Sample records for sensitive detection psd

  1. Novel method of detecting movement of the interference fringes using one-dimensional PSD.

    PubMed

    Wang, Qi; Xia, Ji; Liu, Xu; Zhao, Yong

    2015-06-02

    In this paper, a method of using a one-dimensional position-sensitive detector (PSD) by replacing charge-coupled device (CCD) to measure the movement of the interference fringes is presented first, and its feasibility is demonstrated through an experimental setup based on the principle of centroid detection. Firstly, the centroid position of the interference fringes in a fiber Mach-Zehnder (M-Z) interferometer is solved in theory, showing it has a higher resolution and sensitivity. According to the physical characteristics and principles of PSD, a simulation of the interference fringe's phase difference in fiber M-Z interferometers and PSD output is carried out. Comparing the simulation results with the relationship between phase differences and centroid positions in fiber M-Z interferometers, the conclusion that the output of interference fringes by PSD is still the centroid position is obtained. Based on massive measurements, the best resolution of the system is achieved with 5.15, 625 μm. Finally, the detection system is evaluated through setup error analysis and an ultra-narrow-band filter structure. The filter structure is configured with a one-dimensional photonic crystal containing positive and negative refraction material, which can eliminate background light in the PSD detection experiment. This detection system has a simple structure, good stability, high precision and easily performs remote measurements, which makes it potentially useful in material small deformation tests, refractivity measurements of optical media and optical wave front detection.

  2. High sensitive and throughput screening of Aflatoxin using MALDI-TOF-TOF-PSD-MS/MS

    USDA-ARS?s Scientific Manuscript database

    We have achieved sensitive and efficient detection of aflatoxin B1(AFB1) through matrix-assisted laser desorption/ionization time-of-flight-time-of-flight mass spectrometry (MALDI-TOF-TOF) and post-source decay (PSD) tandem mass spectrometry (MS/MS) using an acetic acid – a-cyano-4-hydroxycinnamic a...

  3. Vibration Measurement Method of a String in Transversal Motion by Using a PSD.

    PubMed

    Yang, Che-Hua; Wu, Tai-Chieh

    2017-07-17

    A position sensitive detector (PSD) is frequently used for the measurement of a one-dimensional position along a line or a two-dimensional position on a plane, but is more often used for measuring static or quasi-static positions. Along with its quick response when measuring short time-spans in the micro-second realm, a PSD is also capable of detecting the dynamic positions of moving objects. In this paper, theoretical modeling and experiments are conducted to explore the frequency characteristics of a vibrating string while moving transversely across a one-dimensional PSD. The theoretical predictions are supported by the experiments. When the string vibrates at its natural frequency while moving transversely, the PSD will detect two frequencies near this natural frequency; one frequency is higher than the natural frequency and the other is lower. Deviations in these two frequencies, which differ from the string's natural frequency, increase while the speed of motion increases.

  4. Vibration Measurement Method of a String in Transversal Motion by Using a PSD

    PubMed Central

    Yang, Che-Hua; Wu, Tai-Chieh

    2017-01-01

    A position sensitive detector (PSD) is frequently used for the measurement of a one-dimensional position along a line or a two-dimensional position on a plane, but is more often used for measuring static or quasi-static positions. Along with its quick response when measuring short time-spans in the micro-second realm, a PSD is also capable of detecting the dynamic positions of moving objects. In this paper, theoretical modeling and experiments are conducted to explore the frequency characteristics of a vibrating string while moving transversely across a one-dimensional PSD. The theoretical predictions are supported by the experiments. When the string vibrates at its natural frequency while moving transversely, the PSD will detect two frequencies near this natural frequency; one frequency is higher than the natural frequency and the other is lower. Deviations in these two frequencies, which differ from the string’s natural frequency, increase while the speed of motion increases. PMID:28714915

  5. Perturbing NR2B-PSD-95 interaction relieves neuropathic pain by inactivating CaMKII-CREB signaling.

    PubMed

    Xu, Fangxia; Zhao, Xin; Liu, Lin; Song, Jia; Zhu, Yingjun; Chu, Shuaishuai; Shao, Xueming; Li, Xiuxiu; Ma, Zhengliang; Gu, Xiaoping

    2017-09-06

    Neuropathic pain is characterized by central sensitization. The interaction between N-methyl-D-aspartate receptors (NMDARs) and postsynaptic density protein-95 (PSD-95) plays a major role in central sensitization. Here, we aimed to investigate the analgesic effect of disruption of the interaction between NMDAR and PSD-95. Chronic dorsal root ganglia compression model rats were used to mimic sciatica. Thermal hyperalgesia and mechanical allodynia were evaluated. The expression of spinal phospho-NR2B, PSD-95, calcium/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element binding protein (CREB) was measured using western blotting. A mimetic peptide Myr-NR2B9c was injected intrathecally to disrupt the interaction between PSD-95 and NR2B and detected by coimmunoprecipitation. Chronic dorsal root ganglia compression surgery induced thermal hyperalgesia and mechanical allodynia, and upregulated pain-related proteins such as phospho-NR2B, PSD-95, CaMKII, and CREB expressions in the spinal cord. Myr-NR2B9c disrupted the interaction between NR2B-containing NMDARs and PSD-95 in the spinal cord. Intrathecal administration of Myr-NR2B9c attenuated neuropathic pain behaviors and downregulated the expressions of phospho-NR2B, PSD-95, CaMKII, and CREB in the spinal cord. The present study indicates that dissociation of NR2B-containing NMDARs from PSD-95 inactivates CaMKII and CREB signaling and relieves pain.

  6. Design on wireless auto-measurement system for lead rail straightness measurement based on PSD

    NASA Astrophysics Data System (ADS)

    Yan, Xiugang; Zhang, Shuqin; Dong, Dengfeng; Cheng, Zhi; Wu, Guanghua; Wang, Jie; Zhou, Weihu

    2016-10-01

    Straightness detection is not only one of the key technologies for the product quality and installation accuracy of all types of lead rail, but also an important dimensional measurement technology. The straightness measuring devices now available have disadvantages of low automation level, limiting by measuring environment, and low measurement efficiency. In this paper, a wireless measurement system for straightness detection based on position sensitive detector (PSD) is proposed. The system has some advantage of high automation-level, convenient, high measurement efficiency, easy to transplanting and expanding, and can detect straightness of lead rail in real-time.

  7. Characterization and genetic mapping of a Photoperiod-sensitive dwarf 1 locus in rice (Oryza sativa L.).

    PubMed

    Li, Riqing; Xia, Jixing; Xu, Yiwei; Zhao, Xiucai; Liu, Yao-Guang; Chen, Yuanling

    2014-01-01

    Plant height is an important agronomic trait for crop architecture and yield. Most known factors determining plant height function in gibberellin or brassinosteroid biosynthesis or signal transduction. Here, we report a japonica rice (Oryza sativa ssp. japonica) dominant dwarf mutant, Photoperiod-sensitive dwarf 1 (Psd1). The Psd1 mutant showed impaired cell division and elongation, and a severe dwarf phenotype under long-day conditions, but nearly normal growth in short-day. The plant height of Psd1 mutant could not be rescued by gibberellin or brassinosteroid treatment. Genetic analysis with R1 and F2 populations determined that Psd1 phenotype was controlled by a single dominant locus. Linkage analysis with 101 tall F2 plants grown in a long-day season, which were derived from a cross between Psd1 and an indica cultivar, located Psd1 locus on chromosome 1. Further fine-mapping with 1017 tall F2 plants determined this locus on an 11.5-kb region. Sequencing analysis of this region detected a mutation site in a gene encoding a putative lipid transfer protein; the mutation produces a truncated C-terminus of the protein. This study establishes the genetic foundation for understanding the molecular mechanisms regulating plant cell division and elongation mediated by interaction between genetic and environmental factors.

  8. Post-synaptic Density-95 (PSD-95) Binding Capacity of G-protein-coupled Receptor 30 (GPR30), an Estrogen Receptor That Can Be Identified in Hippocampal Dendritic Spines*

    PubMed Central

    Akama, Keith T.; Thompson, Louisa I.; Milner, Teresa A.; McEwen, Bruce S.

    2013-01-01

    The estrogen 17β-estradiol (E2) modulates dendritic spine plasticity in the cornu ammonis 1 (CA1) region of the hippocampus, and GPR30 (G-protein coupled estrogen receptor 1 (GPER1)) is an estrogen-sensitive G-protein-coupled receptor (GPCR) that is expressed in the mammalian brain and in specific subregions that are responsive to E2, including the hippocampus. The subcellular localization of hippocampal GPR30, however, remains unclear. Here, we demonstrate that GPR30 immunoreactivity is detected in dendritic spines of rat CA1 hippocampal neurons in vivo and that GPR30 protein can be found in rat brain synaptosomes. GPR30 immunoreactivity is identified at the post-synaptic density (PSD) and in the adjacent peri-synaptic zone, and GPR30 can associate with the spine scaffolding protein PSD-95 both in vitro and in vivo. This PSD-95 binding capacity of GPR30 is specific and determined by the receptor C-terminal tail that is both necessary and sufficient for PSD-95 interaction. The interaction with PSD-95 functions to increase GPR30 protein levels residing at the plasma membrane surface. GPR30 associates with the N-terminal tandem pair of PDZ domains in PSD-95, suggesting that PSD-95 may be involved in clustering GPR30 with other receptors in the hippocampus. We demonstrate that GPR30 has the potential to associate with additional post-synaptic GPCRs, including the membrane progestin receptor, the corticotropin releasing hormone receptor, and the 5HT1a serotonin receptor. These data demonstrate that GPR30 is well positioned in the dendritic spine compartment to integrate E2 sensitivity directly onto multiple inputs on synaptic activity and might begin to provide a molecular explanation as to how E2 modulates dendritic spine plasticity. PMID:23300088

  9. Post-synaptic density-95 (PSD-95) binding capacity of G-protein-coupled receptor 30 (GPR30), an estrogen receptor that can be identified in hippocampal dendritic spines.

    PubMed

    Akama, Keith T; Thompson, Louisa I; Milner, Teresa A; McEwen, Bruce S

    2013-03-01

    The estrogen 17β-estradiol (E2) modulates dendritic spine plasticity in the cornu ammonis 1 (CA1) region of the hippocampus, and GPR30 (G-protein coupled estrogen receptor 1 (GPER1)) is an estrogen-sensitive G-protein-coupled receptor (GPCR) that is expressed in the mammalian brain and in specific subregions that are responsive to E2, including the hippocampus. The subcellular localization of hippocampal GPR30, however, remains unclear. Here, we demonstrate that GPR30 immunoreactivity is detected in dendritic spines of rat CA1 hippocampal neurons in vivo and that GPR30 protein can be found in rat brain synaptosomes. GPR30 immunoreactivity is identified at the post-synaptic density (PSD) and in the adjacent peri-synaptic zone, and GPR30 can associate with the spine scaffolding protein PSD-95 both in vitro and in vivo. This PSD-95 binding capacity of GPR30 is specific and determined by the receptor C-terminal tail that is both necessary and sufficient for PSD-95 interaction. The interaction with PSD-95 functions to increase GPR30 protein levels residing at the plasma membrane surface. GPR30 associates with the N-terminal tandem pair of PDZ domains in PSD-95, suggesting that PSD-95 may be involved in clustering GPR30 with other receptors in the hippocampus. We demonstrate that GPR30 has the potential to associate with additional post-synaptic GPCRs, including the membrane progestin receptor, the corticotropin releasing hormone receptor, and the 5HT1a serotonin receptor. These data demonstrate that GPR30 is well positioned in the dendritic spine compartment to integrate E2 sensitivity directly onto multiple inputs on synaptic activity and might begin to provide a molecular explanation as to how E2 modulates dendritic spine plasticity.

  10. The research of PSD location method in micro laser welding fields

    NASA Astrophysics Data System (ADS)

    Zhang, Qiue; Zhang, Rong; Dong, Hua

    2010-11-01

    In the field of micro laser welding, besides the special requirement in the parameter of lasers, the locating in welding points accurately is very important. The article adopt position sensitive detector (PSD) as hard core, combine optic system, electric circuits and PC and software processing, confirm the location of welding points. The signal detection circuits adopt the special integrate circuit H-2476 to process weak signal. It is an integrated circuit for high-speed, high-sensitivity optical range finding, which has stronger noiseproof feature, combine digital filter arithmetic, carry out repair the any non-ideal factors, increasing the measure precision. The amplifier adopt programmable amplifier LTC6915. The system adapt two dimension stepping motor drive the workbench, computer and corresponding software processing, make sure the location of spot weld. According to different workpieces to design the clamps. The system on-line detect PSD 's output signal in the moving processing. At the workbench moves in the X direction, the filaments offset is detected dynamic. Analyze the X axes moving sampling signal direction could be estimate the Y axes moving direction, and regulate the Y axes moving values. The workbench driver adopt A3979, it is a stepping motor driver with insert transducer and operate easily. It adapts the requirement of location in micro laser welding fields, real-time control to adjust by computer. It can be content up 20 μm's laser micro welding requirement on the whole. Using laser powder cladding technology achieve inter-penetration welding of high quality and reliability.

  11. Organic scintillators with pulse shape discrimination for detection of radiation (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Mabe, Andrew; Carman, M. Leslie; Glenn, Andrew M.; Zaitseva, Natalia P.; Payne, Stephen A.

    2016-09-01

    The detection of neutrons in the presence of gamma-ray fields has important applications in the fields of nuclear physics, homeland security, and medical imaging. Organic scintillators provide several attractive qualities as neutron detection materials including low cost, fast response times, ease of scaling, and the ability to implement pulse shape discrimination (PSD) to discriminate between neutrons and gamma-rays. This talk will focus on amorphous organic scintillators both in plastic form and small-molecule organic glass form. The first section of this talk will describe recent advances and improvements in the performance of PSD-capable plastic scintillators. The primary advances described in regard to modification of the polymer matrix, evaluation of new scintillating dyes, improved fabrication conditions, and implementation of additives which impart superior performance and mechanical properties to PSD-capable plastics as compared to commercially-available plastics and performance comparable to PSD-capable liquids. The second section of this talk will focus on a class of small-molecule organic scintillators based on modified indoles and oligophenylenes which form amorphous glasses as PSD-capable neutron scintillation materials. Though indoles and oligophenylenes have been known for many decades, their PSD properties have not been investigated and their scintillation properties only scantily investigated. Well-developed synthetic methodologies have permitted the synthesis of a library of structural analogs of these compounds as well as the investigation of their scintillation properties. The emission wavelengths of many indoles are in the sensitive region of common photomultiplier tubes, making them appropriate to be used as scintillators in either pure or doped form. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. This work has been supported by the U.S. Department of Energy Office of Nonproliferation Research and Development (NA-22) and by the Defense Threat Reduction Agency (DTRA).

  12. Analysis of surface EMG baseline for detection of hidden muscle activity

    NASA Astrophysics Data System (ADS)

    Zhang, Xu; Zhou, Ping

    2014-02-01

    Objective. This study explored the feasibility of detecting hidden muscle activity in surface electromyogram (EMG) baseline. Approach. Power spectral density (PSD) analysis and multi-scale entropy (MSE) analysis were used. Both analyses were applied to computer simulations of surface EMG baseline with the presence (representing activity data) or absence (representing reference data) of hidden muscle activity, as well as surface electrode array EMG baseline recordings of healthy control and amyotrophic lateral sclerosis (ALS) subjects. Main results. Although the simulated reference data and the activity data yielded no distinguishable difference in the time domain, they demonstrated a significant difference in the frequency and signal complexity domains with the PSD and MSE analyses. For a comparison using pooled data, such a difference was also observed when the PSD and MSE analyses were applied to surface electrode array EMG baseline recordings of healthy control and ALS subjects, which demonstrated no distinguishable difference in the time domain. Compared with the PSD analysis, the MSE analysis appeared to be more sensitive for detecting the difference in surface EMG baselines between the two groups. Significance. The findings implied the presence of a hidden muscle activity in surface EMG baseline recordings from the ALS subjects. To promote the presented analysis as a useful diagnostic or investigatory tool, future studies are necessary to assess the pathophysiological nature or origins of the hidden muscle activity, as well as the baseline difference at the individual subject level.

  13. Analysis of Surface EMG Baseline for Detection of Hidden Muscle Activity

    PubMed Central

    Zhang, Xu; Zhou, Ping

    2014-01-01

    Objective This study explored the feasibility of detecting hidden muscle activity in surface electromyogram (EMG) baseline. Approach Power spectral density (PSD) analysis and multi-scale entropy (MSE) analysis were used respectively. Both analyses were applied to computer simulations of surface EMG baseline with presence (representing activity data) or absence (representing reference data) of hidden muscle activity, as well as surface electrode array EMG baseline recordings of healthy control and amyotrophic lateral sclerosis (ALS) subjects. Main results Although the simulated reference data and the activity data yielded no distinguishable difference in the time domain, they demonstrated a significant difference in the frequency and signal complexity domains with the PSD and MSE analyses. For a comparison using pooled data, such a difference was also observed when the PSD and MSE analyses were applied to surface electrode array EMG baseline recordings of healthy control and ALS subjects, which demonstrated no distinguishable difference in the time domain. Compared with the PSD analysis, the MSE analysis appeared to be more sensitive for detecting the difference in surface EMG baselines between the two groups. Significance The findings implied presence of hidden muscle activity in surface EMG baseline recordings from the ALS subjects. To promote the presented analysis as a useful diagnostic or investigatory tool, future studies are necessary to assess the pathophysiological nature or origins of the hidden muscle activity, as well as the baseline difference at the individual subject level. PMID:24445526

  14. Simulation results of Pulse Shape Discrimination (PSD) for background reduction in INTEGRAL Spectrometer (SPI) germanium detectors

    NASA Technical Reports Server (NTRS)

    Slassi-Sennou, S. A.; Boggs, S. E.; Feffer, P. T.; Lin, R. P.

    1997-01-01

    Pulse Shape Discrimination (PSD) for background reduction will be used in the INTErnational Gamma Ray Astrophysics Laboratory (INTEGRAL) imaging spectrometer (SPI) to improve the sensitivity from 200 keV to 2 MeV. The observation of significant astrophysical gamma ray lines in this energy range is expected, where the dominant component of the background is the beta(sup -) decay in the Ge detectors due to the activation of Ge nuclei by cosmic rays. The sensitivity of the SPI will be improved by rejecting beta(sup -) decay events while retaining photon events. The PSD technique will distinguish between single and multiple site events. Simulation results of PSD for INTEGRAL-type Ge detectors using a numerical model for pulse shape generation are presented. The model was shown to agree with the experimental results for a narrow inner bore closed end cylindrical detector. Using PSD, a sensitivity improvement factor of the order of 2.4 at 0.8 MeV is expected.

  15. Highly Soluble p-Terphenyl and Fluorene Derivatives as Efficient Dopants in Plastic Scintillators for Sensitive Nuclear Material Detection.

    PubMed

    Yemam, Henok A; Mahl, Adam; Tinkham, Jonathan S; Koubek, Joshua T; Greife, Uwe; Sellinger, Alan

    2017-07-03

    Plastic scintillators are commonly used as first-line detectors for special nuclear materials. Current state-of-the-art plastic scintillators based on poly(vinyltoluene) (PVT) matrices containing high loadings (>15.0 wt %) of 2,5-diphenyloxazole (PPO) offer neutron signal discrimination in gamma radiation background (termed pulse shape discrimination, PSD), however, they suffer from poor mechanical properties. In this work, a series of p-terphenyl and fluorene derivatives were synthesized and tested as dopants in PVT based plastic scintillators as possible alternatives to PPO to address the mechanical property issue and to study the PSD mechanism. The derivatives were synthesized from low cost starting materials in high yields using simple chemistry. The photophysical and thermal properties were investigated for their influence on radiation sensitivity/detection performance, and mechanical stability. A direct correlation was found between the melting point of the dopants and the subsequent mechanical properties of the PVT based plastic scintillators. For example, select fluorene derivatives used as dopants produced scintillator samples with mechanical properties exceeding those of the commercial PPO-based scintillators while producing acceptable PSD capabilities. The physical properties of the synthesized dopants were also investigated to examine their effect on the final scintillator samples. Planar derivatives of fluorene were found to be highly soluble in PVT matrices with little to no aggregation induced effects. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Neural complexity in patients with poststroke depression: A resting EEG study.

    PubMed

    Zhang, Ying; Wang, Chunfang; Sun, Changcheng; Zhang, Xi; Wang, Yongjun; Qi, Hongzhi; He, Feng; Zhao, Xin; Wan, Baikun; Du, Jingang; Ming, Dong

    2015-12-01

    Poststroke depression (PSD) is one of the most common emotional disorders affecting post-stroke patients. However, the neurophysiological mechanism remains elusive. This study was aimed to study the relationship between complexity of neural electrical activity and PSD. Resting state eye-closed electroencephalogram (EEG) signals of 16 electrodes were recorded in 21 ischemic poststroke depression (PSD) patients, 22 ischemic poststroke non-depression (PSND) patients and 15 healthy controls (CONT). Lempel-Ziv Complexity (LZC) was used to evaluate changes in EEG complexity in PSD patients. Statistical analysis was performed to explore difference among different groups and electrodes. Correlation between the severity of depression (HDRS) and EEG complexity was determined with pearson correlation coefficients. Receiver operating characteristic (ROC) and binary logistic regression analysis were conducted to estimate the discriminating ability of LZC for PSD in specificity, sensitivity and accuracy. PSD patients showed lower neural complexity compared with PSND and CONT subjects in the whole brain regions. There was no significant difference among different brain regions, and no interactions between group and electrodes. None of the LZC significantly correlated with overall depression severity or differentiated symptom severity of 7 items in PSD patients, but in stroke patients, significant correlation was found between HDRS and LZC in the whole brain regions, especially in frontal and temporal. LZC parameters used for PSD recognition possessed more than 85% in specificity, sensitivity and accuracy, suggesting the feasibility of LZC to serve as screening indicators for PSD. Increased slow wave rhythms were found in PSD patients and clearly correlation was confirmed between neuronal complexity and spectral power of the four EEG rhythms. Lesion location of stroke patients in the study distributed in different brain regions, and most of the PSD patients were mild or moderate in depressive severity. Compared with conventional spectral analysis, complexity of neural activity using LZC was more sensitive and stationary in the measurement of abnormal brain activity in PSD patients and may offer a potential approach to facilitate clinical screening of this disease. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  17. Pulse shape discrimination for background rejection in germanium gamma-ray detectors

    NASA Technical Reports Server (NTRS)

    Feffer, P. T.; Smith, D. M.; Campbell, R. D.; Primbsch, J. H.; Lin, R. P.

    1989-01-01

    A pulse-shape discrimination (PSD) technique is developed to reject the beta-decay background resulting from activation of Ge gamma-ray detectors by cosmic-ray secondaries. These beta decays are a major source of background at 0.2-2 MeV energies in well shielded Ge detector systems. The technique exploits the difference between the detected current pulse shapes of single- and multiple-site energy depositions within the detector: beta decays are primarily single-site events, while photons at these energies typically Compton scatter before being photoelectrically absorbed to produce multiple-site events. Depending upon the amount of background due to sources other than beta decay, PSD can more than double the detector sensitivity.

  18. PSD-95 stabilizes NMDA receptors by inducing the degradation of STEP61.

    PubMed

    Won, Sehoon; Incontro, Salvatore; Nicoll, Roger A; Roche, Katherine W

    2016-08-09

    Phosphorylation regulates surface and synaptic expression of NMDA receptors (NMDARs). Both the tyrosine kinase Fyn and the tyrosine phosphatase striatal-enriched protein tyrosine phosphatase (STEP) are known to target the NMDA receptor subunit GluN2B on tyrosine 1472, which is a critical residue that mediates NMDAR endocytosis. STEP reduces the surface expression of NMDARs by promoting dephosphorylation of GluN2B Y1472, whereas the synaptic scaffolding protein postsynaptic density protein 95 (PSD-95) stabilizes the surface expression of NMDARs. However, nothing is known about a potential functional interaction between STEP and PSD-95. We now report that STEP61 binds to PSD-95 but not to other PSD-95 family members. We find that PSD-95 expression destabilizes STEP61 via ubiquitination and degradation by the proteasome. Using subcellular fractionation, we detect low amounts of STEP61 in the PSD fraction. However, STEP61 expression in the PSD is increased upon knockdown of PSD-95 or in vivo as detected in PSD-95-KO mice, demonstrating that PSD-95 excludes STEP61 from the PSD. Importantly, only extrasynaptic NMDAR expression and currents were increased upon STEP knockdown, as is consistent with low STEP61 localization in the PSD. Our findings support a dual role for PSD-95 in stabilizing synaptic NMDARs by binding directly to GluN2B but also by promoting synaptic exclusion and degradation of the negative regulator STEP61.

  19. PSD-95 stabilizes NMDA receptors by inducing the degradation of STEP61

    PubMed Central

    Won, Sehoon; Incontro, Salvatore; Nicoll, Roger A.; Roche, Katherine W.

    2016-01-01

    Phosphorylation regulates surface and synaptic expression of NMDA receptors (NMDARs). Both the tyrosine kinase Fyn and the tyrosine phosphatase striatal-enriched protein tyrosine phosphatase (STEP) are known to target the NMDA receptor subunit GluN2B on tyrosine 1472, which is a critical residue that mediates NMDAR endocytosis. STEP reduces the surface expression of NMDARs by promoting dephosphorylation of GluN2B Y1472, whereas the synaptic scaffolding protein postsynaptic density protein 95 (PSD-95) stabilizes the surface expression of NMDARs. However, nothing is known about a potential functional interaction between STEP and PSD-95. We now report that STEP61 binds to PSD-95 but not to other PSD-95 family members. We find that PSD-95 expression destabilizes STEP61 via ubiquitination and degradation by the proteasome. Using subcellular fractionation, we detect low amounts of STEP61 in the PSD fraction. However, STEP61 expression in the PSD is increased upon knockdown of PSD-95 or in vivo as detected in PSD-95–KO mice, demonstrating that PSD-95 excludes STEP61 from the PSD. Importantly, only extrasynaptic NMDAR expression and currents were increased upon STEP knockdown, as is consistent with low STEP61 localization in the PSD. Our findings support a dual role for PSD-95 in stabilizing synaptic NMDARs by binding directly to GluN2B but also by promoting synaptic exclusion and degradation of the negative regulator STEP61. PMID:27457929

  20. Local palmitoylation cycles define activity-regulated postsynaptic subdomains

    PubMed Central

    Fukata, Yuko; Dimitrov, Ariane; Boncompain, Gaelle; Vielemeyer, Ole

    2013-01-01

    Distinct PSD-95 clusters are primary landmarks of postsynaptic densities (PSDs), which are specialized membrane regions for synapses. However, the mechanism that defines the locations of PSD-95 clusters and whether or how they are reorganized inside individual dendritic spines remains controversial. Because palmitoylation regulates PSD-95 membrane targeting, we combined a conformation-specific recombinant antibody against palmitoylated PSD-95 with live-cell super-resolution imaging and discovered subsynaptic nanodomains composed of palmitoylated PSD-95 that serve as elementary units of the PSD. PSD-95 in nanodomains underwent continuous de/repalmitoylation cycles driven by local palmitoylating activity, ensuring the maintenance of compartmentalized PSD-95 clusters within individual spines. Plasma membrane targeting of DHHC2 palmitoyltransferase rapidly recruited PSD-95 to the plasma membrane and proved essential for postsynaptic nanodomain formation. Furthermore, changes in synaptic activity rapidly reorganized PSD-95 nano-architecture through plasma membrane–inserted DHHC2. Thus, the first genetically encoded antibody sensitive to palmitoylation reveals an instructive role of local palmitoylation machinery in creating activity-responsive PSD-95 nanodomains, contributing to the PSD (re)organization. PMID:23836932

  1. Protection relay of phase-shifting device with thyristor switch for high voltage power transmission lines

    NASA Astrophysics Data System (ADS)

    Lachugin, V. F.; Panfilov, D. I.; Akhmetov, I. M.; Astashev, M. G.; Shevelev, A. V.

    2014-12-01

    Problems of functioning of differential current protection systems of phase shifting devices (PSD) with mechanically changed coefficient of transformation of shunt transformer are analyzed. Requirements for devices of protection of PSD with thyristor switch are formulated. Based on use of nonlinear models of series-wound and shunt transformers of PSD modes of operation of major protection during PSD, switching to zero load operation and to operation under load and during short circuit operation were studied for testing PSD with failures. Use of the principle of duplicating by devices of differential current protection (with realization of functions of breaking) of failures of separate pares of PSD with thyristor switch was substantiated. To ensure protection sensitivity to the shunt transformer winding short circuit, in particular, to a short circuit that is not implemented in the current differential protection for PSD with mechanical switch, the differential current protection reacting to the amount of primary ampere-turns of high-voltage and low-voltage winding of this transformer was designed. Studies have shown that the use of differential current cutoff instead of overcurrent protection for the shunt transformer wndings allows one to provide the sensitivity during thyristor failure with the formation of a short circuit. The results of simulation mode for the PSD with switch thyristor designed to be installed as switching point of Voskhod-Tatarskaya-Barabinsk 220 kV transmission line point out the efficiency of the developed solutions that ensure reliable functioning of the PSD.

  2. USING LEAKED POWER TO MEASURE INTRINSIC AGN POWER SPECTRA OF RED-NOISE TIME SERIES

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

    Zhu, S. F.; Xue, Y. Q., E-mail: zshifu@mail.ustc.edu.cn, E-mail: xuey@ustc.edu.cn

    Fluxes emitted at different wavebands from active galactic nuclei (AGNs) fluctuate at both long and short timescales. The variation can typically be characterized by a broadband power spectrum, which exhibits a red-noise process at high frequencies. The standard method of estimating the power spectral density (PSD) of AGN variability is easily affected by systematic biases such as red-noise leakage and aliasing, in particular when the observation spans a relatively short period and is gapped. Focusing on the high-frequency PSD that is strongly distorted due to red-noise leakage and usually not significantly affected by aliasing, we develop a novel and observablemore » normalized leakage spectrum (NLS), which sensitively describes the effects of leaked red-noise power on the PSD at different temporal frequencies. Using Monte Carlo simulations, we demonstrate how an AGN underlying PSD sensitively determines the NLS when there is severe red-noise leakage, and thereby how the NLS can be used to effectively constrain the underlying PSD.« less

  3. Singular value decomposition based impulsive noise reduction in multi-frequency phase-sensitive demodulation of electrical impedance tomography

    NASA Astrophysics Data System (ADS)

    Hao, Zhenhua; Cui, Ziqiang; Yue, Shihong; Wang, Huaxiang

    2018-06-01

    As an important means in electrical impedance tomography (EIT), multi-frequency phase-sensitive demodulation (PSD) can be viewed as a matched filter for measurement signals and as an optimal linear filter in the case of Gaussian-type noise. However, the additive noise usually possesses impulsive noise characteristics, so it is a challenging task to reduce the impulsive noise in multi-frequency PSD effectively. In this paper, an approach for impulsive noise reduction in multi-frequency PSD of EIT is presented. Instead of linear filters, a singular value decomposition filter is employed as the pre-stage filtering module prior to PSD, which has advantages of zero phase shift, little distortion, and a high signal-to-noise ratio (SNR) in digital signal processing. Simulation and experimental results demonstrated that the proposed method can effectively eliminate the influence of impulsive noise in multi-frequency PSD, and it was capable of achieving a higher SNR and smaller demodulation error.

  4. Maximizing sensitivity of the psychomotor vigilance test (PVT) to sleep loss.

    PubMed

    Basner, Mathias; Dinges, David F

    2011-05-01

    The psychomotor vigilance test (PVT) is among the most widely used measures of behavioral alertness, but there is large variation among published studies in PVT performance outcomes and test durations. To promote standardization of the PVT and increase its sensitivity and specificity to sleep loss, we determined PVT metrics and task durations that optimally discriminated sleep deprived subjects from alert subjects. Repeated-measures experiments involving 10-min PVT assessments every 2 h across both acute total sleep deprivation (TSD) and 5 days of chronic partial sleep deprivation (PSD). Controlled laboratory environment. 74 healthy subjects (34 female), aged 22-45 years. TSD experiment involving 33 h awake (N = 31 subjects) and a PSD experiment involving 5 nights of 4 h time in bed (N = 43 subjects). In a paired t-test paradigm and for both TSD and PSD, effect sizes of 10 different PVT performance outcomes were calculated. Effect sizes were high for both TSD (1.59-1.94) and PSD (0.88-1.21) for PVT metrics related to lapses and to measures of psychomotor speed, i.e., mean 1/RT (response time) and mean slowest 10% 1/RT. In contrast, PVT mean and median RT outcomes scored low to moderate effect sizes influenced by extreme values. Analyses facilitating only portions of the full 10-min PVT indicated that for some outcomes, high effect sizes could be achieved with PVT durations considerably shorter than 10 min, although metrics involving lapses seemed to profit from longer test durations in TSD. Due to their superior conceptual and statistical properties and high sensitivity to sleep deprivation, metrics involving response speed and lapses should be considered primary outcomes for the 10-min PVT. In contrast, PVT mean and median metrics, which are among the most widely used outcomes, should be avoided as primary measures of alertness. Our analyses also suggest that some shorter-duration PVT versions may be sensitive to sleep loss, depending on the outcome variable selected, although this will need to be confirmed in comparative analyses of separate duration versions of the PVT. Using both sensitive PVT metrics and optimal test durations maximizes the sensitivity of the PVT to sleep loss and therefore potentially decreases the sample size needed to detect the same neurobehavioral deficit. We propose criteria to better standardize the 10-min PVT and facilitate between-study comparisons and meta-analyses.

  5. PSD-95 regulates CRFR1 localization, trafficking and β-arrestin2 recruitment.

    PubMed

    Dunn, Henry A; Chahal, Harpreet S; Caetano, Fabiana A; Holmes, Kevin D; Yuan, George Y; Parikh, Ruchi; Heit, Bryan; Ferguson, Stephen S G

    2016-05-01

    Corticotropin-releasing factor (CRF) is a neuropeptide commonly associated with the hypothalamic-pituitary adrenal axis stress response. Upon release, CRF activates two G protein-coupled receptors (GPCRs): CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2). Although both receptors contribute to mood regulation, CRFR1 antagonists have demonstrated anxiolytic and antidepressant-like properties that may be exploited in the generation of new pharmacological interventions for mental illnesses. Previous studies have demonstrated CRFR1 capable of heterologously sensitizing serotonin 2A receptor (5-HT2AR) signaling: another GPCR implicated in psychiatric disease. Interestingly, this phenomenon was dependent on Postsynaptic density 95 (PSD-95)/Disc Large/Zona Occludens (PDZ) interactions on the distal carboxyl termini of both receptors. In the current study, we demonstrate that endogenous PSD-95 can be co-immunoprecipitated with CRFR1 from cortical brain homogenate, and this interaction appears to be primarily via the PDZ-binding motif. Additionally, PSD-95 colocalizes with CRFR1 within the dendritic projections of cultured mouse neurons in a PDZ-binding motif-dependent manner. In HEK 293 cells, PSD-95 overexpression inhibited CRFR1 endocytosis, whereas PSD-95 shRNA knockdown enhanced CRFR1 endocytosis. Although PSD-95 does not appear to play a significant role in CRF-mediated cAMP or ERK1/2 signaling, PSD-95 was demonstrated to suppress β-arrestin2 recruitment: providing a potential mechanism for PSD-95's inhibition of endocytosis. In revisiting previously documented heterologous sensitization, PSD-95 shRNA knockdown did not prevent CRFR1-mediated enhancement of 5-HT2AR signaling. In conclusion, we have identified and characterized a novel functional relationship between CRFR1 and PSD-95 that may have implications in the design of new treatment strategies for mental illness. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Primary Data Treatment Software for Position-Sensitive Detector of Small-Angle Neutron Scattering Spectrometer in the Isotropic Pattern Scattering Case

    NASA Astrophysics Data System (ADS)

    Soloviev, Alexei; Kutuzov, Sergei; Ivankov, Olexander; Kuklin, Alexander

    2018-02-01

    A new data converter has been created for the new position-sensitive detector (PSD) of small-angle neutron scattering (SANS) spectrometer YuMO. In the isotropic pattern scattering case, it provides the possibility for processing PSD data with the SAS data processing program that has already been in use.

  7. A large 2D PSD for thermal neutron detection

    NASA Astrophysics Data System (ADS)

    Knott, R. B.; Smith, G. C.; Watt, G.; Boldeman, J. W.

    1997-02-01

    A 2D PSD based on a MWPC has been constructed for a small angle neutron scattering instrument. The active area of the detector was 640 × 640 mm 2. To meet the specifications for neutron detection efficiency and spatial resolution, and to minimise parallax, the gas mixture was 190 kPa 3He plus 100 kPa CF 4, and the active volume had a thickness of 30 mm. The design maximum neutron count rate of the detector was 10 5 events per secod. The (calculated) neutron detection efficiency was 60% for 2 Å neutrons and the (measured) neutron energy resolution on the anode grid was typically 20% (fwhm). The location of a neutron detection event within the active area was determined using the wire-by-wire method: the spatial resolution (5 × 5 mm 2) was thereby defined by the wire geometry. A 16-channel charge-sensitive preamplifier/amplifier/comparator module has been developed with a channel sensitivity of 0.1 V/fC, noise line width of 0.4 fC (fwhm) and channel-to-channel cross-talk of less than 5%. The Proportional Counter Operating System (PCOS III) (LeCroy Corp, USA) was used for event encoding. The ECL signals produced by the 16 channel modules were latched in PCOS III by a trigger pulse from the anode and the fast encoders produce a position and width for each event. The information was transferred to a UNIX workstation for accumulation and online display.

  8. Detection system for a β^+ - ν correlation experiment in a magneto-optical trap

    NASA Astrophysics Data System (ADS)

    Melconian, D.; Gorelov, A.; Trinczek, M.; D'Auria, J. M.; Dubé, P.; Giesen, U.; Häusser, O.; Swanson, T.; Ball, G.; Behr, J. A.; Buchmann, L.; Dombsky, M.; Jackson, K. P.; Schmid, J.; Dilling, J.; Alford, W. P.; Wong, W.

    1998-10-01

    Experiments with magneto-optically trapped ^38mK at TRIUMF are currently underway that use a micro-channel plate (MCP) and β telescope to observe the recoiling Ar and β^+ respectively. The β telescope consists of a 5.5cm diameter x 6.5cm BC408 plastic scintillator mounted behind an X-Y position sensitive double-sided Si-strip detector (PSD). Coincidences between the ΔE and E detectors allow an efficient veto of γ backgrounds and provide 1mm spatial resolution of the detected positron. The scintillator was designed with the aid of monte carlo simulations for minimized lineshape tail and uniformity of response to E_β^+ and position, resulting in fracΔ EE = 9.7 % at 1.6MeV. This energy measurement, the < 1ns relative timing between the MCP and scintillator, and the position information from the MCP and PSD together provide overdetermined kinematic information, useful for rejecting backgrounds and assessing systematic errors.

  9. Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by Promoting Interaction to Deeper Domains of PSD-95.

    PubMed

    Hafner, Anne-Sophie; Penn, Andrew C; Grillo-Bosch, Dolors; Retailleau, Natacha; Poujol, Christel; Philippat, Amandine; Coussen, Françoise; Sainlos, Matthieu; Opazo, Patricio; Choquet, Daniel

    2015-04-22

    PSD-95 is a prominent organizer of the postsynaptic density (PSD) that can present a filamentous orientation perpendicular to the plasma membrane. Interactions between PSD-95 and transmembrane proteins might be particularly sensitive to this orientation, as "long" cytoplasmic tails might be required to reach deeper PSD-95 domains. Extension/retraction of transmembrane protein C-tails offer a new way of regulating binding to PSD-95. Using stargazin as a model, we found that enhancing the apparent length of stargazin C-tail through phosphorylation or by an artificial linker was sufficient to potentiate binding to PSD-95, AMPAR anchoring, and synaptic transmission. A linear extension of stargazin C-tail facilitates binding to PSD-95 by preferentially engaging interaction with the farthest located PDZ domains regarding to the plasma membrane, which present a greater affinity for the stargazin PDZ-domain-binding motif. Our study reveals that the concerted orientation of the stargazin C-tail and PSD-95 is a major determinant of synaptic strength. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Maximizing Sensitivity of the Psychomotor Vigilance Test (PVT) to Sleep Loss

    PubMed Central

    Basner, Mathias; Dinges, David F.

    2011-01-01

    Study Objectives: The psychomotor vigilance test (PVT) is among the most widely used measures of behavioral alertness, but there is large variation among published studies in PVT performance outcomes and test durations. To promote standardization of the PVT and increase its sensitivity and specificity to sleep loss, we determined PVT metrics and task durations that optimally discriminated sleep deprived subjects from alert subjects. Design: Repeated-measures experiments involving 10-min PVT assessments every 2 h across both acute total sleep deprivation (TSD) and 5 days of chronic partial sleep deprivation (PSD). Setting: Controlled laboratory environment. Participants: 74 healthy subjects (34 female), aged 22–45 years. Interventions: TSD experiment involving 33 h awake (N = 31 subjects) and a PSD experiment involving 5 nights of 4 h time in bed (N = 43 subjects). Measurements and Results: In a paired t-test paradigm and for both TSD and PSD, effect sizes of 10 different PVT performance outcomes were calculated. Effect sizes were high for both TSD (1.59–1.94) and PSD (0.88–1.21) for PVT metrics related to lapses and to measures of psychomotor speed, i.e., mean 1/RT (response time) and mean slowest 10% 1/RT. In contrast, PVT mean and median RT outcomes scored low to moderate effect sizes influenced by extreme values. Analyses facilitating only portions of the full 10-min PVT indicated that for some outcomes, high effect sizes could be achieved with PVT durations considerably shorter than 10 min, although metrics involving lapses seemed to profit from longer test durations in TSD. Conclusions: Due to their superior conceptual and statistical properties and high sensitivity to sleep deprivation, metrics involving response speed and lapses should be considered primary outcomes for the 10-min PVT. In contrast, PVT mean and median metrics, which are among the most widely used outcomes, should be avoided as primary measures of alertness. Our analyses also suggest that some shorter-duration PVT versions may be sensitive to sleep loss, depending on the outcome variable selected, although this will need to be confirmed in comparative analyses of separate duration versions of the PVT. Using both sensitive PVT metrics and optimal test durations maximizes the sensitivity of the PVT to sleep loss and therefore potentially decreases the sample size needed to detect the same neurobehavioral deficit. We propose criteria to better standardize the 10-min PVT and facilitate between-study comparisons and meta-analyses. Citation: Basner M; Dinges DF. Maximizing sensitivity of the psychomotor vigilance test (PVT) to sleep loss. SLEEP 2011;34(5):581-591. PMID:21532951

  11. Interactions and phosphorylation of postsynaptic density 93 (PSD-93) by extracellular signal-regulated kinase (ERK).

    PubMed

    Guo, Ming-Lei; Xue, Bing; Jin, Dao-Zhong; Mao, Li-Min; Wang, John Q

    2012-07-17

    Postsynaptic density 93 (PSD-93) is a protein enriched at postsynaptic sites. As a key scaffolding protein, PSD-93 forms complexes with the clustering of various synaptic proteins to construct postsynaptic signaling networks and control synaptic transmission. Extracellular signal-regulated kinase (ERK) is a prototypic member of a serine/threonine protein kinase family known as mitogen-activated protein kinase (MAPK). This kinase, especially ERK2 isoform, noticeably resides in peripheral structures of neurons, such as dendritic spines and postsynaptic density areas, in addition to its distribution in the cytoplasm and nucleus, although little is known about specific substrates of ERK at synaptic sites. In this study, we found that synaptic PSD-93 is a direct target of ERK. This was demonstrated by direct protein-protein interactions between purified ERK2 and PSD-93 in vitro. The accurate ERK2-binding region seems to locate at an N-terminal region of PSD-93. In adult rat striatal neurons in vivo, native ERK from synaptosomal fractions also associated with PSD-93. In phosphorylation assays, active ERK2 phosphorylated PSD-93. An accurate phosphorylation site was identified at a serine site (S323). In striatal neurons, immunoprecipitated PSD-93 showed basal phosphorylation at an ERK-sensitive site. Our data provide evidence supporting PSD-93 as a new substrate of the synaptic species of ERK. ERK2 possesses the ability to interact with PSD-93 and phosphorylate PSD-93 at a specific site. Published by Elsevier B.V.

  12. A large 2D PSD for thermal neutron detection

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

    Knott, R.B.; Watt, G.; Boldeman, J.W.

    1996-12-31

    A 2D PSD based on a MWPC has been constructed for a small angle neutron scattering instrument. The active area of the detector was 640 x 640 mm{sup 2}. To meet the specifications for neutron detection efficiency and spatial resolution, and to minimize parallax, the gas mixture was 190 kPa {sup 3}He plus 100 kPa CF{sub 4} and the active volume had a thickness of 30 mm. The design maximum neutron count-rate of the detector was 10{sup 5} events per second. The (calculated) neutron detection efficiency was 60% for 2{angstrom} neutrons and the (measured) neutron energy resolution on the anodemore » grid was typically 20% (fwhm). The location of a neutron detection event within the active area was determined using the wire-by-wire method: the spatial resolution (5 x 5 mm{sup 2}) was thereby defined by the wire geometry. A 16 channel charge-sensitive preamplifier/amplifier/comparator module has been developed with a channel sensitivity of 0.1 V/fC, noise linewidth of 0.4 fC (fwhm) and channel-to-channel cross-talk of less than 5%. The Proportional Counter Operating System (PCOS III) (LeCroy Corp USA) was used for event encoding. The ECL signals produced by the 16 channel modules were latched in PCOS III by a trigger pulse from the anode and the fast encoders produce a position and width for each event. The information was transferred to a UNIX workstation for accumulation and online display.« less

  13. Phase-sensitive detection of acoustically stimulated electromagnetic response in steel

    NASA Astrophysics Data System (ADS)

    Yamada, Hisato; Yotsuji, Junichi; Ikushima, Kenji

    2018-07-01

    The signal amplitude and the phase of acoustically stimulated electromagnetic (ASEM) response have been investigated in steel. In the ASEM method, magnetization is temporally modulated with the radio frequency (rf) of irradiated ultrasonic waves through magnetomechanical coupling. The first-harmonic components of the induced rf dipolar magnetic fields are detected using a resonant loop antenna. The signal amplitude of ASEM waves is determined by the magnitude of local piezomagnetic coefficients on an acoustically excited spot. Here, we divided the ASEM waves into the “in-phase” and “quadrature” components by phase-sensitive detection (PSD). On the basis of the linear response theory, we provided the theoretical formalism of ASEM response by introducing local complex piezomagnetic coefficients, d loc = d‧ + id‧‧. We investigated the magnetic field (H) dependence of the individual components on the different surface conditions of steel plates. The in-phase component [∝ d‧(H)] shows a hysteresis loop on the machined surface of a steel plate, in which d‧(H) switches sign at two finite field values, ±H 0. The inversion of magnetization associated with the applied static fields is thus definitely observed in the PSD measurements. In addition, we measured the hysteresis behaviors on a steel surface with a thin mill scale (iron oxide layers). The hysteresis loop broadens and a significant contribution of the quadrature component [∝ d‧‧(H)] is found. We discuss the origin of the hysteresis behaviors of d‧ and d‧‧ using the Debye relaxation model.

  14. Development of a new signal processor for tetralateral position sensitive detector based on single-chip microcomputer

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

    Huang Meizhen; Shi Longzhao; Wang Yuxing

    2006-08-15

    An inherently nonlinear relation between the output current of the tetralateral position sensitive detector (PSD) and the position of the incident light spot has been found theoretically. Based on single-chip microcomputer and the theoretical relation between output current and position, a new signal processor capable of correcting nonlinearity and reducing position measurement deviation of tetralateral PSD was developed. A tetralateral PSD (S1200, 13x13 mm{sup 2}, Hamamatsu Photonics K.K.) was measured with the new signal processor, a linear relation between the output position of the PSD, and the incident position of the light spot was obtained. In the 60% range ofmore » a 13x13 mm{sup 2} active area, the position nonlinearity (rms) was 0.15% and the position measurement deviation (rms) was {+-}20 {mu}m. Compared with traditional analog signal processor, the new signal processor is of better compatibility, lower cost, higher precision, and easier to be interfaced.« less

  15. Development of a new signal processor for tetralateral position sensitive detector based on single-chip microcomputer

    NASA Astrophysics Data System (ADS)

    Huang, Mei-Zhen; Shi, Long-Zhao; Wang, Yu-Xing; Ni, Yi; Li, Zhen-Qing; Ding, Hai-Feng

    2006-08-01

    An inherently nonlinear relation between the output current of the tetralateral position sensitive detector (PSD) and the position of the incident light spot has been found theoretically. Based on single-chip microcomputer and the theoretical relation between output current and position, a new signal processor capable of correcting nonlinearity and reducing position measurement deviation of tetralateral PSD was developed. A tetralateral PSD (S1200, 13×13mm2, Hamamatsu Photonics K.K.) was measured with the new signal processor, a linear relation between the output position of the PSD, and the incident position of the light spot was obtained. In the 60% range of a 13×13mm2 active area, the position nonlinearity (rms) was 0.15% and the position measurement deviation (rms) was ±20μm. Compared with traditional analog signal processor, the new signal processor is of better compatibility, lower cost, higher precision, and easier to be interfaced.

  16. On-orbit Status and Light Attenuation Behavior of the DAMPE-PSD

    NASA Astrophysics Data System (ADS)

    Li, Y.; Zhang, Y. P.; Zhang, Y. J.; Sun, Z. Y.; Yu, Y. H.; Dong, T. K.; Ma, P. X.; Wang, Y. P.; Yuan, Q.

    2017-11-01

    The DArk Matter Particle Explorer (DAMPE) is a high-resolution multi-purpose space-borne device for detecting the high-energy cosmic-rays like e±, γ-rays, protons, and heavy-ions, which was launched on 2015 December 17th. The Plastic Scintillator Detector (PSD) is the top-most sub-detector of DAMPE. The PSD is designed to measure the charge of incident high-energy particles, and to serve as a veto detector for discriminating γ-rays from the charged particles. In this paper, the on-orbit status of the PSD after launching in terms of high voltage (HV) and temperature stabilities is presented. The temperature and the HV variations of the PSD are less than 1°C and 0.5%, respectively. By using the on-orbit data, the attenuation lengths of PSD bars are obtained according to an empirical formula. A preliminary charge spectrum reconstructed from the X-layer of the PSD is obtained.

  17. Pin1 Modulates the Synaptic Content of NMDA Receptors via Prolyl-Isomerization of PSD-95.

    PubMed

    Antonelli, Roberta; De Filippo, Roberto; Middei, Silvia; Stancheva, Stefka; Pastore, Beatrice; Ammassari-Teule, Martine; Barberis, Andrea; Cherubini, Enrico; Zacchi, Paola

    2016-05-18

    Phosphorylation of serine/threonine residues preceding a proline regulates the fate of its targets through postphosphorylation conformational changes catalyzed by the peptidyl-prolyl cis-/trans isomerase Pin1. By flipping the substrate between two different functional conformations, this enzyme exerts a fine-tuning of phosphorylation signals. Pin1 has been detected in dendritic spines and shafts where it regulates protein synthesis required to sustain the late phase of long-term potentiation (LTP). Here, we demonstrate that Pin1 residing in postsynaptic structures can interact with postsynaptic density protein-95 (PSD-95), a key scaffold protein that anchors NMDA receptors (NMDARs) in PSD via GluN2-type receptor subunits. Pin1 recruitment by PSD-95 occurs at specific serine-threonine/proline consensus motifs localized in the linker region connecting PDZ2 to PDZ3 domains. Upon binding, Pin1 triggers structural changes in PSD-95, thus negatively affecting its ability to interact with NMDARs. In electrophysiological experiments, larger NMDA-mediated synaptic currents, evoked in CA1 principal cells by Schaffer collateral stimulation, were detected in hippocampal slices obtained from Pin1(-/-) mice compared with controls. Similar results were obtained in cultured hippocampal cells expressing a PSD-95 mutant unable to undergo prolyl-isomerization, thus indicating that the action of Pin1 on PSD-95 is critical for this effect. In addition, an enhancement in spine density and size was detected in CA1 principal cells of Pin1(-/-) or in Thy-1GFP mice treated with the pharmacological inhibitor of Pin1 catalytic activity PiB.Our data indicate that Pin1 controls synaptic content of NMDARs via PSD-95 prolyl-isomerization and the expression of dendritic spines, both required for LTP maintenance. PSD-95, a membrane-associated guanylate kinase, is the major scaffolding protein at excitatory postsynaptic densities and a potent regulator of synaptic strength and plasticity. The activity of PSD-95 is tightly controlled by several post-translational mechanisms including proline-directed phosphorylation. This signaling cascade regulates the fate of its targets through postphosphorylation conformational modifications catalyzed by the peptidyl-prolyl cis-/trans isomerase Pin1. Here, we uncover a new role of Pin1 in glutamatergic signaling. By interacting with PSD-95, Pin1 dampens PSD-95 ability to complex with NMDARs, thus negatively affecting NMDAR signaling and spine morphology. Our findings further emphasize the emerging role of Pin1 as a key modulator of synaptic transmission. Copyright © 2016 the authors 0270-6474/16/365437-11$15.00/0.

  18. Setting up a proper power spectral density (PSD) and autocorrelation analysis for material and process characterization

    NASA Astrophysics Data System (ADS)

    Rutigliani, Vito; Lorusso, Gian Francesco; De Simone, Danilo; Lazzarino, Frederic; Rispens, Gijsbert; Papavieros, George; Gogolides, Evangelos; Constantoudis, Vassilios; Mack, Chris A.

    2018-03-01

    Power spectral density (PSD) analysis is playing more and more a critical role in the understanding of line-edge roughness (LER) and linewidth roughness (LWR) in a variety of applications across the industry. It is an essential step to get an unbiased LWR estimate, as well as an extremely useful tool for process and material characterization. However, PSD estimate can be affected by both random to systematic artifacts caused by image acquisition and measurement settings, which could irremediably alter its information content. In this paper, we report on the impact of various setting parameters (smoothing image processing filters, pixel size, and SEM noise levels) on the PSD estimate. We discuss also the use of PSD analysis tool in a variety of cases. Looking beyond the basic roughness estimate, we use PSD and autocorrelation analysis to characterize resist blur[1], as well as low and high frequency roughness contents and we apply this technique to guide the EUV material stack selection. Our results clearly indicate that, if properly used, PSD methodology is a very sensitive tool to investigate material and process variations

  19. Subclinical keratoconus detection by pattern analysis of corneal and epithelial thickness maps with optical coherence tomography

    PubMed Central

    Li, Yan; Chamberlain, Winston; Tan, Ou; Brass, Robert; Weiss, Jack L.; Huang, David

    2016-01-01

    PURPOSE To screen for subclinical keratoconus by analyzing corneal, epithelial, and stromal thickness map patterns with Fourier-domain optical coherence tomography (OCT). SETTING Four centers in the United States. DESIGN Cross-sectional observational study. METHODS Eyes of normal subjects, subclinical keratoconus eyes, and the topographically normal eye of a unilateral keratoconus patient were studied. Corneas were scanned using a 26 000 Hz Fourier-domain OCT system (RTVue). Normal subjects were divided into training and evaluation groups. Corneal, epithelial, and stromal thickness maps and derived diagnostic indices, including pattern standard deviation (PSD) variables and pachymetric map–based keratoconus risk scores were calculated from the OCT data. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the diagnostic accuracy of the indices. RESULTS The study comprised 150 eyes of 83 normal subjects, 50 subclinical keratoconus eyes of 32 patients, and 1 topographically normal eye of a unilateral keratoconus patient. Subclinical keratoconus was characterized by inferotemporal thinning of the cornea, epithelium, and stroma. The PSD values for corneal (P < .001), epithelial (P < .001), and stromal (P = .049) thickness maps were all significantly higher in subclinical keratoconic eyes than in the normal group. The diagnostic accuracy was significantly higher for PSD variables (pachymetric PSD, AUC = 0.941; epithelial PSD, AUC = 0.985; stromal PSD, AUC = 0.924) than for the pachymetric map–based keratoconus risk score (AUC = 0.735). CONCLUSIONS High-resolution Fourier-domain OCT could map corneal, epithelial, and stromal thicknesses. Corneal and sublayer thickness changes in subclinical keratoconus could be detected with high accuracy using PSD variables. These new diagnostic variables might be useful in the detection of early keratoconus. PMID:27026454

  20. Temperature dependence of the plastic scintillator detector for DAMPE

    NASA Astrophysics Data System (ADS)

    Wang, Zhao-Min; Yu, Yu-Hong; Sun, Zhi-Yu; Yue, Ke; Yan, Duo; Zhang, Yong-Jie; Zhou, Yong; Fang, Fang; Huang, Wen-Xue; Chen, Jun-Ling

    2017-01-01

    The Plastic Scintillator Detector (PSD) is one of the main sub-detectors in the DArk Matter Particle Explorer (DAMPE) project. It will be operated over a large temperature range from -10 to 30 °C, so the temperature effect of the whole detection system should be studied in detail. The temperature dependence of the PSD system is mainly contributed by the three parts: the plastic scintillator bar, the photomultiplier tube (PMT), and the Front End Electronics (FEE). These three parts have been studied in detail and the contribution of each part has been obtained and discussed. The temperature coefficient of the PMT is -0.320(±0.033)%/°C, and the coefficient of the plastic scintillator bar is -0.036(±0.038)%/°C. This result means that after subtracting the FEE pedestal, the variation of the signal amplitude of the PMT-scintillator system due to temperature mainly comes from the PMT, and the plastic scintillator bar is not sensitive to temperature over the operating range. Since the temperature effect cannot be ignored, the temperature dependence of the whole PSD has been also studied and a correction has been made to minimize this effect. The correction result shows that the effect of temperature on the signal amplitude of the PSD system can be suppressed. Supported by Strategic Priority Research Program on Space Science of the Chinese Academy of Sciences (XDA04040202-3) and Youth Innovation Promotion Association, CAS

  1. [The relationship between acute inflammatory cytokines, nerve function defect, daily living ability and PSD].

    PubMed

    Li, Ping; Zhang, Qiao-Lian; Li, Shuang-Ying

    2017-02-08

    To investigate the correlation between poststroke depression (PSD) and serum levels of inflammatory cytokines, neurologic impairment, daily life ability in patients with acute cerebral infarction at different time. Two hundreds and eighty patients who admitted to our hospital with a diagnosis of acute infarction excluded the patients mismatch conditions were evaluated by Hamilton depres-sion rating scale (HDRS) to diagnose PSD respectively at admission and 3 months after stroke. Serum inflammatory cytokines high-sensitivity C-reactive protein(hs-CRP), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were determined. NIH stroke scale(NIHSS) and Barthel index for daily life ability were used to evaluate nerve functions. Then we analyzed the correlation between PSD and serum inflammatory cytokines, correlation between PSD and functional impairment and daily life ability at different time. Logistic regression was performed to ana-lyze the risk factors of PSD. The PSD incidence was higher in recovery stage than that in acute stage, but there was no difference. Serum inflammatory cytokines were higher in PSD group at admission than that in non-PSD group. The NIHSS score and Barthel index in PSD group were different from those in non-group at acute and recovery stage. The OR score was 1.765, 1.646, 1.817, 1.188 and 2.015 respec-tively to TNF-α, IL-6 and Barthel index in the acute phase and to NIHSS and Barthel index in recovery stage. The pathogenesis of PSD at different courses of stroke is not same. TNF-α, IL-6 and Barthel index are the independent risk factors of PSD in acute phase, so do NIHSS score and Barthel index in recovery period.

  2. A low cost PSD-based monocular motion capture system

    NASA Astrophysics Data System (ADS)

    Ryu, Young Kee; Oh, Choonsuk

    2007-10-01

    This paper describes a monocular PSD-based motion capture sensor to employ with commercial video game systems such as Microsoft's XBOX and Sony's Playstation II. The system is compact, low-cost, and only requires a one-time calibration at the factory. The system includes a PSD(Position Sensitive Detector) and active infrared (IR) LED markers that are placed on the object to be tracked. The PSD sensor is placed in the focal plane of a wide-angle lens. The micro-controller calculates the 3D position of the markers using only the measured intensity and the 2D position on the PSD. A series of experiments were performed to evaluate the performance of our prototype system. From the experimental results we see that the proposed system has the advantages of the compact size, the low cost, the easy installation, and the high frame rates to be suitable for high speed motion tracking in games.

  3. Subclinical visual involvement in multiple sclerosis: a study by MRI, VEPs, frequency-doubling perimetry, standard perimetry, and contrast sensitivity.

    PubMed

    Sisto, Dario; Trojano, Maria; Vetrugno, Michele; Trabucco, Tiziana; Iliceto, Giovanni; Sborgia, Carlo

    2005-04-01

    To evaluate the effectiveness of visual evoked potentials (VEPs), frequency-doubling perimetry (FDP), standard achromatic perimetry (SAP), contrast sensitivity (CS) test, and magnetic resonance imaging (MRI), isolated or in combination, in detecting subclinical impairment of visual function in multiple sclerosis (MS). Twenty-two eyes of 11 patients affected by clinically definite MS, without a history of optic neuritis and asymptomatic for visual disturbances, underwent full ophthalmic examination and, in addition, VEPs, FDP, SAP, CS, and MRI. Abnormal results were taken to be as follows: for VEPs, a P100 latency >115 ms; for FDP, abnormal mean deviation (MD) or pattern SD (PSD); for SAP, abnormal MD or PSD; for CS, abnormal CS at one spatial frequency, at least; and for MRI, evidence of at least one demyelinating plaque along the visual pathway. VEPs showed abnormal results in 12 eyes (54.4%), FDP in 11 (50%), SAP in 14 (63.6%), CS in 17 (77.1%), and MRI in 16 (72.7%). In only two (9.1%) eyes of the same patient was no abnormality found. No single test detected all the abnormal eyes. Four (18.2%) eyes had pure optic nerve involvement and the remaining 16 (72.7%) had both pre- and postchiasmal involvement. In patients affected by clinically definite MS without history of optic neuritis and no visual symptoms, there is a large prevalence of visual pathway involvement that can be diagnosed only by performing multiple tests. The comparison of the tests is also useful to detect the presence of multiple lesions in the same patient.

  4. Neutron detection with plastic scintillators coupled to solid state photomultiplier detectors

    NASA Astrophysics Data System (ADS)

    Christian, James F.; Johnson, Erik B.; Fernandez, Daniel E.; Vogel, Samuel; Frank, Rebecca; Stoddard, Graham; Stapels, Christopher; Pereira, Jorge; Zegers, Remco

    2017-09-01

    The recent reduction of dark current in Silicon Solid-state photomultipliers (SiSSPMs) makes them an attractive alternative to conventional photomultiplier tubes (PMTs) for scintillation detection applications. Nuclear Physics experiments often require large detector volumes made using scintillation materials, which require sensitive photodetectors, such as a PMTs. PMTs add to the size, fragility, and high-voltage requirements as well as distance requirements for experiments using magnetic fields. This work compares RMD's latest detector modules, denoted as the "year 2 prototype", of plastic scintillators that discriminate gamma and high-energy particle events from neutron events using pulse shape discrimination (PSD) coupled to a SiSSPM to the following two detector modules: a similar "year 1 prototype" and a scintillator coupled to a PMT module. It characterizes the noise floor, relative signal-to-noise ratio (SNR), the timing performance, the PSD figure-of-merit (FOM) and the neutron detection efficiency of RMD's detectors. This work also evaluates the scaling of SiSSPM detector modules to accommodate the volumes needed for many Nuclear Physics experiments. The Si SSPM detector module provides a clear advantage in Nuclear Physics experiments that require the following attributes: discrimination of neutron and gamma-ray events, operation in or near strong magnetic fields, and segmentation of the detector.

  5. Micro Cantilever Movement Detection with an Amorphous Silicon Array of Position Sensitive Detectors

    PubMed Central

    Contreras, Javier; Costa, Daniel; Pereira, Sonia; Fortunato, Elvira; Martins, Rodrigo; Wierzbicki, Rafal; Heerlein, Holger; Ferreira, Isabel

    2010-01-01

    The movement of a micro cantilever was detected via a self constructed portable data acquisition prototype system which integrates a linear array of 32 1D amorphous silicon position sensitive detectors (PSD). The system was mounted on a microscope using a metal structure platform and the movement of the 30 μm wide by 400 μm long cantilever was tracked by analyzing the signals acquired by the 32 sensor array electronic readout system and the relevant data algorithm. The obtained results show a linear behavior of the photocurrent relating X and Y movement, with a non-linearity of about 3%, a spatial resolution of less than 2 μm along the lateral dimension of the sensor as well as of less than 3 μm along the perpendicular dimension of the sensor, when detecting just the micro-cantilever, and a spatial resolution of less than 1 μm when detecting the holding structure. PMID:22163648

  6. Unsupervised online classifier in sleep scoring for sleep deprivation studies.

    PubMed

    Libourel, Paul-Antoine; Corneyllie, Alexandra; Luppi, Pierre-Hervé; Chouvet, Guy; Gervasoni, Damien

    2015-05-01

    This study was designed to evaluate an unsupervised adaptive algorithm for real-time detection of sleep and wake states in rodents. We designed a Bayesian classifier that automatically extracts electroencephalogram (EEG) and electromyogram (EMG) features and categorizes non-overlapping 5-s epochs into one of the three major sleep and wake states without any human supervision. This sleep-scoring algorithm is coupled online with a new device to perform selective paradoxical sleep deprivation (PSD). Controlled laboratory settings for chronic polygraphic sleep recordings and selective PSD. Ten adult Sprague-Dawley rats instrumented for chronic polysomnographic recordings. The performance of the algorithm is evaluated by comparison with the score obtained by a human expert reader. Online detection of PS is then validated with a PSD protocol with duration of 72 hours. Our algorithm gave a high concordance with human scoring with an average κ coefficient > 70%. Notably, the specificity to detect PS reached 92%. Selective PSD using real-time detection of PS strongly reduced PS amounts, leaving only brief PS bouts necessary for the detection of PS in EEG and EMG signals (4.7 ± 0.7% over 72 h, versus 8.9 ± 0.5% in baseline), and was followed by a significant PS rebound (23.3 ± 3.3% over 150 minutes). Our fully unsupervised data-driven algorithm overcomes some limitations of the other automated methods such as the selection of representative descriptors or threshold settings. When used online and coupled with our sleep deprivation device, it represents a better option for selective PSD than other methods like the tedious gentle handling or the platform method. © 2015 Associated Professional Sleep Societies, LLC.

  7. Sensitivity Analysis and Accuracy of a CFD-TFM Approach to Bubbling Bed Using Pressure Drop Fluctuations

    PubMed Central

    Tricomi, Leonardo; Melchiori, Tommaso; Chiaramonti, David; Boulet, Micaël; Lavoie, Jean Michel

    2017-01-01

    Based upon the two fluid model (TFM) theory, a CFD model was implemented to investigate a cold multiphase-fluidized bubbling bed reactor. The key variable used to characterize the fluid dynamic of the experimental system, and compare it to model predictions, was the time-pressure drop induced by the bubble motion across the bed. This time signal was then processed to obtain the power spectral density (PSD) distribution of pressure fluctuations. As an important aspect of this work, the effect of the sampling time scale on the empirical power spectral density (PSD) was investigated. A time scale of 40 s was found to be a good compromise ensuring both simulation performance and numerical validation consistency. The CFD model was first numerically verified by mesh refinement process, after what it was used to investigate the sensitivity with regards to minimum fluidization velocity (as a calibration point for drag law), restitution coefficient, and solid pressure term while assessing his accuracy in matching the empirical PSD. The 2D model provided a fair match with the empirical time-averaged pressure drop, the relating fluctuations amplitude, and the signal’s energy computed as integral of the PSD. A 3D version of the TFM was also used and it improved the match with the empirical PSD in the very first part of the frequency spectrum. PMID:28695119

  8. Sensitivity Analysis and Accuracy of a CFD-TFM Approach to Bubbling Bed Using Pressure Drop Fluctuations.

    PubMed

    Tricomi, Leonardo; Melchiori, Tommaso; Chiaramonti, David; Boulet, Micaël; Lavoie, Jean Michel

    2017-01-01

    Based upon the two fluid model (TFM) theory, a CFD model was implemented to investigate a cold multiphase-fluidized bubbling bed reactor. The key variable used to characterize the fluid dynamic of the experimental system, and compare it to model predictions, was the time-pressure drop induced by the bubble motion across the bed. This time signal was then processed to obtain the power spectral density (PSD) distribution of pressure fluctuations. As an important aspect of this work, the effect of the sampling time scale on the empirical power spectral density (PSD) was investigated. A time scale of 40 s was found to be a good compromise ensuring both simulation performance and numerical validation consistency. The CFD model was first numerically verified by mesh refinement process, after what it was used to investigate the sensitivity with regards to minimum fluidization velocity (as a calibration point for drag law), restitution coefficient, and solid pressure term while assessing his accuracy in matching the empirical PSD. The 2D model provided a fair match with the empirical time-averaged pressure drop, the relating fluctuations amplitude, and the signal's energy computed as integral of the PSD. A 3D version of the TFM was also used and it improved the match with the empirical PSD in the very first part of the frequency spectrum.

  9. TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors.

    PubMed

    Sethuraman, Vijay A; Bae, You Han

    2007-04-02

    A novel drug targeting system for acidic solid tumors has been developed based on ultra pH-sensitive polymer and cell penetrating TAT. The delivery system consisted of two components: 1) A polymeric micelle that has a hydrophobic core made of poly(l-lactic acid) (PLLA) and a hydrophilic shell consisting of polyethylene glycol (PEG) conjugated to TAT (TAT micelle), 2) an ultra pH-sensitive diblock copolymer of poly(methacryloyl sulfadimethoxine) (PSD) and PEG (PSD-b-PEG). The anionic PSD is complexed with cationic TAT of the micelles to achieve the final carrier, which could systemically shield the micelles and expose them at slightly acidic tumor pH. TAT micelles had particle sizes between 20 and 45 nm and their critical micelle concentrations were 3.5 mg/l to 5.5 mg/l. The TAT micelles, upon mixing with pH-sensitive PSD-b-PEG, showed a slight increase in particle size between pH 8.0 and 6.8 (60-90 nm), indicating complexation. As the pH was decreased (pH 6.6 to 6.0) two populations were observed, one that of normal TAT micelles (45 nm) and the other of aggregated hydrophobic PSD-b-PEG. Zeta potential measurements showed similar trend substantiating the shielding/deshielding process. Flow cytometry and confocal microscopy showed significantly higher uptake of TAT micelles at pH 6.6 compared to pH 7.4 indicating shielding at normal pH and deshielding at tumor pH. The confocal microscopy indicated that the TAT not only translocates into the cells but is also seen on the surface of the nucleus. These results strongly indicate that the above micelles would be able to target any hydrophobic drug near the nucleus.

  10. TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors

    PubMed Central

    Sethuraman, Vijay A; Bae, You Han

    2007-01-01

    A novel drug targeting system for acidic solid tumors has been developed based on ultra pH sensitive polymer and cell penetrating TAT. The delivery system consisted of two components: 1) A polymeric micelle that has a hydrophobic core made of Poly(L-lactic acid) (PLLA) and a hydrophilic shell consisting of Polyethylene Glycol (PEG) conjugated to TAT (TATmicelle), 2) An ultra pH sensitive diblock copolymer of poly(methacryloyl sulfadimethoxine) (PSD) and PEG (PSD-b-PEG). The anionic PSD is complexed with cationic TAT of the micelles to achieve the final carrier, which could systemically shield the micelles and expose them at slightly acidic tumor pH. TATmicelles had particle sizes between 20 to 45 nm and their critical micelle concentrations were 3.5 mg/L to 5.5 mg/L. The TATmicelles, upon mixing with pH sensitive PSD-b-PEG, showed slight increase in particle size between pH 8.0 and 6.8 (60–90 nm), indicating complexation. As the pH was decreased (pH 6.6 to 6.0) two populations were observed, one that of normal TAT micelles (45 nm) and the other of aggregated hydrophobic PSD-b-PEG. Zeta potential measurements showed similar trend substantiating the shielding/deshielding process. Flowcytometry and confocal microscopy showed significantly higher uptake of TAT micelles at pH 6.6 compared to pH 7.4 indicating shielding at normal pH and deshielding at tumor pH. The flowcytometry indicated that the TAT not only translocates into the cells but is also seen on the surface of the nucleus. These results strongly indicate that the above drug loaded micelles would be able to target any hydrophobic drug near the nucleus. PMID:17239466

  11. Association of Membrane Rafts and Postsynaptic Density: Proteomics, Biochemical, and Ultrastructural Analyses

    PubMed Central

    Suzuki, Tatsuo; Zhang, Jingping; Miyazawa, Shoko; Liu, Qian; Farzan, Michael R.; Yao, Wei-Dong

    2011-01-01

    Postsynaptic membrane rafts are believed to play important roles in synaptic signaling, plasticity, and maintenance. However, their molecular identities remain elusive. Further, how they interact with the well-established signaling specialization, the postsynaptic density (PSD), is poorly understood. We previously detected a number of conventional PSD proteins in detergent-resistant membranes (DRMs). Here, we have performed LC-MS/MS (liquid chromatography coupled with tandem mass spectrometry) analyses on postsynaptic membrane rafts and PSDs. Our comparative analysis identified an extensive overlap of protein components in the two structures. This overlapping could be explained, at least partly, by a physical association of the two structures. Meanwhile, a significant number of proteins displayed biased distributions to either rafts or PSDs, suggesting distinct roles for the two postsynaptic specializations. Using biochemical and electron microscopic methods, we directly detected membrane raft-PSD complexes. In vitro reconstitution experiments indicated that the formation of raft-PSD complexes was not due to the artificial reconstruction of once-solubilized membrane components and PSD structures, supporting that these complexes occurred in vivo. Taking together, our results provide evidence that postsynaptic membrane rafts and PSDs may be physically associated. Such association could be important in postsynaptic signal integration, synaptic function, and maintenance. PMID:21797867

  12. Motor impairments, striatal degeneration, and altered dopamine-glutamate interplay in mice lacking PSD-95.

    PubMed

    Zhang, Jingping; Saur, Taixiang; Duke, Angela N; Grant, Seth G N; Platt, Donna M; Rowlett, James K; Isacson, Ole; Yao, Wei-Dong

    2014-01-01

    Excessive activation of the N-methyl-d-aspartate (NMDA) receptor and the neurotransmitter dopamine (DA) mediate neurotoxicity and neurodegeneration under many neurological conditions, including Huntington's disease (HD), an autosomal dominant neurodegenerative disease characterized by the preferential loss of medium spiny projection neurons (MSNs) in the striatum. PSD-95 is a major scaffolding protein in the postsynaptic density (PSD) of dendritic spines, where a classical role for PSD-95 is to stabilize glutamate receptors at sites of synaptic transmission. Our recent studies indicate that PSD-95 also interacts with the D1 DA receptor localized in spines and negatively regulates spine D1 signaling. Moreover, PSD-95 forms ternary protein complexes with D1 and NMDA receptors, and plays a role in limiting the reciprocal potentiation between both receptors from being escalated. These studies suggest a neuroprotective role for PSD-95. Here we show that mice lacking PSD-95, resulting from genetic deletion of the GK domain of PSD-95 (PSD-95-ΔGK mice), sporadically develop progressive neurological impairments characterized by hypolocomotion, limb clasping, and loss of DARPP-32-positive MSNs. Electrophysiological experiments indicated that NMDA receptors in mutant MSNs were overactive, suggested by larger, NMDA receptor-mediated miniature excitatory postsynaptic currents (EPSCs) and higher ratios of NMDA- to AMPA-mediated corticostriatal synaptic transmission. In addition, NMDA receptor currents in mutant cortical neurons were more sensitive to potentiation by the D1 receptor agonist SKF81297. Finally, repeated administration of the psychostimulant cocaine at a dose regimen not producing overt toxicity-related phenotypes in normal mice reliably converted asymptomatic mutant mice to clasping symptomatic mice. These results support the hypothesis that deletion of PSD-95 in mutant mice produces concomitant overactivation of both D1 and NMDA receptors that makes neurons more susceptible to NMDA excitotoxicity, causing neuronal damage and neurological impairments. Understanding PSD-95-dependent neuroprotective mechanisms may help elucidate processes underlying neurodegeneration in HD and other neurological disorders.

  13. Cognitive assessments for the early diagnosis of dementia after stroke

    PubMed Central

    Al-Qazzaz, Noor Kamal; Ali, Sawal Hamid; Ahmad, Siti Anom; Islam, Shabiul

    2014-01-01

    The early detection of poststroke dementia (PSD) is important for medical practitioners to customize patient treatment programs based on cognitive consequences and disease severity progression. The aim is to diagnose and detect brain degenerative disorders as early as possible to help stroke survivors obtain early treatment benefits before significant mental impairment occurs. Neuropsychological assessments are widely used to assess cognitive decline following a stroke diagnosis. This study reviews the function of the available neuropsychological assessments in the early detection of PSD, particularly vascular dementia (VaD). The review starts from cognitive impairment and dementia prevalence, followed by PSD types and the cognitive spectrum. Finally, the most usable neuropsychological assessments to detect VaD were identified. This study was performed through a PubMed and ScienceDirect database search spanning the last 10 years with the following keywords: “post-stroke”; “dementia”; “neuro-psychological”; and “assessments”. This study focuses on assessing VaD patients on the basis of their stroke risk factors and cognitive function within the first 3 months after stroke onset. The search strategy yielded 535 articles. After application of inclusion and exclusion criteria, only five articles were considered. A manual search was performed and yielded 14 articles. Twelve articles were included in the study design and seven articles were associated with early dementia detection. This review may provide a means to identify the role of neuropsychological assessments as early PSD detection tests. PMID:25246795

  14. Mathematical Model and Calibration Procedure of a PSD Sensor Used in Local Positioning Systems.

    PubMed

    Rodríguez-Navarro, David; Lázaro-Galilea, José Luis; Bravo-Muñoz, Ignacio; Gardel-Vicente, Alfredo; Domingo-Perez, Francisco; Tsirigotis, Georgios

    2016-09-15

    Here, we propose a mathematical model and a calibration procedure for a PSD (position sensitive device) sensor equipped with an optical system, to enable accurate measurement of the angle of arrival of one or more beams of light emitted by infrared (IR) transmitters located at distances of between 4 and 6 m. To achieve this objective, it was necessary to characterize the intrinsic parameters that model the system and obtain their values. This first approach was based on a pin-hole model, to which system nonlinearities were added, and this was used to model the points obtained with the nA currents provided by the PSD. In addition, we analyzed the main sources of error, including PSD sensor signal noise, gain factor imbalances and PSD sensor distortion. The results indicated that the proposed model and method provided satisfactory calibration and yielded precise parameter values, enabling accurate measurement of the angle of arrival with a low degree of error, as evidenced by the experimental results.

  15. Optimization of A 2-Micron Laser Frequency Stabilization System for a Double-Pulse CO2 Differential Absorption Lidar

    NASA Technical Reports Server (NTRS)

    Chen, Songsheng; Yu, Jirong; Bai, Yingsin; Koch, Grady; Petros, Mulugeta; Trieu, Bo; Petzar, Paul; Singh, Upendra N.; Kavaya, Michael J.; Beyon, Jeffrey

    2010-01-01

    A carbon dioxide (CO2) Differential Absorption Lidar (DIAL) for accurate CO2 concentration measurement requires a frequency locking system to achieve high frequency locking precision and stability. We describe the frequency locking system utilizing Frequency Modulation (FM), Phase Sensitive Detection (PSD), and Proportional Integration Derivative (PID) feedback servo loop, and report the optimization of the sensitivity of the system for the feed back loop based on the characteristics of a variable path-length CO2 gas cell. The CO2 gas cell is characterized with HITRAN database (2004). The method can be applied for any other frequency locking systems referring to gas absorption line.

  16. Validity and sensitivity of a brief psychomotor vigilance test (PVT-B) to total and partial sleep deprivation

    NASA Astrophysics Data System (ADS)

    Basner, Mathias; Mollicone, Daniel; Dinges, David F.

    2011-12-01

    The Psychomotor Vigilance Test (PVT) objectively assesses fatigue-related changes in alertness associated with sleep loss, extended wakefulness, circadian misalignment, and time on task. The standard 10-min PVT is often considered impractical in applied contexts. To address this limitation, we developed a modified brief 3-min version of the PVT (PVT-B). The PVT-B was validated in controlled laboratory studies with 74 healthy subjects (34 female, aged 22-45 years) that participated either in a total sleep deprivation (TSD) study involving 33 h awake ( N=31 subjects) or in a partial sleep deprivation (PSD) protocol involving 5 consecutive nights of 4 h time in bed ( N=43 subjects). PVT and PVT-B were performed regularly during wakefulness. Effect sizes of 5 key PVT outcomes were larger for TSD than PSD and larger for PVT than for PVT-B for all outcomes. Effect size was largest for response speed (reciprocal response time) for both the PVT-B and the PVT in both TSD and PSD. According to Cohen's criteria, effect sizes for the PVT-B were still large (TSD) or medium to large (PSD, except for fastest 10% RT). Compared to the 70% decrease in test duration the 22.7% (range 6.9-67.8%) average decrease in effect size was deemed an acceptable trade-off between duration and sensitivity. Overall, PVT-B performance had faster response times, more false starts and fewer lapses than PVT performance (all p<0.01). After reducing the lapse threshold from 500 to 355 ms for PVT-B, mixed model ANOVAs indicated no differential sensitivity to sleep loss between PVT-B and PVT for all outcome variables (all P>0.15) but the fastest 10% response times during PSD ( P<0.001), and effect sizes increased from 1.38 to 1.49 (TSD) and 0.65 to 0.76 (PSD), respectively. In conclusion, PVT-B tracked standard 10-min PVT performance throughout both TSD and PSD, and yielded medium to large effect sizes. PVT-B may be a useful tool for assessing behavioral alertness in settings where the duration of the 10-min PVT is considered impractical, although further validation in applied settings is needed.

  17. Measurement of pattern roughness and local size variation using CD-SEM: current status

    NASA Astrophysics Data System (ADS)

    Fukuda, Hiroshi; Kawasaki, Takahiro; Kawada, Hiroki; Sakai, Kei; Kato, Takashi; Yamaguchi, Satoru; Ikota, Masami; Momonoi, Yoshinori

    2018-03-01

    Measurement of line edge roughness (LER) is discussed from four aspects: edge detection, PSD prediction, sampling strategy, and noise mitigation, and general guidelines and practical solutions for LER measurement today are introduced. Advanced edge detection algorithms such as wave-matching method are shown effective for robustly detecting edges from low SNR images, while conventional algorithm with weak filtering is still effective in suppressing SEM noise and aliasing. Advanced PSD prediction method such as multi-taper method is effective in suppressing sampling noise within a line edge to analyze, while number of lines is still required for suppressing line to line variation. Two types of SEM noise mitigation methods, "apparent noise floor" subtraction method and LER-noise decomposition using regression analysis are verified to successfully mitigate SEM noise from PSD curves. These results are extended to LCDU measurement to clarify the impact of SEM noise and sampling noise on LCDU.

  18. The skin immune response of rainbow trout, Oncorhynchus mykiss (Walbaum), associated with puffy skin disease (PSD).

    PubMed

    Christie, Lyndsay; van Aerle, Ronny; Paley, Richard K; Verner-Jeffreys, David W; Tidbury, Hannah; Green, Matthew; Feist, Stephen W; Cano, Irene

    2018-07-01

    Puffy skin disease (PSD) is an emerging skin condition which affects rainbow trout, Oncorhynchus mykiss (Walbaum). The transmission pattern of PSD suggests an infectious aetiology, however, the actual causative infectious agent(s) remain(s) unknown. In the present study, the rainbow trout epidermal immune response to PSD was characterised. Skin samples from infected fish were analysed and classified as mild, moderate or severe PSD by gross pathology and histological assessment. The level of expression of 26 immune-associated genes including cytokines, immunoglobulins and cell markers were examined by TaqMan qPCR assays. A significant up-regulation of the gene expression of C3, lysozyme, IL-1β and T-bet and down-regulation of TGFβ and TLR3 was observed in PSD fish compared to control fish. MHCI gene expression was up-regulated only in severe PSD lesions. Histological examinations of the epidermis showed a significant increase in the number of eosinophil cells and dendritic melanocytes in PSD fish. In severe lesions, mild diffuse lymphocyte infiltration was observed. IgT and CD8 positive cells were detected locally in the skin of PSD fish by in situ hybridisation (ISH), however, the gene expression of those genes was not different from control fish. Total IgM in serum of diseased animals was not different from control fish, measured by a sandwich ELISA, nor was significant up regulation of IgM gene expression in PSD lesions observed. Taken together, these results show activation of the complement pathway, up-regulation of a Th17 type response and eosinophilia during PSD. This is typical of a response to extracellular pathogens (i.e. bacteria and parasites) and allergens, commonly associated with acute dermatitis. Copyright © 2018. Published by Elsevier Ltd.

  19. Multitiered and Cooperative Surveillance of Mitochondrial Phosphatidylserine Decarboxylase 1.

    PubMed

    Ogunbona, Oluwaseun B; Onguka, Ouma; Calzada, Elizabeth; Claypool, Steven M

    2017-09-01

    Phosphatidylserine decarboxylase 1 (Psd1p), an ancient enzyme that converts phosphatidylserine to phosphatidylethanolamine in the inner mitochondrial membrane, must undergo an autocatalytic self-processing event to gain activity. Autocatalysis severs the protein into a large membrane-anchored β subunit that noncovalently associates with the small α subunit on the intermembrane space side of the inner membrane. Here, we determined that a temperature sensitive ( ts ) PSD1 allele is autocatalytically impaired and that its fidelity is closely monitored throughout its life cycle by multiple mitochondrial quality control proteases. Interestingly, the proteases involved in resolving misfolded Psd1 ts vary depending on its autocatalytic status. Specifically, the degradation of a Psd1 ts precursor unable to undergo autocatalysis requires the unprecedented cooperative and sequential actions of two inner membrane proteases, Oma1p and Yme1p. In contrast, upon heat exposure postautocatalysis, Psd1 ts β subunits accumulate in protein aggregates that are resolved by Yme1p acting alone, while the released α subunit is degraded in parallel by an unidentified protease. Importantly, the stability of endogenous Psd1p is also influenced by Yme1p. We conclude that Psd1p, the key enzyme required for the mitochondrial pathway of phosphatidylethanolamine production, is closely monitored at several levels and by multiple mitochondrial quality control mechanisms present in the intermembrane space. Copyright © 2017 American Society for Microbiology.

  20. PSD microscopy: a new technique for adaptive local scanning of microscale objects.

    PubMed

    Rahimi, Mehdi; Shen, Yantao

    2017-01-01

    A position-sensitive detector/device (PSD) is a sensor that is capable of tracking the location of a laser beam on its surface. PSDs are used in many scientific instruments and technical applications including but not limited to atomic force microscopy, human eye movement monitoring, mirrors or machine tool alignment, vibration analysis, beam position control and so on. This work intends to propose a new application using the PSD. That is a new microscopy system called scanning PSD microscopy. The working mechanism is about putting an object on the surface of the PSD and fast scanning its area with a laser beam. To achieve a high degree of accuracy and precision, a reliable framework was designed using the PSD. In this work, we first tried to improve the PSD reading and its measurement performance. This was done by minimizing the effects of noise, distortion and other disturbing parameters. After achieving a high degree of confidence, the microscopy system can be implemented based on the improved PSD measurement performance. Later to improve the scanning efficiency, we developed an adaptive local scanning system to scan the whole area of the PSD in a short matter of time. It was validated that our comprehensive and adaptive local scanning method can shorten the scanning time in order of hundreds of times in comparison with the traditional raster scanning without losing any important information about the scanned 2D objects. Methods are also introduced to scan very complicated objects with bifurcations and crossings. By incorporating all these methods, the new microscopy system is capable of scanning very complicated objects in the matter of a few seconds with a resolution that is in order of a few micrometers.

  1. Unsupervised Online Classifier in Sleep Scoring for Sleep Deprivation Studies

    PubMed Central

    Libourel, Paul-Antoine; Corneyllie, Alexandra; Luppi, Pierre-Hervé; Chouvet, Guy; Gervasoni, Damien

    2015-01-01

    Study Objective: This study was designed to evaluate an unsupervised adaptive algorithm for real-time detection of sleep and wake states in rodents. Design: We designed a Bayesian classifier that automatically extracts electroencephalogram (EEG) and electromyogram (EMG) features and categorizes non-overlapping 5-s epochs into one of the three major sleep and wake states without any human supervision. This sleep-scoring algorithm is coupled online with a new device to perform selective paradoxical sleep deprivation (PSD). Settings: Controlled laboratory settings for chronic polygraphic sleep recordings and selective PSD. Participants: Ten adult Sprague-Dawley rats instrumented for chronic polysomnographic recordings Measurements: The performance of the algorithm is evaluated by comparison with the score obtained by a human expert reader. Online detection of PS is then validated with a PSD protocol with duration of 72 hours. Results: Our algorithm gave a high concordance with human scoring with an average κ coefficient > 70%. Notably, the specificity to detect PS reached 92%. Selective PSD using real-time detection of PS strongly reduced PS amounts, leaving only brief PS bouts necessary for the detection of PS in EEG and EMG signals (4.7 ± 0.7% over 72 h, versus 8.9 ± 0.5% in baseline), and was followed by a significant PS rebound (23.3 ± 3.3% over 150 minutes). Conclusions: Our fully unsupervised data-driven algorithm overcomes some limitations of the other automated methods such as the selection of representative descriptors or threshold settings. When used online and coupled with our sleep deprivation device, it represents a better option for selective PSD than other methods like the tedious gentle handling or the platform method. Citation: Libourel PA, Corneyllie A, Luppi PH, Chouvet G, Gervasoni D. Unsupervised online classifier in sleep scoring for sleep deprivation studies. SLEEP 2015;38(5):815–828. PMID:25325478

  2. Evaluation of Visual Field Progression in Glaucoma: Quasar Regression Program and Event Analysis.

    PubMed

    Díaz-Alemán, Valentín T; González-Hernández, Marta; Perera-Sanz, Daniel; Armas-Domínguez, Karintia

    2016-01-01

    To determine the sensitivity, specificity and agreement between the Quasar program, glaucoma progression analysis (GPA II) event analysis and expert opinion in the detection of glaucomatous progression. The Quasar program is based on linear regression analysis of both mean defect (MD) and pattern standard deviation (PSD). Each series of visual fields was evaluated by three methods; Quasar, GPA II and four experts. The sensitivity, specificity and agreement (kappa) for each method was calculated, using expert opinion as the reference standard. The study included 439 SITA Standard visual fields of 56 eyes of 42 patients, with a mean of 7.8 ± 0.8 visual fields per eye. When suspected cases of progression were considered stable, sensitivity and specificity of Quasar, GPA II and the experts were 86.6% and 70.7%, 26.6% and 95.1%, and 86.6% and 92.6% respectively. When suspected cases of progression were considered as progressing, sensitivity and specificity of Quasar, GPA II and the experts were 79.1% and 81.2%, 45.8% and 90.6%, and 85.4% and 90.6% respectively. The agreement between Quasar and GPA II when suspected cases were considered stable or progressing was 0.03 and 0.28 respectively. The degree of agreement between Quasar and the experts when suspected cases were considered stable or progressing was 0.472 and 0.507. The degree of agreement between GPA II and the experts when suspected cases were considered stable or progressing was 0.262 and 0.342. The combination of MD and PSD regression analysis in the Quasar program showed better agreement with the experts and higher sensitivity than GPA II.

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

    Dalla Palma, M.; Quaranta, A.; INFN, Laboratori Nazionali di Legnaro,Viale dell'Universita, 2, 35020 Legnaro - Padova

    In the last decade, attention toward neutron detection has been growing in the scientific community, driven by new requirements in different fields of application ranging from homeland security to medical and material analysis, from research physics, to nuclear energy production. So far neutron detection, with particular attention to fast neutrons, has been mainly based on organic liquid scintillators, owing to their good efficiency and pulse shape discrimination (PSD) capability. Most of these liquids have however some main drawbacks given by toxicity, flammability, volatility and sensitivity to dissolved oxygen that limits the duration and the quality of their performances with worsemore » handiness and increased costs. Phenyl-substituted polysiloxanes could address most of these issues, being characterized by low toxicity, low volatility and low flammability. Their optical properties can be tailored by changing the phenyl distribution and concentration thus allowing to increase the solubility of organic dyes, to modify the fluorescence spectra and to vary the refractive index of the medium. Furthermore, polysiloxanes have been recently exploited for the production of plastic scintillators with very good chemical and thermal stability and very good radiation hardness and the development of polysiloxane liquid scintillators could allow to combine these interesting properties with the supremacy of liquid scintillators as regarding PSD over plastics. For these reasons, the properties of several phenyl-substituted polysiloxane with different phenyl amounts and different viscosities have been investigated, with particular attention to the scintillation response and the pulse shape discrimination capability, and the results of the investigation are reported in this work. More in details, the scintillation light yield towards gamma rays ({sup 60}Co and {sup 137}Cs) of several polysiloxane liquids has been analyzed and compared with the light yield of a commercial non-toxic liquid scintillator (EJ309). The results have been related to the optical characterization of these materials, especially as regarding the fluorescence response, and the best performing material (1,1,5,5-Tetraphenyl 1,3,3,5-Tetramethyl Trisiloxane) showed a scintillation light-yield only slightly lower than EJ309, proving to be a promising candidate for the production of an efficient polysiloxane based liquid scintillator. The results as regarding the neutron-gamma pulse shape discrimination capability of the best performing materials are also reported in this work and the scintillation decay time of these materials are compared to the results of fluorescence lifetime analysis. PSD tests have been performed at CN accelerator in Legnaro National Laboratories with a 2.2 MeV pulsed neutron beam using TOF procedure and the pulses have been analyzed in order to evidence the PSD capability of every sample. The reported results pave the way to the development of a new promising class of non-toxic liquid scintillating materials for neutron detection, with good light output and interesting PSD characteristics. (authors)« less

  4. Comparison of standard automated perimetry with matrix frequency-doubling technology in patients with resolved optic neuritis.

    PubMed

    Sakai, Tsutomu; Matsushima, Masato; Shikishima, Keigo; Kitahara, Kenji

    2007-05-01

    To examine performance characteristics of frequency-doubling perimetry (FDP) in comparison with standard automated perimetry (SAP) in patients with resolved optic neuritis in a short-term follow-up study. Comparative consecutive case series. Twenty patients with resolved optic neuritis and 20 healthy volunteers participated in this study. The subjects were patients who recovered normal vision (1.0 or better) after optic neuritis. The Swedish interactive thresholding algorithm 30-2 program was used for SAP and a full-threshold 30-2 program was used for FDP. Using both forms of perimetry, the mean deviation (MD), pattern standard deviation (PSD), and the percentage of abnormal points significantly depressed <0.5% in the total deviation probability plot were compared. The visual fields were divided into 5 zones, and the mean sensitivity in each zone in affected eyes was compared with that in healthy eyes of the volunteers within 2 weeks of vision recovery and in follow-up after 2 weeks and 2 and 5 months. Standard automated perimetry and FDP showed general depression in the fovea and extrafoveal areas. Correlations between SAP and FDP were statistically significant for MD (Pearson r>0.75; P<0.001) and PSD (r>0.6; P<0.005). Defects detected with FDP were larger than with SAP in 14 eyes (70 %). In follow-up after 2 weeks and again after 2 and 5 months, FDP indicated slower improvement in visual field defects in the fovea and extrafoveal areas, whereas SAP indicated rapid improvement in these defects. Frequency-doubling perimetry is at least comparable with and potentially more sensitive than SAP in detecting visual field defects in resolved optic neuritis. This short-term follow-up study in patients with resolved optic neuritis suggests that FDP detects characteristics of slower recovery more effectively than SAP in the fovea and extrafoveal areas. These properties may allow more accurate detection of visual field defects and may prove advantageous for monitoring of patients with resolved optic neuritis.

  5. Simulated and Real Sheet-of-Light 3D Object Scanning Using a-Si:H Thin Film PSD Arrays.

    PubMed

    Contreras, Javier; Tornero, Josep; Ferreira, Isabel; Martins, Rodrigo; Gomes, Luis; Fortunato, Elvira

    2015-11-30

    A MATLAB/SIMULINK software simulation model (structure and component blocks) has been constructed in order to view and analyze the potential of the PSD (Position Sensitive Detector) array concept technology before it is further expanded or developed. This simulation allows changing most of its parameters, such as the number of elements in the PSD array, the direction of vision, the viewing/scanning angle, the object rotation, translation, sample/scan/simulation time, etc. In addition, results show for the first time the possibility of scanning an object in 3D when using an a-Si:H thin film 128 PSD array sensor and hardware/software system. Moreover, this sensor technology is able to perform these scans and render 3D objects at high speeds and high resolutions when using a sheet-of-light laser within a triangulation platform. As shown by the simulation, a substantial enhancement in 3D object profile image quality and realism can be achieved by increasing the number of elements of the PSD array sensor as well as by achieving an optimal position response from the sensor since clearly the definition of the 3D object profile depends on the correct and accurate position response of each detector as well as on the size of the PSD array.

  6. Performance comparison of NE213 detectors for their application in moisture measurement

    PubMed

    Naqvi; Nagadi; Rehman; Kidwai

    2000-10-01

    The pulse shape discrimination (PSD) characteristic and neutron detection efficiency of NE213 detectors have been measured for their application in moisture measurements using 252Cf and 241Am-Be sources. In PSD studies, neutron peak to valley (Pn/V) ratio and figure of merit M were measured at four different bias values for cylindrical 50, 125 and 250 mm diameter NE213 detectors. The result of this study has shown that better PSD performance with the NE213 detector can be achieved with a smaller volume detector in conjunction with a neutron source with smaller gamma-ray/neutron ratio. The neutron detection efficiency of the 125 mm diameter NE213 detector for 241Am-Be and 252Cf source spectra was determined at 0.85, 1.25 and 1.75 MeV bias energies using the experimental neutron detection efficiency data of the same detector over 0.1-10 MeV energy range. Due to different energy spectra of the 241Am-Be and 252Cf sources, integrated efficiency of the 125 mm diameter NE213 detector for the two sources shows bias dependence. At smaller bias, 252Cf source has larger efficiency but as the bias is increased, the detector has larger efficiency for 241Am-Be source. This study has revealed that NE213 detector has better performance (such as PSD and neutron detection efficiency) in simultaneous detection of neutron and gamma-rays in moisture measurements, if it is used in conjunction with 241Am-Be source at higher detector bias.

  7. Analysis Spectrum of ECG Signal and QRS Detection during Running on Treadmill

    NASA Astrophysics Data System (ADS)

    Agung Suhendra, M.; Ilham R., M.; Simbolon, Artha I.; Faizal A., M.; Munandar, A.

    2018-03-01

    The heart is an important organ in our metabolism in which it controls circulatory and oxygen. The heart exercise is needed one of them using the treadmill to prevent health. To analysis, it using electrocardiograph (ECG) to investigating and diagnosing anomalies of the heart. In this paper, we would like to analysis ECG signals during running on the treadmill with kinds of speeds. There are two analysis ECG signals i.e. QRS detection and power spectrum density (PSD). The result of PSD showed that subject 3 has highly for all subject and the result of QRS detection using pan Tomkins algorithm that a percentage of failed detection is an approaching to 0 % for all subject.

  8. Stabilization of Particle Discrimination Efficiencies for Neutron Spectrum Unfolding With Organic Scintillators

    NASA Astrophysics Data System (ADS)

    Lawrence, Chris C.; Polack, J. K.; Febbraro, Michael; Kolata, J. J.; Flaska, Marek; Pozzi, S. A.; Becchetti, F. D.

    2017-02-01

    The literature discussing pulse-shape discrimination (PSD) in organic scintillators dates back several decades. However, little has been written about PSD techniques that are optimized for neutron spectrum unfolding. Variation in n-γ misclassification rates and in γ/n ratio of incident fields can distort the neutron pulse-height response of scintillators and these distortions can in turn cause large errors in unfolded spectra. New applications in arms-control verification call for detection of lower-energy neutrons, for which PSD is particularly problematic. In this article, we propose techniques for removing distortions on pulse-height response that result from the merging of PSD distributions in the low-pulse-height region. These techniques take advantage of the repeatable shapes of PSD distributions that are governed by the counting statistics of scintillation-photon populations. We validate the proposed techniques using accelerator-based time-of-flight measurements and then demonstrate them by unfolding the Watt spectrum from measurement with a 252Cf neutron source.

  9. Enhancement of sun-tracking with optoelectronic devices

    NASA Astrophysics Data System (ADS)

    Wu, Jiunn-Chi

    2015-09-01

    Sun-tracking is one of the most challenging tasks in implementing CPV. In order to justify the additional complexity of sun-tracking, careful assessment of performance of CPV by monitoring the performance of sun-tracking is vital. Measurement of accuracy of sun-tracking is one of the important tasks in an outdoor test. This study examines techniques with three optoelectronic devices (i.e. position sensitive device (PSD), CCD and webcam). Outdoor measurements indicated that during sunny days (global horizontal insolation (GHI) > 700 W/m2), three devices recorded comparable tracking accuracy of 0.16˜0.3°. The method using a PSD has fastest sampling rate and is able to detect the sun's position without additional image processing. Yet, it cannot identify the sunlight effectively during low insolation. The techniques with a CCD and a webcam enhance the accuracy of centroid of sunlight via the optical lens and image processing. The image quality acquired using a webcam and a CCD is comparable but the webcam is more affordable than that of CCD because it can be assembled with consumer-graded products.

  10. Audible acoustics in high-shear wet granulation: application of frequency filtering.

    PubMed

    Hansuld, Erin M; Briens, Lauren; McCann, Joe A B; Sayani, Amyn

    2009-08-13

    Previous work has shown analysis of audible acoustic emissions from high-shear wet granulation has potential as a technique for end-point detection. In this research, audible acoustic emissions (AEs) from three different formulations were studied to further develop this technique as a process analytical technology. Condenser microphones were attached to three different locations on a PMA-10 high-shear granulator (air exhaust, bowl and motor) to target different sound sources. Size, flowability and tablet break load data was collected to support formulator end-point ranges and interpretation of AE analysis. Each formulation had a unique total power spectral density (PSD) profile that was sensitive to granule formation and end-point. Analyzing total PSD in 10 Hz segments identified profiles with reduced run variability and distinct maxima and minima suitable for routine granulation monitoring and end-point control. A partial least squares discriminant analysis method was developed to automate selection of key 10 Hz frequency groups using variable importance to projection. The results support use of frequency refinement as a way forward in the development of acoustic emission analysis for granulation monitoring and end-point control.

  11. Lambda-cyhalothrin disrupts the up-regulation effect of 17β-estradiol on post-synaptic density 95 protein expression via estrogen receptor α-dependent Akt pathway.

    PubMed

    Wang, Qunan; Xia, Xin; Deng, Xiaomei; Li, Nian; Wu, Daji; Zhang, Long; Yang, Chengwei; Tao, Fangbiao; Zhou, Jiangning

    2016-03-01

    Lambda-cyhalothrin (LCT), one of the type II pyrethroids, has been widely used throughout the world. The estrogenic effect of LCT to increase cell proliferation has been well established. However, whether the estrogenic effect of LCT will influence neurodevelopment has not been investigated. In addition, 17β-Estradiol (E2) plays a crucial role in neurodevelopment and induces an increase in synaptic proteins. The post-synaptic density 95 (PSD95) protein, which is involved in the development of the structure and function of new spines and localized with estrogen receptor α (ERα) at the post-synaptic density (PSD), was detected in our study by using hippocampal neuron cell line HT22. We found that LCT up-regulated PSD95 and ERα expression, estrogen receptor (ER) antagonist ICI182,780 and phosphatidylinositol-4; 5-bisphosphate 3-kinase (PI3K) inhibitor LY294,002 blocked this effect. In addition, LCT disrupted the promotion effect of E2 on PSD95. To investigate whether the observed changes are caused by ERα-dependent signaling activation, we next detected the effects of LCT on the ERα-mediated PI3K-Protein kinase B (PKB/Akt)-eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) pathway. There existed an activation of Akt and the downstream factor 4E-BP1 after LCT treatment. In addition, LCT could disrupt the activation effect of E2 on the Akt pathway. However, no changes in cAMP response element-binding protein (CREB) activation and PSD95 messenger ribonucleic acid (mRNA) were observed. Our findings demonstrated that LCT could increase the PSD95 protein level via the ERα-dependent Akt pathway, and LCT might disrupt the up-regulation effect of E2 on PSD95 protein expression via this signaling pathway. Copyright © 2015. Published by Elsevier B.V.

  12. [The role of BDNF pathway in lambda-cyhalothrin disrupting the promotion of 17β-Estradiol on Post-synaptic Density 95 protein expression in HT22 cell].

    PubMed

    Li, N; Wang, Q N; Wu, D J; Yang, C W; Luo, B B

    2016-07-20

    Objective: To explore the effect of BDNF pathway on lambda-cyhalothrin interfering estrogen promoting the expression of PSD95 in hippocampus neurons. Methods: HT22 cell line were used to, treating with lambda-cyhalothrin (LCT, 50 μmol/L) , 17β-Estradiol (E2, 10 nmol/L) , LCT (50 μmol/L) +TrkB FC (20 μg/ml) , E2 (10 nmol/L) +TrkB FC (20 μg/ml) , LCT (50 μmol/L) +ICI182 780 (1 μmol/L) , E2 (10 nmol/L) + ICI182 780 (1 μmol/L) , LCT (50 μmol/L) +E2 (10 nmol/L) for 24 h. MTT kit was used to detect cell viability. Post-synaptic Density 95 protein expression was measured by western blot. ELISA assay was used to detect the level of brain derived neurotrophic factor (BDNF) of culture supernatant and cell. Results: Campared to Sham, LCT or E2 could promote the expression of PSD95 LCT+ICI could reduce the expresion of BDNF ( P <0.05) , campared to LCT, LCT+TrkB FC could reduce the expression of PSD95 and LCT+ICI cound reduce the expresion of BDNF ( P <0.05) , campared to E2, E2+TrkB FC could reduce the expression of PSD95 and E 2 +ICI could reduce the expression of BDNF ( P <0.05) , campared to E2, LCT+ E2 could reduce the expression of PSD95 and BDNF ( P <0.05) . Conclusion: BDNF pathway plays a key role in E2 promoting the expression of PSD95 in neural cells. Although LCT alone has a similar effect on E2. LCT could disrupt the promotion of E2 on PSD95 expression via BDNF pathway.

  13. Noise effect in an improved conjugate gradient algorithm to invert particle size distribution and the algorithm amendment.

    PubMed

    Wei, Yongjie; Ge, Baozhen; Wei, Yaolin

    2009-03-20

    In general, model-independent algorithms are sensitive to noise during laser particle size measurement. An improved conjugate gradient algorithm (ICGA) that can be used to invert particle size distribution (PSD) from diffraction data is presented. By use of the ICGA to invert simulated data with multiplicative or additive noise, we determined that additive noise is the main factor that induces distorted results. Thus the ICGA is amended by introduction of an iteration step-adjusting parameter and is used experimentally on simulated data and some samples. The experimental results show that the sensitivity of the ICGA to noise is reduced and the inverted results are in accord with the real PSD.

  14. A pilot investigation of the effect of extremely low frequency pulsed electromagnetic fields on humans' heart rate variability.

    PubMed

    Baldi, Emilio; Baldi, Claudio; Lithgow, Brian J

    2007-01-01

    The question whether pulsed electromagnetic field (PEMF) can affect the heart rhythm is still controversial. This study investigates the effects on the cardiocirculatory system of ELF-PEMFs. It is a follow-up to an investigation made of the possible therapeutic effect ELF-PEMFs, using a commercially available magneto therapeutic unit, had on soft tissue injury repair in humans. Modulation of heart rate (HR) or heart rate variability (HRV) can be detected from changes in periodicity of the R-R interval and/or from changes in the numbers of heart-beat/min (bpm), however, R-R interval analysis gives only a quantitative insight into HRV. A qualitative understanding of HRV can be obtained considering the power spectral density (PSD) of the R-R intervals Fourier transform. In this study PSD is the investigative tool used, more specifically the low frequency (LF) PSD and high frequency (HF) PSD ratio (LF/HF) which is an indicator of sympatho-vagal balance. To obtain the PSD value, variations of the R-R time intervals were evaluated from a continuously recorded ECG. The results show a HR variation in all the subjects when they are exposed to the same ELF-PEMF. This variation can be detected by observing the change in the sympatho-vagal equilibrium, which is an indicator of modulation of heart activity. Variation of the LF/HF PSD ratio mainly occurs at transition times from exposure to nonexposure, or vice versa. Also of interest are the results obtained during the exposure of one subject to a range of different ELF-PEMFs. This pilot study suggests that a full investigation into the effect of ELF-PEMFs on the cardiovascular system is justified.

  15. A preliminary examination of the validity and reliability of a new brief rating scale for symptom domains of psychosis: Brief Evaluation of Psychosis Symptom Domains (BE-PSD).

    PubMed

    Takeuchi, Hiroyoshi; Fervaha, Gagan; Lee, Jimmy; Agid, Ofer; Remington, Gary

    2016-09-01

    Brief assessments have the potential to be widely adopted as outcome measures in research but also routine clinical practice. Existing brief rating scales that assess symptoms of schizophrenia or psychosis have a number of limitations including inability to capture five symptom domains of psychosis and a lack of clearly defined operational anchor points for scoring. We developed a new brief rating scale for five symptom domains of psychosis with clearly defined operational anchor points - the Brief Evaluation of Psychosis Symptom Domains (BE-PSD). To examine the psychometric properties of the BE-PSD, fifty patients with schizophrenia or schizoaffective disorder were included in this preliminary cross-sectional study. To test the convergent and discriminant validity of the BE-PSD, correlational analyses were employed using the consensus Positive and Negative Syndrome Scale (PANSS) five-factor model. To examine the inter-rater reliability of the BE-PSD, single measures intraclass correlation coefficients (ICCs) were calculated for 11 patients. The BE-PSD domain scores demonstrated high convergent validity with the corresponding PANSS factor score (rs = 0.81-0.93) as well as good discriminant validity, as evidenced by lower correlations with the other PANSS factors (rs = 0.23-0.62). The BE-PSD also demonstrated excellent inter-rater reliability for each of the domain scores and the total scores (ICC(2,1) = 0.79-0.96). The present preliminary study found the BE-PSD measure to be valid and reliable; however, further studies are needed to establish the psychometric properties of the BE-PSD because of the limitations such as the small sample size and lacking data on test-retest reliability or sensitivity to change. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Neutron-gamma discrimination via PSD plastic scintillator and SiPMs

    NASA Astrophysics Data System (ADS)

    Taggart, M. P.; Payne, C.; Sellin, P. J.

    2016-10-01

    The reduction in availability and inevitable increase in cost of traditional neutron detectors based on the 3He neutron capture reaction has resulted in a concerted effort to seek out new techniques and detection media to meet the needs of national nuclear security. Traditionally, the alternative has been provided through pulse shape discrimination (PSD) using liquid scintillators. However, these are not without their own inherent issues, primarily concerning user safety and ongoing maintenance. A potential system devised to separate neutron and gamma ray pulses utilising the PSD technique takes advantage of recent improvements in silicon photomultiplier (SiPM) technology and the development of plastic scintillators exhibiting the PSD phenomena. In this paper we present the current iteration of this ongoing work having achieved a Figure of Merit (FoM) of 1.39 at 1.5 MeVee.

  17. Recent developments in plastic scintillators with pulse shape discrimination

    NASA Astrophysics Data System (ADS)

    Zaitseva, N. P.; Glenn, A. M.; Mabe, A. N.; Carman, M. L.; Hurlbut, C. R.; Inman, J. W.; Payne, S. A.

    2018-05-01

    The paper reports results of studies conducted to improve scintillation performance of plastic scintillators capable of neutron/gamma pulse-shape discrimination (PSD). Compositional modifications made with the polymer matrix improved physical stability, allowing for increased loads of the primary dye that, in combination with selected secondary dyes, provided enhanced PSD especially important for the lower energy ranges. Additional measurements were made with a newly-introduced PSD plastic EJ-276, that replaces the first commercially produced EJ-299. Comparative studies conducted with the new materials and EJ-309 liquids at large scale (up to 10 cm) show that current plastics may provide scintillation and PSD performance sufficient for the replacement of liquid scintillators. Comparison to stilbene single crystals compliments the information about the status of the solid-state materials recently developed for fast neutron detection applications.

  18. PAUSED encodes the Arabidopsis exportin-t ortholog.

    PubMed

    Hunter, Christine A; Aukerman, Milo J; Sun, Hui; Fokina, Maria; Poethig, R Scott

    2003-08-01

    Los1p/exportin-t (XPOT) mediates the nuclear export of tRNAs in yeast and mammals. The requirements for this transport pathway are unclear, however, because los1 mutations do not affect yeast growth, and the phenotype of XPOT mutations in mammals is unknown. Here, we show that PAUSED (PSD) is the Arabidopsis ortholog of LOS1/XPOT and is capable of rescuing the tRNA export defect of los1 in Brewer's yeast (Saccharomyces cerevisiae), suggesting that its function has been conserved. Putative null alleles of PSD disrupt the initiation of the shoot apical meristem and delay leaf initiation after germination, the emergence of the radicle and lateral roots, and the transition to flowering. Plants doubly mutant for psd and hasty, the Arabidopsis ortholog of exportin 5, are viable but have a more severe phenotype than either single mutant. These results suggest that PSD plays a role in tRNA export in Arabidopsis, but that at least one-and perhaps several-additional tRNA export pathways also exist. The PSD transcript is broadly expressed during development and is alternatively spliced in the 3'-untranslated region. No temporal or spatial difference in the abundance of different splice forms was observed. We propose that the mutant phenotype of psd reflects defects in developmental events and cell/tissue types that require elevated levels of protein synthesis and are therefore acutely sensitive to a reduction in tRNA export.

  19. Technical Note: Out‐of‐field dose measurement at near surface with plastic scintillator detector

    PubMed Central

    Bourgouin, Alexandra; Varfalvy, Nicolas

    2016-01-01

    Out‐of‐field dose depends on multiple factors, making peripheral dosimetry complex. Only a few dosimeters have the required features for measuring peripheral dose. Plastic scintillator dosimeters (PSDs) offer numerous dosimetric advantages as required for out‐of‐field dosimetry. The purpose of this study is to determine the potential of using PSD as a surface peripheral dosimeter. Measurements were performed with a parallel‐plate ion chamber, a small volume ion chamber, and with a PSD. Lateral‐dose measurements (LDM) at 0.5 cm depth and depth‐dose curve (PDD) were made and compared to the dose calculation provided by a treatment planning system (TPS). This study shows that a PSD can measure a dose as low as 0.51±0.17cGy for photon beam and 0.58±0.20cGy for electron beam with a difference of 0.2 and 0.1 cGy compared to a parallel‐plate ion chamber. This study demonstrates the potential of using PSD as an out‐of‐field dosimeter since measurements with PSD avoid averaging over a too‐large depth, at 1 mm diameter, and can make precise measurement at very low dose. Also, electronic equilibrium is easier to reach with PSD due to its small sensitive volume and its water equivalence. PACS number(s): 87.55.N, 87.55.km PMID:27685131

  20. The Role of the Two-Pore Domain Potassium Channel TREK-1 in the Therapeutic Effects of Escitalopram in a Rat Model of Poststroke Depression.

    PubMed

    Lin, Dai-Hua; Zhang, Xiang-Rong; Ye, Dong-Qing; Xi, Guang-Jun; Hui, Jiao-Jie; Liu, Shan-Shan; Li, Lin-Jiang; Zhang, Zhi-Jun

    2015-06-01

    Poststroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. TREK-1, a two-pore-domain potassium channel, has been implicated in the pathogenesis of stroke and depression. The aim of this study was to investigate whether TREK-1 plays a role in the therapeutic effects of the selective serotonin reuptake inhibitor (SSRI) escitalopram in a rat PSD model. The whole-cell patch-clamp technique was performed to assess the effect of escitalopram on recombinant TREK-1 currents in HEK293 cells. The expression of TREK-1 mRNA and protein was measured in the hippocampus and prefrontal cortex (PFC), and neural stem cell (NSC) proliferation was detected in the hippocampal dentate gyrus (DG) in PSD rats after 3 weeks of escitalopram administration. Escitalopram reversibly inhibited TREK-1 currents in a concentration-dependent manner. Chronic treatment with escitalopram significantly reversed the reductions in weight gain, locomotor activity, and sucrose preference in PSD rats. The expressions of TREK-1 mRNA and protein were significantly increased in hippocampal CA1, CA3, DG, and PFC in PSD rats, with the exception of TREK-1 mRNA in hippocampal CA1. NSC proliferation was significantly decreased in hippocampal DG of PSD rats. Escitalopram significantly reversed the regional increases of TREK-1 expression and the reduction of hippocampal NSC proliferation in PSD rats. TREK-1 plays an important role in the therapeutic effects of the SSRI escitalopram in PSD model, making TREK-1 an attractive candidate molecule for further understanding the pathophysiology and treatment of PSD. © 2015 John Wiley & Sons Ltd.

  1. The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury.

    PubMed

    Zhang, Qingxiu; Cheng, Hongyu; Rong, Rong; Yang, Hui; Ji, Qiuhong; Li, Qingjie; Rong, Liangqun; Hu, Gang; Xu, Yun

    2015-12-01

    The aim of the study was to explore the effect of PSD-93 deficiency on the expression of early inflammatory cytokines induced by cerebral ischemia/reperfusion injury. Ten- to twelve-week-old male PSD-93 knockout (PSD-93 KO) mice (C57BL/6 genetic background) and wild-type (WT) littermates were randomly divided into sham and ischemia/reperfusion (I/R) group. The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO) suture method. RT-PCR was used to detect the mRNA expression of IL-6, IL-10, Cox-2, iNOS, and TNF-α4h following reperfusion. Infarct volume at different time points after I/R was analyzed using 2,3,5-triphenyl tetrazolium staining, and neurological damage score (neurological severity scores, NSS) was used to evaluate the effect of PSD-93 gene knockout on the MCAO-induced neurological injury. In WT mice, early I/R injury led to the increase in the mRNA expression of proinflammatory cytokines IL-6, Cox-2, iNOS, and TNF-α that coincided with the decrease in the expression of anti-inflammatory cytokine IL-10, as compared to the sham group (P < 0.05). This effect was markedly attenuated by depleting PSD-93 levels by gene knockout. As compared to sham group, in PSD-93 KO mice I/R4h led to downregulation of Cox-2 and iNOS expression, and increase in the mRNA levels of IL-10 (P < 0.05). In addition, following MCAO, PSD-93 KO mice exhibited improved NSS and reduced infarct volumes, as compared with WT animals. PSD-93 knockout may play a neuroprotective role by mediating the early release of inflammatory cytokines induced by cerebral ischemia.

  2. Reduced thalamic volume in men with antisocial personality disorder or schizophrenia and a history of serious violence and childhood abuse.

    PubMed

    Kumari, V; Gudjonsson, G H; Raghuvanshi, S; Barkataki, I; Taylor, P; Sumich, A; Das, K; Kuipers, E; Ffytche, D H; Das, M

    2013-05-01

    Violent behaviour has been associated with presence of certain mental disorders, most notably antisocial personality disorder (ASPD) and schizophrenia, childhood abuse, and multiple brain abnormalities. This study examined for the first time, to the authors' knowledge, the role of psychosocial deprivation (PSD), including childhood physical and sexual abuse, in structural brain volumes of violent individuals with ASPD or schizophrenia. Fifty-six men (26 with ASPD or schizophrenia and a history of serious violence, 30 non-violent) underwent magnetic resonance imaging and were assessed on PSD. Stereological volumetric brain ratings were examined for group differences and their association with PSD ratings. PSD-brain associations were examined further using voxel-based-morphometry. The findings revealed: reduced thalamic volume in psychosocially-deprived violent individuals, relative to non-deprived violent individuals and healthy controls; negative association between thalamic volume and abuse ratings (physical and sexual) in violent individuals; and trend-level negative associations between PSD and hippocampal and prefrontal volumes in non-violent individuals. The voxel-based-morphometry analysis detected a negative association between PSD and localised grey matter volumes in the left inferior frontal region across all individuals, and additionally in the left middle frontal and precentral gyri in non-violent individuals. Violent mentally-disordered individuals with PSD, relative to those with no or minimal PSD, suffer from an additional brain deficit, i.e., reduced thalamic volume; this may affect sensory information processing, and have implications for management, of these individuals. PSD may have a stronger relationship with volumetric loss of stress-linked regions, namely the frontal cortex, in non-violent individuals. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  3. Comparison of projection skills of deterministic ensemble methods using pseudo-simulation data generated from multivariate Gaussian distribution

    NASA Astrophysics Data System (ADS)

    Oh, Seok-Geun; Suh, Myoung-Seok

    2017-07-01

    The projection skills of five ensemble methods were analyzed according to simulation skills, training period, and ensemble members, using 198 sets of pseudo-simulation data (PSD) produced by random number generation assuming the simulated temperature of regional climate models. The PSD sets were classified into 18 categories according to the relative magnitude of bias, variance ratio, and correlation coefficient, where each category had 11 sets (including 1 truth set) with 50 samples. The ensemble methods used were as follows: equal weighted averaging without bias correction (EWA_NBC), EWA with bias correction (EWA_WBC), weighted ensemble averaging based on root mean square errors and correlation (WEA_RAC), WEA based on the Taylor score (WEA_Tay), and multivariate linear regression (Mul_Reg). The projection skills of the ensemble methods improved generally as compared with the best member for each category. However, their projection skills are significantly affected by the simulation skills of the ensemble member. The weighted ensemble methods showed better projection skills than non-weighted methods, in particular, for the PSD categories having systematic biases and various correlation coefficients. The EWA_NBC showed considerably lower projection skills than the other methods, in particular, for the PSD categories with systematic biases. Although Mul_Reg showed relatively good skills, it showed strong sensitivity to the PSD categories, training periods, and number of members. On the other hand, the WEA_Tay and WEA_RAC showed relatively superior skills in both the accuracy and reliability for all the sensitivity experiments. This indicates that WEA_Tay and WEA_RAC are applicable even for simulation data with systematic biases, a short training period, and a small number of ensemble members.

  4. Sea Ice Detection Based on Differential Delay-Doppler Maps from UK TechDemoSat-1

    PubMed Central

    Zhu, Yongchao; Yu, Kegen; Zou, Jingui; Wickert, Jens

    2017-01-01

    Global Navigation Satellite System (GNSS) signals can be exploited to remotely sense atmosphere and land and ocean surface to retrieve a range of geophysical parameters. This paper proposes two new methods, termed as power-summation of differential Delay-Doppler Maps (PS-D) and pixel-number of differential Delay-Doppler Maps (PN-D), to distinguish between sea ice and sea water using differential Delay-Doppler Maps (dDDMs). PS-D and PN-D make use of power-summation and pixel-number of dDDMs, respectively, to measure the degree of difference between two DDMs so as to determine the transition state (water-water, water-ice, ice-ice and ice-water) and hence ice and water are detected. Moreover, an adaptive incoherent averaging of DDMs is employed to improve the computational efficiency. A large number of DDMs recorded by UK TechDemoSat-1 (TDS-1) over the Arctic region are used to test the proposed sea ice detection methods. Through evaluating against ground-truth measurements from the Ocean Sea Ice SAF, the proposed PS-D and PN-D methods achieve a probability of detection of 99.72% and 99.69% respectively, while the probability of false detection is 0.28% and 0.31% respectively. PMID:28704948

  5. Quantitative characterization of surface topography using spectral analysis

    NASA Astrophysics Data System (ADS)

    Jacobs, Tevis D. B.; Junge, Till; Pastewka, Lars

    2017-03-01

    Roughness determines many functional properties of surfaces, such as adhesion, friction, and (thermal and electrical) contact conductance. Recent analytical models and simulations enable quantitative prediction of these properties from knowledge of the power spectral density (PSD) of the surface topography. The utility of the PSD is that it contains statistical information that is unbiased by the particular scan size and pixel resolution chosen by the researcher. In this article, we first review the mathematical definition of the PSD, including the one- and two-dimensional cases, and common variations of each. We then discuss strategies for reconstructing an accurate PSD of a surface using topography measurements at different size scales. Finally, we discuss detecting and mitigating artifacts at the smallest scales, and computing upper/lower bounds on functional properties obtained from models. We accompany our discussion with virtual measurements on computer-generated surfaces. This discussion summarizes how to analyze topography measurements to reconstruct a reliable PSD. Analytical models demonstrate the potential for tuning functional properties by rationally tailoring surface topography—however, this potential can only be achieved through the accurate, quantitative reconstruction of the PSDs of real-world surfaces.

  6. Research on the detection system of liquid concentration base on birefringence light transmission method

    NASA Astrophysics Data System (ADS)

    Li, Tianze; Zhang, Xia; Hou, Luan; Jiang, Chuan

    2010-10-01

    The characteristics of the beam transmitting in the optical fiber and the liquid medium are analyzed in this paper. On this basis, a new type of semiconductor optical position sensitive detector is used for a receiving device, a light transmission method of birefringence is presented,and a set of opto-electrical detection system which is applied to detect liquid concentration is designed. The system is mainly composed of semiconductor lasers,optical systems, Psd signal conditioning circuit, Single-chip System, A/D conversion circuit and display circuit. Through theoretical analysis and experimental simulations, the accuracy of this system has been verified. Some main factors affecting the test results are analyzed detailedly in this paper. The experiments show that the temperature drift and the light intensity have a very small impact on this system. The system has some advantages, such as the simple structure, high sensitivity, good stability, fast response time, high degree of automation, and so on. It also can achieve the real-time detection of liquid concentration conveniently and accurately. The system can be widely applied in chemical, food, pharmacy and many other industries. It has broad prospects of application.

  7. Neutron/gamma pulse shape discrimination (PSD) in plastic scintillators with digital PSD electronics

    NASA Astrophysics Data System (ADS)

    Hutcheson, Anthony L.; Simonson, Duane L.; Christophersen, Marc; Phlips, Bernard F.; Charipar, Nicholas A.; Piqué, Alberto

    2013-05-01

    Pulse shape discrimination (PSD) is a common method to distinguish between pulses produced by gamma rays and neutrons in scintillator detectors. This technique takes advantage of the property of many scintillators that excitations by recoil protons and electrons produce pulses with different characteristic shapes. Unfortunately, many scintillating materials with good PSD properties have other, undesirable properties such as flammability, toxicity, low availability, high cost, and/or limited size. In contrast, plastic scintillator detectors are relatively low-cost, and easily handled and mass-produced. Recent studies have demonstrated efficient PSD in plastic scintillators using a high concentration of fluorescent dyes. To further investigate the PSD properties of such systems, mixed plastic scintillator samples were produced and tested. The addition of up to 30 wt. % diphenyloxazole (DPO) and other chromophores in polyvinyltoluene (PVT) results in efficient detection with commercial detectors. These plastic scintillators are produced in large diameters up to 4 inches by melt blending directly in a container suitable for in-line detector use. This allows recycling and reuse of materials while varying the compositions. This strategy also avoids additional sample handling and polishing steps required when using removable molds. In this presentation, results will be presented for different mixed-plastic compositions and compared with known scintillating materials

  8. PAUSED Encodes the Arabidopsis Exportin-t Ortholog1

    PubMed Central

    Hunter, Christine A.; Aukerman, Milo J.; Sun, Hui; Fokina, Maria; Poethig, R. Scott

    2003-01-01

    Los1p/exportin-t (XPOT) mediates the nuclear export of tRNAs in yeast and mammals. The requirements for this transport pathway are unclear, however, because los1 mutations do not affect yeast growth, and the phenotype of XPOT mutations in mammals is unknown. Here, we show that PAUSED (PSD) is the Arabidopsis ortholog of LOS1/XPOT and is capable of rescuing the tRNA export defect of los1 in Brewer's yeast (Saccharomyces cerevisiae), suggesting that its function has been conserved. Putative null alleles of PSD disrupt the initiation of the shoot apical meristem and delay leaf initiation after germination, the emergence of the radicle and lateral roots, and the transition to flowering. Plants doubly mutant for psd and hasty, the Arabidopsis ortholog of exportin 5, are viable but have a more severe phenotype than either single mutant. These results suggest that PSD plays a role in tRNA export in Arabidopsis, but that at least one—and perhaps several—additional tRNA export pathways also exist. The PSD transcript is broadly expressed during development and is alternatively spliced in the 3′-untranslated region. No temporal or spatial difference in the abundance of different splice forms was observed. We propose that the mutant phenotype of psd reflects defects in developmental events and cell/tissue types that require elevated levels of protein synthesis and are therefore acutely sensitive to a reduction in tRNA export. PMID:12913168

  9. Studying the protein organization of the postsynaptic density by a novel solid phase- and chemical cross-linking-based technology.

    PubMed

    Liu, Szu-Heng; Cheng, Huei-Hsuan; Huang, San-Yuan; Yiu, Pei-Chun; Chang, Yen-Chung

    2006-06-01

    Agarose beads carrying a cleavable, fluorescent, and photoreactive cross-linking reagent on the surface were synthesized and used to selectively pull out the proteins lining the surface of supramolecules. A quantitative comparison of the abundances of various proteins in the sample pulled out by the beads from supramolecules with their original abundances could provide information on the spatial arrangement of these proteins in the supramolecule. The usefulness of these synthetic beads was successfully verified by trials using a synthetic protein complex consisting of three layers of different proteins on glass coverslips. By using these beads, we determined the interior or superficial locations of five major and 19 minor constituent proteins in the postsynaptic density (PSD), a large protein complex and the landmark structure of asymmetric synapses in the mammalian central nervous system. The results indicate that alpha,beta-tubulins, dynein heavy chain, microtubule-associated protein 2, spectrin, neurofilament H and M subunits, an hsp70 protein, alpha-internexin, dynamin, and PSD-95 protein reside in the interior of the PSD. Dynein intermediate chain, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors, kainate receptors, N-cadherin, beta-catenin, N-ethylmaleimide-sensitive factor, an hsc70 protein, and actin reside on the surface of the PSD. The results further suggest that the N-methyl-d-aspartate receptors and the alpha-subunits of calcium/calmodulin-dependent protein kinase II are likely to reside on the surface of the PSD although with unique local protein organizations. Based on our results and the known interactions between various PSD proteins from data mining, a model for the molecular organization of the PSD is proposed.

  10. System for Measuring Flexing of a Large Spaceborne Structure

    NASA Technical Reports Server (NTRS)

    Scharf, Daniel; Kuhnert, Andreas; Kovalik, Joseph; Hadaegh, Fred; Shaddock, Daniel

    2008-01-01

    An optoelectronic metrology system is used for determining the attitude and flexing of a large spaceborne radar antenna or similar structure. The measurements are needed for accurate pointing of the antenna and correction and control of the phase of the radar signal wavefront. The system includes a dual-field-of-view star tracker; a laser ranging unit (LRU) and a position-sensitive-detector (PSD)-based camera mounted on an optical bench; and fiducial targets at various locations on the structure. The fiducial targets are illuminated in sequence by laser light coupled via optical fibers. The LRU and the PSD provide measurements of the position of each fiducial target in a reference frame attached to the optical bench. During routine operation, the star tracker utilizes one field of view and functions conventionally to determine the orientation of the optical bench. During operation in a calibration mode, the star tracker also utilizes its second field of view, which includes stars that are imaged alongside some of the fiducial targets in the PSD; in this mode, the PSD measurements are traceable to star measurements.

  11. Analysis and Calibration of Sources of Electronic Error in PSD Sensor Response.

    PubMed

    Rodríguez-Navarro, David; Lázaro-Galilea, José Luis; Bravo-Muñoz, Ignacio; Gardel-Vicente, Alfredo; Tsirigotis, Georgios

    2016-04-29

    In order to obtain very precise measurements of the position of agents located at a considerable distance using a sensor system based on position sensitive detectors (PSD), it is necessary to analyze and mitigate the factors that generate substantial errors in the system's response. These sources of error can be divided into electronic and geometric factors. The former stem from the nature and construction of the PSD as well as the performance, tolerances and electronic response of the system, while the latter are related to the sensor's optical system. Here, we focus solely on the electrical effects, since the study, analysis and correction of these are a prerequisite for subsequently addressing geometric errors. A simple calibration method is proposed, which considers PSD response, component tolerances, temperature variations, signal frequency used, signal to noise ratio (SNR), suboptimal operational amplifier parameters, and analog to digital converter (ADC) quantitation SNRQ, etc. Following an analysis of these effects and calibration of the sensor, it was possible to correct the errors, thus rendering the effects negligible, as reported in the results section.

  12. Analysis and Calibration of Sources of Electronic Error in PSD Sensor Response

    PubMed Central

    Rodríguez-Navarro, David; Lázaro-Galilea, José Luis; Bravo-Muñoz, Ignacio; Gardel-Vicente, Alfredo; Tsirigotis, Georgios

    2016-01-01

    In order to obtain very precise measurements of the position of agents located at a considerable distance using a sensor system based on position sensitive detectors (PSD), it is necessary to analyze and mitigate the factors that generate substantial errors in the system’s response. These sources of error can be divided into electronic and geometric factors. The former stem from the nature and construction of the PSD as well as the performance, tolerances and electronic response of the system, while the latter are related to the sensor’s optical system. Here, we focus solely on the electrical effects, since the study, analysis and correction of these are a prerequisite for subsequently addressing geometric errors. A simple calibration method is proposed, which considers PSD response, component tolerances, temperature variations, signal frequency used, signal to noise ratio (SNR), suboptimal operational amplifier parameters, and analog to digital converter (ADC) quantitation SNRQ, etc. Following an analysis of these effects and calibration of the sensor, it was possible to correct the errors, thus rendering the effects negligible, as reported in the results section. PMID:27136562

  13. Assessment of airborne environmental bacteria and related factors in 25 underground railway stations in Seoul, Korea

    NASA Astrophysics Data System (ADS)

    Hwang, Sung Ho; Yoon, Chung Sik; Ryu, Kyong Nam; Paik, Samuel Y.; Cho, Jun Ho

    2010-05-01

    This study assessed bacterial concentrations in indoor air at 25 underground railway stations in Seoul, Korea, and investigated various related factors including the presence of platform screen doors (PSD), depth of the station, year of construction, temperature, relative humidity, and number of passengers. A total of 72 aerosol samples were collected from all the stations. Concentrations of total airborne bacteria (TAB) ranged from not detected (ND) to 4997 CFU m -3, with an overall geometric mean (GM) of 191 CFU m -3. Airborne bacteria were detected at 23 stations (92%) and Gram-negative bacteria (GNB) were detected at two stations (8%). TAB concentrations of four stations (16%) exceeded 800 CFU m -3, the Korea indoor bio-aerosol guideline. The results of the study showed that TAB concentrations at the stations without PSD showed higher TAB concentrations than those with PSD, though not at statistically significant levels. TAB concentrations of deeper stations revealed significantly higher levels than those of shallower stations. Based on this study, it is recommended that mitigation measures be applied to improve the indoor air quality (IAQ) of underground railway stations in Seoul, with focused attention on deeper stations.

  14. Structure-Function Relationship between Flicker-Defined Form Perimetry and Spectral-Domain Optical Coherence Tomography in Glaucoma Suspects.

    PubMed

    Reznicek, Lukas; Muth, Daniel; Vogel, Michaela; Hirneiß, Christoph

    2017-03-01

    To evaluate the relationship between functional parameters of repeated flicker-defined form perimetry (FDF) and structural parameters of spectral-domain optical coherence tomography (SD-OCT) in glaucoma suspects with normal findings in achromatic standard automated perimetry (SAP). Patients with optic nerve heads (ONH) clinically suspicious for glaucoma and normal SAP findings were enrolled in this prospective study. Each participant underwent visual field (VF) testing with FDF perimetry, using the Heidelberg Edge Perimeter (HEP, Heidelberg Engineering, Heidelberg, Germany) at two consecutive visits. Peripapillary RNFL thickness was obtained by SD-OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany). Correlations and regression analyses of global and sectoral peripapillary RNFL thickness with corresponding global and regional VF sensitivities were investigated. A consecutive series of 65 study eyes of 36 patients were prospectively included. The second FDF test (HEP II) was used for analysis. Cluster-point based suspicious VF defects were found in 34 eyes (52%). Significant correlations were observed between mean global MD (PSD) of HEP II and SD-OCT-based global peripapillary RNFL thickness (r = 0.380, p = 0.003 for MD and r = -0.516, p < 0.001 for PSD) and RNFL classification scores (R 2 = 0.157, p = 0.002 for MD and R 2 = 0.172, p = 0.001 for PSD). Correlations between mean global MD and PSD of HEP II and sectoral peripapillary RNFL thickness and classification scores showed highest correlations between function and structure for the temporal superior and temporal inferior sectors whereas sectoral MD and PSD correlated weaker with sectoral RNFL thickness. Correlations between linear RNFL values and untransformed logarithmic MD values for each segment were less significant than correlations between logarithmic MD values and RNFL thickness. In glaucoma suspects with normal SAP, global and sectoral peripapillary RNFL thickness is correlated with sensitivity and VF defects in FDF perimetry.

  15. Information theoretic analysis of canny edge detection in visual communication

    NASA Astrophysics Data System (ADS)

    Jiang, Bo; Rahman, Zia-ur

    2011-06-01

    In general edge detection evaluation, the edge detectors are examined, analyzed, and compared either visually or with a metric for specific an application. This analysis is usually independent of the characteristics of the image-gathering, transmission and display processes that do impact the quality of the acquired image and thus, the resulting edge image. We propose a new information theoretic analysis of edge detection that unites the different components of the visual communication channel and assesses edge detection algorithms in an integrated manner based on Shannon's information theory. The edge detection algorithm here is considered to achieve high performance only if the information rate from the scene to the edge approaches the maximum possible. Thus, by setting initial conditions of the visual communication system as constant, different edge detection algorithms could be evaluated. This analysis is normally limited to linear shift-invariant filters so in order to examine the Canny edge operator in our proposed system, we need to estimate its "power spectral density" (PSD). Since the Canny operator is non-linear and shift variant, we perform the estimation for a set of different system environment conditions using simulations. In our paper we will first introduce the PSD of the Canny operator for a range of system parameters. Then, using the estimated PSD, we will assess the Canny operator using information theoretic analysis. The information-theoretic metric is also used to compare the performance of the Canny operator with other edge-detection operators. This also provides a simple tool for selecting appropriate edgedetection algorithms based on system parameters, and for adjusting their parameters to maximize information throughput.

  16. Study on initiative vibration absorbing technology of optics in strong disturbed environment

    NASA Astrophysics Data System (ADS)

    Jia, Si-nan; Xiong, Mu-di; Zou, Xiao-jie

    2007-12-01

    Strong disturbed environment is apt to cause irregular vibration, which seriously affects optical collimation. To improve the performance of laser beam, three-point dynamic vibration absorbing method is proposed, and laser beam initiative vibration absorbing system is designed. The maladjustment signal is detected by position sensitive device (PSD), three groups of PZT are driven to adjust optical element in real-time, so the performance of output-beam is improved. The coupling model of the system is presented. Multivariable adaptive closed-loop decoupling arithmetic is used to design three-input-three-output decoupling controller, so that high precision dynamic adjusting is realized. Experiments indicate that the system has good shock absorbing efficiency.

  17. Measuring relative-story displacement and local inclination angle using multiple position-sensitive detectors.

    PubMed

    Matsuya, Iwao; Katamura, Ryuta; Sato, Maya; Iba, Miroku; Kondo, Hideaki; Kanekawa, Kiyoshi; Takahashi, Motoichi; Hatada, Tomohiko; Nitta, Yoshihiro; Tanii, Takashi; Shoji, Shuichi; Nishitani, Akira; Ohdomari, Iwao

    2010-01-01

    We propose a novel sensor system for monitoring the structural health of a building. The system optically measures the relative-story displacement during earthquakes for detecting any deformations of building elements. The sensor unit is composed of three position sensitive detectors (PSDs) and lenses capable of measuring the relative-story displacement precisely, even if the PSD unit was inclined in response to the seismic vibration. For verification, laboratory tests were carried out using an Xθ-stage and a shaking table. The static experiment verified that the sensor could measure the local inclination angle as well as the lateral displacement. The dynamic experiment revealed that the accuracy of the sensor was 150 μm in the relative-displacement measurement and 100 μrad in the inclination angle measurement. These results indicate that the proposed sensor system has sufficient accuracy for the measurement of relative-story displacement in response to the seismic vibration.

  18. Classification of driver fatigue in an electroencephalography-based countermeasure system with source separation module.

    PubMed

    Rifai Chai; Naik, Ganesh R; Tran, Yvonne; Sai Ho Ling; Craig, Ashley; Nguyen, Hung T

    2015-08-01

    An electroencephalography (EEG)-based counter measure device could be used for fatigue detection during driving. This paper explores the classification of fatigue and alert states using power spectral density (PSD) as a feature extractor and fuzzy swarm based-artificial neural network (ANN) as a classifier. An independent component analysis of entropy rate bound minimization (ICA-ERBM) is investigated as a novel source separation technique for fatigue classification using EEG analysis. A comparison of the classification accuracy of source separator versus no source separator is presented. Classification performance based on 43 participants without the inclusion of the source separator resulted in an overall sensitivity of 71.67%, a specificity of 75.63% and an accuracy of 73.65%. However, these results were improved after the inclusion of a source separator module, resulting in an overall sensitivity of 78.16%, a specificity of 79.60% and an accuracy of 78.88% (p <; 0.05).

  19. Intrathecal injection of the peptide myr-NR2B9c attenuates bone cancer pain via perturbing N-methyl-D-aspartate receptor-PSD-95 protein interactions in mice.

    PubMed

    Liu, Yue; Cui, Xinlong; Sun, Yu-E; Yang, Xuli; Ni, Kun; Zhou, Yu; Ma, Zhengliang; Gu, Xiaoping

    2014-06-01

    N-methyl-D-aspartate receptor (NMDARs)-dependent central sensitization plays an important role in cancer pain. Binding of NMDAR subunit 2B (NR2B) by postsynaptic density protein-95 (PSD-95) can couple NMDAR activity to intracellular enzymes, such as neuronal nitric oxide synthase (nNOS), facilitate downstream signaling pathways, and modulate NMDAR stability, contributing to synaptic plasticity. In this study, we investigated whether perturbing the specific interaction between spinal NR2B-containing NMDAR and PSD-95, using a peptide-mimetic strategy, could attenuate bone cancer-related pain behaviors. Osteosarcoma cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce progressive bone cancer-related pain behaviors. Western blotting was applied to examine the expression of spinal phospho-Tyr1472 NR2B, nNOS, and PSD-95. We further investigated the effects of intrathecal injection of the mimetic peptide Myr-NR2B9c, which competitively disrupts the interaction between PSD-95 and NR2B, on nociceptive behaviors and on the upregulation of phospho-Tyr1472 NR2B, nNOS, and PSD-95 associated with bone cancer pain in the spinal cord. Inoculation of osteosarcoma cells induced progressive bone cancer pain and resulted in a significant upregulation of phospho-Tyr1472 NR2B, nNOS, and PSD-95. Intrathecal administration of Myr-NR2B9c attenuated bone cancer-evoked mechanical allodynia, thermal hyperalgesia, and reduced spinal phospho-Tyr1472 NR2B, nNOS, and PSD-95 expression. Intrathecal administration of Myr-NR2B9c reduced bone cancer pain. Internalization of spinal NR2B and dissociation NR2B-containing NMDARs activation from downstream nNOS signaling may contribute to the analgesic effects of Myr-NR2B9c. This approach may circumvent the negative consequences associated with blocking NMDARs, and may be a novel strategy for the treatment of bone cancer pain.

  20. High hole mobility p-type GaN with low residual hydrogen concentration prepared by pulsed sputtering

    NASA Astrophysics Data System (ADS)

    Arakawa, Yasuaki; Ueno, Kohei; Kobayashi, Atsushi; Ohta, Jitsuo; Fujioka, Hiroshi

    2016-08-01

    We have grown Mg-doped GaN films with low residual hydrogen concentration using a low-temperature pulsed sputtering deposition (PSD) process. The growth system is inherently hydrogen-free, allowing us to obtain high-purity Mg-doped GaN films with residual hydrogen concentrations below 5 × 1016 cm-3, which is the detection limit of secondary ion mass spectroscopy. In the Mg profile, no memory effect or serious dopant diffusion was detected. The as-deposited Mg-doped GaN films showed clear p-type conductivity at room temperature (RT) without thermal activation. The GaN film doped with a low concentration of Mg (7.9 × 1017 cm-3) deposited by PSD showed hole mobilities of 34 and 62 cm2 V-1 s-1 at RT and 175 K, respectively, which are as high as those of films grown by a state-of-the-art metal-organic chemical vapor deposition apparatus. These results indicate that PSD is a powerful tool for the fabrication of GaN-based vertical power devices.

  1. Are endogenous sex hormones related to DNA damage in paradoxically sleep-deprived female rats?

    PubMed

    Andersen, Monica L; Ribeiro, Daniel A; Alvarenga, Tathiana A; Silva, Andressa; Araujo, Paula; Zager, Adriano; Tenorio, Neuli M; Tufik, Sergio

    2010-02-01

    The aim of this investigation was to evaluate overall DNA damage induced by experimental paradoxical sleep deprivation (PSD) in estrous-cycling and ovariectomized female rats to examine possible hormonal involvement during DNA damage. Intact rats in different phases of the estrous cycle (proestrus, estrus, and diestrus) or ovariectomized female Wistar rats were subjected to PSD by the single platform technique for 96 h or were maintained for the equivalent period as controls in home-cages. After this period, peripheral blood and tissues (brain, liver, and heart) were collected to evaluate genetic damage using the single cell gel (comet) assay. The results showed that PSD caused extensive genotoxic effects in brain cells, as evident by increased DNA migration rates in rats exposed to PSD for 96 h when compared to negative control. This was observed for all phases of the estrous cycle indistinctly. In ovariectomized rats, PSD also led to DNA damage in brain cells. No significant statistically differences were detected in peripheral blood, the liver or heart for all groups analyzed. In conclusion, our data are consistent with the notion that genetic damage in the form of DNA breakage in brain cells induced by sleep deprivation overrides the effects related to endogenous female sex hormones. Copyright 2009 Elsevier Inc. All rights reserved.

  2. Steroid receptor coactivator-1 mediates letrozole induced downregulation of postsynaptic protein PSD-95 in the hippocampus of adult female rats.

    PubMed

    Liu, Mengying; Huangfu, Xuhong; Zhao, Yangang; Zhang, Dongmei; Zhang, Jiqiang

    2015-11-01

    Hippocampus local estrogen which is converted from androgen that catalyzed by aromatase has been shown to play important roles in the regulation of learning and memory as well as cognition through action on synaptic plasticity, but the underlying mechanisms are poorly understood. Steroid receptor coactivator-1 (SRC-1) is one of the coactivators of steroid nuclear receptors; it is widely distributed in brain areas that related to learning and memory, reproductive regulation, sensory and motor information integration. Previous studies have revealed high levels of SRC-1 immunoreactivities in the hippocampus; it is closely related to the levels of synaptic proteins such as PSD-95 under normal development or gonadectomy, but its exact roles in the regulation of these proteins remains unclear. In this study, we used aromatase inhibitor letrozole in vivo and SRC-1 RNA interference in vitro to investigate whether SRC-1 mediated endogenous estrogen regulation of hippocampal PSD-95. The results revealed that letrozole injection synchronously decreased hippocampal SRC-1 and PSD-95 in a dose-dependant manner. Furthermore, when SRC-1 specific shRNA pool was applied to block the expression of SRC-1 in the primary hippocampal neuron culture, both immunocytochemistry and Western blot revealed that levels of PSD-95 were also decreased significantly. Taking together, these results provided the first evidence that SRC-1 mediated endogenous estrogen regulation of hippocampal synaptic plasticity by targeting the expression of synaptic protein PSD-95. Additionally, since letrozole is frequently used to treat estrogen-sensitive breast cancer, the above results also indicate its potential side effects in clinical administration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Prediction of post-stroke dementia using NINDS-CSN 5-minute neuropsychology protocol in acute stroke.

    PubMed

    Lim, Jae-Sung; Oh, Mi Sun; Lee, Ju-Hun; Jung, San; Kim, Chulho; Jang, Min Uk; Lee, Sang-Hwa; Kim, Yeo Jin; Kim, Yerim; Park, Jaeseol; Kang, Yeonwook; Yu, Kyung-Ho; Lee, Byung-Chul

    2017-05-01

    The National Institute of Neurological Disease and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute neuropsychology protocol consists of only verbal tasks, and is proposed as a brief screening method for vascular cognitive impairment. We evaluated its feasibility within two weeks after stroke and ability to predict the development of post-stroke dementia (PSD) at 3 months after stroke. We prospectively enrolled subjects with ischemic stroke within seven days of symptom onset who were consecutively admitted to 12 university hospitals. Neuropsychological assessments using the NINDS-CSN 5-minute and 60-minute neuropsychology protocols were administered within two weeks and at 3 months after stroke onset, respectively. PSD was diagnosed with reference to the American Heart Association/American Stroke Association statement, requiring deficits in at least two cognitive domains. Of 620 patients, 512 (82.6%) were feasible for the NINDS-CSN 5-minute protocol within two weeks after stroke. The incidence of PSD was 16.2% in 308 subjects who had completed follow-up at 3 months after stroke onset. The total score of the NINDS-CSN 5-minute protocol differed significantly between those with and without PSD (4.0 ± 2.7, 7.4 ± 2.7, respectively; p < 0.01). A cut-off value of 6/7 showed reasonable discriminative power (sensitivity 0.82, specificity 0.67, AUC 0.74). The NINDS-CSN 5-minute protocol score was a significant predictor for PSD (adjusted odds ratio 6.32, 95% CI 2.65-15.05). The NINDS-CSN 5-minute protocol is feasible to evaluate cognitive functions in patients with acute ischemic stroke. It might be a useful screening method for early identification of high-risk groups for PSD.

  4. α-Actinin-2 Mediates Spine Morphology and Assembly of the Post-Synaptic Density in Hippocampal Neurons

    PubMed Central

    Hodges, Jennifer L.; Vilchez, Samuel Martin; Asmussen, Hannelore; Whitmore, Leanna A.; Horwitz, Alan Rick

    2014-01-01

    Dendritic spines are micron-sized protrusions that constitute the primary post-synaptic sites of excitatory neurotransmission in the brain. Spines mature from a filopodia-like protrusion into a mushroom-shaped morphology with a post-synaptic density (PSD) at its tip. Modulation of the actin cytoskeleton drives these morphological changes as well as the spine dynamics that underlie learning and memory. Several PSD molecules respond to glutamate receptor activation and relay signals to the underlying actin cytoskeleton to regulate the structural changes in spine and PSD morphology. α-Actinin-2 is an actin filament cross-linker, which localizes to dendritic spines, enriched within the post-synaptic density, and implicated in actin organization. We show that loss of α-actinin-2 in rat hippocampal neurons creates an increased density of immature, filopodia-like protrusions that fail to mature into a mushroom-shaped spine during development. α-Actinin-2 knockdown also prevents the recruitment and stabilization of the PSD in the spine, resulting in failure of synapse formation, and an inability to structurally respond to chemical stimulation of the N-methyl-D-aspartate (NMDA)-type glutamate receptor. The Ca2+-insensitive EF-hand motif in α-actinin-2 is necessary for the molecule's function in regulating spine morphology and PSD assembly, since exchanging it for the similar but Ca2+-sensitive domain from α-actinin-4, another α-actinin isoform, inhibits its function. Furthermore, when the Ca2+-insensitive domain from α-actinin-2 is inserted into α-actinin-4 and expressed in neurons, it creates mature spines. These observations support a model whereby α-actinin-2, partially through its Ca2+-insensitive EF-hand motif, nucleates PSD formation via F-actin organization and modulates spine maturation to mediate synaptogenesis. PMID:25007055

  5. Development of a one-dimensional Position Sensitive Detector for tracking applications

    NASA Astrophysics Data System (ADS)

    Lydecker, Leigh Kent, IV

    Optical Position Sensitive Detectors (PSDs) are a non-contact method of tracking the location of a light spot. Silicon-based versions of such sensors are fabricated with standard CMOS processing, are inexpensive and provide a real-time, analog signal output corresponding to the position of the light spot. Because they are non-contact, they do not degrade over time from surface friction due to repetitive sliding motion associated with standard full contact sliding potentiometers. This results in long, reliable device lifetimes. In this work, an innovative PSD was developed to replace the linear hard contact potentiometer currently being used in a human-computer interface architecture. First, a basic lateral effect PSD was developed to provide real-time positioning of the mouthpiece used in the interface architecture which tracks along a single axis. During the course of this work, multiple device geometries were fabricated and analyzed resulting in a down selection of a final design. This final device design was then characterized in terms of resolution and responsivity and produced in larger quantities as initial prototypes for the test product integration. Finally, an electronic readout circuit was developed in order to interface the dual- line lateral effect PSD developed in this thesis with specifications required for product integration. To simplify position sensing, an innovative type of optical position sensor was developed using a linear photodiodes with back-to-back connections. This so- called Self-Balancing Position Sensitive Detector (SBPSD) requires significantly fewer processing steps than the basic lateral effect position sensitive detector discussed above and eliminates the need for external readout circuitry entirely. Prototype devices were fabricated in this work, and the performance characteristics of these devices were established paving the way for ultimate integration into the target product as well as additional applications.

  6. Examining impacts of mass-diameter (m-D) and area-diameter (A-D) relationships of ice particles on retrievals of effective radius and ice water content from radar and lidar measurements

    NASA Astrophysics Data System (ADS)

    Ham, Seung-Hee; Kato, Seiji; Rose, Fred G.

    2017-03-01

    Mass-diameter (m-D) and projected area-diameter (A-D) relations are often used to describe the shape of nonspherical ice particles. This study analytically investigates how retrieved effective radius (reff) and ice water content (IWC) from radar and lidar measurements depend on the assumption of m-D [m(D) = a Db] and A-D [A(D) = γ Dδ] relationships. We assume that unattenuated reflectivity factor (Z) and visible extinction coefficient (kext) by cloud particles are available from the radar and lidar measurements, respectively. A sensitivity test shows that reff increases with increasing a, decreasing b, decreasing γ, and increasing δ. It also shows that a 10% variation of a, b, γ, and δ induces more than a 100% change of reff. In addition, we consider both gamma and lognormal particle size distributions (PSDs) and examine the sensitivity of reff to the assumption of PSD. It is shown that reff increases by up to 10% with increasing dispersion (μ) of the gamma PSD by 2, when large ice particles are predominant. Moreover, reff decreases by up to 20% with increasing the width parameter (ω) of the lognormal PSD by 0.1. We also derive an analytic conversion equation between two effective radii when different particle shapes and PSD assumptions are used. When applying the conversion equation to nine types of m-D and A-D relationships, reff easily changes up to 30%. The proposed reff conversion method can be used to eliminate the inconsistency of assumptions that made in a cloud retrieval algorithm and a forward radiative transfer model.

  7. Time correlated measurements using plastic scintillators with neutron-photon pulse shape discrimination

    NASA Astrophysics Data System (ADS)

    Richardson, Norman E., IV

    Since the beginning of the nuclear age, there has been a strong demand for the development of efficient technologies for the detection of ionizing radiation. According to the United States' Department of Energy, the accurate assessment of fissile materials is essential in achieving the nonproliferation goals of enhancing safety and security of nuclear fuel cycle and nuclear energy facilities. Nuclear materials can be characterized by the measurement of prompt and delayed neutrons and gamma rays emitted in spontaneous or induced fission reactions and neutrons emitted in fission reactions are the distinctive signatures of nuclear materials. Today, the most widely used neutron detection technologies rely on thermal neutron capture reactions using a moderating material to cause the neutron to lose its energy prior to the detection event. This is necessary because as the fission event occurs, neutrons are emitted carrying high amounts of energy, typically on the order of mega electron volts (MeV). These energetic particles are classified as "fast" neutrons. For detecting the thermal neutrons, the Helium-3 (3He) gas-filled counters are arguably the most widely used technology of neutron detection. 3He counters have been the scientific standard for the nuclear engineering community for several decades, and have earned their place as a reliable technique for the detection of neutrons. However, 3He gas-filled counters have several disadvantages. First, gas-filled counters are not rigid and are sensitive to vibrations. Secondly, gas-filled counters are prone to the count rate limitations due to the physical processes of charge multiplication and transport in the gas medium in the electric field. Lastly, 3He gas-filled counters suffer from a supply shortage of the 3He isotope. As it is stated in [3], this shortage is created by the new demand for Helium-3 due to the deployment of neutron detectors at the borders after the 9/11 attack to help secure the nation against smuggled nuclear and radiological material. Moreover, the production of 3He isotope as a byproduct of security programs was drastically decreased. This isotope shortage coupled with the disadvantages of relying on a detector that requires neutron moderation before the detection of fission neutrons, poses a significant challenge in supporting the existing detection systems and the development of future technologies. To address this problem, a reliable and accurate alternative technology to detect neutrons emitted in fissions must be developed. One such alternative technology that shows promise in this application is the use of scintillators based on solid state materials (plastics) which are sensitive to fast neutrons. However, plastic scintillators are also sensitive to photons. Hence, it is necessary to separate the neutron signals from the photon signals, using the pulse shape discrimination (PSD) analysis. The PSD is based on the comparison of the pulse shapes of digitized signal waveforms. This approach allows for the measurement of fast neutrons without the necessity of their moderation. Because the fission spectrum neutrons are mainly fast, methods employing fast neutron detection are applicable for the assay of fissile materials. In addition, the average time of scintillation of the plastic medium is much shorter than those of the gaseous counters, thus allowing scintillation detectors to be used in high count rate environments. Furthermore, the temporal information of the fast neutron detection using multiple sensors enables the time correlation analysis of the fission neutron multiplicity. The study of time correlation measurements of fast neutrons using the array of plastic scintillators is the basis of this work. The array of four plastic scintillator detectors equipped with the digital data acquisition and analysis system was developed. The digital PSD analysis of detector signals "on-the-fly" was implemented for the array. The time coincidence measurement technique using the list mode was employed for two detectors operating on the single time scale. This was necessary as no fission source was available to be used as a fast neutron multiplicity source. The detection technology was tested using isotopic photon sources and a plutonium-beryllium neutron source. It was shown that the system can be effectively used for fast-neutron multiplicity measurements, through a "proof-of-concept" model, enabling a shorter width of the time coincidence window compared to the 3He counters. This result opens prospects to reduce the false coincidence rates in the neutron multiplicity measurements, thus increasing the sensitivity of nuclear material detection.

  8. Simulations of a PSD Plastic Neutron Collar for Assaying Fresh Fuel

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

    Hausladen, Paul; Newby, Jason; McElroy, Robert Dennis

    The potential performance of a notional active coincidence collar for assaying uranium fuel based on segmented detectors constructed from the new PSD plastic fast organic scintillator with pulse shape discrimination capability was investigated in simulation. Like the International Atomic Energy Agency's present Uranium Neutron Collar for LEU (UNCL), the PSD plastic collar would also function by stimulating fission in the 235U content of the fuel with a moderated 241Am/Li neutron source and detecting instances of induced fission via neutron coincidence counting. In contrast to the moderated detectors of the UNCL, the fast time scale of detection in the scintillator eliminatesmore » statistical errors due to accidental coincidences that limit the performance of the UNCL. However, the potential to detect a single neutron multiple times historically has been one of the properties of organic scintillator detectors that has prevented their adoption for international safeguards applications. Consequently, as part of the analysis of simulated data, a method was developed by which true neutron-neutron coincidences can be distinguished from inter-detector scatter that takes advantage of the position and timing resolution of segmented detectors. Then, the performance of the notional simulated coincidence collar was evaluated for assaying a variety of fresh fuels, including some containing burnable poisons and partial defects. In these simulations, particular attention was paid to the analysis of fast mode measurements. In fast mode, a Cd liner is placed inside the collar to shield the fuel from the interrogating source and detector moderators, thereby eliminating the thermal neutron flux that is most sensitive to the presence of burnable poisons that are ubiquitous in modern nuclear fuels. The simulations indicate that the predicted precision of fast mode measurements is similar to what can be achieved by the present UNCL in thermal mode. For example, the statistical accuracy of a ten-minute measurement of fission coincidences collected in fast mode will be approximately 1% for most fuels of interest, yielding a ~1.4% error after subtraction of a five minute measurement of the spontaneous fissions from 238U in the fuel, a ~2% error in analyzed linear density after accounting for the slope of the calibration curve, and a ~2.9% total error after addition of an assumed systematic error of 2%.« less

  9. A gamma and neutron phoswich read out with SiPM for SPRD

    NASA Astrophysics Data System (ADS)

    Huang, Tuchen; Fu, Qibin; Yuan, Cenxi; Lin, Shaopeng

    2018-02-01

    A gamma and neutron phoswich was developed for spectroscopic personal radiation detectors (SPRDs). It consisted of a Φ25 × 25 mm NaI(Tl) crystal for gamma detection and a Φ25 × 3 mm LiI(Eu) crystal for neutron detection. The phoswich was read out by 8 × 8 ch SiPM array (24 × 24 mm2). Radiations in NaI(Tl) and LiI(Eu) were discriminated by pulse shape, while gammas and neutrons in LiI(Eu) were separated by pulse amplitude. For the LiI(Eu), the gamma equivalent energy for thermal neutrons was measured as 3.6 ± 0.1 MeV, providing satisfactory gamma rejection. For NaI(Tl), the response of SiPM array was well linear in the energy range up to 1408 keV, at which a deviation less than 2% was measured. Digital pulse shape discrimination (PSD) was implemented with an 8-bit digitizer running at 50 MSPS sampling rate and offline analysis. The signal pulses from NaI(Tl) and LiI(Eu) showed significant difference in falling edge allowing effective PSD. The best figure of merit (FOM) was measured as 4.4 ± 0.2 with optimized parameters, providing excellent PSD performance. The energy resolutions for 661.6 keV gamma rays in NaI(Tl) and thermal neutrons in LiI(Eu) were measured as 7.0 ± 0.2% and 11.2 ± 0.2% respectively, with selected PSD threshold.

  10. Pulse-shape discrimination between electron and nuclear recoils in a NaI(Tl) crystal

    NASA Astrophysics Data System (ADS)

    Lee, H. S.; Adhikari, G.; Adhikari, P.; Choi, S.; Hahn, I. S.; Jeon, E. J.; Joo, H. W.; Kang, W. G.; Kim, G. B.; Kim, H. J.; Kim, H. O.; Kim, K. W.; Kim, N. Y.; Kim, S. K.; Kim, Y. D.; Kim, Y. H.; Lee, J. H.; Lee, M. H.; Leonard, D. S.; Li, J.; Oh, S. Y.; Olsen, S. L.; Park, H. K.; Park, H. S.; Park, K. S.; Shim, J. H.; So, J. H.

    2015-08-01

    We report on the response of a high light-output NaI(Tl) crystal to nuclear recoils induced by neutrons from an Am-Be source and compare the results with the response to electron recoils produced by Compton-scattered 662 keV γ-rays from a 137Cs source. The measured pulse-shape discrimination (PSD) power of the NaI(Tl) crystal is found to be significantly improved because of the high light output of the NaI(Tl) detector. We quantify the PSD power with a quality factor and estimate the sensitivity to the interaction rate for weakly interacting massive particles (WIMPs) with nucleons, and the result is compared with the annual modulation amplitude observed by the DAMA/LIBRA experiment. The sensitivity to spin-independent WIMP-nucleon interactions based on 100 kg·year of data from NaI detectors is estimated with simulated experiments, using the standard halo model.

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

    Liu, H; Lin, H; Darafsheh, A

    Purpose: To characterize basic performance of plastic scintillator detectors (PSD) designed for dosimetry of radiation therapy. Methods: The Exradin W1 Scintillator is a plastic scintillating fiber-based detector designed for highly accurate measurement of small radiotherapy fields used in patient plan verification and machine commissioning and QA procedures. The Cerenkov emissions were corrected using spectral separation. The optical signal was converted to electronic signal with a photodiode. We measured its dosimetry performance, including percentage depth dose, output factor, dose and dose rate linear response. We compared the dosimetry results with reference ion chamber measurements. Results: The dosimetry results of PSD agreemore » well with reference ion chamber measurements. For percentage depth dose, the differences between PSD and ion chamber results are on average 1.7±1.1% and 0.8±0.8% with a maximum of 3.5% and 2.7% for 6MV and 15MV beams, respectively. For the output factors, PSD measurements are within 2% from ion chamber results. The dose linear response is within 1% when dose is larger than 20 MU for both 6 MV and 15 MV. The dose rate linear response is within 1% for the entire dose rate used (100 MU/min to 600MU/min). Conclusions: The current design of PSD is feasible for the dosimtry measurement in radiation therapy. This combination of PSD and photodiode system could be extended to multichannel array detection of dose distribution. It might as well be used as range verification in proton therapy. The work is partially supported by: DOD (W81XWH-09-2-0174) and American Cancer Society (IRG-78-002-28)« less

  12. X-ray Variability Characteristics of the Narrow line SEYFERT 1 MKN 766 I: Energy Dependent Timing Properties

    NASA Technical Reports Server (NTRS)

    Markowitz, A.; Turner, T. J.; Papadakis, I.; Arevalo, P.; Reeves, J. N.; Miller, L.

    2007-01-01

    We present the energy-dependent power spectral density (PSD) and cross-spectral properties of Mkn 766 obtained from a six-revolution XMM-Newton observation in 2005. The resulting PSDs, which have highest temporal frequency resolution for an AGN PSD to date, show breaks which increase in temporal frequency as photon energy increases; break frequencies differ by an average of approx.0.4 in the log between the softest and hardest bands. The consistency of the 2001 and 2005 observations variability properties, namely PSD shapes and the linear rms-flux relation, suggests the 2005 observation is simply a low-flux extension of the 2001 observation. The coherence function is measured to be approx.0.6-0.9 at temporal frequencies below the PSD break, and is lower for relatively larger energy band separation; coherence also drops significantly towards zero above the PSD break frequency. Temporal frequency-dependent soft-to-hard time lags are detected in this object for the first time: lags increase towards longer time scales and as energy separation increases. Cross-spectral properties are the thus consistent with previous measurements for Mkn 766 (Vaughan & Fabian 2003) and other accreting black hole systems. The results are discussed in the context of several variability models, including those based on inwardly-propagating viscosity variations in the accretion disk.

  13. PANDORA, a large volume low-energy neutron detector with real-time neutron-gamma discrimination

    NASA Astrophysics Data System (ADS)

    Stuhl, L.; Sasano, M.; Yako, K.; Yasuda, J.; Baba, H.; Ota, S.; Uesaka, T.

    2017-09-01

    The PANDORA (Particle Analyzer Neutron Detector Of Real-time Acquisition) system, which was developed for use in inverse kinematics experiments with unstable isotope beams, is a neutron detector based on a plastic scintillator coupled to a digital readout. PANDORA can be used for any reaction study involving the emission of low energy neutrons (100 keV-10 MeV) where background suppression and an increased signal-to-noise ratio are crucial. The digital readout system provides an opportunity for pulse shape discrimination (PSD) of the detected particles as well as intelligent triggering based on PSD. The figure of merit results of PANDORA are compared to the data in literature. Using PANDORA, 91 ± 1% of all detected neutrons can be separated, while 91 ± 1% of the detected gamma rays can be excluded, reducing the gamma ray background by one order of magnitude.

  14. Development a low-cost carbon monoxide sensor using homemade CW-DFB QCL and board-level electronics

    NASA Astrophysics Data System (ADS)

    Dang, Jingmin; Yu, Haiye; Zheng, Chuantao; Wang, Lijun; Sui, Yuanyuan; Wang, Yiding

    2018-05-01

    A mid-infrared sensor was demonstrated for the detection of carbon monoxide (CO) at trace level. In order to reduce cost, a homemade continuous-wave mode distributed feedback quantum cascade laser (CW-DFB QCL), a mini gas cell with 1.6-m optical length, and some self-development electronic modules were adopted as excitation source, absorption pool, and signal controlling and processing tool, respectively. Wavelength modulation spectroscopy (WMS) and phase sensitive detection (PSD) techniques as well as wavelet filtering software algorithm were used to reduce the influence of light source fluctuation and system noise and to improve measurement precision and sensitivity. Under the selected P(11) absorption line located at 2099.083 cm-1, a limit of detection (LoD) of 26 parts per billion by volume (ppbv) at atmospheric pressure was achieved with a 1-s acquisition time. Allan deviation was used to characterize the long-term performance of the CO sensor, and a measurement precision of ∼3.4 ppbv was observed with an optimal integration time of ∼114 s. As a field measurement, a continuous monitoring on indoor CO concentration for a period of 24 h was conducted, which verified the reliable and robust operation of the developed sensor.

  15. An assembly of proteins and lipid domains regulates transport of phosphatidylserine to phosphatidylserine decarboxylase 2 in Saccharomyces cerevisiae.

    PubMed

    Riekhof, Wayne R; Wu, Wen-I; Jones, Jennifer L; Nikrad, Mrinalini; Chan, Mallory M; Loewen, Christopher J R; Voelker, Dennis R

    2014-02-28

    Saccharomyces cerevisiae uses multiple biosynthetic pathways for the synthesis of phosphatidylethanolamine. One route involves the synthesis of phosphatidylserine (PtdSer) in the endoplasmic reticulum (ER), the transport of this lipid to endosomes, and decarboxylation by PtdSer decarboxylase 2 (Psd2p) to produce phosphatidylethanolamine. Several proteins and protein motifs are known to be required for PtdSer transport to occur, namely the Sec14p homolog PstB2p/Pdr17p; a PtdIns 4-kinase, Stt4p; and a C2 domain of Psd2p. The focus of this work is on defining the protein-protein and protein-lipid interactions of these components. PstB2p interacts with a protein encoded by the uncharacterized gene YPL272C, which we name Pbi1p (PstB2p-interacting 1). PstB2p, Psd2, and Pbi1p were shown to be lipid-binding proteins specific for phosphatidic acid. Pbi1p also interacts with the ER-localized Scs2p, a binding determinant for several peripheral ER proteins. A complex between Psd2p and PstB2p was also detected, and this interaction was facilitated by a cryptic C2 domain at the extreme N terminus of Psd2p (C2-1) as well the previously characterized C2 domain of Psd2p (C2-2). The predicted N-terminal helical region of PstB2p was necessary and sufficient for promoting the interaction with both Psd2p and Pbi1p. Taken together, these results support a model for PtdSer transport involving the docking of a PtdSer donor membrane with an acceptor via specific protein-protein and protein-lipid interactions. Specifically, our model predicts that this process involves an acceptor membrane complex containing the C2 domains of Psd2p, PstB2p, and Pbi1p that ligate to Scs2p and phosphatidic acid present in the donor membrane, forming a zone of apposition that facilitates PtdSer transfer.

  16. THE LONGEST TIMESCALE X-RAY VARIABILITY REVEALS EVIDENCE FOR ACTIVE GALACTIC NUCLEI IN THE HIGH ACCRETION STATE

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

    Zhang Youhong, E-mail: youhong.zhang@mail.tsinghua.edu.cn

    2011-01-01

    The All Sky Monitor (ASM) on board the Rossi X-ray Timing Explorer has continuously monitored a number of active galactic nuclei (AGNs) with similar sampling rates for 14 years, from 1996 January to 2009 December. Utilizing the archival ASM data of 27 AGNs, we calculate the normalized excess variances of the 300-day binned X-ray light curves on the longest timescale (between 300 days and 14 years) explored so far. The observed variance appears to be independent of AGN black-hole mass and bolometric luminosity. According to the scaling relation of black-hole mass (and bolometric luminosity) from galactic black hole X-ray binariesmore » (GBHs) to AGNs, the break timescales that correspond to the break frequencies detected in the power spectral density (PSD) of our AGNs are larger than the binsize (300 days) of the ASM light curves. As a result, the singly broken power-law (soft-state) PSD predicts the variance to be independent of mass and luminosity. Nevertheless, the doubly broken power-law (hard-state) PSD predicts, with the widely accepted ratio of the two break frequencies, that the variance increases with increasing mass and decreases with increasing luminosity. Therefore, the independence of the observed variance on mass and luminosity suggests that AGNs should have soft-state PSDs. Taking into account the scaling of the break timescale with mass and luminosity synchronously, the observed variances are also more consistent with the soft-state than the hard-state PSD predictions. With the averaged variance of AGNs and the soft-state PSD assumption, we obtain a universal PSD amplitude of 0.030 {+-} 0.022. By analogy with the GBH PSDs in the high/soft state, the longest timescale variability supports the standpoint that AGNs are scaled-up GBHs in the high accretion state, as already implied by the direct PSD analysis.« less

  17. Protective effect of total flavones of Abelmoschus manihot L. Medic against poststroke depression injury in mice and its action mechanism.

    PubMed

    Liu, Mei; Jiang, Qiu-Hong; Hao, Ji-Li; Zhou, Lan-Lan

    2009-03-01

    Total flavones of Abelmoschus manihot L. Medic (TFA) is the major active component isolated from the traditional Chinese herb Abelmoschus manihot L. Medic. We investigated the protective effect of TFA against poststroke depression (PSD) injury in mice and its action mechanism. A mouse model of PSD was induced by middle cerebral artery occlusion (MACO) 30 min/reperfusion, followed by isolation feeding and chronic unpredictable mild stress for 2 weeks. Treatment groups received TFA at three different doses (160, 80, and 40 mg/kg, p.o.) or fluoxetine (Flu, 2.5 mg/kg, p.o.) daily for 24 days. Change in behavior, brain tissue malondialdehyde (MDA) levels, and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured. The expression of brain-derived neurotrophic factor (BDNF) was detected by immunohistochemistry, and mRNA expression of BDNF and cAMP response element-binding protein (CREB) analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Treatment with TFA (160, 80, and 40 mg/kg) significantly ameliorated mice escape-directed behavioral impairment induced by PSD, markedly reduced MDA levels, and increased the activity of SOD, GSH-Px close to normal levels. TFA administration also attenuated PSD-induced neuronal death/losses, upregulated expression of BDNF both at mRNA and protein levels, as well as CREB mRNA levels. TFA had a protective effect against PSD injury in mice. Cardioprotection involves the inhibition of lipid peroxidation and upregulation of BDNF-CREB levels in the hippocampus, which may also be important mechanism of its antidepressants. This potential protection makes TFA a promising therapeutic agent for the PSD. (c) 2009 Wiley-Liss, Inc.

  18. Rapid Redistribution of Synaptic PSD-95 in the Neocortex In Vivo

    PubMed Central

    Bureau, Ingrid; Svoboda, Karel

    2006-01-01

    Most excitatory synapses terminate on dendritic spines. Spines vary in size, and their volumes are proportional to the area of the postsynaptic density (PSD) and synaptic strength. PSD-95 is an abundant multi-domain postsynaptic scaffolding protein that clusters glutamate receptors and organizes the associated signaling complexes. PSD-95 is thought to determine the size and strength of synapses. Although spines and their synapses can persist for months in vivo, PSD-95 and other PSD proteins have shorter half-lives in vitro, on the order of hours. To probe the mechanisms underlying synapse stability, we measured the dynamics of synaptic PSD-95 clusters in vivo. Using two-photon microscopy, we imaged PSD-95 tagged with GFP in layer 2/3 dendrites in the developing (postnatal day 10–21) barrel cortex. A subset of PSD-95 clusters was stable for days. Using two-photon photoactivation of PSD-95 tagged with photoactivatable GFP (paGFP), we measured the time over which PSD-95 molecules were retained in individual spines. Synaptic PSD-95 turned over rapidly (median retention times τ r ~ 22–63 min from P10–P21) and exchanged with PSD-95 in neighboring spines by diffusion. PSDs therefore share a dynamic pool of PSD-95. Large PSDs in large spines captured more diffusing PSD-95 and also retained PSD-95 longer than small PSDs. Changes in the sizes of individual PSDs over days were associated with concomitant changes in PSD-95 retention times. Furthermore, retention times increased with developmental age (τ r ~ 100 min at postnatal day 70) and decreased dramatically following sensory deprivation. Our data suggest that individual PSDs compete for PSD-95 and that the kinetic interactions between PSD molecules and PSDs are tuned to regulate PSD size. PMID:17090216

  19. Methacrylate based cross-linkers for improved thermomechanical properties and retention of radiation detection response in plastic scintillators

    NASA Astrophysics Data System (ADS)

    Mahl, Adam; Lim, Allison; Latta, Joseph; Yemam, Henok A.; Greife, Uwe; Sellinger, Alan

    2018-03-01

    Pulse shape discrimination (PSD) is an important method that can efficiently sort and separate neutron and gamma radiation signals. PSD is currently achieved in plastic scintillators by over-doping poly(vinyl toluene) (PVT) matrices with fluorescent molecules. Meaningful separation of the signals requires addition of >20 wt% 2,5-diphenyloxazole (PPO) fluor in PVT. At these concentrations PPO acts as a plasticizer, negatively affecting the physical properties of the final plastic such as hardness, machinability, and thermomechanical stability. This work addresses these issues by implementing a cost-effective solution using cross-linking chemistry via commercially available bisphenol A dimethacrylate (BPA-DM), and a synthesized fluorinated analogue. Both improve the physical properties of over-doped PPO based plastic scintillators without degrading the measured light yield or PSD and Figure of Merit (FoM). In addition, the fluorinated analogue appears to enhance the hydrophobicity of the surface of the plastic scintillators, which may improve the scintillators' resistance to water diffusion and subsequent radiation response degradation. The new formulations improve the feasibility of widely deploying long lifetime PSD capable plastic scintillators in large area coverage assemblies.

  20. Electron- and Photon-stimulated Desorption of Alkali Atoms from Lunar Sample and a Model Mineral Surface

    NASA Technical Reports Server (NTRS)

    Yakshinskiy, B. V.; Madey, T. E.

    2003-01-01

    We report recent results on an investigation of source mechanisms for the origin of alkali atoms in the tenuous planetary atmospheres, with focus on non-thermal processes (photon stimulated desorption (PSD), electron stimulated desorption (ESD), and ion sputtering). Whereas alkaline earth oxides (MgO, CaO) are far more abundant in lunar samples than alkali oxides (Na2O, K2O), the atmosphere of the Moon contains easily measurable concentrations of Na and K, while Ca and Mg are undetected there; traces of Ca have recently been seen in the Moon's atmosphere (10-3 of Na). The experiments have included ESD, PSD and ion sputtering of alkali atoms from model mineral surface (amorphous SiO2) and from a lunar basalt sample obtained from NASA. The comparison is made between ESD and PSD efficiency of monovalent alkalis (Na, K) and divalent alkaline earths (Ba, Ca).The ultrahigh vacuum measurement scheme for ESD and PSD of Na atoms includes a highly sensitive alkali metal detector based on surface ionization, and a time-of-flight technique. For PSD measurements, a mercury arc light source (filtered and chopped) is used. We find that bombardment of the alkali covered surfaces by ultraviolet photons or by low energy electrons (E>4 eV) causes desorption of hot alkali atoms. This results are consistent with the model developed to explain our previous measurements of sodium desorption from a silica surface and from water ice: electron- or photon-induced charge transfer from the substrate to the ionic adsorbate causes formation of a neutral alkali atom in a repulsive configuration, from which desorption occurs. The two-electron charge transfer to cause desorption of divalent alkaline eath ions is a less likely process.The data support the suggestion that PSD by UV solar photons is a dominant source process for alkalis in the tenuous lunar atmosphere.

  1. Effects of the dimeric PSD-95 inhibitor UCCB01-144 in mouse models of pain, cognition and motor function.

    PubMed

    Andreasen, Jesper T; Nasser, Arafat; Caballero-Puntiverio, Maitane; Sahlholt, Maj; Bach, Anders; Gynther, Mikko; Strømgaard, Kristian; Pickering, Darryl S

    2016-06-05

    NMDAR antagonism shows analgesic action in humans and animal pain models, but disrupts cognitive and motor functions. NMDAR-dependent NO production requires tethering of the NMDAR to neuronal NO synthase (nNOS) by the postsynaptic density protein-95 (PSD-95). Perturbing the NMDAR/PSD-95/nNOS interaction has therefore been proposed as an alternative analgesic mechanism. We recently reported that UCCB01-125, a dimeric PSD-95 inhibitor with limited blood-brain-barrier permeability, reduced mechanical hypersensitivity in the complete Freund's adjuvant (CFA) inflammatory pain model, without disrupting cognitive or motor functions. Here, we investigated the analgesic efficacy in the CFA model of UCCB01-144, a PSD-95 inhibitor with improved blood-brain-barrier permeability. To extend the comparison of UCCB01-125 and UCCB01-144, we also tested both compounds in the spared nerve injury (SNI) model of neuropathic pain. Potential cognitive effects of UCCB01-144 were examined using the social transmission of food preference (STFP) test and the V-maze test, and motor coordination was assessed with the rotarod test. UCCB01-144 (10mg/kg) reversed CFA-induced mechanical hypersensitivity after 1h, and completely normalised sensitivity after 24h. In the SNI model, UCCB01-144 (30mg/kg) partially reversed hypersensitivity after 1h, but no effect was observed after 24h. UCCB01-125 did not affect SNI-induced hypersensitivity. Rotarod performance was unaffected by UCCB01-144, but 30mg/kg UCCB01-144 impaired performance in the STFP test. Collectively, UCCB01-144 reversed both CFA and SNI-induced hypersensitivity, but the efficacy in the SNI model was only transient. This suggests that enhanced BBB permeability of PSD-95 inhibitors improves the analgesic action in neuropathic pain states. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans.

    PubMed

    Carroll, Judith E; Cole, Steven W; Seeman, Teresa E; Breen, Elizabeth C; Witarama, Tuff; Arevalo, Jesusa M G; Ma, Jeffrey; Irwin, Michael R

    2016-01-01

    Age-related disease risk has been linked to short sleep duration and sleep disturbances; however, the specific molecular pathways linking sleep loss with diseases of aging are poorly defined. Key cellular events seen with aging, which are thought to contribute to disease, may be particularly sensitive to sleep loss. We tested whether one night of partial sleep deprivation (PSD) would increase leukocyte gene expression indicative of DNA damage responses (DDR), the senescence-associated secretory phenotype (SASP), and senescence indicator p16(INK4a) in older adult humans, who are at increased risk for cellular senescence. Community-dwelling older adults aged 61-86years (n=29; 48% male) underwent an experimental partial sleep deprivation (PSD) protocol over 4 nights, including adaptation, an uninterrupted night of sleep, partial sleep deprivation (sleep restricted 3-7AM), and a subsequent full night of sleep. Blood samples were obtained each morning to assess peripheral blood mononuclear cell (PBMC) gene expression using Illumina HT-12 arrays. Analyses of microarray results revealed that SASP (p<.05) and DDR (p=.08) gene expression were elevated from baseline to PSD nights. Gene expression changes were also observed from baseline to PSD in NFKB2, NBS1 and CHK2 (all p's<.05). The senescence marker p16(INK4a) (CDKN2A) was increased 1day after PSD compared to baseline (p<.01), however confirmatory RT-PCR did not replicate this finding. One night of partial sleep deprivation activates PBMC gene expression patterns consistent with biological aging in this older adult sample. PSD enhanced the SASP and increased the accumulation of damage that initiates cell cycle arrest and promotes cellular senescence. These findings causally link sleep deprivation to the molecular processes associated with biological aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. 40 CFR 52.1131 - Control strategy: Particulate matter.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) (PSD program only), (D)(i)(II) (PSD program only), (D)(ii), and (J) (PSD program only). (e) Approval...) (PSD program only), (D)(i)(II) (PSD program only), (D)(ii), and (J) (PSD program only). [45 FR 2044...

  4. 40 CFR 52.1131 - Control strategy: Particulate matter.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) (PSD program only), (D)(i)(II) (PSD program only), (D)(ii), and (J) (PSD program only). (e) Approval...) (PSD program only), (D)(i)(II) (PSD program only), (D)(ii), and (J) (PSD program only). [45 FR 2044...

  5. 3D scanning characteristics of an amorphous silicon position sensitive detector array system.

    PubMed

    Contreras, Javier; Gomes, Luis; Filonovich, Sergej; Correia, Nuno; Fortunato, Elvira; Martins, Rodrigo; Ferreira, Isabel

    2012-02-13

    The 3D scanning electro-optical characteristics of a data acquisition prototype system integrating a 32 linear array of 1D amorphous silicon position sensitive detectors (PSD) were analyzed. The system was mounted on a platform for imaging 3D objects using the triangulation principle with a sheet-of-light laser. New obtained results reveal a minimum possible gap or simulated defect detection of approximately 350 μm. Furthermore, a first study of the angle for 3D scanning was also performed, allowing for a broad range of angles to be used in the process. The relationship between the scanning angle of the incident light onto the object and the image displacement distance on the sensor was determined for the first time in this system setup. Rendering of 3D object profiles was performed at a significantly higher number of frames than in the past and was possible for an incident light angle range of 15 ° to 85 °.

  6. PSD-95 is required to sustain the molecular organization of the postsynaptic density

    PubMed Central

    Chen, Xiaobing; Nelson, Christopher D; Li, Xiang; Winters, Christine A.; Azzam, Rita; Sousa, Alioscka A.; Leapman, Richard D.; Gainer, Harold; Sheng, Morgan; Reese, Thomas S.

    2011-01-01

    PSD-95, a membrane-associated guanylate kinase (MAGUK), is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength. Here we show that PSD-95 is in an extended configuration and positioned into regular arrays of vertical filaments that contact both glutamate receptors and orthogonal horizontal elements layered deep inside the PSD in rat hippocampal spine synapses. RNAi knockdown of PSD-95 leads to loss of entire patches of PSD material, and EM tomography shows that the patchy loss correlates with loss of PSD-95-containing vertical filaments, horizontal elements associated with the vertical filaments, and putative AMPA, but not NMDA receptor type structures. These observations show that the orthogonal molecular scaffold constructed from PSD-95-containing vertical filaments and their associated horizontal elements is essential for sustaining the three dimensional molecular organization of the PSD. Our findings provide a structural basis for understanding the functional role of PSD-95 at the PSD. PMID:21525273

  7. Acute inactivation of PSD-95 destabilizes AMPA receptors at hippocampal synapses.

    PubMed

    Yudowski, Guillermo A; Olsen, Olav; Adesnik, Hillel; Marek, Kurt W; Bredt, David S

    2013-01-01

    Postsynatptic density protein (PSD-95) is a 95 kDa scaffolding protein that assembles signaling complexes at synapses. Over-expression of PSD-95 in primary hippocampal neurons selectively increases synaptic localization of AMPA receptors; however, mice lacking PSD-95 display grossly normal glutamatergic transmission in hippocampus. To further study the scaffolding role of PSD-95 at excitatory synapses, we generated a recombinant PSD-95-4c containing a tetracysteine motif, which specifically binds a fluorescein derivative and allows for acute and permanent inactivation of PSD-95. Interestingly, acute inactivation of PSD-95 in rat hippocampal cultures rapidly reduced surface AMPA receptor immunostaining, but did not affected NMDA or transferrin receptor localization. Acute photoinactivation of PSD-95 in dissociated neurons causes ∼80% decrease in GluR2 surface staining observed by live-cell microscopy within 15 minutes of PSD-95-4c ablation. These results confirm that PSD-95 stabilizes AMPA receptors at postsynaptic sites and provides insight into the dynamic interplay between PSD-95 and AMPA receptors in live neurons.

  8. The Wide Angle Neutron Diffractometer (WAND) at HFIR: possibilities and future

    NASA Astrophysics Data System (ADS)

    Frontzek, Matthias; Andrews, Katie M.; Chakoumakos, Bryan C.

    The Wide Angle Neutron Diffractometer (WAND) at the High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory (ORNL) has been built and continues to be, a joint project between ORNL and the Japan Atomic Energy Agency. Equipped with a 1-dimensional position sensitive detector (PSD), the instrument is a multi-purpose instrument for both powder and single crystal diffraction. WAND is currently in the process of a 2-phase upgrade to become a world class, general purpose instrument. In phase 1, finished in the beginning of 2016, the whole instrument was practically re-built from scratch, keeping only the front end and the 1-D PSD. Phase 2 will replace the 1-D PSD with the state of the art BNL120 2D-PSD which comes from the Lujan Neutron Scattering Center. We are currently integrating the detector off-line into the data acquisition architecture at HFIR. The new instrument, WAND2, will be available for general users in the proposal call 2018A. In our contribution we present results from experiments on WAND after phase 1. The upgrade now allows mounting the whole suite of available sample environment (50 mK to 1500 K, magnetic fields (5 T), high pressures (4 GPa)). We will further discuss the scientific impact the new capabilities of WAND2 will have.

  9. Retrieval of Snow Properties for Ku- and Ka-band Dual-Frequency Radar

    NASA Technical Reports Server (NTRS)

    Liao, Liang; Meneghini, Robert; Tokay, Ali; Bliven, Larry F.

    2016-01-01

    The focus of this study is on the estimation of snow microphysical properties and the associated bulk parameters such as snow water content and water equivalent snowfall rate for Ku- and Ka-band dual-frequency radar. This is done by exploring a suitable scattering model and the proper particle size distribution (PSD) assumption that accurately represent, in the electromagnetic domain, the micro/macro-physical properties of snow. The scattering databases computed from simulated aggregates for small-to-moderate particle sizes are combined with a simple scattering model for large particle sizes to characterize snow scattering properties over the full range of particle sizes. With use of the single-scattering results, the snow retrieval lookup tables can be formed in a way that directly links the Ku- and Ka-band radar reflectivities to snow water content and equivalent snowfall rate without use of the derived PSD parameters. A sensitivity study of the retrieval results to the PSD and scattering models is performed to better understand the dual-wavelength retrieval uncertainties. To aid in the development of the Ku- and Ka-band dual-wavelength radar technique and to further evaluate its performance, self-consistency tests are conducted using measurements of the snow PSD and fall velocity acquired from the Snow Video Imager Particle Image Probe (SVIPIP) duringthe winter of 2014 at the NASA Wallops Flight Facility site in Wallops Island, Virginia.

  10. Retrieval of Snow Properties for Ku- and Ka-Band Dual-Frequency Radar

    NASA Technical Reports Server (NTRS)

    Liao, Liang; Meneghini, Robert; Tokay, Ali; Bliven, Larry F.

    2016-01-01

    The focus of this study is on the estimation of snow microphysical properties and the associated bulk parameters such as snow water content and water equivalent snowfall rate for Ku- and Ka-band dual-frequency radar. This is done by exploring a suitable scattering model and the proper particle size distribution (PSD) assumption that accurately represent, in the electromagnetic domain, the micro-macrophysical properties of snow. The scattering databases computed from simulated aggregates for small-to-moderate particle sizes are combined with a simple scattering model for large particle sizes to characterize snow-scattering properties over the full range of particle sizes. With use of the single-scattering results, the snow retrieval lookup tables can be formed in a way that directly links the Ku- and Ka-band radar reflectivities to snow water content and equivalent snowfall rate without use of the derived PSD parameters. A sensitivity study of the retrieval results to the PSD and scattering models is performed to better understand the dual-wavelength retrieval uncertainties. To aid in the development of the Ku- and Ka-band dual-wavelength radar technique and to further evaluate its performance, self-consistency tests are conducted using measurements of the snow PSD and fall velocity acquired from the Snow Video Imager Particle Image Probe (SVIPIP) during the winter of 2014 at the NASA Wallops Flight Facility site in Wallops Island, Virginia.

  11. Study of sampling rate influence on neutron-gamma discrimination with stilbene coupled to a silicon photomultiplier.

    PubMed

    Zhang, Jinglong; Moore, Michael E; Wang, Zhonghai; Rong, Zhou; Yang, Chaowen; Hayward, Jason P

    2017-10-01

    Choosing a digitizer with an appropriate sampling rate is often a trade-off between performance and economy. The influence of sampling rates on the neutron-gamma Pulse Shape Discrimination (PSD) with a solid stilbene scintillator coupled to a Silicon Photomultiplier was investigated in this work. Sampling rates from 125MSPS to 2GSPS from a 10-bit digitizer were used to collect detector pulses produced by the interactions of a Cf-252 source. Due to the decreased signal-to-noise ratio (SNR), the PSD performance degraded with reduced sampling rates. The reason of PSD performance degradation was discussed. Then, an efficient combination of filtering and digital signal processing (DSP) was then applied to suppress the timing noise and electronic background noise. The results demonstrate an improved PSD performance especially at low sampling rates, down to 125MSPS. Using filtering and DSP, the ascribed Figure of Merit (FOM) at 125keV ee (± 10keV ee ) increased from 0.95 to 1.02 at 125MSPS. At 300keV ee and above, all the FOMs are better than 2.00. Our study suggests that 250MSPS is a good enough sampling rate for neutron-gamma discrimination in this system in order to be sensitive to neutrons at and above ~ 125keV ee . Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Sensitivity of the stanford sleepiness scale to the effects of cumulative partial sleep deprivation and recovery oversleeping.

    PubMed

    Herscovitch, J; Broughton, R

    1981-01-01

    The sensitivity of the Stanford Sleepiness Scale (SSS) to short-term cumulative partial sleep deprivation (PSD) and subsequent recovery oversleeping was examined. A repeated-measures design included 7 paid healthy undergraduate volunteers, who were normal sleepers (mean sleep time 7.6 hr), and consisted of the following schedule: (a) pre-baseline; (b)sleep reduction of 40% of 1 night (mean, 4.6 hr) for 5 nights; (c) recovery oversleeping for night 1 (mean, 10.6 Hr) and night 2 (mean, 9.1 hr); (d) post-baseline. Daytime performance testing utilized a 1 hr auditory vigilance task and four short-duration (10 min) tests, two of which have been shown sensitive to total and partial sleep loss effects. Subjects completed SSS forms every min while awake and 1-9 scales of mood and energy upon awakening. Subjective measures were analyzed across conditions for mean all-day and task-related SSS values and mood and energy ratings. A correlational analysis investigated individual correspondences between ratings and performance. Results indicate that SSS is sensitive to deficits in alertness following PSD. However, it generally does not predict individual performance efficiency and therefore cannot act as a substitute for performance measures in studies involving chronic sleep loss.

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

    Kwon, Deukwoo; Little, Mark P.; Miller, Donald L.

    Purpose: To determine more accurate regression formulas for estimating peak skin dose (PSD) from reference air kerma (RAK) or kerma-area product (KAP). Methods: After grouping of the data from 21 procedures into 13 clinically similar groups, assessments were made of optimal clustering using the Bayesian information criterion to obtain the optimal linear regressions of (log-transformed) PSD vs RAK, PSD vs KAP, and PSD vs RAK and KAP. Results: Three clusters of clinical groups were optimal in regression of PSD vs RAK, seven clusters of clinical groups were optimal in regression of PSD vs KAP, and six clusters of clinical groupsmore » were optimal in regression of PSD vs RAK and KAP. Prediction of PSD using both RAK and KAP is significantly better than prediction of PSD with either RAK or KAP alone. The regression of PSD vs RAK provided better predictions of PSD than the regression of PSD vs KAP. The partial-pooling (clustered) method yields smaller mean squared errors compared with the complete-pooling method.Conclusion: PSD distributions for interventional radiology procedures are log-normal. Estimates of PSD derived from RAK and KAP jointly are most accurate, followed closely by estimates derived from RAK alone. Estimates of PSD derived from KAP alone are the least accurate. Using a stochastic search approach, it is possible to cluster together certain dissimilar types of procedures to minimize the total error sum of squares.« less

  14. Method and system for controlling the position of a beam of light

    DOEpatents

    Steinkraus, Jr., Robert F.; Johnson, Gary W [Livermore, CA; Ruggiero, Anthony J [Livermore, CA

    2011-08-09

    An method and system for laser beam tracking and pointing is based on a conventional position sensing detector (PSD) or quadrant cell but with the use of amplitude-modulated light. A combination of logarithmic automatic gain control, filtering, and synchronous detection offers high angular precision with exceptional dynamic range and sensitivity, while maintaining wide bandwidth. Use of modulated light enables the tracking of multiple beams simultaneously through the use of different modulation frequencies. It also makes the system resistant to interfering light sources such as ambient light. Beam pointing is accomplished by feeding back errors in the measured beam position to a beam steering element, such as a steering mirror. Closed-loop tracking performance is superior to existing methods, especially under conditions of atmospheric scintillation.

  15. VID22 is required for transcriptional activation of the PSD2 gene in the yeast Saccharomyces cerevisiae.

    PubMed

    Miyata, Non; Miyoshi, Takuya; Yamaguchi, Takanori; Nakazono, Toshimitsu; Tani, Motohiro; Kuge, Osamu

    2015-12-15

    Phosphatidylethanolamine (PE) in the yeast Saccharomyces cerevisiae is synthesized through decarboxylation of phosphatidylserine (PS), catalysed by PS decarboxylase 1 (Psd1p) and 2 (Psd2p) and the cytidine 5'-diphosphate (CDP)-ethanolamine (CDP-Etn) pathway. PSD1 null (psd1Δ) and PSD2 null (psd2Δ) mutants are viable in a synthetic minimal medium, but a psd1Δ psd2Δ double mutant exhibits Etn auxotrophy, which is incorporated into PE through the CDP-Etn pathway. We have previously shown that psd1Δ is synthetic lethal with deletion of VID22 (vid22Δ) [Kuroda et al. (2011) Mol. Microbiol. 80: , 248-265]. In the present study, we found that vid22Δ mutant exhibits Etn auxotrophy under PSD1-depressed conditions. Deletion of VID22 in wild-type and PSD1-depressed cells caused partial defects in PE formation through decarboxylation of PS. The enzyme activity of PS decarboxylase in an extract of vid22Δ cells was ∼70% of that in wild-type cells and similar to that in psd2Δ cells and the PS decarboxylase activity remaining in the PSD1-depressed cells became almost negligible with deletion of VID22. Thus, the vid22Δ mutation was suggested to cause a defect in the Psd2p activity. Furthermore, vid22Δ cells were shown to be defective in expression of the PSD2 gene tagged with 6×HA, the defect being ameliorated by replacement of the native promoter of the PSD2 gene with a CYC1 promoter. In addition, an α-galactosidase reporter assay revealed that the activity of the promoter of the PSD2 gene in vid22Δ cells was ∼5% of that in wild-type cells. These results showed that VID22 is required for transcriptional activation of the PSD2 gene. © 2015 Authors; published by Portland Press Limited.

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

    Lessard, Francois; Archambault, Louis; Plamondon, Mathieu

    Purpose: Photon dosimetry in the kilovolt (kV) energy range represents a major challenge for diagnostic and interventional radiology and superficial therapy. Plastic scintillation detectors (PSDs) are potentially good candidates for this task. This study proposes a simple way to obtain accurate correction factors to compensate for the response of PSDs to photon energies between 80 and 150 kVp. The performance of PSDs is also investigated to determine their potential usefulness in the diagnostic energy range. Methods: A 1-mm-diameter, 10-mm-long PSD was irradiated by a Therapax SXT 150 unit using five different beam qualities made of tube potentials ranging from 80more » to 150 kVp and filtration thickness ranging from 0.8 to 0.2 mmAl + 1.0 mmCu. The light emitted by the detector was collected using an 8-m-long optical fiber and a polychromatic photodiode, which converted the scintillation photons to an electrical current. The PSD response was compared with the reference free air dose rate measured with a calibrated Farmer NE2571 ionization chamber. PSD measurements were corrected using spectra-weighted corrections, accounting for mass energy-absorption coefficient differences between the sensitive volumes of the ionization chamber and the PSD, as suggested by large cavity theory (LCT). Beam spectra were obtained from x-ray simulation software and validated experimentally using a CdTe spectrometer. Correction factors were also obtained using Monte Carlo (MC) simulations. Percent depth dose (PDD) measurements were compensated for beam hardening using the LCT correction method. These PDD measurements were compared with uncorrected PSD data, PDD measurements obtained using Gafchromic films, Monte Carlo simulations, and previous data. Results: For each beam quality used, the authors observed an increase of the energy response with effective energy when no correction was applied to the PSD response. Using the LCT correction, the PSD response was almost energy independent, with a residual 2.1% coefficient of variation (COV) over the 80-150-kVp energy range. Monte Carlo corrections reduced the COV to 1.4% over this energy range. All PDD measurements were in good agreement with one another except for the uncorrected PSD data, in which an over-response was observed with depth (13% at 10 cm with a 100 kVp beam), showing that beam hardening had a non-negligible effect on the PSD response. A correction based on LCT compensated very well for this effect, reducing the over-response to 3%.Conclusion: In the diagnostic energy range, PSDs show high-energy dependence, which can be corrected using spectra-weighted mass energy-absorption coefficients, showing no considerable sign of quenching between these energies. Correction factors obtained by Monte Carlo simulations confirm that the approximations made by LCT corrections are valid. Thus, PSDs could be useful for real-time dosimetry in radiology applications.« less

  17. Backbone dynamics of the antifungal Psd1 pea defensin and its correlation with membrane interaction by NMR spectroscopy.

    PubMed

    de Medeiros, Luciano Neves; Angeli, Renata; Sarzedas, Carolina G; Barreto-Bergter, Eliana; Valente, Ana Paula; Kurtenbach, Eleonora; Almeida, Fabio C L

    2010-02-01

    Plant defensins are cysteine-rich cationic peptides, components of the innate immune system. The antifungal sensitivity of certain exemplars was correlated to the level of complex glycosphingolipids in the membrane of fungi strains. Psd1 is a 46 amino acid residue defensin isolated from pea seeds which exhibit antifungal activity. Its structure is characterized by the so-called cysteine-stabilized alpha/beta motif linked by three loops as determined by two-dimensional NMR. In the present work we explored the measurement of heteronuclear Nuclear Overhauser Effects, R1 and R2 (15)N relaxation ratios, and chemical shift to probe the backbone dynamics of Psd1 and its interaction with membrane mimetic systems with phosphatidylcholine (PC) or dodecylphosphocholine (DPC) with glucosylceramide (CMH) isolated from Fusarium solani. The calculated R2 values predicted a slow motion around the highly conserved among Gly12 residue and also in the region of the Turn3 His36-Trp38. The results showed that Psd1 interacts with vesicles of PC or PC:CMH in slightly different forms. The interaction was monitored by chemical shift perturbation and relaxation properties. Using this approach we could map the loops as the binding site of Psd1 with the membrane. The major binding epitope showed conformation exchange properties in the mus-ms timescale supporting the conformation selection as the binding mechanism. Moreover, the peptide corresponding to part of Loop1 (pepLoop1: Gly12 to Ser19) is also able to interact with DPC micelles acquiring a stable structure and in the presence of DPC:CMH the peptide changes to an extended conformation, exhibiting NOE mainly with the carbohydrate and ceramide parts of CMH. Copyright 2009 Elsevier B.V. All rights reserved.

  18. The integral suspension pressure method (ISP) for precise particle-size analysis by gravitational sedimentation

    NASA Astrophysics Data System (ADS)

    Durner, Wolfgang; Iden, Sascha C.; von Unold, Georg

    2017-01-01

    The particle-size distribution (PSD) of a soil expresses the mass fractions of various sizes of mineral particles which constitute the soil material. It is a fundamental soil property, closely related to most physical and chemical soil properties and it affects almost any soil function. The experimental determination of soil texture, i.e., the relative amounts of sand, silt, and clay-sized particles, is done in the laboratory by a combination of sieving (sand) and gravitational sedimentation (silt and clay). In the latter, Stokes' law is applied to derive the particle size from the settling velocity in an aqueous suspension. Traditionally, there are two methodologies for particle-size analysis from sedimentation experiments: the pipette method and the hydrometer method. Both techniques rely on measuring the temporal change of the particle concentration or density of the suspension at a certain depth within the suspension. In this paper, we propose a new method which is based on the pressure in the suspension at a selected depth, which is an integral measure of all particles in suspension above the measuring depth. We derive a mathematical model which predicts the pressure decrease due to settling of particles as function of the PSD. The PSD of the analyzed sample is identified by fitting the simulated time series of pressure to the observed one by inverse modeling using global optimization. The new method yields the PSD in very high resolution and its experimental realization completely avoids any disturbance by the measuring process. A sensitivity analysis of different soil textures demonstrates that the method yields unbiased estimates of the PSD with very small estimation variance and an absolute error in the clay and silt fraction of less than 0.5%.

  19. The integral suspension pressure method (ISP) for precise particle-size analysis by gravitational sedimentation

    NASA Astrophysics Data System (ADS)

    Durner, Wolfgang; Iden, Sascha C.; von Unold, Georg

    2017-04-01

    The particle-size distribution (PSD) of a soil expresses the mass fractions of various sizes of mineral particles which constitute the soil material. It is a fundamental soil property, closely related to most physical and chemical soil properties and it affects almost any soil function. The experimental determination of soil texture, i.e., the relative amounts of sand, silt, and clay-sized particles, is done in the laboratory by a combination of sieving (sand) and gravitational sedimentation (silt and clay). In the latter, Stokes' law is applied to derive the particle size from the settling velocity in an aqueous suspension. Traditionally, there are two methodologies for particle-size analysis from sedimentation experiments: the pipette method and the hydrometer method. Both techniques rely on measuring the temporal change of the particle concentration or density of the suspension at a certain depth within the suspension. In this paper, we propose a new method which is based on the pressure in the suspension at a selected depth, which is an integral measure of all particles in suspension above the measuring depth. We derive a mathematical model which predicts the pressure decrease due to settling of particles as function of the PSD. The PSD of the analyzed sample is identified by fitting the simulated time series of pressure to the observed one by inverse modeling using global optimization. The new method yields the PSD in very high resolution and its experimental realization completely avoids any disturbance by the measuring process. A sensitivity analysis of different soil textures demonstrates that the method yields unbiased estimates of the PSD with very small estimation variance and an absolute error in the clay and silt fraction of less than 0.5%

  20. Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals.

    PubMed

    Benedict, Christian; Vogel, Heike; Jonas, Wenke; Woting, Anni; Blaut, Michael; Schürmann, Annette; Cedernaes, Jonathan

    2016-12-01

    Changes to the microbial community in the human gut have been proposed to promote metabolic disturbances that also occur after short periods of sleep loss (including insulin resistance). However, whether sleep loss affects the gut microbiota remains unknown. In a randomized within-subject crossover study utilizing a standardized in-lab protocol (with fixed meal times and exercise schedules), we studied nine normal-weight men at two occasions: after two nights of partial sleep deprivation (PSD; sleep opportunity 02:45-07:00 h), and after two nights of normal sleep (NS; sleep opportunity 22:30-07:00 h). Fecal samples were collected within 24 h before, and after two in-lab nights, of either NS or PSD. In addition, participants underwent an oral glucose tolerance test following each sleep intervention. Microbiota composition analysis (V4 16S rRNA gene sequencing) revealed that after two days of PSD vs. after two days of NS, individuals exhibited an increased Firmicutes:Bacteroidetes ratio, higher abundances of the families Coriobacteriaceae and Erysipelotrichaceae, and lower abundance of Tenericutes (all P < 0.05) - previously all associated with metabolic perturbations in animal or human models. However, no PSD vs. NS effect on beta diversity or on fecal short-chain fatty acid concentrations was found. Fasting and postprandial insulin sensitivity decreased after PSD vs. NS (all P < 0.05). Our findings demonstrate that short-term sleep loss induces subtle effects on human microbiota. To what extent the observed changes to the microbial community contribute to metabolic consequences of sleep loss warrants further investigations in larger and more prolonged sleep studies, to also assess how sleep loss impacts the microbiota in individuals who already are metabolically compromised.

  1. α-Actinin Anchors PSD-95 at Postsynaptic Sites.

    PubMed

    Matt, Lucas; Kim, Karam; Hergarden, Anne C; Patriarchi, Tommaso; Malik, Zulfiqar A; Park, Deborah K; Chowdhury, Dhrubajyoti; Buonarati, Olivia R; Henderson, Peter B; Gökçek Saraç, Çiğdem; Zhang, Yonghong; Mohapatra, Durga; Horne, Mary C; Ames, James B; Hell, Johannes W

    2018-03-07

    Despite the central role PSD-95 plays in anchoring postsynaptic AMPARs, how PSD-95 itself is tethered to postsynaptic sites is not well understood. Here we show that the F-actin binding protein α-actinin binds to the very N terminus of PSD-95. Knockdown (KD) of α-actinin phenocopies KD of PSD-95. Mutating lysine at position 10 or lysine at position 11 of PSD-95 to glutamate, or glutamate at position 53 or glutamate and aspartate at positions 213 and 217 of α-actinin, respectively, to lysine impairs, in parallel, PSD-95 binding to α-actinin and postsynaptic localization of PSD-95 and AMPARs. These experiments identify α-actinin as a critical PSD-95 anchor tethering the AMPAR-PSD-95 complex to postsynaptic sites. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Capping of the N-terminus of PSD-95 by calmodulin triggers its postsynaptic release

    PubMed Central

    Zhang, Yonghong; Matt, Lucas; Patriarchi, Tommaso; Malik, Zulfiqar A; Chowdhury, Dhrubajyoti; Park, Deborah K; Renieri, Alessandra; Ames, James B; Hell, Johannes W

    2014-01-01

    Postsynaptic density protein-95 (PSD-95) is a central element of the postsynaptic architecture of glutamatergic synapses. PSD-95 mediates postsynaptic localization of AMPA receptors and NMDA receptors and plays an important role in synaptic plasticity. PSD-95 is released from postsynaptic membranes in response to Ca2+ influx via NMDA receptors. Here, we show that Ca2+/calmodulin (CaM) binds at the N-terminus of PSD-95. Our NMR structure reveals that both lobes of CaM collapse onto a helical structure of PSD-95 formed at its N-terminus (residues 1–16). This N-terminal capping of PSD-95 by CaM blocks palmitoylation of C3 and C5, which is required for postsynaptic PSD-95 targeting and the binding of CDKL5, a kinase important for synapse stability. CaM forms extensive hydrophobic contacts with Y12 of PSD-95. The PSD-95 mutant Y12E strongly impairs binding to CaM and Ca2+-induced release of PSD-95 from the postsynaptic membrane in dendritic spines. Our data indicate that CaM binding to PSD-95 serves to block palmitoylation of PSD-95, which in turn promotes Ca2+-induced dissociation of PSD-95 from the postsynaptic membrane. PMID:24705785

  3. Capping of the N-terminus of PSD-95 by calmodulin triggers its postsynaptic release.

    PubMed

    Zhang, Yonghong; Matt, Lucas; Patriarchi, Tommaso; Malik, Zulfiqar A; Chowdhury, Dhrubajyoti; Park, Deborah K; Renieri, Alessandra; Ames, James B; Hell, Johannes W

    2014-06-17

    Postsynaptic density protein-95 (PSD-95) is a central element of the postsynaptic architecture of glutamatergic synapses. PSD-95 mediates postsynaptic localization of AMPA receptors and NMDA receptors and plays an important role in synaptic plasticity. PSD-95 is released from postsynaptic membranes in response to Ca(2+) influx via NMDA receptors. Here, we show that Ca(2+)/calmodulin (CaM) binds at the N-terminus of PSD-95. Our NMR structure reveals that both lobes of CaM collapse onto a helical structure of PSD-95 formed at its N-terminus (residues 1-16). This N-terminal capping of PSD-95 by CaM blocks palmitoylation of C3 and C5, which is required for postsynaptic PSD-95 targeting and the binding of CDKL5, a kinase important for synapse stability. CaM forms extensive hydrophobic contacts with Y12 of PSD-95. The PSD-95 mutant Y12E strongly impairs binding to CaM and Ca(2+)-induced release of PSD-95 from the postsynaptic membrane in dendritic spines. Our data indicate that CaM binding to PSD-95 serves to block palmitoylation of PSD-95, which in turn promotes Ca(2+)-induced dissociation of PSD-95 from the postsynaptic membrane. © 2014 The Authors.

  4. Conformable large-area position-sensitive photodetectors based on luminescence-collecting silicone waveguides

    NASA Astrophysics Data System (ADS)

    Bartu, Petr; Koeppe, Robert; Arnold, Nikita; Neulinger, Anton; Fallon, Lisa; Bauer, Siegfried

    2010-06-01

    Position sensitive detection schemes based on the lateral photoeffect rely on inorganic semiconductors. Such position sensitive devices (PSDs) are reliable and robust, but preparation with large active areas is expensive and use on curved substrates is impossible. Here we present a novel route for the fabrication of conformable PSDs which allows easy preparation on large areas, and use on curved surfaces. Our device is based on stretchable silicone waveguides with embedded fluorescent dyes, used in conjunction with small silicon photodiodes. Impinging laser light (e.g., from a laser pointer) is absorbed by the dye in the PSD and re-emitted as fluorescence light at a larger wavelength. Due to the isotropic emission from the fluorescent dye molecules, most of the re-emitted light is coupled into the planar silicone waveguide and directed to the edges of the device. Here the light signals are detected via embedded small silicon photodiodes arranged in a regular pattern. Using a mathematical algorithm derived by extensive using of models from global positioning system (GPS) systems and human activity monitoring, the position of light spots is easily calculated. Additionally, the device shows high durability against mechanical stress, when clamped in an uniaxial stretcher and mechanically loaded up to 15% strain. The ease of fabrication, conformability, and durability of the device suggests its use as interface devices and as sensor skin for future robots.

  5. Homozygous deletion of six genes including corneodesmosin on chromosome 6p21.3 is associated with generalized peeling skin disease.

    PubMed

    Teye, Kwesi; Hamada, Takahiro; Krol, Rafal P; Numata, Sanae; Ishii, Norito; Matsuda, Mitsuhiro; Ohata, Chika; Furumura, Minao; Hashimoto, Takashi

    2014-07-01

    Peeling skin syndrome (PSS) is a rare autosomal recessive form of ichthyosis showing skin exfoliation. PSS is divided into acral and generalized PSS, and the latter is further classified into non-inflammatory type (PSS type A) and inflammatory type (PSS type B). PSS type B is now called peeling skin disease (PSD). Different loss-of-function mutations in the corneodesmosin (CDSN) gene have been reported to cause PSD. The aim of this study was to determine genetic basis of disease in a 14-year-old Japanese patient with PSD. Immunohistochemical study showed lack of corneodesmosin (CDSN) in the skin, and standard PCR for genomic DNA failed to amplify CDSN product, suggesting CDSN defect. Multiplex ligation-dependent probe amplification and genomic quantitative real-time PCR analyses detected large homozygous deletion of 59,184bp extending from 40.6kb upstream to 13.2kb downstream of CDSN, which included 6 genes (TCF19, CCHCR1, PSORS1C2, PSORS1C1, CDSN and C6orf15). The continuous gene lost did not result in additional clinical features. Inverted repeats with 85% similarity flanking the deletion breakpoint were considered to mediate the deletion by non-homologous end joining or fork stalling and template switching/microhomology-mediated break-induced replication. Parents were clinically unaffected and were heterozygote carriers of the same deletion, which was absent in 284 ethnically matched control alleles. We also developed simple PCR method, which is useful for detection of this deletion. Although 5 other genes were also deleted, homozygous deletion of CDSN was considered to be responsible for this PSD. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

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

    Brubaker, Erik; Dibble, Dean C.; Mengesha, Wondwosen

    An ideal 3He detector replacement for the near- to medium-term future will use materials that are easy to produce and well understood, while maintaining thermal neutron detection efficiency and gamma rejection close to the 3He standard. Toward this end, we investigated the use of standard alkali halide scintillators interfaced with 6Li and read out with photomultiplier tubes (PMTs). Thermal neutrons are captured on 6Li with high efficiency, emitting high-energy and triton ( 3H) reaction products. These particles deposit energy in the scintillator, providing a thermal neutron signal; discrimination against gamma interactions is possible via pulse shape discrimination (PSD), since heavymore » particles produce faster pulses in alkali halide crystals. We constructed and tested two classes of detectors based on this concept. In one case 6Li is used as a dopant in polycrystalline NaI; in the other case a thin Li foil is used as a conversion layer. In the configurations studied here, these systems are sensitive to both gamma and neutron radiation, with discrimination between the two and good energy resolution for gamma spectroscopy. We present results from our investigations, including measurements of the neutron efficiency and gamma rejection for the two detector types. We also show a comparison with Cs 2LiYCl 6:Ce (CLYC), which is emerging as the standard scintillator for simultaneous gamma and thermal neutron detection, and also allows PSD. We conclude that 6Li foil with CsI scintillating crystals has near-term promise as a thermal neutron detector in applications previously dominated by 3He detectors. The other approach, 6Li-doped alkali halides, has some potential, but require more work to understand material properties and improve fabrication processes.« less

  7. PSD-95 and PSD-93 Play Critical but Distinct Roles in Synaptic Scaling Up and Down

    PubMed Central

    Sun, Qian; Turrigiano, Gina G.

    2011-01-01

    Synaptic scaling stabilizes neuronal firing through the homeostatic regulation of postsynaptic strength, but the mechanisms by which chronic changes in activity lead to bidirectional adjustments in synaptic AMPAR abundance are incompletely understood. Further, it remains unclear to what extent scaling up and scaling down utilize distinct molecular machinery. PSD-95 is a scaffold protein proposed to serve as a binding “slot” that determines synaptic AMPAR content, and synaptic PSD-95 abundance is regulated by activity, raising the possibility that activity-dependent changes in the synaptic abundance of PSD-95 or other MAGUKs drives the bidirectional changes in AMPAR accumulation during synaptic scaling. We found that synaptic PSD-95 and SAP102 (but not PSD-93) abundance were bidirectionally regulated by activity, but these changes were not sufficient to drive homeostatic changes in synaptic strength. Although not sufficient, the PSD-95-MAGUKs were necessary for synaptic scaling, but scaling up and down were differentially dependent on PSD-95 and PSD-93. Scaling down was completely blocked by reduced or enhanced PSD-95, through a mechanism that depended on the PDZ1/2 domains. In contrast scaling up could be supported by either PSD-95 or PSD-93 in a manner that depended on neuronal age, and was unaffected by a superabundance of PSD-95. Taken together, our data suggest that scaling up and down of quantal amplitude is not driven by changes in synaptic abundance of PSD-95-MAGUKs, but rather that the PSD-95 MAGUKs serve as critical synaptic organizers that utilize distinct protein-protein interactions to mediate homeostatic accumulation and loss of synaptic AMPAR. PMID:21543610

  8. Protein Kinase Cϵ (PKCϵ) Promotes Synaptogenesis through Membrane Accumulation of the Postsynaptic Density Protein PSD-95*

    PubMed Central

    Sen, Abhik; Hongpaisan, Jarin; Wang, Desheng; Nelson, Thomas J.; Alkon, Daniel L.

    2016-01-01

    Protein kinase Cϵ (PKCϵ) promotes synaptic maturation and synaptogenesis via activation of synaptic growth factors such as BDNF, NGF, and IGF. However, many of the detailed mechanisms by which PKCϵ induces synaptogenesis are not fully understood. Accumulation of PSD-95 to the postsynaptic density (PSD) is known to lead to synaptic maturation and strengthening of excitatory synapses. Here we investigated the relationship between PKCϵ and PSD-95. We show that the PKCϵ activators dicyclopropanated linoleic acid methyl ester and bryostatin 1 induce phosphorylation of PSD-95 at the serine 295 residue, increase the levels of PSD-95, and enhance its membrane localization. Elimination of the serine 295 residue in PSD-95 abolished PKCϵ-induced membrane accumulation. Knockdown of either PKCϵ or JNK1 prevented PKCϵ activator-mediated membrane accumulation of PSD-95. PKCϵ directly phosphorylated PSD-95 and JNK1 in vitro. Inhibiting PKCϵ, JNK, or calcium/calmodulin-dependent kinase II activity prevented the effects of PKCϵ activators on PSD-95 phosphorylation. Increase in membrane accumulation of PKCϵ and phosphorylated PSD-95 (p-PSD-95S295) coincided with an increased number of synapses and increased amplitudes of excitatory post-synaptic potentials (EPSPs) in adult rat hippocampal slices. Knockdown of PKCϵ also reduced the synthesis of PSD-95 and the presynaptic protein synaptophysin by 30 and 44%, respectively. Prolonged activation of PKCϵ increased synapse number by 2-fold, increased presynaptic vesicle density, and greatly increased PSD-95 clustering. These results indicate that PKCϵ promotes synaptogenesis by activating PSD-95 phosphorylation directly through JNK1 and calcium/calmodulin-dependent kinase II and also by inducing expression of PSD-95 and synaptophysin. PMID:27330081

  9. Protein Kinase Cϵ (PKCϵ) Promotes Synaptogenesis through Membrane Accumulation of the Postsynaptic Density Protein PSD-95.

    PubMed

    Sen, Abhik; Hongpaisan, Jarin; Wang, Desheng; Nelson, Thomas J; Alkon, Daniel L

    2016-08-05

    Protein kinase Cϵ (PKCϵ) promotes synaptic maturation and synaptogenesis via activation of synaptic growth factors such as BDNF, NGF, and IGF. However, many of the detailed mechanisms by which PKCϵ induces synaptogenesis are not fully understood. Accumulation of PSD-95 to the postsynaptic density (PSD) is known to lead to synaptic maturation and strengthening of excitatory synapses. Here we investigated the relationship between PKCϵ and PSD-95. We show that the PKCϵ activators dicyclopropanated linoleic acid methyl ester and bryostatin 1 induce phosphorylation of PSD-95 at the serine 295 residue, increase the levels of PSD-95, and enhance its membrane localization. Elimination of the serine 295 residue in PSD-95 abolished PKCϵ-induced membrane accumulation. Knockdown of either PKCϵ or JNK1 prevented PKCϵ activator-mediated membrane accumulation of PSD-95. PKCϵ directly phosphorylated PSD-95 and JNK1 in vitro Inhibiting PKCϵ, JNK, or calcium/calmodulin-dependent kinase II activity prevented the effects of PKCϵ activators on PSD-95 phosphorylation. Increase in membrane accumulation of PKCϵ and phosphorylated PSD-95 (p-PSD-95(S295)) coincided with an increased number of synapses and increased amplitudes of excitatory post-synaptic potentials (EPSPs) in adult rat hippocampal slices. Knockdown of PKCϵ also reduced the synthesis of PSD-95 and the presynaptic protein synaptophysin by 30 and 44%, respectively. Prolonged activation of PKCϵ increased synapse number by 2-fold, increased presynaptic vesicle density, and greatly increased PSD-95 clustering. These results indicate that PKCϵ promotes synaptogenesis by activating PSD-95 phosphorylation directly through JNK1 and calcium/calmodulin-dependent kinase II and also by inducing expression of PSD-95 and synaptophysin. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. TU-D-209-04: How Useful Are Indirect Dose Metrics for Estimating Peak Skin Dose in Interventional Cardiology?

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

    Jones, A; Pasciak, A

    Purpose: The purpose of this study was to determine if a relationship between indirect dose metrics and PSD could be established for fluoroscopically-guided interventional cardiology procedures. Methods: PSD were measured directly using XR-RV3 radiochromic film for 94 consecutive fluoroscopically guided interventional cardiology procedures performed at two sites. Procedures were both diagnostic and therapeutic in nature. Radiation dose structured reports (RDSR) were collected for each procedure and used to calculate indirect estimates of PSD which were compared to the measured PSD. Reference air kerma (Ka,r) was also compared to the measured PSD. Pearson’s correlation coefficient was calculated for each metric andmore » metrics were compared to measured PSD using a two-tailed t-test. Data were log transformed prior to statistical analysis. Results: Both Ka,r and the calculated PSD were closely correlated with measured PSD at each sites (Ka,r: 0.92 and 0.86, indirect PSD: 0.91 and 0.88). At one site, neither Ka,r nor indirect PSD was significantly different from the measured PSD (p = 0.22 and p=0.054, respectively), while at the second site both Ka,r and indirect PSD were significantly higher than measured PSD (p<0.0001 and p<0.0001, respectively). In almost all cases, both Ka,r and indirect PSD overestimated the true PSD. Conclusions: The use of a range of gantry angles and table positions, along with variation in procedural imaging requirements, limits the utility of indirect dose metrics for predicting PSD for interventional cardiology procedures. A. Kyle Jones and Alexander S. Pasciak are owners of Fluoroscopic Safety, LLC.« less

  11. The Energy-Dependent X-Ray Timing Characteristics of the Narrow Line Seyfert 1 MKN 766

    NASA Technical Reports Server (NTRS)

    Markowitz, A.; Papadakis, I.; Arevalo, P.; Turner, T. J.; Miller, L.; Reeves, J. N.

    2007-01-01

    We present the energy-dependent power spectral density (PSD) and cross-spectral properties of Mkn 766, obtained from combining data obtained during an XMM-Newton observation spanning six revolutions in 2005 with data obtained from an XMM-Newton long-look in 2001. The PSD shapes and rms-flux relations are found to be consistent between the 2001 and 2005 observations, suggesting the 2005 observation is simply a low-flux extension of the 2001 observation and permitting us to combine the two data sets. The resulting PSD has the highest temporal frequency resolution for any AGN PSD measured to date. Applying a broken power-law model yields break frequencies which increase in temporal frequency with photon energy. Obtaining a good fit when assuming energy-independent break frequencies requires the presence of a Lorentzian at 4.6 +/- 0.4 x 10(exp -4)Hz whose strength increases with photon energy, a behavior seen in black hole X-ray binaries. The cross-spectral properties are measured; temporal frequency-dependent soft-to-hard time lags are detected in this object for the first time. Cross-spectral results are consistent with those for other accreting black hole systems. The results are discussed in the context of several variability models, including those based on inwardly-propagating viscosity variations in the accretion disk.

  12. Fast collimated neutron flux measurement using stilbene scintillator and flashy analog-to-digital converter in JT-60U

    NASA Astrophysics Data System (ADS)

    Ishikawa, M.; Itoga, T.; Okuji, T.; Nakhostin, M.; Shinohara, K.; Hayashi, T.; Sukegawa, A.; Baba, M.; Nishitani, T.

    2006-10-01

    A line-integrated neutron emission profile is routinely measured using the radial neutron collimator system in JT-60U tokamak. Stilbene neuron detectors (SNDs), which combine a stilbene organic crystal scintillation detector (SD) with an analog neutron-gamma pulse shape discrimination (PSD) circuit, have been used to measure collimated neutron flux. Although the SND has many advantages as a neutron detector, the maximum count rate is limited up to ˜1×105counts/s due to the analog PSD circuit. To overcome this issue, a digital signal processing system (DSPS) using a flash analog-to-digital converter (Acqiris DC252, 8GHz, 10bits) has been developed at Cyclotron and Radioisotope Center in Tohoku University. In this system anode signals from photomultiplier of the SD are directory stored and digitized. Then, the PSD between neutrons and gamma rays is performed using software. The DSPS has been installed in the vertical neutron collimator system in JT-60U and applied to deuterium experiments. It is confirmed that the PSD is sufficiently performed and collimated neutron flux is successfully measured with count rate up to ˜5×105counts/s without the effect of pileup of detected pulses. The performance of the DSPS as a neutron detector, which supersedes the SND, is demonstrated.

  13. A simplified guide for charged aerosol detection of non-chromophoric compounds-Analytical method development and validation for the HPLC assay of aerosol particle size distribution for amikacin.

    PubMed

    Soliven, Arianne; Haidar Ahmad, Imad A; Tam, James; Kadrichu, Nani; Challoner, Pete; Markovich, Robert; Blasko, Andrei

    2017-09-05

    Amikacin, an aminoglycoside antibiotic lacking a UV chromophore, was developed into a drug product for delivery by inhalation. A robust method for amikacin assay analysis and aerosol particle size distribution (aPSD) determination, with comparable performance to the conventional UV detector was developed using a charged aerosol detector (CAD). The CAD approach involved more parameters for optimization than UV detection due to its sensitivity to trace impurities, non-linear response and narrow dynamic range of signal versus concentration. Through careful selection of the power transformation function value and evaporation temperature, a wider linear dynamic range, improved signal-to-noise ratio and high repeatability were obtained. The influences of mobile phase grade and glassware binding of amikacin during sample preparation were addressed. A weighed (1/X 2 ) least square regression was used for the calibration curve. The limit of quantitation (LOQ) and limit of detection (LOD) for this method were determined to be 5μg/mL and 2μg/mL, respectively. The method was validated over a concentration range of 0.05-2mg/mL. The correlation coefficient for the peak area versus concentration was 1.00 and the y-intercept was 0.2%. The recovery accuracies of triplicate preparations at 0.05, 1.0, and 2.0mg/mL were in the range of 100-101%. The relative standard deviation (S rel ) of six replicates at 1.0mg/mL was 1%, and S rel of five injections at the limit of quantitation was 4%. A robust HPLC-CAD method was developed and validated for the determination of the aPSD for amikacin. The CAD method development produced a simplified procedure with minimal variability in results during: routine operation, transfer from one instrument to another, and between different analysts. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Indigenous design and development of multiPSD array for time of flight neutron spectrometer

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

    Desai, Shraddha S., E-mail: ssdesai@barc.gov.in; Devan, Shylaja; Das, Amrita

    Time of Flight neutron Spectrometer for inelastic neutron scattering studies is being commissioned at Dhruva reactor. Neutron pulse tagging is carried out using the Fermi chopper. Scattered neutrons at maximum possible scattered solid angle are needed to be detected along with the time information at detector. Precise and efficient detection system is essential for measurement of spatial and temporal distribution. Detection area is optimized to cover an angle of 70° in horizontal direction and 23° in vertical direction. Position sensitive detectors (PSDs) are designed with judicial use of precious {sup 3}He gas and a few PSDs with BF{sub 3} gasmore » as suitable alternative for {sup 3}He gas. An array of vertically arranged 1 m long, 50 PSDs, covers the arc length of 2.5 m and detection area 2.5 m{sup 2}. The design of the BF{sub 3} PSDs is supported by investigations on the gas purity, fill gas pressure, drift region, drift field and neutron absorption in cathode wall. Design details and performance of the PSDs are presented in the paper.« less

  15. Continued Data Acquisition Development

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

    Schwellenbach, David

    This task focused on improving techniques for integrating data acquisition of secondary particles correlated in time with detected cosmic-ray muons. Scintillation detectors with Pulse Shape Discrimination (PSD) capability show the most promise as a detector technology based on work in FY13. Typically PSD parameters are determined prior to an experiment and the results are based on these parameters. By saving data in list mode, including the fully digitized waveform, any experiment can effectively be replayed to adjust PSD and other parameters for the best data capture. List mode requires time synchronization of two independent data acquisitions (DAQ) systems: the muonmore » tracker and the particle detector system. Techniques to synchronize these systems were studied. Two basic techniques were identified: real time mode and sequential mode. Real time mode is the preferred system but has proven to be a significant challenge since two FPGA systems with different clocking parameters must be synchronized. Sequential processing is expected to work with virtually any DAQ but requires more post processing to extract the data.« less

  16. Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice.

    PubMed

    Morimura, Naoko; Yasuda, Hiroki; Yamaguchi, Kazuhiko; Katayama, Kei-Ichi; Hatayama, Minoru; Tomioka, Naoko H; Odagawa, Maya; Kamiya, Akiko; Iwayama, Yoshimi; Maekawa, Motoko; Nakamura, Kazuhiko; Matsuzaki, Hideo; Tsujii, Masatsugu; Yamada, Kazuyuki; Yoshikawa, Takeo; Aruga, Jun

    2017-06-12

    Lrfn2/SALM1 is a PSD-95-interacting synapse adhesion molecule, and human LRFN2 is associated with learning disabilities. However its role in higher brain function and underlying mechanisms remain unknown. Here, we show that Lrfn2 knockout mice exhibit autism-like behavioural abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits, together with enhanced learning and memory. In the hippocampus, the levels of synaptic PSD-95 and GluA1 are decreased. The synapses are structurally and functionally immature with spindle shaped spines, smaller postsynaptic densities, reduced AMPA/NMDA ratio, and enhanced LTP. In vitro experiments reveal that synaptic surface expression of AMPAR depends on the direct interaction between Lrfn2 and PSD-95. Furthermore, we detect functionally defective LRFN2 missense mutations in autism and schizophrenia patients. Together, these findings indicate that Lrfn2/LRFN2 serve as core components of excitatory synapse maturation and maintenance, and their dysfunction causes immature/silent synapses with pathophysiological state.

  17. Phosphorylation of threonine-19 of PSD-95 by GSK-3β is required for PSD-95 mobilization and long-term depression.

    PubMed

    Nelson, Christopher D; Kim, Myung Jong; Hsin, Honor; Chen, Yelin; Sheng, Morgan

    2013-07-17

    Activity of glycogen synthase kinase-3β (GSK-3β) is required for long-term depression (LTD) via molecular mechanisms that are incompletely understood. Here, we report that PSD-95, a major scaffold protein of the postsynaptic density (PSD) that promotes synaptic strength, is phosphorylated on threonine-19 (T19) by GSK-3β. In cultured rat hippocampal neurons, phosphorylation of T19 increases rapidly with chemical LTD and is attenuated by pharmacologic or genetic suppression of GSK-3β. In organotypic rat hippocampal slices, we find that a nonphosphorylatable PSD-95 mutant (T19A) tagged with photoactivatable green fluorescent protein (PAGFP) shows enhanced stability in dendritic spines versus wild-type PSD-95, whereas the phosphomimetic mutant (PSD-95-T19D) is more readily dispersed. Further, overexpression of PSD-95-T19A, but not WT-PSD-95, impairs AMPA receptor internalization and the induction of LTD. These data indicate that phosphorylation on T19 by GSK-3β destabilizes PSD-95 within the PSD and is a critical step for AMPA receptor mobilization and LTD.

  18. Activity-dependent regulation of synaptic strength by PSD-95 in CA1 neurons.

    PubMed

    Zhang, Peng; Lisman, John E

    2012-02-01

    CaMKII and PSD-95 are the two most abundant postsynaptic proteins in the postsynaptic density (PSD). Overexpression of either can dramatically increase synaptic strength and saturate long-term potentiation (LTP). To do so, CaMKII must be activated, but the same is not true for PSD-95; expressing wild-type PSD-95 is sufficient. This raises the question of whether PSD-95's effects are simply an equilibrium process [increasing the number of AMPA receptor (AMPAR) slots] or whether activity is somehow involved. To examine this question, we blocked activity in cultured hippocampal slices with TTX and found that the effects of PSD-95 overexpression were greatly reduced. We next studied the type of receptors involved. The effects of PSD-95 were prevented by antagonists of group I metabotropic glutamate receptors (mGluRs) but not by antagonists of ionotropic glutamate receptors. The inhibition of PSD-95-induced strengthening was not simply a result of inhibition of PSD-95 synthesis. To understand the mechanisms involved, we tested the role of CaMKII. Overexpression of a CaMKII inhibitor, CN19, greatly reduced the effect of PSD-95. We conclude that PSD-95 cannot itself increase synaptic strength simply by increasing the number of AMPAR slots; rather, PSD-95's effects on synaptic strength require an activity-dependent process involving mGluR and CaMKII.

  19. In Situ Reductive Synthesis of Structural Supported Gold Nanorods in Porous Silicon Particles for Multifunctional Nanovectors.

    PubMed

    Zhu, Guixian; Liu, Jen-Tsai; Wang, Yuzhen; Zhang, Dechen; Guo, Yi; Tasciotti, Ennio; Hu, Zhongbo; Liu, Xuewu

    2016-05-11

    Porous silicon nanodisks (PSD) were fabricated by the combination of photolithography and electrochemical etching of silicon. By using PSD as a reducing agent, gold nanorods (AuNR) were in situ synthesized in the nanopores of PSD, forming PSD-supported-AuNR (PSD/AuNR) hybrid particles. The formation mechanism of AuNR in porous silicon (pSi) was revealed by exploring the role of pSi reducibility and each chemical in the reaction. With the PSD support, AuNR exhibited a stable morphology without toxic surface ligands (CTAB). The PSD/AuNR hybrid particles showed enhanced plasmonic property compared to free AuNR. Because high-density "hot spots" can be generated by controlling the distribution of AuNR supported in PSD, surface-enhanced raman scattering (SERS) using PSD/AuNR as particle substrates was demonstrated. A multifunctional vector, PSD/AuNR/DOX, composed of doxorubicin (DOX)-loaded PSD/AuNR capped with agarose (agar), was developed for highly efficient, combinatorial cancer treatment. Their therapeutic efficacy was examined using two pancreatic cancer cell lines, PANC-1 and MIA PaCa-2. PSD/AuNR/DOX (20 μg Au and 1.25 μg DOX/mL) effectively destroyed these cells under near-IR laser irradiation (810 nm, 15 J·cm(-2) power, 90 s). Overall, we envision that PSD/AuNR may be a promising injectable, multifunctional nanovector for biomedical application.

  20. Development of CANDLES low background HPGe detector and half-life measurement of 180Tam

    NASA Astrophysics Data System (ADS)

    Chan, W. M.; Kishimoto, T.; Umehara, S.; Matsuoka, K.; Suzuki, K.; Yoshida, S.; Nakajima, K.; Iida, T.; Fushimi, K.; Nomachi, M.; Ogawa, I.; Tamagawa, Y.; Hazama, R.; Takemoto, Y.; Nakatani, N.; Takihira, Y.; Tozawa, M.; Kakubata, H.; Trang, V. T. T.; Ohata, T.; Tetsuno, K.; Maeda, T.; Khai, B. T.; Li, X. L.; Batpurev, T.

    2018-01-01

    A low background HPGe detector system was developed at CANDLES Experimental Hall for multipurpose use. Various low background techniques were employed, including hermatic shield design, radon gas suppression, and background reduction analysis. A new pulse shape discrimination (PSD) method was specially created for coaxial Ge detector. Using this PSD method, microphonics noise and background event at low energy region less than 200 keV can be rejected effectively. Monte Carlo simulation by GEANT4 was performed to acquire the detection efficiency and study the interaction of gamma-rays with detector system. For rare decay measurement, the detector was utilized to detect the nature's most stable isomer tantalum-180m (180Tam) decay. Two phases of tantalum physics run were completed with total livetime of 358.2 days, which Phase II has upgraded shield configuration. The world most stringent half-life limit of 180Tam has been successfully achieved.

  1. A Noise Spectroscopy-Based Selective Gas Sensing with MOX Gas Sensors

    NASA Astrophysics Data System (ADS)

    Gomri, S.; Seguin, J.; Contaret, T.; Fiorido, T.; Aguir, K.

    We propose a new method for obtaining a fluctuation-enhanced sensing (FES) signature of a gas using a single metal oxide (MOX) gas micro sensor. Starting from our model of adsorption-desorption (A-D) noise previously developed, we show theoretically that the product of frequency by the power spectrum density (PSD) of the gas sensing layer resistance fluctuations often has a maximum which is characteristic of the gas. This property was experimentally confirmed in the case of the detection of NO2 and O3 using a WO3 sensing layer. This method could be useful for classifying gases. Furthermore, our noise measurements confirm our previous model showing that PSD of the A-Dnoise in MOX gas sensor is a combination of Lorentzians having a low frequency magnitude and a cut-off frequency which depends on the nature of the detected gas.

  2. Aberrant methylation of PSD disturbs Rac1-mediated immune responses governing neutrophil chemotaxis and apoptosis in ulcerative colitis-associated carcinogenesis.

    PubMed

    Kato, Takaharu; Suzuki, Koichi; Okada, Shinichiro; Kamiyama, Hidenori; Maeda, Takafumi; Saito, Masaaki; Koizumi, Kei; Miyaki, Yuichiro; Konishi, Fumio

    2012-04-01

    We previously reported that the Pleckstrin and Sec7 domain-containing (PSD) gene is preferentially methylated in patients with ulcerative colitis (UC) who developed colorectal cancer (CRC), and is implicated in UC-associated carcinogenesis through its inhibition of apoptosis. This study aimed to determine the potential effect of PSD methylation on its downstream molecule, Ras-related C3 botulinum toxin substrate 1 (Rac1), which governs neutrophil chemotaxis and apoptosis signaling. PSD was knocked down in a normal human fibroblast cell line (HNDF) and a neutrophil-like cell line (HL-60). Both NHDF and HL-60 cells exhibited numerous filamentous-actin (F-actin) rich membrane extensions, resulting in the activation of Rac1; this activation was hampered by PSD silencing. Lipopolysaccharide, a reactive oxygen species (ROS) inducer, stimulated NHDF cells to release ROS and activated caspase‑3/7 in the presence of neutrophils, which was inhibited by PSD knockdown. Migration assays demonstrated that chemotaxis of HL-60 cells was affected by PSD silencing in NHDF cells. Tissue sections from 6 UC patients with CRC and 15 UC patients without CRC were examined. To verify Rac1-mediated chemotaxis in tissue sections, we evaluated the grade of neutrophil infiltration by histological assessment and assessed F-actin and PSD expression by immunohistochemistry. Neutrophil infiltration, F-actin and PSD expression were significantly decreased in specimens from UC patients with PSD methylation compared with those without. Decreased levels of F-actin expression were observed in colorectal mucosa, as well as in infiltrating cells with PSD methylation. PSD expression was preferentially inhibited in colorectal mucosa by PSD methylation, whereas PSD expression was rarely observed in infiltrating cells, regardless of PSD methylation status. These data indicate that aberrant methylation of PSD occurs in UC-associated colorectal mucosa, enabling circumvention of Rac1-mediated immune responses governing neutrophil chemotaxis and apoptosis, and thus plays a pivotal role in the mechanisms underlying UC-associated carcinogenesis.

  3. Plastic Scintillators for Pulse Shape Discrimination of Particle Types in Radiation Detection

    NASA Astrophysics Data System (ADS)

    Hajagos, Tibor Jacob

    Organic scintillators have a long history in the field of radiation detection, dating back to some of the earliest studies of organic photophysics and optoelectronic properties. In particular, plastics have come to dominate the commercial market for organic scintillators, due to their low cost and ease of use and manufacturing, and more notably in spite of their poorer performance in many metrics. While there has been decades of active research since their inception, little progress has been made to improve upon the now well established compositions of commercial plastics, a notable exception being the recent development of plastic scintillators capable of pulse shape discrimination (PSD) of n/gamma radiation, which is of particular interest among governments and industry for the detection of illicit nuclear material and weapons. In recent years, much attention has been paid towards the study of luminescent organic materials, in particular due to the invention and widespread adoption of organic light emitting diode (OLED) based electronic devices, and the knowledge and lessons that have been fundamental to such fields have recently begun to be adopted by the organic scintilator community. In this work, new approaches to the design of both plastic scintillator components, and of the materials as a whole, are described, with particular emphasis paid towards the design and synthesis of small molecule scintillating dyes that are specifically tailored towards the development of PSD-capable plastic scintilators. In the first of these approaches, the design and synthesis of a highly soluble and polymerizable derivative of 9,10-diphenylanthracene is described, and the properties of plastic scintilators fabricated from this dye when copolymerized with poly(vinyl toluene) were investigated. This particular approach was used to demonstrate a proof-of-concept of PSD in highly loaded plastics stabilized through copolymerization of the primary dye, a strategy conceived to address the particular shortcomings of the current generation of PSD plastics. The second general approach investigated is the application of the phenomenon of thermally activated delayed fluorescence (TADF)--most notably a key innovation among the latest developments in OLED technologies--to the enhancement of the performance of organic sicntillators. Several key observations about the potential and efficacy of TADF dyes as novel organic scintillators were made, including a demonstration of the profound effects the TADF phenomenon can have on scintillation properties. These findings suggest that it is quite possible that TADF dyes could eventually enable an entirely new generation of high performance organic scintillators, and PSD-capable plastics in particular.

  4. 40 CFR 124.41 - Definitions applicable to PSD permits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Definitions applicable to PSD permits... PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.41 Definitions applicable to PSD permits. Whenever PSD permits are processed under this part, the following terms shall have...

  5. 40 CFR 124.41 - Definitions applicable to PSD permits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 23 2013-07-01 2013-07-01 false Definitions applicable to PSD permits... PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.41 Definitions applicable to PSD permits. Whenever PSD permits are processed under this part, the following terms shall have...

  6. 40 CFR 124.41 - Definitions applicable to PSD permits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Definitions applicable to PSD permits... PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.41 Definitions applicable to PSD permits. Whenever PSD permits are processed under this part, the following terms shall have...

  7. 40 CFR 124.41 - Definitions applicable to PSD permits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Definitions applicable to PSD permits... PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.41 Definitions applicable to PSD permits. Whenever PSD permits are processed under this part, the following terms shall have...

  8. 40 CFR 124.41 - Definitions applicable to PSD permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Definitions applicable to PSD permits... PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.41 Definitions applicable to PSD permits. Whenever PSD permits are processed under this part, the following terms shall have...

  9. Phosphorylation of Threonine-19 of PSD-95 by GSK-3β is Required for PSD-95 Mobilization and Long-Term Depression

    PubMed Central

    Nelson, Christopher D.; Kim, Myung Jong; Hsin, Honor; Chen, Yelin

    2013-01-01

    Activity of glycogen synthase kinase-3β (GSK-3β) is required for long-term depression (LTD) via molecular mechanisms that are incompletely understood. Here, we report that PSD-95, a major scaffold protein of the postsynaptic density (PSD) that promotes synaptic strength, is phosphorylated on threonine-19 (T19) by GSK-3β. In cultured rat hippocampal neurons, phosphorylation of T19 increases rapidly with chemical LTD and is attenuated by pharmacologic or genetic suppression of GSK-3β. In organotypic rat hippocampal slices, we find that a nonphosphorylatable PSD-95 mutant (T19A) tagged with photoactivatable green fluorescent protein (PAGFP) shows enhanced stability in dendritic spines versus wild-type PSD-95, whereas the phosphomimetic mutant (PSD-95-T19D) is more readily dispersed. Further, overexpression of PSD-95-T19A, but not WT-PSD-95, impairs AMPA receptor internalization and the induction of LTD. These data indicate that phosphorylation on T19 by GSK-3β destabilizes PSD-95 within the PSD and is a critical step for AMPA receptor mobilization and LTD. PMID:23864697

  10. Provider self-disclosure during contraceptive counseling.

    PubMed

    McLean, Merritt; Steinauer, Jody; Schmittdiel, Julie; Chan, Pamela; Dehlendorf, Christine

    2017-02-01

    Provider self-disclosure (PSD) - defined as providers making statements regarding personal information to patients - has not been well characterized in the context of contraceptive counseling. In this study, we describe the incidence, content and context of contraceptive PSD. This mixed methods analysis used data from the Provider-Patient Contraceptive Counseling study, for which 349 family planning patients were recruited from 2009 to 2012 from six clinics in the San Francisco Bay Area. Audio-recordings from their visits were analyzed for the presence or absence of PSD, and those visits with evidence of PSD were analyzed using qualitative methods. The associations of patient and provider demographics and patient satisfaction measures, obtained from survey data, with PSD were analyzed using bivariable and multivariable analyses. Thirty-seven percent of providers showed evidence of PSD during at least one visit, and PSD occurred in 9% of clinic visits. Fifty-four percent of PSD statements were about intrauterine devices. About half of PSD statements occurred prior to the final selection of the contraceptive method and appeared to influence the choice of method. In post-visit surveys, all patients who reported receiving PSD considered it to be appropriate, and patient-reported PSD was not statistically associated with measures of patient satisfaction. This study provides some support for the appropriateness of PSD during family planning encounters, at least as practiced during the sampled visits. Further research could explore whether this counseling strategy has an impact on patients' ability to identify the best contraceptive methods for them. In this study, PSD did not have a demonstrated negative effect on the provider-patient relationship. In almost half of visits, PSD appeared to influence patients' choice of a method; whether this influence is beneficial needs further research. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 75 FR 75658 - Approval and Promulgation of Implementation Plans; Alaska: Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-06

    ... Significant Deterioration (PSD) program to reflect changes to the Federal PSD program relating to the... update Alaska's PSD program to reflect changes to the Federal PSD program that would authorize the State of Alaska to regulate GHGs under its PSD program and establish appropriate emission thresholds for...

  12. Differential localization of SAP102 and PSD-95 is revealed in hippocampal spines using super-resolution light microscopy.

    PubMed

    Zheng, Chan-Ying; Wang, Ya-Xia; Kachar, Bechara; Petralia, Ronald S

    2011-01-01

    Synapse-associated protein 102 (SAP102) and postsynaptic density 95 (PSD-95) are two major cytoskeleton proteins in the postsynaptic density (PSD). Both of them belong to the membrane-associated guanylate kinase (MAGUK) family, which clusters and anchors glutamate receptors and other proteins at synapses. In our previous study, we found that SAP102 and PSD-95 have different distributions, using combined light/electron microscopy (LM/EM) methods.1 Here, we double labeled endogenous SAP102 and PSD-95 in mature hippocampal neurons, and then took images by two different kinds of super resolution microscopy-Stimulated Emission Depletion microscopy (STED) and DeltaVision OMX 3D super resolution microscopy. We found that our 2D and 3D super resolution data were consistent with our previous LM/EM data, showing significant differences in the localization of SAP102 and PSD-95 in spines: SAP102 is distributed in both the PSD and cytoplasm of spines, while PSD-95 is concentrated only in the PSD area. These results indicate functional differences between SAP102 and PSD-95 in synaptic organization and plasticity.

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

    Mesick, Katherine Elizabeth; Coupland, Daniel David S.; Stonehill, Laura Catherine

    Cs 2LiLaBr 6:Ce 3+ (CLLB) is an elpasolite scintillator that offers excellent linearity and gamma-ray energy resolution and sensitivity to thermal neutrons with the ability to perform pulse-shape discrimination (PSD) to distinguish gammas and neutrons. Our investigation of CLLB has indicated the presence of intrinsic radioactive alpha background that we have determined to be from actinium contamination of the lanthanum component. We measured the pulse shapes for gamma, thermal neutron, and alpha events and determined that PSD can be performed to separate the alpha background with a moderate figure of merit of 0.98. Here, we also measured the electron-equivalent-energy ofmore » the alpha particles in CLLB and simulated the intrinsic alpha background from 227Ac to determine the quenching factor of the alphas.« less

  14. Loss of PSD-95 Enrichment is not a Prerequisite for Spine Retraction

    PubMed Central

    Woods, Georgia F.; Oh, Won Chan; Boudewyn, Lauren C.; Mikula, Sarah K.; Zito, Karen

    2011-01-01

    Changes in neuronal structure are thought to underlie long-term behavioral modifications associated with learning and memory. In particular, considerable evidence implicates the destabilization and retraction of dendritic spines along with the loss of spine synapses as an important cellular mechanism for refining brain circuits, yet the molecular mechanisms regulating spine elimination remain ill-defined. The postsynaptic density protein, PSD-95, is highly enriched in dendritic spines and has been associated with spine stability. Because spines with low levels of PSD-95 are more dynamic, and the recruitment of PSD-95 to nascent spines has been associated with spine stabilization, we hypothesized that loss of PSD-95 enrichment would be a prerequisite for spine retraction. To test this hypothesis, we used dual-color time-lapse two-photon microscopy to monitor rat hippocampal pyramidal neurons co-transfected with PSD-95-GFP and DsRed-Express, and we analyzed the relationship between PSD-95-GFP enrichment and spine morphological changes. Consistent with our hypothesis, we found that the majority of spines that retracted were relatively unenriched for PSD-95-GFP. However, in the subset of PSD-95-GFP-enriched spines that retracted, spine shrinkage and loss of PSD-95-GFP were tightly coupled, suggesting that loss of PSD-95-GFP enrichment did not precede spine retraction. Moreover, we found that in some instances spine retraction resulted in a significant enrichment of PSD-95-GFP on the dendritic shaft. Our data support a model of spine retraction in which loss of PSD-95 enrichment is not required prior to the destabilization of spines. PMID:21865455

  15. Structural analysis of the PSD-95 cluster by electron tomography and CEMOVIS: a proposal for the application of the genetically encoded metallothionein tag.

    PubMed

    Hirabayashi, Ai; Fukunaga, Yuko; Miyazawa, Atsuo

    2014-06-01

    Postsynaptic density-95 (PSD-95) accumulates at excitatory postsynapses and plays important roles in the clustering and anchoring of numerous proteins at the PSD. However, a detailed ultrastructural analysis of clusters exclusively consisting of PSD-95 has never been performed. Here, we employed a genetically encoded tag, three tandem repeats of metallothionein (3MT), to study the structure of PSD-95 clusters in cells by electron tomography and cryo-electron microscopy of vitreous sections. We also performed conventional transmission electron microscopy (TEM). Cultured hippocampal neurons expressing a fusion protein of PSD-95 coupled to 3MT (PDS-95-3MT) were incubated with CdCl2 to result in the formation of Cd-bound PSD-95-3MT. Two types of electron-dense deposits composed of Cd-bound PSD-95-3MT were observed in these cells by TEM, as reported previously. Electron tomography revealed the presence of membrane-shaped structures representing PSD-95 clusters at the PSD and an ellipsoidal structure located in the non-synaptic cytoplasm. By TEM, the PSD-95 clusters appeared to be composed of a number of dense cores. In frozen hydrated sections, these dense cores were also found beneath the postsynaptic membrane. Taken together, our findings suggest that dense cores of PSD-95 aggregate to form the larger clusters present in the PSD and the non-synaptic cytoplasm. © The Author 2014. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

    Aalseth, Craig E.; Day, Anthony R.; Fuller, Erin S.

    Abstract A new ultra-low-background proportional counter (ULBPC) design was recently developed at Pacific Northwest National Laboratory (PNNL). This design, along with an ultra-low-background counting system (ULBCS) which provides passive and active shielding with radon exclusion, has been developed to complement a new shallow underground laboratory (~30 meters water-equivalent) constructed at PNNL. After these steps to mitigate dominant backgrounds (cosmic rays, external gamma-rays, radioactivity in materials), remaining background events do not exclusively arise from ionization of the proportional counter gas. Digital pulse-shape discrimination (PSD) is thus employed to further improve measurement sensitivity. In this work, a template shape is generated formore » each individual sample measurement of interest, a "self-calibrating" template. Differences in event topology can also cause differences in pulse shape. In this work, the temporal region analyzed for each event is refined to maximize background discrimination while avoiding unwanted sensitivity to event topology. This digital PSD method is applied to sample and background data, and initial measurement results from a biofuel methane sample are presented in the context of low-background measurements currently being developed.« less

  17. Poststroke depression: prevalence and determinants in Brazilian stroke patients.

    PubMed

    Carod-Artal, Francisco Javier; Ferreira Coral, Luciane; Trizotto, Daniele Stieven; Menezes Moreira, Clarissa

    2009-01-01

    Poststroke depression (PSD) is one of the most important long-term adverse psychosocial consequences in stroke survivors. Our objective was to assess the prevalence of PSD in Brazilian stroke patients and identify significant associated factors. A cross-sectional study of stroke patients consecutively admitted for rehabilitation was conducted. The patients were evaluated by means of the NIH Stroke Scale, Mini-Mental State Examination, Barthel Index, Lawton Scale, modified Rankin Scale, Hospital Anxiety and Depression Scale (HADS), Geriatric Depression Scale (GDS) and MOS-Short Form 36. Patients with a HADS-depression subscale score > or = 11 and/or GDS score > or = 8 were classified as depressed. Three hundred stroke survivors were assessed (mean age: 56.3 years; 51.7% males). Half (46.7%) of the stroke patients had an m-RS score < or = 2. The proportion of stroke patients who scored > or = 11 points on the HADS-depression and HADS-anxiety subscales were 19.2 and 23.7%, respectively. One third (29.7%) had a GDS mean score > or = 8. The GDS scores significantly correlated (p < 0.0001) with the HADS-depression (r = 0.51) and HADS-anxiety subscales (r = 0.54). The prevalence of mood disorders was significantly higher in females than in males (24.8 vs. 14.2%; x(2), p = 0.03). PSD was significantly associated (p < 0.0001) with work status (housewife), education level, lower social and cognitive functioning, dependence in the instrumental activities of daily living and presence of diabetes in the multivariable regression analysis (R adjusted = 0.32). PSD was highly prevalent in the chronic phase of stroke. Early detection and recognition of associated risk factors is important to treat and prevent PSD in a rehabilitation setting. 2009 S. Karger AG, Basel.

  18. Cdk5 regulates PSD-95 ubiquitination in neurons

    PubMed Central

    Bianchetta, Michael J.; Lam, TuKiet T.; Jones, Stephen N.; Morabito, Maria A.

    2011-01-01

    The kinase Cdk5 and its activator p35 have been implicated in drug addiction, neurodegenerative diseases such as Alzheimer’s, learning and memory, and synapse maturation and plasticity. However the molecular mechanisms by which Cdk5 regulates synaptic plasticity are still unclear. PSD-95 is a major postsynaptic scaffolding protein of glutamatergic synapses that regulates synaptic strength and plasticity. PSD-95 is ubiquitinated by the Ubiquitin E3 Ligase Mdm2, and rapid and transient PSD-95 ubiquitination has been implicated in NMDA receptor-induced AMPA receptor endocytosis. Here we demonstrate that genetic or pharmacological reduction of Cdk5 activity increases the interaction of Mdm2 with PSD-95 and enhances PSD-95 ubiquitination without affecting PSD-95 protein levels in vivo in mice, suggesting a non-proteolytic function of ubiquitinated PSD-95 at synapses. We show that PSD-95 ubiquitination correlates with increased interaction with β-adaptin, a subunit of the clathrin adaptor protein complex AP-2. This interaction is increased by genetic reduction of Cdk5 activity or NMDA receptor stimulation and is dependent on Mdm2. Together these results support a function for Cdk5 in regulating PSD-95 ubiqutination and its interaction with AP-2 and suggest a mechanism by which PSD-95 may regulate NMDA receptor-induced AMPA receptor endocytosis. PMID:21849563

  19. Neutron response characterization for an EJ299-33 plastic scintillation detector

    DOE PAGES

    Lawrence, Chris C.; Febbraro, Michael; Massey, Thomas N.; ...

    2014-05-10

    Organic scintillation detectors have shown promise as neutron detectors for characterizing special nuclear materials in various arms-control and homeland security applications. Recent advances have yielded a new plastic scintillator - EJ299-33 - with pulse-shape-discrimination (PSD) capability. Plastic scintillators would have a much expanded range of deployment relative to liquids and crystals. Here in this paper, we present a full characterization of pulse height response to fission-energy neutrons for an EJ299-33 detector with 7.62-by-7.62-cm cylindrical active volume, and compare with an EJ309 liquid scintillator in the same assembly. Scintillation light output relations, energy resolutions, and response matrices are presented for bothmore » detectors. A Continuous spectrum neutron source, obtained via the bombardment of 27Al with 7.44-MeV deuterons at the Edwards Accelerator Facility at Ohio University, was used for the measurement. A new procedure for evaluating and comparing PSD performance is presented which accounts for the effect of the light output relation on the ability to detect low energy neutrons. The EJ299-33 is shown to have considerable deficit in matrix condition, and in PSD figure of merit when compared to EJ309, especially when neutron energy is taken into account. Furthermore the EJ299 is likely to bring a modest PSD capability into a array of held applications that are not accessible to liquids or crystals.« less

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

    Lawrence, Chris C.; Febbraro, Michael; Massey, Thomas N.

    Organic scintillation detectors have shown promise as neutron detectors for characterizing special nuclear materials in various arms-control and homeland security applications. Recent advances have yielded a new plastic scintillator - EJ299-33 - with pulse-shape-discrimination (PSD) capability. Plastic scintillators would have a much expanded range of deployment relative to liquids and crystals. Here in this paper, we present a full characterization of pulse height response to fission-energy neutrons for an EJ299-33 detector with 7.62-by-7.62-cm cylindrical active volume, and compare with an EJ309 liquid scintillator in the same assembly. Scintillation light output relations, energy resolutions, and response matrices are presented for bothmore » detectors. A Continuous spectrum neutron source, obtained via the bombardment of 27Al with 7.44-MeV deuterons at the Edwards Accelerator Facility at Ohio University, was used for the measurement. A new procedure for evaluating and comparing PSD performance is presented which accounts for the effect of the light output relation on the ability to detect low energy neutrons. The EJ299-33 is shown to have considerable deficit in matrix condition, and in PSD figure of merit when compared to EJ309, especially when neutron energy is taken into account. Furthermore the EJ299 is likely to bring a modest PSD capability into a array of held applications that are not accessible to liquids or crystals.« less

  1. Establishing a direct connection between detrended fluctuation analysis and Fourier analysis

    NASA Astrophysics Data System (ADS)

    Kiyono, Ken

    2015-10-01

    To understand methodological features of the detrended fluctuation analysis (DFA) using a higher-order polynomial fitting, we establish the direct connection between DFA and Fourier analysis. Based on an exact calculation of the single-frequency response of the DFA, the following facts are shown analytically: (1) in the analysis of stochastic processes exhibiting a power-law scaling of the power spectral density (PSD), S (f ) ˜f-β , a higher-order detrending in the DFA has no adverse effect in the estimation of the DFA scaling exponent α , which satisfies the scaling relation α =(β +1 )/2 ; (2) the upper limit of the scaling exponents detectable by the DFA depends on the order of polynomial fit used in the DFA, and is bounded by m +1 , where m is the order of the polynomial fit; (3) the relation between the time scale in the DFA and the corresponding frequency in the PSD are distorted depending on both the order of the DFA and the frequency dependence of the PSD. We can improve the scale distortion by introducing the corrected time scale in the DFA corresponding to the inverse of the frequency scale in the PSD. In addition, our analytical approach makes it possible to characterize variants of the DFA using different types of detrending. As an application, properties of the detrending moving average algorithm are discussed.

  2. A Vehicle Active Safety Model: Vehicle Speed Control Based on Driver Vigilance Detection Using Wearable EEG and Sparse Representation.

    PubMed

    Zhang, Zutao; Luo, Dianyuan; Rasim, Yagubov; Li, Yanjun; Meng, Guanjun; Xu, Jian; Wang, Chunbai

    2016-02-19

    In this paper, we present a vehicle active safety model for vehicle speed control based on driver vigilance detection using low-cost, comfortable, wearable electroencephalographic (EEG) sensors and sparse representation. The proposed system consists of three main steps, namely wireless wearable EEG collection, driver vigilance detection, and vehicle speed control strategy. First of all, a homemade low-cost comfortable wearable brain-computer interface (BCI) system with eight channels is designed for collecting the driver's EEG signal. Second, wavelet de-noising and down-sample algorithms are utilized to enhance the quality of EEG data, and Fast Fourier Transformation (FFT) is adopted to extract the EEG power spectrum density (PSD). In this step, sparse representation classification combined with k-singular value decomposition (KSVD) is firstly introduced in PSD to estimate the driver's vigilance level. Finally, a novel safety strategy of vehicle speed control, which controls the electronic throttle opening and automatic braking after driver fatigue detection using the above method, is presented to avoid serious collisions and traffic accidents. The simulation and practical testing results demonstrate the feasibility of the vehicle active safety model.

  3. Performance of a neutron spectrometer based on a PIN diode.

    PubMed

    Agosteo, S; D'Angelo, G; Fazzi, A; Para, A Foglio; Pola, A; Ventura, L; Zotto, P

    2005-01-01

    The neutron spectrometer discussed in this work consists of a PIN diode coupled with a polyethylene converter. Neutrons are detected through the energy deposited by recoil-protons in silicon. The maximum detectable energy is -6 MeV and is imposed by the thickness of the fully depleted layer (300 microm for the present device). The minimum detectable energy which can be assessed with pulse-shape discrimination (PSD) is -0.9 MeV. PSD is performed with a crossover method and setting the diode in the 'reverse-injection' configuration (i.e. with the N+ layer adjacent to the converter). This configuration provides longer collection times for the electron-hole pairs generated by the recoil-protons. The limited interval of detectable energies restricts the application of this spectrometer to low-energy neutron fields, such as the ones which can be produced at facilities hosting low-energy ion accelerators. The capacity to reproduce continuous neutron spectra was investigated by optimising the electronic chain for pulse-shape discrimination. In particular, the spectrometer was irradiated with neutrons that were generated by striking a thick beryllium target with protons of several energies and the measured spectra were compared with data taken from the literature.

  4. A Vehicle Active Safety Model: Vehicle Speed Control Based on Driver Vigilance Detection Using Wearable EEG and Sparse Representation

    PubMed Central

    Zhang, Zutao; Luo, Dianyuan; Rasim, Yagubov; Li, Yanjun; Meng, Guanjun; Xu, Jian; Wang, Chunbai

    2016-01-01

    In this paper, we present a vehicle active safety model for vehicle speed control based on driver vigilance detection using low-cost, comfortable, wearable electroencephalographic (EEG) sensors and sparse representation. The proposed system consists of three main steps, namely wireless wearable EEG collection, driver vigilance detection, and vehicle speed control strategy. First of all, a homemade low-cost comfortable wearable brain-computer interface (BCI) system with eight channels is designed for collecting the driver’s EEG signal. Second, wavelet de-noising and down-sample algorithms are utilized to enhance the quality of EEG data, and Fast Fourier Transformation (FFT) is adopted to extract the EEG power spectrum density (PSD). In this step, sparse representation classification combined with k-singular value decomposition (KSVD) is firstly introduced in PSD to estimate the driver’s vigilance level . Finally, a novel safety strategy of vehicle speed control, which controls the electronic throttle opening and automatic braking after driver fatigue detection using the above method, is presented to avoid serious collisions and traffic accidents. The simulation and practical testing results demonstrate the feasibility of the vehicle active safety model. PMID:26907278

  5. Development of slew-rate-limited time-over-threshold (ToT) ASIC for a multi-channel silicon-based ion detector

    NASA Astrophysics Data System (ADS)

    Uenomachi, M.; Orita, T.; Shimazoe, K.; Takahashi, H.; Ikeda, H.; Tsujita, K.; Sekiba, D.

    2018-01-01

    High-resolution Elastic Recoil Detection Analysis (HERDA), which consists of a 90o sector magnetic spectrometer and a position-sensitive detector (PSD), is a method of quantitative hydrogen analysis. In order to increase sensitivity, a HERDA system using a multi-channel silicon-based ion detector has been developed. Here, as a parallel and fast readout circuit from a multi-channel silicon-based ion detector, a slew-rate-limited time-over-threshold (ToT) application-specific integrated circuit (ASIC) was designed, and a new slew-rate-limited ToT method is proposed. The designed ASIC has 48 channels and each channel consists of a preamplifier, a slew-rate-limited shaping amplifier, which makes ToT response linear, and a comparator. The measured equivalent noise charges (ENCs) of the preamplifier, the shaper, and the ToT on no detector capacitance were 253±21, 343±46, and 560±56 electrons RMS, respectively. The spectra from a 241Am source measured using a slew-rate-limited ToT ASIC are also reported.

  6. 40 CFR 124.19 - Appeal of RCRA, UIC, NPDES, and PSD Permits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Appeal of RCRA, UIC, NPDES, and PSD..., and PSD Permits. (a) Within 30 days after a RCRA, UIC, NPDES, or PSD final permit decision (or a... may also decide on its own initiative to review any condition of any RCRA, UIC, NPDES, or PSD permit...

  7. 40 CFR 124.19 - Appeal of RCRA, UIC, NPDES, and PSD Permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Appeal of RCRA, UIC, NPDES, and PSD..., and PSD Permits. (a) Within 30 days after a RCRA, UIC, NPDES, or PSD final permit decision (or a... may also decide on its own initiative to review any condition of any RCRA, UIC, NPDES, or PSD permit...

  8. 40 CFR 124.19 - Appeal of RCRA, UIC, NPDES, and PSD Permits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Appeal of RCRA, UIC, NPDES, and PSD..., and PSD Permits. (a) Within 30 days after a RCRA, UIC, NPDES, or PSD final permit decision (or a... may also decide on its own initiative to review any condition of any RCRA, UIC, NPDES, or PSD permit...

  9. Relationship between 5-HTTLPR polymorphism and post-stroke depression.

    PubMed

    Guo, W Y; Zhang, Z H; Mu, J L; Liu, D; Zhao, L; Yao, Z Y; Song, J G

    2016-02-19

    Post-stroke depression (PSD) is a mental illness characterized by subjective feelings of depression, cognitive dysfunction, and decreased interest. The serotoninergic system is involved in the pathogenesis of depressive disorders and is regulated by the serotonin transporter gene. The serotonin transporter-linked polymorphic region (5-HTTLPR) has been examined as a factor associated with depression and other mental disorders. This study was performed to explore the relationship between 5-HTTLPR and PSD in a Han Chinese population. In total, 199 patients with PSD and 202 unrelated non-PSD patients were recruited from psychiatric hospitals. Depression was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. Blood samples were collected from all patients for 5-HTTLPR genotyping. Genotype and allele frequencies were compared between the two groups. SS genotype frequency was significantly higher in the PSD group than in the non-PSD group. LL genotype frequency was significantly higher in the non-PSD group than in the PSD group (P < 0.01). This study describes a positive association between 5-HTTLPR and PSD in a Han Chinese population and provides genetic evidence to support the genetic susceptibility of PSD.

  10. Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95.

    PubMed

    Vallejo, Daniela; Codocedo, Juan F; Inestrosa, Nibaldo C

    2017-04-01

    The postsynaptic density (PSD) consists of a lattice-like array of interacting proteins that organizes and stabilizes synaptic receptors, ion channels, structural proteins, and signaling molecules required for normal synaptic transmission and synaptic function. The scaffolding and hub protein postsynaptic density protein-95 (PSD-95) is a major element of central chemical synapses and interacts with glutamate receptors, cell adhesion molecules, and cytoskeletal elements. In fact, PSD-95 can regulate basal synaptic stability as well as the activity-dependent structural plasticity of the PSD and, therefore, of the excitatory chemical synapse. Several studies have shown that PSD-95 is highly enriched at excitatory synapses and have identified multiple protein structural domains and protein-protein interactions that mediate PSD-95 function and trafficking to the postsynaptic region. PSD-95 is also a target of several signaling pathways that induce posttranslational modifications, including palmitoylation, phosphorylation, ubiquitination, nitrosylation, and neddylation; these modifications determine the synaptic stability and function of PSD-95 and thus regulate the fates of individual dendritic spines in the nervous system. In the present work, we review the posttranslational modifications that regulate the synaptic localization of PSD-95 and describe their functional consequences. We also explore the signaling pathways that induce such changes.

  11. The association of GPR85 with PSD-95-neuroligin complex and autism spectrum disorder: a molecular analysis.

    PubMed

    Fujita-Jimbo, Eriko; Tanabe, Yuko; Yu, Zhiling; Kojima, Karin; Mori, Masato; Li, Hong; Iwamoto, Sadahiko; Yamagata, Takanori; Momoi, Mariko Y; Momoi, Takashi

    2015-01-01

    Autism spectrum disorder (ASD) has a complex genetic etiology. Some symptoms and mutated genes, including neuroligin (NLGN), neurexin (NRXN), and SH3 and multiple ankyrin repeat domains protein (SHANK), are shared by schizophrenia and ASD. Little is known about the molecular pathogenesis of ASD. One of the possible molecular pathogenesis is an imbalance of excitatory and inhibitory receptors linked with the NLGN-PSD-95-SHANK complex via postsynaptic density protein/Drosophila disc large tumor suppressor/zonula occludens-1 protein (PDZ) binding. In the present study, we focused on GPR85 as a candidate gene for ASD because the C-terminal amino acid sequence of GPR85 [Thr-Cys-Val-Ile (YCVI)] is classified as a type II PDZ-binding motif, and GPR85 is a risk factor for schizophrenia. GPR85 is an orphan receptor that regulates neural and synaptic plasticity and modulates diverse behaviors, including learning and memory. While searching for molecules that associate with GPR85, we found that GPR85 was associated with postsynaptic density protein (PSD)-95 linked with NLGN in the brain. We examined the proteins that associate with the C-terminal sequence of GPR85 by pull-down assay and immunoblot analysis and searched for a mutation of the GPR85 gene in patients with ASD. We used immunostaining to examine the intracellular localization of mutated GPR85 and its influence on the morphology of cells and neurons. The C-terminal sequence of GPR85 interacted with PSD-95 at PDZ1, while NLGN interacted with PSD-95 at PDZ3. Two male patients with ASD from independent Japanese families possessed inherited missense mutations at conserved sites in GPR85: one had T1033C (M152T) and the other had G1239T (V221L). These mutations were located in a domain related to G protein interaction and signal transduction. In contrast to wild-type GPR85, mutated GPR85 was more preferentially accumulated, causing endoplasmic reticulum stress, and disturbed the dendrite formation of hippocampal neurons. GPR85 associated with the PSD-95 linked with NLGN, which is related to ASD. GPR85 carrying the mutations detected in ASD patients disturbed dendrite formation that could be the candidate for molecular pathogenesis of ASD through the associated NLGN-PSD-95 receptor complex.

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

    Pino, R; Therriault-Proulx, F; Yang, J

    Purpose: To perform dose profile and output factor measurements for the Exradin W1 plastic scintillation detector (PSD) for the Gamma Knife Perfexion (GKP) collimators in a Lucy phantom and to compare these values to an Exradin A16 ion chamber, EBT3 radiochromic film and treatment planning system (TPS) data. Methods: We used the Exradin W1 PSD which has a small volume, near-water equivalent sensitive element. It has also been shown to be energy independent. This new detector is manufactured and distributed by Standard Imaging, Inc. Measurements were performed for all three collimators (4 mm, 8 mm and 16 mm) for themore » GKP. The Lucy phantom with the PSD inserted was moved in small steps to acquire profiles in all three directions. EBT3 film was inserted in the Lucy phantom and exposed to a single shot for each collimator. Relative output factors were measured using the three detectors while profiles acquired with the PSD were compared to the ones measured with EBT3 radiochromic film. Results: Measured output factors relative to the largest collimator are as followsCollimator PS EBT3 A1616mm 1.000 1.000 1.0008mm 0.892 0.881 0.8834mm 0.795 0.793 0.727 The nominal (vendor) OFs for GKP are 1.000, 0.900, and 0.814, for collimators 16 mm, 8 mm and 4 mm, respectively. There is excellent agreement between all profiles measured with the PSD and EBT3 as well as with the TPS data provided by the vendor. Conclusion: Output factors measured with the W1 were consistent with the ones measured with EBT3 and A16 ion chamber. Measured profiles are in excellent agreement. The W1 detector seems well suited for beam QA for Gamma Knife due to its dosimetric characteristics. Sam Beddar would like to disclose a NIH/NCI SBIR Phase II grant (2R44CA153824-02A1) with Standard Imaging, Title: “Water-Equivalent Plastic Scintillation Detectors for Small Field Radiotherapy”.« less

  13. A metabonomic investigation on the biochemical perturbation in post-stroke patients with depressive disorder (PSD).

    PubMed

    Ding, Xinghua; Liu, Ruoxu; Li, Wenkai; Ni, Hengjia; Liu, Yong; Wu, Dandan; Yang, Shuguang; Liu, Jing; Xiao, Bo; Liu, Shaojun

    2016-04-01

    A metabonomics study based on GC/MS and multivariate statistical analysis was performed involving 28 post stroke depressed (PSD) patients, 27 post-stroke non-depressed (PSND) patients and 33 healthy subjects to investigate the biochemical perturbation in their plasma samples. The outcome of this study showed that there was distinctive metabolic profile for PSD patients. Seven sentinel metabolites showed marked perturbations in PSD patients' blood. The introduction of metabonomics approach may provide a novel metabonomic insight about PSD and the sentinel metabolites for classifying PSD.

  14. Methodological issues concerning the application of reliable laser particle sizing in soils

    NASA Astrophysics Data System (ADS)

    de Mascellis, R.; Impagliazzo, A.; Basile, A.; Minieri, L.; Orefice, N.; Terribile, F.

    2009-04-01

    During the past decade, the evolution of technologies has enabled laser diffraction (LD) to become a much widespread means of particle size distribution (PSD), replacing sedimentation and sieve analysis in many scientific fields mainly due to its advantages of versatility, fast measurement and high reproducibility. Despite such developments of the last decade, the soil scientist community has been quite reluctant to replace the good old sedimentation techniques (ST); possibly because of (i) the large complexity of the soil matrix inducing different types of artefacts (aggregates, deflocculating dynamics, etc.), (ii) the difficulties in relating LD results with results obtained through sedimentation techniques and (iii) the limited size range of most LD equipments. More recently LD granulometry is slowly gaining appreciation in soil science also because of some innovations including an enlarged size dynamic range (0,01-2000 m) and the ability to implement more powerful algorithms (e.g. Mie theory). Furthermore, LD PSD can be successfully used in the application of physically based pedo-transfer functions (i.e., Arya and Paris model) for investigations of soil hydraulic properties, due to the direct determination of PSD in terms of volume percentage rather than in terms of mass percentage, thus eliminating the need to adopt the rough approximation of a single value for soil particle density in the prediction process. Most of the recent LD work performed in soil science deals with the comparison with sedimentation techniques and show the general overestimation of the silt fraction following a general underestimation of the clay fraction; these well known results must be related with the different physical principles behind the two techniques. Despite these efforts, it is indeed surprising that little if any work is devoted to more basic methodological issues related to the high sensitivity of LD to the quantity and the quality of the soil samples. Our work aims to both analyse and to suggest technical solutions to address the following key methodological problems: (i) sample representativeness due to the very small amount of soil sample required by LD (e.g. 0,2 g) as compared to ST (e.g. 40 g for densimetry); (ii) PSD reading variability caused by the large number of instantaneous reading on a very small volume of the solution, (iii) the varying soil mineralogy that in turn produce varying refractive indexes affecting PSD results, (iv) the determination of the mass density of the soil samples to compare results with those obtained from ST. Our results, referring to many different soil types (Vertisols, Regosols, Andosols, Calcisols, Luvisols) show that the listed major technical problems can be successfully addressed by the following set of solutions: (i) adequate subsampling in both solid and liquid phases (including a setup of a dilution system); (ii) preliminary study of the PSD variability to reasonably increase the number of readings per each sample; (iii, iv) preliminary sensitivity analysis of both refractive indexes and mass density in accordance to the specific soil mineralogy.

  15. Assessment of peak skin dose in interventional cardiology: A comparison between Gafchromic film and dosimetric software em.dose.

    PubMed

    Greffier, J; Van Ngoc Ty, C; Bonniaud, G; Moliner, G; Ledermann, B; Schmutz, L; Cornillet, L; Cayla, G; Beregi, J P; Pereira, F

    2017-06-01

    To compare the use of a dose mapping software to Gafchromic film measurement for a simplified peak skin dose (PSD) estimation in interventional cardiology procedure. The study was conducted on a total of 40 cardiac procedures (20 complex coronary angioplasty of chronic total occlusion (CTO) and 20 coronary angiography and coronary angioplasty (CA-PTCA)) conducted between January 2014 to December 2015. PSD measurement (PSD Film ) was obtained by placing XR-RV3 Gafchromic under the patient's back for each procedure. PSD (PSD em.dose ) was computed with the software em.dose©. The calculation was performed on the dose metrics collected from the private dose report of each procedure. Two calculation methods (method A: fluoroscopic kerma equally spread on cine acquisition and B: fluoroscopic kerma is added to one air Kerma cine acquisition that contributes to the PSD) were used to calculate the fluoroscopic dose contribution as fluoroscopic data were not recorded in our interventional room. Statistical analyses were carried out to compare PSD Film and PSD em.dose . The PSD Film median (1st quartile; 3rd quartile) was 0.251(0.190;0.336)Gy for CA-PTCA and 1.453(0.767;2.011)Gy for CTO. For method-A, the PSD em.dose was 0.248(0.182;0.369)Gy for CA-PTCA and 1.601(0.892;2.178)Gy for CTO, and 0.267(0.223;0.446)Gy and 1.75 (0.912;2.584)Gy for method-B, respectively. For the two methods, the correlation between PSD Film and PSD em.dose was strong. For all cardiology procedures investigated, the mean deviation between PSD Film and PSD em.dose was 3.4±21.1% for method-A and 17.3%±23.9% for method-B. The dose mapping software is convenient to calculate peak skin dose in interventional cardiology. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  16. Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice

    PubMed Central

    2012-01-01

    Background Postsynaptic density (PSD)-95-like membrane-associated guanylate kinases (PSD-MAGUKs) are scaffold proteins in PSDs that cluster signaling molecules near NMDA receptors. PSD-MAGUKs share a common domain structure, including three PDZ (PDZ1/2/3) domains in their N-terminus. While multiple domains enable the PSD-MAGUKs to bind various ligands, the contribution of each PDZ domain to synaptic organization and function is not fully understood. Here, we focused on the PDZ1/2 domains of PSD-95 that bind NMDA-type receptors, and studied the specific roles of the ligand binding of these domains in the assembly of PSD proteins, synaptic properties of hippocampal neurons, and behavior, using ligand binding-deficient PSD-95 cDNA knockin (KI) mice. Results The KI mice showed decreased accumulation of mutant PSD-95, PSD-93 and AMPA receptor subunits in the PSD fraction of the hippocampus. In the hippocampal CA1 region of young KI mice, basal synaptic efficacy was reduced and long-term potentiation (LTP) was enhanced with intact long-term depression. In adult KI mice, there was no significant change in the magnitude of LTP in CA1, but robustly enhanced LTP was induced at the medial perforant path-dentate gyrus synapses, suggesting that PSD-95 has an age- and subregion-dependent role. In a battery of behavioral tests, KI mice showed markedly abnormal anxiety-like behavior, impaired spatial reference and working memory, and impaired remote memory and pattern separation in fear conditioning test. Conclusions These findings reveal that PSD-95 including its ligand binding of the PDZ1/2 domains controls the synaptic clustering of PSD-MAGUKs and AMPA receptors, which may have an essential role in regulating hippocampal synaptic transmission, plasticity, and hippocampus-dependent behavior. PMID:23268962

  17. Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice.

    PubMed

    Nagura, Hitoshi; Ishikawa, Yasuyuki; Kobayashi, Katsunori; Takao, Keizo; Tanaka, Tomo; Nishikawa, Kouki; Tamura, Hideki; Shiosaka, Sadao; Suzuki, Hidenori; Miyakawa, Tsuyoshi; Fujiyoshi, Yoshinori; Doi, Tomoko

    2012-12-26

    Postsynaptic density (PSD)-95-like membrane-associated guanylate kinases (PSD-MAGUKs) are scaffold proteins in PSDs that cluster signaling molecules near NMDA receptors. PSD-MAGUKs share a common domain structure, including three PDZ (PDZ1/2/3) domains in their N-terminus. While multiple domains enable the PSD-MAGUKs to bind various ligands, the contribution of each PDZ domain to synaptic organization and function is not fully understood. Here, we focused on the PDZ1/2 domains of PSD-95 that bind NMDA-type receptors, and studied the specific roles of the ligand binding of these domains in the assembly of PSD proteins, synaptic properties of hippocampal neurons, and behavior, using ligand binding-deficient PSD-95 cDNA knockin (KI) mice. The KI mice showed decreased accumulation of mutant PSD-95, PSD-93 and AMPA receptor subunits in the PSD fraction of the hippocampus. In the hippocampal CA1 region of young KI mice, basal synaptic efficacy was reduced and long-term potentiation (LTP) was enhanced with intact long-term depression. In adult KI mice, there was no significant change in the magnitude of LTP in CA1, but robustly enhanced LTP was induced at the medial perforant path-dentate gyrus synapses, suggesting that PSD-95 has an age- and subregion-dependent role. In a battery of behavioral tests, KI mice showed markedly abnormal anxiety-like behavior, impaired spatial reference and working memory, and impaired remote memory and pattern separation in fear conditioning test. These findings reveal that PSD-95 including its ligand binding of the PDZ1/2 domains controls the synaptic clustering of PSD-MAGUKs and AMPA receptors, which may have an essential role in regulating hippocampal synaptic transmission, plasticity, and hippocampus-dependent behavior.

  18. Effects of recruitment, growth, and exploitation on walleye population size structure in northern Wisconsin lakes

    USGS Publications Warehouse

    Hansen, Michael J.; Nate, Nancy A.

    2014-01-01

    We evaluated the dynamics of walleye Sander vitreus population size structure, as indexed by the proportional size distribution (PSD) of quality-length fish, in Escanaba Lake during 1967–2003 and in 204 other lakes in northern Wisconsin during 1990–2011. We estimated PSD from angler-caught walleyes in Escanaba Lake and from spring electrofishing in 204 other lakes, and then related PSD to annual estimates of recruitment to age-3, length at age 3, and annual angling exploitation rate. In Escanaba Lake during 1967–2003, annual estimates of PSD were highly dynamic, growth (positively) explained 35% of PSD variation, recruitment explained only 3% of PSD variation, and exploitation explained only 7% of PSD variation. In 204 other northern Wisconsin lakes during 1990–2011, PSD varied widely among lakes, recruitment (negatively) explained 29% of PSD variation, growth (positively) explained 21% of PSD variation, and exploitation explained only 4% of PSD variation. We conclude that population size structure was most strongly driven by recruitment and growth, rather than exploitation, in northern Wisconsin walleye populations. Studies of other species over wide spatial and temporal ranges of recruitment, growth, and mortality are needed to determine which dynamic rate most strongly influences population size structure of other species. Our findings indicate a need to be cautious about assuming exploitation is a strong driver of walleye population size structure.

  19. 40 CFR 52.1519 - Identification of plan-conditional approval.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Air Act (CAA) elements 110(a)(2)(A), (C) only as it relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (E)(ii), and (J) only as it relates to the PSD program. This conditional... relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (E)(ii), and (J) only as it...

  20. 40 CFR 52.1519 - Identification of plan-conditional approval.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Air Act (CAA) elements 110(a)(2)(A), (C) only as it relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (E)(ii), and (J) only as it relates to the PSD program. This conditional... relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (E)(ii), and (J) only as it...

  1. The Kepler Light Curves of AGN: A Detailed Analysis

    DOE PAGES

    Smith, Krista Lynne; Mushotzky, Richard F.; Boyd, Patricia T.; ...

    2018-04-25

    Here, we present a comprehensive analysis of 21 light curves of Type 1 active galactic nuclei (AGN) from the Kepler spacecraft. First, we describe the necessity and development of a customized pipeline for treating Kepler data of stochastically variable sources like AGN. We then present the light curves, power spectral density functions (PSDs), and flux histograms. The light curves display an astonishing variety of behaviors, many of which would not be detected in ground-based studies, including switching between distinct flux levels. Six objects exhibit PSD flattening at characteristic timescales that roughly correlate with black hole mass. These timescales are consistentmore » with orbital timescales or free-fall accretion timescales. We check for correlations of variability and high-frequency PSD slope with accretion rate, black hole mass, redshift, and luminosity. We find that bolometric luminosity is anticorrelated with both variability and steepness of the PSD slope. We do not find evidence of the linear rms–flux relationships or lognormal flux distributions found in X-ray AGN light curves, indicating that reprocessing is not a significant contributor to optical variability at the 0.1%–10% level.« less

  2. The Kepler Light Curves of AGN: A Detailed Analysis

    NASA Astrophysics Data System (ADS)

    Smith, Krista Lynne; Mushotzky, Richard F.; Boyd, Patricia T.; Malkan, Matt; Howell, Steve B.; Gelino, Dawn M.

    2018-04-01

    We present a comprehensive analysis of 21 light curves of Type 1 active galactic nuclei (AGN) from the Kepler spacecraft. First, we describe the necessity and development of a customized pipeline for treating Kepler data of stochastically variable sources like AGN. We then present the light curves, power spectral density functions (PSDs), and flux histograms. The light curves display an astonishing variety of behaviors, many of which would not be detected in ground-based studies, including switching between distinct flux levels. Six objects exhibit PSD flattening at characteristic timescales that roughly correlate with black hole mass. These timescales are consistent with orbital timescales or free-fall accretion timescales. We check for correlations of variability and high-frequency PSD slope with accretion rate, black hole mass, redshift, and luminosity. We find that bolometric luminosity is anticorrelated with both variability and steepness of the PSD slope. We do not find evidence of the linear rms–flux relationships or lognormal flux distributions found in X-ray AGN light curves, indicating that reprocessing is not a significant contributor to optical variability at the 0.1%–10% level.

  3. Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice

    PubMed Central

    Morimura, Naoko; Yasuda, Hiroki; Yamaguchi, Kazuhiko; Katayama, Kei-ichi; Hatayama, Minoru; Tomioka, Naoko H.; Odagawa, Maya; Kamiya, Akiko; Iwayama, Yoshimi; Maekawa, Motoko; Nakamura, Kazuhiko; Matsuzaki, Hideo; Tsujii, Masatsugu; Yamada, Kazuyuki; Yoshikawa, Takeo; Aruga, Jun

    2017-01-01

    Lrfn2/SALM1 is a PSD-95-interacting synapse adhesion molecule, and human LRFN2 is associated with learning disabilities. However its role in higher brain function and underlying mechanisms remain unknown. Here, we show that Lrfn2 knockout mice exhibit autism-like behavioural abnormalities, including social withdrawal, decreased vocal communications, increased stereotyped activities and prepulse inhibition deficits, together with enhanced learning and memory. In the hippocampus, the levels of synaptic PSD-95 and GluA1 are decreased. The synapses are structurally and functionally immature with spindle shaped spines, smaller postsynaptic densities, reduced AMPA/NMDA ratio, and enhanced LTP. In vitro experiments reveal that synaptic surface expression of AMPAR depends on the direct interaction between Lrfn2 and PSD-95. Furthermore, we detect functionally defective LRFN2 missense mutations in autism and schizophrenia patients. Together, these findings indicate that Lrfn2/LRFN2 serve as core components of excitatory synapse maturation and maintenance, and their dysfunction causes immature/silent synapses with pathophysiological state. PMID:28604739

  4. The Kepler Light Curves of AGN: A Detailed Analysis

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

    Smith, Krista Lynne; Mushotzky, Richard F.; Boyd, Patricia T.

    Here, we present a comprehensive analysis of 21 light curves of Type 1 active galactic nuclei (AGN) from the Kepler spacecraft. First, we describe the necessity and development of a customized pipeline for treating Kepler data of stochastically variable sources like AGN. We then present the light curves, power spectral density functions (PSDs), and flux histograms. The light curves display an astonishing variety of behaviors, many of which would not be detected in ground-based studies, including switching between distinct flux levels. Six objects exhibit PSD flattening at characteristic timescales that roughly correlate with black hole mass. These timescales are consistentmore » with orbital timescales or free-fall accretion timescales. We check for correlations of variability and high-frequency PSD slope with accretion rate, black hole mass, redshift, and luminosity. We find that bolometric luminosity is anticorrelated with both variability and steepness of the PSD slope. We do not find evidence of the linear rms–flux relationships or lognormal flux distributions found in X-ray AGN light curves, indicating that reprocessing is not a significant contributor to optical variability at the 0.1%–10% level.« less

  5. Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs.

    PubMed

    Zhu, Jinwei; Zhou, Qingqing; Shang, Yuan; Li, Hao; Peng, Mengjuan; Ke, Xiao; Weng, Zhuangfeng; Zhang, Rongguang; Huang, Xuhui; Li, Shawn S C; Feng, Guoping; Lu, Youming; Zhang, Mingjie

    2017-12-26

    The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities. Guided by the structural data, we developed potent non-phosphorylated GK inhibitory peptides capable of blocking the PSD-95/SAPAP interaction and interfering with PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are genetically encodable for investigating the functions of the PSD-95/SAPAP interaction in vivo. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2.

    PubMed

    Zheng, Sika; Gray, Erin E; Chawla, Geetanjali; Porse, Bo Torben; O'Dell, Thomas J; Black, Douglas L

    2012-01-15

    Postsynaptic density protein 95 (PSD-95) is essential for synaptic maturation and plasticity. Although its synaptic regulation has been widely studied, the control of PSD-95 cellular expression is not understood. We found that Psd-95 was controlled post-transcriptionally during neural development. Psd-95 was transcribed early in mouse embryonic brain, but most of its product transcripts were degraded. The polypyrimidine tract binding proteins PTBP1 and PTBP2 repressed Psd-95 (also known as Dlg4) exon 18 splicing, leading to premature translation termination and nonsense-mediated mRNA decay. The loss of first PTBP1 and then of PTBP2 during embryonic development allowed splicing of exon 18 and expression of PSD-95 late in neuronal maturation. Re-expression of PTBP1 or PTBP2 in differentiated neurons inhibited PSD-95 expression and impaired the development of glutamatergic synapses. Thus, expression of PSD-95 during early neural development is controlled at the RNA level by two PTB proteins whose sequential downregulation is necessary for synapse maturation.

  7. Intercomparison of Large-Eddy Simulations of Arctic Mixed-Phase Clouds: Importance of Ice Size Distribution Assumptions

    NASA Technical Reports Server (NTRS)

    Ovchinnikov, Mikhail; Ackerman, Andrew S.; Avramov, Alexander; Cheng, Anning; Fan, Jiwen; Fridlind, Ann M.; Ghan, Steven; Harrington, Jerry; Hoose, Corinna; Korolev, Alexei; hide

    2014-01-01

    Large-eddy simulations of mixed-phase Arctic clouds by 11 different models are analyzed with the goal of improving understanding and model representation of processes controlling the evolution of these clouds. In a case based on observations from the Indirect and Semi-Direct Aerosol Campaign (ISDAC), it is found that ice number concentration, Ni, exerts significant influence on the cloud structure. Increasing Ni leads to a substantial reduction in liquid water path (LWP), in agreement with earlier studies. In contrast to previous intercomparison studies, all models here use the same ice particle properties (i.e., mass-size, mass-fall speed, and mass-capacitance relationships) and a common radiation parameterization. The constrained setup exposes the importance of ice particle size distributions (PSDs) in influencing cloud evolution. A clear separation in LWP and IWP predicted by models with bin and bulk microphysical treatments is documented and attributed primarily to the assumed shape of ice PSD used in bulk schemes. Compared to the bin schemes that explicitly predict the PSD, schemes assuming exponential ice PSD underestimate ice growth by vapor deposition and overestimate mass-weighted fall speed leading to an underprediction of IWP by a factor of two in the considered case. Sensitivity tests indicate LWP and IWP are much closer to the bin model simulations when a modified shape factor which is similar to that predicted by bin model simulation is used in bulk scheme. These results demonstrate the importance of representation of ice PSD in determining the partitioning of liquid and ice and the longevity of mixed-phase clouds.

  8. Postsynaptic degeneration as revealed by PSD-95 reduction occurs after advanced Aβ and tau pathology in transgenic mouse models of Alzheimer's disease.

    PubMed

    Shao, Charles Y; Mirra, Suzanne S; Sait, Hameetha B R; Sacktor, Todd C; Sigurdsson, Einar M

    2011-09-01

    Impairment of synaptic plasticity underlies memory dysfunction in Alzheimer's disease (AD). Molecules involved in this plasticity such as PSD-95, a major postsynaptic scaffold protein at excitatory synapses, may play an important role in AD pathogenesis. We examined the distribution of PSD-95 in transgenic mice of amyloidopathy (5XFAD) and tauopathy (JNPL3) as well as in AD brains using double-labeling immunofluorescence and confocal microscopy. In wild type control mice, PSD-95 primarily labeled neuropil with distinct distribution in hippocampal apical dendrites. In 3-month-old 5XFAD mice, PSD-95 distribution was similar to that of wild type mice despite significant Aβ deposition. However, in 6-month-old 5XFAD mice, PSD-95 immunoreactivity in apical dendrites markedly decreased and prominent immunoreactivity was noted in neuronal soma in CA1 neurons. Similarly, PSD-95 immunoreactivity disappeared from apical dendrites and accumulated in neuronal soma in 14-month-old, but not in 3-month-old, JNPL3 mice. In AD brains, PSD-95 accumulated in Hirano bodies in hippocampal neurons. Our findings support the notion that either Aβ or tau can induce reduction of PSD-95 in excitatory synapses in hippocampus. Furthermore, this PSD-95 reduction is not an early event but occurs as the pathologies advance. Thus, the time-dependent PSD-95 reduction from synapses and accumulation in neuronal soma in transgenic mice and Hirano bodies in AD may mark postsynaptic degeneration that underlies long-term functional deficits.

  9. Interaction partners of PSD-93 studied by X-ray crystallography and fluorescence polarization spectroscopy.

    PubMed

    Fiorentini, Monica; Bach, Anders; Strømgaard, Kristian; Kastrup, Jette S; Gajhede, Michael

    2013-04-01

    PSD-93 (chapsyn-110, DLG2) is a member of the family of membrane-associated guanylate kinase (MAGUK) proteins. The MAGUK proteins are involved in receptor localization and signalling pathways. The best characterized MAGUK protein, PSD-95, is known to be involved in NMDA receptor signalling via its PDZ domains. The PDZ domains of PSD-95 and PSD-93 are structurally very similar, but relatively little is known about the function of PSD-93. PSD-93 has been suggested to interact with GluD2 from the family of ionotropic glutamate receptors. Here, the interactions of four residues (GTSI) representing the extreme C-terminus of GluD2 with PSD-93 PDZ1 have been investigated in the crystalline phase. Two different binding modes of these residues were observed, suggesting that the peptide is not tightly bound to PSD-93 PDZ1. In accordance, the two N-terminal PSD-93 PDZ domains show no appreciable binding affinity for a GluD2-derived C-terminal octapeptide, whereas micromolar affinity was observed for a GluN2B-derived C-terminal octapeptide. This indicates that if present, the interactions between GluD2 and PSD-93 involve more than the extreme terminus of the receptor. In contrast, the tumour-suppressor protein SCRIB PDZ3 shows low micromolar affinity towards the GluD2-derived octapeptide, which is in agreement with previous findings using high-throughput assays.

  10. 40 CFR 52.530 - Significant deterioration of air quality.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Air Resource Management that establishes prevention of significant deterioration (PSD) applicability...-emitting sources and issue GHG PSD permits. FDEP's December 19, 2013 SIP revision also includes a GHG PSD Permit Transition Plan which governs the transition from EPA administering GHG PSD permitting...

  11. Analysis on frequency response of trans-impedance amplifier (TIA) for signal-to-noise ratio (SNR) enhancement in optical signal detection system using lock-in amplifier (LIA)

    NASA Astrophysics Data System (ADS)

    Kim, Ji-Hoon; Jeon, Su-Jin; Ji, Myung-Gi; Park, Jun-Hee; Choi, Young-Wan

    2017-02-01

    Lock-in amplifier (LIA) has been widely used in optical signal detection systems because it can measure small signal under high noise level. Generally, The LIA used in optical signal detection system is composed of transimpedance amplifier (TIA), phase sensitive detector (PSD) and low pass filter (LPF). But commercial LIA using LPF is affected by flicker noise. To avoid flicker noise, there is 2ω detection LIA using BPF. To improve the dynamic reserve (DR) of the 2ω LIA, the signal to noise ratio (SNR) of the TIA should be improved. According to the analysis of frequency response of the TIA, the noise gain can be minimized by proper choices of input capacitor (Ci) and feed-back network in the TIA in a specific frequency range. In this work, we have studied how the SNR of the TIA can be improved by a proper choice of frequency range. We have analyzed the way to control this frequency range through the change of passive component in the TIA. The result shows that the variance of the passive component in the TIA can change the specific frequency range where the noise gain is minimized in the uniform gain region of the TIA.

  12. Development of Software to Model AXAF-I Image Quality

    NASA Technical Reports Server (NTRS)

    Geary, Joseph; Hawkins, Lamar; Ahmad, Anees; Gong, Qian

    1997-01-01

    This report describes work conducted on Delivery Order 181 between October 1996 through June 1997. During this period software was written to: compute axial PSD's from RDOS AXAF-I mirror surface maps; plot axial surface errors and compute PSD's from HDOS "Big 8" axial scans; plot PSD's from FITS format PSD files; plot band-limited RMS vs axial and azimuthal position for multiple PSD files; combine and organize PSD's from multiple mirror surface measurements formatted as input to GRAZTRACE; modify GRAZTRACE to read FITS formatted PSD files; evaluate AXAF-I test results; improve and expand the capabilities of the GT x-ray mirror analysis package. During this period work began on a more user-friendly manual for the GT program, and improvements were made to the on-line help manual.

  13. Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome

    PubMed Central

    Ifrim, Marius F.; Williams, Kathryn R.

    2015-01-01

    Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein (FMRP), an RNA binding protein that regulates translation of numerous target mRNAs, some of which are dendritically localized. Our previous biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR-125a in regulating the translation of PSD-95 mRNA. However, the local translation of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR-125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95 fusion protein was directly visualized in dendrites and spines using single-molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of the PSD-95 3′UTR. The basal translation rates of Venus-PSD-95 mRNA was increased in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which correlated with a transient elevation of endogenous PSD-95 within dendrites. Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a, previously shown to bind PSD-95 3′UTR, was mutated. This study provides direct support for the hypothesis that local translation within dendrites and spines is dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a critical regulator of synaptic structure and function, may affect the spatiotemporal control of PSD-95 levels and affect dendritic spine development and synaptic plasticity in FXS. PMID:25948262

  14. Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome.

    PubMed

    Ifrim, Marius F; Williams, Kathryn R; Bassell, Gary J

    2015-05-06

    Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein (FMRP), an RNA binding protein that regulates translation of numerous target mRNAs, some of which are dendritically localized. Our previous biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR-125a in regulating the translation of PSD-95 mRNA. However, the local translation of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR-125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95 fusion protein was directly visualized in dendrites and spines using single-molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of the PSD-95 3'UTR. The basal translation rates of Venus-PSD-95 mRNA was increased in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which correlated with a transient elevation of endogenous PSD-95 within dendrites. Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a, previously shown to bind PSD-95 3'UTR, was mutated. This study provides direct support for the hypothesis that local translation within dendrites and spines is dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a critical regulator of synaptic structure and function, may affect the spatiotemporal control of PSD-95 levels and affect dendritic spine development and synaptic plasticity in FXS. Copyright © 2015 the authors 0270-6474/15/357116-15$15.00/0.

  15. SU-E-T-167: Characterization of In-House Plastic Scintillator Detectors Array for Radiation Therapy

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

    Zhu, T; Liu, H; Dimofte, A

    Purpose: To characterize basic performance of plastic scintillator detectors (PSD) array designed for dosimetry of radiation therapy. Methods: An in-house PSD array has been developed by placing single point PSD into customized 2D holder. Each point PSD is a plastic scintillating fiber-based detector designed for highly accurate measurement of small radiotherapy fields used in patient plan verification and machine commissioning and QA procedures. A parallel fiber without PSD is used for Cerenkov separation by subtracting from PSD readings. Cerenkov separation was confirmed by optical spectroscopy. Alternative Cerenkov separation approaches are also investigated. The optical signal was converted to electronic signalmore » with a photodiode and then subsequently amplified. We measured its dosimetry performance, including percentage depth dose and output factor, and compared with reference ion chamber measurements. The PSD array is then placed along the radiation beam for multiple point dose measurement, representing subsets of PDD measurements, or perpendicular to the beam for profile measurements. Results: The dosimetry results of PSD point measurements agree well with reference ion chamber measurements. For percentage depth dose, the maximal differences between PSD and ion chamber results are 3.5% and 2.7% for 6MV and 15MV beams, respectively. For the output factors, PSD measurements are within 3% from ion chamber results. PDD and profile measurement with PSD array are also performed. Conclusions: The current design of multichannel PSD array is feasible for the dosimetry measurement in radiation therapy. Dose distribution along or perpendicular to the beam path could be measured. It might as well be used as range verification in proton therapy.A PS hollow fiber detector will be investigated to eliminate the Cerenkov radiation effect so that all 32 channels can be used.« less

  16. Phase II Upgrade of the GERDA Experiment for the Search of Neutrinoless Double Beta Decay

    NASA Astrophysics Data System (ADS)

    Majorovits, B.

    Observation of neutrinoless double beta decay could answer the question regarding the Majorana or Dirac nature of neutrinos. The GERDA experiment utilizes HPGe detectors enriched with the isotope 76Ge to search for this process. Recently the GERDA collaboration has unblinded data of Phase I of the experiment. In order to further improve the sensitivity of the experiment, additionally to the coaxial detectors used, 30 BEGe detectors made from germanium enriched in 76Ge will be deployed in GERDA Phase II. BEGe detectors have superior PSD capability, thus the background can be further reduced. The liquid argon surrounding the detector array will be instrumented in order to reject background by detecting scintillation light induced in the liquid argon by radiation. After a short introduction the hardware preparations for GERDA Phase II as well as the processing and characterization of the 30 BEGe detectors are discussed.

  17. Detergent-dependent separation of postsynaptic density, membrane rafts and other subsynaptic structures from the synaptic plasma membrane of rat forebrain.

    PubMed

    Zhao, LiYing; Sakagami, Hiroyuki; Suzuki, Tatsuo

    2014-10-01

    We systematically investigated the purification process of post-synaptic density (PSD) and post-synaptic membrane rafts (PSRs) from the rat forebrain synaptic plasma membranes by examining the components and the structures of the materials obtained after the treatment of synaptic plasma membranes with TX-100, n-octyl β-d-glucoside (OG) or 3-([3-cholamidopropyl]dimethylammonio)-2-hydroxy-1-propanesulfonate (CHAPSO). These three detergents exhibited distinct separation profiles for the synaptic subdomains. Type I and type II PSD proteins displayed mutually exclusive distribution. After TX-100 treatment, type I PSD was recovered in two fractions: a pellet and an insoluble fraction 8, which contained partially broken PSD-PSR complexes. Conventional PSD was suggested to be a mixture of these two PSD pools and did not contain type II PSD. An association of type I PSD with PSRs was identified in the TX-100 treatment, and those with type II PSD in the OG and CHAPSO treatments. An association of GABA receptors with gephyrin was easily dissociated. OG at a high concentration solubilized the type I PSD proteins. CHAPSO treatment resulted in a variety of distinct fractions, which contained certain novel structures. Two different pools of GluA, either PSD or possibly raft-associated, were identified in the OG and CHAPSO treatments. These results are useful in advancing our understanding of the structural organization of synapses at the molecular level. We systematically investigated the purification process of post-synaptic density (PSD) and synaptic membrane rafts by examining the structures obtained after treatment of the SPMs with TX-100, n-octyl β-d-glucoside or CHAPSO. Differential distribution of type I and type II PSD, synaptic membrane rafts, and other novel subdomains in the SPM give clues to understand the structural organization of synapses at the molecular level. © 2014 International Society for Neurochemistry.

  18. Power Spectral Density Specification and Analysis of Large Optical Surfaces

    NASA Technical Reports Server (NTRS)

    Sidick, Erkin

    2009-01-01

    The 2-dimensional Power Spectral Density (PSD) can be used to characterize the mid- and the high-spatial frequency components of the surface height errors of an optical surface. We found it necessary to have a complete, easy-to-use approach for specifying and evaluating the PSD characteristics of large optical surfaces, an approach that allows one to specify the surface quality of a large optical surface based on simulated results using a PSD function and to evaluate the measured surface profile data of the same optic in comparison with those predicted by the simulations during the specification-derivation process. This paper provides a complete mathematical description of PSD error, and proposes a new approach in which a 2-dimentional (2D) PSD is converted into a 1-dimentional (1D) one by azimuthally averaging the 2D-PSD. The 1D-PSD calculated this way has the same unit and the same profile as the original PSD function, thus allows one to compare the two with each other directly.

  19. PSD Camera Based Position and Posture Control of Redundant Robot Considering Contact Motion

    NASA Astrophysics Data System (ADS)

    Oda, Naoki; Kotani, Kentaro

    The paper describes a position and posture controller design based on the absolute position by external PSD vision sensor for redundant robot manipulator. The redundancy enables a potential capability to avoid obstacle while continuing given end-effector jobs under contact with middle link of manipulator. Under contact motion, the deformation due to joint torsion obtained by comparing internal and external position sensor, is actively suppressed by internal/external position hybrid controller. The selection matrix of hybrid loop is given by the function of the deformation. And the detected deformation is also utilized in the compliant motion controller for passive obstacle avoidance. The validity of the proposed method is verified by several experimental results of 3link planar redundant manipulator.

  20. 76 FR 31241 - Prevention of Significant Deterioration (PSD) Program; Massachusetts; Announcing Delegation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-31

    ... Deterioration (PSD) Program; Massachusetts; Announcing Delegation Agreement Between EPA and Massachusetts... authority to implement and enforce the Federal Prevention of Significant Deterioration (PSD) program to the MassDEP. Therefore, effective that date, MassDEP is the implementing authority for the PSD program in...

  1. 75 FR 59081 - Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ... Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations AGENCY: Environmental Protection... the prevention of significant deterioration (PSD) construction permit program under the Federal Clean... potentially subject to the PSD construction permit program. On July 16, 2010, Michigan submitted revisions...

  2. Identification of PSD-95 Depalmitoylating Enzymes.

    PubMed

    Yokoi, Norihiko; Fukata, Yuko; Sekiya, Atsushi; Murakami, Tatsuro; Kobayashi, Kenta; Fukata, Masaki

    2016-06-15

    Postsynaptic density (PSD)-95, the most abundant postsynaptic scaffolding protein, plays a pivotal role in synapse development and function. Continuous palmitoylation cycles on PSD-95 are essential for its synaptic clustering and regulation of AMPA receptor function. However, molecular mechanisms for palmitate cycling on PSD-95 remain incompletely understood, as PSD-95 depalmitoylating enzymes remain unknown. Here, we isolated 38 mouse or rat serine hydrolases and found that a subset specifically depalmitoylated PSD-95 in heterologous cells. These enzymes showed distinct substrate specificity. α/β-Hydrolase domain-containing protein 17 members (ABHD17A, 17B, and 17C), showing the strongest depalmitoylating activity to PSD-95, showed different localization from other candidates in rat hippocampal neurons, and were distributed to recycling endosomes, the dendritic plasma membrane, and the synaptic fraction. Expression of ABHD17 in neurons selectively reduced PSD-95 palmitoylation and synaptic clustering of PSD-95 and AMPA receptors. Furthermore, taking advantage of the acyl-PEGyl exchange gel shift (APEGS) method, we quantitatively monitored the palmitoylation stoichiometry and the depalmitoylation kinetics of representative synaptic proteins, PSD-95, GluA1, GluN2A, mGluR5, Gαq, and HRas. Unexpectedly, palmitate on all of them did not turn over in neurons. Uniquely, most of the PSD-95 population underwent rapid palmitoylation cycles, and palmitate cycling on PSD-95 decelerated accompanied by its increased stoichiometry as synapses developed, probably contributing to postsynaptic receptor consolidation. Finally, inhibition of ABHD17 expression dramatically delayed the kinetics of PSD-95 depalmitoylation. This study suggests that local palmitoylation machinery composed of synaptic DHHC palmitoylating enzymes and ABHD17 finely controls the amount of synaptic PSD-95 and synaptic function. Protein palmitoylation, the most common lipid modification, dynamically regulates neuronal protein localization and function. Its unique reversibility is conferred by DHHC-type palmitoyl acyl transferases (palmitoylating enzymes) and still controversial palmitoyl-protein thioesterases (depalmitoylating enzymes). Here, we identified the membrane-anchored serine hydrolases, ABHD17A, 17B, and 17C, as the physiological PSD-95 depalmitoylating enzymes that regulate PSD-95 palmitoylation cycles in neurons. This study describes the first direct evidence for the neuronal depalmitoylating enzyme and provides a new aspect of the dynamic regulatory mechanisms of synaptic development and synaptic plasticity. In addition, our established APEGS assay, which provides unbiased and quantitative information about the palmitoylation state and dynamics, revealed the distinct regulatory mechanisms for synaptic palmitoylation. Copyright © 2016 Yokoi, Fukata et al.

  3. Identification of PSD-95 Depalmitoylating Enzymes

    PubMed Central

    Yokoi, Norihiko; Sekiya, Atsushi; Murakami, Tatsuro; Kobayashi, Kenta

    2016-01-01

    Postsynaptic density (PSD)-95, the most abundant postsynaptic scaffolding protein, plays a pivotal role in synapse development and function. Continuous palmitoylation cycles on PSD-95 are essential for its synaptic clustering and regulation of AMPA receptor function. However, molecular mechanisms for palmitate cycling on PSD-95 remain incompletely understood, as PSD-95 depalmitoylating enzymes remain unknown. Here, we isolated 38 mouse or rat serine hydrolases and found that a subset specifically depalmitoylated PSD-95 in heterologous cells. These enzymes showed distinct substrate specificity. α/β-Hydrolase domain-containing protein 17 members (ABHD17A, 17B, and 17C), showing the strongest depalmitoylating activity to PSD-95, showed different localization from other candidates in rat hippocampal neurons, and were distributed to recycling endosomes, the dendritic plasma membrane, and the synaptic fraction. Expression of ABHD17 in neurons selectively reduced PSD-95 palmitoylation and synaptic clustering of PSD-95 and AMPA receptors. Furthermore, taking advantage of the acyl-PEGyl exchange gel shift (APEGS) method, we quantitatively monitored the palmitoylation stoichiometry and the depalmitoylation kinetics of representative synaptic proteins, PSD-95, GluA1, GluN2A, mGluR5, Gαq, and HRas. Unexpectedly, palmitate on all of them did not turn over in neurons. Uniquely, most of the PSD-95 population underwent rapid palmitoylation cycles, and palmitate cycling on PSD-95 decelerated accompanied by its increased stoichiometry as synapses developed, probably contributing to postsynaptic receptor consolidation. Finally, inhibition of ABHD17 expression dramatically delayed the kinetics of PSD-95 depalmitoylation. This study suggests that local palmitoylation machinery composed of synaptic DHHC palmitoylating enzymes and ABHD17 finely controls the amount of synaptic PSD-95 and synaptic function. SIGNIFICANCE STATEMENT Protein palmitoylation, the most common lipid modification, dynamically regulates neuronal protein localization and function. Its unique reversibility is conferred by DHHC-type palmitoyl acyl transferases (palmitoylating enzymes) and still controversial palmitoyl-protein thioesterases (depalmitoylating enzymes). Here, we identified the membrane-anchored serine hydrolases, ABHD17A, 17B, and 17C, as the physiological PSD-95 depalmitoylating enzymes that regulate PSD-95 palmitoylation cycles in neurons. This study describes the first direct evidence for the neuronal depalmitoylating enzyme and provides a new aspect of the dynamic regulatory mechanisms of synaptic development and synaptic plasticity. In addition, our established APEGS assay, which provides unbiased and quantitative information about the palmitoylation state and dynamics, revealed the distinct regulatory mechanisms for synaptic palmitoylation. PMID:27307232

  4. The relationship between PSD-95 clustering and spine stability in vivo.

    PubMed

    Cane, Michele; Maco, Bohumil; Knott, Graham; Holtmaat, Anthony

    2014-02-05

    The appearance and disappearance of dendritic spines, accompanied by synapse formation and elimination may underlie the experience-dependent reorganization of cortical circuits. The exact temporal relationship between spine and synapse formation in vivo remains unclear, as does the extent to which synapse formation enhances the stability of newly formed spines and whether transient spines produce synapses. We used in utero electroporation of DsRedExpress- and eGFP-tagged postsynaptic density protein 95 (PSD-95) to investigate the relationship between spine and PSD stability in mouse neocortical L2/3 pyramidal cells in vivo. Similar to previous studies, spines and synapses appeared and disappeared, even in naive animals. Cytosolic spine volumes and PSD-95-eGFP levels in spines covaried over time, suggesting that the strength of many individual synapses continuously changes in the adult neocortex. The minority of newly formed spines acquired PSD-95-eGFP puncta. Spines that failed to acquire a PSD rarely survived for more than a day. Although PSD-95-eGFP accumulation was associated with increased spine lifetimes, most new spines with a PSD did not convert into persistent spines. This indicates that transient spines may serve to produce short-lived synaptic contacts. Persistent spines that were destined to disappear showed, on average, reduced PSD-95-eGFP levels well before the actual pruning event. Altogether, our data indicate that the PSD size relates to spine stability in vivo.

  5. TrkB and protein kinase Mζ regulate synaptic localization of PSD-95 in developing cortex.

    PubMed

    Yoshii, Akira; Murata, Yasunobu; Kim, Jihye; Zhang, Chao; Shokat, Kevan M; Constantine-Paton, Martha

    2011-08-17

    Postsynaptic density 95 (PSD-95), the major scaffold at excitatory synapses, is critical for synapse maturation and learning. In rodents, eye opening, the onset of pattern vision, triggers a rapid movement of PSD-95 from visual neuron somata to synapses. We showed previously that the PI3 kinase-Akt pathway downstream of BDNF/TrkB signaling stimulates synaptic delivery of PSD-95 via vesicular transport. However, vesicular transport requires PSD-95 palmitoylation to attach it to a lipid membrane. Also, PSD-95 insertion at synapses is known to require this lipid modification. Here, we show that BDNF/TrkB signaling is also necessary for PSD-95 palmitoylation and its transport to synapses in mouse visual cortical layer 2/3 neurons. However, palmitoylation of PSD-95 requires the activation of another pathway downstream of BDNF/TrkB, namely, signaling through phospholipase Cγ and the brain-specific PKC variant protein kinase M ζ (PKMζ). We find that PKMζ selectively regulates phosphorylation of the palmitoylation enzyme ZDHHC8. Inhibition of PKMζ results in a reduction of synaptic PSD-95 accumulation in vivo, which can be rescued by overexpressing ZDHHC8. Therefore, TrkB and PKMζ, two critical regulators of synaptic plasticity, facilitate PSD-95 targeting to synapses. These results also indicate that palmitoylation can be regulated by a trophic factor. Our findings have implications for neurodevelopmental disorders as well as aging brains.

  6. TrkB and PKMζ regulate synaptic localization of PSD-95 in developing cortex

    PubMed Central

    Yoshii, Akira; Murata, Yasunobu; Kim, Jihye; Zhang, Chao; Shokat, Kevan M.; Constantine-Paton, Martha

    2011-01-01

    Post-synaptic density 95 (PSD-95), the major scaffold at excitatory synapses, is critical for synapse maturation and learning. In rodents, eye opening, the onset of pattern vision, triggers a rapid movement of PSD-95 from visual neuron somata to synapses. We previously showed that the PI3 kinase-Akt pathway downstream of BDNF/TrkB signaling stimulates synaptic delivery of PSD-95 via vesicular transport. However, vesicular transport requires PSD-95 palmitoylation to attach it to a lipid membrane. Also PSD-95 insertion at synapses is known to require this lipid modification. Here, we show that BDNF/TrkB signaling is also necessary for PSD-95 palmitoylation and its transport to synapses in mouse visual cortical layer 2/3 neurons. However, palmitoylation of PSD-95 requires the activation of another pathway downstream of BDNF/TrkB, namely signaling through PLCγ and the brain-specific PKC variant PKMζ. We find that PKMζ selectively regulates phosphorylation of the palmitoylation enzyme ZDHHC8. Inhibition of PKMζ results in a reduction of synaptic PSD-95 accumulation in vivo, which can be rescued by over-expression ZDHHC8. Therefore, TrkB and PKMζ, two critical regulators of synaptic plasticity, facilitate PSD-95 targeting to synapses. These results also indicate that palmitoylation can be regulated by a trophic factor. Our findings have implications for neurodevelopmental disorders as well as ageing brains. PMID:21849550

  7. Epigenetic editing of the Dlg4/PSD95 gene improves cognition in aged and Alzheimer's disease mice.

    PubMed

    Bustos, Fernando J; Ampuero, Estibaliz; Jury, Nur; Aguilar, Rodrigo; Falahi, Fahimeh; Toledo, Jorge; Ahumada, Juan; Lata, Jaclyn; Cubillos, Paula; Henríquez, Berta; Guerra, Miguel V; Stehberg, Jimmy; Neve, Rachael L; Inestrosa, Nibaldo C; Wyneken, Ursula; Fuenzalida, Marco; Härtel, Steffen; Sena-Esteves, Miguel; Varela-Nallar, Lorena; Rots, Marianne G; Montecino, Martin; van Zundert, Brigitte

    2017-12-01

    The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9). These epi-editors altered critical histone marks and subsequently Dlg4/PSD95 expression, which, importantly, impacted several hippocampal neuron plasticity processes. Intriguingly, transduction of the artificial transcription factor PSD95-VP64 rescued memory deficits in aged and Alzheimer's disease mice. Conclusively, this work validates PSD95 as a key player in memory and establishes epigenetic editing as a potential therapy to treat human neurological disorders. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Effects of different periods of paradoxical sleep deprivation and sleep recovery on lipid and glucose metabolism and appetite hormones in rats.

    PubMed

    Brianza-Padilla, Malinalli; Bonilla-Jaime, Herlinda; Almanza-Pérez, Julio César; López-López, Ana Laura; Sánchez-Muñoz, Fausto; Vázquez-Palacios, Gonzalo

    2016-03-01

    Sleep has a fundamental role in the regulation of energy balance, and it is an essential and natural process whose precise impacts on health and disease have not yet been fully elucidated. The aim of this study was to assess the consequences of different periods of paradoxical sleep deprivation (PSD) and recovery from PSD on lipid profile, oral glucose tolerance test (OGTT) results, and changes in insulin, corticosterone, ghrelin, and leptin concentrations. Three-month-old male Wistar rats weighing 250-350 g were submitted to 24, 96, or 192 h of PSD or 192 h of PSD with 480 h of recovery. The PSD was induced by the multiple platforms method. Subsequently, the animals were submitted to an OGTT. One day later, the animals were killed and the levels of triglycerides, total cholesterol, lipoproteins (low-density lipoprotein, very-low-density lipoprotein, and high-density lipoprotein), insulin, ghrelin, leptin, and corticosterone in plasma were quantified. There was a progressive decrease in body weight with increasing duration of PSD. The PSD induced basal hypoglycemia over all time periods evaluated. Evaluation of areas under the curve revealed progressive hypoglycemia only after 96 and 192 h of PSD. There was an increase in corticosterone levels after 192 h of PSD. We conclude that PSD induces alterations in metabolism that are reversed after a recovery period of 20 days.

  9. Inferring Cirrus Size Distributions Through Satellite Remote Sensing and Microphysical Databases

    NASA Technical Reports Server (NTRS)

    Mitchell, David; D'Entremont, Robert P.; Lawson, R. Paul

    2010-01-01

    Since cirrus clouds have a substantial influence on the global energy balance that depends on their microphysical properties, climate models should strive to realistically characterize the cirrus ice particle size distribution (PSD), at least in a climatological sense. To date, the airborne in situ measurements of the cirrus PSD have contained large uncertainties due to errors in measuring small ice crystals (D<60 m). This paper presents a method to remotely estimate the concentration of the small ice crystals relative to the larger ones using the 11- and 12- m channels aboard several satellites. By understanding the underlying physics producing the emissivity difference between these channels, this emissivity difference can be used to infer the relative concentration of small ice crystals. This is facilitated by enlisting temperature-dependent characterizations of the PSD (i.e., PSD schemes) based on in situ measurements. An average cirrus emissivity relationship between 12 and 11 m is developed here using the Moderate Resolution Imaging Spectroradiometer (MODIS) satellite instrument and is used to retrieve the PSD based on six different PSD schemes. The PSDs from the measurement-based PSD schemes are compared with corresponding retrieved PSDs to evaluate differences in small ice crystal concentrations. The retrieved PSDs generally had lower concentrations of small ice particles, with total number concentration independent of temperature. In addition, the temperature dependence of the PSD effective diameter De and fall speed Vf for these retrieved PSD schemes exhibited less variability relative to the unmodified PSD schemes. The reduced variability in the retrieved De and Vf was attributed to the lower concentrations of small ice crystals in the retrieved PSD.

  10. 40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

  11. 40 CFR 52.1837 - Original identification of plan section.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... deterioration of air quality (PSD) regulations to incorporate the nitrogen dioxide (NO2) increments and to make... permitting of new PSD sources, PSD major modifications, and sources to be located in nonattainment areas. (23... changes in the Federal PSD permitting regulations for utility pollution control projects, PM-10 increments...

  12. 40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 23 2013-07-01 2013-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

  13. 40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

  14. 40 CFR 52.1837 - Original identification of plan section.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... deterioration of air quality (PSD) regulations to incorporate the nitrogen dioxide (NO2) increments and to make... permitting of new PSD sources, PSD major modifications, and sources to be located in nonattainment areas. (23... changes in the Federal PSD permitting regulations for utility pollution control projects, PM-10 increments...

  15. 40 CFR 52.1837 - Original identification of plan section.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... deterioration of air quality (PSD) regulations to incorporate the nitrogen dioxide (NO2) increments and to make... permitting of new PSD sources, PSD major modifications, and sources to be located in nonattainment areas. (23... changes in the Federal PSD permitting regulations for utility pollution control projects, PM-10 increments...

  16. 40 CFR 52.1837 - Original identification of plan section.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... deterioration of air quality (PSD) regulations to incorporate the nitrogen dioxide (NO2) increments and to make... permitting of new PSD sources, PSD major modifications, and sources to be located in nonattainment areas. (23... changes in the Federal PSD permitting regulations for utility pollution control projects, PM-10 increments...

  17. 76 FR 7546 - Proposed Information Collection; Comment Request; Prohibited Species Donation (PSD) Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-10

    ... Collection; Comment Request; Prohibited Species Donation (PSD) Program AGENCY: National Oceanic and... species donation (PSD) program for Pacific salmon and Pacific halibut has effectively reduced regulatory... distribution of salmon and halibut. The PSD program requires a collection-of-information so that NMFS can...

  18. 76 FR 81836 - Approval and Promulgation of Air Quality Implementation Plans; New Mexico; Albuquerque/Bernalillo...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... Significant Deterioration (PSD) program to establish appropriate emission thresholds for determining which new stationary sources and modification projects become subject to Albuquerque/Bernalillo County's PSD permitting..., New Mexico December 15, 2010 PSD SIP revision because the Agency has determined that this PSD SIP...

  19. 77 FR 36442 - Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-19

    ... Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations AGENCY: Environmental Protection... Significant Deterioration (PSD) construction permit program of State of Michigan's State Implementation Plan (SIP) to meet the Clean Air Act (CAA) requirements for PSD in Class I Areas attaining the National...

  20. 76 FR 26933 - Approval and Promulgation of Implementation Plans; Connecticut: Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-10

    ... Significant Deterioration (PSD) program. First, the revision provides Connecticut with authority to issue PSD... determining which new stationary sources and modification projects become subject to Connecticut's PSD... required to apply its PSD program to GHG- emitting sources, and unless it does so (or unless EPA...

  1. 40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

  2. 40 CFR 52.1837 - Original identification of plan section.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... deterioration of air quality (PSD) regulations to incorporate the nitrogen dioxide (NO2) increments and to make... permitting of new PSD sources, PSD major modifications, and sources to be located in nonattainment areas. (23... changes in the Federal PSD permitting regulations for utility pollution control projects, PM-10 increments...

  3. 40 CFR 124.42 - Additional procedures for PSD permits affecting Class I areas.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Additional procedures for PSD permits... (CONTINUED) WATER PROGRAMS PROCEDURES FOR DECISIONMAKING Specific Procedures Applicable to PSD Permits § 124.42 Additional procedures for PSD permits affecting Class I areas. (a) The Regional Administrator...

  4. 75 FR 70254 - PSD and Title V Permitting Guidance for Greenhouse Gases

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-17

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OAR-2010-0841; FRL-9228-2] PSD and Title V Permitting..., ``PSD and Title V Permitting Guidance for Greenhouse Gases'' on its significant guidance Internet Web... guidance titled, ``PSD and Title V Permitting Guidance for Greenhouse Gases.'' This document has been...

  5. Development of the GDM system for imaging the internal structure of the Usu Cryptodome

    NASA Astrophysics Data System (ADS)

    Tanaka, H. K. M.; Kusagaya, T.; Taketa, A.; Oshima, H.; Maekawa, T.

    2012-04-01

    We developed a multilayer, scintillator based, segmented muon hodoscope whose number of layers can increase systematically by combining newly developed muon read out modules. The precise selection of muon trajectories from other cosmic ray background components are one of the most important processes for cosmic ray muon radiography. As the size of the target becomes larger, the muon path length in the target becomes longer, and thus the flux of the penetrating muon substantially decreases and the effect of the background (BG) noise becomes significant. The most probable source to create a BG track is the simultaneously arriving, vertical electromagnetic (EM) shower. When the EM shower hits only one point on each position sensitive detector (PSD), a hodoscope that consists of two PSD layers creates a fake muon track. This is because each shower particle is a charged particle and it is difficult for us to separate it from a muon. Another possible source degrading the quality of the measurement comes from the uncertainty in the muon spectrum model. Radiography using the propagation of muons utilizes a muon energy spectrum and a specific muon propagation model through matter. Conventionally, after passing through the target the integrated muon flux is compared with the muon flux directly from the sky to calculate the muon transmission. In this work, we attempted to reduce the vertical EM shower originated background events and to screen the low energy muons with energies below 10 GeV, by constructing a multi-layered, rotational muon hodoscope named GDM (gradient of density measurement). The maximum detectable thickness (MDT) of the GDM was designed to be 4 km.w.e. The trajectory of the cosmic-ray muons was measured by four or more PSD layers while the low energy muons were screened in the process of GDM analysis. We measured the internal structure of the 1910 cryptodome of Usu volcano located in Hokkaido, Japan during 290 hours with +/-2% precision in the density measurement. The obtained image is different from its conventional picture.

  6. SU-F-T-09: In Phantom Full-Implant Validation of Plastic Scintillation Detectors for in Vivo Dosimetry During Low Dose Rate Brachytherapy

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

    Therriault-Proulx, F; Bruno, T; Beddar, S

    Purpose: To validate in a water phantom the use of plastic scintillation detectors to measure dose to the urethra and the rectal wall during a clinically realistic low dose rate (LDR) brachytherapy implant. Methods: A template was designed to replicate a clinically realistic LDR brachytherapy prostate implant inside a water phantom. Twenty-two catheters were inserted, including one mimicking the urethra and another the rectal wall. The needles inserted in the remaining 20 catheters were composed of thin-walled nylon tubes in which I-125 radioactive seeds (Air Kerma Strengths of (0.328±0.020)U) were abutted together with plastic spacers to replicate a typical loading.more » A plastic scintillation detector (PSD) with a 5-mm long × 1-mm diameter sensitive element was first placed inside the urethra and 1-second measurements were performed for 60s after each needle implant. Measurements were also performed at multiple positions along the urethra once all the needles were inserted. The procedure was then repeated with the PSD placed at the rectal wall. Results: Individual dose-rates ranging from 0.07µGy/s to 1.5µGy/s were measured after each needle implant. The average absolute relative differences were (6.2±3.6)% and (6.9±6.5)% to the values calculated with the TG-43 formalism, for the urethra and rectal wall respectively. These results are within expectations from the error uncertainty budget once accounting for uncertainties in seeds’ strength and positioning. Interestingly, the PSD allowed for unplanned error detection as the study was performed. Finally, the measured dose after the full implant at different positions along the mimicked organs at risk were in agreement with TG-43 values for all of the positions tested. Conclusion: Plastic scintillation detectors could be used as in vivo detectors for LDR brachytherapy as they would provide accurate dose information after each needle implant as well as along the organs at risk at the end of the implant.« less

  7. Facility Overview and Double-Focusing Thermal Triple-Axis Spectrometer at the NCNR

    NASA Astrophysics Data System (ADS)

    Lynn, Jeffrey

    2012-02-01

    We will briefly overview the neutron scattering instrumentation at the NCNR, but will focus the talk on the capabilities of the new thermal triple-axis spectrometer is located at the BT-7 beam port [1]. This spectrometer takes full advantage of the large 165 mm diameter reactor beam to tailor the dual 20x20 cm^2 double-focusing monochromator system to provide monochromatic fluxes exceeding 10^8 n/cm^2/s onto the sample. The two monochromators installed are PG(002) and Cu(220), which provide incident energies for 5 meV to above 500 meV. The computer controlled analyzer system offers six standard modes of operation, including a diffraction detector, a position-sensitive detector (PSD) in diffraction mode, horizontal energy focusing analyzer with detector, a Q-E mode employing a flat analyzer and PSD, a constant-E mode with the analyzer crystal system and PSD, and a conventional mode with a selection of S"oller collimators and detector. Additional configurations for specific measurement needs are also available. The capabilities and performance will be discussed and examples of published data presented. [4pt] [1] J. W. Lynn, Y. Chen, S. Chang, Y. Zhao, S. Chi, W. Ratcliff, II, B. G. Ueland, and R. W. Erwin, J. Research NIST 117 (in press).

  8. Optimal design of a high accuracy photoelectric auto-collimator based on position sensitive detector

    NASA Astrophysics Data System (ADS)

    Yan, Pei-pei; Yang, Yong-qing; She, Wen-ji; Liu, Kai; Jiang, Kai; Duan, Jing; Shan, Qiusha

    2018-02-01

    A kind of high accuracy Photo-electric auto-collimator based on PSD was designed. The integral structure composed of light source, optical lens group, Position Sensitive Detector (PSD) sensor, and its hardware and software processing system constituted. Telephoto objective optical type is chosen during the designing process, which effectively reduces the length, weight and volume of the optical system, as well as develops simulation-based design and analysis of the auto-collimator optical system. The technical indicators of auto-collimator presented by this paper are: measuring resolution less than 0.05″; a field of view is 2ω=0.4° × 0.4° measuring range is +/-5' error of whole range measurement is less than 0.2″. Measuring distance is 10m, which are applicable to minor-angle precise measuring environment. Aberration analysis indicates that the MTF close to the diffraction limit, the spot in the spot diagram is much smaller than the Airy disk. The total length of the telephoto lens is only 450mm by the design of the optical machine structure optimization. The autocollimator's dimension get compact obviously under the condition of the image quality is guaranteed.

  9. Mechanism underlying selective regulation of G protein-gated inwardly rectifying potassium channels by the psychostimulant-sensitive sorting nexin 27

    PubMed Central

    Balana, Bartosz; Maslennikov, Innokentiy; Kwiatkowski, Witek; Stern, Kalyn M.; Bahima, Laia; Choe, Senyon; Slesinger, Paul A.

    2011-01-01

    G protein-gated inwardly rectifying potassium (GIRK) channels are important gatekeepers of neuronal excitability. The surface expression of neuronal GIRK channels is regulated by the psychostimulant-sensitive sorting nexin 27 (SNX27) protein through a class I (-X-Ser/Thr-X-Φ, where X is any residue and Φ is a hydrophobic amino acid) PDZ-binding interaction. The G protein-insensitive inward rectifier channel (IRK1) contains the same class I PDZ-binding motif but associates with a different synaptic PDZ protein, postsynaptic density protein 95 (PSD95). The mechanism by which SNX27 and PSD95 discriminate these channels was previously unclear. Using high-resolution structures coupled with biochemical and functional analyses, we identified key amino acids upstream of the channel's canonical PDZ-binding motif that associate electrostatically with a unique structural pocket in the SNX27-PDZ domain. Changing specific charged residues in the channel's carboxyl terminus or in the PDZ domain converts the selective association and functional regulation by SNX27. Elucidation of this unique interaction site between ion channels and PDZ-containing proteins could provide a therapeutic target for treating brain diseases. PMID:21422294

  10. 40 CFR 124.3 - Application for a permit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... person who requires a permit under the RCRA, UIC, NPDES, or PSD programs shall complete, sign, and submit....21 (PSD), and 122.1 (NPDES). Applications are not required for RCRA permits by rule (§ 270.60...), 144.31 (UIC), 40 CFR 52.21 (PSD), and 122.21 (NPDES). (3) Permit applications (except for PSD permits...

  11. 75 FR 19567 - Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NSR...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-15

    ...-AP80 Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NSR... changed our interpretation of the PSD and nonattainment NSR regulations relating to the definition of... Historic Approach Under both the nonattainment NSR provisions of the CAA as well as the PSD provisions, a...

  12. 40 CFR 52.270 - Significant deterioration of air quality.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... applicable State plan for the State of California. (b) District PSD Plans. (1) The PSD rules for Sacramento... of PSD increments. (ii) Those projects which are major stationary sources or major modifications... 83-01, 5/6/83. (2) The PSD rules for North Coast Unified Air Quality Management District are approved...

  13. 40 CFR 124.3 - Application for a permit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... person who requires a permit under the RCRA, UIC, NPDES, or PSD programs shall complete, sign, and submit....21 (PSD), and 122.1 (NPDES). Applications are not required for RCRA permits by rule (§ 270.60...), 144.31 (UIC), 40 CFR 52.21 (PSD), and 122.21 (NPDES). (3) Permit applications (except for PSD permits...

  14. Evaluating soybean breeding lines developed from differenct sources of resistance to phomopsis seed decay

    USDA-ARS?s Scientific Manuscript database

    Phomopsis seed decay (PSD) causes poor soybean seed quality worldwide. The primary causal agent of PSD is Phomopsis longicolla (syn. Diaporthe longicolla). Breeding for PSD-resistance is the most effective long-term strategy to control this disease. To develop soybean lines with resistance to PSD, m...

  15. 40 CFR 124.3 - Application for a permit.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... person who requires a permit under the RCRA, UIC, NPDES, or PSD programs shall complete, sign, and submit....21 (PSD), and 122.1 (NPDES). Applications are not required for RCRA permits by rule (§ 270.60...), 144.31 (UIC), 40 CFR 52.21 (PSD), and 122.21 (NPDES). (3) Permit applications (except for PSD permits...

  16. 75 FR 55978 - Approval and Promulgation of Air Quality Implementation Plans; Texas; Revisions to the New Source...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-15

    ... Implementation Plan (SIP); Prevention of Significant Deterioration (PSD) AGENCY: Environmental Protection Agency... Texas PSD State Implementation Plan (SIP). EPA is approving a SIP revision submitted February 1, 2006... Texas PSD SIP; it merely approves reorganization and renumbering of the Texas PSD SIP rules. Further...

  17. 76 FR 30832 - Approval and Promulgation of Air Quality Implementation Plans; West Virginia; Permits for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-27

    ... for the prevention of significant deterioration (PSD) areas in West Virginia. This action will also add the Federally equivalent provisions to the rules for the PSD program as they pertain to... (CUs) to make the West Virginia PSD program consistent with the Federal PSD program. This action is...

  18. 40 CFR 52.270 - Significant deterioration of air quality.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... applicable State plan for the State of California. (b) District PSD Plans. (1) The PSD rules for Sacramento... of PSD increments. (ii) Those projects which are major stationary sources or major modifications... 83-01, 5/6/83. (2) The PSD rules for North Coast Unified Air Quality Management District are approved...

  19. 40 CFR 52.270 - Significant deterioration of air quality.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... applicable State plan for the State of California. (b) District PSD Plans. (1) The PSD rules for Sacramento... of PSD increments. (ii) Those projects which are major stationary sources or major modifications... 83-01, 5/6/83. (2) The PSD rules for North Coast Unified Air Quality Management District are approved...

  20. 40 CFR 124.3 - Application for a permit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... person who requires a permit under the RCRA, UIC, NPDES, or PSD programs shall complete, sign, and submit....21 (PSD), and 122.1 (NPDES). Applications are not required for RCRA permits by rule (§ 270.60...), 144.31 (UIC), 40 CFR 52.21 (PSD), and 122.21 (NPDES). (3) Permit applications (except for PSD permits...

  1. 76 FR 2589 - Approval and Promulgation of Implementation Plans; Mississippi: Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-14

    ... clarify that the version of Mississippi's Prevention of Significant Deterioration (PSD) regulations... Mississippi's PSD regulations includes both a SIP revision approved by EPA on December 20, 2010, and a SIP... oxides (NO X ) as a precursor to ozone for PSD purposes) was included in the PSD rules that were...

  2. 77 FR 56124 - Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD and NSR Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-12

    ... Promulgation of Air Quality Implementation Plans; Michigan; PSD and NSR Regulations AGENCY: Environmental... the prevention of significant deterioration (PSD) construction permit program for the purpose of... approving Michigan's request to revise its SIP to add rule R. 336.2816 to be consistent with Federal PSD...

  3. 40 CFR 52.270 - Significant deterioration of air quality.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... applicable State plan for the State of California. (b) District PSD Plans. (1) The PSD rules for Sacramento... of PSD increments. (ii) Those projects which are major stationary sources or major modifications... 83-01, 5/6/83. (2) The PSD rules for North Coast Unified Air Quality Management District are approved...

  4. Coxsackievirus and adenovirus receptor (CAR) mediates trafficking of acid sensing ion channel 3 (ASIC3) via PSD-95.

    PubMed

    Excoffon, Katherine J D A; Kolawole, Abimbola O; Kusama, Nobuyoshi; Gansemer, Nicholas D; Sharma, Priyanka; Hruska-Hageman, Alesia M; Petroff, Elena; Benson, Christopher J

    2012-08-17

    We have previously shown that the Coxsackievirus and adenovirus receptor (CAR) can interact with post-synaptic density 95 (PSD-95) and localize PSD-95 to cell-cell junctions. We have also shown that activity of the acid sensing ion channel (ASIC3), a H(+)-gated cation channel that plays a role in mechanosensation and pain signaling, is negatively modulated by PSD-95 through a PDZ-based interaction. We asked whether CAR and ASIC3 simultaneously interact with PSD-95, and if so, whether co-expression of these proteins alters their cellular distribution and localization. Results indicate that CAR and ASIC3 co-immunoprecipitate only when co-expressed with PSD-95. CAR also brings both PSD-95 and ASIC3 to the junctions of heterologous cells. Moreover, CAR rescues PSD-95-mediated inhibition of ASIC3 currents. These data suggest that, in addition to activity as a viral receptor and adhesion molecule, CAR can play a role in trafficking proteins, including ion channels, in a PDZ-based scaffolding complex. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Ezh1 and Ezh2 differentially regulate PSD-95 gene transcription in developing hippocampal neurons.

    PubMed

    Henriquez, Berta; Bustos, Fernando J; Aguilar, Rodrigo; Becerra, Alvaro; Simon, Felipe; Montecino, Martin; van Zundert, Brigitte

    2013-11-01

    Polycomb Repressive Complex 2 (PRC2) mediates transcriptional silencing by catalyzing histone H3 lysine 27 trimethylation (H3K27me3), but its role in the maturation of postmitotic mammalian neurons remains largely unknown. We report that the PRC2 paralogs Ezh1 and Ezh2 are differentially expressed during hippocampal development. We show that depletion of Ezh2 leads to increased expression of PSD-95, a critical plasticity gene, and that reduced PSD-95 gene transcription is correlated with enrichment of Ezh2 at the PSD-95 gene promoter; however, the H3K27me3 epigenetic mark is not present at the PSD-95 gene promoter, likely due to the antagonizing effects of the H3S28P and H3K27Ac marks and the activity of the H3K27 demethylases JMJD3 and UTX. In contrast, increased PSD-95 gene transcription is accompanied by the presence of Ezh1 and elongation-engaged RNA Polymerase II complexes at the PSD-95 gene promoter, while knock-down of Ezh1 reduces PSD-95 transcription. These results indicate that Ezh1 and Ezh2 have antagonistic roles in regulating PSD-95 transcription. © 2013.

  6. Race/ethnic Differences in Post-stroke Depression (PSD): Findings from the Stroke Warning Information and Faster Treatment (SWIFT) Study.

    PubMed

    Goldmann, Emily; Roberts, Eric T; Parikh, Nina S; Lord, Aaron S; Boden-Albala, Bernadette

    2016-01-21

    Post-stroke depression (PSD) is common and associated with poor stroke outcomes, but few studies have examined race/ethnic disparities in PSD. Given the paucity of work and inconsistent findings in this important area of research, our study aimed to examine race/ethnic differences in depression in a multi-ethnic cohort of stroke patients. Longitudinal. Prospective trial of a post-stroke educational intervention. 1,193 mild/moderate ischemic stroke/transient ischemic attack (TIA) patients. We used the Center for Epidemiologic Studies Depression (CES-D) Scale to assess subthreshold (CES-D score 8-15) and full (CES-D score ≥ 16) depression at one month ("early") and 12 months ("late") following stroke. Multinomial logistic regression analyses examined the association between race/ethnicity and early and late PSD separately. The prevalence of subthreshold and full PSD was 22.5% and 32.6% in the early period and 22.0% and 27.4% in the late period, respectively. Hispanics had 60% lower odds of early full PSD compared with non-Hispanic Whites after adjusting for other covariates (OR=.4, 95% CI: .2, .8). Race/ethnicity was not significantly associated with late PSD. Hispanic stroke patients had half the odds of PSD in early period compared with Whites, but no difference was found in the later period. Further studies comparing trajectories of PSD between race/ethnic groups may further our understanding of race/ethnic disparities in PSD and help identify effective interventions.

  7. PSD-93 Attenuates Amyloid-β-Mediated Cognitive Dysfunction by Promoting the Catabolism of Amyloid-β.

    PubMed

    Yu, Linjie; Liu, Yi; Yang, Hui; Zhu, Xiaolei; Cao, Xiang; Gao, Jun; Zhao, Hui; Xu, Yun

    2017-01-01

    Amyloid-β (Aβ) is a key neuropathological hallmark of Alzheimer's disease (AD). Postsynaptic density protein 93 (PSD-93) is a key scaffolding protein enriched at postsynaptic sites. The aim of the present study was to examine whether PSD-93 overexpression could alleviate Aβ-induced cognitive dysfunction in APPswe/PS1dE9 (APP/PS1) mice by reducing Aβ levels in the brain. The level of PSD-93 was significantly decreased in the hippocampus of 6-month-old APP/PS1 mice compared with that in wild-type mice. Following lentivirus-mediated PSD-93 overexpression, cognitive function, synaptic function, and amyloid burden were investigated. The open field test, Morris water maze test, and fear condition test revealed that PSD-93 overexpression ameliorated spatial memory deficits in APP/PS1 mice. The facilitation of long-term potentiation induction was observed in APP/PS1 mice after PSD-93 overexpression. The expression of somatostatin receptor 4 (SSTR4) and neprilysin was increased, while the amyloid plaque load and Aβ levels were decreased in the brains of APP/PS1 mice. Moreover, PSD-93 interacted with SSTR4 and affected the level of SSTR4 on cell membrane, which was associated with the ubiquitination. Together, these findings suggest that PSD-93 attenuates spatial memory deficits and decreases amyloid levels in APP/PS1 mice, which might be associated with Aβ catabolism, and overexpression of PSD-93 might be a potential therapy for AD.

  8. An Assessment of Common Approaches to Estimating Peak Skin Dose Resulting From Fluoroscopically Guided Interventions

    NASA Astrophysics Data System (ADS)

    Smith, Caleb Martin

    Fluoroscopy guided procedures are increasing in complexity, and with that, Peak Skin Doses (PSD) that produce cutaneous radiation injury are a growing concern. Direct measurement of PSD is possible, but the decision to do so must be made in advance. PSD estimates and correctly monitoring their possible deterministic skin injuries are important to patient care. Three methods of indirect PSD estimation are examined for nine cases at MedStar Georgetown University Hospital. The aim of the study is to determine the magnitude of variation between these three methods for estimating the PSD. Method 1 (Fluoroscopy Time and Maximum Entrance Skin Exposure) was used at MedStar Georgetown University Hospital up until 2016. Methods 2 and 3 incorporate procedure information (Reference Point Air Kerma, Source-to-Patent distance, and Backscatter Factor) from DICOM (Digital Imaging and Communications in Medicine) tags into PSD estimates. Method 1 PSD estimates are vastly different, by as much as 136%, than those from Methods 2 and 3. Method 2 and 3 PSD estimates differ very little, 7.3% or less. Governing bodies have discounted Method 1 as a reliable dose metric because of its poor correlation with PSD. The accuracy of Method 2 is suitable to determine PSD and which dose band a patient fits so their injuries can be accurately monitored. Method 3, the most time intensive approach, should only be used in the case of a sentinel event where a full investigation is warranted.

  9. PSD-Zip70 Deficiency Causes Prefrontal Hypofunction Associated with Glutamatergic Synapse Maturation Defects by Dysregulation of Rap2 Activity.

    PubMed

    Mayanagi, Taira; Yasuda, Hiroki; Sobue, Kenji

    2015-10-21

    Dysregulation of synapse formation and plasticity is closely related to the pathophysiology of psychiatric and neurodevelopmental disorders. The prefrontal cortex (PFC) is particularly important for executive functions such as working memory, cognition, and emotional control, which are impaired in the disorders. PSD-Zip70 (Lzts1/FEZ1) is a postsynaptic density (PSD) protein predominantly expressed in the frontal cortex, olfactory bulb, striatum, and hippocampus. Here we found that PSD-Zip70 knock-out (PSD-Zip70KO) mice exhibit working memory and cognitive defects, and enhanced anxiety-like behaviors. These abnormal behaviors are caused by impaired glutamatergic synapse transmission accompanied by tiny-headed immature dendritic spines in the PFC, due to aberrant Rap2 activation, which has roles in synapse formation and plasticity. PSD-Zip70 modulates the Rap2 activity by interacting with SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) in the postsynapse. Furthermore, suppression of the aberrant Rap2 activation in the PFC rescued the behavioral defects in PSD-Zip70KO mice. Our data demonstrate a critical role for PSD-Zip70 in Rap2-dependent spine synapse development in the PFC and underscore the importance of this regulation in PFC-dependent behaviors. PSD-Zip70 deficiency causes behavioral defects in working memory and cognition, and enhanced anxiety due to prefrontal hypofunction. This study revealed that PSD-Zip70 plays essential roles in glutamatergic synapse maturation via modulation of the Rap2 activity in the PFC. PSD-Zip70 interacts with both SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) and modulates the Rap2 activity in postsynaptic sites. Our results provide a novel Rap2-specific regulatory mechanism in synaptic maturation involving PSD-Zip70. Copyright © 2015 the authors 0270-6474/15/3514327-14$15.00/0.

  10. WE-E-18A-03: How Accurately Can the Peak Skin Dose in Fluoroscopy Be Determined Using Indirect Dose Metrics?

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

    Jones, A; Pasciak, A

    Purpose: Skin dosimetry is important for fluoroscopically-guided interventions, as peak skin doses (PSD) that Result in skin reactions can be reached during these procedures. The purpose of this study was to assess the accuracy of different indirect dose estimates and to determine if PSD can be calculated within ±50% for embolization procedures. Methods: PSD were measured directly using radiochromic film for 41 consecutive embolization procedures. Indirect dose metrics from procedures were collected, including reference air kerma (RAK). Four different estimates of PSD were calculated and compared along with RAK to the measured PSD. The indirect estimates included a standard method,more » use of detailed information from the RDSR, and two simplified calculation methods. Indirect dosimetry was compared with direct measurements, including an analysis of uncertainty associated with film dosimetry. Factors affecting the accuracy of the indirect estimates were examined. Results: PSD calculated with the standard calculation method were within ±50% for all 41 procedures. This was also true for a simplified method using a single source-to-patient distance (SPD) for all calculations. RAK was within ±50% for all but one procedure. Cases for which RAK or calculated PSD exhibited large differences from the measured PSD were analyzed, and two causative factors were identified: ‘extreme’ SPD and large contributions to RAK from rotational angiography or runs acquired at large gantry angles. When calculated uncertainty limits [−12.8%, 10%] were applied to directly measured PSD, most indirect PSD estimates remained within ±50% of the measured PSD. Conclusions: Using indirect dose metrics, PSD can be determined within ±50% for embolization procedures, and usually to within ±35%. RAK can be used without modification to set notification limits and substantial radiation dose levels. These results can be extended to similar procedures, including vascular and interventional oncology. Film dosimetry is likely an unnecessary effort for these types of procedures.« less

  11. Doped luminescent materials and particle discrimination using same

    DOEpatents

    Doty, F. Patrick; Allendorf, Mark D; Feng, Patrick L

    2014-10-07

    Doped luminescent materials are provided for converting excited triplet states to radiative hybrid states. The doped materials may be used to conduct pulse shape discrimination (PSD) using luminescence generated by harvested excited triplet states. The doped materials may also be used to detect particles using spectral shape discrimination (SSD).

  12. Combining functional and structural tests improves the diagnostic accuracy of relevance vector machine classifiers

    PubMed Central

    Racette, Lyne; Chiou, Christine Y.; Hao, Jiucang; Bowd, Christopher; Goldbaum, Michael H.; Zangwill, Linda M.; Lee, Te-Won; Weinreb, Robert N.; Sample, Pamela A.

    2009-01-01

    Purpose To investigate whether combining optic disc topography and short-wavelength automated perimetry (SWAP) data improves the diagnostic accuracy of relevance vector machine (RVM) classifiers for detecting glaucomatous eyes compared to using each test alone. Methods One eye of 144 glaucoma patients and 68 healthy controls from the Diagnostic Innovations in Glaucoma Study were included. RVM were trained and tested with cross-validation on optimized (backward elimination) SWAP features (thresholds plus age; pattern deviation (PD); total deviation (TD)) and on Heidelberg Retina Tomograph II (HRT) optic disc topography features, independently and in combination. RVM performance was also compared to two HRT linear discriminant functions (LDF) and to SWAP mean deviation (MD) and pattern standard deviation (PSD). Classifier performance was measured by the area under the receiver operating characteristic curves (AUROCs) generated for each feature set and by the sensitivities at set specificities of 75%, 90% and 96%. Results RVM trained on combined HRT and SWAP thresholds plus age had significantly higher AUROC (0.93) than RVM trained on HRT (0.88) and SWAP (0.76) alone. AUROCs for the SWAP global indices (MD: 0.68; PSD: 0.72) offered no advantage over SWAP thresholds plus age, while the LDF AUROCs were significantly lower than RVM trained on the combined SWAP and HRT feature set and on HRT alone feature set. Conclusions Training RVM on combined optimized HRT and SWAP data improved diagnostic accuracy compared to training on SWAP and HRT parameters alone. Future research may identify other combinations of tests and classifiers that can also improve diagnostic accuracy. PMID:19528827

  13. 40 CFR 52.181 - Significant deterioration of air quality.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...—submittal of the PSD Supplement Arkansas Plan of Implementation for Pollution Control (the “PSD Supplement... April 10, 1981); (2) June 3, 1988—submittal of revisions to the PSD Supplement (revised and adopted by the ACPCE on March 25, 1988); (3) June 19, 1990—submittal of revisions to the PSD Supplement (revised...

  14. 40 CFR 52.919 - Identification of plan-conditional approval.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... sections 110(a)(2)(C) and 110(a)(2)(J) as they both relate to Prevention of Significant Deterioration (PSD... requirements promulgated in the New Source Review (NSR) PM2.5 Rule related to the PM2.5 standard for their PSD... specific enforceable measures related the structural PSD requirements of the PSD and NNSR requirements...

  15. 40 CFR 52.379 - Control strategy: PM2.5.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... to CAA sections 110(a)(2)(A), (C) only as it related to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This conditional approval is contingent upon Connecticut taking... related to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This...

  16. 40 CFR 52.379 - Control strategy: PM2.5.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... to CAA sections 110(a)(2)(A), (C) only as it related to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This conditional approval is contingent upon Connecticut taking... related to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This...

  17. 40 CFR 52.181 - Significant deterioration of air quality.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...—submittal of the PSD Supplement Arkansas Plan of Implementation for Pollution Control (the “PSD Supplement... April 10, 1981); (2) June 3, 1988—submittal of revisions to the PSD Supplement (revised and adopted by the ACPCE on March 25, 1988); (3) June 19, 1990—submittal of revisions to the PSD Supplement (revised...

  18. 40 CFR 52.919 - Identification of plan-conditional approval.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... sections 110(a)(2)(C) and 110(a)(2)(J) as they both relate to Prevention of Significant Deterioration (PSD... requirements promulgated in the New Source Review (NSR) PM2.5 Rule related to the PM2.5 standard for their PSD... specific enforceable measures related the structural PSD requirements of the PSD and NNSR requirements...

  19. 40 CFR 124.3 - Application for a permit.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... requires a permit under the RCRA, UIC, NPDES, or PSD programs shall complete, sign, and submit to the Director an application for each permit required under §§ 270.1 (RCRA), 144.1 (UIC), 40 CFR 52.21 (PSD... (UIC), 40 CFR 52.21 (PSD), and 122.21 (NPDES). (3) Permit applications (except for PSD permits) must...

  20. 40 CFR 52.181 - Significant deterioration of air quality.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...—submittal of the PSD Supplement Arkansas Plan of Implementation for Pollution Control (the “PSD Supplement... April 10, 1981); (2) June 3, 1988—submittal of revisions to the PSD Supplement (revised and adopted by the ACPCE on March 25, 1988); (3) June 19, 1990—submittal of revisions to the PSD Supplement (revised...

  1. 40 CFR 52.920 - Identification of plan.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Requirements—Other Sources 10/23/01 66 FR 53660 11/16/83 2.07 Public Notification for Title V, PSD, and Offset...) related to PSD requirements and 110(a)(2)(J) related to PSD requirements, EPA conditionally approved these...)(D)(i), With respect to sections 110(a)(2)(C) related to PSD requirements and 110(a)(2)(J) related to...

  2. 40 CFR 52.920 - Identification of plan.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Requirements—Other Sources 10/23/01 66 FR 53660 11/16/83 2.07 Public Notification for Title V, PSD, and Offset...) related to PSD requirements and 110(a)(2)(J) related to PSD requirements, EPA conditionally approved these...)(D)(i), With respect to sections 110(a)(2)(C) related to PSD requirements and 110(a)(2)(J) related to...

  3. Pulse-shape discrimination and energy quenching of alpha particles in Cs 2LiLaBr 6:Ce 3+

    DOE PAGES

    Mesick, Katherine Elizabeth; Coupland, Daniel David S.; Stonehill, Laura Catherine

    2016-10-19

    Cs 2LiLaBr 6:Ce 3+ (CLLB) is an elpasolite scintillator that offers excellent linearity and gamma-ray energy resolution and sensitivity to thermal neutrons with the ability to perform pulse-shape discrimination (PSD) to distinguish gammas and neutrons. Our investigation of CLLB has indicated the presence of intrinsic radioactive alpha background that we have determined to be from actinium contamination of the lanthanum component. We measured the pulse shapes for gamma, thermal neutron, and alpha events and determined that PSD can be performed to separate the alpha background with a moderate figure of merit of 0.98. Here, we also measured the electron-equivalent-energy ofmore » the alpha particles in CLLB and simulated the intrinsic alpha background from 227Ac to determine the quenching factor of the alphas.« less

  4. Comparing multifocal VEP and standard automated perimetry in high-risk ocular hypertension and early glaucoma.

    PubMed

    Fortune, Brad; Demirel, Shaban; Zhang, Xian; Hood, Donald C; Patterson, Emily; Jamil, Annisa; Mansberger, Steven L; Cioffi, George A; Johnson, Chris A

    2007-03-01

    To compare the diagnostic performance of multifocal visual evoked potential (mfVEP) and standard automated perimetry (SAP), in eyes with high-risk ocular hypertension or early glaucoma. Both eyes of 185 individuals with high-risk ocular hypertension or early glaucoma were evaluated. Subjects ranged in age from 37 to 87 (mean +/- SD: 61 +/- 11 years). Pattern-reversal mfVEPs were obtained by using VERIS (Electro-Diagnostic Imaging, San Mateo, CA) with a four-electrode array and were analyzed with custom software. SAP visual fields (SITA-standard; Carl Zeiss Meditec, Inc., Dublin, CA) were obtained within 22.3 +/- 27.0 days of the mfVEP. Stereo disc photographs and Heidelberg Retina Tomograph (HRT) images were obtained during one visit, which was within 24.8 +/- 50.4 days of the mfVEP and 33.1 +/- 62.9 days of the SAP visual field. Abnormalities on the mfVEP were defined by using a variety of cluster criteria: SAP with pattern standard deviation (PSD) P

  5. PSD95: A synaptic protein implicated in schizophrenia or autism?

    PubMed

    Coley, Austin A; Gao, Wen-Jun

    2018-03-02

    The molecular components of the postsynaptic density (PSD) in excitatory synapses of the brain are currently being investigated as one of the major etiologies of neurodevelopmental disorders such as schizophrenia (SCZ) and autism. Postsynaptic density protein-95 (PSD-95) is a major regulator of synaptic maturation by interacting, stabilizing and trafficking N-methyl-d-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isox-azoleproprionic acid receptors (AMPARs) to the postsynaptic membrane. Recently, there has been overwhelming evidence that associates PSD-95 disruption with cognitive and learning deficits observed in SCZ and autism. For instance, recent genomic and sequencing studies of psychiatric patients highlight the aberrations at the PSD of glutamatergic synapses that include PSD-95 dysfunction. In animal studies, PSD-95 deficiency shows alterations in NMDA and AMPA-receptor composition and function in specific brain regions that may contribute to phenotypes observed in neuropsychiatric pathologies. In this review, we describe the role of PSD-95 as an essential scaffolding protein during synaptogenesis and neurodevelopment. More specifically, we discuss its interactions with NMDA receptor subunits that potentially affect glutamate transmission, and the formation of silent synapses during critical time points of neurodevelopment. Furthermore, we describe how PSD-95 may alter dendritic spine morphologies, thus regulating synaptic function that influences behavioral phenotypes in SCZ versus autism. Understanding the role of PSD-95 in the neuropathologies of SCZ and autism will give an insight of the cellular and molecular attributes in the disorders, thus providing treatment options in patients affected. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Sick of inequality: gender and support for paid sick days.

    PubMed

    Lindemann, Danielle J; Houser, Linda; White, Karen

    2015-01-01

    The availability of paid sick days (PSD) is on the forefront of policy issues relating to women's health and well-being. Previous research regarding PSD and other forms of family-work balance legislation has linked access to paid time off from work for addressing one's own or another's health concerns to a range of health benefits for working women and their families. In general, public support for such policies is high, but little work has tested the extent to which support extends to PSD. Researchers have yet to engage in a rigorous statistical analysis of public opinion on PSD, including whether opinion varies by gender. Using data from a 2013 poll of adults in New Jersey (n = 925), we bridged this research gap by conducting the first multivariate analysis of public attitudes toward PSD. As expected, we found markedly high levels of support for PSD across all respondents, with a preponderance of most sociodemographic categories supporting proposed PSD legislation in New Jersey. We also found that gender was a strong predictor of support for PSD, with women significantly (odds ratio, 1.916; p ≤ .01) more likely than men to be in favor of such legislation. We discuss the implications of our findings for future work on PSD as well as for research concerning women, wellness, and work-life legislation more broadly. Published by Elsevier Inc.

  7. 40 CFR 52.1019 - Identification of plan-conditional approval.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...), (C) only as it relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This conditional approval is contingent upon... conditionally approved for CAA elements 110(a)(2)(A), (C) only as it relates to the PSD program, (D)(i)(II) only...

  8. 40 CFR 52.1019 - Identification of plan-conditional approval.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...), (C) only as it relates to the PSD program, (D)(i)(II) only as it relates to the PSD program, (D)(ii), (E)(ii), and (J) only as it relates to the PSD program. This conditional approval is contingent upon... conditionally approved for CAA elements 110(a)(2)(A), (C) only as it relates to the PSD program, (D)(i)(II) only...

  9. 40 CFR 124.19 - Appeal of RCRA, UIC, NPDES and PSD Permits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 23 2013-07-01 2013-07-01 false Appeal of RCRA, UIC, NPDES and PSD... PSD Permits. (a) Petitioning for review of a permit decision. (1) Initiating an appeal. Appeal from a RCRA, UIC, NPDES, or PSD final permit decision issued under § 124.15 of this part, or a decision to...

  10. 40 CFR 124.19 - Appeal of RCRA, UIC, NPDES and PSD Permits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 22 2014-07-01 2013-07-01 true Appeal of RCRA, UIC, NPDES and PSD... PSD Permits. (a) Petitioning for review of a permit decision. (1) Initiating an appeal. Appeal from a RCRA, UIC, NPDES, or PSD final permit decision issued under § 124.15 of this part, or a decision to...

  11. 76 FR 142 - Notice of Prevention of Significant Deterioration Final Determination for Russell City Energy Center

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-03

    ... Deterioration (PSD) Permit issued to Russell City Energy Center, LLC by the Bay Area Air Quality Management... under authority of a PSD delegation agreement dated February 4, 2008, issued a PSD permit to Russell... Petitions for Review of the PSD decision with the EAB. The EAB issued an Order denying the Petitions for...

  12. PKMζ is necessary and sufficient for synaptic clustering of PSD-95.

    PubMed

    Shao, Charles Y; Sondhi, Rachna; van de Nes, Paula S; Sacktor, Todd Charlton

    2012-07-01

    The persistent activity of protein kinase Mzeta (PKMζ), a brain-specific, constitutively active protein kinase C isoform, maintains synaptic long-term potentiation (LTP). Structural remodeling of the postsynaptic density is believed to contribute to the expression of LTP. We therefore examined the role of PKMζ in reconfiguring PSD-95, the major postsynaptic scaffolding protein at excitatory synapses. In primary cultures of hippocampal neurons, PKMζ activity was critical for increasing the size of PSD-95 clusters during chemical LTP (cLTP). Increasing PKMζ activity by overexpressing the kinase in hippocampal neurons was sufficient to increase PSD-95 cluster size, spine size, and postsynaptic AMPAR subunit GluA2. Overexpression of an inactive mutant of PKMζ did not increase PSD-95 clustering, and applications of the ζ-pseudosubstrate inhibitor ZIP reversed the PKMζ-mediated increases in PSD-95 clustering, indicating that the activity of PKMζ is necessary to induce and maintain the increased size of PSD-95 clusters. Thus the persistent activity of PKMζ is both necessary and sufficient for maintaining increases of PSD-95 clusters, providing a unified mechanism for long-term functional and structural modifications of synapses. Copyright © 2011 Wiley Periodicals, Inc.

  13. Postsynaptic density protein (PSD)-95 expression is markedly decreased in the hippocampal CA1 region after experimental ischemia-reperfusion injury.

    PubMed

    Yan, Bing Chun; Park, Joon Ha; Ahn, Ji Hyeon; Lee, Jae-Chul; Won, Moo-Ho; Kang, Il-Jun

    2013-07-15

    Synaptic plasticity is important for functional recovery after cerebral ischemic injury. In the present study, we investigated chronological change in the immunoreactivity of PSD-95, a kind of postsynaptic density protein, in the hippocampus proper (CA1-3 regions) after 5 min of transient cerebral ischemia in gerbils. PSD-95 immunoreactivity was observed in MAP-2-immunoreactive dendrites in the CA1-3 regions of the sham group. The PSD-95 immunoreactivity was shown as beaded structure in the MAP-2-immunoreactive dendrites. However, PSD-95 immunoreactivity began to be dramatically decreased in MAP-2-immunoreactive dendrites in the CA1 region, not CA2-3 region, at early time after ischemia-reperfusion. At 5 days after ischemia-reperfusion, MAP-2 immunoreactivity almost disappeared in the ischemic CA1 region, and PSD-95 immunoreactivity was much lower than that in the sham group. In brief, PSD-95 immunoreactivity in the CA1 dendrites was markedly decreased at early time after ischemia-reperfusion. We suggest that decreased PSD-95 immunoreactivity in the ischemic CA1 region may lead to a deficit of postsynaptic plasticity in the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling.

    PubMed

    Nikonenko, Irina; Boda, Bernadett; Steen, Sylvain; Knott, Graham; Welker, Egbert; Muller, Dominique

    2008-12-15

    Postsynaptic density 95 (PSD-95) is an important regulator of synaptic structure and plasticity. However, its contribution to synapse formation and organization remains unclear. Using a combined electron microscopic, genetic, and pharmacological approach, we uncover a new mechanism through which PSD-95 regulates synaptogenesis. We find that PSD-95 overexpression affected spine morphology but also promoted the formation of multiinnervated spines (MISs) contacted by up to seven presynaptic terminals. The formation of multiple contacts was specifically prevented by deletion of the PDZ(2) domain of PSD-95, which interacts with nitric oxide (NO) synthase (NOS). Similarly, PSD-95 overexpression combined with small interfering RNA-mediated down-regulation or the pharmacological blockade of NOS prevented axon differentiation into varicosities and multisynapse formation. Conversely, treatment of hippocampal slices with an NO donor or cyclic guanosine monophosphate analogue induced MISs. NOS blockade also reduced spine and synapse density in developing hippocampal cultures. These results indicate that the postsynaptic site, through an NOS-PSD-95 interaction and NO signaling, promotes synapse formation with nearby axons.

  15. PSD-95 alters microtubule dynamics via an association with EB3

    PubMed Central

    Sweet, Eric S.; Previtera, Michelle L.; Fernández, Jose R.; Charych, Erik I.; Tseng, Chia-Yi; Kwon, Munjin; Starovoytov, Valentin; Zheng, James Q.; Firestein, Bonnie L.

    2011-01-01

    Little is known about how the neuronal cytoskeleton is regulated when a dendrite decides whether to branch or not. Previously, we reported that postsynaptic density protein 95 (PSD-95) acts as a stop signal for dendrite branching. It is yet to be elucidated how PSD-95 affects the cytoskeleton and how this regulation relates to the dendritic arbor. Here, we show that the SH3 (src homology 3) domain of PSD-95 interacts with a proline-rich region within the microtubule end-binding protein EB3. Overexpression of PSD-95 or mutant EB3 results in a decreased lifetime of EB3 comets in dendrites. In line with these data, transfected rat neurons show that overexpression of PSD-95 results in less organized microtubules at dendritic branch points and decreased dendritogensis. The interaction between PSD-95 and EB3 elucidates a function for a novel region of EB3 and provides a new and important mechanism for the regulation of microtubules in determining dendritic morphology. PMID:21248129

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

    Sobolewska, M. A.; Siemiginowska, A.; Kelly, B. C.

    We study the γ-ray variability of 13 blazars observed with the Fermi/Large Area Telescope (LAT). These blazars have the most complete light curves collected during the first four years of the Fermi sky survey. We model them with the Ornstein-Uhlenbeck (OU) process or a mixture of the OU processes. The OU process has power spectral density (PSD) proportional to 1/f {sup α} with α changing at a characteristic timescale, τ{sub 0}, from 0 (τ >> τ{sub 0}) to 2 (τ << τ{sub 0}). The PSD of the mixed OU process has two characteristic timescales and an additional intermediate region withmore » 0 < α < 2. We show that the OU model provides a good description of the Fermi/LAT light curves of three blazars in our sample. For the first time, we constrain a characteristic γ-ray timescale of variability in two BL Lac sources, 3C 66A and PKS 2155-304 (τ{sub 0} ≅ 25 days and τ{sub 0} ≅ 43 days, respectively, in the observer's frame), which are longer than the soft X-ray timescales detected in blazars and Seyfert galaxies. We find that the mixed OU process approximates the light curves of the remaining 10 blazars better than the OU process. We derive limits on their long and short characteristic timescales, and infer that their Fermi/LAT PSD resemble power-law functions. We constrain the PSD slopes for all but one source in the sample. We find hints for sub-hour Fermi/LAT variability in four flat spectrum radio quasars. We discuss the implications of our results for theoretical models of blazar variability.« less

  17. Structural Damage Identification in Stiffened Plate Fatigue Specimens Using Piezoelectric Active Sensing

    DTIC Science & Technology

    2011-09-01

    isolated AO mode first arrival, recorded at PZT 2, is shown at 3 different fatigue levels. Figure 5. The area under the PSD curve, calculated twice...Structural Damage Identification in Stiffened Plate Fatigue Specimens Using Piezoelectric Active Sensing B. L. GRISSO, G. PARK, L. W. SALVINO...with several challenges including limited performance knowledge of the materials, aluminum sensitization, structural fatigue performance, and

  18. Artifacts Of Spectral Analysis Of Instrument Readings

    NASA Technical Reports Server (NTRS)

    Wise, James H.

    1995-01-01

    Report presents experimental and theoretical study of some of artifacts introduced by processing outputs of two nominally identical low-frequency-reading instruments; high-sensitivity servo-accelerometers mounted together and operating, in conjunction with signal-conditioning circuits, as seismometers. Processing involved analog-to-digital conversion with anti-aliasing filtering, followed by digital processing including frequency weighting and computation of different measures of power spectral density (PSD).

  19. How accurately can the peak skin dose in fluoroscopy be determined using indirect dose metrics?

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

    Jones, A. Kyle, E-mail: kyle.jones@mdanderson.org; Ensor, Joe E.; Pasciak, Alexander S.

    Purpose: Skin dosimetry is important for fluoroscopically-guided interventions, as peak skin doses (PSD) that result in skin reactions can be reached during these procedures. There is no consensus as to whether or not indirect skin dosimetry is sufficiently accurate for fluoroscopically-guided interventions. However, measuring PSD with film is difficult and the decision to do so must be madea priori. The purpose of this study was to assess the accuracy of different types of indirect dose estimates and to determine if PSD can be calculated within ±50% using indirect dose metrics for embolization procedures. Methods: PSD were measured directly using radiochromicmore » film for 41 consecutive embolization procedures at two sites. Indirect dose metrics from the procedures were collected, including reference air kerma. Four different estimates of PSD were calculated from the indirect dose metrics and compared along with reference air kerma to the measured PSD for each case. The four indirect estimates included a standard calculation method, the use of detailed information from the radiation dose structured report, and two simplified calculation methods based on the standard method. Indirect dosimetry results were compared with direct measurements, including an analysis of uncertainty associated with film dosimetry. Factors affecting the accuracy of the different indirect estimates were examined. Results: When using the standard calculation method, calculated PSD were within ±35% for all 41 procedures studied. Calculated PSD were within ±50% for a simplified method using a single source-to-patient distance for all calculations. Reference air kerma was within ±50% for all but one procedure. Cases for which reference air kerma or calculated PSD exhibited large (±35%) differences from the measured PSD were analyzed, and two main causative factors were identified: unusually small or large source-to-patient distances and large contributions to reference air kerma from cone beam computed tomography or acquisition runs acquired at large primary gantry angles. When calculated uncertainty limits [−12.8%, 10%] were applied to directly measured PSD, most indirect PSD estimates remained within ±50% of the measured PSD. Conclusions: Using indirect dose metrics, PSD can be determined within ±35% for embolization procedures. Reference air kerma can be used without modification to set notification limits and substantial radiation dose levels, provided the displayed reference air kerma is accurate. These results can reasonably be extended to similar procedures, including vascular and interventional oncology. Considering these results, film dosimetry is likely an unnecessary effort for these types of procedures when indirect dose metrics are available.« less

  20. Durable fear memories require PSD-95

    PubMed Central

    Fitzgerald, Paul J.; Pinard, Courtney R.; Camp, Marguerite C.; Feyder, Michael; Sah, Anupam; Bergstrom, Hadley; Graybeal, Carolyn; Liu, Yan; Schlüter, Oliver; Grant, Seth G.N.; Singewald, Nicolas; Xu, Weifeng; Holmes, Andrew

    2014-01-01

    Traumatic fear memories are highly durable but also dynamic, undergoing repeated reactivation and rehearsal over time. While overly persistent fear memories underlie anxiety disorders such as posttraumatic stress disorder, the key neural and molecular mechanisms underlying fear memory durability remain unclear. Post-synaptic density 95 (PSD-95) is a synaptic protein regulating glutamate receptor anchoring, synaptic stability and certain types of memory. Employing a loss-of-function mutant mouse lacking the guanylate kinase domain of PSD-95 (PSD-95GK), we analyzed the contribution of PSD-95 to fear memory formation and retrieval, and sought to identify the neural basis of PSD-95-mediated memory maintenance using ex vivo immediate-early gene mapping, in vivo neuronal recordings and viral-mediated knockdown approaches. We show that PSD-95 is dispensable for the formation and expression of recent fear memories, but essential for the formation of precise and flexible fear memories and for the maintenance of memories at remote time points. The failure of PSD-95GK mice to retrieve remote cued fear memories was associated with hypoactivation of the infralimbic cortex (IL) (not anterior cingulate (ACC) or prelimbic cortex), reduced IL single-unit firing and bursting, and attenuated IL gamma and theta oscillations. Adeno-associated PSD-95 virus-mediated knockdown in the IL, not ACC, was sufficient to impair recent fear extinction and remote fear memory, and remodel IL dendritic spines. Collectively, these data identify PSD-95 in the IL as a critical mechanism supporting the durability of fear memories over time. These preclinical findings have implications for developing novel approaches to treating trauma-based anxiety disorders that target the weakening of overly persistent fear memories. PMID:25510511

  1. Durable fear memories require PSD-95.

    PubMed

    Fitzgerald, P J; Pinard, C R; Camp, M C; Feyder, M; Sah, A; Bergstrom, H C; Graybeal, C; Liu, Y; Schlüter, O M; Grant, S G; Singewald, N; Xu, W; Holmes, A

    2015-07-01

    Traumatic fear memories are highly durable but also dynamic, undergoing repeated reactivation and rehearsal over time. Although overly persistent fear memories underlie anxiety disorders, such as posttraumatic stress disorder, the key neural and molecular mechanisms underlying fear memory durability remain unclear. Postsynaptic density 95 (PSD-95) is a synaptic protein regulating glutamate receptor anchoring, synaptic stability and certain types of memory. Using a loss-of-function mutant mouse lacking the guanylate kinase domain of PSD-95 (PSD-95(GK)), we analyzed the contribution of PSD-95 to fear memory formation and retrieval, and sought to identify the neural basis of PSD-95-mediated memory maintenance using ex vivo immediate-early gene mapping, in vivo neuronal recordings and viral-mediated knockdown (KD) approaches. We show that PSD-95 is dispensable for the formation and expression of recent fear memories, but essential for the formation of precise and flexible fear memories and for the maintenance of memories at remote time points. The failure of PSD-95(GK) mice to retrieve remote cued fear memory was associated with hypoactivation of the infralimbic (IL) cortex (but not the anterior cingulate cortex (ACC) or prelimbic cortex), reduced IL single-unit firing and bursting, and attenuated IL gamma and theta oscillations. Adeno-associated virus-mediated PSD-95 KD in the IL, but not the ACC, was sufficient to impair recent fear extinction and remote fear memory, and remodel IL dendritic spines. Collectively, these data identify PSD-95 in the IL as a critical mechanism supporting the durability of fear memories over time. These preclinical findings have implications for developing novel approaches to treating trauma-based anxiety disorders that target the weakening of overly persistent fear memories.

  2. Pima County Department of Environmental Quality PSD Delegation Agreement

    EPA Pesticide Factsheets

    This delegation agreement is for the entire Prevention of Significant Deterioration (PSD) program. This allows Pima County Air Quality District (Pima County ACQD) to issue PSD permits using 40 CFR 52.21

  3. PSD-93 deletion inhibits Fyn-mediated phosphorylation of NR2B and protects against focal cerebral ischemia.

    PubMed

    Zhang, Meijuan; Li, Qingjie; Chen, Ling; Li, Jie; Zhang, Xin; Chen, Xiang; Zhang, Qingxiu; Shao, Yuan; Xu, Yun

    2014-08-01

    Modification of N-methyl-d-aspartate receptor (NMDAR)-mediated excitotoxicity appears to be a potential target in the treatment of ischemic stroke. Postsynaptic density protein-93 (PSD-93) specifically binds the C-terminal tails of the NMDAR, which is critical to couple NMDAR activity to specific intracellular signaling. This study is to investigate whether PSD-93 disruption displays neuroprotection in a focal ischemic stroke model of adult mice and, if it does, to explore possible mechanisms. It was found that, following middle cerebral artery occlusion (MCAO), PSD-93 knockout (KO) mice manifested significant reductions in infarcted volume, neurological deficits and number of degenerated neurons. PSD-93 deletion also reduced cultured cortical neuronal death caused by glucose and oxygen deprivation (OGD). Ischemic long term potentiation (i-LTP) could not be induced in the PSD-93 KO group and wild type (WT) groups pretreated with either AP-5 (NMDAR inhibitor) or PP2 (Src family inhibitor). PSD-93 KO decreased the phosphorylation of the NR2B at Tyr1472 and the interaction between NR2B and Fyn after MCAO. Together, our study demonstrated that PSD-93 KO confers profound neuroprotection against ischemic brain injury, which probably links to the inhibitory effect on Fyn-mediated phosphorylation of NR2B caused by PSD-93 deletion. These findings may provide a novel avenue for the treatment of ischemic stroke. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Winter precipitation particle size distribution measurement by Multi-Angle Snowflake Camera

    NASA Astrophysics Data System (ADS)

    Huang, Gwo-Jong; Kleinkort, Cameron; Bringi, V. N.; Notaroš, Branislav M.

    2017-12-01

    From the radar meteorology viewpoint, the most important properties for quantitative precipitation estimation of winter events are 3D shape, size, and mass of precipitation particles, as well as the particle size distribution (PSD). In order to measure these properties precisely, optical instruments may be the best choice. The Multi-Angle Snowflake Camera (MASC) is a relatively new instrument equipped with three high-resolution cameras to capture the winter precipitation particle images from three non-parallel angles, in addition to measuring the particle fall speed using two pairs of infrared motion sensors. However, the results from the MASC so far are usually presented as monthly or seasonally, and particle sizes are given as histograms, no previous studies have used the MASC for a single storm study, and no researchers use MASC to measure the PSD. We propose the methodology for obtaining the winter precipitation PSD measured by the MASC, and present and discuss the development, implementation, and application of the new technique for PSD computation based on MASC images. Overall, this is the first study of the MASC-based PSD. We present PSD MASC experiments and results for segments of two snow events to demonstrate the performance of our PSD algorithm. The results show that the self-consistency of the MASC measured single-camera PSDs is good. To cross-validate PSD measurements, we compare MASC mean PSD (averaged over three cameras) with the collocated 2D Video Disdrometer, and observe good agreements of the two sets of results.

  5. PSD-95 regulates synaptic kainate receptors at mouse hippocampal mossy fiber-CA3 synapses.

    PubMed

    Suzuki, Etsuko; Kamiya, Haruyuki

    2016-06-01

    Kainate-type glutamate receptors (KARs) are the third class of ionotropic glutamate receptors whose activation leads to the unique roles in regulating synaptic transmission and circuit functions. In contrast to AMPA receptors (AMPARs), little is known about the mechanism of synaptic localization of KARs. PSD-95, a major scaffold protein of the postsynaptic density, is a candidate molecule that regulates the synaptic KARs. Although PSD-95 was shown to bind directly to KARs subunits, it has not been tested whether PSD-95 regulates synaptic KARs in intact synapses. Using PSD-95 knockout mice, we directly investigated the role of PSD-95 in the KARs-mediated components of synaptic transmission at hippocampal mossy fiber-CA3 synapse, one of the synapses with the highest density of KARs. Mossy fiber EPSCs consist of AMPA receptor (AMPAR)-mediated fast component and KAR-mediated slower component, and the ratio was significantly reduced in PSD-95 knockout mice. The size of KARs-mediated field EPSP reduced in comparison with the size of the fiber volley. Analysis of KARs-mediated miniature EPSCs also suggested reduced synaptic KARs. All the evidence supports critical roles of PSD-95 in regulating synaptic KARs. Copyright © 2015 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  6. The effect of particle size distribution on the design of urban stormwater control measures

    USGS Publications Warehouse

    Selbig, William R.; Fienen, Michael N.; Horwatich, Judy A.; Bannerman, Roger T.

    2016-01-01

    An urban pollutant loading model was used to demonstrate how incorrect assumptions on the particle size distribution (PSD) in urban runoff can alter the design characteristics of stormwater control measures (SCMs) used to remove solids in stormwater. Field-measured PSD, although highly variable, is generally coarser than the widely-accepted PSD characterized by the Nationwide Urban Runoff Program (NURP). PSDs can be predicted based on environmental surrogate data. There were no appreciable differences in predicted PSD when grouped by season. Model simulations of a wet detention pond and catch basin showed a much smaller surface area is needed to achieve the same level of solids removal using the median value of field-measured PSD as compared to NURP PSD. Therefore, SCMs that used the NURP PSD in the design process could be unnecessarily oversized. The median of measured PSDs, although more site-specific than NURP PSDs, could still misrepresent the efficiency of an SCM because it may not adequately capture the variability of individual runoff events. Future pollutant loading models may account for this variability through regression with environmental surrogates, but until then, without proper site characterization, the adoption of a single PSD to represent all runoff conditions may result in SCMs that are under- or over-sized, rendering them ineffective or unnecessarily costly.

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

    Wurtz, R.; Kaplan, A.

    Pulse shape discrimination (PSD) is a variety of statistical classifier. Fully-­realized statistical classifiers rely on a comprehensive set of tools for designing, building, and implementing. PSD advances rely on improvements to the implemented algorithm. PSD advances can be improved by using conventional statistical classifier or machine learning methods. This paper provides the reader with a glossary of classifier-­building elements and their functions in a fully-­designed and operational classifier framework that can be used to discover opportunities for improving PSD classifier projects. This paper recommends reporting the PSD classifier’s receiver operating characteristic (ROC) curve and its behavior at a gamma rejectionmore » rate (GRR) relevant for realistic applications.« less

  8. PSD-95 promotes synaptogenesis and multiinnervated spine formation through nitric oxide signaling

    PubMed Central

    Nikonenko, Irina; Boda, Bernadett; Steen, Sylvain; Knott, Graham; Welker, Egbert; Muller, Dominique

    2008-01-01

    Postsynaptic density 95 (PSD-95) is an important regulator of synaptic structure and plasticity. However, its contribution to synapse formation and organization remains unclear. Using a combined electron microscopic, genetic, and pharmacological approach, we uncover a new mechanism through which PSD-95 regulates synaptogenesis. We find that PSD-95 overexpression affected spine morphology but also promoted the formation of multiinnervated spines (MISs) contacted by up to seven presynaptic terminals. The formation of multiple contacts was specifically prevented by deletion of the PDZ2 domain of PSD-95, which interacts with nitric oxide (NO) synthase (NOS). Similarly, PSD-95 overexpression combined with small interfering RNA–mediated down-regulation or the pharmacological blockade of NOS prevented axon differentiation into varicosities and multisynapse formation. Conversely, treatment of hippocampal slices with an NO donor or cyclic guanosine monophosphate analogue induced MISs. NOS blockade also reduced spine and synapse density in developing hippocampal cultures. These results indicate that the postsynaptic site, through an NOS–PSD-95 interaction and NO signaling, promotes synapse formation with nearby axons. PMID:19075115

  9. Live Imaging of Endogenous PSD-95 Using ENABLED: A Conditional Strategy to Fluorescently Label Endogenous Proteins

    PubMed Central

    Fortin, Dale A.; Tillo, Shane E.; Yang, Guang; Rah, Jong-Cheol; Melander, Joshua B.; Bai, Suxia; Soler-Cedeño, Omar; Qin, Maozhen; Zemelman, Boris V.; Guo, Caiying

    2014-01-01

    Stoichiometric labeling of endogenous synaptic proteins for high-contrast live-cell imaging in brain tissue remains challenging. Here, we describe a conditional mouse genetic strategy termed endogenous labeling via exon duplication (ENABLED), which can be used to fluorescently label endogenous proteins with near ideal properties in all neurons, a sparse subset of neurons, or specific neuronal subtypes. We used this method to label the postsynaptic density protein PSD-95 with mVenus without overexpression side effects. We demonstrated that mVenus-tagged PSD-95 is functionally equivalent to wild-type PSD-95 and that PSD-95 is present in nearly all dendritic spines in CA1 neurons. Within spines, while PSD-95 exhibited low mobility under basal conditions, its levels could be regulated by chronic changes in neuronal activity. Notably, labeled PSD-95 also allowed us to visualize and unambiguously examine otherwise-unidentifiable excitatory shaft synapses in aspiny neurons, such as parvalbumin-positive interneurons and dopaminergic neurons. Our results demonstrate that the ENABLED strategy provides a valuable new approach to study the dynamics of endogenous synaptic proteins in vivo. PMID:25505322

  10. Anchoring and synaptic stability of PSD-95 is driven by ephrin-B3.

    PubMed

    Hruska, Martin; Henderson, Nathan T; Xia, Nan L; Le Marchand, Sylvain J; Dalva, Matthew B

    2015-11-01

    Organization of signaling complexes at excitatory synapses by membrane-associated guanylate kinase (MAGUK) proteins regulates synapse development, plasticity, senescence and disease. Post-translational modification of MAGUK family proteins can drive their membrane localization, yet it is unclear how these intracellular proteins are targeted to sites of synaptic contact. Here we show using super-resolution imaging, biochemical approaches and in vivo models that the trans-synaptic organizing protein ephrin-B3 controls the synaptic localization and stability of PSD-95 and links these events to changes in neuronal activity via negative regulation of a newly identified mitogen-associated protein kinase (MAPK)-dependent phosphorylation site on ephrin-B3, Ser332. Unphosphorylated ephrin-B3 was enriched at synapses, and interacted directly with and stabilized PSD-95 at synapses. Activity-induced phosphorylation of Ser332 dispersed ephrin-B3 from synapses, prevented the interaction with PSD-95 and enhanced the turnover of PSD-95. Thus, ephrin-B3 specifies the synaptic localization of PSD-95 and likely links the synaptic stability of PSD-95 to changes in neuronal activity.

  11. [Changes in facial nerve function, morphology and neurotrophic factor III expression following three types of facial nerve injury].

    PubMed

    Zhang, Lili; Wang, Haibo; Fan, Zhaomin; Han, Yuechen; Xu, Lei; Zhang, Haiyan

    2011-01-01

    To study the changes in facial nerve function, morphology and neurotrophic factor III (NT-3) expression following three types of facial nerve injury. Changes in facial nerve function (in terms of blink reflex (BF), vibrissae movement (VM) and position of nasal tip) were assessed in 45 rats in response to three types of facial nerve injury: partial section of the extratemporal segment (group one), partial section of the facial canal segment (group two) and complete transection of the facial canal segment lesion (group three). All facial nerves specimen were then cut into two parts at the site of the lesion after being taken from the lesion site on 1st, 7th, 21st post-surgery-days (PSD). Changes of morphology and NT-3 expression were evaluated using the improved trichrome stain and immunohistochemistry techniques ,respectively. Changes in facial nerve function: In group 1, all animals had no blink reflex (BF) and weak vibrissae movement (VM) at the 1st PSD; The blink reflex in 80% of the rats recovered partly and the vibrissae movement in 40% of the rats returned to normal at the 7th PSD; The facial nerve function in 600 of the rats was almost normal at the 21st PSD. In group 2, all left facial nerve paralyzed at the 1st PSD; The blink reflex partly recovered in 40% of the rats and the vibrissae movement was weak in 80% of the rats at the 7th PSD; 8000 of the rats'BF were almost normal and 40% of the rats' VM completely recovered at the 21st PSD. In group 3, The recovery couldn't happen at anytime. Changes in morphology: In group 1, the size of nerve fiber differed in facial canal segment and some of myelin sheath and axons degenerated at the 7th PSD; The fibres' degeneration turned into regeneration at the 21st PSD; In group 2, the morphologic changes in this group were familiar with the group 1 while the degenerated fibers were more and dispersed in transection at the 7th PSD; Regeneration of nerve fibers happened at the 21st PSD. In group 3, most of the fibers crumbled at the 7th PSD and no regeneration was seen at the 21st PSD. Changes in NT-3: Positive staining of NT-3 was largely observed in axons at the 7th PSD, although little NT-3 was seen in the normal fibers. Facial palsy of the rats in group 2 was more extensive than that in group 1 and their function partly recovers at the 21st PSD. The fibres' degeneration occurs not only dispersed throughout the injury site but also occurred throught the length of the nerve. NT-3 immunoreactivity increased in activated fibers after partial transection.

  12. Study on phase noise induced by 1/f noise of the modulator drive circuit in high-sensitivity fiber optic gyroscope

    NASA Astrophysics Data System (ADS)

    Teng, Fei; Jin, Jing; Li, Yong; Zhang, Chunxi

    2018-05-01

    The contribution of modulator drive circuit noise as a 1/f noise source to the output noise of the high-sensitivity interferometric fiber optic gyroscope (IFOG) was studied here. A noise model of closed-loop IFOG was built. By applying the simulated 1/f noise sequence into the model, a gyroscope output data series was acquired, and the corresponding power spectrum density (PSD) and the Allan variance curve were calculated to analyze the noise characteristic. The PSD curve was in the spectral shape of 1/f, which verifies that the modulator drive circuit induced a low frequency 1/f phase noise into the gyroscope. The random walk coefficient (RWC), a standard metric to characterize the noise performance of the IFOG, was calculated according to the Allan variance curve. Using an operational amplifier with an input 1/f noise of 520 nV/√Hz at 1 Hz, the RWC induced by this 1/f noise was 2 × 10-4°/√h, which accounts for 63% of the total RWC. To verify the correctness of the noise model we proposed, a high-sensitivity gyroscope prototype was built and tested. The simulated Allan variance curve gave a good rendition of the prototype actual measured curve. The error percentage between the simulated RWC and the measured value was less than 13%. According to the model, a noise reduction method is proposed and the effectiveness is verified by the experiment.

  13. Practical Findings from Applying the PSD Model for Evaluating Software Design Specifications

    NASA Astrophysics Data System (ADS)

    Räisänen, Teppo; Lehto, Tuomas; Oinas-Kukkonen, Harri

    This paper presents practical findings from applying the PSD model to evaluating the support for persuasive features in software design specifications for a mobile Internet device. On the one hand, our experiences suggest that the PSD model fits relatively well for evaluating design specifications. On the other hand, the model would benefit from more specific heuristics for evaluating each technique to avoid unnecessary subjectivity. Better distinction between the design principles in the social support category would also make the model easier to use. Practitioners who have no theoretical background can apply the PSD model to increase the persuasiveness of the systems they design. The greatest benefit of the PSD model for researchers designing new systems may be achieved when it is applied together with a sound theory, such as the Elaboration Likelihood Model. Using the ELM together with the PSD model, one may increase the chances for attitude change.

  14. Properties of pattern standard deviation in open-angle glaucoma patients with hemi-optic neuropathy and bi-optic neuropathy.

    PubMed

    Heo, Dong Won; Kim, Kyoung Nam; Lee, Min Woo; Lee, Sung Bok; Kim, Chang-Sik

    2017-01-01

    To evaluate the properties of pattern standard deviation (PSD) according to localization of the glaucomatous optic neuropathy. We enrolled 242 eyes of 242 patients with primary open-angle glaucoma, with a best-corrected visual acuity ≥ 20/25, and no media opacity. Patients were examined via dilated fundus photography, spectral-domain optical coherence tomography, and Humphrey visual field examination, and divided into those with hemi-optic neuropathy (superior or inferior) and bi-optic neuropathy (both superior and inferior). We assessed the relationship between mean deviation (MD) and PSD. Using broken stick regression analysis, the tipping point was identified, i.e., the point at which MD became significantly associated with a paradoxical reversal of PSD. In 91 patients with hemi-optic neuropathy, PSD showed a strong correlation with MD (r = -0.973, β = -0.965, p < 0.001). The difference between MD and PSD ("-MD-PSD") was constant (mean, -0.32 dB; 95% confidence interval, -2.48~1.84 dB) regardless of visual field defect severity. However, in 151 patients with bi-optic neuropathy, a negative correlation was evident between "-MD-PSD" and MD (r2 = 0.907, p < 0.001). Overall, the MD tipping point was -14.0 dB, which was close to approximately 50% damage of the entire visual field (p < 0.001). Although a false decrease of PSD usually begins at approximately 50% visual field damage, in patients with hemi-optic neuropathy, the PSD shows no paradoxical decrease and shows a linear correlation with MD.

  15. 75 FR 56106 - Notice of Prevention of Significant Deterioration Final Determination for Power Holdings of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-15

    ... Deterioration (PSD) permit issued to Power Holdings of Illinois, LLC, by the Illinois Environmental Protection... under authority of a PSD delegation agreement, issued a PSD permit to Power Holdings of Illinois, LLC...

  16. A novel CMOS transducer for giant magnetoresistance sensors.

    PubMed

    Luong, Van Su; Lu, Chih-Cheng; Yang, Jing-Wen; Jeng, Jen-Tzong

    2017-02-01

    In this work, an ASIC (application specific integrated circuits) transducer circuit for field modulated giant magnetoresistance (GMR) sensors was designed and fabricated using a 0.18-μm CMOS process. The transducer circuits consist of a frequency divider, a digital phase shifter, an instrument amplifier, and an analog mixer. These comprise a mix of analog and digital circuit techniques. The compact chip size of 1.5 mm × 1.5 mm for both analog and digital parts was achieved using the TSMC18 1P6M (1-polysilicon 6-metal) process design kit, and the characteristics of the system were simulated using an HSpice simulator. The output of the transducer circuit is the result of the first harmonic detection, which resolves the modulated field using a phase sensitive detection (PSD) technique and is proportional to the measured magnetic field. When the dual-bridge GMR sensor is driven by the transducer circuit with a current of 10 mA at 10 kHz, the observed sensitivity of the field sensor is 10.2 mV/V/Oe and the nonlinearity error was 3% in the linear range of ±1 Oe. The performance of the system was also verified by rotating the sensor system horizontally in earth's magnetic field and recording the sinusoidal output with respect to the azimuth angle, which exhibits an error of less than ±0.04 Oe. These results prove that the ASIC transducer is suitable for driving the AC field modulated GMR sensors applied to geomagnetic measurement.

  17. Visual-spatial learning impairments are associated with hippocampal PSD-95 protein dysregulation in a mouse model of fragile X syndrome.

    PubMed

    Gandhi, Réno M; Kogan, Cary S; Messier, Claude; Macleod, Lindsey S

    2014-03-05

    Fragile X syndrome is the most common cause of inherited intellectual disability and is caused by the lack of fragile X mental retardation protein (FMRP) expression. In-vitro findings in mice and post-mortem autopsies in humans are characterized by dendritic spine abnormalities in the absence of Fmrp/FMRP. Biochemical and electrophysiological studies have identified postsynaptic density protein (PSD)-95 as having an established role in dendritic morphology as well as a molecular target of Fmrp. How Fmrp affects the expression of PSD-95 following behavioral learning is unknown. In the current study, wild type controls and Fmr1 knockout mice were trained in a subset of the Hebb-Williams (H-W) mazes. Dorsal hippocampal PSD-95 protein levels relative to a stable cytoskeleton protein (β-tubulin) were measured. We report a significant upregulation of PSD-95 protein levels in wild type mice, whereas training-related protein increases were blunted in Fmr1 knockout mice. In addition, there was a significant negative correlation between mean total errors on the mazes and PSD-95 protein levels. The coefficient of determination indicated that the mean total errors on the H-W mazes accounted for 35% of the variance in PSD-95 protein levels. These novel findings suggest that reduced PSD-95-associated postsynaptic plasticity may contribute to the learning and memory deficits observed in human fragile X syndrome patients.

  18. Clinical outcomes of EUS-guided drainage of debris-containing pancreatic pseudocysts: a large multicenter study.

    PubMed

    Yang, Dennis; Amin, Sunil; Gonzalez, Susana; Mullady, Daniel; Edmundowicz, Steven A; DeWitt, John M; Khashab, Mouen A; Wang, Andrew Y; Nagula, Satish; Buscaglia, Jonathan M; Bucobo, Juan Carlos; Wagh, Mihir S; Draganov, Peter V; Stevens, Tyler; Vargo, John J; Khara, Harshit S; Diehl, David L; Keswani, Rajesh N; Komanduri, Srinadh; Yachimski, Patrick S; Prabhu, Anoop; Kwon, Richard S; Watson, Rabindra R; Goodman, Adam J; Benias, Petros; Carr-Locke, David L; DiMaio, Christopher J

    2017-02-01

    Background and study aims  Data on clinical outcomes of endoscopic drainage of debris-free pseudocysts (PDF) versus pseudocysts containing solid debris (PSD) are very limited. The aims of this study were to compare treatment outcomes between patients with PDF vs. PSD undergoing endoscopic ultrasound (EUS)-guided drainage via transmural stents. Patients and methods  Retrospective review of 142 consecutive patients with pseudocysts who underwent EUS-guided transmural drainage (TM) from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TM technical success, treatment outcomes (symptomatic and radiologic resolution), need for endoscopic re-intervention at follow-up, and adverse events (AEs). Results  TM was performed in 90 patients with PDF and 52 with PSD. Technical success: PDF 87 (96.7 %) vs. PSD 51 (98.1 %). There was no difference in the rates for endoscopic re-intervention (5.5 % in PDF vs. 11.5 % in PSD; P =  0.33) or AEs (12.2 % in PDF vs. 19.2 % in PSD; P  = 0.33). Median long-term follow-up after stent removal was 297 days (interquartile range [IQR]: 59 - 424 days) for PDF and 326 days (IQR: 180 - 448 days) for PSD ( P  = 0.88). There was a higher rate of short-term radiologic resolution of PDF (45; 66.2 %) vs. PSD (21; 51.2 %) (OR = 0.30; 95 % CI: 0.13 - 0.72; P  = 0.009). There was no difference in long-term symptomatic resolution (PDF: 70.4 % vs. PSD: 66.7 %; P  = 0.72) or radiologic resolution (PDF: 68.9 % vs. PSD: 78.6 %; P  = 0.72) Conclusions  There was no difference in need for endoscopic re-intervention, AEs or long-term treatment outcomes in patients with PDF vs. PSD undergoing EUS-guided drainage with transmural stents. Based on these results, the presence of solid debris in pancreatic fluid collections does not appear to be associated with a poorer outcome.

  19. 40 CFR 52.1586 - Section 110(a)(2) infrastructure requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and the 1997 and 2006 PM2.5 NAAQS are disapproved for the following sections 110(a)(2)(C) (PSD program only), (D)(i)(II) (PSD program only), (D)(ii), and (J) (PSD program only). These requirements are being...

  20. 40 CFR 52.1586 - Section 110(a)(2) infrastructure requirements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and the 1997 and 2006 PM2.5 NAAQS are disapproved for the following sections 110(a)(2)(C) (PSD program only), (D)(i)(II) (PSD program only), (D)(ii), and (J) (PSD program only). These requirements are being...

  1. Postsynaptic localization of PSD-95 is regulated by all three pathways downstream of TrkB signaling.

    PubMed

    Yoshii, Akira; Constantine-Paton, Martha

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) and its receptor TrkB regulate synaptic plasticity. TrkB triggers three downstream signaling pathways; Phosphatidylinositol 3-kinase (PI3K), Phospholipase Cγ (PLCγ) and Mitogen activated protein kinases/Extracellular signal-regulated kinases (MAPK/ERK). We previously showed two distinct mechanisms whereby BDNF-TrkB pathway controls trafficking of PSD-95, which is the major scaffold at excitatory synapses and is critical for synapse maturation. BDNF activates the PI3K-Akt pathway and regulates synaptic delivery of PSD-95 via vesicular transport (Yoshii and Constantine-Paton, 2007). BDNF-TrkB signaling also triggers PSD-95 palmitoylation and its transport to synapses through the phosphorylation of the palmitoylation enzyme ZDHHC8 by a protein kinase C (PKC; Yoshii etal., 2011). The second study used PKC inhibitors chelerythrine as well as a synthetic zeta inhibitory peptide (ZIP) which was originally designed to block the brain-specific PKC isoform protein kinase Mϖ (PKMϖ). However, recent studies raise concerns about specificity of ZIP. Here, we assessed the contribution of TrkB and its three downstream pathways to the synaptic distribution of endogenous PSD-95 in cultured neurons using chemical and genetic interventions. We confirmed that TrkB, PLC, and PI3K were critical for the postsynaptic distribution of PSD-95. Furthermore, suppression of MAPK/ERK also disrupted PSD-95 expression. Next, we examined the contribution of PKC. While both chelerythrine and ZIP suppressed the postsynaptic localization of PSD-95, RNA interference for PKMϖ did not have a significant effect. This result suggests that the ZIP peptide, widely used as the "specific" PKMϖ antagonist by many investigators may block a PKC variant other than PKMϖ such as PKCλ/ι. Our results indicate that TrkB regulates postsynaptic localization of PSD-95 through all three downstream pathways, but also recommend further work to identify other PKC variants that regulate palmitoylation and synaptic localization of PSD-95.

  2. Postsynaptic density 95 (PSD-95) serine 561 phosphorylation regulates a conformational switch and bidirectional dendritic spine structural plasticity.

    PubMed

    Wu, Qian; Sun, Miao; Bernard, Laura P; Zhang, Huaye

    2017-09-29

    Postsynaptic density 95 (PSD-95) is a major synaptic scaffolding protein that plays a key role in bidirectional synaptic plasticity, which is a process important for learning and memory. It is known that PSD-95 shows increased dynamics upon induction of plasticity. However, the underlying structural and functional changes in PSD-95 that mediate its role in plasticity remain unclear. Here we show that phosphorylation of PSD-95 at Ser-561 in its guanylate kinase (GK) domain, which is mediated by the partitioning-defective 1 (Par1) kinases, regulates a conformational switch and is important for bidirectional plasticity. Using a fluorescence resonance energy transfer (FRET) biosensor, we show that a phosphomimetic mutation of Ser-561 promotes an intramolecular interaction between GK and the nearby Src homology 3 (SH3) domain, leading to a closed conformation, whereas a non-phosphorylatable S561A mutation or inhibition of Par1 kinase activity decreases SH3-GK interaction, causing PSD-95 to adopt an open conformation. In addition, S561A mutation facilitates the interaction between PSD-95 and its binding partners. Fluorescence recovery after photobleaching imaging reveals that the S561A mutant shows increased stability, whereas the phosphomimetic S561D mutation increases PSD-95 dynamics at the synapse. Moreover, molecular replacement of endogenous PSD-95 with the S561A mutant blocks dendritic spine structural plasticity during chemical long-term potentiation and long-term depression. Endogenous Ser-561 phosphorylation is induced by synaptic NMDA receptor activation, and the SH3-GK domains exhibit a Ser-561 phosphorylation-dependent switch to a closed conformation during synaptic plasticity. Our results provide novel mechanistic insight into the regulation of PSD-95 in dendritic spine structural plasticity through phosphorylation-mediated regulation of protein dynamics and conformation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Boivin, Jonathan, E-mail: jonathan.boivin.1@ulaval.ca; Beaulieu, Luc; Beddar, Sam

    Purpose: The authors’ objective was to systematically assess the performance of seven photodetectors used in plastic scintillation dosimetry. The authors also propose some guidelines for selecting an appropriate detector for a specific application. Methods: The plastic scintillation detector (PSD) consisted of a 1-mm diameter, 10-mm long plastic scintillation fiber (BCF-60), which was optically coupled to a clear 10-m long optical fiber of the same diameter. A light-tight plastic sheath covered both fibers and the scintillator end was sealed. The clear fiber end was connected to one of the following photodetectors: two polychromatic cameras (one with an optical lens and onemore » with a fiber optic taper replacing the lens), a monochromatic camera with an optical lens, a PIN photodiode, an avalanche photodiode (APD), or a photomultiplier tube (PMT). A commercially available W1 PSD was also included in the study, but it relied on its own fiber and scintillator. Each PSD was exposed to both low-energy beams (120, 180, and 220 kVp) from an orthovoltage unit and high-energy beams (6 and 23 MV) from a linear accelerator. Various dose rates were tested to identify the operating range and accuracy of each photodetector. Results: For all photodetectors, the relative uncertainty was less than 5% for dose rates higher than 3 mGy/s. The cameras allowed multiple probes to be used simultaneously, but they are less sensitive to low-light signals. The PIN, APD, and PMT had higher sensitivity, making them more suitable for low dose rate and out-of-field dose monitoring. The relative uncertainty of the PMT was less than 1% at the lowest dose rate achieved (0.10 mGy/s), suggesting that it was optimal for use in live dosimetry. Conclusions: For dose rates higher than 3 mGy/s, the PIN diode is the most effective photodetector in terms of performance/cost ratio. For lower dose rates, such as those seen in interventional radiology or high-gradient radiotherapy, PMTs are the optimal choice.« less

  4. Live imaging of endogenous PSD-95 using ENABLED: a conditional strategy to fluorescently label endogenous proteins.

    PubMed

    Fortin, Dale A; Tillo, Shane E; Yang, Guang; Rah, Jong-Cheol; Melander, Joshua B; Bai, Suxia; Soler-Cedeño, Omar; Qin, Maozhen; Zemelman, Boris V; Guo, Caiying; Mao, Tianyi; Zhong, Haining

    2014-12-10

    Stoichiometric labeling of endogenous synaptic proteins for high-contrast live-cell imaging in brain tissue remains challenging. Here, we describe a conditional mouse genetic strategy termed endogenous labeling via exon duplication (ENABLED), which can be used to fluorescently label endogenous proteins with near ideal properties in all neurons, a sparse subset of neurons, or specific neuronal subtypes. We used this method to label the postsynaptic density protein PSD-95 with mVenus without overexpression side effects. We demonstrated that mVenus-tagged PSD-95 is functionally equivalent to wild-type PSD-95 and that PSD-95 is present in nearly all dendritic spines in CA1 neurons. Within spines, while PSD-95 exhibited low mobility under basal conditions, its levels could be regulated by chronic changes in neuronal activity. Notably, labeled PSD-95 also allowed us to visualize and unambiguously examine otherwise-unidentifiable excitatory shaft synapses in aspiny neurons, such as parvalbumin-positive interneurons and dopaminergic neurons. Our results demonstrate that the ENABLED strategy provides a valuable new approach to study the dynamics of endogenous synaptic proteins in vivo. Copyright © 2014 the authors 0270-6474/14/3416698-15$15.00/0.

  5. Decoding power-spectral profiles from FMRI brain activities during naturalistic auditory experience.

    PubMed

    Hu, Xintao; Guo, Lei; Han, Junwei; Liu, Tianming

    2017-02-01

    Recent studies have demonstrated a close relationship between computational acoustic features and neural brain activities, and have largely advanced our understanding of auditory information processing in the human brain. Along this line, we proposed a multidisciplinary study to examine whether power spectral density (PSD) profiles can be decoded from brain activities during naturalistic auditory experience. The study was performed on a high resolution functional magnetic resonance imaging (fMRI) dataset acquired when participants freely listened to the audio-description of the movie "Forrest Gump". Representative PSD profiles existing in the audio-movie were identified by clustering the audio samples according to their PSD descriptors. Support vector machine (SVM) classifiers were trained to differentiate the representative PSD profiles using corresponding fMRI brain activities. Based on PSD profile decoding, we explored how the neural decodability correlated to power intensity and frequency deviants. Our experimental results demonstrated that PSD profiles can be reliably decoded from brain activities. We also suggested a sigmoidal relationship between the neural decodability and power intensity deviants of PSD profiles. Our study in addition substantiates the feasibility and advantage of naturalistic paradigm for studying neural encoding of complex auditory information.

  6. Transcriptional response to deletion of the phosphatidylserine decarboxylase Psd1p in the yeast Saccharomyces cerevisiae.

    PubMed

    Gsell, Martina; Mascher, Gerald; Schuiki, Irmgard; Ploier, Birgit; Hrastnik, Claudia; Daum, Günther

    2013-01-01

    In the yeast, Saccharomyces cerevisiae, the synthesis of the essential phospholipid phosphatidylethanolamine (PE) is accomplished by a network of reactions which comprises four different pathways. The enzyme contributing most to PE formation is the mitochondrial phosphatidylserine decarboxylase 1 (Psd1p) which catalyzes conversion of phosphatidylserine (PS) to PE. To study the genome wide effect of an unbalanced cellular and mitochondrial PE level and in particular the contribution of Psd1p to this depletion we performed a DNA microarray analysis with a ∆psd1 deletion mutant. This approach revealed that 54 yeast genes were significantly up-regulated in the absence of PSD1 compared to wild type. Surprisingly, marked down-regulation of genes was not observed. A number of different cellular processes in different subcellular compartments were affected in a ∆psd1 mutant. Deletion mutants bearing defects in all 54 candidate genes, respectively, were analyzed for their growth phenotype and their phospholipid profile. Only three mutants, namely ∆gpm2, ∆gph1 and ∆rsb1, were affected in one of these parameters. The possible link of these mutations to PE deficiency and PSD1 deletion is discussed.

  7. Simultaneous data communication and position sensing with an impact ionization engineered avalanche photodiode array for free space optical communication

    NASA Astrophysics Data System (ADS)

    Ferraro, Mike S.; Mahon, Rita; Rabinovich, William S.; Murphy, James L.; Dexter, James L.; Clark, William R.; Waters, William D.; Vaccaro, Kenneth; Krejca, Brian D.

    2017-02-01

    Photodetectors in free space optical communication systems perform two functions: reception of data communication signals and position sensing for pointing, tracking, and stabilization. Traditionally, the optical receive path in an FSO system is split into separate paths for data detection and position sensing. The need for separate paths is a consequence of conflicting performance criteria between position sensitive detectors (PSD) and data detectors. Combining the functionality of both detector types requires that the combinational sensor not only have the bandwidth to support high data rate communication but the active area and spatial discrimination to accommodate position sensing. In this paper we present a large area, concentric five element impact ionization engineered avalanche photodiode array rated for bandwidths beyond 1GHz with a measured carrier ionization ratio of less than 0.1 at moderate APD gains. The integration of this array as a combinational sensor in an FSO system is discussed along with the development of a pointing and stabilization algorithm.

  8. Constraining the Origin of Phobos with the Elpasolite Planetary Ice and Composition Spectrometer (EPICS) - Simulated Performance

    NASA Astrophysics Data System (ADS)

    Nowicki, S. F.; Mesick, K.; Coupland, D. D. S.; Dallmann, N. A.; Feldman, W. C.; Stonehill, L. C.; Hardgrove, C.; Dibb, S.; Gabriel, T. S. J.; West, S.

    2017-12-01

    Elpasolites are a promising new family of inorganic scintillators that can detect both gamma rays and neutrons within a single detector volume, reducing the instrument size, weight, and power (SWaP), all of which are critical for planetary science missions. The ability to distinguish between neutron and gamma events is done through pulse shape discrimination (PSD). The Elpasolite Planetary Ice and Composition Spectrometer (EPICS) utilizes elpasolites in a next-generation, highly capable, low-SWaP gamma-ray and neutron spectrometer. We present simulated capabilities of EPICS sensitivities to neutron and gamma-rays, and demonstrate how EPICS can constrain the origin of Phobos between the following three main hypotheses: 1) accretion after a giant impact with Mars, 2) co-accretion with Mars, and 3) capture of an external body. The MCNP6 code was used to calculate the neutron and gamma-ray flux that escape the surface of Phobos, and GEANT4 to model the response of the EPICS instrument on orbit around Phobos.

  9. 40 CFR 124.5 - Modification, revocation and reissuance, or termination of permits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... §§ 123.25 (NPDES), 145.11 (UIC), 233.26 (404), and 271.14 (RCRA).) Permits (other than PSD permits) may... requirements of § 124.3. (g)(1) (Reserved for PSD Modification Provisions). (2) PSD permits may be terminated...

  10. 40 CFR 124.5 - Modification, revocation and reissuance, or termination of permits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... §§ 123.25 (NPDES), 145.11 (UIC), 233.26 (404), and 271.14 (RCRA).) Permits (other than PSD permits) may... requirements of § 124.3. (g)(1) (Reserved for PSD Modification Provisions). (2) PSD permits may be terminated...

  11. 40 CFR 124.5 - Modification, revocation and reissuance, or termination of permits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... §§ 123.25 (NPDES), 145.11 (UIC), 233.26 (404), and 271.14 (RCRA).) Permits (other than PSD permits) may... requirements of § 124.3. (g)(1) (Reserved for PSD Modification Provisions). (2) PSD permits may be terminated...

  12. 40 CFR 124.5 - Modification, revocation and reissuance, or termination of permits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... §§ 123.25 (NPDES), 145.11 (UIC), 233.26 (404), and 271.14 (RCRA).) Permits (other than PSD permits) may... requirements of § 124.3. (g)(1) (Reserved for PSD Modification Provisions). (2) PSD permits may be terminated...

  13. 40 CFR 124.5 - Modification, revocation and reissuance, or termination of permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... §§ 123.25 (NPDES), 145.11 (UIC), 233.26 (404), and 271.14 (RCRA).) Permits (other than PSD permits) may... requirements of § 124.3. (g)(1) (Reserved for PSD Modification Provisions). (2) PSD permits may be terminated...

  14. 40 CFR 52.2219 - Conditional approval.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... EPA is conditionally approving TDEC's submittal with respect to the PSD requirements of CAA sections... enforceable provisions for PSD increments as detailed in TDEC's October 4, 2012, commitment letter. Tennessee... PSD increments as described in the State's letter of commitment. (d) Conditional Approval—Submittal...

  15. New Variance-Reducing Methods for the PSD Analysis of Large Optical Surfaces

    NASA Technical Reports Server (NTRS)

    Sidick, Erkin

    2010-01-01

    Edge data of a measured surface map of a circular optic result in large variance or "spectral leakage" behavior in the corresponding Power Spectral Density (PSD) data. In this paper we present two new, alternative methods for reducing such variance in the PSD data by replacing the zeros outside the circular area of a surface map by non-zero values either obtained from a PSD fit (method 1) or taken from the inside of the circular area (method 2).

  16. PSD-95 interacts with NBCn1 and enhances channel-like activity without affecting Na/HCO(3) cotransport.

    PubMed

    Lee, Soojung; Yang, Han Soo; Kim, Eunjin; Ju, Eun Ji; Kwon, Min Hyung; Dudley, R Kyle; Smith, Yoland; Yun, C Chris; Choi, Inyeong

    2012-01-01

    The sodium/bicarbonate transporter NBCn1 plays an essential role in intracellular pH regulation and transepithelial HCO(3)(-) movement in the body. NBCn1 also has sodium channel-like activity uncoupled to Na/HCO(3) cotransport. We previously reported that NBCn1 interacts with the postsynaptic density protein PSD-95 in the brain. Here, we elucidated the structural determinant and functional consequence of NBCn1/PSD-95 interaction. In rat hippocampal CA3 neurons, NBCn1 was localized to the postsynaptic membranes of both dendritic shafts and spines and occasionally to the presynaptic membranes. A GST/NBCn1 fusion protein containing the C-terminal 131 amino acids of NBCn1 pulled down PSD-95 from rat brain lysates, whereas GST/NBCn1-ΔETSL (deletion of the last four amino acids) and GST/NBCn2 (NCBE) lacking the same ETSL did not. NBCn1 and PSD-95 were coimmunoprecipitated in HEK 293 cells, and their interaction did not affect the efficacy of PSD-95 to bind to the NMDA receptor NR2A. PSD-95 has negligible effects on intracellular pH changes mediated by NBCn1 in HEK 293 cells and Xenopus oocytes. However, PSD-95 increased an ionic conductance produced by NBCn1 channel-like activity. This increase was abolished by NBCn1-ΔETSL or by the peptide containing the last 15 amino acids of NBCn1. Our data suggest that PSD-95 interacts with NBCn1 and increases its channel-like activity while negligibly affecting Na/HCO(3) cotransport. The possibility that the channel-like activity occurs via an intermolecular cavity of multimeric NBCn1 proteins is discussed. Copyright © 2012 S. Karger AG, Basel.

  17. Small RNAs regulate the biocontrol property of fluorescent Pseudomonas strain Psd.

    PubMed

    Upadhyay, Anamika; Kochar, Mandira; Upadhyay, Ashutosh; Tripathy, Soumya; Rajam, Manchikatla Venkat; Srivastava, Sheela

    2017-03-01

    The production of biocontrol factors by Pseudomonads is reported to be controlled at the post-transcriptional level by the GacS/GacA signal transduction pathway. This involves RNA-binding translational repressor proteins, RsmA and RsmE, and the small regulatory RNAs (sRNAs) RsmX, RsmY, and RsmZ. While the former represses genes involved in secondary metabolite production, the latter relieves this repression at the end of exponential growth. We have studied the fluorescent Pseudomonas strain Psd, possessing good biocontrol potential, and confirmed the presence of rsmY and rsmZ by PCR amplification. Gene constructs for all the three small RNAs (RsmX, RsmY and RsmZ) carried on broad host-range plasmid, pME6032 were mobilized into strain Psd. Expression analysis of gacA in the recombinant strains over-expressing rsmX (Psd-pME7320), rsmY (Psd-pME6359) and rsmZ (Psd-pME6918) revealed a significant upregulation of the response regulator. Besides, a remarkable down-regulation of rsmA was also reported in all the strains. The variant strains were found to produce comparatively higher levels of phenazines. Indole acetic acid levels were higher to some extent, and strain Psd-pME6918 also showed elevated production of HCN. The tomato seedlings infected with Fusarium oxysporum and Verticillium dahliae in the presence of culture filtrate of the recombinant strains showed better plant protection response in comparison to the wild-type strain Psd. These results suggest that small RNAs are important determinants in regulation of the biocontrol property of strain Psd. Copyright © 2016 Elsevier GmbH. All rights reserved.

  18. PSD-95 family MAGUKs are essential for anchoring AMPA and NMDA receptor complexes at the postsynaptic density

    PubMed Central

    Chen, Xiaobing; Levy, Jonathan M.; Hou, Austin; Winters, Christine; Azzam, Rita; Sousa, Alioscka A.; Leapman, Richard D.; Nicoll, Roger A.; Reese, Thomas S.

    2015-01-01

    The postsynaptic density (PSD)-95 family of membrane-associated guanylate kinases (MAGUKs) are major scaffolding proteins at the PSD in glutamatergic excitatory synapses, where they maintain and modulate synaptic strength. How MAGUKs underlie synaptic strength at the molecular level is still not well understood. Here, we explore the structural and functional roles of MAGUKs at hippocampal excitatory synapses by simultaneous knocking down PSD-95, PSD-93, and synapse-associated protein (SAP)102 and combining electrophysiology and transmission electron microscopic (TEM) tomography imaging to analyze the resulting changes. Acute MAGUK knockdown greatly reduces synaptic transmission mediated by α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) and N-methyl-d-aspartate receptors (NMDARs). This knockdown leads to a significant rise in the number of silent synapses, diminishes the size of PSDs without changes in pre- or postsynaptic membrane, and depletes the number of membrane-associated PSD-95–like vertical filaments and transmembrane structures, identified as AMPARs and NMDARs by EM tomography. The differential distribution of these receptor-like structures and dependence of their abundance on PSD size matches that of AMPARs and NMDARs in the hippocampal synapses. The loss of these structures following MAGUK knockdown tracks the reduction in postsynaptic AMPAR and NMDAR transmission, confirming the structural identities of these two types of receptors. These results demonstrate that MAGUKs are required for anchoring both types of glutamate receptors at the PSD and are consistent with a structural model where MAGUKs, corresponding to membrane-associated vertical filaments, are the essential structural proteins that anchor and organize both types of glutamate receptors and govern the overall molecular organization of the PSD. PMID:26604311

  19. Identification of N-methyl-D-aspartic acid (NMDA) receptor subtype-specific binding sites that mediate direct interactions with scaffold protein PSD-95.

    PubMed

    Cousins, Sarah L; Stephenson, F Anne

    2012-04-13

    N-methyl-D-aspartate (NMDA) neurotransmitter receptors and the postsynaptic density-95 (PSD-95) membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins are integral components of post-synaptic macromolecular signaling complexes that serve to propagate glutamate responses intracellularly. Classically, NMDA receptor NR2 subunits associate with PSD-95 MAGUKs via a conserved ES(E/D)V amino acid sequence located at their C termini. We previously challenged this dogma to demonstrate a second non-ES(E/D)V PSD-95-binding site in both NMDA receptor NR2A and NR2B subunits. Here, using a combination of co-immunoprecipitations from transfected mammalian cells, yeast two-hybrid interaction assays, and glutathione S-transferase (GST) pulldown assays, we show that NR2A subunits interact directly with PSD-95 via the C-terminal ESDV motif and additionally via an Src homology 3 domain-binding motif that associates with the Src homology 3 domain of PSD-95. Peptide inhibition of co-immunoprecipitations of NR2A and PSD-95 demonstrates that both the ESDV and non-ESDV sites are required for association in native brain tissue. Furthermore, we refine the non-ESDV site within NR2B to residues 1149-1157. These findings provide a molecular basis for the differential association of NMDA receptor subtypes with PSD-95 MAGUK scaffold proteins. These selective interactions may contribute to the organization, lateral mobility, and ultimately the function of NMDA receptor subtypes at synapses. Furthermore, they provide a more general molecular mechanism by which the scaffold, PSD-95, may discriminate between potential interacting partner proteins.

  20. Identification of N-Methyl-d-aspartic Acid (NMDA) Receptor Subtype-specific Binding Sites That Mediate Direct Interactions with Scaffold Protein PSD-95*

    PubMed Central

    Cousins, Sarah L.; Stephenson, F. Anne

    2012-01-01

    N-methyl-d-aspartate (NMDA) neurotransmitter receptors and the postsynaptic density-95 (PSD-95) membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins are integral components of post-synaptic macromolecular signaling complexes that serve to propagate glutamate responses intracellularly. Classically, NMDA receptor NR2 subunits associate with PSD-95 MAGUKs via a conserved ES(E/D)V amino acid sequence located at their C termini. We previously challenged this dogma to demonstrate a second non-ES(E/D)V PSD-95-binding site in both NMDA receptor NR2A and NR2B subunits. Here, using a combination of co-immunoprecipitations from transfected mammalian cells, yeast two-hybrid interaction assays, and glutathione S-transferase (GST) pulldown assays, we show that NR2A subunits interact directly with PSD-95 via the C-terminal ESDV motif and additionally via an Src homology 3 domain-binding motif that associates with the Src homology 3 domain of PSD-95. Peptide inhibition of co-immunoprecipitations of NR2A and PSD-95 demonstrates that both the ESDV and non-ESDV sites are required for association in native brain tissue. Furthermore, we refine the non-ESDV site within NR2B to residues 1149–1157. These findings provide a molecular basis for the differential association of NMDA receptor subtypes with PSD-95 MAGUK scaffold proteins. These selective interactions may contribute to the organization, lateral mobility, and ultimately the function of NMDA receptor subtypes at synapses. Furthermore, they provide a more general molecular mechanism by which the scaffold, PSD-95, may discriminate between potential interacting partner proteins. PMID:22375001

  1. PSD-95 family MAGUKs are essential for anchoring AMPA and NMDA receptor complexes at the postsynaptic density.

    PubMed

    Chen, Xiaobing; Levy, Jonathan M; Hou, Austin; Winters, Christine; Azzam, Rita; Sousa, Alioscka A; Leapman, Richard D; Nicoll, Roger A; Reese, Thomas S

    2015-12-15

    The postsynaptic density (PSD)-95 family of membrane-associated guanylate kinases (MAGUKs) are major scaffolding proteins at the PSD in glutamatergic excitatory synapses, where they maintain and modulate synaptic strength. How MAGUKs underlie synaptic strength at the molecular level is still not well understood. Here, we explore the structural and functional roles of MAGUKs at hippocampal excitatory synapses by simultaneous knocking down PSD-95, PSD-93, and synapse-associated protein (SAP)102 and combining electrophysiology and transmission electron microscopic (TEM) tomography imaging to analyze the resulting changes. Acute MAGUK knockdown greatly reduces synaptic transmission mediated by α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) and N-methyl-d-aspartate receptors (NMDARs). This knockdown leads to a significant rise in the number of silent synapses, diminishes the size of PSDs without changes in pre- or postsynaptic membrane, and depletes the number of membrane-associated PSD-95-like vertical filaments and transmembrane structures, identified as AMPARs and NMDARs by EM tomography. The differential distribution of these receptor-like structures and dependence of their abundance on PSD size matches that of AMPARs and NMDARs in the hippocampal synapses. The loss of these structures following MAGUK knockdown tracks the reduction in postsynaptic AMPAR and NMDAR transmission, confirming the structural identities of these two types of receptors. These results demonstrate that MAGUKs are required for anchoring both types of glutamate receptors at the PSD and are consistent with a structural model where MAGUKs, corresponding to membrane-associated vertical filaments, are the essential structural proteins that anchor and organize both types of glutamate receptors and govern the overall molecular organization of the PSD.

  2. PSD-95 Interacts with NBCn1 and Enhances Channel-like Activity without Affecting Na/HCO3 Cotransport

    PubMed Central

    Lee, Soojung; Yang, Han Soo; Kim, Eunjin; Ju, Eun Ji; Kwon, Min Hyung; Dudley, R. Kyle; Smith, Yoland; Yun, C. Chris; Choi, Inyeong

    2013-01-01

    Background/Aims The sodium/bicarbonate transporter NBCn1 plays an essential role in intracellular pH regulation and transepithelial HCO3− movement in the body. NBCn1 also has sodium channel-like activity uncoupled to Na/HCO3 cotransport. We previously reported that NBCn1 interacts with the postsynaptic density protein PSD-95 in the brain. Here, we elucidated the structural determinant and functional consequence of NBCn1/PSD-95 interaction. Methods: Results In rat hippocampal CA3 neurons, NBCn1 was localized to the postsynaptic membranes of both dendritic shafts and spines and occasionally to the presynaptic membranes. A GST/NBCn1 fusion protein containing the C-terminal 131 amino acids of NBCn1 pulled down PSD-95 from rat brain lysates, whereas GST/NBCn1-ΔETSL (deletion of the last four amino acids) and GST/NBCn2 (NCBE) lacking the same ETSL did not. NBCn1 and PSD-95 were coimmunoprecipitated in HEK 293 cells, and their interaction did not affect the efficacy of PSD-95 to bind to the NMDA receptor NR2A. PSD-95 has negligible effects on intracellular pH changes mediated by NBCn1 in HEK 293 cells and Xenopus oocytes. However, PSD-95 increased an ionic conductance produced by NBCn1 channel-like activity. This increase was abolished by NBCn1-ΔETSL or by the peptide containing the last 15 amino acids of NBCn1. Conclusion Our data suggest that PSD-95 interacts with NBCn1 and increases its channel-like activity while negligibly affecting Na/HCO3 cotransport. The possibility that the channel-like activity occurs via an intermolecular cavity of multimeric NBCn1 proteins is discussed. PMID:23183381

  3. G quadruplex RNA structures in PSD-95 mRNA: potential regulators of miR-125a seed binding site accessibility.

    PubMed

    Stefanovic, Snezana; Bassell, Gary J; Mihailescu, Mihaela Rita

    2015-01-01

    Fragile X syndrome (FXS) is the most common inherited form of intellectual disability caused by the CGG trinucleotide expansion in the 3'-untranslated region of the FMR1 gene on the X chromosome, that silences the expression of the Fragile X mental retardation protein (FMRP). FMRP has been shown to bind to a G-rich region within the PSD-95 mRNA which encodes for the postsynaptic density protein 95 (PSD-95), and together with the microRNA miR-125a, to play an important role in the reversible inhibition of the PSD-95 mRNA translation in neurons. The loss of FMRP in Fmr1 KO mice disables this translation control in the production of the PSD-95 protein. Interestingly, the miR-125a binding site on PSD-95 mRNA is embedded in the G-rich region bound by FMRP and postulated to adopt one or more G quadruplex structures. In this study, we have used different biophysical techniques to validate and characterize the formation of parallel G quadruplex structures and binding of miR-125a to its complementary sequence located within the 3' UTR of PSD-95 mRNA. Our results indicate that the PSD-95 mRNA G-rich region folds into alternate G quadruplex conformations that coexist in equilibrium. miR-125a forms a stable complex with PSD-95 mRNA, as evident by characteristic Watson-Crick base-pairing that coexists with one of the G quadruplex forms, suggesting a novel mechanism for G quadruplex structures to regulate the access of miR-125a to its binding site. © 2014 Stefanovic et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  4. G quadruplex RNA structures in PSD-95 mRNA: potential regulators of miR-125a seed binding site accessibility

    PubMed Central

    Stefanovic, Snezana; Bassell, Gary J.

    2015-01-01

    Fragile X syndrome (FXS) is the most common inherited form of intellectual disability caused by the CGG trinucleotide expansion in the 3′-untranslated region of the FMR1 gene on the X chromosome, that silences the expression of the Fragile X mental retardation protein (FMRP). FMRP has been shown to bind to a G-rich region within the PSD-95 mRNA which encodes for the postsynaptic density protein 95 (PSD-95), and together with the microRNA miR-125a, to play an important role in the reversible inhibition of the PSD-95 mRNA translation in neurons. The loss of FMRP in Fmr1 KO mice disables this translation control in the production of the PSD-95 protein. Interestingly, the miR-125a binding site on PSD-95 mRNA is embedded in the G-rich region bound by FMRP and postulated to adopt one or more G quadruplex structures. In this study, we have used different biophysical techniques to validate and characterize the formation of parallel G quadruplex structures and binding of miR-125a to its complementary sequence located within the 3′ UTR of PSD-95 mRNA. Our results indicate that the PSD-95 mRNA G-rich region folds into alternate G quadruplex conformations that coexist in equilibrium. miR-125a forms a stable complex with PSD-95 mRNA, as evident by characteristic Watson–Crick base-pairing that coexists with one of the G quadruplex forms, suggesting a novel mechanism for G quadruplex structures to regulate the access of miR-125a to its binding site. PMID:25406362

  5. Peeling skin diseases: 21 cases from Turkey and a review of the literature.

    PubMed

    Köse, O; Safali, M; Koç, E; Arca, E; Açikgöz, G; Özmen, I; Yeniay, Y

    2012-07-01

    Peeling skin diseases (PSD) refer to a group of rare autosomal recessive dermatosis which are characterized by spontaneous, continual peeling of the skin. Three different clinical pictures can be distinguished: Inflammatory PSD also referred to as peeling skin syndrome (PSS) type B, non-inflammatory PSD also referred to as PSS type A, and localized forms i.e. acral type PSS. To characterize the clinical and histopathological features of PSD in Turkey. We retrospectively reviewed the medical records and clinical photographs of patients who were given diagnosis of PSD and conducted histopathological evaluation of skin biopsies to identify the site of cleavage. Also we evaluated the cases including age, gender, age onset, clinical and histological findings, family history, associated disorders and PSD type. Twenty-one patients with PSD were seen at Gulhane School of Medicine in Ankara between the years 1994 and 2010 in this retrospective study. All patients were men. Their ages were between 20 and 26 years (22.44±2.30, Mean age±SD). Of the patients, eight cases (40%) were type A, eight cases (40%) were type B, and five cases (20%) were acral type PSS. Eleven cases (52%) had parental consanguinity. Keratoderma, cheilitis, keratosis pilaris, melanonichia, clubbing, hyperhidrosis, onychodystrophy were observed in eight cases as an accompanying disorder. In this case series, PSD occurred rarely and also showed generally mild course of disease in Turkey and most likely related to consanguineous of marriages. Future investigations on PSD will contribute to our progressing alternative targets for pathogenesis-based therapy. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

  6. Evaluating Disease Severity in Chronic Pain Patients with and without Fibromyalgia: A Comparison of the Symptom Impact Questionnaire and the Polysymptomatic Distress Scale.

    PubMed

    Friend, Ronald; Bennett, Robert M

    2015-12-01

    To compare the relative effectiveness of the Polysymptomatic Distress Scale (PSD) with the Symptom Impact Questionnaire (SIQR), the disease-neutral revision of the updated Fibromyalgia Impact Questionnaire (FIQR), in their ability to assess disease activity in patients with rheumatic disorders both with and without fibromyalgia (FM). The study included 321 patients from 8 clinical practices with some 16 different chronic pain disorders. Disease severity was assessed by the Medical Outcomes Study Short Form-36 (SF-36). Univariate analyses were used to assess the magnitude of PSD and SIQR correlations with SF-36 subscales. Hierarchical stepwise regression was used to evaluate the unique contribution of the PSD and SIQR to the SF-36. Random forest regression probed the relative importance of the SIQR and PSD components as predictors of SF-36. The correlations with the SF-36 subscales were significantly higher for the SIQR (0.48 to 0.78) than the PSD (0.29 to 0.56; p < 0.001). Stepwise regression revealed that the SIQR was contributing additional unique variance on SF-36 subscales, which was not the case for the PSD. Random forest regression showed SIQR Function, Symptoms, and Global Impact subscales were more important predictors of SF-36 than the PSD. The single SIQR pain item contributed 55% of SF-36 pain variance compared to 23% with the 19-point WPI (the Widespread Pain Index component of PSD). The SIQR, the disease-neutral revision of the updated FIQ, has several important advantages over the PSD in the evaluation of disease severity in chronic pain disorders.

  7. Digital pulse shape discrimination.

    PubMed

    Miller, L F; Preston, J; Pozzi, S; Flaska, M; Neal, J

    2007-01-01

    Pulse-shape discrimination (PSD) has been utilised for about 40 years as a method to obtain estimates for dose in mixed neutron and photon fields. Digitizers that operate close to GHz are currently available at a reasonable cost, and they can be used to directly sample signals from photomultiplier tubes. This permits one to perform digital PSD rather than the traditional, and well-established, analogoue techniques. One issue that complicates PSD for neutrons in mixed fields is that the light output characteristics of typical scintillators available for PSD, such as BC501A, vary as a function of energy deposited in the detector. This behaviour is more easily accommodated with digital processing of signals than with analogoue signal processing. Results illustrate the effectiveness of digital PSD.

  8. Power-spectral-density relationship for retarded differential equations

    NASA Technical Reports Server (NTRS)

    Barker, L. K.

    1974-01-01

    The power spectral density (PSD) relationship between input and output of a set of linear differential-difference equations of the retarded type with real constant coefficients and delays is discussed. The form of the PSD relationship is identical with that applicable to unretarded equations. Since the PSD relationship is useful if and only if the system described by the equations is stable, the stability must be determined before applying the PSD relationship. Since it is sometimes difficult to determine the stability of retarded equations, such equations are often approximated by simpler forms. It is pointed out that some common approximations can lead to erroneous conclusions regarding the stability of a system and, therefore, to the possibility of obtaining PSD results which are not valid.

  9. 40 CFR 52.2134 - Original identification of plan section.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... for ozone nonattainment areas, PSD NOX increment regulations, and regulations listing the definition..., paragraph 4; covering PSD. These regulations were effective August 24, 1990, and submitted September 18... 4 covering PSD. These regulations were effective June 26, 1992, and submitted July 23, 1992. (ii...

  10. 40 CFR 52.2134 - Original identification of plan section.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... for ozone nonattainment areas, PSD NOX increment regulations, and regulations listing the definition..., paragraph 4; covering PSD. These regulations were effective August 24, 1990, and submitted September 18... 4 covering PSD. These regulations were effective June 26, 1992, and submitted July 23, 1992. (ii...

  11. 40 CFR 52.2134 - Original identification of plan section.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... for ozone nonattainment areas, PSD NOX increment regulations, and regulations listing the definition..., paragraph 4; covering PSD. These regulations were effective August 24, 1990, and submitted September 18... 4 covering PSD. These regulations were effective June 26, 1992, and submitted July 23, 1992. (ii...

  12. 40 CFR 52.2134 - Original identification of plan section.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... for ozone nonattainment areas, PSD NOX increment regulations, and regulations listing the definition..., paragraph 4; covering PSD. These regulations were effective August 24, 1990, and submitted September 18... 4 covering PSD. These regulations were effective June 26, 1992, and submitted July 23, 1992. (ii...

  13. Agrobacterium tumefaciens-mediated transformation of the soybean pathogen Phomopsis longicolla

    USDA-ARS?s Scientific Manuscript database

    Phomopsis seed decay (PSD) of soybean is caused primarily by the fungal pathogen Phomopsis longicolla. PSD impairs seed germination, reduces seedling vigor, and can substantially reduce stand establishment. In hot and humid conditions, PSD can cause significant yield losses. Few studies have explore...

  14. Evaluation of the membrane lipid selectivity of the pea defensin Psd1.

    PubMed

    Gonçalves, Sónia; Teixeira, Alexandre; Abade, João; de Medeiros, Luciano Neves; Kurtenbach, Eleonora; Santos, Nuno C

    2012-05-01

    Psd1, a 46 amino acid residues defensin isolated from the pea Pisum sativum seeds, exhibits anti-fungal activity by a poorly understood mechanism of action. In this work, the interaction of Psd1 with biomembrane model systems of different lipid compositions was assessed by fluorescence spectroscopy. Partition studies showed a marked lipid selectivity of this antimicrobial peptide (AMP) toward lipid membranes containing ergosterol (the main sterol in fungal membranes) or specific glycosphingolipid components, with partition coefficients (K(p)) reaching uncommonly high values of 10(6). By the opposite, Psd1 does not partition to cholesterol-enriched lipid bilayers, such as mammalian cell membranes. The Psd1 mutants His36Lys and Gly12Glu present a membrane affinity loss relative to the wild type. Fluorescence quenching data obtained using acrylamide and membrane probes further clarify the mechanism of action of this peptide at the molecular level, pointing out the potential therapeutic use of Psd1 as a natural antimycotic agent. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Ca2+/calmodulin binding to PSD-95 mediates homeostatic synaptic scaling down.

    PubMed

    Chowdhury, Dhrubajyoti; Turner, Matthew; Patriarchi, Tommaso; Hergarden, Anne C; Anderson, David; Zhang, Yonghong; Sun, Junqing; Chen, Chao-Yin; Ames, James B; Hell, Johannes W

    2018-01-04

    Postsynaptic density protein-95 (PSD-95) localizes AMPA-type glutamate receptors (AMPARs) to postsynaptic sites of glutamatergic synapses. Its postsynaptic displacement is necessary for loss of AMPARs during homeostatic scaling down of synapses. Here, we demonstrate that upon Ca 2+ influx, Ca 2+ /calmodulin (Ca 2+ /CaM) binding to the N-terminus of PSD-95 mediates postsynaptic loss of PSD-95 and AMPARs during homeostatic scaling down. Our NMR structural analysis identified E17 within the PSD-95 N-terminus as important for binding to Ca 2+ /CaM by interacting with R126 on CaM. Mutating E17 to R prevented homeostatic scaling down in primary hippocampal neurons, which is rescued via charge inversion by ectopic expression of CaM R 126E , as determined by analysis of miniature excitatory postsynaptic currents. Accordingly, increased binding of Ca 2+ /CaM to PSD-95 induced by a chronic increase in Ca 2+ influx is a critical molecular event in homeostatic downscaling of glutamatergic synaptic transmission. © 2017 The Authors.

  16. Involvement of a putative substrate binding site in the biogenesis and assembly of phosphatidylserine decarboxylase 1 from Saccharomyces cerevisiae.

    PubMed

    Di Bartolomeo, Francesca; Doan, Kim Nguyen; Athenstaedt, Karin; Becker, Thomas; Daum, Günther

    2017-07-01

    In the yeast Saccharomyces cerevisiae, the mitochondrial phosphatidylserine decarboxylase 1 (Psd1p) produces the largest amount of cellular phosphatidylethanolamine (PE). Psd1p is synthesized as a larger precursor on cytosolic ribosomes and then imported into mitochondria in a three-step processing event leading to the formation of an α-subunit and a β-subunit. The α-subunit harbors a highly conserved motif, which was proposed to be involved in phosphatidylserine (PS) binding. Here, we present a molecular analysis of this consensus motif for the function of Psd1p by using Psd1p variants bearing either deletions or point mutations in this region. Our data show that mutations in this motif affect processing and stability of Psd1p, and consequently the enzyme's activity. Thus, we conclude that this consensus motif is essential for structural integrity and processing of Psd1p. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Hadron calorimeter (PSD) with new photo-detectors (MPPC) in NA61 experiment at CERN

    NASA Astrophysics Data System (ADS)

    Golubeva, M.; Guber, F.; Ivashkin, A.; Izvestnyy, A.; Kurepin, A.; Morozov, S.; Petukhov, O.; Selyuzhenkov, I.; Svintsov, I.; Taranenko, A.

    2017-01-01

    The Projectile Spectator Detector (PSD) is a segmented hadron calorimeter used in NA61 experiment (CERN) to determine a collision centrality as well as an event plane orientation in nucleus-nucleus collisions. The main goal of the experiment includes studying the onset of de-confinement and searching for the critical point of strongly interacting matter. It is of crucial importance to have a precise characterization of the event class with the PSD for the analysis of event-by-event observables. The PSD has been already used for centrality selection on trigger level in measurements of Be+Be and Ar+Sc reactions at beam energies 13 - 158 AGeV and Pb+Pb reaction at beam energy 30 AGeV. In 2016, the central modules of PSD have been equipped with new Hamamatsu MPPC silicon photo-detectors in order to extend dynamic range for studying Pb+Pb reaction at the full energy range 13 - 158 AGeV. Results of the PSD response on proton and lead beams are presented.

  18. Low Serum Levels of Uric Acid are Associated With Development of Poststroke Depression.

    PubMed

    Gu, Yingying; Han, Bin; Wang, Liping; Chang, Yaling; Zhu, Lin; Ren, Wenwei; Yan, Mengjiao; Zhang, Xiangyang; He, Jincai

    2015-11-01

    Poststroke depression (PSD) is a frequent complication of stroke that has been associated with poorer outcome of stroke patients. This study sought to examine the possible association between serum uric acid levels and the development of PSD.We recruited 196 patients with acute ischemic stroke and 100 healthy volunteers. Serum uric acid levels were tested by uricase-PAP method within 24 hr after admission. Neuropsychological evaluations were conducted at 3-month poststroke. The 17-item Hamilton Depression Scale was used to assess depressive symptoms. Diagnosis of PSD was made in accordance with DSM-IV criteria for depression. Multivariate analyses were conducted using logistic regression models.Fifty-six patients (28.6%) were diagnosed as having PSD at 3 months. PSD patients showed significantly lower levels of uric acid at baseline as compared to non-PSD patients (237.02 ± 43.43 vs 309.10 ± 67.44 μmol/L, t = -8.86, P < 0.001). In multivariate analyses, uric acid levels (≤239.0 and ≥328.1 μmol/L) were independently associated with the development of PSD (OR, 7.76; 95% confidence interval [CI], 2.56-23.47, P < 0.001 and OR, 0.05; 95% CI, 0.01-0.43, P = 0.01, respectively) after adjustment for possible variables.Serum uric acid levels at admission are found to be correlated with PSD and may predict its development at 3 months after stroke.

  19. Effects of environmental enrichment and paradoxical sleep deprivation on open-field behavior of amphetamine-treated mice.

    PubMed

    Fukushiro, Daniela Fukue; Calzavara, Mariana Bendlin; Trombin, Thaís Fernanda; Lopez, Giorgia Batlle; Abílio, Vanessa Costhek; Andersen, Monica Levy; Tufik, Sergio; Frussa-Filho, Roberto

    2007-11-23

    Environmental enrichment or paradoxical sleep deprivation (PSD) has been shown to modify some responses elicited by drugs of abuse. The aims of the present study were to examine the effects of environmental enrichment and PSD, conducted separately or in association, on open-field behavior elicited by amphetamine (AMP) in mice. Male C57BL/6 mice were randomly assigned to live in either an enriched environmental condition (EC) or a standard environmental condition (SC) for 12 months since weaning. Some of the EC and SC mice were sleep deprived for 48 h, while others were maintained in their home-cages. Immediately after PSD or home-cage stay, the animals received an ip injection of saline, 2.5 mg/kg AMP or 5.0 mg/kg AMP. Fifteen minutes later, their open-field behavior was quantified. Whereas PSD enhanced total and peripheral locomotor activity of acutely AMP-treated mice, environmental enrichment presented only a trend toward enhancement. When PSD and environmental enrichment were combined, an increase in the total and peripheral locomotion frequencies of AMP-treated animals, similar to that observed after PSD, was revealed. In addition, PSD, environmental enrichment or their combination did not modify the effects of AMP on the other open-field behavioral parameters that were analyzed. The present findings demonstrate that some (but not all) of the behavioral effects caused by AMP acute administration can be similarly and specifically enhanced by both environmental enrichment and PSD in C57BL/6 mice.

  20. 40 CFR 52.2522 - Approval status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Federal regulatory SIP requirements for PSD applicable as of the August 31, 2011 SIP revision submission..., October 1, 2009, October 26, 2011, and February 17, 2012 which address the PSD-related requirements set... February 17, 2012 submitted to meet the PSD-related infrastructure SIP obligations set forth at CAA...

  1. 40 CFR 124.1 - Purpose and scope.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... issuing, modifying, revoking and reissuing, or terminating all RCRA, UIC, PSD and NPDES “permits... requirements for PSD permits. Subpart D contains specific procedural requirements for NPDES permits. Subpart G...)). Part 124 does not apply to PSD permits issued by an approved State. (f) To coordinate decisionmaking...

  2. 50 CFR 679.26 - Prohibited Species Donation Program.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ALASKA Management Measures § 679.26 Prohibited Species Donation Program. (a) Authorized species. The PSD... maintain adequate funding for the distribution of fish under the PSD program. (vii) A copy of the applicant... received under the PSD program, including sufficient liability insurance to cover public interests relating...

  3. 40 CFR 124.1 - Purpose and scope.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... issuing, modifying, revoking and reissuing, or terminating all RCRA, UIC, PSD and NPDES “permits... requirements for PSD permits. Subpart D contains specific procedural requirements for NPDES permits. Subpart G...)). Part 124 does not apply to PSD permits issued by an approved State. (f) To coordinate decisionmaking...

  4. 40 CFR 124.1 - Purpose and scope.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... issuing, modifying, revoking and reissuing, or terminating all RCRA, UIC, PSD and NPDES “permits... requirements for PSD permits. Subpart D contains specific procedural requirements for NPDES permits. Subpart G...)). Part 124 does not apply to PSD permits issued by an approved State. (f) To coordinate decisionmaking...

  5. 40 CFR 52.522 - Approval status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... prevention of significant deterioration (PSD) requirements for the regulation of greenhouse gas emissions. EPA is disapproving FDEP's submittal with respect to the PSD requirements of CAA sections 110(a)(2)(C... related to PSD requirements for the regulation of greenhouse gas emissions. [45 FR 17143, Mar. 18, 1980...

  6. Evaluating soybean cultivars for resistance to Phomopsis seed decay in Mississippi

    USDA-ARS?s Scientific Manuscript database

    Phomopsis seed decay (PSD) of soybean reduces seed quality, germination and seedling vigor. PSD has been problematic in most soybean production areas including Mississippi (MS). Planting resistant cultivars is one of the most effective means to control PSD. However, very few soybean cultivars resis...

  7. 40 CFR 124.1 - Purpose and scope.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... issuing, modifying, revoking and reissuing, or terminating all RCRA, UIC, PSD and NPDES “permits... requirements for PSD permits. Subpart D contains specific procedural requirements for NPDES permits. Subpart G...)). Part 124 does not apply to PSD permits issued by an approved State. (f) To coordinate decisionmaking...

  8. 40 CFR 69.31 - New exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... This exemption applies solely to the PSD major source baseline date and trigger date in the... applicable requirement that is triggered by, implemented or calculated from the PSD major source baseline... the Northern Mariana Islands, use January 13, 1997 as the PSD major source baseline date and trigger...

  9. 40 CFR 52.200 - Original identification of plan section.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... plan to incorporate Federal Prevention of Significant Deterioration (PSD) Regulations 40 CFR 52.21 by... Plan for Prevention of Significant Deterioration (PSD) of Air Quality Supplement Arkansas Plan of Implementation for Air Pollution Control (PSD nitrogen dioxide increments), as adopted on May 25, 1990, by the...

  10. 50 CFR 679.26 - Prohibited Species Donation Program.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ALASKA Management Measures § 679.26 Prohibited Species Donation Program. (a) Authorized species. The PSD... maintain adequate funding for the distribution of fish under the PSD program. (vii) A copy of the applicant... received under the PSD program, including sufficient liability insurance to cover public interests relating...

  11. 50 CFR 679.26 - Prohibited Species Donation Program.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ALASKA Management Measures § 679.26 Prohibited Species Donation Program. (a) Authorized species. The PSD... maintain adequate funding for the distribution of fish under the PSD program. (vii) A copy of the applicant... received under the PSD program, including sufficient liability insurance to cover public interests relating...

  12. 40 CFR 124.1 - Purpose and scope.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... issuing, modifying, revoking and reissuing, or terminating all RCRA, UIC, PSD and NPDES “permits... requirements for PSD permits. Subpart D contains specific procedural requirements for NPDES permits. Subpart G...)). Part 124 does not apply to PSD permits issued by an approved State. (f) To coordinate decisionmaking...

  13. 50 CFR 679.26 - Prohibited Species Donation Program.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ALASKA Management Measures § 679.26 Prohibited Species Donation Program. (a) Authorized species. The PSD... distribution of fish under the PSD program. (vii) A copy of the applicant's articles of incorporation and... full responsibility for the documentation and disposition of fish received under the PSD program...

  14. 40 CFR 52.200 - Original identification of plan section.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... plan to incorporate Federal Prevention of Significant Deterioration (PSD) Regulations 40 CFR 52.21 by... Plan for Prevention of Significant Deterioration (PSD) of Air Quality Supplement Arkansas Plan of Implementation for Air Pollution Control (PSD nitrogen dioxide increments), as adopted on May 25, 1990, by the...

  15. 40 CFR 52.200 - Original identification of plan section.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... plan to incorporate Federal Prevention of Significant Deterioration (PSD) Regulations 40 CFR 52.21 by... Plan for Prevention of Significant Deterioration (PSD) of Air Quality Supplement Arkansas Plan of Implementation for Air Pollution Control (PSD nitrogen dioxide increments), as adopted on May 25, 1990, by the...

  16. EPA-MassDEP Prevention of Significant Deterioration (PSD) Delegation Agreement

    EPA Pesticide Factsheets

    In April 2011, an agreement for delegation of the federal PSD program was executed by EPA Region 1 to the MassDEP. This agreement sets forth the terms & conditions according to which the MassDEP agrees to implement and enforce the federal PSD regulations.

  17. A New Sensor Based Upon a Rotating-Coil Electromagnetic Induction Concept

    DTIC Science & Technology

    2006-12-01

    of determining the transmitter coil position. The position must be known to produce a reference signal for the synchronous detector described in...schematically shown in Figure 14.3 Figure 14. Block diagram of the lock-in amplifier. This AC to DC conversion is performed by a phase- sensitive ... detector (PSD). It rectifies only the signal of interest while suppressing the noise or interfering signal components that may accompany the signal. To

  18. A new development on measurement and control software of SANS BATAN spectrometer (SMARTer) in Serpong, Indonesia

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

    Bharoto,; Suparno, Nadi; Putra, Edy Giri Rachman

    In 2005, the main computer for data acquisition and control system of Small-angle Neutron Scattering (SANS) BATAN Spectrometer (SMARTer) was replaced since it halted to operate the spectrometer. According to this replacement, the new software for data acquisition and control system has been developed in-house. Visual Basic programming language is used in developing the software. In the last two years, many developments have been made both in the hardware and also the software to conduct the experiment is more effective and efficient. Lately, the previous motor controller card (ISA Card) was replaced with the programmable motor controller card (PCI Card)more » for driving one motor of position sensitive detector (PSD), eight motors of four collimators, and six motors of six pinhole discs. This new control system software makes all motors can be moved simultaneously, then it reduces significantly the consuming time of setting up the instrument before running the experiment. Along with that development, the new data acquisition software under MS Windows operating system is also developed to drive a beam stopper in X-Y directions as well as to read the equipment status such as position of the collimators and PSD, to acquire neutron counts on monitor and PSD detectors, and also to manage 12 samples position automatically. A timer object which is set in one second to read the equipment status via serial port of the computer (RS232C), and general purpose interface board (GPIB) for reading the total counts of each pixel of the PSD from histogram memory was used in this new software. The experiment result displayed in real time on the main window, and the data is saved in the special format for further data reduction and analysis. The new software has been implemented and performed for experiment using a preset count or preset time mode for absolute scattering intensity method.« less

  19. A new development on measurement and control software of SANS BATAN spectrometer (SMARTer) in Serpong, Indonesia

    NASA Astrophysics Data System (ADS)

    Bharoto, Suparno, Nadi; Putra, Edy Giri Rachman

    2015-04-01

    In 2005, the main computer for data acquisition and control system of Small-angle Neutron Scattering (SANS) BATAN Spectrometer (SMARTer) was replaced since it halted to operate the spectrometer. According to this replacement, the new software for data acquisition and control system has been developed in-house. Visual Basic programming language is used in developing the software. In the last two years, many developments have been made both in the hardware and also the software to conduct the experiment is more effective and efficient. Lately, the previous motor controller card (ISA Card) was replaced with the programmable motor controller card (PCI Card) for driving one motor of position sensitive detector (PSD), eight motors of four collimators, and six motors of six pinhole discs. This new control system software makes all motors can be moved simultaneously, then it reduces significantly the consuming time of setting up the instrument before running the experiment. Along with that development, the new data acquisition software under MS Windows operating system is also developed to drive a beam stopper in X-Y directions as well as to read the equipment status such as position of the collimators and PSD, to acquire neutron counts on monitor and PSD detectors, and also to manage 12 samples position automatically. A timer object which is set in one second to read the equipment status via serial port of the computer (RS232C), and general purpose interface board (GPIB) for reading the total counts of each pixel of the PSD from histogram memory was used in this new software. The experiment result displayed in real time on the main window, and the data is saved in the special format for further data reduction and analysis. The new software has been implemented and performed for experiment using a preset count or preset time mode for absolute scattering intensity method.

  20. Effective phase function of light scattered at small angles by polydisperse particulate media

    NASA Astrophysics Data System (ADS)

    Turcu, I.

    2008-06-01

    Particles with typical dimensions higher than the light wavelength and relative refraction indexes close to one, scatter light mainly in the forward direction where the scattered light intensity has a narrow peak. For particulate media accomplishing these requirements the light scattered at small angles in a far-field detecting set-up can be described analytically by an effective phase function (EPF) even in the multiple scattering regime. The EPF model which was built for monodispersed systems has been extended to polydispersed media. The main ingredients consist in the replacement of the single particle phase function and of the optical thickness with their corresponding averaged values. Using a Gamma particle size distribution (PSD) as a testing model, the effect of polydispersity was systematically investigated. The increase of the average radius or/and of the PSD standard deviation leads to the decrease of the angular spreading of the small angle scattered light.

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

    Lombigit, L., E-mail: lojius@nm.gov.my; Yussup, N., E-mail: nolida@nm.gov.my; Ibrahim, Maslina Mohd

    A digital n/γ pulse shape discrimination (PSD) system is currently under development at Instrumentation and Automation Centre, Malaysian Nuclear Agency. This system aims at simultaneous detection of fast neutron and gamma ray in mixed radiations environment. This work reports the system characterization performed on the liquid scintillation detector (BC-501A) and digital pulse shape discrimination (DPSD) system. The characterization involves measurement of electron light output from the BC-501A detector and energy channels calibration of the pulse height spectra acquired with DPSD system using set of photon reference sources. The main goal of this experiment is to calibrate the ADC channel ofmore » our DPSD system, characterized the BC-501 detector and find the position of Compton edge which later could be used as threshold for the n/γ PSD experiment. The detector resolution however is worse as compared to other published data but it is expected as our detector has a smaller active volume.« less

  2. 75 FR 59179 - Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [EPA-R05-OAR-2010-0657; FRL-9205-7] Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations AGENCY: Environmental Protection... requirements of the prevention of significant deterioration (PSD) construction permit program in Michigan...

  3. 40 CFR 52.343 - Significant deterioration of air quality.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... constructed prior to September 2, 1986 and which have not otherwise subjected themselves to Colorado's PSD permitting regulations after September 2, 1986, either through application to Colorado for a PSD permit (in the case of those sources which improperly constructed without obtaining a PSD permit) or through...

  4. 7 CFR 760.1301 - Administration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Administrator” in this part), and will be carried out by FSA's Price Support Division (PSD) and Kansas City... PSD, KCMO, a State committee, or a county committee will preclude the Administrator, FSA, or a... determination made by PSD, KCMO, a State committee, or a county committee. (f) The Deputy Administrator may...

  5. 7 CFR 760.1301 - Administration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Administrator” in this part), and will be carried out by FSA's Price Support Division (PSD) and Kansas City... PSD, KCMO, a State committee, or a county committee will preclude the Administrator, FSA, or a... determination made by PSD, KCMO, a State committee, or a county committee. (f) The Deputy Administrator may...

  6. 76 FR 27898 - Approval and Promulgation of Air Quality Implementation Plans; Virginia; Prevention of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-13

    ... greenhouse gas (GHG) Prevention of Significant Deterioration (PSD) permitting provisions as promulgated on June 3, 2010 in the Tailoring Rule. The SIP revision modifies Virginia's PSD program to [[Page 27899... become subject to Virginia's PSD permitting requirements for their GHG emissions. EPA is approving...

  7. 7 CFR 760.1301 - Administration.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Administrator” in this part), and will be carried out by FSA's Price Support Division (PSD) and Kansas City... PSD, KCMO, a State committee, or a county committee will preclude the Administrator, FSA, or a... determination made by PSD, KCMO, a State committee, or a county committee. (f) The Deputy Administrator may...

  8. 76 FR 35380 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-17

    ... processing. The proposed SIP revision modifies Indiana's Prevention of Significant Deterioration (PSD... modification projects become subject to Indiana's PSD permitting requirements for their greenhouse gas (GHG... EPA regulations regarding PSD permitting for GHGs. DATES: Comments must be received on or before July...

  9. 7 CFR 760.1301 - Administration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Administrator” in this part), and will be carried out by FSA's Price Support Division (PSD) and Kansas City... PSD, KCMO, a State committee, or a county committee will preclude the Administrator, FSA, or a... determination made by PSD, KCMO, a State committee, or a county committee. (f) The Deputy Administrator may...

  10. 40 CFR 69.41 - New exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Significant Deterioration of Air Quality (PSD) permit issued to HOVIC; and shall include as a minimum, the... purpose of implementing the ICS at nearby locations approved by EPA and specified in the PSD permit. The... the NAAQS. (e) HOVIC must comply with all fuel switching requirements, contained in HOVIC's PSD permit...

  11. 77 FR 11744 - Approval and Promulgation of Implementation Plans; Tennessee: Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-28

    ... New Source Review (NSR) Prevention of Significant Deterioration (PSD) program. Specifically, the SIP... modification projects become subject to Tennessee's PSD permitting requirements for GHG emissions. This rule... thresholds in the Tennessee SIP for GHG PSD requirements. EPA is approving Tennessee's January 11, 2012, SIP...

  12. 78 FR 50360 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Infrastructure SIP...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-19

    ... National Ambient Air Quality Standards; Indiana PSD; Indiana State Board Requirements AGENCY: Environmental... from Indiana addressing EPA's requirements for the prevention of significant deterioration (PSD... (PSD elements), or EPA-R05-OAR-2012-0988 (state board requirements), by one of the following methods: 1...

  13. 40 CFR 52.343 - Significant deterioration of air quality.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... constructed prior to September 2, 1986 and which have not otherwise subjected themselves to Colorado's PSD permitting regulations after September 2, 1986, either through application to Colorado for a PSD permit (in the case of those sources which improperly constructed without obtaining a PSD permit) or through...

  14. 76 FR 15852 - Approval and Promulgation of Implementation Plans; Nebraska: Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-22

    ... significant deterioration (PSD) preconstruction permitting program. The first applies to revisions relating to permitting of greenhouse gas (GHG) emissions under the PSD program. The second applies to revisions..., includes two significant changes impacting the regulation of GHGs under Nebraska's PSD program. First, the...

  15. 77 FR 73316 - Approval of Air Quality Implementation Plans; California; Eastern Kern, Imperial, Placer, and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-10

    ... adopt and implement a SIP- approved Prevention of Significant Deterioration (PSD) permit program. We are...--Prevention of Significant Deterioration (PSD) Permit Program, PCAPCD Rule 518--Prevention of Significant Deterioration (PSD) Permit Program, and YSAQMD Rule 3.24-- Prevention of Significant Deterioration. The approval...

  16. 76 FR 59334 - Approval and Promulgation of Air Quality Implementation Plans; New Mexico; Albuquerque/Bernalillo...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ... Prevention of Significant Deterioration (PSD) program to establish appropriate emission thresholds for... County's PSD permitting requirements for their greenhouse gas (GHG) emissions. Due to the SIP Narrowing Rule, 75 FR 82536, starting on January 2, 2011, the approved Albuquerque/Bernalillo County SIP's PSD...

  17. 76 FR 9658 - Approval and Promulgation of Implementation Plans; Kansas: Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-22

    ... greenhouse gas (GHG) under Kansas's New Source Review (NSR) Prevention of Significant Deterioration (PSD) program. First, the SIP revision provides the State of Kansas with authority to issue PSD permits... stationary sources and modification projects become subject to Kansas's PSD permitting requirements for their...

  18. 76 FR 40303 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Modifications to Indiana...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ... Significant Deterioration (PSD) and Nonattainment New Source Review (NNSR) rules. The amendments include grammatical changes, corrections to numbering, addition of definitions consistent with Federal PSD and NNSR... Federal PSD and NNSR regulations. DATES: Comments must be received on or before August 8, 2011. ADDRESSES...

  19. Final PSD Permit Extension Letter - Energy Answers Arecibo, LLC/Energy Answers Arecibo Puerto Rico Renewable Energy Project, PR

    EPA Pesticide Factsheets

    This page contains the Final PSD Permit Extension Letter for Energy Answers Arecibo Puerto Rico Renewable Energy Project, issued on April 10, 2017 and the EPA Public Announcement for Final PSD Permit Extension for Energy Answers Arecibo, PR.

  20. 40 CFR 69.41 - New exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Significant Deterioration of Air Quality (PSD) permit issued to HOVIC; and shall include as a minimum, the... purpose of implementing the ICS at nearby locations approved by EPA and specified in the PSD permit. The... the NAAQS. (e) HOVIC must comply with all fuel switching requirements, contained in HOVIC's PSD permit...

  1. 75 FR 81863 - Approval and Promulgation of Implementation Plans; Alabama: Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ... Deterioration (PSD) program. Specifically, the SIP revision establishes appropriate emission thresholds for determining which new stationary sources and modification projects become subject to Alabama's PSD permitting requirements for their GHG emissions. The change is necessary because without it, on January 2, 2011, PSD...

  2. 77 FR 58027 - Approval and Promulgation of Implementation Plans; Florida: New Source Review-Prevention of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-19

    ... revision modifies Florida's New Source Review (NSR) Prevention of Significant Deterioration (PSD) permitting regulations to adopt, into the Florida SIP, federal NSR PSD requirements for the fine particulate... Implementation Rule and the 2010 PM 2.5 PSD Increment, Significant Impact [[Page 58028

  3. 40 CFR 52.824 - Original identification of plan section.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... attainment and unclassified areas of the state (PSD) were submitted on March 9, 1987, by the Iowa Department... review/PSD regulations. (47) Revised Chapters 22 and 23 regulations pertaining to stack height credits..., incorporates by reference revised EPA PSD rules pertaining to NO X increments. (i) Incorporation by reference...

  4. 40 CFR 52.343 - Significant deterioration of air quality.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... constructed prior to September 2, 1986 and which have not otherwise subjected themselves to Colorado's PSD permitting regulations after September 2, 1986, either through application to Colorado for a PSD permit (in the case of those sources which improperly constructed without obtaining a PSD permit) or through...

  5. 40 CFR 52.343 - Significant deterioration of air quality.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... constructed prior to September 2, 1986 and which have not otherwise subjected themselves to Colorado's PSD permitting regulations after September 2, 1986, either through application to Colorado for a PSD permit (in the case of those sources which improperly constructed without obtaining a PSD permit) or through...

  6. 75 FR 14401 - Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [EPA-R05-OAR-2007-1043; FRL-9129-6] Approval and Promulgation of Air Quality Implementation Plans; Michigan; PSD Regulations AGENCY: Environmental Protection... (CAA). The revisions consist of requirements of the prevention of significant deterioration (PSD...

  7. 40 CFR 69.41 - New exemptions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Significant Deterioration of Air Quality (PSD) permit issued to HOVIC; and shall include as a minimum, the... purpose of implementing the ICS at nearby locations approved by EPA and specified in the PSD permit. The... the NAAQS. (e) HOVIC must comply with all fuel switching requirements, contained in HOVIC's PSD permit...

  8. Characterization and variability of particle size distributions in Hudson Bay, Canada

    NASA Astrophysics Data System (ADS)

    Xi, Hongyan; Larouche, Pierre; Tang, Shilin; Michel, Christine

    2014-06-01

    Particle size distribution (PSD) plays a significant role in many aspects of aquatic ecosystems, including phytoplankton dynamics, sediment fluxes, and optical scattering from particulates. As of yet, little is known on the variability of particle size distribution in marine ecosystems. In this study, we investigated the PSD properties and variability in Hudson Bay based on measurements from a laser diffractometer (LISST-100X Type-B) in concert with biogeochemical parameters collected during summer 2010. Results show that most power-law fitted PSD slopes ranged from 2.5 to 4.5, covering nearly the entire range observed for natural waters. Offshore waters showed a predominance of smaller particles while near the coast, the effect of riverine inputs on PSD were apparent. Particulate inorganic matter contributed more to total suspended matter in coastal waters leading to lower PSD slopes than offshore. The depth distribution of PSD slopes shows that larger particles were associated with the pycnocline. Below the pycnocline, smaller particles dominated the spectra. A comparison between a PSD slope-based method to derive phytoplankton size class (PSC) and pigment-based derived PSC showed the two methods agreed relatively well. This study provides valuable baseline information on particle size properties and phytoplankton composition estimates in a sub-arctic environment subject to rapid environmental change.

  9. Early Growth Response 1 (Egr-1) Regulates N-Methyl-d-aspartate Receptor (NMDAR)-dependent Transcription of PSD-95 and α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor (AMPAR) Trafficking in Hippocampal Primary Neurons*

    PubMed Central

    Qin, Xike; Jiang, Yongjun; Tse, Yiu Chung; Wang, Yunling; Wong, Tak Pan; Paudel, Hemant K.

    2015-01-01

    The N-methyl-d-aspartate receptor (NMDAR) controls synaptic plasticity and memory function and is one of the major inducers of transcription factor Egr-1 in the hippocampus. However, how Egr-1 mediates the NMDAR signal in neurons has remained unclear. Here, we show that the hippocampus of mice lacking Egr-1 displays electrophysiology properties and ultrastructure that are similar to mice overexpressing PSD-95, a major scaffolding protein of postsynaptic density involved in synapse formation, synaptic plasticity, and synaptic targeting of AMPA receptors (AMPARs), which mediate the vast majority of excitatory transmission in the CNS. We demonstrate that Egr-1 is a transcription repressor of the PSD-95 gene and is recruited to the PSD-95 promoter in response to NMDAR activation. Knockdown of Egr-1 in rat hippocampal primary neurons blocks NMDAR-induced PSD-95 down-regulation and AMPAR endocytosis. Likewise, overexpression of Egr-1 in rat hippocampal primary neurons causes reduction in PSD-95 protein level and promotes AMPAR endocytosis. Our data indicate that Egr-1 is involved in NMDAR-mediated PSD-95 down-regulation and AMPAR endocytosis, a process important in the expression of long term depression. PMID:26475861

  10. Differential Roles of Postsynaptic Density-93 Isoforms in Regulating Synaptic Transmission

    PubMed Central

    Krüger, Juliane M.; Favaro, Plinio D.; Liu, Mingna; Kitlińska, Agata; Huang, Xiaojie; Raabe, Monika; Akad, Derya S.; Liu, Yanling; Urlaub, Henning; Dong, Yan; Xu, Weifeng

    2013-01-01

    In the postsynaptic density of glutamatergic synapses, the discs large (DLG)-membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins coordinates a multiplicity of signaling pathways to maintain and regulate synaptic transmission. Postsynaptic density-93 (PSD-93) is the most variable paralog in this family; it exists in six different N-terminal isoforms. Probably because of the structural and functional variability of these isoforms, the synaptic role of PSD-93 remains controversial. To accurately characterize the synaptic role of PSD-93, we quantified the expression of all six isoforms in the mouse hippocampus and examined them individually in hippocampal synapses. Using molecular manipulations, including overexpression, gene knockdown, PSD-93 knock-out mice combined with biochemical assays, and slice electrophysiology both in rat and mice, we demonstrate that PSD-93 is required at different developmental synaptic states to maintain the strength of excitatory synaptic transmission. This strength is differentially regulated by the six isoforms of PSD-93, including regulations of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-active and inactive synapses, and activity-dependent modulations. Collectively, these results demonstrate that alternative combinations of N-terminal PSD-93 isoforms and DLG-MAGUK paralogs can fine-tune signaling scaffolds to adjust synaptic needs to regulate synaptic transmission. PMID:24068818

  11. Hybrid organic/inorganic position-sensitive detectors based on PEDOT:PSS/n-Si

    NASA Astrophysics Data System (ADS)

    Javadi, Mohammad; Gholami, Mahdiyeh; Torbatiyan, Hadis; Abdi, Yaser

    2018-03-01

    Various configurations like p-n junctions, metal-semiconductor Schottky barriers, and metal-oxide-semiconductor structures have been widely used in position-sensitive detectors. In this report, we propose a PEDOT:PSS/n-Si heterojunction as a hybrid organic/inorganic configuration for position-sensitive detectors. The influence of the thickness of the PEDOT:PSS layer, the wavelength of incident light, and the intensity of illumination on the device performance are investigated. The hybrid PSD exhibits very high sensitivity (>100 mV/mm), excellent nonlinearity (<3%), and a response correlation coefficient (>0.995) with a response time of <4 ms to the inhomogeneous IR illumination. The presented hybrid configuration also benefits from a straightforward low-temperature fabrication process. These advantages of the PEDOT:PSS/n-Si heterojunction are very promising for developing a new class of position-sensitive detectors based on the hybrid organic/inorganic junctions.

  12. Ultra-Bright and -Stable Red and Near-Infrared Squaraine Fluorophores for In Vivo Two-Photon Imaging

    PubMed Central

    Podgorski, Kaspar; Terpetschnig, Ewald; Klochko, Oleksii P.; Obukhova, Olena M.; Haas, Kurt

    2012-01-01

    Fluorescent dyes that are bright, stable, small, and biocompatible are needed for high-sensitivity two-photon imaging, but the combination of these traits has been elusive. We identified a class of squaraine derivatives with large two-photon action cross-sections (up to 10,000 GM) at near-infrared wavelengths critical for in vivo imaging. We demonstrate the biocompatibility and stability of a red-emitting squaraine-rotaxane (SeTau-647) by imaging dye-filled neurons in vivo over 5 days, and utility for sensitive subcellular imaging by synthesizing a specific peptide-conjugate label for the synaptic protein PSD-95. PMID:23251670

  13. Enhanced detection and identification of Shiga toxin 1 and 2 from pathogenic bacteria by MALDI-TOF-TOF-MS/MS-PSD and top-down proteomic analysis

    USDA-ARS?s Scientific Manuscript database

    Shiga toxin producing Escherichia coli (STEC) represent a continuing threat to the Nation’s food supply and public health. Shiga toxin genes (stx) are encoded in lambda-like bacteriophages whose genome is inserted into the bacterial DNA. Environmental stress can trigger bacteriophage replication a...

  14. A remotely triggered fast neutron detection instrument based on a plastic organic scintillator

    NASA Astrophysics Data System (ADS)

    Jones, A. R.; Aspinall, M. D.; Joyce, M. J.

    2018-02-01

    A detector system for the characterization of radiation fields of both fast neutrons and γ rays is described comprising of a gated photomultiplier tube (PMT), an EJ299-33 solid organic scintillator detector, and an external trigger circuit. The objective of this development was to conceive a means by which the PMT in such a system can be actuated remotely during the high-intensity bursts of pulsed γ-ray contamination that can arise during active interrogation procedures. The system is used to detect neutrons and γ rays using established pulse-shape discrimination (PSD) techniques. The gating circuit enables the PMT to be switched off remotely. This is compatible with use during intense radiation transients to avoid saturation and the disruption of the operation of the PMT during the burst. Data are presented in the form of pulse-height spectra and PSD scatter plots for the system triggered with a strobed light source. These confirm that the gain of the system and the throughput for both triggered and un-triggered scenarios are as expected, given the duty cycle of the stimulating radiation. This demonstrates that the triggering function does not perturb the system response of the detector.

  15. A remotely triggered fast neutron detection instrument based on a plastic organic scintillator.

    PubMed

    Jones, A R; Aspinall, M D; Joyce, M J

    2018-02-01

    A detector system for the characterization of radiation fields of both fast neutrons and γ rays is described comprising of a gated photomultiplier tube (PMT), an EJ299-33 solid organic scintillator detector, and an external trigger circuit. The objective of this development was to conceive a means by which the PMT in such a system can be actuated remotely during the high-intensity bursts of pulsed γ-ray contamination that can arise during active interrogation procedures. The system is used to detect neutrons and γ rays using established pulse-shape discrimination (PSD) techniques. The gating circuit enables the PMT to be switched off remotely. This is compatible with use during intense radiation transients to avoid saturation and the disruption of the operation of the PMT during the burst. Data are presented in the form of pulse-height spectra and PSD scatter plots for the system triggered with a strobed light source. These confirm that the gain of the system and the throughput for both triggered and un-triggered scenarios are as expected, given the duty cycle of the stimulating radiation. This demonstrates that the triggering function does not perturb the system response of the detector.

  16. Spinal serum-inducible and glucocorticoid-inducible kinase 1 mediates neuropathic pain via kalirin and downstream PSD-95-dependent NR2B phosphorylation in rats.

    PubMed

    Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Yuan; Hsieh, Ming-Chun; Lin, Tzer-Bin

    2013-03-20

    The coupling of the spinal postsynaptic density-95 (PSD-95) with the glutamatergic N-methyl-d-aspartate receptor NR2B subunit and the subsequent NR2B phosphorylation contribute to pain-related plasticity. Increasing evidence reveals that kalirin, a Rho-guanine nucleotide exchange factor, modulates PSD-95-NR2B-dependent neuroplasticity. Our laboratory recently demonstrated that serum-inducible and glucocorticoid-inducible kinase 1 (SGK1) participates in inflammation-associated pain hypersensitivity by modulating spinal glutamatergic neurotransmission. Because kalirin is one of the proteins in PSD that is highly phosphorylated by various kinases, we tested whether kalirin could be a downstream target of spinal SGK1 that participates in neuropathic pain development via regulation of the PSD-95-NR2B coupling-dependent phosphorylation of NR2B. We observed that spinal nerve ligation (SNL, L5) in male Sprague Dawley rats resulted in behavioral allodynia, which was associated with phosphorylated SGK1 (pSGK1), kalirin, and phosphorylated NR2B (pNR2B) expression and an increase in pSGK1-kalirin-PSD-95-pNR2B coprecipitation in the ipsilateral dorsal horn (L4-L5). SNL-enhanced kalirin immunofluorescence was coincident with pSGK1, PSD-95, and pNR2B immunoreactivity. Small-interfering RNA (siRNA) that targeted spinal kalirin mRNA expression (10 μg, 10 μl; i.t.) reduced SNL-induced allodynia, kalirin and pNR2B expression, as well as kalirin-PSD-95 and PSD-95-pNR2B coupling and costaining without affecting SGK1 phosphorylation. Daily administration of GSK-650394 (an SGK1 antagonist; 100 nm, 10 μl, i.t.) not only exhibited effects similar to the kalirin mRNA-targeting siRNA but also attenuated pSGK1-kalirin costaining and SGK1-kalirin coupling. We suggest that nerve injury could induce spinal SGK1 phosphorylation that subsequently interacts with and upregulates kalirin to participate in neuropathic pain development via PSD-95-NR2B coupling-dependent NR2B phosphorylation.

  17. IB-11PSEUDO-PROGRESSION (PsdPg) IS A HARBINGER OF A MORE EFFECTIVE ANTI-TUMOR RESPONSE

    PubMed Central

    Sturla, Lisa; Donahue, John; Machan, Jason; Delamonte, Suzanne; Jeyapalan, Suriya

    2014-01-01

    BACKGROUND: PsdPg is the increased contrast enhancement, high choline/creatine ratio and increased perfusion observed in the residual tumor bed of high-grade glioma patients after completion of temozolomide/radiation. It resolves within 3-6 months and incidence ranges from 10 - 31%. Though correlated with longer patient survival, its pathological basis is unclear. We used a cytokine/chemokine focused approach to compare the tumor microenvironment in pre- and post-treatment tumor tissue from patients with PsdPg to patients with true progression (TP). METHODS: We obtained pre-treatment formalin fixed paraffin embedded (FFPE) tissue from 35 GBM patients and post-treatment FFPE tissue from five patients with PsdPg and TP. A quantitative PCR array and custom Quantigene 2.0 multiplex was used to quantify gene expression corresponding to major cytokines/chemokines. An 18-gene signature was used to determine the macrophage polarization score (cumulative M2-associated cytokine expression - cumulative M1-associated cytokine expression). Immunohistochemistry (IHC) was used to confirm significantly different targets at the protein level. RESULTS: IHC revealed 7-fold higher B-cell infiltration in TP patients as compared to patients with PsdPg (p = 0.003). Macrophage and T-cell infiltration were not significantly different between the two groups. Nevertheless, the cytokines associated with macrophage polarization indicated pro-tumorigenic (M2) polarization in TP patients while PsdPg patients exhibited classical anti-tumorigenic (M1) polarization. TP patients had a 10-fold higher M2 score (p = 0.03) compared to PsdPg patients. The M1 score of tissue from PsdPg patients post-treatment was 25-fold higher than their pre-treatment tissue (p = 0.01). Analysis of a 7-gene signature associated with natural killer (NK) cell recruitment and activation showed a 8-fold higher expression in pre-treatment tissue from PsdPg patients compared to TP patients (p = 0.009) suggesting that NK cells, which are mediators of anti-tumor immunity, play an important role in pseudo-progression. CONCLUSIONS: These data suggest a more effective anti-tumor immune response in PsdPg patients, which may explain their longer overall survival.

  18. Evaluation of the New MALDI Matrix 4-Chloro-α-Cyanocinnamic Acid

    PubMed Central

    Leszyk, John D.

    2010-01-01

    MALDI-TOF continues to be an important tool for many proteomic studies. Recently, a new rationally designed matrix 4-chloro-α-cyanocinnamic acid was introduced, which is reported to have superior performance as compared with the “gold standard” α-cyano-4-hydroxycinnamic acid (CHCA).1 In this study, the performance of this new matrix, using the Shimadzu Biotech Axima TOF2 (Shimadzu Biotech, Manchester, UK), was investigated. The overall sequence coverage as well as sensitivity of this matrix were compared with CHCA using standard protein tryptic digests. The performance of this matrix with labile peptides, such as phosphopeptides and 4-sulfophenyl isothiocynate-derivatized peptides, to facilitate de novo sequencing was also explored. This matrix was found to be better performing than CHCA in overall sensitivity and showed better sequence coverage at low-digest levels, partly as a result of less of a bias for arginine-containing peptides. It also showed as much as a tenfold improvement in sensitivity with labile peptides on standard stainless-steel targets. In addition, as a result of the much cooler nature of this matrix, labile peptides are readily seen intact with much less fragmentation in mass spectrometry (MS) mode. This matrix was also evaluated in the MS/MS fragmentation modes of post-source decay (PSD) and collisional-induced dissociation (CID). It was found that fragmentation occurs readily in CID, however as a result of the very cool nature of this new matrix, the PSD fragments were quite weak. This matrix promises to be an important addition to the already extensive array of MALDI matrices. PMID:20592871

  19. The association of different types of cerebral infarction with post-stroke depression and cognitive impairment.

    PubMed

    Tu, Jun; Wang, Ling-Xiao; Wen, Hong-Feng; Xu, Yi-Cheng; Wang, Pei-Fu

    2018-06-01

    The aim of this study was to investigate post-stroke depression (PSD) and cognitive impairments in patients with different types of cerebral infarction.A total of 110 patients with cerebral infarction treated in our hospital from January 2015 to February 2016 were included in present study. Forty-seven patients were PSD patients and 63 patients were non-PSD patients. The Hamilton Depression Rating Scale (HAMD) and Mini-Mental State Examination (MMSE) were employed to assess depression and cognition of patientsAmong PSD patients, the proportion of patients with partial anterior circulation infarction (PACI, 68.75%) was significantly higher than patients with lacunar circulation infarction (LACI, 29.17%) and posterior circulation infarction (POCI, 26.67%) (P < .05). No significant difference was found in PSD patients with LACI and POCI (P > .05). The MMSE score of patients with PACI (18.05 ± 2.61) was lower than patients with POCI and LACI (P < .05), however, no significant difference was found in patients with LACI and POCI (P > 0.05). The incidences of cognitive impairment in patients with PACI, LACI, and POCI were 12.50%, 14.58%, and 13.33%, respectively. The MMSE score of PSD patients (21.23 ± 2.12) was significantly lower than non-PSD patients (P < .05).Compared with LACI and POCI patients, PACI patients had a higher incidence of PSD and impaired cognitive functions. In addition, affective disorders such as depression may be correlated with cognitive impairment in patients with cerebral infarction.

  20. Bidirectional control of postsynaptic density-95 (PSD-95) clustering by Huntingtin.

    PubMed

    Parsons, Matthew P; Kang, Rujun; Buren, Caodu; Dau, Alejandro; Southwell, Amber L; Doty, Crystal N; Sanders, Shaun S; Hayden, Michael R; Raymond, Lynn A

    2014-02-07

    Huntington disease is associated with early alterations in corticostriatal synaptic function that precede cell death, and it is postulated that ameliorating such changes may delay clinical onset and/or prevent neurodegeneration. Although many of these synaptic alterations are thought to be attributable to a toxic gain of function of the mutant huntingtin protein, the role that nonpathogenic huntingtin (HTT) plays in synaptic function is relatively unexplored. Here, we compare the immunocytochemical localization of a major postsynaptic scaffolding protein, PSD-95, in striatal neurons from WT mice and mice overexpressing HTT with 18 glutamine repeats (YAC18, nonpathogenic). We found that HTT overexpression resulted in a palmitoylation- and BDNF-dependent increase in PSD-95 clustering at synaptic sites in striatal spiny projection neurons (SPNs) co-cultured with cortical neurons. Surprisingly, the latter effect was mediated presynaptically, as HTT overexpression in cortical neurons alone was sufficient to increase PSD-95 clustering in the postsynaptic SPNs. In contrast, antisense oligonucleotide knockdown of HTT in WT co-cultures resulted in a significant reduction of PSD-95 clustering in SPNs. Notably, despite these bidirectional changes in PSD-95 clustering, we did not observe an alteration in basal electrophysiological measures of AMPA and NMDA receptors. Thus, unlike in previous studies in the hippocampus, enhanced or decreased PSD-95 clustering alone was insufficient to drive AMPA or NMDA receptors into or out of SPN synapses. In all, our results demonstrate that nonpathogenic HTT can indeed influence synaptic protein localization and uncover a novel role of HTT in PSD-95 distribution.

  1. Bidirectional Control of Postsynaptic Density-95 (PSD-95) Clustering by Huntingtin*

    PubMed Central

    Parsons, Matthew P.; Kang, Rujun; Buren, Caodu; Dau, Alejandro; Southwell, Amber L.; Doty, Crystal N.; Sanders, Shaun S.; Hayden, Michael R.; Raymond, Lynn A.

    2014-01-01

    Huntington disease is associated with early alterations in corticostriatal synaptic function that precede cell death, and it is postulated that ameliorating such changes may delay clinical onset and/or prevent neurodegeneration. Although many of these synaptic alterations are thought to be attributable to a toxic gain of function of the mutant huntingtin protein, the role that nonpathogenic huntingtin (HTT) plays in synaptic function is relatively unexplored. Here, we compare the immunocytochemical localization of a major postsynaptic scaffolding protein, PSD-95, in striatal neurons from WT mice and mice overexpressing HTT with 18 glutamine repeats (YAC18, nonpathogenic). We found that HTT overexpression resulted in a palmitoylation- and BDNF-dependent increase in PSD-95 clustering at synaptic sites in striatal spiny projection neurons (SPNs) co-cultured with cortical neurons. Surprisingly, the latter effect was mediated presynaptically, as HTT overexpression in cortical neurons alone was sufficient to increase PSD-95 clustering in the postsynaptic SPNs. In contrast, antisense oligonucleotide knockdown of HTT in WT co-cultures resulted in a significant reduction of PSD-95 clustering in SPNs. Notably, despite these bidirectional changes in PSD-95 clustering, we did not observe an alteration in basal electrophysiological measures of AMPA and NMDA receptors. Thus, unlike in previous studies in the hippocampus, enhanced or decreased PSD-95 clustering alone was insufficient to drive AMPA or NMDA receptors into or out of SPN synapses. In all, our results demonstrate that nonpathogenic HTT can indeed influence synaptic protein localization and uncover a novel role of HTT in PSD-95 distribution. PMID:24347167

  2. Hysteresis in suspended sediment to turbidity relations due to changing particle size distributions

    USGS Publications Warehouse

    Landers, Mark N.; Sturm, Terry W.

    2013-01-01

    Turbidity (T) is the most ubiquitous of surrogate technologies used to estimate suspended-sediment concentration (SSC). The effects of sediment size on turbidity are well documented; however, effects from changes in particle size distributions (PSD) are rarely evaluated. Hysteresis in relations of SSC-to-turbidity (SSC~T) for single stormflow events was observed and quantified for a data set of 195 concurrent measurements of SSC, turbidity, discharge, velocity, and volumetric PSD collected during five stormflows in 2009–2010 on Yellow River at Gees Mill Road in metropolitan Atlanta, Georgia. Regressions of SSC-normalized turbidity (T/SSC) on concurrently measured PSD percentiles show an inverse, exponential influence of particle size on turbidity that is not constant across the size range of the PSD. The majority of the influence of PSD on T/SSC is from particles of fine-silt and smaller sizes (finer than 16 microns). This study shows that small changes in the often assumed stability of the PSD are significant to SSC~T relations. Changes of only 5 microns in the fine silt and smaller size fractions of suspended sediment PSD can produce hysteresis in the SSC~T rating that can increase error and produce bias. Observed SSC~T hysteresis may be an indicator of changes in sediment properties during stormflows and of potential changes in sediment sources. Trends in the PSD time series indicate that sediment transport is capacity-limited for sand-sized sediment in the channel and supply-limited for fine silt and smaller sediment from the hillslope.

  3. Impairment of male reproductive function after sleep deprivation.

    PubMed

    Alvarenga, Tathiana A; Hirotsu, Camila; Mazaro-Costa, Renata; Tufik, Sergio; Andersen, Monica L

    2015-05-01

    To evaluate the influence of sleep loss on sexual behavior, hormone levels, sperm parameters, and testis-specific gene expression in male rats. Experimental research. Animal laboratory. Male adult Wistar-Hannover rats. Sexually experienced rats were subjected to paradoxic sleep deprivation (PSD) for 96 hours or sleep restriction (SR) for 21 days or kept in their home cage as control (CTRL). Sexual behavior, hormone levels, sperm parameters and expression of stress and nitric oxide-related genes were evaluated. PSD significantly decreased sexual behavior compared with the CTRL group, whereas SR had no effect. The PSD group had significantly lower testosterone levels than the CTRL group. Both PSD and SR groups had lower sperm viabilities than the CTRL group. The decrease in the number of live sperm compared with the CTRL group was larger in the PSD group than in the SR group. Regarding testicular gene expression, both PSD and SR led to an increase of iNOS and hydroxysteroid 11β-dehydrogenase 1 expressions compared with the CTRL group. These changes were more pronounced in the PSD group. A significant increase in endothelial nitric oxide synthase expression was observed in the PSD groups compared with the CTRL group. No changes were observed in dimethylarginine dimethylaminohydrolase 1 and casein kinase 2β-polypeptide expressions. Sleep loss can promote marked changes in the male reproductive system of rats, particularly affecting spermatic function in part by interfering in the testicular nitric oxide pathway. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. 76 FR 59899 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-28

    ... Significant Deterioration (PSD) program to establish appropriate emission thresholds for determining which new... emissions above the thresholds established in the PSD regulations. DATES: This final rule is effective on... of GHG, and that do not limit PSD applicability to GHGs to the higher thresholds in the Tailoring...

  5. 75 FR 82246 - Action To Ensure Authority To Issue Permits Under the Prevention of Significant Deterioration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-30

    ... Deterioration (PSD) program to sources of greenhouse gases (GHGs). This action will ensure that a permitting authority--EPA--is available in these states as of January 2, 2011, when PSD becomes applicable to GHG-emitting sources, to issue preconstruction PSD permits and thereby facilitate construction or expansion...

  6. 40 CFR 52.2522 - Approval status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... requirements for PSD applicable as of the August 31, 2011 SIP revision submission date, EPA is acknowledging... February 17, 2012 which address the PSD-related requirements set forth in CAA section 110(a)(2)(D)(i)(II..., 2007, April 3, 2008, October 1, 2009, October 26, 2011, and February 17, 2012 submitted to meet the PSD...

  7. 78 FR 40968 - Notice of Extension of Deadline to Commence Construction Under Clean Air Act Prevention of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-09

    ...'') has extended the Prevention of Significant Deterioration (``PSD'') permit deadline for commencing construction for a final Clean Air Act PSD permit that authorizes Avenal Power Center, LLC (``APC'') to...: EPA's PSD permit for the AEP became effective on August 18, 2011, and included a deadline for...

  8. 78 FR 2354 - Approval and Promulgation of Air Quality Implementation Plans; Arkansas; Prevention of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-11

    ...) Prevention of Significant Deterioration (PSD) program updates the Arkansas SIP to incorporate by reference (IBR) requirements for the Federal PSD permitting program under EPA's November 29, 2005 Phase 2 8-hour Ozone Implementation rule. The November 6, 2012 proposed SIP revision to the Arkansas NSR PSD program...

  9. Assessment of soybean breeding lines for resistance to Phomopsis seed decay from field trials in Stoneville, Mississippi

    USDA-ARS?s Scientific Manuscript database

    Phomopsis seed decay (PSD) is one of the most important seed diseases in soybean. A fungal pathogen, Phomopsis longicolla (syn. Diaporthe longicolla), is the primary causal agent of PSD. Planting PSD-resistant soybean cultivars is the most effective strategy to manage this disease. However, few comm...

  10. 40 CFR 52.1773 - Conditional approval.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Deterioration (PSD) infrastructure requirements for the 1997 annual and 2006 24-hour fine particulate matter... to the PM2.5 standard for their PSD program and committing to providing the necessary SIP revision to... PM2.5 Rule (including PM2.5 PSD Increment-SILs-SMC, as it relates to PM2.5 increments to meet the...

  11. 40 CFR 52.1773 - Conditional approval.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Deterioration (PSD) infrastructure requirements for the 1997 annual and 2006 24-hour fine particulate matter... to the PM2.5 standard for their PSD program and committing to providing the necessary SIP revision to... PM2.5 Rule (including PM2.5 PSD Increment-SILs-SMC, as it relates to PM2.5 increments to meet the...

  12. 40 CFR 52.1620 - Identification of plan.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... prohibit interference with maintenance and PSD measures in any other state. Interstate transport for the... interference with maintenance and PSD measures in any other state. Sunland Park 1997 8-Hour Ozone Maintenance... other states' programs for PSD for the 1997 and 2008 Ozone and the 1997 and 2006 PM2.5 NAAQS Bernalillo...

  13. 76 FR 7116 - Approval and Promulgation of Implementation Plans; Alaska: Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-09

    ... revision updates Alaska's Prevention of Significant Deterioration (PSD) program to reflect changes to the Federal PSD program relating to the permitting of greenhouse gas (GHG) emissions. DATES: This action is... Federal PSD program as of August 2, 2010 relating to the permitting of GHGs. In the proposal, EPA made the...

  14. 78 FR 54602 - Approval and Promulgation of State Implementation Plans; Utah: Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-05

    ... Prevention of Significant Deterioration (PSD) program and other SIP provisions. These revisions were...'s regulations with the GHG emission thresholds established in EPA's ``PSD and Title V Greenhouse Gas... to approve the GHG (as it relates to the PSD program) revisions because the Agency has determined...

  15. 76 FR 49708 - Approval and Promulgation of Implementation Plans; Iowa: Prevention of Significant Deterioration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-11

    ... regulation of Greenhouse Gases (GHGs) under Iowa's Prevention of Significant Deterioration (PSD) program..., 2010. It is intended to align Iowa's regulations with the ``PSD and Title V Greenhouse Gas Tailoring... the Clean Air Act (CAA or Act) and EPA regulations regarding PSD permitting for GHGs. DATES: Comments...

  16. 75 FR 56027 - Approval and Promulgation of Air Quality Implementation Plans; Texas; Revisions to the New Source...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-15

    ... Implementation Plan (SIP); Prevention of Significant Deterioration (PSD) AGENCY: Environmental Protection Agency (EPA). ACTION: Proposed rule. SUMMARY: EPA is proposing to approve revisions to the Texas PSD State... revision submitted July 16, 2010. This action makes no significant changes to the Texas PSD SIP; it merely...

  17. Evaluating soybean germplasm and commercial varieties for resistance to Phomopsis seed decay

    USDA-ARS?s Scientific Manuscript database

    Soybean Phomopsis seed decay (PSD) is the major cause of poor seed quality in most soybean production areas of the United States. Very few soybean cultivars currently available for planting in the US have resistance to PSD. To identify new sources of resistance to PSD, a multistate and multiyear res...

  18. 76 FR 20907 - Approval and Promulgation of Air Quality Implementation Plans; New Mexico; Prevention of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-14

    ... revision modifies New Mexico's Prevention of Significant Deterioration (PSD) program to establish... subject to New Mexico's PSD permitting requirements for their greenhouse gas (GHG) emissions. Due to the SIP Narrowing Rule, 75 FR 82536, starting on January 2, 2011, the approved New Mexico SIP's PSD...

  19. 75 FR 27191 - Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NSR): Aggregation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-14

    ... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Parts 51 and 52 [EPA-HQ-OAR-2003-0064, FRL-9151-3] RIN 2060-AP80 Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NSR... of the Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NSR...

  20. 78 FR 19596 - Approval and Promulgation of Air Quality Implementation Plans; Arkansas; Prevention of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-02

    ...) Prevention of Significant Deterioration (PSD) program updates the Arkansas SIP to incorporate by reference (IBR) requirements for the federal PSD permitting program under EPA's November 29, 2005 Phase 2 8-hour Ozone Implementation rule. The November 6, 2012, SIP revision to the Arkansas NSR PSD program provides...

  1. 76 FR 26192 - Revisions to the California State Implementation Plan, Northern Sonoma County Air Pollution...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-06

    ...-approved Prevention of Significant Deterioration (PSD) permit programs. These revisions update the definitions used in the districts' PSD permit programs. DATES: This rule is effective on July 5, 2011 without... Deterioration (PSD) permit program. Both the NSCAPCD and MCAQMD are currently designated as attainment or...

  2. 76 FR 40242 - Approval and Promulgation of Air Quality Implementation Plans; Indiana; Modifications to Indiana...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-08

    ... Deterioration (PSD) and Nonattainment New Source Review (NNSR) rules. The amendments include grammatical changes, corrections to numbering, addition of definitions consistent with Federal PSD and NNSR regulations, and... revisions to EPA for approval on November 24, 2010. They are consistent with the current Federal PSD and...

  3. 75 FR 70140 - Approval and Promulgation of Implementation Plans; New York Prevention of Significant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-17

    ... Significant Deterioration of Air Quality (PSD) and Nonattainment New Source Review (NNSR) State regulations. These revisions create a new New York State PSD regulation program and modify the existing New York... EPA is taking no action at this time on the PSD permitting threshold provisions to the extent that...

  4. Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development.

    PubMed

    Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

    2013-05-28

    The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5-PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation-dependent CDKL5-PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutations may be implicated in the pathogenesis of CDKL5-related disorders.

  5. Anchoring and Synaptic stability of PSD-95 is driven by ephrin-B3

    PubMed Central

    Hruska, Martin; Henderson, Nathan T.; Xia, Nan L.; Le Marchand, Sylvain J.; Dalva, Matthew B.

    2015-01-01

    Summary Organization of signaling complexes at excitatory synapses by Membrane Associated Guanylate Kinase (MAGUK) proteins regulates synapse development, plasticity, senescence, and disease. Post-translational modification of MAGUK family proteins can drive their membrane localization, yet it is unclear how these intracellular proteins are targeted to sites of synaptic contact. Here we show using super-resolution imaging, biochemical approaches, and in vivo models that the trans-synaptic organizing protein, ephrin-B3, controls the synaptic localization and stability of PSD-95 and links these events to changes in neuronal activity via negative regulation of a novel MAPK-dependent phosphorylation site on ephrin-B3 (S332). Unphosphorylated ephrin-B3 is enriched at synapses, interacts directly with and stabilizes PSD-95 at synapses. Activity induced phosphorylation of S332 disperses ephrin-B3 from synapses, prevents the interaction with, and enhances the turnover of PSD-95. Thus, ephrin-B3 specifies the synaptic localization of PSD-95 and likely links the synaptic stability of PSD-95 to changes in neuronal activity. PMID:26479588

  6. A model for regulation by SynGAP-α1 of binding of synaptic proteins to PDZ-domain 'Slots' in the postsynaptic density

    PubMed Central

    Walkup, Ward G; Mastro, Tara L; Schenker, Leslie T; Vielmetter, Jost; Hu, Rebecca; Iancu, Ariella; Reghunathan, Meera; Bannon, Barry Dylan; Kennedy, Mary B

    2016-01-01

    SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 isoform binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95, the principal PSD scaffold, and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-α1 regulates the composition of the PSD by restricting binding to the PDZ domains of PSD-95. We show that phosphorylation by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Polo-like kinase-2 (PLK2) decreases its affinity for the PDZ domains by several fold, which would free PDZ domains for occupancy by other proteins. Finally, we show that three critical postsynaptic signaling proteins that bind to the PDZ domains of PSD-95 are present in higher concentration in PSDs isolated from mice with a heterozygous deletion of synGAP. DOI: http://dx.doi.org/10.7554/eLife.16813.001 PMID:27623146

  7. A Statitstical Study of Energetic Electron Phase Space Density with RBSP and BD-IES Data

    NASA Astrophysics Data System (ADS)

    Chen, X.; Zong, Q.; Zhou, X.; Zou, H.; Wang, Y.

    2017-12-01

    We present a statistical study of energetic electron phase space density (PSD) with combined observations from the Magnetic Electron Ion Spectrometer (MagEIS) instruments onboard the Van Allen Probes and the Image Electron Spectrometer (BD-IES) onboard an inclined geosynchronous orbit satellite. The electron PSD as a function of the adiabatic invariants is derived using one year data (Nov. 2015 to Oct. 2016) of these instruments. The orbits of the satellites cover a wide range of L-shells, allowing for the distribution of electron PSD throughout the radiation belt (L* 1 to 10). A persistent peak of energetic electron ( 30 to 1000 MeV/G) PSD is unambiguously identified at L* 5.5, which may help to understand the role of local acceleration and radial diffusion in the dynamics of energetic electrons. In addition, the electron PSD shows a power-law distribution with the exponent varying from about -2 to -4 depending on L*. The variance of electron PSD during storm and substorm activities indicating by SYMH and AE indices are also discussed.

  8. Palmitoylation-dependent CDKL5–PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development

    PubMed Central

    Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

    2013-01-01

    The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5–PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation-dependent CDKL5–PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutations may be implicated in the pathogenesis of CDKL5-related disorders. PMID:23671101

  9. Immunolocalization of NR1, NR2A, and PSD-95 in rat hippocampal subregions during postnatal development.

    PubMed

    Ling, Wei; Chang, Lirong; Song, Yizhi; Lu, Tao; Jiang, Yuhua; Li, Youxiang; Wu, Yan

    2012-05-01

    Although the expression of NMDARs and synaptic-associated proteins has been widely studied, the temporospatial distribution of NMDAR subunits and synaptic proteins in different hippocampal subregions during postnatal development still lacks detailed information, and the relationship between NR1 or NR2 subunits and PSD-95 family proteins is controversial. In this study, we used immunofluorescent staining to assess NR1 or NR2A and PSD-95 expressions and the relationship between them in CA1, CA3, and DG of rat hippocampus on postnatal (P) days: P0, P4, P7, P10, P14, P21, P28, P56. The results showed that from P0 to P56, NR1, NR2A, and PSD-95 expressions increased gradually, and the time points of their expression peak differed in CA1, CA3, and DG during postnatal development. Interestingly, although the expression of PSD-95 was positively correlated to both NR1 and NR2A, the NR1 and PSD-95 coexpressed puncta were greatest in CA3, while NR2A and PSD-95 coexpressed puncta were greatest in CA1, compared to other subregions. Surprisingly, at P21, among different strata of CA1, the area of highest expression of NR2A was dramatically changed from stratum pyramidale to stratum polymorphum and stratum moleculare, and returned to stratum pyramidale gradually on the later observed days again, indicating that P21 may be one critical timepoint during postnatal development in CA1. The specific temporospatial distribution pattern of NR1, NR2A, and PSD-95 might be related to the different physiological functions during postnatal development. Discovering the alteration of the relationship between PSD-95 and NMDAR subunits expression may be helpful for understanding mechanisms and therapy of neurodegenerative diseases. Copyright © 2011 Elsevier GmbH. All rights reserved.

  10. SU-F-P-44: A Direct Estimate of Peak Skin Dose for Interventional Fluoroscopy Procedures

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

    Weir, V; Zhang, J

    Purpose: There is an increasing demand for medical physicist to calculate peak skin dose (PSD) for interventional fluoroscopy procedures. The dose information (Dose-Area-Product and Air Kerma) displayed in the console cannot directly be used for this purpose. Our clinical experience shows that the use of the existing methods may overestimate or underestimate PSD. This study attempts to develop a direct estimate of PSD from the displayed dose metrics. Methods: An anthropomorphic torso phantom was used for dose measurements for a common fluoroscopic procedure. Entrance skin doses were measured with a Piranha solid state point detector placed on the table surfacemore » below the torso phantom. An initial “reference dose rate” (RE) measurement was conducted by comparing the displayed dose rate (mGy/min) to the dose rate measured. The distance from table top to focal spot was taken as the reference distance (RD at the RE. Table height was then adjusted. The displayed air kerma and DAP were recorded and sent to three physicists to estimate PSD. An inverse square correction was applied to correct displayed air kerma at various table heights. The PSD estimated by physicists and the PSD by the proposed method were then compared with the measurements. The estimated DAPs were compared to displayed DAP readings (mGycm2). Results: The difference between estimated PSD by the proposed method and direct measurements was less than 5%. For the same set of data, the estimated PSD by each of three physicists is different from measurements by ±52%. The DAP calculated by the proposed method and displayed DAP readings in the console is less than 20% at various table heights. Conclusion: PSD may be simply estimated from displayed air kerma or DAP if the distance between table top and tube focal spot or if x-ray beam area on table top is available.« less

  11. Investigation of pore size and energy distributions by statistical physics formalism applied to agriculture products

    NASA Astrophysics Data System (ADS)

    Aouaini, Fatma; Knani, Salah; Yahia, Manel Ben; Bahloul, Neila; Ben Lamine, Abdelmottaleb; Kechaou, Nabil

    2015-12-01

    In this paper, we present a new investigation that allows determining the pore size distribution (PSD) in a porous medium. This PSD is achieved by using the desorption isotherms of four varieties of olive leaves. This is by the means of statistical physics formalism and Kelvin's law. The results are compared with those obtained with scanning electron microscopy. The effect of temperature on the distribution function of pores has been studied. The influence of each parameter on the PSD is interpreted. A similar function of adsorption energy distribution, AED, is deduced from the PSD.

  12. Toward a real-time in vivo dosimetry system using plastic scintillation detectors

    PubMed Central

    Archambault, Louis; Briere, Tina M.; Pönisch, Falk; Beaulieu, Luc; Kuban, Deborah A.; Lee, Andrew; Beddar, Sam

    2010-01-01

    Purpose In this work, we present and validate a plastic scintillation detector (PSD) system designed for real-time multi-probe in vivo measurements. Methods and Materials The PSDs were built with a dose-sensitive volume of 0.4 mm3. PSDs were assembled into modular detector patches, each containing 5 closely packed PSDs. Continuous dose readings were performed every 150 ms, with a gap between consecutive readings of less than 0.3 ms. We first studied the effect of electron multiplication. We then assessed system performance in acrylic and anthropomorphic pelvic phantoms. Results The PSDs are compatible with clinical rectal balloons and are easily inserted into the anthropomorphic phantom. With an electron multiplication average gain factor of 40, a twofold increase in the signal-to-noise ratio was observed, making near real-time dosimetry feasible. Under calibration conditions, the PSDs agreed with ion chamber measurements to 0.08%. Precision, evaluated as a function of the total dose delivered, ranged from 2.3% at 2 cGy to 0.4% at 200 cGy. Conclusion Real-time PSD measurements are highly accurate and precise. These PSDs can be mounted onto rectal balloons, transforming these clinical devices into in vivo dose detectors without modifying current clinical practice. Real-time monitoring of the dose delivered near the rectum during prostate radiation therapy should help radiation oncologists protect this sensitive normal structure. PMID:20231074

  13. DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy

    PubMed Central

    Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan

    2017-01-01

    Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95–nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95–nNOS interactions in MHE. PMID:28932186

  14. Early Growth Response 1 (Egr-1) Regulates N-Methyl-d-aspartate Receptor (NMDAR)-dependent Transcription of PSD-95 and α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor (AMPAR) Trafficking in Hippocampal Primary Neurons.

    PubMed

    Qin, Xike; Jiang, Yongjun; Tse, Yiu Chung; Wang, Yunling; Wong, Tak Pan; Paudel, Hemant K

    2015-12-04

    The N-methyl-d-aspartate receptor (NMDAR) controls synaptic plasticity and memory function and is one of the major inducers of transcription factor Egr-1 in the hippocampus. However, how Egr-1 mediates the NMDAR signal in neurons has remained unclear. Here, we show that the hippocampus of mice lacking Egr-1 displays electrophysiology properties and ultrastructure that are similar to mice overexpressing PSD-95, a major scaffolding protein of postsynaptic density involved in synapse formation, synaptic plasticity, and synaptic targeting of AMPA receptors (AMPARs), which mediate the vast majority of excitatory transmission in the CNS. We demonstrate that Egr-1 is a transcription repressor of the PSD-95 gene and is recruited to the PSD-95 promoter in response to NMDAR activation. Knockdown of Egr-1 in rat hippocampal primary neurons blocks NMDAR-induced PSD-95 down-regulation and AMPAR endocytosis. Likewise, overexpression of Egr-1 in rat hippocampal primary neurons causes reduction in PSD-95 protein level and promotes AMPAR endocytosis. Our data indicate that Egr-1 is involved in NMDAR-mediated PSD-95 down-regulation and AMPAR endocytosis, a process important in the expression of long term depression. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. A framework to understand the variations of PSD-95 expression in brain aging and in Alzheimer's disease.

    PubMed

    Savioz, Armand; Leuba, Geneviève; Vallet, Philippe G

    2014-11-01

    The postsynaptic density protein PSD-95 is a major element of synapses. PSD-95 is involved in aging, Alzheimer's disease (AD) and numerous psychiatric disorders. However, contradictory data about PSD-95 expression in aging and AD have been reported. Indeed in AD versus control brains PSD-95 varies according to regions, increasing in the frontal cortex, at least in a primary stage, and decreasing in the temporal cortex. In contrast, in transgenic mouse models of aging and AD PSD-95 expression is decreased, in behaviorally aged impaired versus unimpaired rodents it can decrease or increase and finally, it is increased in rodents grown in enriched environments. Different factors explain these contradictory results in both animals and humans, among others concomitant psychiatric endophenotypes, such as depression. The possible involvement of PSD-95 in reactive and/or compensatory mechanisms during AD progression is underscored, at least before the occurrence of important synaptic elimination. Thus, in AD but not in AD transgenic mice, enhanced expression might precede the diminution commonly observed in advanced aging. A two-compartments cell model, separating events taking place in cell bodies and synapses, is presented. Overall these data suggest that AD research will progress by untangling pathological from protective events, a prerequisite for effective therapeutic strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy.

    PubMed

    Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan

    2017-01-01

    Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95-nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95-nNOS interactions in MHE.

  17. Development of Fast Measurement System of Neutron Emission Profile Using a Digital Signal Processing Technique in JT-60U

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

    Ishikawa, M.; Shinohara, K.; Itoga, T.

    2008-03-12

    Neutron emission profiles are routinely measured in JT-60U Tokamak. Stinbene neuron detectors (SNDs), which combine a Stilbene organic crystal scintillation detector (Stilbene detector) with an analog neutron-gamma pulse shape discrimination (PSD) circuit, have been used to measure neutron flux efficiently. Although the SND has many advantages as a neutron detector, the maximum count rate is limited up to {approx}1x 10{sup 5} counts/s due to the dead time of the analog PSD circuit. To overcome this issue, a digital signal processing (DSP) system using a Flash-ADC has been developed. In this system, anode signals from the photomultiplier of the Stilbene detectormore » are fed to the Flash ADC and digitized. Then, the PSD between neutrons and gamma-rays are performed using software. The photomultiplier tube is also modified to suppress and correct gain fluctuation of the photomultiplier. The DSP system has been installed in the center channel of the vertical neutron collimator system in JT-60U and applied to measurements of neutron flux in JT-60U experiments. Neutron flux are successfully measured with count rate up to {approx}1x 10{sup 6} counts/s without the effect of pile up of detected pulses. The performance of the DSP system as a neutron detector is demonstrated.« less

  18. 40 CFR 124.6 - Draft permits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 270.32 (RCRA) (except for PSD permits))); (2) All compliance schedules under §§ 122.47 (NPDES), 144.53 (UIC), 233.10 (404), or 270.33 (RCRA) (except for PSD permits); (3) All monitoring requirements under §§ 122.48 (NPDES), 144.54 (UIC), 233.11 (404), or 270.31 (RCRA) (except for PSD permits); and (4) For: (i...

  19. 76 FR 2581 - Action To Ensure Authority To Issue Permits Under the Prevention of Significant Deterioration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-14

    ... or Act) Prevention of Significant Deterioration (PSD) program to sources of greenhouse gases (GHGs... issue preconstruction PSD permits to GHG- emitting sources. This action is related to EPA's recent final rule, the GHG PSD SIP Call, published on December 13, 2010, in which EPA made a finding of substantial...

  20. 40 CFR 124.6 - Draft permits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 270.32 (RCRA) (except for PSD permits))); (2) All compliance schedules under §§ 122.47 (NPDES), 144.53 (UIC), 233.10 (404), or 270.33 (RCRA) (except for PSD permits); (3) All monitoring requirements under §§ 122.48 (NPDES), 144.54 (UIC), 233.11 (404), or 270.31 (RCRA) (except for PSD permits); and (4) For: (i...

  1. 77 FR 58032 - Approval and Promulgation of Implementation Plans; New Mexico; Albuquerque/Bernalillo County...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-19

    ... prevention of significant deterioration (PSD) measures required in the SIP of any other state, with regard to... modify the PSD SIP to include nitrogen oxides (NO X ) as an ozone precursor. EPA is approving revisions to the Albuquerque/Bernalillo County PSD SIP that identify the PM 2.5 precursors and establish...

  2. 40 CFR 124.6 - Draft permits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 270.32 (RCRA) (except for PSD permits))); (2) All compliance schedules under §§ 122.47 (NPDES), 144.53 (UIC), 233.10 (404), or 270.33 (RCRA) (except for PSD permits); (3) All monitoring requirements under §§ 122.48 (NPDES), 144.54 (UIC), 233.11 (404), or 270.31 (RCRA) (except for PSD permits); and (4) For: (i...

  3. 78 FR 6818 - Notice of Issuance of Prevention of Significant Deterioration Modification and Part 71 Operating...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-31

    ..., EPA issued a Modification to a Prevention of Significant Deterioration (PSD) permit to NRG Backup..., Minnesota. The modified PSD permit changes the required interval of nitrogen oxide performance testing for... comment period, which ended on October 19, 2012, EPA received a comment on the modified draft PSD permit...

  4. 40 CFR 124.6 - Draft permits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 270.32 (RCRA) (except for PSD permits))); (2) All compliance schedules under §§ 122.47 (NPDES), 144.53 (UIC), 233.10 (404), or 270.33 (RCRA) (except for PSD permits); (3) All monitoring requirements under §§ 122.48 (NPDES), 144.54 (UIC), 233.11 (404), or 270.31 (RCRA) (except for PSD permits); and (4) For: (i...

  5. 77 FR 65305 - Approval of Air Quality Implementation Plans; California; San Joaquin Valley Unified Air...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-26

    ... incorporates District Rule 2410-- Prevention of Significant Deterioration (PSD)--into the California SIP to establish a PSD permit program for pre-construction review of certain new and modified major stationary... provides an adequate PSD permitting program as required by section 110 and part C of title I of the CAA...

  6. 77 FR 62200 - Approval and Promulgation of Implementation Plans; New Mexico; Revisions to the New Source Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-12

    ... Plan (SIP); Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NNSR... approve revisions to the New Mexico SIP to update the New Mexico NNSR and PSD SIP permitting programs.... New Mexico submitted the PSD and NNSR SIP permitting revisions in two SIP submittals on June 11, 2009...

  7. 40 CFR 124.6 - Draft permits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 270.32 (RCRA) (except for PSD permits))); (2) All compliance schedules under §§ 122.47 (NPDES), 144.53 (UIC), 233.10 (404), or 270.33 (RCRA) (except for PSD permits); (3) All monitoring requirements under §§ 122.48 (NPDES), 144.54 (UIC), 233.11 (404), or 270.31 (RCRA) (except for PSD permits); and (4) For: (i...

  8. Measuring the Unmeasurable: Upholding Rigor in Quantitative Studies of Personal and Social Development in Outdoor Adventure Education

    ERIC Educational Resources Information Center

    Scrutton, Roger; Beames, Simon

    2015-01-01

    Outdoor adventure education (OAE) has a long history of being credited with the personal and social development (PSD) of its participants. PSD is notoriously difficult to measure quantitatively, yet stakeholders demand statistical evidence that given approaches to eliciting PSD are effective in their methods. Rightly or wrongly, many stakeholders…

  9. The utility of presacral drainage in penetrating rectal injuries in adult and pediatric patients.

    PubMed

    Savoie, Kate B; Beazley, Thomas M; Cleveland, Brent; Khaneki, Sina; Markel, Troy A; Hammer, Peter M; Savage, Stephanie; Williams, Regan F

    2017-11-01

    With changing weaponry associated with injuries in civilian trauma, there is no clinical census on the utility of presacral drainage (PSD) in penetrating rectal injuries (PRIs), particularly in pediatric patients. Patients with PRI from July 2004-June 2014 treated at two free-standing children's hospitals and two adult level 1 trauma centers were compared by age (pediatric patients ≤16 years) and PSD. A stratified analysis was performed based on age. The primary outcome was pelvic/presacral abscess. We identified 81 patients with PRI; 19 pediatric, 62 adult. Forty patients had PSD; only three pediatric patients had a drain. Adult patients were more likely to have sustained gunshot wounds (84%), whereas pediatric patients were more likely to sustain impalement injuries (59%). Pediatric patients were more likely to have distal extraperitoneal injuries (56% versus 27% in adults, P = 0.03). PSD was more common in adult patients (59% versus 14%, P = 0.0004), African-Americans (71% versus 11% Caucasian, P < 0.01), and those sustaining gun shot wounds (63% versus 18% impalement, P < 0.01); only race remained significant in stratified analysis for both adult and pediatric patients. There were three cases of pelvic/presacral abscess, all in the adult patients (P = 0.31); one patient with PSD and two without PSD (P = 0.58). In stratified analysis, there were no differences in any infectious complication between those with and without PSD. Pelvic/presacral abscess is a rare complication of PRI, especially in pediatric patients. PSD is not associated with decreased rates of infectious complications and may not be necessary in the treatment of PRI. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Decrease in neuronal nicotinic acetylcholine receptor subunit and PSD-93 transcript levels in the male mouse MPG after cavernous nerve injury or explant culture.

    PubMed

    Girard, Beatrice M; Merriam, Laura A; Tompkins, John D; Vizzard, Margaret A; Parsons, Rodney L

    2013-11-15

    Quantitative real-time PCR was used to test whether cavernous nerve injury leads to a decrease in major pelvic ganglia (MPG) neuronal nicotinic ACh receptor (nAChR) subunit and postsynaptic density (PSD)-93 transcript levels. Subunits α3, β4, and α7, commonly expressed in the MPG, were selected for analysis. After 72 h in explant culture, MPG transcript levels for α3, β4, α7, and PSD-93 were significantly depressed. Three days after cavernous nerve axotomy or crush in vivo, transcript levels for α3, β4, and PSD-93, but not for α7, were significantly depressed. Three days after dissection of the cavernous nerve free of underlying tissue and application of a 5-mm lateral stretch (manipulation), transcript levels for α3 and PSD-93 were also significantly decreased. Seven days after all three surgical procedures, α3 transcript levels remained depressed, but PSD-93 transcript levels were still decreased only after axotomy or nerve crush. At 30 days postsurgery, transcript levels for the nAChR subunits and PSD-93 had recovered. ACh-induced currents were significantly smaller in MPG neurons dissociated from 3-day explant cultured ganglia than from those recorded in neurons dissociated from acutely isolated ganglia; this observation provides direct evidence showing that a decrease in nAChR function was coincident with a decrease in nAChR subunit transcript levels. We conclude that a downregulation of nAChR subunit and PSD-93 expression after cavernous nerve injury, or even manipulation, could interrupt synaptic transmission within the MPG and thus contribute to the loss of neural control of urogenital organs after pelvic surgeries.

  11. Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity

    PubMed Central

    Ma, Qi; Ruan, Hongyu; Peng, Lisheng; Zhang, Mingjie; Gack, Michaela U.

    2017-01-01

    Ubiquitination-directed proteasomal degradation of synaptic proteins, presumably mediated by lysine 48 (K48) of ubiquitin, is a key mechanism in synapse and neural circuit remodeling. However, more than half of polyubiquitin (polyUb) species in the mammalian brain are estimated to be non-K48; among them, the most abundant is Lys 63 (K63)-linked polyUb chains that do not tag substrates for degradation but rather modify their properties and activity. Virtually nothing is known about the role of these nonproteolytic polyUb chains at the synapse. Here we report that K63-polyUb chains play a significant role in postsynaptic protein scaffolding and synaptic strength and plasticity. We found that the postsynaptic scaffold PSD-95 (postsynaptic density protein 95) undergoes K63 polyubiquitination, which markedly modifies PSD-95’s scaffolding potentials, enables its synaptic targeting, and promotes synapse maturation and efficacy. TNF receptor-associated factor 6 (TRAF6) is identified as a direct E3 ligase for PSD-95, which, together with the E2 complex Ubc13/Uev1a, assembles K63-chains on PSD-95. In contrast, CYLD (cylindromatosis tumor-suppressor protein), a K63-specific deubiquitinase enriched in postsynaptic densities, cleaves K63-chains from PSD-95. We found that neuronal activity exerts potent control of global and synaptic K63-polyUb levels and, through NMDA receptors, drives rapid, CYLD-mediated PSD-95 deubiquitination, mobilizing and depleting PSD-95 from synapses. Silencing CYLD in hippocampal neurons abolishes NMDA-induced chemical long-term depression. Our results unveil a previously unsuspected role for nonproteolytic polyUb chains in the synapse and illustrate a mechanism by which a PSD-associated K63-linkage–specific ubiquitin machinery acts on a major postsynaptic scaffold to regulate synapse organization, function, and plasticity. PMID:28973854

  12. Hot-spot model for accretion disc variability as random process. II. Mathematics of the power-spectrum break frequency

    NASA Astrophysics Data System (ADS)

    Pecháček, T.; Goosmann, R. W.; Karas, V.; Czerny, B.; Dovčiak, M.

    2013-08-01

    Context. We study some general properties of accretion disc variability in the context of stationary random processes. In particular, we are interested in mathematical constraints that can be imposed on the functional form of the Fourier power-spectrum density (PSD) that exhibits a multiply broken shape and several local maxima. Aims: We develop a methodology for determining the regions of the model parameter space that can in principle reproduce a PSD shape with a given number and position of local peaks and breaks of the PSD slope. Given the vast space of possible parameters, it is an important requirement that the method is fast in estimating the PSD shape for a given parameter set of the model. Methods: We generated and discuss the theoretical PSD profiles of a shot-noise-type random process with exponentially decaying flares. Then we determined conditions under which one, two, or more breaks or local maxima occur in the PSD. We calculated positions of these features and determined the changing slope of the model PSD. Furthermore, we considered the influence of the modulation by the orbital motion for a variability pattern assumed to result from an orbiting-spot model. Results: We suggest that our general methodology can be useful for describing non-monotonic PSD profiles (such as the trend seen, on different scales, in exemplary cases of the high-mass X-ray binary Cygnus X-1 and the narrow-line Seyfert galaxy Ark 564). We adopt a model where these power spectra are reproduced as a superposition of several Lorentzians with varying amplitudes in the X-ray-band light curve. Our general approach can help in constraining the model parameters and in determining which parts of the parameter space are accessible under various circumstances.

  13. Chemical Compensation of Mitochondrial Phospholipid Depletion in Yeast and Animal Models of Parkinson’s Disease

    PubMed Central

    Wang, Shaoxiao; Zhang, Siyuan; Xu, Chuan; Barron, Addie; Galiano, Floyd; Patel, Dhaval; Lee, Yong Joo; Caldwell, Guy A.; Caldwell, Kim A.

    2016-01-01

    We have been investigating the role that phosphatidylethanolamine (PE) and phosphatidylcholine (PC) content plays in modulating the solubility of the Parkinson’s disease protein alpha-synuclein (α-syn) using Saccharomyces cerevisiae and Caenorhabditis elegans. One enzyme that synthesizes PE is the conserved enzyme phosphatidylserine decarboxylase (Psd1/yeast; PSD-1/worms), which is lodged in the inner mitochondrial membrane. We previously found that decreasing the level of PE due to knockdown of Psd1/psd-1 affects the homeostasis of α-syn in vivo. In S. cerevisiae, the co-occurrence of low PE and α-syn in psd1Δ cells triggers mitochondrial defects, stress in the endoplasmic reticulum, misprocessing of glycosylphosphatidylinositol-anchored proteins, and a 3-fold increase in the level of α-syn. The goal of this study was to identify drugs that rescue this phenotype. We screened the Prestwick library of 1121 Food and Drug Administration-approved drugs using psd1Δ + α-syn cells and identified cyclosporin A, meclofenoxate hydrochloride, and sulfaphenazole as putative protective compounds. The protective activity of these drugs was corroborated using C. elegans in which α-syn is expressed specifically in the dopaminergic neurons, with psd-1 depleted by RNAi. Worm populations were examined for dopaminergic neuron survival following psd-1 knockdown. Exposure to cyclosporine, meclofenoxate, and sulfaphenazole significantly enhanced survival at day 7 in α-syn-expressing worm populations whereby 50–55% of the populations displayed normal neurons, compared to only 10–15% of untreated animals. We also found that all three drugs rescued worms expressing α-syn in dopaminergic neurons that were deficient in the phospholipid cardiolipin following cardiolipin synthase (crls-1) depletion by RNAi. We discuss how these drugs might block α-syn pathology in dopaminergic neurons. PMID:27736935

  14. Application of year-round atmospheric transmission data, collected with the MSRT multiband transmissometer during the FATMOSE trial in the False Bay area

    NASA Astrophysics Data System (ADS)

    de Jong, Arie N.; van Eijk, Alexander M. J.; Cohen, Leo H.; Fritz, Peter J.; Gunter, Willem H.; Vrahimis, George; October, Faith J.

    2011-09-01

    The FATMOSE trial (False Bay Atmospheric Experiment) is a continuation of the cooperative work between TNO and IMT on atmospheric propagation and point target detection and identification in a maritime environment, South Africa). The atmospheric transmission, being of major importance for target detection, was measured with the MSRT multiband optical/IR transmissometer over a path of 15.7 km over sea. Simultaneously a set of instruments was installed on a midpath lighthouse for collection of local meteorological data, including turbulence, scintillation, sea surface temperature and visibility. The multiband transmission data allow the retrieval of the size distribution (PSD) of the particles (aerosols) in the transmission path. The retrieved PSD's can be correlated with the weather data such as windspeed, wind direction, relative humidity and visibility. This knowledge will lead to better atmospheric propagation models. The measurement period covered nearly a full year, starting in November 2009 and ending in October 2010. The False Bay site is ideal for studies on propagation effects over sea because of the large variety of weather conditions, including high windspeed, expected from the South East with maritime air masses, as well as Northerly winds, expected to bring warm and dry air from the continent. From an operational point of view the False Bay area is interesting, being representative for the scenery around the African coast with warships in an active protecting role in the battle against piracy. The yearround transmission data are an important input for range performance calculations of electro-optical sensors against maritime targets. The data support the choice of the proper spectral band and contain statistical information about the detection ranges to be expected. In this paper details on the instrumentation will be explained as well as the methods of calibration and PSD retrieval. Data are presented for various weather conditions, showing correlations between different parameters and including statistical behaviour over the year. Examples will be shown of special conditions such as refractive gain, gravity waves and showers.

  15. 40 CFR 52.875 - Original identification of plan section.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... applicable to stationary sources subject to prevention of significant deterioration (PSD) permit requirements... interim stack height policy for each PSD permit issued until such time as EPA revises its general stack... submitted rule revisions to K.A.R. 28-19-17, the PSD rule; to K.A.R. 28-19-19, the CEM rule; and to K.A.R...

  16. 40 CFR 52.1620 - Identification of plan.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... maintenance and PSD measures in any other state. Interstate transport for the 1997 ozone and PM2.5 NAAQS New Mexico 9/17/2007 11/26/2010, 75 FR 72688 Revisions to prohibit interference with maintenance and PSD... for PSD for the 1997 and 2008 Ozone and the 1997 and 2006 PM2.5 NAAQS Bernalillo County 8/16/2010 8/19...

  17. 40 CFR 52.2479 - Contents of the federally approved, State submitted implementation plan.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-087 Prevention of significant deterioration (PSD) [02/19/91] 173-405-091 Special studies [02/19/91] 2... deterioration (PSD) [02/19/91] 173-410-100 Special studies [02/19/91] 2.2.415 WAC 173-415 Primary Aluminum...] 173-415-051 Prevention of significant deterioration (PSD) [02/19/91] 173-415-060 Monitoring and...

  18. 76 FR 55799 - Approval of Clean Air Act Prevention of Significant Deterioration Permit Issued to Avenal Power...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... Deterioration (PSD) permit application submitted by Avenal Power Center, LLC to authorize construction of the Avenal Energy Project. DATES: The EPA's PSD permit for the Avenal Energy Project became effective and...: The EPA issued a PSD permit on May 27, 2011, to Avenal Power Center, LLC for the Avenal Energy Project...

  19. 40 CFR 52.875 - Original identification of plan section.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... applicable to stationary sources subject to prevention of significant deterioration (PSD) permit requirements... interim stack height policy for each PSD permit issued until such time as EPA revises its general stack... submitted rule revisions to K.A.R. 28-19-17, the PSD rule; to K.A.R. 28-19-19, the CEM rule; and to K.A.R...

  20. 40 CFR 52.2479 - Contents of the federally approved, State submitted implementation plan.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-087 Prevention of significant deterioration (PSD) [02/19/91] 173-405-091 Special studies [02/19/91] 2... deterioration (PSD) [02/19/91] 173-410-100 Special studies [02/19/91] 2.2.415 WAC 173-415 Primary Aluminum...] 173-415-051 Prevention of significant deterioration (PSD) [02/19/91] 173-415-060 Monitoring and...

  1. 78 FR 4339 - Approval and Promulgation of Implementation Plans; New Mexico; Revisions to the New Source Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-22

    ... Plan (SIP); Prevention of Significant Deterioration (PSD) and Nonattainment New Source Review (NNSR... revisions to the New Mexico SIP to update the New Mexico NNSR and PSD SIP permitting programs consistent... submitted the PSD and NNSR SIP permitting revisions in two SIP submittals on June 11, 2009 and May 23, 2011...

  2. 40 CFR 52.875 - Original identification of plan section.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... applicable to stationary sources subject to prevention of significant deterioration (PSD) permit requirements... interim stack height policy for each PSD permit issued until such time as EPA revises its general stack... submitted rule revisions to K.A.R. 28-19-17, the PSD rule; to K.A.R. 28-19-19, the CEM rule; and to K.A.R...

  3. 40 CFR 52.875 - Original identification of plan section.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... applicable to stationary sources subject to prevention of significant deterioration (PSD) permit requirements... interim stack height policy for each PSD permit issued until such time as EPA revises its general stack... submitted rule revisions to K.A.R. 28-19-17, the PSD rule; to K.A.R. 28-19-19, the CEM rule; and to K.A.R...

  4. Participatory System Dynamics Modeling: Increasing Stakeholder Engagement and Precision to Improve Implementation Planning in Systems.

    PubMed

    Zimmerman, Lindsey; Lounsbury, David W; Rosen, Craig S; Kimerling, Rachel; Trafton, Jodie A; Lindley, Steven E

    2016-11-01

    Implementation planning typically incorporates stakeholder input. Quality improvement efforts provide data-based feedback regarding progress. Participatory system dynamics modeling (PSD) triangulates stakeholder expertise, data and simulation of implementation plans prior to attempting change. Frontline staff in one VA outpatient mental health system used PSD to examine policy and procedural "mechanisms" they believe underlie local capacity to implement evidence-based psychotherapies (EBPs) for PTSD and depression. We piloted the PSD process, simulating implementation plans to improve EBP reach. Findings indicate PSD is a feasible, useful strategy for building stakeholder consensus, and may save time and effort as compared to trial-and-error EBP implementation planning.

  5. Shear strength and microstructure of polydisperse packings: The effect of size span and shape of particle size distribution.

    PubMed

    Azéma, Emilien; Linero, Sandra; Estrada, Nicolas; Lizcano, Arcesio

    2017-08-01

    By means of extensive contact dynamics simulations, we analyzed the effect of particle size distribution (PSD) on the strength and microstructure of sheared granular materials composed of frictional disks. The PSDs are built by means of a normalized β function, which allows the systematic investigation of the effects of both, the size span (from almost monodisperse to highly polydisperse) and the shape of the PSD (from linear to pronouncedly curved). We show that the shear strength is independent of the size span, which substantiates previous results obtained for uniform distributions by packing fraction. Notably, the shear strength is also independent of the shape of the PSD, as shown previously for systems composed of frictionless disks. In contrast, the packing fraction increases with the size span, but decreases with more pronounced PSD curvature. At the microscale, we analyzed the connectivity and anisotropies of the contacts and forces networks. We show that the invariance of the shear strength with the PSD is due to a compensation mechanism which involves both geometrical sources of anisotropy. In particular, contact orientation anisotropy decreases with the size span and increases with PSD curvature, while the branch length anisotropy behaves inversely.

  6. Interaction of nNOS with PSD-95 negatively controls regenerative repair after stroke.

    PubMed

    Luo, Chun-Xia; Lin, Yu-Hui; Qian, Xiao-Dan; Tang, Ying; Zhou, Hai-Hui; Jin, Xing; Ni, Huan-Yu; Zhang, Feng-Yun; Qin, Cheng; Li, Fei; Zhang, Yu; Wu, Hai-Yin; Chang, Lei; Zhu, Dong-Ya

    2014-10-01

    Stroke is a major public health concern. The lack of effective therapies heightens the need for new therapeutic targets. Mammalian brain has the ability to rewire itself to restore lost functionalities. Promoting regenerative repair, including neurogenesis and dendritic remodeling, may offer a new therapeutic strategy for the treatment of stroke. Here, we report that interaction of neuronal nitric oxide synthase (nNOS) with the protein postsynaptic density-95 (PSD-95) negatively controls regenerative repair after stroke in rats. Dissociating nNOS-PSD-95 coupling in neurons promotes neuronal differentiation of neural stem cells (NSCs), facilitates the migration of newborn cells into the injured area, and enhances neurite growth of newborn neurons and dendritic spine formation of mature neurons in the ischemic brain of rats. More importantly, blocking nNOS-PSD-95 binding during the recovery stage improves stroke outcome via the promotion of regenerative repair in rats. Histone deacetylase 2 in NSCs may mediate the role of nNOS-PSD-95 association. Thus, nNOS-PSD-95 can serve as a target for regenerative repair after stroke. Copyright © 2014 the authors 0270-6474/14/3413535-14$15.00/0.

  7. The magnetic structure and palaeomagnetic recording fidelity of sub-micron greigite (Fe3S4)

    NASA Astrophysics Data System (ADS)

    Valdez-Grijalva, Miguel A.; Nagy, Lesleis; Muxworthy, Adrian R.; Williams, Wyn; Fabian, Karl

    2018-02-01

    We present the results of a finite-element micromagnetic model of 30nm to 300nm greigite (Fe3S4) grains with a variety of equant morphologies. This grain size range covers the magnetic single-domain (SD) to pseudo single-domain (PSD) transition, and possibly also the PSD to multi-domain (MD) transition. The SD-PSD threshold d0 is determined to be 50nm ≤d0 ≤ 56nm depending on grain shape. The nudged elastic-band method was used to determine the room temperature energy barriers between stable states and thus the blocking volumes. It is found that, in the absence of interparticle magnetostatic interactions, the magnetisation of equant SD greigite is not stable on a geological scale and only PSD grains ≥ 70nm can be expected to carry a stable magnetisation over billion-year timescales, i.e., all non-interacting SD particles are essentially superparamagnetic. We further identify a mechanism for the PSD to multi-domain (MD) transition, which is of a continuous nature from PSD nucleation up to 300nm, when structures typical of MD behaviour like closure domains begin to form.

  8. PSD-95 promotes the stabilization of young synaptic contacts.

    PubMed

    Taft, Christine E; Turrigiano, Gina G

    2014-01-05

    Maintaining a population of stable synaptic connections is probably of critical importance for the preservation of memories and functional circuitry, but the molecular dynamics that underlie synapse stabilization is poorly understood. Here, we use simultaneous time-lapse imaging of post synaptic density-95 (PSD-95) and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) to investigate the dynamics of protein composition at axodendritic (AD) contacts. Our data reveal that this composition is highly dynamic, with both proteins moving into and out of the same synapse independently, so that synapses cycle rapidly between states in which they are enriched for none, one or both proteins. We assessed how PSD-95 and CaMKII interact at stable and transient AD sites and found that both phospho-CaMKII and PSD-95 are present more often at stable than labile contacts. Finally, we found that synaptic contacts are more stable in older neurons, and this process can be mimicked in younger neurons by overexpression of PSD-95. Taken together, these data show that synaptic protein composition is highly variable over a time-scale of hours, and that PSD-95 is probably a key synaptic protein that promotes synapse stability.

  9. Determinants of Psychosocial Difficulties Experienced by Persons with Brain Disorders: Towards a ‘Horizontal Epidemiology’ Approach

    PubMed Central

    Sabariego, Carla; Coenen, Michaela; Ballert, Carolina; Cabello, Maria; Leonardi, Matilde; Anczewska, Marta; Pitkänen, Tuuli; Raggi, Alberto; Mellor, Blanca; Covelli, Venusia; Świtaj, Piotr; Levola, Jonna; Schiavolin, Silvia; Chrostek, Anna; Bickenbach, Jerome; Chatterji, Somnath; Cieza, Alarcos

    2015-01-01

    Background Persons with brain disorders experience significant psychosocial difficulties (PSD) in daily life, e.g. problems with managing daily routine or emotional lability, and the level of the PSD depends on social, physical and political environments, and psychologic-personal determinants. Our objective is to determine a brief set of environmental and psychologic-personal factors that are shared determinants of PSD among persons with different brain disorders. Methods Cross-sectional study, convenience sample of persons with either dementia, stroke, multiple sclerosis, epilepsy, migraine, depression, schizophrenia, substance dependence or Parkinson’s disease. Random forest regression and classical linear regression were used in the analyses. Results 722 subjects were interviewed in four European countries. The brief set of determinants encompasses presence of comorbidities, health status appraisal, stressful life events, personality changes, adaptation, self-esteem, self-worth, built environment, weather, and health problems in the family. Conclusions The identified brief set of common determinants of PSD can be used to support the implementation of cross-cutting interventions, social actions and policy tools to lower PSD experienced by persons with brain disorders. This set complements a recently proposed reliable and valid direct metric of PSD for brain disorders called PARADISE24. PMID:26675663

  10. Spinal SIRPα1-SHP2 interaction regulates spinal nerve ligation-induced neuropathic pain via PSD-95-dependent NR2B activation in rats.

    PubMed

    Peng, Hsien-Yu; Chen, Gin-Den; Lai, Cheng-Yuang; Hsieh, Ming-Chun; Lin, Tzer-Bin

    2012-05-01

    The fact that neuropathic pain mechanisms are not well understood is a major impediment in the development of effective clinical treatments. We examined whether the interaction between signal regulatory protein alpha 1 (SIRPα1) and Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2), and the downstream spinal SHP2/postsynaptic density 95 (PSD-95)/N-methyl-d-aspartate receptor NR2B subunit signaling cascade play a role in neuropathic pain. Following spinal nerve ligation (L5), we assessed tactile allodynia using the von Frey filament test and analyzed dorsal horn samples (L4-5) by Western blotting, reverse transcription polymerase chain reaction, coimmunoprecipitation, and immunofluorescence. Nerve ligation induced allodynia, SIRPα1, SHP2, phosphorylated SHP2 (pSHP2), and phosphorylated NR2B (pNR2B) expression, and SHP2-PSD-95, pSHP2-PSD-95, PSD-95-NR2B, and PSD-95-pNR2B coimmunoprecipitation in the ipsilateral dorsal horn. In allodynic rats, injury-induced SHP2 immunoreactivity was localized in the ipsilateral dorsal horn neurons and coincident with PSD-95 and NR2B immunoreactivity. SIRPα1 silencing using small interfering RNA (siRNA; 1, 3, or 5μg/rat for 7days) prevented injury-induced allodynia and the associated changes in protein expression, phosphorylation, and coimmunoprecipitation. Intrathecal administration of NSC-87877 (an SHP2 antagonist; 1, 10, or 100μM/rat) and SIRPα1-neutralizing antibodies (1, 10, or 30μg/rat) suppressed spinal nerve ligation-induced allodynia, spinal SHP2 and NR2B phosphorylation, and SHP2/phosphorylated SHP2-PSD-95 and PSD-95-NR2B/phosphorylated NR2B coprecipitation. SHP2 siRNA led to similar effects as the NSC-87877 and SIRPα1 antibody treatments, except it prevented the allodynia-associated spinal SHP2 expression. In conclusion, our results suggest that a spinal SIRPα1-SHP2 interaction exists that subsequently triggers SHP2/PSD-95/NR2B signaling, thereby playing a role in neuropathic pain development. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  11. N-(1-Naphthyl) Ethylenediamine Dinitrate: A New Matrix for Negative Ion MALDI-TOF MS Analysis of Small Molecules

    NASA Astrophysics Data System (ADS)

    Chen, Rui; Chen, Suming; Xiong, Caiqiao; Ding, Xunlei; Wu, Chih-Che; Chang, Huan-Cheng; Xiong, Shaoxiang; Nie, Zongxiu

    2012-09-01

    An organic salt, N-(1-naphthyl) ethylenediamine dinitrate (NEDN), with rationally designed properties of a strong UV absorbing chromophore, hydrogen binding and nitrate anion donors, has been employed as a matrix to analyze small molecules ( m/z < 1000) such as oligosaccharides, peptides, metabolites and explosives using negative ion matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Compared with conventional matrixes such as α-cyano-4-hydroxycinnamic acid (CCA) and 2,5-dihydroxybenzoic acid (DHB), NEDN provides a significant improvement in detection sensitivity and yields very few matrix-associated fragment and cluster ions interfering with MS analysis. For low-molecular-weight saccharides, the lowest detection limit achieved ranges from 500 amol to 5 pmol, depending on the molecular weight and the structure of the analytes. Additionally, the mass spectra in the lower mass range ( m/z < 200) consist of only nitrate and nitric acid cluster ions, making the matrix particularly useful for structural identification of oligosaccharides by post-source decay (PSD) MALDI-MS. Such a characteristic is illustrated by using maltoheptaose as a model system. This work demonstrates that NEDN is a novel negative ion-mode matrix for MALDI-MS analysis of small molecules with nitrate anion attachment.

  12. Diabetes mellitus is associated with late-onset post-stroke depression.

    PubMed

    Zhang, Yu; He, Ji-Rong; Liang, Huai-Bin; Lu, Wen-Jing; Yang, Guo-Yuan; Liu, Jian-Rong; Zeng, Li-Li

    2017-10-15

    To explore the associated factors of late-onset post-stroke depression (PSD). A total of 251 patients with acute ischemic stroke were recruited. The evaluation of depression was performed 2 weeks after ischemia. 206 patients showing no depression in 2 weeks were followed up. They were divided into late-onset PSD group and non-depressed group by clinical interview with Hamilton depression scale score 3 months after stroke. On the first day following hospitalization, the clinical data including age, gender, educational level and vascular risk factors were recorded. The severity, etiological subtype and location of stroke were evaluated. The inflammatory mediators, glucose and lipid levels were recorded on the day of admission. The association between clinical factors and late-onset PSD was explored by logistic regression analysis. The ROC analysis was performed to evaluate the predicting power of the clinical factors. 187 of 206 patients completed the assessment 3 months after stroke. 19 (10.16%) patients were diagnosed as late onset PSD. Diabetes mellitus was an independent risk factor for late-onset PSD (OR 2.675, p = 0.047). ROC analysis demonstrated that glucose and HbA1C could predict late-onset PSD with specificity of 84.4%. The sample of our study was small. The results should be further confirmed in a larger cohort of patients with acute ischemic stroke. The acute ischemic stroke patients with diabetes mellitus were more tendered to suffer late-onset PSD. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Functional MRI evidence for fine motor praxis dysfunction in children with persistent speech disorders

    PubMed Central

    Redle, Erin; Vannest, Jennifer; Maloney, Thomas; Tsevat, Rebecca K.; Eikenberry, Sarah; Lewis, Barbara; Shriberg, Lawrence D.; Tkach, Jean; Holland, Scott K.

    2014-01-01

    Children with persistent speech disorders (PSD) often present with overt or subtle motor deficits; the possibility that speech disorders and motor deficits could arise from a shared neurological base is currently unknown. Functional MRI (fMRI) was used to examine the brain networks supporting fine motor praxis in children with PSD and without clinically identified fine motor deficits. Methods This case-control study included 12 children with PSD (mean age 7.42 years, 4 female) and 12 controls (mean age 7.44 years, 4 female). Children completed behavioral evaluations using standardized motor assessments and parent reported functional measures. During fMRI scanning, participants completed a cued finger tapping task contrasted passive listening. A general linear model approach identified brain regions associated with finger tapping in each group and regions that differed between groups. The relationship between regional fMRI activation and fine motor skill was assessed using a regression analysis. Results Children with PSD had significantly poorer results for rapid speech production and fine motor praxis skills, but did not differ on classroom functional skills. Functional MRI results showed that children with PSD had significantly more activation in the cerebellum during finger tapping. Positive correlations between performance on a fine motor praxis test and activation multiple cortical regions were noted for children with PSD but not for controls. Conclusions Over-activation in the cerebellum during a motor task may reflect a subtle abnormality in the non-speech motor neural circuitry in children with PSD. PMID:25481413

  14. The Glutamatergic Aspects of Schizophrenia Molecular Pathophysiology: Role of the Postsynaptic Density, and Implications for Treatment

    PubMed Central

    Iasevoli, Felice; Tomasetti, Carmine; Buonaguro, Elisabetta F.; de Bartolomeis, Andrea

    2014-01-01

    Schizophrenia is one of the most debilitating psychiatric diseases with a lifetime prevalence of approximately 1%. Although the specific molecular underpinnings of schizophrenia are still unknown, evidence has long linked its pathophysiology to postsynaptic abnormalities. The postsynaptic density (PSD) is among the molecular structures suggested to be potentially involved in schizophrenia. More specifically, the PSD is an electron-dense thickening of glutamatergic synapses, including ionotropic and metabotropic glutamate receptors, cytoskeletal and scaffolding proteins, and adhesion and signaling molecules. Being implicated in the postsynaptic signaling of multiple neurotransmitter systems, mostly dopamine and glutamate, the PSD constitutes an ideal candidate for studying dopamine-glutamate disturbances in schizophrenia. Recent evidence suggests that some PSD proteins, such as PSD-95, Shank, and Homer are implicated in severe behavioral disorders, including schizophrenia. These findings, further corroborated by genetic and animal studies of schizophrenia, offer new insights for the development of pharmacological strategies able to overcome the limitations in terms of efficacy and side effects of current schizophrenia treatment. Indeed, PSD proteins are now being considered as potential molecular targets against this devastating illness. The current paper reviews the most recent hypotheses on the molecular mechanisms underlying schizophrenia pathophysiology. First, we review glutamatergic dysfunctions in schizophrenia and we provide an update on postsynaptic molecules involvement in schizophrenia pathophysiology by addressing both human and animal studies. Finally, the possibility that PSD proteins may represent potential targets for new molecular interventions in psychosis will be discussed. PMID:24851087

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

    Dosemeci, Ayse, E-mail: dosemeca@mail.nih.gov; Thein, Soe; Yang, Yijung

    Highlights: Black-Right-Pointing-Pointer CYLD is a deubiquitinase specific for lysine63-linked polyubiquitins. Black-Right-Pointing-Pointer Presence of CYLD in PSDs is established by biochemistry and immunoEM. Black-Right-Pointing-Pointer CYLD accumulates on PSDs upon depolarization of neurons. Black-Right-Pointing-Pointer Accumulation of CYLD at PSDs may regulate trafficking/degradation of synaptic proteins. -- Abstract: Polyubiquitin chains on proteins flag them for distinct fates depending on the type of polyubiquitin linkage. While lysine48-linked polyubiquitination directs proteins to proteasomal degradation, lysine63-linked polyubiquitination promotes different protein trafficking and is involved in autophagy. Here we show that postsynaptic density (PSD) fractions from adult rat brain contain deubiquitinase activity that targets both lysine48 andmore » lysine63-linked polyubiquitins. Comparison of PSD fractions with parent subcellular fractions by Western immunoblotting reveals that CYLD, a deubiquitinase specific for lysine63-linked polyubiquitins, is highly enriched in the PSD fraction. Electron microscopic examination of hippocampal neurons in culture under basal conditions shows immunogold label for CYLD at the PSD complex in approximately one in four synapses. Following depolarization by exposure to high K+, the proportion of CYLD-labeled PSDs as well as the labeling intensity of CYLD at the PSD increased by more than eighty percent, indicating that neuronal activity promotes accumulation of CYLD at the PSD. An increase in postsynaptic CYLD following activity would promote removal of lysine63-polyubiquitins from PSD proteins and thus could regulate their trafficking and prevent their autophagic degradation.« less

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

    Gagnon, Jean-Christophe; Theriault, Dany; Guillot, Mathieu

    Purpose: To compare the performance of plastic scintillation detectors (PSD) for quality assurance (QA) in stereotactic radiosurgery conditions to a microion-chamber (IC), Gafchromic EBT2 films, 60 008 shielded photon diode (SD) and unshielded diodes (UD), and assess a new 2D crosshair array prototype adapted to small field dosimetry. Methods: The PSD consists of a 1 mm diameter by 1 mm long scintillating fiber (BCF-60, Saint-Gobain, Inc.) coupled to a polymethyl-methacrylate optical fiber (Eska premier, Mitsubishi Rayon Co., Ltd., Tokyo, Japan). Output factors (S{sub c,p}) for apertures used in radiosurgery ranging from 4 to 40 mm in diameter have been measured.more » The PSD crosshair array (PSDCA) is a water equivalent device made up of 49 PSDs contained in a 1.63 cm radius area. Dose profiles measurements were taken for radiosurgery fields using the PSDCA and were compared to other dosimeters. Moreover, a typical stereotactic radiosurgery treatment using four noncoplanar arcs was delivered on a spherical phantom in which UD, IC, or PSD was placed. Using the Xknife planning system (Integra Radionics Burlington, MA), 15 Gy was prescribed at the isocenter, where each detector was positioned. Results: Output Factors measured by the PSD have a mean difference of 1.3% with Gafchromic EBT2 when normalized to a 10 x 10 cm{sup 2} field, and 1.0% when compared with UD measurements normalized to the 35 mm diameter cone. Dose profiles taken with the PSD crosshair array agreed with other single detectors dose profiles in spite of the presence of the 49 PSDs. Gamma values comparing 1D dose profiles obtained with PSD crosshair array with Gafchromic EBT2 and UD measured profiles shows 98.3% and 100.0%, respectively, of detector passing the gamma acceptance criteria of 0.3 mm and 2%. The dose measured by the PSD for a complete stereotactic radiosurgery treatment is comparable to the planned dose corrected for its SD-based S{sub c,p} within 1.4% and 0.7% for 5 and 35 mm diameter cone, respectively. Furthermore, volume averaging of the IC can be observed for the 5 mm aperture where it differs by as much as 9.1% compared to the PSD measurement. The angular dependency of the UD is also observed, unveiled by an under-response around 2.5% of both 5 and 35 mm apertures. Conclusions: Output Factors and dose profiles measurements performed, respectively, with the PSD and the PSDCA were in agreement with those obtained with the UD and EBT2 films. For stereotactic radiosurgery treatment verification, the PSD gives accurate results compared to the planning system and the IC once the latter is corrected to compensate for the averaging effect of the IC. The PSD provides precise results when used as a single detector or in a dense array, resulting in a great potential for stereotactic radiosurgery QA measurements.« less

  17. Chip Scale, Ultra Sensitive Opto Mechanical Acceleration and Force Sensors

    DTIC Science & Technology

    2017-12-01

    an accelerometer of the same mechanical design as that studied in part A. and shown in Fig. 3. One side of the zipper optical cavity is connected to...Ref. [13]. “Endevco 752A13” is Ref. [30]. “Zipper” is our own work on zipper photonic crystals from Ref. [31]. II Accelerometer Noise and Design ...limit, the shot noise of the light field also imparts a force on , and cause motion of, the mechanical resonator. The acceleration PSD due to back-action

  18. 77 FR 64237 - Notice of Approval of Clean Air Act Prevention of Significant Deterioration Permit Issued to the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-19

    ... Air Act Prevention of Significant Deterioration (PSD) permit for the City of Palmdale (City) for the construction of the Palmdale Hybrid Power Project (PHPP). DATES: EPA Region 9 issued a final PSD permit... decision can obtain them at http://www.epa.gov/eab/ . A copy of the PSD permit is also available at http...

  19. Structural Origins of Scintillation: Metal Organic Frameworks as a Nanolaboratory

    DTIC Science & Technology

    2016-06-01

    scintillation response and thus the ability to perform neutron/gamma particle discrimination via pulse-shape discrimination ( PSD ). Unfortunately, the...defined an alternative approach towards particle discrimination that addresses the limitations of conventional PSD organic scintillators. This approach...discrimination ( PSD ), for which the prompt component of the scintillation response is quenched for high specific energy loss (dE/dX) particles such as protons

  20. Impairment of TrkB-PSD-95 Signaling in Angelman Syndrome

    PubMed Central

    Cao, Cong; Rioult-Pedotti, Mengia S.; Migani, Paolo; Yu, Crystal J.; Tiwari, Rakesh; Parang, Keykavous; Spaller, Mark R.; Goebel, Dennis J.; Marshall, John

    2013-01-01

    Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) TrkB receptor signaling, which is known to be essential for both the induction and maintenance of LTP. We report that TrkB signaling in the AS mouse is defective, and show that reduction of Arc expression to control levels rescues the signaling deficits. Moreover, the association of the postsynaptic density protein PSD-95 with TrkB is critical for intact BDNF signaling, and elevated levels of Arc were found to impede PSD-95/TrkB association. In Ube3A deficient mice, the BDNF-induced recruitment of PSD-95, as well as PLCγ and Grb2-associated binder 1 (Gab1) with TrkB receptors was attenuated, resulting in reduced activation of PLCγ-α-calcium/calmodulin-dependent protein kinase II (CaMKII) and PI3K-Akt, but leaving the extracellular signal-regulated kinase (Erk) pathway intact. A bridged cyclic peptide (CN2097), shown by nuclear magnetic resonance (NMR) studies to uniquely bind the PDZ1 domain of PSD-95 with high affinity, decreased the interaction of Arc with PSD-95 to restore BDNF-induced TrkB/PSD-95 complex formation, signaling, and facilitate the induction of LTP in AS mice. We propose that the failure of TrkB receptor signaling at synapses in AS is directly linked to elevated levels of Arc associated with PSD-95 and PSD-95 PDZ-ligands may represent a promising approach to reverse cognitive dysfunction. PMID:23424281

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