organization of dopamine (DA) release events in freely behaving animals relies on a set of characteristic features that are adapted to the dynamic dopaminergic control of pituitary prolactin secretion, a key reproductive hormone. First, locally generated DA release signals are organized over more than four orders of magnitude (0.001 Hz–10 Hz). Second, these DA events are finely tuned within and between frequency domains as building blocks that recur over days to weeks. Third, an integration time window is detected across the ME and consists of high-frequency DA discharges that are coordinated within the minutes range. Thus, a hierarchical combination of time-scaled neuroendocrine signals displays local–global integration to connect brain–pituitary rhythms and pace hormone secretion. PMID:28193889

Tailored Algorithm for Sensitivity Enhancement of Gas Concentration Sensors Based on Tunable Laser Absorption Spectroscopy.

PubMed

Vargas-Rodriguez, Everardo; Guzman-Chavez, Ana Dinora; Baeza-Serrato, Roberto

2018-06-04

In this work, a novel tailored algorithm to enhance the overall sensitivity of gas concentration sensors based on the Direct Absorption Tunable Laser Absorption Spectroscopy (DA-ATLAS) method is presented. By using this algorithm, the sensor sensitivity can be custom-designed to be quasi constant over a much larger dynamic range compared with that obtained by typical methods based on a single statistics feature of the sensor signal output (peak amplitude, area under the curve, mean or RMS). Additionally, it is shown that with our algorithm, an optimal function can be tailored to get a quasi linear relationship between the concentration and some specific statistics features over a wider dynamic range. In order to test the viability of our algorithm, a basic C 2 H 2 sensor based on DA-ATLAS was implemented, and its experimental measurements support the simulated results provided by our algorithm.

Predicting Flow Reversals in a Computational Fluid Dynamics Simulated Thermosyphon Using Data Assimilation.

PubMed

Reagan, Andrew J; Dubief, Yves; Dodds, Peter Sheridan; Danforth, Christopher M

2016-01-01

A thermal convection loop is a annular chamber filled with water, heated on the bottom half and cooled on the top half. With sufficiently large forcing of heat, the direction of fluid flow in the loop oscillates chaotically, dynamics analogous to the Earth's weather. As is the case for state-of-the-art weather models, we only observe the statistics over a small region of state space, making prediction difficult. To overcome this challenge, data assimilation (DA) methods, and specifically ensemble methods, use the computational model itself to estimate the uncertainty of the model to optimally combine these observations into an initial condition for predicting the future state. Here, we build and verify four distinct DA methods, and then, we perform a twin model experiment with the computational fluid dynamics simulation of the loop using the Ensemble Transform Kalman Filter (ETKF) to assimilate observations and predict flow reversals. We show that using adaptively shaped localized covariance outperforms static localized covariance with the ETKF, and allows for the use of less observations in predicting flow reversals. We also show that a Dynamic Mode Decomposition (DMD) of the temperature and velocity fields recovers the low dimensional system underlying reversals, finding specific modes which together are predictive of reversal direction.

Predicting Flow Reversals in a Computational Fluid Dynamics Simulated Thermosyphon Using Data Assimilation

PubMed Central

Reagan, Andrew J.; Dubief, Yves; Dodds, Peter Sheridan; Danforth, Christopher M.

2016-01-01

A thermal convection loop is a annular chamber filled with water, heated on the bottom half and cooled on the top half. With sufficiently large forcing of heat, the direction of fluid flow in the loop oscillates chaotically, dynamics analogous to the Earth’s weather. As is the case for state-of-the-art weather models, we only observe the statistics over a small region of state space, making prediction difficult. To overcome this challenge, data assimilation (DA) methods, and specifically ensemble methods, use the computational model itself to estimate the uncertainty of the model to optimally combine these observations into an initial condition for predicting the future state. Here, we build and verify four distinct DA methods, and then, we perform a twin model experiment with the computational fluid dynamics simulation of the loop using the Ensemble Transform Kalman Filter (ETKF) to assimilate observations and predict flow reversals. We show that using adaptively shaped localized covariance outperforms static localized covariance with the ETKF, and allows for the use of less observations in predicting flow reversals. We also show that a Dynamic Mode Decomposition (DMD) of the temperature and velocity fields recovers the low dimensional system underlying reversals, finding specific modes which together are predictive of reversal direction. PMID:26849061

123I-FP-CIT SPECT imaging in early diagnosis of dementia in patients with and without a vascular component

PubMed Central

Garriga, Marina; Milà, Marta; Mir, Manzoor; Al-Baradie, Raid; Huertas, Sonia; Castejon, Cesar; Casas, Laura; Badenes, Dolors; Giménez, Nuria; Font, M. Angels; Gonzalez, Jose M.; Ysamat, Maria; Aguilar, Miguel; Slevin, Mark; Krupinski, Jerzy

2015-01-01

Alzheimer’s disease (AD) and vascular dementia (VaD) are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. 123I-FP-CIT SPECT (DaTScan) is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD), and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyze the vascular contribution towards dementia and mild cognitive impairment (MCI). We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. One-hundred and five patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score (FRS) and by structural neuroimaging using Wahlund Scale Total Score (WSTS). Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p < 0.01). Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on DaTScan. PMID:26190980

Vulnerable Parkin Loss-of-Function Drosophila Dopaminergic Neurons Have Advanced Mitochondrial Aging, Mitochondrial Network Loss and Transiently Reduced Autophagosome Recruitment.

PubMed

Cackovic, Juliana; Gutierrez-Luke, Susana; Call, Gerald B; Juba, Amber; O'Brien, Stephanie; Jun, Charles H; Buhlman, Lori M

2018-01-01

Selective degeneration of substantia nigra dopaminergic (DA) neurons is a hallmark pathology of familial Parkinson's disease (PD). While the mechanism of degeneration is elusive, abnormalities in mitochondrial function and turnover are strongly implicated. An Autosomal Recessive-Juvenile Parkinsonism (AR-JP) Drosophila melanogaster model exhibits DA neurodegeneration as well as aberrant mitochondrial dynamics and function. Disruptions in mitophagy have been observed in parkin loss-of-function models, and changes in mitochondrial respiration have been reported in patient fibroblasts. Whether loss of parkin causes selective DA neurodegeneration in vivo as a result of lost or decreased mitophagy is unknown. This study employs the use of fluorescent constructs expressed in Drosophila DA neurons that are functionally homologous to those of the mammalian substantia nigra. We provide evidence that degenerating DA neurons in parkin loss-of-function mutant flies have advanced mitochondrial aging, and that mitochondrial networks are fragmented and contain swollen organelles. We also found that mitophagy initiation is decreased in park ( Drosophila parkin/PARK2 ortholog) homozygous mutants, but autophagosome formation is unaffected, and mitochondrial network volumes are decreased. As the fly ages, autophagosome recruitment becomes similar to control, while mitochondria continue to show signs of damage, and climbing deficits persist. Interestingly, aberrant mitochondrial morphology, aging and mitophagy initiation were not observed in DA neurons that do not degenerate. Our results suggest that parkin is important for mitochondrial homeostasis in vulnerable Drosophila DA neurons, and that loss of parkin-mediated mitophagy may play a role in degeneration of relevant DA neurons or motor deficits in this model.

Nicotine- and methamphetamine-induced dopamine release evaluated with in-vivo binding of radiolabelled raclopride to dopamine D2 receptors: comparison with in-vivo microdialysis data.

PubMed

Kim, Sang Eun; Han, Seung-Moo

2009-07-01

The effect of substances which alter extracellular dopamine (DA) concentration has been studied by measuring changes in the binding of radiolabelled raclopride, a DA D2 receptor ligand that is sensitive to endogenous DA. To better characterize the relationship between extracellular DA concentration and DA D2 receptor binding of raclopride, we compared the changes of extracellular DA concentration (measured using in-vivo microdialysis) and in-vivo [3H]raclopride binding induced by different doses of methamphetamine (Meth) and nicotine, drugs that enhance DA release with and without blocking DA transporters (DATs), respectively, in rat striatum. Nicotine elicited a modest increase of striatal extrasynaptic extracellular DA, while Meth produced a marked increase of striatal extrasynaptic DA in a dose-dependent manner. There was a close correlation between the decrease in [3H]raclopride in-vivo binding and the increase in extrasynaptic DA concentration induced by both nicotine (r2=0.95, p<0.001) and Meth (r2=0.98, p=0.001), supporting the usefulness of the radiolabelled raclopride-binding measurement for the non-invasive assessment of DA release following interventions in the living brain. However, the linear regression analysis revealed that the ratio of percent DA increase to percent [3H]raclopride binding reduction was 25-fold higher for Meth (34.8:1) than for nicotine (1.4:1). The apparent discrepancy in the extrasynaptic DA-[3H]raclopride binding relationship between the DA-enhancing drugs with and without DAT-blocking property indicates that the competition between endogenous DA and radiolabelled raclopride takes place at the intrasynaptic rather than extrasynaptic DA D2 receptors and reflects synaptic concentration of DA.

Glycosylation site-targeted PEGylation of glucose oxidase retains native enzymatic activity.

PubMed

Ritter, Dustin W; Roberts, Jason R; McShane, Michael J

2013-04-10

Targeted PEGylation of glucose oxidase at its glycosylation sites was investigated to determine the effect on enzymatic activity, as well as the bioconjugate's potential in an optical biosensing assay. Methoxy-poly(ethylene glycol)-hydrazide (4.5kDa) was covalently coupled to periodate-oxidized glycosylation sites of glucose oxidase from Aspergillus niger. The bioconjugate was characterized using gel electrophoresis, liquid chromatography, mass spectrometry, and dynamic light scattering. Gel electrophoresis data showed that the PEGylation protocol resulted in a drastic increase (ca. 100kDa) in the apparent molecular mass of the protein subunit, with complete conversion to the bioconjugate; liquid chromatography data corroborated this large increase in molecular size. Mass spectrometry data proved that the extent of PEGylation was six poly(ethylene glycol) chains per glucose oxidase dimer. Dynamic light scattering data indicated the absence of higher-order oligomers in the PEGylated GOx sample. To assess stability, enzymatic activity assays were performed in triplicate at multiple time points over the course of 29 days in the absence of glucose, as well as before and after exposure to 5% w/v glucose for 24h. At a confidence level of 95%, the bioconjugate's performance was statistically equivalent to native glucose oxidase in terms of activity retention over the 29 day time period, as well as following the 24h glucose exposure. Finally, the bioconjugate was entrapped within a poly(2-hydroxyethyl methacrylate) hydrogel containing an oxygen-sensitive phosphor, and the construct was shown to respond approximately linearly with a 220±73% signal change (n=4, 95% confidence interval) over the physiologically-relevant glucose range (i.e., 0-400mg/dL); to our knowledge, this represents the first demonstration of PEGylated glucose oxidase incorporated into an optical biosensing assay. Copyright © 2013 Elsevier Inc. All rights reserved.

Local dynamic subgrid-scale models in channel flow

NASA Technical Reports Server (NTRS)

Cabot, William H.

1994-01-01

The dynamic subgrid-scale (SGS) model has given good results in the large-eddy simulation (LES) of homogeneous isotropic or shear flow, and in the LES of channel flow, using averaging in two or three homogeneous directions (the DA model). In order to simulate flows in general, complex geometries (with few or no homogeneous directions), the dynamic SGS model needs to be applied at a local level in a numerically stable way. Channel flow, which is inhomogeneous and wall-bounded flow in only one direction, provides a good initial test for local SGS models. Tests of the dynamic localization model were performed previously in channel flow using a pseudospectral code and good results were obtained. Numerical instability due to persistently negative eddy viscosity was avoided by either constraining the eddy viscosity to be positive or by limiting the time that eddy viscosities could remain negative by co-evolving the SGS kinetic energy (the DLk model). The DLk model, however, was too expensive to run in the pseudospectral code due to a large near-wall term in the auxiliary SGS kinetic energy (k) equation. One objective was then to implement the DLk model in a second-order central finite difference channel code, in which the auxiliary k equation could be integrated implicitly in time at great reduction in cost, and to assess its performance in comparison with the plane-averaged dynamic model or with no model at all, and with direct numerical simulation (DNS) and/or experimental data. Other local dynamic SGS models have been proposed recently, e.g., constrained dynamic models with random backscatter, and with eddy viscosity terms that are averaged in time over material path lines rather than in space. Another objective was to incorporate and test these models in channel flow.

Examination of Rapid Dopamine Dynamics with Fast Scan Cyclic Voltammetry During Intra-oral Tastant Administration in Awake Rats.

PubMed

Wickham, Robert J; Park, Jinwoo; Nunes, Eric J; Addy, Nii A

2015-08-12

Rapid, phasic dopamine (DA) release in the mammalian brain plays a critical role in reward processing, reinforcement learning, and motivational control. Fast scan cyclic voltammetry (FSCV) is an electrochemical technique with high spatial and temporal (sub-second) resolution that has been utilized to examine phasic DA release in several types of preparations. In vitro experiments in single-cells and brain slices and in vivo experiments in anesthetized rodents have been used to identify mechanisms that mediate dopamine release and uptake under normal conditions and in disease models. Over the last 20 years, in vivo FSCV experiments in awake, freely moving rodents have also provided insight of dopaminergic mechanisms in reward processing and reward learning. One major advantage of the awake, freely moving preparation is the ability to examine rapid DA fluctuations that are time-locked to specific behavioral events or to reward or cue presentation. However, one limitation of combined behavior and voltammetry experiments is the difficulty of dissociating DA effects that are specific to primary rewarding or aversive stimuli from co-occurring DA fluctuations that mediate reward-directed or other motor behaviors. Here, we describe a combined method using in vivo FSCV and intra-oral infusion in an awake rat to directly investigate DA responses to oral tastants. In these experiments, oral tastants are infused directly to the palate of the rat--bypassing reward-directed behavior and voluntary drinking behavior--allowing for direct examination of DA responses to tastant stimuli.

Myelin management by the 18.5–kDa and 21.5–kDa classic myelin basic protein isoforms

PubMed Central

Harauz, George; Boggs, Joan M.

2013-01-01

The classic myelin basic protein (MBP) splice isoforms range in nominal molecular mass from 14 to 21.5 kDa, and arise from the gene in the oligodendrocyte lineage (Golli) in maturing oligodendrocytes. The 18.5-kDa isoform that predominates in adult myelin adheres the cytosolic surfaces of oligodendrocyte membranes together, and forms a two-dimensional molecular sieve restricting protein diffusion into compact myelin. However, this protein has additional roles including cytoskeletal assembly and membrane extension, binding to SH3-domains, participation in Fyn-mediated signaling pathways, sequestration of phosphoinositides, and maintenance of calcium homeostasis. Of the diverse post-translational modifications of this isoform, phosphorylation is the most dynamic, and modulates 18.5-kDa MBP’s protein-membrane and protein-protein interactions, indicative of a rich repertoire of functions. In developing and mature myelin, phosphorylation can result in microdomain or even nuclear targeting of the protein, supporting the conclusion that 18.5-kDa MBP has significant roles beyond membrane adhesion. The full-length, early-developmental 21.5-kDa splice isoform is predominantly karyophilic due to a non-traditional P-Y nuclear localization signal, with effects such as promotion of oligodendrocyte proliferation. We discuss in vitro and recent in vivo evidence for multifunctionality of these classic basic proteins of myelin, and argue for a systematic evaluation of the temporal and spatial distributions of these protein isoforms, and their modified variants, during oligodendrocyte differentiation. PMID:23398367

Intervertebral disk width in dogs with and without clinical signs of disk associated cervical spondylomyelopathy

PubMed Central

2012-01-01

Background Disk-associated cervical spondylomyelopathy (DA-CSM) is a multifactorial neurological disorder in which progressive caudal cervical spinal cord compression is mainly caused by one or more intervertebral disk protrusions. The Doberman pinscher breed seems predisposed for this condition. The underlying cause and pathophysiology of DA-CSM are currently unknown. Recently, wider intervertebral disks have been put forward as a risk factor for development of clinically relevant DA-CSM. However, little is known about other factors affecting intervertebral disk width. Therefore the aim of this study was to assess the association between intervertebral disk width, measured on magnetic resonance imaging (MRI), and clinical status, age, gender and intervertebral disk location in dogs with and without clinical signs of DA-CSM. Methods Doberman pinschers with clinical signs of DA-CSM (N=17),clinically normal Doberman pinschers (N=20), and clinically normal English Foxhounds (N=17), underwent MRI of the cervical vertebral column. On sagittal T2-weighted images, intervertebral disk width was measured from C2-C3 to C6-C7. Intra –and interobserver agreement were assessed on a subset of 20 of the 54 imaging studies. Results Intervertebral disk width was not significantly different between Doberman pinschers with clinical signs of DA-CSM, clinically normal Doberman pinschers or clinically normal English Foxhounds (p=0.43). Intervertebral disk width was positively associated with increasing age (p=0.029). Each monthly increase in age resulted in an increase of disk width by 0.0057mm. Intervertebral disk width was not significantly affected by gender (p=0.056), but was significantly influenced by intervertebral disk location (p <0.0001). The assessed measurements were associated with a good intra –and interobserver agreement. Conclusions The present study does not provide evidence that wider intervertebral disks are associated with clinical status in dogs with and without DA-CSM. Instead, it seems that cervical intervertebral disk width in dogs is positively associated with increase in age. PMID:22839697

Pulmonary Impairment and Risk Assessment in a Diacetyl-Exposed Population: Microwave Popcorn Workers.

PubMed

Park, Robert M; Gilbert, Stephen J

2018-06-01

The butter flavoring additive, diacetyl (DA), can cause bronchiolitis obliterans (BO) by inhalation. A risk assessment was performed using data from a microwave popcorn manufacturing plant. Current employees' medical history and pulmonary function tests together with air sampling over a 2.7-year period were used to analyze forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC). The exposure responses for declining pulmonary function and for possible early onset of BO were estimated using multiple regression methods. Several exposure metrics were investigated; benchmark dose and excess lifetime risk of impairment were calculated. Forty-six percent of the population had less than 6 months exposure to DA. Percent-of-predicted FEV1 declined with cumulative exposure (0.40 per ppm-yr, P < 10) as did percent FEV1/FVC (0.13 per ppm-yr, P = 0.0004). Lifetime respiratory impairment prevalence of one per thousand resulted from 0.005 ppm DA and one per thousand lifetime incidence of impairment was predicted for 0.002 ppm DA. DA exposures, often exceeding 1 ppm in the past, place workers at high risk of pulmonary impairment.

Prior methamphetamine self-administration attenuates the dopaminergic deficits caused by a subsequent methamphetamine exposure.

PubMed

McFadden, Lisa M; Vieira-Brock, Paula L; Hanson, Glen R; Fleckenstein, Annette E

2015-06-01

Others and we have reported that prior methamphetamine (METH) exposure attenuates the persistent striatal dopaminergic deficits caused by a subsequent high-dose "binge" METH exposure. The current study investigated intermediate neurochemical changes that may contribute to, or serve to predict, this resistance. Rats self-administered METH or saline for 7 d. On the following day (specifically, 16 h after the conclusion of the final METH self-administration session), rats received a binge exposure of METH or saline (so as to assess the impact of prior METH self-administration), or were sacrificed without a subsequent METH exposure (i.e., to assess the status of the rats at what would have been the initiation of the binge METH treatment). Results revealed that METH self-administration per se decreased striatal dopamine (DA) transporter (DAT) function and DA content, as assessed 16 h after the last self-administration session. Exposure to a binge METH treatment beginning at this 16-h time point decreased DAT function and DA content as assessed 1 h after the binge METH exposure: this effect on DA content (but not DAT function) was attenuated if rats previously self-administered METH. In contrast, 24 h after the binge METH treatment prior METH self-administration: 1) attenuated deficits in DA content, DAT function and vesicular monoamine transporter-2 function; and 2) prevented increases in glial fibrillary acidic protein and DAT complex immunoreactivity. These data suggest that changes 24 h, but not 1 h, after binge METH exposure are predictive of tolerance against the persistence of neurotoxic changes following binge METH exposures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Digital radiographic evaluation of mandibular third molar for age estimation in young adults and adolescents of South Indian population using modified Demirjian's method

PubMed Central

Mohammed, Rezwana Begum; Koganti, Ravichandra; Kalyan, Siva V.; Tircouveluri, Saritha; Singh, Johar Rajvinder; Srinivasulu, Enganti

2014-01-01

In recent years, it has become increasingly important to determine the age of living people for a variety of reasons, including identifying criminal and legal responsibility and for many other social events such as birth certificate, marriage, beginning a job, joining the army and retirement Objectives: The aim of this study was to assess the developmental stages of mandibular third molar for estimation of dental age (DA) in different age groups and to evaluate the possible correlation between DA and chronological age (CA) in South Indian population. Materials and Methods: Digital orthopantomography of 330 subjects (165 males, 165 females) who fit the study and the criteria were obtained. Assessment of mandibular third molar development was performed using Demirjian et al., modified method and DA was assessed using tooth specific stages. Results and Discussion: The present study showed a significant correlation between DA and CA in both males and females. Third molar development commenced around 9 years and root completion takes place around 18.9 years in males and in females 9 years and 18.6 years respectively. Demirjian modified method underestimated the mean age of males by 0.8 years and females by 0.5 years and also showed that females mature earlier than males in selected population. Conclusion: Digital radiographic assessment of mandibular third molar development can be used to generate mean DA using Demirjian modified method and also the estimated age range for an individual of unknown CA. Since the Demirjian method is based on French-Canadian population, to enhance the accuracy of forensic age estimates based on third molar development, the use of population-specific standards is recommended. PMID:25177143

Digital radiographic evaluation of mandibular third molar for age estimation in young adults and adolescents of South Indian population using modified Demirjian's method.

PubMed

Mohammed, Rezwana Begum; Koganti, Ravichandra; Kalyan, Siva V; Tircouveluri, Saritha; Singh, Johar Rajvinder; Srinivasulu, Enganti

2014-09-01

In recent years, it has become increasingly important to determine the age of living people for a variety of reasons, including identifying criminal and legal responsibility and for many other social events such as birth certificate, marriage, beginning a job, joining the army and retirement. The aim of this study was to assess the developmental stages of mandibular third molar for estimation of dental age (DA) in different age groups and to evaluate the possible correlation between DA and chronological age (CA) in South Indian population. Digital orthopantomography of 330 subjects (165 males, 165 females) who fit the study and the criteria were obtained. Assessment of mandibular third molar development was performed using Demirjian et al., modified method and DA was assessed using tooth specific stages. The present study showed a significant correlation between DA and CA in both males and females. Third molar development commenced around 9 years and root completion takes place around 18.9 years in males and in females 9 years and 18.6 years respectively. Demirjian modified method underestimated the mean age of males by 0.8 years and females by 0.5 years and also showed that females mature earlier than males in selected population. Digital radiographic assessment of mandibular third molar development can be used to generate mean DA using Demirjian modified method and also the estimated age range for an individual of unknown CA. Since the Demirjian method is based on French-Canadian population, to enhance the accuracy of forensic age estimates based on third molar development, the use of population-specific standards is recommended.

USMILGP Colombia: Transforming Security Cooperation in the Global War on Terrorism

DTIC Science & Technology

2006-12-01

68 1. Peace Process ............................................................. 69 2. Economic Reform...72 D. ASSESSMENT OF PLAN COLOMBIA ...................................... 73 1. Peace Process ...xiv DA Department of the Army DA Direct Action DAO Defense Attaché Office DAS Departamento Administrativo de Seguridad DCM Deputy Chief of Mission

Sensitivity Analysis of a Lagrangian Sea Ice Model

NASA Astrophysics Data System (ADS)

Rabatel, Matthias; Rampal, Pierre; Bertino, Laurent; Carrassi, Alberto; Jones, Christopher K. R. T.

2017-04-01

Large changes in the Arctic sea ice have been observed in the last decades in terms of the ice thickness, extension and drift. Understanding the mechanisms behind these changes is of paramount importance to enhance our modeling and forecasting capabilities. For 40 years, models have been developed to describe the non-linear dynamical response of the sea ice to a number of external and internal factors. Nevertheless, there still exists large deviations between predictions and observations. There are related to incorrect descriptions of the sea ice response and/or to the uncertainties about the different sources of information: parameters, initial and boundary conditions and external forcing. Data assimilation (DA) methods are used to combine observations with models, and there is nowadays an increasing interest of DA for sea-ice models and observations. We consider here the state-of-the art sea-ice model, neXtSIM te{Rampal2016a}, which is based on a time-varying Lagrangian mesh and makes use of the Elasto-Brittle rheology. Our ultimate goal is designing appropriate DA scheme for such a modelling facility. This contribution reports about the first milestone along this line: a sensitivity analysis in order to quantify forecast error to guide model development and to set basis for further Lagrangian DA methods. Specific features of the sea-ice dynamics in relation to the wind are thus analysed. Virtual buoys are deployed across the Arctic domain and their trajectories of motion are analysed. The simulated trajectories are also compared to real buoys trajectories observed. The model response is also compared with that one from a model version not including internal forcing to highlight the role of the rheology. Conclusions and perspectives for the general DA implementation are also discussed. \\bibitem{Rampal2016a} P. Rampal, S. Bouillon, E. Ólason, and M. Morlighem. ne{X}t{SIM}: a new {L}agrangian sea ice model. The Cryosphere, 10 (3): 1055-1073, 2016.

Studies of New Fused Benzazepine as Selective Dopamine D3 Receptor Antagonists Using 3D-QSAR, Molecular Docking and Molecular Dynamics

PubMed Central

Liu, Jing; Li, Yan; Zhang, Shuwei; Xiao, Zhengtao; Ai, Chunzhi

2011-01-01

In recent years, great interest has been paid to the development of compounds with high selectivity for central dopamine (DA) D3 receptors, an interesting therapeutic target in the treatment of different neurological disorders. In the present work, based on a dataset of 110 collected benzazepine (BAZ) DA D3 antagonists with diverse kinds of structures, a variety of in silico modeling approaches, including comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), homology modeling, molecular docking and molecular dynamics (MD) were carried out to reveal the requisite 3D structural features for activity. Our results show that both the receptor-based (Q2 = 0.603, R2ncv = 0.829, R2pre = 0.690, SEE = 0.316, SEP = 0.406) and ligand-based 3D-QSAR models (Q2 = 0.506, R2ncv =0.838, R2pre = 0.794, SEE = 0.316, SEP = 0.296) are reliable with proper predictive capacity. In addition, a combined analysis between the CoMFA, CoMSIA contour maps and MD results with a homology DA receptor model shows that: (1) ring-A, position-2 and R3 substituent in ring-D are crucial in the design of antagonists with higher activity; (2) more bulky R1 substituents (at position-2 of ring-A) of antagonists may well fit in the binding pocket; (3) hydrophobicity represented by MlogP is important for building satisfactory QSAR models; (4) key amino acids of the binding pocket are CYS101, ILE105, LEU106, VAL151, PHE175, PHE184, PRO254 and ALA251. To our best knowledge, this work is the first report on 3D-QSAR modeling of the new fused BAZs as DA D3 antagonists. These results might provide information for a better understanding of the mechanism of antagonism and thus be helpful in designing new potent DA D3 antagonists. PMID:21541053

Studies of new fused benzazepine as selective dopamine D3 receptor antagonists using 3D-QSAR, molecular docking and molecular dynamics.

PubMed

Liu, Jing; Li, Yan; Zhang, Shuwei; Xiao, Zhengtao; Ai, Chunzhi

2011-02-18

In recent years, great interest has been paid to the development of compounds with high selectivity for central dopamine (DA) D3 receptors, an interesting therapeutic target in the treatment of different neurological disorders. In the present work, based on a dataset of 110 collected benzazepine (BAZ) DA D3 antagonists with diverse kinds of structures, a variety of in silico modeling approaches, including comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), homology modeling, molecular docking and molecular dynamics (MD) were carried out to reveal the requisite 3D structural features for activity. Our results show that both the receptor-based (Q(2) = 0.603, R(2) (ncv) = 0.829, R(2) (pre) = 0.690, SEE = 0.316, SEP = 0.406) and ligand-based 3D-QSAR models (Q(2) = 0.506, R(2) (ncv) =0.838, R(2) (pre) = 0.794, SEE = 0.316, SEP = 0.296) are reliable with proper predictive capacity. In addition, a combined analysis between the CoMFA, CoMSIA contour maps and MD results with a homology DA receptor model shows that: (1) ring-A, position-2 and R(3) substituent in ring-D are crucial in the design of antagonists with higher activity; (2) more bulky R(1) substituents (at position-2 of ring-A) of antagonists may well fit in the binding pocket; (3) hydrophobicity represented by MlogP is important for building satisfactory QSAR models; (4) key amino acids of the binding pocket are CYS101, ILE105, LEU106, VAL151, PHE175, PHE184, PRO254 and ALA251. To our best knowledge, this work is the first report on 3D-QSAR modeling of the new fused BAZs as DA D3 antagonists. These results might provide information for a better understanding of the mechanism of antagonism and thus be helpful in designing new potent DA D3 antagonists.

An improvement of LLNA:DA to assess the skin sensitization potential of chemicals.

PubMed

Zhang, Hongwei; Shi, Ying; Wang, Chao; Zhao, Kangfeng; Zhang, Shaoping; Wei, Lan; Dong, Li; Gu, Wen; Xu, Yongjun; Ruan, Hongjie; Zhi, Hong; Yang, Xiaoyan

2017-01-01

We developed a modified local lymph node assay based on ATP (LLNA:DA), termed the Two-Stage LLNA:DA, to further reduce the animal numbers in the identification of sensitizers. In the Two-Stage LLNA:DA procedure, 13 chemicals ranging from non-sensitizers to extreme sensitizers were selected. The first stage used reduced LLNA:DA (rLLNA:DA) to screen out sensitive chemicals. The second stage used LLNA:DA based on OECD 442 (A) to classify those potential sensitizers screened out in the first stage. In the first stage, the SIs of the methyl methacrylate, salicylic acid, methyl salicylate, ethyl salicylate, isopropanol and propanediol were below 1.8 and need not to be tested in the second step. Others continued to be tested by LLNA:DA. In the second stage, sodium lauryl sulphate and xylene were classified as weak sensitizers. a-hexyl cinnamic aldehyde and eugenol were moderate sensitizers. Benzalkonium chloride and glyoxal were strong sensitizers, and phthalic anhydride was an extreme sensitizer. The 9/9, 11/12, 10/11, and 8/13 (positive or negative only) categories of the Two-Stage LLNA:DA were consistent with those from the other methods (LLNA, LLNA:DA, GPMT/BT and HMT/HPTA), suggesting that Two-Stage LLNA:DA have a high coincidence rate with reported data. In conclusion, The Two-Stage LLNA:DA is in line with the "3R" rules, and can be a modification of LLNA:DA but needs more study.

Fluctuating hydrogen-bond networks govern anomalous electron transfer kinetics in a blue copper protein.

PubMed

Kretchmer, Joshua S; Boekelheide, Nicholas; Warren, Jeffrey J; Winkler, Jay R; Gray, Harry B; Miller, Thomas F

2018-06-12

We combine experimental and computational methods to address the anomalous kinetics of long-range electron transfer (ET) in mutants of Pseudomonas aeruginosa azurin. ET rates and driving forces for wild type (WT) and three N47X mutants (X = L, S, and D) of Ru(2,2'-bipyridine) 2 (imidazole)(His83) azurin are reported. An enhanced ET rate for the N47L mutant suggests either an increase of the donor-acceptor (DA) electronic coupling or a decrease in the reorganization energy for the reaction. The underlying atomistic features are investigated using a recently developed nonadiabatic molecular dynamics method to simulate ET in each of the azurin mutants, revealing unexpected aspects of DA electronic coupling. In particular, WT azurin and all studied mutants exhibit more DA compression during ET (>2 Å) than previously recognized. Moreover, it is found that DA compression involves an extended network of hydrogen bonds, the fluctuations of which gate the ET reaction, such that DA compression is facilitated by transiently rupturing hydrogen bonds. It is found that the N47L mutant intrinsically disrupts this hydrogen-bond network, enabling particularly facile DA compression. This work, which reveals the surprisingly fluctional nature of ET in azurin, suggests that hydrogen-bond networks can modulate the efficiency of long-range biological ET. Copyright © 2018 the Author(s). Published by PNAS.

Dynamic changes in dopamine neuron function after DNSP-11 treatment: effects in vivo and increased ERK 1/2 phosphorylation in vitro.

PubMed

Fuqua, Joshua L; Littrell, Ofelia M; Lundblad, Martin; Turchan-Cholewo, Jadwiga; Abdelmoti, Lina G; Galperin, Emilia; Bradley, Luke H; Cass, Wayne A; Gash, Don M; Gerhardt, Greg A

2014-04-01

Glial cell-line derived neurotrophic factor (GDNF) has demonstrated robust effects on dopamine (DA) neuron function and survival. A post-translational processing model of the human GDNF proprotein theorizes the formation of smaller, amidated peptide(s) from the proregion that exhibit neurobiological function, including an 11-amino-acid peptide named dopamine neuron stimulating peptide-11 (DNSP-11). A single treatment of DNSP-11 was delivered to the substantia nigra in the rat to investigate effects on DA-neuron function. Four weeks after treatment, potassium (K+) and D-amphetamine evoked DA release were studied in the striatum using microdialysis. There were no significant changes in DA-release after DNSP-11 treatment determined by microdialysis. Dopamine release was further examined in discrete regions of the striatum using high-speed chronoamperometry at 1-, 2-, and 4-weeks after DNSP-11 treatment. Two weeks after DNSP-11 treatment, potassium-evoked DA release was increased in specific subregions of the striatum. However, spontaneous locomotor activity was unchanged by DNSP-11 treatment. In addition, we show that a single treatment of DNSP-11 in the MN9D dopaminergic neuronal cell line results in phosphorylation of ERK1/2, which suggests a novel cellular mechanism responsible for increases in DA function. Copyright © 2014 Elsevier Inc. All rights reserved.

Snow multivariable data assimilation for hydrological predictions in Alpine sites

NASA Astrophysics Data System (ADS)

Piazzi, Gaia; Thirel, Guillaume; Campo, Lorenzo; Gabellani, Simone; Stevenin, Hervè

2017-04-01

Snowpack dynamics (snow accumulation and ablation) strongly impacts on hydrological processes in Alpine areas. During the winter season the presence of snow cover (snow accumulation) reduces the drainage in the basin with a resulting lower watershed time of concentration in case of possible rainfall events. Moreover, the release of the significant water volume stored in winter (snowmelt) considerably contributes to the total discharge during the melting period. Therefore when modeling hydrological processes in snow-dominated catchments the quality of predictions deeply depends on how the model succeeds in catching snowpack dynamics. The integration of a hydrological model with a snow module allows improving predictions of river discharges. Besides the well-known modeling limitations (uncertainty in parameterizations; possible errors affecting both meteorological forcing data and initial conditions; approximations in boundary conditions), there are physical factors that make an exhaustive reconstruction of snow dynamics complicated: snow intermittence in space and time, stratification and slow phenomena like metamorphism processes, uncertainty in snowfall evaluation, wind transportation, etc. Data Assimilation (DA) techniques provide an objective methodology to combine several independent snow-related data sources (model simulations, ground-based measurements and remote sensed observations) in order to obtain the most likely estimate of snowpack state. This study presents SMASH (Snow Multidata Assimilation System for Hydrology), a multi-layer snow dynamic model strengthened by a multivariable DA framework for hydrological purposes. The model is physically based on mass and energy balances and can be used to reproduce the main physical processes occurring within the snowpack: accumulation, density dynamics, melting, sublimation, radiative balance, heat and mass exchanges. The model is driven by observed forcing meteorological data (air temperature, wind velocity, relative air humidity, precipitation and incident solar radiation) to provide a complete estimate of snowpack state. The implementation of a DA scheme enables to assimilate simultaneously ground-based observations of different snow-related variables (snow depth, snow density, surface temperature and albedo). SMASH performances are evaluated by using observed data supplied by meteorological stations located in three experimental Alpine sites: Col de Porte (1325 m, France); Torgnon (2160 m, Italy); Weissfluhjoch (2540 m, Switzerland). A comparison analysis between the resulting performaces of Particle Filter and Ensemble Kalman Filter schemes is shown.

Roles of Fragile X Mental Retardation Protein in Dopaminergic Stimulation-induced Synapse-associated Protein Synthesis and Subsequent α-Amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) Receptor Internalization*

PubMed Central

Wang, Hansen; Kim, Susan S.; Zhuo, Min

2010-01-01

Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of α-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome. PMID:20457613

Roles of fragile X mental retardation protein in dopaminergic stimulation-induced synapse-associated protein synthesis and subsequent alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) receptor internalization.

PubMed

Wang, Hansen; Kim, Susan S; Zhuo, Min

2010-07-09

Fragile X syndrome, the most common form of inherited mental retardation, is caused by the absence of the RNA-binding protein fragile X mental retardation protein (FMRP). FMRP regulates local protein synthesis in dendritic spines. Dopamine (DA) is involved in the modulation of synaptic plasticity. Activation of DA receptors can regulate higher brain functions in a protein synthesis-dependent manner. Our recent study has shown that FMRP acts as a key messenger for DA modulation in forebrain neurons. Here, we demonstrate that FMRP is critical for DA D1 receptor-mediated synthesis of synapse-associated protein 90/PSD-95-associated protein 3 (SAPAP3) in the prefrontal cortex (PFC). DA D1 receptor stimulation induced dynamic changes of FMRP phosphorylation. The changes in FMRP phosphorylation temporally correspond with the expression of SAPAP3 after D1 receptor stimulation. Protein phosphatase 2A, ribosomal protein S6 kinase, and mammalian target of rapamycin are the key signaling molecules for FMRP linking DA D1 receptors to SAPAP3. Knockdown of SAPAP3 did not affect surface expression of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-4-propionate (AMPA) GluR1 receptors induced by D1 receptor activation but impaired their subsequent internalization in cultured PFC neurons; the subsequent internalization of GluR1 was also impaired in Fmr1 knock-out PFC neurons, suggesting that FMRP may be involved in subsequent internalization of GluR1 through regulating the abundance of SAPAP3 after DA D1 receptor stimulation. Our study thus provides further insights into FMRP involvement in DA modulation and may help to reveal the molecular mechanisms underlying impaired learning and memory in fragile X syndrome.

N-octanoyl-dopamine is a potent inhibitor of platelet function.

PubMed

Ait-Hsiko, Lamia; Kraaij, Tineke; Wedel, Johannes; Theisinger, Bastian; Theisinger, Sonja; Yard, Benito; Bugert, Peter; Schedel, Angelika

2013-01-01

Dopamine (DA) is a co-agonist for platelet activation; yet, donor DA treatment is associated with improved transplantation outcome in renal and heart recipients. Recently, N-octanoyl-dopamine (NOD) was developed which displays superior effects compared to DA in terms of graft protecting properties. Whereas DA is a known platelet co-agonist, the effect of NOD on platelet function is unknown. This is a hypothesis generating study with the aim to assess the effects and molecular mechanisms of NOD and NOD-like compounds on platelet function. The influence of DA, NOD, and NOD-like compounds on platelet responses to classical agonists (adenosine 5'-diphosphate (ADP), U46619) was investigated in six healthy donors by applying whole blood aggregometry (Multiplate®) and flow cytometry for Pac-1, CD62P, and CD63 expression. Changes in platelet cAMP concentrations were assessed by ELISA. While DA showed synergy in platelet activation by ADP and U46619, NOD caused significant inhibition of platelet function both in whole blood aggregometry and flow cytometry. The inhibitory effect of NOD was not mediated via cAMP levels. The nonredox-active NOD-analog N-octanoyl-tyramine had no effects on platelet function. Acetylated NOD conferred to NOD by intracellular esterases showed similar inhibitory effects as NOD. In contrast to DA, NOD is a potent inhibitor of platelet function most likely through intracellular redox-active processes. This adds to the overall protective effect of NOD on pre-transplantation injury and makes NOD an attractive candidate compound for donor or organ conditioning prior to transplantation.

Protein complex formation and intranuclear dynamics of NAC1 in cancer cells.

PubMed

Nakayama, Naomi; Kato, Hiroaki; Sakashita, Gyosuke; Nariai, Yuko; Nakayama, Kentaro; Kyo, Satoru; Urano, Takeshi

2016-09-15

Nucleus accumbens-associated protein 1 (NAC1) is a cancer-related transcription regulator protein that is also involved in the pluripotency and differentiation of embryonic stem cells. NAC1 is overexpressed in various carcinomas including ovarian, cervical, breast, and pancreatic carcinomas. NAC1 knock-down was previously shown to result in the apoptosis of ovarian cancer cell lines and to rescue their sensitivity to chemotherapy, suggesting that NAC1 may be a potential therapeutic target, but protein complex formation and the dynamics of intranuclear NAC1 in cancer cells remain poorly understood. In this study, analysis of HeLa cell lysates by fast protein liquid chromatography (FPLC) on a sizing column showed that the NAC1 peak corresponded to an apparent molecular mass of 300-500 kDa, which is larger than the estimated molecular mass (58 kDa) of the protein. Furthermore, live cell photobleaching analyses with green fluorescent protein (GFP)-fused NAC1 proteins revealed the intranuclear dynamics of NAC1. Collectively our results demonstrate that NAC1 forms a protein complex to function as a transcriptional regulator in cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Lectins as probes for assessing the accessibility of N-linked glycans in relation to the conformational changes of fibronectin.

PubMed

Agniel, Rémy; Vendrely, Charlotte; Poulouin, Laurent; Bascetin, Rümeyza; Benachour, Hamanou; Gallet, Olivier; Leroy-Dudal, Johanne

2015-12-01

Fibronectin, a ≈ 450-kDa protein with 4-9% (w/w) glycosylation, is a key component of extracellular matrices and has a high conformational lability regarding its functions. However, the accessibility and the role of glycosylated moieties associated with the conformational changes of fibronectin are poorly understood. Using lectins as probes, we developed an approach comprising dynamic light scattering, turbidimetry measurements, and isothermal titration calorimetry to assess the accessibility of glycosylated moieties of fibronectin undergoing thermal-induced conformational changes. Among a set of 14 lectins, fibronectin mainly reacted with mannose-binding lectins, specifically concanavalin A. When temperature was raised from 25 to 50 °C, fibronectin underwent progressive unfolding, but the conformation of concanavalin A was unaffected. Dynamic light scattering, turbidimetry measurements, and isothermal titration calorimetry showed increased concanavalin A binding to fibronectin during progressive thermal-induced unfolding of the protein core. Such data suggest that mannosylated residues are progressively exposed as fibronectin unfolds. Because oligosaccharide moieties can be differently exposed to cells, and the cell's responses could be modified physiologically or pathologically, modulation of fibronectin sugar chains could be relevant to its biological functions. Thus, lectins might be useful tools to probe the glycosylation accessibility accompanying changes in protein core folding, for which a better understanding would be of value for biological and biomedical research. Copyright © 2015 John Wiley & Sons, Ltd.

Airspace Dimension Assessment with nanoparticles reflects lung density as quantified by MRI

PubMed Central

Jakobsson, Jonas K; Löndahl, Jakob; Olsson, Lars E; Diaz, Sandra; Zackrisson, Sophia; Wollmer, Per

2018-01-01

Background Airspace Dimension Assessment with inhaled nanoparticles is a novel method to determine distal airway morphology. This is the first empirical study using Airspace Dimension Assessment with nanoparticles (AiDA) to estimate distal airspace radius. The technology is relatively simple and potentially accessible in clinical outpatient settings. Method Nineteen never-smoking volunteers performed nanoparticle inhalation tests at multiple breath-hold times, and the difference in nanoparticle concentration of inhaled and exhaled gas was measured. An exponential decay curve was fitted to the concentration of recovered nanoparticles, and airspace dimensions were assessed from the half-life of the decay. Pulmonary tissue density was measured using magnetic resonance imaging (MRI). Results The distal airspace radius measured by AiDA correlated with lung tissue density as measured by MRI (ρ = −0.584; p = 0.0086). The linear intercept of the logarithm of the exponential decay curve correlated with forced expiratory volume in one second (FEV1) (ρ = 0.549; p = 0.0149). Conclusion The AiDA method shows potential to be developed into a tool to assess conditions involving changes in distal airways, eg, emphysema. The intercept may reflect airway properties; this finding should be further investigated.

Prognosis of carotid dissecting aneurysms

PubMed Central

Larsson, Susanna C.; King, Alice; Madigan, Jeremy; Levi, Christopher; Norris, John W.

2017-01-01

Objective: To determine the natural history of dissecting aneurysm (DA) and whether DA is associated with an increased recurrent stroke risk and whether type of antithrombotic drugs (antiplatelets vs anticoagulants) modifies the persistence or development of DA. Methods: We included 264 patients with extracranial cervical artery dissection (CAD) from the Cervical Artery Dissection in Stroke Study (CADISS), a multicenter prospective study that compared antiplatelet with anticoagulation therapy. Logistic regression was used to estimate age- and sex-adjusted odds ratios. We conducted a systematic review of published studies assessing the natural history of DA and stroke risk in patients with non-surgically-treated extracranial CAD with DA. Results: In CADISS, DA was present in 24 of 264 patients at baseline. In 36 of 248 patients with follow-up neuroimaging at 3 months, 12 of the 24 baseline DAs persisted, and 24 new DA had developed. There was no association between treatment allocation (antiplatelets vs anticoagulants) and whether DA at baseline persisted at follow-up or whether new DA developed. During 12 months of follow-up, stroke occurred in 1 of 48 patients with DA and in 7 of 216 patients without DA (age- and sex-adjusted odds ratio 0.84; 95% confidence interval 0.10–7.31; p = 0.88). Published studies, mainly retrospective, showed a similarly low risk of stroke and no evidence of an increased stroke rate in patients with DA. Conclusions: The results of CADISS provide evidence suggesting that DAs may have benign prognosis and therefore medical treatment should be considered. PMID:28087823

A Behavioral and Genetic Dissection of Two Forms of Olfactory Plasticity in Caenorhabditis elegans: Adaptation and Habituation

PubMed Central

Bernhard, Nirit; van der Kooy, Derek

2000-01-01

Continuous presentation of an olfactory stimulus causes a decrement of the chemotaxis response in the nematode Caenorhabditis elegans. However, the differences between the learning process of habituation (a readily reversible decrease in behavioral response) and other types of olfactory plasticity such as adaptation (a decrement in response due to sensory fatigue, which cannot be dishabituated) have not been addressed. The volatile odorant diacetyl (DA) was used within a single paradigm to assess the distinct processes of olfactory adaptation and habituation. Preexposing and testing worms to 100% DA vapors caused a chemotaxis decrement that was not reversible despite the presentation of potentially dishabituating stimuli. This DA adaptation was abolished in worms with an odr-10 mutation (encoding a high-affinity DA receptor on the AWA neuron), even though naive chemotaxis remained unaffected. Conversely, DA adaptation remained intact in odr-1 mutants (defective in AWC neuron-mediated olfactory behavior), even though naive chemotaxis to DA decreased. Surprisingly, exposure to vapors of intermediate concentrations of DA (0.01% and 25%) did not cause worms to exhibit any response decrement. In contrast to preexposure to high DA concentrations, preexposure to low DA concentrations (0.001%) produced habituation of the chemotaxis response (a dishabituating stimulus could reverse the response decrement back to baseline levels). The distinct behavioral effects produced by DA preexposure highlight a concentration-dependent dissociation between two decremental olfactory processes: adaptation at high DA concentrations versus habituation at low DA concentrations. PMID:10940320

Mapping Dopamine Function in Primates Using Pharmacologic Magnetic Resonance Imaging

PubMed Central

Sanchez-Pernaute, Rosario; Brownell, Anna-Liisa; Chen, Yin-Ching Iris; Isacson, Ole

2008-01-01

Dopamine (DA) receptors play a central role in such diverse pathologies as Parkinson's disease, schizophrenia, and drug abuse. We used an amphetamine challenge combined with pharmacologic magnetic resonance imaging (phMRI) to map DA-associated circuitry in nonhuman primates with high sensitivity and spatial resolution. Seven control cynomolgous monkeys and 10 MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated parkinsonian primates were studied longitudinally using both positron emission tomography (PET) and phMRI. Amphetamine challenge (2.5 mg/kg, i.v.) in control monkeys increased relative cerebral blood volume (rCBV) in a number of brain regions not described previously, such as parafascicular thalamus, precentral gyrus, and dentate nucleus of the cerebellum. With the high spatial resolution, we were also able to readily identify changes in rCBV in the anterior cingulate, substantia nigra, ventral tegmental area, caudate (tail and head), putamen, and nucleus accumbens. Amphetamine induced decreases in rCBV in occipital and posterior parietal cortices. Parkinsonian primates had a prominent loss of response to amphetamine, with relative sparing of the nucleus accumbens and parafascicular thalamus. There was a significant correlation between rCBV loss in the substantia nigra and both PET imaging of dopamine transporters and behavioral measures. Monkeys with partial lesions as defined by 2β-carbomethoxy-3β-(4-fluorophenyl) tropane binding to dopamine transporters showed recruitment of premotor and motor cortex after amphetamine stimulus similar to what has been noted in Parkinson's patients during motor tasks. These data indicate that phMRI is a powerful tool for assessment of dynamic changes associated with normal and dysfunctional DA brain circuitry in primates. PMID:15509742

Plankton Production Biology

DTIC Science & Technology

2013-09-30

population dynamics (growth rate, production, mortality) of copepod nauplii in the field or captured water columns (mesocosms). Since biology...36-45, doi:10.1016/j.dsr.2012.03.001, 2012. PUBLICATIONS Banse, K., Naqvi, S.W.A., Narvekar, P.V., Postel, J.R., Jayakumar , D.A. Oxygen minimum

Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.

PubMed

Choi, Yoon Jin; Lee, Dong Ho; Choi, Myung Gyu; Lee, Sung Joon; Kim, Sung Kook; Song, Geun Am; Rhee, Poong Lyul; Jung, Hwoon Yong; Kang, Dae Hwan; Lee, Yong Chan; Lee, Si Hyung; Choi, Suck Chei; Shim, Ki Nam; Seol, Sang Yong; Moon, Jeong Seop; Shin, Yong Woon; Kim, Hyun Soo; Lee, Soo Teik; Cho, Jin Woong; Choi, Eun Kwang; Lee, Oh Young; Jang, Jin Seok

2017-11-01

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670). © 2017 The Korean Academy of Medical Sciences.

Volumetric-modulated arc therapy in postprostatectomy radiotherapy patients: A planning comparison study

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

Forde, Elizabeth, E-mail: eforde@tcd.ie; Kneebone, Andrew; Northern Clinical School, University of Sydney, New South Wales

2013-10-01

The purpose of this study was to compare postprostatectomy planning for volumetric-modulated arc therapy (VMAT) with both single arc (SA) and double arcs (DA) against dynamic sliding window intensity-modulated radiotherapy (IMRT). Ten cases were planned with IMRT, SA VMAT, and DA VMAT. All cases were planned to achieve a minimum dose of 68 Gy to 95% of the planning target volume (PTV) and goals to limit rectal volume >40 Gy to 35% and >65 Gy to 17%, and bladder volumes >40 Gy to 50% and >65 Gy to 25%. Plans were averaged across the 10 patients and compared for meanmore » dose, conformity, homogeneity, rectal and bladder doses, and monitor units. The mean dose to the clinical target volume and PTV was significantly higher (p<0.05) for SA compared with DA or IMRT. The homogeneity index was not significantly different: SA = 0.09; DA = 0.08; and IMRT = 0.07. The rectal V40 was lowest for the DA plan. The rectal V20 was significantly lower (p<0.05) for both the VMAT plans compared with IMRT. There were no significant differences for bladder V40 or rectal and bladder V65. The IMRT plans required 1400 MU compared with 745 for DA and 708 for SA. This study shows that for equivalent dose coverage, SA and DA VMAT plans result in higher mean doses to the clinical target volume and PTV. This greater dose heterogeneity is balanced by improved low-range rectal doses and halving of the monitor units.« less

The future of PanDA in ATLAS distributed computing

NASA Astrophysics Data System (ADS)

De, K.; Klimentov, A.; Maeno, T.; Nilsson, P.; Oleynik, D.; Panitkin, S.; Petrosyan, A.; Schovancova, J.; Vaniachine, A.; Wenaus, T.

2015-12-01

Experiments at the Large Hadron Collider (LHC) face unprecedented computing challenges. Heterogeneous resources are distributed worldwide at hundreds of sites, thousands of physicists analyse the data remotely, the volume of processed data is beyond the exabyte scale, while data processing requires more than a few billion hours of computing usage per year. The PanDA (Production and Distributed Analysis) system was developed to meet the scale and complexity of LHC distributed computing for the ATLAS experiment. In the process, the old batch job paradigm of locally managed computing in HEP was discarded in favour of a far more automated, flexible and scalable model. The success of PanDA in ATLAS is leading to widespread adoption and testing by other experiments. PanDA is the first exascale workload management system in HEP, already operating at more than a million computing jobs per day, and processing over an exabyte of data in 2013. There are many new challenges that PanDA will face in the near future, in addition to new challenges of scale, heterogeneity and increasing user base. PanDA will need to handle rapidly changing computing infrastructure, will require factorization of code for easier deployment, will need to incorporate additional information sources including network metrics in decision making, be able to control network circuits, handle dynamically sized workload processing, provide improved visualization, and face many other challenges. In this talk we will focus on the new features, planned or recently implemented, that are relevant to the next decade of distributed computing workload management using PanDA.

Scientific Studies of the High-Latitude Ionosphere with the Ionosphere Dynamics and ElectroDynamics - Data Assimilation (IDED-DA) Model

DTIC Science & Technology

2014-09-23

conduct simulations with a high-latitude data assimilation model. The specific objectives are to study magnetosphere-ionosphere ( M -I) coupling processes...based on three physics-based models, including a magnetosphere-ionosphere ( M -I) electrodynamics model, an ionosphere model, and a magnetic...inversion code. The ionosphere model is a high-resolution version of the Ionosphere Forecast Model ( IFM ), which is a 3-D, multi-ion model of the ionosphere

EFFECTS OF DIFFERENT WARM-UP PROGRAMS ON GOLF PERFORMANCE IN ELITE MALE GOLFERS

PubMed Central

Macfarlane, Alison

2012-01-01

Background: The physical demands required of the body to execute a shot in golf are enormous. Current evidence suggests that warm-up involving static stretching is detrimental to immediate performance in golf as opposed to active dynamic stretching. However the effect of resistance exercises during warm-up before golf on immediate performance is unknown. Therefore, the purpose of this study was to assess the effects of three different warm-up programs on immediate golf performance. Methods: Fifteen elite male golfers completed three different warm-up programs over three sessions on non-consecutive days. After each warm-up program each participant hit ten maximal drives with the ball flight and swing analyzed with Flightscope® to record maximum club head speed (MCHS), maximal driving distance (MDD), driving accuracy (DA), smash factor (SF) and consistent ball strike (CBS). Results: Repeated measures ANOVA tests showed statistically significant difference within 3 of the 5 factors of performance (MDD, CBS and SF). Subsequently, a paired t-test then showed statistically significant (p<0.05) improvements occurred in each of these three factors in the group performing a combined active dynamic and functional resistance (FR) warm-up as opposed to either the active dynamic (AD) warm-up or the combined AD with weights warm-up (WT). There were no statistically significant differences observed between the AD warm-up and the WT warm-up for any of the five performance factors and no statistical significant difference between any of the warm-ups for maximum clubhead speed (MCHS) and driving accuracy (DA). Conclusion: Performing a combined AD and FR warm up with Theraband® leads to significant increase in immediate performance of certain factors of the golf drive compared to performing an AD warm-up by itself or a combined AD with WT warm-up. No significant difference was observed between the three warm-up groups when looking at immediate effect on driving accuracy or maximum club head speed. The addition of functional resistance activities to active dynamic stretching has immediate benefits to elite male golfers in relation to some factors of their performance. Level of Evidence: This study is a Quantitative Experimental design using repeated measures and multiple crossovers. It cannot be classified using the descriptive level of evidence. PMID:23936749

Crowding Induces Complex Ergodic Diffusion and Dynamic Elongation of Large DNA Molecules

PubMed Central

Chapman, Cole D.; Gorczyca, Stephanie; Robertson-Anderson, Rae M.

2015-01-01

Despite the ubiquity of molecular crowding in living cells, the effects of crowding on the dynamics of genome-sized DNA are poorly understood. Here, we track single, fluorescent-labeled large DNA molecules (11, 115 kbp) diffusing in dextran solutions that mimic intracellular crowding conditions (0–40%), and determine the effects of crowding on both DNA mobility and conformation. Both DNAs exhibit ergodic Brownian motion and comparable mobility reduction in all conditions; however, crowder size (10 vs. 500 kDa) plays a critical role in the underlying diffusive mechanisms and dependence on crowder concentration. Surprisingly, in 10-kDa dextran, crowder influence saturates at ∼20% with an ∼5× drop in DNA diffusion, in stark contrast to exponentially retarded mobility, coupled to weak anomalous subdiffusion, with increasing concentration of 500-kDa dextran. Both DNAs elongate into lower-entropy states (compared to random coil conformations) when crowded, with elongation states that are gamma distributed and fluctuate in time. However, the broadness of the distribution of states and the time-dependence and length scale of elongation length fluctuations depend on both DNA and crowder size with concentration having surprisingly little impact. Results collectively show that mobility reduction and coil elongation of large crowded DNAs are due to a complex interplay between entropic effects and crowder mobility. Although elongation and initial mobility retardation are driven by depletion interactions, subdiffusive dynamics, and the drastic exponential slowing of DNA, up to ∼300×, arise from the reduced mobility of larger crowders. Our results elucidate the highly important and widely debated effects of cellular crowding on genome-sized DNA. PMID:25762333

Tonic 5nM DA Stabilizes Neuronal Output by Enabling Bidirectional Activity-Dependent Regulation of the Hyperpolarization Activated Current via PKA and Calcineurin

PubMed Central

Krenz, Wulf-Dieter C.; Rodgers, Edmund W.; Baro, Deborah J.

2015-01-01

Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP’s first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output. PMID:25692473

Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.

PubMed

Krenz, Wulf-Dieter C; Rodgers, Edmund W; Baro, Deborah J

2015-01-01

Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP's first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.

Amphetamine modulates brain signal variability and working memory in younger and older adults.

PubMed

Garrett, Douglas D; Nagel, Irene E; Preuschhof, Claudia; Burzynska, Agnieszka Z; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R; Bäckman, Lars; Lindenberger, Ulman

2015-06-16

Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD(BOLD)) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.

Amphetamine modulates brain signal variability and working memory in younger and older adults

PubMed Central

Garrett, Douglas D.; Nagel, Irene E.; Preuschhof, Claudia; Burzynska, Agnieszka Z.; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J.; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R.; Bäckman, Lars; Lindenberger, Ulman

2015-01-01

Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI–based blood oxygen level-dependent (BOLD) signal variability (SDBOLD) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SDBOLD levels in the presence of AMPH. Drug session order greatly moderated change–change relations between AMPH-driven SDBOLD and reaction time means (RTmean) and SDs (RTSD). Older adults who received AMPH in the first session tended to improve in RTmean and RTSD when SDBOLD was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SDBOLD decreased (for RTmean) or no effect at all (for RTSD). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics. PMID:26034283

Single nucleotide editing without DNA cleavage using CRISPR/Cas9-deaminase in the sea urchin embryo.

PubMed

Shevidi, Saba; Uchida, Alicia; Schudrowitz, Natalie; Wessel, Gary M; Yajima, Mamiko

2017-12-01

A single base pair mutation in the genome can result in many congenital disorders in humans. The recent gene editing approach using CRISPR/Cas9 has rapidly become a powerful tool to replicate or repair such mutations in the genome. These approaches rely on cleaving DNA, while presenting unexpected risks. In this study, we demonstrate a modified CRISPR/Cas9 system fused to cytosine deaminase (Cas9-DA), which induces a single nucleotide conversion in the genome. Cas9-DA was introduced into sea urchin eggs with sgRNAs targeted for SpAlx1, SpDsh, or SpPks, each of which is critical for skeletogenesis, embryonic axis formation, or pigment formation, respectively. We found that both Cas9 and Cas9-DA edit the genome, and cause predicted phenotypic changes at a similar efficiency. Cas9, however, resulted in significant deletions in the genome centered on the gRNA target sequence, whereas Cas9-DA resulted in single or double nucleotide editing of C to T conversions within the gRNA target sequence. These results suggest that the Cas9-DA approach may be useful for manipulating gene activity with decreased risks of genomic aberrations. Developmental Dynamics 246:1036-1046, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Epothilone D prevents binge methamphetamine-mediated loss of striatal dopaminergic markers.

PubMed

Killinger, Bryan A; Moszczynska, Anna

2016-02-01

Exposure to binge methamphetamine (METH) can result in a permanent or transient loss of dopaminergic (DAergic) markers such as dopamine (DA), dopamine transporter, and tyrosine hydroxylase (TH) in the striatum. We hypothesized that the METH-induced loss of striatal DAergic markers was, in part, due to a destabilization of microtubules (MTs) in the nigrostriatal DA pathway that ultimately impedes anterograde axonal transport of these markers. To test this hypothesis, adult male Sprague-Dawley rats were treated with binge METH or saline in the presence or absence of epothilone D (EpoD), a MT-stabilizing compound, and assessed 3 days after the treatments for the levels of several DAergic markers as well as for the levels of tubulins and their post-translational modifications (PMTs). Binge METH induced a loss of stable long-lived MTs within the striatum but not within the substantia nigra pars compacta (SNpc). Treatment with a low dose of EpoD increased the levels of markers of stable MTs and prevented METH-mediated deficits in several DAergic markers in the striatum. In contrast, administration of a high dose of EpoD appeared to destabilize MTs and potentiated the METH-induced deficits in several DAergic markers. The low-dose EpoD also prevented the METH-induced increase in striatal DA turnover and increased behavioral stereotypy during METH treatment. Together, these results demonstrate that MT dynamics plays a role in the development of METH-induced losses of several DAergic markers in the striatum and may mediate METH-induced degeneration of terminals in the nigrostriatal DA pathway. Our study also demonstrates that MT-stabilizing drugs such as EpoD have a potential to serve as useful therapeutic agents to restore function of DAergic nerve terminals following METH exposure when administered at low doses. Administration of binge methamphetamine (METH) negatively impacts neurotransmission in the nigrostriatal dopamine (DA) system. The effects of METH include decreasing the levels of DAergic markers in the striatum. We have determined that high-dose METH destabilizes microtubules in this pathway, which is manifested by decreased levels of acetylated (Acetyl) and detyrosinated (Detyr) α-tubulin (I). A microtubule stabilizing agent epothilone D protects striatal microtubules form the METH-induced loss of DAergic markers (II). These findings provide a new strategy for protection form METH - restoration of proper axonal transport. © 2015 International Society for Neurochemistry.

Composition of the water-soluble fraction of different cheeses.

PubMed

Taborda, Gonzalo; Molina, Elena; Martínez-Castro, Isabel; Ramos, Mercedes; Amigo, Lourdes

2003-01-01

Volatile and nonvolatile compounds present in the water-soluble fraction (WSF) and water-soluble fraction with molecular weight lower than 1000 Da (WSF < 1000 Da) of six Spanish cheeses, Cabrales, Idiazábal, Mahón, Manchego, Roncal, and a goat's milk cheese, were analyzed. Different nitrogen fractions (determined by Kjeldahl method), caseins (by capillary electrophoresis), peptides and amino acids (by HPLC), and volatile components (by dynamic headspace coupled to GC-MS) as well as mineral content in the cheese fractions were analyzed and compared. The different nitrogen and volatile compounds identified in the WSF were characteristic of each cheese variety. Cabrales cheese displayed the highest content of free amino acids and the highest quantity and variety of volatile compounds. The WSF < 1000 Da fraction was less representative, especially for volatile compounds, as some of the components were lost in the ultrafiltration. Alcohols were better recovered than ketones and esters.

Forgetting in Reinforcement Learning Links Sustained Dopamine Signals to Motivation

PubMed Central

Morita, Kenji

2016-01-01

It has been suggested that dopamine (DA) represents reward-prediction-error (RPE) defined in reinforcement learning and therefore DA responds to unpredicted but not predicted reward. However, recent studies have found DA response sustained towards predictable reward in tasks involving self-paced behavior, and suggested that this response represents a motivational signal. We have previously shown that RPE can sustain if there is decay/forgetting of learned-values, which can be implemented as decay of synaptic strengths storing learned-values. This account, however, did not explain the suggested link between tonic/sustained DA and motivation. In the present work, we explored the motivational effects of the value-decay in self-paced approach behavior, modeled as a series of ‘Go’ or ‘No-Go’ selections towards a goal. Through simulations, we found that the value-decay can enhance motivation, specifically, facilitate fast goal-reaching, albeit counterintuitively. Mathematical analyses revealed that underlying potential mechanisms are twofold: (1) decay-induced sustained RPE creates a gradient of ‘Go’ values towards a goal, and (2) value-contrasts between ‘Go’ and ‘No-Go’ are generated because while chosen values are continually updated, unchosen values simply decay. Our model provides potential explanations for the key experimental findings that suggest DA's roles in motivation: (i) slowdown of behavior by post-training blockade of DA signaling, (ii) observations that DA blockade severely impairs effortful actions to obtain rewards while largely sparing seeking of easily obtainable rewards, and (iii) relationships between the reward amount, the level of motivation reflected in the speed of behavior, and the average level of DA. These results indicate that reinforcement learning with value-decay, or forgetting, provides a parsimonious mechanistic account for the DA's roles in value-learning and motivation. Our results also suggest that when biological systems for value-learning are active even though learning has apparently converged, the systems might be in a state of dynamic equilibrium, where learning and forgetting are balanced. PMID:27736881

Forgetting in Reinforcement Learning Links Sustained Dopamine Signals to Motivation.

PubMed

Kato, Ayaka; Morita, Kenji

2016-10-01

It has been suggested that dopamine (DA) represents reward-prediction-error (RPE) defined in reinforcement learning and therefore DA responds to unpredicted but not predicted reward. However, recent studies have found DA response sustained towards predictable reward in tasks involving self-paced behavior, and suggested that this response represents a motivational signal. We have previously shown that RPE can sustain if there is decay/forgetting of learned-values, which can be implemented as decay of synaptic strengths storing learned-values. This account, however, did not explain the suggested link between tonic/sustained DA and motivation. In the present work, we explored the motivational effects of the value-decay in self-paced approach behavior, modeled as a series of 'Go' or 'No-Go' selections towards a goal. Through simulations, we found that the value-decay can enhance motivation, specifically, facilitate fast goal-reaching, albeit counterintuitively. Mathematical analyses revealed that underlying potential mechanisms are twofold: (1) decay-induced sustained RPE creates a gradient of 'Go' values towards a goal, and (2) value-contrasts between 'Go' and 'No-Go' are generated because while chosen values are continually updated, unchosen values simply decay. Our model provides potential explanations for the key experimental findings that suggest DA's roles in motivation: (i) slowdown of behavior by post-training blockade of DA signaling, (ii) observations that DA blockade severely impairs effortful actions to obtain rewards while largely sparing seeking of easily obtainable rewards, and (iii) relationships between the reward amount, the level of motivation reflected in the speed of behavior, and the average level of DA. These results indicate that reinforcement learning with value-decay, or forgetting, provides a parsimonious mechanistic account for the DA's roles in value-learning and motivation. Our results also suggest that when biological systems for value-learning are active even though learning has apparently converged, the systems might be in a state of dynamic equilibrium, where learning and forgetting are balanced.

Stockton Lake Survey and Assessment. National Register Assessment of Prehistoric Archeological Sites 23DA407 and 23DA408 and Historic Properties Survey in the Stockton Lake Project, Cedar and Dade Counties, Missouri

DTIC Science & Technology

1993-01-01

Elevation 890 HPA Reports Stockton Lake Survey and Assessment page 38 23CE46723CE398 .1 IYAR CPA .COWN if Y 344 CD meer 50 suvexae sitvey area transect...Stockton Lake. The shelter is within the emergency floodpool of the lake. Some deposits north of the beck wall appuoxitmtely 5 to 6 feet my stiU be...point ha some tip damage and one baa corner mintin Arrow point sftm (Sallisaw variant?) 1 0.9 Am*a between remaining side notch and coaesve bowe

The pharmacology of effort-related choice behavior: Dopamine, depression, and individual differences.

PubMed

Salamone, John D; Correa, Merce; Yohn, Samantha; Lopez Cruz, Laura; San Miguel, Noemi; Alatorre, Luisa

2016-06-01

This review paper is focused upon the involvement of mesolimbic dopamine (DA) and related brain systems in effort-based processes. Interference with DA transmission affects instrumental behavior in a manner that interacts with the response requirements of the task, such that rats with impaired DA transmission show a heightened sensitivity to ratio requirements. Impaired DA transmission also affects effort-related choice behavior, which is assessed by tasks that offer a choice between a preferred reinforcer that has a high work requirement vs. less preferred reinforcer that can be obtained with minimal effort. Rats and mice with impaired DA transmission reallocate instrumental behavior away from food-reinforced tasks with high response costs, and show increased selection of low reinforcement/low cost options. Tests of effort-related choice have been developed into models of pathological symptoms of motivation that are seen in disorders such as depression and schizophrenia. These models are being employed to explore the effects of conditions associated with various psychopathologies, and to assess drugs for their potential utility as treatments for effort-related symptoms. Studies of the pharmacology of effort-based choice may contribute to the development of treatments for symptoms such as psychomotor slowing, fatigue or anergia, which are seen in depression and other disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

EFFECTS OF CHRONIC ANTIDEPRESSANT DRUG ADMINISTRATION AND ELECTROCONVULSIVE SHOCK ON ACTIVITY OF DOPAMINERGIC NEURONS IN THE VENTRAL TEGMENTUM

PubMed Central

West, Charles Hutchison Keesor; Weiss, Jay Michael

2010-01-01

Increasing attention is now focused on reduced dopaminergic neurotransmission in the forebrain as participating in depression. The present paper assessed whether effective antidepressant (AD) treatments might counteract, or compensate for, such a change by altering the neuronal activity of dopaminergic neurons in the ventral tegmental area (VTA-DA neurons), the cell bodies of the mesocorticolimbic dopaminergic system. Eight AD drugs or vehicle were administered to rats for 14 days via subcutaneously-implanted minipumps, at which time single-unit electrophysiological activity of VTA-DA neurons was recorded under anesthesia. Also, animals received a series of five electroconvulsive shocks (ECS) or control procedures, after which VTA-DA activity was measured either three or five days after the last ECS. Results showed that the chronic administration of all AD drugs tested except for the monoamine oxidase inhibitor increased the spontaneous firing rate of VTA-DA neurons, while effects on “burst” firing activity were found to be considerably less notable or consistent. ECS increased both spontaneous firing rate and burst firing of VTA-DA neurons. It is suggested that the effects observed are consistent with reports of increased dopamine release in regions to which VTA neurons project after effective AD treatment. However, it is further suggested that changes in VTA-DA neuronal activity in response to AD treatment should be most appropriately assessed under conditions associated with depression, such as stressful conditions. PMID:20482941

Dynamic Analyses of Alternative Polyadenylation from RNA-Seq Reveal 3′-UTR Landscape Across 7 Tumor Types

PubMed Central

Xia, Zheng; Donehower, Lawrence A; Cooper, Thomas A.; Neilson, Joel R.; Wheeler, David A.; Wagner, Eric J.; Li, Wei

2015-01-01

Alternative polyadenylation (APA) is a pervasive mechanism in the regulation of most human genes, and its implication in diseases including cancer is only beginning to be appreciated. Since conventional APA profiling has not been widely adopted, global cancer APA studies are very limited. Here we develop a novel bioinformatics algorithm (DaPars) for the de novo identification of dynamic APAs from standard RNA-seq. When applied to 358 TCGA Pan-Cancer tumor/normal pairs across 7 tumor types, DaPars reveals 1,346 genes with recurrent and tumor-specific APAs. Most APA genes (91%) have shorter 3′ UTRs in tumors that can avoid miRNA-mediated repression, including glutaminase (GLS), a key metabolic enzyme for tumor proliferation. Interestingly, selected APA events add strong prognostic power beyond common clinical and molecular variables, suggesting their potential as novel prognostic biomarkers. Finally, our results implicate CstF64, an essential polyadenylation factor, as a master regulator of 3′ UTR shortening across multiple tumor types. PMID:25409906

Hydrodynamic Determinants of Cell Necrosis and Molecular Delivery Produced by Pulsed Laser Microbeam Irradiation of Adherent Cells

PubMed Central

Compton, Jonathan L.; Hellman, Amy N.; Venugopalan, Vasan

2013-01-01

Time-resolved imaging, fluorescence microscopy, and hydrodynamic modeling were used to examine cell lysis and molecular delivery produced by picosecond and nanosecond pulsed laser microbeam irradiation in adherent cell cultures. Pulsed laser microbeam radiation at λ = 532 nm was delivered to confluent monolayers of PtK2 cells via a 40×, 0.8 NA microscope objective. Using laser microbeam pulse durations of 180–1100 ps and pulse energies of 0.5–10.5 μJ, we examined the resulting plasma formation and cavitation bubble dynamics that lead to laser-induced cell lysis, necrosis, and molecular delivery. The cavitation bubble dynamics are imaged at times of 0.5 ns to 50 μs after the pulsed laser microbeam irradiation, and fluorescence assays assess the resulting cell viability and molecular delivery of 3 kDa dextran molecules. Reductions in both the threshold laser microbeam pulse energy for plasma formation and the cavitation bubble energy are observed with decreasing pulse duration. These energy reductions provide for increased precision of laser-based cellular manipulation including cell lysis, cell necrosis, and molecular delivery. Hydrodynamic analysis reveals critical values for the shear-stress impulse generated by the cavitation bubble dynamics governs the location and spatial extent of cell necrosis and molecular delivery independent of pulse duration and pulse energy. Specifically, cellular exposure to a shear-stress impulse J≳0.1 Pa s ensures cell lysis or necrosis, whereas exposures in the range of 0.035≲J≲0.1 Pa s preserve cell viability while also enabling molecular delivery of 3 kDa dextran. Exposure to shear-stress impulses of J≲0.035 Pa s leaves the cells unaffected. Hydrodynamic analysis of these data, combined with data from studies of 6 ns microbeam irradiation, demonstrates the primacy of shear-stress impulse in determining cellular outcome resulting from pulsed laser microbeam irradiation spanning a nearly two-orders-of-magnitude range of pulse energy and pulse duration. These results provide a mechanistic foundation and design strategy applicable to a broad range of laser-based cellular manipulation procedures. PMID:24209868

Molecular dynamics simulations suggest changes in electrostatic interactions as a potential mechanism through which serine phosphorylation inhibits DNA Polymerase β's activity.

PubMed

Homouz, Dirar; Joyce-Tan, Kwee Hong; Shahir Shamsir, Mohd; Moustafa, Ibrahim M; Idriss, Haitham

2018-01-01

DNA polymerase β is a 39kDa enzyme that is a major component of Base Excision Repair in human cells. The enzyme comprises two major domains, a 31kDa domain responsible for the polymerase activity and an 8kDa domain, which bind ssDNA and has a deoxyribose phosphate (dRP) lyase activity. DNA polymerase β was shown to be phosphorylated in vitro with protein kinase C (PKC) at serines 44 and 55 (S44 and S55), resulting in loss of its polymerase enzymic activity, but not its ability to bind ssDNA. In this study, we investigate the potential phosphorylation-induced structural changes for DNA polymerase β using molecular dynamics. The simulations show drastic conformational changes of the polymerase structure as a result of S44 phosphorylation. Phosphorylation-induced conformational changes transform the closed (active) enzyme structure into an open one. Further analysis of the results points to a key hydrogen bond and newly formed salt bridges as potential drivers of these structural fluctuations. The changes observed with S44/55 and S55 phosphorylation were less dramatic than S44 and the integrity of the H-bond was not compromised. Thus the phosphorylation of S44 is likely the major contributor to structural fluctuations that lead to loss of enzymatic activity. Copyright © 2017. Published by Elsevier Inc.

Randomised clinical trial: relief of upper gastrointestinal symptoms by an acid pocket-targeting alginate-antacid (Gaviscon Double Action) - a double-blind, placebo-controlled, pilot study in gastro-oesophageal reflux disease.

PubMed

Thomas, E; Wade, A; Crawford, G; Jenner, B; Levinson, N; Wilkinson, J

2014-03-01

The alginate-antacid, Gaviscon Double Action (Gaviscon DA; Reckitt Benckiser, Slough, UK) suppresses reflux after meals by creating a gel-like barrier that caps and displaces the acid pocket distal to the oesophago-gastric junction. The effect of Gaviscon DA on reflux and dyspepsia symptoms has not yet been demonstrated with a modern trial design. A pilot study to assess the efficacy and safety of Gaviscon DA compared with matched placebo for decreasing upper gastrointestinal symptoms in symptomatic gastro-oesophageal reflux disease (GERD) patients. A randomised, double-blind, parallel group study was performed in 110 patients with symptoms of GERD. Patients received Gaviscon DA or placebo tablets for 7 consecutive days. The primary endpoint compared the change in overall Reflux Disease Questionnaire (RDQ) symptom score (combined heartburn/regurgitation/dyspepsia). Secondary endpoints assessed individual dimensions, GERD dimension (heartburn and regurgitation) and overall treatment evaluation (OTE). There was a greater decrease in overall RDQ symptom score in the Gaviscon DA group compared with the placebo group (Least Squares Mean difference -0.55; P = 0.0033), and for each of the dimensions independently. Patients in the Gaviscon DA group evaluated their overall treatment response higher than patients in the placebo group [mean (standard deviation) OTE 4.1 (2.44) vs. 1.9 (3.34); P = 0.0005]. No differences in the incidence of adverse events were observed between treatment groups. Gaviscon DA decreases reflux and dyspeptic symptoms in GERD patients compared with matched placebo and has a favourable benefit-risk balance. Larger scale clinical investigations of medications targeting the acid pocket are warranted. (EudraCT, 2012-002188-84). © 2014 John Wiley & Sons Ltd.

Prepuberal intranasal dopamine treatment in an animal model of ADHD ameliorates deficient spatial attention, working memory, amino acid transmitters and synaptic markers in prefrontal cortex, ventral and dorsal striatum.

PubMed

Ruocco, L A; Treno, C; Gironi Carnevale, U A; Arra, C; Mattern, C; Huston, J P; de Souza Silva, M A; Nikolaus, S; Scorziello, A; Nieddu, M; Boatto, G; Illiano, P; Pagano, C; Tino, A; Sadile, A G

2014-09-01

Intranasal application of dopamine (IN-DA) has been shown to increase motor activity and to release DA in the ventral (VS) and dorsal striatum (DS) of rats. The aim of the present study was to assess the effects of IN-DA treatment on parameters of DA and excitatory amino acid (EAA) function in prepuberal rats of the Naples high-excitability (NHE) line, an animal model for attention-deficit hyperactivity disorder (ADHD) and normal random bred (NRB) controls. NHE and NRB rats were daily administered IN-DA (0.075, 0.15, 0.30 mg/kg) or vehicle for 15 days from postnatal days 28-42 and subsequently tested in the Làt maze and in the Eight-arm radial Olton maze. Soluble and membrane-trapped L-glutamate (L-Glu) and L-aspartate (L-Asp) levels as well as NMDAR1 subunit protein levels were determined after sacrifice in IN-DA- and vehicle-treated NHE and NRB rats in prefrontal cortex (PFc), DS and VS. Moreover, DA transporter (DAT) protein and tyrosine hydroxylase (TH) levels were assessed in PFc, DS, VS and mesencephalon (MES) and in ventral tegmental area (VTA) and substantia nigra, respectively. In NHE rats, IN-DA (0.30 mg/kg) decreased horizontal activity and increased nonselective attention relative to vehicle, whereas the lower dose (0.15 mg/kg) increased selective spatial attention. In NHE rats, basal levels of soluble EAAs were reduced in PFc and DS relative to NRB controls, while membrane-trapped EAAs were elevated in VS. Moreover, basal NMDAR1 subunit protein levels were increased in PFc, DS and VS relative to NRB controls. In addition, DAT protein levels were elevated in PFc and VS relative to NRB controls. IN-DA led to a number of changes of EAA, NMDAR1 subunit protein, TH and DAT protein levels in PFc, DS, VS, MES and VTA, in both NHE and NRB rats with significant differences between lines. Our findings indicate that the NHE rat model of ADHD may be characterized by (1) prefrontal and striatal DAT hyperfunction, indicative of DA hyperactivty, and (2) prefrontal and striatal NMDA receptor hyperfunction indicative of net EAA hyperactivty. IN-DA had ameliorative effects on activity level, attention, and working memory, which are likely to be associated with DA action at inhibitory D2 autoreceptors, leading to a reduction in striatal DA hyperactivity and, possibly, DA action on striatal EAA levels, resulting in a decrease of striatal EAA hyperfunction (with persistence of prefrontal EAA hyperfunction). Previous studies on IN-DA treatment in rodents have indicated antidepressant, anxiolytic and anti-parkinsonian effects in relation to enhanced central DAergic activity. Our present results strengthen the prospects of potential therapeutic applications of intranasal  DA by indicating an enhancement of selective attention and working memory in a deficit model.

Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

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

Asensio, S.; Goldstein, R.; Asensio, S.

Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to nondrug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [{sup 11}C]raclopride and positron emission tomography and response tomore » monetary reward was measured (an average of three years later) with functional magnetic resonance imaging in seven cocaine-addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a nondrug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine-addicted individuals.« less

Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later

PubMed Central

Asensio, Samuel; Romero, Maria J.; Romero, Francisco J.; Wong, Christopher; Alia-Klein, Nelly; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Volkow, Nora D.; Goldstein, Rita Z.

2009-01-01

Low levels of dopamine (DA) D2 receptor availability at a resting baseline have been previously reported in drug addicted individuals and have been associated with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2 receptor availability along with the reduced ventral frontal metabolism is thought to underlie compromised sensitivity to non-drug reward, a core characteristic of drug addiction. We therefore hypothesized that variability in DA D2 receptor availability at baseline will covary with dynamic responses to monetary reward in addicted individuals. Striatal DA D2 receptor availability was measured with [11C]raclopride and positron emission tomography and response to monetary reward was measured (an average of 3 years later) with functional magnetic resonance imaging in seven cocaine addicted individuals. Results show that low DA D2 receptor availability in the dorsal striatum was associated with decreased thalamic response to monetary reward; while low availability in ventral striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32) response to monetary reward. These preliminary results, that need to be replicated in larger sample sizes and validated with healthy controls, suggest that resting striatal DA D2 receptor availability predicts variability in functional responses to a non-drug reinforcer (money) in prefrontal cortex, implicated in behavioral monitoring, and in thalamus, implicated in conditioned responses and expectation, in cocaine addicted individuals. PMID:20034014

The effects of divided attention on encoding processes under incidental and intentional learning instructions: underlying mechanisms?

PubMed

Naveh-Benjamin, Moshe; Guez, Jonathan; Hara, Yoko; Brubaker, Matthew S; Lowenschuss-Erlich, Iris

2014-01-01

Divided attention (DA) at encoding has been shown to significantly disrupt later memory for the studied information. However, what type of processing gets disrupted during DA remains unresolved. In this study, we assessed the degree to which strategic effortful processes are affected under DA by comparing the effects of DA at encoding under intentional and pure incidental learning instructions. In three experiments, participants studied list of words or word pairs under either full or divided attention. Results of three experiments, which used different methodologies, converged to show that the effects of DA at encoding reduce memory performance to the same degree under incidental and intentional learning. Secondary task performance indicated that encoding under intentional learning instructions was more effortful than under incidental learning instructions. In addition, the results indicated enhanced attention to the initial appearance of the words under both types of learning instructions. Results are interpreted to imply that other processes, rather than only strategic effortful ones, might be affected by DA at encoding.

Ensemble Analysis of Variational Assimilation of Hydrologic and Hydrometeorological Data into Distributed Hydrologic Model

NASA Astrophysics Data System (ADS)

Lee, H.; Seo, D.; Koren, V.

2008-12-01

A prototype 4DVAR (four-dimensional variational) data assimilator for gridded Sacramento soil-moisture accounting and kinematic-wave routing models in the Hydrology Laboratory's Research Distributed Hydrologic Model (HL-RDHM) has been developed. The prototype assimilates streamflow and in-situ soil moisture data and adjusts gridded precipitation and climatological potential evaporation data to reduce uncertainty in the model initial conditions for improved monitoring and prediction of streamflow and soil moisture at the outlet and interior locations within the catchment. Due to large degrees of freedom involved, data assimilation (DA) into distributed hydrologic models is complex. To understand and assess sensitivity of the performance of DA to uncertainties in the model initial conditions and in the data, two synthetic experiments have been carried out in an ensemble framework. Results from the synthetic experiments shed much light on the potential and limitations with DA into distributed models. For initial real-world assessment, the prototype DA has also been applied to the headwater basin at Eldon near the Oklahoma-Arkansas border. We present these results and describe the next steps.

Determining rotational dynamics of the guanidino group of arginine side chains in proteins by carbon-detected NMR† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7cc04821a

PubMed Central

Gerecht, Karola; Figueiredo, Angelo Miguel

2017-01-01

Arginine residues are imperative for many active sites and protein-interaction interfaces. A new NMR-based method is presented to determine the rotational dynamics around the Nε–Cζ bond of arginine side chains. An application to a 19 kDa protein shows that the strengths of interactions involving arginine side chains can be characterised. PMID:28840203

Test-retest reliability of Brazilian version of Memorial Symptom Assessment Scale for assessing symptoms in cancer patients.

PubMed

Menezes, Josiane Roberta de; Luvisaro, Bianca Maria Oliveira; Rodrigues, Claudia Fernandes; Muzi, Camila Drumond; Guimarães, Raphael Mendonça

2017-01-01

To assess the test-retest reliability of the Memorial Symptom Assessment Scale translated and culturally adapted into Brazilian Portuguese. The scale was applied in an interview format for 190 patients with various cancers type hospitalized in clinical and surgical sectors of the Instituto Nacional de Câncer José de Alencar Gomes da Silva and reapplied in 58 patients. Data from the test-retest were double typed into a Microsoft Excel spreadsheet and analyzed by the weighted Kappa. The reliability of the scale was satisfactory in test-retest. The weighted Kappa values obtained for each scale item had to be adequate, the largest item was 0.96 and the lowest was 0.69. The Kappa subscale was also evaluated and values were 0.84 for high frequency physic symptoms, 0.81 for low frequency physical symptoms, 0.81 for psychological symptoms, and 0.78 for Global Distress Index. High level of reliability estimated suggests that the process of measurement of Memorial Symptom Assessment Scale aspects was adequate. Avaliar a confiabilidade teste-reteste da versão traduzida e adaptada culturalmente para o português do Brasil do Memorial Symptom Assessment Scale. A escala foi aplicada em forma de entrevista em 190 pacientes com diversos tipos de câncer internados nos setores clínicos e cirúrgicos do Instituto Nacional de Câncer José de Alencar Gomes da Silva e reaplicada em 58 pacientes. Os dados dos testes-retestes foram inseridos num banco de dados por dupla digitação independente em Excel e analisados pelo Kappa ponderado. A confiabilidade da escala mostrou-se satisfatória nos testes-retestes. Os valores do Kappa ponderado obtidos para cada item da escala apresentaram-se adequados, sendo o maior item de 0,96 e o menor de 0,69. Também se avaliou o Kappa das subescalas, sendo de 0,84 para sintomas físicos de alta frequência, de 0,81 para sintomas físicos de baixa frequência, de 0,81 também para sintomas psicológicos, e de 0,78 para Índice Geral de Sofrimento. Altos níveis de confiabilidade estimados permitem concluir que o processo de aferição dos itens do Memorial Symptom Assessment Scale foi adequado.

Development and pilot‐testing of a Decision Aid for use among Chinese women facing breast cancer surgery

PubMed Central

Au, Angel H.Y.; Lam, Wendy W.T.; Chan, Miranda C.M.; Or, Amy Y.M.; Kwong, Ava; Suen, Dacita; Wong, Annie L.; Juraskova, Ilona; Wong, Teresa W.T.; Fielding, Richard

2011-01-01

Abstract Background  Women choosing breast cancer surgery encounter treatment decision‐making (TDM) difficulties, which can cause psychological distress. Decision Aids (DAs) may facilitate TDM, but there are no DAs designed for Chinese populations. We developed a DA for Chinese women newly diagnosed with breast cancer, for use during the initial surgical consultation. Aims  Conduct a pilot study to assess the DA acceptability and utility among Chinese women diagnosed with breast cancer. Methods  Women preferred the DA in booklet format. A booklet was developed and revised and evaluated in two consecutive pilot studies (P1 and P2). On concluding their initial diagnostic consultation, 95 and 38 Chinese women newly diagnosed with breast cancer received the draft and revised draft DA booklet, respectively. Four‐day post‐consultation, women had questionnaires read out to them and to which they responded assessing attitudes towards the DA and their understanding of treatment options. Results  The original DA was read/partially read by 66/22% (n = 84) of women, whilst the revised version was read/partially read by 74/16% (n = 35), including subliterate women (χ2 = 0.76, P = 0.679). Knowledge scores varied with the extent the booklet was read (P1: F = 12.68, d.f. 2, P < 0.001; P2: F = 3.744, d.f. 2, P = 0.034). The revised, shorter version was graphically rich and resulted in improved perceived utility, [except for the ‘treatment options’ (χ2 = 5.50, P = 0.019) and ‘TDM guidance’ (χ2 = 8.19, P = 0.004) sections] without increasing anxiety (F = 0.689, P = 0.408; F = 3.45, P = 0.073). Conclusion  The DA was perceived as acceptable and useful for most women. The DA effectiveness is currently being evaluated using a randomized controlled trial. PMID:21223468

A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise.

PubMed

Jung, Chang Hee; Park, Cheol-Young; Ahn, Kyu-Joeng; Kim, Nan-Hee; Jang, Hak-Chul; Lee, Moon-Kyu; Park, Joong-Yeol; Chung, Choon-Hee; Min, Kyung-Wan; Sung, Yeon-Ah; Park, Jeong-Hyun; Kim, Sung Jin; Lee, Hyo Jung; Park, Sung-Woo

2015-03-01

DA-1229 is a novel, potent and selective dipeptidyl peptidase-4 (DPP-IV) inhibitor that is orally bioavailable. We aimed to evaluate the optimal dose, efficacy and safety of DA-1229, in Korean subjects with type 2 diabetes mellitus suboptimally controlled with diet and exercise. We enrolled 158 patients (mean age, 53 years and a mean BMI, 25.6 kg/m(2) ). The mean baseline fasting plasma glucose level, HbA1c and duration of diabetes were 8.28 mmol/L, 7.6% (60 mmol/mol) and 3.9 years, respectively. After 2 or 6 weeks of an exercise and diet program followed by 2 weeks of a placebo period, the subjects were randomized into one of four groups for a 12-week active treatment period: placebo, 2.5, 5 or 10 mg of DA-1229. All three doses of DA-1229 significantly reduced HbA1c from baseline compared to the placebo group (-0.09 in the placebo group vs. -0.56, -0.66 and -0.61% in 2.5, 5 and 10-mg groups, respectively) but without any significant differences between the doses. Insulin secretory function, as assessed by homeostasis model assessment β-cell, the insulinogenic index, 2-h oral glucose tolerance test (OGTT) C-peptide and post-OGTT C-peptide area under the curve (AUC)0-2h, significantly improved with DA-1229 treatment. The incidence of adverse events was similar between the treatment groups and DA-1229 did not affect body weight or induce hypoglycaemic events. DA-1229 monotherapy (5 mg for 12 weeks) improved HbA1c, fasting plasma glucose level, OGTT results and β-cell function. This drug was well tolerated in Korean subjects with type 2 diabetes mellitus. © 2014 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons, Ltd.

ADVANCED URBANIZED METEOROLOGICAL MODELING AND AIR QUALITY SIMULATIONS WITH CMAQ AT NEIGHBORHOOD SCALES

EPA Science Inventory

We present results from a study testing the new boundary layer parameterization method, the canopy drag approach (DA) which is designed to explicitly simulate the effects of buildings, street and tree canopies on the dynamic, thermodynamic structure and dispersion fields in urban...

Towards an Analytic Foundation for Network Architecture

DTIC Science & Technology

2010-12-31

SUPPLEMENTARY NOTES N/A 14. ABSTRACT In this project, we develop the analytic tools of stochastic optimization for wireless network design and apply them...and Mung Chiang, “ DaVinci : Dynamically Adaptive Virtual Networks for a Customized Internet,” in Proc. ACM SIGCOMM CoNext Conference, December 2008

On the Developing Role of Physical Models in Engineering Design Education

ERIC Educational Resources Information Center

Green, Graham; Smrcek, Ladislav

2006-01-01

Recent research, undertaken using participative observation methods within the Leonardo Da Vinci project "Open-Dynamic-Design", provides evidence that EU industrial practice continues to value the flexibility of physical models across a range of disciplines. This research is placed within the philosophical educational framework…

Efficacy and safety of darbepoetin alfa initiated at hemoglobin ≤10 g/dL in patients with stage IV cancer and chemotherapy-induced anemia.

PubMed

Boccia, Ralph V; Henry, David H; Belton, Laura; Bohac, Chet; Ghazal, Hassan H

2016-12-01

Data on efficacy and safety of darbepoetin alfa (DA) administered at hemoglobin (Hb) ≤10 g/dL are limited. In this analysis, we examined DA's efficacy and safety in patients with Stage IV cancers and chemotherapy-induced anemia (CIA) initiated on DA at Hb ≤10 g/dL. Data for patients with Stage IV cancers and CIA and who initiated DA at Hb ≤10 g/dL were extracted from three phase 3 trials identified in a central database of Amgen-sponsored DA studies in CIA. Efficacy outcomes were assessed by achievement of Hb increases of ≥1 g/dL and ≥2 g/dL and red blood cell (RBC) or whole blood transfusion requirements. Data were analyzed for all patients with baseline Hb ≤10 g/dL, and by the subgroups of patients with baseline Hb ≥9 to ≤10 g/dL versus <9 g/dL. Crude and Kaplan-Meier proportions of patients who experienced each outcome and time (days) to each outcome were summarized by treatment. Meta-analysis (fixed-effects inverse-variance model) was performed to compare outcomes for DA versus placebo. Safety was assessed by occurrence of adverse events. Data from 213 patients were analyzed: DA, n = 115; placebo, n = 98. More patients in the DA versus the placebo subgroup achieved Hb increase of ≥1 g/dL (72% vs. 36%; HR: 2.92, 95% CI: 1.95, 4.39) and ≥2 g/dL (44% vs. 18%; HR: 2.98, 95% CI: 1.71, 5.21) during the first 12 treatment weeks. Median times to Hb increase of ≥1 g/dL and ≥2 g/dL were 36 days and 78 days for DA, respectively. RBC or whole blood transfusions were less common in patients in the DA versus the placebo subgroup (24% vs. 45%; HR: 0.44, 95% CI: 0.27, 0.73). No new safety issues were reported. Our results confirm that DA use in patients with Stage IV cancer and CIA is more effective than placebo at increasing Hb levels and at reducing transfusion needs when DA treatment is initiated at Hb ≤10 g/dL. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Indium tin oxide-coated glass modified with reduced graphene oxide sheets and gold nanoparticles as disposable working electrodes for dopamine sensing in meat samples

NASA Astrophysics Data System (ADS)

Yang, Jiang; Strickler, J. Rudi; Gunasekaran, Sundaram

2012-07-01

Sensitive, rapid, and accurate detection of dopamine (DA) at low cost is needed for clinical diagnostic and therapeutic purposes as well as to prevent illegal use of DA in animal feed. We employed a simple approach to synthesize reduced graphene oxide sheets (rGOS) and gold nanoparticles (AuNPs) at room temperature on indium tin oxide-coated glass (ITO) slides as disposable working electrodes for sensing DA. Graphene oxide (GO) was directly reduced on ITO to remove oxygenated species via a rapid and green process without using chemical reducing reagents. AuNPs were electrochemically deposited in situ on rGOS-ITO with fairly uniform density and size. The sensitivity of the AuNPs-rGOS-ITO sensor for DA detection is 62.7 μA mM-1 cm-2 with good selectivity against common electrochemically interfering species such as ascorbic acid (AA) and uric acid (UA), and the detection limit measured by differential pulse voltammetry (DPV), at a signal-noise ratio of 3, was 6.0 × 10-8 M. The electrochemical catalysis of DA was proven to be a surface process with an electron transfer coefficient (α) of 0.478 and a rate constant (ks) of 1.456 s-1. It correlates well with the conventional UV-vis spectrophotometric approach (R = 0.9973) but with more than thrice the dynamic range (up to 4.5 mM). The sensor also exhibited good stability and capability to detect DA in beef samples, and thus is a promising candidate for simple and inexpensive sub-nanomolar detection of DA, especially in the presence of UV-absorbing compounds.

The effect of a dopamine antagonist on conditioning of sexual arousal in women.

PubMed

Brom, Mirte; Laan, Ellen; Everaerd, Walter; Spinhoven, Philip; Trimbos, Baptist; Both, Stephanie

2016-04-01

Dopamine (DA) plays a key role in reward-seeking behaviours. Accumulating evidence from animal and human studies suggests that human sexual reward learning may also depend on DA transmission. However, research on the role of DA in human sexual reward learning is completely lacking. To investigate whether DA antagonism attenuates classical conditioning of sexual response in humans. Healthy women were randomly allocated to one of two treatment conditions: haloperidol (n = 29) or placebo (n = 29). A differential conditioning paradigm was applied with genital vibrostimulation as unconditional stimulus (US) and neutral pictures as conditional stimuli (CSs). Genital arousal was assessed, and ratings of affective value and subjective sexual arousal were obtained. Haloperidol administration affected unconditional genital responding. However, no significant effects of medication were found for conditioned responding. No firm conclusions can be drawn about whether female sexual reward learning implicates DA transmission since the results do not lend themselves to unambiguous interpretation.

Metal speciation in landfill leachates with a focus on the influence of organic matter

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

Claret, Francis, E-mail: f.claret@brgm.fr; Tournassat, Christophe; Crouzet, Catherine

Highlights: > This study characterises the heavy-metal content in leachates collected from eight landfills in France. > Most of the metals are concentrated in the <30 kDa fraction, while Pb, Cu and Cd are associated with larger particles. > Metal complexation with OM is not sufficient to explain apparent supersaturation of metals with sulphide minerals. - Abstract: This study characterises the heavy-metal content in leachates collected from eight landfills in France. In order to identify heavy metal occurrence in the different size fractions of leachates, a cascade filtration protocol was applied directly in the field, under a nitrogen gas atmospheremore » to avoid metal oxidation. The results of analyses performed on the leachates suggest that most of the metals are concentrated in the <30 kDa fraction, while lead, copper and cadmium show an association with larger particles. Initial speciation calculations, without considering metal association with organic matter, suggest that leachate concentrations in lead, copper, nickel and zinc are super-saturated with respect to sulphur phases. Speciation calculations that account for metal complexation with organic matter, considered as fulvic acids based on C1(s) NEXAFS spectroscopy, show that this mechanism is not sufficient to explain such deviation from equilibrium conditions. It is therefore hypothesized that the deviation results also from the influence of biological activity on the kinetics of mineral phase precipitation and dissolution, thus providing a dynamic system. The results of chemical analyses of sampled fluids are compared with speciation calculations and some implications for the assessment of metal mobility and natural attenuation in a context of landfill risk assessment are discussed.« less

Impact of a web-based prostate cancer treatment decision aid on patient-reported decision process parameters: results from the Prostate Cancer Patient Centered Care trial.

PubMed

Cuypers, Maarten; Lamers, Romy E D; Kil, Paul J M; van de Poll-Franse, Lonneke V; de Vries, Marieke

2018-05-12

To compare patients' evaluation of the treatment decision-making process in localized prostate cancer between counseling that included an online decision aid (DA) and standard counseling. Eighteen Dutch hospitals were randomized to DA counseling (n = 235) or the control group with standard counseling (n = 101) in a pragmatic, cluster randomized controlled trial. The DA was provided to patients at, or soon after diagnosis. Decisional conflict, involvement, knowledge, and satisfaction with information were assessed with a questionnaire after treatment decision-making. Anxiety and depression served as covariates. The levels of decision involvement and conflict were comparable between patients in both groups. Patients with a DA felt more knowledgeable but scored equally well on a knowledge test as patients without a DA. Small significant negative effects were found on satisfaction with information and preparation for decision-making. A preference for print over online and depression and anxiety symptoms was negatively associated with satisfaction and conflict scores in the DA group. The DA aimed to support shared decision-making, while outcomes for a majority of DA users were comparable to patients who received standard counseling. Patients, who are less comfortable with the online DA format or experience anxiety or depression symptoms, could require more guidance toward shared decision-making. To evaluate long-term DA effects, follow-up evaluation on treatment satisfaction and decisional regret will be done.

Onsite Gaseous Centrifuge Enrichment Plant UF6 Cylinder Destructive Analysis

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

Anheier, Norman C.; Cannon, Bret D.; Qiao, Hong

2012-07-17

The IAEA safeguards approach for gaseous centrifuge enrichment plants (GCEPs) includes measurements of gross, partial, and bias defects in a statistical sampling plan. These safeguard methods consist principally of mass and enrichment nondestructive assay (NDA) verification. Destructive assay (DA) samples are collected from a limited number of cylinders for high precision offsite mass spectrometer analysis. DA is typically used to quantify bias defects in the GCEP material balance. Under current safeguards measures, the operator collects a DA sample from a sample tap following homogenization. The sample is collected in a small UF6 sample bottle, then sealed and shipped under IAEAmore » chain of custody to an offsite analytical laboratory. Current practice is expensive and resource intensive. We propose a new and novel approach for performing onsite gaseous UF6 DA analysis that provides rapid and accurate assessment of enrichment bias defects. DA samples are collected using a custom sampling device attached to a conventional sample tap. A few micrograms of gaseous UF6 is chemically adsorbed onto a sampling coupon in a matter of minutes. The collected DA sample is then analyzed onsite using Laser Ablation Absorption Ratio Spectrometry-Destructive Assay (LAARS-DA). DA results are determined in a matter of minutes at sufficient accuracy to support reliable bias defect conclusions, while greatly reducing DA sample volume, analysis time, and cost.« less

Inventory on the dietary assessment tools available and needed in africa: a prerequisite for setting up a common methodological research infrastructure for nutritional surveillance, research, and prevention of diet-related non-communicable diseases.

PubMed

Pisa, Pedro T; Landais, Edwige; Margetts, Barrie; Vorster, Hester H; Friedenreich, Christine M; Huybrechts, Inge; Martin-Prevel, Yves; Branca, Francesco; Lee, Warren T K; Leclercq, Catherine; Jerling, Johann; Zotor, Francis; Amuna, Paul; Al Jawaldeh, Ayoub; Aderibigbe, Olaide Ruth; Amoussa, Waliou Hounkpatin; Anderson, Cheryl A M; Aounallah-Skhiri, Hajer; Atek, Madjid; Benhura, Chakare; Chifamba, Jephat; Covic, Namukolo; Dary, Omar; Delisle, Hélène; El Ati, Jalila; El Hamdouchi, Asmaa; El Rhazi, Karima; Faber, Mieke; Kalimbira, Alexander; Korkalo, Liisa; Kruger, Annamarie; Ledo, James; Machiweni, Tatenda; Mahachi, Carol; Mathe, Nonsikelelo; Mokori, Alex; Mouquet-Rivier, Claire; Mutie, Catherine; Nashandi, Hilde Liisa; Norris, Shane A; Onabanjo, Oluseye Olusegun; Rambeloson, Zo; Saha, Foudjo Brice U; Ubaoji, Kingsley Ikechukwu; Zaghloul, Sahar; Slimani, Nadia

2018-01-02

To carry out an inventory on the availability, challenges, and needs of dietary assessment (DA) methods in Africa as a pre-requisite to provide evidence, and set directions (strategies) for implementing common dietary methods and support web-research infrastructure across countries. The inventory was performed within the framework of the "Africa's Study on Physical Activity and Dietary Assessment Methods" (AS-PADAM) project. It involves international institutional and African networks. An inventory questionnaire was developed and disseminated through the networks. Eighteen countries responded to the dietary inventory questionnaire. Various DA tools were reported in Africa; 24-Hour Dietary Recall and Food Frequency Questionnaire were the most commonly used tools. Few tools were validated and tested for reliability. Face-to-face interview was the common method of administration. No computerized software or other new (web) technologies were reported. No tools were standardized across countries. The lack of comparable DA methods across represented countries is a major obstacle to implement comprehensive and joint nutrition-related programmes for surveillance, programme evaluation, research, and prevention. There is a need to develop new or adapt existing DA methods across countries by employing related research infrastructure that has been validated and standardized in other settings, with the view to standardizing methods for wider use.

Methylphenidate and Cocaine Self-Administration Produce Distinct Dopamine Terminal Alterations

PubMed Central

Calipari, Erin S.; Ferris, Mark J.; Melchior, James R.; Bermejo, Kristel; Salahpour, Ali; Roberts, David C. S.; Jones, Sara R.

2012-01-01

Methylphenidate (MPH) is a commonly abused psychostimulant prescribed for the treatment of attention deficit hyperactivity disorder. MPH has a mechanism of action similar to cocaine (COC) and is commonly characterized as a dopamine transporter (DAT) blocker. While there has been extensive work aimed at understanding dopamine (DA) nerve terminal changes following COC self-administration, very little is known about the effects of MPH self-administration on the DA system. We used fast scan cyclic voltammetry in nucleus accumbens core slices from animals with a five-day self-administration history of 40 injections/day of either MPH (0.56 mg/kg) or COC (1.5 mg/kg) to explore alterations in baseline DA release and uptake kinetics as well as alterations in the interaction of each compound with the DAT. Although MPH and COC have similar behavioral effects, the consequences of self-administration on DA system parameters were found to be divergent. We show that COC self-administration reduced DAT levels and maximal rates of DA uptake, as well as reducing electrically stimulated release, suggesting decreased DA terminal function. In contrast, MPH self-administration increased DAT levels, DA uptake rates, and DA release, suggesting enhanced terminal function, which was supported by findings of increased metabolite/DA tissue content ratios. Tyrosine hydroxylase mRNA, protein and phosphorylation levels were also assessed in both groups. Additionally, COC self-administration reduced COC-induced DAT inhibition, while MPH self-administration increased MPH-induced DAT inhibition, suggesting opposite pharmacodynamic effects of these two drugs. These findings suggest that the factors governing DA system adaptations are more complicated than simple DA uptake blockade. PMID:22458761

Supramolecular control of the spin-dependent dynamics of long-lived charge-separated states at the micellar interface as studied by magnetic field effect.

PubMed

Miura, Tomoaki

2013-05-30

Spin selectivity in long-lived charge separation at the micellar interface is studied using the magnetic field effect (MFE). An amphiphilic viologen is complexed with a nonionic surfactant to form a supramolecular acceptor cage, of which the size is controlled by the acceptor concentration, as confirmed by dynamic light scattering measurement. Photoinduced electron transfer (ET) from a guest polyaromatic molecule to the viologen moiety is observed spin-dependently with time-resolved fluorescence (trFL) and transient absorption (TA). A negative MFE on the radical yield is successfully observed, which indicates generation of singlet-born long-lived radical pair that is realized by supramolecular control of the donor-acceptor (D-A) distances. The dominance of the singlet-precursor MFE is sensitive to the acceptor concentration, which presumably affects the D-A distance as well as the cage size. However, theoretical analysis of the MFE gives large recombination rates of ca. 10(8) s(-1), which indicate the contribution of spin-allowed recombination of the pseudocontact radical pair generated by still active in-cage diffusion. Dependence of the viologen concentration and alkyl chain length on the recombination and escape dynamics is discussed in terms of precursor spin states and the microenvironments in the cage.

Adapting to Mother Nature's changing climatic conditions: Flexible stocking for enhancing profitability of Wyoming ranchers

USDA-ARS?s Scientific Manuscript database

Ranching is a dynamic business in which profitability is impacted by changing weather and climatic conditions. A ranch-level model using a representative ranch in southeastern Wyoming was used to compare economic outcomes from growing season precipitation scenarios of: 1) historical precipitation da...

Measuring Blast-Related Intracranial Pressure Within the Human Head

DTIC Science & Technology

2010-08-01

an d stagnation pressures; stagnation pr essure , also called incident pre ssure, consists of static and dynamic pressure combined and subsequent da...represent a n oticeable decrease in IC pr essure that happened before the IC pressure started to increase. This behavior is very noticeable in all

Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

PubMed

Anselmi, L; Toti, L; Bove, C; Travagli, R A

2017-11-01

Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

Chronic lithium treatment rectifies maladaptive dopamine release in the nucleus accumbens.

PubMed

Can, Adem; Frost, Douglas O; Cachope, Roger; Cheer, Joseph F; Gould, Todd D

2016-11-01

Chronic lithium treatment effectively reduces behavioral phenotypes of mania in humans and rodents. The mechanisms by which lithium exerts these actions are poorly understood. Pre-clinical and clinical evidence have implicated increased mesolimbic dopamine (DA) neurotransmission with mania. We used fast-scan cyclic voltammetry to characterize changes in extracellular DA concentrations in the nucleus accumbens (NAc) core evoked by 20 and 60 Hz electrical stimulation of the ventral tegmental area (VTA) in C57BL6/J mice treated either acutely or chronically with lithium. The effects of chronic lithium treatment on the availability of DA for release were assessed by depleting readily releasable DA using short inter-train intervals, or administering d-amphetamine acutely to mobilize readily releasable DA. Chronic, but not acute, lithium treatment decreased the amplitude of DA responses in the NAc following 60 Hz pulse train stimulation. Neither lithium treatment altered the kinetics of DA release or reuptake. Chronic treatment did not impact the progressive reduction in the amplitude of DA responses when, using 20 or 60 Hz pulse trains, the VTA was stimulated every 6 s to deplete DA. Specifically, the amplitude of DA responses to 60 Hz pulse trains was initially reduced compared to control mice, but by the fifth pulse train, there was no longer a treatment effect. However, chronic lithium treatment attenuated d-amphetamine-induced increases in DA responses to 20 Hz pulse trains stimulation. Our data suggest that long-term administration of lithium may ameliorate mania phenotypes by normalizing the readily releasable DA pool in VTA axon terminals in the NAc. Read the Editorial Highlight for this article on Page 520. © 2016 International Society for Neurochemistry.

Effect of 14-kDa and 47-kDa protein molecules of age garlic extract on peritoneal macrophages.

PubMed

Daneshmandi, Saeed; Hajimoradi, Monire; Ahmadabad, Hasan Namdar; Hassan, Zuhair Mohammad; Roudbary, Maryam; Ghazanfari, Tooba

2011-03-01

Garlic (Allium sativum), traditionally being used as a spice worldwide, has different applications and is claimed to possess beneficial effects in several health ailments such as tumor and atherosclerosis. Garlic is also an immunomodulator and its different components are responsible for different properties. The present work aimed to assess the effect of protein fractions of garlic on peritoneal macrophages. 14-kDa and 47-kDa protein fractions of garlic were purified. Mice peritoneal macrophages were lavaged and cultured in a microtiter plate and exposed to different concentrations of garlic proteins. MTT assay was performed to evaluate the viability of macrophage. The amount of nitric oxide (NO) was detected in culture supernatants of macrophages by Griess reagent and furthermore, the cytotoxicity study of culture supernatants was carried out on WEHI-164 fibrosarcoma cell line as tumor necrosis factor-α bioassay. MTT assay results for both 14-kDa and 47-kDa protein fractions of stimulated macrophages were not significant (P > 0.05). Both 14-kDa and 47-kDa fractions significantly suppressed production of NO from macrophages (P = 0.007 and P = 0.003, respectively). Cytotoxicity of macrophages' supernatant on WEHI-164 fibrosarcoma cells was not affected by garlic protein fractions (P = 0.066 for 14-kDa and P = 0.085 for 47-kDa fractions). according to our finding, 14-kDa and 47-kDa fractions of aged garlic extract are able to suppress NO production from macrophages, which can be used as a biological advantage. These molecules had no cytotoxic effect on macrophages and do not increase tumoricidal property of macrophages.

Partial dopaminergic denervation-induced impairment in stimulus discrimination acquisition in parkinsonian rats: a model for early Parkinson's disease.

PubMed

Eagle, Andrew L; Olumolade, Oluyemi O; Otani, Hajime

2015-03-01

Parkinson's disease (PD) produces progressive nigrostriatal dopamine (DA) denervation resulting in cognitive and motor impairment. However, it is unknown whether cognitive impairments, such as instrumental learning deficits, are associated with the early stage PD-induced mild DA denervation. The current study sought to model early PD-induced instrumental learning impairments by assessing the effects of low dose (5.5μg), bilateral 6OHDA-induced striatal DA denervation on acquisition of instrumental stimulus discrimination in rats. 6OHDA (n=20) or sham (n=10) lesioned rats were tested for stimulus discrimination acquisition either 1 or 2 weeks post surgical lesion. Stimulus discrimination acquisition across 10 daily sessions was used to assess discriminative accuracy, or a probability measure of the shift toward reinforced responding under one stimulus condition (Sd) away from extinction, when reinforcement was withheld, under another (S(d) phase). Striatal DA denervation was assayed by tyrosine hydroxylase (TH) staining intensity. Results indicated that 6OHDA lesions produced significant loss of dorsal striatal TH staining intensity and marked impairment in discrimination acquisition, without inducing akinetic motor deficits. Rather 6OHDA-induced impairment was associated with perseveration during extinction (S(Δ) phase). These findings suggest that partial, bilateral striatal DA denervation produces instrumental learning deficits, prior to the onset of gross motor impairment, and suggest that the current model is useful for investigating mild nigrostriatal DA denervation associated with early stage clinical PD. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Complete daVinci versus laparoscopic pyeloplasty: cost analysis.

PubMed

Bhayani, Sam B; Link, Richard E; Varkarakis, John M; Kavoussi, Louis R

2005-04-01

Computer-assisted pyeloplasty with the daVinci system is an emerging technique to treat ureteropelvic junction (UPJ) obstruction. A relative cost analysis was performed assessing this technology in comparison with purely laparoscopic pyeloplasty. Eight patients underwent computer-assisted (daVinci) dismembered pyeloplasty (CP) via a transperitoneal four-port approach. They were compared with 13 patients who underwent purely laparoscopic pyeloplasty (LP). All patients had a primary UPJ obstruction and were matched for age, sex, and body mass index. The cost of equipment and capital depreciation for both procedures, as well as assessment of room set-up time, takedown time, and personnel were analyzed. Surgeons and nursing staff for both groups were experienced in both laparoscopy and daVinci procedures. One- and two-way financial analysis was performed to assess relative costs. The mean set-up and takedown time was 71 minutes for CP and 49 minutes for LP. The mean length of stay was 2.3 days for CP and 2.5 days for LP. The mean operating room (OR) times for CP and LP were 176 and 210 minutes, respectively. There were no complications in either group. One-way cost analysis with an economic model showed that LP is more cost effective than CP at our hospital if LP OR time is <338 minutes. With adjustment to a volume of 500 daVinci cases/year, CP is still not as cost effective as LP. Two-way sensitivity analysis shows that in-room time must still be <130 minutes and yearly cases must be >500 to obtain cost equivalence for CP. Perioperative parameters for CP are encouraging. However, the costs are a clear disadvantage. In our hospital, it is more cost effective to teach and perform LP than to perform CP.

Simultaneous assessment of glomerular filtration and barrier function in live zebrafish

PubMed Central

Kotb, Ahmed M.; Müller, Tobias; Xie, Jing; Anand-Apte, Bela; Endlich, Nicole

2014-01-01

The zebrafish pronephros is a well-established model to study glomerular development, structure, and function. A few methods have been described to evaluate glomerular barrier function in zebrafish larvae so far. However, there is a need to assess glomerular filtration as well. In the present study, we extended the available methods by simultaneously measuring the intravascular clearances of Alexa fluor 647-conjugated 10-kDa dextran and FITC-conjugated 500-kDa dextran as indicators of glomerular filtration and barrier function, respectively. After intravascular injection of the dextrans, mean fluorescence intensities of both dextrans were measured in the cardinal vein of living zebrafish (4 days postfertilization) by confocal microscopy over time. We demonstrated that injected 10-kDa dextran was rapidly cleared from the circulation, became visible in the lumen of the pronephric tubule, quickly accumulated in tubular cells, and was detectably excreted at the cloaca. In contrast, 500-kDa dextran could not be visualized in the tubule at any time point. To check whether alterations in glomerular function can be quantified by our method, we injected morpholino oligonucleotides (MOs) against zebrafish nonmuscle myosin heavy chain IIA (zMyh9) or apolipoprotein L1 (zApol1). While glomerular filtration was reduced in zebrafish nonmuscle myosin heavy chain IIA MO-injected larvae, glomerular barrier function remained intact. In contrast, in zebrafish apolipoprotein L1 MO-injected larvae, glomerular barrier function was compromised as 500-kDa dextran disappeared from the circulation and became visible in tubular cells. In summary, we present a novel method that allows to simultaneously assess glomerular filtration and barrier function in live zebrafish. PMID:25298528

Implementing Treat-to-Target Practices for Chronic Pain Through Shared Decision Making: Requisites, Prospects, and Challenges.

PubMed

Falzer, Paul R

2017-02-01

Treat-to-target (T2T) includes a target or goal, standard symptom assessment, and a treatment decision. In specialties that threat chronic pain, T2T is expected to be implemented collaboratively. The ability of patients to participate fully has been questioned, but these concerns have not been demonstrated empirically. The current study examined how patient self-assessed symptom measures and illness beliefs affect their willingness to change their current treatment. A total of 157 patients with rheumatoid arthritis completed a standard "disease activity" (DA) battery consisting of current joint pain, recent pain, daily functioning, and generality disability assessments, along with an illness belief questionnaire and a willingness to change measure. Data were collected at 2-month intervals over a 6-month period. Single and multiple influences on willingness to change were examined using linear mixed models. Willingness is strongly and directly associated with DA scores. Beliefs that were significant as single factors became nonsignificant once DA scores were introduced. The findings established a strong and consistent link between DA scores and willingness, and ruled out the prospect that illness beliefs mediate or moderate this relationship. It was also found that willingness to change is directly related to the number of significant self-reported symptoms. Concerns about the ability of patients to participate in a collaborative implementation of T2T were not substantiated. Future studies can examine the subtle interplay of goals, assessments, and treatment decisions and clarify outstanding issues about the practice of clinical decision making. © 2016 World Institute of Pain.

DA 5505: a novel topical formulation of terbinafine that enhances skin penetration and retention.

PubMed

Thapa, Raj Kumar; Han, Sang-Duk; Park, Hyoung Geun; Son, Miwon; Jun, Joon Ho; Kim, Jong Oh

2015-01-01

Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.

ATLAS WORLD-cloud and networking in PanDA

NASA Astrophysics Data System (ADS)

Barreiro Megino, F.; De, K.; Di Girolamo, A.; Maeno, T.; Walker, R.; ATLAS Collaboration

2017-10-01

The ATLAS computing model was originally designed as static clouds (usually national or geographical groupings of sites) around the Tier 1 centres, which confined tasks and most of the data traffic. Since those early days, the sites’ network bandwidth has increased at 0(1000) and the difference in functionalities between Tier 1s and Tier 2s has reduced. After years of manual, intermediate solutions, we have now ramped up to full usage of World-cloud, the latest step in the PanDA Workload Management System to increase resource utilization on the ATLAS Grid, for all workflows (MC production, data (re)processing, etc.). We have based the development on two new site concepts. Nuclei sites are the Tier 1s and large Tier 2s, where tasks will be assigned and the output aggregated, and satellites are the sites that will execute the jobs and send the output to their nucleus. PanDA dynamically pairs nuclei and satellite sites for each task based on the input data availability, capability matching, site load and network connectivity. This contribution will introduce the conceptual changes for World-cloud, the development necessary in PanDA, an insight into the network model and the first half-year of operational experience.

Dependence of the immune response to coccidiosis on the age of rabbit suckling.

PubMed

Pakandl, Michal; Hlásková, Lenka; Poplstein, Martin; Chromá, Vera; Vodicka, Tomás; Salát, Jirí; Mucksová, Jitka

2008-11-01

To study the immune response to coccidiosis, the suckling rabbits were inoculated with 2,000 oocysts of either Eimeria intestinalis or Eimeria flavescens at 19, 22, 25, 29, and 33 days of age (DA) and in the case of E. intestinalis at 14 and 16 DA as well and sacrificed 14 days later. Another group served as an uninfected control and the rabbits were killed at the same age as their infected counterparts. Unlike the antibody response, the parameters reflecting cellular immunity (total number of leukocytes in mesenteric lymph nodes, lymphocyte proliferation upon stimulation with specific antigen and the dynamics of CD4+ and CD8+ cell proportions in the intestinal epithelium at the specific site of parasite development) were significantly changed from about 25 DA onwards. In contrast to the rabbits infected with weakly immunogenic coccidium E. flavescens, the proportions of CD4+ and CD8+ lymphocytes in intraepithelial lymphocytes from the specific site of parasite development were considerably changed after infection with highly immunogenic species E. intestinalis. As the immune system of sucklings from about 25 DA reacts to the infection, this age may be considered in terms of vaccination against coccidiosis.

Open source data assimilation framework for hydrological modeling

NASA Astrophysics Data System (ADS)

Ridler, Marc; Hummel, Stef; van Velzen, Nils; Katrine Falk, Anne; Madsen, Henrik

2013-04-01

An open-source data assimilation framework is proposed for hydrological modeling. Data assimilation (DA) in hydrodynamic and hydrological forecasting systems has great potential to improve predictions and improve model result. The basic principle is to incorporate measurement information into a model with the aim to improve model results by error minimization. Great strides have been made to assimilate traditional in-situ measurements such as discharge, soil moisture, hydraulic head and snowpack into hydrologic models. More recently, remotely sensed data retrievals of soil moisture, snow water equivalent or snow cover area, surface water elevation, terrestrial water storage and land surface temperature have been successfully assimilated in hydrological models. The assimilation algorithms have become increasingly sophisticated to manage measurement and model bias, non-linear systems, data sparsity (time & space) and undetermined system uncertainty. It is therefore useful to use a pre-existing DA toolbox such as OpenDA. OpenDA is an open interface standard for (and free implementation of) a set of tools to quickly implement DA and calibration for arbitrary numerical models. The basic design philosophy of OpenDA is to breakdown DA into a set of building blocks programmed in object oriented languages. To implement DA, a model must interact with OpenDA to create model instances, propagate the model, get/set variables (or parameters) and free the model once DA is completed. An open-source interface for hydrological models exists capable of all these tasks: OpenMI. OpenMI is an open source standard interface already adopted by key hydrological model providers. It defines a universal approach to interact with hydrological models during simulation to exchange data during runtime, thus facilitating the interactions between models and data sources. The interface is flexible enough so that models can interact even if the model is coded in a different language, represent processes from a different domain or have different spatial and temporal resolutions. An open source framework that bridges OpenMI and OpenDA is presented. The framework provides a generic and easy means for any OpenMI compliant model to assimilate observation measurements. An example test case will be presented using MikeSHE, and OpenMI compliant fully coupled integrated hydrological model that can accurately simulate the feedback dynamics of overland flow, unsaturated zone and saturated zone.

Interfacial hydration, dynamics and electron transfer: multi-scale ET modeling of the transient [myoglobin, cytochrome b5] complex.

PubMed

Keinan, Shahar; Nocek, Judith M; Hoffman, Brian M; Beratan, David N

2012-10-28

Formation of a transient [myoglobin (Mb), cytochrome b(5) (cyt b(5))] complex is required for the reductive repair of inactive ferri-Mb to its functional ferro-Mb state. The [Mb, cyt b(5)] complex exhibits dynamic docking (DD), with its cyt b(5) partner in rapid exchange at multiple sites on the Mb surface. A triple mutant (Mb(3M)) was designed as part of efforts to shift the electron-transfer process to the simple docking (SD) regime, in which reactive binding occurs at a restricted, reactive region on the Mb surface that dominates the docked ensemble. An electrostatically-guided brownian dynamics (BD) docking protocol was used to generate an initial ensemble of reactive configurations of the complex between unrelaxed partners. This ensemble samples a broad and diverse array of heme-heme distances and orientations. These configurations seeded all-atom constrained molecular dynamics simulations (MD) to generate relaxed complexes for the calculation of electron tunneling matrix elements (T(DA)) through tunneling-pathway analysis. This procedure for generating an ensemble of relaxed complexes combines the ability of BD calculations to sample the large variety of available conformations and interprotein distances, with the ability of MD to generate the atomic level information, especially regarding the structure of water molecules at the protein-protein interface, that defines electron-tunneling pathways. We used the calculated T(DA) values to compute ET rates for the [Mb(wt), cyt b(5)] complex and for the complex with a mutant that has a binding free energy strengthened by three D/E → K charge-reversal mutations, [Mb(3M), cyt b(5)]. The calculated rate constants are in agreement with the measured values, and the mutant complex ensemble has many more geometries with higher T(DA) values than does the wild-type Mb complex. Interestingly, water plays a double role in this electron-transfer system, lowering the tunneling barrier as well as inducing protein interface remodeling that screens the repulsion between the negatively-charged propionates of the two hemes.

Consequences of partial and severe dopaminergic lesion on basal ganglia oscillatory activity and akinesia.

PubMed

Tseng, Kuei Y; Kargieman, Lucila; Gacio, Sebastian; Riquelme, Luis A; Murer, M Gustavo

2005-11-01

Severe chronic dopamine (DA) depletion increases the proportion of neurons in the basal ganglia that fire rhythmic bursts of action potential (LFO units) synchronously with the cortical oscillations. Here we report on how different levels of mesencephalic DA denervation affect substantia nigra pars reticulata (SNpr) neuronal activity in the rat and its relationship to akinesia (stepping test). Chronic nigrostriatal lesion induced with 0 (control group), 4, 6 or 8 microg of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle resulted in a dose-dependent decrease of tyrosine hydroxylase positive (TH+) neurons in the SN and ventral tegmental area (VTA). Although 4 microg of 6-OHDA reduced the number of TH+ neurons in the SN by approximately 60%, both stepping test performance and SNpr neuronal activity remained indistinguishable from control animals. By contrast, animals that received 6 microg of 6-OHDA showed a marked reduction of TH+ cells in the SN ( approximately 75%) and VTA ( approximately 55%), a significant stepping test deficit and an increased proportion of LFO units. These changes were not dramatically enhanced with 8 microg 6-OHDA, a dose that induced an extensive DA lesion (> 95%) in the SN and approximately 70% reduction of DA neurons in the VTA. These results suggest a threshold level of DA denervation for both the appearance of motor deficits and LFO units. Thus, the presence of LFO activity in the SNpr is not related to a complete nigrostriatal DA neuron depletion (ultimate stage parkinsonism); instead, it may reflect a functional disruption of cortico-basal ganglia dynamics associated with clinically relevant stages of the disease.

Toward Differentiated Assessment in a Public College in Oman

ERIC Educational Resources Information Center

Ali, Holi Ibrahim Holi

2015-01-01

Differentiated assessment (DA) seeks to address the individual differences between students and provides them with the appropriate assessment strategy. This paper looks into the possibility of implementing differentiated assessment in a public college in Oman. Additionally, it attempts to explore teachers' views about the possibility of…

Health and innovation: economic dynamics and Welfare State in Brazil.

PubMed

Gadelha, Carlos Augusto Grabois; Braga, Patrícia Seixas da Costa

2016-11-03

The effective enforcement of the access to healthcare as fundamental right requires an important theoretical and political effort at linking the often contradictory economic and social dimensions of development. This study suggests the need for a systemic view of policies related to the industrial base and innovation in health and the construction of the Brazilian Unified National Health System (SUS). The authors investigate the relations between health, innovation, and development, seeking to show and update the political, economic, and social determinants of the recent Brazilian experience with the Health Economic-Industrial Complex (HEIC). They discuss how the agenda for innovation and domestic industrial production in health gained a central place in the project for construction of the SUS. The article thus seeks to link inherent issues from the agenda for development, production, and innovation to social policy in healthcare, as observed in recent years, and based on this analysis, points to political and conceptual challenges for implementing the SUS, especially as regards strengthening its technological and industrial base. As a byproduct, the article develops an analytical and factual focus on the consolidation of the HEIC in Brazil, both as a dynamic vector of industrial development, generating investment, income, employment, and innovations, and as a decisive element for reducing vulnerability and structural dependence in health. The authors aim to show that strengthening the SUS and orienting it to social needs is an essential part of building a social Welfare State in Brazil. Resumo: A efetivação da saúde como um direito fundamental exige importante esforço, teórico e político, de articulação das dimensões econômicas e sociais, por vezes contraditórias, do desenvolvimento. Este trabalho indica a necessidade de um olhar sistêmico das políticas relacionadas à base produtiva e de inovação em saúde e à construção do Sistema Único de Saúde (SUS). Investiga as relações entre saúde, inovação e desenvolvimento, buscando mostrar e atualizar os determinantes políticos, econômicos e sociais da experiência brasileira recente relacionada ao Complexo Econômico-Industrial da Saúde (CEIS). Mostra como a agenda da inovação e da produção nacional em saúde ganhou centralidade no projeto de construção do SUS. O artigo procura, assim, articular questões inerentes à agenda do desenvolvimento, da produção e da inovação com a política social em saúde, tal como observado nos últimos anos e, valendo-se de sua análise, aponta desafios políticos e conceituais para a efetivação do SUS, em especial no que se refere ao fortalecimento de sua base tecnológica e produtiva. Como desdobramento, desenvolve um enfoque analítico e factual que relaciona a consolidação do CEIS no Brasil tanto como um vetor dinâmico do desenvolvimento industrial, gerando investimento, renda, emprego e inovações, quanto como elemento decisivo para a redução da vulnerabilidade e da dependência estrutural em saúde. Procura mostrar que seu fortalecimento e direcionamento para as necessidades sociais é parte essencial da construção de um Estado de Bem-Estar Social no Brasi.

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica

PubMed Central

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 (DaCBF4), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4-overexpressing transgenic rice plant (Ubi:DaCBF4) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice. PMID:29774046

Norepinephrine Activates Dopamine D4 Receptors in the Rat Lateral Habenula

PubMed Central

Root, David H.; Hoffman, Alexander F.; Good, Cameron H.; Zhang, Shiliang; Gigante, Eduardo

2015-01-01

The lateral habenula (LHb) is involved in reward and aversion and is reciprocally connected with dopamine (DA)-containing brain regions, including the ventral tegmental area (VTA). We used a multidisciplinary approach to examine the properties of DA afferents to the LHb in the rat. We find that >90% of VTA tyrosine hydroxylase (TH) neurons projecting to the LHb lack vesicular monoamine transporter 2 (VMAT2) mRNA, and there is little coexpression of TH and VMAT2 protein in this mesohabenular pathway. Consistent with this, electrical stimulation of LHb did not evoke DA-like signals, assessed with fast-scan cyclic voltammetry. However, electrophysiological currents that were inhibited by L741,742, a DA-D4-receptor antagonist, were observed in LHb neurons when DA uptake or degradation was blocked. To prevent DA activation of D4 receptors, we repeated this experiment in LHb slices from DA-depleted rats. However, this did not disrupt D4 receptor activation initiated by the dopamine transporter inhibitor, GBR12935. As the LHb is also targeted by noradrenergic afferents, we examined whether GBR12935 activation of DA-D4 receptors occurred in slices depleted of norepinephrine (NE). Unlike DA, NE depletion prevented the activation of DA-D4 receptors. Moreover, direct application of NE elicited currents in LHb neurons that were blocked by L741,742, and GBR12935 was found to be a more effective blocker of NE uptake than the NE-selective transport inhibitor nisoxetine. These findings demonstrate that NE is released in the rat LHb under basal conditions and that it activates DA-D4 receptors. Therefore, NE may be an important regulator of LHb function. PMID:25716845

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate

PubMed Central

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-01-01

The central extended amygdala (CEA) has been conceptualized as a ‘macrosystem’ that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the ‘limbic-associative’ striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning. PMID:28220796

Chronic treatment of DA-8159, a new phosphodiesterase type V inhibitor, attenuates endothelial dysfunction in stroke-prone spontaneously hypertensive rat.

PubMed

Choi, Seul Min; Kim, Jee Eun; Kang, Kyung Koo

2006-02-09

This study examined the effects of chronic treatment of a new phosphodiesterase type 5 inhibitor, DA-8159, on endothelial dysfunction in stroke-prone spontaneously hypertensive rats (SHR-SP). Six-week-old male SHR-SP were divided into 4 groups; vehicle control, DA-8159 1, 3, and 10 mg/kg/day. During a 32-week experimental period, the animals were administered DA-8159 orally and fed a 4% NaCl-loaded diet. The systolic blood pressure was measured every two weeks throughout the experimental period using the tail-cuff method. At the end of experiments, the vascular function (acetylcholine-induced vasodilation) in the endothelium-intact aortic rings was investigated. In addition, the mortality, the left ventricular hypertrophy index, the plasma parameters and the incidence of a cerebral infarction were assessed. In the DA-8159 treated-rats, the vascular reactivity improved significantly in a dose-dependent manner. Although DA-8159 did not alter the elevation of the systolic blood pressure directly, the 3 and 10 mg/kg/day DA-8159 treatment delayed the early death caused by stroke. DA-8159 significantly reduced the left ventricular heart weight/body weight ratio compared with the vehicle control group. Furthermore, the DA-8159 treatment significantly increased the plasma nitric oxide, cGMP, and the total antioxidative status. The DA-8159 treatment also reduced the occurrence of stroke-associated cerebral damage. These results indicate that DA-8159 can ameliorate an endothelial dysfunction-related vascular injury. Therefore, pharmacological intervention aimed at attenuating an endothelial dysfunction is important and might be useful in both preventing and treating endothelial dysfunction-related complications.

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica.

PubMed

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 ( DaCBF4 ), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4 -overexpressing transgenic rice plant ( Ubi:DaCBF4 ) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice.

The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig.

PubMed

Hussain, Zahid; Rhee, Kwang Won; Lee, Young Ju; Park, Hyojin

2016-07-30

Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig. The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig. DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles. DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD.

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

PubMed

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

The Application of Ultra-High-Performance Liquid Chromatography Coupled with a LTQ-Orbitrap Mass Technique to Reveal the Dynamic Accumulation of Secondary Metabolites in Licorice under ABA Stress.

PubMed

Li, Da; Xu, Guojie; Ren, Guangxi; Sun, Yufeng; Huang, Ying; Liu, Chunsheng

2017-10-20

The traditional medicine licorice is the most widely consumed herbal product in the world. Although much research work on studying the changes in the active compounds of licorice has been reported, there are still many areas, such as the dynamic accumulation of secondary metabolites in licorice, that need to be further studied. In this study, the secondary metabolites from licorice under two different methods of stress were investigated by ultra-high-performance liquid chromatography coupled with hybrid linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS). A complex continuous coordination of flavonoids and triterpenoids in a network was modulated by different methods of stress during growth. The results showed that a total of 51 secondary metabolites were identified in licorice under ABA stress. The partial least squares-discriminate analysis (PLS-DA) revealed the distinction of obvious compounds among stress-specific districts relative to ABA stress. The targeted results showed that there were significant differences in the accumulation patterns of the deeply targeted 41 flavonoids and 10 triterpenoids compounds by PCA and PLS-DA analyses. To survey the effects of flavonoid and triterpenoid metabolism under ABA stress, we inspected the stress-specific metabolic changes. Our study testified that the majority of flavonoids and triterpenoids were elevated in licorice under ABA stress, while the signature metabolite affecting the dynamic accumulation of secondary metabolites was detected. Taken together, our results suggest that ABA-specific metabolite profiling dynamically changed in terms of the biosynthesis of flavonoids and triterpenoids, which may offer new trains of thought on the regular pattern of dynamic accumulation of secondary metabolites in licorice at the metabolite level. Our results also provide a reference for clinical applications and directional planting and licorice breeding.

Conformational preferences of DNA following damage by aristolochic acids: Structural and energetic insights into the different mutagenic potential of the ALI and ALII-N(6)-dA adducts.

PubMed

Kathuria, Preetleen; Sharma, Purshotam; Abendong, Minette N; Wetmore, Stacey D

2015-04-21

Aristolochic acids (AAI and AAII), produced by the Aristolochiaceae family of plants, are classified as group I (human) carcinogens by the International Agency for Research on Cancer. These acids are metabolized in cells to yield aristolactams (ALI and ALII, respectively), which further form bulky adducts with the purine nucleobases. Specifically, the adenine lesions are more persistent in cells and have been associated with chronic renal diseases and related carcinogenesis. To understand the structural basis of the nephrotoxicity induced by AAs, the ALI-N(6)-dA and ALII-N(6)-dA lesions are systematically studied using computational methods. Density functional theory calculations indicate that the aristolactam moiety intrinsically prefers a planar conformation with respect to adenine. Nucleoside and nucleotide models suggest that the anti and syn orientations about the glycosidic bond are isoenergetic for both adducts. Molecular dynamics simulations and free energy calculations reveal that the anti base-displaced intercalated conformation is the most stable conformer for both types of AL-N(6)-dA adducted DNA, which agrees with previous experimental work on the ALII-N(6)-dA adduct and thereby validates our approach. Interestingly, this conformer differs from the dominant conformations adopted by other N6-linked adenine lesions, including those derived from polycyclic aromatic hydrocarbons. Furthermore, the second most stable syn base-displaced intercalated conformation lies closer in energy to the anti base-displaced intercalated conformation for ALI-N(6)-dA compared to ALII-N(6)-dA. This indicates that a mixture of conformations may be detectable for ALI-N(6)-dA in DNA. If this enhanced conformational flexibility of double-stranded DNA persists when bound to a lesion-bypass polymerase, this provides a possible structural explanation for the previously observed greater nephrotoxic potential for the ALI versus ALII-N(6)-dA adduct. In addition, the structural characteristics of the preferred conformations of adducted DNA explain the resistance of these adducts to repair and thereby add to our current understanding of the toxicity of AAs within living cells.

The Protective Effect of Pregnancy on Risk for Drug Abuse: A Population, Co-relative, Co-spouse, and Within-Individual Analysis

PubMed Central

Kendler, Kenneth S.; Ohlsson, Henrik; Svikis, Dace S.; Sundquist, Kristina; Sundquist, Jan

2017-01-01

Objective To determine whether pregnancy is an intrinsic motivator for drug abuse (DA) cessation. Method We conducted, in Swedish females born 1980–1990 who gave birth at ages 20–35 (N=149,512), prospective cohort, co-relative, co-spouse, and within-person analyses of registration for DA during pregnancy. DA was assessed from medical, criminal and pharmacy registries. Results In the population, rates of DA were lower during pregnancy (unadjusted OR=0.67, 95% CIs 0.60–0.74). Compared to population results, the negative association between pregnancy and DA was moderately stronger in cousins (OR=0.49, 0.39–0.62) and substantially stronger in siblings (OR=0.35, 0.24–0.51) discordant for pregnancy. The estimated OR for DA in pregnancy-discordant monozygotic twins was even stronger: 0.17 (0.10–0.31). Within-individuals, the OR for DA while pregnant compared to an equivalent pre-pregnancy interval was similar to that seen in pregnancy-discordant monozygotic twins: 0.22 (0.19–0.26). Compared to cohabiting fathers, mothers had a greater reduction in risk for DA during pregnancy (OR=0.40, 0.34–0.47). Pregnancy was more protective in those with low parental education and without a cohabiting actively drug abusing father. Compared to pre-pregnancy baseline, within-individual analyses indicate risk for DA is also substantially reduced post-partum e.g. day 0–242 OR=0.13 (0.11–0.16). Conclusions Risk for DA in women is substantially reduced during pregnancy. Multiple analyses suggest that this association is largely causal, suggesting that pregnancy is indeed a strong intrinsic motivator for DA cessation. Similar strong protective effects may be present immediately post-partum. Our results have implications for our etiologic models of DA and especially for contingency management programs seeking to reduce DA risk. PMID:28595490

Drought Dynamics and Food Security in Ukraine

NASA Astrophysics Data System (ADS)

Kussul, N. M.; Kogan, F.; Adamenko, T. I.; Skakun, S. V.; Kravchenko, O. M.; Kryvobok, O. A.; Shelestov, A. Y.; Kolotii, A. V.; Kussul, O. M.; Lavrenyuk, A. M.

2012-12-01

In recent years food security became a problem of great importance at global, national and regional scale. Ukraine is one of the most developed agriculture countries and one of the biggest crop producers in the world. According to the 2011 statistics provided by the USDA FAS, Ukraine was the 8th largest exporter and 10th largest producer of wheat in the world. Therefore, identifying current and projecting future trends in climate and agriculture parameters is a key element in providing support to policy makers in food security. This paper combines remote sensing, meteorological, and modeling data to investigate dynamics of extreme events, such as droughts, and its impact on agriculture production in Ukraine. Two main problems have been considered in the study: investigation of drought dynamics in Ukraine and its impact on crop production; and investigation of crop growth models for yield and production forecasting and its comparison with empirical models that use as a predictor satellite-derived parameters and meteorological observations. Large-scale weather disasters in Ukraine such as drought were assessed using vegetation health index (VHI) derived from satellite data. The method is based on estimation of green canopy stress/no stress from indices, characterizing moisture and thermal conditions of vegetation canopy. These conditions are derived from the reflectance/emission in the red, near infrared and infrared parts of solar spectrum measured by the AVHRR flown on the NOAA afternoon polar-orbiting satellites since 1981. Droughts were categorized into exceptional, extreme, severe and moderate. Drought area (DA, in % from total Ukrainian area) was calculated for each category. It was found that maximum DA over past 20 years was 10% for exceptional droughts, 20% for extreme droughts, 50% for severe droughts, and 80% for moderate droughts. Also, it was shown that in general the drought intensity and area did not increase considerably over past 10 years. Analysis of interrelation between DA of different categories at oblast level with agriculture production will be discussed as well. A comparative study was carried out to assess three approaches to forecast winter wheat yield in Ukraine at oblast level: (i) empirical regression-based model that uses as a predictor 16-day NDVI composites derived from MODIS at the 250 m resolution, (ii) empirical regression-based model that uses as predictors meteorological parameters, and (iii) adapted for Ukraine Crop Growth Monitoring System (CGMS) that is based on WOFOST crop growth simulation model and meteorological parameters. These three approaches were calibrated for 2000-2009 and 2000-2010 data, and compared while performing forecasts on independent data for 2010 and 2011. For 2010, the best results in terms of root mean square error (RMSE, by oblast, deviation of predicted values from official statistics) were achieved using CGMS models: 0.3 t/ha. For NDVI and meteorological models RMSE values were 0.79 and 0.77 t/ha, respectively. When forecasting winter wheat yield for 2011, the following RMSE values were obtained: 0.58 t/ha for CGMS, 0.56 t/ha for meteorological model, and 0.62 t/ha for NDVI. In this case performance of all three approaches was relatively the same. Acknowledgements. This work was supported by the U.S. CRDF Grant "Analysis of climate change & food security based on remote sensing & in situ data sets" (UKB2-2972-KV-09).

Isolation and initial structural characterization of a 27 kDa protein from Zingiber officinale

NASA Astrophysics Data System (ADS)

Rasheed, Saima; Malik, Shoaib Ahmad; Falke, Sven; Arslan, Ali; Fazel, Ramin; Schlüter, Hartmut; Betzel, Christian; Choudhary, M. Iqbal

2018-03-01

Zingiber officinale Roscoe (Ginger) is a widely used traditional medicinal plant (for different ailments such as arthritis, constipation, and hypertension). This article describes the isolation and characterization of a so far unknown protein from ginger rhizomes applying ion exchange, affinity, size-exclusion chromatography, small angle X-ray scattering (SAXS), and mass spectrometry techniques. One-dimensional Coomassie-stained SDS-PAGE was performed under non-reducing conditions, showing one band corresponding to approx. 27 kDa. Dynamic light scattering (DLS) analysis of the protein solution revealed monodispersity and a monomeric state of the purified protein. Circular dichroism (CD) spectroscopy strongly indicated a β-sheet-rich protein, and disordered regions. MALDI-TOF-MS, and LC-MS/MS analysis resulted in the identification of 27.29 kDa protein, having 32.13% and 25.34% sequence coverage with Zingipain-1 and 2, respectively. The monomeric state and molecular weight were verified by small angle X-ray scattering (SAXS) studies. An elongated ab-initio model was calculated based on the scattering intensity distribution.

Complementary study of molecular dynamics and domain sizes in heterogenous nanocomposites PBT/DA-C{sub 60} and PBT/TCNEO-C{sub 60}

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

Woźniak-Braszak, A., E-mail: abraszak@amu.edu.pl; Baranowski, M.; Jurga, K.

2014-05-28

A comprehensive study of molecular dynamics and structure in new heterogenous nanocomposites based on poly(butylene terephthalate) and nanoparticles C{sub 60} modified by n-decylamine or tetracyanoethylene oxide has been performed. The domain structure of new nanocomposites has been investigated by Fourier transform infrared spectroscopy, wide-angle X-ray scattering, and differential scanning calorimetry techniques. Solid-state {sup 1}H NMR techniques were used to study molecular dynamics and domain sizes in new nanocomposites. Information about the electronic properties of these nanocomposites was obtained by means of electron paramagnetic resonance method. It was shown that the structure and molecular dynamics of new nanocomposites were strongly dependentmore » on the properties and concentration of fullerene derivates.« less

Fluid Dynamic Aspects of Wind Energy Conversion

DTIC Science & Technology

1979-07-01

numbers, i.e. for relatively large-scale turbines). This might be acceptable for a single production unit (reduction of tooling costs), but looses its...Behind a Wing via Comparison of Measurements and Calculations. NLR TR 74063 U (July 1974). 4.17 Foley, W.M.: From DaVinci to the Piesent - a Review of

A Flight Dynamic Model of Aircraft Spinning

DTIC Science & Technology

1990-06-01

r Zaw rate about body axes S Aircraft wing area V Flight path velocity 3 a Angle of attack Sideslip angle 6, Aileron deflection, positive when right...Tests, May/June 1983 PartI. Unpublished data report. 6. MARTIN, C.A. and SECOMB, D.A. ; RAAF BPTA Phase II Wind Tun - nel Tests: Rotary Balance Tests

Endothelial Ca2+ oscillations reflect VEGFR signaling-regulated angiogenic capacity in vivo

PubMed Central

Yokota, Yasuhiro; Nakajima, Hiroyuki; Wakayama, Yuki; Muto, Akira; Kawakami, Koichi; Fukuhara, Shigetomo; Mochizuki, Naoki

2015-01-01

Sprouting angiogenesis is a well-coordinated process controlled by multiple extracellular inputs, including vascular endothelial growth factor (VEGF). However, little is known about when and how individual endothelial cell (EC) responds to angiogenic inputs in vivo. Here, we visualized endothelial Ca2+ dynamics in zebrafish and found that intracellular Ca2+ oscillations occurred in ECs exhibiting angiogenic behavior. Ca2+ oscillations depended upon VEGF receptor-2 (Vegfr2) and Vegfr3 in ECs budding from the dorsal aorta (DA) and posterior cardinal vein, respectively. Thus, visualizing Ca2+ oscillations allowed us to monitor EC responses to angiogenic cues. Vegfr-dependent Ca2+ oscillations occurred in migrating tip cells as well as stalk cells budding from the DA. We investigated how Dll4/Notch signaling regulates endothelial Ca2+ oscillations and found that it was required for the selection of single stalk cell as well as tip cell. Thus, we captured spatio-temporal Ca2+ dynamics during sprouting angiogenesis, as a result of cellular responses to angiogenic inputs. DOI: http://dx.doi.org/10.7554/eLife.08817.001 PMID:26588168

Enrichment desired quality chitosan fraction and advance yield by sequential static and static-dynamic supercritical CO2.

PubMed

Hsieh, Yi-Yin; Chin, Hui Yen; Tsai, Min-Lang

2015-11-20

This study aimed to establish the sequential static and static-dynamic supercritical carbon dioxide (SDCO2) fractionation conditions to obtain a higher yield and desired chitosan with lower polydispersity index (PDI) and higher degree of deacetylation (DD). The yield increased with increasing DD of used chitosan and amount of cosolvent. The yield of acetic acid cosolvent was higher than those of malic and citric acid cosolvents. SDCO2, compared to static supercritical carbon dioxide, has higher yield. The yield of extracted chitosan was 5.82-14.70% by SDCO2/acetic acid, which increases with increasing pressure. The DD of fractionated chitosan increased from 66.1% to 70.81-85.33%, while the PDI decreased from 3.97 to 1.69-3.16. The molecular weight changed from 622kDa to 412-649kDa, which increased as density of supercritical carbon dioxide increases. Hence, higher DD and lower PDI extracted chitosan can be obtained through controlling the temperature and pressure of SDCO2. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of DA-6034, a flavonoid derivative, on mucin-like glycoprotein and ocular surface integrity in a rabbit model.

PubMed

Choi, Seul Min; Seo, Mi Jeong; Lee, Yeong Geon; Lee, Min Jung; Jeon, Hyung Jun; Kang, Kyung Koo; Ahn, Byoung Ok; Yoo, Moohi

2009-01-01

This study was designed to assess whether DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone monohydrate), a new synthetic derivative of eupatilin, increases secretion of mucin-like glycoprotein and some mucins species in conjunctiva and cornea, and contributes to the preservation of ocular surface integrity. Human conjunctival and corneal epithelial cells were incubated with DA-6034 (1-250 microM). To investigate mucin secreting activity more directly, isolated rat conjunctival goblet cells were also used. Corneal protection was investigated using a desiccation-induced rabbit model of dry eye syndrome. It was found that DA-6034 increased mucin-like glycoprotein levels of both conjunctival and corneal epithelial cells at concentrations above 100 microM. Using human conjunctival epithelial cells, it was demonstrated that treatment with DA-6034 (200 microM) significantly increased production of some mucins species including MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC16. DA-6034 also significantly increased MUC5AC production from conjunctival goblet cells isolated from rats. In the rabbit desiccation model, an ophthalmic suspension containing 3% DA-6034 significantly reduced corneal damage induced by desiccation. These results suggest that DA-6034 is a good candidate for treatment of dry eye through maintaining ocular surface integrity, which might be related to mucin secretion.

A comparative pharmacokinetic and tolerability analysis of the novel orotic acid salt form of tenofovir disoproxil and the fumaric acid salt form in healthy subjects

PubMed Central

Kim, Yu Kyong; Choi, Mun Ju; Oh, Tae Young; Yu, Kyung-Sang; Lee, SeungHwan

2017-01-01

A novel orotic acid salt form of tenofovir disoproxil (DA-2802) was developed and is expected to replace the fumaric acid salt form. The pharmacokinetic (PK) characteristics and tolerability profiles of DA-2802 were compared to those of tenofovir disoproxil fumarate (TDF, Viread®) in healthy subjects. A randomized, open-label, single-dose study was conducted in 36 healthy subjects using a two-treatment, two-period, and two-sequence crossover design. Subjects received a single oral dose of 319 mg DA-2802 or 300 mg TDF, during each period, with a 7-day washout. Serial blood samples were collected pre-dosing and up to 72 hours post-dosing in each period, for determination of serum tenofovir concentration, which was measured by ultra-performance liquid chromatography-tandem mass spectrometry. A non-compartmental method was used to obtain PK parameters of tenofovir. For comparison between the two tenofovir disoproxil salts, the 90% confidence intervals (90% CIs) of geometric mean ratios of DA-2802 to TDF for the maximum concentration (Cmax) and the area under the concentration–time curve to the last quantifiable concentration (AUC0–t) were determined. The tolerability profiles of tenofovir were assessed by evaluation of adverse events and vital signs, physical examination, ECG, and clinical laboratory tests. The serum tenofovir concentration–time profiles of DA-2802 or TDF were comparable in 32 subjects who completed the study. In both profiles, a two-compartmental elimination with first-order elimination kinetics in the terminal phase was reported in a few subjects, showing a secondary peak in the initial phase of elimination. The geometric mean ratio (90% CI) of DA-2802 to TDF was 0.898 (0.815–0.990) for Cmax and 0.904 (0.836–0.978) for AUC0–t. There were no clinically significant findings in the tolerability assessments. DA-2802 showed comparable PK characteristics and tolerability profiles to TDF. PMID:29158663

Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release

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

Volkow, Nora D.; Wang, Gene-Jack; Smith, Lisa

Metamphetamine’s widepread abuse and concerns that it may increase Parkinson’s disease led us to assess if the reported loss of dopamine transporters (DAT) in methamphetamine abusers (MA) reflected damage to dopamine neurons. Using PET with [ 11C]cocaine to measure DAT, and with [ 11C]raclopride to measure dopamine release (assessed as changes in specific binding of [ 11C]raclopride between placebo and methylphenidate), which was used as marker of dopamine neuronal function, we show that MA (n=16), tested during early detoxification, had lower DAT (20-30%) but overall normal DA release in striatum (except for a small decrease in left putamen), when comparedmore » to controls (n=15). In controls, DAT were positively correlated with DA release (higher DAT associated with larger DA increases), consistent with DAT serving as markers of DA terminals. In contrast, MA showed a trend for a negative correlation (p=0.07) (higher DAT associated with lower DA increases), consistent with reduced DA re-uptake following DAT downregulation. MA who remained abstinent nine-months later (n=9) showed significant increases in DAT (20%) but methylphenidate-induced dopamine increases did not change. In contrast, in controls, DAT did not change when retested 9 months later but methylphenidate-induced dopamine increases in ventral striatum were reduced (p=0.05). Baseline D2/D3 receptors in caudate were lower in MA than in controls and did not change with detoxification, nor did they change in the controls upon retest. The loss of DAT in the MA, which was not associated with a concomitant reduction in dopamine release as would have been expected if DAT loss reflected DA terminal degneration; as well as the recovery of DAT after protracted detoxification, which was not associated with increased dopamine release as would have been expected if DAT increases reflected terminal regeneration, indicate that the loss of DAT in these MA does not reflect degeneration of dopamine terminals.« less

Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release.

PubMed

Volkow, Nora D; Wang, Gene-Jack; Smith, Lisa; Fowler, Joanna S; Telang, Frank; Logan, Jean; Tomasi, Dardo

2015-11-01

Methamphetamine's widepread abuse and concerns that it might increase Parkinson's disease led us to assess if the reported loss of dopamine transporters (DAT) in methamphetamine abusers (MA) reflected damage to dopamine neurons. Using PET with [(11)C]cocaine to measure DAT, and with [(11)C]raclopride to measure dopamine release (assessed as changes in specific binding of [(11)C]raclopride between placebo and methylphenidate), which was used as a marker of dopamine neuronal function, we show that MA (n=16), tested during early detoxification, had lower DAT (20-30%) but overall normal DA release in striatum (except for a small decrease in left putamen), when compared to controls (n=15). In controls, DAT were positively correlated with DA release (higher DAT associated with larger DA increases), consistent with DAT serving as markers of DA terminals. In contrast, MA showed a trend for a negative correlation (p=0.07) (higher DAT associated with lower DA increases), consistent with reduced DA re-uptake following DAT downregulation. MA who remained abstinent nine-months later (n=9) showed significant increases in DAT (20%) but methylphenidate-induced dopamine increases did not change. In contrast, in controls, DAT did not change when retested 9 months later but methylphenidate-induced dopamine increases in ventral striatum were reduced (p=0.05). Baseline D2/D3 receptors in caudate were lower in MA than in controls and did not change with detoxification, nor did they change in the controls upon retest. The loss of DAT in the MA, which was not associated with a concomitant reduction in dopamine release as would have been expected if DAT loss reflected DA terminal degneration; as well as the recovery of DAT after protracted detoxification, which was not associated with increased dopamine release as would have been expected if DAT increases reflected terminal regeneration, indicate that the loss of DAT in these MA does not reflect degeneration of dopamine terminals. Published by Elsevier Inc.

Recovery of dopamine transporters with methamphetamine detoxification is not linked to changes in dopamine release

DOE PAGES

Volkow, Nora D.; Wang, Gene-Jack; Smith, Lisa; ...

2015-07-21

Metamphetamine’s widepread abuse and concerns that it may increase Parkinson’s disease led us to assess if the reported loss of dopamine transporters (DAT) in methamphetamine abusers (MA) reflected damage to dopamine neurons. Using PET with [ 11C]cocaine to measure DAT, and with [ 11C]raclopride to measure dopamine release (assessed as changes in specific binding of [ 11C]raclopride between placebo and methylphenidate), which was used as marker of dopamine neuronal function, we show that MA (n=16), tested during early detoxification, had lower DAT (20-30%) but overall normal DA release in striatum (except for a small decrease in left putamen), when comparedmore » to controls (n=15). In controls, DAT were positively correlated with DA release (higher DAT associated with larger DA increases), consistent with DAT serving as markers of DA terminals. In contrast, MA showed a trend for a negative correlation (p=0.07) (higher DAT associated with lower DA increases), consistent with reduced DA re-uptake following DAT downregulation. MA who remained abstinent nine-months later (n=9) showed significant increases in DAT (20%) but methylphenidate-induced dopamine increases did not change. In contrast, in controls, DAT did not change when retested 9 months later but methylphenidate-induced dopamine increases in ventral striatum were reduced (p=0.05). Baseline D2/D3 receptors in caudate were lower in MA than in controls and did not change with detoxification, nor did they change in the controls upon retest. The loss of DAT in the MA, which was not associated with a concomitant reduction in dopamine release as would have been expected if DAT loss reflected DA terminal degneration; as well as the recovery of DAT after protracted detoxification, which was not associated with increased dopamine release as would have been expected if DAT increases reflected terminal regeneration, indicate that the loss of DAT in these MA does not reflect degeneration of dopamine terminals.« less

Clinical assessment of dysphagia in neurodegeneration (CADN): development, validity and reliability of a bedside tool for dysphagia assessment.

PubMed

Vogel, Adam P; Rommel, Natalie; Sauer, Carina; Horger, Marius; Krumm, Patrick; Himmelbach, Marc; Synofzik, Matthis

2017-06-01

Screening assessments for dysphagia are essential in neurodegenerative disease. Yet there are no purpose-built tools to quantify swallowing deficits at bedside or in clinical trials. A quantifiable, brief, easy to administer assessment that measures the impact of dysphagia and predicts the presence or absence of aspiration is needed. The Clinical Assessment of Dysphagia in Neurodegeneration (CADN) was designed by a multidisciplinary team (neurology, neuropsychology, speech pathology) validated against strict methodological criteria in two neurodegenerative diseases, Parkinson's disease (PD) and degenerative ataxia (DA). CADN comprises two parts, an anamnesis (part one) and consumption (part two). Two-thirds of patients were assessed using reference tests, the SWAL-QOL symptoms subscale (part one) and videofluoroscopic assessment of swallowing (part two). CADN has 11 items and can be administered and scored in an average of 7 min. Test-retest reliability was established using correlation and Bland-Altman plots. 125 patients with a neurodegenerative disease were recruited; 60 PD and 65 DA. Validity was established using ROC graphs and correlations. CADN has sensitivity of 79 and 84% and specificity 71 and 69% for parts one and two, respectively. Significant correlations with disease severity were also observed (p < 0.001) for PD with small to large associations between disease severity and CADN scores for DA. Cutoff scores were identified that signal the presence of clinically meaningful dysphagia symptomatology and risk of aspiration. The CADN is a reliable, valid, brief, quantifiable, and easily deployed assessment of swallowing in neurodegenerative disease. It is thus ideally suited for both clinical bedside assessment and future multicentre clinical trials in neurodegenerative disease.

Assessment of multifunctional activity of bioactive peptides derived from fermented milk by specific Lactobacillus plantarum strains.

PubMed

Aguilar-Toalá, J E; Santiago-López, L; Peres, C M; Peres, C; Garcia, H S; Vallejo-Cordoba, B; González-Córdova, A F; Hernández-Mendoza, A

2017-01-01

Milk-derived bioactive peptides with a single activity (e.g., antioxidant, immunomodulatory, or antimicrobial) have been previously well documented; however, few studies describe multifunctional bioactive peptides, which may be preferred over single-activity peptides, as they can simultaneously trigger, modulate, or inhibit multiple physiological pathways. Hence, the aim of this study was to assess the anti-inflammatory, antihemolytic, antioxidant, antimutagenic, and antimicrobial activities of crude extracts (CE) and peptide fractions (<3 and 3-10 kDa) obtained from fermented milks with specific Lactobacillus plantarum strains. Overall, CE showed higher activity than both peptide fractions (<3 and 3-10 kDa) in most of the activities assessed. Furthermore, activity of <3 kDa was generally higher, or at least equal, to the 3 to 10 kDa peptide fractions. In particular, L. plantarum 55 crude extract or their fractions showed the higher anti-inflammatory (723.68-1,759.43μg/mL of diclofenac sodium equivalents), antihemolytic (36.65-74.45% of inhibition), and antioxidant activity [282.8-362.3µmol of Trolox (Sigma-Aldrich, St. Louis, MO) equivalents]. These results provide valuable evidence of multifunctional role of peptides derived of fermented milk by the action of specific L. plantarum strains. Thus, they may be considered for the development of biotechnological products to be used to reduce the risk of disease or to enhance a certain physiological function. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Early assessment of feasibility and technical specificities of transoral robotic surgery using the da Vinci Xi.

PubMed

Gorphe, Philippe; Von Tan, Jean; El Bedoui, Sophie; Hartl, Dana M; Auperin, Anne; Qassemyar, Quentin; Moya-Plana, Antoine; Janot, François; Julieron, Morbize; Temam, Stephane

2017-12-01

The latest generation Da Vinci ® Xi™ Surgical System Robot released has not been evaluated to date in transoral surgery for head and neck cancers. We report here the 1-year results of a non-randomized phase II multicentric prospective trial aimed at assessing its feasibility and technical specificities. Our primary objective was to evaluate the feasibility of transoral robotic surgery using the da Vinci ® Xi™ Surgical System Robot. The secondary objective was to assess peroperative outcomes. Twenty-seven patients, mean age 62.7 years, were included between May 2015 and June 2016 with tumors affecting the following sites: oropharynx (n = 21), larynx (n = 4), hypopharynx (n = 1), parapharyngeal space (n = 1). Eighteen patients were included for primary treatment, three for a local recurrence, and six for cancer in a previously irradiated field. Three were reconstructed with a FAMM flap and 6 with a free ALT flap. The mean docking time was 12 min. "Chopsticking" of surgical instruments was very rare. During hospitalization following surgery, 3 patients experienced significant bleeding between day 8 and 9 that required surgical transoral hemostasis (n = 1) or endovascular embolization (n = 2). Transoral robotic surgery using the da Vinci ® Xi™ Surgical System Robot proved feasible with technological improvements compared to previous generation surgical system robots and with a similar postoperative course. Further technological progress is expected to be of significant benefit to the patients.

Predictive value of general movements' quality in low-risk infants for minor neurological dysfunction and behavioural problems at preschool age.

PubMed

Bennema, Anne N; Schendelaar, Pamela; Seggers, Jorien; Haadsma, Maaike L; Heineman, Maas Jan; Hadders-Algra, Mijna

2016-03-01

General movement (GM) assessment is a well-established tool to predict cerebral palsy in high-risk infants. Little is known on the predictive value of GM assessment in low-risk populations. To assess the predictive value of GM quality in early infancy for the development of the clinically relevant form of minor neurological dysfunction (complex MND) and behavioral problems at preschool age. Prospective cohort study. A total of 216 members of the prospective Groningen Assisted Reproductive Techniques (ART) cohort study were included in this study. ART did not affect neurodevelopmental outcome of these relatively low-risk infants born to subfertile parents. GM quality was determined at 2 weeks and 3 months. At 18 months and 4 years, the Hempel neurological examination was used to assess MND. At 4 years, parents completed the Child Behavior Checklist; this resulted in the total problem score (TPS), internalizing problem score (IPS), and externalizing problem score (EPS). Predictive values of definitely (DA) and mildly (MA) abnormal GMs were calculated. DA GMs at 2 weeks were associated with complex MND at 18 months and atypical TPS and IPS at 4 years (all p<0.05). Sensitivity and positive predictive value of DA GMs at 2 weeks were rather low (13%-60%); specificity and negative predictive value were excellent (92%-99%). DA GMs at 3 months occurred too infrequently to calculate prediction. MA GMs were not associated with outcome. GM quality as a single predictor for complex MND and behavioral problems at preschool age has limited clinical value in children at low risk for developmental disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Human IgG Antibody Response to Aedes Nterm-34kDa Salivary Peptide, an Epidemiological Tool to Assess Vector Control in Chikungunya and Dengue Transmission Area

PubMed Central

Elanga Ndille, Emmanuel; Doucoure, Souleymane; Poinsignon, Anne; Mouchet, François; Cornelie, Sylvie; D’Ortenzio, Eric; DeHecq, Jean Sébastien; Remoue, Franck

2016-01-01

Background Arboviral diseases are an important public health concerns. Vector control remains the sole strategy to fight against these diseases. Because of the important limits of methods currently used to assess human exposure to Aedes mosquito bites, much effort is being devoted to develop new indicators. Recent studies have reported that human antibody (Ab) responses to Aedes aegypti Nterm-34kDa salivary peptide represent a promising biomarker tool to evaluate the human-Aedes contact. The present study aims investigate whether such biomarker could be used for assessing the efficacy of vector control against Aedes. Methodology/Principal findings Specific human IgG response to the Nterm-34kDa peptide was assessed from 102 individuals living in urban area of Saint-Denis at La Reunion Island, Indian Ocean, before and after the implementation of vector control against Aedes mosquitoes. IgG response decreased after 2 weeks (P < 0.0001), and remained low for 4 weeks post-intervention (P = 0.0002). The specific IgG decrease was associated with the decline of Aedes mosquito density, as estimated by entomological parameters and closely correlated to vector control implementation and was not associated with the use of individual protection, daily commuting outside of the house, sex and age. Our findings indicate a probable short-term decrease of human exposure to Aedes bites just after vector control implementation. Conclusion/Significance Results provided in the present study indicate that IgG Ab response to Aedes aegypti Nterm-34kDa salivary peptide could be a relevant short-time indicator for evaluating the efficacy of vector control interventions against Aedes species. PMID:27906987

Human IgG Antibody Response to Aedes Nterm-34kDa Salivary Peptide, an Epidemiological Tool to Assess Vector Control in Chikungunya and Dengue Transmission Area.

PubMed

Elanga Ndille, Emmanuel; Doucoure, Souleymane; Poinsignon, Anne; Mouchet, François; Cornelie, Sylvie; D'Ortenzio, Eric; DeHecq, Jean Sébastien; Remoue, Franck

2016-12-01

Arboviral diseases are an important public health concerns. Vector control remains the sole strategy to fight against these diseases. Because of the important limits of methods currently used to assess human exposure to Aedes mosquito bites, much effort is being devoted to develop new indicators. Recent studies have reported that human antibody (Ab) responses to Aedes aegypti Nterm-34kDa salivary peptide represent a promising biomarker tool to evaluate the human-Aedes contact. The present study aims investigate whether such biomarker could be used for assessing the efficacy of vector control against Aedes. Specific human IgG response to the Nterm-34kDa peptide was assessed from 102 individuals living in urban area of Saint-Denis at La Reunion Island, Indian Ocean, before and after the implementation of vector control against Aedes mosquitoes. IgG response decreased after 2 weeks (P < 0.0001), and remained low for 4 weeks post-intervention (P = 0.0002). The specific IgG decrease was associated with the decline of Aedes mosquito density, as estimated by entomological parameters and closely correlated to vector control implementation and was not associated with the use of individual protection, daily commuting outside of the house, sex and age. Our findings indicate a probable short-term decrease of human exposure to Aedes bites just after vector control implementation. Results provided in the present study indicate that IgG Ab response to Aedes aegypti Nterm-34kDa salivary peptide could be a relevant short-time indicator for evaluating the efficacy of vector control interventions against Aedes species.

Initial evaluation of an ultrasound measure for assessing the activity of skin lesions in juvenile localized scleroderma.

PubMed

Li, S C; Liebling, M S; Haines, K A; Weiss, J E; Prann, A

2011-05-01

To evaluate the construct validity of 2 proposed measures (the Ultrasound Disease Activity [U-DA] and the Tissue Thickness Score [TTS]) for evaluating sonographic differences in juvenile localized scleroderma skin lesions. We conducted a retrospective review of juvenile localized scleroderma patients who had ultrasound scans of their skin lesions between October 2005 and February 2009. Imaged lesions were classified as active or inactive based upon clinical assessment. Lesions had to have been imaged within 1 month of a clinic visit or have the same clinical assessment during both the visit before and the visit after the scan. Two physicians scored the scans using the U-DA, which scores for differences in lesion echogenicity and vascularity compared with normal tissue. Tissue thickness differences were evaluated by percent differences and by using the TTS. Wilcoxon's rank sum test was performed to assess differences. We studied 52 scans from 21 patients, 32 scans of active skin lesions and 20 scans of inactive skin lesions. Features reported by clinicians as indicative of active disease included erythema, warmth, violaceous color, new lesion, expansion of lesion, and induration. The U-DA was significantly different between active and inactive skin lesions (P = 0.0010) with significant differences found for the parameters of total echogenicity, hypodermis echogenicity, and deep tissue layer vascularity (P = 0.0014, P = 0.0023, and P = 0.0374, respectively). No significant differences were found for tissue layer thickness or TTS. The U-DA may be a useful tool in the identification of localized scleroderma activity. Further study is needed to prospectively evaluate the validity, reliability, and sensitivity of this potential monitoring tool. Copyright © 2011 by the American College of Rheumatology.

Relevant principal component analysis applied to the characterisation of Portuguese heather honey.

PubMed

Martins, Rui C; Lopes, Victor V; Valentão, Patrícia; Carvalho, João C M F; Isabel, Paulo; Amaral, Maria T; Batista, Maria T; Andrade, Paula B; Silva, Branca M

2008-01-01

The main purpose of this study was the characterisation of 'Serra da Lousã' heather honey by using novel statistical methodology, relevant principal component analysis, in order to assess the correlations between production year, locality and composition. Herein, we also report its chemical composition in terms of sugars, glycerol and ethanol, and physicochemical parameters. Sugars profiles from 'Serra da Lousã' heather and 'Terra Quente de Trás-os-Montes' lavender honeys were compared and allowed the discrimination: 'Serra da Lousã' honeys do not contain sucrose, generally exhibit lower contents of turanose, trehalose and maltose and higher contents of fructose and glucose. Different localities from 'Serra da Lousã' provided groups of samples with high and low glycerol contents. Glycerol and ethanol contents were revealed to be independent of the sugars profiles. These data and statistical models can be very useful in the comparison and detection of adulterations during the quality control analysis of 'Serra da Lousã' honey.

Spatiotemporal chaos in the dynamics of buoyantly and diffusively unstable chemical fronts

NASA Astrophysics Data System (ADS)

Baroni, M. P. M. A.; Guéron, E.; De Wit, A.

2012-03-01

Nonlinear dynamics resulting from the interplay between diffusive and buoyancy-driven Rayleigh-Taylor (RT) instabilities of autocatalytic traveling fronts are analyzed numerically for various values of the relevant parameters. These are the Rayleigh numbers of the reactant A and autocatalytic product B solutions as well as the ratio D =DB/DA between the diffusion coefficients of the two key chemical species. The interplay between the coarsening dynamics characteristic of the RT instability and the constant short wavelength modulation of the diffusive instability can lead in some regimes to complex dynamics dominated by irregular succession of birth and death of fingers. By using spectral entropy measurements, we characterize the transition between order and spatial disorder in this system. The analysis of the power spectrum and autocorrelation function, moreover, identifies similarities between the various spatial patterns. The contribution of the diffusive instability to the complex dynamics is discussed.

Enhanced reaction kinetics and reactive mixing scale dynamics in mixing fronts under shear flow for arbitrary Damköhler numbers

NASA Astrophysics Data System (ADS)

Bandopadhyay, Aditya; Le Borgne, Tanguy; Méheust, Yves; Dentz, Marco

2017-02-01

Mixing fronts, where fluids of different chemical compositions mix with each other, are known to represent hotspots of chemical reaction in hydrological systems. These fronts are typically subjected to velocity gradients, ranging from the pore scale due to no slip boundary conditions at fluid solid interfaces, to the catchment scale due to permeability variations and complex geometry of the Darcy velocity streamlines. A common trait of these processes is that the mixing interface is strained by shear. Depending on the Péclet number Pe , which represents the ratio of the characteristic diffusion time to the characteristic shear time, and the Damköhler number Da , which represents the ratio of the characteristic diffusion time to the characteristic reaction time, the local reaction rates can be strongly impacted by the dynamics of the mixing interface. So far, this impact has been characterized mostly either in kinetics-limited or in mixing-limited conditions, that is, for either low or high Da. Here the coupling of shear flow and chemical reactivity is investigated for arbitrary Damköhler numbers, for a bimolecular reaction and an initial interface with separated reactants. Approximate analytical expressions for the global production rate and reactive mixing scale are derived based on a reactive lamella approach that allows for a general coupling between stretching enhanced mixing and chemical reactions. While for Pe < Da , reaction kinetics and stretching effects are decoupled, a scenario which we name "weak stretching", for Pe > Da , we uncover a "strong stretching" scenario where new scaling laws emerge from the interplay between reaction kinetics, diffusion, and stretching. The analytical results are validated against numerical simulations. These findings shed light on the effect of flow heterogeneity on the enhancement of chemical reaction and the creation of spatially localized hotspots of reactivity for a broad range of systems ranging from kinetic limited to mixing limited situations.

Habitat Modeling and Preferences of Marine Mammals as Function of Oceanographic Characteristics: Development of Predictive Tools for Assessing the Risks and the Impacts Due to Sound Emissions

DTIC Science & Technology

2011-09-30

Arianna Azzellino Piazza Leonardo da Vinci , 32, 20133 Milano, Italy phone: (+39) 02-239-964-31 fax: (+39) 02-239-964-99 email...WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Polytechnic University of Milan,Piazza Leonardo da Vinci , 32,20133 Milano, Italy

Multi-centre evaluation of two daily disposable contact lenses.

PubMed

Walker, Jon; Young, Graeme; Hunt, Chris; Henderson, Terri

2007-05-01

To evaluate the clinical performance of two daily disposable contact lenses: 1-DAY ACUVUE (1DA) (etafilcon A, Johnson & Johnson Vision Care) and FOCUS DAILIES with AquaComfort (FD) (nelfilcon A, CIBA Vision, Inc.), which contains a quickly released moisture enhancing agent, polyvinyl alcohol (PVA). This was a 1-week, daily wear, subject-masked, bilateral, parallel group study with subjects randomly assigned to one of two daily disposable soft contact lenses. Subjects were existing soft contact lens wearers in the age range 18-39 years with a spherical refraction between -0.50 and -6.00 D. Subjects were assessed at baseline and after 1 week. Assessments included both subjective (symptoms, wearing time, vision) and objective (lens fit and ocular health) outcomes. Twenty clinical sites enrolled 282 subjects (74% female) of whom 276 (98%) successfully completed the study. Significantly more 1DA wearers reported higher mean comfort scores than with FD (3.95 versus 3.41, respectively, P<0.0001). End-of-day comfort means were also significantly higher with the 1DA group compared to the FD group (3.3 versus 3.0, P=0.03). The 1DA group reported significantly longer mean overall wearing time (1DA was worn on average 0.66+/-0.30 h longer than FD, P=0.03) and longer mean comfortable wearing time (1DA was worn on average 1.73+/-0.35 h longer than FD, P<0.0001). The 1DA lens generally showed significantly better on-eye fitting in terms of movement in primary (P<0.0001) and upgaze (P<0.0001) and ease of removal from the eye (92% versus 63%, P<0.0001) compared to FD. There was significantly less corneal staining observed with the 1DA wearing eyes compared with the FD wearing eyes (23% versus 45%, respectively, P<0.0001). Finally, there was a weak correlation between corneal staining and comfort for FD (r=0.27, P=0.002, n=136), but not for 1DA (r=-0.11, P=0.18, n=140). Subjective and objective clinical performance differences between two commonly used daily disposable lenses highlight that, although both lenses may be considered as clinically acceptable, these lenses should not be regarded as interchangeable.

Health literacy in pregnant women facing prenatal screening may explain their intention to use a patient decision aid: a short report.

PubMed

Delanoë, Agathe; Lépine, Johanie; Leiva Portocarrero, Maria Esther; Robitaille, Hubert; Turcotte, Stéphane; Lévesque, Isabelle; Wilson, Brenda J; Giguère, Anik M C; Légaré, France

2016-07-11

It has been suggested that health literacy may impact the use of decision aids (DAs) among patients facing difficult decisions. Embedded in the pilot test of a questionnaire, this study aimed to measure the association between health literacy and pregnant women's intention to use a DA to decide about prenatal screening. We recruited a convenience sample of 45 pregnant women in three clinical sites (family practice teaching unit, birthing center and obstetrical ambulatory care clinic). We asked participating women to complete a self-administered questionnaire assessing their intention to use a DA to decide about prenatal screening and assessed their health literacy levels using one subjective and two objective scales. Two of the three scales discriminated between levels of health literacy (three numeracy questions and three health literacy questions). We found a positive correlation between pregnant women's intention to use a DA and subjective health literacy (Spearman coefficient, Rho 0.32, P = 0.04) but not objective health literacy (Spearman coefficient, Rho 0.07, P = 0.65). Hence subjective health literacy may affect the intention to use a DA among pregnant women facing a decision about prenatal screening. Special attention should be given to pregnant women with lower health literacy levels to increase their intention to use a DA and ensure that every pregnant women can give informed and value-based consent to prenatal screening.

Circulatory Insufficiency and Hypotension Related to the Ductus Arteriosus in Neonates

PubMed Central

Rios, Danielle R.; Bhattacharya, Soume; Levy, Philip T.; McNamara, Patrick J.

2018-01-01

The biological role of the ductus arteriosus (DA) in neonates varies from an innocent bystander role during normal postnatal transition, to a supportive role when there is compromise to either systemic or pulmonary blood flow, to a pathological state in the presence of hemodynamically significant systemic to pulmonary shunts, as occurs in low birth weight infants. Among a wide array of clinical manifestations arising due to the ductal entity, systemic circulatory insufficiency and hypotension are of significant concern as they are particularly challenging to manage. An understanding of the physiologic interplay between the DA and the circulatory system is the key to developing appropriate targeted therapeutic strategies. In this review, we discuss the relationship of systemic hypotension to the DA, emphasizing the importance of critical thinking and a precise individual approach to intensive care support. We particularly focus on the variable states of hypotension arising directly due to a hemodynamically significant DA or seen in the period following successful surgical ligation. In addition, we explore the mechanistic contributions of the ductus to circulatory insufficiency that may manifest during the transitional period, states of maladapted transition (such as acute pulmonary hypertension of the newborn), and congenital heart disease (both ductal dependent and non-ductal dependent lesions). Understanding the dynamic modulator role of the ductus according to the ambient physiology enables a more precise approach to management. We review the pathophysiology, clinical manifestations, diagnosis, monitoring, and therapeutic intervention for the spectrum of DA-related circulatory compromise. PMID:29600242

Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex.

PubMed

Devoto, Paola; Flore, Giovanna; Saba, Pierluigi; Frau, Roberto; Gessa, Gian L

2015-10-01

Disulfiram has been claimed to be useful in cocaine addiction therapy, its efficacy being attributed to dopamine-beta-hydroxylase (DBH) inhibition. Our previous results indicate that disulfiram and the selective DBH inhibitor nepicastat increase extracellular dopamine (DA) in the rat medial prefrontal cortex (mPFC), and markedly potentiated cocaine-induced increase. Concomitantly, in rats with cocaine self-administration history, cocaine-seeking behavior induced by drug priming was prevented, probably through overstimulation of D1 receptors due to the DA increase. The present research was aimed at studying the neurochemical mechanisms originating the enhanced DA release. Noradrenergic system ablation was attained by intracerebroventricular (i.c.v.) administration of the neurotoxin anti-DBH-saporin (aDBH-sap). DA, noradrenaline (NA), and DOPAC were assessed by HPLC after ex vivo tissue extraction or in vivo microdialysis. Control and denervated rats were subjected to microdialysis in the mPFC and caudate nucleus to evaluate the effect of nepicastat-cocaine combination on extracellular DA levels and their regulation by α2-adrenoceptors. Fifteen days after neurotoxin or its vehicle administration, tissue and extracellular NA were reduced to less than 2% the control value, while extracellular DA was increased by approximately 100%. In control rats, nepicastat given alone and in combination with cocaine increased extracellular DA by about 250% and 1100%, respectively. In denervated rats, nepicastat slightly affected extracellular DA, while in combination with cocaine increased extracellular DA by 250%. No differences were found in the caudate nucleus. Clonidine almost totally reversed the extracellular DA elevation produced by nepicastat-cocaine combination, while it was ineffective in denervated rats. This research shows that the increase of extracellular DA produced by nepicastat alone or in combination with cocaine was prevented by noradrenergic denervation. The results indicate that nepicastat enhances DA release from noradrenergic terminals supposedly by removing NA from α2-autoreceptors. In addition to the inhibition of DA uptake, the latter mechanism may explain the synergistic effect of cocaine on nepicastat-induced DA release.

Docking and molecular dynamics simulations of the Fyn-SH3 domain with free and phospholipid bilayer-associated 18.5-kDa myelin basic protein (MBP)-Insights into a noncanonical and fuzzy interaction.

PubMed

Bessonov, Kyrylo; Vassall, Kenrick A; Harauz, George

2017-07-01

The molecular details of the association between the human Fyn-SH3 domain, and the fragment of 18.5-kDa myelin basic protein (MBP) spanning residues S38-S107 (denoted as xα2-peptide, murine sequence numbering), were studied in silico via docking and molecular dynamics over 50-ns trajectories. The results show that interaction between the two proteins is energetically favorable and heavily dependent on the MBP proline-rich region (P93-P98) in both aqueous and membrane environments. In aqueous conditions, the xα2-peptide/Fyn-SH3 complex adopts a "sandwich"-like structure. In the membrane context, the xα2-peptide interacts with the Fyn-SH3 domain via the proline-rich region and the β-sheets of Fyn-SH3, with the latter wrapping around the proline-rich region in a form of a clip. Moreover, the simulations corroborate prior experimental evidence of the importance of upstream segments beyond the canonical SH3-ligand. This study thus provides a more-detailed glimpse into the context-dependent interaction dynamics and importance of the β-sheets in Fyn-SH3 and proline-rich region of MBP. Proteins 2017; 85:1336-1350. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

DA-9701 on gastric motility in patients with Parkinson's disease: A randomized controlled trial.

PubMed

Shin, Cheol Min; Lee, Yoon Jin; Kim, Jong-Min; Lee, Jee Young; Kim, Kyung-Joon; Choi, Yoon Jin; Kim, Nayoung; Lee, Dong Ho

2018-04-21

To evaluate the effect of DA-9701, a novel prokinetic drug, on gastric motility evaluated by magnetic resonance imaging in patients with Parkinson's disease (PD). Forty PD patients were randomly allocated to receive either domperidone or DA-9701. Their gastric functions were evaluated using magnetic resonance imaging before and after 4-week treatment period. Information on levodopa daily dose, disease duration, and Unified PD Rating Scale scores was collected. In 18 patients (domperidone: 9, DA-9701: 9), plasma levodopa concentrations were determined. Primary outcome was assessed by a one-sided 95% confidence interval to show non-inferiority of DA-9701 vs. domperidone with a pre-determined non-inferiority margin of -10%. Thirty-eight participants (19 men and 19 women; mean age, 67.1 years) completed the study protocol (domperidone: DA-9701 = 19:19). Gastric emptying rate at 120 min (2-hr GER) was comparable between the 2 groups; it was not correlated with levodopa daily dose or disease duration or Unified PD Rating Scale scores (all p > 0.05). DA-9701 was not inferior to domperidone in changes of 2-hr GERs before and after the treatment (absolute difference, 4.0 %; one-sided 95% confidence interval, - 3.7 to infinity). However, a significant increase in 2-hr GER was observed only in DA-9701 group (54.5% and 61.8%, before and after treatment, respectively, p < 0.05). Plasma levodopa concentration showed an insignificant but increasing trend in DA-9701 group. There were neither adverse reactions nor deteriorations of parkinsonian symptoms observed in the study participants. DA-9701 can be used for the patients with PD to enhance gastric motility without aggravating PD symptoms (ClinicalTrials.gov number: NCT03022201). Copyright © 2018 Elsevier Ltd. All rights reserved.

Efficacy of DA-9701 (Motilitone) in Functional Dyspepsia Compared to Pantoprazole: A Multicenter, Randomized, Double-blind, Non-inferiority Study.

PubMed

Jung, Hye-Kyung; Lee, Kwang Jae; Choi, Myung-Gyu; Park, Hyojin; Lee, Joon Seong; Rhee, Poong-Lyul; Kim, Nayoung; Park, KyungSik; Choi, Suck Chei; Lee, Oh Young; Huh, Kyu Chan; Song, Geun Am; Hong, Su Jin; Sohn, Chong Il; Jung, Hwoon-Yong; Lee, Yong Chan; Rew, Jong Sun; Jee, Sam Ryong; Kwon, Joong Goo

2016-04-30

The effect of proton pump inhibitors (PPI) in Asian functional dyspepsia (FD) patients has not been well established as in Westerncountries. DA-9701, a novel prokinetic agent, stimulates gastric emptying and modulates visceral hypersensitivity in vivo and in human studies. This study was conducted to compare the efficacy of DA-9701 with a conventional PPI in mono or combination therapy in patients with FD. In this double-blind, randomized, non-inferiority trial, 389 patients diagnosed with FD using Rome III criteria were allocated among3 groups: 30-mg DA-9701 t.i.d (means 3 times a day), 40-mg pantoprazole, and 30-mg DA-9701 t.i.d + 40-mg pantoprazole. Theprimary efficacy end-point was a global assessment of the patient binary response or response on a 5-Likert scale after 4 weeks. The global symptomatic improvement was 60.5% in the DA-9701 group, 65.6% in the pantoprazole group, and 63.5% in the DA-9701 + pantoprazole group using a 5-Likert scale at week 4 with no significant difference among 3 groups (P = 0.685). Symptomimprovement measured by binary outcome was significantly achieved in each of the 3 groups, but not different among groups.Patients in all treatment groups reported significant improvement in the response rate and symptoms according to FD subtypes anddyspepsia-related quality of life (P < 0.001), but there were no significant differences among the 3 groups. DA-9701 improves global and individual symptoms and increases dyspepsia-specific quality of life in patients with FD. The efficacyof DA-9701 monotherapy is comparable with pantoprazole and there is no additive effect with combination of DA-9701 andpantoprazole in patients with FD.

Insights into the Modulation of Dopamine Transporter Function by Amphetamine, Orphenadrine, and Cocaine Binding

PubMed Central

Cheng, Mary Hongying; Block, Ethan; Hu, Feizhuo; Cobanoglu, Murat Can; Sorkin, Alexander; Bahar, Ivet

2015-01-01

Human dopamine (DA) transporter (hDAT) regulates dopaminergic signaling in the central nervous system by maintaining the synaptic concentration of DA at physiological levels, upon reuptake of DA into presynaptic terminals. DA translocation involves the co-transport of two sodium ions and the channeling of a chloride ion, and it is achieved via alternating access between outward-facing (OF) and inward-facing states of DAT. hDAT is a target for addictive drugs, such as cocaine, amphetamine (AMPH), and therapeutic antidepressants. Our recent quantitative systems pharmacology study suggested that orphenadrine (ORPH), an anticholinergic agent and anti-Parkinson drug, might be repurposable as a DAT drug. Previous studies have shown that DAT-substrates like AMPH or -blockers like cocaine modulate the function of DAT in different ways. However, the molecular mechanisms of modulation remained elusive due to the lack of structural data on DAT. The newly resolved DAT structure from Drosophila melanogaster opens the way to a deeper understanding of the mechanism and time evolution of DAT–drug/ligand interactions. Using a combination of homology modeling, docking analysis, molecular dynamics simulations, and molecular biology experiments, we performed a comparative study of the binding properties of DA, AMPH, ORPH, and cocaine and their modulation of hDAT function. Simulations demonstrate that binding DA or AMPH drives a structural transition toward a functional form predisposed to translocate the ligand. In contrast, ORPH appears to inhibit DAT function by arresting it in the OF open conformation. The analysis shows that cocaine and ORPH competitively bind DAT, with the binding pose and affinity dependent on the conformational state of DAT. Further assays show that the effect of ORPH on DAT uptake and endocytosis is comparable to that of cocaine. PMID:26106364

Life events and quality of life in female patients with dermatitis artefacta: a comparative study with siblings and controls.

PubMed

El Kissi, Yousri; Chhoumi, Maha; Nakhli, Jaafar; Kenani, Nesrine; Denguezli, Mohamed; Nouira, Rafiaa; Ben Hadj Ali, Bechir

2014-10-01

If the severity of dermatitis artefacta (DA) is accepted by most authors, few published studies have sought to clarify its etiology and impact. It is in this context that this work aimed to compare Life Events (LE) and quality of life (QoL) scores in patients with DA, in their siblings and in control patients with other chronic dermatological diseases. This is a descriptive and comparative cross-sectional study carried out in the dermatology department of Farhat Hached hospital in Sousse, Tunisia. Thirty female patients diagnosed with DA according to DSM-IV criteria were retrospectively recruited. For each patient with DA, one of her sisters, the closest in age, was enrolled in the siblings group. The control group consisted of thirty female patients with other chronic dermatological diseases, matched with DA patients for age and duration of disease progression. Assessment was based on Paykel inventory for LE and on SF-36 for QoL. Compared to both control groups, DA patients reported more LE with more objective negative impact of these events and had a lower score and more often impaired mean global score of QoL. LE would have a role in the pathogenesis of DA which seems to alter the QoL of patients. These results could help to improve the understanding of DA and incite clinicians to focus not only on the diagnosis and treatment of DA but also on the impact of this disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Protective effect of DA-9401 in finasteride-induced apoptosis in rat testis: inositol requiring kinase 1 and c-Jun N-terminal kinase pathway.

PubMed

Soni, Kiran Kumar; Shin, Yu Seob; Choi, Bo Ram; Karna, Keshab Kumar; Kim, Hye Kyung; Lee, Sung Won; Kim, Chul Young; Park, Jong Kwan

2017-01-01

Finasteride is used to treat male pattern baldness and benign prostatic hyperplasia. This study investigated the toxicity of finasteride and recovery by DA-9401 using Sprague Dawley (SD) rats. Forty adult male SD rats were assigned to four groups: control (CTR), finasteride 1 mg/kg/day (F), finasteride 1 mg/kg + DA-9401 100 mg/kg/day (F + DA 100) and finasteride 1 mg/kg + DA-9401 200 mg/kg/day (F + DA 200). Treatments were by oral delivery once daily for 90 consecutive days. The gross anatomical parameters assessed included: genital organ weight; vas deferens sperm count and sperm motility; testosterone, dihydrotestosterone (DHT) and malondialdehyde levels; and histological and terminal deoxynucleotidyl transferase enzyme mediated dUTP nick-end labeling (TUNEL) staining of testis for spermatogenic cell density, Johnsen's score and apoptosis. Testicular tissue was also used for evaluating endoplasmic reticulum (ER) stress and apoptotic proteins. Epididymis weight, seminal vesicle weight, prostate weight, penile weight and vas deferens sperm motility showed significant differences between the F group and the CTR, F + DA 100 and F + DA 200 groups. There was no significant change in the testosterone level. DHT level decreased significantly in the F group compared with the CTR group. Testis tissue revealed significant changes in spermatogenic cell density, Johnsen's score and apoptotic index. Western blot showed significant changes in the ER stress and apoptotic markers. Finasteride resulted in reduced fertility and increased ER stress and apoptotic markers, which were recovered by administration of DA-9401 in the SD rats.

Assessing the magnitude of recent compositional changes in marine ecosystems: a conservation paleobiology case study from the Persian Gulf

NASA Astrophysics Data System (ADS)

Albano, Paolo G.; Tomašových, Adam; Stachowitsch, Michael; Zuschin, Martin

2015-04-01

Nearly every modern marine ecosystem has experienced major changes due to anthropogenic stressors such as habitat modification, pollution, overexploitation and climate change. However, our knowledge of ecosystem dynamics in a historical time-frame (decades to few centuries) is restricted by the lack of direct, recorded human observations: properly designed ecological surveys have been conducted for comparatively short durations in the last few decades only, and in merely a few localities, poorly representative of large-scale phenomena. A unique but under-exploited source of information is hidden in death assemblages (DAs), the taxonomically identifiable, dead or discarded organic remains in a seabed. Due to the slow degradation of hard skeletal parts such as shells in the sea, DAs represent archives that accumulate information on species composition and community states over time and are inert to recent changes. Assessing the degree in compositional and ecological similarity between living (LAs) and death assemblages can be used to reconstruct the degree of recent community disturbances. Previous studies have shown that live-dead (LD) agreement tends to be poorer in anthropogenically disturbed settings, because LAs respond faster than DAs to pressures, thus increasing the LD disagreement in composition. As a complementary approach, age dating of shells (using radiocarbon calibrated amino acid racemization) allows identifying the timing of ecosystem change. These approaches help recognize community shifts in time, overcoming the lack of direct observation. As a case study, we present the results of applying these techniques to the impacts of oil platforms on the benthic assemblages in the Persian (Arabian) Gulf. This semi-enclosed basin originated 12,500 years ago and currently hosts the highest concentration of infrastructures for oil and gas extraction in the world. Moreover, it has been affected by major oil spills. Contaminants show a weak gradient within each of two oilfields, which does not explain the variation in taxonomic composition and abundance of the LA. Therefore, we would expect the LD agreement to be mainly determined by time-averaging, inducing an increase in species richness and in evenness in the DA. In contrast to this expectation, rarefied species richness and evenness were not higher in the DA. However, this finding was largely determined by the dominance in the DA of a single bivalve species, Ervilia purpurea, which represented 40% of the whole DA, but was totally absent from the LA. The removal of E. purpurea from the dataset led to results in accordance with expectations. The reasons for the absence in the LA of E. purpurea are currently being investigated with dating techniques to determine the age of the youngest specimens and its relation to the history of the basin and the age of the major pollution events.

Defining donor and acceptor strength in conjugated copolymers

NASA Astrophysics Data System (ADS)

Hedström, Svante; Wang, Ergang; Persson, Petter

2017-03-01

The progress in efficiency of organic photovoltaic devices is largely driven by the development of new donor-acceptor (D-A) copolymers. The number of possible D-A combinations escalates rapidly with the ever-increasing number of donor and acceptor units, and the design process often involves a trial-and-error approach. We here present a computationally efficient methodology for the prediction of optical and electronic properties of D-A copolymers based on density functional theory calculations of donor- and acceptor-only homopolymers. Ten donors and eight acceptors are studied, as well as all of their 80 D-A copolymer combinations, showing absorption energies of 1.3-2.3 eV, and absorption strengths varying by up to a factor of 2.5. Focus lies on exhibited trends in frontier orbital energies, optical band gaps, and absorption intensities, as well as their relation to the molecular structure. Based on the results, we define the concept of donor and acceptor strength, and calculate this quantity for all investigated units. The light-harvesting capabilities of the 80 D-A copolymers were also assessed. This gives a valuable theoretical guideline to the design of D-A copolymers with the potential to reduce the synthesis efforts in the development of new polymers.

Impact of spatio-temporal scale of adjustment on variational assimilation of hydrologic and hydrometeorological data in operational distributed hydrologic models

NASA Astrophysics Data System (ADS)

Lee, H.; Seo, D.; McKee, P.; Corby, R.

2009-12-01

One of the large challenges in data assimilation (DA) into distributed hydrologic models is to reduce the large degrees of freedom involved in the inverse problem to avoid overfitting. To assess the sensitivity of the performance of DA to the dimensionality of the inverse problem, we design and carry out real-world experiments in which the control vector in variational DA (VAR) is solved at different scales in space and time, e.g., lumped, semi-distributed, and fully-distributed in space, and hourly, 6 hourly, etc., in time. The size of the control vector is related to the degrees of freedom in the inverse problem. For the assessment, we use the prototype 4-dimenational variational data assimilator (4DVAR) that assimilates streamflow, precipitation and potential evaporation data into the NWS Hydrology Laboratory’s Research Distributed Hydrologic Model (HL-RDHM). In this talk, we present the initial results for a number of basins in Oklahoma and Texas.

Caída de tefra y su influencia sobre la estructura y dinámica de los bosques andinos de Nothofagus en el Parque Nacional Puyehue, Chile

Treesearch

Mauricio Montiel; Mauro E González; Charles M Crisafulli

2016-01-01

Tephra fall influences the structure and dynamics of Andean Nothofagus (beech) forests in Puyehue National Park, Chile. Forest mortality and subsequent establishment, structure and composition have been affected by the eruption of the Puyehue-Cordon Caulle volcano complex.

Adventures in Modeling: Exploring Complex, Dynamic Systems with StarLogo.

ERIC Educational Resources Information Center

Colella, Vanessa Stevens; Klopfer, Eric; Resnick, Mitchel

For thousands of years people from da Vinci to Einstein have created models to help them better understand patterns and processes in the world around them. Computers make it easier for novices to build and explore their own models and learn new scientific ideas in the process. This book introduces teachers and students to designing, creating, and…

Extended capability of the integrated transport analysis suite, TASK3D-a, for LHD experiment

NASA Astrophysics Data System (ADS)

Yokoyama, M.; Seki, R.; Suzuki, C.; Sato, M.; Emoto, M.; Murakami, S.; Osakabe, M.; Tsujimura, T. Ii.; Yoshimura, Y.; Ido, T.; Ogawa, K.; Satake, S.; Suzuki, Y.; Goto, T.; Ida, K.; Pablant, N.; Gates, D.; Warmer, F.; Vincenzi, P.; Simulation Reactor Research Project, Numerical; LHD Experiment Group

2017-12-01

The integrated transport analysis suite, TASK3D-a (Analysis), has been developed to be capable for routine whole-discharge analyses of plasmas confined in three-dimensional (3D) magnetic configurations such as the LHD. The routine dynamic energy balance analysis for NBI-heated plasmas was made possible in the first version released in September 2012. The suite has been further extended through implementing additional modules for neoclassical transport and ECH deposition for 3D configurations. A module has also been added for creating systematic data for the International Stellarator-Heliotron Confinement and Profile Database. Improvement of neutral beam injection modules for multiple-ion species plasmas and loose coupling with a large-simulation code are also highlights of recent developments.

Effect of atomoxetine on hyperactivity in an animal model of attention-deficit/hyperactivity disorder (ADHD).

PubMed

Moon, Su Jin; Kim, Chang Ju; Lee, Yeon Jung; Hong, Minha; Han, Juhee; Bahn, Geon Ho

2014-01-01

Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD). To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus. Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined. The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner. Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway.

Effect of Atomoxetine on Hyperactivity in an Animal Model of Attention-Deficit/Hyperactivity Disorder (ADHD)

PubMed Central

Moon, Su Jin; Kim, Chang Ju; Lee, Yeon Jung; Hong, Minha; Han, Juhee; Bahn, Geon Ho

2014-01-01

Background Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD). Purpose To investigate the therapeutic effects of atomoxetine on the motor activity in relation to the expression of the dopamine (DA) D2 receptor based on the hypothesis that DA system hypofunction causes ADHD symptoms, which would correlate with extensive D2 receptor overproduction and a lack of DA synthesis in specific brain regions: prefrontal cortex (PFC), striatum, and hypothalamus. Methods Young male spontaneously hypertensive rats (SHR), animal models of ADHD, were randomly divided into four groups according to the daily dosage of atomoxetine and treated for 21 consecutive days. The animals were assessed using an open-field test, and the DA D2 receptor expression was examined. Results The motor activity improved continuously in the group treated with atomoxetine at a dose of 1 mg/Kg/day than in the groups treated with atomoxetine at a dose of 0.25 mg/Kg/day or 0.5 mg/Kg/day. With respect to DA D2 receptor immunohistochemistry, we observed significantly increased DA D2 receptor expression in the PFC, striatum, and hypothalamus of the SHRs as compared to the WKY rats. Treatment with atomoxetine significantly decreased DA D2 expression in the PFC, striatum, and hypothalamus of the SHRs, in a dose-dependent manner. Conclusion Hyperactivity in young SHRs can be improved by treatment with atomoxetine via the DA D2 pathway. PMID:25271814

Developing a multidisciplinary approach within the ED towards domestic violence presentations.

PubMed

Basu, Subhashis; Ratcliffe, Giles

2014-03-01

To improve the detection and quality of care of patients who attend the emergency department (ED) with confirmed or suspected domestic abuse (DA). A quality improvement report on the design, implementation and evaluation of a specialised service and structured training programme to detect and manage DA presentations within an emergency medicine department. The study was set in the ED at the Northern General Hospital, Sheffield, UK. Key measures for improvement included introducing a service within the ED to help staff manage DA and coordinate responses; improve staff confidence in detecting DA; develop a structured and consistent process by which to manage DA presentations. An Independent Domestic Violence Advocate service was introduced into the department in July 2011 through a multiagency agreement. A structured training and education programme was delivered to ED staff. A 'communications form' was developed for DA risk assessment and case management. The process was reviewed quarterly. One hundred and seventy-two referrals were made to the service (121 distinct clients) over a 12-month period. Staff reported greater confidence in detecting DA, and community partners highlighted the role the service had in improving DA detection and care quality within the city. Strong leadership and prioritising the issue within the department has facilitated the development of the process and contributed substantially to its success. Support from community partners has been invaluable in tailoring the service and education programme to the needs of staff and patients within the department.

Respiratory Displacement of the Thoracic Aorta: Physiological Phenomenon With Potential Implications for Thoracic Endovascular Repair

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

Weber, Tim Frederik, E-mail: tim.weber@med.uni-heidelberg.d; Tetzlaff, Ralf; Rengier, Fabian

The purpose of this study was to assess the magnitude and direction of respiratory displacement of the ascending and descending thoracic aorta during breathing maneuvers. In 11 healthy nonsmokers, dynamic magnetic resonance imaging was performed in transverse orientation at the tracheal bifurcation during maximum expiration and inspiration as well as tidal breathing. The magnitude and direction of aortic displacement was determined relatively to resting respiratory position for the ascending (AA) and descending (DA) aorta. To estimate a respiratory threshold for occurrence of distinct respiratory aortic motion, the latter was related to the underlying change in anterior-posterior thorax diameter. Compound displacementmore » between maximum expiration and inspiration was 24.3 {+-} 6.0 mm for the AA in the left anterior direction and 18.2 {+-} 5.5 mm for the DA in the right anterior direction. The mean respiratory thorax excursion during tidal breathing was 8.9 {+-} 2.8 mm. The respiratory threshold, i.e., the increase in thorax diameter necessary to result in respiratory aortic displacement, was estimated to be 15.7 mm. The data suggest that after a threshold of respiratory thorax excursion is exceeded, respiration is accompanied by significant displacement of the thoracic aorta. Although this threshold may not be reached during tidal breathing in the majority of individuals, segmental differences during forced respiration impact on aortic geometry, may result in additional extrinsic forces on the aortic wall, and may be of significance for aortic prostheses designed for thoracic endovascular aortic repair.« less

Measured daylighting potential of a static optical louver system under real sun and sky conditions

DOE PAGES

Konis, Kyle; Lee, Eleanor S.

2015-05-04

Side-by-side comparisons were made over solstice-to-solstice changes in sun and sky conditions between an optical louver system (OLS) and a conventional Venetian blind set at a horizontal slat angle and located inboard of a south-facing, small-area, clerestory window in a full-scale office testbed. Daylight autonomy (DA), window luminance, and ceiling luminance uniformity were used to assess performance. The performance of both systems was found to have significant seasonal variation, where performance under clear sky conditions improved as maximum solar altitude angles transitioned from solstice to equinox. Although the OLS produced fewer hours per day of DA on average than themore » Venetian blind, the OLS never exceeded the designated 2000 cd/m2 threshold for window glare. In contrast, the Venetian blind was found to exceed the visual discomfort threshold over a large fraction of the day during equinox conditions. Notably, these peak periods of visual discomfort occurred during the best periods of daylighting performance. Luminance uniformity was analyzed using calibrated high dynamic range luminance images. Under clear sky conditions, the OLS was found to increase the luminance of the ceiling as well as produce a more uniform distribution. Furthermore, compared to conventional venetian blinds, the static optical sunlight redirecting system studied has the potential to significantly reduce the annual electrical lighting energy demand of a daylit space and improve the quality from the perspective of building occupants by consistently transmitting useful daylight while eliminating window glare.« less

Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain.

PubMed

Bannister, Kirsty; Qu, Chaoling; Navratilova, Edita; Oyarzo, Janice; Xie, Jennifer Yanhua; King, Tamara; Dickenson, Anthony H; Porreca, Frank

2017-12-01

Gabapentin (GBP) is a first-line therapy for neuropathic pain, but its mechanisms and sites of action remain uncertain. We investigated GBP-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal GBP reversed evoked mechanical hypersensitivity and produced conditioned place preference (CPP) and dopamine (DA) release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal GBP also significantly inhibited dorsal horn wide-dynamic-range neuronal responses to a range of evoked stimuli in SNL rats. By contrast, GBP microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP, and elicited NAc DA release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on wide-dynamic-range neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous GBP-induced CPP and NAc DA release but failed to block its inhibition of tactile allodynia. Gabapentin, therefore, can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity, and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from nonopioid analgesics, GBP requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain-motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of GBP's analgesic effects in patients.

Vault-poly-ADP-ribose polymerase in the Octopus vulgaris brain: a regulatory factor of actin polymerization dynamic.

PubMed

De Maio, Anna; Natale, Emiliana; Rotondo, Sergio; Di Cosmo, Anna; Faraone-Mennella, Maria Rosaria

2013-09-01

Our previous behavioural, biochemical and immunohistochemical analyses conducted in selected regions (supra/sub oesophageal masses) of the Octopus vulgaris brain detected a cytoplasmic poly-ADP-ribose polymerase (more than 90% of total enzyme activity). The protein was identified as the vault-free form of vault-poly-ADP-ribose polymerase. The present research extends and integrates the biochemical characterization of poly-ADP-ribosylation system, namely, reaction product, i.e., poly-ADP-ribose, and acceptor proteins, in the O. vulgaris brain. Immunochemical analyses evidenced that the sole poly-ADP-ribose acceptor was the octopus cytoskeleton 50-kDa actin. It was present in both free, endogenously poly-ADP-ribosylated form (70kDa) and in complex with V-poly-ADP-ribose polymerase and poly-ADP-ribose (260kDa). The components of this complex, alkali and high salt sensitive, were purified and characterized. The kind and the length of poly-ADP-ribose corresponded to linear chains of 30-35 ADP-ribose units, in accordance with the features of the polymer synthesized by the known vault-poly-ADP-ribose polymerase. In vitro experiments showed that V-poly-ADP-ribose polymerase activity of brain cytoplasmic fraction containing endogenous actin increased upon the addition of commercial actin and was highly reduced by ATP. Anti-actin immunoblot of the mixture in the presence and absence of ATP showed that the poly-ADP-ribosylation of octopus actin is a dynamic process balanced by the ATP-dependent polymerization of the cytoskeleton protein, a fundamental mechanism for synaptic plasticity. © 2013 Elsevier Inc. All rights reserved.

A weakly-constrained data assimilation approach to address rainfall-runoff model structural inadequacy in streamflow prediction

NASA Astrophysics Data System (ADS)

Lee, Haksu; Seo, Dong-Jun; Noh, Seong Jin

2016-11-01

This paper presents a simple yet effective weakly-constrained (WC) data assimilation (DA) approach for hydrologic models which accounts for model structural inadequacies associated with rainfall-runoff transformation processes. Compared to the strongly-constrained (SC) DA, WC DA adjusts the control variables less while producing similarly or more accurate analysis. Hence the adjusted model states are dynamically more consistent with those of the base model. The inadequacy of a rainfall-runoff model was modeled as an additive error to runoff components prior to routing and penalized in the objective function. Two example modeling applications, distributed and lumped, were carried out to investigate the effects of the WC DA approach on DA results. For distributed modeling, the distributed Sacramento Soil Moisture Accounting (SAC-SMA) model was applied to the TIFM7 Basin in Missouri, USA. For lumped modeling, the lumped SAC-SMA model was applied to nineteen basins in Texas. In both cases, the variational DA (VAR) technique was used to assimilate discharge data at the basin outlet. For distributed SAC-SMA, spatially homogeneous error modeling yielded updated states that are spatially much more similar to the a priori states, as quantified by Earth Mover's Distance (EMD), than spatially heterogeneous error modeling by up to ∼10 times. DA experiments using both lumped and distributed SAC-SMA modeling indicated that assimilating outlet flow using the WC approach generally produce smaller mean absolute difference as well as higher correlation between the a priori and the updated states than the SC approach, while producing similar or smaller root mean square error of streamflow analysis and prediction. Large differences were found in both lumped and distributed modeling cases between the updated and the a priori lower zone tension and primary free water contents for both WC and SC approaches, indicating possible model structural deficiency in describing low flows or evapotranspiration processes for the catchments studied. Also presented are the findings from this study and key issues relevant to WC DA approaches using hydrologic models.

Peer Deviance, Parental Divorce, and Genetic Risk in the Prediction of Drug Abuse in a Nationwide Swedish Sample

PubMed Central

Kendler, Kenneth S.; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2014-01-01

IMPORTANCE Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA). OBJECTIVES To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels. DESIGN, SETTING, AND PARTICIPANTS Studies of future DA registration in 1 401 698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA. MAIN OUTCOMES AND MEASURES Drug abuse recorded in medical, legal, or pharmacy registry records. RESULTS Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure. CONCLUSIONS AND RELEVANCE With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors. PMID:24576925

Peer deviance, parental divorce, and genetic risk in the prediction of drug abuse in a nationwide Swedish sample: evidence of environment-environment and gene-environment interaction.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Kristina; Sundquist, Jan

2014-04-01

Peer deviance (PD) strongly predicts externalizing psychopathologic conditions but has not been previously assessable in population cohorts. We sought to develop such an index of PD and to clarify its effects on risk of drug abuse (DA). To examine how strongly PD increases the risk of DA and whether this community-level liability indicator interacts with key DA risk factors at the individual and family levels. Studies of future DA registration in 1,401,698 Swedish probands born from January 1, 1970, through December 31, 1985, and their adolescent peers in approximately 9200 small community areas. Peer deviance was defined as the proportion of individuals born within 5 years of the proband living in the same small community when the proband was 15 years old who eventually were registered for DA. Drug abuse recorded in medical, legal, or pharmacy registry records. Peer deviance was associated with future DA in the proband, with rates of DA in older and male peers more strongly predictive than in younger or female peers. The predictive power of PD was only slightly attenuated by adding measures of community deprivation, collective efficacy, or family socioeconomic status. Probands whose parents were divorced were more sensitive to the pathogenic effects of high PD environments. A robust positive interaction was also seen between genetic risk of DA (indexed by rates of DA in first-, second-, and third-degree relatives) and PD exposure. With sufficient data, PD can be measured in populations and strongly predicts DA. In a nationwide sample, risk factors at the level of the individual (genetic vulnerability), family (parental loss), and community (PD) contribute substantially to risk of DA. Individuals at elevated DA risk because of parental divorce or high genetic liability are more sensitive to the pathogenic effects of PD. Although the effect of our PD measure on DA liability cannot be explained by standard measures of community or family risk, we cannot, with available data, discriminate definitively between the effect of true peer effects and other unmeasured risk factors.

Long-Term Monitoring of Cased Pipelines Using Longrange Guided-Wave Technique

DOT National Transportation Integrated Search

2009-05-19

Integrity management programs for gas transmission pipelines are required by The Office of Pipeline Safety (OPS)/DOT. Direct Assessment (DA) and 'Other Technologies' have become the focus of assessment options for pipeline integrity on cased crossing...

External Corrosion Direct Assessment for Unique Threats to Underground Pipelines

DOT National Transportation Integrated Search

2007-11-01

External corrosion direct assessment process (ECDA) implemented in accordance with the NACE Recommended Practice RP0502-02 relies on above ground DA techniques to prioritize locations at risk for corrosion. Two special cases warrant special considera...

C-terminal interactions mediate the quaternary dynamics of αB-crystallin

PubMed Central

Hilton, Gillian R.; Hochberg, Georg K. A.; Laganowsky, Arthur; McGinnigle, Scott I.; Baldwin, Andrew J.; Benesch, Justin L. P.

2013-01-01

αB-crystallin is a highly dynamic, polydisperse small heat-shock protein that can form oligomers ranging in mass from 200 to 800 kDa. Here we use a multifaceted mass spectrometry approach to assess the role of the C-terminal tail in the self-assembly of αB-crystallin. Titration experiments allow us to monitor the binding of peptides representing the C-terminus to the αB-crystallin core domain, and observe individual affinities to both monomeric and dimeric forms. Notably, we find that binding the second peptide equivalent to the core domain dimer is considerably more difficult than the first, suggesting a role of the C-terminus in regulating assembly. This finding motivates us to examine the effect of point mutations in the C-terminus in the full-length protein, by quantifying the changes in oligomeric distribution and corresponding subunit exchange rates. Our results combine to demonstrate that alterations in the C-terminal tail have a significant impact on the thermodynamics and kinetics of αB-crystallin. Remarkably, we find that there is energy compensation between the inter- and intra-dimer interfaces: when one interaction is weakened, the other is strengthened. This allosteric communication between binding sites on αB-crystallin is likely important for its role in binding target proteins. PMID:23530258

Benchmark model correction of monitoring system based on Dynamic Load Test of Bridge

NASA Astrophysics Data System (ADS)

Shi, Jing-xian; Fan, Jiang

2018-03-01

Structural health monitoring (SHM) is a field of research in the area, and it’s designed to achieve bridge safety and reliability assessment, which needs to be carried out on the basis of the accurate simulation of the finite element model. Bridge finite element model is simplified of the structural section form, support conditions, material properties and boundary condition, which is based on the design and construction drawings, and it gets the calculation models and the results.But according to the design and specification requirements established finite element model due to its cannot fully reflect the true state of the bridge, so need to modify the finite element model to obtain the more accurate finite element model. Based on Da-guan river crossing of Ma - Zhao highway in Yunnan province as the background to do the dynamic load test test, we find that the impact coefficient of the theoretical model of the bridge is very different from the coefficient of the actual test, and the change is different; according to the actual situation, the calculation model is adjusted to get the correct frequency of the bridge, the revised impact coefficient found that the modified finite element model is closer to the real state, and provides the basis for the correction of the finite model.

Preliminary evidence that negative symptom severity relates to multilocus genetic profile for dopamine signaling capacity and D2 receptor binding in healthy controls and in schizophrenia.

PubMed

Eisenstein, Sarah A; Bogdan, Ryan; Chen, Ling; Moerlein, Stephen M; Black, Kevin J; Perlmutter, Joel S; Hershey, Tamara; Barch, Deanna M

2017-03-01

Deficits in central, subcortical dopamine (DA) signaling may underlie negative symptom severity, particularly anhedonia, in healthy individuals and in schizophrenia. To investigate these relationships, we assessed negative symptoms with the Schedule for the Assessment of Negative Symptoms and the Brief Negative Symptom Scale (BNSS) and self-reported anhedonia with the Scales for Physical and Social Anhedonia (SPSA), Temporal Experience of Pleasure Scale, and Snaith-Hamilton Pleasure Scale in 36 healthy controls (HC), 27 siblings (SIB) of individuals with schizophrenia, and 66 individuals with schizophrenia or schizoaffective disorder (SCZ). A subset of participants (N = 124) were genotyped for DA-related polymorphisms in genes for DRD4, DRD2/ANKK1, DAT1, and COMT, which were used to construct biologically-informed multi-locus genetic profile (MGP) scores reflective of subcortical dopaminergic signaling. DA receptor type 2 (D2R) binding was assessed among a second subset of participants (N = 23) using PET scans with the D2R-selective, non-displaceable radioligand (N-[ 11 C]methyl)benperidol. Higher MGP scores, reflecting elevated subcortical dopaminergic signaling capacity, were associated with less negative symptom severity, as measured by the BNSS, across all participants. In addition, higher striatal D2R binding was associated with less physical and social anhedonia, as measured by the SPSA, across HC, SIB, and SCZ. The current preliminary findings support the hypothesis that subcortical DA function may contribute to negative symptom severity and self-reported anhedonia, independent of diagnostic status. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preliminary Evidence that Negative Symptom Severity Relates to Multilocus Genetic Profile for Dopamine Signaling Capacity and D2 Receptor Binding in Healthy Controls and in Schizophrenia

PubMed Central

Eisenstein, Sarah A.; Bogdan, Ryan; Chen, Ling; Moerlein, Stephen M.; Black, Kevin J.; Perlmutter, Joel S.; Hershey, Tamara; Barch, Deanna M.

2017-01-01

Deficits in central, subcortical dopamine (DA) signaling may underlie negative symptom severity, particularly anhedonia, in healthy individuals and in schizophrenia. To investigate these relationships, we assessed negative symptoms with the Schedule for the Assessment of Negative Symptoms and the Brief Negative Symptom Scale (BNSS) and self-reported anhedonia with the Scales for Physical and Social Anhedonia (SPSA), Temporal Experience of Pleasure Scale, and Snaith-Hamilton Pleasure Scale in 36 healthy controls (HC), 27 siblings (SIB) of individuals with schizophrenia, and 66 individuals with schizophrenia or schizoaffective disorder (SCZ). A subset of participants (N = 124) were genotyped for DA-related polymorphisms in genes for DRD4, DRD2/ANKK1, DAT1, and COMT, which were used to construct biologically-informed multi-locus genetic profile (MGP) scores reflective of subcortical dopaminergic signaling. DA receptor type 2 (D2R) binding was assessed among a second subset of participants (N = 23) using PET scans with the D2R-selective, non-displaceable radioligand (N-[11C]methyl)benperidol. Higher MGP scores, reflecting elevated subcortical dopaminergic signaling capacity, were associated with less negative symptom severity, as measured by the BNSS, across all participants. In addition, higher striatal D2R binding was associated with less physical and social anhedonia, as measured by the SPSA, across HC, SIB, and SCZ. The current preliminary findings support the hypothesis that subcortical DA function may contribute to negative symptom severity and self-reported anhedonia, independent of diagnostic status. PMID:27886638

The Douro estuarine plume: Detection, processes and dynamics =

NASA Astrophysics Data System (ADS)

Mendes, Renato Paulo dos Santos

O Douro e um dos maiores rios da Peninsula Iberica, constituindo a maior descarga de agua doce para o Oceano Atlântico na costa noroeste portuguesa. A sua pluma estuarina tem particular relevância na dinâmica costeira e na modulacao de fenomenos biogeoquimicos. Sao objetivos desta dissertacao contribuir para a compreensao dos processos fisicos associados a geracao e propagacao da pluma estuarina do Rio Douro no oceano, assim como para o conhecimento dos seus padroes de dispersao e da forma como estes alteram a hidrologia e a circulacao costeira, considerando os agentes forcadores tipicos deste fenomeno (caudal fluvial, vento e mare) e indices climaticos relevantes. Para concretizacao destes objetivos foram desenvolvidas e aplicadas metodologias inovadoras de processamento de dados de detecao remota, assim como novas implementacoes estuarinas e costeiras de modelos numericos. Atraves de imagens MODIS, otimizadas para o estudo de fenomenos costeiros, efetuou-se uma detecao rigorosa da pluma. Identificou-se uma relacao entre o sinal turbido nLw555 e o caudal, demonstrando-se este produto como um bom proxy para a observacao da pluma no oceano. As escalas temporais e espaciais da pluma foram caraterizadas atraves destas imagens, combinadas com dados de caudal fluvial, mare, vento e precipitacao, e tambem com indices climaticos relevantes. Para compreender a propagacao da pluma e caracterizar a sua dinâmica e impacto na circulacao costeira, foi desenvolvida uma aplicacao 3D de modelos estuarinos e costeiros com malhas aninhadas de resolucao variavel. Definiramse e analisaram-se diferentes cenarios de vento e descarga fluvial. A interacao da pluma do Rio Douro e do Minho foi ainda analisada atraves dos resultados de simulacoes baseadas num evento de inverno. Os compositos turbidos mostraram que a pluma e facilmente detetada quando o caudal e maior que 500 m3 s??1. A descarga fluvial e o vento sao os principais forcadores da sua propagacao, enquanto a mare e apenas importante na regiao proxima a embocadura do estuario. Observaram-se relacoes a uma escala interanual entre a turbidez da pluma e os indices climaticos East Atlantic e NAO, com uma correlacao maxima identificada com 1 e 3 meses de desfasamento, respetivamente. Com base nos resultados das simulacoes efetuadas, a pluma e classificada como de larga escala e de advecao superficial, apresentando caracteristicas de uma pluma prototipica. Em condicoes de caudal moderado a elevado, a descarga estuarina e suficiente para gerar uma corrente costeira para norte sem acao do vento. Em eventos de ventos leste, a propagacao da pluma e similar ao caso sem vento, com um aumento da velocidade da corrente. Uma corrente costeira para sul e unicamente identificada sob condicoes de forte vento de oeste. Ventos de norte tendem a estender a pluma para o largo, com uma inclinacao na direcao sudoeste, enquanto ventos de sul intensificam a corrente para norte, sendo a mistura das plumas do Douro e do Minho uma consequencia possivel. A analise desta interacao apontou a contribuicao do Douro como importante na estabilizacao da WIBP e nas trocas de agua entre o oceano e as Rias Baixas. A interacao da pluma do Douro com estuarios localizados a sul da sua foz e a confirmacao in situ da recirculacao observada nos resultados numericos afiguram-se como temas relevantes para investigacoes futuras. None

SAGES TAVAC safety and effectiveness analysis: da Vinci ® Surgical System (Intuitive Surgical, Sunnyvale, CA).

PubMed

Tsuda, Shawn; Oleynikov, Dmitry; Gould, Jon; Azagury, Dan; Sandler, Bryan; Hutter, Matthew; Ross, Sharona; Haas, Eric; Brody, Fred; Satava, Richard

2015-10-01

The da Vinci(®) Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) is a computer-assisted (robotic) surgical system designed to enable and enhance minimally invasive surgery. The Food and Drug Administration (FDA) has cleared computer-assisted surgical systems for use by trained physicians in an operating room environment for laparoscopic surgical procedures in general, cardiac, colorectal, gynecologic, head and neck, thoracic and urologic surgical procedures. There are substantial numbers of peer-reviewed papers regarding the da Vinci(®) Surgical System, and a thoughtful assessment of evidence framed by clinical opinion is warranted. The SAGES da Vinci(®) TAVAC sub-committee performed a literature review of the da Vinci(®) Surgical System regarding gastrointestinal surgery. Conclusions by the sub-committee were vetted by the SAGES TAVAC Committee and SAGES Executive Board. Following revisions, the document was evaluated by the TAVAC Committee and Executive Board again for final approval. Several conclusions were drawn based on expert opinion organized by safety, efficacy, and cost for robotic foregut, bariatric, hepatobiliary/pancreatic, colorectal surgery, and single-incision cholecystectomy. Gastrointestinal surgery with the da Vinci(®) Surgical System is safe and comparable, but not superior to standard laparoscopic approaches. Although clinically acceptable, its use may be costly for select gastrointestinal procedures. Current data are limited to the da Vinci(®) Surgical System; further analyses are needed.

Development of a patient decision aid prototype for adults with obstructive sleep apnea.

PubMed

Trenaman, Logan; Munro, Sarah; Almeida, Fernanda; Ayas, Najib; Hicklin, James; Bansback, Nick

2016-05-01

To describe the development and assess the usability of a patient decision aid (PtDA) prototype designed for newly diagnosed, treatment-naïve, obstructive sleep apnea (OSA) patients. A web-based PtDA was developed which focuses on two first-line treatment options: continuous positive airway pressure (CPAP) and mandibular advancement splints (MAS). Development was guided by the International Patient Decision Aid Standards (IPDAS). Usability was assessed in individuals at high risk for OSA based on the STOP-Bang questionnaire, the patient acceptance of decision aid, the System Usability Scale (SUS), and content analysis of open-ended user feedback. Eighty eligible participants completed the survey. The mean age was 54 years (SD = 8.9), 60 % of the sample was male, 78 % were university-educated, and 64 % were employed full-time. Participants took an average of 13.7 min (SD = 9.6) to complete the PtDA, with 39 participants choosing CPAP, 25 choosing MAS, and 16 choosing no treatment. The mean SUS score was 78.22 (SD = 15.13). The majority of individuals thought the PtDA was useful in making a decision (n = 77, 96 %) and would recommend it to others (n = 77, 96 %), while a third (n = 26, 33 %) thought it was slanted towards CPAP. The SUS indicated that the PtDA was acceptable and useful for participants. And useful for participants. User feedback has been used to improve the prototype, which will now undergo further testing in patients at the Vancouver Sleep Disorders Clinic.

A comparison of ED and direct admission care of cancer patients with febrile neutropenia.

PubMed

Owolabi, Diwura K; Rowland, Richard; King, Lauren; Miller, Rick; Hegde, Gajanan G; Shang, Jennifer; Lister, John; Venkat, Arvind

2015-07-01

We compared the quality of care in admitted febrile neutropenic cancer patients presenting through the emergency department (ED) vs those directly admitted (DA) from the clinic or infusion center. We hypothesized that the quality of care would be comparable between these 2 pathways. We conducted a retrospective, observational cohort study of all adult cancer patients hospitalized with subjective or objective fever (≥100.4°F) and documented neutropenia (absolute neutrophil count ≤1000/mm(3)) from January 1, 2011 to June 30, 2013, at 2 hospitals. Two investigators retrieved data including patient age, sex, race, tumor type, blood culture growth, temperature (actual or reported), pathway to admission (ED or DA), time to antibiotic administration, length of stay, and the Multinational Association for Supportive Care in Cancer (MASCC) risk score. The primary outcome measures were time to antibiotic administration, appropriateness of antibiotic(s) administered based on published guidelines, length of stay, and MASCC score-based risk assessment. We used the t test for the difference between 2 means with unequal population variances to compare these outcome measures between ED and DA patients. One hundred twenty-seven visits met inclusion criteria (42 [33%] ED visits, 85 [67%] DA visits). Mean time to antibiotic administration, mean length of stay, appropriateness of antibiotics, and MASCC score-based risk assessment were comparable between ED and DA visits (P>.05 for all comparisons). The quality of care for febrile neutropenia in patients presenting through the ED was comparable to those directly admitted to the hospital in this 2-center study. Copyright © 2015 Elsevier Inc. All rights reserved.

Discourse analysis and social constructionism.

PubMed

White, Robert

2004-10-01

Discourse analysis (DA) is underpinned by a social constructionist orientation to knowledge. Social constructionism rests on the philosophical assumptions that multiple versions of the world are legitimate; that texts are open to multiple readings; and that language is non-representational. As social constructionism is relativistic, the status of 'evidence' generated by DA is questionable from more traditional research perspectives. On a common-sense level, people obviously construct meaning in relation to their lives. Thus, DA can help us to examine constructions of meaning in relation to nursing care. Equally, the discourse analyst constructs one possible meaning in relation to a phenomenon that may compete with other versions. Multiplicity does not necessarily entail anarchy, and competing versions prevent authoritarianism and loss of freedom. However, judgements have to be made about competing versions, for example, by assessing the level of 'facticity', or referring to the ethics embedded in the cultural context. In this paper, Bob White discusses DA as a form of qualitative research that offers promise for nursing research. Subsequent papers will examine the methodology and methods of DA and its application to nursing research.

Discourse analysis and social constructionism.

PubMed

White, Robert

2004-01-01

Discourse analysis (DA) is underpinned by a social constructionist orientation to knowledge. Social constructionism rests on the philosophical assumptions that multiple versions of the world are legitimate; that texts are open to multiple readings; and that language is non-representational. As social constructionism is relativistic, the status of 'evidence' generated by DA is questionable from more traditional research perspectives. On a common-sense level, people obviously construct meaning in relation to their lives. Thus, DA can help us to examine constructions of meaning in relation to nursing care. Equally the discourse analyst constructs one possible meaning in relation to a phenomenon that may compete with other versions. Multiplicity does not necessarily entail anarchy and competing versions prevent authoritarianism and loss of freedom. However, judgements have to be made about competing versions, for example, by assessing the level of 'facticity', or referring to the ethics embedded in the cultural context. In this paper, Bob White discusses DA as a form of qualitative research that offers promise for nursing research. Subsequent papers will examine the methodology and methods of DA and its application to nursing research.

Automated Support for da Vinci Surgical System

DTIC Science & Technology

2011-05-01

MScore, which provides objective assessment measuring robotic surgery skills across all computed metrics (Figure 7). In addition to viewing single ...holding an object. Data Collection & Analysis (Task 5)  Preliminary Experiments  During the first phase of data collection, a single performance of...a single task (anastomosis) trial was recorded from six different users – three each for the da Vinci and the dV-Trainer platforms. On each platform

Failure of Cleaning Verification in Pharmaceutical Industry Due to Uncleanliness of Stainless Steel Surface.

PubMed

Haidar Ahmad, Imad A; Blasko, Andrei

2017-08-11

The aim of this work is to identify the parameters that affect the recovery of pharmaceutical residues from the surface of stainless steel coupons. A series of factors were assessed, including drug product spike levels, spiking procedure, drug-excipient ratios, analyst-to-analyst variability, intraday variability, and cleaning procedure of the coupons. The lack of a well-defined procedure that consistently cleaned the coupon surface was identified as the major contributor to low and variable recoveries. Assessment of cleaning the surface of the coupons with clean-in-place solutions (CIP) gave high recovery (>90%) and reproducible results (Srel≤4%) regardless of the conditions that were assessed previously. The approach was successfully applied for cleaning verification of small molecules (MW <1,000 Da) as well as large biomolecules (MW up to 50,000 Da).

Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency: Twelve-Month Results of the DEFINITIVE AR Study.

PubMed

Zeller, Thomas; Langhoff, Ralf; Rocha-Singh, Krishna J; Jaff, Michael R; Blessing, Erwin; Amann-Vesti, Beatrice; Krzanowski, Marek; Peeters, Patrick; Scheinert, Dierk; Torsello, Giovanni; Sixt, Sebastian; Tepe, Gunnar

2017-09-01

Studies assessing drug-coated balloons (DCB) for the treatment of femoropopliteal artery disease are encouraging. However, challenging lesions, such as severely calcified, remain difficult to treat with DCB alone. Vessel preparation with directional atherectomy (DA) potentially improves outcomes of DCB. DEFINITIVE AR study (Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency-A Pilot Study of Anti-Restenosis Treatment) was a multicenter randomized trial designed to estimate the effect of DA before DCB to facilitate the development of future end point-driven randomized studies. One hundred two patients with claudication or rest pain were randomly assigned 1:1 to DA+DCB (n=48) or DCB alone (n=54), and 19 additional patients with severely calcified lesions were treated with DA+DCB. Mean lesion length was 11.2±4.0 cm for DA+DCB and 9.7±4.1 cm for DCB ( P =0.05). Predilation rate was 16.7% for DA+DCB versus 74.1% for DCB; postdilation rate was 6.3% for DA+DCB versus 33.3% for DCB. Technical success was superior for DA+DCB (89.6% versus 64.2%; P =0.004). Overall bail-out stenting rate was 3.7%, and rate of flow-limiting dissections was 19% for DCB and 2% for DA+DCB ( P =0.01). One-year primary outcome of angiographic percent diameter stenosis was 33.6±17.7% for DA+DCB versus 36.4±17.6% for DCB ( P =0.48), and clinically driven target lesion revascularization was 7.3% for DA+DCB and 8.0% for DCB ( P =0.90). Duplex ultrasound patency was 84.6% for DA+DCB, 81.3% for DCB ( P =0.78), and 68.8% for calcified lesions. Freedom from major adverse events at 1 year was 89.3% for DA+DCB and 90.0% for DCB ( P =0.86). DA+DCB treatment was effective and safe, but the study was not powered to show significant differences between the 2 methods of revascularization in 1-year follow-up. An adequately powered randomized trial is warranted. http://www.clinicaltrials.gov. Unique Identifier: NCT01366482. Copyright © 2017 The Author(s).

Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency

PubMed Central

Langhoff, Ralf; Rocha-Singh, Krishna J.; Jaff, Michael R.; Blessing, Erwin; Amann-Vesti, Beatrice; Krzanowski, Marek; Peeters, Patrick; Scheinert, Dierk; Torsello, Giovanni; Sixt, Sebastian; Tepe, Gunnar

2017-01-01

Background— Studies assessing drug-coated balloons (DCB) for the treatment of femoropopliteal artery disease are encouraging. However, challenging lesions, such as severely calcified, remain difficult to treat with DCB alone. Vessel preparation with directional atherectomy (DA) potentially improves outcomes of DCB. Methods and Results— DEFINITIVE AR study (Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency—A Pilot Study of Anti-Restenosis Treatment) was a multicenter randomized trial designed to estimate the effect of DA before DCB to facilitate the development of future end point-driven randomized studies. One hundred two patients with claudication or rest pain were randomly assigned 1:1 to DA+DCB (n=48) or DCB alone (n=54), and 19 additional patients with severely calcified lesions were treated with DA+DCB. Mean lesion length was 11.2±4.0 cm for DA+DCB and 9.7±4.1 cm for DCB (P=0.05). Predilation rate was 16.7% for DA+DCB versus 74.1% for DCB; postdilation rate was 6.3% for DA+DCB versus 33.3% for DCB. Technical success was superior for DA+DCB (89.6% versus 64.2%; P=0.004). Overall bail-out stenting rate was 3.7%, and rate of flow-limiting dissections was 19% for DCB and 2% for DA+DCB (P=0.01). One-year primary outcome of angiographic percent diameter stenosis was 33.6±17.7% for DA+DCB versus 36.4±17.6% for DCB (P=0.48), and clinically driven target lesion revascularization was 7.3% for DA+DCB and 8.0% for DCB (P=0.90). Duplex ultrasound patency was 84.6% for DA+DCB, 81.3% for DCB (P=0.78), and 68.8% for calcified lesions. Freedom from major adverse events at 1 year was 89.3% for DA+DCB and 90.0% for DCB (P=0.86). Conclusions— DA+DCB treatment was effective and safe, but the study was not powered to show significant differences between the 2 methods of revascularization in 1-year follow-up. An adequately powered randomized trial is warranted. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique Identifier: NCT01366482. PMID:28916599

Validation Test Report for the Arctic Cap Nowcast/Forecast System as a Fractures/Leads and Polynyas Product

DTIC Science & Technology

2015-05-26

and Lipscomb, 2004) to describe the ice dynamics and compute strain rates. It incorporates the standard ridging scheme of Thorndike et al. (1975...Forecast System (ACNFS). NRL/MR/7320—10- 9287, Naval Research Laboratory, Stennis Space Center, MS, 55 pp. Thorndike , A.S., D.A. Rothrock, G.A. Maykut, and

International Workshop on Gravel-Bed Rivers. Dynamics of Gravel-Bed Rivers (3rd), held in Firenze - Poggio a Caiano Italy on September 24-28, 1990

DTIC Science & Technology

1990-07-31

Geol., 22, 97-120. Wymer, J.J. (1968). Lower Palaeolithic Archaeology in Britain, John Baker, London. Wymer, J.J. (1976), The interpretation of... Palaeolithic cultural and faunal material found in Pleistocene sediments, in, Geo-archaeology, Davidson, D.A. and Shackley, M.L. (eds.), Duckworth, London, pp

Dynamics of Flow in the Region of the Tsugaru Strait.

DTIC Science & Technology

1981-03-01

possessed sufficient initial vrticity at a strait outlet. Beardslev and Hart (1978) pro- duced anal yr i c sol It i ons -t the out t low ci rcul at ion for a...38. ’da , M . , 1934, Hlydrographical studies based on simll taneous oceano - ,graphi cal surveys made in the Japan Sea and i ts adjacent waters during

Data-Driven Model Uncertainty Estimation in Hydrologic Data Assimilation

NASA Astrophysics Data System (ADS)

Pathiraja, S.; Moradkhani, H.; Marshall, L.; Sharma, A.; Geenens, G.

2018-02-01

The increasing availability of earth observations necessitates mathematical methods to optimally combine such data with hydrologic models. Several algorithms exist for such purposes, under the umbrella of data assimilation (DA). However, DA methods are often applied in a suboptimal fashion for complex real-world problems, due largely to several practical implementation issues. One such issue is error characterization, which is known to be critical for a successful assimilation. Mischaracterized errors lead to suboptimal forecasts, and in the worst case, to degraded estimates even compared to the no assimilation case. Model uncertainty characterization has received little attention relative to other aspects of DA science. Traditional methods rely on subjective, ad hoc tuning factors or parametric distribution assumptions that may not always be applicable. We propose a novel data-driven approach (named SDMU) to model uncertainty characterization for DA studies where (1) the system states are partially observed and (2) minimal prior knowledge of the model error processes is available, except that the errors display state dependence. It includes an approach for estimating the uncertainty in hidden model states, with the end goal of improving predictions of observed variables. The SDMU is therefore suited to DA studies where the observed variables are of primary interest. Its efficacy is demonstrated through a synthetic case study with low-dimensional chaotic dynamics and a real hydrologic experiment for one-day-ahead streamflow forecasting. In both experiments, the proposed method leads to substantial improvements in the hidden states and observed system outputs over a standard method involving perturbation with Gaussian noise.

Field Tolerances for the Triplet Quadrupoles of the LHC High Luminosity Lattice

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

Nosochkov, Yuri; Cai, Y.; Jiao, Y.

2012-06-25

It has been proposed to implement the so-called Achromatic Telescopic Squeezing (ATS) scheme in the LHC high luminosity (HL) lattice to reduce beta functions at the Interaction Points (IP) up to a factor of 8. As a result, the nominal 4.5 km peak beta functions reached in the Inner Triplets (IT) at collision will be increased by the same factor. This, therefore, justifies the installation of new, larger aperture, superconducting IT quadrupoles. The higher beta functions will enhance the effects of the triplet quadrupole field errors leading to smaller beam dynamic aperture (DA). To maintain the acceptable DA, the effectsmore » of the triplet field errors must be re-evaluated, thus specifying new tolerances. Such a study has been performed for the so-called '4444' collision option of the HL-LHC layout version SLHCV3.01, where the IP beta functions are reduced by a factor of 4 in both planes with respect to a pre-squeezed value of 60 cm at two collision points. The dynamic aperture calculations were performed using SixTrack. The impact on the triplet field quality is presented.« less

76 FR 2388 - National Toxicology Program (NTP); NTP Interagency Center for the Evaluation of Alternative...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-13

... Nonradioactive Versions of the Murine Local Lymph Node Assay (LLNA) for Assessing Allergic Contact Dermatitis... Assay: BrdU-ELISA, A Nonradioactive Alternative Test Method to Assess the Allergic Contact Dermatitis... Lymph Node Assay: DA, A Nonradioactive Alternative Test Method to Assess the Allergic Contact Dermatitis...

Effects of amphetamine on striatal dopamine release, open-field activity, and play in Fischer 344 and Sprague-Dawley rats.

PubMed

Siviy, Stephen M; McDowell, Lana S; Eck, Samantha R; Turano, Alexandra; Akopian, Garnik; Walsh, John P

2015-12-01

Previous work from our laboratories has shown that juvenile Fischer 344 (F344) rats are less playful than other strains and also appear to be compromised in dopamine (DA) functioning. To determine whether the dysfunctional play in this strain is associated with deficits in the handling and delivery of vesicular DA, the following experiments assessed the extent to which F344 rats are differentially sensitive to the effects of amphetamine. When exposed to amphetamine, striatal slices obtained from F344 rats showed a small increase in unstimulated DA release when compared with slices from Sprague-Dawley rats; they also showed a more rapid high K+-mediated release of DA. These data provide tentative support for the hypothesis that F344 rats have a higher concentration of cytoplasmic DA than Sprague-Dawley rats. When rats were tested for activity in an open field, F344 rats presented a pattern of results that was consistent with either an enhanced response to amphetamine (3 mg/kg) or a more rapid release of DA (10 mg/kg). Although there was some indication that amphetamine had a dose-dependent differential effect on play in the two strains, play in F344 rats was not enhanced to any degree by amphetamine. Although these results are not consistent with our working hypothesis that F344 rats are less playful because of a deficit in vesicular release of DA, they still suggest that this strain may be a useful model for better understanding the role of DA in social behavior during the juvenile period.

A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity

USGS Publications Warehouse

Lefebvre, Kathi A.; Frame, Elizabeth R.; Gulland, Frances; Hansen, John D.; Kendrick, Preston S.; Beyer, Richard P.; Bammler, Theo K.; Farin, Frederico M.; Hiolski, Emma M.; Smith, Donald R.; Marcinek, David J.

2012-01-01

The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

A novel antibody-based biomarker for chronic algal toxin exposure and sub-acute neurotoxicity.

PubMed

Lefebvre, Kathi A; Frame, Elizabeth R; Gulland, Frances; Hansen, John D; Kendrick, Preston S; Beyer, Richard P; Bammler, Theo K; Farin, Frederico M; Hiolski, Emma M; Smith, Donald R; Marcinek, David J

2012-01-01

The neurotoxic amino acid, domoic acid (DA), is naturally produced by marine phytoplankton and presents a significant threat to the health of marine mammals, seabirds and humans via transfer of the toxin through the foodweb. In humans, acute exposure causes a neurotoxic illness known as amnesic shellfish poisoning characterized by seizures, memory loss, coma and death. Regular monitoring for high DA levels in edible shellfish tissues has been effective in protecting human consumers from acute DA exposure. However, chronic low-level DA exposure remains a concern, particularly in coastal and tribal communities that subsistence harvest shellfish known to contain low levels of the toxin. Domoic acid exposure via consumption of planktivorous fish also has a profound health impact on California sea lions (Zalophus californianus) affecting hundreds of animals yearly. Due to increasing algal toxin exposure threats globally, there is a critical need for reliable diagnostic tests for assessing chronic DA exposure in humans and wildlife. Here we report the discovery of a novel DA-specific antibody response that is a signature of chronic low-level exposure identified initially in a zebrafish exposure model and confirmed in naturally exposed wild sea lions. Additionally, we found that chronic exposure in zebrafish caused increased neurologic sensitivity to DA, revealing that repetitive exposure to DA well below the threshold for acute behavioral toxicity has underlying neurotoxic consequences. The discovery that chronic exposure to low levels of a small, water-soluble single amino acid triggers a detectable antibody response is surprising and has profound implications for the development of diagnostic tests for exposure to other pervasive environmental toxins.

A latent class analysis of drug abuse in a national Swedish sample.

PubMed

Kendler, K S; Ohlsson, H; Sundquist, K; Sundquist, J

2013-10-01

Drug abuse (DA) is a clinically heterogeneous syndrome. Using medical, legal, death and pharmacy records covering the entire population of Sweden, could we uncover meaningful subtypes of DA? We performed a latent class analysis (LCA) on all individuals in Sweden born 1950–1993 who were registered with DA or its consequences (n=192,501) and then validated these classes using demographics, patterns of co-morbidity with alcohol use disorder (AUD), non-DA crime and psychiatric illness, and the pattern of aggregation and co-aggregation in sibling pairs. The best-fit LCA had six classes : (1) low-frequency pure criminal, (2) high-frequency medical criminal, (3) low-frequency pure medical, (4) high-frequency medical, (5) prescription and (6) death. Each class had a distinct pattern of demographic features and co-morbidity and aggregated within sibling pairs with at least moderate specificity. For example, class 2 was characterized by early age at registration, low educational attainment, high male preponderance, high rates of AUDs, strong resemblance within sibling pairs [odds ratio (OR) 12.6] and crime and the highest risk for DA in siblings (20.0%). By contrast, class 5 had a female preponderance, late age at registration, low rates of crime and AUDs, high rates of psychiatric illness, high familiality within sibling pairs (OR 14.7) but the lowest observed risk for DA in siblings (8.9%). DA as assessed by public records is a heterogeneous syndrome. Familial factors contribute substantially to this heterogeneity. Advances in our understanding of etiological processes leading to DA will be aided by a consideration of this heterogeneity.

Proteolytic processing of connective tissue growth factor in normal ocular tissues and during corneal wound healing.

PubMed

Robinson, Paulette M; Smith, Tyler S; Patel, Dilan; Dave, Meera; Lewin, Alfred S; Pi, Liya; Scott, Edward W; Tuli, Sonal S; Schultz, Gregory S

2012-12-13

Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is up-regulated by TGF-β and mediates most key fibrotic actions of TGF-β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. This study addresses the role of proteolytic processing of CTGF in human corneal fibroblasts (HCF) stimulated with TGF-β, normal ocular tissues and wounded corneas. Proteolytic processing of CTGF in HCF cultures, normal animal eyes, and excimer laser wounded rat corneas were examined by Western blot. The identity of a 21-kDa band was determined by tandem mass spectrometry, and possible alternative splice variants of CTGF were assessed by 5' Rapid Amplification of cDNA Ends (RACE). HCF stimulated by TGF-β contained full length 38-kDa CTGF and fragments of 25, 21, 18, and 13 kDa, while conditioned medium contained full length 38- and a 21-kDa fragment of CTGF that contained the middle "hinge" region of CTGF. Fragmentation of recombinant CTGF incubated in HCF extracts was blocked by the aspartate protease inhibitor, pepstatin. Normal mouse, rat, and rabbit whole eyes and rabbit ocular tissues contained abundant amounts of C-terminal 25- and 21-kDa fragments and trace amounts of 38-kDa CTGF, although no alternative transcripts were detected. All forms of CTGF (38, 25, and 21 kDa) were detected during healing of excimer ablated rat corneas, peaking on day 11. Proteolytic processing of 38-kDa CTGF occurs during corneal wound healing, which may have important implications in regulation of corneal scar formation.

Effects of CDP-choline on striatal dopamine level and behavior in rats.

PubMed

Shibuya, M; Kageyama, N; Taniguchi, T; Hidaka, H; Fujiwara, M

1981-02-01

To further assess the effects of CDP (cytidine diphosphate)-choline on Parkinsonian symptoms, striatal dopamine (DA) was measured fluorometrically in rats after injection of CDP-choline. CDP-choline (300 mg/kg, i.p.) increased the DA content in the striatum (p less than 0.05) one hour after injection. The behavioral effect of CDP-choline was then tested in rats in which the unilateral nigro-striatal DA neurons had degenerated following an intranigral injection of 6-hydroxydopamine (6-OHDA). CDP-choline alone did not produce behavioral changes in these rats. However, pretreatment with a single dose of CDP-choline (900 mg/kg, i.p.) suppressed both the apomorphine-induced contralateral and the d-amphetamine-induced ipsilateral circling. The same dose of CDP-choline suppressed the number of treadmill revolutions in mice. On the other hand, a 7-day consecutive treatment with 300 mg/kg of CDP-choline enhanced the apomorphine-induced contralateral circling (by 42%, p less than 0.05). The same treatment with CDP-choline raised the striatal DA content by 29% (p less than 0.05) on the intact side, but not on the 6-OHDA injected side. These results indicate that CDP-choline has either a direct nor an indirect DA agonistic effect. The increase in DA content, decrease in locomotion and enhancement of the effect of apomorphine can be explained on the hypothesis that CDP-choline may act as an antagonist on the DA neurons and receptors. The validity of this apparently paradoxical use of CDP-choline with antagonistic effect on DA neurons in the treatment of Parkinson's disease is discussed.

Striatal dopaminergic modulation of reinforcement learning predicts reward-oriented behavior in daily life.

PubMed

Kasanova, Zuzana; Ceccarini, Jenny; Frank, Michael J; Amelsvoort, Thérèse van; Booij, Jan; Heinzel, Alexander; Mottaghy, Felix; Myin-Germeys, Inez

2017-07-01

Much human behavior is driven by rewards. Preclinical neurophysiological and clinical positron emission tomography (PET) studies have implicated striatal phasic dopamine (DA) release as a primary modulator of reward processing. However, the relationship between experimental reward-induced striatal DA release and responsiveness to naturalistic rewards, and therefore functional relevance of these findings, has been elusive. We therefore combined, for the first time, a DA D 2/3 receptor [ 18 F]fallypride PET during a probabilistic reinforcement learning (RL) task with a six day ecological momentary assessments (EMA) of reward-related behavior in the everyday life of 16 healthy volunteers. We detected significant reward-induced DA release in the bilateral putamen, caudate nucleus and ventral striatum, the extent of which was associated with better behavioral performance on the RL task across all regions. Furthermore, individual variability in the extent of reward-induced DA release in the right caudate nucleus and ventral striatum modulated the tendency to be actively engaged in a behavior if the active engagement was previously deemed enjoyable. This study suggests a link between striatal reward-related DA release and ecologically relevant reward-oriented behavior, suggesting an avenue for the inquiry into the DAergic basis of optimal and impaired motivational drive. Copyright © 2017 Elsevier B.V. All rights reserved.

A Low-Noise, Wideband Preamplifier for a Fourier-Transform Ion Cyclotron Resonance Mass Spectrometer

PubMed Central

Mathur, Raman; Knepper, Ronald W.; O'Connor, Peter B.

2009-01-01

FTMS performance parameters such as limits of detection, dynamic range, sensitivity, and even mass accuracy and resolution can be greatly improved by enhancing its detection circuit. An extended investigation of significant design considerations for optimal signal-to-noise ratio in an FTMS detection circuit are presented. A low noise amplifier for an FTMS is developed based on the discussed design rules. The amplifier has a gain of ≈ 3500 and a bandwidth of 10 kHz - 1 MHz corresponding to m/z range of 100 Da to 10 kDa (at 7 Tesla). The performance of the amplifier was tested on a MALDI-FTMS, and has demonstrated a 25-fold reduction in noise in a mass spectrum of C60 compared to that of a commercial amplifier. PMID:18029195

Bacteriocins from Gram-Negative Bacteria: A Classification?

NASA Astrophysics Data System (ADS)

Rebuffat, Sylvie

Bacteria produce an arsenal of toxic peptides and proteins, which are termed bacteriocins and play a role in mediating the dynamics of microbial populations and communities. Bacteriocins from Gram-negative bacteria arise mainly from Enterobacteriaceae. They assemble into two main families: high molecular mass modular proteins (30-80 kDa) termed colicins and low molecular mass peptides (between 1 and 10 kDa) termed microcins. The production of colicins is mediated by the SOS response regulon, which plays a role in the response of many bacteria to DNA damages. Microcins are highly stable hydrophobic peptides that are produced under stress conditions, particularly nutrient depletion. Colicins and microcins are found essentially in Escherichia coli, but several other Gram-negative species also produce bacteriocin-like substances. This chapter presents the basis of a classification of colicins and microcins.

Optimizing ATLAS code with different profilers

NASA Astrophysics Data System (ADS)

Kama, S.; Seuster, R.; Stewart, G. A.; Vitillo, R. A.

2014-06-01

After the current maintenance period, the LHC will provide higher energy collisions with increased luminosity. In order to keep up with these higher rates, ATLAS software needs to speed up substantially. However, ATLAS code is composed of approximately 6M lines, written by many different programmers with different backgrounds, which makes code optimisation a challenge. To help with this effort different profiling tools and techniques are being used. These include well known tools, such as the Valgrind suite and Intel Amplifier; less common tools like Pin, PAPI, and GOoDA; as well as techniques such as library interposing. In this paper we will mainly focus on Pin tools and GOoDA. Pin is a dynamic binary instrumentation tool which can obtain statistics such as call counts, instruction counts and interrogate functions' arguments. It has been used to obtain CLHEP Matrix profiles, operations and vector sizes for linear algebra calculations which has provided the insight necessary to achieve significant performance improvements. Complimenting this, GOoDA, an in-house performance tool built in collaboration with Google, which is based on hardware performance monitoring unit events, is used to identify hot-spots in the code for different types of hardware limitations, such as CPU resources, caches, or memory bandwidth. GOoDA has been used in improvement of the performance of new magnetic field code and identification of potential vectorization targets in several places, such as Runge-Kutta propagation code.

Motion generation of robotic surgical tasks: learning from expert demonstrations.

PubMed

Reiley, Carol E; Plaku, Erion; Hager, Gregory D

2010-01-01

Robotic surgical assistants offer the possibility of automating portions of a task that are time consuming and tedious in order to reduce the cognitive workload of a surgeon. This paper proposes using programming by demonstration to build generative models and generate smooth trajectories that capture the underlying structure of the motion data recorded from expert demonstrations. Specifically, motion data from Intuitive Surgical's da Vinci Surgical System of a panel of expert surgeons performing three surgical tasks are recorded. The trials are decomposed into subtasks or surgemes, which are then temporally aligned through dynamic time warping. Next, a Gaussian Mixture Model (GMM) encodes the experts' underlying motion structure. Gaussian Mixture Regression (GMR) is then used to extract a smooth reference trajectory to reproduce a trajectory of the task. The approach is evaluated through an automated skill assessment measurement. Results suggest that this paper presents a means to (i) extract important features of the task, (ii) create a metric to evaluate robot imitative performance (iii) generate smoother trajectories for reproduction of three common medical tasks.

Assessing site formation and assemblage integrity through stone tool refitting at Gruta da Oliveira (Almonda karst system, Torres Novas, Portugal): A Middle Paleolithic case study

PubMed Central

Zilhão, João

2018-01-01

We use stone tool refitting to assess palimpsest formation and stratigraphic integrity in the basal units of the Gruta da Oliveira archeo-stratigraphic sequence, layers 15–27, which TL and U-series dating places in late Marine Isotope Stage (MIS) 5 or early MIS 4. As in most karst contexts, the formation of this succession involved multiple and complex phenomena, including subsidence, bioturbation, carnivore activity and runoff as agents of potential post-depositional disturbance. During phases of stabilization, such as represented by layers 15, 21 and 22, the excavated area was inhabited and refits corroborate that post-depositional displacement is negligible. Layers 23–25 and 16–19 correspond to subdivisions that slice thick geological units primarily formed of material derived from the cave’s entrance via slope dynamics. Refit links are consistent with rapid fill-up of the interstitial spaces found in the Karren-like bedrock (for layers 23–25), or left between large boulders after major roof-collapse events (for layers 16–19). Layers 26 (the “Mousterian Cone”) and 27 are a “bottom-of-hourglass” deposit underlying the main sedimentary body; the refits show that this deposit consists of material derived from layers 15–25 that gravitated through fissures open in the sedimentary column above. Layer 20, at the interface between two major stratigraphic ensembles, requires additional analysis. Throughout, we found significant vertical dispersion along the contact between sedimentary fill and cave wall. Given these findings, a preliminary analysis of technological change across the studied sequence organized the lithic assemblages into five ensembles: layer 15; layers 16–19; layer 20; layers 21–22; layers 23–25. The lower ensembles show higher percentages of flint and of the Levallois method. Uniquely at the site, the two upper ensembles feature bifaces and cleavers. PMID:29451892

Anti-MRSA malleable liposomes carrying chloramphenicol for ameliorating hair follicle targeting.

PubMed

Hsu, Ching-Yun; Yang, Shih-Chun; Sung, Calvin T; Weng, Yi-Han; Fang, Jia-You

2017-01-01

Pathogens usually invade hair follicles when skin infection occurs. The accumulated bacteria in follicles are difficult to eradicate. The present study aimed to assess the cutaneous and follicular delivery of chloramphenicol (Cm)-loaded liposomes and the antibacterial activity of these liposomes against methicillin-resistant Staphylococcus aureus (MRSA). Skin permeation was conducted by in vitro Franz diffusion cell. The anti-MRSA potential was checked using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), a well diffusion test, and intracellular MRSA killing. The classic, dimyristoylphosphatidylcholine (DMPC), and deoxycholic acid (DA) liposomes had a vesicle size of 98, 132, and 239 nm, respectively. The incorporation of DMPC or DA into the liposomes increased the bilayer fluidity. The malleable vesicles containing DMPC and DA showed increased follicular Cm uptake over the control solution by 1.5- and 2-fold, respectively. The MIC and MBC of DA liposomes loaded with Cm were 62.5 and 62.5-125 μg/mL, comparable to free Cm. An inhibition zone about 2-fold higher was achieved by DA liposomes as compared to the free control at a Cm dose of 0.5 mg/mL. DA liposomes also augmented antibacterial activity on keratinocyte-infected MRSA. The deformable liposomes had good biocompatibility against keratinocytes and neutrophils (viability >80%). In vivo administration demonstrated that DA liposomes caused negligible toxicity on the skin, based on physiological examination and histology. These data suggest the potential application of malleable liposomes for follicular targeting and the treatment of MRSA-infected dermatologic conditions.

Poly(ethyleneimines) in dermal applications: biocompatibility and antimicrobial effects.

PubMed

Wiegand, Cornelia; Bauer, Marius; Hipler, Uta-Christina; Fischer, Dagmar

2013-11-01

Cationic polyamines, such as poly(ethyleneimines) (PEIs), may recommend themselves for antimicrobial applications as they can interact with microbial membranes resulting in their disruption. The purpose of the study was the assessment of biocompatibility and antibacterial activity of PEIs with different architectures (branched (b) and linear (l)) and molar masses (0.8-750 kDa). lPEI and bPEI exhibited a strong antibacterial activity against Staphylococcus aureus and Escherichia coli with a more pronounced effect on the Gram-positive bacteria. lPEIs further demonstrated a higher antibacterial efficacy compared to bPEIs but no significant differences between 5 and 25 kDa were observed. In accordance, antibacterial activity of bPEI did not specifically depend on molar mass. Only slightly lower minimal inhibitory concentrations (MIC) were observed at 5 kDa (S. aureus) and 25 kDa (E. coli) in the tests. As PEIs are compelling candidates for use in antimicrobial treatment, two basic aspects have to be investigated: treatment effectiveness and safety. PEIs clearly induced molecular weight dependent cytotoxic effects in vitro. PEIs with low molecular weight (0.8 and 5 kDa) exhibited higher biocompatibility. Nonetheless, the results confirmed a low genotoxic potential of lPEI and bPEIs. In conclusion, 2.5 kDa-lPEI and 0.8 kDa-bPEI can be recommended for use as antimicrobial polymers in dermal applications due to their high biocompatibility with concomitant antibacterial efficacy. Copyright © 2013 Elsevier B.V. All rights reserved.

MK-801-induced behavioural sensitisation alters dopamine release and turnover in rat prefrontal cortex.

PubMed

Cui, Xiaoying; Lefevre, Emilia; Turner, Karly M; Coelho, Carlos M; Alexander, Suzy; Burne, Thomas H J; Eyles, Darryl W

2015-02-01

Repeated exposure to psychostimulants that either increase dopamine (DA) release or target N-methyl-D-aspartate (NMDA) receptors can induce behavioural sensitisation, a phenomenon that may be important for the processes of addiction and even psychosis. A critical component of behavioural sensitisation is an increase in DA release within mesocorticolimbic circuits. In particular, sensitisation to amphetamine leads to increased DA release within well-known sub-cortical brain regions and also regulatory regions such as prefrontal cortex (PFC). However, it is unknown how DA release within the PFC of animals is altered by sensitisation to NMDA receptor antagonists. The aims of the present study were twofold, firstly to examine whether a single dose of dizocilpine maleate (MK-801) could induce long-term behavioural sensitisation and secondly to examine DA release in the PFC of sensitised rats. Behavioural sensitisation was assessed by measuring locomotion after drug exposure. DA release in the PFC was measured using freely moving microdialysis. We show that a single dose of MK-801 can induce sensitisation to subsequent MK-801 exposure in a high percentage of rats (66 %). Furthermore, rats sensitised to MK-801 have altered DA release and turnover in the PFC compared with non-sensitised rats. Schizophrenia patients have been postulated to have 'endogenous sensitisation' to psychostimulants. MK-801-induced sensitised rats, in particular when compared with non-sensitised rats, provide a useful model for studying PFC dysfunction in schizophrenia.

Effects of hot-iron disbudding, using regional anaesthesia with and without carprofen, on cortisol and behaviour of calves.

PubMed

Stilwell, G; Lima, M S; Carvalho, R C; Broom, D M

2012-04-01

The objective of this study was to assess cortisol and behaviour changes in calves hot-iron disbudded after different analgesic protocols. We assessed the response of 27 calves at 1, 3, 6 and 24 h after disbudding with regional anaesthesia (DA), regional anaesthesia plus carprofen (DAC), disbudded only (D) or sham-disbudded (ND). At 1h cortisol was higher in D compared with all other groups. At 3h DA showed higher cortisol than ND but did not differ from baseline. At 15 min and 1h pain-related behaviours were more frequent in the D group than in all other groups. Group D (3 h) and DA (3 and 6 h) showed more ear flicks and head rubs compared with DAC and ND. We concluded that head rubbing, head shaking and ear flicking are useful behaviours for evaluating pain after hot-iron disbudding. Disbudding causes severe pain in calves and only the association of regional anaesthesia with carprofen assures good welfare for 24 h. Copyright © 2011 Elsevier Ltd. All rights reserved.

Visual degradation in Leonardo da Vinci's iconic self-portrait: A nanoscale study

NASA Astrophysics Data System (ADS)

Conte, A. Mosca; Pulci, O.; Misiti, M. C.; Lojewska, J.; Teodonio, L.; Violante, C.; Missori, M.

2014-06-01

The discoloration of ancient paper, due to the development of oxidized groups acting as chromophores in its chief component, cellulose, is responsible for severe visual degradation in ancient artifacts. By adopting a non-destructive approach based on the combination of optical reflectance measurements and time-dependent density functional theory ab-initio calculations, we describe and quantify the chromophores affecting Leonardo da Vinci's iconic self-portrait. Their relative concentrations are very similar to those measured in modern and ancient samples aged in humid environments. This analysis quantifies the present level of optical degradation of the Leonardo da Vinci's self-portrait which, compared with future measurements, will assess its degradation rate. This is a fundamental information in order to plan appropriate conservation strategies.

Proximal soil sensing and sensor fusion for soil health assessment

USDA-ARS?s Scientific Manuscript database

Assessment of soil health involves determining how well a soil is performing its biological, chemical, and physical functions relative to its inherent potential. Due to high costs, labor requirements, and soil disturbance, traditional laboratory analyses cannot provide high resolution soil health da...

Dopaminergic modulation of effort-related choice behavior as assessed by a progressive ratio chow feeding choice task: pharmacological studies and the role of individual differences.

PubMed

Randall, Patrick A; Pardo, Marta; Nunes, Eric J; López Cruz, Laura; Vemuri, V Kiran; Makriyannis, Alex; Baqi, Younis; Müller, Christa E; Correa, Mercè; Salamone, John D

2012-01-01

Mesolimbic dopamine (DA) is involved in behavioral activation and effort-related processes. Rats with impaired DA transmission reallocate their instrumental behavior away from food-reinforced tasks with high response requirements, and instead select less effortful food-seeking behaviors. In the present study, the effects of several drug treatments were assessed using a progressive ratio (PROG)/chow feeding concurrent choice task. With this task, rats can lever press on a PROG schedule reinforced by a preferred high-carbohydrate food pellet, or alternatively approach and consume the less-preferred but concurrently available laboratory chow. Rats pass through each ratio level 15 times, after which the ratio requirement is incremented by one additional response. The DA D(2) antagonist haloperidol (0.025-0.1 mg/kg) reduced number of lever presses and highest ratio achieved but did not reduce chow intake. In contrast, the adenosine A(2A) antagonist MSX-3 increased lever presses and highest ratio achieved, but decreased chow consumption. The cannabinoid CB1 inverse agonist and putative appetite suppressant AM251 decreased lever presses, highest ratio achieved, and chow intake; this effect was similar to that produced by pre-feeding. Furthermore, DA-related signal transduction activity (pDARPP-32(Thr34) expression) was greater in nucleus accumbens core of high responders (rats with high lever pressing output) compared to low responders. Thus, the effects of DA antagonism differed greatly from those produced by pre-feeding or reduced CB1 transmission, and it appears unlikely that haloperidol reduces PROG responding because of a general reduction in primary food motivation or the unconditioned reinforcing properties of food. Furthermore, accumbens core signal transduction activity is related to individual differences in work output.

Modulation of risk/reward decision making by dopaminergic transmission within the basolateral amygdala.

PubMed

Larkin, Joshua D; Jenni, Nicole L; Floresco, Stan B

2016-01-01

Dopamine (DA) transmission within cortico-limbic-striatal circuitry is integral in modulating decisions involving reward uncertainty. The basolateral amygdala (BLA) also plays a role in these processes, yet how DA transmission within this nucleus regulates cost/benefit decision making is unknown. We investigated the contribution of DA transmission within the BLA to risk/reward decision making assessed with a probabilistic discounting task. Rats were well-trained to choose between a small/certain reward and a large/risky reward, with the probability of obtaining the larger reward decreasing (100-12.5 %) or increasing (12.5-100 %) over a session. We examined the effects of antagonizing BLA D1 (SCH 23390, 0.1-1 μg) or D2 (eticlopride, 0.1-1 μg) receptors, as well as intra-BLA infusions of agonists for D1 (SKF 81297, 0.1-1 μg) and D2 (quinpirole, 1-10 μg) receptors. We also assessed how DA receptor stimulation may induce differential effects related to baseline levels of risky choice. BLA D1 receptor antagonism reduced risky choice by decreasing reward sensitivity, whereas D2 antagonism did not affect overall choice patterns. Stimulation of BLA D1 receptors optimized decision making in a baseline-dependent manner: in risk-averse rats, infusions of a lower dose of SKF81297 increased risky choice when reward probabilities were high (50 %), whereas in risk-prone rats, this drug reduced risky choice when probabilities were low (12.5 %). Quinpirole reduced risky choice in risk-prone rats, enhancing lose-shift behavior. These data highlight previously uncharacterized roles for BLA DA D1 and D2 receptors in biasing choice during risk/reward decision making through mediation of reward/negative feedback sensitivity.

Making hard choices easier: a prospective, multicentre study to assess the efficacy of a fertility-related decision aid in young women with early-stage breast cancer

PubMed Central

Peate, M; Meiser, B; Cheah, B C; Saunders, C; Butow, P; Thewes, B; Hart, R; Phillips, K-A; Hickey, M; Friedlander, M

2012-01-01

Background: Fertility is a priority for many young women with breast cancer. Women need to be informed about interventions to retain fertility before chemotherapy so as to make good quality decisions. This study aimed to prospectively evaluate the efficacy of a fertility-related decision aid (DA). Methods: A total of 120 newly diagnosed early-stage breast cancer patients from 19 Australian oncology clinics, aged 18–40 years and desired future fertility, were assessed on decisional conflict, knowledge, decision regret, and satisfaction about fertility-related treatment decisions. These were measured at baseline, 1 and 12 months, and were examined using linear mixed effects models. Results: Compared with usual care, women who received the DA had reduced decisional conflict (β=−1.51; 95%CI: −2.54 to 0.48; P=0.004) and improved knowledge (β=0.09; 95%CI: 0.01–0.16; P=0.02), after adjusting for education, desire for children and baseline uncertainty. The DA was associated with reduced decisional regret at 1 year (β=−3.73; 95%CI: −7.12 to −0.35; P=0.031), after adjusting for education. Women who received the DA were more satisfied with the information received on the impact of cancer treatment on fertility (P<0.001), fertility options (P=0.005), and rated it more helpful (P=0.002), than those who received standard care. Conclusion: These findings support widespread use of this DA shortly after diagnosis (before chemotherapy) among younger breast cancer patients who have not completed their families. PMID:22415294

Conformational changes in human Hsp70 induced by high hydrostatic pressure produce oligomers with ATPase activity but without chaperone activity.

PubMed

Araujo, Thaís L S; Borges, Julio Cesar; Ramos, Carlos H; Meyer-Fernandes, José Roberto; Oliveira Júnior, Reinaldo S; Pascutti, Pedro G; Foguel, Debora; Palhano, Fernando L

2014-05-13

We investigated the folding of the 70 kDa human cytosolic inducible protein (Hsp70) in vitro using high hydrostatic pressure as a denaturing agent. We followed the structural changes in Hsp70 induced by high hydrostatic pressure using tryptophan fluorescence, molecular dynamics, circular dichroism, high-performance liquid chromatography gel filtration, dynamic light scattering, ATPase activity, and chaperone activity. Although monomeric, Hsp70 is very sensitive to hydrostatic pressure; after pressure had been removed, the protein did not return to its native sate but instead formed oligomeric species that lost chaperone activity but retained ATPase activity.

Geometric effects in the electronic transport of deformed nanotubes

NASA Astrophysics Data System (ADS)

Santos, Fernando; Fumeron, Sébastien; Berche, Bertrand; Moraes, Fernando

2016-04-01

Quasi-two-dimensional systems may exibit curvature, which adds three-dimensional influence to their internal properties. As shown by da Costa (1981 Phys. Rev. A 23 1982-7), charged particles moving on a curved surface experience a curvature-dependent potential which greatly influence their dynamics. In this paper, we study the electronic ballistic transport in deformed nanotubes. The one-electron Schrödinger equation with open boundary conditions is solved numerically with a flexible MAPLE code made available as supplementary data. We find that the curvature of the deformations indeed has strong effects on the electron dynamics, suggesting its use in the design of nanotube-based electronic devices.

Dynamic elementary mode modelling of non-steady state flux data.

PubMed

Folch-Fortuny, Abel; Teusink, Bas; Hoefsloot, Huub C J; Smilde, Age K; Ferrer, Alberto

2018-06-18

A novel framework is proposed to analyse metabolic fluxes in non-steady state conditions, based on the new concept of dynamic elementary mode (dynEM): an elementary mode activated partially depending on the time point of the experiment. Two methods are introduced here: dynamic elementary mode analysis (dynEMA) and dynamic elementary mode regression discriminant analysis (dynEMR-DA). The former is an extension of the recently proposed principal elementary mode analysis (PEMA) method from steady state to non-steady state scenarios. The latter is a discriminant model that permits to identify which dynEMs behave strongly different depending on the experimental conditions. Two case studies of Saccharomyces cerevisiae, with fluxes derived from simulated and real concentration data sets, are presented to highlight the benefits of this dynamic modelling. This methodology permits to analyse metabolic fluxes at early stages with the aim of i) creating reduced dynamic models of flux data, ii) combining many experiments in a single biologically meaningful model, and iii) identifying the metabolic pathways that drive the organism from one state to another when changing the environmental conditions.

Improving estimates of water resources in a semi-arid region by assimilating GRACE data into the PCR-GLOBWB hydrological model

NASA Astrophysics Data System (ADS)

Tangdamrongsub, Natthachet; Steele-Dunne, Susan C.; Gunter, Brian C.; Ditmar, Pavel G.; Sutanudjaja, Edwin H.; Sun, Yu; Xia, Ting; Wang, Zhongjing

2017-04-01

An accurate estimation of water resources dynamics is crucial for proper management of both agriculture and the local ecology, particularly in semi-arid regions. Imperfections in model physics, uncertainties in model land parameters and meteorological data, as well as the human impact on land changes often limit the accuracy of hydrological models in estimating water storages. To mitigate this problem, this study investigated the assimilation of terrestrial water storage variation (TWSV) estimates derived from the Gravity Recovery And Climate Experiment (GRACE) data using an ensemble Kalman filter (EnKF) approach. The region considered was the Hexi Corridor in northern China. The hydrological model used for the analysis was PCR-GLOBWB, driven by satellite-based forcing data from April 2002 to December 2010. The impact of the GRACE data assimilation (DA) scheme was evaluated in terms of the TWSV, as well as the variation of individual hydrological storage estimates. The capability of GRACE DA to adjust the storage level was apparent not only for the entire TWSV but also for the groundwater component. In this study, spatially correlated errors in GRACE data were taken into account, utilizing the full error variance-covariance matrices provided as a part of the GRACE data product. The benefits of this approach were demonstrated by comparing the EnKF results obtained with and without taking into account error correlations. The results were validated against in situ groundwater data from five well sites. On average, the experiments showed that GRACE DA improved the accuracy of groundwater storage estimates by as much as 25 %. The inclusion of error correlations provided an equal or greater improvement in the estimates. In contrast, a validation against in situ streamflow data from two river gauges showed no significant benefits of GRACE DA. This is likely due to the limited spatial and temporal resolution of GRACE observations. Finally, results of the GRACE DA study were used to assess the status of water resources over the Hexi Corridor over the considered 9-year time interval. Areally averaged values revealed that TWS, soil moisture, and groundwater storages over the region decreased with an average rate of approximately 0.2, 0.1, and 0.1 cm yr-1 in terms of equivalent water heights, respectively. A particularly rapid decline in TWS (approximately -0.4 cm yr-1) was seen over the Shiyang River basin located in the southeastern part of Hexi Corridor. The reduction mostly occurred in the groundwater layer. An investigation of the relationship between water resources and agricultural activities suggested that groundwater consumption required to maintain crop yield in the growing season for this specific basin was likely the cause of the groundwater depletion.

An electrochemical sensor prepared by sonochemical one-pot synthesis of multi-walled carbon nanotube-supported cobalt nanoparticles for the simultaneous determination of paracetamol and dopamine.

PubMed

Kutluay, Aysegul; Aslanoglu, Mehmet

2014-08-11

Multi-walled carbon nanotubes (MWCNTs) functionalized by cobalt nanoparticles were obtained using a single step chemical deposition method in an ultrasonic bath. The composite material was characterized using scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). The electroactivity of the cobalt-functionalized MWCNTs was assessed in respect to the electrooxidation of paracetamol (PAR) and dopamine (DA). It was found that the carbon nanotube supported cobalt nanoparticles have significantly higher catalytic properties. The proposed electrode has been applied for the simultaneous determination of PAR and DA. The modified electrode could resolve the overlapped voltammetric waves of PAR and DA into two well-defined voltammetric peaks with peak to peak separation of about 203 mV. On the other hand, the presence of potential drug interfering compounds AA and UA did not affect the voltammetric responses of PAR and DA. The current of oxidation peaks showed a linear dependent on the concentrations of PAR and DA in the range of 5.2×10(-9)-4.5×10(-7) M (R(2)=0.9987) and 5.0×10(-8)-3.0×10(-6) M (R(2)=0.9999), respectively. The detection limits of 1.0×10(-9) M and 1.5×10(-8) M were obtained for PAR and DA, respectively. The proposed electrode showed good stability (peak current change: 4.9% with and RSD of 2.6% for PAR; 5.5% with and RSD of 3.0% for DA over 3 weeks), reproducibility (RSD 2.3% for PAR and RSD 1.5% for DA), repeatability (RSD 2.25% for PAR and RSD 2.50% for DA) and high recovery (99.7% with an RSD of 1.3% for PAR; 100.8% with an RSD of 1.8% for DA). The proposed method was successfully applied to the determination of PAR and DA in pharmaceuticals. Copyright © 2014. Published by Elsevier B.V.

Investigation of an enhanced resolution triple quadrupole mass spectrometer for high-throughput liquid chromatography/tandem mass spectrometry assays.

PubMed

Yang, Liyu; Amad, Ma'an; Winnik, Witold M; Schoen, Alan E; Schweingruber, Hans; Mylchreest, Iain; Rudewicz, Patrick J

2002-01-01

Triple quadrupole mass spectrometers, when operated in multiple reaction monitoring (MRM) mode, offer a unique combination of sensitivity, specificity, and dynamic range. Consequently, the triple quadrupole is the workhorse for high-throughput quantitation within the pharmaceutical industry. However, in the past, the unit mass resolution of quadrupole instruments has been a limitation when interference from matrix or metabolites cannot be eliminated. With recent advances in instrument design, triple quadrupole instruments now afford mass resolution of less than 0.1 Dalton (Da) full width at half maximum (FWHM). This paper describes the evaluation of an enhanced resolution triple quadrupole mass spectrometer for high-throughput bioanalysis with emphasis on comparison of selectivity, sensitivity, dynamic range, precision, accuracy, and stability under both unit mass (1 Da FWHM) and enhanced (

Dopamine Neurons Change the Type of Excitability in Response to Stimuli

PubMed Central

Gutkin, Boris S.; Lapish, Christopher C.; Kuznetsov, Alexey

2016-01-01

The dynamics of neuronal excitability determine the neuron’s response to stimuli, its synchronization and resonance properties and, ultimately, the computations it performs in the brain. We investigated the dynamical mechanisms underlying the excitability type of dopamine (DA) neurons, using a conductance-based biophysical model, and its regulation by intrinsic and synaptic currents. Calibrating the model to reproduce low frequency tonic firing results in N-methyl-D-aspartate (NMDA) excitation balanced by γ-Aminobutyric acid (GABA)-mediated inhibition and leads to type I excitable behavior characterized by a continuous decrease in firing frequency in response to hyperpolarizing currents. Furthermore, we analyzed how excitability type of the DA neuron model is influenced by changes in the intrinsic current composition. A subthreshold sodium current is necessary for a continuous frequency decrease during application of a negative current, and the low-frequency “balanced” state during simultaneous activation of NMDA and GABA receptors. Blocking this current switches the neuron to type II characterized by the abrupt onset of repetitive firing. Enhancing the anomalous rectifier Ih current also switches the excitability to type II. Key characteristics of synaptic conductances that may be observed in vivo also change the type of excitability: a depolarized γ-Aminobutyric acid receptor (GABAR) reversal potential or co-activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) leads to an abrupt frequency drop to zero, which is typical for type II excitability. Coactivation of N-methyl-D-aspartate receptors (NMDARs) together with AMPARs and GABARs shifts the type I/II boundary toward more hyperpolarized GABAR reversal potentials. To better understand how altering each of the aforementioned currents leads to changes in excitability profile of DA neuron, we provide a thorough dynamical analysis. Collectively, these results imply that type I excitability in dopamine neurons might be important for low firing rates and fine-tuning basal dopamine levels, while switching excitability to type II during NMDAR and AMPAR activation may facilitate a transient increase in dopamine concentration, as type II neurons are more amenable to synchronization by mutual excitation. PMID:27930673

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.

PubMed

Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

2015-04-14

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

PubMed Central

Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

2015-01-01

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [11C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors. PMID:25871974

A comparative study of DA-9601 and misoprostol for prevention of NSAID-associated gastroduodenal injury in patients undergoing chronic NSAID treatment.

PubMed

Lee, Oh Young; Kang, Dae-Hwan; Lee, Dong Ho; Chung, Il-Kwun; Jang, Jae Young; Jang, Jae-Young; Kim, Jin-Il; Cho, Jin-Woong; Rew, Jong-Sun; Lee, Kang-Moon; Kim, Kyoung Oh; Choi, Myung-Gyu; Lee, Sang-Woo; Lee, Soo-Teik; Kim, Tae-Oh; Shin, Yong-Woon; Seol, Sang-Yong

2014-10-01

Misoprostol is reported to prevent non-steroidal anti-inflammatory drug (NSAID)-associated gastroduodenal complications. There is, however, limited information regarding the efficacy of DA-9601 in this context. We performed a comparative study on the relative efficacy of DA-9601 and misoprostol for prevention of NSAID-associated complications. In this multicenter, double-blinded, active-controlled, stratified randomized, parallel group, non-inferiority trial, 520 patients who were to be treated with an NSAID (aceclofenac, 100 mg, twice daily) over a 4-week period were randomly assigned to groups for coincidental treatment with DA-9601 (60 mg, thrice daily) (236 patients for full analysis) or misoprostol (200 μg, thrice daily) (242 patients for full analysis). [corrected]. The primary endpoint was the gastric protection rate, and secondary endpoints were the duodenal protection rate and ulcer incidence rate. Endpoints were assessed by endoscopy after the 4-week treatment period. Drug-related adverse effects, including gastrointestinal (GI) symptoms, were also compared. At week 4, the gastric protection rates with DA-9601 and misoprostol were 81.4 % (192/236) and 89.3 % (216/242), respectively. The difference between the groups was -14.2 %, indicating non-inferiority of DA-9601 to misoprostol. Adverse event rates were not different between the two groups; however, the total scores for GI symptoms before and after administration were significantly lower in the DA-9601 group than in the misoprostol group (-0.2 ± 2.8 vs 1.2 ± 3.2; p < 0.0001). DA-9601 is as effective as misoprostol in preventing NSAID-associated gastroduodenal complications, and has a superior adverse GI effect profile.

Caffeine increases striatal dopamine D 2/D 3 receptor availability in the human brain

DOE PAGES

Volkow, N. D.; Wang, G. -J.; Logan, J.; ...

2015-04-14

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A 2A receptors (A 2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [ 11C]raclopride (DA D 2/D 3 receptor radioligand sensitive to endogenous DA) to assess ifmore » caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D 2/D 3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D 2/D 3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D 2/D 3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D 2/D 3 receptor availability. Instead, we interpret our findings to reflect an increase in D 2/D 3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D 2/D 3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D 2/D 3 receptors.« less

Complexity of VTA DA neural activities in response to PFC transection in nicotine treated rats.

PubMed

Chen, Ting Y; Zhang, Die; Dragomir, Andrei; Akay, Yasemin M; Akay, Metin

2011-02-27

The dopaminergic (DA) neurons in the ventral tegmental area (VTA) are widely implicated in the addiction and natural reward circuitry of the brain. These neurons project to several areas of the brain, including prefrontal cortex (PFC), nucleus accubens (NAc) and amygdala. The functional coupling between PFC and VTA has been demonstrated, but little is known about how PFC mediates nicotinic modulation in VTA DA neurons. The objectives of this study were to investigate the effect of acute nicotine exposure on the VTA DA neuronal firing and to understand how the disruption of communication from PFC affects the firing patterns of VTA DA neurons. Extracellular single-unit recordings were performed on Sprague-Dawley rats and nicotine was administered after stable recording was established as baseline. In order to test how input from PFC affects the VTA DA neuronal firing, bilateral transections were made immediate caudal to PFC to mechanically delete the interaction between VTA and PFC. The complexity of the recorded neural firing was subsequently assessed using a method based on the Lempel-Ziv estimator. The results were compared with those obtained when computing the entropy of neural firing. Exposure to nicotine triggered a significant increase in VTA DA neurons firing complexity when communication between PFC and VTA was present, while transection obliterated the effect of nicotine. Similar results were obtained when entropy values were estimated. Our findings suggest that PFC plays a vital role in mediating VTA activity. We speculate that increased firing complexity with acute nicotine administration in PFC intact subjects is due to the close functional coupling between PFC and VTA. This hypothesis is supported by the fact that deletion of PFC results in minor alterations of VTA DA neural firing when nicotine is acutely administered.

Modulation of cue-induced firing of ventral tegmental area dopamine neurons by leptin and ghrelin

PubMed Central

van der Plasse, G; van Zessen, R; Luijendijk, M C M; Erkan, H; Stuber, G D; Ramakers, G M J; Adan, R A H

2015-01-01

Background/objectives: The rewarding value of palatable foods contributes to overconsumption, even in satiated subjects. Midbrain dopaminergic activity in response to reward-predicting environmental stimuli drives reward-seeking and motivated behavior for food rewards. This mesolimbic dopamine (DA) system is sensitive to changes in energy balance, yet it has thus far not been established whether reward signaling of DA neurons in vivo is under control of hormones that signal appetite and energy balance such as ghrelin and leptin. Subjects/methods: We trained rats (n=11) on an operant task in which they could earn two different food rewards. We then implanted recording electrodes in the ventral tegmental area (VTA), and recorded from DA neurons during behavior. Subsequently, we assessed the effects of mild food restriction and pretreatment with the adipose tissue-derived anorexigenic hormone leptin or the orexigenic hormone ghrelin on VTA DA reward signaling. Results: Animals showed an increase in performance following mild food restriction (P=0.002). Importantly, food-cue induced DA firing increased when animals were food restricted (P=0.02), but was significantly attenuated after leptin pretreatment (P=0.00). While ghrelin did affect baseline DA activity (P=0.025), it did not affect cue-induced firing (P⩾0.353). Conclusions: Metabolic signals, such as leptin, affect food seeking, a process that is dependent on the formation of cue-reward outcomes and involves midbrain DA signaling. These data show that food restriction engages the encoding of food cues by VTA DA neurons at a millisecond level and leptin suppresses this activity. This suggests that leptin is a key in linking metabolic information to reward signaling. PMID:26183405

Caffeine increases striatal dopamine D 2/D 3 receptor availability in the human brain

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

Volkow, N. D.; Wang, G. -J.; Logan, J.

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A 2A receptors (A 2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [ 11C]raclopride (DA D 2/D 3 receptor radioligand sensitive to endogenous DA) to assess ifmore » caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D 2/D 3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D 2/D 3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D 2/D 3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D 2/D 3 receptor availability. Instead, we interpret our findings to reflect an increase in D 2/D 3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D 2/D 3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D 2/D 3 receptors.« less

Formation of Hirano Bodies Induced by Expression of an Actin Cross-Linking Protein with a Gain-of-Function Mutation

PubMed Central

Maselli, Andrew; Furukawa, Ruth; Thomson, Susanne A. M.; Davis, Richard C.; Fechheimer, Marcus

2003-01-01

Hirano bodies are paracrystalline actin filament-containing structures reported to be associated with a variety of neurodegenerative diseases. However, the biological function of Hirano bodies remains poorly understood, since nearly all prior studies of these structures were done with postmortem samples of tissue. In the present study, we generated a full-length form of a Dictyostelium 34-kDa actin cross-linking protein with point mutations in the first putative EF hand, termed 34-kDa ΔEF1. The 34-kDa ΔEF1 protein binds calcium normally but has activated actin binding that is unregulated by calcium. The expression of the 34-kDa ΔEF1 protein in Dictyostelium induces the formation of Hirano bodies, as assessed by both fluorescence microscopy and transmission electron microscopy. Dictyostelium cells bearing Hirano bodies grow normally, indicating that Hirano bodies are not associated with cell death and are not deleterious to cell growth. Moreover, the expression of the 34-kDa ΔEF1 protein rescues the phenotypes of cells lacking the 34-kDa protein and cells lacking both the 34-kDa protein and α-actinin. Finally, the expression of the 34-kDa ΔEF1 protein also initiates the formation of Hirano bodies in cultured mouse fibroblasts. These results show that the failure to regulate the activity and/or affinity of an actin cross-linking protein can provide a signal for the formation of Hirano bodies. More generally, the formation of Hirano bodies is a cellular response to or a consequence of aberrant function of the actin cytoskeleton. PMID:12912897

OpenDA Open Source Generic Data Assimilation Environment and its Application in Process Models

NASA Astrophysics Data System (ADS)

El Serafy, Ghada; Verlaan, Martin; Hummel, Stef; Weerts, Albrecht; Dhondia, Juzer

2010-05-01

Data Assimilation techniques are essential elements in state-of-the-art development of models and their optimization with data in the field of groundwater, surface water and soil systems. They are essential tools in calibration of complex modelling systems and improvement of model forecasts. The OpenDA is a new and generic open source data assimilation environment for application to a choice of physical process models, applied to case dependent domains. OpenDA was introduced recently when the developers of Costa, an open-source TU Delft project [http://www.costapse.org; Van Velzen and Verlaan; 2007] and those of the DATools from the former WL|Delft Hydraulics [El Serafy et al 2007; Weerts et al. 2009] decided to join forces. OpenDA makes use of a set of interfaces that describe the interaction between models, observations and data assimilation algorithms. It focuses on flexible applications in portable systems for modelling geophysical processes. It provides a generic interfacing protocol that allows combination of the implemented data assimilation techniques with, in principle, any time-stepping model duscribing a process(atmospheric processes, 3D circulation, 2D water level, sea surface temperature, soil systems, groundwater etc.). Presently, OpenDA features filtering techniques and calibration techniques. The presentation will give an overview of the OpenDA and the results of some of its practical applications. Application of data assimilation in portable operational forecasting systems—the DATools assimilation environment, El Serafy G.Y., H. Gerritsen, S. Hummel, A. H. Weerts, A.E. Mynett and M. Tanaka (2007), Journal of Ocean Dynamics, DOI 10.1007/s10236-007-0124-3, pp.485-499. COSTA a problem solving environment for data assimilation applied for hydrodynamical modelling, Van Velzen and Verlaan (2007), Meteorologische Zeitschrift, Volume 16, Number 6, December 2007 , pp. 777-793(17). Application of generic data assimilation tools (DATools) for flood forecasting purposes, A.H. Weerts, G.Y.H. El Serafy, S. Hummel, J. Dhondia, and H. Gerritsen (2009), accepted by Geoscience & Computers.

Solubility and binding properties of PEGylated lysozyme derivatives with increasing molecular weight on hydrophobic-interaction chromatographic resins.

PubMed

Müller, Egbert; Josic, Djuro; Schröder, Tim; Moosmann, Anna

2010-07-09

Dynamic binding capacities and resolution of PEGylated lysozyme derivatives with varying molecular weights of poly (ethylene) glycol (PEG) with 5 kDa, 10 kDa and 30 kDa for HIC resins and columns are presented. To find the optimal range for the operating conditions, solubility studies were performed by high-throughput analyses in a 96-well plate format, and optimal salt concentrations and pH values were determined. The solubility of PEG-proteins was strongly influenced by the length of the PEG moiety. Large differences in the solubilities of PEGylated lysozymes in two different salts, ammonium sulfate and sodium chloride were found. Solubility of PEGylated lysozyme derivatives in ammonium sulfate decreases with increased length of attached PEG chains. In sodium chloride all PEGylated lysozyme derivatives are fully soluble in a concentration range between 0.1 mg protein/ml and 10 mg protein/ml. The binding capacities for PEGylated lysozyme to HIC resins are dependent on the salt type and molecular weight of the PEG polymer. In both salt solutions, ammonium sulfate and sodium chloride, the highest binding capacity of the resin was found for 5 kDa PEGylated lysozyme. For both native lysozyme and 30 kDa mono-PEGylated lysozyme the binding capacities were lower. In separation experiments on a TSKgel Butyl-NPR hydrophobic-interaction column with ammonium sulfate as mobile phase, the elution order was: native lysozyme, 5 kDa mono-PEGylated lysozyme and oligo-PEGylated lysozyme. This elution order was found to be reversed when sodium chloride was used. Furthermore, the resolution of the three mono-PEGylated forms was not possible with this column and ammonium sulfate as mobile phase. In 4 M sodium chloride a resolution of all PEGylated lysozyme forms was achieved. A tentative explanation for these phenomena can be the increased solvation of the PEG polymers in sodium chloride which changes the usual attractive hydrophobic forces in ammonium sulfate to more repulsive hydration forces in this hydrotrophic salt.

The experience of rural families in the face of cancer.

PubMed

Girardon-Perlini, Nara Marilene Oliveira; Ângelo, Margareth

2017-01-01

To understand the meanings of cancer within the experience of rural families and how such meanings influence family dynamics. Qualitative study guided by Symbolic Interactionism as a theoretical framework and Grounded Theory as a methodological framework. Six rural families (18 participants) undergoing the experience of having a relative with cancer participated in the interview. Constant comparative analysis of data allowed the elaboration of an explanatory substantive theory, defined by the main category Caregiving to support the family world, which represents the family's symbolic actions and strategies to reconcile care for the patient and care for family life. Throughout the experience, rural families seek to preserve the interconnected symbolic elements that provide support for the family world: family unit, land, work and care. Compreender os significados do câncer presentes na experiência de famílias rurais e como esses significados influenciam a dinâmica familiar. Estudo qualitativo orientado pelo Interacionismo Simbólico como referencial teórico e pela Teoria Fundamentada nos Dados como referencial metodológico. Participaram, por meio de entrevista, seis famílias rurais (18 participantes) que estavam vivendo a experiência de ter um familiar com câncer. A análise comparativa constante dos dados permitiu a elaboração de uma teoria substantiva explicativa da experiência, definida pela categoria central Cuidando para manter o mundo da família amparado, que representa as ações e estratégias simbólicas da família visando a conciliar o cuidado do familiar doente e o cuidado da vida familiar. Ao longo da experiência, a família rural procura preservar os elementos simbólicos que, conectados, constituem o amparo do mundo da família: a unidade familiar, a terra, o trabalho e o cuidado.

Gene-by-environment interactions that disrupt mitochondrial homeostasis cause neurodegeneration in C. elegans Parkinson's models.

PubMed

Kim, Hanna; Perentis, Rylee J; Caldwell, Guy A; Caldwell, Kim A

2018-05-10

Parkinson's disease (PD) is a complex multifactorial disorder where environmental factors interact with genetic susceptibility. Accumulating evidence suggests that mitochondria have a central role in the progression of neurodegeneration in sporadic and/or genetic forms of PD. We previously reported that exposure to a secondary metabolite from the soil bacterium, Streptomyces venezuelae, results in age- and dose-dependent dopaminergic (DA) neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons. Initial characterization of this environmental factor indicated that neurodegeneration occurs through a combination of oxidative stress, mitochondrial complex I impairment, and proteostatic disruption. Here we present extended evidence to elucidate the interaction between this bacterial metabolite and mitochondrial dysfunction in the development of DA neurodegeneration. We demonstrate that it causes a time-dependent increase in mitochondrial fragmentation through concomitant changes in the gene expression of mitochondrial fission and fusion components. In particular, the outer mitochondrial membrane fission and fusion genes, drp-1 (a dynamin-related GTPase) and fzo-1 (a mitofusin homolog), are up- and down-regulated, respectively. Additionally, eat-3, an inner mitochondrial membrane fusion component, an OPA1 homolog, is also down regulated. These changes are associated with a metabolite-induced decline in mitochondrial membrane potential and enhanced DA neurodegeneration that is dependent on PINK-1 function. Genetic analysis also indicates an association between the cell death pathway and drp-1 following S. ven exposure. Metabolite-induced neurotoxicity can be suppressed by DA-neuron-specific RNAi knockdown of eat-3. AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) ameliorated metabolite- or PINK-1-induced neurotoxicity; however, it enhanced neurotoxicity under normal conditions. These studies underscore the critical role of mitochondrial dynamics in DA neurodegeneration. Moreover, given the largely undefined environmental components of PD etiology, these results highlight a response to an environmental factor that defines distinct mechanisms underlying a potential contributor to the progressive DA neurodegeneration observed in PD.

Comodulation of dopamine and serotonin on prefrontal cortical rhythms: a theoretical study

PubMed Central

Wang, Da-Hui; Wong-Lin, KongFatt

2013-01-01

The prefrontal cortex (PFC) is implicated to play an important role in cognitive control. Abnormal PFC activities and rhythms have been observed in some neurological and neuropsychiatric disorders, and evidences suggest influences from the neuromodulators dopamine (DA) and serotonin (5-HT). Despite the high level of interest in these brain systems, the combined effects of DA and 5-HT modulation on PFC dynamics remain unknown. In this work, we build a mathematical model that incorporates available experimental findings to systematically study the comodulation of DA and 5-HT on the network behavior, focusing on beta and gamma band oscillations. Single neuronal model shows pyramidal cells with 5-HT1A and 2A receptors can be non-monotonically modulated by 5-HT. Two-population excitatory-inhibitory type network consisting of pyramidal cells with D1 receptors can provide rich repertoires of oscillatory behavior. In particular, 5-HT and DA can modulate the amplitude and frequency of the oscillations, which can emerge or cease, depending on receptor types. Certain receptor combinations are conducive for the robustness of the oscillatory regime, or the existence of multiple discrete oscillatory regimes. In a multi-population heterogeneous model that takes into account possible combination of receptors, we demonstrate that robust network oscillations require high DA concentration. We also show that selective D1 receptor antagonists (agonists) tend to suppress (enhance) network oscillations, increase the frequency from beta toward gamma band, while selective 5-HT1A antagonists (agonists) act in opposite ways. Selective D2 or 5-HT2A receptor antagonists (agonists) can lead to decrease (increase) in oscillation amplitude, but only 5-HT2A antagonists (agonists) can increase (decrease) the frequency. These results are comparable to some pharmacological effects. Our work illustrates the complex mechanisms of DA and 5-HT when operating simultaneously through multiple receptors. PMID:23935568

The mental health care model in Brazil: analyses of the funding, governance processes, and mechanisms of assessment.

PubMed

Trapé, Thiago Lavras; Campos, Rosana Onocko

2017-03-23

This study aims to analyze the current status of the mental health care model of the Brazilian Unified Health System, according to its funding, governance processes, and mechanisms of assessment. We have carried out a documentary analysis of the ordinances, technical reports, conference reports, normative resolutions, and decrees from 2009 to 2014. This is a time of consolidation of the psychosocial model, with expansion of the health care network and inversion of the funding for community services with a strong emphasis on the area of crack cocaine and other drugs. Mental health is an underfunded area within the chronically underfunded Brazilian Unified Health System. The governance model constrains the progress of essential services, which creates the need for the incorporation of a process of regionalization of the management. The mechanisms of assessment are not incorporated into the health policy in the bureaucratic field. There is a need to expand the global funding of the area of health, specifically mental health, which has been shown to be a successful policy. The current focus of the policy seems to be archaic in relation to the precepts of the psychosocial model. Mechanisms of assessment need to be expanded. Analisar o estágio atual do modelo de atenção à saúde mental do Sistema Único de Saúde, segundo seu financiamento, processos de governança e mecanismos de avaliação. Foi realizada uma análise documental de portarias, informes técnicos, relatórios de conferência, resoluções e decretos de 2009 a 2014. Trata-se de um momento de consolidação do modelo psicossocial, com ampliação da rede assistencial, inversão de financiamento para serviços comunitários com forte ênfase na área de crack e outras drogas. A saúde mental é uma área subfinanciada dentro do subfinanciamento crônico do Sistema Único de Saúde. O modelo de governança constrange o avanço de serviços essenciais, havendo a necessidade da incorporação de um processo de regionalização da gestão. Os mecanismos avaliativos no campo burocrático se mostram pouco incorporados à política de saúde. É necessário ampliar o financiamento global da saúde e específico da saúde mental, que vem se constituindo como uma política exitosa. O foco atual da política se mostra anacrônico aos preceitos do modelo psicossocial. Aponta-se a necessidade de ampliação de mecanismos avaliativos.

Comparison of standard laparoscopic distal pancreatectomy with minimally invasive distal pancreatectomy using the da Vinci S system.

PubMed

Ito, Masahiro; Asano, Yukio; Shimizu, Tomohiro; Uyama, Ichiro; Horiguchi, Akihiko

2014-01-01

Minimally invasive procedures for pancreatic pathologies are increasingly being used, including distal pancreatectomy. This study aimed to assess the indications for and outcomes of the da Vinci distal pancreatectomy procedure. We reviewed the medical records of patients who underwent pancreatic head resection from April 2009 to September 2013. Four patients (mean age, 52.7 years) underwent da Vinci distal pancreatectomy and 10 (mean age, 68.0 +/- 12.1 years) underwent laparoscopic distal pancreatectomy. The mean surgical duration was 292 +/- 153 min and 306 +/- 29 min, the mean blood loss was 153 +/- 71 mL and 61.7 +/- 72 mL, and the mean postoperative length of stay was 24 +/- 11 days and 14 +/- 3 days in the da Vinci distal pancreatectomy and laparoscopic distal pancreatectomy groups, respectively. One patient who underwent da Vinci distal pancreatectomy developed a pancreatic fistula, while 2 patients in the laparoscopic distal pancreatectomy group developed splenic ischemia and gastric torsion, respectively. Laparoscopic and robotic pancreatic resection were both safe and feasible in selected patients with distal pancreatic pathologies. Further studies are necessary to clarify the role of robotic surgery in the advanced laparoscopic era.

Nutritional improvement of corn pasta-like product with broad bean (Vicia faba) and quinoa (Chenopodium quinoa).

PubMed

Giménez, M A; Drago, S R; Bassett, M N; Lobo, M O; Sammán, N C

2016-05-15

In this study, the nutritional quality of pasta-like product (spaghetti-type), made with corn (Zea mays) flour enriched with 30% broad bean (Vicia faba) flour and 20% of quinoa (Chenopodium quinoa) flour, was determined. Proximate chemical composition and iron, zinc and dietary fiber were determined. A biological assay was performed to assess the protein value using net protein utilization (NPU), true digestibility (TD) and protein digestibility-corrected amino acid score (PDCAAS). Iron and zinc availability were estimated by measuring dialyzable mineral fraction (%Da) resulting from in vitro gastrointestinal digestion. Nutritionally improved, gluten-free spaghetti (NIS) showed significantly increased NPU and decreased TD compared with a non-enriched control sample. One NIS-portion supplied 10-20% of recommended fiber daily intake. Addition of quinoa flour had a positive effect on the FeDa% as did broad bean flour on ZnDa%. EDTA increased Fe- and ZnDa% in all NIS-products, but it also impaired sensorial quality. Copyright © 2016. Published by Elsevier Ltd.

Isolation, identification and synthesis of four novel antioxidant peptides from rice residue protein hydrolyzed by multiple proteases.

PubMed

Yan, Qiao-Juan; Huang, Lin-Hua; Sun, Qian; Jiang, Zheng-Qiang; Wu, Xia

2015-07-15

Multiple proteases were optimized to hydrolyze the rice residue protein (RRP) to produce novel antioxidant peptides. An antioxidant peptide fraction (RRPB3) with IC50 of 0.25 mg/ml was purified from the RRP hydrolysate using membrane ultrafiltration followed by size exclusion chromatography and reversed-phase FPLC. RRPB3 was found to include four peptides (RRPB3 I-IV) and their amino acid sequences were RPNYTDA (835.9 Da), TSQLLSDQ (891.0 Da), TRTGDPFF (940.0 Da) and NFHPQ (641.7 Da), respectively. Furthermore, four peptides were chemically synthesized and their antioxidant activities were assessed by DPPH radical scavenging, ABTS radical scavenging assay and FRAP-Fe(3+) reducing assay, respectively. Both RRPB3 I and III showed synergistic antioxidant activity compared to each of them used alone. All four synthetic peptides showed excellent stability against simulated gastrointestinal proteases. Therefore, the peptides isolated from RRP may be used as potential antioxidants in the food and drug industries. Copyright © 2015 Elsevier Ltd. All rights reserved.

Metabolomics of Breast Cancer Using High-Resolution Magic Angle Spinning Magnetic Resonance Spectroscopy: Correlations with 18F-FDG Positron Emission Tomography-Computed Tomography, Dynamic Contrast-Enhanced and Diffusion-Weighted Imaging MRI.

PubMed

Yoon, Haesung; Yoon, Dahye; Yun, Mijin; Choi, Ji Soo; Park, Vivian Youngjean; Kim, Eun-Kyung; Jeong, Joon; Koo, Ja Seung; Yoon, Jung Hyun; Moon, Hee Jung; Kim, Suhkmann; Kim, Min Jung

2016-01-01

Our goal in this study was to find correlations between breast cancer metabolites and conventional quantitative imaging parameters using high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) and to find breast cancer subgroups that show high correlations between metabolites and imaging parameters. Between August 2010 and December 2013, we included 53 female patients (mean age 49.6 years; age range 32-75 years) with a total of 53 breast lesions assessed by the Breast Imaging Reporting and Data System. They were enrolled under the following criteria: breast lesions larger than 1 cm in diameter which 1) were suspicious for malignancy on mammography or ultrasound (US), 2) were pathologically confirmed to be breast cancer with US-guided core-needle biopsy (CNB) 3) underwent 3 Tesla MRI with dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) and positron emission tomography-computed tomography (PET-CT), and 4) had an attainable immunohistochemistry profile from CNB. We acquired spectral data by HR-MAS MRS with CNB specimens and expressed the data as relative metabolite concentrations. We compared the metabolites with the signal enhancement ratio (SER), maximum standardized FDG uptake value (SUV max), apparent diffusion coefficient (ADC), and histopathologic prognostic factors for correlation. We calculated Spearman correlations and performed a partial least squares-discriminant analysis (PLS-DA) to further classify patient groups into subgroups to find correlation differences between HR-MAS spectroscopic values and conventional imaging parameters. In a multivariate analysis, the PLS-DA models built with HR-MAS MRS metabolic profiles showed visible discrimination between high and low SER, SUV, and ADC. In luminal subtype breast cancer, compared to all cases, high SER, ADV, and SUV were more closely clustered by visual assessment. Multiple metabolites were correlated with SER and SUV in all cases. Multiple metabolites showed correlations with SER and SUV in the ER positive, HER2 negative, and Ki-67 negative groups. High levels of PC, choline, and glycine acquired from HR-MAS MRS using CNB specimens were noted in the high SER group via DCE MRI and the high SUV group via PET-CT, with significant correlations between choline and SER and between PC and SUV. Further studies should investigate whether HR-MAS MRS using CNB specimens can provide similar or more prognostic information than conventional quantitative imaging parameters.

Dermal white adipose tissue undergoes major morphological changes during the spontaneous and induced murine hair follicle cycling: a reappraisal.

PubMed

Foster, April R; Nicu, Carina; Schneider, Marlon R; Hinde, Eleanor; Paus, Ralf

2018-07-01

In murine skin, dermal white adipose tissue (DWAT) undergoes major changes in thickness in synchrony with the hair cycle (HC); however, the underlying mechanisms remain unclear. We sought to elucidate whether increased DWAT thickness during anagen is mediated by adipocyte hypertrophy or adipogenesis, and whether lipolysis or apoptosis can explain the decreased DWAT thickness during catagen. In addition, we compared HC-associated DWAT changes between spontaneous and depilation-induced hair follicle (HF) cycling to distinguish between spontaneous and HF trauma-induced events. We show that HC-dependent DWAT remodelling is not an artefact caused by fluctuations in HF down-growth, and that dermal adipocyte (DA) proliferation and hypertrophy are HC-dependent, while classical DA apoptosis is absent. However, none of these changes plausibly accounts for HC-dependent oscillations in DWAT thickness. Contrary to previous studies, in vivo BODIPY uptake suggests that increased DWAT thickness during anagen occurs via hypertrophy rather than hyperplasia. From immunohistomorphometry, DWAT thickness likely undergoes thinning during catagen by lipolysis. Hence, we postulate that progressive, lipogenesis-driven DA hypertrophy followed by dynamic switches between lipogenesis and lipolysis underlie DWAT fluctuations in the spontaneous HC, and dismiss apoptosis as a mechanism of DWAT reduction. Moreover, the depilation-induced HC displays increased DWAT thickness, area, and DA number, but decreased DA volume/area compared to the spontaneous HC. Thus, DWAT shows additional, novel HF wounding-related responses during the induced HC. This systematic reappraisal provides important pointers for subsequent functional and mechanistic studies, and introduces the depilation-induced murine HC as a model for dissecting HF-DWAT interactions under conditions of wounding/stress.

Fostering Informed Decisions: Impact of a Decision Aid Among Men Registered to Undergo Mass Screening for Prostate Cancer in a Randomized Controlled Trial

PubMed Central

Williams, Randi M.; Davis, Kimberly M.; Luta, George; Edmond, Sara N.; Dorfman, Caroline S.; Schwartz, Marc D.; Lynch, John; Ahaghotu, Chiledum; Taylor, Kathryn L.

2013-01-01

Objective Screening asymptomatic men for prostate cancer is controversial and informed decision making is recommended. Within two prostate cancer screening programs, we evaluated the impact of a print-based decision aid (DA) on decision-making outcomes. Methods Men (N=543) were 54.9 (SD=8.1) years old and 61% were African-American. The 2 (booklet type: DA vs. usual care (UC)) × 2 (delivery mode: Home vs. Clinic) randomized controlled trial assessed decisional and screening outcomes at baseline, two-months, and 13-months. Results Intention-to-treat linear regression analyses using generalized estimating equations revealed that DA participants reported improved knowledge relative to UC (B=.41, p<.05). For decisional conflict, per-protocol analyses revealed a group by time interaction (B = −.69, p<.05), indicating that DA participants were less likely to report decisional conflict at two-months compared to UC participants (OR=.49, 95% CI: .26–.91, p<.05). Conclusion This is the first randomized trial to evaluate a DA in the context of free mass screening, a challenging setting in which to make an informed decision. The DA was highly utilized by participants, improved knowledge and reduced decisional conflict. Practice implications These results are valuable in understanding ways to improve the decisions of men who seek screening and can be easily implemented within many settings. PMID:23357414

The Asymmetrical Effects of Divided Attention on Encoding and Retrieval Processes: A Different View Based on an Interference with the Episodic Register

PubMed Central

Guez, Jonathan; Naveh-Benjamin, Moshe

2013-01-01

In this study, we evaluate the conceptualization of encoding and retrieval processes established in previous studies that used a divided attention (DA) paradigm. These studies indicated that there were considerable detrimental effects of DA at encoding on later memory performance, but only minimal effects, if any, on divided attention at retrieval. We suggest that this asymmetry in the effects of DA on memory can be due, at least partially, to a confound between the memory phase (encoding and retrieval) and the memory requirements of the task (memory “for” encoded information versus memory “at” test). To control for this confound, we tested memory for encoded information and for retrieved information by introducing a second test that assessed memory for the retrieved information from the first test. We report the results of four experiments that use measures of memory performance, retrieval latency, and performance on the concurrent task, all of which consistently show that DA at retrieval strongly disrupts later memory for the retrieved episode, similarly to the effects of DA at encoding. We suggest that these symmetrical disruptive effects of DA at encoding and retrieval on later retrieval reflect a disruption of an episodic buffer (EB) or episodic register component (ER), rather than a failure of encoding or retrieval operations per se. PMID:24040249

The asymmetrical effects of divided attention on encoding and retrieval processes: a different view based on an interference with the episodic register.

PubMed

Guez, Jonathan; Naveh-Benjamin, Moshe

2013-01-01

In this study, we evaluate the conceptualization of encoding and retrieval processes established in previous studies that used a divided attention (DA) paradigm. These studies indicated that there were considerable detrimental effects of DA at encoding on later memory performance, but only minimal effects, if any, on divided attention at retrieval. We suggest that this asymmetry in the effects of DA on memory can be due, at least partially, to a confound between the memory phase (encoding and retrieval) and the memory requirements of the task (memory "for" encoded information versus memory "at" test). To control for this confound, we tested memory for encoded information and for retrieved information by introducing a second test that assessed memory for the retrieved information from the first test. We report the results of four experiments that use measures of memory performance, retrieval latency, and performance on the concurrent task, all of which consistently show that DA at retrieval strongly disrupts later memory for the retrieved episode, similarly to the effects of DA at encoding. We suggest that these symmetrical disruptive effects of DA at encoding and retrieval on later retrieval reflect a disruption of an episodic buffer (EB) or episodic register component (ER), rather than a failure of encoding or retrieval operations per se.

Output control of da Vinci surgical system's surgical graspers.

PubMed

Johnson, Paul J; Schmidt, David E; Duvvuri, Umamaheswar

2014-01-01

The number of robot-assisted surgeries performed with the da Vinci surgical system has increased significantly over the past decade. The articulating movements of the robotic surgical grasper are controlled by grip controls at the master console. The user interface has been implicated as one contributing factor in surgical grasping errors. The goal of our study was to characterize and evaluate the user interface of the da Vinci surgical system in controlling surgical graspers. An angular manipulator with force sensors was used to increment the grip control angle as grasper output angles were measured. Input force at the grip control was simultaneously measured throughout the range of motion. Pressure film was used to assess the maximum grasping force achievable with the endoscopic grasping tool. The da Vinci robot's grip control angular input has a nonproportional relationship with the grasper instrument output. The grip control mechanism presents an intrinsic resistant force to the surgeon's fingertips and provides no haptic feedback. The da Vinci Maryland graspers are capable of applying up to 5.1 MPa of local pressure. The angular and force input at the grip control of the da Vinci robot's surgical graspers is nonproportional to the grasper instrument's output. Understanding the true relationship of the grip control input to grasper instrument output may help surgeons understand how to better control the surgical graspers and promote fewer grasping errors. Copyright © 2014 Elsevier Inc. All rights reserved.

Development and preliminary user testing of the DCIDA (Dynamic computer interactive decision application) for 'nudging' patients towards high quality decisions.

PubMed

Bansback, Nick; Li, Linda C; Lynd, Larry; Bryan, Stirling

2014-08-01

Patient decision aids (PtDA) are developed to facilitate informed, value-based decisions about health. Research suggests that even when informed with necessary evidence and information, cognitive errors can prevent patients from choosing the option that is most congruent with their own values. We sought to utilize principles of behavioural economics to develop a computer application that presents information from conventional decision aids in a way that reduces these errors, subsequently promoting higher quality decisions. The Dynamic Computer Interactive Decision Application (DCIDA) was developed to target four common errors that can impede quality decision making with PtDAs: unstable values, order effects, overweighting of rare events, and information overload. Healthy volunteers were recruited to an interview to use three PtDAs converted to the DCIDA on a computer equipped with an eye tracker. Participants were first used a conventional PtDA, and then subsequently used the DCIDA version. User testing was assessed based on whether respondents found the software both usable: evaluated using a) eye-tracking, b) the system usability scale, and c) user verbal responses from a 'think aloud' protocol; and useful: evaluated using a) eye-tracking, b) whether preferences for options were changed, and c) and the decisional conflict scale. Of the 20 participants recruited to the study, 11 were male (55%), the mean age was 35, 18 had at least a high school education (90%), and 8 (40%) had a college or university degree. Eye-tracking results, alongside a mean system usability scale score of 73 (range 68-85), indicated a reasonable degree of usability for the DCIDA. The think aloud study suggested areas for further improvement. The DCIDA also appeared to be useful to participants wherein subjects focused more on the features of the decision that were most important to them (21% increase in time spent focusing on the most important feature). Seven subjects (25%) changed their preferred option when using DCIDA. Preliminary results suggest that DCIDA has potential to improve the quality of patient decision-making. Next steps include larger studies to test individual components of DCIDA and feasibility testing with patients making real decisions.

Values clarification in a decision aid about fertility preservation: does it add to information provision?

PubMed Central

2014-01-01

Background We aimed to evaluate the effect of a decision aid (DA) with information only compared to a DA with values clarification exercise (VCE), and to study the role of personality and information seeking style in DA-use, decisional conflict (DC) and knowledge. Methods Two scenario-based experiments were conducted with two different groups of healthy female participants. Dependent measures were: DC, knowledge, and DA-use (time spent, pages viewed, VCE used). Respondents were randomized between a DA with information only (VCE-) and a DA with information plus a VCE(VCE+) (experiment 1), or between information only (VCE-), information plus VCE without referral to VCE(VCE+), and information plus a VCE with specific referral to the VCE, requesting participants to use the VCE(VCE++) (experiment 2). In experiment 2 we additionally measured personality (neuroticism/conscientiousness) and information seeking style (monitoring/blunting). Results Experiment 1. There were no differences in DC, knowledge or DA-use between VCE- (n=70) and VCE+ (n=70). Both DAs lead to a mean gain in knowledge from 39% at baseline to 73% after viewing the DA. Within VCE+, VCE-users (n=32, 46%) reported less DC compared to non-users. Since there was no difference in DC between VCE- and VCE+, this is likely an effect of VCE-use in a self-selected group, and not of the VCE per se. Experiment 2. There were no differences in DC or knowledge between VCE- (n=65), VCE+ (n=66), VCE++ (n=66). In all groups, knowledge increased on average from 42% at baseline to 72% after viewing the DA. Blunters viewed fewer DA-pages (R=0.38, p<.001). More neurotic women were less certain (R=0.18, p<.01) and felt less supported in decision making (R=0.15, p<.05); conscientious women felt more certain (R=-0.15, p<.05) and had more knowledge after viewing the DA (R=0.15, p<.05). Conclusions Both DAs lead to increased knowledge in healthy populations making hypothetical decisions, and use of the VCE did not improve knowledge or DC. Personality characteristics were associated to some extent with DA-use, information seeking styles with aspects of DC. More research is needed to make clear recommendations regarding the need for tailoring of information provision to personality characteristics, and to assess the effect of VCE use in actual patients. PMID:25106453

Kiss-and-Run Is a Significant Contributor to Synaptic Exocytosis and Endocytosis in Photoreceptors

PubMed Central

Wen, Xiangyi; Saltzgaber, Grant W.; Thoreson, Wallace B.

2017-01-01

Accompanying sustained release in darkness, rod and cone photoreceptors exhibit rapid endocytosis of synaptic vesicles. Membrane capacitance measurements indicated that rapid endocytosis retrieves at least 70% of the exocytotic membrane increase. One mechanism for rapid endocytosis is kiss-and-run fusion where vesicles briefly contact the plasma membrane through a small fusion pore. Release can also occur by full-collapse in which vesicles merge completely with the plasma membrane. We assessed relative contributions of full-collapse and kiss-and-run in salamander photoreceptors using optical techniques to measure endocytosis and exocytosis of large vs. small dye molecules. Incubation with small dyes (SR101, 1 nm; 3-kDa dextran-conjugated Texas Red, 2.3 nm) loaded rod and cone synaptic terminals much more readily than larger dyes (10-kDa Texas Red, 4.6 nm; 10-kDa pHrodo, 4.6 nm; 70-kDa Texas Red, 12 nm) consistent with significant uptake through 2.3–4.6 nm fusion pores. By using total internal reflection fluorescence microscopy (TIRFM) to image individual vesicles, when rods were incubated simultaneously with Texas Red and AlexaFluor-488 dyes conjugated to either 3-kDa or 10-kDa dextran, more vesicles loaded small molecules than large molecules. Using TIRFM to detect release by the disappearance of dye-loaded vesicles, we found that SR101 and 3-kDa Texas Red were released from individual vesicles more readily than 10-kDa and 70-kDa Texas Red. Although 10-kDa pHrodo was endocytosed poorly like other large dyes, the fraction of release events was similar to SR101 and 3-kDa Texas Red. We hypothesize that while 10-kDa pHrodo may not exit through a fusion pore, release of intravesicular protons can promote detection of fusion events by rapidly quenching fluorescence of this pH-sensitive dye. Assuming that large molecules can only be released by full-collapse whereas small molecules can be released by both modes, our results indicate that 50%–70% of release from rods involves kiss-and-run with 2.3–4.6 nm fusion pores. Rapid retrieval of vesicles by kiss-and-run may limit membrane disruption of release site function during ongoing release at photoreceptor ribbon synapses. PMID:28979188

Anti-inflammatory effect of garlic 14-kDa protein on LPS-stimulated-J774A.1 macrophages.

PubMed

Rabe, Shahrzad Zamani Taghizadeh; Ghazanfari, Tooba; Siadat, Zahra; Rastin, Maryam; Rabe, Shahin Zamani Taghizadeh; Mahmoudi, Mahmoud

2015-04-01

Garlic 14-kDa protein is purified from garlic (Allium sativum L.) which is used in traditional medicine and exerts various immunomodulatory activities. The present study investigated the suppressive effect of garlic 14-kDa protein on LPS-induced expression of pro-inflammatory mediators and underlying mechanism in inflammatory macrophages. J774A.1 macrophages were treated with 14-kDa protein (5-30 μg/ml) with/without LPS (1 μg/ml) and the production of inflammatory mediators such as prostaglandin E2 (PGE2), TNF-α, and IL-1β released were measured using ELISA. Nitric oxide (NO) production was determined using the Griess method. The anti-inflammatory activity of 14-kDa protein was examined by measuring inducible nitric oxide synthase and cyclooxygenase-2 proteins using western blot. The expression of nuclear NF-κB p65 subunit was assessed by western blot. Garlic 14-kDa protein significantly inhibited the excessive production of NO, PGE, TNF-α, and IL-1β in lipopolysaccharide (LPS)-activated J774A.1 macrophages in a concentration-related manner without cytotoxic effect. Western blot analysis demonstrated that garlic 14-kDa protein suppressed corresponding inducible NO synthase expression and activated cyclooxygenase-2 protein expression. The inhibitory effect was mediated partly by a reduction in the activity and expression of transcription factor NF-κB protein. Our results suggested, for the first time, garlic 14-kDa protein exhibits anti-inflammatory properties in macrophages possibly by suppressing the inflammatory mediators via the inhibition of transcription factor NF-κB signaling pathway. The traditional use of garlic as anti-inflammatory remedy could be ascribed partly to 14-kDa protein content. This protein might be a useful candidate for controlling inflammatory diseases and further investigations in vivo.

Tuning aggregation of microemulsion droplets and silica nanoparticles using solvent mixtures.

PubMed

Salabat, Alireza; Eastoe, Julian; Mutch, Kevin J; Tabor, Rico F

2008-02-15

The effect of solvent on stability of water-in-oil microemulsions has been studied with AOT (sodium bis(2-ethylhexyl)sulfosuccinate) and different solvent mixtures of n-heptane, toluene and dodecane. Dynamic light scattering DLS was used to monitor the apparent diffusion coefficient D(A) and effective microemulsion droplet diameter on changing composition of the solvent. Interdroplet attractive interactions, as indicated by variations in D(A), can be tuned by formulation of appropriate solvent mixtures using heptane, toluene, and dodecane. In extreme cases, solvent mixtures can be used to induce phase transitions in the microemulsions. Aggregation and stability of model AOT-stabilized silica nanoparticles in different solvents were also investigated to explore further these solvent effects. For both systems the state of aggregation can be correlated with the effective molecular volume of the solvent V(mol)(eff) mixture.

Web-Based Decision Aid to Assist Help-Seeking Choices for Young People Who Self-Harm: Outcomes From a Randomized Controlled Feasibility Trial.

PubMed

Rowe, Sarah L; Patel, Krisna; French, Rebecca S; Henderson, Claire; Ougrin, Dennis; Slade, Mike; Moran, Paul

2018-01-30

Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement for parental consent is a key barrier to intervention research on self-harm in the school setting. Adaptations to the research design and the intervention are needed before generalizable research about DAs can be successfully conducted in a school setting. International Standard Randomized Controlled Trial registry: ISRCTN11230559; http://www.isrctn.com/ISRCTN11230559 (Archived by WebCite at http://www.webcitation.org/6wqErsYWG). ©Sarah L Rowe, Krisna Patel, Rebecca S French, Claire Henderson, Dennis Ougrin, Mike Slade, Paul Moran. Originally published in JMIR Mental Health (http://mental.jmir.org), 30.01.2018.

Web-Based Decision Aid to Assist Help-Seeking Choices for Young People Who Self-Harm: Outcomes From a Randomized Controlled Feasibility Trial

PubMed Central

Patel, Krisna; French, Rebecca S; Henderson, Claire; Ougrin, Dennis; Slade, Mike; Moran, Paul

2018-01-01

Background Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. Objective The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. Methods We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Results Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. Conclusions A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement for parental consent is a key barrier to intervention research on self-harm in the school setting. Adaptations to the research design and the intervention are needed before generalizable research about DAs can be successfully conducted in a school setting. Trial Registration International Standard Randomized Controlled Trial registry: ISRCTN11230559; http://www.isrctn.com/ISRCTN11230559 (Archived by WebCite at http://www.webcitation.org/6wqErsYWG) PMID:29382626

Leveraging human genetic and adverse outcome pathway (AOP) data to inform susceptibility in human health risk assessment

EPA Science Inventory

Estimation of susceptibility differences in human health risk assessment (HHRA) has been challenged by a lack of available susceptibility and variability data after exposure to a specific environmental chemical or pharmaceutical. With the increasingly large number of available da...

Familiar companions diminish cocaine conditioning and attenuate cocaine-stimulated dopamine release in the nucleus accumbens.

PubMed

Tzeng, Wen-Yu; Cherng, Chian-Fang G; Wang, Shyi-Wu; Yu, Lung

2016-06-01

This study aimed to assess the impact of companions on the rewarding effects of cocaine. Three cage mates, serving as companions, were housed with each experimental mouse throughout cocaine-place conditioning in a cocaine-induced conditioned place preference (CPP) paradigm using conditioning doses of 10 and 20mg/kg. The presence of companions decreased the magnitude of the CPP. At 20mg/kg, cocaine stimulated dopamine (DA) release in the nucleus accumbens as evidenced by a significant decrease in total (spontaneous and electrical stimulation-provoked) DA release in accumbal superfusate samples. The presence of companions prevented this cocaine-stimulated DA release; such a reduction in cocaine-induced DA release may account for the reduction in the magnitude of the CPP in the presence of the companions. Furthermore, cocaine pretreatment (2.5mg/kg) was found to prevent the companion-produced decreases in cocaine (10mg/kg/conditioning)-induced CPP as well as the cocaine (10mg/kg)-stimulated DA release. Moreover, the presence of methamphetamine (MA) (1mg/kg)-treated companions decreased cocaine (20mg/kg/conditioning)-induced CPP and prevented the cocaine (20mg/kg)-stimulated DA release. Finally, the presence of companions decreased the magnitude of the CPP could not seem to be accounted for by cocaine-stimulated corticosterone (CORT) release. Taken together, these results indicate that familiar companions, regardless of their pharmacological status, may exert dampening effects on CPP induced by moderate to high conditioning doses of cocaine, at least in part, by preventing cocaine-stimulated DA release in the nucleus accumbens. Copyright © 2016 Elsevier B.V. All rights reserved.

Feasibility and acceptability of a decision aid designed for people facing advanced or terminal illness: a pilot randomized trial.

PubMed

Matlock, Dan D; Keech, Tarah A E; McKenzie, Marlene B; Bronsert, Michael R; Nowels, Carolyn T; Kutner, Jean S

2014-02-01

Patients nearing the end of their lives face an array of difficult decisions. This study was designed to assess the feasibility and acceptability of a decision aid (DA) designed for patients facing advanced or terminal illness. We conducted a pilot randomized clinical trial of Health Dialog's Looking Ahead: choices for medical care when you're seriously ill DA (booklet and DVD) applied to patients on a hospital-based palliative care (PC) service. University of Colorado Hospital - December 2009 and May 2010. All adult, English-speaking patients or their decision makers were potentially eligible. Patients were not approached if they were in isolation, did not speak English or if any provider felt that they were not appropriate because of issues such as family conflict or actively dying. All participants received a standard PC consultation. Participants in the intervention arm also received a copy of the DA. Measurements Primary outcomes included decision conflict and knowledge. Participants in the intervention arm also completed an acceptability questionnaire and qualitative exit interviews. Of the 239 patients or decision makers, 51(21%) enrolled in the trial. The DA had no significant effect on decision conflict or knowledge. Exit interviews indicated it was acceptable and empowering, although they wished they had access to the DA earlier. While the DA was acceptable, feasibility was limited by late-life illness challenges. Future trials of this DA should be performed on patients earlier in their illness trajectory and should include additional outcome measures such as self-efficacy and confidence. © 2011 John Wiley & Sons Ltd.

Fluorescence characterization of fractionated dissolved organic matter in the five tributaries of Poyang Lake, China.

PubMed

Yan, Caixia; Liu, Huihui; Sheng, Yanru; Huang, Xian; Nie, Minghua; Huang, Qi; Baalousha, Mohammed

2018-10-01

Characterization of natural colloids is the key to understand pollutant fate and transport in the environment. The present study investigates the relationship between size and fluorescence properties of colloidal organic matter (COM) from five tributaries of Poyang Lake. Colloids were size-fractionated using cross-flow ultrafiltration and their fluorescence properties were measured by three-dimensional excitation-emission matrix fluorescence spectroscopy (3D-EEM). Parallel factor analysis (PARAFAC) and/or Self-organizing map (SOM) were applied to assess fluorescence properties as proxy indicators for the different size of colloids. PARAFAC analysis identified four fluorescence components including three humic-like components (C1-C3) and a protein-like component (C4). These four fluorescence components, and in particular the protein-like component, are primarily present in <1 kDa phase. For the colloidal fractions (1-10 kDa, 10-100 kDa, and 100 kDa-0.7 μm), the majority of fluorophores are associated with the smallest size fraction. SOM analysis demonstrated that relatively high fluorescence intensity and aromaticity occur primarily in <1 kDa phase, followed by 1-10 kDa colloids. Coupling PARAFAC and SOM facilitate the visualization and interpretation of the relationship between colloidal size and fluorescence properties with fewer input variables, shorter running time, higher reliability, and nondestructive results. Fluorescence indices analysis reveals that the smallest colloidal fraction (1-10 kDa) was dominated by higher humified and less autochthonous COM. Copyright © 2018 Elsevier B.V. All rights reserved.

Mephedrone Does not Damage Dopamine Nerve Endings of the Striatum but Enhances the Neurotoxicity of Methamphetamine, Amphetamine and MDMA

PubMed Central

Angoa-Pérez, Mariana; Kane, Michael J.; Briggs, Denise I.; Francescutti, Dina M.; Sykes, Catherine E.; Shah, Mrudang M.; Thomas, David M.; Kuhn, Donald M.

2012-01-01

Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its reuptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamine-induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20 or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (4 injections of 2.5 or 5.0 mg/kg at 2 hr intervals). The integrity of DA nerve endings of the striatum was assessed through measures of DA, DAT and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and MDMA on DA nerve endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. Because mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA nerve endings mask a potentially dangerous interaction with drugs that are often co-abused with it, leading to heightened neurotoxicity. PMID:23205838

Anti-MRSA malleable liposomes carrying chloramphenicol for ameliorating hair follicle targeting

PubMed Central

Sung, Calvin T; Weng, Yi-Han; Fang, Jia-You

2017-01-01

Pathogens usually invade hair follicles when skin infection occurs. The accumulated bacteria in follicles are difficult to eradicate. The present study aimed to assess the cutaneous and follicular delivery of chloramphenicol (Cm)-loaded liposomes and the antibacterial activity of these liposomes against methicillin-resistant Staphylococcus aureus (MRSA). Skin permeation was conducted by in vitro Franz diffusion cell. The anti-MRSA potential was checked using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), a well diffusion test, and intracellular MRSA killing. The classic, dimyristoylphosphatidylcholine (DMPC), and deoxycholic acid (DA) liposomes had a vesicle size of 98, 132, and 239 nm, respectively. The incorporation of DMPC or DA into the liposomes increased the bilayer fluidity. The malleable vesicles containing DMPC and DA showed increased follicular Cm uptake over the control solution by 1.5- and 2-fold, respectively. The MIC and MBC of DA liposomes loaded with Cm were 62.5 and 62.5–125 μg/mL, comparable to free Cm. An inhibition zone about 2-fold higher was achieved by DA liposomes as compared to the free control at a Cm dose of 0.5 mg/mL. DA liposomes also augmented antibacterial activity on keratinocyte-infected MRSA. The deformable liposomes had good biocompatibility against keratinocytes and neutrophils (viability >80%). In vivo administration demonstrated that DA liposomes caused negligible toxicity on the skin, based on physiological examination and histology. These data suggest the potential application of malleable liposomes for follicular targeting and the treatment of MRSA-infected dermatologic conditions. PMID:29184410

Anxiety and depressive disorders in dialysis patients: association to health-related quality of life and mortality.

PubMed

Preljevic, Valjbona T; Østhus, Tone Brit Hortemo; Os, Ingrid; Sandvik, Leiv; Opjordsmoen, Stein; Nordhus, Inger Hilde; Dammen, Toril

2013-01-01

To examine the associations between depressive/anxiety disorders (DAs), perceived health-related quality of life (HRQOL) and mortality in dialysis patients. Patients were assessed for depressive and DAs with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders. The HRQOL was assessed with the Medical Outcome Short Form 36 (MOS SF-36), and the Beck Depression Inventory and Hospital Anxiety and Depression Scale were also applied. Sociodemographic, clinical and laboratory data were also collected. Patients with depressive disorders reported more impaired HRQOL on four of the eight subscales, while those with a depressive disorder comorbid with DA reported more impairment on all MOS SF-36 subscales compared to those without any psychiatric disorder. During the observation period, 50% of those with depression, 28% of those with anxiety and 33% of patients with DA disorder died. A survival analysis did not indicate that patients with depressive or DAs had a higher mortality than patients without such disorders. Dialysis patients with depressive disorders reported impaired HRQOL, whereas those with DAs did not. Patients with DA reported the most serious HRQOL impairment. No evidence was obtained to support the hypothesis that depressive and DAs contributed to compromised survival in dialysis patients. In patients with depression, DAs should also be assessed as they significantly contribute to impaired HRQOL. Copyright © 2013 Elsevier Inc. All rights reserved.

Dopamine in the nucleus accumbens core, but not shell, increases during signaled food reward and decreases during delayed extinction.

PubMed

Biesdorf, C; Wang, A-L; Topic, B; Petri, D; Milani, H; Huston, J P; de Souza Silva, M A

2015-09-01

Microdialysis studies in rat have generally shown that appetitive stimuli release dopamine (DA) in the nucleus accumbens (NAc) shell and core. Here we examined the release of DA in the NAc during delivery of reward (food) and during extinction of food reward in the freely moving animal by use of in vivo microdialysis and HPLC. Fifty-two male Wistar rats were trained to receive food reward associated with appearance of cue-lights in a Skinner-box during in vivo microdialysis. Different behavioral protocols were used to assess the effects of extinction on DA and its metabolites. Results Exp. 1: (a) During a 20-min period of cued reward delivery, DA increased significantly in the NAc core, but not shell subregion; (b) for the next 60min period half of the rats underwent immediate extinction (with the CS light presented during non-reward) and the other half did not undergo extinction to the cue lights (CS was not presented during non-reward). DA remained significantly increased in both groups, providing no evidence for a decrease in DA during extinction in either NAc core or shell regions. (c) In half of the animals of the group that was not subjected to extinction, the cue lights were turned on for 30min, thus, initiating extinction to cue CS at a 1h delay from the period of reward. In this group DA in the NAc core, but not shell, significantly decreased. Behavioral analysis showed that while grooming is an indicator of extinction-induced behavior, glances toward the cue-lights (sign tracking) are an index of resistance to extinction. Results Exp. 2: (a) As in Exp. 1, during a 30-min period of cued reward delivery, DA levels again increased significantly in the NAc core but not in the NAc shell. (b) When extinction (the absence of reward with the cue lights presented) was administered 24h after the last reward session, DA again significantly decreased in the NAc core, but not in the NAc shell. (a) These results confirm the importance of DA release in the NAc for reward-related states, with DA increasing in the core, but not shell subregion. (b) They provide first evidence that during the withholding of expected reward, DA decreases in the NAc core, but not shell region. (c) This decrease in DA appears only after a delay between delivery of reward and extinction likely due to it being masked by persisting DA release. We hypothesize the decrease in extinction-induced release of DA in the NAc core to be a marker for the despair/depression that is known to accompany the failure to obtain expected rewards/reinforcers. Copyright © 2015 Elsevier Inc. All rights reserved.

Cross-Cultural adaptation of the General Functioning Scale of the Family.

PubMed

Pires, Thiago; Assis, Simone Gonçalves de; Avanci, Joviana Quintes; Pesce, Renata Pires

2016-06-27

To describe the process of cross-cultural adaptation of the General Functioning Scale of the Family, a subscale of the McMaster Family Assessment Device, for the Brazilian population. The General Functioning Scale of the Family was translated into Portuguese and administered to 500 guardians of children in the second grade of elementary school in public schools of Sao Gonçalo, Rio de Janeiro, Southeastern Brazil. The types of equivalences investigated were: conceptual and of items, semantic, operational, and measurement. The study involved discussions with experts, translations and back-translations of the instrument, and psychometric assessment. Reliability and validity studies were carried out by internal consistency testing (Cronbach's alpha), Guttman split-half correlation model, Pearson correlation coefficient, and confirmatory factor analysis. Associations between General Functioning of the Family and variables theoretically associated with the theme (father's or mother's drunkenness and violence between parents) were estimated by odds ratio. Semantic equivalence was between 90.0% and 100%. Cronbach's alpha ranged from 0.79 to 0.81, indicating good internal consistency of the instrument. Pearson correlation coefficient ranged between 0.303 and 0.549. Statistical association was found between the general functioning of the family score and the theoretically related variables, as well as good fit quality of the confirmatory analysis model. The results indicate the feasibility of administering the instrument to the Brazilian population, as it is easy to understand and a good measurement of the construct of interest. Descrever o processo de adaptação transcultural da escala de Funcionamento Geral da Família, subescala da McMaster Family Assessment Device, para a população brasileira. A escala de Funcionamento Geral da Família, original no idioma inglês, foi traduzida para o português e aplicada a 500 responsáveis de crianças do segundo ano do ensino fundamental de escolas públicas do município de São Gonçalo, Rio de Janeiro. Os tipos de equivalências investigados foram: conceitual e de itens, semântica, operacional, e mensuração. O estudo envolveu discussão com especialistas, traduções e retraduções do instrumento e avaliação psicométrica. Foi realizado estudo de confiabilidade e validade, por testagem da consistência interna (alpha de Cronbach), da correlação pelo método de split-half de Guttman e do coeficiente de correlação de Pearson, e por análise fatorial confirmatória. Associações entre Funcionamento Geral da Família e variáveis teoricamente associadas ao tema (embriaguez do pai ou da mãe e violência entre os pais) foram analisadas por estimação de razão de chance. A equivalência semântica encontrada foi entre 90,0% e 100%. O alfa de Cronbach variou de 0,79 a 0,81, indicando boa consistência interna do instrumento. O coeficiente de correlação de Pearson oscilou entre 0,303 e 0,549. Encontrou-se associação estatística entre o escore de funcionamento geral da família e as variáveis teoricamente relacionadas e constatou-se boa qualidade dos ajustes do modelo de análise confirmatória. Os resultados obtidos indicam a aplicabilidade do instrumento na população brasileira, que se mostra de fácil compreensão e boa aferição do constructo de interesse.

Designing and defining dynamic protein cage nanoassemblies in solution

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

Lai, Y. -T.; Hura, G. L.; Dyer, K. N.

Central challenges in the design of large and dynamic macromolecular assemblies for synthetic biology lie in developing effective methods for testing design strategies and their outcomes, including comprehensive assessments of solution behavior. Here, we created and validated an advanced design of a 600-kDa protein homododecamer that self-assembles into a symmetric tetrahedral cage. The monomeric unit is composed of a trimerizing apex-forming domain genetically linked to an edge-forming dimerizing domain. Enhancing the crystallographic results, high-throughput small-angle x-ray scattering (SAXS) comprehensively contrasted our modifications under diverse solution conditions. To generate a phase diagram associating structure and assembly, we developed force plots thatmore » measure dissimilarity among multiple SAXS data sets. These new tools, which provided effective feedback on experimental constructs relative to design, have general applicability in analyzing the solution behavior of heterogeneous nanosystems and have been made available as a web-based application. Specifically, our results probed the influence of solution conditions and symmetry on stability and structural adaptability, identifying the dimeric interface as the weak point in the assembly. Force plots comparing SAXS data sets further reveal more complex and controllable behavior in solution than captured by our crystal structures. Lastly, these methods for objectively and comprehensively comparing SAXS profiles for systems critically affected by solvent conditions and structural heterogeneity provide an enabling technology for advancing the design and bioengineering of nanoscale biological materials.« less

Designing and defining dynamic protein cage nanoassemblies in solution

DOE PAGES

Lai, Y. -T.; Hura, G. L.; Dyer, K. N.; ...

2016-12-14

Central challenges in the design of large and dynamic macromolecular assemblies for synthetic biology lie in developing effective methods for testing design strategies and their outcomes, including comprehensive assessments of solution behavior. Here, we created and validated an advanced design of a 600-kDa protein homododecamer that self-assembles into a symmetric tetrahedral cage. The monomeric unit is composed of a trimerizing apex-forming domain genetically linked to an edge-forming dimerizing domain. Enhancing the crystallographic results, high-throughput small-angle x-ray scattering (SAXS) comprehensively contrasted our modifications under diverse solution conditions. To generate a phase diagram associating structure and assembly, we developed force plots thatmore » measure dissimilarity among multiple SAXS data sets. These new tools, which provided effective feedback on experimental constructs relative to design, have general applicability in analyzing the solution behavior of heterogeneous nanosystems and have been made available as a web-based application. Specifically, our results probed the influence of solution conditions and symmetry on stability and structural adaptability, identifying the dimeric interface as the weak point in the assembly. Force plots comparing SAXS data sets further reveal more complex and controllable behavior in solution than captured by our crystal structures. Lastly, these methods for objectively and comprehensively comparing SAXS profiles for systems critically affected by solvent conditions and structural heterogeneity provide an enabling technology for advancing the design and bioengineering of nanoscale biological materials.« less

HEALTH CONDITIONS LINKED TO AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH DARK ADAPTATION.

PubMed

Laíns, Inês; Miller, John B; Mukai, Ryo; Mach, Steven; Vavvas, Demetrios; Kim, Ivana K; Miller, Joan W; Husain, Deeba

2018-06-01

To determine the association between dark adaption (DA) and different health conditions linked with age-related macular degeneration (AMD). Cross-sectional study, including patients with AMD and a control group. Age-related macular degeneration was graded according to the Age-Related Eye Disease Study (AREDS) classification. We obtained data on medical history, medications, and lifestyle. Dark adaption was assessed with the extended protocol (20 minutes) of AdaptDx (MacuLogix). For analyses, the right eye or the eye with more advanced AMD was selected. Multivariate linear and logistic regressions were performed, accounting for age and AMD stage. Seventy-eight subjects (75.6% AMD; 24.4% controls) were included. Multivariate assessments revealed that body mass index (BMI; β = 0.30, P = 0.045), taking AREDS vitamins (β = 5.51, P < 0.001), and family history of AMD (β = 2.68, P = 0.039) were significantly associated with worse rod intercept times. Abnormal DA (rod intercept time ≥ 6.5 minutes) was significantly associated with family history of AMD (β = 1.84, P = 0.006), taking AREDS supplements (β = 1.67, P = 0.021) and alcohol intake (β = 0.07, P = 0.017). Besides age and AMD stage, a higher body mass index, higher alcohol intake, and a family history of AMD seem to impair DA. In this cohort, the use of AREDS vitamins was also statistically linked with impaired DA, most likely because of an increased severity of disease in subjects taking them.

Three-Dimensional Dynamic Loading of Sand

DTIC Science & Technology

2011-02-01

strength yield strength of 40 MPa. In addition the inclusion of grain-on-grain stiction (friction) plays a major role in the compaction of sand at low...strains Figure 5 Stress-strain behavior for various grain and strength configurations When compared to experimental stre ss-strain data, both...of Materials, DYMAT 2009 Brussels Belgium, pg 1545–1551 [xi] Crawford, D.A. 2005. Using mesoscale modeling to investigate the role of material

Dust acoustic shock waves in magnetized dusty plasma

NASA Astrophysics Data System (ADS)

Yashika, GHAI; Nimardeep, KAUR; Kuldeep, SINGH; N, S. SAINI

2018-07-01

We have presented a theoretical study of the dust acoustic (DA) shock structures in a magnetized, electron depleted dusty plasma in the presence of two temperature superthermal ions. By deriving a Korteweg–de Vries–Burgers equation and studying its shock solution, we aim to highlight the effects of magnetic field and obliqueness on various properties of the DA shock structures in the presence of kappa-distributed two temperature ion population. The present model is motivated by the observations of Geotail spacecraft in the Earth's magnetotail and it is seen that the different physical parameters such as superthermality of the cold and hot ions, the cold to hot ion temperature ratio, the magnetic field strength, obliqueness and the dust kinematic viscosity greatly influence the dynamics of the shock structures so formed. The results suggest that the variation of superthermalities of the cold and hot ions have contrasting effects on both positive and negative polarity shock structures. Moreover, it is noted that the presence of the ambient magnetic field affects the dispersive properties of the medium and tends to make the shock structures less wide and more abrupt. The findings of present investigation may be useful in understanding the dynamics of shock waves in dusty plasma environments containing two temperature ions where the electrons are significantly depleted.

Weakened Intracellular Zn2+-Buffering in the Aged Dentate Gyrus and Its Involvement in Erasure of Maintained LTP.

PubMed

Takeda, Atsushi; Tamano, Haruna; Murakami, Taku; Nakada, Hiroyuki; Minamino, Tatsuya; Koike, Yuta

2018-05-01

Memory is lost by the increased influx of extracellular Zn 2+ into neurons. It is possible that intracellular Zn 2+ dynamics is modified even at non-zincergic medial perforant pathway-dentate granule cell synapses along with aging and that vulnerability to the modification is linked to age-related cognitive decline. To examine these possibilities, vulnerability of long-term potentiation (LTP) maintenance, which underlies memory retention, to modification of synaptic Zn 2+ dynamics was compared between young and aged rats. The influx of extracellular Zn 2+ into dentate granule cells was increased in aged rats after injection of high K + into the dentate gyrus, but not in young rats. This increase impaired maintained LTP in aged rats. However, the impairment was rescued by co-injection of CaEDTA, an extracellular Zn 2+ chelator, or CNQX, an AMPA receptor antagonist, which suppressed the Zn 2+ influx. Maintained LTP was also impaired in aged rats after injection of ZnAF-2DA into the dentate gyrus that chelates intracellular Zn 2+ , but not in young rats. Interestingly, the capacity of chelating intracellular Zn 2+ with intracellular ZnAF-2 was almost lost in the aged dentate gyrus 2 h after injection of ZnAF-2DA into the dentate gyrus, suggesting that intracellular Zn 2+ -buffering is weakened in the aged dentate gyrus, compared to the young dentate gyrus. In the dentate gyrus of aged rats, maintained LTP is more vulnerable to modification of intracellular Zn 2+ dynamics than in young rats, probably due to weakened intracellular Zn 2+ -buffering.

Ionospheric Storm Reconstructions with a Multimodel Ensemble Prdiction System (MEPS) of Data Assimilation Models: Mid and Low Latitude Dynamics

NASA Astrophysics Data System (ADS)

Schunk, R. W.; Scherliess, L.; Eccles, V.; Gardner, L. C.; Sojka, J. J.; Zhu, L.; Pi, X.; Mannucci, A. J.; Komjathy, A.; Wang, C.; Rosen, G.

2016-12-01

As part of the NASA-NSF Space Weather Modeling Collaboration, we created a Multimodel Ensemble Prediction System (MEPS) for the Ionosphere-Thermosphere-Electrodynamics system that is based on Data Assimilation (DA) models. MEPS is composed of seven physics-based data assimilation models that cover the globe. Ensemble modeling can be conducted for the mid-low latitude ionosphere using the four GAIM data assimilation models, including the Gauss Markov (GM), Full Physics (FP), Band Limited (BL) and 4DVAR DA models. These models can assimilate Total Electron Content (TEC) from a constellation of satellites, bottom-side electron density profiles from digisondes, in situ plasma densities, occultation data and ultraviolet emissions. The four GAIM models were run for the March 16-17, 2013, geomagnetic storm period with the same data, but we also systematically added new data types and re-ran the GAIM models to see how the different data types affected the GAIM results, with the emphasis on elucidating differences in the underlying ionospheric dynamics and thermospheric coupling. Also, for each scenario the outputs from the four GAIM models were used to produce an ensemble mean for TEC, NmF2, and hmF2. A simple average of the models was used in the ensemble averaging to see if there was an improvement of the ensemble average over the individual models. For the scenarios considered, the ensemble average yielded better specifications than the individual GAIM models. The model differences and averages, and the consequent differences in ionosphere-thermosphere coupling and dynamics will be discussed.

Development of Patients' Decision Aid for Older Women With Stage I Breast Cancer Considering Radiotherapy After Lumpectomy

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

Wong, Jennifer; D'Alimonte, Laura; Angus, Jan

Purpose: To develop a patient decision aid (PtDA) for older women with Stage I, pathologically node negative, estrogen receptor-positive progesterone receptor-positive breast cancer who are considering adjuvant radiotherapy after lumpectomy and to examine its impact on patients' decision making. Methods and Materials: A PtDA was developed and evaluated in three steps according to the Ottawa Decision Support Framework: (1) needs assessment (n = 16); (2) Pilot I to examine PtDA acceptability (n = 12); and (3) Pilot II, a pretest posttest (n = 38) with older women with estrogen receptor-positive progesterone receptor-positive breast cancer after lumpectomy who were receiving adjuvantmore » radiation therapy. Measures included patients' satisfaction with the PtDA, self-reported decisional conflict, level of distress, treatment-related knowledge, and choice predisposition. Results: The PtDA is a booklet that details each adjuvant treatment option's benefits, risks, and side effects tailored to the patient's clinical profile; includes a values clarification exercise; and includes steps to guide patients towards their decision. On the basis of qualitative comments and satisfaction ratings, all women thought that the PtDA was helpful and informative. In comparison with their baseline scores, patients had a statistically significant (p < 0.05) reduction in decisional conflict (adjusted mean difference [AMD], -7.18; 95% confidence interval [CI], -13.50 to 12.59); increased clarity of the benefits and risks (AMD, -10.86; CI, -20.33 to 21.49); and improved general treatment knowledge (AMD, 8.99; CI, 2.88-10.28) after using the PtDA. General trends were also reported in the patients' choice predisposition scores that suggested potential differences in treatment decision after PtDA use. Conclusions: This study provides evidence that this PtDA may be a helpful educational tool for this group of women. The quality of care for older breast cancer patients may be enhanced by the use of a tailored PtDA to help patients be better informed about their treatment options.« less

Intersectionality and risk for ischemic heart disease in Sweden: Categorical and anti-categorical approaches.

PubMed

Wemrell, Maria; Mulinari, Shai; Merlo, Juan

2017-03-01

Intersectionality theory can contribute to epidemiology and public health by furthering understanding of power dynamics driving production of health disparities, and increasing knowledge about heterogeneities within, and overlap between, social categories. Drawing on McCall, we relate the first of these potential contributions to categorical intersectionality and the second to anti-categorical intersectionality. Both approaches are used in study of risk of ischemic heart disease (IHD), based on register data on 3.6 million adults residing in Sweden by 2010, followed for three years. Categorical intersectionality is here coupled with between-group differences in average risk calculation, as we use intersectional categorizations while estimating odds ratios through logistic regressions. The anti-categorical approach is operationalized through measurement of discriminatory accuracy (DA), i.e., capacity to accurately categorize individuals with or without a certain outcome, through computation of the area under the curve (AUC). Our results show substantial differences in average risk between intersectional groupings. The DA of social categorizations is found to be low, however, due to outcome variability within and overlap between categories. We argue that measures of DA should be used for proper interpretation of differences in average risk between social (or any other) categories. Tension between average between-group risk and the DA of categorizations, which can be related to categorical and anti-categorical intersectional analyses, should be made explicit and discussed to a larger degree in epidemiology and public health. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development and Implementation of Dynamic Scripts to Execute Cycled WRF/GSI Forecasts

NASA Technical Reports Server (NTRS)

Zavodsky, Bradley; Srikishen, Jayanthi; Berndt, Emily; Li, Quanli; Watson, Leela

2014-01-01

Automating the coupling of data assimilation (DA) and modeling systems is a unique challenge in the numerical weather prediction (NWP) research community. In recent years, the Development Testbed Center (DTC) has released well-documented tools such as the Weather Research and Forecasting (WRF) model and the Gridpoint Statistical Interpolation (GSI) DA system that can be easily downloaded, installed, and run by researchers on their local systems. However, developing a coupled system in which the various preprocessing, DA, model, and postprocessing capabilities are all integrated can be labor-intensive if one has little experience with any of these individual systems. Additionally, operational modeling entities generally have specific coupling methodologies that can take time to understand and develop code to implement properly. To better enable collaborating researchers to perform modeling and DA experiments with GSI, the Short-term Prediction Research and Transition (SPoRT) Center has developed a set of Perl scripts that couple GSI and WRF in a cycling methodology consistent with the use of real-time, regional observation data from the National Centers for Environmental Prediction (NCEP)/Environmental Modeling Center (EMC). Because Perl is open source, the code can be easily downloaded and executed regardless of the user's native shell environment. This paper will provide a description of this open-source code and descriptions of a number of the use cases that have been performed by SPoRT collaborators using the scripts on different computing systems.

Assessment of central dopaminergic function using plasma-free homovanillic acid after debrisoquin administration.

PubMed

Riddle, M A; Leckman, J F; Cohen, D J; Anderson, M; Ort, S I; Caruso, K A; Shaywitz, B A

1986-01-01

Central dopaminergic (DA) function in children and adults was assessed by monitoring plasma-free levels of the dopamine metabolite homovanillic acid (pHVA) before and after a single oral dose and chronic oral administration of debrisoquin. Debrisoquin inhibits peripheral metabolism of dopamine to HVA and does not cross the blood-brain barrier. By reducing peripheral formation of HVA through the use of debrisoquin, the remaining HVA in plasma more accurately reflects central DA activity. Debrisoquin administration resulted in marked reductions of pHVA in each of 12 patients studied. Eleven of the 12 subjects tolerated debrisoquin without physical or behavioral side effects. The debrisoquin administration method appears to be a safe and potentially valid technique for evaluating aspects of central dopaminergic function in children and adults.

Metal Speciation in Landfill Leachates with a Focus on the Influence of Organic Matter

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

F Claret; C Tournassat; C Crouzet

This study characterizes the heavy-metal content in leachates collected from eight landfills in France. In order to identify heavy metal occurrence in the different size fractions of leachates, a cascade filtration protocol was applied directly in the field, under a nitrogen gas atmosphere to avoid metal oxidation. The results of analyses performed on the leachates suggest that most of the metals are concentrated in the <30 kDa fraction, while lead, copper and cadmium show an association with larger particles. Initial speciation calculations, without considering metal association with organic matter, suggest that leachate concentrations in lead, copper, nickel and zinc aremore » super-saturated with respect to sulphur phases. Speciation calculations that account for metal complexation with organic matter, considered as fulvic acids based on C1(s) NEXAFS spectroscopy, show that this mechanism is not sufficient to explain such deviation from equilibrium conditions. It is therefore hypothesized that the deviation results also from the influence of biological activity on the kinetics of mineral phase precipitation and dissolution, thus providing a dynamic system. The results of chemical analyses of sampled fluids are compared with speciation calculations and some implications for the assessment of metal mobility and natural attenuation in a context of landfill risk assessment are discussed.« less

Comparative assessment of passive surveillance in disease-free and endemic situation: Example of Brucella melitensis surveillance in Switzerland and in Bosnia and Herzegovina

PubMed Central

Hadorn, Daniela C; Haracic, Sabina Seric; Stärk, Katharina DC

2008-01-01

Background Globalization and subsequent growth in international trade in animals and animal products has increased the importance of international disease reporting. Efficient and reliable surveillance systems are needed in order to document the disease status of a population at a given time. In this context, passive surveillance plays an important role in early warning systems. However, it is not yet routinely integrated in the assessment of disease surveillance systems because different factors like the disease awareness (DA) of people reporting suspect cases influence the detection performance of passive surveillance. In this paper, we used scenario tree methodology in order to evaluate and compare the quality and benefit of abortion testing (ABT) for Brucella melitensis (Bm) between the disease free situation in Switzerland (CH) and a hypothetical disease free situation in Bosnia and Herzegovina (BH), taking into account DA levels assumed for the current endemic situation in BH. Results The structure and input parameters of the scenario tree were identical for CH and BH with the exception of population data in small ruminants and the DA in farmers and veterinarians. The sensitivity analysis of the stochastic scenario tree model showed that the small ruminant population structure and the DA of farmers were important influential parameters with regard to the unit sensitivity of ABT in both CH and BH. The DA of both farmers and veterinarians was assumed to be higher in BH than in CH due to the current endemic situation in BH. Although the same DA cannot necessarily be assumed for the modelled hypothetical disease free situation as for the actual endemic situation, it shows the importance of the higher vigilance of people reporting suspect cases on the probability that an average unit processed in the ABT-component would test positive. Conclusion The actual sensitivity of passive surveillance approaches heavily depends on the context in which they are applied. Scenario tree modelling allows for the evaluation of such passive surveillance system components under assumed disease free situation. Despite data gaps, this is a real opportunity to compare different situations and to explore consequences of changes that could be made. PMID:19099610

Comparative assessment of passive surveillance in disease-free and endemic situation: example of Brucella melitensis surveillance in Switzerland and in Bosnia and Herzegovina.

PubMed

Hadorn, Daniela C; Haracic, Sabina Seric; Stärk, Katharina D C

2008-12-22

Globalization and subsequent growth in international trade in animals and animal products has increased the importance of international disease reporting. Efficient and reliable surveillance systems are needed in order to document the disease status of a population at a given time. In this context, passive surveillance plays an important role in early warning systems. However, it is not yet routinely integrated in the assessment of disease surveillance systems because different factors like the disease awareness (DA) of people reporting suspect cases influence the detection performance of passive surveillance. In this paper, we used scenario tree methodology in order to evaluate and compare the quality and benefit of abortion testing (ABT) for Brucella melitensis (Bm) between the disease free situation in Switzerland (CH) and a hypothetical disease free situation in Bosnia and Herzegovina (BH), taking into account DA levels assumed for the current endemic situation in BH. The structure and input parameters of the scenario tree were identical for CH and BH with the exception of population data in small ruminants and the DA in farmers and veterinarians. The sensitivity analysis of the stochastic scenario tree model showed that the small ruminant population structure and the DA of farmers were important influential parameters with regard to the unit sensitivity of ABT in both CH and BH. The DA of both farmers and veterinarians was assumed to be higher in BH than in CH due to the current endemic situation in BH. Although the same DA cannot necessarily be assumed for the modelled hypothetical disease free situation as for the actual endemic situation, it shows the importance of the higher vigilance of people reporting suspect cases on the probability that an average unit processed in the ABT-component would test positive. The actual sensitivity of passive surveillance approaches heavily depends on the context in which they are applied. Scenario tree modelling allows for the evaluation of such passive surveillance system components under assumed disease free situation. Despite data gaps, this is a real opportunity to compare different situations and to explore consequences of changes that could be made.

Initializing carbon cycle predictions from the Community Land Model by assimilating global biomass observations

NASA Astrophysics Data System (ADS)

Fox, A. M.; Hoar, T. J.; Smith, W. K.; Moore, D. J.

2017-12-01

The locations and longevity of terrestrial carbon sinks remain uncertain, however it is clear that in order to predict long-term climate changes the role of the biosphere in surface energy and carbon balance must be understood and incorporated into earth system models (ESMs). Aboveground biomass, the amount of carbon stored in vegetation, is a key component of the terrestrial carbon cycle, representing the balance of uptake through gross primary productivity (GPP), losses from respiration, senescence and mortality over hundreds of years. The best predictions of current and future land-atmosphere fluxes are likely from the integration of process-based knowledge contained in models and information from observations of changes in carbon stocks using data assimilation (DA). By exploiting long times series, it is possible to accurately detect variability and change in carbon cycle dynamics through monitoring ecosystem states, for example biomass derived from vegetation optical depth (VOD), and use this information to initialize models before making predictions. To make maximum use of information about the current state of global ecosystems when using models we have developed a system that combines the Community Land Model (CLM) with the Data Assimilation Research Testbed (DART), a community tool for ensemble DA. This DA system is highly innovative in its complexity, completeness and capabilities. Here we described a series of activities, using both Observation System Simulation Experiments (OSSEs) and real observations, that have allowed us to quantify the potential impact of assimilating VOD data into CLM-DART on future land-atmosphere fluxes. VOD data are particularly suitable to use in this activity due to their long temporal coverage and appropriate scale when combined with CLM, but their absolute values rely on many assumptions. Therefore, we have had to assess the implications of the VOD retrieval algorithms, with an emphasis on detecting uncertainty due to assumptions and inputs in the algorithms that are incompatible with those encoded within CLM. It is probable that VOD describes changes in biomass more accurately than absolute values, so in additional to sequential assimilation of observations, we have tested alternative filter algorithms, and assimilating VOD anomalies.

Time-dependent effects of perfluorinated compounds on viability in cerebellar granule neurons: Dependence on carbon chain length and functional group attached.

PubMed

Berntsen, Hanne Friis; Bjørklund, Cesilie Granum; Audinot, Jean-Nicolas; Hofer, Tim; Verhaegen, Steven; Lentzen, Esther; Gutleb, Arno Christian; Ropstad, Erik

2017-12-01

The toxicity of long chained perfluoroalkyl acids (PFAAs) has previously been reported to be related to the length of the perfluorinated carbon chain and functional group attached. In the present study, we compared the cytotoxicity of six PFAAs, using primary cultures of rat cerebellar granule neurons (CGNs). Two perfluoroalkyl sulfonic acids (PFSAs, chain length C 6 and C 8 ) and four perfluoroalkyl carboxylic acids (PFCAs, chain length C 8 -C 11 ) were studied. These PFAAs have been detected in human blood and the brain tissue of mammals. The cell viability trypan blue and MTT assays were used to determine toxicity potencies (based on LC 50 values) after 24h exposure (in descending order): perfluoroundecanoic acid (PFUnDA)≥perfluorodecanoic acid (PFDA)>perfluorooctanesulfonic acid potassium salt (PFOS)>perfluorononanoic acid (PFNA)>perfluorooctanoic acid (PFOA)>perfluorohexanesulfonic acid potassium salt (PFHxS). Concentrations of the six PFAAs that produced equipotent effects after 24h exposure were used to further explore the dynamics of viability changes during this period. Therefore viability was assessed at 10, 30, 60, 90, 120 and 180min as well as 6, 12, 18 and 24h. A difference in the onset of reduction in viability was observed, occurring relatively quickly (30-60min) for PFOS, PFDA and PFUnDA, and much slower (12-24h) for PFHxS, PFOA and PFNA. A slight protective effect of vitamin E against PFOA, PFNA and PFOS-induced reduction in viability indicated a possible involvement of oxidative stress. PFOA and PFOS did not induce lipid peroxidation on their own, but significantly accelerated cumene hydroperoxide-induced lipid peroxidation. When distribution of the six PFAAs in the CGN-membrane was investigated using NanoSIMS50 imaging, two distinct patterns appeared. Whereas PFHxS, PFOS and PFUnDA aggregated in large hotspots, PFOA, PFNA and PFDA showed a more dispersed distribution pattern. In conclusion, the toxicity of the investigated PFAAs increased with increasing carbon chain length. For molecules with a similar chain length, a sulfonate functional group led to greater toxicity than a carboxyl group. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a benthic multimetric index for the Serra da Bocaina bioregion in Southeast Brazil.

PubMed

Baptista, D F; Henriques-Oliveira, A L; Oliveira, R B S; Mugnai, R; Nessimian, J L; Buss, D F

2013-08-01

Brazil faces a challenge to develop biomonitoring tools to be used in water quality assessment programs, but few multimetric indices were developed so far. This study is part of an effort to test and implement programs using benthic macroinvertebrates as bioindicators in Rio de Janeiro State. Our aim was first to test the Multimetric Index for Serra dos Órgãos (SOMI) for a different area--Serra da Bocaina (SB)--in the same ecoregion. We sampled 27 streams of different sizes and altitudes in the SB region. Despite the environmental similarities, results indicated biological differences between reference sites of the two regions. Considering these differences, we decided to develop an index specific for the SB region, the Serra da Bocaina Multimetric Index (MISB). We tested twenty-two metrics for sensitivity to impairment and redundancy, and six metrics were considered valid to integrate the MISB: Family Richness, Trichoptera Richness, % Coleoptera, % Diptera, IBE-IOC index, EPT / Chironomidae ratio. A test of the MISB in eleven sites indicated it was more related to land-use and water physico-chemical parameters than with altitude or stream width, being a useful tool for the monitoring and assessment of streams in the bioregion.

Effects of intrinsic aerobic capacity and ovariectomy on voluntary wheel running and nucleus accumbens dopamine receptor gene expression.

PubMed

Park, Young-Min; Kanaley, Jill A; Padilla, Jaume; Zidon, Terese; Welly, Rebecca J; Will, Matthew J; Britton, Steven L; Koch, Lauren G; Ruegsegger, Gregory N; Booth, Frank W; Thyfault, John P; Vieira-Potter, Victoria J

2016-10-01

Rats selectively bred for high (HCR) and low (LCR) aerobic capacity show a stark divergence in wheel running behavior, which may be associated with the dopamine (DA) system in the brain. HCR possess greater motivation for voluntary running along with greater brain DA activity compared to LCR. We recently demonstrated that HCR are not immune to ovariectomy (OVX)-associated reductions in spontaneous cage (i.e. locomotor) activity. Whether HCR and LCR rats differ in their OVX-mediated voluntary wheel running response is unknown. To determine whether HCR are protected from OVX-associated reduction in voluntary wheel running. Forty female HCR and LCR rats (age ~27weeks) had either SHM or OVX operations, and given access to a running wheel for 11weeks. Weekly wheel running distance was monitored throughout the intervention. Nucleus accumbens (NAc) was assessed for mRNA expression of DA receptors at sacrifice. Compared to LCR, HCR ran greater distance and had greater ratio of excitatory/inhibitory DA mRNA expression (both line main effects, P<0.05). Wheel running distance was significantly, positively correlated with the ratio of excitatory/inhibitory DA mRNA expression across animals. In both lines, OVX reduced wheel running (P<0.05). Unexpectedly, although HCR started with significantly greater voluntary wheel running, they had greater OVX-induced reduction in wheel running than LCR such that no differences were found 11weeks after OVX between HCROVX and LCROVX (interaction, P<0.05). This significant reduction in wheel running in HCR was associated with an OVX-mediated reduction in the ratio of excitatory/inhibitory DA mRNA expression. The DA system in the NAc region may play a significant role in motivation to run in female rats. Compared to LCR, HCR rats run significantly more, which associates with greater ratio of excitatory/inhibitory DA mRNA expression. However, despite greater inherent motivation to run and an associated brain DA mRNA expression profile, HCR rats are not protected against OVX-induced reduction in wheel running or OVX-mediated reduction in the ratio of excitatory/inhibitory DA receptor mRNA expression. OVX-mediated reduction in motivated physical activity may be partially explained by a reduced ratio of excitatory/inhibitory DA receptor mRNA expression for which intrinsic fitness does not confer protection. Copyright © 2016 Elsevier Inc. All rights reserved.

Refining Stimulus Parameters in Assessing Infant Speech Perception Using Visual Reinforcement Infant Speech Discrimination: Sensation Level.

PubMed

Uhler, Kristin M; Baca, Rosalinda; Dudas, Emily; Fredrickson, Tammy

2015-01-01

Speech perception measures have long been considered an integral piece of the audiological assessment battery. Currently, a prelinguistic, standardized measure of speech perception is missing in the clinical assessment battery for infants and young toddlers. Such a measure would allow systematic assessment of speech perception abilities of infants as well as the potential to investigate the impact early identification of hearing loss and early fitting of amplification have on the auditory pathways. To investigate the impact of sensation level (SL) on the ability of infants with normal hearing (NH) to discriminate /a-i/ and /ba-da/ and to determine if performance on the two contrasts are significantly different in predicting the discrimination criterion. The design was based on a survival analysis model for event occurrence and a repeated measures logistic model for binary outcomes. The outcome for survival analysis was the minimum SL for criterion and the outcome for the logistic regression model was the presence/absence of achieving the criterion. Criterion achievement was designated when an infant's proportion correct score was >0.75 on the discrimination performance task. Twenty-two infants with NH sensitivity participated in this study. There were 9 males and 13 females, aged 6-14 mo. Testing took place over two to three sessions. The first session consisted of a hearing test, threshold assessment of the two speech sounds (/a/ and /i/), and if time and attention allowed, visual reinforcement infant speech discrimination (VRISD). The second session consisted of VRISD assessment for the two test contrasts (/a-i/ and /ba-da/). The presentation level started at 50 dBA. If the infant was unable to successfully achieve criterion (>0.75) at 50 dBA, the presentation level was increased to 70 dBA followed by 60 dBA. Data examination included an event analysis, which provided the probability of criterion distribution across SL. The second stage of the analysis was a repeated measures logistic regression where SL and contrast were used to predict the likelihood of speech discrimination criterion. Infants were able to reach criterion for the /a-i/ contrast at statistically lower SLs when compared to /ba-da/. There were six infants who never reached criterion for /ba-da/ and one never reached criterion for /a-i/. The conditional probability of not reaching criterion by 70 dB SL was 0% for /a-i/ and 21% for /ba-da/. The predictive logistic regression model showed that children were more likely to discriminate the /a-i/ even when controlling for SL. Nearly all normal-hearing infants can demonstrate discrimination criterion of a vowel contrast at 60 dB SL, while a level of ≥70 dB SL may be needed to allow all infants to demonstrate discrimination criterion of a difficult consonant contrast. American Academy of Audiology.

What can the National Lake Assessment Tell Us about Ecosystem Service Benefits in Lakes

EPA Science Inventory

The condition of lakes, ponds, and reservoirs is often viewed as existing along a continuum from pristine to impacted. The 2007 National Lake Survey was conducted to assess the condition of the nation’s lakes. Over 1,000 lakes were surveyed and detailed physical and chemical da...

Assessing Nation-wide Distributions of Contaminant Levels in Selected Finfish and Shellfish from the Estuaries of the United States

EPA Science Inventory

The toxicity of mercury is well documented and has led to laws and regulations governing its use and disposal; however mercury contamination of coastal and estuarine biota continues to be of public concern. The U.S. EPA Environmental Monitoring and Assessment Program provided da...

Should the United States Army Adapt New Conditions in Its HIV Policy to Allow Eligible HIV Positive Soldiers the Ability to Serve Overseas

DTIC Science & Technology

2017-06-09

Institutes of Health OCONUS Outside the Continental United States PCS Permanent Change of Station PEB Physical Evaluation Board PEP Post-Exposure...a Physical Evaluation Board (PEB) (DA 2014a 14; DA 2016, 23). “For Active Army Soldiers and RC Soldiers on active duty for more than 30 days...based upon the information from the MEB (Kem 2017). This includes assessing if the Soldier is physically capable of performing their MOS duties and

Habitat Modeling of Marine Mammals as Function of Oceanographic Characteristics; Development of Predictive Tools for Assessing and Managing the Risks and the Impacts due to Sound Emissions

DTIC Science & Technology

2010-09-30

Arianna Azzellino Piazza Leonardo da Vinci , 32, 20133 Milano, Italy. phone: (+39) 02-239-964-31 fax: (+39) 02-239-964-99 email...5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Piazza Leonardo da Vinci , 32,20133...Manning CRV Leonardo RV Urania Positve Effort * (km) 2339.39 1700.54 3401.03 504 BW sightings 0 24 2 16 BW cluster of acoustic detections

Habitat Modeling and Preferences of Marine Mammals as a Function of Oceanographic Characteristics; Development of Predictive Tools for Assessing the Risks and the Impacts Due to Sound Emissions

DTIC Science & Technology

2012-09-30

Arianna Azzellino Piazza Leonardo da Vinci , 32, 20133 Milano, Italy. phone: (+39) 02-239-964-31 fax: (+39) 02-239-964-99 email...PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Piazza Leonardo da Vinci , 32, 20133 Milano, Italy. 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING...ITS A. Magnagni ITS A. Magnagni T-boat Manning CRV Leonardo RV Urania Positve Effort * (km) 2339.39 1700.54 3401.03 504 BW sightings 0

[The incidence of the pituitary autoantibodies in Addison disease].

PubMed

Gut, Paweł; Kosowicz, Jerzy; Ziemnicka, Katarzyna; Baczyk, Maciej; Sowiński, Jerzy

2008-01-01

Addison disease (primary insufficience of adrenal cortex) characterized by clinical signs and symptoms associated with deficiency of adrenal hormones. The most frequent etiopathogenesis of Addison disease is related with autoimmunization. In sera of Addison patients are detectable autoantibodies against another endocrine glands. The aim of the study was evaluation of pituitary autoantibodies in Addison disease patients using immunoblotting methods. Studies were performed in 19 Addison disease patients, 16 women (age range: 28-63 yrs, median: 43.5 +/- 8.9) and 3 men (age range: 18-45 yrs, median: 30.6 +/- 9.8). All patients presented signs and symptoms typical of primary insufficiency of adrenal cortex. Sera of control subjects were obtained from 10 healthy blood donors, 7 women, 3 men (age range 21-45 yrs, median: 30.6 +/- 7.1). Incidence of pituitary autoantibodies was assessed by polyacrylamide electrophoresis gel and western-blotting. Pituitary microsomes were obtained from human pituitary tissues by ultracentrifugation and solubilisation in 1% desoxycholic acid. In 14 sera from 19 we detected autoantibodies against pituitary microsomal antigen 67 kDa, 12 sera were recting with 60 kDa and 10 sera with 55 kDa. It is important to note that 10 sera were reacting with 67 and 55 kDa, and 9 sera with 55, 60 and 67 kDa. In sera of Addison disease patients autoantibodies against pituitary microsomal antigens can be frequently detected. The most frequent are antibodies against 55, 60 and 67 kDa antigens.

Dynamin-mediated endocytosis is required for tube closure, cell intercalation, and biased apical expansion during epithelial tubulogenesis in the Drosophila ovary

PubMed Central

Peters, Nathaniel C.

2015-01-01

Most metazoans are able to grow beyond a few hundred cells and to support differentiated tissues because they elaborate multicellular, epithelial tubes that are indispensable for nutrient and gas exchange. To identify and characterize the cellular behaviors and molecular mechanisms required for the morphogenesis of epithelial tubes (i.e., tubulogenesis), we have turned to the D. melanogaster ovary. Here, epithelia surrounding the developing egg chambers first pattern, then form and extend a set of simple, paired, epithelial tubes, the dorsal appendage (DA) tubes, and they create these structures in the absence of cell division or cell death. This genetically tractable system lets us assess the relative contributions that coordinated changes in cell shape, adhesion, orientation, and migration make to basic epithelial tubulogenesis. We find that Dynamin, a conserved regulator of endocytosis and the cytoskeleton, serves a key role in DA tubulogenesis. We demonstrate that Dynamin is required for distinct aspects of DA tubulogenesis: DA-tube closure, DA-tube-cell intercalation, and biased apical-luminal cell expansion. We provide evidence that Dynamin promotes these processes by facilitating endocytosis of cell-cell and cell-matrix adhesion complexes, and we find that precise levels and sub-cellular distribution of E-Cadherin and specific Integrin subunits impact DA tubulogenesis. Thus, our studies identify novel morphogenetic roles (i.e., tube closure and biased apical expansion), and expand upon established roles (i.e., cell intercalation and adhesion remodeling), for Dynamin in tubulogenesis. PMID:26542010

Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients.

PubMed

da Silva, Tatiana Pereira; Giacoia-Gripp, Carmem Beatriz Wagner; Schmaltz, Carolina A; Sant'Anna, Flavia Marinho; Saad, Maria Helena; Matos, Juliana Arruda de; de Lima E Silva, Julio Castro Alves; Rolla, Valeria Cavalcanti; Morgado, Mariza Gonçalves

2017-09-06

Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution. This is a longitudinal study nested in a clinical trial, where cART was initiated during the baseline visit (D0), which occurred 30 ± 10 days after the introduction of anti-TB therapy. Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. The production of IFN-γ upon in vitro stimulation with Mtb antigens purified protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at baseline and follow-up visits. Sixty-one patients, all ART-naïve, were selected and included in the immune reconstitution analysis; seven (11.5%) developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and increased in the first 60 days after cART initiation. In multivariate analysis, the variables independently associated with increased IFN-γ production in response to PPD antigen were CD4 + T cell counts <200 cells/mm 3 at baseline, age, site of tuberculosis, 800 mg efavirenz dose and follow-up CD4 + T cell counts. Moreover, the factors associated with the production of IFN-γ in response to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4 + T cell counts at follow-up visits of ≥200 cells/mm 3 . These findings highlight the differences in immune response according to the specificity of the Mtb antigen, which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-γ production elicited by PPD and 38 kDa/CFP-10 antigens have a greater magnitude compared to ESAT-6 and are associated with different factors. The low response to ESAT-6, even during immune restoration, suggests that this antigen is not adequate to assess the immune response of immunosuppressed TB-HIV patients.

Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters

PubMed Central

Can, Adem; Zanos, Panos; Moaddel, Ruin; Kang, Hye Jin; Dossou, Katinia S. S.; Wainer, Irving W.; Cheer, Joseph F.; Frost, Douglas O.; Huang, Xi-Ping

2016-01-01

Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine’s antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition. These antidepressant actions of (2S,6S;2R,6R)-HNK, or other metabolites, as well as ketamine’s side effects, including abuse potential, may be related to direct effects on components of the dopaminergic (DAergic) system. Here, brain and blood distribution/clearance and pharmacodynamic analyses at DA receptors (D1–D5) and the DA, norepinephrine, and serotonin transporters were assessed for ketamine and its major metabolites (norketamine, dehydronorketamine, and HNKs). Additionally, we measured electrically evoked mesolimbic DA release and decay using fast-scan cyclic voltammetry following acute administration of subanesthetic doses of ketamine (2, 10, and 50 mg/kg, i.p.). Following ketamine injection, ketamine, norketamine, and multiple hydroxynorketamines were detected in the plasma and brain of mice. Dehydronorketamine was detectable in plasma, but concentrations were below detectable limits in the brain. Ketamine did not alter the magnitude or kinetics of evoked DA release in the nucleus accumbens in anesthetized mice. Neither ketamine’s enantiomers nor its metabolites had affinity for DA receptors or the DA, noradrenaline, and serotonin transporters (up to 10 μM). These results suggest that neither the side effects nor antidepressant actions of ketamine or ketamine metabolites are associated with direct effects on mesolimbic DAergic neurotransmission. Previously observed in vivo changes in DAergic neurotransmission following ketamine administration are likely indirect. PMID:27469513

Augmentation of Heroin Seeking Following Chronic Food Restriction in the Rat: Differential Role for Dopamine Transmission in the Nucleus Accumbens Shell and Core.

PubMed

D'Cunha, Tracey M; Daoud, Emilie; Rizzo, Damaris; Bishop, Audrey B; Russo, Melissa; Mourra, Gabrielle; Hamel, Laurie; Sedki, Firas; Shalev, Uri

2017-04-01

Caloric restriction during drug abstinence increases the risk for relapse in addicts. In rats, chronic food restriction during a period of withdrawal following heroin self-administration augments heroin seeking. The mechanisms underlying this effect are largely unknown. Here, we investigated the role of nucleus accumbens (NAc) shell and core dopamine (DA) in food restriction-induced augmentation of heroin seeking. Rats were trained to self-administer heroin (0.1 mg/kg/infusion) for 10 days. Next, rats were moved to the animal colony for a withdrawal period, during which rats were food restricted to 90% of their original body weight (FDR group) or given unrestricted access to food (sated group). On day 14 of food restriction, rats were returned to the operant conditioning chambers for a heroin-seeking test under extinction conditions. Extracellular DA levels were assessed using in vivo microdialysis. In separate experiments, the DA D1-like receptor antagonist SCH39166 (12.5, 25.0, or 50.0 ng/side) was administered into the NAc before the heroin-seeking test. In the NAc shell, pre-test exposure to the heroin-associated context increased DA only in FDR rats; but in the NAc core, DA increased regardless of feeding condition. Food restriction significantly augmented heroin seeking and increased DA in the NAc shell and core during the test. Intra-NAc shell administration of SCH39166 decreased heroin seeking in all rats. In contrast, in the NAc core, SCH39166 selectively decreased the augmentation of heroin-seeking induced by chronic food restriction. Taken together, these results suggest that activation of the DA D1-like receptor in the NAc core is important for food restriction-induced augmentation of heroin seeking.

Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity.

PubMed

Dunn, Julia P; Kessler, Robert M; Feurer, Irene D; Volkow, Nora D; Patterson, Bruce W; Ansari, Mohammad S; Li, Rui; Marks-Shulman, Pamela; Abumrad, Naji N

2012-05-01

Midbrain dopamine (DA) neurons, which are involved with reward and motivation, are modulated by hormones that regulate food intake (insulin, leptin, and acyl ghrelin [AG]). We hypothesized that these hormones are associated with deficits in DA signaling in obesity. We assessed the relationships between fasting levels of insulin and leptin, and AG, BMI, and insulin sensitivity index (S(I)) with the availability of central DA type 2 receptor (D2R). We measured D2R availability using positron emission tomography and [(18)F]fallypride (radioligand that competes with endogenous DA) in lean (n = 8) and obese (n = 14) females. Fasting hormones were collected prior to scanning and S(I) was determined by modified oral glucose tolerance test. Parametric image analyses revealed associations between each metabolic measure and D2R. The most extensive findings were negative associations of AG with clusters involving the striatum and inferior temporal cortices. Regional regression analyses also found extensive negative relationships between AG and D2R in the caudate, putamen, ventral striatum (VS), amygdala, and temporal lobes. S(I) was negatively associated with D2R in the VS, while insulin was not. In the caudate, BMI and leptin were positively associated with D2R availability. The direction of associations of leptin and AG with D2R availability are consistent with their opposite effects on DA levels (decreasing and increasing, respectively). After adjusting for BMI, AG maintained a significant relationship in the VS. We hypothesize that the increased D2R availability in obese subjects reflects relatively reduced DA levels competing with the radioligand. Our findings provide evidence for an association between the neuroendocrine hormones and DA brain signaling in obese females.

Assessment of in vivo organ-uptake and in silico prediction of CYP mediated metabolism of DA-Phen, a new dopaminergic agent.

PubMed

Sutera, Flavia Maria; Giannola, Libero Italo; Murgia, Denise; De Caro, Viviana

2017-12-01

The drug development process strives to predict metabolic fate of a drug candidate, together with its uptake in major organs, whether they act as target, deposit or metabolism sites, to the aim of establish a relationship between the pharmacodynamics and the pharmacokinetics and highlight the potential toxicity of the drug candidate. The present study was aimed at evaluating the in vivo uptake of 2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) - a new dopaminergic neurotransmission modulator, in target and non-target organs of animal subjects and integrating these data with SMARTCyp results, an in silico method that predicts the sites of cytochrome P450-mediated metabolism of drug-like molecules. Wistar rats, subjected to two different behavioural studies in which DA-Phen was intraperitoneally administrated at a dose equal to 0.03mmol/kg, were sacrificed after the experimental protocols and their major organs were analysed to quantify the drug uptake. The data obtained were integrated with in silico prediction of potential metabolites of DA-Phen using the SmartCYP predictive tool. DA-Phen reached quantitatively the Central Nervous System and the results showed that the amide bond of the DA-Phen is scarcely hydrolysed as it was found intact in analyzed organs. As a consequence, it is possible to assume that DA-Phen acts as dopaminergic modulator per se and not as a Dopamine prodrug, thus avoiding peripheral release and toxic side effects due to the endogenous neurotransmitter. Furthermore the identification of potential metabolites related to biotransformation of the drug candidate leads to a more careful evaluation of the appropriate route of administration for future intended therapeutic aims and potential translation into clinical studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intra-accumbens injections of the adenosine A2A agonist CGS 21680 affect effort-related choice behavior in rats

PubMed Central

Font, Laura; Mingote, Susana; Farrar, Andrew M.; Pereira, Mariana; Worden, Lila; Stopper, Colin; Port, Russell G.

2009-01-01

Rationale Nucleus accumbens dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired accumbens DA transmission reallocate their behavior away from food-reinforced activities that have high response requirements and instead select less-effortful types of food-seeking behavior. Although accumbens DA is considered a critical component of the brain circuitry regulating effort-related processes, emerging evidence also implicates adenosine A2A receptors. Objective The present work was undertaken to test the hypothesis that accumbens A2A receptor stimulation would produce effects similar to those produced by DA depletion or antagonism. Materials and methods Three experiments assessed the effects of the adenosine A2A agonist CGS 21680 on performance of a concurrent choice task (lever pressing for preferred food vs. intake of less preferred chow) that is known to be sensitive to DA antagonists and accumbens DA depletions. Results Systemic injections of CGS 21680 reduced lever pressing but did not increase feeding. In contrast, bilateral infusions of the adenosine A2A receptor agonist CGS 21680 (6.0–24.0 ng) into the nucleus accumbens decreased lever pressing for the preferred food but substantially increased consumption of the less preferred chow. Injections of CGS 21680 into a control site dorsal to the accumbens were ineffective. Conclusions Taken together, these results are consistent with the hypothesis that local stimulation of adenosine A2A receptors in nucleus accumbens produces behavioral effects similar to those induced by accumbens DA depletions. Accumbens adenosine A2A receptors appear to be a component of the brain circuitry regulating effort-related choice behavior. PMID:18491078

Dopamine D₂-Like Receptors and Behavioral Economics of Food Reinforcement.

PubMed

Soto, Paul L; Hiranita, Takato; Xu, Ming; Hursh, Steven R; Grandy, David K; Katz, Jonathan L

2016-03-01

Previous studies suggest dopamine (DA) D2-like receptor involvement in the reinforcing effects of food. To determine contributions of the three D2-like receptor subtypes, knockout (KO) mice completely lacking DA D2, D3, or D4 receptors (D2R, D3R, or D4R KO mice) and their wild-type (WT) littermates were exposed to a series of fixed-ratio (FR) food-reinforcement schedules in two contexts: an open economy with additional food provided outside the experimental setting and a closed economy with all food earned within the experimental setting. A behavioral economic model was used to quantify reinforcer effectiveness with food pellets obtained as a function of price (FR schedule value) plotted to assess elasticity of demand. Under both economies, as price increased, food pellets obtained decreased more rapidly (ie, food demand was more elastic) in DA D2R KO mice compared with WT littermates. Extinction of responding was studied in two contexts: by eliminating food deliveries and by delivering food independently of responding. A hyperbolic model quantified rates of extinction. Extinction in DA D2R KO mice occurred less rapidly compared with WT mice in both contexts. Elasticity of food demand was higher in DA D4R KO than WT mice in the open, but not closed, economy. Extinction of responding in DA D4R KO mice was not different from that in WT littermates in either context. No differences in elasticity of food demand or extinction rate were obtained in D3R KO mice and WT littermates. These results indicate that the D2R is the primary DA D2-like receptor subtype mediating the reinforcing effectiveness of food.

Asymptomatic Elite Adolescent Tennis Players' Signs of Tendinosis in Their Dominant Shoulder Compared With Their Nondominant Shoulder

PubMed Central

Johansson, Fredrik R.; Skillgate, Eva; Adolfsson, Anders; Jenner, Göran; DeBri, Edin; Swärdh, Leif; Cools, Ann M.

2015-01-01

Context Tennis is an asymmetric overhead sport with specific muscle-activation patterns, especially eccentrically in the rotator cuff. Magnetic resonance imaging (MRI) findings in asymptomatic adolescent elite tennis players have not previously been reported. Objective The first aim of the study was to describe MRI findings regarding adaptations or abnormalities, as well as muscle cross-sectional area (CSA), of the rotator cuff. The second aim of the study was to investigate the rotator cuff based on the interpretation of the MRI scans as normal versus abnormal, with the subdivision based on the grade of tendinosis, and its association with eccentric rotator cuff strength in the dominant arm (DA) of the asymptomatic elite adolescent tennis player. Setting Testing environment at the radiology department of Medicinsk Röntgen AB. Patients or Other Participants Thirty-five asymptomatic elite tennis players (age = 17.4 ± 2.7 years) were selected based on ranking and exposure time. Intervention(s) We assessed MRI scans and measured the CSA of the rotator cuff muscle. The non-DA (NDA) was used as a control. In addition, eccentric testing of the external rotators of the DA was performed with a handheld dynamometer. Results The DA and NDA displayed different frequencies of infraspinatus tendinosis (grade 1 changes) (P < .05). Rotator cuff measurements revealed larger infraspinatus and teres minor CSA (P < .05) in the DA than in the NDA. Mean eccentric external-rotation strength in the DA stratified by normal tendon and tendinosis was not different between groups (P = .723). Conclusions Asymptomatic adolescent elite tennis players demonstrated infraspinatus tendinosis more frequently in the DA than in the NDA. Clinicians must recognize these tendon changes in order to modify conditioning and performance programs appropriately. PMID:26651279

Mephedrone does not damage dopamine nerve endings of the striatum, but enhances the neurotoxicity of methamphetamine, amphetamine, and MDMA.

PubMed

Angoa-Pérez, Mariana; Kane, Michael J; Briggs, Denise I; Francescutti, Dina M; Sykes, Catherine E; Shah, Mrudang M; Thomas, David M; Kuhn, Donald M

2013-04-01

Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its re-uptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamine-induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20, or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (four injections of 2.5 or 5.0 mg/kg at 2 h intervals). The integrity of DA nerve endings of the striatum was assessed through measures of DA, DAT, and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and 3,4-methylenedioxymethamphetamine on DA nerve endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. As mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA nerve endings mask a potentially dangerous interaction with drugs that are often co-abused with it, leading to heightened neurotoxicity. © 2012 International Society for Neurochemistry.

The Role of Endogenous Serotonin in Methamphetamine-Induced Neurotoxicity to Dopamine Nerve Endings of the Striatum

PubMed Central

Thomas, David M.; Angoa-Pérez, Mariana; Francescutti-Verbeem, Dina M.; Shah, Mrudang M.; Kuhn, Donald M.

2010-01-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the striatum where long-term DA depletion and microglial activation are maximal. Endogenous DA has been implicated as a critical participant in METH-induced neurotoxicity, most likely as a substrate for non-enzymatic oxidation by METH-generated reactive oxygen species (ROS). The striatum is also extensively innervated by serotonin (5HT) nerve endings and this neurochemical system is modified by METH in much the same manner as seen in DA nerve endings (i.e., increased release of 5HT, loss of function in tryptophan hydroxylase and the serotonin transporter, long-term depletion of 5HT stores). 5HT can also be modified by ROS to form highly reactive species that damage neurons but its role in METH neurotoxicity has not been assessed. Increases in 5HT levels with 5HTP do not change METH-induced neurotoxicity to the DA nerve endings as revealed by reductions in DA, tyrosine hydroxylase and dopamine transporter levels. Partial reductions in 5HT with p-chlorophenylalanine (PCPA) are without effect on METH toxicity, despite the fact that PCPA largely prevents METH-induced hyperthermia. Mice lacking the gene for brain tryptophan hydroxylase 2 are devoid of brain 5HT and respond to METH in the same manner as wild-type controls, despite showing enhanced drug-induced hyperthermia. Taken together, the present results indicate that endogenous 5HT does not appear to play a role in METH-induced damage to DA nerve endings of the striatum. PMID:20722968

The role of endogenous serotonin in methamphetamine-induced neurotoxicity to dopamine nerve endings of the striatum.

PubMed

Thomas, David M; Angoa Pérez, Mariana; Francescutti-Verbeem, Dina M; Shah, Mrudang M; Kuhn, Donald M

2010-11-01

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the striatum where long-term DA depletion and microglial activation are maximal. Endogenous DA has been implicated as a critical participant in METH-induced neurotoxicity, most likely as a substrate for non-enzymatic oxidation by METH-generated reactive oxygen species. The striatum is also extensively innervated by serotonin (5HT) nerve endings and this neurochemical system is modified by METH in much the same manner as seen in DA nerve endings (i.e., increased release of 5HT, loss of function in tryptophan hydroxylase and the serotonin transporter, long-term depletion of 5HT stores). 5HT can also be modified by reactive oxygen species to form highly reactive species that damage neurons but its role in METH neurotoxicity has not been assessed. Increases in 5HT levels with 5-hydroxytryptophan do not change METH-induced neurotoxicity to the DA nerve endings as revealed by reductions in DA, tyrosine hydroxylase and dopamine transporter levels. Partial reductions in 5HT with p-chlorophenylalanine are without effect on METH toxicity, despite the fact that p-chlorophenylalanine largely prevents METH-induced hyperthermia. Mice lacking the gene for brain tryptophan hydroxylase 2 are devoid of brain 5HT and respond to METH in the same manner as wild-type controls, despite showing enhanced drug-induced hyperthermia. Taken together, the present results indicate that endogenous 5HT does not appear to play a role in METH-induced damage to DA nerve endings of the striatum. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.

Dopamine D2-Like Receptors and Behavioral Economics of Food Reinforcement

PubMed Central

Soto, Paul L; Hiranita, Takato; Xu, Ming; Hursh, Steven R; Grandy, David K; Katz, Jonathan L

2016-01-01

Previous studies suggest dopamine (DA) D2-like receptor involvement in the reinforcing effects of food. To determine contributions of the three D2-like receptor subtypes, knockout (KO) mice completely lacking DA D2, D3, or D4 receptors (D2R, D3R, or D4R KO mice) and their wild-type (WT) littermates were exposed to a series of fixed-ratio (FR) food-reinforcement schedules in two contexts: an open economy with additional food provided outside the experimental setting and a closed economy with all food earned within the experimental setting. A behavioral economic model was used to quantify reinforcer effectiveness with food pellets obtained as a function of price (FR schedule value) plotted to assess elasticity of demand. Under both economies, as price increased, food pellets obtained decreased more rapidly (ie, food demand was more elastic) in DA D2R KO mice compared with WT littermates. Extinction of responding was studied in two contexts: by eliminating food deliveries and by delivering food independently of responding. A hyperbolic model quantified rates of extinction. Extinction in DA D2R KO mice occurred less rapidly compared with WT mice in both contexts. Elasticity of food demand was higher in DA D4R KO than WT mice in the open, but not closed, economy. Extinction of responding in DA D4R KO mice was not different from that in WT littermates in either context. No differences in elasticity of food demand or extinction rate were obtained in D3R KO mice and WT littermates. These results indicate that the D2R is the primary DA D2-like receptor subtype mediating the reinforcing effectiveness of food. PMID:26205210

High-resolution NMR spectroscopy of encapsulated proteins dissolved in low-viscosity fluids

PubMed Central

Nucci, Nathaniel V.; Valentine, Kathleen G.; Wand, A. Joshua

2014-01-01

High-resolution multi-dimensional solution NMR is unique as a biophysical and biochemical tool in its ability to examine both the structure and dynamics of macromolecules at atomic resolution. Conventional solution NMR approaches, however, are largely limited to examinations of relatively small (< 25 kDa) molecules, mostly due to the spectroscopic consequences of slow rotational diffusion. Encapsulation of macromolecules within the protective nanoscale aqueous interior of reverse micelles dissolved in low viscosity fluids has been developed as a means through which the ‘slow tumbling problem’ can be overcome. This approach has been successfully applied to diverse proteins and nucleic acids ranging up to 100 kDa, considerably widening the range of biological macromolecules to which conventional solution NMR methodologies may be applied. Recent advances in methodology have significantly broadened the utility of this approach in structural biology and molecular biophysics. PMID:24656086

Propaganda and Philanthropy: The Institute Bento da Rocha Cabral, the Lisbon Site of Biochemistry (1925-1953).

PubMed

Carneiro, Ana; Amaral, Isabel

2015-05-01

This paper focuses on the internal organization and dynamics of the Institute Bento da Rocha Cabral (IRC) in Lisbon, a privately-funded institution devoted to biomedical research, from the particular vantage point of its laboratory of biochemistry; in particular, the process through which the institution turned from medically-related to chemically-related research in the period spanning from 1925 to 1953. The history of the IRC raises interesting questions regarding the social politics of science as it materialized the desire of leading physicians of the Faculty of Medicine of Lisbon to create proper physical facilities for medically-related scientific research. We argue that the process which led to the creation of the IRC coincided with the gradual professional and political ascendance of physicians in Portuguese society initiated in the late nineteenth century, and is closely associated with Portuguese republicanism and the process of Lisbon becoming the scientific capital.

Dealing with Uncertainties in Initial Orbit Determination

NASA Technical Reports Server (NTRS)

Armellin, Roberto; Di Lizia, Pierluigi; Zanetti, Renato

2015-01-01

A method to deal with uncertainties in initial orbit determination (IOD) is presented. This is based on the use of Taylor differential algebra (DA) to nonlinearly map the observation uncertainties from the observation space to the state space. When a minimum set of observations is available DA is used to expand the solution of the IOD problem in Taylor series with respect to measurement errors. When more observations are available high order inversion tools are exploited to obtain full state pseudo-observations at a common epoch. The mean and covariance of these pseudo-observations are nonlinearly computed by evaluating the expectation of high order Taylor polynomials. Finally, a linear scheme is employed to update the current knowledge of the orbit. Angles-only observations are considered and simplified Keplerian dynamics adopted to ease the explanation. Three test cases of orbit determination of artificial satellites in different orbital regimes are presented to discuss the feature and performances of the proposed methodology.

Evaluation of Technologies to Prevent Precipitation During Water Recovery from Urine

NASA Technical Reports Server (NTRS)

Broyan, James L., Jr.; Pickering, Karen D.; Adam, Niklas M.; Mitchell, Julie L.; Anderson, Molly S.; Carter, Layne; Muirhead, Dean; Gazda, Daniel B.

2011-01-01

The International Space Station (ISS) Urine Processor Assembly (UPA) experienced a hardware failure in the Distillation Assembly (DA) in October 2010. Initially the UPA was operated to recover 85% of the water from urine through distillation, concentrating the contaminants in the remaining urine. The DA failed due to precipitation of calcium sulfate (gypsum) which caused a loss of UPA function. The ISS UPA operations have been modified to only recover 70% of the water minimizing gypsum precipitation risk but substantially increasing water resupply needs. This paper describes the feasibility assessment of several technologies (ion exchange, chelating agents, threshold inhibitors, and Lorentz devices) to prevent gypsum precipitation. The feasibility assessment includes the development of assessment methods, chemical modeling, bench top testing, and validation testing in a flight-like ground UPA unit. Ion exchange technology has been successfully demonstrated and has been recommended for further development. The incorporation of the selected technology will enable water recovery to be increased from 70% back to the original 85% and improve the ISS water balance.

Nonlinear Hyperbolic Equations - Theory, Computation Methods, and Applications. Volume 24. Note on Numerical Fluid Mechanics

DTIC Science & Technology

1989-01-01

Calculations and Experiments (B.van den Berg/ D.A. Humphreysl E. Krause /J.P. F. Lindhout) Volume 20 Proceedings of the Seventh GAMM-Conference on...GRID METHODS FOR HYPERBOLIC PROBLEMS Wolfgang Hackbusch Sigrid Hagemann Institut fUr Informatik und Praktische Mathematik Christian-Albrechts...Euler Equations. Proceedings of the 8th Inter- national Conference on Numerical Methods in Fluid Dynamics (E. Krause , ed.), Aachen, 1988. Springer

A Fixed-Wing Aircraft Simulation Tool for Improving the efficiency of DoD Acquisition

DTIC Science & Technology

2015-10-05

simulation tool , CREATETM-AV Helios [12-14], a high fidelity rotary wing vehicle simulation tool , and CREATETM-AV DaVinci [15-16], a conceptual through...05/2015 Oct 2008-Sep 2015 A Fixed-Wing Aircraft Simulation Tool for Improving the Efficiency of DoD Acquisition Scott A. Morton and David R...multi-disciplinary fixed-wing virtual aircraft simulation tool incorporating aerodynamics, structural dynamics, kinematics, and kinetics. Kestrel allows

The Security Dynamics of Demographic Factors

DTIC Science & Technology

2000-01-01

Tianjin, Manila, Cairo, Seoul, Istanbul, Rio de Janeiro , Buenos Aires, Lahore, Hyderabad, Bangkok, Lima, and Tehran. Chapter Four THE SECURITY...Street, Santa Monica, CA, 90407-2138, e -mail Julie_DaVanzo@rand.org, or visit the project’s Web site at http://www.rand.org/popmatters For more...Third and finally, some basic recommendations for U.S. pol- icy will be offered in light of the emerging demographic realities. WHAT DO WE MEAN BY

ASSESSMENT OF BODY FAT IN OBESE PATIENTS PREOPERATIVELY FOR BARIATRIC SURGERY.

PubMed

Fernandez, Mônica; Toimil, Rosana Farah; Rasslan, Zied; Ilias, Elias Jirjoss; Gradinar, Ana Lúcia Torloni; Malheiros, Carlos Alberto

The study of body composition in patient candidates for bariatric surgery is directly related to the increase and distribution of body fat in the development of cardiovascular disease. To correlate anthropometric indicators and bioelectrical impedance in the assessment of body fat in female candidates for bariatric surgery. Cross-sectional, observational study of 88 women. The weight, height, body mass index and waist circumference data were evaluated in the anthropometric analysis. The body fat was determinate by bioelectrical impedance conducted according to the manufacturer´s recommended technique with a specific severe obesity formula. The patients were divided into two subgroups according to the average waist circumference and body mass index for better analysis of the results. The group had a mean age of 39.7 years (±7.2), average weight of 125.6 kg (±16.2), mean body mass index of 48.7 kg/m2 (±6.4) and the mean waist circumference 137.6 cm (±12.4). Negative and significant relationship between BMI values waist circumference and resistance obtained by bioelectrical impedance ​​were found. By analyzing the two groups the mean BMI and waist circumference, a significant relationship was observed, ie, the higher the degree of obesity less resistance was obtained by bioelectrical impedance. The higher is the obesity the lower is value found for resistance. The increase of anthropometric indicators (BMI and waist circumference) determined reduction in resistance and reactance obtained by bioelectrical impedance analysis in obese women candidates to bariatric surgery. O estudo da composição corporal em pacientes candidatas à cirurgia bariátrica tem relação direta com o aumento e distribuição da gordura corporal e no desenvolvimento de doenças cardiovasculares. Estudar a correlação entre indicadores antropométricos e da bioimpedância elétrica na avaliação da gordura corporal em mulheres candidatas à cirurgia bariátrica. Estudo transversal, observacional com 88 pacientes. Na análise antropométrica foram avaliados os dados de peso, altura, IMC e circunferência da cintura. Para bioimpedância elétrica utilizou-se a técnica recomendada pelo fabricante do aparelho e fórmula específica para obeso grave na determinação da gordura corporal. Para melhor análise dos resultados as pacientes foram divididas em dois subgrupos de acordo com a média de circunferência da cintura e IMC. O grupo apresentou média de idade 39,7 anos (±7,2), média de peso 125,6 kg (±16,2), média de IMC 48,7 kg/m2 (±6,4) e média de circunferência da cintura 137,6 cm (±12,4). Foram encontradas relações negativas e significativas entre os valores de IMC, circunferência da cintura e a resistência obtida através da bioimpedância elétrica. Ao analisar os dois subgrupos de valores médios de IMC e circunferência da cintura, observou-se relação significativa, ou seja, quanto maior o grau de obesidade menor é a resistência obtida através da bioimpedância elétrica. O aumento dos indicadores antropométricos (IMC e circunferência da cintura) determinaram redução nas variáveis resistência e reatância obtidas pela bioimpedância elétrica em mulheres candidatas à cirurgia bariátrica.

Compensatory Mitigation Rule Draft Environmental Assessment

EPA Pesticide Factsheets

Draft Compensatory Mitigation Rule intended to promote regulatory efficiency by establishing standards and criteria that would apply to compensatory mitigation required for DA permits issued under Section 404 of the Clean Water Act.

[Haptic tracking control for minimally invasive robotic surgery].

PubMed

Xu, Zhaohong; Song, Chengli; Wu, Wenwu

2012-06-01

Haptic feedback plays a significant role in minimally invasive robotic surgery (MIRS). A major deficiency of the current MIRS is the lack of haptic perception for the surgeon, including the commercially available robot da Vinci surgical system. In this paper, a dynamics model of a haptic robot is established based on Newton-Euler method. Because it took some period of time in exact dynamics solution, we used a digital PID arithmetic dependent on robot dynamics to ensure real-time bilateral control, and it could improve tracking precision and real-time control efficiency. To prove the proposed method, an experimental system in which two Novint Falcon haptic devices acting as master-slave system has been developed. Simulations and experiments showed proposed methods could give instrument force feedbacks to operator, and bilateral control strategy is an effective method to master-slave MIRS. The proposed methods could be used to tele-robotic system.

Microalgae fractionation using steam explosion, dynamic and tangential cross-flow membrane filtration.

PubMed

Lorente, E; Hapońska, M; Clavero, E; Torras, C; Salvadó, J

2017-08-01

In this study, the microalga Nannochloropsis gaditana was subjected to acid catalysed steam explosion treatment and the resulting exploded material was subsequently fractionated to separate the different fractions (lipids, sugars and solids). Conventional and vibrational membrane setups were used with several polymeric commercial membranes. Two different routes were followed: 1) filtration+lipid solvent extraction and 2) lipid solvent extraction+filtration. Route 1 revealed to be much better since the used membrane for filtration was able to permeate the sugar aqueous phase and retained the fraction containing lipids; after this, an extraction required a much lower amount of solvent and a better recovering yield. Filtration allowed complete lipid rejection. Dynamic filtration improved permeability compared to the tangential cross-flow filtration. Best membrane performance was achieved using a 5000Da membrane with the dynamic system, obtaining a permeability of 6L/h/m 2 /bar. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of DA-9701 on Gastric Motor Function Assessed by Magnetic Resonance Imaging in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Min, Yang Won; Min, Byung-Hoon; Kim, Seonwoo; Choi, Dongil; Rhee, Poong-Lyul

2015-01-01

Improving gastric accommodation and gastric emptying is an attractive physiological treatment target in patients with functional dyspepsia (FD). We evaluated the effect of DA-9701, a new drug for FD, on gastric motor function after a meal in healthy volunteers using magnetic resonance imaging (MRI). Forty healthy volunteers were randomly allocated to receive either DA-9701 or placebo. After 5 days of treatment, subjects underwent gastric MRI (60 min before and 15, 30, 45, 60, 90, and 120 min after a liquid test meal). Gastric volume was measured through 3-dimensional reconstruction from MRI data. We analyzed 4 outcome variables including changes in total gastric volume (TGV), proximal TGV, and proximal to distal TGV ratio after a meal and gastric emptying rates after adjusting values at the pre-test meal. Changes in TGV and proximal TGV after a meal did not differ between the DA-9701 and placebo groups (difference between groups -25.9 mL, 95% confidence interval [CI] -54.0 to 2.3 mL, P = 0.070 and -2.9 mL, 95% CI -30.3 to 24.5 mL, P = 0.832, respectively). However, pre-treatment with DA-9701 increased postprandial proximal to distal TGV ratio more than placebo (difference between groups 0.93, 95% CI 0.08 to 1.79, P = 0.034). In addition, pre-treatment with DA-9701 significantly increased gastric emptying as compared with placebo (mean difference between groups 3.41%, 95% CI 0.54% to 6.29%, P = 0.021, by mixed model for repeated measures). Our results suggested that DA-9701 enhances gastric emptying and does not significantly affect gastric accommodation in healthy volunteers. Further studies to confirm whether DA-9701 enhances these gastric motor functions in patients with FD are warranted. ClinicalTrials.gov NCT02091635.

Alginate antacid (Gaviscon DA) chewable tablets reduce esophageal acid exposure in Chinese patients with gastroesophageal reflux disease and heartburn symptoms.

PubMed

Yuan, Yao Zong; Fang, Jing Yuan; Zou, Duo Wu; Levinson, Nigel; Jenner, Bartosz; Wilkinson, Joanne

2016-11-01

To assess the efficacy of Gaviscon Double Action (DA) alginate antacid chewable tablets for reducing esophageal acid exposure in Chinese patients with gastroesophageal reflux disease (GERD). Altogether 44 patients reporting moderate to severe heartburn symptoms underwent two pH monitoring visits. The treatment sequence was randomized to patients received DA alginate antacid or placebo at one visit and the alternate treatment 7 days later. After a standardized reflux-provoking meal, patients took four tablets of DA alginate antacid or placebo. Esophageal pH was measured for 4 h post-dosing using an electrode positioned 5 cm above the lower esophageal sphincter. The primary end-point was the percentage of 4-h post-dosing period with pH <4. Secondary end-points were number of acid reflux episodes (pH <4), longest reflux time and DeMeester scores. All 44 patients completed the study and provided data for analysis. With DA alginate antacid, the mean percentage time with pH <4 was 5.1%, significantly less (P = 0.0003) than with placebo (14.8%). DA alginate antacid was statistically significantly superior (P = 0.0290) to placebo (from at least twofold to threefold better) for all other end-points. Two patients reported two mild adverse events (AEs) that resolved within a month of completing the study. No patients had serious and/or severe AEs and none withdrew due to AEs. DA alginate antacid was statistically significantly superior to placebo in reducing post-prandial acid exposure without serious clinically relevant health risks. These findings suggest DA alginate antacid tablets are appropriate for treating acid reflux in Chinese GERD patients with heartburn symptoms. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.