Simulation of Watts Bar Unit 1 Initial Startup Tests with Continuous Energy Monte Carlo Methods

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

Godfrey, Andrew T; Gehin, Jess C; Bekar, Kursat B

2014-01-01

The Consortium for Advanced Simulation of Light Water Reactors* is developing a collection of methods and software products known as VERA, the Virtual Environment for Reactor Applications. One component of the testing and validation plan for VERA is comparison of neutronics results to a set of continuous energy Monte Carlo solutions for a range of pressurized water reactor geometries using the SCALE component KENO-VI developed by Oak Ridge National Laboratory. Recent improvements in data, methods, and parallelism have enabled KENO, previously utilized predominately as a criticality safety code, to demonstrate excellent capability and performance for reactor physics applications. The highlymore » detailed and rigorous KENO solutions provide a reliable nu-meric reference for VERAneutronics and also demonstrate the most accurate predictions achievable by modeling and simulations tools for comparison to operating plant data. This paper demonstrates the performance of KENO-VI for the Watts Bar Unit 1 Cycle 1 zero power physics tests, including reactor criticality, control rod worths, and isothermal temperature coefficients.« less

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-01-01

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

Scaling: An Items Module

ERIC Educational Resources Information Center

Tong, Ye; Kolen, Michael J.

2010-01-01

"Scaling" is the process of constructing a score scale that associates numbers or other ordered indicators with the performance of examinees. Scaling typically is conducted to aid users in interpreting test results. This module describes different types of raw scores and scale scores, illustrates how to incorporate various sources of…

5HT(1A) and 5HT(1B) receptors of medial prefrontal cortex modulate anxiogenic-like behaviors in rats.

PubMed

Solati, Jalal; Salari, Ali-Akbar; Bakhtiari, Amir

2011-10-31

Medial prefrontal cortex (MPFC) is one of the brain regions which play an important role in emotional behaviors. The purpose of the present study was to evaluate the role of 5HT(1A) and 5HT(1B) receptors of the MPFC in modulation of anxiety behaviors in rats. The elevated plus maze (EPM) which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used. Bilateral intra-MPFC administration of 5HT(1A) receptor agonist, 8-OH-DPAT (5, 10, and 50 ng/rat) decreased the percentages of open arm time (OAT%) and open arm entries (OAE%), indicating an anxiogenic response. Moreover, administration of 5HT(1A) receptor antagonist, NAN-190 (0.25, 0.5, and 1 μg/rat) significantly increased OAT% and OAE%. Pre-treatment administration of NAN-190 (0.5 μg/rat), which was injected into the MPFC, reversed the anxiogenic effects of 8-OH-DPAT (5, 10, and 50 ng/rat). Intra-MPFC microinjection of 5HT(1B) receptor agonist, CGS-12066A (0.25, 0.5, and 1 μg/rat) significantly decreased OAT% and OAE%, without any change in locomotor activity, indicating an anxiogenic effect. However, injection of 5HT(1B) receptor antagonist, SB-224289 (0.5, 1, and 2 μg/rat) into the MPFC showed no significant effect. In conclusion, these findings suggest that 5HT(1A) and 5HT(1B) receptors of the MPFC region modulate anxiogenic-like behaviors in rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Measurement in Sensory Modulation: The Sensory Processing Scale Assessment

PubMed Central

Miller, Lucy J.; Sullivan, Jillian C.

2014-01-01

OBJECTIVE. Sensory modulation issues have a significant impact on participation in daily life. Moreover, understanding phenotypic variation in sensory modulation dysfunction is crucial for research related to defining homogeneous groups and for clinical work in guiding treatment planning. We thus evaluated the new Sensory Processing Scale (SPS) Assessment. METHOD. Research included item development, behavioral scoring system development, test administration, and item analyses to evaluate reliability and validity across sensory domains. RESULTS. Items with adequate reliability (internal reliability >.4) and discriminant validity (p < .01) were retained. Feedback from the expert panel also contributed to decisions about retaining items in the scale. CONCLUSION. The SPS Assessment appears to be a reliable and valid measure of sensory modulation (scale reliability >.90; discrimination between group effect sizes >1.00). This scale has the potential to aid in differential diagnosis of sensory modulation issues. PMID:25184464

Modeling hydrodynamics, water temperature, and water quality in the Klamath River upstream of Keno Dam, Oregon, 2006-09

USGS Publications Warehouse

Sullivan, Annett B.; Rounds, Stewart A.; Deas, Michael L.; Asbill, Jessica R.; Wellman, Roy E.; Stewart, Marc A.; Johnston, Matthew W.; Sogutlugil, I. Ertugrul

2011-01-01

. * Water temperatures ranged from near freezing in winter to near 30 degrees C at some locations and periods in summer; seasonal water temperature patterns were similar at the inflow and outflow. Although vertical temperature stratification was not present at most times and locations, weak stratification could persist for periods up to 1-2 weeks, especially in the downstream parts of the reach. Thermal stratification was important in controlling vertical variations in water quality. * The specific conductance, and thus density, of tributaries within the reach usually was higher than that of the river itself, so that inflows tended to sink below the river surface. This was especially notable for inflows from the Klamath Straits Drain, which tended to sink to the bottom of the Klamath River at its confluence and not mix vertically for several miles downstream. * The model was able to capture most of the seasonal changes in the algal population by modeling that population with three algal groups: blue-green algae, diatoms, and other algae. The blooms of blue-green algae, consisting mostly of Aphanizomenon flos aquae that entered from Upper Klamath Lake, were dominant, dwarfing the populations of the other two algae groups in summer. A large part of the blue-green algae population that entered this reach from upstream tended to settle out, die, and decompose, especially in the upper part of the Link-Keno reach. Diatoms reached a maximum in spring and other algae in midsummer. * Organic matter, occurring in both dissolved and particulate forms, was critical to the water quality of this reach of the Klamath River, and was strongly tied to nutrient and dissolved-oxygen dynamics. Dissolved and particulate organic matter were subdivided into labile (quickly decaying) and refractory (slowing decaying) groups for modeling purposes. The particulate matter in summer, consisting largely of dead blue-green algae, decayed quickly. Consequently, this particulate matt

Use of SCALE Continuous-Energy Monte Carlo Tools for Eigenvalue Sensitivity Coefficient Calculations

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

Perfetti, Christopher M; Rearden, Bradley T

2013-01-01

The TSUNAMI code within the SCALE code system makes use of eigenvalue sensitivity coefficients for an extensive number of criticality safety applications, such as quantifying the data-induced uncertainty in the eigenvalue of critical systems, assessing the neutronic similarity between different critical systems, and guiding nuclear data adjustment studies. The need to model geometrically complex systems with improved fidelity and the desire to extend TSUNAMI analysis to advanced applications has motivated the development of a methodology for calculating sensitivity coefficients in continuous-energy (CE) Monte Carlo applications. The CLUTCH and Iterated Fission Probability (IFP) eigenvalue sensitivity methods were recently implemented in themore » CE KENO framework to generate the capability for TSUNAMI-3D to perform eigenvalue sensitivity calculations in continuous-energy applications. This work explores the improvements in accuracy that can be gained in eigenvalue and eigenvalue sensitivity calculations through the use of the SCALE CE KENO and CE TSUNAMI continuous-energy Monte Carlo tools as compared to multigroup tools. The CE KENO and CE TSUNAMI tools were used to analyze two difficult models of critical benchmarks, and produced eigenvalue and eigenvalue sensitivity coefficient results that showed a marked improvement in accuracy. The CLUTCH sensitivity method in particular excelled in terms of efficiency and computational memory requirements.« less

Experiment module concepts study. Volume 5 book 1, appendix A: Shuttle only task

NASA Technical Reports Server (NTRS)

1970-01-01

Results of a preliminary investigation of the effect on the candidate experiment program implementation of experiment module operations in the absence of an orbiting space station and with the availability of the space shuttle orbiter vehicle only are presented. The fundamental hardware elements for shuttle-only operation of the program are: (1) integrated common experiment modules CM-1, CM-3, and CM-4, together with the propulsion slice; (2) support modules capable of supplying on-orbit crew life support, power, data management, and other services normally provided by a space station; (3) dormancy kits to enable normally attached modules to remain in orbit while shuttle returns to earth; and (4) shuttle orbiter. Preliminary cost estimates for 30 day on-orbit and 5 day on-orbit capabilities for a four year implementation period are $4.2 billion and $2.1 billion, respectively.

Fuel burnup analysis for IRIS reactor using MCNPX and WIMS-D5 codes

NASA Astrophysics Data System (ADS)

Amin, E. A.; Bashter, I. I.; Hassan, Nabil M.; Mustafa, S. S.

2017-02-01

International Reactor Innovative and Secure (IRIS) reactor is a compact power reactor designed with especial features. It contains Integral Fuel Burnable Absorber (IFBA). The core is heterogeneous both axially and radially. This work provides the full core burn up analysis for IRIS reactor using MCNPX and WIMDS-D5 codes. Criticality calculations, radial and axial power distributions and nuclear peaking factor at the different stages of burnup were studied. Effective multiplication factor values for the core were estimated by coupling MCNPX code with WIMS-D5 code and compared with SAS2H/KENO-V code values at different stages of burnup. The two calculation codes show good agreement and correlation. The values of radial and axial powers for the full core were also compared with published results given by SAS2H/KENO-V code (at the beginning and end of reactor operation). The behavior of both radial and axial power distribution is quiet similar to the other data published by SAS2H/KENO-V code. The peaking factor values estimated in the present work are close to its values calculated by SAS2H/KENO-V code.

EFT-1 Crew Module on Display at KSC Visitor Complex

NASA Image and Video Library

2017-04-12

The Orion crew module from Exploration Flight Test 1 (EFT-1) is on display at nearby NASA Kennedy Space Center Visitor Complex in Florida. The crew module is part of the NASA Now exhibit in the IMAX Theater. Also in view is a scale model of NASA's Space Launch System rocket and Orion spacecraft on the mobile launcher. The Orion EFT-1 spacecraft launched atop a United Launch Alliance Delta IV rocket Dec. 5, 2014, from Space Launch Complex 37 at Cape Canaveral Air Force Station. The spacecraft built for humans traveled 3,604 miles above Earth and splashed down about 4.5 hours later in the Pacific Ocean.

SCALE: A modular code system for performing standardized computer analyses for licensing evaluation. Functional modules F1--F8 -- Volume 2, Part 1, Revision 4

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

Greene, N.M.; Petrie, L.M.; Westfall, R.M.

SCALE--a modular code system for Standardized Computer Analyses Licensing Evaluation--has been developed by Oak Ridge National Laboratory at the request of the US Nuclear Regulatory Commission. The SCALE system utilizes well-established computer codes and methods within standard analysis sequences that (1) allow an input format designed for the occasional user and/or novice, (2) automate the data processing and coupling between modules, and (3) provide accurate and reliable results. System development has been directed at problem-dependent cross-section processing and analysis of criticality safety, shielding, heat transfer, and depletion/decay problems. Since the initial release of SCALE in 1980, the code system hasmore » been heavily used for evaluation of nuclear fuel facility and package designs. This revision documents Version 4.2 of the system. The manual is divided into three volumes: Volume 1--for the control module documentation; Volume 2--for functional module documentation; and Volume 3--for documentation of the data libraries and subroutine libraries.« less

Multi-scale reflection modulator-based optical interconnects

NASA Astrophysics Data System (ADS)

Nair, Rohit

This dissertation describes the design, analysis, and experimental validation of micro- and macro-optical components for implementing optical interconnects at multiple scales for varied applications. Three distance scales are explored: millimeter, centimeter, and meter-scales. At the millimeter-scale, we propose the use of optical interconnects at the intra-chip level. With the rapid scaling down of CMOS critical dimensions in accordance to Moore's law, the bandwidth requirements of global interconnects in microprocessors has exceeded the capabilities of metal links. These are the wires that connect the most remote parts of the chip and are disproportionately problematic in terms of chip area and power consumption. Consequently, in the mid-2000s, we saw a shift in the chip architecture: a move towards multicore designs. However, this only delays the inevitable communication bottleneck between cores. To satisfy this bandwidth, we propose to replace the global metal interconnects with optical interconnects. We propose to use the hybrid integration of silicon with GaAs/AlAs-based multiple quantum well devices as optical modulators and photodetectors along with polymeric waveguides to transport the light. We use grayscale lithography to fabricate curved facets into the waveguides to couple light into the modulators and photodetectors. Next, at the chip-to-chip level in high-performance multiprocessor computing systems, communication distances vary from a few centimeters to tens of centimeters. An optical design for coupling light from off-chip lasers to on-chip surface-normal modulators is proposed in order to implement chip-to-chip free-space optical interconnects. The method uses a dual-prism module constructed from prisms made of two different glasses. The various alignment tolerances of the proposed system are investigated and found to be well within pick-and-place accuracies. For the off-chip lasers, vertical cavity surface emitting lasers (VCSELs) are proposed

OGO 5 observations of Pc 5 waves - Particle flux modulations

NASA Technical Reports Server (NTRS)

Kokubun, S.; Kivelson, M. G.; Mcpherron, R. L.; Russell, C. T.; West, H. I., Jr.

1977-01-01

An investigation is conducted concerning the modulations of particle fluxes associated with Pc 5 waves in the region beyond the plasmapause. A study of thermal flux modulations indicates that some of the density enhancements observed are not spatial structures but are spurious features caused by temporal flux variations associated with hydromagnetic waves. A resonance model of the energetic particle flux modulations is discussed. Energetic particle modulations are also considered. The reported observations reveal that modulations are dominant at energies of about 100 keV for electrons and at 100 keV to 1 MeV for protons. This may indicate that the bounce resonance interaction is not important for Pc 5 waves.

The discriminative capacity of CBCL/1½-5-DSM5 scales to identify disruptive and internalizing disorders in preschool children.

PubMed

de la Osa, Nuria; Granero, Roser; Trepat, Esther; Domenech, Josep Maria; Ezpeleta, Lourdes

2016-01-01

This paper studies the discriminative capacity of CBCL/1½-5 (Manual for the ASEBA Preschool-Age Forms & Profiles, University of Vermont, Research Center for Children, Youth, & Families, Burlington, 2000) DSM5 scales attention deficit and hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), anxiety and depressive problems for detecting the presence of DSM5 (DSM5 diagnostic and statistical manual of mental disorders, APA, Arlington, 2013) disorders, ADHD, ODD, Anxiety and Mood disorders, assessed through diagnostic interview, in children aged 3-5. Additionally, we compare the clinical utility of the CBCL/1½-5-DSM5 scales with respect to analogous CBCL/1½-5 syndrome scales. A large community sample of 616 preschool children was longitudinally assessed for the stated age group. Statistical analysis was based on ROC procedures and binary logistic regressions. ADHD and ODD CBCL/1½-5-DSM5 scales achieved good discriminative ability to identify ADHD and ODD interview's diagnoses, at any age. CBCL/1½-5-DSM5 Anxiety scale discriminative capacity was fair for unspecific anxiety disorders in all age groups. CBCL/1½-5-DSM5 depressive problems' scale showed the poorest discriminative capacity for mood disorders (including depressive episode with insufficient symptoms), oscillating into the poor-to-fair range. As a whole, DSM5-oriented scales generally did not provide evidence better for discriminative capacity than syndrome scales in identifying DSM5 diagnoses. CBCL/1½-5-DSM5 scales discriminate externalizing disorders better than internalizing disorders for ages 3-5. Scores on the ADHD and ODD CBCL/1½-5-DSM5 scales can be used to screen for DSM5 ADHD and ODD disorders in general populations of preschool children.

Comparisons of the Impact Responses of a 1/5-Scale Model and a Full-Scale Crashworthy Composite Fuselage Section

NASA Technical Reports Server (NTRS)

Jackson, Karen E.; Fasanella, Edwin L.; Lyle, Karen H.

2003-01-01

A 25-fps vertical drop test of a 1/5-scale model composite fuselage section was conducted to replicate a previous test of a full-scale fuselage section. The purpose of the test was to obtain experimental data characterizing the impact response of the 1/5-scale model fuselage section for comparison with the corresponding full-scale data. This comparison is performed to assess the scaling procedures and to determine if scaling effects are present. For the drop test, the 1/5-scale model fuselage section was configured in a similar manner as the full-scale section, with lead masses attached to the floor through simulated seat rails. Scaled acceleration and velocity responses are compared and a general assessment of structural damage is made. To further quantify the data correlation, comparisons of the average acceleration data are made as a function of floor location and longitudinal position. Also, the percentage differences in the velocity change (area under the acceleration curve) and the velocity change squared (proportional to kinetic energy) are compared as a function of floor location. Finally, correlation coefficients are calculated for corresponding 1/5- and full-scale data channels and these values are plotted versus floor location. From a scaling perspective, the differences between the 1/5- and full-scale tests are relatively small, indicating that appropriate scaling procedures were used in fabricating the test specimens and in conducting the experiments. The small differences in the scaled test data are attributed to minor scaling anomalies in mass, potential energy, and impact attitude.

Macrophyte and pH buffering updates to the Klamath River water-quality model upstream of Keno Dam, Oregon

USGS Publications Warehouse

Sullivan, Annett B.; Rounds, Stewart A.; Asbill-Case, Jessica R.; Deas, Michael L.

2013-01-01

A hydrodynamic, water temperature, and water-quality model of the Link River to Keno Dam reach of the upper Klamath River was updated to account for macrophytes and enhanced pH buffering from dissolved organic matter, ammonia, and orthophosphorus. Macrophytes had been observed in this reach by field personnel, so macrophyte field data were collected in summer and fall (June-October) 2011 to provide a dataset to guide the inclusion of macrophytes in the model. Three types of macrophytes were most common: pondweed (Potamogeton species), coontail (Ceratophyllum demersum), and common waterweed (Elodea canadensis). Pondweed was found throughout the Link River to Keno Dam reach in early summer with densities declining by mid-summer and fall. Coontail and common waterweed were more common in the lower reach near Keno Dam and were at highest density in summer. All species were most dense in shallow water (less than 2 meters deep) near shore. The highest estimated dry weight biomass for any sample during the study was 202 grams per square meter for coontail in August. Guided by field results, three macrophyte groups were incorporated into the CE-QUAL-W2 model for calendar years 2006-09. The CE-QUAL-W2 model code was adjusted to allow the user to initialize macrophyte populations spatially across the model grid. The default CE-QUAL-W2 model includes pH buffering by carbonates, but does not include pH buffering by organic matter, ammonia, or orthophosphorus. These three constituents, especially dissolved organic matter, are present in the upper Klamath River at concentrations that provide substantial pH buffering capacity. In this study, CE-QUAL-W2 was updated to include this enhanced buffering capacity in the simulation of pH. Acid dissociation constants for ammonium and phosphoric acid were taken from the literature. For dissolved organic matter, the number of organic acid groups and each group's acid dissociation constant (Ka) and site density (moles of sites per mole of

Sexual behavior modulates contextual fear memory through dopamine D1/D5 receptors.

PubMed

Bai, Hua-Yi; Cao, Jun; Liu, Na; Xu, Lin; Luo, Jian-Hong

2009-03-01

Traumatic events always lead to aversive emotional memory, i.e., fear memory. In contrast, positive events in daily life such as sex experiences seem to reduce aversive memory after aversive events. Thus, we hypothesized that post-traumatic pleasurable experiences, especially instinctive behaviors such as sex, might modulate traumatic memory through a memory competition mechanism. Here, we first report that male rats persistently expressed much lower fear responses when exposed to females, but not when exposed to males, for 24 h immediately after contextual fear conditioning. Remarkably, this effect of sexual behavior was blocked by either systemic or intrahippocampal injection of the dopamine D1/D5 receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) and was mimicked by systemic but not intrahippocampal injection of the D1/D5 receptor agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol hydrochloride (SKF39393). Furthermore, as a candidate mechanism underlying contextual fear memory, the impaired induction of hippocampal long-term potentiation (LTP) elicited by conditioned fear was rescued in male rats immediately exposed to female but not male rats for 24 h. Systemic injection of the dopamine D1/D5 receptor antagonist SCH23390 or agonist SKF38393 prevented or mimicked the effect of sexual behavior on the impaired induction of hippocampal LTP. Thus, our finding suggests that dopaminergic functions may, at least partially, govern competition between contextual fear and enjoyable memories through the modulation of hippocampal LTP.

4G/5G polymorphism modulates PAI-1 circulating levels in obese women.

PubMed

Fernandes, Karla S; Sandrim, Valéria C

2012-05-01

The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases.

5nsec Dead time multichannel scaling system for Mössbauer spectrometer

NASA Astrophysics Data System (ADS)

Verrastro, C.; Trombetta, G.; Pita, A.; Saragovi, C.; Duhalde, S.

1991-11-01

A PC programmable and fast multichannel scaling module has been designed to use a commercial Mössbauer spectrometer. This module is based on a 10 single chip 8 bits microcomputer (MC6805) and on a 35 fast ALU, which allows a high performance and low cost system. The module can operate in a stand-alone mode. Data analysis are performed in real time display, on XT/AT IBM PC or compatibles. The channels are ranged between 256 and 4096, the maximum number of counts is 232-1 per channel, the dwell time is 3 μsec and the dead time between channels is 5 nsec. A friendly software display the real time spectrum and offers menues with different options at each state.

The IAEA coordinated research programme on HTGR uncertainty analysis: Phase I status and Ex. I-1 prismatic reference results

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

Bostelmann, Friederike; Strydom, Gerhard; Reitsma, Frederik

The quantification of uncertainties in design and safety analysis of reactors is today not only broadly accepted, but in many cases became the preferred way to replace traditional conservative analysis for safety and licensing analysis. The use of a more fundamental methodology is also consistent with the reliable high fidelity physics models and robust, efficient, and accurate codes available today. To facilitate uncertainty analysis applications a comprehensive approach and methodology must be developed and applied, in contrast to the historical approach where sensitivity analysis were performed and uncertainties then determined by a simplified statistical combination of a few important inputmore » parameters. New methodologies are currently under development in the OECD/NEA Light Water Reactor (LWR) Uncertainty Analysis in Best-Estimate Modelling (UAM) benchmark activity. High Temperature Gas-cooled Reactor (HTGR) designs require specific treatment of the double heterogeneous fuel design and large graphite quantities at high temperatures. The IAEA has therefore launched a Coordinated Research Project (CRP) on HTGR Uncertainty Analysis in Modelling (UAM) in 2013 to study uncertainty propagation specifically in the HTGR analysis chain. Two benchmark problems are defined, with the prismatic design represented by the General Atomics (GA) MHTGR-350 and a 250 MW modular pebble bed design similar to the Chinese HTR-PM. Work has started on the first phase and the current CRP status is reported in the paper. A comparison of the Serpent and SCALE/KENO-VI reference Monte Carlo results for Ex. I-1 of the MHTGR-350 design is also included. It was observed that the SCALE/KENO-VI Continuous Energy (CE) k ∞ values were 395 pcm (Ex. I-1a) to 803 pcm (Ex. I-1b) higher than the respective Serpent lattice calculations, and that within the set of the SCALE results, the KENO-VI 238 Multi-Group (MG) k ∞ values were up to 800 pcm lower than the KENO-VI CE values. The use of the

The IAEA coordinated research programme on HTGR uncertainty analysis: Phase I status and Ex. I-1 prismatic reference results

DOE PAGES

Bostelmann, Friederike; Strydom, Gerhard; Reitsma, Frederik; ...

2016-01-11

The quantification of uncertainties in design and safety analysis of reactors is today not only broadly accepted, but in many cases became the preferred way to replace traditional conservative analysis for safety and licensing analysis. The use of a more fundamental methodology is also consistent with the reliable high fidelity physics models and robust, efficient, and accurate codes available today. To facilitate uncertainty analysis applications a comprehensive approach and methodology must be developed and applied, in contrast to the historical approach where sensitivity analysis were performed and uncertainties then determined by a simplified statistical combination of a few important inputmore » parameters. New methodologies are currently under development in the OECD/NEA Light Water Reactor (LWR) Uncertainty Analysis in Best-Estimate Modelling (UAM) benchmark activity. High Temperature Gas-cooled Reactor (HTGR) designs require specific treatment of the double heterogeneous fuel design and large graphite quantities at high temperatures. The IAEA has therefore launched a Coordinated Research Project (CRP) on HTGR Uncertainty Analysis in Modelling (UAM) in 2013 to study uncertainty propagation specifically in the HTGR analysis chain. Two benchmark problems are defined, with the prismatic design represented by the General Atomics (GA) MHTGR-350 and a 250 MW modular pebble bed design similar to the Chinese HTR-PM. Work has started on the first phase and the current CRP status is reported in the paper. A comparison of the Serpent and SCALE/KENO-VI reference Monte Carlo results for Ex. I-1 of the MHTGR-350 design is also included. It was observed that the SCALE/KENO-VI Continuous Energy (CE) k ∞ values were 395 pcm (Ex. I-1a) to 803 pcm (Ex. I-1b) higher than the respective Serpent lattice calculations, and that within the set of the SCALE results, the KENO-VI 238 Multi-Group (MG) k ∞ values were up to 800 pcm lower than the KENO-VI CE values. The use of the

PedsQL Neurofibromatosis Type 1 Module for children, adolescents and young adults: feasibility, reliability, and validity.

PubMed

Nutakki, Kavitha; Varni, James W; Swigonski, Nancy L

2018-04-01

The objective of the present study was to report on the measurement properties of the Pediatric Quality of Life Inventory (PedsQL) Neurofibromatosis Type 1 Module for pediatric patients ages 5-25 from the perspectives of patients and parents. The 104-item PedsQL NF1 Module and 23-item PedsQL Generic Core Scales were completed in a multi-site national study by 323 patients and 335 parents (343 families). Patients were diagnosed with NF1 using the National Institutes of Health diagnostic criteria. In addition to a Total Scale Score, 18 unidimensional scales were derived measuring skin itch bother, skin sensations, pain, pain impact, pain management, cognitive functioning, speech, fine motor, balance, vision, perceived physical appearance, communication, worry, treatment anxiety, medicines, stomach discomfort, constipation, and diarrhea. The PedsQL NF1 Module Scales evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report α = 0.98; parent proxy-report α = 0.98), and good to excellent reliability for the 18 individual scales (patient self-report α = 0.71-0.96; parent proxy-report α = 0.73-0.98). Intercorrelations with the Generic Core Scales supported construct validity. Factor analysis supported the unidimensionality of the 18 individual scales. The PedsQL NF1 Module Scales demonstrated acceptable to excellent measurement properties, and may be utilized as standardized metrics to assess NF1-specific symptoms and problems in clinical research and practice in children, adolescents, and young adults.

Adenosine transiently modulates stimulated dopamine release in the caudate putamen via A1 receptors

PubMed Central

Ross, Ashley E.; Venton, B. Jill

2014-01-01

Adenosine modulates dopamine in the brain via A1 and A2A receptors, but that modulation has only been characterized on a slow time scale. Recent studies have characterized a rapid signaling mode of adenosine that suggests a possible rapid modulatory role. Here, fast-scan cyclic voltammetry was used to characterize the extent to which transient adenosine changes modulate stimulated dopamine release (5 pulses at 60 Hz) in rat caudate putamen brain slices. Exogenous adenosine was applied and dopamine concentration monitored. Adenosine only modulated dopamine when it was applied 2 or 5 s before stimulation. Longer time intervals and bath application of 5 µM adenosine did not decrease dopamine release. Mechanical stimulation of endogenous adenosine 2s before dopamine stimulation also decreased stimulated dopamine release by 41 ± 7 %, similar to the 54 ± 6 % decrease in dopamine after exogenous adenosine application. Dopamine inhibition by transient adenosine was recovered within 10 minutes. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) blocked the dopamine modulation, whereas dopamine modulation was unaffected by the A2A receptor antagonist SCH 442416. Thus, transient adenosine changes can transiently modulate phasic dopamine release via A1 receptors. These data demonstrate that adenosine has a rapid, but transient, modulatory role in the brain. PMID:25219576

Outlook and Challenges of Perovskite Solar Cells toward Terawatt-Scale Photovoltaic Module Technology

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

Zhu, Kai; Kim, Donghoe; Whitaker, James B

Rapid development of perovskite solar cells (PSCs) during the past several years has made this photovoltaic (PV) technology a serious contender for potential large-scale deployment on the terawatt scale in the PV market. To successfully transition PSC technology from the laboratory to industry scale, substantial efforts need to focus on scalable fabrication of high-performance perovskite modules with minimum negative environmental impact. Here, we provide an overview of the current research and our perspective regarding PSC technology toward future large-scale manufacturing and deployment. Several key challenges discussed are (1) a scalable process for large-area perovskite module fabrication; (2) less hazardous chemicalmore » routes for PSC fabrication; and (3) suitable perovskite module designs for different applications.« less

GCN5L1 modulates cross-talk between mitochondria and cell signaling to regulate FoxO1 stability and gluconeogenesis.

PubMed

Wang, Lingdi; Scott, Iain; Zhu, Lu; Wu, Kaiyuan; Han, Kim; Chen, Yong; Gucek, Marjan; Sack, Michael N

2017-09-12

The mitochondrial enriched GCN5-like 1 (GCN5L1) protein has been shown to modulate mitochondrial protein acetylation, mitochondrial content and mitochondrial retrograde signaling. Here we show that hepatic GCN5L1 ablation reduces fasting glucose levels and blunts hepatic gluconeogenesis without affecting systemic glucose tolerance. PEPCK and G6Pase transcript levels are downregulated in hepatocytes from GCN5L1 liver specific knockout mice and their upstream regulator, FoxO1 protein levels are decreased via proteasome-dependent degradation and via reactive oxygen species mediated ERK-1/2 phosphorylation. ERK inhibition restores FoxO1, gluconeogenic enzyme expression and glucose production. Reconstitution of mitochondrial-targeted GCN5L1 blunts mitochondrial ROS, ERK activation and increases FoxO1, gluconeogenic enzyme expression and hepatocyte glucose production. We suggest that mitochondrial GCN5L1 modulates post-translational control of FoxO1, regulates gluconeogenesis and controls metabolic pathways via mitochondrial ROS mediated ERK activation. Exploring mechanisms underpinning GCN5L1 mediated ROS signaling may expand our understanding of the role of mitochondria in gluconeogenesis control.Hepatic gluconeogenesis is tightly regulated at transcriptional level and is essential for survival during prolonged fasting. Here Wang et al. show that the mitochondrial enriched GCN5-like 1 protein controls hepatic glucose production by regulating FoxO1 protein levels via proteasome-dependent degradation and, in turn, gluconeogenic gene expression.

Stress-induced alterations in 5-HT1A receptor transcriptional modulators NUDR and Freud-1.

PubMed

Szewczyk, Bernadeta; Kotarska, Katarzyna; Daigle, Mireille; Misztak, Paulina; Sowa-Kucma, Magdalena; Rafalo, Anna; Curzytek, Katarzyna; Kubera, Marta; Basta-Kaim, Agnieszka; Nowak, Gabriel; Albert, Paul R

2014-11-01

The effect of stress on the mRNA and protein level of the 5-HT1A receptor and two of its key transcriptional modulators, NUDR and Freud-1, was examined in the prefrontal cortex (PFC) and hippocampus (Hp) using rodent models: olfactory bulbectomy (OB) and prenatal stress (PS) in male and female rats; chronic mild stress in male rats (CMS) and pregnancy stress. In PFC, CMS induced the most widespread changes, with significant reduction in both mRNA and protein levels of NUDR, 5-HT1A receptor and in Freud-1 mRNA; while in Hp 5-HT1A receptor and Freud-1 protein levels were also decreased. In male, but not female OB rats PFC Freud-1 and 5-HT1A receptor protein levels were reduced, while in Hp 5-HT1A receptor, Freud-1 and NUDR mRNA's but not protein were reduced. In PS rats PFC 5-HT1A receptor protein was reduced more in females than males; while in Hp Freud-1 protein was increased in females. In pregnancy stress, PFC NUDR, Freud-1 and 5-HT1A protein receptor levels were reduced, and in HP 5-HT1A receptor protein levels were also reduced; in HP only NUDR and Freud-1 mRNA levels were reduced. Overall, CMS and stress during pregnancy produced the most salient changes in 5-HT1A receptor and transcription factor expression, suggesting a primary role for altered transcription factor expression in chronic regulation of 5-HT1A receptor expression. By contrast, OB (in males) and PS (in females) produced gender-specific reductions in PFC 5-HT1A receptor protein levels, suggesting a role for post-transcriptional regulation. These and previous data suggest that chronic stress might be a key regulator of NUDR/Freud-1 gene expression.

Stress-induced alterations in 5-HT1A receptor transcriptional modulators NUDR and Freud-1

PubMed Central

Szewczyk, Bernadeta; Kotarska, Katarzyna; Daigle, Mireille; Misztak, Paulina; Sowa-Kucma, Magdalena; Rafalo, Anna; Curzytek, Katarzyna; Kubera, Marta; Basta-Kaim, Agnieszka; Nowak, Gabriel; Albert, Paul R

2015-01-01

The effect of stress on the mRNA and protein level of the 5-HT1A receptor and two of its key transcriptional modulators, NUDR and Freud-1, was examined in the prefrontal cortex (PFC) and hippocampus (Hp) using rodent models: olfactory bulbectomy (OB) and prenatal stress (PS) in male and female rats; chronic mild stress in male rats (CMS) and pregnancy stress. In PFC, CMS induced the most widespread changes, with significant reduction in both mRNA and protein levels of NUDR, 5-HT1A receptor and in Freud-1 mRNA; while in Hp 5-HT1A receptor and Freud-1 protein levels were also decreased. In male, but not female OB rats PFC Freud-1 and 5-HT1A receptor protein levels were reduced, while in Hp 5-HT1A receptor, Freud-1 and NUDR mRNA’s but not protein were reduced. In PS rats PFC 5-HT1A receptor protein was reduced more in females than males; while in Hp Freud-1 protein was increased in females. In pregnancy stress, PFC NUDR, Freud-1 and 5-HT1A protein receptor levels were reduced, and in HP 5-HT1A receptor protein levels were also reduced; in HP only NUDR and Freud-1 mRNA levels were reduced. Overall, CMS and stress during pregnancy produced the most salient changes in 5-HT1A receptor and transcription factor expression, suggesting a primary role for altered transcription factor expression in chronic regulation of 5-HT1A receptor expression. By contrast, OB (in males) and PS (in females) produced gender-specific reductions in PFC 5-HT1A receptor protein levels, suggesting a role for post-transcriptional regulation. These and previous data suggest that chronic stress might be a key regulator of NUDR/Freud-1 gene expression. PMID:24946016

Scaling vectors of attoJoule per bit modulators

NASA Astrophysics Data System (ADS)

Sorger, Volker J.; Amin, Rubab; Khurgin, Jacob B.; Ma, Zhizhen; Dalir, Hamed; Khan, Sikandar

2018-01-01

Electro-optic modulation performs the conversion between the electrical and optical domain with applications in data communication for optical interconnects, but also for novel optical computing algorithms such as providing nonlinearity at the output stage of optical perceptrons in neuromorphic analog optical computing. While resembling an optical transistor, the weak light-matter-interaction makes modulators 105 times larger compared to their electronic counterparts. Since the clock frequency for photonics on-chip has a power-overhead sweet-spot around tens of GHz, ultrafast modulation may only be required in long-distance communication, not for short on-chip links. Hence, the search is open for power-efficient on-chip modulators beyond the solutions offered by foundries to date. Here, we show scaling vectors towards atto-Joule per bit efficient modulators on-chip as well as some experimental demonstrations of novel plasmonic modulators with sub-fJ/bit efficiencies. Our parametric study of placing different actively modulated materials into plasmonic versus photonic optical modes shows that 2D materials overcompensate their miniscule modal overlap by their unity-high index change. Furthermore, we reveal that the metal used in plasmonic-based modulators not only serves as an electrical contact, but also enables low electrical series resistances leading to near-ideal capacitors. We then discuss the first experimental demonstration of a photon-plasmon-hybrid graphene-based electro-absorption modulator on silicon. The device shows a sub-1 V steep switching enabled by near-ideal electrostatics delivering a high 0.05 dB V-1 μm-1 performance requiring only 110 aJ/bit. Improving on this demonstration, we discuss a plasmonic slot-based graphene modulator design, where the polarization of the plasmonic mode aligns with graphene’s in-plane dimension; where a push-pull dual-gating scheme enables 2 dB V-1 μm-1 efficient modulation allowing the device to be just 770 nm

CEF1/CDC5 alleles modulate transitions between catalytic conformations of the spliceosome

PubMed Central

Query, Charles C.; Konarska, Maria M.

2012-01-01

Conformational change within the spliceosome is required between the first and second catalytic steps of pre-mRNA splicing. A prior genetic screen for suppressors of an intron mutant that stalls between the two steps yielded both prp8 and non-prp8 alleles that suppressed second-step splicing defects. We have now identified the strongest non-prp8 suppressors as alleles of the NTC (Prp19 complex) component, CEF1. These cef1 alleles generally suppress second-step defects caused by a variety of intron mutations, mutations in U6 snRNA, or deletion of the second-step protein factor Prp17, and they can activate alternative 3′ splice sites. Genetic and functional interactions between cef1 and prp8 alleles suggest that they modulate the same event(s) in the first-to-second-step transition, most likely by stabilization of the second-step spliceosome; in contrast, alleles of U6 snRNA that also alter this transition modulate a distinct event, most likely by stabilization of the first-step spliceosome. These results implicate a myb-like domain of Cef1/CDC5 in interactions that modulate conformational states of the spliceosome and suggest that alteration of these events affects splice site use, resulting in alternative splicing-like patterns in yeast. PMID:22408182

Review of revised Klamath River Total Maximum Daily Load models from Link River Dam to Keno Dam, Oregon

USGS Publications Warehouse

Rounds, Stewart A.; Sullivan, Annett B.

2013-01-01

Flow and water-quality models are being used to support the development of Total Maximum Daily Load (TMDL) plans for the Klamath River downstream of Upper Klamath Lake (UKL) in south-central Oregon. For riverine reaches, the RMA-2 and RMA-11 models were used, whereas the CE-QUAL-W2 model was used to simulate pooled reaches. The U.S. Geological Survey (USGS) was asked to review the most upstream of these models, from Link River Dam at the outlet of UKL downstream through the first pooled reach of the Klamath River from Lake Ewauna to Keno Dam. Previous versions of these models were reviewed in 2009 by USGS. Since that time, important revisions were made to correct several problems and address other issues. This review documents an assessment of the revised models, with emphasis on the model revisions and any remaining issues. The primary focus of this review is the 19.7-mile Lake Ewauna to Keno Dam reach of the Klamath River that was simulated with the CE-QUAL-W2 model. Water spends far more time in the Lake Ewauna to Keno Dam reach than in the 1-mile Link River reach that connects UKL to the Klamath River, and most of the critical reactions affecting water quality upstream of Keno Dam occur in that pooled reach. This model review includes assessments of years 2000 and 2002 current conditions scenarios, which were used to calibrate the model, as well as a natural conditions scenario that was used as the reference condition for the TMDL and was based on the 2000 flow conditions. The natural conditions scenario included the removal of Keno Dam, restoration of the Keno reef (a shallow spot that was removed when the dam was built), removal of all point-source inputs, and derivation of upstream boundary water-quality inputs from a previously developed UKL TMDL model. This review examined the details of the models, including model algorithms, parameter values, and boundary conditions; the review did not assess the draft Klamath River TMDL or the TMDL allocations

Tianeptine: 5-HT uptake sites and 5-HT(1-7) receptors modulate memory formation in an autoshaping Pavlovian/instrumental task.

PubMed

Meneses, Alfredo

2002-05-01

Recent studies using invertebrate and mammal species have revealed that, endogenous serotonin (5-hydroxytryptamine, 5-HT) modulates cognitive processes, particularly learning and memory, though, at present, it is unclear the manner, where, and how long 5-HT systems are involved. Hence in this work, an attempt was made to study the effects of 5-HT endogenous on memory formation, using a 5-HT uptake facilitator (tianeptine) and, selective 5-HT(1-7) receptor antagonists to determine whether 5-HT uptake sites and which 5-HT receptors are involved, respectively. Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task, which has been useful to detect changes on memory formation elicited by drugs or aging. On interaction experiments, ketanserin (5-HT(1D/2A/2C) antagonist) slightly enhanced tianeptine effects, while WAY 100635 (5-HT(1A) antagonist), SB-224289 (5-HT(1B) inverse agonist), SB-200646 (5-HT(2B/2C) antagonist), ondansetron (5-HT(3) antagonist), GR 127487 (5-HT(4) antagonist), Ro 04-6790 (5-HT(6) antagonist), DR 4004 (5-HT(7) antagonist), or fluoxetine (an inhibitor of 5-HT reuptake) blocked the facilitatory tianeptine effect. Notably, together tianeptine and Ro 04-6790 impaired learning consolidation. Moreover, 5-HT depletion completely reversed the tianeptine effect. Tianeptine also normalized an impaired memory elicited by scopolamine (an antimuscarinic) or dizocilpine (non-competitive glutamatergic antagonist), while partially reversed that induced by TFMPP (5-HT(1B/1D/2A-2C/7) agonist/antagonist). Finally, tianeptine-fluoxetine coadministration had no effect on learning consolidation; nevertheless, administration of an acetylcholinesterase inhibitor, phenserine, potentiated subeffective tianeptine or fluoxetine doses. Collectively, these data confirmed that endogenously 5-HT modulates, via uptake sites and 5-HT(1-7) receptors, memory consolidation, and are consistent with the

Millwright Apprenticeship. Related Training Modules. 5.1-5.16 Drafting.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This packet, part of the instructional materials for the Oregon apprenticeship program for millwright training, contains 16 modules covering drafting. The modules provide information on the following topics: types of drawing and views, sketching, blueprint reading/working drawings, working drawings for machines and welding, machine and welding…

Crashworthy Evaluation of a 1/5-Scale Model Composite Fuselage Concept

NASA Technical Reports Server (NTRS)

Jackson, Karen E.; Fasanella, Edwin L.

1999-01-01

A 1/5-scale model composite fuselage concept for light aircraft and rotorcraft has been developed to satisfy structural and flight loads requirements and to satisfy design goals for improved crashworthiness. The 1/5-scale model fuselage consists of a relatively rigid upper section which forms the passenger cabin, a stiff structural floor, and an energy absorbing subfloor which is designed to limit impact forces during a crash event. The focus of the present paper is to describe the crashworthy evaluation of the fuselage concept through impact testing and finite element simulation using the nonlinear, explicit transient dynamic code, MSC/DYTRAN. The energy absorption behavior of two different subfloor configurations was determined through quasi-static crushing tests. For the dynamic evaluation, each subfloor configuration was incorporated into a 1/5-scale model fuselage section, which was impacted at 31 ft/s vertical velocity onto a rigid surface. The experimental data demonstrate that the fuselage section with a foam-filled subfloor configuration satisfied the impact design requirement. In addition, the fuselage section maintained excellent energy absorption behavior for a 31 ft/s vertical drop test with a 15 deg-roll impact attitude. Good correlation was obtained between the experimental data and analytical results for both impact conditions.

Water-quality modeling of Klamath Straits Drain recirculation, a Klamath River wetland, and 2011 conditions for the Link River to Keno Dam reach of the Klamath River, Oregon

USGS Publications Warehouse

Sullivan, Annett B.; Sogutlugil, I. Ertugrul; Deas, Michael L.; Rounds, Stewart A.

2014-01-01

The upper Klamath River and adjacent Lost River are interconnected basins in south-central Oregon and northern California. Both basins have impaired water quality with Total Maximum Daily Loads (TMDLs) in progress or approved. In cooperation with the Bureau of Reclamation, the U.S. Geological Survey (USGS) and Watercourse Engineering, Inc., have conducted modeling and research to inform management of these basins for multiple purposes, including agriculture, endangered species protection, wildlife refuges, and adjacent and downstream water users. A water-quality and hydrodynamic model (CE-QUAL-W2) of the Link River to Keno Dam reach of the Klamath River for 2006–09 is one of the tools used in this work. The model can simulate stage, flow, water velocity, ice cover, water temperature, specific conductance, suspended sediment, nutrients, organic matter in bed sediment and the water column, three algal groups, three macrophyte groups, dissolved oxygen, and pH. This report documents two model scenarios and a test of the existing model applied to year 2011, which had exceptional water quality. The first scenario examined the water-quality effects of recirculating Klamath Straits Drain flows into the Ady Canal, to conserve water and to decrease flows from the Klamath Straits Drain to the Klamath River. The second scenario explicitly incorporated a 2.73×106 m2 (675 acre) off-channel connected wetland into the CE-QUAL-W2 framework, with the wetland operating from May 1 through October 31. The wetland represented a managed treatment feature to decrease organic matter loads and process nutrients. Finally, the summer of 2011 showed substantially higher dissolved-oxygen concentrations in the Link-Keno reach than in other recent years, so the Link-Keno model (originally developed for 2006–09) was run with 2011 data as a test of model parameters and rates and to develop insights regarding the reasons for the improved water-quality conditions.

Understanding the cell-to-module efficiency gap in Cu(In,Ga)(S,Se)2 photovoltaics scale-up

NASA Astrophysics Data System (ADS)

Bermudez, Veronica; Perez-Rodriguez, Alejandro

2018-06-01

Cu(In,Ga)(S,Se)2 (CIGS) solar cells show record efficiencies comparable to those of crystalline Si-based technologies. Their industrial module production costs are also comparable to those of Si photovoltaics in spite of their much lower production volume. However, the competitiveness of CIGS is compromised by the difference in performance between cell and module scales, known as the cell-to-module efficiency gap, which is significantly higher than in competing industrial photovoltaic technologies. In this Review, we quantify the main cell-to-module efficiency loss mechanisms and discuss the various strategies explored in academia and industry to reduce the efficiency gap: new transparent conductive oxides, hybrid modularization approaches and the use of wide-bandgap solar absorbers in the 1.4-1.5 eV range. To implement these strategies, research gaps relating to various device layers need to be filled.

SCALE Code System

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

Jessee, Matthew Anderson

The SCALE Code System is a widely-used modeling and simulation suite for nuclear safety analysis and design that is developed, maintained, tested, and managed by the Reactor and Nuclear Systems Division (RNSD) of Oak Ridge National Laboratory (ORNL). SCALE provides a comprehensive, verified and validated, user-friendly tool set for criticality safety, reactor and lattice physics, radiation shielding, spent fuel and radioactive source term characterization, and sensitivity and uncertainty analysis. Since 1980, regulators, licensees, and research institutions around the world have used SCALE for safety analysis and design. SCALE provides an integrated framework with dozens of computational modules including three deterministicmore » and three Monte Carlo radiation transport solvers that are selected based on the desired solution strategy. SCALE includes current nuclear data libraries and problem-dependent processing tools for continuous-energy (CE) and multigroup (MG) neutronics and coupled neutron-gamma calculations, as well as activation, depletion, and decay calculations. SCALE includes unique capabilities for automated variance reduction for shielding calculations, as well as sensitivity and uncertainty analysis. SCALE’s graphical user interfaces assist with accurate system modeling, visualization of nuclear data, and convenient access to desired results.SCALE 6.2 provides many new capabilities and significant improvements of existing features.New capabilities include:• ENDF/B-VII.1 nuclear data libraries CE and MG with enhanced group structures,• Neutron covariance data based on ENDF/B-VII.1 and supplemented with ORNL data,• Covariance data for fission product yields and decay constants,• Stochastic uncertainty and correlation quantification for any SCALE sequence with Sampler,• Parallel calculations with KENO,• Problem-dependent temperature corrections for CE calculations,• CE shielding and criticality accident alarm system analysis with

Scale-4 Analysis of Pressurized Water Reactor Critical Configurations: Volume 2-Sequoyah Unit 2 Cycle 3

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

Bowman, S.M.

1995-01-01

The requirements of ANSI/ANS 8.1 specify that calculational methods for away-from-reactor criticality safety analyses be validated against experimental measurements. If credit for the negative reactivity of the depleted (or spent) fuel isotopics is desired, it is necessary to benchmark computational methods against spent fuel critical configurations. This report summarizes a portion of the ongoing effort to benchmark away-from-reactor criticality analysis methods using critical configurations from commercial pressurized-water reactors. The analysis methodology selected for all the calculations reported herein is based on the codes and data provided in the SCALE-4 code system. The isotopic densities for the spent fuel assemblies inmore » the critical configurations were calculated using the SAS2H analytical sequence of the SCALE-4 system. The sources of data and the procedures for deriving SAS2H input parameters are described in detail. The SNIKR code module was used to extract the necessary isotopic densities from the SAS2H results and provide the data in the format required by the SCALE criticality analysis modules. The CSASN analytical sequence in SCALE-4 was used to perform resonance processing of the cross sections. The KENO V.a module of SCALE-4 was used to calculate the effective multiplication factor (k{sub eff}) of each case. The SCALE-4 27-group burnup library containing ENDF/B-IV (actinides) and ENDF/B-V (fission products) data was used for all the calculations. This volume of the report documents the SCALE system analysis of three reactor critical configurations for the Sequoyah Unit 2 Cycle 3. This unit and cycle were chosen because of the relevance in spent fuel benchmark applications: (1) the unit had a significantly long downtime of 2.7 years during the middle of cycle (MOC) 3, and (2) the core consisted entirely of burned fuel at the MOC restart. The first benchmark critical calculation was the MOC restart at hot, full-power (HFP) critical

Scaled Lunar Module Jet Erosion Experiments

NASA Technical Reports Server (NTRS)

Land, Norman S.; Scholl, Harland F.

1966-01-01

An experimental research program was conducted on the erosion of particulate surfaces by a jet exhaust. These experiments were scaled to represent the lunar module (LM) during landing. A conical cold-gas nozzle simulating the lunar module nozzle was utilized. The investigation was conducted within a large vacuum chamber by using gravel or glass beads as a simulated soil. The effects of thrust, descent speed, nozzle terminal height, particle size on crater size, and visibility during jet erosion were determined.

Large scale modulation of high frequency acoustic waves in periodic porous media.

PubMed

Boutin, Claude; Rallu, Antoine; Hans, Stephane

2012-12-01

This paper deals with the description of the modulation at large scale of high frequency acoustic waves in gas saturated periodic porous media. High frequencies mean local dynamics at the pore scale and therefore absence of scale separation in the usual sense of homogenization. However, although the pressure is spatially varying in the pores (according to periodic eigenmodes), the mode amplitude can present a large scale modulation, thereby introducing another type of scale separation to which the asymptotic multi-scale procedure applies. The approach is first presented on a periodic network of inter-connected Helmholtz resonators. The equations governing the modulations carried by periodic eigenmodes, at frequencies close to their eigenfrequency, are derived. The number of cells on which the carrying periodic mode is defined is therefore a parameter of the modeling. In a second part, the asymptotic approach is developed for periodic porous media saturated by a perfect gas. Using the "multicells" periodic condition, one obtains the family of equations governing the amplitude modulation at large scale of high frequency waves. The significant difference between modulations of simple and multiple mode are evidenced and discussed. The features of the modulation (anisotropy, width of frequency band) are also analyzed.

Serotonin inputs to the dorsal BNST modulate anxiety in a 5-HT1A receptor dependent manner

PubMed Central

Garcia-Garcia, Alvaro L.; Canetta, Sarah; Stujenske, Joseph M.; Burghardt, Nesha S.; Ansorge, Mark S.; Dranovsky, Alex; Leonardo, E. David

2017-01-01

Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in humans and rodents. While the dorsal part of the BNST (dBNST) receives dense 5-HT innervation, whether and how 5-HT in the dBNST normally modulates anxiety remains unclear. Using optogenetics, we demonstrate that activation of 5-HT terminals in the dBNST reduces anxiety in a highly anxiogenic environment. Further analysis revealed that optogenetic inhibition of 5-HT inputs into the dBNST increases anxiety in a less anxiogenic environment. We found that 5-HT predominantly hyperpolarizes dBNST neurons, reducing their activity in a manner that can be blocked by a 5-HT1A antagonist. Finally, we demonstrate that activation of 5-HT1A receptors in the dBNST is necessary for the anxiolytic effect observed following optogenetic stimulation of 5-HT inputs into the dBNST. These data reveal that 5-HT release in the dBNST modulates anxiety-like behavior via 5-HT1A receptors under naturalistic conditions. PMID:28761080

Serotonin inputs to the dorsal BNST modulate anxiety in a 5-HT1A receptor-dependent manner.

PubMed

Garcia-Garcia, A L; Canetta, S; Stujenske, J M; Burghardt, N S; Ansorge, M S; Dranovsky, A; Leonardo, E D

2017-08-01

Serotonin (5-HT) neurons project from the raphe nuclei throughout the brain where they act to maintain homeostasis. Here, we study 5-HT inputs into the bed nucleus of the stria terminalis (BNST), a major subdivision of the extended amygdala that has been proposed to regulate responses to anxiogenic environments in humans and rodents. While the dorsal part of the BNST (dBNST) receives dense 5-HT innervation, whether and how 5-HT in the dBNST normally modulates anxiety remains unclear. Using optogenetics, we demonstrate that activation of 5-HT terminals in the dBNST reduces anxiety in a highly anxiogenic environment. Further analysis revealed that optogenetic inhibition of 5-HT inputs into the dBNST increases anxiety in a less anxiogenic environment. We found that 5-HT predominantly hyperpolarizes dBNST neurons, reducing their activity in a manner that can be blocked by a 5-HT 1A antagonist. Finally, we demonstrate that activation of 5-HT 1A receptors in the dBNST is necessary for the anxiolytic effect observed following optogenetic stimulation of 5-HT inputs into the dBNST. These data reveal that 5-HT release in the dBNST modulates anxiety-like behavior via 5-HT 1A receptors under naturalistic conditions.Molecular Psychiatry advance online publication, 1 August 2017; doi:10.1038/mp.2017.165.

Stationary Engineers Apprenticeship. Related Training Modules. 5.1-5.17 Electricity/Electronics.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This packet of 17 learning modules on electricity/electronics is one of 20 such packets developed for apprenticeship training for stationary engineers. Introductory materials are a complete listing of all available modules and a supplementary reference list. Each module contains some or all of these components: goal, performance indicators,…

Reliability and Validity of the Turkish Version of the PedsQL 3.0 Cancer Module for 2- to 7-Year-Old and the PedsQL 4.0 Generic Core Scales for 5- to 7-Year-Old: The Hacettepe University Experience.

PubMed

Yıldız Kabak, Vesile; Yakut, Yavuz; Çetin, Mualla; Düger, Tülin

2016-09-05

The aim of this study was to investigate the reliability and validity of the Turkish version of the Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module for 2- to 7-year-old and the PedsQL 4.0 Generic Core Scales for 5- to 7-year-old in childhood cancer. The PedsQL 3.0 Cancer Module and PedsQL 4.0 Generic Core Scales were administered to children with cancer and their parents at Hacettepe University. Internal consistency was determined by using Cronbach's alpha and test-retest reliability was determined by using the intraclass correlation coefficient (ICC). Construct validity was assessed by comparing the results of the PedsQL 3.0 Cancer Module with those of the PedsQL 4.0 Generic Core Scales. Cronbach's alpha of the PedsQL 3.0 Cancer Module varied from 0.803 to 0.873 and that of the PedsQL 4.0 Generic Core Scales from 0.665 to 0.841. Test-retest ICC values of the PedsQL 3.0 Cancer Module varied from 0.877 to 0.949 and those of the PedsQL 4.0 Generic Core Scales from 0.681 to 0.824. The correlation of the PedsQL 3.0 Cancer Module with subscale scores of the PedsQL 4.0 Generic Core Scales showed that there were excellent to fair correlations between the two scales. The relationship between parent proxy-report and child self-report of the PedsQL 3.0 Cancer Module had very good correlation (r=0.694, p<0.001), as did the PedsQL 4.0 Generic Core Scales (r=0.540, p=0.002). This study demonstrated the reliability, validity, and feasibility of the Turkish version of the PedsQL 3.0 Cancer Module in 2- to 4-year-old and 5- to 7-year-old and the PedsQL 4.0 Generic Core Scales in 5- to 7-year-old in childhood cancer.

Reliability and Validity of the Turkish Version of the PedsQL 3.0 Cancer Module for 2- to 7-Year-Old and the PedsQL 4.0 Generic Core Scales for 5- to 7-Year-Old: The Hacettepe University Experience

PubMed Central

Yıldız Kabak, Vesile; Yakut, Yavuz; Çetin, Mualla; Düger, Tülin

2016-01-01

Objective: The aim of this study was to investigate the reliability and validity of the Turkish version of the Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module for 2- to 7-year-old and the PedsQL 4.0 Generic Core Scales for 5- to 7-year-old in childhood cancer. Materials and Methods: The PedsQL 3.0 Cancer Module and PedsQL 4.0 Generic Core Scales were administered to children with cancer and their parents at Hacettepe University. Internal consistency was determined by using Cronbach’s alpha and test-retest reliability was determined by using the intraclass correlation coefficient (ICC). Construct validity was assessed by comparing the results of the PedsQL 3.0 Cancer Module with those of the PedsQL 4.0 Generic Core Scales. Results: Cronbach’s alpha of the PedsQL 3.0 Cancer Module varied from 0.803 to 0.873 and that of the PedsQL 4.0 Generic Core Scales from 0.665 to 0.841. Test-retest ICC values of the PedsQL 3.0 Cancer Module varied from 0.877 to 0.949 and those of the PedsQL 4.0 Generic Core Scales from 0.681 to 0.824. The correlation of the PedsQL 3.0 Cancer Module with subscale scores of the PedsQL 4.0 Generic Core Scales showed that there were excellent to fair correlations between the two scales. The relationship between parent proxy-report and child self-report of the PedsQL 3.0 Cancer Module had very good correlation (r=0.694, p<0.001), as did the PedsQL 4.0 Generic Core Scales (r=0.540, p=0.002). Conclusion: This study demonstrated the reliability, validity, and feasibility of the Turkish version of the PedsQL 3.0 Cancer Module in 2- to 4-year-old and 5- to 7-year-old and the PedsQL 4.0 Generic Core Scales in 5- to 7-year-old in childhood cancer. PMID:27095607

Multiple Regulatory Modules Are Required for Scale-to-Feather Conversion.

PubMed

Wu, Ping; Yan, Jie; Lai, Yung-Chih; Ng, Chen Siang; Li, Ang; Jiang, Xueyuan; Elsey, Ruth M; Widelitz, Randall; Bajpai, Ruchi; Li, Wen-Hsiung; Chuong, Cheng-Ming

2018-02-01

The origin of feathers is an important question in Evo-Devo studies, with the eventual evolution of vaned feathers which are aerodynamic, allowing feathered dinosaurs and early birds to fly and venture into new ecological niches. Studying how feathers and scales are developmentally specified provides insight into how a new organ may evolve. We identified feather-associated genes using genomic analyses. The candidate genes were tested by expressing them in chicken and alligator scale forming regions. Ectopic expression of these genes induced intermediate morphotypes between scales and feathers which revealed several major morphogenetic events along this path: Localized growth zone formation, follicle invagination, epithelial branching, feather keratin differentiation, and dermal papilla formation. In addition to molecules known to induce feathers on scales (retinoic acid, β-catenin), we identified novel scale-feather converters (Sox2, Zic1, Grem1, Spry2, Sox18) which induce one or more regulatory modules guiding these morphogenetic events. Some morphotypes resemble filamentous appendages found in feathered dinosaur fossils, whereas others exhibit characteristics of modern avian feathers. We propose these morpho-regulatory modules were used to diversify archosaur scales and to initiate feather evolution. The regulatory combination and hierarchical integration may have led to the formation of extant feather forms. Our study highlights the importance of integrating discoveries between developmental biology and paleontology. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Volcanic signature of Basin and Range extension on the shrinking Cascade arc, Klamath Falls-Keno area, Oregon

NASA Astrophysics Data System (ADS)

Priest, George R.; Hladky, Frank R.; Mertzman, Stanley A.; Murray, Robert B.; Wiley, Thomas J.

2013-08-01

geologic mapping of the Klamath Falls-Keno area revealed the complex relationship between subduction, crustal extension, and magmatic composition of the southern Oregon Cascade volcanic arc. Volcanism in the study area at 7-4 Ma consisted of calc-alkaline basaltic andesite and andesite lava flowing over a relatively flat landscape. Local angular unconformities are evidence that Basin and Range extension began at by at least 4 Ma and continues today with fault blocks tilting at a long-term rate of 2°/Ma to 3°/Ma. Minimum NW-SE extension is 1.5 km over 28 km ( 5%). High-alumina olivine tholeiite (HAOT) or low-K, low-Ti transitional high-alumina olivine tholeiite (LKLT) erupted within and adjacent to the back edge of the calc-alkaline arc as the edge receded westward at a rate of 10 km/Ma at 2.7-0.45 Ma. The volcanic front migrated east much slower than the back arc migrated west: 0 km/Ma for 6-0.4 Ma calc-alkaline rocks; 0.7 km/Ma, if 6 Ma HAOT-LKLT is included; and 1 km/Ma, if highly differentiated 17-30 Ma volcanic rocks of the early Western Cascades are included. Declining convergence probably decreased asthenospheric corner flow, decreasing width of calc-alkaline and HAOT-LKLT volcanism and the associated heat flow anomaly, the margins of which focused on Basin and Range extension and leakage of HAOT-LKLT magma to the surface. This declining corner flow combined with steepening slab dip shifted the back arc west. Compensation of extension by volcanic intrusion and extrusion allowed growth of imposing range-front fault scarps only behind the trailing edge of the shrinking arc.

Solar Trees: First Large-Scale Demonstration of Fully Solution Coated, Semitransparent, Flexible Organic Photovoltaic Modules.

PubMed

Berny, Stephane; Blouin, Nicolas; Distler, Andreas; Egelhaaf, Hans-Joachim; Krompiec, Michal; Lohr, Andreas; Lozman, Owen R; Morse, Graham E; Nanson, Lana; Pron, Agnieszka; Sauermann, Tobias; Seidler, Nico; Tierney, Steve; Tiwana, Priti; Wagner, Michael; Wilson, Henry

2016-05-01

The technology behind a large area array of flexible solar cells with a unique design and semitransparent blue appearance is presented. These modules are implemented in a solar tree installation at the German pavilion in the EXPO2015 in Milan/IT. The modules show power conversion efficiencies of 4.5% and are produced exclusively using standard printing techniques for large-scale production.

ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition

PubMed Central

Wang, Belinda; Krall, Elsa Beyer; Aguirre, Andrew James; Kim, Miju; Widlund, Hans Ragnar; Doshi, Mihir Bhavik; Sicinska, Ewa; Sulahian, Rita; Goodale, Amy; Cowley, Glenn Spencer; Piccioni, Federica; Doench, John Gerard; Root, David Edward; Hahn, William Chun

2017-01-01

SUMMARY Intrinsic resistance and RTK-RAS-MAPK pathway reactivation has limited the effectiveness of MEK and RAF inhibitors (MAPKi) in RAS- and RAF-mutant cancers. To identify genes that modulate sensitivity to MAPKi, we performed genome scale CRISPR-Cas9 loss-of-function screens in two KRAS-mutant pancreatic cancer cell lines treated with the MEK1/2 inhibitor trametinib. Loss of CIC, a transcriptional repressor of ETV1, 4, and 5, promoted survival in the setting of MAPKi in cancer cells derived from several lineages. ATXN1L deletion, which reduces CIC protein, or ectopic expression of ETV1, 4, or 5 also modulated sensitivity to trametinib. ATXN1L expression inversely correlates with response to MAPKi inhibition in clinical studies. These observations identify the ATXN1L-CIC-ETS transcription factor axis as a mediator of resistance to MAPKi. PMID:28178529

Recovery of Large Angular Scale CMB Polarization for Instruments Employing Variable-Delay Polarization Modulators

NASA Technical Reports Server (NTRS)

Miller, N. J.; Chuss, D. T.; Marriage, T. A.; Wollack, E. J.; Appel, J. W.; Bennett, C. L.; Eimer, J.; Essinger-Hileman, T.; Fixsen, D. J.; Harrington, K.;

Low Voltage Alarm Apprenticeship. Related Training Modules. 2.1-5.3 Electricity/Electronics.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This packet of 29 learning modules on electricity/electronics is 1 of 8 such packets developed for apprenticeship training for low voltage alarm. Introductory materials are a complete listing of all available modules and a supplementary reference list. Each module contains some or all of these components: goal, performance indicators, study guide…

R&D issues in scale-up and manufacturing of amorphous silicon tandem modules

NASA Astrophysics Data System (ADS)

Arya, R. R.; Carlson, D. E.; Chen, L. F.; Ganguly, G.; He, M.; Lin, G.; Middya, R.; Wood, G.; Newton, J.; Bennett, M.; Jackson, F.; Willing, F.

1999-03-01

R & D on amorphous silicon based tandem junction devices has improved the throughtput, the material utilization, and the performance of devices on commercial tin oxide coated glass. The tandem junction technology has been scaled-up to produce 8.6 Ft2 monolithically integrated modules in manufacturing at the TF1 plant. Optimization of performance and stability of these modules is ongoing.

E-ELT M5 field stabilisation unit scale 1 demonstrator design and performances evaluation

NASA Astrophysics Data System (ADS)

Casalta, J. M.; Barriga, J.; Ariño, J.; Mercader, J.; San Andrés, M.; Serra, J.; Kjelberg, I.; Hubin, N.; Jochum, L.; Vernet, E.; Dimmler, M.; Müller, M.

2010-07-01

The M5 Field stabilization Unit (M5FU) for European Extremely Large Telescope (E-ELT) is a fast correcting optical system that shall provide tip-tilt corrections for the telescope dynamic pointing errors and the effect of atmospheric tiptilt and wind disturbances. A M5FU scale 1 demonstrator (M5FU1D) is being built to assess the feasibility of the key elements (actuators, sensors, mirror, mirror interfaces) and the real-time control algorithm. The strict constraints (e.g. tip-tilt control frequency range 100Hz, 3m ellipse mirror size, mirror first Eigen frequency 300Hz, maximum tip/tilt range +/- 30 arcsec, maximum tiptilt error < 40 marcsec) have been a big challenge for developing the M5FU Conceptual Design and its scale 1 demonstrator. The paper summarises the proposed design for the final unit and demonstrator and the measured performances compared to the applicable specifications.

Evidence of Rentian Scaling of Functional Modules in Diverse Biological Networks.

PubMed

How, Javier J; Navlakha, Saket

2018-06-12

Biological networks have long been known to be modular, containing sets of nodes that are highly connected internally. Less emphasis, however, has been placed on understanding how intermodule connections are distributed within a network. Here, we borrow ideas from engineered circuit design and study Rentian scaling, which states that the number of external connections between nodes in different modules is related to the number of nodes inside the modules by a power-law relationship. We tested this property in a broad class of molecular networks, including protein interaction networks for six species and gene regulatory networks for 41 human and 25 mouse cell types. Using evolutionarily defined modules corresponding to known biological processes in the cell, we found that all networks displayed Rentian scaling with a broad range of exponents. We also found evidence for Rentian scaling in functional modules in the Caenorhabditis elegans neural network, but, interestingly, not in three different social networks, suggesting that this property does not inevitably emerge. To understand how such scaling may have arisen evolutionarily, we derived a new graph model that can generate Rentian networks given a target Rent exponent and a module decomposition as inputs. Overall, our work uncovers a new principle shared by engineered circuits and biological networks.

RECOVERY OF LARGE ANGULAR SCALE CMB POLARIZATION FOR INSTRUMENTS EMPLOYING VARIABLE-DELAY POLARIZATION MODULATORS

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

Miller, N. J.; Marriage, T. A.; Appel, J. W.

2016-02-20

Variable-delay Polarization Modulators (VPMs) are currently being implemented in experiments designed to measure the polarization of the cosmic microwave background on large angular scales because of their capability for providing rapid, front-end polarization modulation and control over systematic errors. Despite the advantages provided by the VPM, it is important to identify and mitigate any time-varying effects that leak into the synchronously modulated component of the signal. In this paper, the effect of emission from a 300 K VPM on the system performance is considered and addressed. Though instrument design can greatly reduce the influence of modulated VPM emission, some residualmore » modulated signal is expected. VPM emission is treated in the presence of rotational misalignments and temperature variation. Simulations of time-ordered data are used to evaluate the effect of these residual errors on the power spectrum. The analysis and modeling in this paper guides experimentalists on the critical aspects of observations using VPMs as front-end modulators. By implementing the characterizations and controls as described, front-end VPM modulation can be very powerful for mitigating 1/f noise in large angular scale polarimetric surveys. None of the systematic errors studied fundamentally limit the detection and characterization of B-modes on large scales for a tensor-to-scalar ratio of r = 0.01. Indeed, r < 0.01 is achievable with commensurately improved characterizations and controls.« less

R&D issues in scale-up and manufacturing of amorphous silicon tandem modules

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

Arya, R.R.; Carlson, D.E.; Chen, L.F.

1999-03-01

R & D on amorphous silicon based tandem junction devices has improved the throughtput, the material utilization, and the performance of devices on commercial tin oxide coated glass. The tandem junction technology has been scaled-up to produce 8.6&hthinsp;Ft{sup 2} monolithically integrated modules in manufacturing at the TF1 plant. Optimization of performance and stability of these modules is ongoing. {copyright} {ital 1999 American Institute of Physics.}

Block 5 documentation and solar modules

NASA Technical Reports Server (NTRS)

1985-01-01

Design and fabrication of Spire Corporation's Block 5 photovoltaic flat plate module is reviewed. These modules exhibited power of about 70 watts under standard test conditions. Results of performance and environmental testing are provided.

ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition.

PubMed

Wang, Belinda; Krall, Elsa Beyer; Aguirre, Andrew James; Kim, Miju; Widlund, Hans Ragnar; Doshi, Mihir Bhavik; Sicinska, Ewa; Sulahian, Rita; Goodale, Amy; Cowley, Glenn Spencer; Piccioni, Federica; Doench, John Gerard; Root, David Edward; Hahn, William Chun

2017-02-07

Intrinsic resistance and RTK-RAS-MAPK pathway reactivation has limited the effectiveness of MEK and RAF inhibitors (MAPKi) in RAS- and RAF-mutant cancers. To identify genes that modulate sensitivity to MAPKi, we performed genome-scale CRISPR-Cas9 loss-of-function screens in two KRAS mutant pancreatic cancer cell lines treated with the MEK1/2 inhibitor trametinib. Loss of CIC, a transcriptional repressor of ETV1, ETV4, and ETV5, promoted survival in the setting of MAPKi in cancer cells derived from several lineages. ATXN1L deletion, which reduces CIC protein, or ectopic expression of ETV1, ETV4, or ETV5 also modulated sensitivity to trametinib. ATXN1L expression inversely correlates with response to MAPKi inhibition in clinical studies. These observations identify the ATXN1L-CIC-ETS transcription factor axis as a mediator of resistance to MAPKi. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

An Instructional Module on Mokken Scale Analysis

ERIC Educational Resources Information Center

Wind, Stefanie A.

2017-01-01

Mokken scale analysis (MSA) is a probabilistic-nonparametric approach to item response theory (IRT) that can be used to evaluate fundamental measurement properties with less strict assumptions than parametric IRT models. This instructional module provides an introduction to MSA as a probabilistic-nonparametric framework in which to explore…

A 4-channel coil array interconnection by analog direct modulation optical link for 1.5-T MRI.

PubMed

Yuan, Jing; Wei, Juan; Shen, Gary X

2008-10-01

Optical glass fiber shows great advantages over coaxial cables in terms of electromagnetic interference, thus, it should be considered a potential alternative for magnetic resonance imaging (MRI) receive coil interconnection, especially for a large number coil array at high field. In this paper, we propose a 4-channel analog direct modulation optical link for a 1.5-T MRI coil array interconnection. First, a general direct modulated optical link is compared to an external modulated optical link. And then the link performances of the proposed direct modulated optical link, including power gain, frequency response, and dynamic range, are analyzed and measured. Phantom and in vivo head images obtained using this optical link are demonstrated for comparison with those obtained by cable connections. The signal-to-noise (SNR) analysis shows that the optical link achieves 6%-8% SNR a improvement over coaxial cables by elimination of electrical interference between cables during MR signal transmission.

An improved method to characterise the modulation of small-scale turbulent by large-scale structures

NASA Astrophysics Data System (ADS)

Agostini, Lionel; Leschziner, Michael; Gaitonde, Datta

2015-11-01

A key aspect of turbulent boundary layer dynamics is ``modulation,'' which refers to degree to which the intensity of coherent large-scale structures (LS) cause an amplification or attenuation of the intensity of the small-scale structures (SS) through large-scale-linkage. In order to identify the variation of the amplitude of the SS motion, the envelope of the fluctuations needs to be determined. Mathis et al. (2009) proposed to define this latter by low-pass filtering the modulus of the analytic signal built from the Hilbert transform of SS. The validity of this definition, as a basis for quantifying the modulated SS signal, is re-examined on the basis of DNS data for a channel flow. The analysis shows that the modulus of the analytic signal is very sensitive to the skewness of its PDF, which is dependent, in turn, on the sign of the LS fluctuation and thus of whether these fluctuations are associated with sweeps or ejections. The conclusion is that generating an envelope by use of a low-pass filtering step leads to an important loss of information associated with the effects of the local skewness of the PDF of the SS on the modulation process. An improved Hilbert-transform-based method is proposed to characterize the modulation of SS turbulence by LS structures

Module Degradation Mechanisms Studied by a Multi-Scale Approach

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

Johnston, Steve; Al-Jassim, Mowafak; Hacke, Peter

2016-11-21

A key pathway to meeting the Department of Energy SunShot 2020 goals is to reduce financing costs by improving investor confidence through improved photovoltaic (PV) module reliability. A comprehensive approach to further understand and improve PV reliability includes characterization techniques and modeling from module to atomic scale. Imaging techniques, which include photoluminescence, electroluminescence, and lock-in thermography, are used to locate localized defects responsible for module degradation. Small area samples containing such defects are prepared using coring techniques and are then suitable and available for microscopic study and specific defect modeling and analysis.

Millwright Apprenticeship. Related Training Modules. 8.1-8.5 Turbines.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This packet, part of the instructional materials for the Oregon apprenticeship program for millwright training, contains five modules covering turbines. The modules provide information on the following topics: types, components, and auxiliaries of steam turbines; operation and maintenance of steam turbines; and gas turbines. Each module consists…

Millwright Apprenticeship. Related Training Modules. 10.1-10.5 Combustion.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This packet, part of the instructional materials for the Oregon apprenticeship program for millwright training, contains five modules covering combustion. The modules provide information on the following topics: the combustion process, types of fuel, air and fuel gases, heat transfer, and combustion in wood. Each module consists of a goal,…

Millwright Apprenticeship. Related Training Modules. 15.1-15.5 Miscellaneous.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This packet of five learning modules on miscellaneous topics is one of six such packets developed for apprenticeship training for millwrights. Introductory materials are a complete listing of all available modules and a supplementary reference list. Each module contains some or all of these components: goal, performance indicators, study guide (a…

Flavonoid-rich extract of Chromolaena odorata modulate circulating GLP-1 in Wistar rats: computational evaluation of TGR5 involvement.

PubMed

Omotuyi, Olaposi Idowu; Nash, Oyekanmi; Inyang, Olumide Kayode; Ogidigo, Joyce; Enejoh, Ojochenemi; Okpalefe, Okiemute; Hamada, Tsuyoshi

2018-02-01

Chromolaena odorata is a major bio-resource in folkloric treatment of diabetes. In the present study, its anti-diabetic component and underlying mechanism were investigated. A library containing 140 phytocompounds previously characterized from C. odorata was generated and docked (Autodock Vina) into homology models of dipeptidyl peptidase (DPP)-4, Takeda-G-protein-receptor-5 (TGR5), glucagon-like peptide 1 (GLP1) receptor, renal sodium dependent glucose transporter (SGLUT)-1/2 and nucleotide-binding oligomerization domain (NOD) proteins 1&2. GLP-1 gene (RT-PCR) modulation and its release (EIA) by C. odorata were confirmed in vivo. From the docking result above, TGR5 was identified as a major target for two key C. odorata flavonoids (5,7-dihydroxy-6-4-dimethoxyflavanone and homoesperetin-7-rutinoside); sodium taurocholate and C. odorata powder included into the diet of the animals both raised the intestinal GLP-1 expression versus control ( p  < 0.05); When treated with flavonoid-rich extract of C. odorata (CoF) or malvidin, circulating GLP-1 increased by 130.7% in malvidin-treated subjects (0 vs. 45 min). CoF treatment also resulted in 128.5 and 275% increase for 10 and 30 mg/kg b.w., respectively. The results of this study support that C. odorata flavonoids may modulate the expression of GLP-1 and its release via TGR5. This finding may underscore its anti-diabetic potency.

Headstart German Program. Module 5.

ERIC Educational Resources Information Center

Defense Language Inst., Monterey, CA.

This is the fifth module of 10 in the German Headstart program. Each of the 3 units in the module contains objectives, exercises, and a self-evaluation quiz. In addition, there are several supplementary exercises and self-evaluations. The objective of this module is to enable the student to use and understand: (1) courtesy expressions; (2) time…

GCR Modulation by Small-Scale Features in the Interplanetary Medium

NASA Astrophysics Data System (ADS)

Jordan, A. P.; Spence, H. E.; Blake, J. B.; Mulligan, T. L.; Shaul, D. N.; Galametz, M.

2007-12-01

In an effort to uncover the properties of structures in the interplanetary medium (IPM) that modulate galactic cosmic rays (GCR) on short time-scales (from hours to days), we study periods of differing conditions in the IPM. We analyze GCR variations from spacecraft both inside and outside the magnetosphere, using the High Sensitivity Telescope (HIST) on Polar and the Spectrometer for INTEGRAL (SPI). We seek causal correlations between the observed GCR modulations and structures in the solar wind plasma and interplanetary magnetic field, as measured concurrently with ACE and/or Wind. Our analysis spans time-/size-scale variations ranging from classic Forbush decreases (Fds), to substructure embedded within Fds, to much smaller amplitude and shorter duration variations observed during comparatively benign interplanetary conditions. We compare and contrast the conditions leading to the range of different GCR responses to modulating structures in the IPM.

The 1.06 micrometer wideband laser modulator: Fabrication and life testing

NASA Technical Reports Server (NTRS)

Teague, J. R.

1975-01-01

The design, fabrication, testing and delivery of an optical modulator which will operate with a mode-locked Nd:YAG laser at 1.06 micrometers were performed. The system transfers data at a nominal rate of 400 Mbps. This wideband laser modulator can transmit either Pulse Gated Binary Modulation (PGBM) or Pulse Polarization Binary Modulation (PPBM) formats. The laser beam enters the modulator and passes through both crystals; approximately 1% of the transmitted beam is split from the main beam and analyzed for the AEC signal; the remaining part of the beam exits the modulator. The delivered modulator when initially aligned and integrated with laser and electronics performed very well. The optical transmission was 69.5%. The static extinction ratio was 69:1. A 1000 hour life test was conducted with the delivered modulator. A 63 bit pseudorandom code signal was used as a driver input. At the conclusion of the life test the modulator optical transmission was 71.5% and the static extinction ratio 65:1.

Comparing multi-module connections in membrane chromatography scale-up.

PubMed

Yu, Zhou; Karkaria, Tishtar; Espina, Marianela; Hunjun, Manjeet; Surendran, Abera; Luu, Tina; Telychko, Julia; Yang, Yan-Ping

2015-07-20

Membrane chromatography is increasingly used for protein purification in the biopharmaceutical industry. Membrane adsorbers are often pre-assembled by manufacturers as ready-to-use modules. In large-scale protein manufacturing settings, the use of multiple membrane modules for a single batch is often required due to the large quantity of feed material. The question as to how multiple modules can be connected to achieve optimum separation and productivity has been previously approached using model proteins and mass transport theories. In this study, we compare the performance of multiple membrane modules in series and in parallel in the production of a protein antigen. Series connection was shown to provide superior separation compared to parallel connection in the context of competitive adsorption. Copyright © 2015 Elsevier B.V. All rights reserved.

Characteristics of 5M modulated martensite in Ni-Mn-Ga magnetic shape memory alloys

NASA Astrophysics Data System (ADS)

Ćakır, A.; Acet, M.; Righi, L.; Albertini, F.; Farle, M.

2015-09-01

The applicability of the magnetic shape memory effect in Ni-Mn-based martensitic Heusler alloys is closely related to the nature of the crystallographically modulated martensite phase in these materials. We study the properties of modulated phases as a function of temperature and composition in three magnetic shape memory alloys Ni49.8Mn25.0Ga25.2, Ni49.8Mn27.1Ga23.1 and Ni49.5Mn28.6Ga21.9. The effect of substituting Ga for Mn leads to an anisotropic expansion of the lattice, where the b-parameter of the 5M modulated structure increases and the a and c-parameters decrease with increasing Ga concentration. The modulation vector is found to be both temperature and composition dependent. The size of the modulation vector corresponds to an incommensurate structure for Ni49.8Mn25.0Ga25.2 at all temperatures. For the other samples the modulation is incommensurate at low temperatures but reaches a commensurate value of q ≈ 0.400 close to room temperature. The results show that commensurateness of the 5M modulated structure is a special case of incommensurate 5M at a particular temperature.

Vibration test of 1/5 scale H-II launch vehicle

NASA Astrophysics Data System (ADS)

Morino, Yoshiki; Komatsu, Keiji; Sano, Masaaki; Minegishi, Masakatsu; Morita, Toshiyuki; Kohsetsu, Y.

In order to predict dynamic loads on the newly designed Japanese H-II launch vehicle, the adequacy of prediction methods has been assessed by the dynamic scale model testing. The three-dimensional dynamic model was used in the analysis to express coupling effects among axial, lateral (pitch and yaw) and torsional vibrations. The liquid/tank interaction was considered by use of a boundary element method. The 1/5 scale model of the H-II launch vehicle was designed to simulate stiffness and mass properties of important structural parts, such as core/SRB junctions, first and second stage Lox tanks and engine mount structures. Modal excitation of the test vehicle was accomplished with 100-1000 N shakers which produced random or sinusoidal vibrational forces. The vibrational response of the test vehicle was measured at various locations with accelerometers and pressure sensor. In the lower frequency range, corresmpondence between analysis and experiment was generally good. The basic procedures in analysis seem to be adequate so far, but some improvements in mathematical modeling are suggested by comparison of test and analysis.

Development of a SCALE Tool for Continuous-Energy Eigenvalue Sensitivity Coefficient Calculations

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

Perfetti, Christopher M; Rearden, Bradley T

2013-01-01

Two methods for calculating eigenvalue sensitivity coefficients in continuous-energy Monte Carlo applications were implemented in the KENO code within the SCALE code package. The methods were used to calculate sensitivity coefficients for several criticality safety problems and produced sensitivity coefficients that agreed well with both reference sensitivities and multigroup TSUNAMI-3D sensitivity coefficients. The newly developed CLUTCH method was observed to produce sensitivity coefficients with high figures of merit and low memory requirements, and both continuous-energy sensitivity methods met or exceeded the accuracy of the multigroup TSUNAMI-3D calculations.

Low frequency steady-state brain responses modulate large scale functional networks in a frequency-specific means.

PubMed

Wang, Yi-Feng; Long, Zhiliang; Cui, Qian; Liu, Feng; Jing, Xiu-Juan; Chen, Heng; Guo, Xiao-Nan; Yan, Jin H; Chen, Hua-Fu

2016-01-01

Neural oscillations are essential for brain functions. Research has suggested that the frequency of neural oscillations is lower for more integrative and remote communications. In this vein, some resting-state studies have suggested that large scale networks function in the very low frequency range (<1 Hz). However, it is difficult to determine the frequency characteristics of brain networks because both resting-state studies and conventional frequency tagging approaches cannot simultaneously capture multiple large scale networks in controllable cognitive activities. In this preliminary study, we aimed to examine whether large scale networks can be modulated by task-induced low frequency steady-state brain responses (lfSSBRs) in a frequency-specific pattern. In a revised attention network test, the lfSSBRs were evoked in the triple network system and sensory-motor system, indicating that large scale networks can be modulated in a frequency tagging way. Furthermore, the inter- and intranetwork synchronizations as well as coherence were increased at the fundamental frequency and the first harmonic rather than at other frequency bands, indicating a frequency-specific modulation of information communication. However, there was no difference among attention conditions, indicating that lfSSBRs modulate the general attention state much stronger than distinguishing attention conditions. This study provides insights into the advantage and mechanism of lfSSBRs. More importantly, it paves a new way to investigate frequency-specific large scale brain activities. © 2015 Wiley Periodicals, Inc.

A Rab5 GTPase module is important for autophagosome closure

PubMed Central

Lipatova, Zhanna; Sun, Dan; Zhu, Xiaolong; Li, Rui; Wu, Zulin; You, Weiming; Cong, Xiaoxia; Zhou, Yiting; Gyurkovska, Valeriya; Liu, Yutao; Li, Qunli; Li, Wenjing; Cheng, Jie; Segev, Nava

2017-01-01

In the conserved autophagy pathway, the double-membrane autophagosome (AP) engulfs cellular components to be delivered for degradation in the lysosome. While only sealed AP can productively fuse with the lysosome, the molecular mechanism of AP closure is currently unknown. Rab GTPases, which regulate all intracellular trafficking pathways in eukaryotes, also regulate autophagy. Rabs function in GTPase modules together with their activators and downstream effectors. In yeast, an autophagy-specific Ypt1 GTPase module, together with a set of autophagy-related proteins (Atgs) and a phosphatidylinositol-3-phosphate (PI3P) kinase, regulates AP formation. Fusion of APs and endosomes with the vacuole (the yeast lysosome) requires the Ypt7 GTPase module. We have previously shown that the Rab5-related Vps21, within its endocytic GTPase module, regulates autophagy. However, it was not clear which autophagy step it regulates. Here, we show that this module, which includes the Vps9 activator, the Rab5-related Vps21, the CORVET tethering complex, and the Pep12 SNARE, functions after AP expansion and before AP closure. Whereas APs are not formed in mutant cells depleted for Atgs, sealed APs accumulate in cells depleted for the Ypt7 GTPase module members. Importantly, depletion of individual members of the Vps21 module results in a novel phenotype: accumulation of unsealed APs. In addition, we show that Vps21-regulated AP closure precedes another AP maturation step, the previously reported PI3P phosphatase-dependent Atg dissociation. Our results delineate three successive steps in the autophagy pathway regulated by Rabs, Ypt1, Vps21 and Ypt7, and provide the first insight into the upstream regulation of AP closure. PMID:28934205

Modulatory effect of the 5-HT1A agonist buspirone and the mixed non-hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience.

PubMed

Pokorny, Thomas; Preller, Katrin H; Kraehenmann, Rainer; Vollenweider, Franz X

2016-04-01

The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose-dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 µg/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness (OB) including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Stationary Engineers Apprenticeship. Related Training Modules. 15.1-15.5 Turbines.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This learning module, one in a series of 20 related training modules for apprentice stationary engineers, deals with turbines. addressed in the individual instructional packages included in the module are the following topics: types and components of steam turbines, steam turbine auxiliaries, operation and maintenance of steam turbines, and gas…

Stationary Engineers Apprenticeship. Related Training Modules. 16.1-16.5 Combustion.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This learning module, one in a series of 20 related training modules for apprentice stationary engineers, deals with combustion. Addressed in the individual instructional packages included in the module are the following topics: the combustion process, types of fuel, air and flue gases, heat transfer during combustion, and wood combustion. Each…

Stationary Engineers Apprenticeship. Related Training Modules. 4.1-4.5 Tools.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This packet of five learning modules on tools is one of 20 such packets developed for apprenticeship training for stationary engineers. Introductory materials are a complete listing of all available modules and a supplementary reference list. Each module contains some or all of these components: a lesson goal, performance indicators, study guide…

The PedsQL in pediatric cerebral palsy: reliability and validity of the Chinese version pediatric quality of life inventory 4.0 generic core scales and 3.0 cerebral palsy module.

PubMed

Yang, Xue; Xiao, Nong; Yan, Jianying

2011-03-01

This investigation examines the reliability, validity, and sensitivity of the Chinese version Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales and 3.0 cerebral palsy (CP) Module in pediatric CP. The study sample was comprised of 126 parents of children with CP between the ages of 2 and 12 years including 18 child respondents 5-12 years of age. Mean age of the 87 boys (69.0%) and 39 girls (31.0%) was 4 years 1 month (SD 2 years 2 month). Reliability was demonstrated for the PedsQL 4.0 (α = 0.86 child, 0.89 parent) and CP Module (α = 0.91 child, 0.96 parent). The PedsQL 4.0 distinguished between healthy children and children with CP. Construct validity of the CP Module was supported through an analysis of the intercorrelations between the Generic Core Scale scores and the CP Module Scale scores and exploratory factor analysis of PedsQL items. The findings provide support for the measurement properties of the Chinese version PedsQL 4.0 Generic Core Scales and 3.0 CP Module in pediatric CP.

Opposite monosynaptic scaling of BLP–vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory

PubMed Central

Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

2016-01-01

Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP–vCA1 connection. Optogenetic disruption of BLP–vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP–vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP–vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP–vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory. PMID:27411738

Opposite monosynaptic scaling of BLP-vCA1 inputs governs hopefulness- and helplessness-modulated spatial learning and memory.

PubMed

Yang, Ying; Wang, Zhi-Hao; Jin, Sen; Gao, Di; Liu, Nan; Chen, Shan-Ping; Zhang, Sinan; Liu, Qing; Liu, Enjie; Wang, Xin; Liang, Xiao; Wei, Pengfei; Li, Xiaoguang; Li, Yin; Yue, Chenyu; Li, Hong-Lian; Wang, Ya-Li; Wang, Qun; Ke, Dan; Xie, Qingguo; Xu, Fuqiang; Wang, Liping; Wang, Jian-Zhi

2016-07-14

Different emotional states lead to distinct behavioural consequences even when faced with the same challenging events. Emotions affect learning and memory capacities, but the underlying neurobiological mechanisms remain elusive. Here we establish models of learned helplessness (LHL) and learned hopefulness (LHF) by exposing animals to inescapable foot shocks or with anticipated avoidance trainings. The LHF animals show spatial memory potentiation with excitatory monosynaptic upscaling between posterior basolateral amygdale (BLP) and ventral hippocampal CA1 (vCA1), whereas the LHL show memory deficits with an attenuated BLP-vCA1 connection. Optogenetic disruption of BLP-vCA1 inputs abolishes the effects of LHF and impairs synaptic plasticity. By contrast, targeted BLP-vCA1 stimulation rescues the LHL-induced memory deficits and mimics the effects of LHF. BLP-vCA1 stimulation increases synaptic transmission and dendritic plasticity with the upregulation of CREB and intrasynaptic AMPA receptors in CA1. These findings indicate that opposite excitatory monosynaptic scaling of BLP-vCA1 controls LHF- and LHL-modulated spatial memory, revealing circuit-specific mechanisms linking emotions to memory.

Langley Full-Scale Tunnel Investigation of a 1/3-Scale Model of the Chance Vought XF5U-1 Airplane

NASA Technical Reports Server (NTRS)

Lange, Roy H.; Cocke, Bennie W., Jr.; Proterra, Anthony J.

1946-01-01

The results of an investigation of a 1/3-scale model of the Chance Vought XF5U-1 airplane in the Langley full-scale tunnel are presented in this report. The maximum lift and stalling characteristics of several model configurations, the longitudinal stability characteristics of the model, and the effectiveness of the control surfaces were determined with the propellers removed. The propulsive characteristics, the effect of propeller operation on the lift, and the static thrust of the model propellers were determined at several propeller-blade angles. The results with the propellers removed showed that the maximum lift coefficient of the complete model configuration was only 0.97 was compared with the value of 1.31 for the model configuration in which the engine-air ducts and canopy are removed. The model with the propellers removed (normal center-of-gravity position) has a positive static margin, stick fixed, varying from 5 to 13 percent of the mean aerodynamic chord throughout the unstalled range of lift coefficients. The unit horizontal tail is sufficiently powerful to trim the airplane with the propellers removed throughout the unstalled range of lift coefficients. The peak propulsive efficiencies for beta = 20 degrees and beta = 30 degrees were increased 7 percent at C(sub L) congruent to 0.67 and 20 percent at C(sub L) congruent to 0.74, respectively, with the propellers rotating upward in the center than with the propellers rotating downward in the center. Indications are that the minimum forward-flight speed of the airplane for full-power operation at sea level will be about 90 miles per hour. Decreasing the weight and increasing the power reduced this value of minimum speed and there were no indications from the results of a lower limit to the minimum speed.

Evaluation of novel scoring system named 5-5-5 exacerbation grading scale for allergic conjunctivitis disease.

PubMed

Shoji, Jun; Inada, Noriko; Sawa, Mitsuru

2009-12-01

The objective of this study is to evaluate the practical usefulness of a scoring system using the 5-5-5 exacerbation grading scale for allergic conjunctivitis disease (ACD). Subjects were 103 patients with ACD including 40 patients with vernal keratoconjunctivitis (VKC), 20 patients with atopic keratoconjunctivitis (AKC), and 43 patients with allergic conjunctivitis (AC). The 5-5-5 exacerbation grading scale consists of the following 3 graded groups of clinical observations: the 100-point-grade group (100 points for each observation) includes active giant papillae, gelatinous infiltrates of the limbus, exfoliative epithelial keratopathy, shield ulcer and papillary proliferation at lower palpebral conjunctiva; the 10-point-grade group (10 points for each observation) includes blepharitis, papillary proliferation with velvety appearance, Horner-Trantas spots, edema of bulbal conjunctiva, and superficial punctate keratopathy; and the 1-point-grade group (1 point for each observation) includes papillae at upper palpebral conjunctiva, follicular lesion at lower palpebral conjunctiva, hyperemia of palpebral conjunctiva, hyperemia of bulbal conjunctiva, and lacrimal effusion. The total points in each grade group were determined as the severity score of the 5-5-5 exacerbation grading scale. The median severity scores of the 5-5-5 exacerbation grading scale in VKC, AKC and AC were 243 (range: 12-444), 32.5 (11-344), and 13 (2-33), respectively. The severity score of each ACD disease type was significantly different (P < 0.001, Kruskal-Wallis test). The severity of each type of ACD was classified as severe, moderate, or mild according to the severity score. The 5-5-5 exacerbation grading scale is a useful clinical tool for grading the severity of each type of ACD.

Large voltage modulation in superconducting quantum interference devices with submicron-scale step-edge junctions

NASA Astrophysics Data System (ADS)

Lam, Simon K. H.

2017-09-01

A promising direction to improve the sensitivity of a SQUID is to increase its junction's normal resistance value, Rn, as the SQUID modulation voltage scales linearly with Rn. As a first step to develop highly sensitive single layer SQUID, submicron scale YBCO grain boundary step edge junctions and SQUIDs with large Rn were fabricated and studied. The step-edge junctions were reduced to submicron scale to increase their Rn values using focus ion beam, FIB and the measurement of transport properties were performed from 4.3 to 77 K. The FIB induced deposition layer proves to be effective to minimize the Ga ion contamination during the FIB milling process. The critical current-normal resistance value of submicron junction at 4.3 K was found to be 1-3 mV, comparable to the value of the same type of junction in micron scale. The submicron junction Rn value is in the range of 35-100 Ω, resulting a large SQUID modulation voltage in a wide temperature range. This performance promotes further investigation of cryogen-free, high field sensitivity SQUID applications at medium low temperature, e.g. at 40-60 K.

Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators.

PubMed

Han, Changho; Chatterjee, Arindam; Noetzel, Meredith J; Panarese, Joseph D; Smith, Emery; Chase, Peter; Hodder, Peter; Niswender, Colleen; Conn, P Jeffrey; Lindsley, Craig W; Stauffer, Shaun R

2015-01-15

Results from a 2012 high-throughput screen of the NIH Molecular Libraries Small Molecule Repository (MLSMR) against the human muscarinic receptor subtype 1 (M1) for positive allosteric modulators is reported. A content-rich screen utilizing an intracellular calcium mobilization triple-addition protocol allowed for assessment of all three modes of pharmacology at M1, including agonist, positive allosteric modulator, and antagonist activities in a single screening platform. We disclose a dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-one hit (DBPQ, CID 915409) and examine N-benzyl pharmacophore/SAR relationships versus previously reported quinolin-3(5H)-ones and isatins, including ML137. SAR and consideration of recently reported crystal structures, homology modeling, and structure-function relationships using point mutations suggests a shared binding mode orientation at the putative common allosteric binding site directed by the pendant N-benzyl substructure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Large scale structures around radio galaxies at z ~ 1.5

NASA Astrophysics Data System (ADS)

Galametz, A.; De Breuck, C.; Vernet, J.; Stern, D.; Rettura, A.; Marmo, C.; Omont, A.; Allen, M.; Seymour, N.

2009-11-01

We explore the environments of two radio galaxies at z ~ 1.5, 7C 1751+6809 and 7C 1756+6520, using deep optical and near-infrared imaging. Our data cover 15×15 arcmin2 fields around the radio galaxies. We develop and apply BzK color criteria to select cluster member candidates around the radio galaxies and find no evidence of an overdensity of red galaxies within 2 Mpc of 7C 1751+6809. In contrast, 7C 1756+6520 shows a significant overdensity of red galaxies within 2 Mpc of the radio galaxy, by a factor of 3.1±0.8 relative to the four MUSYC fields. At small separation (r < 6 arcsec), this radio galaxy also has one z > 1.4 evolved galaxy candidate, one z > 1.4 star-forming galaxy candidate, and an AGN candidate (at indeterminate redshift). This is suggestive of several close-by companions. Several concentrations of red galaxies are also noticed in the full 7C 1756+6520 field, forming a possible large-scale structure of evolved galaxies with a NW-SE orientation. We construct the color-magnitude diagram of red galaxies found near 7C 1756+6520 (r < 2 Mpc), and find a clear red sequence that is truncated at Ks ~ 21.5 (AB). We also find an overdensity of mid-infrared selected AGN in the surroundings of 7C 1756+6520. These results are suggestive of a proto-cluster at high redshift. Tables 2-6 are only available in electronic form at http://www.aanda.org

Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex

PubMed Central

Corcoran, Andrea E.; Brust, Rachael D.; Chang, YoonJeung; Nattie, Eugene E.

2017-01-01

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 (Tac1) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1, referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine-N-oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO2. Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using genetic

Activity of Tachykinin1-Expressing Pet1 Raphe Neurons Modulates the Respiratory Chemoreflex.

PubMed

Hennessy, Morgan L; Corcoran, Andrea E; Brust, Rachael D; Chang, YoonJeung; Nattie, Eugene E; Dymecki, Susan M

2017-02-15

Homeostatic control of breathing, heart rate, and body temperature relies on circuits within the brainstem modulated by the neurotransmitter serotonin (5-HT). Mounting evidence points to specialized neuronal subtypes within the serotonergic neuronal system, borne out in functional studies, for the modulation of distinct facets of homeostasis. Such functional differences, read out at the organismal level, are likely subserved by differences among 5-HT neuron subtypes at the cellular and molecular levels, including differences in the capacity to coexpress other neurotransmitters such as glutamate, GABA, thyrotropin releasing hormone, and substance P encoded by the Tachykinin-1 ( Tac1 ) gene. Here, we characterize in mice a 5-HT neuron subtype identified by expression of Tac1 and the serotonergic transcription factor gene Pet1 , referred to as the Tac1-Pet1 neuron subtype. Transgenic cell labeling showed Tac1-Pet1 soma resident largely in the caudal medulla. Chemogenetic [clozapine -N- oxide (CNO)-hM4Di] perturbation of Tac1-Pet1 neuron activity blunted the ventilatory response of the respiratory CO 2 chemoreflex, which normally augments ventilation in response to hypercapnic acidosis to restore normal pH and PCO 2 Tac1-Pet1 axonal boutons were found localized to brainstem areas implicated in respiratory modulation, with highest density in motor regions. These findings demonstrate that the activity of a Pet1 neuron subtype with the potential to release both 5-HT and substance P is necessary for normal respiratory dynamics, perhaps via motor outputs that engage muscles of respiration and maintain airway patency. These Tac1-Pet1 neurons may act downstream of Egr2-Pet1 serotonergic neurons, which were previously established in respiratory chemoreception, but do not innervate respiratory motor nuclei. SIGNIFICANCE STATEMENT Serotonin (5-HT) neurons modulate physiological processes and behaviors as diverse as body temperature, respiration, aggression, and mood. Using

PedsQL™ Eosinophilic Esophagitis Module: Feasibility, Reliability and Validity

PubMed Central

Franciosi, James P.; Hommel, Kevin A.; Bendo, Cristiane B.; King, Eileen C.; Collins, Margaret H.; Eby, Michael D.; Marsolo, Keith; Abonia, J. Pablo; von Tiehl, Karl F.; Putnam, Philip E.; Greenler, Alexandria J.; Greenberg, Allison B.; Bryson, Ronald A.; Davis, Carla M.; Olive, Anthony P.; Gupta, Sandeep K.; Erwin, Elizabeth A.; Klinnert, Mary D.; Spergel, Jonathan M.; Denham, Jolanda M.; Furuta, Glenn T.; Rothenberg, Marc E.; Varni, James W.

2014-01-01

Objective Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory condition with a paucity of information on health-related quality of life (HRQOL). The objective of the study was to report on the measurement properties of the PedsQL™ EoE Module. Methods The PedsQL™ EoE Module was completed in a multisite study by 196 pediatric EoE patients and 262 EoE parents. Results The PedsQL™ EoE Module scales evidenced excellent feasibility (0.6%–3.1% missing), excellent group comparison reliability across total scale scores (patient α = 0.93; parent proxy α = 0.94), good reliability for the seven individual scales (patient α = 0.75–0.87; parent proxy α = 0.81–0.92), excellent test-retest reliability (patient ICC = 0.88; parent ICC= 0.82), demonstrated no floor effects and low ceiling effects, and demonstrated a high percentage of scaling success for most scales. Intercorrelations with the PedsQL™ Generic Core Scales were in the medium (0.30) to large (0.50) range. PedsQL™ EoE Module scores were worse among patients with active histologic disease (> 5 eos/hpf) compared to those in remission (patient self-report: 63.3 vs. 69.9 [p<0.05]; parent proxy-report: 65.1 vs. 72.3 [p<0.01]), and those treated with dietary restrictions compared to those with no restrictions (patient self-report: 61.6 vs. 74.3 [p< 0.01]; parent proxy-report: 65.5 vs. 74.7 [p<0.01]). Conclusions The results demonstrate excellent measurement properties of the PedsQL™ EoE Module. Patients with active histologic disease and those treated with dietary restrictions demonstrated worse PedsQL™ scores. The PedsQL™ EoE Module may be utilized in evaluation of pediatric EoE disease-specific HRQOL in clinical research and practice. PMID:23478422

Few-fJ/bit data transmissions using directly modulated lambda-scale embedded active region photonic-crystal lasers

NASA Astrophysics Data System (ADS)

Takeda, Koji; Sato, Tomonari; Shinya, Akihiko; Nozaki, Kengo; Kobayashi, Wataru; Taniyama, Hideaki; Notomi, Masaya; Hasebe, Koichi; Kakitsuka, Takaaki; Matsuo, Shinji

2013-07-01

A low operating energy is needed for nanocavity lasers designed for on-chip photonic network applications. On-chip nanocavity lasers must be driven by current because they act as light sources driven by electronic circuits. Here, we report the high-speed direct modulation of a lambda-scale embedded active region photonic-crystal (LEAP) laser that holds three records for any type of laser operated at room temperature: a low threshold current of 4.8 µA, a modulation current efficiency of 2.0 GHz µA-0.5 and an operating energy of 4.4 fJ bit-1. Five major technologies make this performance possible: a compact buried heterostructure, a photonic-crystal nanocavity, a lateral p-n junction realized by ion implantation and thermal diffusion, an InAlAs sacrificial layer and current-blocking trenches. We believe that an output power of 2.17 µW and an operating energy of 4.4 fJ bit-1 will enable us to realize on-chip photonic networks in combination with the recently developed highly sensitive receivers.

Macrogenomic engineering via modulation of the scaling of chromatin packing density.

PubMed

Almassalha, Luay M; Bauer, Greta M; Wu, Wenli; Cherkezyan, Lusik; Zhang, Di; Kendra, Alexis; Gladstein, Scott; Chandler, John E; VanDerway, David; Seagle, Brandon-Luke L; Ugolkov, Andrey; Billadeau, Daniel D; O'Halloran, Thomas V; Mazar, Andrew P; Roy, Hemant K; Szleifer, Igal; Shahabi, Shohreh; Backman, Vadim

2017-11-01

Many human diseases result from the dysregulation of the complex interactions between tens to thousands of genes. However, approaches for the transcriptional modulation of many genes simultaneously in a predictive manner are lacking. Here, through the combination of simulations, systems modelling and in vitro experiments, we provide a physical regulatory framework based on chromatin packing-density heterogeneity for modulating the genomic information space. Because transcriptional interactions are essentially chemical reactions, they depend largely on the local physical nanoenvironment. We show that the regulation of the chromatin nanoenvironment allows for the predictable modulation of global patterns in gene expression. In particular, we show that the rational modulation of chromatin density fluctuations can lead to a decrease in global transcriptional activity and intercellular transcriptional heterogeneity in cancer cells during chemotherapeutic responses to achieve near-complete cancer cell killing in vitro. Our findings represent a 'macrogenomic engineering' approach to modulating the physical structure of chromatin for whole-scale transcriptional modulation.

The PedsQL in pediatric cancer: reliability and validity of the Pediatric Quality of Life Inventory Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module.

PubMed

Varni, James W; Burwinkle, Tasha M; Katz, Ernest R; Meeske, Kathy; Dickinson, Paige

2002-04-01

The Pediatric Quality of Life Inventory (PedsQL) is a modular instrument designed to measure health-related quality of life (HRQOL) in children and adolescents ages 2-18 years. The PedsQL 4.0 Generic Core Scales are multidimensional child self-report and parent proxy-report scales developed as the generic core measure to be integrated with the PedsQL disease specific modules. The PedsQL Multidimensional Fatigue Scale was designed to measure fatigue in pediatric patients. The PedsQL 3.0 Cancer Module was designed to measure pediatric cancer specific HRQOL. The PedsQL Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module were administered to 339 families (220 child self-reports; 337 parent proxy-reports). Internal consistency reliability for the PedsQL Generic Core Total Scale Score (alpha = 0.88 child, 0.93 parent report), Multidimensional Fatigue Total Scale Score (alpha = 0.89 child, 0.92 parent report) and most Cancer Module Scales (average alpha = 0.72 child, 0.87 parent report) demonstrated reliability acceptable for group comparisons. Validity was demonstrated using the known-groups method. The PedsQL distinguished between healthy children and children with cancer as a group, and among children on-treatment versus off-treatment. The validity of the PedsQL Multidimensional Fatigue Scale was further demonstrated through hypothesized intercorrelations with dimensions of generic and cancer specific HRQOL. The results demonstrate the reliability and validity of the PedsQL Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module in pediatric cancer. The PedsQL may be utilized as an outcome measure in clinical trials, research, and clinical practice. Copyright 2002 American Cancer Society.

Rrp5p, Noc1p and Noc2p form a protein module which is part of early large ribosomal subunit precursors in S. cerevisiae

PubMed Central

Hierlmeier, Thomas; Merl, Juliane; Sauert, Martina; Perez-Fernandez, Jorge; Schultz, Patrick; Bruckmann, Astrid; Hamperl, Stephan; Ohmayer, Uli; Rachel, Reinhard; Jacob, Anja; Hergert, Kristin; Deutzmann, Rainer; Griesenbeck, Joachim; Hurt, Ed; Milkereit, Philipp; Baßler, Jochen; Tschochner, Herbert

2013-01-01

Eukaryotic ribosome biogenesis requires more than 150 auxiliary proteins, which transiently interact with pre-ribosomal particles. Previous studies suggest that several of these biogenesis factors function together as modules. Using a heterologous expression system, we show that the large ribosomal subunit (LSU) biogenesis factor Noc1p of Saccharomyces cerevisiae can simultaneously interact with the LSU biogenesis factor Noc2p and Rrp5p, a factor required for biogenesis of the large and the small ribosomal subunit. Proteome analysis of RNA polymerase-I-associated chromatin and chromatin immunopurification experiments indicated that all members of this protein module and a specific set of LSU biogenesis factors are co-transcriptionally recruited to nascent ribosomal RNA (rRNA) precursors in yeast cells. Further ex vivo analyses showed that all module members predominantly interact with early pre-LSU particles after the initial pre-rRNA processing events have occurred. In yeast strains depleted of Noc1p, Noc2p or Rrp5p, levels of the major LSU pre-rRNAs decreased and the respective other module members were associated with accumulating aberrant rRNA fragments. Therefore, we conclude that the module exhibits several binding interfaces with pre-ribosomes. Taken together, our results suggest a co- and post-transcriptional role of the yeast Rrp5p–Noc1p–Noc2p module in the structural organization of early LSU precursors protecting them from non-productive RNase activity. PMID:23209026

Stationary Engineers Apprenticeship. Related Training Modules. 10.1-10.5 Machine Components.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This packet of five learning modules on machine components is one of 20 such packets developed for apprenticeship training for stationary engineers. Introductory materials are a complete listing of all available modules and a supplementary reference list. Each module contains some or all of these components: goal, performance indicators, statement…

Revealing the Hidden Relationship by Sparse Modules in Complex Networks with a Large-Scale Analysis

PubMed Central

Jiao, Qing-Ju; Huang, Yan; Liu, Wei; Wang, Xiao-Fan; Chen, Xiao-Shuang; Shen, Hong-Bin

2013-01-01

One of the remarkable features of networks is module that can provide useful insights into not only network organizations but also functional behaviors between their components. Comprehensive efforts have been devoted to investigating cohesive modules in the past decade. However, it is still not clear whether there are important structural characteristics of the nodes that do not belong to any cohesive module. In order to answer this question, we performed a large-scale analysis on 25 complex networks with different types and scales using our recently developed BTS (bintree seeking) algorithm, which is able to detect both cohesive and sparse modules in the network. Our results reveal that the sparse modules composed by the cohesively isolated nodes widely co-exist with the cohesive modules. Detailed analysis shows that both types of modules provide better characterization for the division of a network into functional units than merely cohesive modules, because the sparse modules possibly re-organize the nodes in the so-called cohesive modules, which lack obvious modular significance, into meaningful groups. Compared with cohesive modules, the sizes of sparse ones are generally smaller. Sparse modules are also found to have preferences in social and biological networks than others. PMID:23762457

DIRECT MODULATION OF P2X1 RECEPTOR-CHANNELS BY THE LIPID PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE

PubMed Central

Bernier, Louis-Philippe; Ase, Ariel R.; Tong, Xinkang; Hamel, Edith; Blais, Dominique; Zhao, Qi; Logothetis, Diomedes E.; Séguéla, Philippe

2012-01-01

The P2X1 receptor-channels activated by extracellular ATP contribute to the neurogenic component of smooth muscle contraction in vascular beds and genito-urinary tracts of rodents and humans. In the present study, we investigated the interactions of plasma membrane phosphoinositides with P2X1 ATP receptors and their physiological consequences. In an isolated rat mesenteric artery preparation, we observed a strong inhibition of P2X1-mediated constrictive responses by depletion of PI(4,5)P2 with the PI4-kinase inhibitor wortmannin. Using the Xenopus oocyte expression system, we provided electrophysiological evidence that lowering PI(4,5)P2 levels with wortmannin significantly decreases P2X1 currents amplitude and recovery. Previously reported modulation of recovery of desensitized P2X1 currents by phospholipase C-coupled 5-HT2A metabotropic receptors was also found wortmannin-sensitive. Treatment with wortmannin alters the kinetics of P2X1 activation and inactivation without changing its sensitivity to ATP. The functional impact of wortmannin on P2X1 currents could be reversed by addition of intracellular PI(4,5)P2, but not PI(3,4,5)P3. and direct application of PI(4,5)P2 to excised inside-out macropatches rescued P2X1 currents from rundown. We showed that the proximal region of the intracellular C-terminus of P2X1 subunit directly binds to PI(4,5)P2 and other anionic phospholipids, and we identified the basic residue K364 as a critical determinant for phospholipid binding and sensitivity to wortmannin. Overall, these results indicate that PI(4,5)P2 plays a key role in the expression of full native and heterologous P2X1 function by regulating the amplitude, recovery and kinetics of ionotropic ATP responses through direct receptor-lipid interactions. PMID:18523136

Low Voltage Alarm Apprenticeship. Related Training Modules. 29.1-29.5 Drawing.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This packet of five learning modules on drawing is one of eight such packets developed for apprenticeship training for low voltage alarm. Introductory materials are a complete listing of all available modules and a supplementary reference list. Each module contains some or all of these components: goal, performance indicators, study guide (a check…

1H-cyclopentapyrimidine-2,4(1H,3H)-dione-related ionotropic glutamate receptors ligands. structure-activity relationships and identification of potent and Selective iGluR5 modulators.

PubMed

Butini, Stefania; Pickering, Darryl S; Morelli, Elena; Coccone, Salvatore Sanna; Trotta, Francesco; De Angelis, Meri; Guarino, Egeria; Fiorini, Isabella; Campiani, Giuseppe; Novellino, Ettore; Schousboe, Arne; Christensen, Jeppe K; Gemma, Sandra

2008-10-23

(S)-CPW399 ((S)-1) is a potent and excitotoxic AMPA receptor partial agonist. Modifying the cyclopentane ring of (S)-1, we developed two of the most potent and selective functional antagonists (5 and 7) for kainate receptor (KA-R) subunit iGluR5. Derivatives 5 and 7, with their unique pharmacological profile, may lead to a better understanding of the different roles and modes of action of iGluR1-5 subunits, paving the way for the synthesis of new potent, subunit selective iGluR5 modulators.

Hls5 regulated erythroid differentiation by modulating GATA-1 activity.

PubMed

Endersby, Raelene; Majewski, Ian J; Winteringham, Louise; Beaumont, Jennifer G; Samuels, Amy; Scaife, Robin; Lim, Esther; Crossley, Merlin; Klinken, S Peter; Lalonde, Jean-Philippe

2008-02-15

Hemopoietic lineage switch (Hls) 5 and 7 were originally isolated as genes up-regulated during an erythroid-to-myeloid lineage switch. We have shown previously that Hls7/Mlf1 imposes a monoblastoid phenotype on erythroleukemic cells. Here we show that Hls5 impedes erythroid maturation by restricting proliferation and inhibiting hemoglobin synthesis; however, Hls5 does not influence the morphology of erythroid cells. Under the influence of GATA-1, Hls5 relocates from cytoplasmic granules to the nucleus where it associates with both FOG-1 and GATA-1. In the nucleus, Hls5 is able to suppress GATA-1-mediated transactivation and reduce GATA-1 binding to DNA. We conclude that Hls5 and Hls7/Mlf1 act cooperatively to induce biochemical and phenotypic changes associated with erythroid/myeloid lineage switching.

Pregnane and Xenobiotic Receptor gene expression in liver cells is modulated by Ets-1 in synchrony with transcription factors Pax5, LEF-1 and c-jun

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

Kumari, Sangeeta; Saradhi, Mallampati; Rana, Manjul

2015-01-15

Nuclear receptor PXR is predominantly expressed in liver and intestine. Expression of PXR is observed to be dysregulated in various metabolic disorders indicating its involvement in disease development. However, information available on mechanisms of PXR self-regulation is fragmentary. The present investigation identifies some of the regulatory elements responsible for its tight regulation and low cellular expression. Here, we report that the PXR-promoter is a target for some key transcription factors like PU.1/Ets-1, Pax5, LEF-1 and c-Jun. Interestingly, we observed that PXR-promoter responsiveness to Pax5, LEF-1 and c-Jun, is considerably enhanced by Ets transcription factors (PU.1 and Ets-1). Co-transfection of cellsmore » with Ets-1, LEF-1 and c-Jun increased PXR-promoter activity by 5-fold and also induced expression of endogenous human PXR. Site-directed mutagenesis and transfection studies revealed that two Ets binding sites and two of the three LEF binding sites in the PXR-promoter are functional and have a positive effect on PXR transcription. Results suggest that expression of Ets family members, in conjunction with Pax5, LEF-1 and c-Jun, lead to coordinated up-regulation of PXR gene transcription. Insights obtained on the regulation of PXR gene have relevance in offering important cues towards normal functioning as well as development of several metabolic disorders via PXR signaling. - Highlights: • The study identified cis-regulatory elements in the nuclear receptor PXR promoter. • Several trans-acting factors modulating the PXR-promoter have been identified. • PU.1/Ets-1, Pax5, LEF-1, c-Jun, LyF-VI and NF-1 act as modulators of the PXR-promoter. • Ets-1 in conjunction with LEF-1 and c-Jun exhibit 5-fold activation of the PXR-promoter. • Insights into PXR-regulation have relevance in normal and pathological conditions.« less

Modulation of sphingosine-1-phosphate in inflammatory bowel disease.

PubMed

Peyrin-Biroulet, Laurent; Christopher, Ronald; Behan, Dominic; Lassen, Cheryl

2017-05-01

Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, involve an inappropriate immune reaction in the digestive tract, causing a variety of disabling symptoms. The advent of monoclonal antibodies (anti-tumor necrosis factor, anti-integrin, anti-interleukin -23) has revolutionized IBD management. Nevertheless, these agents, with potential for immunogenicity, are associated with high rates of response loss and disease relapse over time. They are also associated with high production costs. Sphingosine-1-phosphate (S1P), a membrane-derived lysophospholipid signaling molecule, is implicated in a vast array of physiological and pathophysiological processes, primarily via extracellular activation of S1P1-S1P5 receptors. S1P1, S1P4 and S1P5 are involved in regulation of the immune system, while S1P2 and S1P3 may be associated with cardiovascular, pulmonary, and theoretical cancer-related risks. Targeting S1P receptors for inflammatory conditions has been successful in clinical trials leading to approval of the non-selective S1P modulator, fingolimod, for relapsing forms of multiple sclerosis. However, the association of this non-selective S1P modulator with serious adverse events provides the rationale for developing more selective S1P receptor modulators. Until recently, three S1P modulators with differing selectivity for S1P receptors were in clinical development for IBD: ozanimod (RPC1063), etrasimod (APD334) and amiselimod (MT-1303). The development of amiselimod has been stopped as Biogen are currently focusing on other drugs in its portfolio. Following encouraging results from the Phase 2 TOUCHSTONE trial, a Phase 3 trial of the S1P modulator ozanimod in patients with moderate-to-severe ulcerative colitis is ongoing. Etrasimod is also being tested in a phase 2 trial in ulcerative colitis. These pipeline medications can be administered orally and may avoid the formation of anti-drug antibodies that can lead to treatment failure with

Large space telescope, phase A. Volume 5: Support systems module

NASA Technical Reports Server (NTRS)

1972-01-01

The development and characteristics of the support systems module for the Large Space Telescope are discussed. The following systems and described: (1) thermal control, (2) electrical, (3) communication and data landing, (4) attitude control system, and (5) structural features. Analyses of maintainability and reliability considerations are included.

Dopamine modulates an intrinsic mGluR5-mediated depolarization underlying prefrontal persistent activity

PubMed Central

Sidiropoulou, Kyriaki; Lu, Fang-Min; Fowler, Melissa A.; Xiao, Rui; Phillips, Christopher; Ozkan, Emin D.; Zhu, Michael X.; White, Francis J.; Cooper, Donald C.

2009-01-01

Intrinsic properties of neurons that enable them to maintain depolarized, persistently activated states in the absence of sustained input are poorly understood. In short-term memory tasks, individual prefrontal cortical (PFC) neurons are capable of maintaining persistent action potential output during delay periods between informative cues and behavioral responses. Dopamine and drugs of abuse alter PFC function and working memory possibly by modulating intrinsic neuronal properties. Here we use patch-clamp recording of layer 5 PFC pyramidal neurons to identify an action potential burst-evoked intrinsic mGluR5-mediated postsynaptic depolarization that initiates an activated state. Depolarization occurs in the absence of recurrent synaptic activity and is reduced by a postsynaptic dopamine D1/5 receptor pathway. The depolarization is substantially diminished following behavioral sensitization to cocaine; moreover the D1/5 receptor modulation is lost. We propose the burst-evoked intrinsic depolarization to be a novel form of short-term cellular memory that is modulated by dopamine and cocaine experience. PMID:19169252

Discovery of 1,5-Disubstituted Pyridones: A New Class of Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor

PubMed Central

2010-01-01

A series of 1,5-disubstituted pyridones was identified as positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 2 (mGluR2) via high throughput screening (HTS). Subsequent SAR exploration led to the identification of several compounds with improved in vitro activity. Lead compound 8 was further profiled and found to attenuate the increase in PCP induced locomotor activity in mice. PMID:22778815

Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P2 levels

PubMed Central

Dai, Gucan; Yu, Haijie; Traynor-Kaplan, Alexis

2016-01-01

Myo-inositol is an important cellular osmolyte in autoregulation of cell volume and fluid balance, particularly for mammalian brain and kidney cells. We find it also regulates excitability. Myo-inositol is the precursor of phosphoinositides, key signaling lipids including phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. However, whether myo-inositol accumulation during osmoregulation affects signaling and excitability has not been fully explored. We found that overexpression of the Na+/myo-inositol cotransporter (SMIT1) and myo-inositol supplementation enlarged intracellular PI(4,5)P2 pools, modulated several PI(4,5)P2-dependent ion channels including KCNQ2/3 channels, and attenuated the action potential firing of superior cervical ganglion neurons. Further experiments using the rapamycin-recruitable phosphatase Sac1 to hydrolyze PI(4)P and the P4M probe to visualize PI(4)P suggested that PI(4)P levels increased after myo-inositol supplementation with SMIT1 expression. Elevated relative levels of PIP and PIP2 were directly confirmed using mass spectrometry. Inositol trisphosphate production and release of calcium from intracellular stores also were augmented after myo-inositol supplementation. Finally, we found that treatment with a hypertonic solution mimicked the effect we observed with SMIT1 overexpression, whereas silencing tonicity-responsive enhancer binding protein prevented these effects. These results show that ion channel function and cellular excitability are under regulation by several “physiological” manipulations that alter the PI(4,5)P2 setpoint. We demonstrate a previously unrecognized linkage between extracellular osmotic changes and the electrical properties of excitable cells. PMID:27217553

AgMIP 1.5°C Assessment: Mitigation and Adaptation at Coordinated Global and Regional Scales

NASA Astrophysics Data System (ADS)

Rosenzweig, C.

2016-12-01

The AgMIP 1.5°C Coordinated Global and Regional Integrated Assessments of Climate Change and Food Security (AgMIP 1.5 CGRA) is linking site-based crop and livestock models with similar models run on global grids, and then links these biophysical components with economics models and nutrition metrics at regional and global scales. The AgMIP 1.5 CGRA assessment brings together experts in climate, crop, livestock, economics, nutrition, and food security to define the 1.5°C Protocols and guide the process throughout the assessment. Scenarios are designed to consistently combine elements of intertwined storylines of future society including socioeconomic development (Shared Socioeconomic Pathways), greenhouse gas concentrations (Representative Concentration Pathways), and specific pathways of agricultural sector development (Representative Agricultural Pathways). Shared Climate Policy Assumptions will be extended to provide additional agricultural detail on mitigation and adaptation strategies. The multi-model, multi-disciplinary, multi-scale integrated assessment framework is using scenarios of economic development, adaptation, mitigation, food policy, and food security. These coordinated assessments are grounded in the expertise of AgMIP partners around the world, leading to more consistent results and messages for stakeholders, policymakers, and the scientific community. The early inclusion of nutrition and food security experts has helped to ensure that assessment outputs include important metrics upon which investment and policy decisions may be based. The CGRA builds upon existing AgMIP research groups (e.g., the AgMIP Wheat Team and the AgMIP Global Gridded Crop Modeling Initiative; GGCMI) and regional programs (e.g., AgMIP Regional Teams in Sub-Saharan Africa and South Asia), with new protocols for cross-scale and cross-disciplinary linkages to ensure the propagation of expert judgment and consistent assumptions.

Solar Modulation of the MJO on Intraseasonal Time Scales

NASA Astrophysics Data System (ADS)

Hood, L. L.

2017-12-01

During the last two years, several groups have reported evidence for an influence of the stratospheric quasi-biennial oscillation (QBO) on the boreal winter Madden-Julian Oscillation (MJO). Specifically, DJF mean MJO amplitudes are somewhat larger on average during the easterly QBO phase at 50 hPa (QBOE) than during the westerly phase (QBOW). A possible mechanism is decreased static stability in the tropical lowermost stratosphere caused by increased upwelling associated with the QBO mean meridional circulation during periods of easterly vertical wind shear. It has also been recently proposed that interannual variability of the boreal winter MJO is influenced by tropical upwelling changes associated with the 11-year solar cycle. The modulation is such that MJO amplitudes are especially large under QBOE/SMIN conditions and especially small under QBOW/SMAX conditions (Hood, GRL, 2017). Here, evidence is presented of a modulation of MJO amplitudes under solar maximum conditions by solar variability on the time scale of the solar rotation period (about 27 days). Specifically, normalized occurrence rates of MJO events with amplitudes greater than a chosen threshold are calculated as a function of phase lag relative to peaks in solar UV flux occurring on the solar rotational time scale. All MJO phases and four solar maximum periods are considered (1979-83; 1989-93; 1999-03; 2011-15). The data are further edited to eliminate periods with relatively weak UV variations. About 130 strong "cycles" remain after editing. When MJO events with amplitudes greater than 1.5 are considered, significant reductions of MJO occurrence rates and associated increases in static stability in the tropical lower stratosphere over the warm pool region are obtained several days following solar UV peaks. The reductions in occurrence rate occur during the December to May period when the MJO is most active and are largest when the QBO is in its easterly phase. For example, under the latter

Feasibility, reliability, and validity of the Pediatric Quality of Life Inventory ™ generic core scales, cancer module, and multidimensional fatigue scale in long-term adult survivors of pediatric cancer.

PubMed

Robert, Rhonda S; Paxton, Raheem J; Palla, Shana L; Yang, Grace; Askins, Martha A; Joy, Shaini E; Ater, Joann L

2012-10-01

Most health-related quality of life assessments are designed for either children or adults and have not been evaluated for adolescent and young adult survivors of pediatric cancer. The objective of this study was to examine the feasibility, reliability, and validity of the Pediatric Quality of Life Inventory (PedsQL ™ Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale in adult survivors of pediatric cancer. Adult survivors (n = 64; Mean age 35 year old; >2 years after treatment) completed the PedsQL™ Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale. Feasibility was examined with floor and ceiling effects; and internal consistency was determined by Cronbach's coefficient alpha calculations. Inter-factor correlations were also assessed. Significant ceiling effects were observed for the scales of social function, nausea, procedural anxiety, treatment anxiety, and communication. Internal consistency for all subscales was within the recommended ranges (α ≥ 0.70). Moderate to strong correlations between most Cancer Module and Generic Core Scales (r = 0.25 to r = 0.76) and between the Multidimensional Fatigue Scale and Generic Core Scales (r = 0.37 to r = 0.73). The PedsQL™ Generic Core Scales, Cancer Module, and Multidimensional Fatigue Scale appear to be feasible for an older population of pediatric cancer survivors; however, some of the Cancer Module Scales (nausea, procedural/treatment anxiety, and communication) were deemed not relevant for long-term survivors. More information is needed to determine whether the issues addressed by these modules are meaningful to long-term adult survivors of pediatric cancers. Copyright © 2012 Wiley Periodicals, Inc.

Third generation design solar cell module LSA task 5, large scale production

NASA Technical Reports Server (NTRS)

1980-01-01

A total of twelve (12) preproduction modules were constructed, tested, and delivered. A concept to the frame assembly was designed and proven to be quite reliable. This frame design, as well as the rest of the assembly, was designed with future high volume production and the use of automated equipment in mind.

The incommensurately modulated(1 - x)Ta 2O 5· xWO 3, 0 ≤ x ≤ 0.267 solid solution

NASA Astrophysics Data System (ADS)

Schmid, Siegbert; Withers, Ray L.; Thompson, John G.

1992-08-01

The phase(1 - x)Ta 2O 5 · WO 3, 0 ≤ x ≤ 0.267 has been studied by X-ray powder diffraction and transmission electron microscopy. It was previously described as an infinite series of anion-deficient, α-UO 3-type "line phases," with compositions resulting from intergrowths of different blocks made up by small numbers of α-UO 3-type cells. More correctly(1 - x)Ta 2O 5· xWO 3, 0 ≤ x ≤ 0.267 is described as an incommensurately modulated structure with a linearly composition-dependent primary modulation wave-vector qprim. = qb*. The underlying orthorhombically distorted α-UO 3-type parent structure has space group symmetry Cmmm ( a ≈ 6.20-6.14, b ≈ 3.66, c ≈ 3.89-3.85Å). Characteristic extinction conditions imply a superspace group symmetry of P : Cmmmm : s, -1,1. The four previously reported crystal structures in the solid solution field are examined by means of apparent valence calculations. Crystal chemical reasons are proposed for the width of the composition range,0 ≤ x ≤ 0.267, observed for the title phase.

Scaling behavior of the thermal conductivity of width-modulated nanowires and nanofilms for heat transfer control at the nanoscale.

PubMed

Zianni, Xanthippi; Jean, Valentin; Termentzidis, Konstantinos; Lacroix, David

2014-11-21

We report on scaling behavior of the thermal conductivity of width-modulated nanowires and nanofilms that have been studied with the phonon Monte Carlo technique. It has been found that the reduction of the thermal conductivity scales with the nanostructure transmissivity, a property entirely determined by the modulation geometry, irrespectively of the material choice. Tuning of the thermal conductivity is possible by the nanostructure width-modulation without strict limitations for the modulation profile. In addition, a very significant constriction thermal resistance due to width-discontinuity has been identified, in analogy to the contact thermal resistance between two dissimilar materials. The constriction thermal resistance also scales with the modulated nanostructure transmissivity. Our conclusions are generic indicating that a wide range of materials can be used for the modulated nanostructures. Direct heat flow control can be provided by designing the nanostructure width-modulation.

Rescue Manual. Module 5.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Instructional Materials Lab.

This learner manual for rescuers covers the current techniques or practices required in the rescue service. The fifth of 10 modules contains information on hazardous materials. Key points, an introduction, and conclusion accompany substantive material in this module. In addition, the module contains a Department of Transportation guide chart on…

Nonlinear modulation near the Lighthill instability threshold in 2+1 Whitham theory

NASA Astrophysics Data System (ADS)

Bridges, Thomas J.; Ratliff, Daniel J.

2018-04-01

The dispersionless Whitham modulation equations in 2+1 (two space dimensions and time) are reviewed and the instabilities identified. The modulation theory is then reformulated, near the Lighthill instability threshold, with a slow phase, moving frame and different scalings. The resulting nonlinear phase modulation equation near the Lighthill surfaces is a geometric form of the 2+1 two-way Boussinesq equation. This equation is universal in the same sense as Whitham theory. Moreover, it is dispersive, and it has a wide range of interesting multi-periodic, quasi-periodic and multi-pulse localized solutions. For illustration the theory is applied to a complex nonlinear 2+1 Klein-Gordon equation which has two Lighthill surfaces in the manifold of periodic travelling waves. This article is part of the theme issue `Stability of nonlinear waves and patterns and related topics'.

Metabolic impact of shivering during therapeutic temperature modulation: the Bedside Shivering Assessment Scale.

PubMed

Badjatia, Neeraj; Strongilis, Evangelia; Gordon, Errol; Prescutti, Mary; Fernandez, Luis; Fernandez, Andres; Buitrago, Manuel; Schmidt, J Michael; Ostapkovich, Noeleen D; Mayer, Stephan A

2008-12-01

Therapeutic temperature modulation is widely used in neurocritical care but commonly causes shivering, which can hamper the cooling process and result in increases in systemic metabolism. We sought to validate a grading scale to assist in the monitoring and control of shivering. A simple 4-point Bedside Shivering Assessment Scale was validated against continuous assessments of resting energy expenditure, oxygen consumption, and carbon dioxide production as measured by indirect calorimetry. Therapeutic temperature modulation for fever control or the induction of hypothermia was achieved with the use of a surface or endovascular device. Expected energy expenditure was calculated using the Harris-Benedict equation. A hypermetabolic index was calculated from the ratio of resting of energy expenditure to energy expenditure. Fifty consecutive cerebrovascular patients underwent indirect calorimetry between January 2006 and June 2007. Fifty-six percent were women, and mean age 63+/-16 years. The majority underwent fever control (n=40 [80%]) with a surface cooling device (n=44 [87%]) and had signs of shivering (Bedside Shivering Assessment Scale >0, 64% [n=34 of 50]). Low serum magnesium was independently associated with the presence of shivering (Bedside Shivering Assessment Scale >0; OR, 6.8; 95% CI, 1.7 to 28.0; P=0.01). The Bedside Shivering Assessment Scale was independently associated with the hypermetabolic index (W=16.3, P<0.001), oxygen consumption (W=26.3, P<0.001), resting energy expenditure (W=27.2, P<0.001), and carbon dioxide production (W=18.2, P<0.001) with a high level of interobserver reliability (kappa(w)=0.84, 95% CI, 0.81 to 0.86). The Bedside Shivering Assessment Scale is a simple and reliable tool for evaluating the metabolic stress of shivering.

48 CFR 34.005-5 - Full-scale development contracts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Full-scale development... SPECIAL CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION General 34.005-5 Full-scale development contracts. Whenever practicable, the full-scale development contracts should provide for the contractors to...

48 CFR 34.005-5 - Full-scale development contracts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Full-scale development... SPECIAL CATEGORIES OF CONTRACTING MAJOR SYSTEM ACQUISITION General 34.005-5 Full-scale development contracts. Whenever practicable, the full-scale development contracts should provide for the contractors to...

Mena binds α5 integrin directly and modulates α5β1 function.

PubMed

Gupton, Stephanie L; Riquelme, Daisy; Hughes-Alford, Shannon K; Tadros, Jenny; Rudina, Shireen S; Hynes, Richard O; Lauffenburger, Douglas; Gertler, Frank B

2012-08-20

Mena is an Ena/VASP family actin regulator with roles in cell migration, chemotaxis, cell-cell adhesion, tumor cell invasion, and metastasis. Although enriched in focal adhesions, Mena has no established function within these structures. We find that Mena forms an adhesion-regulated complex with α5β1 integrin, a fibronectin receptor involved in cell adhesion, motility, fibronectin fibrillogenesis, signaling, and growth factor receptor trafficking. Mena bound directly to the carboxy-terminal portion of the α5 cytoplasmic tail via a 91-residue region containing 13 five-residue "LERER" repeats. In fibroblasts, the Mena-α5 complex was required for "outside-in" α5β1 functions, including normal phosphorylation of FAK and paxillin and formation of fibrillar adhesions. It also supported fibrillogenesis and cell spreading and controlled cell migration speed. Thus, fibroblasts require Mena for multiple α5β1-dependent processes involving bidirectional interactions between the extracellular matrix and cytoplasmic focal adhesion proteins.

Mena binds α5 integrin directly and modulates α5β1 function

PubMed Central

Riquelme, Daisy; Hughes-Alford, Shannon K.; Tadros, Jenny; Rudina, Shireen S.; O.Hynes, Richard; Lauffenburger, Douglas

2012-01-01

Mena is an Ena/VASP family actin regulator with roles in cell migration, chemotaxis, cell–cell adhesion, tumor cell invasion, and metastasis. Although enriched in focal adhesions, Mena has no established function within these structures. We find that Mena forms an adhesion-regulated complex with α5β1 integrin, a fibronectin receptor involved in cell adhesion, motility, fibronectin fibrillogenesis, signaling, and growth factor receptor trafficking. Mena bound directly to the carboxy-terminal portion of the α5 cytoplasmic tail via a 91-residue region containing 13 five-residue “LERER” repeats. In fibroblasts, the Mena–α5 complex was required for “outside-in” α5β1 functions, including normal phosphorylation of FAK and paxillin and formation of fibrillar adhesions. It also supported fibrillogenesis and cell spreading and controlled cell migration speed. Thus, fibroblasts require Mena for multiple α5β1-dependent processes involving bidirectional interactions between the extracellular matrix and cytoplasmic focal adhesion proteins. PMID:22908313

Peroxiredoxin 5 modulates immune response in Drosophila

PubMed Central

Radyuk, Svetlana N.; Michalak, Katarzyna; Klichko, Vladimir I.; Benes, Judith; Orr, William C.

2010-01-01

Background Peroxiredoxins are redox-sensing enzymes with multiple cellular functions. Previously, we reported on the potent antioxidant function of Drosophila peroxiredoxin 5 (dPrx5). Studies with mammalian and human cells suggest that peroxiredoxins can modulate immune-related signaling. Methods Survivorship studies and bacteriological analysis were used to determine resistance of flies to fungal and bacterial infections. RT-PCR and immunoblot analyses determined expression of dPrx5 and immunity factors in response to bacterial challenge. Double mutants for dprx5 gene and genes comprising the Imd/Relish and dTak1/Basket branches of the immune signaling pathways were used in epistatic analysis. Results The dprx5 mutant flies were more resistant to bacterial infection than controls, while flies overexpressing dPrx5 were more susceptible. The enhanced resistance to bacteria was accompanied by rapid induction of the Imd-dependent antimicrobial peptides, phosphorylation of the JNK kinase Basket and altered transcriptional profiling of the transient response genes, puckered, ets21C and relish, while the opposite effects were observed in flies over-expressing dPrx5. Epistatic analysis of double mutants, using attacin D and Puckered as read outs of activation of the Imd and JNK pathways, implicated dPrx5 function in the control of the dTak1-JNK arm of immune signaling. Conclusions Differential effects on fly survivorship suggested a trade-off between the antioxidant and immune functions of dPrx5. Molecular and epistatic analyses identified dPrx5 as a negative regulator in the dTak1-JNK arm of immune signaling. General significance Our findings suggest that peroxiredoxins play an important modulatory role in the Drosophila immune response. PMID:20600624

Design and test of 1/5th scale horizontal axis tidal current turbine

NASA Astrophysics Data System (ADS)

Liu, Hong-wei; Zhou, Hong-bin; Lin, Yong-gang; Li, Wei; Gu, Hai-gang

2016-06-01

Tidal current energy is prominent and renewable. Great progress has been made in the exploitation technology of tidal current energy all over the world in recent years, and the large scale device has become the trend of tidal current turbine (TCT) for its economies. Instead of the similarity to the wind turbine, the tidal turbine has the characteristics of high hydrodynamic efficiency, big thrust, reliable sealing system, tight power transmission structure, etc. In this paper, a 1/5th scale horizontal axis tidal current turbine has been designed, manufactured and tested before the full scale device design. Firstly, the three-blade horizontal axis rotor was designed based on traditional blade element momentum theory and its hydrodynamic performance was predicted in numerical model. Then the power train system and stand-alone electrical control unit of tidal current turbine, whose performances were accessed through the bench test carried out in workshop, were designed and presented. Finally, offshore tests were carried out and the power performance of the rotor was obtained and compared with the published literatures, and the results showed that the power coefficient was satisfactory, which agrees with the theoretical predictions.

High Frequency GaAs Bulk Acousto-Optic Devices For Modulators And Frequency Shifters At 1.3um And 1.5um In Fiber-Optics

NASA Astrophysics Data System (ADS)

Soos, J. I.; Rosemeier, R. G.

1989-02-01

The edge of a transmission window for a GaAs Bragg cell starts about lum, which allows this material to be used for infrared fiber-optic applications, especially at 1.3um and 1.5um. The single crystal of GaAs is acoustically anisotropic and has the highest figure of merit, M2, along <111> direction for a longitudinal mode sound wave. Recently, Brimrose has designed and fabricated an acousto-optic modulator from GaAs operating at a carrier frequency of 2.3 GHz with a diffraction efficiency of 4%/RF watt.

Experience with specifications applicable to certification. [of photovoltaic modules for large-scale application

NASA Technical Reports Server (NTRS)

Ross, R. G., Jr.

1982-01-01

The Jet Propulsion Laboratory has developed a number of photovoltaic test and measurement specifications to guide the development of modules toward the requirements of future large-scale applications. Experience with these specifications and the extensive module measurement and testing that has accompanied their use is examined. Conclusions are drawn relative to three aspects of product certification: performance measurement, endurance testing and safety evaluation.

ATXN1L, CIC, and ETS Transcription Factors Modulate Sensitivity to MAPK Pathway Inhibition | Office of Cancer Genomics

Cancer.gov

Intrinsic resistance and RTK-RAS-MAPK pathway reactivation has limited the effectiveness of MEK and RAF inhibitors (MAPKi) in RAS- and RAF-mutant cancers. To identify genes that modulate sensitivity to MAPKi, we performed genome-scale CRISPR-Cas9 loss-of-function screens in two KRAS mutant pancreatic cancer cell lines treated with the MEK1/2 inhibitor trametinib. Loss of CIC, a transcriptional repressor of ETV1, ETV4, and ETV5, promoted survival in the setting of MAPKi in cancer cells derived from several lineages.

Modulation of the immune-related gene responses to protect mice against Japanese encephalitis virus using the antimicrobial peptide, tilapia hepcidin 1-5.

PubMed

Huang, Han-Ning; Rajanbabu, Venugopal; Pan, Chieh-Yu; Chan, Yi-Lin; Hui, Cho-Fat; Chen, Jyh-Yih; Wu, Chang-Jer

2011-10-01

Japanese encephalitis virus (JEV), a neurotropic flavivirus, is one of the major causes of acute encephalitis in humans. After infection, it is commonly associated with inflammatory reactions and neurological disease. There is still no effective antiviral drug available against Japanese encephalitis virus infection. Recently, a number of investigators found that antimicrobial peptide (AMPs) present a broad range of biological activities including antimicrobial and immunomodulatory activities. In this study, we found that an AMP, tilapia hepcidin (TH)1-5, caused no harm to either cells or test animals during the test course and could control JEV viral infection in BHK-21 cells. Mice co-injected with TH1-5/JEV and subsequently subjected to JEV re-challenge survived and behaved normally. The neuroprotective effects were associated with marked decreases in: (i) the viral load and viral replication within the brain, (ii) neuronal death, and (iii) secondary inflammation resulting from microglial activation. TH1-5 was also determined to enhance adaptive immunity by elevating levels of anti-JEV-neutralizing antibodies in the serum. The microarray data also showed that TH1-5 modulated Socs-6, interleukin (IL)-6, Toll-like receptor (TLR)-1, TLR-7, caspase-4, interferon (IFN)-β1, ATF-3, and several immune-responsive genes to protect mice against JEV infection. In addition, TH1-5 was confirmed to modulate the expressions of several proinflammatory and immune-responsive genes, such as IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-α, IFN-γ and monocyte chemoattractant protein (MCP)-1 at both the transcriptional and translational levels in JEV-infected mice. In conclusion, our findings provide mechanistic insights into the actions of TH1-5 against JEV. Results from our in vivo and in vitro experiments clearly indicate that TH1-5 has antiviral, neuroprotective, anti-inflammatory, and immunomodulatory activities. Furthermore, TH1-5 successfully reduced the

Measuring health-related quality of life in Hungarian children with heart disease: psychometric properties of the Hungarian version of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and the Cardiac Module.

PubMed

Berkes, Andrea; Pataki, István; Kiss, Mariann; Kemény, Csilla; Kardos, László; Varni, James W; Mogyorósy, Gábor

2010-01-28

The aim of the study was to investigate the psychometric properties of the Hungarian version of the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales and Cardiac Module. The PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Cardiac Module was administered to 254 caregivers of children (aged 2-18 years) and to 195 children (aged 5-18 years) at a pediatric cardiology outpatient unit. A postal survey on a demographically group-matched sample of the general population with 525 caregivers of children (aged 2-18 years) and 373 children (aged 5-18 years) was conducted with the PedsQL 4.0 Generic Core Scale. Responses were described, compared over subgroups of subjects, and were used to assess practical utility, distributional coverage, construct validity, internal consistency, and inter-reporter agreement of the instrument. The moderate scale-level mean percentage of missing item responses (range 1.8-2.3%) supported the feasibility of the Generic Core Scales for general Hungarian children. Minimal to moderate ceiling effects and no floor effects were found on the Generic Core Scales. We observed stronger ceiling than floor effects in the Cardiac Module. Most of the scales showed satisfactory reliability with Cronbach's alpha estimates exceeding 0.70. Generally, moderate to good agreement was found between self- and parent proxy-reports in the patient and in the comparison group (intraclass correlation coefficient range 0.52-0.77), but remarkably low agreement in the perceived physical appearance subscale in the age group 5-7 years (0.18) and for the treatment II scale (problems on taking heart medicine) scale of the Cardiac Module in children aged 8-12 years (0.39). Assessing the construct validity of the questionnaires, statistically significant difference was found between the patient group and the comparison group only in the Physical Functioning Scale scores (p = 0.003) of the child self-report component, and in Physical (p = 0.022), Emotional, (p = 0

Observing the Cosmic Microwave Background Polarization with Variable-delay Polarization Modulators for the Cosmology Large Angular Scale Surveyor

NASA Astrophysics Data System (ADS)

Harrington, Kathleen; CLASS Collaboration

2018-01-01

The search for inflationary primordial gravitational waves and the optical depth to reionization, both through their imprint on the large angular scale correlations in the polarization of the cosmic microwave background (CMB), has created the need for high sensitivity measurements of polarization across large fractions of the sky at millimeter wavelengths. These measurements are subjected to instrumental and atmospheric 1/f noise, which has motivated the development of polarization modulators to facilitate the rejection of these large systematic effects.Variable-delay polarization modulators (VPMs) are used in the Cosmology Large Angular Scale Surveyor (CLASS) telescopes as the first element in the optical chain to rapidly modulate the incoming polarization. VPMs consist of a linearly polarizing wire grid in front of a moveable flat mirror; varying the distance between the grid and the mirror produces a changing phase shift between polarization states parallel and perpendicular to the grid which modulates Stokes U (linear polarization at 45°) and Stokes V (circular polarization). The reflective and scalable nature of the VPM enables its placement as the first optical element in a reflecting telescope. This simultaneously allows a lock-in style polarization measurement and the separation of sky polarization from any instrumental polarization farther along in the optical chain.The Q-Band CLASS VPM was the first VPM to begin observing the CMB full time in 2016. I will be presenting its design and characterization as well as demonstrating how modulating polarization significantly rejects atmospheric and instrumental long time scale noise.

Designing modulators of 5-hydroxytryptamine signaling to treat abuse disorders.

PubMed

van de Wiel, Sandra M W; Verheij, Michel M; Homberg, Judith R

2014-11-01

There are currently no treatments approved by the FDA to effectively treat cocaine dependence. Research of recent years has gradually revealed the importance of 5-hydroxytryptamine (5-HT) in the reinforcing and rewarding effects of cocaine and the potential for relapse. Brain-derived neurotropic factor (BDNF) is an important modulator of the serotonergic system and 5-HT modulates BDNF expression. Their reciprocal interaction is of crucial importance for synaptic plasticity during long-term cocaine intake. Thus, agents modifying BDNF-5-HT interactions might have therapeutic potential for cocaine dependence by reversing the altered brain structure that underlies relapse after cocaine withdrawal. On the basis of the available literature, the authors propose an interaction between BDNF and the serotonergic system in the response to cocaine and during cocaine intake. Furthermore, they discuss putative therapies that are based on 5-HT and BDNF. Recent studies are beginning to elucidate the role of 5-HT and BDNF in cocaine addiction. Additionally, animal studies modeling addiction-like drug intake will only further help to gain a better understanding of how to treat cocaine addiction. Based on the current evidence, the authors believe that BDNF, as a modulator of the serotonergic pathway, or 5-HT, as a modulator of the BDNF system, represent a valuable target to treat drug addiction, which may yield novel therapeutics in the future.

An interprofessional learning module on asthma health promotion.

PubMed

Saini, Bandana; Shah, Smita; Kearey, Phoebe; Bosnic-Anticevich, Sinthia; Grootjans, John; Armour, Carol

2011-03-10

To develop, implement, and evaluate a new interprofessional learning module that focused on asthma health promotion called Taking Action Together for Asthma. Faculty members in medicine, nursing, and pharmacy courses recruited 10 students each to participate in a 3-day interprofessional learning module. Students received extensive materials including a workbook to document their expectations and experience; completed a 1-day interprofessional workshop; received training in the Triple A (Adolescent Asthma Action) program; and went into high schools and taught the Triple A program to students in interprofessional teams. Before and after participating in the module, students completed a questionnaire consisting of 3 previously validated instruments: the Asthma Knowledge for Health Professionals Scale, Attitudes Toward Health Care Teams Scale, and Readiness for Interprofessional Learning Scale (RIPLS). Seventeen students completed both the pre- and post-module scales and significant changes were seen only in means scores for the Attitude Toward Healthcare Teams (81.0 ± 4.7 to 85.2 ± 5.9) and the Teamwork and Collaboration subscale of the RIPLS (41.4 ± 2.7 to 43.2 ± 2.7). Health promotion activities offer a viable mechanism for fostering interprofessional learning among health professions students.

Lunar Module 5 ascent stage being moved for mating with adapter

NASA Technical Reports Server (NTRS)

1969-01-01

Interior view of the Kennedy Space Center's (KSC) Manned Spacecraft Operations Building showing Lunar Module 5 being moved from workstand for mating with its Spacecraft Lunar Module Adapter (SLA). LM-5 is scheduled to be flown on the Apollo 11 lunar landing mission.

Nuclear Technology. Course 27: Metrology. Module 27-5, Tolerancing.

ERIC Educational Resources Information Center

Selleck, Ben; Espy, John

This fifth in a series of eight modules for a course titled Metrology describes the application of the American National Standard (ANSI Y14.5-1973) for dimensioning and tolerancing and gives guidance on interpreting form and location controls consistent with the national standard. The module follows a typical format that includes the following…

PTGER4 Expression-Modulating Polymorphisms in the 5p13.1 Region Predispose to Crohn's Disease and Affect NF-κB and XBP1 Binding Sites

PubMed Central

Czamara, Darina; Pasciuto, Giulia; Diegelmann, Julia; Wetzke, Martin; Olszak, Torsten; Wolf, Christiane; Müller-Myhsok, Bertram; Balschun, Tobias; Achkar, Jean-Paul; Kamboh, M. Ilyas; Franke, Andre; Duerr, Richard H.; Brand, Stephan

2012-01-01

Background Genome-wide association studies identified a PTGER4 expression-modulating region on chromosome 5p13.1 as Crohn's disease (CD) susceptibility region. The study aim was to test this association in a large cohort of patients with inflammatory bowel disease (IBD) and to elucidate genotypic and phenotypic interactions with other IBD genes. Methodology/Principal Findings A total of 7073 patients and controls were genotyped: 844 CD and 471 patients with ulcerative colitis and 1488 controls were analyzed for the single nucleotide polymorphisms (SNPs) rs4495224 and rs7720838 on chromosome 5p13.1. The study included two replication cohorts of North American (CD: n = 684; controls: n = 1440) and of German origin (CD: n = 1098; controls: n = 1048). Genotype-phenotype, epistasis and transcription factor binding analyses were performed. In the discovery cohort, an association of rs4495224 (p = 4.10×10−5; 0.76 [0.67–0.87]) and of rs7720838 (p = 6.91×10−4; 0.81 [0.71–0.91]) with susceptibility to CD was demonstrated. These associations were confirmed in both replication cohorts. In silico analysis predicted rs4495224 and rs7720838 as essential parts of binding sites for the transcription factors NF-κB and XBP1 with higher binding scores for carriers of the CD risk alleles, providing an explanation of how these SNPs might contribute to increased PTGER4 expression. There was no association of the PTGER4 SNPs with IBD phenotypes. Epistasis detected between 5p13.1 and ATG16L1 for CD susceptibility in the discovery cohort (p = 5.99×10−7 for rs7720838 and rs2241880) could not be replicated in both replication cohorts arguing against a major role of this gene-gene interaction in the susceptibility to CD. Conclusions/Significance We confirmed 5p13.1 as a major CD susceptibility locus and demonstrate by in silico analysis rs4495224 and rs7720838 as part of binding sites for NF-κB and XBP1. Further functional studies are necessary to

Klamath River Water Quality Data from Link River Dam to Keno Dam, Oregon, 2008

USGS Publications Warehouse

Sullivan, Annett B.; Deas, Michael L.; Asbill, Jessica; Kirshtein, Julie D.; Butler, Kenna D.; Vaughn, Jennifer

2009-01-01

This report documents sampling and analytical methods and presents field data from a second year of an ongoing study on the Klamath River from Link River Dam to Keno Dam in south central Oregon; this dataset will form the basis of a hydrodynamic and water quality model. Water quality was sampled weekly at six mainstem and two tributary sites from early April through early November, 2008. Constituents reported herein include field-measured water-column parameters (water temperature, pH, dissolved oxygen concentration, specific conductance); total nitrogen and phosphorus; particulate carbon and nitrogen; total iron; filtered orthophosphate, nitrite, nitrite plus nitrate, ammonia, organic carbon, and iron; specific UV absorbance at 254 nanometers; chlorophyll a; phytoplankton and zooplankton enumeration and species identification; and bacterial abundance and morphological subgroups. Sampling program results indicated: *Most nutrient and carbon concentrations were lowest in spring, increased starting in mid-June, remained elevated in the summer, and decreased in fall. Dissolved nitrite plus nitrate had a different seasonal cycle and was below detection or at low concentration in summer. *Although total nitrogen and total phosphorus concentrations did not show large differences from upstream to downstream, filtered ammonia and orthophosphate concentrations increased in the downstream direction and particulate carbon and particulate nitrogen generally decreased in the downstream direction. *Large bacterial cells made up most of the bacteria biovolume, though cocci were the most numerous bacteria type. Cocci, with diameters of 0.1 to 0.2 micrometers, were smaller than the filter pore sizes used to separate dissolved from particulate matter. *Phytoplankton biovolumes were dominated by diatoms in spring and by the blue-green alga Aphanizomenon flos-aquae after mid-June. Another blue-green, Anabaena flos-aquae, was noted in samples from late May to late June. Phytoplankton

PTH modulation of NCC activity regulates TRPV5 Ca2+ reabsorption.

PubMed

Hoover, Robert S; Tomilin, Viktor; Hanson, Lauren; Pochynyuk, Oleh; Ko, Benjamin

2016-01-15

Since parathyroid hormone (PTH) is known to increase transient receptor potential vanilloid (TRPV)5 activity and decrease Na(+)-Cl(-) cotransporter (NCC) activity, we hypothesized that decreased NCC-mediated Na(+) reabsorption contributes to the enhanced TRPV5 Ca(2+) reabsorption seen with PTH. To test this, we used mDCT15 cells expressing functional TRPV5 and ruthenium red-sensitive (45)Ca(2+) uptake. PTH increased (45)Ca(2+) uptake to 8.8 ± 0.7 nmol·mg(-1)·min(-1) (n = 4, P < 0.01) and decreased NCC activity from 75.4 ± 2.7 to 20.3 ± 1.3 nmol·mg(-1)·min(-1) (n = 4, P < 0.01). Knockdown of Ras guanyl-releasing protein (RasGRP)1 had no baseline effect on (45)Ca(2+) uptake but significantly attenuated the response to PTH from a 45% increase (6.0 ± 0.2 to 8.7 ± 0.4 nmol·mg(-1)·min(-1)) in control cells to only 20% in knockdown cells (6.1 ± 0.1 to 7.3 ± 0.2 nmol·mg(-1)·min(-1), n = 4, P < 0.01). Inhibition of PKC and PKA resulted in further attenuation of the PTH effect. RasGRP1 knockdown decreased the magnitude of the TRPV5 response to PTH (7.9 ± 0.1 nmol·mg(-1)·min(-1) for knockdown compared with 9.1 ± 0.1 nmol·mg(-1)·min(-1) in control), and the addition of thiazide eliminated this effect (a nearly identical 9.0 ± 0.1 nmol·mg(-1)·min(-1)). This indicates that functionally active NCC is required for RasGRP1 knockdown to impact the PTH effect on TRPV5 activity. Knockdown of with no lysine kinase (WNK)4 resulted in an attenuation of the increase in PTH-mediated TRPV5 activity. TRPV5 activity increased by 36% compared with 45% in control (n = 4, P < 0.01 between PTH-treated groups). PKC blockade further attenuated the PTH effect, whereas combined PKC and PKA blockade in WNK4KD cells abolished the effect. We conclude that modulation of NCC activity contributes to the response to PTH, implying a role for hormonal modulation of NCC activity in distal Ca(2+) handling.

5 CFR 532.233 - Preparation for full-scale wage surveys.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Preparation for full-scale wage surveys... REGULATIONS PREVAILING RATE SYSTEMS Prevailing Rate Determinations § 532.233 Preparation for full-scale wage... the local wage survey committee. (e) Selection and appointment of data collectors. (1) The local wage...

A cryogenic multichannel electronically scanned pressure module

NASA Technical Reports Server (NTRS)

Shams, Qamar A.; Fox, Robert L.; Adcock, Edward E.; Kahng, Seun K.

1992-01-01

Consideration is given to a cryogenic multichannel electronically scanned pressure (ESP) module developed and tested over an extended temperature span from -184 to +50 C and a pressure range of 0 to 5 psig. The ESP module consists of 32 pressure sensor dice, four analog 8 differential-input multiplexers, and an amplifier circuit, all of which are packaged in a physical volume of 2 x 1 x 5/8 in with 32 pressure and two reference ports. Maximum nonrepeatability is measured at 0.21 percent of full-scale output. The ESP modules have performed consistently well over 15 times over the above temperature range and continue to work without any sign of degradation. These sensors are also immune to repeated thermal shock tests over a temperature change of 220 C/sec.

Mechanisms of dopamine D1 receptor-mediated ERK1/2 activation in the parkinsonian striatum and their modulation by metabotropic glutamate receptor type 5.

PubMed

Fieblinger, Tim; Sebastianutto, Irene; Alcacer, Cristina; Bimpisidis, Zisis; Maslava, Natallia; Sandberg, Sabina; Engblom, David; Cenci, M Angela

2014-03-26

In animal models of Parkinson's disease, striatal overactivation of ERK1/2 via dopamine (DA) D1 receptors is the hallmark of a supersensitive molecular response associated with dyskinetic behaviors. Here we investigate the pathways involved in D1 receptor-dependent ERK1/2 activation using acute striatal slices from rodents with unilateral 6-hydroxydopamine (6-OHDA) lesions. Application of the dopamine D1-like receptor agonist SKF38393 induced ERK1/2 phosphorylation and downstream signaling in the DA-denervated but not the intact striatum. This response was mediated through a canonical D1R/PKA/MEK1/2 pathway and independent of ionotropic glutamate receptors but blocked by antagonists of L-type calcium channels. Coapplication of an antagonist of metabotropic glutamate receptor type 5 (mGluR5) or its downstream signaling molecules (PLC, PKC, IP3 receptors) markedly attenuated SKF38393-induced ERK1/2 activation. The role of striatal mGluR5 in D1-dependent ERK1/2 activation was confirmed in vivo in 6-OHDA-lesioned animals treated systemically with SKF38393. In one experiment, local infusion of the mGluR5 antagonist MTEP in the DA-denervated rat striatum attenuated the activation of ERK1/2 signaling by SKF38393. In another experiment, 6-OHDA lesions were applied to transgenic mice with a cell-specific knockdown of mGluR5 in D1 receptor-expressing neurons. These mice showed a blunted striatal ERK1/2 activation in response to SFK38393 treatment. Our results reveal that D1-dependent ERK1/2 activation in the DA-denervated striatum depends on a complex interaction between PKA- and Ca(2+)-dependent signaling pathways that is critically modulated by striatal mGluR5.

Dopamine modulation of transient receptor potential vanilloid type 1 (TRPV1) receptor in dorsal root ganglia neurons.

PubMed

Chakraborty, Saikat; Rebecchi, Mario; Kaczocha, Martin; Puopolo, Michelino

2016-03-15

The transient receptor potential vanilloid type 1 (TRPV1) receptor plays a key role in the modulation of nociceptor excitability. To address whether dopamine can modulate the activity of TRPV1 channels in nociceptive neurons, the effects of dopamine and dopamine receptor agonists were tested on the capsaicin-activated current recorded from acutely dissociated small diameter (<27 μm) dorsal root ganglia (DRG) neurons. Dopamine or SKF 81297 (an agonist at D1/D5 receptors), caused inhibition of both inward and outward currents by ∼60% and ∼48%, respectively. The effect of SKF 81297 was reversed by SCH 23390 (an antagonist at D1/D5 receptors), confirming that it was mediated by activation of D1/D5 dopamine receptors. In contrast, quinpirole (an agonist at D2 receptors) had no significant effect on the capsaicin-activated current. Inhibition of the capsaicin-activated current by SKF 81297 was mediated by G protein coupled receptors (GPCRs), and highly dependent on external calcium. The inhibitory effect of SKF 81297 on the capsaicin-activated current was not affected when the protein kinase A (PKA) activity was blocked with H89, or when the protein kinase C (PKC) activity was blocked with bisindolylmaleimide II (BIM). In contrast, when the calcium-calmodulin-dependent protein kinase II (CaMKII) was blocked with KN-93, the inhibitory effect of SKF 81297 on the capsaicin-activated current was greatly reduced, suggesting that activation of D1/D5 dopamine receptors may be preferentially linked to CaMKII activity. We suggest that modulation of TRPV1 channels by dopamine in nociceptive neurons may represent a way for dopamine to modulate incoming noxious stimuli. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

A series connection architecture for large-area organic photovoltaic modules with a 7.5% module efficiency.

PubMed

Hong, Soonil; Kang, Hongkyu; Kim, Geunjin; Lee, Seongyu; Kim, Seok; Lee, Jong-Hoon; Lee, Jinho; Yi, Minjin; Kim, Junghwan; Back, Hyungcheol; Kim, Jae-Ryoung; Lee, Kwanghee

2016-01-05

The fabrication of organic photovoltaic modules via printing techniques has been the greatest challenge for their commercial manufacture. Current module architecture, which is based on a monolithic geometry consisting of serially interconnecting stripe-patterned subcells with finite widths, requires highly sophisticated patterning processes that significantly increase the complexity of printing production lines and cause serious reductions in module efficiency due to so-called aperture loss in series connection regions. Herein we demonstrate an innovative module structure that can simultaneously reduce both patterning processes and aperture loss. By using a charge recombination feature that occurs at contacts between electron- and hole-transport layers, we devise a series connection method that facilitates module fabrication without patterning the charge transport layers. With the successive deposition of component layers using slot-die and doctor-blade printing techniques, we achieve a high module efficiency reaching 7.5% with area of 4.15 cm(2).

An Interprofessional Learning Module on Asthma Health Promotion

PubMed Central

Shah, Smita; Kearey, Phoebe; Bosnic-Anticevich, Sinthia; Grootjans, John; Armour, Carol

2011-01-01

Objective To develop, implement, and evaluate a new interprofessional learning module that focused on asthma health promotion called Taking Action Together for Asthma. Design Faculty members in medicine, nursing, and pharmacy courses recruited 10 students each to participate in a 3-day interprofessional learning module. Students received extensive materials including a workbook to document their expectations and experience; completed a 1-day interprofessional workshop; received training in the Triple A (Adolescent Asthma Action) program; and went into high schools and taught the Triple A program to students in interprofessional teams. Assessment Before and after participating in the module, students completed a questionnaire consisting of 3 previously validated instruments: the Asthma Knowledge for Health Professionals Scale, Attitudes Toward Health Care Teams Scale, and Readiness for Interprofessional Learning Scale (RIPLS). Seventeen students completed both the pre- and post-module scales and significant changes were seen only in means scores for the Attitude Toward Healthcare Teams (81.0 ± 4.7 to 85.2 ± 5.9) and the Teamwork and Collaboration subscale of the RIPLS (41.4 ± 2.7 to 43.2 ± 2.7). Conclusion Health promotion activities offer a viable mechanism for fostering interprofessional learning among health professions students. PMID:21519420

Development of Subjective Well-Being Increasing Strategies Scale for Children (1-5 Ages) Their Mothers Use

ERIC Educational Resources Information Center

Eryilmaz, Ali; Sapsaglam, Özkan

2018-01-01

Subjective well-being is a sign of positive mental health of children. The aim of the present study is to develop subjective well-being increasing strategies scale for children whose mothers' uses are varied 1 to 5. In this study, there were 195 mothers whose mean ages were 31, 49 and standard deviation were 4,71. Satisfaction with life, positive…

PTGER4 expression-modulating polymorphisms in the 5p13.1 region predispose to Crohn's disease and affect NF-κB and XBP1 binding sites.

PubMed

Glas, Jürgen; Seiderer, Julia; Czamara, Darina; Pasciuto, Giulia; Diegelmann, Julia; Wetzke, Martin; Olszak, Torsten; Wolf, Christiane; Müller-Myhsok, Bertram; Balschun, Tobias; Achkar, Jean-Paul; Kamboh, M Ilyas; Franke, Andre; Duerr, Richard H; Brand, Stephan

2012-01-01

Genome-wide association studies identified a PTGER4 expression-modulating region on chromosome 5p13.1 as Crohn's disease (CD) susceptibility region. The study aim was to test this association in a large cohort of patients with inflammatory bowel disease (IBD) and to elucidate genotypic and phenotypic interactions with other IBD genes. A total of 7073 patients and controls were genotyped: 844 CD and 471 patients with ulcerative colitis and 1488 controls were analyzed for the single nucleotide polymorphisms (SNPs) rs4495224 and rs7720838 on chromosome 5p13.1. The study included two replication cohorts of North American (CD: n = 684; controls: n = 1440) and of German origin (CD: n = 1098; controls: n = 1048). Genotype-phenotype, epistasis and transcription factor binding analyses were performed. In the discovery cohort, an association of rs4495224 (p = 4.10×10⁻⁵; 0.76 [0.67-0.87]) and of rs7720838 (p = 6.91×10⁻⁴; 0.81 [0.71-0.91]) with susceptibility to CD was demonstrated. These associations were confirmed in both replication cohorts. In silico analysis predicted rs4495224 and rs7720838 as essential parts of binding sites for the transcription factors NF-κB and XBP1 with higher binding scores for carriers of the CD risk alleles, providing an explanation of how these SNPs might contribute to increased PTGER4 expression. There was no association of the PTGER4 SNPs with IBD phenotypes. Epistasis detected between 5p13.1 and ATG16L1 for CD susceptibility in the discovery cohort (p = 5.99×10⁻⁷ for rs7720838 and rs2241880) could not be replicated in both replication cohorts arguing against a major role of this gene-gene interaction in the susceptibility to CD. We confirmed 5p13.1 as a major CD susceptibility locus and demonstrate by in silico analysis rs4495224 and rs7720838 as part of binding sites for NF-κB and XBP1. Further functional studies are necessary to confirm the results of our in silico analysis and to analyze if

Real-time characterization of cannabinoid receptor 1 (CB1 ) allosteric modulators reveals novel mechanism of action.

PubMed

Cawston, Erin E; Redmond, William J; Breen, Courtney M; Grimsey, Natasha L; Connor, Mark; Glass, Michelle

2013-10-01

The cannabinoid receptor type 1 (CB1 ) has an allosteric binding site. The drugs ORG27569 {5-chloro-3-ethyl-N-[2-[4-(1-piperidinyl)phenyl]ethyl]-1H-indole-2-carboxamide} and PSNCBAM-1 {1-(4-chlorophenyl)-3-[3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl]urea} have been extensively characterized with regard to their effects on signalling of the orthosteric ligand CP55,940 {(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol}, and studies have suggested that these allosteric modulators increase binding affinity but act as non-competitive antagonists in functional assays. To gain a deeper understanding of allosteric modulation of CB1 , we examined real-time signalling and trafficking responses of the receptor in the presence of allosteric modulators. Studies of CB1 signalling were carried out in HEK 293 and AtT20 cells expressing haemagglutinin-tagged human and rat CB1 . We measured real-time accumulation of cAMP, activation and desensitization of potassium channel-mediated cellular hyperpolarization and CB1 internalization. ORG27569 and PSNCBAM-1 produce a complex, concentration and time-dependent modulation of agonist-mediated regulation of cAMP levels, as well as an increased rate of desensitization of CB1 -mediated cellular hyperpolarization and a decrease in agonist-induced receptor internalization. Contrary to previous studies characterizing allosteric modulators at CB1, this study suggests that the mechanism of action is not non-competitive antagonism of signalling, but rather that enhanced binding results in an increased rate of receptor desensitization and reduced internalization, which results in time-dependent modulation of cAMP signalling. The observed effect of the allosteric modulators is therefore dependent on the time frame over which the signalling response occurs. This finding may have important consequences for the potential therapeutic application of these compounds. © 2013 The British Pharmacological Society.

Modulatory effects of plant phenols on human multidrug-resistance proteins 1, 4 and 5 (ABCC1, 4 and 5).

PubMed

Wu, Chung-Pu; Calcagno, Anna Maria; Hladky, Stephen B; Ambudkar, Suresh V; Barrand, Margery A

2005-09-01

Plant flavonoids are polyphenolic compounds, commonly found in vegetables, fruits and many food sources that form a significant portion of our diet. These compounds have been shown to interact with several ATP-binding cassette transporters that are linked with anticancer and antiviral drug resistance and, as such, may be beneficial in modulating drug resistance. This study investigates the interactions of six common polyphenols; quercetin, silymarin, resveratrol, naringenin, daidzein and hesperetin with the multidrug-resistance-associated proteins, MRP1, MRP4 and MRP5. At nontoxic concentrations, several of the polyphenols were able to modulate MRP1-, MRP4- and MRP5-mediated drug resistance, though to varying extents. The polyphenols also reversed resistance to NSC251820, a compound that appears to be a good substrate for MRP4, as predicted by data-mining studies. Furthermore, most of the polyphenols showed direct inhibition of MRP1-mediated [3H]dinitrophenyl S-glutathione and MRP4-mediated [3H]cGMP transport in inside-out vesicles prepared from human erythrocytes. Also, both quercetin and silymarin were found to inhibit MRP1-, MRP4- and MRP5-mediated transport from intact cells with high affinity. They also had significant effects on the ATPase activity of MRP1 and MRP4 without having any effect on [32P]8-azidoATP[alphaP] binding to these proteins. This suggests that these flavonoids most likely interact at the transporter's substrate-binding sites. Collectively, these results suggest that dietary flavonoids such as quercetin and silymarin can modulate transport activities of MRP1, -4 and -5. Such interactions could influence bioavailability of anticancer and antiviral drugs in vivo and thus, should be considered for increasing efficacy in drug therapies.

STS-40 Spacelab Life Science 1 (SLS-1) module in OV-102's payload bay (PLB)

NASA Image and Video Library

1991-06-14

STS040-610-010 (5-14 June 1991) --- The blue and white Earth forms the backdrop for this scene of the Spacelab Life Sciences (SLS-1) module in the cargo bay of the Earth-orbiting Columbia. The view was photographed through Columbia's aft flight deck windows with a handheld Rolleiflex camera. Seven crewmembers spent nine days in space aboard Columbia. Part of the tunnel/airlock system that linked them to the SLS-1 module is seen in center foreground.

MEMS-based flexible reflective analog modulators (FRAM) for projection displays: a technology review and scale-down study

NASA Astrophysics Data System (ADS)

Picard, Francis; Ilias, Samir; Asselin, Daniel; Boucher, Marc-André; Duchesne, François; Jacob, Michel; Larouche, Carl; Vachon, Carl; Niall, Keith K.; Jerominek, Hubert

2011-02-01

A MEMS based technology for projection display is reviewed. This technology relies on mechanically flexible and reflective microbridges made of aluminum alloy. A linear array of such micromirrors is combined with illumination and Schlieren optics to produce a pixels line. Each microbridge in the array is individually controlled using electrostatic actuation to adjust the pixels intensities. Results of the simulation, fabrication and characterization of these microdevices are presented. Activation voltages below 250 V with response times below 10 μs were obtained for 25 μm × 25 μm micromirrors. With appropriate actuation voltage waveforms, response times of 5 μs and less are achievable. A damage threshold of the mirrors above 8 kW/cm2 has been evaluated. Development of the technology has produced projector engines demonstrating this light modulation principle. The most recent of these engines is DVI compatible and displays VGA video streams at 60 Hz. Recently applications have emerged that impose more stringent requirements on the dimensions of the MEMS array and associated optical system. This triggered a scale down study to evaluate the minimum micromirror size achievable, the impact of this reduced size on the damage threshold and the achievable minimum size of the associated optical system. Preliminary results of this scale down study are reported. FRAM with active surface as small as 5 μm × 5 μm have been investigated. Simulations have shown that such micromirrors could be activated with 107 V to achieve f-number of 1.25. The damage threshold has been estimated for various FRAM sizes. Finally, design of a conceptual miniaturized projector based on 1000×1 array of 5 μm × 5 μm micromirrors is presented. The volume of this projector concept is about 12 cm3.

VIBRATING PERVAPORATION MODULES: EFFECT OF MODULE DESIGN ON PERFORMANCE

EPA Science Inventory

A third commercial-scale vibrating pervaporation membrane module was fabricated and evaluated for the separation of volatile organic compounds (VOCs) from aqueous solutions. Experiments with surrogate solutions of four hydrophobic VOCs (1,1,1-trichloroethane (TCA), trichloroethy...

Sulfonyl-containing modulators of serotonin 5-HT6 receptors and their pharmacophore models

NASA Astrophysics Data System (ADS)

Ivachtchenko, A. V.

2014-05-01

Data published in recent years on the synthesis of serotonin 5-HT6 receptor modulators are summarized. Modulators with high affinity for 5-HT6 receptors exhibiting different degrees of selectivity — from highly selective to semiselective and multimodal — are described. Clinical trial results are reported for the most promising serotonin 5-HT6 receptor modulators attracting special attention of medicinal chemists. The bibliography includes 128 references.

A series connection architecture for large-area organic photovoltaic modules with a 7.5% module efficiency

PubMed Central

Hong, Soonil; Kang, Hongkyu; Kim, Geunjin; Lee, Seongyu; Kim, Seok; Lee, Jong-Hoon; Lee, Jinho; Yi, Minjin; Kim, Junghwan; Back, Hyungcheol; Kim, Jae-Ryoung; Lee, Kwanghee

2016-01-01

The fabrication of organic photovoltaic modules via printing techniques has been the greatest challenge for their commercial manufacture. Current module architecture, which is based on a monolithic geometry consisting of serially interconnecting stripe-patterned subcells with finite widths, requires highly sophisticated patterning processes that significantly increase the complexity of printing production lines and cause serious reductions in module efficiency due to so-called aperture loss in series connection regions. Herein we demonstrate an innovative module structure that can simultaneously reduce both patterning processes and aperture loss. By using a charge recombination feature that occurs at contacts between electron- and hole-transport layers, we devise a series connection method that facilitates module fabrication without patterning the charge transport layers. With the successive deposition of component layers using slot-die and doctor-blade printing techniques, we achieve a high module efficiency reaching 7.5% with area of 4.15 cm2. PMID:26728507

N1-acetyl substituted pyrrolidine derivative CIP-A5: a novel compound that could ameliorate liver cirrhosis through modulation of hepatic stellate cell activity.

PubMed

Wang, Xiao-Dan; Gao, Zu-Hua; Xue, Xia; Cheng, Yan-Na; Yue, Pan; Fang, Xu-Wen; Qu, Xian-Jun

2011-06-01

(2S,4R)-methyl 1-acetyl-4-(N-(4-bromophenyl)sulfamoyloxy)pyrrolidine-2-carboxylate (CIP-A5) is the N1-acetyl substituted pyrrolidine derivative which was designed against the structure of matrix metalloproteinase (MMP-2) and MMP-9. CIP-A5 has been considered as a candidate compound for treatment of liver cirrhosis. In this study, we evaluated the efficacy of CIP-A5 on the activity of hepatic stellate cells. CIP-A5 prevented the transforming growth factor β (TGF-β)-induced proliferation of hepatic stellate HSC-T6 cells as estimated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. CIP-A5 stimulated MMPs activity as evidenced by an increase of degradation of succinylated gelatin. Gelatin zymography analysis showed that CIP-A5 stimulated the secretion and activity of MMP-2 and MMP-9 in HSC-T6 cells. This stimulatory effect on MMPs was verified by the observation of increased expression of MMP-2 and MMP-9 as evaluated by Western blot assay. At the same time, a significant decrease of the expression of tissue inhibitors of matrix metalloproteinases-1 (TIMP-1) was observed, suggesting a modulation of the balance of MMPs/TIMPs in hepatic stellate cells. CIP-A5 treatment also resulted in suppression of the profibrogenic cytokines, such as TGF-β, tumor necrosis factor alpha (TNF-α) and connective tissue growth factor (CTGF) in HSC-T6 cells. CIP-A5 did not have cytotoxicity to human normal hepatic cells. These results implied that CIP-A5 could selectively ameliorate the process of liver cirrhosis through modulation of activated hepatic stellate cell activity, which offers hope for prevention and treatment of this devastating end-stage liver disease. Copyright © 2011 Elsevier Ltd. All rights reserved.

The development of a multi-dimensional gambling accessibility scale.

PubMed

Hing, Nerilee; Haw, John

2009-12-01

The aim of the current study was to develop a scale of gambling accessibility that would have theoretical significance to exposure theory and also serve to highlight the accessibility risk factors for problem gambling. Scale items were generated from the Productivity Commission's (Australia's Gambling Industries: Report No. 10. AusInfo, Canberra, 1999) recommendations and tested on a group with high exposure to the gambling environment. In total, 533 gaming venue employees (aged 18-70 years; 67% women) completed a questionnaire that included six 13-item scales measuring accessibility across a range of gambling forms (gaming machines, keno, casino table games, lotteries, horse and dog racing, sports betting). Also included in the questionnaire was the Problem Gambling Severity Index (PGSI) along with measures of gambling frequency and expenditure. Principal components analysis indicated that a common three factor structure existed across all forms of gambling and these were labelled social accessibility, physical accessibility and cognitive accessibility. However, convergent validity was not demonstrated with inconsistent correlations between each subscale and measures of gambling behaviour. These results are discussed in light of exposure theory and the further development of a multi-dimensional measure of gambling accessibility.

FFMPD scales: Comparisons with the FFM, PID-5, and CAT-PD-SF.

PubMed

Crego, Cristina; Oltmanns, Joshua R; Widiger, Thomas A

2018-01-01

A series of 8 Five Factor Model Personality Disorder (FFMPD) scales have been developed to assess, from the perspective of the Five Factor Model (FFM), the maladaptive traits included within DSM-5 Section II personality disorders. An extensive body of FFMPD research has accumulated. However, for the most part, each study has been confined to the scales within 1 particular FFMPD Inventory. The current study considered 36 FFMPD scales, at least 1 from each of the 8 FFMPD inventories, including 8 scales considered to be from neuroticism, 8 from extraversion, 5 from openness, 8 from agreeableness, and 7 from conscientiousness. Their convergent, discriminant, and structural relationship with the FFM was considered, and compared with the structural relationship with the FFM obtained by the Personality Inventory for DSM-5 (PID-5) and the Computerized Adaptive Test-Personality Disorder-Static Form (CAT-PD-SF). Support for an FFM structure was obtained (albeit with agreeableness defining 1 factor and antagonism a separate factor). Similarities and differences across the FFMPD, PID-5, and CAT-PD-SF scales were highlighted. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Recognising Axionic Dark Matter by Compton and de-Broglie Scale Modulation of Pulsar Timing

NASA Astrophysics Data System (ADS)

De Martino, Ivan; Broadhurst, Tom; Tye, S.-H. Henry; Chiueh, Tzihong; Schive, Hsi-Yu; Lazkoz, Ruth

2017-11-01

Light Axionic Dark Matter, motivated by string theory, is increasingly favored for the "no-WIMP era". Galaxy formation is suppressed below a Jeans scale, of ≃ 10^8 M_⊙ by setting the axion mass to, m_B ˜ 10^{-22}eV, and the large dark cores of dwarf galaxies are explained as solitons on the de-Broglie scale. This is persuasive, but detection of the inherent scalar field oscillation at the Compton frequency, ω_B= (2.5 months)^{-1}(m_B/10^{-22}eV), would be definitive. By evolving the coupled Schrödinger-Poisson equation for a Bose-Einstein condensate, we predict the dark matter is fully modulated by de-Broglie interference, with a dense soliton core of size ≃ 150pc, at the Galactic center. The oscillating field pressure induces General Relativistic time dilation in proportion to the local dark matter density and pulsars within this dense core have detectably large timing residuals, of ≃ 400nsec/(m_B/10^{-22}eV). This is encouraging as many new pulsars should be discovered near the Galactic center with planned radio surveys. More generally, over the whole Galaxy, differences in dark matter density between pairs of pulsars imprints a pairwise Galactocentric signature that can be distinguished from an isotropic gravitational wave background.

Vibration Sensitivity of a Wide-Temperature Electronically Scanned Pressure Measurement (ESP) Module

NASA Technical Reports Server (NTRS)

Zuckerwar, Allan J.; Garza, Frederico R.

2001-01-01

A vibration sensitivity test was conducted on a Wide-Temperature ESP module. The test object was Module "M4," a 16-channel, 4 psi unit scheduled for installation in the Arc Sector of NTF. The module was installed on a vibration exciter and loaded to positive then negative full-scale pressures (+/-2.5 psid). Test variables were the following: Vibration frequencies: 20, 55, 75 Hz. Vibration level: 1 g. Vibration axes: X, Y, Z. The pressure response was measured on each channel, first without and then with the vibration turned on, and the difference analyzed by means of the statistical t-test. The results show that the vibration sensitivity does not exceed 0.01% Full Scale Output per g (with the exception of one channel on one axis) to a 95 percent confidence level. This specification, limited by the resolution of the pressure source, lies well below the total uncertainty specification of 0.1 percent Full Scale Output.

Hybrid Parallelization of Adaptive MHD-Kinetic Module in Multi-Scale Fluid-Kinetic Simulation Suite

DOE PAGES

Borovikov, Sergey; Heerikhuisen, Jacob; Pogorelov, Nikolai

2013-04-01

The Multi-Scale Fluid-Kinetic Simulation Suite has a computational tool set for solving partially ionized flows. In this paper we focus on recent developments of the kinetic module which solves the Boltzmann equation using the Monte-Carlo method. The module has been recently redesigned to utilize intra-node hybrid parallelization. We describe in detail the redesign process, implementation issues, and modifications made to the code. Finally, we conduct a performance analysis.

In-line monitoring technique with visible light from 1.3 microm-band SHG module for optical access systems.

PubMed

Kubo, Takahiro; Taniguchi, Tomohiro; Tadanaga, Osamu; Sakurai, Naoya; Kimura, Hideaki; Hadama, Hisaya; Asobe, Masaki

2010-02-01

We propose an in-line monitoring technique that uses 650 nm visible light for performing maintenance work on Fiber-to-the-home (FTTH) network quickly without the need for measuring skills or external devices. This technique is characterized by visible light (650 nm) generated by an SHG module from the 1.3 microm-band line signal. We fabricate a 1.3 microm-band quasi phase matched LiNbO(3) (QPM-LN) module, and the measure the 650 nm second harmonic (SH) power to test the proposed short-pulse modulation method. The results confirm the feasibility of the short-pulse modulation method with different peak factors (PFs) (1.0-7.3). We also examine the effect of short-pulse modulation on system performance at the optical receiver by measuring the bit error rate (BER) of received data (1.25 Gb/s). The BER is basically unaffected by the PF (1.0-5.5). This means that the proposed technique has little influence on data reception as regards PF (1.0-5.5).

Product Module Rig Test

NASA Technical Reports Server (NTRS)

Holdeman, James D. (Technical Monitor); Chiappetta, Louis, Jr.; Hautman, Donald J.; Ols, John T.; Padget, Frederick C., IV; Peschke, William O. T.; Shirley, John A.; Siskind, Kenneth S.

2004-01-01

The low emissions potential of a Rich-Quench-Lean (RQL) combustor for use in the High Speed Civil Transport (HSCT) application was evaluated as part of Work Breakdown Structure (WBS) 1.0.2.7 of the NASA Critical Propulsion Components (CPC) Program under Contract NAS3-27235. Combustion testing was conducted in cell 1E of the Jet Burner Test Stand at United Technologies Research Center. Specifically, a Rich-Quench-Lean combustor, utilizing reduced scale quench technology implemented in a quench vane concept in a product-like configuration (Product Module Rig), demonstrated the capability of achieving an emissions index of nitrogen oxides (NOx EI) of 8.5 gm/Kg fuel at the supersonic flight condition (relative to the program goal of 5 gm/Kg fuel). Developmental parametric testing of various quench vane configurations in the more fundamental flametube, Single Module Rig Configuration, demonstrated NOx EI as low as 5.2. All configurations in both the Product Module Rig configuration and the Single Module Rig configuration demonstrated exceptional efficiencies, greater than 99.95 percent, relative to the program goal of 99.9 percent efficiency at supersonic cruise conditions. Sensitivity of emissions to quench orifice design parameters were determined during the parametric quench vane test series in support of the design of the Product Module Rig configuration. For the rectangular quench orifices investigated, an aspect ratio (length/width) of approximately 2 was found to be near optimum. An optimum for orifice spacing was found to exist at approximately 0.167 inches, resulting in 24 orifices per side of a quench vane, for the 0.435 inch quench zone channel height investigated in the Single Module Rig. Smaller quench zone channel heights appeared to be beneficial in reducing emissions. Measurements were also obtained in the Single Module Rig configuration on the sensitivity of emissions to the critical combustor parameters of fuel/air ratio, pressure drop, and residence

The dual PH domain protein Opy1 functions as a sensor and modulator of PtdIns(4,5)P₂ synthesis.

PubMed

Ling, Yading; Stefan, Christopher J; Macgurn, Jason A; Audhya, Anjon; Emr, Scott D

2012-06-29

Phosphatidylinositol-4,5-bisphosphate, PtdIns(4,5)P(2), is an essential signalling lipid that regulates key processes such as endocytosis, exocytosis, actin cytoskeletal organization and calcium signalling. Maintaining proper levels of PtdIns(4,5)P(2) at the plasma membrane (PM) is crucial for cell survival and growth. We show that the conserved PtdIns(4)P 5-kinase, Mss4, forms dynamic, oligomeric structures at the PM that we term PIK patches. The dynamic assembly and disassembly of Mss4 PIK patches may provide a mechanism to precisely modulate Mss4 kinase activity, as needed, for localized regulation of PtdIns(4,5)P(2) synthesis. Furthermore, we identify a tandem PH domain-containing protein, Opy1, as a novel Mss4-interacting protein that partially colocalizes with PIK patches. Based upon genetic, cell biological, and biochemical data, we propose that Opy1 functions as a coincidence detector of the Mss4 PtdIns(4)P 5-kinase and PtdIns(4,5)P(2) and serves as a negative regulator of PtdIns(4,5)P(2) synthesis at the PM. Our results also suggest that additional conserved tandem PH domain-containing proteins may play important roles in regulating phosphoinositide signalling.

Study on the removal efficiency of UF membranes using bacteriophages in bench-scale and semi-technical scale.

PubMed

Kreissel, K; Bösl, M; Lipp, P; Franzreb, M; Hambsch, B

2012-01-01

To determine the removal efficiency of ultrafiltration (UF) membranes for nano-particles in the size range of viruses the state of the art uses challenge tests with virus-spiked water. This work focuses on bench-scale and semi-technical scale experiments. Different experimental parameters influencing the removal efficiency of the tested UF membrane modules were analyzed and evaluated for bench- and semi-technical scale experiments. Organic matter in the water matrix highly influenced the removal of the tested bacteriophages MS2 and phiX174. Less membrane fouling (low ΔTMP) led to a reduced phage reduction. Increased flux positively affected phage removal in natural waters. The tested bacteriophages MS2 and phiX174 revealed different removal properties. MS2, which is widely used as a model organism to determine virus removal efficiencies of membranes, mostly showed a better removal than phiX174 for the natural water qualities tested. It seems that MS2 is possibly a less conservative surrogate for human enteric virus removal than phiX174. In bench-scale experiments log removal values (LRV) for MS2 of 2.5-6.0 and of 2.5-4.5 for phiX174 were obtained for the examined range of parameters. Phage removal obtained with differently fabricated semi-technical modules was quite variable for comparable parameter settings, indicating that module fabrication can lead to differing results. Potting temperature and module size were identified as influencing factors. In conclusion, careful attention has to be paid to the choice of experimental settings and module potting when using bench-scale or semi-technical scale experiments for UF membrane challenge tests.

The large-scale modulation of cosmic rays in mid-1982: Its dependence on heliospheric longitude and radius

NASA Technical Reports Server (NTRS)

Pyle, K. R.; Simpson, J. A.

1985-01-01

Near solar maximum, a series of large radial solar wind shocks in June and July 1982 provided a unique opportunity to study the solar modulation of galactic cosmic rays with an array of spacecraft widely separated both in heliocentric radius and longitude. By eliminating hysteresis effects it is possible to begin to separate radial and azimuthal effects in the outer heliosphere. On the large scale, changes in modulation (both the increasing and recovery phases) propagate outward at close to the solar wind velocity, except for the near-term effects of solar wind shocks, which may propagate at a significantly higher velocity. In the outer heliosphere, azimuthal effects are small in comparison with radial effects for large-scale modulation at solar maximum.

Brain STAT5 signaling modulates learning and memory formation.

PubMed

Furigo, Isadora C; Melo, Helen M; Lyra E Silva, Natalia M; Ramos-Lobo, Angela M; Teixeira, Pryscila D S; Buonfiglio, Daniella C; Wasinski, Frederick; Lima, Eliana R; Higuti, Eliza; Peroni, Cibele N; Bartolini, Paolo; Soares, Carlos R J; Metzger, Martin; de Felice, Fernanda G; Donato, Jose

2018-06-01

The signal transducer and activator of transcription 5 (STAT5) is a transcription factor recruited by numerous cytokines. STAT5 is important for several physiological functions, including body and tissue growth, mammary gland development, immune system and lipid metabolism. However, the role of STAT5 signaling for brain functions is still poorly investigated, especially regarding cognitive aspects. Therefore, the objective of the present study was to investigate whether brain STAT5 signaling modulates learning and memory formation. For this purpose, brain-specific STAT5 knockout (STAT5 KO) mice were studied in well-established memory tests. Initially, we confirmed a robust reduction in STAT5a and STAT5b mRNA levels in different brain structures of STAT5 KO mice. STAT5 KO mice showed no significant alterations in metabolism, growth, somatotropic axis and spontaneous locomotor activity. In contrast, brain-specific STAT5 ablation impaired learning and memory formation in the novel object recognition, Barnes maze and contextual fear conditioning tests. To unravel possible mechanisms that might underlie the memory deficits of STAT5 KO mice, we assessed neurogenesis in the hippocampus, but no significant differences were observed between groups. On the other hand, reduced insulin-like growth factor-1 (IGF-1) mRNA expression was found in the hippocampus and hypothalamus of STAT5 KO mice. These findings collectively indicate that brain STAT5 signaling is required to attain normal learning and memory. Therefore, STAT5 is an important downstream cellular mechanism shared by several cytokines to regulate cognitive functions.

Amplitude-Phase Modulation, Topological Horseshoe and Scaling Attractor of a Dynamical System

NASA Astrophysics Data System (ADS)

Li, Chun-Lai; Li, Wen; Zhang, Jing; Xie, Yuan-Xi; Zhao, Yi-Bo

2016-09-01

A three-dimensional autonomous chaotic system is discussed in this paper. Some basic dynamical properties of the system, including phase portrait, Poincaré map, power spectrum, Kaplan-Yorke dimension, Lyapunov exponent spectra, signal amplitude and topological horseshoe are studied theoretically and numerically. The main finding by analysis is that the signal amplitude can be modulated via controlling the coefficients of the linear term, cross-product term and squared term simultaneously or respectively, and the phase of x3 can be modulated by the product of the coefficients of the linear term and cross-product term. Furthermore, scaling chaotic attractors of this system are achieved by modified projective synchronization with an optimization-based linear coupling method, which is safer for secure communications than the existed synchronization scheme since the scaling factors can be regarded as the security encoding key. Supported by Hunan Provincial Natural Science Foundation of China under Grant No. 2016JJ4036, University Natural Science Foundation of Jiangsu Province under Grant No. 14KJB120007 and the National Natural Science Foundation of China under Grant Nos. 11504176 and 11602084

Molecular Mechanism of Action for Allosteric Modulators and Agonists in CC-chemokine Receptor 5 (CCR5).

PubMed

Karlshøj, Stefanie; Amarandi, Roxana Maria; Larsen, Olav; Daugvilaite, Viktorija; Steen, Anne; Brvar, Matjaž; Pui, Aurel; Frimurer, Thomas Michael; Ulven, Trond; Rosenkilde, Mette Marie

2016-12-23

The small molecule metal ion chelators bipyridine and terpyridine complexed with Zn 2+ (ZnBip and ZnTerp) act as CCR5 agonists and strong positive allosteric modulators of CCL3 binding to CCR5, weak modulators of CCL4 binding, and competitors for CCL5 binding. Here we describe their binding site using computational modeling, binding, and functional studies on WT and mutated CCR5. The metal ion Zn 2+ is anchored to the chemokine receptor-conserved Glu-283 VII:06/7.39 Both chelators interact with aromatic residues in the transmembrane receptor domain. The additional pyridine ring of ZnTerp binds deeply in the major binding pocket and, in contrast to ZnBip, interacts directly with the Trp-248 VI:13/6.48 microswitch, contributing to its 8-fold higher potency. The impact of Trp-248 was further confirmed by ZnClTerp, a chloro-substituted version of ZnTerp that showed no inherent agonism but maintained positive allosteric modulation of CCL3 binding. Despite a similar overall binding mode of all three metal ion chelator complexes, the pyridine ring of ZnClTerp blocks the conformational switch of Trp-248 required for receptor activation, thereby explaining its lack of activity. Importantly, ZnClTerp becomes agonist to the same extent as ZnTerp upon Ala mutation of Ile-116 III:16/3.40 , a residue that constrains the Trp-248 microswitch in its inactive conformation. Binding studies with 125 I-CCL3 revealed an allosteric interface between the chemokine and the small molecule binding site, including residues Tyr-37 I:07/1.39 , Trp-86 II:20/2.60 , and Phe-109 III:09/3.33 The small molecules and CCL3 approach this interface from opposite directions, with some residues being mutually exploited. This study provides new insight into the molecular mechanism of CCR5 activation and paves the way for future allosteric drugs for chemokine receptors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Size matters: plasticity in metabolic scaling shows body-size may modulate responses to climate change.

PubMed

Carey, Nicholas; Sigwart, Julia D

2014-08-01

Variability in metabolic scaling in animals, the relationship between metabolic rate ( R: ) and body mass ( M: ), has been a source of debate and controversy for decades. R: is proportional to MB: , the precise value of B: much debated, but historically considered equal in all organisms. Recent metabolic theory, however, predicts B: to vary among species with ecology and metabolic level, and may also vary within species under different abiotic conditions. Under climate change, most species will experience increased temperatures, and marine organisms will experience the additional stressor of decreased seawater pH ('ocean acidification'). Responses to these environmental changes are modulated by myriad species-specific factors. Body-size is a fundamental biological parameter, but its modulating role is relatively unexplored. Here, we show that changes to metabolic scaling reveal asymmetric responses to stressors across body-size ranges; B: is systematically decreased under increasing temperature in three grazing molluscs, indicating smaller individuals were more responsive to warming. Larger individuals were, however, more responsive to reduced seawater pH in low temperatures. These alterations to the allometry of metabolism highlight abiotic control of metabolic scaling, and indicate that responses to climate warming and ocean acidification may be modulated by body-size. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

JY1 time scale: a new Kalman-filter time scale designed at NIST

NASA Astrophysics Data System (ADS)

Yao, Jian; Parker, Thomas E.; Levine, Judah

2017-11-01

We report on a new Kalman-filter hydrogen-maser time scale (i.e. JY1 time scale) designed at the National Institute of Standards and Technology (NIST). The JY1 time scale is composed of a few hydrogen masers and a commercial Cs clock. The Cs clock is used as a reference clock to ease operations with existing data. Unlike other time scales, the JY1 time scale uses three basic time-scale equations, instead of only one equation. Also, this time scale can detect a clock error (i.e. time error, frequency error, or frequency drift error) automatically. These features make the JY1 time scale stiff and less likely to be affected by an abnormal clock. Tests show that the JY1 time scale deviates from the UTC by less than  ±5 ns for ~100 d, when the time scale is initially aligned to the UTC and then is completely free running. Once the time scale is steered to a Cs fountain, it can maintain the time with little error even if the Cs fountain stops working for tens of days. This can be helpful when we do not have a continuously operated fountain or when the continuously operated fountain accidentally stops, or when optical clocks run occasionally.

Nuclear Technology. Course 28: Welding Inspection. Module 28-5, Qualifications.

ERIC Educational Resources Information Center

Espy, John

This fifth in a series of ten modules for a course titled Welding Inspection describes qualification requirements for welding procedures and welders and the role of the nuclear quality assurance/quality control technician. The module follows a typical format that includes the following sections: (1) introduction, (2) module prerequisites, (3)…

Launch and Functional Considerations Guiding the Scaling and Design of Rigid Inflatable Habitat Modules

NASA Astrophysics Data System (ADS)

Bell, L.

2002-01-01

The Sasakawa International Center for Space Architecture (SICSA) has a long history of projects that involve design of space structures, including habitats for low-Earth orbit (LEO) and planetary applications. Most of these facilities and component systems are planned to comply with size, geometry and mass restrictions imposed by the Space Shuttle Orbiter's payload and lift/landing abort restrictions. These constraints limit launch elements to approximately 15 ft. diameter, 40 ft. long cylindrical dimensions weighing no more than approximately 25 metric tons. It is clear that future success of commercial space programs such as tourism will hinge upon the availability of bigger and more efficient Earth to LEO launch vehicles which can greatly reduce transportation and operational costs. This will enable development and utilization of larger habitat modules and other infrastructure elements which can be deployed with fewer launches and on-orbit assembly procedures. The sizing of these new heavy lift launchers should be scaled to optimize habitat functionality and efficiency, just as the habitat designs must consider optimization of launch vehicle economy. SICSA's planning studies address these vehicle and habitat optimization priorities as parallel and interdependent considerations. The allowable diameter of habitat modules established by launch vehicle capacity dictates functionally acceptable internal configuration options. Analyses of these options relative to practical dimensions for Earth-to-orbit launch vehicle scaling were conducted for two general schemes. The "bologna slice" configuration stacks the floors within a predominately cylindrical or spherical envelope, producing circular areas. The "banana split" approach divides a cylindrical module longitudinally, creating floors that are generally rectangular in shape. The assessments established minimum sizes for reasonable utility and efficiency. The bologna slice option. This configuration is only acceptable

A spin-modulated telescope for measurement of cosmic microwave background anisotropy

NASA Astrophysics Data System (ADS)

Staren, John William

The measurement of anisotropy in the Cosmic Microwave Background (CMB) advances our knowledge of the early Universe from which the radiation originated. The angular power spectrum of CMB anisotropy at sub-degree scales depends heavily on comsological parameters such as Ob, O 0 and H0. In pursuit of critical power spectrum measurements over a range of angular scales, a spin-modulated telescope with a single cryogenic amplifier used in a total power radiometer is designed, built and tested. The new technique of spin-modulation with a spinning flat mirror canted 2.5° relative to its spin axis modulates the beam in a 10° oval pattern on the sky at 2.5 Hz. This rapid two-dimensional modulation of the beam is tested at balloon altitudes to minimize the atmospheric offset and determine the efficacy of the scan and telescope design. Maps of over 600 and 400 square degrees are made of regions observed using the spin-modulation and a 20° azimuth scan. These maps yield a 95% confidence level flat band power upper limit of DeltaTℓ = Tcmb(ℓ(ℓ + 1)Cℓ/2pi)0.5 < 77 muK at ℓ = 38 and are free of systematics effects and striping due to long-term drifts in our amplifier to the levels tested here. Planning for the next telescope, with multiple amplifiers, is performed to ensure its success.

EFT-1 Crew Module Move to KSC Visitor Complex for Exhibit Display

NASA Image and Video Library

2017-04-10

The Orion crew module that traveled into space on Exploration Fight Test 1 (EFT-1) completed a different kind of trip recently at NASA's Kennedy Space Center in Florida. Secured on a custom-made ground support equipment transporter, Orion was moved from the Neil Armstrong Operations and Checkout Building to the Kennedy Space Center Visitor Complex, less than three miles down the road. The crew module will become part of the NASA Now exhibit inside the IMAX theater at the complex.The Orion spacecraft launched atop a United Launch Alliance Delta IV rocket Dec. 5, 2014, from Space Launch Complex 37 at Cape Canaveral Air Force Station in Florida. During the mission, the spacecraft traveled 3,604 miles above Earth, the first U.S. spacecraft designed to carry humans to go beyond low-Earth orbit in 42 years. The Orion crew module splashed down approximately 4.5 hours later in the Pacific Ocean, 600 miles off the shore of California.

CFD analysis of a full-scale ceramic kiln module under actual operating conditions

NASA Astrophysics Data System (ADS)

Milani, Massimo; Montorsi, Luca; Stefani, Matteo; Venturelli, Matteo

2017-11-01

The paper focuses on the CFD analysis of a full-scale module of an industrial ceramic kiln under actual operating conditions. The multi-dimensional analysis includes the real geometry of a ceramic kiln module employed in the preheating and firing sections and investigates the heat transfer between the tiles and the burners' flame as well as the many components that comprise the module. Particular attention is devoted to the simulation of the convective flow field in the upper and lower chambers and to the effects of radiation on the different materials is addressed. The assessment of the radiation contribution to the tiles temperature is paramount to the improvement of the performance of the kiln in terms of energy efficiency and fuel consumption. The CFD analysis is combined to a lumped and distributed parameter model of the entire kiln in order to simulate the module behaviour at the boundaries under actual operating conditions. Finally, the CFD simulation is employed to address the effects of the module operating conditions on the tiles' temperature distribution in order to improve the temperature uniformity as well as to enhance the energy efficiency of the system and thus to reduce the fuel consumption.

Signal transducer and activator of transcription 5B (STAT5B) modulates adipocyte differentiation via MOF.

PubMed

Gao, Peng; Zhang, Yuchao; Liu, Yuantao; Chen, Jicui; Zong, Chen; Yu, Cong; Cui, Shang; Gao, Weina; Qin, Dandan; Sun, Wenchuan; Li, Xia; Wang, Xiangdong

2015-12-01

The role and mechanism of signal transducer and activator of transcription 5B (STAT5B) in adipogenesis remain unclear. In this study, our data showed that Males absent on the first (MOF) protein expression was increased during 3 T3-L1 preadipocytes differentiation accompanied with STAT5B expression increasing. Over-expression STAT5B enhanced MOF promoter trans-activation in HeLa cells. Mutagenesis assay and ChIP analysis exhibited that STAT5B was able to bind MOF promoter. Knocking-down STAT5B in 3 T3-L1 preadipocytes led to decreased expression of MOF, but resulted in increased expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid-binding protein 4 (Fabp4), which were important factors or enzymes for adipogenesis. We also found that knocking-down MOF in 3 T3-L1 preadipocytes resulted in increased expression of PPARγ, C/EBPα and Fabp4, which was in the same trend as STAT5B knocking-down. Over-expression MOF resulted in reduced promoter trans-activation activity of C/EBPα. These results suggest that STAT5B and MOF work as negative regulators in adipogenesis, and STAT5B modulates preadipocytes differentiation partially by regulating MOF expression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Recognizing Axionic Dark Matter by Compton and de Broglie Scale Modulation of Pulsar Timing.

PubMed

De Martino, Ivan; Broadhurst, Tom; Tye, S-H Henry; Chiueh, Tzihong; Schive, Hsi-Yu; Lazkoz, Ruth

2017-12-01

Light axionic dark matter, motivated by string theory, is increasingly favored for the "no weakly interacting massive particle era". Galaxy formation is suppressed below a Jeans scale of ≃10^{8}  M_{⊙} by setting the axion mass to m_{B}∼10^{-22}  eV, and the large dark cores of dwarf galaxies are explained as solitons on the de Broglie scale. This is persuasive, but detection of the inherent scalar field oscillation at the Compton frequency ω_{B}=(2.5  months)^{-1}(m_{B}/10^{-22}  eV) would be definitive. By evolving the coupled Schrödinger-Poisson equation for a Bose-Einstein condensate, we predict the dark matter is fully modulated by de Broglie interference, with a dense soliton core of size ≃150  pc, at the Galactic center. The oscillating field pressure induces general relativistic time dilation in proportion to the local dark matter density and pulsars within this dense core have detectably large timing residuals of ≃400  nsec/(m_{B}/10^{-22}  eV). This is encouraging as many new pulsars should be discovered near the Galactic center with planned radio surveys. More generally, over the whole Galaxy, differences in dark matter density between pairs of pulsars imprints a pairwise Galactocentric signature that can be distinguished from an isotropic gravitational wave background.

Collaborative Research: Quantifying the Uncertainties of Aerosol Indirect Effects and Impacts on Decadal-Scale Climate Variability in NCAR CAM5 and CESM1

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

Nenes, Athanasios

The goal of this proposed project is to assess the climatic importance and sensitivity of aerosol indirect effect (AIE) to cloud and aerosol processes and feedbacks, which include organic aerosol hygroscopicity, cloud condensation nuclei (CCN) activation kinetics, Giant CCN, cloud-scale entrainment, ice nucleation in mixed-phase and cirrus clouds, and treatment of subgrid variability of vertical velocity. A key objective was to link aerosol, cloud microphysics and dynamics feedbacks in CAM5 with a suite of internally consistent and integrated parameterizations that provide the appropriate degrees of freedom to capture the various aspects of the aerosol indirect effect. The proposal integrated newmore » parameterization elements into the cloud microphysics, moist turbulence and aerosol modules used by the NCAR Community Atmospheric Model version 5 (CAM5). The CAM5 model was then used to systematically quantify the uncertainties of aerosol indirect effects through a series of sensitivity tests with present-day and preindustrial aerosol emissions. New parameterization elements were developed as a result of these efforts, and new diagnostic tools & methodologies were also developed to quantify the impacts of aerosols on clouds and climate within fully coupled models. Observations were used to constrain key uncertainties in the aerosol-cloud links. Advanced sensitivity tools were developed and implements to probe the drivers of cloud microphysical variability with unprecedented temporal and spatial scale. All these results have been published in top and high impact journals (or are in the final stages of publication). This proposal has also supported a number of outstanding graduate students.« less

Space Power Free-Piston Stirling Engine Scaling Study

NASA Technical Reports Server (NTRS)

Jones, D.

1989-01-01

The design feasibility study is documented of a single cylinder, free piston Stirling engine/linear alternator (FPSE/LA) power module generating 150 kW-electric (kW sub e), and the determination of the module's maximum feasible power level. The power module configuration was specified to be a single cylinder (single piston, single displacer) FPSE/LA, with tuning capacitors if required. The design requirements were as follows: (1) Maximum electrical power output; (2) Power module thermal efficiency equal to or greater than 20 percent at a specific mass of 5 to 8 kg/kW(sub e); (3) Heater wall temperature/cooler wall temperature = 1050 K/525 K; (4) Sodium heat-pipe heat transport system, pumped loop NaK (sodium-potassium eutectic mixture) rejection system; (5) Maximum power module vibration amplitude = 0.0038 cm; and (6) Design life = 7 years (60,000 hr). The results show that a single cylinder FPSE/LA is capable of meeting program goals and has attractive scaling attributes over the power range from 25 to 150 kW(sub e). Scaling beyond the 150 kW(sub e) power level, the power module efficiency falls and the power module specific mass reaches 10 kg/kW(sub e) at a power output of 500 kW(sub e). A discussion of scaling rules for the engine, alternator, and heat transport systems is presented, along with a detailed description of the conceptual design of a 150 kW(sub e) power module that meets the requirements. Included is a discussion of the design of a dynamic balance system. A parametric study of power module performance conducted over the power output range of 25 to 150 kW(sub e) for temperature ratios of 1.7, 2.0, 2.5, and 3.0 is presented and discussed. The results show that as the temperature ratio decreases, the efficiency falls and specific mass increases. At a temperature ratio of 1.7, the 150 kW(sub e) power module cannot satisfy both efficiency and specific mass goals. As the power level increases from 25 to 150 kW(sub e) at a fixed temperature ratio, power

The role of large—scale BECCS in the pursuit of the 1.5°C target: an Earth system model perspective

NASA Astrophysics Data System (ADS)

Muri, Helene

2018-04-01

The increasing awareness of the many damaging aspects of climate change has prompted research into ways of reducing and reversing the anthropogenic increase in carbon concentrations in the atmosphere. Most emission scenarios stabilizing climate at low levels, such as the 1.5 °C target as outlined by the Paris Agreement, require large-scale deployment of Bio-Energy with Carbon Capture and Storage (BECCS). Here, the potential of large-scale BECCS deployment in contributing towards the 1.5 °C global warming target is evaluated using an Earth system model, as well as associated climate responses and carbon cycle feedbacks. The geographical location of the bioenergy feedstock is shown to be key to the success of such measures in the context of temperature targets. Although net negative emissions were reached sooner, by ∼6 years, and scaled up, land use change emissions and reductions in forest carbon sinks outweigh these effects in one scenario. Re-cultivating mid-latitudes was found to be beneficial, on the other hand, contributing in the right direction towards the 1.5 °C target, only by ‑0.1 °C and ‑54 Gt C in avoided emissions, however. Obstacles remain related to competition for land from nature preservation and food security, as well as the technological availability of CCS.

Measuring health-related quality of life in children with cancer living in Mainland China: feasibility, reliability and validity of the Chinese Mandarin version of PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module.

PubMed

Ji, Yi; Chen, Siyuan; Li, Kai; Xiao, Nong; Yang, Xue; Zheng, Shan; Xiao, Xianmin

2011-11-23

The Pediatric Quality of Life Inventory (PedsQL) is widely used instrument to measure pediatric health-related quality of life (HRQOL) for children aged 2 to 18 years. The purpose of the current study was to investigate the feasibility, reliability and validity of the Chinese mandarin version of the PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module in a group of Chinese children with cancer. The PedsQL 4.0 Genetic Core Scales and the PedsQL 3.0 Cancer Module were administered to children with cancer (aged 5-18 years) and parents of such children (aged 2-18 years). For comparison, a survey on a demographically group-matched sample of the general population with children (aged 5-18) and parents of children (aged 2-18 years) was conducted with the PedsQL 4.0 Genetic Core Scales. The minimal mean percentage of missing item responses (except the School Functioning scale) supported the feasibility of the PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module for Chinese children with cancer. Most of the scales showed satisfactory reliability with Cronbach's α of exceeding 0.70, and all scales demonstrated sufficient test-retest reliability. Assessing the clinical validity of the questionnaires, statistically significant difference was found between healthy children and children with cancer, and between children on-treatment versus off-treatment ≥12 months. Positive significant correlations were observed between the scores of the PedsQL 4.0 Generic Core Scale and the PedsQL 3.0 Cancer Module. Exploratory factor analysis demonstrated sufficient factorial validity. Moderate to good agreement was found between child self- and parent proxy-reports. The findings support the feasibility, reliability and validity of the Chinese Mandarin version of PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module in children with cancer living in mainland China.

Developing Sensitive and Selective Nanosensors: A Single Molecule - Multiple Excitation Source Approach. Altairnano Lithium Ion Nano-scaled Titanate Oxide Cell and Module Abuse Testing

DTIC Science & Technology

2012-03-13

Source Approach Part II. Altairnano Lithium Ion Nano-scaled Titanate Oxide Cell and Module Abuse Testing 14. ABSTRACT 16. SECURITY CLASSIFICATION OF...Lithium Ion Nano-scaled Titanate Oxide Cell and Module Abuse Testing Report Title ABSTRACT This final report for Contract W911NF-09-C-0135 transmits the...prototype development. The second (Part II.) is "Altairnano Lithium Ion Nano-scaled Titanate Oxide Cell and Module Abuse Test Report". The

Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus.

PubMed

Taylor Meadows, Kristen R; Steinberg, Marcos W; Clemons, Bryan; Stokes, Matthew E; Opiteck, Gregory J; Peach, Robert; Scott, Fiona L

2018-01-01

Ozanimod (RPC1063) is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) and receptor 5 (S1PR5), which has shown therapeutic benefit in clinical trials of relapsing multiple sclerosis and ulcerative colitis. Ozanimod and its active metabolite, RP-101075, exhibit a similar specificity profile at the S1P receptor family in vitro and pharmacodynamic profile in vivo. The NZBWF1 mouse model was used in therapeutic dosing mode to assess the potential benefit of ozanimod and RP-101075 in an established animal model of systemic lupus erythematosus. Compared with vehicle-treated animals, ozanimod and RP-101075 reduced proteinuria over the duration of the study and serum blood urea nitrogen at termination. Additionally, ozanimod and RP-101075 reduced kidney disease in a dose-dependent manner, as measured by histological assessment of mesangial expansion, endo- and exo-capillary proliferation, interstitial infiltrates and fibrosis, glomerular deposits, and tubular atrophy. Further exploration into gene expression changes in the kidney demonstrate that RP-101075 also significantly reduced expression of fibrotic and immune-related genes in the kidneys. Of note, RP-101075 lowered the number of plasmacytoid dendritic cells, a major source of interferon alpha in lupus patients, and reduced all B and T cell subsets in the spleen. Given the efficacy demonstrated by ozanimod and its metabolite RP-101075 in the NZBWF1 preclinical animal model, ozanimod may warrant clinical evaluation as a potential treatment for systemic lupus erythematosus.

Low Voltage Alarm Apprenticeship. Related Training Modules. 1.1-1.14 Trade Math.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This packet of 14 learning modules on trade math is 1 of 8 such packets developed for apprenticeship training for low voltage alarm. Introductory materials are a complete listing of all available modules and a supplementary reference list. Each module contains some or all of these components: goal, performance indicators, study guide (a check list…

Unified Technical Concepts. Module 5: Resistance.

ERIC Educational Resources Information Center

Technical Education Research Center, Waco, TX.

This concept module on resistance is one of thirteen modules that provide a flexible, laboratory-based physics instructional package designed to meet the specialized needs of students in two-year, postsecondary technical schools. Each of the thirteen concept modules discusses a single physics concept and how it is applied to each energy system.…

SCALE Code System 6.2.1

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

Rearden, Bradley T.; Jessee, Matthew Anderson

The SCALE Code System is a widely-used modeling and simulation suite for nuclear safety analysis and design that is developed, maintained, tested, and managed by the Reactor and Nuclear Systems Division (RNSD) of Oak Ridge National Laboratory (ORNL). SCALE provides a comprehensive, verified and validated, user-friendly tool set for criticality safety, reactor and lattice physics, radiation shielding, spent fuel and radioactive source term characterization, and sensitivity and uncertainty analysis. Since 1980, regulators, licensees, and research institutions around the world have used SCALE for safety analysis and design. SCALE provides an integrated framework with dozens of computational modules including three deterministicmore » and three Monte Carlo radiation transport solvers that are selected based on the desired solution strategy. SCALE includes current nuclear data libraries and problem-dependent processing tools for continuous-energy (CE) and multigroup (MG) neutronics and coupled neutron-gamma calculations, as well as activation, depletion, and decay calculations. SCALE includes unique capabilities for automated variance reduction for shielding calculations, as well as sensitivity and uncertainty analysis. SCALE’s graphical user interfaces assist with accurate system modeling, visualization of nuclear data, and convenient access to desired results.« less

Large scale validation of the M5L lung CAD on heterogeneous CT datasets.

PubMed

Torres, E Lopez; Fiorina, E; Pennazio, F; Peroni, C; Saletta, M; Camarlinghi, N; Fantacci, M E; Cerello, P

2015-04-01

M5L, a fully automated computer-aided detection (CAD) system for the detection and segmentation of lung nodules in thoracic computed tomography (CT), is presented and validated on several image datasets. M5L is the combination of two independent subsystems, based on the Channeler Ant Model as a segmentation tool [lung channeler ant model (lungCAM)] and on the voxel-based neural approach. The lungCAM was upgraded with a scan equalization module and a new procedure to recover the nodules connected to other lung structures; its classification module, which makes use of a feed-forward neural network, is based of a small number of features (13), so as to minimize the risk of lacking generalization, which could be possible given the large difference between the size of the training and testing datasets, which contain 94 and 1019 CTs, respectively. The lungCAM (standalone) and M5L (combined) performance was extensively tested on 1043 CT scans from three independent datasets, including a detailed analysis of the full Lung Image Database Consortium/Image Database Resource Initiative database, which is not yet found in literature. The lungCAM and M5L performance is consistent across the databases, with a sensitivity of about 70% and 80%, respectively, at eight false positive findings per scan, despite the variable annotation criteria and acquisition and reconstruction conditions. A reduced sensitivity is found for subtle nodules and ground glass opacities (GGO) structures. A comparison with other CAD systems is also presented. The M5L performance on a large and heterogeneous dataset is stable and satisfactory, although the development of a dedicated module for GGOs detection could further improve it, as well as an iterative optimization of the training procedure. The main aim of the present study was accomplished: M5L results do not deteriorate when increasing the dataset size, making it a candidate for supporting radiologists on large scale screenings and clinical programs.

Chattanooga Math Trail: Community Mathematics Modules, Volume 1.

ERIC Educational Resources Information Center

McAllister, Deborah A.; Mealer, Adrian; Moyer, Peggy S.; McDonald, Shirley A.; Peoples, John B.

This collection of community mathematics modules, or "math trail", is appropriate for middle grades and high school students (grades 5-12). Collectively, the modules pay attention to all 10 of the National Council of Teachers of Mathematics (NCTM) standards which include five content standards (Number and Operations, Algebra, Geometry,…

Selective progesterone receptor modulators 1: use during pregnancy.

PubMed

Benagiano, Giuseppe; Bastianelli, Carlo; Farris, Manuela

2008-10-01

A large number of synthetic compounds known as selective progesterone receptor modulators can bind to progesterone receptors: the ligands exhibit a spectrum of activities ranging from pure antagonism to a mixture of agonism and antagonism. Only a dozen or so selective progesterone receptor modulators have been tested to any significant extent: among them are mifepristone (RU 486), asoprisnil (J867), onapristone (ZK 98 299), ulipristal (CDB 2914), Proellex() (CDB 4124), ORG 33628 and ORG 31710. Their clinical applications during pregnancy are discussed. A careful evaluation of existing major review papers and recently published articles was carried out focusing on mifepristone, the most widely studied selective progesterone receptor modulator, which was first used for the voluntary interruption of an early gestation. Other selective progesterone receptor modulators, especially those with partial agonist action, have shown little activity during pregnancy in animal models. Besides early and late voluntary interruption of gestation, selective progesterone receptor modulators have been tested in a variety of obstetrical situations: to obtain a ripening of the cervix, for the medical management of early embryonic loss and foetal death, for the induction of labour at term and for the medical treatment of extra-uterine pregnancies. The only applications that seem worthy of large-scale utilisation during pregnancy are voluntary interruption of early and late gestation, medical management of early delayed miscarriage and late foetal demise.

IAC-1.5 - INTEGRATED ANALYSIS CAPABILITY

NASA Technical Reports Server (NTRS)

Vos, R. G.

1994-01-01

The objective of the Integrated Analysis Capability (IAC) system is to provide a highly effective, interactive analysis tool for the integrated design of large structures. IAC was developed to interface programs from the fields of structures, thermodynamics, controls, and system dynamics with an executive system and a database to yield a highly efficient multi-disciplinary system. Special attention is given to user requirements such as data handling and on-line assistance with operational features, and the ability to add new modules of the user's choice at a future date. IAC contains an executive system, a database, general utilities, interfaces to various engineering programs, and a framework for building interfaces to other programs. IAC has shown itself to be effective in automating data transfer among analysis programs. The IAC system architecture is modular in design. 1) The executive module contains an input command processor, an extensive data management system, and driver code to execute the application modules. 2) Technical modules provide standalone computational capability as well as support for various solution paths or coupled analyses. 3) Graphics and model generation modules are supplied for building and viewing models. 4) Interface modules provide for the required data flow between IAC and other modules. 5) User modules can be arbitrary executable programs or JCL procedures with no pre-defined relationship to IAC. 6) Special purpose modules are included, such as MIMIC (Model Integration via Mesh Interpolation Coefficients), which transforms field values from one model to another; LINK, which simplifies incorporation of user specific modules into IAC modules; and DATAPAC, the National Bureau of Standards statistical analysis package. The IAC database contains structured files which provide a common basis for communication between modules and the executive system, and can contain unstructured files such as NASTRAN checkpoint files, DISCOS plot files

IAC-1.5 - INTEGRATED ANALYSIS CAPABILITY

NASA Technical Reports Server (NTRS)

Vos, R. G.

1994-01-01

The objective of the Integrated Analysis Capability (IAC) system is to provide a highly effective, interactive analysis tool for the integrated design of large structures. IAC was developed to interface programs from the fields of structures, thermodynamics, controls, and system dynamics with an executive system and a database to yield a highly efficient multi-disciplinary system. Special attention is given to user requirements such as data handling and on-line assistance with operational features, and the ability to add new modules of the user's choice at a future date. IAC contains an executive system, a database, general utilities, interfaces to various engineering programs, and a framework for building interfaces to other programs. IAC has shown itself to be effective in automating data transfer among analysis programs. The IAC system architecture is modular in design. 1) The executive module contains an input command processor, an extensive data management system, and driver code to execute the application modules. 2) Technical modules provide standalone computational capability as well as support for various solution paths or coupled analyses. 3) Graphics and model generation modules are supplied for building and viewing models. 4) Interface modules provide for the required data flow between IAC and other modules. 5) User modules can be arbitrary executable programs or JCL procedures with no pre-defined relationship to IAC. 6) Special purpose modules are included, such as MIMIC (Model Integration via Mesh Interpolation Coefficients), which transforms field values from one model to another; LINK, which simplifies incorporation of user specific modules into IAC modules; and DATAPAC, the National Bureau of Standards statistical analysis package. The IAC database contains structured files which provide a common basis for communication between modules and the executive system, and can contain unstructured files such as NASTRAN checkpoint files, DISCOS plot files

Sphingosine 1-Phosphate Receptor Modulators and Drug Discovery

PubMed Central

Park, Soo-Jin; Im, Dong-Soon

2017-01-01

Initial discovery on sphingosine 1-phosphate (S1P) as an intracellular second messenger was faced unexpectedly with roles of S1P as a first messenger, which subsequently resulted in cloning of its G protein-coupled receptors, S1P1–5. The molecular identification of S1P receptors opened up a new avenue for pathophysiological research on this lipid mediator. Cellular and molecular in vitro studies and in vivo studies on gene deficient mice have elucidated cellular signaling pathways and the pathophysiological meanings of S1P receptors. Another unexpected finding that fingolimod (FTY720) modulates S1P receptors accelerated drug discovery in this field. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials. In addition, more selective S1P receptor modulators with better pharmacokinetic profiles and fewer side effects are under development. Some of them are being clinically tested in the contexts of multiple sclerosis and other autoimmune and inflammatory disorders, such as, psoriasis, Crohn’s disease, ulcerative colitis, polymyositis, dermatomyositis, liver failure, renal failure, acute stroke, and transplant rejection. In this review, the authors discuss the state of the art regarding the status of drug discovery efforts targeting S1P receptors and place emphasis on potential clinical applications. PMID:28035084

25Gb/s 1V-driving CMOS ring modulator with integrated thermal tuning.

PubMed

Li, Guoliang; Zheng, Xuezhe; Yao, Jin; Thacker, Hiren; Shubin, Ivan; Luo, Ying; Raj, Kannan; Cunningham, John E; Krishnamoorthy, Ashok V

2011-10-10

We report a high-speed ring modulator that fits many of the ideal qualities for optical interconnect in future exascale supercomputers. The device was fabricated in a 130 nm SOI CMOS process, with 7.5 μm ring radius. Its high-speed section, employing PN junction that works at carrier-depletion mode, enables 25 Gb/s modulation and an extinction ratio >5 dB with only 1V peak-to-peak driving. Its thermal tuning section allows the device to work in broad wavelength range, with a tuning efficiency of 0.19 nm/mW. Based on microwave characterization and circuit modeling, the modulation energy is estimated ~7 fJ/bit. The whole device fits in a compact 400 μm2 footprint.

Topographical modulation of macrophage phenotype by shrink-film multi-scale wrinkles.

PubMed

Wang, Tingting; Luu, Thuy U; Chen, Aaron; Khine, Michelle; Liu, Wendy F

2016-06-24

The host immune response to foreign materials is a major hurdle for implanted medical devices. To control this response, modulation of macrophage behavior has emerged as a promising strategy, given their prominent role in inflammation and wound healing. Towards this goal, we explore the effect of biomimetic multi-scale wrinkles on macrophage adhesion and expression of phenotype markers. We find that macrophages elongate along the direction of the uniaxial wrinkles made from shape memory polymers, and express more arginase-1 and IL-10, and less TNF-α, suggesting polarization towards an alternatively activated, anti-inflammatory phenotype. Materials were further implanted in the subcutaneous space of mice and tissue surrounding the material evaluated by histology and immunohistochemistry. We found that material surface topography altered the distribution of collagen deposition in the adjacent tissue, with denser collagen tissue observed near flat materials when compared to wrinkled materials. Furthermore, cells surrounding wrinkled materials exhibited higher arginase-1 expression. Together these data suggest that wrinkled material surfaces promote macrophage alternative activation, and may influence the foreign body response to implants.

Keno-21: Fundamental Issues in the Design of Geophysical Simulation Experiments and Resource Allocation in Climate Modelling

NASA Astrophysics Data System (ADS)

Smith, L. A.

2001-05-01

Many sources of uncertainty come into play when modelling geophysical systems by simulation. These include uncertainty in the initial condition, uncertainty in model parameter values (and the parameterisations themselves) and error in the model class from which the model(s) was selected. In recent decades, climate simulations have focused resources on reducing the last of these by including more and more details into the model. One can question when this ``kitchen sink'' approach should be complimented with realistic estimates of the impact from other uncertainties noted above. Indeed while the impact of model error can never be fully quantified, as all simulation experiments are interpreted a the rosy scenario which assumes a priori that nothing crucial is missing, the impact of other uncertainties can be quantified at only the cost of computational power; as illustrated, for example, in ensemble climate modelling experiments like Casino-21. This talk illustrates the interplay uncertainties in the context of a trivial nonlinear system and an ensemble of models. The simple systems considered in this small scale experiment, Keno-21, are meant to illustrate issues of experimental design; they are not intended to provide true climate simulations. The use of simulation models with huge numbers of parameters given limited data is usually justified by an appeal to the Laws of Physics: the number of free degrees-of-freedom are many fewer than the number of variables; both variables, parameterisations, and parameter values are constrained by ``the physics" and the resulting simulation yields a realistic reproduction of the entire planet's climate system to within reasonable bounds. But what bounds? exactly? In a single model run under transient forcing scenario, there are good statistical grounds for considering only large space and time averages; most of these reasons vanish if an ensemble of runs are made. Ensemble runs can quantify the (in)ability of a model to provide

Spin-Tunnel Investigation of a 1/20-Scale Model of the Northrop F-5E Airplane

NASA Technical Reports Server (NTRS)

Scher, Stanley H.; White, William L.

1977-01-01

An investigation has been conducted in the Langley spin tunnel to determine the spin and recovery characteristics of a 1/20-scale model of the Northrop F-5E airplane. The investigation included erect and inverted spins, a range of center-of- gravity locations and moments of inertia, symmetric and asymmetric store loadings, and a determination of the parachute size required for emergency spin recovery. The effects of increased elevator trailing-edge-up deflections, of leading-edge and trailing-edge flap deflections, and of simulating the geometry of large external stores were also determined.

Long noncoding RNA lnc-sox5 modulates CRC tumorigenesis by unbalancing tumor microenvironment.

PubMed

Wu, Kaiming; Zhao, Zhenxian; Liu, Kuanzhi; Zhang, Jian; Li, Guanghua; Wang, Liang

2017-07-03

Long non-coding RNAs (LncRNAs) have been recently regarded as systemic regulators in multiple biologic processes including tumorigenesis. In this study, we observed the expression of lncRNA lnc-sox5 was significantly increased in colorectal cancer (CRC). Despite the CRC cell growth, cell cycle and cell apoptosis was not affected by lnc-sox5 knock-down, lnc-sox5 knock-down suppressed CRC cell migration and invasion. In addition, xenograft animal model suggested that lnc-sox5 knock-down significantly suppressed the CRC tumorigenesis. Our results also showed that the expression of indoleamine 2,3-dioxygenase 1 (IDO1) was significantly reduced by lnc-sox5 knock-down and therefore modulated the infiltration and cytotoxicity of CD3 + CD8 + T cells. Taken together, these results suggested that lnc-sox5 unbalances tumor microenvironment to regulate colorectal cancer progression.

Earth Observatory Satellite system definition study. Report 5: System design and specifications. Volume 4: Mission peculiar spacecraft segment and module specifications

NASA Technical Reports Server (NTRS)

1974-01-01

The specifications for the Earth Observatory Satellite (EOS) peculiar spacecraft segment and associated subsystems and modules are presented. The specifications considered include the following: (1) wideband communications subsystem module, (2) mission peculiar software, (3) hydrazine propulsion subsystem module, (4) solar array assembly, and (5) the scanning spectral radiometer.

Modulation of tyrosine hydroxylase expression by melatonin in human SH-SY5Y neuroblastoma cells.

PubMed

McMillan, Catherine R; Sharma, Rohita; Ottenhof, Tom; Niles, Lennard P

2007-06-04

We have previously reported in vivo preservation of tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis, following treatment with physiological doses of melatonin, in a 6-hydroxydopamine model of Parkinson's disease. Based on these findings, we postulated that melatonin would similarly modulate the expression of TH in vitro. Therefore, using human SH-SY5Y neuroblastoma cells which can differentiate into dopaminergic neurons following treatment with retinoic acid, we first examined whether these cells express melatonin receptors. Subsequently, the physiological dose-dependent effects of melatonin on TH expression were examined in both undifferentiated and differentiated cells. The novel detection of the G protein-coupled melatonin MT(1) receptor in SH-SY5Y cells by RT-PCR was confirmed by sequencing and Western blotting. In addition, following treatment of SH-SY5Y cells with melatonin (0.1-100 nM) for 24h, Western analysis revealed a significant increase in TH protein levels. A biphasic response, with significant increases in TH protein at 0.5 and 1 nM melatonin and a reversal at higher doses was seen in undifferentiated cells; whereas in differentiated cells, melatonin was effective at doses of 1 and 100 nM. These findings suggest a physiological role for melatonin in modulating TH expression, possibly via the MT(1) receptor.

Development and performance of pulse-width-modulated static inverter and converter modules

NASA Technical Reports Server (NTRS)

Pittman, P. F.; Gourash, F.; Birchenough, A. G.; Pittman, P. F.; Ravas, R. J.; Hall, W. G.

1971-01-01

Pulse-width-modulated inverter and converter modules are being developed for modular aerospace electrical power systems. The modules, rate 2.5 kilowatts per module and 10-minute - 150-percent overload, operate from 56 volts dc. The converter module provides two output voltages: a nominal link voltage of 200 volts dc when used with the inverter, and 150 volts dc to a load bus when used separately. The inverter module output is 400-hertz, sinusoidal, three-phase, 120/208 volts. Tests of breadboard models with standard parts and integrated circuits show rated power efficiencies of 71.4 and 85.1 percent and voltage regulation of 5 and 3.1 percent for inverter and converter modules, respectively. Sine-wave output distortion is 0.74 percent.

Femtojoule-scale all-optical latching and modulation via cavity nonlinear optics.

PubMed

Kwon, Yeong-Dae; Armen, Michael A; Mabuchi, Hideo

2013-11-15

We experimentally characterize Hopf bifurcation phenomena at femtojoule energy scales in a multiatom cavity quantum electrodynamical (cavity QED) system and demonstrate how such behaviors can be exploited in the design of all-optical memory and modulation devices. The data are analyzed by using a semiclassical model that explicitly treats heterogeneous coupling of atoms to the cavity mode. Our results highlight the interest of cavity QED systems for ultralow power photonic signal processing as well as for fundamental studies of mesoscopic nonlinear dynamics.

Allosteric modulation of sigma-1 receptors elicits anti-seizure activities.

PubMed

Guo, Lin; Chen, Yanke; Zhao, Rui; Wang, Guanghui; Friedman, Eitan; Zhang, Ao; Zhen, Xuechu

2015-08-01

Application of orthosteric sigma-1 receptor agonists as anti-seizure drugs has been hindered by questionable efficacy and potential adverse effects. Here, we have investigated the anti-seizure effects of the novel and potent allosteric modulator of sigma-1 receptors, SKF83959 and its derivative SOMCL-668 (3-methyl-phenyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol). The anti-seizure effects of SKF83959 were investigated in three mouse models, maximal electroshock seizures, pentylenetetrazole-induced convulsions and kainic acid-induced 'status epilepticus'. Also, in rats, the cortical epileptiform activity induced by topical application of picrotoxin was recorded in electrocorticograms. In rat hippocampal brain slices, effects of the drugs on the high potassium-evoked epileptiform local field potentials were studied. Anti-seizure activities of SOMCL-668, a newly developed sigma-1 receptor selective allosteric modulator, were also investigated. SKF83959 (20, 40 mg·kg(-1) ) exhibited anti -seizure actitity in the three mouse models and reduced the cortical epileptiform activity without alteration of spontaneous motor activity and motor coordination. These effects were blocked by the sigma-1 receptor antagonist BD1047, but not the dopamine D1 receptor antagonist SCH23390. SKF83959 alone did not directly inhibit the epileptiform firing of CA3 neurons induced by high potassium in hippocampal slices, but did potentiate inhibition by the orthosteric sigma-1 receptor agonist SKF10047. Lastly, a selective sigma-1 receptor allosteric modulator SOMCL-668, which does not bind to dopamine receptors, exerted similar anti-seizure activities. SKF83959 and SOMCL-668 displayed anti-seizure activities, indicating that allosteric modulation of sigma-1 receptors may provide a novel approach for discovering new anti-seizure drugs. © 2015 The British Pharmacological Society.

Serotonin 5-HT2C receptor-independent expression of hypothalamic NOR1, a novel modulator of food intake and energy balance, in mice

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

Nonogaki, Katsunori, E-mail: knonogaki-tky@umin.ac.jp; Department of Lifestyle Medicine, Biomedical Engineering Center, Tohoku University; Kaji, Takao

2009-08-21

NOR1, Nur77 and Nurr1 are orphan nuclear receptors and members of the NR4A subfamily. Here, we report that the expression of hypothalamic NOR1 was remarkably decreased in mildly obese {beta}-endorphin-deficient mice and obese db/db mice with the leptin receptor mutation, compared with age-matched wild-type mice, whereas there were no genotypic differences in the expression of hypothalamic Nur77 or Nurr1 in these animals. The injection of NOR1 siRNA oligonucleotide into the third cerebral ventricle significantly suppressed food intake and body weight in mice. On the other hand, the decreases in hypothalamic NOR1 expression were not found in non-obese 5-HT2C receptor-deficient mice.more » Moreover, systemic administration of m-chlorophenylpiperazine (mCPP), a 5-HT2C/1B receptor agonist, had no effect on hypothalamic NOR1 expression, while suppressing food intake in {beta}-endorphin-deficient mice. These findings suggest that 5-HT2C receptor-independent proopiomelanocortin-derived peptides regulate the expression of hypothalamic NOR1, which is a novel modulator of feeding behavior and energy balance.« less

Electro-optic Modulation in Single-crystal Film of DAST Measured at 1.55 microns

NASA Astrophysics Data System (ADS)

Titus, Jitto; Swamy, Rajendra; Govindan Kutty, Srivatsa; Khatavkar, Sanchit; Thakur, Mrinal

2003-03-01

Exceptionally large electro-optic coefficient and high-speed modulation at 750 nm in DAST single-crystal film has been recently reported.[1] In this presentation, our measurement of electro-optic modulation in DAST single-crystal film at 1.55 microns will be discussed. The single-crystal film was prepared by the modified shear method. The modulation measurement was performed in the transverse configuration using the field-induced birefringence method. A semiconductor laser was used for this experiment. The light beam was propagated perpendicular to the film and the modulation was recorded for an ac field applied along the dipole axis on the film. About 6.5at a low field leading to a magnitude of the electro-optic coefficient (r11) of about 200 pm/V at 1.55 microns. 1. M. Thakur, A. Mishra, J. Titus and A.C. Ahyi, APL, 81 3738 (2002).

Millivolt Modulation of Plasmonic Metasurface Optical Response via Ionic Conductance.

PubMed

Thyagarajan, Krishnan; Sokhoyan, Ruzan; Zornberg, Leonardo; Atwater, Harry A

2017-08-01

A plasmonic metasurface with an electrically tunable optical response that operates at strikingly low modulation voltages is experimentally demonstrated. The fabricated metasurface shows up to 30% relative change in reflectance in the visible spectral range upon application of 5 mV and 78% absolute change in reflectance upon application of 100 mV of bias. The designed metasurface consists of nanostructured silver and indium tin oxide (ITO) electrodes which are separated by 5 nm thick alumina. The millivolt-scale optical modulation is attributed to a new modulation mechanism, in which transport of silver ions through alumina dielectric leads to bias-induced nucleation and growth of silver nanoparticles in the ITO counter-electrode, altering the optical extinction response. This transport mechanism, which occurs at applied electric fields of 1 mV nm -1 , provides a new approach to use of ionic transport for electrical control over light-matter interactions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tarelin uses Liulin-5 Electronic Block in the MRM-1

NASA Image and Video Library

2013-01-10

ISS034-E-021230 (10 Jan. 2013) --- Russian cosmonaut Evgeny Tarelkin, Expedition 34 flight engineer, uses the Liulin-5 Electronic Block behind a panel in the Rassvet Mini-Research Module 1 (MRM1) of the International Space Station.

Double-modulation of 5-Fluorouracil by methotrexate and leucovorin in advanced colorectal-carcinoma.

PubMed

Leone, B; Romero, A; Rabinovich, M; Vallejo, C; Bianco, A; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Paris, A; Lacava, J

1993-11-01

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and leucovorin (LV) as first line chemotherapy in advanced colorectal carcinoma. Between January 1990, and April 1992, 42 patients with metastatic or advanced recurrent (inoperable) colorectal cancer were entered into the study. Therapy consisted of a sequential combination of MTX, LV and 5-FU. MTX was administered at a dose of 150 mg/m2 over 20 minutes I.V. infusion at hour (h) 0, followed 19 h later by LV 50 mg/m2 over 2 h infusion. 5-FU 900 mg/m2 was given by I.V. push injection at h 20. Starting 24 h after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 h for six doses. Treatment was repeated every 15 days until progressive disease, severe toxicity, or death. Four patients were considered not evaluable for response. Objective regression (OR) was observed in 14 of 38 patients (37%, 95% confidence interval 23-53%). Two patients (5%) obtained complete response (CR) and 12 (32%) partial response (PR). Median time to treatment failure was 6 months (range 1-21). Median survival for the whole group of patients was 13 months (range 1-27). Toxicity was within acceptable limits but one therapy-related death due to severe leukopenia and sepsis was observed. Double modulation of 5-FU with MTX and low dose of LV is an active regimen against advanced colorectal carcinoma and represents a promising strategy that should be further explored.

Transparent building-integrated PV modules. Phase 1: Comprehensive report

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

NONE

1998-09-28

This Comprehensive Report encompasses the activities that have been undertaken by Kiss + Cathcart, Architects, in conjunction with Energy Photovoltaics, Incorporated (EPV), to develop a flexible patterning system for thin-film photovoltaic (PV) modules for building applications. There are two basic methods for increasing transparency/light transmission by means of patterning the PV film: widening existing scribe lines, or scribing a second series of lines perpendicular to the first. These methods can yield essentially any degree of light transmission, but both result in visible patterns of light and dark on the panel surface. A third proposed method is to burn a gridmore » of dots through the films, independent of the normal cell scribing. This method has the potential to produce a light-transmitting panel with no visible pattern. Ornamental patterns at larger scales can be created using combinations of these techniques. Kiss + Cathcart, Architects, in conjunction with EPV are currently developing a complementary process for the large-scale lamination of thin-film PVs, which enables building integrated (BIPV) modules to be produced in sizes up to 48 in. x 96 in. Flexible laser patterning will be used for three main purposes, all intended to broaden the appeal of the product to the building sector: To create semitransparent thin-film modules for skylights, and in some applications, for vision glazing.; to create patterns for ornamental effects. This application is similar to fritted glass, which is used for shading, visual screening, graphics, and other purposes; and to allow BIPV modules to be fabricated in various sizes and shapes with maximum control over electrical characteristics.« less

Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus

PubMed Central

Taylor Meadows, Kristen R.; Steinberg, Marcos W.; Clemons, Bryan; Stokes, Matthew E.; Opiteck, Gregory J.; Peach, Robert; Scott, Fiona L.

2018-01-01

Ozanimod (RPC1063) is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) and receptor 5 (S1PR5), which has shown therapeutic benefit in clinical trials of relapsing multiple sclerosis and ulcerative colitis. Ozanimod and its active metabolite, RP-101075, exhibit a similar specificity profile at the S1P receptor family in vitro and pharmacodynamic profile in vivo. The NZBWF1 mouse model was used in therapeutic dosing mode to assess the potential benefit of ozanimod and RP-101075 in an established animal model of systemic lupus erythematosus. Compared with vehicle-treated animals, ozanimod and RP-101075 reduced proteinuria over the duration of the study and serum blood urea nitrogen at termination. Additionally, ozanimod and RP-101075 reduced kidney disease in a dose-dependent manner, as measured by histological assessment of mesangial expansion, endo- and exo-capillary proliferation, interstitial infiltrates and fibrosis, glomerular deposits, and tubular atrophy. Further exploration into gene expression changes in the kidney demonstrate that RP-101075 also significantly reduced expression of fibrotic and immune-related genes in the kidneys. Of note, RP-101075 lowered the number of plasmacytoid dendritic cells, a major source of interferon alpha in lupus patients, and reduced all B and T cell subsets in the spleen. Given the efficacy demonstrated by ozanimod and its metabolite RP-101075 in the NZBWF1 preclinical animal model, ozanimod may warrant clinical evaluation as a potential treatment for systemic lupus erythematosus. PMID:29608575

Using Lunar Module Shadows To Scale the Effects of Rocket Exhaust Plumes

NASA Technical Reports Server (NTRS)

2008-01-01

Excavating granular materials beneath a vertical jet of gas involves several physical mechanisms. These occur, for example, beneath the exhaust plume of a rocket landing on the soil of the Moon or Mars. We performed a series of experiments and simulations (Figure 1) to provide a detailed view of the complex gas-soil interactions. Measurements taken from the Apollo lunar landing videos (Figure 2) and from photographs of the resulting terrain helped demonstrate how the interactions extrapolate into the lunar environment. It is important to understand these processes at a fundamental level to support the ongoing design of higher fidelity numerical simulations and larger-scale experiments. These are needed to enable future lunar exploration wherein multiple hardware assets will be placed on the Moon within short distances of one another. The high-velocity spray of soil from the landing spacecraft must be accurately predicted and controlled or it could erode the surfaces of nearby hardware. This analysis indicated that the lunar dust is ejected at an angle of less than 3 degrees above the surface, the results of which can be mitigated by a modest berm of lunar soil. These results assume that future lunar landers will use a single engine. The analysis would need to be adjusted for a multiengine lander. Figure 3 is a detailed schematic of the Lunar Module camera calibration math model. In this chart, formulas relating the known quantities, such as sun angle and Lunar Module dimensions, to the unknown quantities are depicted. The camera angle PSI is determined by measurement of the imaged aspect ratio of a crater, where the crater is assumed to be circular. The final solution is the determination of the camera calibration factor, alpha. Figure 4 is a detailed schematic of the dust angle math model, which again relates known to unknown parameters. The known parameters now include the camera calibration factor and Lunar Module dimensions. The final computation is the ejected

Modulation of cannabinoid signaling by hippocampal 5-HT4 serotonergic system in fear conditioning.

PubMed

Nasehi, Mohammad; Farrahizadeh, Maryam; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

2016-09-01

Behavioral studies have suggested a key role for the cannabinoid system in the modulation of conditioned fear memory. Likewise, much of the literature has revealed that the serotonergic system affects Pavlovian fear conditioning and extinction. A high level of functional overlap between the serotonin and cannabinoid systems has also been reported. To clarify the interaction between the hippocampal serotonin (5-HT4) receptor and the cannabinoid CB1 receptor in the acquisition of fear memory, the effects of 5-HT4 agents, arachidonylcyclopropylamide (ACPA; CB1 receptor agonist), and the combined use of these drugs on fear learning were studied in a fear conditioning task in adult male NMRI mice. Pre-training intraperitoneal administration of ACPA (0.1 mg/kg) decreased the percentage of freezing time in both context- and tone-dependent fear conditions, suggesting impairment of the acquisition of fear memory. Pre-training, intra-hippocampal (CA1) microinjection of RS67333, a 5-HT4 receptor agonist, at doses of 0.1 and 0.2 or 0.2 µg/mouse impaired contextual and tone fear memory, respectively. A subthreshold dose of RS67333 (0.005 µg/mouse) did not alter the ACPA response in either condition. Moreover, intra-CA1 microinjection of RS23597 as a 5-HT4 receptor antagonist did not alter context-dependent fear memory acquisition, but it did impair tone-dependent fear memory acquisition. However, a subthreshold dose of the RS23597 (0.01 µg/mouse) potentiated ACPA-induced fear memory impairment in both conditions. Therefore, we suggest that the blockade of hippocampal 5-HT4 serotonergic system modulates cannabinoid signaling induced by the activation of CB1 receptors in conditioned fear. © The Author(s) 2016.

α5 nAChR modulation of the prefrontal cortex makes attention resilient.

PubMed

Howe, William M; Brooks, Julie L; Tierney, Patrick L; Pang, Jincheng; Rossi, Amie; Young, Damon; Dlugolenski, Keith; Guillmette, Ed; Roy, Marc; Hales, Katherine; Kozak, Rouba

2018-03-01

A loss-of-function polymorphism in the α5 nicotinic acetylcholine receptor (nAChR) subunit gene has been linked to both drug abuse and schizophrenia. The α5 nAChR subunit is strategically positioned in the prefrontal cortex (PFC), where a loss-of-function in this subunit may contribute to cognitive disruptions in both disorders. However, the specific contribution of α5 to PFC-dependent cognitive functions has yet to be illustrated. In the present studies, we used RNA interference to knockdown the α5 nAChR subunit in the PFC of adult rats. We provide evidence that through its contribution to cholinergic modulation of cholinergic modulation of neurons in the PFC, the α5 nAChR plays a specific role in the recovery of attention task performance following distraction. Our combined data reveal the potent ability of this subunit to modulate the PFC and cognitive functions controlled by this brain region that are impaired in disease.

Using scale and feather traits for module construction provides a functional approach to chicken epidermal development.

PubMed

Bao, Weier; Greenwold, Matthew J; Sawyer, Roger H

2017-11-01

Gene co-expression network analysis has been a research method widely used in systematically exploring gene function and interaction. Using the Weighted Gene Co-expression Network Analysis (WGCNA) approach to construct a gene co-expression network using data from a customized 44K microarray transcriptome of chicken epidermal embryogenesis, we have identified two distinct modules that are highly correlated with scale or feather development traits. Signaling pathways related to feather development were enriched in the traditional KEGG pathway analysis and functional terms relating specifically to embryonic epidermal development were also enriched in the Gene Ontology analysis. Significant enrichment annotations were discovered from customized enrichment tools such as Modular Single-Set Enrichment Test (MSET) and Medical Subject Headings (MeSH). Hub genes in both trait-correlated modules showed strong specific functional enrichment toward epidermal development. Also, regulatory elements, such as transcription factors and miRNAs, were targeted in the significant enrichment result. This work highlights the advantage of this methodology for functional prediction of genes not previously associated with scale- and feather trait-related modules.

Effect of Rocket-Motor Operation on the Drag of Three 1/5-Scale Hermes A-3A Models in Free Flight

NASA Technical Reports Server (NTRS)

Jackson, H. Herbert

1954-01-01

Three 1/5-scale models of the Hermes A-3A missile have been flown to determine the effect of rocket-motor operation on the drag corresponding to various altitude and Mach number combinations. The flights covered a Mach number range from 0.5 to 1.8, and ratios of jet-exit static pressure to free-stream static pressure from 0.8 to 1.8. The results indicate that the power-on drag of the missile should be the same as the power-off drag at Mach number 1.3 and slightly less than the power-off drag at Mach number 1.55.

Particle Cooler/Generator Module in the MRM1

NASA Image and Video Library

2014-01-13

ISS038-E-029764 (13 Jan. 2014) --- Russian cosmonaut Oleg Kotov, Expedition 38 commander, sets up the Particle Cooler/Generator Module for the Kaplya-2 experiment in the Rassvet Mini-Research Module 1 (MRM1) of the International Space Station.

Scale-Up of the Electrodeposition of ZnO/Eosin Y Hybrid Thin Films for the Fabrication of Flexible Dye-Sensitized Solar Cell Modules.

PubMed

Bittner, Florian; Oekermann, Torsten; Wark, Michael

2018-02-02

The low-temperature fabrication of flexible ZnO photo-anodes for dye-sensitized solar cells (DSSCs) by templated electrochemical deposition of films was performed in an enlarged and technical simplified deposition setup to demonstrate the feasibility of the scale-up of the deposition process. After extraction of eosin Y (EY) from the initially deposited ZnO/EY hybrid films, mesoporous ZnO films with an area of about 40 cm² were reproducibly obtained on fluorine doped tin oxide (FTO)-glass as well as flexible indium tin oxide (ITO)-polyethylenterephthalate (PET) substrates. With a film thickness of up to 9 µm and a high specific surface area of up to about 77 m²·cm -3 the ZnO films on the flexible substrates show suitable properties for DSSCs. Operative flexible DSSC modules proved the suitability of the ZnO films for use as DSSC photo-anodes. Under a low light intensity of about 0.007 sun these modules achieved decent performance parameters with conversion efficiencies of up to 2.58%. With rising light intensity the performance parameters deteriorated, leading to conversion efficiencies below 1% at light intensities above 0.5 sun. The poor performance of the modules under high light intensities can be attributed to their high series resistances.

Scale-Up of the Electrodeposition of ZnO/Eosin Y Hybrid Thin Films for the Fabrication of Flexible Dye-Sensitized Solar Cell Modules

PubMed Central

Oekermann, Torsten

2018-01-01

The low-temperature fabrication of flexible ZnO photo-anodes for dye-sensitized solar cells (DSSCs) by templated electrochemical deposition of films was performed in an enlarged and technical simplified deposition setup to demonstrate the feasibility of the scale-up of the deposition process. After extraction of eosin Y (EY) from the initially deposited ZnO/EY hybrid films, mesoporous ZnO films with an area of about 40 cm2 were reproducibly obtained on fluorine doped tin oxide (FTO)-glass as well as flexible indium tin oxide (ITO)–polyethylenterephthalate (PET) substrates. With a film thickness of up to 9 µm and a high specific surface area of up to about 77 m2·cm−3 the ZnO films on the flexible substrates show suitable properties for DSSCs. Operative flexible DSSC modules proved the suitability of the ZnO films for use as DSSC photo-anodes. Under a low light intensity of about 0.007 sun these modules achieved decent performance parameters with conversion efficiencies of up to 2.58%. With rising light intensity the performance parameters deteriorated, leading to conversion efficiencies below 1% at light intensities above 0.5 sun. The poor performance of the modules under high light intensities can be attributed to their high series resistances. PMID:29393910

Spin-Tunnel Investigation of a 1/30-Scale Model of the North American A-5 Airplane

NASA Technical Reports Server (NTRS)

Lee, Henry A.

1964-01-01

An investigation has been made to determine the erect and. inverted spin and recovery characteristics of a 1/30-scale dynamic model of the North American A-5A airplane. Tests were made for the basic flight design loading with the center of gravity at 30-percent mean aerodynamic chord and also for a forward position and a rearward position with the center of gravity at 26-percent and 40-percent mean aerodynamic chord, respectively. Tests were also made to determine the effect of full external wing tanks on both wings, and of an asymmetrical condition when only one full tank is carried.

The 40 KW of Solar Cell Modules for the Large Scale Production Task a Low Cost Silicon Solar Array Project

NASA Technical Reports Server (NTRS)

Jones, G. T.

1977-01-01

Forty kilowatts of solar cell modules was produced in this program. This is equivalent to 4123 modules. The average power output per module was 9.7 watts at 16.5 volts, 60 C and 100 mW/sq cm. The peak production rate was 200 modules per week which is equal to 1.9 kW per week. This rate was sustained for over four and one-half months and is equivalent to 100 kW per year. This final report covers the solar cell module design, electrical and power performance, module preproduction environmental test results, production and shipping schedule, program summary, and delivery. A cost analysis section is written. Particular emphasis on the percentage of labor and material utilized in constructing a solar cell module is presented. Also included are cost reduction recommendations.

Measuring health-related quality of life in children with cancer living in mainland China: feasibility, reliability and validity of the Chinese mandarin version of PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module

PubMed Central

2011-01-01

Background The Pediatric Quality of Life Inventory (PedsQL) is widely used instrument to measure pediatric health-related quality of life (HRQOL) for children aged 2 to 18 years. The purpose of the current study was to investigate the feasibility, reliability and validity of the Chinese mandarin version of the PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module in a group of Chinese children with cancer. Methods The PedsQL 4.0 Genetic Core Scales and the PedsQL 3.0 Cancer Module were administered to children with cancer (aged 5-18 years) and parents of such children (aged 2-18 years). For comparison, a survey on a demographically group-matched sample of the general population with children (aged 5-18) and parents of children (aged 2-18 years) was conducted with the PedsQL 4.0 Genetic Core Scales. Result The minimal mean percentage of missing item responses (except the School Functioning scale) supported the feasibility of the PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module for Chinese children with cancer. Most of the scales showed satisfactory reliability with Cronbach's α of exceeding 0.70, and all scales demonstrated sufficient test-retest reliability. Assessing the clinical validity of the questionnaires, statistically significant difference was found between healthy children and children with cancer, and between children on-treatment versus off-treatment ≥12 months. Positive significant correlations were observed between the scores of the PedsQL 4.0 Generic Core Scale and the PedsQL 3.0 Cancer Module. Exploratory factor analysis demonstrated sufficient factorial validity. Moderate to good agreement was found between child self- and parent proxy-reports. Conclusion The findings support the feasibility, reliability and validity of the Chinese Mandarin version of PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module in children with cancer living in mainland China. PMID:22111968

Tetrahydronaphthyridine and Dihydronaphthyridinone Ethers As Positive Allosteric Modulators of the Metabotropic Glutamate Receptor 5 (mGlu5)

PubMed Central

2015-01-01

Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu5) represent a promising therapeutic strategy for the treatment of schizophrenia. Starting from an acetylene-based lead from high throughput screening, an evolved bicyclic dihydronaphthyridinone was identified. We describe further refinements leading to both dihydronaphthyridinone and tetrahydronaphthyridine mGlu5 PAMs containing an alkoxy-based linkage as an acetylene replacement. Exploration of several structural features including western pyridine ring isomers, positional amides, linker connectivity/position, and combinations thereof, reveal that these bicyclic modulators generally exhibit steep SAR and within specific subseries display a propensity for pharmacological mode switching at mGlu5 as well as antagonist activity at mGlu3. Structure–activity relationships within a dihydronaphthyridinone subseries uncovered 12c (VU0405372), a selective mGlu5 PAM with good in vitro potency, low glutamate fold-shift, acceptable DMPK properties, and in vivo efficacy in an amphetamine-based model of psychosis. PMID:24914612

Laura Users Manual: 5.1-41601

NASA Technical Reports Server (NTRS)

Mazaheri, Alireza; Gnoffo, Peter A.; Johnston, Christopher O.; Kleb, Bil

2009-01-01

This users manual provides in-depth information concerning installation and execution of LAURA, version 5. LAURA is a structured, multi-block, computational aerothermodynamic simulation code. Version 5 represents a major refactoring of the original Fortran 77 LAURA code toward a modular structure afforded by Fortran 95. The refactoring improved usability and maintainability by eliminating the requirement for problem-dependent re-compilations, providing more intuitive distribution of functionality, and simplifying interfaces required for multiphysics coupling. As a result, LAURA now shares gas-physics modules, MPI modules, and other low-level modules with the FUN3D unstructured-grid code. In addition to internal refactoring, several new features and capabilities have been added, e.g., a GNU-standard installation process, parallel load balancing, automatic trajectory point sequencing, free-energy minimization, and coupled ablation and flowfield radiation.

Tarelin uses Liulin-5 Electronic Block in the MRM-1

NASA Image and Video Library

2013-01-10

ISS034-E-021232 (10 Jan. 2013) --- Russian cosmonaut Evgeny Tarelkin, Expedition 34 flight engineer, looks at his watch while using the Liulin-5 Electronic Block behind a panel in the Rassvet Mini-Research Module 1 (MRM1) of the International Space Station.

Development and validation of an Overreporting Scale for the Personality Inventory for DSM-5 (PID-5).

PubMed

Sellbom, Martin; Dhillon, Sonya; Bagby, R Michael

2018-05-01

Our aim in the current study was to develop a validity scale for the Personality Inventory for DSM-5 (PID-5) to detect noncredible overreported responding. To this end, we used a rare symptoms approach and identified extreme response options on PID-5 items that were infrequently endorsed by students in 3 different university samples (N = 1,370) and in a psychiatric patient sample (N = 194). The resulting 10-item scale (the PID-5-ORS) produced adequate-to-good estimates of internal reliability and was significantly correlated with the Minnesota Multiphasic Personality Inventory-2 Restructued Form (MMPI-2-RF) overreporting validity scales, providing evidence of concurrent validity. The criterion validity of the PID-5-ORS was demonstrated in an analog simulation design study. More specifically, university students instructed to overreport (n = 80) scored substantially higher on the PID-5-ORS relative to both a group of genuine psychiatric patients and students instructed to complete the PID-5 under standard (honest) instructions (n = 161); the effect size magnitudes associated with these differences were large. Classification accuracy analyses further revealed that high scores on the PID-5-ORS were associated with high specificity (and thus, low rates of false positive classifications) in differentiating overreporters from genuine patients, with sensitivity being somewhat weaker. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

How could the family-scale photovoltaic module help the poor farmer out of poverty and reduce CO2 emission?

NASA Astrophysics Data System (ADS)

Qiu, Xu; Jin, Ran

2016-04-01

China, the world's most populous country, is facing great opportunities and challenges. On the one hand, China's increasing economy is raising hundreds of millions of people out of poverty. On the other hand, there are still 100 million of whose daily income is less than 1 US dollar. In addition, China is the world's largest solar panel producer and also the largest emitter of greenhouse gases. Could we find a feasible way to use solar panels to help the poor and meanwhile reduce CO2 emissions? To do this, we reviewed the literature and investigated the related field sites and institutions in China. Results show that the extension of family-scale photovoltaic modules to countryside could help. The 3 kW-module is recommended for widely distribution because its technology is mature and the cost is relatively low (3500 US dollars). Besides their own use to improve their living standard, farmers can sell the excess electricity to the grid at the price of 0.17 UD/kWh. The farmer's annual income could be increased by 460-615 US dollars by selling electricity, and this is equivalent to half of their annual income in many rural regions. The photovoltaic module can be used for 25 years and the payback period is 7 years. In addition to its economic benefit, the photovoltaic module can reduce CO2 emissions by 0.93 kg/kWh. This is equivalent to annual reduction of 3000-4000 kg CO2 per family. Therefore, it is concluded that the family-scale photovoltaic module not only can help the farmers out of poverty but also can reduce CO2 emissions significantly. To promote its sustainable development, it is worthwhile to further investigations its business models as well as the effects of long-term support policies under different social and nature conditions.

Comparison between utility of the Thai Pediatric Quality of Life Inventory 4.0 Generic Core Scales and 3.0 Cerebral Palsy Module.

PubMed

Tantilipikorn, Pinailug; Watter, Pauline; Prasertsukdee, Saipin

2013-03-01

Health-related quality of life (HRQOL) is increasingly being considered in the management of patients with various conditions. HRQOL instruments can be broadly classified as generic or disease-specific measures. Several generic HRQOL instruments in different languages have been developed for paediatric populations including the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) Generic Core Scale. This tool and a condition-specific tool, PedsQL 3.0 Cerebral Palsy (CP) Module, are widely used in children with CP. No psychometric properties have been reported for Thai PedsQL 4.0. Therefore, this study aimed to explore the psychometric properties of the Thai version of the PedsQL 4.0 Generic Core Scales and compare these with the values for the Thai PedsQL 3.0 CP Module reported previously. Thai PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 CP Module were completed, respectively, by children with CP and their parents or caregivers twice within 2-4 weeks. Respondents were 97 parents or caregivers and 54 children. Minimal missing data were found in most scales. Acceptable internal consistency was supported, except for Emotional, Social, and School Functioning. Intraclass correlation coefficients for parent-proxy report and self-report were good to excellent (0.625-0.849). The feasibility and reliability of the Thai PedsQL 4.0 Generic Core Scales were supported. The Thai PedsQL 3.0 CP Module showed higher values for the psychometric properties. Low-to-good correlations were found among the scales between the PedsQL 4.0 Generic Core Scales and the 3.0 CP Module. Both instruments could be used to measure HRQOL for children with CP, and may provide different information.

Creatinine metabolite, HMH (5-hydroxy-1-methylhydantoin; NZ-419), modulates bradykinin-induced changes in vascular smooth muscle cells.

PubMed

Ienaga, Kazuharu; Sohn, Mimi; Naiki, Mitsuru; Jaffa, Ayad A

2014-06-01

A creatinine metabolite, 5-hydroxy-1-methylhydantoin (HMH: NZ-419), a hydroxyl radical scavenger, has previously been shown to confer renoprotection by inhibiting the progression of chronic kidney disease in rats. In the current study, we demonstrate that HMH modulates the effects of glucose and bradykinin (BK) in vascular smooth muscle cell (VSMC). HMH a novel anti-oxidant drug completely suppressed the expression of B2-kinin receptors (B2KR) in response to high glucose (25 mM) stimulation in VSMC and was also shown to attenuate the effects of BK on VSMC remodeling. HMH inhibited the BK-induced increase in MAPK phosphorylation and attenuated the increase in connective tissue growth factor (CTGF) protein levels in VSMC. These findings suggest that HMH may confer vascular protection against high glucose concentrations and BK-stimulation to ameliorate vascular injury and remodeling through its anti-oxidant properties.

Role of TRPV1 in acupuncture modulation of reflex excitatory cardiovascular responses.

PubMed

Guo, Zhi-Ling; Fu, Liang-Wu; Su, Hou-Fen; Tjen-A-Looi, Stephanie C; Longhurst, John C

2018-05-01

We have shown that acupuncture, including manual and electroacupuncture (MA and EA), at the P5-6 acupoints stimulates afferent fibers in the median nerve (MN) to modulate sympathoexcitatory cardiovascular reflexes through central regulation of autonomic function. However, the mechanisms underlying acupuncture activation of these sensory afferent nerves and their cell bodies in the dorsal root ganglia (DRG) are unclear. Transient receptor potential vanilloid type 1 (TRPV1) is present in sensory nerve fibers distributed in the general region of acupoints like ST36 and BL 40 located in the hindlimb. However, the contribution of TRPV1 to activation of sensory nerves by acupuncture, leading to modulation of pressor responses, has not been studied. We hypothesized that TRPV1 participates in acupuncture's activation of sensory afferents and their associated cell bodies in the DRG to modulate pressor reflexes. Local injection of iodoresiniferatoxin (Iodo-RTX; a selective TRPV1 antagonist), but not 5% DMSO (vehicle), into the P6 acupoint on the forelimb reversed the MA's inhibition of pressor reflexes induced by gastric distension (GD). Conversely, inhibition of GD-induced sympathoexcitatory responses by EA at P5-6 was unchanged after administration of Iodo-RTX into P5-6. Single-unit activity of Group III or IV bimodal afferents sensitive to both mechanical and capsaicin stimuli responded to MA stimulation at P6. MA-evoked activity was attenuated significantly ( P < 0.05) by local administration of Iodo-RTX ( n = 12) but not by 5% DMSO ( n = 12) into the region of the P6 acupoint in rats. Administration of Iodo-RTX into P5-6 did not reduce bimodal afferent activity evoked by EA stimulation ( n = 8). Finally, MA at P6 and EA at P5-6 induced phosphorylation of extracellular signal-regulated kinases (ERK; an intracellular signaling messenger involved in cellular excitation) in DRG neurons located at C 7-8 spinal levels receiving MN inputs. After TRPV1 was knocked down in the

Colorectal Cancer Metastases Settle in the Hepatic Microenvironment Through α5β1 Integrin.

PubMed

Pelillo, Chiara; Bergamo, Alberta; Mollica, Hilaria; Bestagno, Marco; Sava, Gianni

2015-10-01

Colorectal cancer (CRC) metastasis dissemination to secondary sites represents the critical point for the patient's survival. The microenvironment is crucial to cancer progression, influencing tumour cell behaviour by modulating the expression and activation of molecules such as integrins, the cell-extracellular matrix interacting proteins participating in different steps of the tumour metastatic process. In this work, we investigated the role of α5β1 integrin and how the microenvironment influences this adhesion molecule, in a model of colon cancer progression to the liver. The culture medium conditioned by the IHH hepatic cell line, and the extracellular matrix (ECM) proteins, modulate the activation of α5β1 integrin in the colon cancer cell line HCT-116, and drives FAK phosphorylation during the process of cell adhesion to fibronectin, one of the main components of liver ECM. In these conditions, α5β1 modulates the expression/activity of another integrin, α2β1, involved in the cell adhesion to collagen I. These results suggest that α5β1 integrin holds a leading role in HCT-116 colorectal cancer cells adhesion to the ECM through the modulation of the intracellular focal adhesion kinase FAK and the α2β1 integrin activity. The driving role of the tumour microenvironment on CRC dissemination, here detected, and described, strengthens and adds new value to the concept that α5β1 integrin can be an appropriate and relevant therapeutic target for the control of CRC metastases. © 2015 Wiley Periodicals, Inc.

STS-40 Payload Specialist Hughes-Fulford "flies" through SLS-1 module

NASA Image and Video Library

1991-06-14

STS040-212-006 (5-14 June 1991) --- Payload specialist Millie Hughes-Fulford floats through the Spacelab Life Sciences (SLS-1) module aboard the Earth-orbiting Columbia. Astronaut James P. Bagian, mission specialist, is at the blood draw station in the background. The scene was photographed with a 35mm camera.

Dissolved oxygen analysis, TMDL model comparison, and particulate matter shunting—Preliminary results from three model scenarios for the Klamath River upstream of Keno Dam, Oregon

USGS Publications Warehouse

Sullivan, Annett B.; Rounds, Stewart A.; Deas, Michael L.; Sogutlugil, I. Ertugrul

2012-01-01

Efforts are underway to identify actions that would improve water quality in the Link River to Keno Dam reach of the Upper Klamath River in south-central Oregon. To provide further insight into water-quality improvement options, three scenarios were developed, run, and analyzed using previously calibrated CE-QUAL-W2 hydrodynamic and water-quality models. Additional scenarios are under development as part of this ongoing study. Most of these scenarios evaluate changes relative to a "current conditions" model, but in some cases a "natural conditions" model was used that simulated the reach without the effect of point and nonpoint sources and set Upper Klamath Lake at its Total Maximum Daily Load (TMDL) targets. These scenarios were simulated using a model developed by the U.S. Geological Survey (USGS) and Watercourse Engineering, Inc. for the years 2006–09, referred to here as the "USGS model." Another model of the reach was developed by Tetra Tech, Inc. for years 2000 and 2002 to support the Klamath River TMDL process; that model is referred to here as the "TMDL model." The three scenarios described in this report included (1) an analysis of whether this reach of the Upper Klamath River would be in compliance with dissolved oxygen standards if sources met TMDL allocations, (2) an application of more recent datasets to the TMDL model with comparison to results from the USGS model, and (3) an examination of the effect on dissolved oxygen in the Klamath River if particulate material were stopped from entering Klamath Project diversion canals. Updates and modifications to the USGS model are in progress, so in the future these scenarios will be reanalyzed with the updated model and the interim results presented here will be superseded. Significant findings from this phase of the investigation include: * The TMDL analysis used depth-averaged dissolved oxygen concentrations from model output for comparison with dissolved oxygen standards. The Oregon dissolved oxygen

Transcriptome analysis of medaka following epinecidin-1 and TH1-5 treatment of NNV infection.

PubMed

Wang, Yi-Da; Rajanbabu, Venugopal; Chen, Jyh-Yih

2015-01-01

Nervous necrosis virus (NNV) infects a wide range of larval and juvenile fish species, thereby causing enormous economic losses in the aquaculture industry. Possible solutions to this problem include the use of antimicrobial peptides (AMPs), which directly inhibit bacterial growth, and also modulate host signaling mechanisms. The AMPs epinecidin (Epi)-1 and Tilapia hepcidin (TH) 1-5 have been demonstrated to be effective against Nervous necrosis virus infection in medaka (Oryzias latipes). However, the underlying molecular mechanisms are yet to be explored. Here, microarray analyses were performed to examine how NNV infection and/or epinecidin-1 or TH1-5 treatment affects gene expression in medaka; such analyses enabled the prediction of host signaling pathways affected by virus infection and/or regulated by epinecidin-1 and TH1-5. Transcriptome analysis revealed altered expression of genes involved in B cell activation, T cell activation, adipocytokine signaling, and mast cell activation. We subsequently used real-time PCR to analyze expression of key genes involved in these signaling mechanisms. Medaka infected with NNV exhibited up-regulation of PVALB, CEBPA, IFIM, IFN, IL-6ST, NF-kB2, SOC3, SP1, and TGFB1, and such increases were prevented by pre-treatment with epinecidin-1 or TH1-5. Immunohistochemistry using the anti-NNV antibody to stain brain and eye sections revealed that epinecidin-1 treatment during or after infection clears viral load, while TH1-5 treatment only reduces viral numbers if applied during infection. These observations demonstrate that epinecidin-1 and TH1-5 modulate NNV-induced host signaling mechanisms, thereby preventing viral multiplication in host organisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

HYDRATE v1.5 OPTION OF TOUGH+ v1.5

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

Moridis, George

HYDRATE v1.5 is a numerical code that for the simulation of the behavior of hydrate-bearing geologic systems, and represents the third update of the code since its first release [Moridis et al., 2008]. It is an option of TOUGH+ v1.5 [Moridis and Pruess, 2014], a successor to the TOUGH2 [Pruess et al., 1999, 2012] family of codes for multi-component, multiphase fluid and heat flow developed at the Lawrence Berkeley National Laboratory. HYDRATE v1.5 needs the TOUGH+ v1.5 core code in order to compile and execute. It is written in standard FORTRAN 95/2003, and can be run on any computational platformmore » (workstation, PC, Macintosh) for which such compilers are available. By solving the coupled equations of mass and heat balance, the fully operational TOUGH+HYDRATE code can model the non-isothermal gas release, phase behavior and flow of fluids and heat under conditions typical of common natural CH 4-hydrate deposits (i.e., in the permafrost and in deep ocean sediments) in complex geological media at any scale (from laboratory to reservoir) at which Darcy's law is valid. TOUGH+HYDRATE v1.5 includes both an equilibrium and a kinetic model of hydrate formation and dissociation. The model accounts for heat and up to four mass components, i.e., water, CH 4, hydrate, and water-soluble inhibitors such as salts or alcohols. These are partitioned among four possible phases (gas phase, liquid phase, ice phase and hydrate phase). Hydrate dissociation or formation, phase changes and the corresponding thermal effects are fully described, as are the effects of inhibitors. The model can describe all possible hydrate dissociation mechanisms, i.e., depressurization, thermal stimulation, salting-out effects and inhibitor-induced effects.« less

The longstanding challenge of the nanocrystallization of 1,3,5-trinitroperhydro-1,3,5-triazine (RDX)

PubMed Central

Spitzer, Denis

2017-01-01

Research efforts for realizing safer and higher performance energetic materials are continuing unabated all over the globe. While the thermites – pyrotechnic compositions of an oxide and a metal – have been finely tailored thanks to progress in other sectors, organic high explosives are still stagnating. The most symptomatic example is the longstanding challenge of the nanocrystallization of 1,3,5-trinitroperhydro-1,3,5-triazine (RDX). Recent advances in crystallization processes and milling technology mark the beginning of a new area which will hopefully lead the pyroelectric industry to finally embrace nanotechnology. This work reviews the previous and current techniques used to crystallize RDX at a submicrometer scale or smaller. Several key points are highlighted then discussed, such as the smallest particle size and its morphology, and the scale-up capacity and the versatility of the process. PMID:28326236

Equatorial Annual Oscillation with QBO-driven 5-year Modulation in NCEP Data

NASA Technical Reports Server (NTRS)

Mayr, H. G.; Mengel, J. G.; Huang, F. T.; Nash, E. R.

2007-01-01

An analysis is presented of the zonal wind and temperature variations supplied by the National Center for Environmental Prediction (NCEP), which have been assimilated in the Reanalysis and the Climate Prediction Center (CCP) data sets. The derived zonal-mean variations are employed. Stimulated by modeling studies, the data are separated into the hemispherically symmetric and anti-symmetric components, and spectral analysis is applied to study the annual 12-month oscillation and Quasi-biennial Oscillation (QBO). For data samples that cover as much as 40 years, the results reveal a pronounced 5-year modulation of the symmetric AO in the lower stratosphere, which is confined to equatorial latitudes. This modulation is also inferred for the temperature variations but extends to high latitudes, qualitatively consistent with published model results. A comparison between different data samples indicates that the signature of the 5-year oscillation is larger when the QBO of 30 months is more pronounced. Thus there is circumstantial evidence that this periodicity of the QBO is involved in generating the oscillation. The spectral analysis shows that there is a weak anti-symmetric 5-year oscillation in the zonal winds, which could interact with the large antisymmetric A0 to produce the modulation of the symmetric AO as was shown in earlier modeling studies. According to these studies, the 30-month QBO tends to be synchronized by the equatorial Semi-annual Oscillation (SAO), and this would explain why the inferred 5-year modulation is observed to persist and is phase locked over several cycles.

Improved ATIR concentrator photovoltaic module

NASA Astrophysics Data System (ADS)

Adriani, Paul M.; Mao, Erwang

2013-09-01

Novel aggregated total internal reflection (ATIR) concentrator photovoltaic module design comprises 2-D shaped primary and secondary optics that effectively combine optical efficiency, low profile, convenient range of acceptance angles, reliability, and manufacturability. This novel optical design builds upon previous investigations by improving the shapes of primary and secondary optics to enable improved long-term reliability and manufacturability. This low profile, low concentration (5x to 10x) design fits well with one-axis trackers that are often used for flat plate crystalline silicon photovoltaic modules in large scale ground mount installations. Standard mounting points, materials, and procedures apply without changes from flat plate modules.

Whole Module Offgas Test Report: Space-Xl Dragon Module

NASA Technical Reports Server (NTRS)

James, John T.

2012-01-01

On September 26 and September 28,2012 a chemist from the JSC Toxicology Group acquired samples of air in 500 m1 evacuated canisters from the sealed Space-Xl Dragon Module. One sample was also acquired from Space-X Facility near the module at the start of the test. Samples of the module air were taken in triplicate once the module had been sealed, and then taken again in triplicate 1.98 days later. Ofthe triplicate samples, the first served as a line purge, and the last two were analyzed. The results of 5 samples are reported.

Coordinating AgMIP data and models across global and regional scales for 1.5°C and 2.0°C assessments

NASA Astrophysics Data System (ADS)

Rosenzweig, Cynthia; Ruane, Alex C.; Antle, John; Elliott, Joshua; Ashfaq, Muhammad; Chatta, Ashfaq Ahmad; Ewert, Frank; Folberth, Christian; Hathie, Ibrahima; Havlik, Petr; Hoogenboom, Gerrit; Lotze-Campen, Hermann; MacCarthy, Dilys S.; Mason-D'Croz, Daniel; Contreras, Erik Mencos; Müller, Christoph; Perez-Dominguez, Ignacio; Phillips, Meridel; Porter, Cheryl; Raymundo, Rubi M.; Sands, Ronald D.; Schleussner, Carl-Friedrich; Valdivia, Roberto O.; Valin, Hugo; Wiebe, Keith

2018-05-01

The Agricultural Model Intercomparison and Improvement Project (AgMIP) has developed novel methods for Coordinated Global and Regional Assessments (CGRA) of agriculture and food security in a changing world. The present study aims to perform a proof of concept of the CGRA to demonstrate advantages and challenges of the proposed framework. This effort responds to the request by the UN Framework Convention on Climate Change (UNFCCC) for the implications of limiting global temperature increases to 1.5°C and 2.0°C above pre-industrial conditions. The protocols for the 1.5°C/2.0°C assessment establish explicit and testable linkages across disciplines and scales, connecting outputs and inputs from the Shared Socio-economic Pathways (SSPs), Representative Agricultural Pathways (RAPs), Half a degree Additional warming, Prognosis and Projected Impacts (HAPPI) and Coupled Model Intercomparison Project Phase 5 (CMIP5) ensemble scenarios, global gridded crop models, global agricultural economics models, site-based crop models and within-country regional economics models. The CGRA consistently links disciplines, models and scales in order to track the complex chain of climate impacts and identify key vulnerabilities, feedbacks and uncertainties in managing future risk. CGRA proof-of-concept results show that, at the global scale, there are mixed areas of positive and negative simulated wheat and maize yield changes, with declines in some breadbasket regions, at both 1.5°C and 2.0°C. Declines are especially evident in simulations that do not take into account direct CO2 effects on crops. These projected global yield changes mostly resulted in increases in prices and areas of wheat and maize in two global economics models. Regional simulations for 1.5°C and 2.0°C using site-based crop models had mixed results depending on the region and the crop. In conjunction with price changes from the global economics models, productivity declines in the Punjab, Pakistan, resulted in

Coordinating AgMIP data and models across global and regional scales for 1.5°C and 2.0°C assessments.

PubMed

Rosenzweig, Cynthia; Ruane, Alex C; Antle, John; Elliott, Joshua; Ashfaq, Muhammad; Chatta, Ashfaq Ahmad; Ewert, Frank; Folberth, Christian; Hathie, Ibrahima; Havlik, Petr; Hoogenboom, Gerrit; Lotze-Campen, Hermann; MacCarthy, Dilys S; Mason-D'Croz, Daniel; Contreras, Erik Mencos; Müller, Christoph; Perez-Dominguez, Ignacio; Phillips, Meridel; Porter, Cheryl; Raymundo, Rubi M; Sands, Ronald D; Schleussner, Carl-Friedrich; Valdivia, Roberto O; Valin, Hugo; Wiebe, Keith

2018-05-13

The Agricultural Model Intercomparison and Improvement Project (AgMIP) has developed novel methods for Coordinated Global and Regional Assessments (CGRA) of agriculture and food security in a changing world. The present study aims to perform a proof of concept of the CGRA to demonstrate advantages and challenges of the proposed framework. This effort responds to the request by the UN Framework Convention on Climate Change (UNFCCC) for the implications of limiting global temperature increases to 1.5°C and 2.0°C above pre-industrial conditions. The protocols for the 1.5°C/2.0°C assessment establish explicit and testable linkages across disciplines and scales, connecting outputs and inputs from the Shared Socio-economic Pathways (SSPs), Representative Agricultural Pathways (RAPs), Half a degree Additional warming, Prognosis and Projected Impacts (HAPPI) and Coupled Model Intercomparison Project Phase 5 (CMIP5) ensemble scenarios, global gridded crop models, global agricultural economics models, site-based crop models and within-country regional economics models. The CGRA consistently links disciplines, models and scales in order to track the complex chain of climate impacts and identify key vulnerabilities, feedbacks and uncertainties in managing future risk. CGRA proof-of-concept results show that, at the global scale, there are mixed areas of positive and negative simulated wheat and maize yield changes, with declines in some breadbasket regions, at both 1.5°C and 2.0°C. Declines are especially evident in simulations that do not take into account direct CO 2 effects on crops. These projected global yield changes mostly resulted in increases in prices and areas of wheat and maize in two global economics models. Regional simulations for 1.5°C and 2.0°C using site-based crop models had mixed results depending on the region and the crop. In conjunction with price changes from the global economics models, productivity declines in the Punjab, Pakistan, resulted in

Subplane collision probabilities method applied to control rod cusping in 2D/1D

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

Graham, Aaron M.; Collins, Benjamin S.; Stimpson, Shane G.

The MPACT code is being jointly developed by the University of Michigan and Oak Ridge National Laboratory. It uses the 2D/1D method to solve neutron transport problems for reactors. The 2D/1D method decomposes the problem into a stack of 2D planes, and uses a high fidelity transport method to resolve all heterogeneity in each plane. These planes are then coupled axially using a lower order solver. Using this scheme, 3D solutions to the transport equation can be obtained at a much lower cost.One assumption made by the 2D/1D method is that the materials are axially homogeneous for each 2D plane.more » Violation of this assumption requires homogenization, which can significantly reduce the accuracy of the calculation. This paper presents two new subgrid methods to address this issue. The first method is polynomial decusping, a simple correction used to address control rods partially inserted into a 2D plane. The second is the subplane collision probabilities method, which is a more accurate, more robust subgrid method that can be applied to other axial heterogeneities.Each method was applied to a variety of problems. Results were compared to fine mesh solutions which had no axial heterogeneity and to Monte Carlo reference solutions generated using KENO-VI. It was shown that the polynomial decusping method was effective in many cases, but it had some limitations, with 3D pin power errors as high as 25% compared to KENO-VI. In conclusion, the subplane collision probabilities method performed much better, lowering the maximum pin power error to less than 5% in every calculation.« less

Subplane collision probabilities method applied to control rod cusping in 2D/1D

DOE PAGES

Graham, Aaron M.; Collins, Benjamin S.; Stimpson, Shane G.; ...

2018-04-06

The MPACT code is being jointly developed by the University of Michigan and Oak Ridge National Laboratory. It uses the 2D/1D method to solve neutron transport problems for reactors. The 2D/1D method decomposes the problem into a stack of 2D planes, and uses a high fidelity transport method to resolve all heterogeneity in each plane. These planes are then coupled axially using a lower order solver. Using this scheme, 3D solutions to the transport equation can be obtained at a much lower cost.One assumption made by the 2D/1D method is that the materials are axially homogeneous for each 2D plane.more » Violation of this assumption requires homogenization, which can significantly reduce the accuracy of the calculation. This paper presents two new subgrid methods to address this issue. The first method is polynomial decusping, a simple correction used to address control rods partially inserted into a 2D plane. The second is the subplane collision probabilities method, which is a more accurate, more robust subgrid method that can be applied to other axial heterogeneities.Each method was applied to a variety of problems. Results were compared to fine mesh solutions which had no axial heterogeneity and to Monte Carlo reference solutions generated using KENO-VI. It was shown that the polynomial decusping method was effective in many cases, but it had some limitations, with 3D pin power errors as high as 25% compared to KENO-VI. In conclusion, the subplane collision probabilities method performed much better, lowering the maximum pin power error to less than 5% in every calculation.« less

1.5 nm fabrication of test patterns for characterization of metrological systems

DOE PAGES

Babin, Sergey; Calafiore, Giuseppe; Peroz, Christophe; ...

2015-11-06

Any metrology tool is only as good as it is calibrated. The characterization of metrology systems requires test patterns at a scale about ten times smaller than the measured features. The fabrication of patterns with linewidths down to 1.5 nm is described. The test sample was designed in such a way that the distribution of linewidths appears to be random at any location. This pseudorandom test pattern is used to characterize dimensional metrology equipment over its entire dynamic range by extracting the modulation transfer function of the system. The test pattern contains alternating lines of silicon and tungsten silicide, eachmore » according to its designed width. As a result, the fabricated test samples were imaged using a transmission electron microscope, a scanning electron microscope, and an atomic force microscope. (C) 2015 American Vacuum Society.« less

[Internal consistency and criterion validity and reliability of the Mexican Version of the Child Behavior Checklist 1.5-5 (CBCL/1.5-5)].

PubMed

Albores-Gallo, Lilia; Hernández-Guzmán, Laura; Hasfura-Buenaga, Cecilia; Navarro-Luna, Enrique

To investigate the validity and internal consistency of the Mexican version of the CBCL/1.5 -5 that assesses the most common psychopathology in pre-school children in clinical and epidemiological settings. A total of 438 parents from two groups, clinical-psychiatric (N= 62) and community (N= 376) completed the CBCL/1.5-5/Mexican version. The internal consistency was high for total problems α=0.95, and internalized α=0.89 and externalized α=0.91 subscales. The test re-test (one week) using the intraclass correlation coefficient (ICC) was ≥ 0.95 for the internalized, externalized, and total problems subscales. The ROC curve for the criterion status of clinically-referred vs. non-referred using the total problems scale ≥ 24 resulted in an AUC (area under curve) of 0.77, a specificity 0.73, and a sensitivity of 0.70. The CBCL/1.5 -5/Mexican version is a reliable and valid tool. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Nuclear Technology. Course 31: Quality Assurance Practices. Module 31-5, Nonconforming Materials.

ERIC Educational Resources Information Center

Pritchard, Jim; Espy, John

This fifth in a series of eight modules for a course titled Quality Assurance Practices describes the essential elements of a nonconforming material control system, including purpose and application. The module follows a typical format that includes the following sections: (1) introduction, (2) module prerequisites, (3) objectives, (4) notes to…

A-7E Software Module Guide.

DTIC Science & Technology

1981-12-08

o 14 A& B:2.1 Function Driver Module.. ..... .... 14’ ’: B:2.2 Shared Services Module . . . o o . 0 -15 M’ 5:3 Software Decision Module...2.1.13 Weapon Release Functions... ........24 C:2.l.14 Ground Test Functions .. ........... 24 C:2.2 Shared Services Module Decomposition. ........24 C...Driver (FD) Module supported by a Shared Services (SS) Module. B:2.1 FUNCTION DRIVER MODULE The Function Driver Module consists of a set of individual

Kinesin-5, a mitotic microtubule-associated motor protein, modulates neuronal migration

PubMed Central

Falnikar, Aditi; Tole, Shubha; Baas, Peter W.

2011-01-01

Kinesin-5 (also called Eg5 or kif11) is a homotetrameric motor protein that functions by modulating microtubule (MT)–MT interactions. In the case of mitosis, kinesin-5 slows the rate of separation of the half-spindles. In the case of the axon, kinesin-5 limits the frequency of transport of short MTs, and also limits the rate of axonal growth. Here we show that experimental inhibition of kinesin-5 in cultured migratory neurons results in a faster but more randomly moving neuron with a shorter leading process. As is the case with axons of stationary neurons, short MT transport frequency is notably enhanced in the leading process of the migratory neuron when kinesin-5 is inhibited. Conversely, overexpression of kinesin-5, both in culture and in developing cerebral cortex, causes migration to slow and even cease. Regions of anti-parallel MT organization behind the centrosome were shown to be especially rich in kinesin-5, implicating these regions as potential sites where kinesin-5 forces may be especially relevant. We posit that kinesin-5 acts as a “brake” on MT–MT interactions that modulates the advance of the entire MT apparatus. In so doing, kinesin-5 regulates the rate and directionality of neuronal migration and possibly the cessation of migration when the neuron reaches its destination. PMID:21411631

High-accuracy self-calibration method for dual-axis rotation-modulating RLG-INS

NASA Astrophysics Data System (ADS)

Wei, Guo; Gao, Chunfeng; Wang, Qi; Wang, Qun; Long, Xingwu

2017-05-01

Inertial navigation system has been the core component of both military and civil navigation systems. Dual-axis rotation modulation can completely eliminate the inertial elements constant errors of the three axes to improve the system accuracy. But the error caused by the misalignment angles and the scale factor error cannot be eliminated through dual-axis rotation modulation. And discrete calibration method cannot fulfill requirements of high-accurate calibration of the mechanically dithered ring laser gyroscope navigation system with shock absorbers. This paper has analyzed the effect of calibration error during one modulated period and presented a new systematic self-calibration method for dual-axis rotation-modulating RLG-INS. Procedure for self-calibration of dual-axis rotation-modulating RLG-INS has been designed. The results of self-calibration simulation experiment proved that: this scheme can estimate all the errors in the calibration error model, the calibration precision of the inertial sensors scale factor error is less than 1ppm and the misalignment is less than 5″. These results have validated the systematic self-calibration method and proved its importance for accuracy improvement of dual -axis rotation inertial navigation system with mechanically dithered ring laser gyroscope.

SCALE Continuous-Energy Eigenvalue Sensitivity Coefficient Calculations

DOE PAGES

Perfetti, Christopher M.; Rearden, Bradley T.; Martin, William R.

2016-02-25

Sensitivity coefficients describe the fractional change in a system response that is induced by changes to system parameters and nuclear data. The Tools for Sensitivity and UNcertainty Analysis Methodology Implementation (TSUNAMI) code within the SCALE code system makes use of eigenvalue sensitivity coefficients for an extensive number of criticality safety applications, including quantifying the data-induced uncertainty in the eigenvalue of critical systems, assessing the neutronic similarity between different critical systems, and guiding nuclear data adjustment studies. The need to model geometrically complex systems with improved fidelity and the desire to extend TSUNAMI analysis to advanced applications has motivated the developmentmore » of a methodology for calculating sensitivity coefficients in continuous-energy (CE) Monte Carlo applications. The Contributon-Linked eigenvalue sensitivity/Uncertainty estimation via Tracklength importance CHaracterization (CLUTCH) and Iterated Fission Probability (IFP) eigenvalue sensitivity methods were recently implemented in the CE-KENO framework of the SCALE code system to enable TSUNAMI-3D to perform eigenvalue sensitivity calculations using continuous-energy Monte Carlo methods. This work provides a detailed description of the theory behind the CLUTCH method and describes in detail its implementation. This work explores the improvements in eigenvalue sensitivity coefficient accuracy that can be gained through the use of continuous-energy sensitivity methods and also compares several sensitivity methods in terms of computational efficiency and memory requirements.« less

The C-module-binding factor supports amplification of TRE5-A retrotransposons in the Dictyostelium discoideum genome.

PubMed

Bilzer, Annika; Dölz, Heike; Reinhardt, Alexander; Schmith, Anika; Siol, Oliver; Winckler, Thomas

2011-01-01

Retrotransposable elements are molecular parasites that have invaded the genomes of virtually all organisms. Although retrotransposons encode essential proteins to mediate their amplification, they also require assistance by host cell-encoded machineries that perform functions such as DNA transcription and repair. The retrotransposon TRE5-A of the social amoeba Dictyostelium discoideum generates a notable amount of both sense and antisense RNAs, which are generated from element-internal promoters, located in the A module and the C module, respectively. We observed that TRE5-A retrotransposons depend on the C-module-binding factor (CbfA) to maintain high steady-state levels of TRE5-A transcripts and that CbfA supports the retrotransposition activity of TRE5-A elements. The carboxy-terminal domain of CbfA was found to be required and sufficient to mediate the accumulation of TRE5-A transcripts, but it did not support productive retrotransposition of TRE5-A. This result suggests different roles for CbfA protein domains in the regulation of TRE5-A retrotransposition frequency in D. discoideum cells. Although CbfA binds to the C module in vitro, the factor regulates neither C-module nor A-module promoter activity in vivo. We speculate that CbfA supports the amplification of TRE5-A retrotransposons by suppressing the expression of an as yet unidentified component of the cellular posttranscriptional gene silencing machinery.

STS-40 MS Seddon, wearing blindfold, sleeps in SLS-1 module

NASA Image and Video Library

1991-06-14

STS040-31-020 (5-14 June 1991) --- During the nine-day mission, some of the crew slept in the SLS-1 module. Astronaut Rhea Seddon, using various restraints, sleeps horizontally in this scene. The image was one of 25 visuals used by the STS-40 crew at its Post Flight Press Conference (PFPC) on June 28, 1991.

Experimental study of the effect of 2/1 classical tearing mode on (intermediate, small)-scale microturbulence in the core of an EAST L mode plasma

NASA Astrophysics Data System (ADS)

Sun, P. J.; Li, Y. D.; Ren, Y.; Zhang, X. D.; Wu, G. J.; Lyu, B.; Shi, T. H.; Xu, L. Q.; Wang, F. D.; Li, Q.; Zhang, J. Z.; Hu, L. Q.; Li, J. G.; the EAST Team

2018-02-01

In this paper, we report an experimental study of the effect of a m/n = -2/-1 (m, n being poloidal and toroidal mode number, separately) classical tearing mode on (intermediate, small)-scale microturbulence (see the definition in section 1) in the core of an EAST L mode plasma discharge. The microturbulence at different scales k ⊥ = 10, 18 and 26 cm-1 (i.e., {k}\\perp {ρ }i˜ 2, 3.6 and 5.2, respectively. Here, {ρ }i is the ion gyroradius and k ⊥ is the perpendicular wavenumber) were measured simultaneously by the EAST multi-channel tangential CO2 laser collective scattering diagnostics. Experimental results confirm that the decrease of microturbulent Doppler shift ({f}{{Doppler}}={k}t{v}t/2π ), inversely correlated to the increase of microturbulent mean frequency (defined in equation (1)), is due to the 2/1 tearing mode. Temporal evolution of frequency-integrated spectral power S tot of microturbulence, found to be correlated with the width of 2/1 magnetic island, suggests the modulation effect on microturbulence by the tearing mode beyond Doppler shift effect. Modulation effects on microturbulence by the tearing mode are further demonstrated by the correlation between microturbulent envelope and magnetic fluctuations.

Distinct circuits underlie the effects of 5-HT1B receptors on aggression and impulsivity

PubMed Central

Nautiyal, Katherine M.; Tanaka, Kenji F.; Barr, Mary M.; Tritschler, Laurent; Le Dantec, Yannick; David, Denis J.; Gardier, Alain M.; Blanco, Carlos; Hen, René; Ahmari, Susanne E.

2015-01-01

Summary Impulsive and aggressive behaviors are both modulated by serotonergic signaling, specifically through the serotonin 1B receptor (5-HT1BR). 5-HT1BR knockout mice show increased aggression and impulsivity, and 5-HT1BR polymorphisms are associated with aggression and drug addiction in humans. To dissect the mechanisms by which the 5-HT1BR affects these phenotypes, we developed a mouse model to spatially and temporally regulate 5-HT1BR expression. Our results demonstrate that forebrain 5-HT1B heteroreceptors expressed during an early postnatal period contribute to the development of the neural systems underlying adult aggression. However, distinct heteroreceptors acting during adulthood are involved in mediating impulsivity. Correlating with the impulsivity, dopamine in the nucleus accumbens is elevated in the absence of 5-HT1BRs, and normalized following adult rescue of the receptor. Overall, these data show that while adolescent expression of 5-HT1BRs influences aggressive behavior, a distinct set of 5-HT1B receptors modulate impulsive behavior during adulthood. PMID:25892302

Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1.

PubMed

Maher, Christina M; Thomas, Jeffrey D; Haas, Derick A; Longen, Charles G; Oyer, Halley M; Tong, Jane Y; Kim, Felix J

2018-02-01

Emerging evidence suggests that Sigma1 ( SIGMAR1 , also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small-molecule modulators of Sigma1 alter endoplasmic reticulum (ER)-associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type I integral membrane glycoprotein that is cotranslationally inserted into the ER and is processed and transported through the secretory pathway. Once at the surface of cancer cells, PD-L1 acts as a T-cell inhibitory checkpoint molecule and suppresses antitumor immunity. Here, we demonstrate that in Sigma1-expressing triple-negative breast and androgen-independent prostate cancer cells, PD-L1 protein levels were suppressed by RNAi knockdown of Sigma1 and by small-molecule inhibition of Sigma1. Sigma1-mediated action was confirmed by pharmacologic competition between Sigma1-selective inhibitor and activator ligands. When administered alone, the Sigma1 inhibitor decreased cell surface PD-L1 expression and suppressed functional interaction of PD-1 and PD-L1 in a coculture of T cells and cancer cells. Conversely, the Sigma1 activator increased PD-L1 cell surface expression, demonstrating the ability to positively and negatively modulate Sigma1 associated PD-L1 processing. We discovered that the Sigma1 inhibitor induced degradation of PD-L1 via autophagy, by a mechanism distinct from bulk macroautophagy or general ER stress-associated autophagy. Finally, the Sigma1 inhibitor suppressed IFNγ-induced PD-L1. Our data demonstrate that small-molecule Sigma1 modulators can be used to regulate PD-L1 in cancer cells and trigger its degradation by selective autophagy. Implications: Sigma1 modulators sequester and eliminate PD-L1 by autophagy, thus preventing functional PD-L1 expression at the cell surface. This

An assessment of flow data from Klamath River sites between Link River Dam and Keno Dam, south-central Oregon

USGS Publications Warehouse

Risley, John C.; Hess, Glen W.; Fisher, Bruce J.

2006-01-01

Records of diversion and return flows for water years 1961?2004 along a reach of the Klamath River between Link River and Keno Dams in south-central Oregon were evaluated to determine the cause of a water-balance inconsistency in the hydrologic data. The data indicated that the reach was losing flow in the 1960s and 1970s and gaining flow in the 1980s and 1990s. The absolute mean annual net water-balance difference in flows between the first and second half of the 44-year period (1961-2004) was approximately 103,000 acre-feet per year (acre-ft/yr). The quality of the diversion and return-flow records used in the water balance was evaluated using U.S. Geological Survey (USGS) criteria for accuracy. With the exception of the USGS Klamath River at Keno record, which was rated as 'good' or 'excellent,' the eight other flow records, all from non-USGS flow-measurement sites, were rated as 'poor' by USGS standards due to insufficient data-collection documentation and a lack of direct discharge measurements to verify the rating curves. The record for the Link River site, the most upstream in the study area, included both river and westside power canal flows. Because of rating curve biases, the river flows might have been overestimated by 25,000 acre-ft/yr on average from water years 1961 to 1982 and underestimated by 7,000 acre-ft/yr on average from water years 1983 to 2004. For water years 1984-2004, westside power canal flows might have been underestimated by 11,000 acre-ft/yr. Some diversion and return flows (for mostly agricultural, industrial, and urban use) along the Klamath River study reach, not measured continuously and not included in the water-balance equation, also were evaluated. However, the sum of these diversion and return flows was insufficient to explain the water-balance inconsistency. The possibility that ground-water levels in lands adjacent to the river rose during water years 1961-2004 and caused an increase in ground-water discharge to the river

Efficient pump module coupling >1kW from a compact detachable fiber

NASA Astrophysics Data System (ADS)

Dogan, M.; Chin, R. H.; Fulghum, S.; Jacob, J. H.; Chin, A. K.

2018-02-01

In the most developed fiber amplifiers, optical pump power is introduced into the 400μm-diameter, 0.46NA first cladding of the double-clad, Yb-doped, gain fiber, using a (6+1):1 multi-mode fiber combiner. For this configuration, the core diameter and numerical aperture of the pump delivery fibers have maximum values of 225μm and 0.22, respectively. This paper presents the first fiber-coupled laser-diode pump module emitting more than 1kW of claddingmode- stripped power from a detachable 225μm, 0.22NA delivery fiber at 976nm. The electrical-to-optical power conversion efficiency at 1kW is 50%. The FWHM spectral width at 1kW output is 4nm and has an excellent overlap with the narrow absorption spectrum of ytterbium in glass. Six of these pump modules attached to a (6+1):1 multimode combiner enable a 5-6kW, single-mode, Yb-doped fiber amplifier.

An ‘environment to nucleus’ signaling system operates in B lymphocytes: redox status modulates BSAP/Pax-5 activation through Ref-1 nuclear translocation

PubMed Central

Tell, Gianluca; Zecca, Alessandro; Pellizzari, Lucia; Spessotto, Paola; Colombatti, Alfonso; Kelley, Mark R.; Damante, Giuseppe; Pucillo, Carlo

2000-01-01

The Ref-1 (also called APE or HAP1) protein is a bifunctional enzyme impacting on a wide variety of important cellular functions. It acts as a major member of the DNA base excision repair pathway. Moreover, Ref-1 stimulates the DNA-binding activity of several transcription factors (TFs) through the reduction of highly reactive cysteine residues. Therefore, it represents a mechanism that regulates eukaryotic gene expression in a fast way. However, it has been demonstrated that external stimuli directly act on Ref-1 by increasing its expression levels, a time-consuming mechanism representing a paradox in terms of rapidity of TF regulation. In this paper we demonstrate that this is only an apparent paradox. Exposure of B lymphocytes to H2O2 induced a rapid and sustained increase in Ref-1 protein levels in the nucleus as evaluated by both western blot analysis and by pulse–chase experiments. A time course, two color in situ immunocytochemistry indicated that the up-regulation of Ref-1 in the nucleus at <30 min was primarily the consequence of translocation of its cytoplasmic form. This early nuclear accumulation is effective in modulating the DNA-binding activity of the B cell-specific activator protein BSAP/Pax-5. In fact, EMSA experiments demonstrate that a transient interaction with Ref-1 up-regulates the DNA-binding activity of BSAP/Pax-5. Moreover, in a co-transfection experiment, Ref-1 increased the BSAP/Pax-5 activating effect on an oligomerized BSAP/Pax-5 binding site of the CD19 promoter by 5- to 8-fold. Thus, Ref-1 mediates its effect by up-regulating the DNA-binding activity of BSAP/Pax-5, accounting for a new and fast outside/inside pathway of signaling in B cells. PMID:10666449

Numerical study on the thermal management system of a liquid metal battery module

NASA Astrophysics Data System (ADS)

Guo, Zhenlin; Xu, Cheng; Li, Wei; Zhu, Fangfang; Li, Haomiao; Wang, Kangli; Cheng, Shijie; Jiang, Kai

2018-07-01

Liquid metal battery (LMB), with three-liquid-layer structure and high operating temperature (300-700 °C), is a newly emerging technology for large scale energy storage applications. A thermal management system is critical to achieve satisfied LMB performance and extend the life of batteries. In this work, an improved coupling model composing of a 3D heat-transfer model and a 1D electrochemical model is developed for the thermal analysis of a Li||Sb-Sn LMBs module (5.5 kWh). Key results including transient values, the contribution ratio of heat sources, temperature homogeneity and distribution, as well as the energy efficiency of the battery module, are presented. Based on the coupling model, the changeable-power-heating mode, sand filling material and vacuum insulation are further proposed to achieve the high energy efficiency and optimal performance of the LMBs module. Moreover, the LMBs module can achieve "self-heating" when operated at 0.2 C charge/discharge, under the vacuum insulation (0.01 W m-1 K-1 thermal conductivity, 100 mm thickness), requiring no external heating to keep the batteries at operating temperature.

Unusual strain glassy phase in Fe doped Ni2Mn1.5In0.5

NASA Astrophysics Data System (ADS)

Nevgi, R.; Priolkar, K. R.

2018-01-01

Fe doped Ni2Mn1.5In0.5, particularly, Ni2Mn1.4Fe0.1In0.5, despite having an incommensurate, modulated 7M martensitic structure at room temperature exhibits frequency dependent behavior of storage modulus and loss which obeys the Vogel-Fulcher law as well as shows ergodicity breaking between zero field cooled and field cooled strain measurements just above the transition temperature. Both frequency dependence and ergodicity breaking are characteristics of a strain glassy phase and occur due to the presence of strain domains which are large enough to present signatures of long range martensitic order in diffraction but are non-interacting with other strain domains due to the presence of Fe impurities.

Implication of Taylor's hypothesis on amplitude modulation

NASA Astrophysics Data System (ADS)

Howland, Michael; Yang, Xiang

2017-11-01

Amplitude modulation is a physical phenomenon which describes the non-linear inter-scale interaction between large and small scales in a turbulent wall-bounded flow. The amplitude of the small scale fluctuations are modulated by the large scale flow structures. Due to the increase of amplitude modulation as a function of Reynolds number (Reτ = δuτ / ν), this phenomenon is frequently studied using experimental temporal 1D signals, taken using hot-wire anemometry. Typically, Taylor's frozen turbulence hypothesis has been invoked where the convection by velocity fluctuations is neglected and the mean velocity is used as the convective velocity. At high Reynolds numbers, turbulent fluctuations are comparable to the mean velocity in the near wall region (y+ O(10)), and as a result, using a constant global convective velocity systematically locally compresses or stretches a velocity signal when converting from temporal to spatial domain given a positive or negative fluctuation respectively. Despite this, temporal hot-wire data from wind tunnel or field experiments of high Reynolds number boundary layer flows can still be used for measuring modulation provided that the local fluid velocity is used as the local convective velocity. MH is funded through the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1656518 and the Stanford Graduate Fellowship. XY is funded by the US AFOSR, Grant No. 1194592-1-TAAHO monitored by Dr. Ivett Leyva.

Earth Observatory Satellite system definition study. Report 5: System design and specifications. Volume 3: General purpose spacecraft segment and module specifications

NASA Technical Reports Server (NTRS)

1974-01-01

The specifications for the Earth Observatory Satellite (EOS) general purpose aircraft segment are presented. The satellite is designed to provide attitude stabilization, electrical power, and a communications data handling subsystem which can support various mission peculiar subsystems. The various specifications considered include the following: (1) structures subsystem, (2) thermal control subsystem, (3) communications and data handling subsystem module, (4) attitude control subsystem module, (5) power subsystem module, and (6) electrical integration subsystem.

Scale-dependent performances of CMIP5 earth system models in simulating terrestrial vegetation carbon

NASA Astrophysics Data System (ADS)

Jiang, L.; Luo, Y.; Yan, Y.; Hararuk, O.

2013-12-01

Mitigation of global changes will depend on reliable projection for the future situation. As the major tools to predict future climate, Earth System Models (ESMs) used in Coupled Model Intercomparison Project Phase 5 (CMIP5) for the IPCC Fifth Assessment Report have incorporated carbon cycle components, which account for the important fluxes of carbon between the ocean, atmosphere, and terrestrial biosphere carbon reservoirs; and therefore are expected to provide more detailed and more certain projections. However, ESMs are never perfect; and evaluating the ESMs can help us to identify uncertainties in prediction and give the priorities for model development. In this study, we benchmarked carbon in live vegetation in the terrestrial ecosystems simulated by 19 ESMs models from CMIP5 with an observationally estimated data set of global carbon vegetation pool 'Olson's Major World Ecosystem Complexes Ranked by Carbon in Live Vegetation: An Updated Database Using the GLC2000 Land Cover Product' by Gibbs (2006). Our aim is to evaluate the ability of ESMs to reproduce the global vegetation carbon pool at different scales and what are the possible causes for the bias. We found that the performance CMIP5 ESMs is very scale-dependent. While CESM1-BGC, CESM1-CAM5, CESM1-FASTCHEM and CESM1-WACCM, and NorESM1-M and NorESM1-ME (they share the same model structure) have very similar global sums with the observation data but they usually perform poorly at grid cell and biome scale. In contrast, MIROC-ESM and MIROC-ESM-CHEM simulate the best on at grid cell and biome scale but have larger differences in global sums than others. Our results will help improve CMIP5 ESMs for more reliable prediction.

Beam-induced electron modulations observed during TSS 1R

NASA Astrophysics Data System (ADS)

Rubin, A. G.; Burke, W. J.; Gough, M. P.; Machuzak, J. S.; Gentile, L. C.; Huang, C. Y.; Hardy, D. A.; Thompson, D. C.; Raitt, W. J.

1999-08-01

We report on modulations of electron fluxes at megahertz frequencies measured by the Shuttle Potential and Return Electron Experiment (SPREE) during fast pulsed electron gun (FPEG) beam experiments conducted after the tether break event of the Tethered Satellite System Reflight. Six intervals of sustained modulations were identified while FPEG emitted a 100 mA beam of 1 kev electrons. During five events the beam pitch angle αB was near 90° and the modulations were near even or odd half harmonics of the electron gyrofrequency fce. In the sixth event with 60°>=αB>=45°, electron modulations were near estimated values of the electron plasma frequency fpe and 2fpe. Whenever SPREE detected beam electrons modulated at a given frequency, secondary electrons were also modulated at the same frequency over a broad range of energies. Occasionally, some secondary electrons were modulated simultaneously at a second frequency. Multiple frequencies were related as ratios of low integers. In one case the beam electrons were simultaneously modulated at 0.8 MHz and 1.25 kHz. SPREE measurements suggest that the beam electrons propagate in cylindrical shells whose inner edge is marked by steep spatial gradients in fluxes at 1 keV [Hardy et al., 1995]. Inside the shell, electron distribution functions have positive slopes ∂f/∂v⊥>0 at velocities near that of the beam. Velocity space gradients act as free-energy sources to drive cavity modes that alter the instantaneous guiding centers of electrons causing SPREE to sample alternating parts of the beam cylinder's inner edge. Associated time-varying electric fields also modulated the fluxes of secondary electrons reaching SPREE. Other cavity modes may be excited through nonlinear processes [Calvert, 1982]. With αB far from 90°, electrons in the beam cylinder evolved toward bump-on-tail distributions to excite large-amplitude Langmuir modulations at fpe and its harmonics [Klimas, 1983]. Low-frequency modulations are attributed

No-scale SU( 5) super-GUTs

DOE PAGES

Ellis, John; Evans, Jason L.; Nagata, Natsumi; ...

2017-04-12

We reconsider the minimal SU( 5) grand unified theory (GUT) in the context of no-scale supergravity inspired by string compactification scenarios, assuming that the soft supersymmetry-breaking parameters satisfy universality conditions at some input scale M in above the GUT scale M GUT. When setting up such a no-scale super-GUT model, special attention must be paid to avoiding the Scylla of rapid proton decay and the Charybdis of an excessive density of cold dark matter, while also having an acceptable mass for the Higgs boson. Furthermore, we do not find consistent solutions if none of the matter and Higgs fields aremore » assigned to twisted chiral supermultiplets, even in the presence of Giudice–Masiero terms. But, consistent solutions may be found if at least one fiveplet of GUT Higgs fields is assigned to a twisted chiral supermultiplet, with a suitable choice of modular weights. Spin-independent dark matter scattering may be detectable in some of these consistent solutions.« less

Network-State Modulation of Power-Law Frequency-Scaling in Visual Cortical Neurons

PubMed Central

Béhuret, Sébastien; Baudot, Pierre; Yger, Pierre; Bal, Thierry; Destexhe, Alain; Frégnac, Yves

2009-01-01

Various types of neural-based signals, such as EEG, local field potentials and intracellular synaptic potentials, integrate multiple sources of activity distributed across large assemblies. They have in common a power-law frequency-scaling structure at high frequencies, but it is still unclear whether this scaling property is dominated by intrinsic neuronal properties or by network activity. The latter case is particularly interesting because if frequency-scaling reflects the network state it could be used to characterize the functional impact of the connectivity. In intracellularly recorded neurons of cat primary visual cortex in vivo, the power spectral density of Vm activity displays a power-law structure at high frequencies with a fractional scaling exponent. We show that this exponent is not constant, but depends on the visual statistics used to drive the network. To investigate the determinants of this frequency-scaling, we considered a generic recurrent model of cortex receiving a retinotopically organized external input. Similarly to the in vivo case, our in computo simulations show that the scaling exponent reflects the correlation level imposed in the input. This systematic dependence was also replicated at the single cell level, by controlling independently, in a parametric way, the strength and the temporal decay of the pairwise correlation between presynaptic inputs. This last model was implemented in vitro by imposing the correlation control in artificial presynaptic spike trains through dynamic-clamp techniques. These in vitro manipulations induced a modulation of the scaling exponent, similar to that observed in vivo and predicted in computo. We conclude that the frequency-scaling exponent of the Vm reflects stimulus-driven correlations in the cortical network activity. Therefore, we propose that the scaling exponent could be used to read-out the “effective” connectivity responsible for the dynamical signature of the population signals measured

Network-state modulation of power-law frequency-scaling in visual cortical neurons.

PubMed

El Boustani, Sami; Marre, Olivier; Béhuret, Sébastien; Baudot, Pierre; Yger, Pierre; Bal, Thierry; Destexhe, Alain; Frégnac, Yves

2009-09-01

Various types of neural-based signals, such as EEG, local field potentials and intracellular synaptic potentials, integrate multiple sources of activity distributed across large assemblies. They have in common a power-law frequency-scaling structure at high frequencies, but it is still unclear whether this scaling property is dominated by intrinsic neuronal properties or by network activity. The latter case is particularly interesting because if frequency-scaling reflects the network state it could be used to characterize the functional impact of the connectivity. In intracellularly recorded neurons of cat primary visual cortex in vivo, the power spectral density of V(m) activity displays a power-law structure at high frequencies with a fractional scaling exponent. We show that this exponent is not constant, but depends on the visual statistics used to drive the network. To investigate the determinants of this frequency-scaling, we considered a generic recurrent model of cortex receiving a retinotopically organized external input. Similarly to the in vivo case, our in computo simulations show that the scaling exponent reflects the correlation level imposed in the input. This systematic dependence was also replicated at the single cell level, by controlling independently, in a parametric way, the strength and the temporal decay of the pairwise correlation between presynaptic inputs. This last model was implemented in vitro by imposing the correlation control in artificial presynaptic spike trains through dynamic-clamp techniques. These in vitro manipulations induced a modulation of the scaling exponent, similar to that observed in vivo and predicted in computo. We conclude that the frequency-scaling exponent of the V(m) reflects stimulus-driven correlations in the cortical network activity. Therefore, we propose that the scaling exponent could be used to read-out the "effective" connectivity responsible for the dynamical signature of the population signals measured

Flexible organic tandem solar modules: a story of up-scaling

NASA Astrophysics Data System (ADS)

Spyropoulos, George D.; Kubis, Peter; Li, Ning; Lucera, Luca; Salvador, Michael; Baran, Derya; Machui, Florian; Ameri, Tayebeh; Voigt, Monika M.; Brabec, Christoph J.

2014-10-01

The competition in the field of solar energy between Organic Photovoltaics (OPVs) and several Inorganic Photovoltaic technologies is continuously increasing to reach the ultimate purpose of energy supply from inexpensive and easily manufactured solar cell units. Solution-processed printing techniques on flexible substrates attach a tremendous opportunity to the OPVs for the accomplishment of low-cost and large area applications. Furthermore, tandem architectures came to boost up even more OPVs by increasing the photon-harvesting properties of the device. In this work, we demonstrate the road of realizing flexible organic tandem solar modules constructed by a fully roll-to-roll compatible processing. The modules exhibit an efficiency of 5.4% with geometrical fill factors beyond 80% and minimized interconnection-resistance losses. The processing involves low temperature (<70 °C), coating methods compatible with slot die coating and high speed and precision laser patterning.

Magnetic effect on oxide-scale growth of Fe-5Cr alloy

NASA Astrophysics Data System (ADS)

Zhou, C. H.; Li, X. W.; Wang, S. H.; Ma, H. T.

2018-01-01

The oxidation behaviour of Fe-5Cr alloy was investigated at 650°C in the presence of magnetic field. Results indicated that the oxide scales were both consisted of an outer Fe-oxide scale and an inner mixed-oxide scale in the presence or absence of magnetic field. The oxide-scale growth of Fe-5Cr alloy, gained by measuring the oxide-scale thickness, was verified to follow parabolic lawyer. And the oxidation kinetics showed that the applied magnetic field retarded the oxide-scale growth of Fe-5Cr alloy.

Splicing Factor 1 Modulates Dietary Restriction and TORC1 Pathway Longevity in C. elegans

PubMed Central

Heintz, Caroline; Escoubas, Caroline; Zhang, Yue; Weir, Heather J.; Dutta, Sneha; Silva-García, Carlos Giovanni; Bruun, Gitte Hoffmann; Morantte, Ianessa; Hoxhaj, Gerta; Manning, Brendan D.; Andresen, Brage S.; Mair, William B.

2016-01-01

Ageing is driven by a loss of transcriptional and protein homeostasis1–3 and is the key risk factor for multiple chronic diseases. Interventions that attenuate or reverse systemic dysfunction seen with age therefore have potential to reduce overall disease risk in the elderly. Pre-mRNA splicing is a fundamental link between gene expression and the proteome, and deregulation of the splicing machinery is linked to multiple age-related chronic diseases4,5. However, the role of splicing homeostasis in healthy ageing remains unclear. Here we demonstrate that pre-mRNA splicing homeostasis is a biomarker and predictor of life expectancy in Caenorhabditis elegans. Using transcriptomics and in-depth splicing analysis in young and old animals fed ad libitum or on dietary restriction (DR), we find defects in global pre-mRNA splicing with age that are reduced by DR via the branch point binding protein (BBP)/splicing factor 1 (SFA-1). We show that SFA-1 is specifically required for lifespan extension both by DR, and modulation of TORC1 pathway components AMPK, RAGA-1 and RSKS-1/S6 Kinase. Lastly, we demonstrate that overexpression of SFA-1 is sufficient to extend lifespan. Together, these data demonstrate a role for RNA splicing homeostasis in DR longevity and suggest modulation of specific spliceosome components can prolong healthy ageing. PMID:27919065

SPE5 Sub-Scale Test Series Summary Report

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

Vandersall, Kevin S.; Reeves, Robert V.; DeHaven, Martin R.

2016-01-14

A series of 2 SPE5 sub-scale tests were performed to experimentally confirm that a booster system designed and evaluated in prior tests would properly initiate the PBXN-110 case charge fill. To conduct the experiments, a canister was designed to contain the nominally 50 mm diameter booster tube with an outer fill of approximately 150 mm diameter by 150 mm in length. The canisters were filled with PBXN-110 at NAWS-China Lake and shipped back to LLNL for testing in the High Explosives Applications Facility (HEAF). Piezoelectric crystal pins were placed on the outside of the booster tube before filling, and amore » series of piezoelectric crystal pins along with Photonic Doppler Velocimetry (PDV) probes were placed on the outer surface of the canister to measure the relative timing and magnitude of the detonation. The 2 piezoelectric crystal pins integral to the booster design were also utilized along with a series of either piezoelectric crystal pins or piezoelectric polymer pads on the top of the canister or outside case that utilized direct contact, gaps, or different thicknesses of RTV cushions to obtain time of arrival data to evaluate the response in preparation for the large-scale SPE5 test. To further quantify the margin of the booster operation, the 1st test (SPE5SS1) was functioned with both detonators and the 2nd test (SPE5SS2) was functioned with only 1 detonator. A full detonation of the material was observed in both experiments as observed by the pin timing and PDV signals. The piezoelectric pads were found to provide a greater measured signal magnitude during the testing with an RTV layer present, and the improved response is due to the larger measurement surface area of the pad. This report will detail the experiment design, canister assembly for filling, final assembly, experiment firing, presentation of the diagnostic results, and a discussion of the results.« less

Myeloid Cell 5-Lipoxygenase Activating Protein Modulates the Response to Vascular Injury

PubMed Central

Yu, Zhou; Ricciotti, Emanuela; Miwa, Takashi; Liu, Shulin; Ihida-Stansbury, Kaori; Landersberg, Gavin; Jones, Peter L.; Scalia, Rosario; Song, Wenchao; Assoian, Richard K.; FitzGerald, Garret A.

2013-01-01

Rationale Human genetics have implicated the 5- lipoxygenase (5-LO) enzyme in the pathogenesis of cardiovascular disease and an inhibitor of the 5-LO activating protein (FLAP) is in clinical development for asthma. Objective Here we determined whether FLAP deletion modifies the response to vascular injury. Methods and Results Vascular remodeling was characterized 4 weeks after femoral arterial injury in FLAP knockout (FLAP KO) mice and wild type (WT) controls. Both neointimal hyperplasia and the intima/media ratio of the injured artery were significantly reduced in the FLAP KOs while endothelial integrity was preserved. Lesional myeloid cells were depleted and vascular smooth muscle cell (VSMC) proliferation, as reflected by bromodeoxyuridine (BrdU) incorporation, was markedly attenuated by FLAP deletion. Inflammatory cytokine release from FLAP KO macrophages was depressed and their restricted ability to induce VSMC migration ex vivo was rescued with leukotriene B4 (LTB4). FLAP deletion restrained injury and attenuated upregulation of the extracellular matrix protein, tenascin C (TNC), which affords a scaffold for VSMC migration. Correspondingly, the phenotypic modulation of VSMC to a more synthetic phenotype, reflected by morphological change, loss of α-smooth muscle cell actin and upregulation of vascular cell adhesion molecule (VCAM) -1 was also suppressed in FLAP KO mice. Transplantation of FLAP replete myeloid cells rescued the proliferative response to vascular injury. Conclusion Expression of lesional FLAP in myeloid cells promotes LTB4 dependent VSMC phenotypic modulation, intimal migration and proliferation. PMID:23250985

Apollo 16/AS-511/LM-11 operational calibration curves. Volume 1: Calibration curves for command service module CSM 113

NASA Technical Reports Server (NTRS)

Demoss, J. F. (Compiler)

1971-01-01

Calibration curves for the Apollo 16 command service module pulse code modulation downlink and onboard display are presented. Subjects discussed are: (1) measurement calibration curve format, (2) measurement identification, (3) multi-mode calibration data summary, (4) pulse code modulation bilevel events listing, and (5) calibration curves for instrumentation downlink and meter link.

Antiviral function of tilapia hepcidin 1-5 and its modulation of immune-related gene expressions against infectious pancreatic necrosis virus (IPNV) in Chinook salmon embryo (CHSE)-214 cells.

PubMed

Rajanbabu, Venugopal; Chen, Jyh-Yih

2011-01-01

Antimicrobial peptides, small cysteine-rich molecules, play vital roles in host defense mechanisms against pathogen infection. Recently, tilapia hepcidin (TH)1-5, was characterized, and its antimicrobial functions against several pathogens were reported. Herein, we investigated the antiviral functions of TH1-5 against infectious pancreatic necrosis virus (IPNV) in Chinook salmon embryo (CHSE)-214 cells. The presence of TH1-5 enhanced the survival of CHSE-214 cells infected with IPNV. Additionally, the number of plaques formed by the cytopathic effect of IPNV in CHSE-214 cells decreased when IPNV was preincubated with TH1-5. This observation demonstrates the antiviral function of TH1-5. Real-time PCR studies showed the modulation of interleukin, annexin, and other viral-responsive gene expressions by TH1-5. When TH1-5 and IPNV were used to co-treat CHSE-214 cells, then cells were re-challenged with IPNV at 24h, the cells did not survive the IPNV infection. This shows that in the absence of TH1-5, viral re-challenge killed CHSE-214 cells. In conclusion TH1-5 protected CHSE-214 cells against IPNV by direct antimicrobial and immunomodulatory functions. Copyright © 2010 Elsevier Ltd. All rights reserved.

Star Power: Providing for the Gifted & Talented. Module 5. Enrichment Activities for the Gifted/Talented.

ERIC Educational Resources Information Center

Mallis, Jackie; Gilman, Sharlene

The document presents Module 5, enrichment activities for the gifted/talented, of the Star Power modules developed for school personnel who have an interest in or a need to explore the area of gifted and talented education. It is explained in an introductory section that the modules can be used for independent study, for small group interaction,…

The combined effects of the 5-HTTLPR and 5-HTR1A genes modulates the relationship between negative life events and major depressive disorder in a Chinese population.

PubMed

Zhang, Kerang; Xu, Qi; Xu, Yong; Yang, Hong; Luo, Jinxiu; Sun, Yan; Sun, Ning; Wang, Shan; Shen, Yan

2009-04-01

Serotonin transporter (5-HTT) and 5-HT receptor (5-HTR) involved in the neurotransmission of 5-HT may play an important role in the development of major depression disorder (MDD). Several lines of evidence suggested that the gene-environment interaction may confer susceptibility to depression. The aim of this study is to analyze the combined effect of four serotonin-related genes and two environmental factors on MDD in a Chinese population. This study recruited a total of 401 patients with MDD and 391 age- and gender-matched control subjects. They were all Chinese Han origin. Negative life events and objective social supports were assessed using standard rating scales. Six polymorphisms in the four serotonin-related genes (5-HTT, 5-HTR1A, 5-HTR1B and 5-HTR2A) were selected to detect. The analyses of the gene-environment interactions were performed by the Multifactor Dimensionality Reduction (MDR). Allelic associations between patients with MDD and controls were observed for the polymorphism of 5-HTTLPR and for rs6295 at the 5-HTR1A locus. The 5-HTTLPR polymorphism was associated with negative life events on MDD. A three-way interaction between the 5-HTTLPR polymorphism, rs6295 and negative life events on MDD was found in the individuals aged from 20 years to 29 years. In addition, the individuals carrying the L/L genotype of 5-HTTLPR could be susceptible to MDD when exposed to negative life events. The 5-HTTLPR polymorphism may modify the interaction between negative life events and MDD in the Chinese population. To our knowledge, this is the first report on the combined effect for the 5-HTTLPR polymorphism and 5-HTR1A genes on modifying the response to negative life events conferring susceptibility to MDD in the 20-29 year group.

General Conformity Training Module 2.5: Proactive Role for Federal Agencies

EPA Pesticide Factsheets

Module 2.5 explains how taking a proactive role will allow a federal agency to more effectively participate in newly promulgated programs under the General Conformity Regulations, such as the emission reduction credits and the emission budgets programs.

Direct molecular regulation of the myogenic determination gene Myf5 by Pax3, with modulation by Six1/4 factors, is exemplified by the -111 kb-Myf5 enhancer.

PubMed

Daubas, Philippe; Buckingham, Margaret E

2013-04-15

The Myf5 gene plays an important role in myogenic determination during mouse embryo development. Multiple genomic regions of the Mrf4-Myf5 locus have been characterised as enhancer sequences responsible for the complex spatiotemporal expression of the Myf5 gene at the onset of myogenesis. These include an enhancer sequence, located at -111 kb upstream of the Myf5 transcription start site, which is responsible of Myf5 activation in ventral somitic domains (Ribas et al., 2011. Dev. Biol. 355, 372-380). We show that the -111 kb-Myf5 enhancer also directs transgene expression in some limb muscles, and is active at foetal as well as embryonic stages. We have carried out further characterisation of the regulation of this enhancer and show that the paired-box Pax3 transcription factor binds to it in vitro as in vivo, and that Pax binding sites are essential for its activity. This requirement is independent of the previously reported regulation by TEAD transcription factors. Six1/4 which, like Pax3, are important upstream regulators of myogenesis, also bind in vivo to sites in the -111 kb-Myf5 enhancer and modulate its activity. The -111 kb-Myf5 enhancer therefore shares common functional characteristics with another Myf5 regulatory sequence, the hypaxial and limb 145 bp-Myf5 enhancer, both being directly regulated in vivo by Pax3 and Six1/4 proteins. However, in the case of the -111 kb-Myf5 enhancer, Six has less effect and we conclude that Pax regulation plays a major role in controlling this aspect of the Myf5 gene expression at the onset of myogenesis in the embryo. Copyright © 2013 Elsevier Inc. All rights reserved.

Gray scale operation of a multichannel optical convolver using the Semetex magnetooptic spatial light modulator

NASA Technical Reports Server (NTRS)

Davis, Jeffrey A.; Day, Timothy; Lilly, Roger A.; Taber, Donald B.; Liu, Hua-Kuang

1988-01-01

A new multichannel optical correlator/convolver architecture which uses an acoustooptic light modulator for the input channel and a Semetex magnetooptic spatial light modulator (MOSLM) for the set of parallel reference channels is presented. Details of the anamorphic optical system are discussed. Experimental results illustrate the use of the system as a convolver for performing digital multiplication by analog convolution (DMAC). A limited gray scale capability for data stored by the MOSLM is demonstrated by implementing this DMAC algorithm with trinary logic. Use of the MOSLM allows the number of parallel channels for the convolver to be increased significantly compared with previously reported techniques while retaining the capability for updating both channels at high speeds.

Gray Scale Operation Of A Multichannel Optical Convolver Using The Semetex Magnetooptic Spatial Light Modulator

NASA Astrophysics Data System (ADS)

Davis, Jeffrey A.; Day, Timothy; Lilly, Roger A.; Taber, Donald B.; Liu, Hua-Kuang; Davis, J. A.; Day, T.; Lilly, R. A.; Taber, D. B.; Liu, H.-K.

1988-02-01

We present a new multichannel optical correlator/convolver architecture which uses an acoustooptic light modulator (AOLM) for the input channel and a Semetex magnetooptic spatial light modulator (MOSLM) for the set of parallel reference channels. Details of the anamorphic optical system are discussed. Experimental results illustrate use of the system as a convolver for performing digital multiplication by analog convolution (DMAC). A limited gray scale capability for data stored by the MOSLM is demonstrated by implementing this DMAC algorithm with trinary logic. Use of the MOSLM allows the number of parallel channels for the convolver to be increased significantly compared with previously reported techniques while retaining the capability for updating both channels at high speeds.

Gray scale operation of a multichannel optical convolver using the Semetex magnetooptic spatial light modulator

NASA Astrophysics Data System (ADS)

Davis, Jeffrey A.; Day, Timothy; Lilly, Roger A.; Taber, Donald B.; Liu, Hua-Kuang

A new multichannel optical correlator/convolver architecture which uses an acoustooptic light modulator for the input channel and a Semetex magnetooptic spatial light modulator (MOSLM) for the set of parallel reference channels is presented. Details of the anamorphic optical system are discussed. Experimental results illustrate the use of the system as a convolver for performing digital multiplication by analog convolution (DMAC). A limited gray scale capability for data stored by the MOSLM is demonstrated by implementing this DMAC algorithm with trinary logic. Use of the MOSLM allows the number of parallel channels for the convolver to be increased significantly compared with previously reported techniques while retaining the capability for updating both channels at high speeds.

Study Modules for Calculus-Based General Physics. [Includes Modules 3-5: Planar Motion; Newton's Laws; and Vector Multiplication].

ERIC Educational Resources Information Center

Fuller, Robert G., Ed.; And Others

This is part of a series of 42 Calculus Based Physics (CBP) modules totaling about 1,000 pages. The modules include study guides, practice tests, and mastery tests for a full-year individualized course in calculus-based physics based on the Personalized System of Instruction (PSI). The units are not intended to be used without outside materials;…

The obesity-associated transcription factor ETV5 modulates circulating glucocorticoids

PubMed Central

Gutierrez-Aguilar, Ruth; Thompson, Abigail; Marchand, Nathalie; Dumont, Patrick; Woods, Stephen C.; de Launoit, Yvan; Seeley, Randy J.; Ulrich-Lai, Yvonne M.

2015-01-01

The transcription factor E-twenty-six version 5 (ETV5) has been linked with obesity in genome-wide association studies. Moreover, ETV5-deficient mice (knockout; KO) have reduced body weight, lower fat mass, and are resistant to diet-induced obesity, directly linking ETV5 to the regulation of energy balance and metabolism. ETV5 is expressed in hypothalamic brain regions that regulate both metabolism and HPA axis activity, suggesting that ETV5 may also modulate HPA axis function. In order to test this possibility, plasma corticosterone levels were measured in ETV5 KO and wildtype (WT) mice before (pre-stress) and after (post-stress) a mild stressor (intraperitoneal injection). ETV5 deficiency increased both pre- and post-stress plasma corticosterone, suggesting that loss of ETV5 elevated glucocorticoid tone. Consistent with this idea, ETV5 KO mice have reduced thymus weight, suggestive of increased glucocorticoid-induced thymic involution. ETV5 deficiency also decreased the mRNA expression of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and vasopressin receptor 1A in the hypothalamus, without altering vasopressin, corticotropin-releasing hormone, or oxytocin mRNA expression. In order to test whether reduced MR and GR expression affected glucocorticoid negative feedback, a dexamethasone suppression test was performed. Dexamethasone reduced plasma corticosterone in both ETV5 KO and WT mice, suggesting that glucocorticoid negative feedback was unaltered by ETV5 deficiency. In summary, these data suggest that the obesity-associated transcription factor ETV5 normally acts to diminish circulating glucocorticoids. This might occur directly via ETV5 actions on HPA-regulatory brain circuitry, and/or indirectly via ETV5-induced alterations in metabolic factors that then influence the HPA axis. PMID:25813907

Wnt modulates MCL1 to control cell survival in triple negative breast cancer

PubMed Central

2014-01-01

Background Triple negative breast cancer (TNBC) has higher rates of recurrence and distant metastasis, and poorer outcome as compared to non-TNBC. Aberrant activation of WNT signaling has been detected in TNBC, which might be important for triggering oncogenic conversion of breast epithelial cell. Therefore, we directed our focus on identifying the WNT ligand and its underlying mechanism in TNBC cells. Methods We performed large-scale analysis of public microarray data to screen the WNT ligands and the clinical significance of the responsible ligand in TNBC. WNT5B was identified and its overexpression in TNBC was confirmed by immunohistochemistry staining, Western blot and ELISA. ShRNA was used to knockdown WNT5B expression (shWNT5B). Cellular functional alteration with shWNT5B treatment was determined by using wound healing assay, mammosphere assay; while cell cycle and apoptosis were examined by flowcytometry. Mitochondrial morphology was photographed by electron microscope. Biological change of mitochondria was detected by RT-PCR and oxygen consumption assay. Activation of WNT pathway and its downstream targets were evaluated by liciferase assay, immunohistochemistry staining and immunoblot analysis. Statistical methods used in the experiments besides microarray analysis was two-tailed t-test. Results WNT5B was elevated both in the tumor and the patients’ serum. Suppression of WNT5B remarkably impaired cell growth, migration and mammosphere formation. Additionally, G0/G1 cell cycle arrest and caspase-independent apoptosis was observed. Study of the possible mechanism indicated that these effects occurred through suppression of mitochondrial biogenesis, as evidenced by reduced mitochondrial DNA (MtDNA) and compromised oxidative phosphorylation (OXPHOS). In Vivo and in vitro data uncovered that WNT5B modulated mitochondrial physiology was mediated by MCL1, which was regulated by WNT/β-catenin responsive gene, Myc. Clinic data analysis revealed that both WNT5B

The C-Module-Binding Factor Supports Amplification of TRE5-A Retrotransposons in the Dictyostelium discoideum Genome ▿

PubMed Central

Bilzer, Annika; Dölz, Heike; Reinhardt, Alexander; Schmith, Anika; Siol, Oliver; Winckler, Thomas

2011-01-01

Retrotransposable elements are molecular parasites that have invaded the genomes of virtually all organisms. Although retrotransposons encode essential proteins to mediate their amplification, they also require assistance by host cell-encoded machineries that perform functions such as DNA transcription and repair. The retrotransposon TRE5-A of the social amoeba Dictyostelium discoideum generates a notable amount of both sense and antisense RNAs, which are generated from element-internal promoters, located in the A module and the C module, respectively. We observed that TRE5-A retrotransposons depend on the C-module-binding factor (CbfA) to maintain high steady-state levels of TRE5-A transcripts and that CbfA supports the retrotransposition activity of TRE5-A elements. The carboxy-terminal domain of CbfA was found to be required and sufficient to mediate the accumulation of TRE5-A transcripts, but it did not support productive retrotransposition of TRE5-A. This result suggests different roles for CbfA protein domains in the regulation of TRE5-A retrotransposition frequency in D. discoideum cells. Although CbfA binds to the C module in vitro, the factor regulates neither C-module nor A-module promoter activity in vivo. We speculate that CbfA supports the amplification of TRE5-A retrotransposons by suppressing the expression of an as yet unidentified component of the cellular posttranscriptional gene silencing machinery. PMID:21076008

Development of Prototype Outcomes-Based Training Modules for Aesthetic Dentistry

ERIC Educational Resources Information Center

Andres, Maricar Joy T.; Borabo, Milagros L.

2015-01-01

The objective of the study is to know the essential components of Aesthetic Dentistry that will be a basis for prototype Outcomes-based training modules. Using a 5-point Likert scale, the researcher-made questionnaire assessed the different elements of Aesthetic Dentistry which are needed in the designing of the training module, the manner of…

Delft3D turbine turbulence module v. 1.0.0

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

Chartrand, Chris; Jagers, Bert

2016-08-25

The DOE has funded Sandia National Labs (SNL) to develop an open-source modeling tool to guide the design and layout of marine hydrokinetic (MHK) arrays to maximize power production while minimizing environmental effects. This modeling framework simulates flows through and around a MHK arrays while quantifying environmental responses. As an augmented version of the Dutch company, Deltares’s, environmental hydrodynamics code, Delft3D, Delft3D-CEC includes a new module that simulates energy conversion (momentum withdrawal) by MHK current energy conversion devices with commensurate changes in the turbulent kinetic energy and its dissipation rate. The Following is a description of Deltares’s open-source code Delft3Dmore » from which Delft3D-CEC is built upon. “Delft3D is a world leading 3D modeling suite to investigate hydrodynamics, sediment transport and morphology and water quality for fluvial, estuarine and coastal environments. As per 1 January 2011, the Delft3D flow (FLOW), morphology (MOR) and waves (WAVE) modules are available in open source. The software is used and has proven his capabilities on many places around the world, like the Netherlands, USA, Hong Kong, Singapore, Australia, Venice, etc. The software is continuously improved and developed with innovating advanced modelling techniques as consequence of the research work of our institute and to stay world leading. The FLOW module is the heart of Delft3D and is a multi-dimensional (2D or 3D) hydrodynamic (and transport) simulation programme which calculates non-steady flow and transport phenomena resulting from tidal and meteorological forcing on a curvilinear, boundary fitted grid or sperical coordinates. In 3D simulations, the vertical grid is defined following the so-called sigma coordinate approach or Z-layer approach. The MOR module computes sediment transport (both suspended and bed total load) and morphological changes for an arbitrary number of cohesive and non-cohesive fractions. Both

Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization

PubMed Central

Vivekananda, Umesh; Novak, Pavel; Bello, Oscar D.; Korchev, Yuri E.; Krishnakumar, Shyam S.; Volynski, Kirill E.; Kullmann, Dimitri M.

2017-01-01

Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog–digital modulation is depolarization-mediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization. We recorded instead from small boutons supplied by intact axons identified with scanning ion conductance microscopy in primary hippocampal cultures and asked how distinct potassium channels interact in determining the basal spike width and its modulation by subthreshold somatic depolarization. Pharmacological or genetic deletion of Kv1.1 broadened presynaptic spikes without preventing further prolongation by brief depolarizing somatic prepulses. A heterozygous mouse model of episodic ataxia type 1 harboring a dominant Kv1.1 mutation had a similar broadening effect on basal spike shape as deletion of Kv1.1; however, spike modulation by somatic prepulses was abolished. These results argue that the Kv1.1 subunit is not necessary for subthreshold modulation of spike width. However, a disease-associated mutant subunit prevents the interplay of analog and digital transmission, possibly by disrupting the normal stoichiometry of presynaptic potassium channels. PMID:28193892

Acidosis Differentially Modulates Inactivation in NaV1.2, NaV1.4, and NaV1.5 Channels

PubMed Central

Vilin, Yury Y.; Peters, Colin H.; Ruben, Peter C.

2012-01-01

NaV channels play a crucial role in neuronal and muscle excitability. Using whole-cell recordings we studied effects of low extracellular pH on the biophysical properties of NaV1.2, NaV1.4, and NaV1.5, expressed in cultured mammalian cells. Low pH produced different effects on different channel subtypes. Whereas NaV1.4 exhibited very low sensitivity to acidosis, primarily limited to partial block of macroscopic currents, the effects of low pH on gating in NaV1.2 and NaV1.5 were profound. In NaV1.2 low pH reduced apparent valence of steady-state fast inactivation, shifted the τ(V) to depolarizing potentials and decreased channels availability during onset to slow and use-dependent inactivation (UDI). In contrast, low pH delayed open-state inactivation in NaV1.5, right-shifted the voltage-dependence of window current, and increased channel availability during onset to slow and UDI. These results suggest that protons affect channel availability in an isoform-specific manner. A computer model incorporating these results demonstrates their effects on membrane excitability. PMID:22701426

Role of 5-HT5A and 5-HT1B/1D receptors in the antinociception produced by ergotamine and valerenic acid in the rat formalin test.

PubMed

Vidal-Cantú, Guadalupe C; Jiménez-Hernández, Mildred; Rocha-González, Héctor I; Villalón, Carlos M; Granados-Soto, Vinicio; Muñoz-Islas, Enriqueta

2016-06-15

Sumatriptan, dihydroergotamine and methysergide inhibit 1% formalin-induced nociception by activation of peripheral 5-HT1B/1D receptors. This study set out to investigate the pharmacological profile of the antinociception produced by intrathecal and intraplantar administration of ergotamine (a 5-HT1B/1D and 5-HT5A/5B receptor agonist) and valerenic acid (a partial agonist at 5-HT5A receptors). Intraplantar injection of 1% formalin in the right hind paw resulted in spontaneous flinching behavior of the injected hindpaw of female Wistar rats. Intrathecal ergotamine (15nmol) or valerenic acid (1 nmol) blocked in a dose dependent manner formalin-induced nociception. The antinociception by intrathecal ergotamine (15nmol) or valerenic acid (1nmol) was partly or completely blocked by intrathecal administration of the antagonists: (i) methiothepin (non-selective 5-HT5A/5B; 0.01-0.1nmol); (ii) SB-699551 (selective 5-HT5A; up to 10nmol); (iii) anti-5-HT5A antibody; (iv) SB-224289 (selective 5-HT1B; 0.1-1nmol); or (v) BRL-15572 (selective 5-HT1D; 0.1-1nmol). Likewise, antinociception by intraplantar ergotamine (15nmol) and valerenic acid (10nmol) was: (i) partially blocked by methiothepin (1nmol), SB-699551 (10nmol) or SB-224289 (1nmol); and (ii) abolished by BRL-15572 (1nmol). The above doses of antagonists (which did not affect per se the formalin-induced nociception) were high enough to completely block their respective receptors. Our results suggest that ergotamine and valerenic acid produce antinociception via 5-HT5A and 5-HT1B/1D receptors located at both spinal and peripheral sites. This provides new evidence for understanding the modulation of nociceptive pathways in inflammatory pain. Copyright © 2016 Elsevier B.V. All rights reserved.

[Diagnostic test scale SI5: Assessment of sacroiliac joint dysfunction].

PubMed

Acevedo González, Juan C; Quintero Oliveros, Silvia

2015-01-01

Sacroiliac joint dysfunction is a known cause of low back pain. We think that a diagnostic score scale (SI5) may be performed to assess diagnostic utility of clinical signs of sacroiliac joint dysfunction. The primary aim of the present study was to conduct the pilot study of our new diagnostic score scale, the SI5, for sacroiliac joint syndrome. We reviewed the literature on clinical characteristics, diagnostic tests and imaging most commonly used in diagnosing sacroiliac joint dysfunction. Our group evaluated the diagnostic utility of these aspects and we used those considered most representative to develop the SI5 diagnostic scale. The SI5 scale was applied to 22 patients with low back pain; afterwards, the standard test for diagnosing this pathology (selective blockage of the SI joint) was also performed on these patients. The sensitivity and specificity for each sign were also assessed and the diagnostic scale called SI5 was then proposed, based on these data. The most sensitive clinical tests for diagnosing SI joint dysfunction were 2 patient-reported clinical characteristics, the Laguerre Test, sacroiliac rocking test and Yeomans test (greater than 80% sensitivity). The tests with greatest diagnostic specificity (>80%) were the Lewitt test, Piedallu test and Gillet test. The proposed SI5 test score scale showed sensitivity of 73% and specificity of 71%. Sacroiliac joint syndrome has been shown to produce low back pain frequently; however, the diagnostic value of examination tests for sacroiliac joint pain has been questioned by other authors. The pilot study on the SI5 diagnostic score scale showed good sensitivity and specificity. However, the process of statistical validation of the SI5 needs to be continued. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

A large-scale dataset of solar event reports from automated feature recognition modules

NASA Astrophysics Data System (ADS)

Schuh, Michael A.; Angryk, Rafal A.; Martens, Petrus C.

2016-05-01

The massive repository of images of the Sun captured by the Solar Dynamics Observatory (SDO) mission has ushered in the era of Big Data for Solar Physics. In this work, we investigate the entire public collection of events reported to the Heliophysics Event Knowledgebase (HEK) from automated solar feature recognition modules operated by the SDO Feature Finding Team (FFT). With the SDO mission recently surpassing five years of operations, and over 280,000 event reports for seven types of solar phenomena, we present the broadest and most comprehensive large-scale dataset of the SDO FFT modules to date. We also present numerous statistics on these modules, providing valuable contextual information for better understanding and validating of the individual event reports and the entire dataset as a whole. After extensive data cleaning through exploratory data analysis, we highlight several opportunities for knowledge discovery from data (KDD). Through these important prerequisite analyses presented here, the results of KDD from Solar Big Data will be overall more reliable and better understood. As the SDO mission remains operational over the coming years, these datasets will continue to grow in size and value. Future versions of this dataset will be analyzed in the general framework established in this work and maintained publicly online for easy access by the community.

Label Review Training: Module 1: Label Basics, Page 29

EPA Pesticide Factsheets

This module of the pesticide label review training provides basic information about pesticides, their labeling and regulation, and the core principles of pesticide label review. This page is a quiz on Module 1.

Force Characteristics in the Submerged and Planing Condition of a 1/5.78-Scale Model of a Hydro-Ski-Wheel Combination for the Grumman JRF-5 Airplane. TED No. NACA DE 357

NASA Technical Reports Server (NTRS)

Land, Norman S.; Pelz, Charles A.

1952-01-01

Force characteristics determined from tank tests of a 1/5.78 scale model of a hydro-ski-wheel combination for the Grumman JRF-5 airplane are presented. The model was tested in both the submerged and planing conditions over a range of trim, speed, and load sufficiently large to represent the most probable full-size conditions.

Optical correlator using very-large-scale integrated circuit/ferroelectric-liquid-crystal electrically addressed spatial light modulators

NASA Technical Reports Server (NTRS)

Turner, Richard M.; Jared, David A.; Sharp, Gary D.; Johnson, Kristina M.

1993-01-01

The use of 2-kHz 64 x 64 very-large-scale integrated circuit/ferroelectric-liquid-crystal electrically addressed spatial light modulators as the input and filter planes of a VanderLugt-type optical correlator is discussed. Liquid-crystal layer thickness variations that are present in the devices are analyzed, and the effects on correlator performance are investigated through computer simulations. Experimental results from the very-large-scale-integrated / ferroelectric-liquid-crystal optical-correlator system are presented and are consistent with the level of performance predicted by the simulations.

Ammonia. Training Module 5.110.2.77.

ERIC Educational Resources Information Center

Kirkwood Community Coll., Cedar Rapids, IA.

This document is an instructional module package prepared in objective form for use by an instructor familiar with analytical procedures for determining ammonia nitrogen concentrations in a water or wastewater sample. Included are objectives, instructor guides, student handouts, and transparency masters. This module considers preliminary…

Phytophthora infestans RXLR Effector AVR1 Interacts with Exocyst Component Sec5 to Manipulate Plant Immunity1[OPEN

PubMed Central

Du, Yu; Mpina, Mohamed H.; Birch, Paul R.J.; Bouwmeester, Klaas; Govers, Francine

2015-01-01

Phytophthora infestans secretes numerous RXLR effectors that modulate host defense and thereby pave the way for successful invasion. Here, we show that the RXLR effector AVR1 is a virulence factor that promotes colonization and suppresses callose deposition, a hallmark of basal defense. To identify host targets of AVR1, we performed yeast two-hybrid screens and selected Sec5 as a candidate. Sec5 is a subunit of the exocyst, a protein complex that is involved in vesicle trafficking. AVR1-like (A-L), a close homolog of AVR1, also acts as a virulence factor, but unlike AVR1, A-L does not suppress CRINKLER2 (CRN2)-induced cell death or interact with Sec5. Compared with AVR1, A-L is shorter and lacks the carboxyl-terminal tail, the T-region that is crucial for CRN2-induced cell death suppression and Sec5 interaction. In planta analyses revealed that AVR1 and Sec5 are in close proximity, and coimmunoprecipitation confirmed the interaction. Sec5 is required for secretion of the pathogenesis-related protein PR-1 and callose deposition and also plays a role in CRN2-induced cell death. Our findings show that P. infestans manipulates an exocyst subunit and thereby potentially disturbs vesicle trafficking, a cellular process that is important for basal defense. This is a novel strategy that oomycete pathogens exploit to modulate host defense. PMID:26336092

Spectro-temporal modulation masking patterns reveal frequency selectivity.

PubMed

Oetjen, Arne; Verhey, Jesko L

2015-02-01

The present study investigated the possibility that the human auditory system demonstrates frequency selectivity to spectro-temporal amplitude modulations. Threshold modulation depth for detecting sinusoidal spectro-temporal modulations was measured using a generalized masked threshold pattern paradigm with narrowband masker modulations. Four target spectro-temporal modulations were examined, differing in their temporal and spectral modulation frequencies: a temporal modulation of -8, 8, or 16 Hz combined with a spectral modulation of 1 cycle/octave and a temporal modulation of 4 Hz combined with a spectral modulation of 0.5 cycles/octave. The temporal center frequencies of the masker modulation ranged from 0.25 to 4 times the target temporal modulation. The spectral masker-modulation center-frequencies were 0, 0.5, 1, 1.5, and 2 times the target spectral modulation. For all target modulations, the pattern of average thresholds for the eight normal-hearing listeners was consistent with the hypothesis of a spectro-temporal modulation filter. Such a pattern of modulation-frequency sensitivity was predicted on the basis of psychoacoustical data for purely temporal amplitude modulations and purely spectral amplitude modulations. An analysis of separability indicates that, for the present data set, selectivity in the spectro-temporal modulation domain can be described by a combination of a purely spectral and a purely temporal modulation filter function.

[5-HT(1A) receptors are involved in the modulation of respiratory rhythmical discharge activity in the medulla oblongata slice preparation of neonatal rats].

PubMed

Qin, Zheng; Wu, Zhong-Hai; Wang, Xiao-Feng

2007-06-25

The present study was carried out to determine the role of 5-HT(1A) receptors in the generation and modulation of basic respiratory rhythm. Neonatal (aged 0-3 d) Sprague-Dawley rats of either sex were used. The medulla oblongata slice was prepared and the surgical procedure was performed in the modified Kreb's solution (MKS) with continuous carbogen (95% O2 and 5% CO2), and ended in 3 min. In cold MKS, a 600-700 microm single transverse slice was cut, which was rostral to the edge of area postrema and retained the hypoglossal nerve roots and some parts of the ventral respiratory group. The preparation was quickly transferred to a recording chamber and continuously perfused with carbogen-saturated MKS at a rate of 4-6 mL/min at 27-29 degrees C. Glass adsorb-electrodes containing Ag-AgCl needle were attached to the ventral roots of the hypoglossal nerve. Respiratory rhythmical discharge activity (RRDA) of the rootlets of hypoglossal nerve was recorded. Ten medulla oblongata slice preparations were divided into two groups. In group I, 5-HT(1A) receptor specific agonist (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (8-OHDPAT, 20 micromol/L) was added into the perfusion solution for 10 min first, after washing out, the 5-HT(1A) antagonist [4-iodo-N-[2-[4-methoxyphenyl]-1-piperazinyl]ethyl]-N-2-pyridynyl-benzamide hydrochloride] (PMPPI, 10 micromol/L) was applied to the perfusion solution for 10 min. In group II, after application of 8-OHDPAT for 10 min, additional PMPPI was added into the perfusion solution for 10 min. The discharges of the rootlets of hypoglossal nerve were recorded. Signals were amplified and band-pass filtered (100-3.3 kHz). Data were sampled (1-10 kHz) and stored in the computer via BL-420 biological signal processing system. Our results showed that 8-OHDPAT increased the respiratory cycle (RC) and expiratory time (TE) as well as reduced the integral amplitude (IA), but the changes of the inspiratory time (TI) were not statistically

Construction, wind tunnel testing and data analysis for a 1/5 scale ultra-light wing model

NASA Technical Reports Server (NTRS)

James, Michael D.; Smith, Howard W.

1993-01-01

This report documents the construction, wind tunnel testing, and data analysis of a 1/5 scale ultra-light wing section. Wind tunnel testing provided accurate and meaningful lift, drag, and pitching moment data. This data was processed and graphically presented as follows: C(sub L) vs. gamma; C(sub D) vs. gamma; C(sub M) vs. gamma; and C(sub L) vs. C(sub D). The wing fabric flexure was found to be significant and its possible effects on aerodynamic data was discussed. The fabric flexure is directly related to wing angle of attack and airspeed. Different wing section shapes created by fabric flexure are presented with explanations of the types of pressures that act upon the wing surface. This report provides conclusive aerodynamic data for ultra-light wings.

Modulation of Kalirin-7 Expression by Hippocampal CA1 5-HT1B Receptors in Spatial Memory Consolidation.

PubMed

Zhou, Meng-He; Sun, Fang-Fang; Xu, Chang; Chen, Hui-Bin; Qiao, Hui; Cai, Xiang; Ma, Xin-Ming; An, Shu-Cheng

2018-06-24

Serotonin 5-HT1B receptors (5-HT1BRs) are distributed in hippocampal CA1 and play a pivotal role in cognitive function. Activation of 5-HT1BRs regulates synaptic plasticity at the excitatory synapses in the hippocampus. However, the role and its underlying mechanism of 5-HT1BR activation-mediated glutamatergic synaptic plasticity in spatial memory are not fully understood. In this study, spatial memory of Sprague-Dawley (SD) rats was assessed in a Morris water maze after bilateral dorsal hippocampal CA1 infusion of the 5-HT1BR antagonist GR55562 (25 μg/μL) or agonist CP93129 (25 μg/μL). GR55562 did not affect the spatial memory acquisition but significantly increased the target quadrant preference during the memory consolidation probe performed 14 d after the training session, while CP93129 impaired the memory consolidation process. Moreover, GR55562 significantly increased, while CP93129 significantly decreased, the density of dendritic spines on the distal apical dendrites of CA1 pyramidal neurons. Furthermore, western blot experiments indicated that GR55562 significantly increased, but CP93129 significantly reduced, the expression of Kalirin-7 (Kal-7), PSD95, and GluA2/3 subunits of AMPA receptors. Our results suggest that Kal-7 and Kal-7-mediatedalteration of AMPA receptor subtype expression may play crucial roles in the impact of hippocampal CA1 5-HT1BR activation on spatial memory consolidation. Copyright © 2018. Published by Elsevier B.V.

Serotonin receptor 1A–modulated phosphorylation of glycine receptor α3 controls breathing in mice

PubMed Central

Manzke, Till; Niebert, Marcus; Koch, Uwe R.; Caley, Alex; Vogelgesang, Steffen; Hülsmann, Swen; Ponimaskin, Evgeni; Müller, Ulrike; Smart, Trevor G.; Harvey, Robert J.; Richter, Diethelm W.

2010-01-01

Rhythmic breathing movements originate from a dispersed neuronal network in the medulla and pons. Here, we demonstrate that rhythmic activity of this respiratory network is affected by the phosphorylation status of the inhibitory glycine receptor α3 subtype (GlyRα3), which controls glutamatergic and glycinergic neuronal discharges, subject to serotonergic modulation. Serotonin receptor type 1A–specific (5-HTR1A–specific) modulation directly induced dephosphorylation of GlyRα3 receptors, which augmented inhibitory glycine-activated chloride currents in HEK293 cells coexpressing 5-HTR1A and GlyRα3. The 5-HTR1A–GlyRα3 signaling pathway was distinct from opioid receptor signaling and efficiently counteracted opioid-induced depression of breathing and consequential apnea in mice. Paradoxically, this rescue of breathing originated from enhanced glycinergic synaptic inhibition of glutamatergic and glycinergic neurons and caused disinhibition of their target neurons. Together, these effects changed respiratory phase alternations and ensured rhythmic breathing in vivo. GlyRα3-deficient mice had an irregular respiratory rhythm under baseline conditions, and systemic 5-HTR1A activation failed to remedy opioid-induced respiratory depression in these mice. Delineation of this 5-HTR1A–GlyRα3 signaling pathway offers a mechanistic basis for pharmacological treatment of opioid-induced apnea and other breathing disturbances caused by disorders of inhibitory synaptic transmission, such as hyperekplexia, hypoxia/ischemia, and brainstem infarction. PMID:20978350

Preservation affinity in consensus modules among stages of HIV-1 progression.

PubMed

Mosaddek Hossain, Sk Md; Ray, Sumanta; Mukhopadhyay, Anirban

2017-03-20

Analysis of gene expression data provides valuable insights into disease mechanism. Investigating relationship among co-expression modules of different stages is a meaningful tool to understand the way in which a disease progresses. Identifying topological preservation of modular structure also contributes to that understanding. HIV-1 disease provides a well-documented progression pattern through three stages of infection: acute, chronic and non-progressor. In this article, we have developed a novel framework to describe the relationship among the consensus (or shared) co-expression modules for each pair of HIV-1 infection stages. The consensus modules are identified to assess the preservation of network properties. We have investigated the preservation patterns of co-expression networks during HIV-1 disease progression through an eigengene-based approach. We discovered that the expression patterns of consensus modules have a strong preservation during the transitions of three infection stages. In particular, it is noticed that between acute and non-progressor stages the preservation is slightly more than the other pair of stages. Moreover, we have constructed eigengene networks for the identified consensus modules and observed the preservation structure among them. Some consensus modules are marked as preserved in two pairs of stages and are analyzed further to form a higher order meta-network consisting of a group of preserved modules. Additionally, we observed that module membership (MM) values of genes within a module are consistent with the preservation characteristics. The MM values of genes within a pair of preserved modules show strong correlation patterns across two infection stages. We have performed an extensive analysis to discover preservation pattern of co-expression network constructed from microarray gene expression data of three different HIV-1 progression stages. The preservation pattern is investigated through identification of consensus modules

Modulation of K(Ca)3.1 channels by eicosanoids, omega-3 fatty acids, and molecular determinants.

PubMed

Kacik, Michael; Oliván-Viguera, Aida; Köhler, Ralf

2014-01-01

Cytochrome P450- and ω-hydrolase products (epoxyeicosatrienoic acids (EETs), hydroxyeicosatetraeonic acid (20-HETE)), natural omega-3 fatty acids (ω3), and pentacyclic triterpenes have been proposed to contribute to a wide range of vaso-protective and anti-fibrotic/anti-cancer signaling pathways including the modulation of membrane ion channels. Here we studied the modulation of intermediate-conductance Ca(2+)/calmodulin-regulated K(+) channels (K(Ca)3.1) by EETs, 20-HETE, ω3, and pentacyclic triterpenes and the structural requirements of these fatty acids to exert channel blockade. We studied modulation of cloned human hK(Ca)3.1 and the mutant hK(Ca)3.1(V275A) in HEK-293 cells, of rK(Ca)3.1 in aortic endothelial cells, and of mK(Ca)3.1 in 3T3-fibroblasts by inside-out and whole-cell patch-clamp experiments, respectively. In inside-out patches, Ca(2+)-activated hK(Ca)3.1 were inhibited by the ω3, DHA and α-LA, and the ω6, AA, in the lower µmolar range and with similar potencies. 5,6-EET, 8,9-EET, 5,6-DiHETE, and saturated arachidic acid, had no appreciable effects. In contrast, 14,15-EET, its stable derivative, 14,15-EEZE, and 20-HETE produced channel inhibition. 11,12-EET displayed less inhibitory activity. The K(Ca)3.1(V275A) mutant channel was insensitive to any of the blocking EETs. Non-blocking 5,6-EET antagonized the inhibition caused by AA and augmented cloned hK(Ca)3.1 and rK(Ca)3.1 whole-cell currents. Pentacyclic triterpenes did not modulate K(Ca)3.1 currents. Inhibition of K(Ca)3.1 by EETs (14,15-EET), 20-HETE, and ω3 critically depended on the presence of electron double bonds and hydrophobicity within the 10 carbons preceding the carboxyl-head of the molecules. From the physiological perspective, metabolism of AA to non-blocking 5,6,- and 8,9-EET may cause AA-de-blockade and contribute to cellular signal transduction processes influenced by these fatty acids.

COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: effects on the negative symptom response to clozapine.

PubMed

Bosia, Marta; Lorenzi, Cristina; Pirovano, Adele; Guglielmino, Carmelo; Cocchi, Federica; Spangaro, Marco; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto

2015-01-01

Clozapine is still considered the gold standard for treatment-resistant schizophrenia patients; however, up to 40% of patients do not respond adequately. Identifying potential predictors of clinical response to this last-line antipsychotic could represent an important goal for treatment. Among these, functional polymorphisms involved in dopamine system modulation, known to be disrupted in schizophrenia, may play a role. We examined the COMT Val158Met polymorphism, which plays a key role in dopamine regulation at the prefrontal level, and the 5-HT1A-R -1019 C/G polymorphism, a target of clozapine activity involved in the interaction between the serotonin and dopamine systems. 107 neuroleptic-refractory, biologically unrelated Italian patients (70 males and 37 females) with a DSM-IV diagnosis of schizophrenia who were being treated with clozapine were recruited. Psychopathology was assessed by the Positive and Negative Symptoms Scale (PANSS) at the beginning of treatment, and at weeks 8 and 12. Genomic DNA was extracted from venous blood samples. COMT rs4680 (Val158Met) and 5-HT1A-R rs6295 (-1019 C/G) polymorphisms were analyzed by PCR-based restriction fragment length and direct sequencing, respectively. We found a significant effect of COMT and 5-HT1A-R on the PANSS Negative Subscale variation, with greater improvement among COMT Val/Val and 5-HT1A-R G/G subjects. The findings support the hypothesis that COMT rs4680 and 5-HT1A-R rs6295 polymorphisms could influence the negative symptom response to clozapine, probably through modulation of the dopaminergic system.

1.5% root-mean-square flat-intensity laser beam formed using a binary-amplitude spatial light modulator.

PubMed

Liang, Jinyang; Kohn, Rudolph N; Becker, Michael F; Heinzen, Daniel J

2009-04-01

We demonstrate a digital micromirror device (DMD)-based optical system that converts a spatially noisy quasi-Gaussian to an eighth-order super-Lorentzian flat-top beam. We use an error-diffusion algorithm to design the binary pattern for the Texas Instruments DLP device. Following the DMD, a telescope with a pinhole low-pass filters the beam and scales it to the desired sized image. Experimental measurements show a 1% root-mean-square (RMS) flatness over a diameter of 0.28 mm in the center of the flat-top beam and better than 1.5% RMS flatness over its entire 1.43 mm diameter. The power conversion efficiency is 37%. We develop an alignment technique to ensure that the DMD pattern is correctly positioned on the incident beam. An interferometric measurement of the DMD surface flatness shows that phase uniformity is maintained in the output beam. Our approach is highly flexible and is able to produce not only flat-top beams with different parameters, but also any slowly varying target beam shape. It can be used to generate the homogeneous optical lattice required for Bose-Einstein condensate cold atom experiments.

Low-Energy Tunable Self-Modulated Nanolasers (1.1 SHORT-TERM INNOVATIVE RESEARCH (STIR) PROGRAM)

DTIC Science & Technology

2016-09-28

Optoelectronics: Low -Energy Tunable Self- Modulated Nanolasers (1.1 SHORT-TERM INNOVATIVE RESEARCH (STIR) PROGRAM) Our goal was to exploit Quantum...reviewed journals: Final Report: Optoelectronics: Low -Energy Tunable Self-Modulated Nanolasers (1.1 SHORT-TERM INNOVATIVE RESEARCH (STIR) PROGRAM...metal layer. By optimizing the thickness of the low index shield between the metal and semiconductor, the gain threshold of the laser can be

Modulation of taste sensitivity by GLP-1 signaling in taste buds.

PubMed

Martin, Bronwen; Dotson, Cedrick D; Shin, Yu-Kyong; Ji, Sunggoan; Drucker, Daniel J; Maudsley, Stuart; Munger, Steven D

2009-07-01

Modulation of sensory function can help animals adjust to a changing external and internal environment. Even so, mechanisms for modulating taste sensitivity are poorly understood. Using immunohistochemical, biochemical, and behavioral approaches, we found that the peptide hormone glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) are expressed in mammalian taste buds. Furthermore, we found that GLP-1 signaling plays an important role in the modulation of taste sensitivity: GLP-1R knockout mice exhibit a dramatic reduction in sweet taste sensitivity as well as an enhanced sensitivity to umami-tasting stimuli. Together, these findings suggest a novel paracrine mechanism for the hormonal modulation of taste function in mammals.

Orion EM-1 Crew Module Adapter Move to Clean Room

NASA Image and Video Library

2016-11-29

Inside the Neil Armstrong Operations and Checkout Building high bay at NASA’s Kennedy Space Center in Florida, the Orion crew module adapter (CMA) for Exploration Mission 1 (EM-1) is being moved to a clean room. The CMA will undergo propellant and environmental control and life support system tube installation and welding. The adapter will connect the Orion crew module to the European Space Agency-provided service module. The Orion spacecraft will launch atop NASA’s Space Launch System rocket on EM-1, its first deep space mission, in late 2018.

Orion EM-1 Crew Module Adapter Move to Clean Room

NASA Image and Video Library

2016-11-29

Inside the Neil Armstrong Operations and Checkout Building high bay at NASA’s Kennedy Space Center in Florida, Lockheed Martin technicians move the Orion crew module adapter (CMA) for Exploration Mission 1 (EM-1) into a clean room. The CMA will undergo propellant and environmental control and life support system tube installation and welding. The adapter will connect the Orion crew module to the European Space Agency-provided service module. The Orion spacecraft will launch atop NASA’s Space Launch System rocket on EM-1, its first deep space mission, in late 2018.

Orion EM-1 Crew Module Adapter Move to Clean Room

NASA Image and Video Library

2016-11-29

Inside the Neil Armstrong Operations and Checkout Building high bay at NASA’s Kennedy Space Center in Florida, Lockheed Martin technicians begin to move the Orion crew module adapter (CMA) for Exploration Mission 1 (EM-1) to a clean room. The CMA will undergo propellant and environmental control and life support system tube installation and welding. The adapter will connect the Orion crew module to the European Space Agency-provided service module. The Orion spacecraft will launch atop NASA’s Space Launch System rocket on EM-1, its first deep space mission, in late 2018.

Orion EM-1 Crew Module Adapter Move to Clean Room

NASA Image and Video Library

2016-11-29

Inside the Neil Armstrong Operations and Checkout Building high bay at NASA’s Kennedy Space Center in Florida, Lockheed Martin technicians move the Orion crew module adapter (CMA) for Exploration Mission 1 (EM-1) toward a clean room. The CMA will undergo propellant and environmental control and life support system tube installation and welding. The adapter will connect the Orion crew module to the European Space Agency-provided service module. The Orion spacecraft will launch atop NASA’s Space Launch System rocket on EM-1, its first deep space mission, in late 2018.

Stabilizing the body centered cubic crystal in titanium alloys by a nano-scale concentration modulation

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

Wang, H. L.; Shah, S. A. A.; Hao, Y. L.

It is well-known that the body centered cubic (bcc) crystal in titanium alloys reaches its stability limit as the electron-to-atom (e/a) ratio of the alloy drops down to ~4.24. This critical value, however, is much higher than that of a multifunctional bcc type alloy (e/a = 4.15). Here we demonstrate that a nano-scale concentration modulation created by spinodal decomposition is what stabilizes the bcc crystal of the alloy. Aided by such a nano-scale concentration heterogeneity, unexpected properties from its chemically homogeneous counterpart are obtained. This provides a new strategy to design functional titanium alloys by tuning the spinodal decomposition.

Arabidopsis Glutamate Receptor Homolog3.5 Modulates Cytosolic Ca2+ Level to Counteract Effect of Abscisic Acid in Seed Germination1[OPEN

PubMed Central

Kong, Dongdong; Ju, Chuanli; Parihar, Aisha; Kim, So; Cho, Daeshik; Kwak, June M.

2015-01-01

Seed germination is a critical step in a plant’s life cycle that allows successful propagation and is therefore strictly controlled by endogenous and environmental signals. However, the molecular mechanisms underlying germination control remain elusive. Here, we report that the Arabidopsis (Arabidopsis thaliana) glutamate receptor homolog3.5 (AtGLR3.5) is predominantly expressed in germinating seeds and increases cytosolic Ca2+ concentration that counteracts the effect of abscisic acid (ABA) to promote germination. Repression of AtGLR3.5 impairs cytosolic Ca2+ concentration elevation, significantly delays germination, and enhances ABA sensitivity in seeds, whereas overexpression of AtGLR3.5 results in earlier germination and reduced seed sensitivity to ABA. Furthermore, we show that Ca2+ suppresses the expression of ABSCISIC ACID INSENSITIVE4 (ABI4), a key transcription factor involved in ABA response in seeds, and that ABI4 plays a fundamental role in modulation of Ca2+-dependent germination. Taken together, our results provide molecular genetic evidence that AtGLR3.5-mediated Ca2+ influx stimulates seed germination by antagonizing the inhibitory effects of ABA through suppression of ABI4. These findings establish, to our knowledge, a new and pivotal role of the plant glutamate receptor homolog and Ca2+ signaling in germination control and uncover the orchestrated modulation of the AtGLR3.5-mediated Ca2+ signal and ABA signaling via ABI4 to fine-tune the crucial developmental process, germination, in Arabidopsis. PMID:25681329

Turbidity. Training Module 5.240.2.77.

ERIC Educational Resources Information Center

Bonte, John L.; Davidson, Arnold C.

This document is an instructional module package prepared in objective form for use by an instructor familiar with candle turbidimeter and the nephelometric method of turbidity analysis. Included are objectives, an instructor guide, student handout, and transparency masters. A video tape is also available from the author. This module considers use…

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

Rearden, Bradley T; Marshall, William BJ J

In the course of criticality code validation, outlier cases are frequently encountered. Historically, the causes of these unexpected results could be diagnosed only through comparison with other similar cases or through the known presence of a unique component of the critical experiment. The sensitivity and uncertainty (S/U) analysis tools available in the SCALE 6.1 code system provide a much broader range of options to examine underlying causes of outlier cases. This paper presents some case studies performed as a part of the recent validation of the KENO codes in SCALE 6.1 using S/U tools to examine potential causes of biases.

Temporal modulations in speech and music.

PubMed

Ding, Nai; Patel, Aniruddh D; Chen, Lin; Butler, Henry; Luo, Cheng; Poeppel, David

2017-10-01

Speech and music have structured rhythms. Here we discuss a major acoustic correlate of spoken and musical rhythms, the slow (0.25-32Hz) temporal modulations in sound intensity and compare the modulation properties of speech and music. We analyze these modulations using over 25h of speech and over 39h of recordings of Western music. We show that the speech modulation spectrum is highly consistent across 9 languages (including languages with typologically different rhythmic characteristics). A different, but similarly consistent modulation spectrum is observed for music, including classical music played by single instruments of different types, symphonic, jazz, and rock. The temporal modulations of speech and music show broad but well-separated peaks around 5 and 2Hz, respectively. These acoustically dominant time scales may be intrinsic features of speech and music, a possibility which should be investigated using more culturally diverse samples in each domain. Distinct modulation timescales for speech and music could facilitate their perceptual analysis and its neural processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

RNA Modulates the Interaction between Influenza A Virus NS1 and Human PABP1.

PubMed

Arias-Mireles, Bryan H; de Rozieres, Cyrus M; Ly, Kevin; Joseph, Simpson

2018-05-25

Nonstructural protein 1 (NS1) is a multifunctional protein involved in preventing host-interferon response in influenza A virus (IAV). Previous studies have indicated that NS1 also stimulates the translation of viral mRNA by binding to conserved sequences in the viral 5'-UTR. Additionally, NS1 binds to poly(A) binding protein 1 (PABP1) and eukaryotic initiation factor 4G (eIF4G). The interaction of NS1 with the viral 5'-UTR, PABP1, and eIF4G has been suggested to specifically enhance the translation of viral mRNAs. In contrast, we report that NS1 does not directly bind to sequences in the viral 5'-UTR, indicating that NS1 is not responsible for providing the specificity to stimulate viral mRNA translation. We also monitored the interaction of NS1 with PABP1 using a new, quantitative FRET assay. Our data show that NS1 binds to PABP1 with high affinity; however, the binding of double-stranded RNA (dsRNA) to NS1 weakens the binding of NS1 to PABP1. Correspondingly, the binding of PABP1 to NS1 weakens the binding of NS1 to double-stranded RNA (dsRNA). In contrast, the affinity of PABP1 for binding to poly(A) RNA is not significantly changed by NS1. We propose that the modulation of NS1·PABP1 interaction by dsRNA may be important for the viral cycle.

Biochemical modulation of 5-fluorouracil by methotrexate in patients with advanced gastric carcinoma.

PubMed

Pérez, J E; Lacava, J A; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Romero Acuña, L A; Langhi, M J; Romero Acuña, J M; Vallejo, C T; Leone, B A; Machiavelli, M R; Romero, A O

1998-10-01

A phase II trial was conducted to evaluate the efficacy and toxicity of a modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) (with leucovorin (LV) rescue) as first-line chemotherapy in patients with locally advanced (inoperable) or metastatic gastric carcinoma. From July 1993 through August 1996, 36 patients with advanced gastric carcinoma received a regimen that consisted of: MTX 200 mg/m2 diluted in 250 ml normal saline by intravenous infusion over 20 minutes at hour 0; 5-FU 1,200 mg/m2 intravenous push injection at hour 20. Beginning 24 hours after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 hours for six doses. Cycles were repeated every 15 days. One patient was not assessable for response. Objective regression was observed in 15 of 37 patients (43%; 95% confidence interval, 26%-60%). One patient (3%) achieved complete response and 14 (40%) achieved partial response. No change was recorded in 14 patients (40%) and progressive disease was noted in six patients (17%). The median time to treatment failure was 7 months and the median survival was 12 months. Toxicity was within acceptable limits but one therapy-related death resulting from severe leukopenia occurred. The dose-limiting toxicity was mucositis. Five episodes of grade 3 or 4 stomatitis were observed and caused dosage modifications of MTX and 5-FU. Biochemical modulation of 5-FU by MTX appears as an attractive modality in patients with advanced gastric cancer. Further investigation both in experimental and clinical fields is needed to clearly define its role and to design the best modulatory strategy.

Nutrient-induced glucagon like peptide-1 release is modulated by serotonin.

PubMed

Ripken, Dina; van der Wielen, Nikkie; Wortelboer, Heleen M; Meijerink, Jocelijn; Witkamp, Renger F; Hendriks, Henk F J

2016-06-01

Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists. Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50mM) and rebaudioside A (12.5mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release. Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155μM) further enhanced casein and safflower oil induced-serotonin release. Exposure of ileal tissue segments to serotonin (30μM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100μM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10μM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of fluorescent particle size on the modulation efficiency of ultrasound-modulated fluorescence.

PubMed

Liu, Yuan; Yuan, Baohong; Vignola, Joseph

2012-01-01

To investigate whether the size of fluorescent particles affects the modulation efficiency of ultrasound-modulated fluorescence (UMF), we measured UMF and DC (direct current) signals of the fluorescence emission from four different sized fluorescent particles: (1) three carboxylate-modified fluorescent microspheres (FM) with diameters of 20 nm, 200 nm, and 1.0 µm and (2) streptavidin-conjugated Alexa Fluor 647 with a diameter of approximately 5 nm. The UMF and DC signals were simultaneously measured using a broadband lock-in amplifier and a narrowband amplifier, respectively. The ratio of the UMF strength to the DC signal strength is defined as the modulation efficiency. This modulation efficiency was then used to evaluate the effects of fluorophore size and concentration. Results show that the modulation efficiency was improved by approximately a factor of two when the size of the fluorescent particles is increased from 5 nm to 1 µm. In addition, the linear relationship between the UMF strength and ultrasound pressure (observed in our previous study) were maintained regardless of the fluorescent particle sizes.

Effect of fluorescent particle size on the modulation efficiency of ultrasound-modulated fluorescence

PubMed Central

Liu, Yuan; Yuan, Baohong; Vignola, Joseph

2013-01-01

To investigate whether the size of fluorescent particles affects the modulation efficiency of ultrasound-modulated fluorescence (UMF), we measured UMF and DC (direct current) signals of the fluorescence emission from four different sized fluorescent particles: (1) three carboxylate-modified fluorescent microspheres (FM) with diameters of 20 nm, 200 nm, and 1.0 µm and (2) streptavidin-conjugated Alexa Fluor 647 with a diameter of approximately 5 nm. The UMF and DC signals were simultaneously measured using a broadband lock-in amplifier and a narrowband amplifier, respectively. The ratio of the UMF strength to the DC signal strength is defined as the modulation efficiency. This modulation efficiency was then used to evaluate the effects of fluorophore size and concentration. Results show that the modulation efficiency was improved by approximately a factor of two when the size of the fluorescent particles is increased from 5 nm to 1 µm. In addition, the linear relationship between the UMF strength and ultrasound pressure (observed in our previous study) were maintained regardless of the fluorescent particle sizes. PMID:24179476

A finite-volume module for all-scale Earth-system modelling at ECMWF

NASA Astrophysics Data System (ADS)

Kühnlein, Christian; Malardel, Sylvie; Smolarkiewicz, Piotr

2017-04-01

We highlight recent advancements in the development of the finite-volume module (FVM) (Smolarkiewicz et al., 2016) for the IFS at ECMWF. FVM represents an alternative dynamical core that complements the operational spectral dynamical core of the IFS with new capabilities. Most notably, these include a compact-stencil finite-volume discretisation, flexible meshes, conservative non-oscillatory transport and all-scale governing equations. As a default, FVM solves the compressible Euler equations in a geospherical framework (Szmelter and Smolarkiewicz, 2010). The formulation incorporates a generalised terrain-following vertical coordinate. A hybrid computational mesh, fully unstructured in the horizontal and structured in the vertical, enables efficient global atmospheric modelling. Moreover, a centred two-time-level semi-implicit integration scheme is employed with 3D implicit treatment of acoustic, buoyant, and rotational modes. The associated 3D elliptic Helmholtz problem is solved using a preconditioned Generalised Conjugate Residual approach. The solution procedure employs the non-oscillatory finite-volume MPDATA advection scheme that is bespoke for the compressible dynamics on the hybrid mesh (Kühnlein and Smolarkiewicz, 2017). The recent progress of FVM is illustrated with results of benchmark simulations of intermediate complexity, and comparison to the operational spectral dynamical core of the IFS. C. Kühnlein, P.K. Smolarkiewicz: An unstructured-mesh finite-volume MPDATA for compressible atmospheric dynamics, J. Comput. Phys. (2017), in press. P.K. Smolarkiewicz, W. Deconinck, M. Hamrud, C. Kühnlein, G. Mozdzynski, J. Szmelter, N.P. Wedi: A finite-volume module for simulating global all-scale atmospheric flows, J. Comput. Phys. 314 (2016) 287-304. J. Szmelter, P.K. Smolarkiewicz: An edge-based unstructured mesh discretisation in geospherical framework, J. Comput. Phys. 229 (2010) 4980-4995.

Mutations in IRX5 impair craniofacial development and germ cell migration via SDF1.

PubMed

Bonnard, Carine; Strobl, Anna C; Shboul, Mohammad; Lee, Hane; Merriman, Barry; Nelson, Stanley F; Ababneh, Osama H; Uz, Elif; Güran, Tülay; Kayserili, Hülya; Hamamy, Hanan; Reversade, Bruno

2012-05-13

Using homozygosity mapping and locus resequencing, we found that alterations in the homeodomain of the IRX5 transcription factor cause a recessive congenital disorder affecting face, brain, blood, heart, bone and gonad development. We found through in vivo modeling in Xenopus laevis embryos that Irx5 modulates the migration of progenitor cell populations in branchial arches and gonads by repressing Sdf1. We further found that transcriptional control by Irx5 is modulated by direct protein-protein interaction with two GATA zinc-finger proteins, GATA3 and TRPS1; disruptions of these proteins also cause craniofacial dysmorphisms. Our findings suggest that IRX proteins integrate combinatorial transcriptional inputs to regulate key signaling molecules involved in the ontogeny of multiple organs during embryogenesis and homeostasis.

Redesign of Glenn Research Center D1 Flywheel Module

NASA Technical Reports Server (NTRS)

Jansen, Ralph H.; Wagner, Robert C.; Duffy, Kirsten P.; Hervol, David S.; Storozuk, Ronald J.; Dever, Timothy P.; Anzalone, Salvatore M.; Trudell, Jeffrey J.; Konno, Kevin E.; Kenny, Andrew

2002-01-01

Glenn Research Center has completed the redesign of the D1 flywheel module. The redesign includes a new rotor with a composite rim, motor/generator, touchdown bearings, sensors, and a magnetic actuator. The purpose of the relatively low cost module upgrade is to enable it to continuously operate throughout its speed range of 0 to 60,000 RPM. The module will be used as part of a combined attitude control and bus regulation experiment.

Spatial Scaling of the Profile of Selective Attention in the Visual Field.

PubMed

Gannon, Matthew A; Knapp, Ashley A; Adams, Thomas G; Long, Stephanie M; Parks, Nathan A

2016-01-01

Neural mechanisms of selective attention must be capable of adapting to variation in the absolute size of an attended stimulus in the ever-changing visual environment. To date, little is known regarding how attentional selection interacts with fluctuations in the spatial expanse of an attended object. Here, we use event-related potentials (ERPs) to investigate the scaling of attentional enhancement and suppression across the visual field. We measured ERPs while participants performed a task at fixation that varied in its attentional demands (attentional load) and visual angle (1.0° or 2.5°). Observers were presented with a stream of task-relevant stimuli while foveal, parafoveal, and peripheral visual locations were probed by irrelevant distractor stimuli. We found two important effects in the N1 component of visual ERPs. First, N1 modulations to task-relevant stimuli indexed attentional selection of stimuli during the load task and further correlated with task performance. Second, with increased task size, attentional modulation of the N1 to distractor stimuli showed a differential pattern that was consistent with a scaling of attentional selection. Together, these results demonstrate that the size of an attended stimulus scales the profile of attentional selection across the visual field and provides insights into the attentional mechanisms associated with such spatial scaling.

Free-Spinning-Tunnel Tests of a 1/16-Scale Model of the Chance Vought XF5U-1 Airplane, TED No. NACA 2349

NASA Technical Reports Server (NTRS)

White, Richard P.

1947-01-01

Spin tests of a 1/16-scale model of the Chance Vought XF5U-1 airplane have been performed in the Langley 20-foot free-spinning tunnel. The effect of control position and movement upon the erect and inverted spin and recovery characteristics ae well as the effects of propellers, of stability flaps, and of various revisions to the design configuration have been determined for the normal fighter loading. The investigation also included spin recovery parachute, tumbling, and pilot-escape tests. For the original design configuration, with or without windmilling propellers, the recovery characteristics of the model were considered unsatisfactory. Increasing the maximum upward deflection of the ailavators from 45 deg to 65 deg resulted in greatly improved recovery characteristics. Dimensional revisions to the original airplane configuration, which satisfactorily improved the general spin and recovery characteristics of the model, consisted of: (1) a supplementary vertical tail 34 inches by 59 inches (full-scale) attached to a boom 80 inches aft of the trailing edge of the airplane in the plane of symmetry, (2) a large semispan undersurface spoiler placed along the airplane quarter-chord line and opened on the outboard side in a spin, or (3) two additional vertical tails 64 inches by 52 inches (full-scale) located at the tips of the ailavators. A satisfactory parachute arrangement for emergency spin recovery from demonstration spins was found to be an arrangement consisting of a 13.3-foot parachute attached by a 30-foot towline to the arresting gear mast on the airplane and opened simultaneously with an 8-foot parachute on the outboard end of the wing attached by a 3-foot towline. Tests indicated that pilot escape from a spin would be extremely hazardous unless the pilot is mechanically ejected from the cockpit. Model tumbling tests indicated that the airplane would not tumble.

Orion EM-1 Crew Module Adapter Move to Clean Room

NASA Image and Video Library

2016-11-29

Inside the Neil Armstrong Operations and Checkout Building high bay at NASA's Kennedy Space Center in Florida, Lockheed Martin technicians secure a protective cover around the Orion crew module adapter (CMA) for Exploration Mission 1 (EM-1) for its move to a clean room. The CMA will undergo propellant and environmental control and life support system tube installation and welding. The adapter will connect the Orion crew module to the European Space Agency-provided service module. The Orion spacecraft will launch atop NASA’s Space Launch System rocket on EM-1, its first deep space mission, in late 2018.

Orion EM-1 Crew Module Adapter Move to Clean Room

NASA Image and Video Library

2016-11-29

Inside the Neil Armstrong Operations and Checkout Building high bay at NASA’s Kennedy Space Center in Florida, a Lockheed Martin technician secures a protective cover around the Orion crew module adapter (CMA) for Exploration Mission 1 (EM-1) for its move to a clean room The CMA will undergo propellant and environmental control and life support system tube installation and welding. The adapter will connect the Orion crew module to the European Space Agency-provided service module. The Orion spacecraft will launch atop NASA’s Space Launch System rocket on EM-1, its first deep space mission, in late 2018.

Orion EM-1 Crew Module Adapter Move to Clean Room

NASA Image and Video Library

2016-11-29

Inside the Neil Armstrong Operations and Checkout Building high bay at NASA’s Kennedy Space Center in Florida, Lockheed Martin technicians secure a protective cover around the Orion crew module adapter (CMA) for Exploration Mission 1 (EM-1) for its move to a clean room. The CMA will undergo propellant and environmental control and life support system tube installation and welding. The adapter will connect the Orion crew module to the European Space Agency-provided service module. The Orion spacecraft will launch atop NASA’s Space Launch System rocket on EM-1, its first deep space mission, in late 2018.

Orion EM-1 Crew Module Adapter Move to Clean Room

NASA Image and Video Library

2016-11-29

Inside the Neil Armstrong Operations and Checkout Building high bay at NASA’s Kennedy Space Center in Florida, a protective cover is installed around the Orion crew module adapter (CMA) for Exploration Mission 1 (EM-1) for its move to a clean room. The CMA will undergo propellant and environmental control and life support system tube installation and welding. The adapter will connect the Orion crew module to the European Space Agency-provided service module. The Orion spacecraft will launch atop NASA’s Space Launch System rocket on EM-1, its first deep space mission, in late 2018.

Orion EM-1 Crew Module Adapter Move to Clean Room

NASA Image and Video Library

2016-11-29

Inside the Neil Armstrong Operations and Checkout Building high bay at NASA’s Kennedy Space Center in Florida, Lockheed Martin technicians are preparing the Orion crew module adapter (CMA) for Exploration Mission 1 (EM-1) for the move into a clean room. The CMA will undergo propellant and environmental control and life support system tube installation and welding. The adapter will connect the Orion crew module to the European Space Agency-provided service module. The Orion spacecraft will launch atop NASA’s Space Launch System rocket on EM-1, its first deep space mission, in late 2018.

Orion EM-1 Crew Module Adapter Move to Clean Room

NASA Image and Video Library

2016-11-29

Inside the Neil Armstrong Operations and Checkout Building high bay at NASA's Kennedy Space Center in Florida, Lockheed Martin technicians secure a protective cover around the Orion crew module adapter (CMA) for Exploration Mission 1 (EM-1) for its move to a clean. The CMA will undergo propellant and environmental control and life support system tube installation and welding. The adapter will connect the Orion crew module to the European Space Agency-provided service module. The Orion spacecraft will launch atop NASA’s Space Launch System rocket on EM-1, its first deep space mission, in late 2018.

Orion EM-1 Crew Module Adapter Move to Clean Room

NASA Image and Video Library

2016-11-29

Inside the Neil Armstrong Operations and Checkout Building high bay at NASA’s Kennedy Space Center in Florida, the Orion crew module adapter (CMA) for Exploration Mission 1 (EM-1) is in a clean room with protective walls secured around it. The adapter will undergo propellant and environmental control and life support system tube installation and welding. The adapter will connect the Orion crew module to the European Space Agency-provided service module. The Orion spacecraft will launch atop NASA’s Space Launch System rocket on EM-1, its first deep space mission, in late 2018.

Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity.

PubMed

Scott, F L; Clemons, B; Brooks, J; Brahmachary, E; Powell, R; Dedman, H; Desale, H G; Timony, G A; Martinborough, E; Rosen, H; Roberts, E; Boehm, M F; Peach, R J

2016-06-01

Sphingosine1-phosphate (S1P) receptors mediate multiple events including lymphocyte trafficking, cardiac function, and endothelial barrier integrity. Stimulation of S1P1 receptors sequesters lymphocyte subsets in peripheral lymphoid organs, preventing their trafficking to inflamed tissue sites, modulating immunity. Targeting S1P receptors for treating autoimmune disease has been established in clinical studies with the non-selective S1P modulator, FTY720 (fingolimod, Gilenya™). The purpose of this study was to assess RPC1063 for its therapeutic utility in autoimmune diseases. The specificity and potency of RPC1063 (ozanimod) was evaluated for all five S1P receptors, and its effect on cell surface S1P1 receptor expression, was characterized in vitro. The oral pharmacokinetic (PK) parameters and pharmacodynamic effects were established in rodents, and its activity in three models of autoimmune disease (experimental autoimmune encephalitis, 2,4,6-trinitrobenzenesulfonic acid colitis and CD4(+) CD45RB(hi) T cell adoptive transfer colitis) was assessed. RPC1063 was specific for S1P1 and S1P5 receptors, induced S1P1 receptor internalization and induced a reversible reduction in circulating B and CCR7(+) T lymphocytes in vivo. RPC1063 showed high oral bioavailability and volume of distribution, and a circulatory half-life that supports once daily dosing. Oral RPC1063 reduced inflammation and disease parameters in all three autoimmune disease models. S1P receptor selectivity, favourable PK properties and efficacy in three distinct disease models supports the clinical development of RPC1063 for the treatment of relapsing multiple sclerosis and inflammatory bowel disease, differentiates RPC1063 from other S1P receptor agonists, and could result in improved safety outcomes in the clinic. © 2016 The British Pharmacological Society.

Helms in Node 1/Unity module

NASA Image and Video Library

2001-04-07

ISS002-E-5511 (07 April 2001) --- Astronaut Susan J. Helms, Expedition Two flight engineer, pauses from moving through the Node 1 / Unity module of the International Space Station (ISS) to pose for a photograph. This image was recorded with a digital still camera.

Millwright Apprenticeship. Related Training Modules. 17.1-17.13 Hydraulics.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

This packet of 13 learning modules on hydraulics is 1 of 6 such packets developed for apprenticeship training for millwrights. Introductory materials are a complete listing of all available modules and a supplementary reference list. Each module contains some or all of these components: goal, performance indicators, study guide (a check list of…

A thermal scale modeling study for Apollo and Apollo applications, volume 1

NASA Technical Reports Server (NTRS)

Shannon, R. L.

1972-01-01

The program is reported for developing and demonstrating the capabilities of thermal scale modeling as a thermal design and verification tool for Apollo and Apollo Applications Projects. The work performed for thermal scale modeling of STB; cabin atmosphere/spacecraft cabin wall thermal interface; closed loop heat rejection radiator; and docked module/spacecraft thermal interface are discussed along with the test facility requirements for thermal scale model testing of AAP spacecraft. It is concluded that thermal scale modeling can be used as an effective thermal design and verification tool to provide data early in a spacecraft development program.

Wavelength-modulation-spectroscopy for real-time, in situ NO detection in combustion gases with a 5.2 μm quantum-cascade laser

NASA Astrophysics Data System (ADS)

Chao, X.; Jeffries, J. B.; Hanson, R. K.

2012-03-01

A mid-infrared absorption strategy with calibration-free wavelength-modulation-spectroscopy (WMS) has been developed and demonstrated for real-time, in situ detection of nitric oxide in particulate-laden combustion-exhaust gases up to temperatures of 700 K. An external-cavity quantum-cascade laser (ECQCL) near 5.2 μm accessed the fundamental absorption band of NO, and a wavelength-scanned, 1 f-normalized WMS with second-harmonic detection (WMS-2 f/1 f) strategy was developed. Due to the external-cavity laser architecture, large nonlinear intensity modulation (IM) was observed when the wavelength was modulated by injection-current modulation, and the IM indices were also found to be strongly wavelength-dependent as the center wavelength was scanned with piezoelectric tuning of the cavity. A quantitative model of the 1 f-normalized WMS-2 f signal was developed and validated under laboratory conditions. A sensor was subsequently designed, built and demonstrated for real-time, in situ measurements of NO across a 3 m path in the particulate-laden exhaust of a pulverized-coal-fired power plant boiler. The 1 f-normalized WMS-2 f method proved to have better noise immunity for non-absorption transmission, than wavelength-scanned direct absorption. A 0.3 ppm-m detection limit was estimated using the R15.5 transition near 1927 cm-1 with 1 s averaging. Mid-infrared QCL-based NO absorption with 1 f-normalized WMS-2 f detection shows excellent promise for practical sensing in the combustion exhaust.

Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs) Part III: Discovery of 4-(5-oxopyrrolidine-1-yl)benzonitrile derivative 2f as a clinical candidate.

PubMed

Aikawa, Katsuji; Asano, Moriteru; Ono, Koji; Habuka, Noriyuki; Yano, Jason; Wilson, Keith; Fujita, Hisashi; Kandori, Hitoshi; Hara, Takahito; Morimoto, Megumi; Santou, Takashi; Yamaoka, Masuo; Nakayama, Masaharu; Hasuoka, Atsushi

2017-07-01

We previously reported that 4-(pyrrolidin-1-yl)benzonitrile derivative 1b was a selective androgen receptor modulator (SARM) that exhibited anabolic effects on organs such as muscles and the central nervous system (CNS), but neutral effects on the prostate. From further modification, we identified that 4-(5-oxopyrrolidine-1-yl)benzonitrile derivative 2a showed strong AR binding affinity with improved metabolic stabilities. Based on these results, we tried to enhance the AR agonistic activities by modifying the substituents of the 5-oxopyrrolidine ring. As a consequence, we found that 4-[(2S,3S)-2-ethyl-3-hydroxy-5-oxopyrrolidin-1-yl]-2-(trifluoromethyl)benzonitrile (2f) had ideal SARM profiles in Hershberger assay and sexual behavior induction assay. Furthermore, 2f showed good pharmacokinetic profiles in rats, dogs, monkeys, excellent nuclear selectivity and acceptable toxicological profiles. We also determined its binding mode by obtaining the co-crystal structures with AR. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cloning and differential expression of steroid 5 alpha-reductase type 1 (Srd5a1) and type 2 (Srd5a2) from the Harderian glands of hamsters.

PubMed

Ramos, Luis; Chávez, Bertha; Vilchis, Felipe

2010-04-01

In hamsters, the Harderian glands (HGs) exhibit a marked sexual dimorphism which is thought to depend on dihydrotestosterone (DHT); however, it is unclear whether hamster HGs contain one or more 5 alpha-reductases and whether these enzymes are differentially expressed in males and females. In this study, we isolated specific cDNAs for 5 alpha-reductase 1 (Srd5a1) and 5 alpha-reductase 2 (Srd5a2), determined their sequences and investigated their expression in the HG of both sexes. Isozyme 1, cloned from liver mRNA, encodes a protein of 255 amino acids (aa); isozyme 2 cDNA, isolated from the epididymis encodes a 254-aa protein. When assayed in transfected HEK-293 cells, the type 1 isozyme displayed activity over a broad pH range (6.5-8), while isozyme 2 had a pH optimum of 5.5. Both isoenzymes efficiently catalyzed the in vitro transformation of T into DHT, with apparent K(m) values of 7.1 and 1.9 micromol/L for Srd5a1 and Srd5a2, respectively. Real-time PCR analysis revealed higher mRNA levels for Srd5a1 than for Srd5a2. Expression of both isoenzymes increased slightly in HGs of castrated males and showed variations during the estrous cycle in females. Hormonal replacement with 17beta-estradiol administered to spayed females induced the up-regulation of Srd5a2 mRNA levels. Altogether, our results demonstrated that both Srd5a1 and Srd5a2 are expressed in HGs without clear differences between males and females. The biochemical characteristics and relative expression of these 5 alpha-reductases support the view that both isozymes may play a relevant role in modulating androgen signaling in HG. (c) 2009 Elsevier Inc. All rights reserved.

Selective Modulation of K+ Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons.

PubMed

Zhao, Chen; Su, Min; Wang, Yingzi; Li, Xinmeng; Zhang, Yongxue; Du, Xiaona; Zhang, Hailin

2017-01-01

The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K + channel modulators.

Selective Modulation of K+ Channel Kv7.4 Significantly Affects the Excitability of DRN 5-HT Neurons

PubMed Central

Zhao, Chen; Su, Min; Wang, Yingzi; Li, Xinmeng; Zhang, Yongxue; Du, Xiaona; Zhang, Hailin

2017-01-01

The serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN) is implicated in various mood- and emotion-related disorders, such as anxiety, fear and stress. Abnormal activity of DRN 5-HT neurons is the key factor in the development of these disorders. Here, we describe a crucial role for the Kv7.4 potassium channel in modulating DRN 5-HT neuronal excitability. We demonstrate that Kv7.4 is selectively expressed in 5-HT neurons of the DRN. Using selective Kv7.4 opener fasudil and Kv7.4 knock-out mice, we demonstrate that Kv7.4 is a potent modulator of DRN 5-HT neuronal excitability. Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4. The current study suggests a new strategy for treating psychiatric disorders related to altered activity of DRN 5-HT neurons using K+ channel modulators. PMID:29311835

Structural modulation and luminescent properties of four Cd{sup II} coordination architectures based on 3-(pyridin-4-yl)-5-(pyrazin-2-yl)-1H-1,2,4-triazole and flexible/rigid dicarboxylate ligands

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

Xia, Liang; Dong, Wen-Wen, E-mail: dongww1@126.com; Ye, Xiao

To systematically investigate the influence of the flexible or rigid auxiliary ligands on the structures and properties of transition metal compounds, we synthesized four new d{sup 10} coordination polymers (CPs) from 3-(pyridin-4-yl)-5-(pyrazin-2-yl)-1H-1,2,4-triazole (4-Hpzpt) and flexible/rigid dicarboxylate ligands, [Cd(4-pzpt){sub 2}]{sub n} (1), [Cd{sub 3}(4-pzpt){sub 2}(suc){sub 2}]{sub n} (2), [Cd{sub 2}(4-Hpzpt)(nbc){sub 2}(H{sub 2}O)]{sub n} (3) and ([Cd{sub 2}(4-pzpt){sub 2}(tfbdc)(H{sub 2}O){sub 4}]·H{sub 2}O){sub n} (4) (H{sub 2}suc=1,2-ethanedicarboxylic acid, H{sub 2}nbc=hthalene-1,4-dicarboxylic acid, H{sub 2}tfbdc =2,3,5,6-tetrafluoroterephthalic acid). Single crystal X-ray analysis indicates that compound 1 shows a 4{sup 4}-sql layer, which is extended to a 3D network via nonclassical C–H{sup …}N hydrogen bonds. Compound 2more » possesses a 6-connected pcu-4{sup 12}0.6{sup 3} net composed of trinuclear Cd{sup II}-clusters. Compound 3 represents a rare 3D (3,4,4,5)-connected topology with a Schläfli symbol of (4·6·7)(4·5{sup 3}·7{sup 2})(5{sup 3}·6·7·9)(4{sup 2}·5{sup 5}·6·7{sup 2}). Compound 4 exhibits a 2D+2D→2D parallel interpenetrated 6{sup 3}-hcb network. The adjacent 2D networks are interdigitated with each other to form the resulting 3D supramolecular architecture through classical O–H{sup …}N and O–H{sup …}O hydrogen bonds. Structural diversities indicate that the nature of flexible/rigid-dicarboxlates plays crucial roles in modulating structures of these compounds. Moreover, the luminescent properties of them have been briefly investigated. - Graphical abstract: Four new Cd{sup II} coordination architectures constructed from the primary ligand 4-Hpzpt and flexible/rigid dicarboxylate coligands. Structural diversities indicate that the nature of flexible/rigid-dicarboxlates plays crucial roles in modulating structures of these compounds. And more, the thermal stability and luminescence are discussed. - Highlights

Systemic modulation of serotonergic synapses via reuptake blockade or 5HT1A receptor antagonism does not alter perithreshold taste sensitivity in rats.