Computer enhancement of radiographs

NASA Technical Reports Server (NTRS)

Dekaney, A.; Keane, J.; Desautels, J.

1973-01-01

Examination of three relevant noise processes and the image degradation associated with Marshall Space Flight Center's (MSFC) X-ray/scanning system was conducted for application to computer enhancement of radiographs using MSFC's digital filtering techniques. Graininess of type M, R single coat and R double coat X-ray films was quantified as a function of density level using root-mean-square (RMS) granularity. Quantum mottle (including film grain) was quantified as a function of the above film types, exposure level, specimen material and thickness, and film density using RMS granularity and power spectral density (PSD). For various neutral-density levels the scanning device used in digital conversion of radiographs was examined for noise characteristics which were quantified by RMS granularity and PSD. Image degradation of the entire pre-enhancement system (MG-150 X-ray device; film; and optronics scanner) was measured using edge targets to generate modulation transfer functions (MTF). The four parameters were examined as a function of scanning aperture sizes of approximately 12.5 25 and 50 microns.

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.

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

Estimating maximum instantaneous distortion from inlet total pressure rms and PSD measurements. [Root Mean Square and Power Spectral Density methods

NASA Technical Reports Server (NTRS)

Melick, H. C., Jr.; Ybarra, A. H.; Bencze, D. P.

1975-01-01

An inexpensive method is developed to determine the extreme values of instantaneous inlet distortion. This method also provides insight into the basic mechanics of unsteady inlet flow and the associated engine reaction. The analysis is based on fundamental fluid dynamics and statistical methods to provide an understanding of the turbulent inlet flow and quantitatively relate the rms level and power spectral density (PSD) function of the measured time variant total pressure fluctuations to the strength and size of the low pressure regions. The most probable extreme value of the instantaneous distortion is then synthesized from this information in conjunction with the steady state distortion. Results of the analysis show the extreme values to be dependent upon the steady state distortion, the measured turbulence rms level and PSD function, the time on point, and the engine response characteristics. Analytical projections of instantaneous distortion are presented and compared with data obtained by a conventional, highly time correlated, 40 probe instantaneous pressure measurement system.

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.

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

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

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.

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

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

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.

Evaluate error correction ability of magnetorheological finishing by smoothing spectral function

NASA Astrophysics Data System (ADS)

Wang, Jia; Fan, Bin; Wan, Yongjian; Shi, Chunyan; Zhuo, Bin

2014-08-01

Power Spectral Density (PSD) has been entrenched in optics design and manufacturing as a characterization of mid-high spatial frequency (MHSF) errors. Smoothing Spectral Function (SSF) is a newly proposed parameter that based on PSD to evaluate error correction ability of computer controlled optical surfacing (CCOS) technologies. As a typical deterministic and sub-aperture finishing technology based on CCOS, magnetorheological finishing (MRF) leads to MHSF errors inevitably. SSF is employed to research different spatial frequency error correction ability of MRF process. The surface figures and PSD curves of work-piece machined by MRF are presented. By calculating SSF curve, the correction ability of MRF for different spatial frequency errors will be indicated as a normalized numerical value.

Assessing a learning process with functional ANOVA estimators of EEG power spectral densities.

PubMed

Gutiérrez, David; Ramírez-Moreno, Mauricio A

2016-04-01

We propose to assess the process of learning a task using electroencephalographic (EEG) measurements. In particular, we quantify changes in brain activity associated to the progression of the learning experience through the functional analysis-of-variances (FANOVA) estimators of the EEG power spectral density (PSD). Such functional estimators provide a sense of the effect of training in the EEG dynamics. For that purpose, we implemented an experiment to monitor the process of learning to type using the Colemak keyboard layout during a twelve-lessons training. Hence, our aim is to identify statistically significant changes in PSD of various EEG rhythms at different stages and difficulty levels of the learning process. Those changes are taken into account only when a probabilistic measure of the cognitive state ensures the high engagement of the volunteer to the training. Based on this, a series of statistical tests are performed in order to determine the personalized frequencies and sensors at which changes in PSD occur, then the FANOVA estimates are computed and analyzed. Our experimental results showed a significant decrease in the power of [Formula: see text] and [Formula: see text] rhythms for ten volunteers during the learning process, and such decrease happens regardless of the difficulty of the lesson. These results are in agreement with previous reports of changes in PSD being associated to feature binding and memory encoding.

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.

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

Dissociation of nNOS from PSD-95 promotes functional recovery after cerebral ischaemia in mice through reducing excessive tonic GABA release from reactive astrocytes.

PubMed

Lin, Yu-Hui; Liang, Hai-Ying; Xu, Ke; Ni, Huan-Yu; Dong, Jian; Xiao, Hui; Chang, Lei; Wu, Hai-Yin; Li, Fei; Zhu, Dong-Ya; Luo, Chun-Xia

2018-02-01

Mechanisms underlying functional recovery after stroke are little known, and effective drug intervention during the delayed stage is desirable. One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein, Tat-nNOS-N 1-133 , or systemic administration of a small-molecule, ZL006, from day 4 to day 10 after photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri-infarct cortex and ameliorated motor functional outcome. We also demonstrated improved neuroplasticity including increased dendrite spine density and synaptogenesis after reducing excessive tonic inhibition by nNOS-PSD-95 dissociation. Levels of gamma-aminobutyric acid (GABA) and GABA transporter-3/4 (GAT-3/4) are increased in the reactive astrocytes in the peri-infarct cortex. The GAT-3/4-selective antagonist SNAP-5114 reduced tonic inhibition and promoted function recovery, suggesting that increased tonic inhibition in the peri-infarct cortex was due to GABA release from reversed GAT-3/4 in reactive astrocytes. Treatments with Tat-nNOS-N 1-133 or ZL006 after ischaemia inhibited astrocyte activation and GABA production, prevented the reversal of GAT-3/4, and consequently decreased excessive tonic inhibition and ameliorated functional outcome. The underlying molecular mechanisms were associated with epigenetic inhibition of glutamic acid decarboxylase 67 and monoamine oxidase B expression through reduced NO production. The nNOS-PSD-95 interaction is thus a potential target for functional restoration after stroke and ZL006, a small molecule inhibitor of this interaction, is a promising pharmacological lead compound. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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

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

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.

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.

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.

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.

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

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.

The Postsynaptic Density Proteins Homer and Shank Form a Polymeric Network Structure

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

Hayashi, M.; Tang, C; Verpelli, C

2009-01-01

The postsynaptic density (PSD) is crucial for synaptic functions, but the molecular architecture retaining its structure and components remains elusive. Homer and Shank are among the most abundant scaffolding proteins in the PSD, working synergistically for maturation of dendritic spines. Here, we demonstrate that Homer and Shank, together, form a mesh-like matrix structure. Crystallographic analysis of this region revealed a pair of parallel dimeric coiled coils intercalated in a tail-to-tail fashion to form a tetramer, giving rise to the unique configuration of a pair of N-terminal EVH1 domains at each end of the coiled coil. In neurons, the tetramerization ismore » required for structural integrity of the dendritic spines and recruitment of proteins to synapses. We propose that the Homer-Shank complex serves as a structural framework and as an assembly platform for other PSD proteins.« less

Specific interaction of postsynaptic densities with membrane rafts isolated from synaptic plasma membranes.

PubMed

Liu, Qian; Yao, Wei-Dong; Suzuki, Tatsuo

2013-06-01

Postsynaptic membrane rafts are believed to play important roles in synaptic signaling, plasticity, and maintenance. We recently demonstrated the presence, at the electron microscopic level, of complexes consisting of membrane rafts and postsynaptic densities (PSDs) in detergent-resistant membranes (DRMs) prepared from synaptic plasma membranes (SPMs) ( Suzuki et al., 2011 , J Neurochem, 119, 64-77). To further explore these complexes, here we investigated the nature of the binding between purified SPM-DRMs and PSDs in vitro. In binding experiments, we used SPM-DRMs prepared after treating SPMs with n-octyl-β-d-glucoside, because at concentrations of 1.0% or higher it completely separates SPM-DRMs and PSDs, providing substantially PSD-free unique SPM-DRMs as well as DRM-free PSDs. PSD binding to PSD-free DRMs was identified by mass spectrometry, Western blotting, and electron microscopy. PSD proteins were not incorporated into SPMs, and significantly less PSD proteins were incorporated into DRMs prepared from liver membranes, providing in vitro evidence that binding of PSDs to DRMs is specific and suggestion of the presence of specific interacting molecules. These specific interactions may have important roles in synaptic development, function, and plasticity in vivo. In addition, the binding system we developed may be a good tool to search for binding molecules and binding mechanisms between PSDs and rafts.

Subcellular Organization of CaMKII in Rat Hippocampal Pyramidal Neurons

PubMed Central

Ding, Jin-Dong; Kennedy, Mary B.; Weinberg, Richard J.

2015-01-01

Calcium/calmodulin-dependent protein kinase II (CaM-KII) plays a key role in N-methyl-D-aspartate (NMDA) receptor-dependent long-term synaptic plasticity; its location is critical for signal transduction, and may provide clues that further elucidate its function. We therefore examined the subcellular localization of CaMKII in CA1 stratum radiatum of adult rat hippocampus, by using immuno-electron microscopy after chemical fixation. When tissue was fixed quickly, the concentration of CaMKIIα (assessed by pre-embedding immunogold) was significantly higher in dendritic shafts than in spine heads. However, when tissue was fixed 5 minutes after perfusion with normal saline, the density of labeling decreased in dendritic shaft while increasing in spine heads, implying rapid translocation into the spine during brief perimortem stress. Likewise, in quickly fixed tissue, CaMKII within spine heads was found at comparable concentrations in the “proximal” half (adjacent to the spine neck) and the “distal” half (containing the postsynaptic density [PSD]), whereas after delayed fixation, label density increased in the distal side of the spine head, suggesting that CaMKII within the spine head moves toward the PSD during this interval. To estimate its distribution at the synapse in vivo, we performed postembedding immunogold staining for CaMKII in quick-fixed tissue, and found that the enzyme did not concentrate primarily within the central matrix of the PSD. Instead, labeling density peaked ∼40 nm inside the postsynaptic membrane, at the cytoplasmic fringe of the PSD. Labeling within 25 nm of the postsynaptic membrane concentrated at the lateral edge of the synapse. This lateral “PSD core” pool of CaMKII may play a special role in synaptic plasticity. PMID:23749614

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.

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.

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.

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.

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.

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

A Specific Nutrient Combination Attenuates the Reduced Expression of PSD-95 in the Proximal Dendrites of Hippocampal Cell Body Layers in a Mouse Model of Phenylketonuria.

PubMed

Bruinenberg, Vibeke M; van Vliet, Danique; Attali, Amos; de Wilde, Martijn C; Kuhn, Mirjam; van Spronsen, Francjan J; van der Zee, Eddy A

2016-03-26

The inherited metabolic disease phenylketonuria (PKU) is characterized by increased concentrations of phenylalanine in the blood and brain, and as a consequence neurotransmitter metabolism, white matter, and synapse functioning are affected. A specific nutrient combination (SNC) has been shown to improve synapse formation, morphology and function. This could become an interesting new nutritional approach for PKU. To assess whether treatment with SNC can affect synapses, we treated PKU mice with SNC or an isocaloric control diet and wild-type (WT) mice with an isocaloric control for 12 weeks, starting at postnatal day 31. Immunostaining for post-synaptic density protein 95 (PSD-95), a post-synaptic density marker, was carried out in the hippocampus, striatum and prefrontal cortex. Compared to WT mice on normal chow without SNC, PKU mice on the isocaloric control showed a significant reduction in PSD-95 expression in the hippocampus, specifically in the granular cell layer of the dentate gyrus, with a similar trend seen in the cornus ammonis 1 (CA1) and cornus ammonis 3 (CA3) pyramidal cell layer. No differences were found in the striatum or prefrontal cortex. PKU mice on a diet supplemented with SNC showed improved expression of PSD-95 in the hippocampus. This study gives the first indication that SNC supplementation has a positive effect on hippocampal synaptic deficits in PKU mice.

Deletion of densin-180 results in abnormal behaviors associated with mental illness and reduces mGluR5 and DISC1 in the postsynaptic density fraction.

PubMed

Carlisle, Holly J; Luong, Tinh N; Medina-Marino, Andrew; Schenker, Leslie; Khorosheva, Eugenia; Indersmitten, Tim; Gunapala, Keith M; Steele, Andrew D; O'Dell, Thomas J; Patterson, Paul H; Kennedy, Mary B

2011-11-09

Densin is an abundant scaffold protein in the postsynaptic density (PSD) that forms a high-affinity complex with αCaMKII and α-actinin. To assess the function of densin, we created a mouse line with a null mutation in the gene encoding it (LRRC7). Homozygous knock-out mice display a wide variety of abnormal behaviors that are often considered endophenotypes of schizophrenia and autism spectrum disorders. At the cellular level, loss of densin results in reduced levels of α-actinin in the brain and selective reduction in the localization of mGluR5 and DISC1 in the PSD fraction, whereas the amounts of ionotropic glutamate receptors and other prominent PSD proteins are unchanged. In addition, deletion of densin results in impairment of mGluR- and NMDA receptor-dependent forms of long-term depression, alters the early dynamics of regulation of CaMKII by NMDA-type glutamate receptors, and produces a change in spine morphology. These results indicate that densin influences the function of mGluRs and CaMKII at synapses and contributes to localization of mGluR5 and DISC1 in the PSD fraction. They are consistent with the hypothesis that mutations that disrupt the organization and/or dynamics of postsynaptic signaling complexes in excitatory synapses can cause behavioral endophenotypes of mental illness.

Proteomic analysis of PSD-93 knockout mice following the induction of ischemic cerebral injury.

PubMed

Rong, Rong; Yang, Hui; Rong, Liangqun; Wei, Xiue; Li, Qingjie; Liu, Xiaomei; Gao, Hong; Xu, Yun; Zhang, Qingxiu

2016-03-01

Postsynaptic density protein-93 (PSD-93) is enriched in the postsynaptic density and is involved in N-methyl-d-aspartate receptor (NMDAR) triggered neurotoxicity through PSD-93/NMDAR/nNOS signaling pathway. In the present study, we found that PSD-93 deficiency reduced infarcted volume and neurological deficits induced by transient middle cerebral artery occlusion (tMCAO) in the mice. To identify novel targets of PSD-93 related neurotoxicity, we applied isobaric tags for relative and absolute quantitative (iTRAQ) labeling and combined this labeling with on-line two-dimensional LC/MS/MS technology to elucidate the changes in protein expression in PSD-93 knockout mice following tMCAO. The proteomic data set consisted of 1892 proteins. Compared to control group, differences in expression levels in ischemic group >1.5-fold and <0.66-fold were considered as differential expression. A total of 104 unique proteins with differential abundance levels were identified, among which 17 proteins were selected for further validation. Gene ontology analysis using UniProt database revealed that these differentially expressed proteins are involved in diverse function such as synaptic transmission, neuronal neurotransmitter and ion transport, modification of organelle membrane components. Moreover, network analysis revealed that the interacting proteins were involved in the transport of synaptic vesicles, the integrity of synaptic membranes and the activation of the ionotropic glutamate receptors NMDAR1 and NMDAR2B. Finally, RT-PCR and Western blot analysis showed that SynGAP, syntaxin-1A, protein kinase C β, and voltage-dependent L-type calcium channels were inhibited by ischemia-reperfusion. Identification of these proteins provides valuable clues to elucidate the mechanisms underlying the actions of PSD-93 in ischemia-reperfusion induced neurotoxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

A model for AGN variability on multiple time-scales

NASA Astrophysics Data System (ADS)

Sartori, Lia F.; Schawinski, Kevin; Trakhtenbrot, Benny; Caplar, Neven; Treister, Ezequiel; Koss, Michael J.; Urry, C. Megan; Zhang, C. E.

2018-05-01

We present a framework to link and describe active galactic nuclei (AGN) variability on a wide range of time-scales, from days to billions of years. In particular, we concentrate on the AGN variability features related to changes in black hole fuelling and accretion rate. In our framework, the variability features observed in different AGN at different time-scales may be explained as realisations of the same underlying statistical properties. In this context, we propose a model to simulate the evolution of AGN light curves with time based on the probability density function (PDF) and power spectral density (PSD) of the Eddington ratio (L/LEdd) distribution. Motivated by general galaxy population properties, we propose that the PDF may be inspired by the L/LEdd distribution function (ERDF), and that a single (or limited number of) ERDF+PSD set may explain all observed variability features. After outlining the framework and the model, we compile a set of variability measurements in terms of structure function (SF) and magnitude difference. We then combine the variability measurements on a SF plot ranging from days to Gyr. The proposed framework enables constraints on the underlying PSD and the ability to link AGN variability on different time-scales, therefore providing new insights into AGN variability and black hole growth phenomena.

Chronic intermittent ethanol exposure and withdrawal leads to adaptations in nucleus accumbens core postsynaptic density proteome and dendritic spines.

PubMed

Uys, Joachim D; McGuier, Natalie S; Gass, Justin T; Griffin, William C; Ball, Lauren E; Mulholland, Patrick J

2016-05-01

Alcohol use disorder is a chronic relapsing brain disease characterized by the loss of ability to control alcohol (ethanol) intake despite knowledge of detrimental health or personal consequences. Clinical and pre-clinical models provide strong evidence for chronic ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the nucleus accumbens (NAc). However, the neural mechanisms that contribute to aberrant glutamatergic signaling in ethanol-dependent individuals in this critical brain structure remain unknown. Using an unbiased proteomic approach, we investigated the effects of chronic intermittent ethanol (CIE) exposure on neuroadaptations in postsynaptic density (PSD)-enriched proteins in the NAc of ethanol-dependent mice. Compared with controls, CIE exposure significantly changed expression levels of 50 proteins in the PSD-enriched fraction. Systems biology and functional annotation analyses demonstrated that the dysregulated proteins are expressed at tetrapartite synapses and critically regulate cellular morphology. To confirm this latter finding, the density and morphology of dendritic spines were examined in the NAc core of ethanol-dependent mice. We found that CIE exposure and withdrawal differentially altered dendrite diameter and dendritic spine density and morphology. Through the use of quantitative proteomics and functional annotation, these series of experiments demonstrate that ethanol dependence produces neuroadaptations in proteins that modify dendritic spine morphology. In addition, these studies identified novel PSD-related proteins that contribute to the neurobiological mechanisms of ethanol dependence that drive maladaptive structural plasticity of NAc neurons. © 2015 Society for the Study of Addiction.

The polarity protein partitioning-defective 1 (PAR-1) regulates dendritic spine morphogenesis through phosphorylating postsynaptic density protein 95 (PSD-95).

PubMed

Wu, Qian; DiBona, Victoria L; Bernard, Laura P; Zhang, Huaye

2012-08-31

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95.

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.

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

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.

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

Power Laws from Linear Neuronal Cable Theory: Power Spectral Densities of the Soma Potential, Soma Membrane Current and Single-Neuron Contribution to the EEG

PubMed Central

Pettersen, Klas H.; Lindén, Henrik; Tetzlaff, Tom; Einevoll, Gaute T.

2014-01-01

Power laws, that is, power spectral densities (PSDs) exhibiting behavior for large frequencies f, have been observed both in microscopic (neural membrane potentials and currents) and macroscopic (electroencephalography; EEG) recordings. While complex network behavior has been suggested to be at the root of this phenomenon, we here demonstrate a possible origin of such power laws in the biophysical properties of single neurons described by the standard cable equation. Taking advantage of the analytical tractability of the so called ball and stick neuron model, we derive general expressions for the PSD transfer functions for a set of measures of neuronal activity: the soma membrane current, the current-dipole moment (corresponding to the single-neuron EEG contribution), and the soma membrane potential. These PSD transfer functions relate the PSDs of the respective measurements to the PSDs of the noisy input currents. With homogeneously distributed input currents across the neuronal membrane we find that all PSD transfer functions express asymptotic high-frequency power laws with power-law exponents analytically identified as for the soma membrane current, for the current-dipole moment, and for the soma membrane potential. Comparison with available data suggests that the apparent power laws observed in the high-frequency end of the PSD spectra may stem from uncorrelated current sources which are homogeneously distributed across the neural membranes and themselves exhibit pink () noise distributions. While the PSD noise spectra at low frequencies may be dominated by synaptic noise, our findings suggest that the high-frequency power laws may originate in noise from intrinsic ion channels. The significance of this finding goes beyond neuroscience as it demonstrates how power laws with a wide range of values for the power-law exponent α may arise from a simple, linear partial differential equation. PMID:25393030

Power laws from linear neuronal cable theory: power spectral densities of the soma potential, soma membrane current and single-neuron contribution to the EEG.

PubMed

Pettersen, Klas H; Lindén, Henrik; Tetzlaff, Tom; Einevoll, Gaute T

2014-11-01

Power laws, that is, power spectral densities (PSDs) exhibiting 1/f(α) behavior for large frequencies f, have been observed both in microscopic (neural membrane potentials and currents) and macroscopic (electroencephalography; EEG) recordings. While complex network behavior has been suggested to be at the root of this phenomenon, we here demonstrate a possible origin of such power laws in the biophysical properties of single neurons described by the standard cable equation. Taking advantage of the analytical tractability of the so called ball and stick neuron model, we derive general expressions for the PSD transfer functions for a set of measures of neuronal activity: the soma membrane current, the current-dipole moment (corresponding to the single-neuron EEG contribution), and the soma membrane potential. These PSD transfer functions relate the PSDs of the respective measurements to the PSDs of the noisy input currents. With homogeneously distributed input currents across the neuronal membrane we find that all PSD transfer functions express asymptotic high-frequency 1/f(α) power laws with power-law exponents analytically identified as α∞(I) = 1/2 for the soma membrane current, α∞(p) = 3/2 for the current-dipole moment, and α∞(V) = 2 for the soma membrane potential. Comparison with available data suggests that the apparent power laws observed in the high-frequency end of the PSD spectra may stem from uncorrelated current sources which are homogeneously distributed across the neural membranes and themselves exhibit pink (1/f) noise distributions. While the PSD noise spectra at low frequencies may be dominated by synaptic noise, our findings suggest that the high-frequency power laws may originate in noise from intrinsic ion channels. The significance of this finding goes beyond neuroscience as it demonstrates how 1/f(α) power laws with a wide range of values for the power-law exponent α may arise from a simple, linear partial differential equation.

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.

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.

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.

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.

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.

Inverse estimation of the spheroidal particle size distribution using Ant Colony Optimization algorithms in multispectral extinction technique

NASA Astrophysics Data System (ADS)

He, Zhenzong; Qi, Hong; Wang, Yuqing; Ruan, Liming

2014-10-01

Four improved Ant Colony Optimization (ACO) algorithms, i.e. the probability density function based ACO (PDF-ACO) algorithm, the Region ACO (RACO) algorithm, Stochastic ACO (SACO) algorithm and Homogeneous ACO (HACO) algorithm, are employed to estimate the particle size distribution (PSD) of the spheroidal particles. The direct problems are solved by the extended Anomalous Diffraction Approximation (ADA) and the Lambert-Beer law. Three commonly used monomodal distribution functions i.e. the Rosin-Rammer (R-R) distribution function, the normal (N-N) distribution function, and the logarithmic normal (L-N) distribution function are estimated under dependent model. The influence of random measurement errors on the inverse results is also investigated. All the results reveal that the PDF-ACO algorithm is more accurate than the other three ACO algorithms and can be used as an effective technique to investigate the PSD of the spheroidal particles. Furthermore, the Johnson's SB (J-SB) function and the modified beta (M-β) function are employed as the general distribution functions to retrieve the PSD of spheroidal particles using PDF-ACO algorithm. The investigation shows a reasonable agreement between the original distribution function and the general distribution function when only considering the variety of the length of the rotational semi-axis.

Inflammatory Pain May Induce Cognitive Impairment Through an Interlukin-6-Dependent and Postsynaptic Density-95-Associated Mechanism

PubMed Central

Yang, Longqiu; Xin, Xin; Zhang, Jie; Zhang, Lei; Dong, Yuanlin; Zhang, Yiying; Mao, Jianren; Xie, Zhongcong

2014-01-01

Background Pain might be associated with cognitive impairment in humans. However, the characterization of such effects in a preclinical model and the investigation of the underlying mechanisms remain largely to be determined. We therefore sought to establish a system to determine the effect of pain on cognitive function in mice. Methods Complete Freund's adjuvant (CFA) was injected in the hindpaw of 5–8-month-old wild-type and interleukin-6 knockout mice. Learning and memory function, and the levels of interleukin-6 and postsynaptic density (PSD)-95 in the cortex and hippocampus of mice were assessed. Results We found that the CFA injection induced pain in the mice at 3 and 7 days after injection and decreased the freezing time [30.1 (16.5) seconds versus 56.8 (28.1) seconds, P = 0.023] in the tone test, which assesses the hippocampus-independent learning and memory function, but not in a context test of Fear Conditioning System [15.8 (6.7) seconds versus 18.6 (8.8) seconds, P = 0.622], which assesses the hippocampus-dependent learning and memory function, at 3 days after injection. Consistently, the CFA injection increased interleukin-6 [248% (11.6) versus 100% (7.9), P < 0.0001] and decreased the PSD-95 [40% (10.0) versus 100% (20.3), P < 0.0001] level in the cortex, but not hippocampus [95%(8.6) versus 100%(9.3), P = 0.634], in the mice. The CFA injection induced neither reduction in the cortex PSD-95 levels nor cognitive impairment in the interleukin-6 knockout mice. Conclusion These results suggest that pain induced by CFA injection might increase interleukin-6 levels and decrease PSD-95 levels in the cortex, but not hippocampus of mice, leading to hippocampus-independent cognitive impairment in mice. These findings call for further investigation to determine the role of pain in cognitive function. PMID:24878682

Inflammatory pain may induce cognitive impairment through an interlukin-6-dependent and postsynaptic density-95-associated mechanism.

PubMed

Yang, Longqiu; Xin, Xin; Zhang, Jie; Zhang, Lei; Dong, Yuanlin; Zhang, Yiying; Mao, Jianren; Xie, Zhongcong

2014-08-01

Pain might be associated with cognitive impairment in humans. However, the characterization of such effects in a preclinical model and the investigation of the underlying mechanisms remain largely to be determined. We therefore sought to establish a system to determine the effect of pain on cognitive function in mice. Complete Freund's adjuvant (CFA) was injected in the hindpaw of 5- to 8-month-old wild-type and interleukin-6 knockout mice. Learning and memory function, and the levels of interleukin-6 and postsynaptic density (PSD)-95 in the cortex and hippocampus of mice were assessed. We found that the CFA injection-induced pain in the mice at 3 and 7 days after injection and decreased the freezing time (30.1 [16.5] vs 56.8 [28.1] seconds, P =0.023) in the tone test, which assesses the hippocampus-independent learning and memory function, but not in a context test of Fear Conditioning System (15.8 [6.7] vs 18.6 [8.8] seconds, P =0.622), which assesses the hippocampus-dependent learning and memory function, at 3 days after injection. Consistently, the CFA injection increased interleukin-6 (248% [11.6] vs 100% [7.9], P < 0.0001) and decreased the PSD-95 (40% [10.0] vs 100% [20.3], P < 0.0001) level in the cortex, but not hippocampus (95% [8.6] vs 100% [9.3], P =0.634), in the mice. The CFA injection induced neither reduction in the cortex PSD-95 levels nor cognitive impairment in the interleukin-6 knockout mice. These results suggest that pain induced by CFA injection might increase interleukin-6 levels and decrease PSD-95 levels in the cortex, but not hippocampus of mice, leading to hippocampus-independent cognitive impairment in mice. These findings call for further investigation to determine the role of pain in cognitive function.

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

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.

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.

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

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.

Pathological reorganization of NMDA receptors subunits and postsynaptic protein PSD-95 distribution in Alzheimer's disease.

PubMed

Leuba, Genevieve; Vernay, Andre; Kraftsik, Rudolf; Tardif, Eric; Riederer, Beat Michel; Savioz, Armand

2014-01-01

In Alzheimer's disease (AD), synaptic alterations play a major role and are often correlated with cognitive changes. In order to better understand synaptic modifications, we compared alterations in NMDA receptors and postsynaptic protein PSD-95 expression in the entorhinal cortex (EC) and frontal cortex (FC; area 9) of AD and control brains. We combined immunohistochemical and image analysis methods to quantify on consecutive sections the distribution of PSD-95 and NMDA receptors GluN1, GluN2A and GluN2B in EC and FC from 25 AD and control cases. The density of stained receptors was analyzed using multivariate statistical methods to assess the effect of neurodegeneration. In both regions, the number of neuronal profiles immunostained for GluN1 receptors subunit and PSD-95 protein was significantly increased in AD compared to controls (3-6 fold), while the number of neuronal profiles stained for GluN2A and GluN2B receptors subunits was on the contrary decreased (3-4 fold). The increase in marked neuronal profiles was more prominent in a cortical band corresponding to layers 3 to 5 with large pyramidal cells. Neurons positive for GluN1 or PSD-95 staining were often found in the same localization on consecutive sections and they were also reactive for the anti-tau antibody AD2, indicating a neurodegenerative process. Differences in the density of immunoreactive puncta representing neuropile were not statistically significant. Altogether these data indicate that GluN1 and PSD-95 accumulate in the neuronal perikarya, but this is not the case for GluN2A and GluN2B, while the neuropile compartment is less subject to modifications. Thus, important variations in the pattern of distribution of the NMDA receptors subunits and PSD-95 represent a marker in AD and by impairing the neuronal network, contribute to functional deterioration.

Data Series Subtraction with Unknown and Unmodeled Background Noise

NASA Technical Reports Server (NTRS)

Vitale, Stefano; Congedo, Giuseppe; Dolesi, Rita; Ferroni, Valerio; Hueller, Mauro; Vetrugno, Daniele; Weber, William Joseph; Audley, Heather; Danzmann, Karsten; Diepholz, Ingo;

Hippocampal dendritic spines modifications induced by perinatal asphyxia.

PubMed

Saraceno, G E; Castilla, R; Barreto, G E; Gonzalez, J; Kölliker-Frers, R A; Capani, F

2012-01-01

Perinatal asphyxia (PA) affects the synaptic function and morphological organization. In previous works, we have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia leading to long-term ubi-protein accumulation. Since F-actin is highly concentrated in dendritic spines, modifications in its organization could be related with alterations induced by hypoxia in the central nervous system (CNS). In the present study, we investigate the effects of PA on the actin cytoskeleton of hippocampal postsynaptic densities (PSD) in 4-month-old rats. PSD showed an increment in their thickness and in the level of ubiquitination. Correlative fluorescence-electron microscopy photooxidation showed a decrease in the number of F-actin-stained spines in hippocampal excitatory synapses subjected to PA. Although western blot analysis also showed a slight decrease in β-actin in PSD in PA animals, the difference was not significant. Taken together, this data suggests that long-term actin cytoskeleton might have role in PSD alterations which would be a spread phenomenon induced by PA.

Hippocampal Dendritic Spines Modifications Induced by Perinatal Asphyxia

PubMed Central

Saraceno, G. E.; Castilla, R.; Barreto, G. E.; Gonzalez, J.; Kölliker-Frers, R. A.; Capani, F.

2012-01-01

Perinatal asphyxia (PA) affects the synaptic function and morphological organization. In previous works, we have shown neuronal and synaptic changes in rat neostriatum subjected to hypoxia leading to long-term ubi-protein accumulation. Since F-actin is highly concentrated in dendritic spines, modifications in its organization could be related with alterations induced by hypoxia in the central nervous system (CNS). In the present study, we investigate the effects of PA on the actin cytoskeleton of hippocampal postsynaptic densities (PSD) in 4-month-old rats. PSD showed an increment in their thickness and in the level of ubiquitination. Correlative fluorescence-electron microscopy photooxidation showed a decrease in the number of F-actin-stained spines in hippocampal excitatory synapses subjected to PA. Although Western Blot analysis also showed a slight decrease in β-actin in PSD in PA animals, the difference was not significant. Taken together, this data suggests that long-term actin cytoskeleton might have role in PSD alterations which would be a spread phenomenon induced by PA. PMID:22645692

The Polarity Protein Partitioning-defective 1 (PAR-1) Regulates Dendritic Spine Morphogenesis through Phosphorylating Postsynaptic Density Protein 95 (PSD-95)*

PubMed Central

Wu, Qian; DiBona, Victoria L.; Bernard, Laura P.; Zhang, Huaye

2012-01-01

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95. PMID:22807451

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.

Exact nonstationary responses of rectangular thin plate on Pasternak foundation excited by stochastic moving loads

NASA Astrophysics Data System (ADS)

Chen, Guohai; Meng, Zeng; Yang, Dixiong

2018-01-01

This paper develops an efficient method termed as PE-PIM to address the exact nonstationary responses of pavement structure, which is modeled as a rectangular thin plate resting on bi-parametric Pasternak elastic foundation subjected to stochastic moving loads with constant acceleration. Firstly, analytical power spectral density (PSD) functions of random responses for thin plate are derived by integrating pseudo excitation method (PEM) with Duhamel's integral. Based on PEM, the new equivalent von Mises stress (NEVMS) is proposed, whose PSD function contains all cross-PSD functions between stress components. Then, the PE-PIM that combines the PEM with precise integration method (PIM) is presented to achieve efficiently stochastic responses of the plate by replacing Duhamel's integral with the PIM. Moreover, the semi-analytical Monte Carlo simulation is employed to verify the computational results of the developed PE-PIM. Finally, numerical examples demonstrate the high accuracy and efficiency of PE-PIM for nonstationary random vibration analysis. The effects of velocity and acceleration of moving load, boundary conditions of the plate and foundation stiffness on the deflection and NEVMS responses are scrutinized.

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

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

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

Acceleration of Relativistic Electrons: A Comparison of Two Models

NASA Astrophysics Data System (ADS)

Green, J. C.; Kivelson, M. G.

2001-12-01

Observations of relativistic electron fluxes show order of magnitude increases during some geomagnetic storms. Many electron acceleration models have been proposed to explain the flux enhancements but attempts to validate these models have yielded ambiguous results. Here we examine two models of electron acceleration, radial diffusion via enhanced ULF wave activity [Elkington et al.,1999] and acceleration by resonant interaction with whistler waves[Summers,1998; Roth et al.,1999]. Two methods are used to compare observations with features predicted by the models. First, the evolution of phase space density as a function of L during flux enhancement events is evaluated. The phase space density (PSD) is calculated at constant first, second and third adiabatic invariants using data obtained by the CEPPAD-HIST instrument and the MFE instrument onboard the Polar spacecraft. Liouville's theorem states that PSD calculated at constant adiabatic invariants does not change with time unless some mechanism violates one of the invariants. The radial diffusion model predicts that only the flux invariant will be violated during the acceleration process while acceleration by whistler waves violates the first invariant. Therefore, the two models predict a different evolution of the PSD as a function of time and L. Previous examinations of the evolution of PSD have yielded ambiguous results because PSD calculations are highly dependent on the global accuracy of magnetic field models. We examine the PSD versus L profiles for a series of geomagnetic storms and in addition determine how errors in the Tsyganenko 96 field model affect the results by comparing the measured magnetic field to the model magnetic field used in the calculations. Second, the evolution of the relativistic electron pitch angle distributions is evaluated. Previous studies of pitch angle distributions were limited because few spacecraft have the necessary instrumentation and global coverage. The CEPPAD-HIST instrument measures 16 look directions and along with measurements from the MFE experiment allows calculation of complete pitch angle distributions. The evolving orbit of the Polar spacecraft over the 6 years mission has given measurements over a wide range of L and local time. Using data extending over the entire mission we use superposed epoch analysis to examine the evolution of pitch angle distributions during flux enhancement events as a function of L, magnetic local time, and storm phase.

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

Tao-Cheng, Jung-Hwa; Yang, Yijung; Bayer, K. Ulrich

Highlights: • NMDA-induces accumulation of Shank at the postsynaptic density. • Shank accumulation is preferential to the distal region of the postsynaptic density. • Shank accumulation is mediated by CaMKII. - Abstract: Shank is a specialized scaffold protein present in high abundance at the postsynaptic density (PSD). Using pre-embedding immunogold electron microscopy on cultured hippocampal neurons, we had previously demonstrated further accumulation of Shank at the PSD under excitatory conditions. Here, using the same experimental protocol, we demonstrate that a cell permeable CaMKII inhibitor, tatCN21, blocks NMDA-induced accumulation of Shank at the PSD. Furthermore we show that NMDA application changesmore » the distribution pattern of Shank at the PSD, promoting a 7–10 nm shift in the median distance of Shank labels away from the postsynaptic membrane. Inhibition of CaMKII with tatCN21 also blocks this shift in the distribution of Shank. Altogether these results imply that upon activation of NMDA receptors, CaMKII mediates accumulation of Shank, preferentially at the distal regions of the PSD complex extending toward the cytoplasm.« less

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.

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.

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

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

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.

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.

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.

Increased power spectral density in resting-state pain-related brain networks in fibromyalgia.

PubMed

Kim, Ji-Young; Kim, Seong-Ho; Seo, Jeehye; Kim, Sang-Hyon; Han, Seung Woo; Nam, Eon Jeong; Kim, Seong-Kyu; Lee, Hui Joong; Lee, Seung-Jae; Kim, Yang-Tae; Chang, Yongmin

2013-09-01

Fibromyalgia (FM), characterized by chronic widespread pain, is known to be associated with heightened responses to painful stimuli and atypical resting-state functional connectivity among pain-related regions of the brain. Previous studies of FM using resting-state functional magnetic resonance imaging (rs-fMRI) have focused on intrinsic functional connectivity, which maps the spatial distribution of temporal correlations among spontaneous low-frequency fluctuation in functional MRI (fMRI) resting-state data. In the current study, using rs-fMRI data in the frequency domain, we investigated the possible alteration of power spectral density (PSD) of low-frequency fluctuation in brain regions associated with central pain processing in patients with FM. rsfMRI data were obtained from 19 patients with FM and 20 age-matched healthy female control subjects. For each subject, the PSDs for each brain region identified from functional connectivity maps were computed for the frequency band of 0.01 to 0.25 Hz. For each group, the average PSD was determined for each brain region and a 2-sample t test was performed to determine the difference in power between the 2 groups. According to the results, patients with FM exhibited significantly increased frequency power in the primary somatosensory cortex (S1), supplementary motor area (SMA), dorsolateral prefrontal cortex, and amygdala. In patients with FM, the increase in PSD did not show an association with depression or anxiety. Therefore, our findings of atypical increased frequency power during the resting state in pain-related brain regions may implicate the enhanced resting-state baseline neural activity in several brain regions associated with pain processing in FM. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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

EEG sensorimotor rhythms' variation and functional connectivity measures during motor imagery: linear relations and classification approaches.

PubMed

Stefano Filho, Carlos A; Attux, Romis; Castellano, Gabriela

2017-01-01

Hands motor imagery (MI) has been reported to alter synchronization patterns amongst neurons, yielding variations in the mu and beta bands' power spectral density (PSD) of the electroencephalography (EEG) signal. These alterations have been used in the field of brain-computer interfaces (BCI), in an attempt to assign distinct MI tasks to commands of such a system. Recent studies have highlighted that information may be missing if knowledge about brain functional connectivity is not considered. In this work, we modeled the brain as a graph in which each EEG electrode represents a node. Our goal was to understand if there exists any linear correlation between variations in the synchronization patterns-that is, variations in the PSD of mu and beta bands-induced by MI and alterations in the corresponding functional networks. Moreover, we (1) explored the feasibility of using functional connectivity parameters as features for a classifier in the context of an MI-BCI; (2) investigated three different types of feature selection (FS) techniques; and (3) compared our approach to a more traditional method using the signal PSD as classifier inputs. Ten healthy subjects participated in this study. We observed significant correlations ( p  < 0.05) with values ranging from 0.4 to 0.9 between PSD variations and functional network alterations for some electrodes, prominently in the beta band. The PSD method performed better for data classification, with mean accuracies of (90 ± 8)% and (87 ± 7)% for the mu and beta band, respectively, versus (83 ± 8)% and (83 ± 7)% for the same bands for the graph method. Moreover, the number of features for the graph method was considerably larger. However, results for both methods were relatively close, and even overlapped when the uncertainties of the accuracy rates were considered. Further investigation regarding a careful exploration of other graph metrics may provide better alternatives.

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

Flexible and scalable methods for quantifying stochastic variability in the era of massive time-domain astronomical data sets

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

Kelly, Brandon C.; Becker, Andrew C.; Sobolewska, Malgosia

2014-06-10

We present the use of continuous-time autoregressive moving average (CARMA) models as a method for estimating the variability features of a light curve, and in particular its power spectral density (PSD). CARMA models fully account for irregular sampling and measurement errors, making them valuable for quantifying variability, forecasting and interpolating light curves, and variability-based classification. We show that the PSD of a CARMA model can be expressed as a sum of Lorentzian functions, which makes them extremely flexible and able to model a broad range of PSDs. We present the likelihood function for light curves sampled from CARMA processes, placingmore » them on a statistically rigorous foundation, and we present a Bayesian method to infer the probability distribution of the PSD given the measured light curve. Because calculation of the likelihood function scales linearly with the number of data points, CARMA modeling scales to current and future massive time-domain data sets. We conclude by applying our CARMA modeling approach to light curves for an X-ray binary, two active galactic nuclei, a long-period variable star, and an RR Lyrae star in order to illustrate their use, applicability, and interpretation.« less

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.

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.

Fine structure of synapses of the central nervous system in resinless sections.

PubMed

Cohen, R S; Wolosewick, J J; Becker, R P; Pappas, G D

1983-10-01

The cytoskeleton has been implicated in neuronal function, particularly in axonal transport, excitability at axonal membranes, and movement of synaptic vesicles at preganglionic endings. The present study demonstrates the presence of a pre- and postsynaptic cytoskeleton in resinless sections of CNS tissue by use of the polyethylene glycol (PEG) technique of Wolosewick (1980) viewed by conventional transmission EM, scanning transmission EM, and surface scanning EM. The PEG technique permits visualization of the cytoskeletal network unobscured by the electron scattering properties of epoxy embedment. In the presynaptic process, synaptic vesicles appear to be suspended in a filamentous network that is contiguous with the synaptic vesicle membrane and with the presynaptic plasma membrane and its dense material. In the postsynaptic process, the postsynaptic density (PSD) is seen in intimate contact with the postsynaptic membrane. En face images of the PSD in some synapses appear as a torus. Emanating from the filamentous web of the PSD are filaments which extend to the adjacent plasma membrane. We conclude that membranous synaptic elements are contiguous with a three-dimensional lattice network that is similar to that described in whole unembedded cells (Wolosewick and Porter, 1976). Moreover, the synaptic densities represent a specialized elaboration of the cytoskeleton.

Kepler Observations of Rapid Optical Variability in Active Galactic Nuclei

NASA Technical Reports Server (NTRS)

Mushotzky, R. F.; Edelson, R.; Baumgartner, W. H.; Gandhi, P.

2012-01-01

Over three quarters in 2010 - 2011, Kepler monitored optical emission from four active galactic nuclei (AGN) with approx 30 min sampling, > 90% duty cycle and approx < 0.1% repeatability. These data determined the AGN optical fluctuation power spectral density functions (PSDs) over a wide range in temporal frequency. Fits to these PSDs yielded power law slopes of -2.6 to -3.3, much steeper than typically seen in the X-rays. We find evidence that individual AGN exhibit intrinsically different PSD slopes. The steep PSD fits are a challenge to recent AGN variability models but seem consistent with first order MRI theoretical calculations of accretion disk fluctuations.

Investigation of the Deposition and Densification Parameters on the Mechanical Properties of Pressurized Spray Deposited (PSD) 3-D Printed Ceramic Components

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

Menchhofer, Paul A.; Becker, Benjamin

Oak Ridge National Laboratory (ORNL) and HotEnd Works teamed to investigate the use of pressurized spray deposition (PSD) technology for the production of ceramic parts via additive manufacturing. Scanning electron microscopy of sintered parts provided by HotEnd Works revealed voids large enough to compromise the mechanical properties of PSD manufactured parts. Scanning electron microscopy and particle size analysis of the alumina oxide powder feedstocks indicated that the powders contained some large particles and some agglomerations in the powder. Further classification of the powder feedstocks and removal of the agglomerates by sonication in the liquid used for the PSD process aremore » recommended. Analysis of sintered parts indicated that the sonic modulus for the alumina part is consistent with other known values for alumina. The density for this part was determined by standard Archimedes immersion density methods and was found to be > 99.7 % of the theoretical density for pure alumina.« less

Testing relativistic electron acceleration mechanisms

NASA Astrophysics Data System (ADS)

Green, Janet Carol

2002-09-01

This dissertation tests models of relativistic electron acceleration in the earth's outer radiation belt. The models fall into two categories: external and internal. External acceleration models transport and accelerate electrons from a source region in the outer magnetosphere to the inner magnetosphere. Internal acceleration models accelerate a population of electrons already present in the inner magnetosphere. In this dissertation, we test one specific external acceleration mechanism, perform a general test that differentiates between internal and external acceleration models, and test one promising internal acceleration model. We test the models using Polar-HIST data that we transform into electron phase space density (PSD) as a function of adiabatic invariants. We test the ultra low frequency (ULF) wave enhanced radial diffusion external acceleration mechanism by looking for a causal relationship between increased wave power and increased electron PSD at three L* values. One event with increased wave power at two L* values and no subsequent PSD increase does not support the model suggesting that ULF wave power alone is not sufficient to cause an electron response. Excessive loss of electrons and the duration of wave power do not explain the lack of a PSD enhancement at low L*. We differentiate between internal and external acceleration mechanisms by examining the radial profile of electron PSD. We observe PSD profiles that depend on local time. Nightside profiles are highly dependent on the magnetic field model used to calculate PSD as a function of adiabatic invariants and are not reliable. Dayside PSD profiles are more robust and consistent with internal acceleration of electrons. We test one internal acceleration model, the whistler/electromagnetic ion cyclotron wave model, by comparing observed pitch angle distributions to those predicted by the model using a superposed epoch analysis. The observations show pitch angle distributions corresponding to electrons with energy >=4.0 MeV becoming more peaked at 90° during the storm recovery phase. The observation is consistent with but does not confirm the model. Our tests indicate that relativistic electrons are accelerated by an internal source acceleration mechanism but we do not identify a unique mechanism.

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.

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).

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

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.

Electrical and Ca2+ signaling in dendritic spines of substantia nigra dopaminergic neurons

PubMed Central

Hage, Travis A; Sun, Yujie; Khaliq, Zayd M

2016-01-01

Little is known about the density and function of dendritic spines on midbrain dopamine neurons, or the relative contribution of spine and shaft synapses to excitability. Using Ca2+ imaging, glutamate uncaging, fluorescence recovery after photobleaching and transgenic mice expressing labeled PSD-95, we comparatively analyzed electrical and Ca2+ signaling in spines and shaft synapses of dopamine neurons. Dendritic spines were present on dopaminergic neurons at low densities in live and fixed tissue. Uncaging-evoked potential amplitudes correlated inversely with spine length but positively with the presence of PSD-95. Spine Ca2+ signals were less sensitive to hyperpolarization than shaft synapses, suggesting amplification of spine head voltages. Lastly, activating spines during pacemaking, we observed an unexpected enhancement of spine Ca2+ midway throughout the spike cycle, likely involving recruitment of NMDA receptors and voltage-gated conductances. These results demonstrate functionality of spines in dopamine neurons and reveal a novel modulation of spine Ca2+ signaling during pacemaking. DOI: http://dx.doi.org/10.7554/eLife.13905.001 PMID:27163179

Ensemble Mean Density and its Connection to Other Microphysical Properties of Falling Snow as Observed in Southern Finland

NASA Technical Reports Server (NTRS)

Tiira, Jussi; Moisseev, Dmitri N.; Lerber, Annakaisa von; Ori, Davide; Tokay, Ali; Bliven, Larry F.; Petersen, Walter

2016-01-01

In this study measurements collected during winters 2013/2014 and 2014/2015 at the University of Helsinki measurement station in Hyytiala are used to investigate connections between ensemble mean snow density, particle fall velocity and parameters of the particle size distribution (PSD). The density of snow is derived from measurements of particle fall velocity and PSD, provided by a particle video imager, and weighing gauge measurements of precipitation rate. Validity of the retrieved density values is checked against snow depth measurements. A relation retrieved for the ensemble mean snow density and median volume diameter is in general agreement with previous studies, but it is observed to vary significantly from one winter to the other. From these observations, characteristic mass- dimensional relations of snow are retrieved. For snow rates more than 0.2mm/h, a correlation between the intercept parameter of normalized gamma PSD and median volume diameter was observed.

Ensemble mean density and its connection to other microphysical properties of falling snow as observed in Southern Finland

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

Tiira, Jussi; Moisseev, Dmitri N.; von Lerber, Annakaisa

In this study measurements collected during winters 2013/2014 and 2014/2015 at the University of Helsinki measurement station in Hyytiala are used to investigate connections between ensemble mean snow density, particle fall velocity and parameters of the particle size distribution (PSD). The density of snow is derived from measurements of particle fall velocity and PSD, provided by a particle video imager, and weighing gauge measurements of precipitation rate. Validity of the retrieved density values is checked against snow depth measurements. Here, a relation retrieved for the ensemble mean snow density and median volume diameter is in general agreement with previous studies,more » but it is observed to vary significantly from one winter to the other. From these observations, characteristic mass–dimensional relations of snow are retrieved. For snow rates more than 0.2 mm h -1, a correlation between the intercept parameter of normalized gamma PSD and median volume diameter was observed.« less

Ensemble mean density and its connection to other microphysical properties of falling snow as observed in Southern Finland

DOE PAGES

Tiira, Jussi; Moisseev, Dmitri N.; von Lerber, Annakaisa; ...

2016-09-28

In this study measurements collected during winters 2013/2014 and 2014/2015 at the University of Helsinki measurement station in Hyytiala are used to investigate connections between ensemble mean snow density, particle fall velocity and parameters of the particle size distribution (PSD). The density of snow is derived from measurements of particle fall velocity and PSD, provided by a particle video imager, and weighing gauge measurements of precipitation rate. Validity of the retrieved density values is checked against snow depth measurements. Here, a relation retrieved for the ensemble mean snow density and median volume diameter is in general agreement with previous studies,more » but it is observed to vary significantly from one winter to the other. From these observations, characteristic mass–dimensional relations of snow are retrieved. For snow rates more than 0.2 mm h -1, a correlation between the intercept parameter of normalized gamma PSD and median volume diameter was observed.« less

The impact of the characteristics of volcanic ash on forecasting.

NASA Astrophysics Data System (ADS)

Beckett, Frances; Hort, Matthew; Millington, Sarah; Stevenson, John; Witham, Claire

2013-04-01

The eruption of Eyjafjallajökull during April - May 2010 and Grímsvötn in May 2011, Iceland, caused the widespread dispersion of volcanic ash across the NE Atlantic, and ultimately into UK and European airspace. This resulted in thousands of flights to and from affected countries across Europe to be cancelled. The Met Office, UK, is the home of the London VAAC, a Volcanic Ash Advisory Centre, and as such is responsible for providing reports and forecasts for the movement of volcanic ash clouds covering the UK, Iceland and the north-eastern part of the North Atlantic ocean. To forecast the dispersion of volcanic ash requires that the sedimentation of ash particles through the atmosphere is effectively modelled. The settling velocity of an ash particle is a function of its size, shape and density, plus the density and viscosity of the air through which it is falling. We consider the importance of characterising the physical properties of ash when modelling the long range dispersion of ash particles through the atmosphere. Using the Reynolds number dependent scheme employed by NAME, the Lagrangian particle model used operationally by the Met Office, we calculate the settling velocity and thus the maximum travel distance of an ash particle through an idealised atmosphere as a function of its size, shape and density. The results are compared to measured particle sizes from deposits across Europe following the eruption of Eyjafjallajökull in 2010. Further, the particle size distribution (PSD) of ash in a volcanic cloud with time is modelled using NAME: the particle density distribution and particle shape factor are varied and the modelled PSD compared to the PSD measured in the ash cloud during the eruption of Eyjafjallajökull in 2010 by the FAAM research aircraft. The influence of the weather on PSD is also considered by comparing model output using an idealised atmosphere to output using NWP driven meteorological fields. We discuss the sensitivity of forecasts of the dispersion of volcanic ash to the representation of particle characteristics in NAME, the importance of representing the weather in ash fall models, and the implications of these results for the operational forecasting of volcanic ash dispersion at the London VAAC.

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

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

X-ray fluctuation timescale and Black Hole mass relation in AGN

NASA Astrophysics Data System (ADS)

Wandel, Amri; Malkan, Mathew

We analyze the fluctuations in the X-ray flux of 20 AGN (mainly Seyfert 1 galaxies) monitored by RXTE and XMM-Newton with a sampling frequency ranging from hours to years, using structure function (SF) analysis. We derive SFs over four orders of magnitude in the time domain (0.03-300 days). Most objects show a characteristic time scale, where the SF flattens or changes slope. For 10 objects with published power-spectral density (PSD) the break time scales in the SF and PSD are similar and show a good correlation. We also find a significant correlation between the SF timescale and the mass of the central black hole, determined for most objects by reverberation mapping.

Multiscaling properties of coastal waters particle size distribution from LISST in situ measurements

NASA Astrophysics Data System (ADS)

Pannimpullath Remanan, R.; Schmitt, F. G.; Loisel, H.; Mériaux, X.

2013-12-01

An eulerian high frequency sampling of particle size distribution (PSD) is performed during 5 tidal cycles (65 hours) in a coastal environment of the eastern English Channel at 1 Hz. The particle data are recorded using a LISST-100x type C (Laser In Situ Scattering and Transmissometry, Sequoia Scientific), recording volume concentrations of particles having diameters ranging from 2.5 to 500 mu in 32 size classes in logarithmic scale. This enables the estimation at each time step (every second) of the probability density function of particle sizes. At every time step, the pdf of PSD is hyperbolic. We can thus estimate PSD slope time series. Power spectral analysis shows that the mean diameter of the suspended particles is scaling at high frequencies (from 1s to 1000s). The scaling properties of particle sizes is studied by computing the moment function, from the pdf of the size distribution. Moment functions at many different time scales (from 1s to 1000 s) are computed and their scaling properties considered. The Shannon entropy at each time scale is also estimated and is related to other parameters. The multiscaling properties of the turbidity (coefficient cp computed from the LISST) are also consider on the same time scales, using Empirical Mode Decomposition.

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.

Modified Spectral Fatigue Methods for S-N Curves With MIL-HDBK-5J Coefficients

NASA Technical Reports Server (NTRS)

Irvine, Tom; Larsen, Curtis

2016-01-01

The rainflow method is used for counting fatigue cycles from a stress response time history, where the fatigue cycles are stress-reversals. The rainflow method allows the application of Palmgren-Miner's rule in order to assess the fatigue life of a structure subject to complex loading. The fatigue damage may also be calculated from a stress response power spectral density (PSD) using the semi-empirical Dirlik, Single Moment, Zhao-Baker and other spectral methods. These methods effectively assume that the PSD has a corresponding time history which is stationary with a normal distribution. This paper shows how the probability density function for rainflow stress cycles can be extracted from each of the spectral methods. This extraction allows for the application of the MIL-HDBK-5J fatigue coefficients in the cumulative damage summation. A numerical example is given in this paper for the stress response of a beam undergoing random base excitation, where the excitation is applied separately by a time history and by its corresponding PSD. The fatigue calculation is performed in the time domain, as well as in the frequency domain via the modified spectral methods. The result comparison shows that the modified spectral methods give comparable results to the time domain rainflow counting method.

Experimental power spectral density analysis for mid- to high-spatial frequency surface error control.

PubMed

Hoyo, Javier Del; Choi, Heejoo; Burge, James H; Kim, Geon-Hee; Kim, Dae Wook

2017-06-20

The control of surface errors as a function of spatial frequency is critical during the fabrication of modern optical systems. A large-scale surface figure error is controlled by a guided removal process, such as computer-controlled optical surfacing. Smaller-scale surface errors are controlled by polishing process parameters. Surface errors of only a few millimeters may degrade the performance of an optical system, causing background noise from scattered light and reducing imaging contrast for large optical systems. Conventionally, the microsurface roughness is often given by the root mean square at a high spatial frequency range, with errors within a 0.5×0.5  mm local surface map with 500×500 pixels. This surface specification is not adequate to fully describe the characteristics for advanced optical systems. The process for controlling and minimizing mid- to high-spatial frequency surface errors with periods of up to ∼2-3  mm was investigated for many optical fabrication conditions using the measured surface power spectral density (PSD) of a finished Zerodur optical surface. Then, the surface PSD was systematically related to various fabrication process parameters, such as the grinding methods, polishing interface materials, and polishing compounds. The retraceable experimental polishing conditions and processes used to produce an optimal optical surface PSD are presented.

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.

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.

Dendritic Spine Instability in a Mouse Model of CDKL5 Disorder Is Rescued by Insulin-like Growth Factor 1.

PubMed

Della Sala, Grazia; Putignano, Elena; Chelini, Gabriele; Melani, Riccardo; Calcagno, Eleonora; Michele Ratto, Gian; Amendola, Elena; Gross, Cornelius T; Giustetto, Maurizio; Pizzorusso, Tommaso

2016-08-15

CDKL5 (cyclin-dependent kinase-like 5) is mutated in many severe neurodevelopmental disorders, including atypical Rett syndrome. CDKL5 was shown to interact with synaptic proteins, but an in vivo analysis of the role of CDKL5 in dendritic spine dynamics and synaptic molecular organization is still lacking. In vivo two-photon microscopy of the somatosensory cortex of Cdkl5(-/y) mice was applied to monitor structural dynamics of dendritic spines. Synaptic function and plasticity were measured using electrophysiological recordings of excitatory postsynaptic currents and long-term potentiation in brain slices and assessing the expression of synaptic postsynaptic density protein 95 (PSD-95). Finally, we studied the impact of insulin-like growth factor 1 (IGF-1) treatment on CDKL5 null mice to restore the synaptic deficits. Adult mutant mice showed a significant reduction in spine density and PSD-95-positive synaptic puncta, a reduction of persistent spines, and impaired long-term potentiation. In juvenile mutants, short-term spine elimination, but not formation, was dramatically increased. Exogenous administration of IGF-1 rescued defective rpS6 phosphorylation, spine density, and PSD-95 expression. Endogenous cortical IGF-1 levels were unaffected by CDKL5 deletion. These data demonstrate that dendritic spine stabilization is strongly regulated by CDKL5. Moreover, our data suggest that IGF-1 treatment could be a promising candidate for clinical trials in CDKL5 patients. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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.

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.

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%.

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%

Alternative splicing modulates Kv channel clustering through a molecular ball and chain mechanism

NASA Astrophysics Data System (ADS)

Zandany, Nitzan; Marciano, Shir; Magidovich, Elhanan; Frimerman, Teddy; Yehezkel, Rinat; Shem-Ad, Tzilhav; Lewin, Limor; Abdu, Uri; Orr, Irit; Yifrach, Ofer

2015-03-01

Ion channel clustering at the post-synaptic density serves a fundamental role in action potential generation and transmission. Here, we show that interaction between the Shaker Kv channel and the PSD-95 scaffold protein underlying channel clustering is modulated by the length of the intrinsically disordered C terminal channel tail. We further show that this tail functions as an entropic clock that times PSD-95 binding. We thus propose a ‘ball and chain’ mechanism to explain Kv channel binding to scaffold proteins, analogous to the mechanism describing channel fast inactivation. The physiological relevance of this mechanism is demonstrated in that alternative splicing of the Shaker channel gene to produce variants of distinct tail lengths resulted in differential channel cell surface expression levels and clustering metrics that correlate with differences in affinity of the variants for PSD-95. We suggest that modulating channel clustering by specific spatial-temporal spliced variant targeting serves a fundamental role in nervous system development and tuning.

Low-Luminosity AGN As Analogues of Galactic Black Holes in the Low/Hard State: Evidence from X-Ray Timing of NGC 4258

NASA Technical Reports Server (NTRS)

Markowitz, A.; Uttley, P.

2005-01-01

We present a broadband power spectral density function (PSD) measured from extensive RXTE monitoring data of the low-luminosity AGN NGC 4258, which has an accurate, maser-determined black hole mass of (3.9 plus or minus 0.1) x 10(exp 7) solar mass. We constrain the PSD break time scale to be greater than 4.5 d at greater than 90% confidence, which appears to rule out the possibility that NGC 4258 is an analogue of black hole X-ray binaries (BHXRBs) in the high/soft state. In this sense, the PSD of NGC 4258 is different to that of some more-luminous Seyferts, which appear similar to the PSDs of high/soft state X-ray binaries. This result supports previous analogies between LLAGN and X-ray binaries in the low/hard state based on spectral energy distributions, indicating that the AGN/BHXRB analogy is valid across a broad range of accretion rates.

Integration of the Two-Dimensional Power Spectral Density into Specifications for the X-ray Domain -- Problems and Opportunities

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

McKinney, Wayne R.; Howells, M. R.; Yashchuk, V. V.

2008-09-30

An implementation of the two-dimensional statistical scattering theory of Church and Takacs for the prediction of scattering from x-ray mirrors is presented with a graphical user interface. The process of this development has clarified several problems which are of significant interest to the synchrotron community. These problems have been addressed to some extent, for example, for large astronomical telescopes, and at the National Ignition Facility for normal incidence optics, but not in the synchrotron community for grazing incidence optics. Since it is based on the Power Spectral Density (PSD) to provide a description of the deviations from ideal shape ofmore » the surface, accurate prediction of the scattering requires an accurate estimation of the PSD. Specifically, the spatial frequency range of measurement must be the correct one for the geometry of use of the optic--including grazing incidence and coherence effects, and the modifications to the PSD of the Optical Transfer Functions (OTF) of the measuring instruments must be removed. A solution for removal of OTF effects has been presented previously, the Binary Pseudo-Random Grating. Typically, the frequency range of a single instrument does not cover the range of interest, requiring the stitching together of PSD estimations. This combination generates its own set of difficulties in two dimensions. Fitting smooth functions to two dimensional PSDs, particularly in the case of spatial non-isotropy of the surface, which is often the case for optics in synchrotron beam lines, can be difficult. The convenient, and physically accurate fractal for one dimension does not readily transfer to two dimensions. Finally, a completely statistical description of scattering must be integrated with a deterministic low spatial frequency component in order to completely model the intensity near the image. An outline for approaching these problems, and our proposed experimental program is given.« less

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

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.

Ovarian steroids increase PSD-95 expression and dendritic spines in the dorsal raphe of ovariectomized macaques.

PubMed

Rivera, Heidi M; Bethea, Cynthia L

2013-12-01

Estradiol (E) and progesterone (P) promote spinogenesis in several brain areas. Intracellular signaling cascades that promote spinogenesis involve RhoGTPases, glutamate signaling and synapse assembly. We found that in serotonin neurons, E ± P administration increases (a) gene and protein expression of RhoGTPases, (b) gene expression of glutamate receptors, and (c) gene expression of pivotal synapse assembly proteins. Therefore, in this study we determined whether structural changes in dendritic spines in the dorsal raphe follow the observed changes in gene and protein expression. Dendritic spines were examined with immunogold silver staining of a spine marker protein, postsynaptic density-95 (PSD-95) and with Golgi staining. In the PSD-95 study, adult Ovx monkeys received placebo, E, P, or E + P for 1 month (n = 3/group). Sections were immunostained for PSD-95 and the number of PSD-95-positive puncta was determined with stereology. E, P, and E + P treatment significantly increased the total number of PSD-95-positive puncta (ANOVA, P = 0.04). In the golgi study, adult Ovx monkeys received placebo, E or E + P for 1 month (n = 3-4) and the midbrain was golgi-stained. A total of 80 neurons were analyzed with Neurolucida software. There was a significant difference in spine density that depended on branch order (two-way ANOVA). E + P treatment significantly increased spine density in higher-order (3°-5°) dendritic branches relative to Ovx group (Bonferroni, P < 0.05). In summary, E + P leads to the elaboration of dendritic spines on dorsal raphe neurons. The ability of E to induce PSD-95, but not actual spines, suggests either a sampling or time lag issue. Increased spinogenesis on serotonin dendrites would facilitate excitatory glutamatergic input and, in turn, increase serotonin neurotransmission throughout the brain. Copyright © 2013 Wiley Periodicals, Inc.

Melatonin improves neuroplasticity by upregulating the growth-associated protein-43 (GAP-43) and NMDAR postsynaptic density-95 (PSD-95) proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral ischemia even during a long-term recovery period.

PubMed

Juan, Wei-Sheng; Huang, Sheng-Yang; Chang, Che-Chao; Hung, Yu-Chang; Lin, Yu-Wen; Chen, Tsung-Ying; Lee, Ai-Hua; Lee, Ai-Chiang; Wu, Tian-Shung; Lee, E-Jian

2014-03-01

Recent evidence shows that the NMDAR postsynaptic density-95 (PSD-95), growth-associated protein-43 (GAP-43), and matrix metalloproteinase-9 (MMP-9) protein enhance neuroplasticity at the subacute stage of stroke. Here, we evaluated whether melatonin would modulate the PSD-95, GAP-43, and MMP-9 proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to experimental stroke. Adult male Sprague-Dawley rats were treated with melatonin (5 mg/kg) or vehicle at reperfusion onset after transient occlusion of the right middle cerebral artery (tMCAO) for 90 min. Animals were euthanized for Western immunoblot analyses for the PSD-95 and GAP-43 proteins and gelatin zymography for the MMP-9 activity at 7 days postinsult. Another set of animals was sacrificed for histologic and Golgi-Cox-impregnated sections at 28 days postinsult. In cultured neurons exposed to glutamate excitotoxicity, melatonin significantly upregulated the GAP-43 and PSD-95 expressions and improved dendritic aborizations (P<0.05, respectively). Relative to controls, melatonin-treated stroke animals caused a significant improvement in GAP-43 and PSD-95 expressions as well as the MMP-9 activity in the ischemic brain (P<0.05). Consequently, melatonin also significantly promoted the dendritic spine density and reduced infarction in the ischemic brain, and improved neurobehaviors as well at 28 days postinsult (P<0.05, respectively). Together, melatonin upregulates GAP-43, PSD-95, and MMP-9 proteins, which likely accounts for its actions to improve neuroplasticity in cultured neurons exposed to glutamate excitotoxicity and to enhance long-term neuroprotection, neuroplasticity, and brain remodeling in stroke rats. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[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.

PSD-95 uncoupling from NMDA receptors by Tat- N-dimer ameliorates neuronal depolarization in cortical spreading depression.

PubMed

Kucharz, Krzysztof; Søndergaard Rasmussen, Ida; Bach, Anders; Strømgaard, Kristian; Lauritzen, Martin

2017-05-01

Cortical spreading depression is associated with activation of NMDA receptors, which interact with the postsynaptic density protein 95 (PSD-95) that binds to nitric oxide synthase (nNOS). Here, we tested whether inhibition of the nNOS/PSD-95/NMDA receptor complex formation by anti-ischemic compound, UCCB01-144 (Tat- N-dimer) ameliorates the persistent effects of cortical spreading depression on cortical function. Using in vivo two-photon microscopy in somatosensory cortex in mice, we show that fluorescently labelled Tat- N-dimer readily crosses blood-brain barrier and accumulates in nerve cells during the first hour after i.v. injection. The Tat- N-dimer suppressed stimulation-evoked synaptic activity by 2-20%, while cortical blood flow and cerebral oxygen metabolic (CMRO 2 ) responses were preserved. During cortical spreading depression, the Tat- N-dimer reduced the average amplitude of the negative shift in direct current potential by 33% (4.1 mV). Furthermore, the compound diminished the average depression of spontaneous electrocorticographic activity by 11% during first 40 min of post-cortical spreading depression recovery, but did not mitigate the suppressing effect of cortical spreading depression on cortical blood flow and CMRO 2 . We suggest that uncoupling of PSD-95 from NMDA receptors reduces overall neuronal excitability and the amplitude of the spreading depolarization wave. These findings may be of interest for understanding the neuroprotective effects of the nNOS/PSD-95 uncoupling in stroke.

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

Assay of Calcium Transients and Synapses in Rat Hippocampal Neurons by Kinetic Image Cytometry and High-Content Analysis: An In Vitro Model System for Postchemotherapy Cognitive Impairment.

PubMed

McDonough, Patrick M; Prigozhina, Natalie L; Basa, Ranor C B; Price, Jeffrey H

2017-07-01

Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days. Kinetic Image Cytometry™ (KIC™) methods were developed to quantify spontaneously occurring intracellular calcium transients representing the activity of the neurons, and high-content analysis (HCA) methods were developed to quantify the expression, colocalization, and puncta formed by synaptic proteins (postsynaptic density protein-95 [PSD-95] and presynaptic protein Synapsin-1 [Syn-1]). As quantified by KIC, FSK increased the occurrence and synchronization of the calcium transients indicating stimulatory effects on RHN activity, whereas TAM had inhibitory effects. As quantified by HCA, FSK also increased PSD-95 puncta and PSD-95:Syn-1 colocalization, whereas ES increased the puncta of both PSD-95 and Syn-1 with little effect on colocalization. The estrogen receptor antagonist FUL also increased PSD-95 puncta. In contrast, TAM reduced Syn-1 and PSD-95:Syn-1 colocalization, consistent with its inhibitory effects on the calcium transients. Thus TAM reduced activity and synapse formation by the RHNs, which may relate to the ability of this agent to cause PCCI. The results illustrate that KIC and HCA can be used to quantify neurotoxic and neuroprotective effects of chemicals in RHNs to investigate mechanisms and potential therapeutics for PCCI.

VLF Wave Local Acceleration & ULF Wave Radial Diffusion: The Importance of K-Dependent PSD Analysis for Diagnosing the cause of Radiation Belt Acceleration.

NASA Astrophysics Data System (ADS)

Ozeke, L.; Mann, I. R.; Claudepierre, S. G.; Morley, S.; Henderson, M. G.; Baker, D. N.; Kletzing, C.; Spence, H. E.

2017-12-01

We present results showing the temporal evolution of electron Phase Space Density (PSD) in the outer radiation belt during the most intense geomagnetic storm of the last decade which occurred on March 17th 2015. Based on observations of growing local PSD peaks at fixed first and second adiabatic invariants of M=1000 MeV/G and K=0.18 G1/2Re respectively, previous studies argued that the outer radiation belt flux enhancement that occurred during this storm resulted from local acceleration driven by VLF waves. Here we show that the vast majority of the outer radiation belt consisted of electrons with much lower K-values than 0.18 G1/2Re, and that at these lower K-values there is no clear evidence of growing local PSD peaks consistent with that expected from local acceleration. Contrary to prior studies we show that the outer radiation belt flux enhancement is consistent with inward radial diffusion driven by ULF waves and present evidence that the growing local PSD peaks at K=0.18 G1/2Re and M=1000 MeV/G result from pitch-angle scattering of lower-K electrons to K=0.18 G1/2Re. In addition, we also show that the observed outer radiation belt flux enhancement during this geomagnetic storm can be reproduced using a radial diffusion model driven by measured ULF waves without including any local acceleration. These results highlight the importance of careful analysis of the electron PSD profiles as a function of L* over a range of fixed first, M and second K, adiabatic invariants to correctly determine the mechanism responsible for the electron flux enhancements observed in the outer radiation belt.

The gray area between synapse structure and function-Gray's synapse types I and II revisited.

PubMed

Klemann, Cornelius J H M; Roubos, Eric W

2011-11-01

On the basis of ultrastructural parameters, the concept was formulated that asymmetric Type I and symmetric Type II synapses are excitatory and inhibitory, respectively. This "functional Gray synapses concept" received strong support from the demonstration of the excitatory neurotransmitter glutamate in Type I synapses and of the inhibitory neurotransmitter γ-aminobutyric acid in Type II synapses, and is still frequently used in modern literature. However, morphological and functional evidence has accumulated that the concept is less tenable. Typical features of synapses like shape and size of presynaptic vesicles and synaptic cleft and presence of a postsynaptic density (PsD) do not always fit the postulated (excitatory/inhibitory) function of Gray's synapses. Furthermore, synapse function depends on postsynaptic receptors and associated signal transduction mechanisms rather than on presynaptic morphology and neurotransmitter type. Moreover, the notion that many synapses are difficult to classify as either asymmetric or symmetric has cast doubt on the assumption that the presence of a PsD is a sign of excitatory synaptic transmission. In view of the morphological similarities of the PsD in asymmetric synapses with membrane junctional structures such as the zonula adherens and the desmosome, asymmetric synapses may play a role as links between the postsynaptic and presynaptic membrane, thus ensuring long-term maintenance of interneuronal communication. Symmetric synapses, on the other hand, might be sites of transient communication as takes place during development, learning, memory formation, and pathogenesis of brain disorders. Confirmation of this idea might help to return the functional Gray synapse concept its central place in neuroscience. Copyright © 2011 Wiley-Liss, Inc.

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

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.

[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.

Determining the von Mises stress power spectral density for frequency domain fatigue analysis including out-of-phase stress components

NASA Astrophysics Data System (ADS)

Bonte, M. H. A.; de Boer, A.; Liebregts, R.

2007-04-01

This paper provides a new formula to take into account phase differences in the determination of an equivalent von Mises stress power spectral density (PSD) from multiple random inputs. The obtained von Mises PSD can subsequently be used for fatigue analysis. The formula was derived for use in the commercial vehicle business and was implemented in combination with Finite Element software to predict and analyse fatigue failure in the frequency domain.

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.

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.

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

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.

Kalirin, a Key Player in Synapse Formation, Is Implicated in Human Diseases

PubMed Central

Mandela, Prashant; Ma, Xin-Ming

2012-01-01

Synapse formation is considered to be crucial for learning and memory. Understanding the underlying molecular mechanisms of synapse formation is a key to understanding learning and memory. Kalirin-7, a major isoform of Kalirin in adult rodent brain, is an essential component of mature excitatory synapses. Kalirin-7 interacts with multiple PDZ-domain-containing proteins including PSD95, spinophilin, and GluR1 through its PDZ-binding motif. In cultured hippocampal/cortical neurons, overexpression of Kalirin-7 increases spine density and spine size whereas reduction of endogenous Kalirin-7 expression decreases synapse number, and spine density. In Kalirin-7 knockout mice, spine length, synapse number, and postsynaptic density (PSD) size are decreased in hippocampal CA1 pyramidal neurons; these morphological alterations are accompanied by a deficiency in long-term potentiation (LTP) and a decreased spontaneous excitatory postsynaptic current (sEPSC) frequency. Human Kalirin-7, also known as Duo or Huntingtin-associated protein-interacting protein (HAPIP), is equivalent to rat Kalirin-7. Recent studies show that Kalirin is relevant to many human diseases such as Huntington's Disease, Alzheimer's Disease, ischemic stroke, schizophrenia, depression, and cocaine addiction. This paper summarizes our recent understanding of Kalirin function. PMID:22548195

Kalirin, a key player in synapse formation, is implicated in human diseases.

PubMed

Mandela, Prashant; Ma, Xin-Ming

2012-01-01

Synapse formation is considered to be crucial for learning and memory. Understanding the underlying molecular mechanisms of synapse formation is a key to understanding learning and memory. Kalirin-7, a major isoform of Kalirin in adult rodent brain, is an essential component of mature excitatory synapses. Kalirin-7 interacts with multiple PDZ-domain-containing proteins including PSD95, spinophilin, and GluR1 through its PDZ-binding motif. In cultured hippocampal/cortical neurons, overexpression of Kalirin-7 increases spine density and spine size whereas reduction of endogenous Kalirin-7 expression decreases synapse number, and spine density. In Kalirin-7 knockout mice, spine length, synapse number, and postsynaptic density (PSD) size are decreased in hippocampal CA1 pyramidal neurons; these morphological alterations are accompanied by a deficiency in long-term potentiation (LTP) and a decreased spontaneous excitatory postsynaptic current (sEPSC) frequency. Human Kalirin-7, also known as Duo or Huntingtin-associated protein-interacting protein (HAPIP), is equivalent to rat Kalirin-7. Recent studies show that Kalirin is relevant to many human diseases such as Huntington's Disease, Alzheimer's Disease, ischemic stroke, schizophrenia, depression, and cocaine addiction. This paper summarizes our recent understanding of Kalirin function.

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

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.

Predicting CH4 adsorption capacity of microporous carbon using N2 isotherm and a new analytical model

USGS Publications Warehouse

Sun, Jielun; Chen, S.; Rostam-Abadi, M.; Rood, M.J.

1998-01-01

A new analytical pore size distribution (PSD) model was developed to predict CH4 adsorption (storage) capacity of microporous adsorbent carbon. The model is based on a 3-D adsorption isotherm equation, derived from statistical mechanical principles. Least squares error minimization is used to solve the PSD without any pre-assumed distribution function. In comparison with several well-accepted analytical methods from the literature, this 3-D model offers relatively realistic PSD description for select reference materials, including activated carbon fibers. N2 and CH4 adsorption data were correlated using the 3-D model for commercial carbons BPL and AX-21. Predicted CH4 adsorption isotherms, based on N2 adsorption at 77 K, were in reasonable agreement with the experimental CH4 isotherms. Modeling results indicate that not all the pores contribute the same percentage Vm/Vs for CH4 storage due to different adsorbed CH4 densities. Pores near 8-9 A?? shows higher Vm/Vs on the equivalent volume basis than does larger pores.

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

Fragile X Mental Retardation Protein Regulates the Levels of Scaffold Proteins and Glutamate Receptors in Postsynaptic Densities*

PubMed Central

Schütt, Janin; Falley, Katrin; Richter, Dietmar; Kreienkamp, Hans-Jürgen; Kindler, Stefan

2009-01-01

Functional absence of fragile X mental retardation protein (FMRP) causes the fragile X syndrome, a hereditary form of mental retardation characterized by a change in dendritic spine morphology. The RNA-binding protein FMRP has been implicated in regulating postsynaptic protein synthesis. Here we have analyzed whether the abundance of scaffold proteins and neurotransmitter receptor subunits in postsynaptic densities (PSDs) is altered in the neocortex and hippocampus of FMRP-deficient mice. Whereas the levels of several PSD components are unchanged, concentrations of Shank1 and SAPAP scaffold proteins and various glutamate receptor subunits are altered in both adult and juvenile knock-out mice. With the exception of slightly increased hippocampal SAPAP2 mRNA levels in adult animals, altered postsynaptic protein concentrations do not correlate with similar changes in total and synaptic levels of corresponding mRNAs. Thus, loss of FMRP in neurons appears to mainly affect the translation and not the abundance of particular brain transcripts. Semi-quantitative analysis of RNA levels in FMRP immunoprecipitates showed that in the mouse brain mRNAs encoding PSD components, such as Shank1, SAPAP1–3, PSD-95, and the glutamate receptor subunits NR1 and NR2B, are associated with FMRP. Luciferase reporter assays performed in primary cortical neurons from knock-out and wild-type mice indicate that FMRP silences translation of Shank1 mRNAs via their 3′-untranslated region. Activation of metabotropic glutamate receptors relieves translational suppression. As Shank1 controls dendritic spine morphology, our data suggest that dysregulation of Shank1 synthesis may significantly contribute to the abnormal spine development and function observed in brains of fragile X syndrome patients. PMID:19640847

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.

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.

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.

Simulation of Ground Winds Time Series for the NASA Crew Launch Vehicle (CLV)

NASA Technical Reports Server (NTRS)

Adelfang, Stanley I.

2008-01-01

Simulation of wind time series based on power spectrum density (PSD) and spectral coherence models for ground wind turbulence is described. The wind models, originally developed for the Shuttle program, are based on wind measurements at the NASA 150-m meteorological tower at Cape Canaveral, FL. The current application is for the design and/or protection of the CLV from wind effects during on-pad exposure during periods from as long as days prior to launch, to seconds or minutes just prior to launch and seconds after launch. The evaluation of vehicle response to wind will influence the design and operation of constraint systems for support of the on-pad vehicle. Longitudinal and lateral wind component time series are simulated at critical vehicle locations. The PSD model for wind turbulence is a function of mean wind speed, elevation and temporal frequency. Integration of the PSD equation over a selected frequency range yields the variance of the time series to be simulated. The square root of the PSD defines a low-pass filter that is applied to adjust the components of the Fast Fourier Transform (FFT) of Gaussian white noise. The first simulated time series near the top of the launch vehicle is the inverse transform of the adjusted FFT. Simulation of the wind component time series at the nearest adjacent location (and all other succeeding next nearest locations) is based on a model for the coherence between winds at two locations as a function of frequency and separation distance, where the adjacent locations are separated vertically and/or horizontally. The coherence function is used to calculate a coherence weighted FFT of the wind at the next nearest location, given the FFT of the simulated time series at the previous location and the essentially incoherent FFT of the wind at the selected location derived a priori from the PSD model. The simulated time series at each adjacent location is the inverse Fourier transform of the coherence weighted FFT. For a selected design case, the equations, the process and the simulated time series at multiple vehicle stations are presented.

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

Adsorption of binary gas mixtures in heterogeneous carbon predicted by density functional theory: on the formation of adsorption azeotropes.

PubMed

Ritter, James A; Pan, Huanhua; Balbuena, Perla B

2010-09-07

Classical density functional theory (DFT) was used to predict the adsorption of nine different binary gas mixtures in a heterogeneous BPL activated carbon with a known pore size distribution (PSD) and in single, homogeneous, slit-shaped carbon pores of different sizes. By comparing the heterogeneous results with those obtained from the ideal adsorbed solution theory and with those obtained in the homogeneous carbon, it was determined that adsorption nonideality and adsorption azeotropes are caused by the coupled effects of differences in the molecular size of the components in a gas mixture and only slight differences in the pore sizes of a heterogeneous adsorbent. For many binary gas mixtures, selectivity was found to be a strong function of pore size. As the width of a homogeneous pore increases slightly, the selectivity for two different sized adsorbates may change from being greater than unity to less than unity. This change in selectivity can be accompanied by the formation of an adsorption azeotrope when this same binary mixture is adsorbed in a heterogeneous adsorbent with a PSD, like in BPL activated carbon. These results also showed that the selectivity exhibited by a heterogeneous adsorbent can be dominated by a small number of pores that are very selective toward one of the components in the gas mixture, leading to adsorption azeotrope formation in extreme cases.

Power Spectrum Density of Long-Term MAXI Data

NASA Astrophysics Data System (ADS)

Sugimoto, Juri; Mihara, Tatehiro; Sugizaki, Mutsumi; Serino, Motoko; Kitamoto, Shunji; Sato, Ryousuke; Ueda, Yoshihiro; Ueno, Shiro

Monitor of All-sky X-ray Image (MAXI) on the International Space Station has been observing the X-ray sky since 2009 August 15. It has accumulated the X-ray data for about four years, so far. X-ray objects are usually variable and their variability can be studied by the power spectrum density (PSD) of the X-ray light curves. We applied our method to calculate PSDs of several kinds of objects observed with MAXI. We obtained significant PSDs from 16 Seyfert galaxies. For blackhole binary Cygnus X-1 there was a difference in the shape of PSD between the hard state and the soft state. For high mass X-ray binaries, Cen X-3, SMC X-1, and LMC X-4, there were several peaks in the PSD corresponding to the orbital period and the superorbital period.

Role of proBDNF and BDNF in dendritic spine plasticity and depressive-like behaviors induced by an animal model of depression.

PubMed

Qiao, Hui; An, Shu-Cheng; Xu, Chang; Ma, Xin-Ming

2017-05-15

Major depressive disorder (MDD) is one of the most common psychiatric disorder, but the underlying mechanisms are largely unknown. Increasing evidence shows that brain-derived neurotrophic factor (BDNF) plays an important role in the structural plasticity induced by depression. Considering the opposite effects of BDNF and its precursor proBDNF on neural plasticity, we hypothesized that the balance of BDNF and proBDNF plays a critical role in chronic unpredicted mild stress (CUMS)-induced depressive-like behaviors and structural plasticity in the rodent hippocampus. The aims of this study were to compare the functions of BDNF and proBDNF in the CUMS-induced depressive-like behaviors, and determine the effects of BDNF and proBDNF on expressions of kalirin-7, postsynaptic density protein 95 (PSD95) and NMDA receptor subunit NR2B in the hippocampus of stressed and naïve control rats, respectively. Our results showed that CUMS induced depressive-like behaviors, caused a decrease in the ratio of BDNF/proBDNF in the hippocampus and resulted in a reduction in spine density in hippocampal CA1 pyramidal neurons; these alterations were accompanied by a decrease in the levels of kalirin-7, PSD95 and NR2B in the hippocampus. Injection of exogenous BDNF into the CA1 area of stressed rats reversed CUMS-induced depressive-like behaviors and prevented CUMS-induced spine loss and decrease in kalirin-7, NR2B and PSD95 levels. In contrast, injection of exogenous proBDNF into the CA1 region of naïve rats caused depressive-like behavior and an accompanying decrease in both spine density and the levels of kalirin-7, NR2B and PSD95. Taken together, our results suggest that the ratio of BDNF to proBDNF in the hippocampus plays a key role in CUMS-induced depressive-like behaviors and alterations of dendritic spines in hippocampal CA1 pyramidal neurons. Kalirin-7 may play an important role during this process. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Functional MRI evidence for fine motor praxis dysfunction in children with persistent speech disorders.

PubMed

Redle, Erin; Vannest, Jennifer; Maloney, Thomas; Tsevat, Rebecca K; Eikenberry, Sarah; Lewis, Barbara; Shriberg, Lawrence D; Tkach, Jean; Holland, Scott K

2015-02-09

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. This case-control study included 12 children with PSD (mean age 7.42 years, four female) and 12 controls (mean age 7.44 years, four 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. 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. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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.

Daniell method for power spectral density estimation in atomic force microscopy

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

Labuda, Aleksander

An alternative method for power spectral density (PSD) estimation—the Daniell method—is revisited and compared to the most prevalent method used in the field of atomic force microscopy for quantifying cantilever thermal motion—the Bartlett method. Both methods are shown to underestimate the Q factor of a simple harmonic oscillator (SHO) by a predictable, and therefore correctable, amount in the absence of spurious deterministic noise sources. However, the Bartlett method is much more prone to spectral leakage which can obscure the thermal spectrum in the presence of deterministic noise. By the significant reduction in spectral leakage, the Daniell method leads to amore » more accurate representation of the true PSD and enables clear identification and rejection of deterministic noise peaks. This benefit is especially valuable for the development of automated PSD fitting algorithms for robust and accurate estimation of SHO parameters from a thermal spectrum.« less

The radiation-belt electron phase-space-density response to stream-interaction regions: A study combining multi-point observations, data-assimilation, and physics-based modeling

NASA Astrophysics Data System (ADS)

Kellerman, A. C.; Shprits, Y.; McPherron, R. L.; Kondrashov, D. A.; Weygand, J. M.; Zhu, H.; Drozdov, A.

2017-12-01

Presented is an analysis of the phase-space density (PSD) response to the stream-interaction region (SIR), which utilizes a reanalysis dataset principally comprised of the data-assimilative Versatile Electron Radiation Belt (VERB) code, Van Allen Probe and GOES observations. The dataset spans the period 2012-2017, and includes several SIR (and CIR) storms. The PSD is examined for evidence of injections, transport, acceleration, and loss by considering the instantaneous and time-averaged change at adiabatic invariant values that correspond to ring-current, relativistic, and ultra-relativistic energies. In the solar wind, the following variables in the slow and fast wind on either side of the stream interface (SI) are considered in each case: the coronal hole polarity, IMF, solar wind speed, density, pressure, and SI tilt angle. In the magnetosphere, the Dst, AE, and past PSD state are considered. Presented is an analysis of the dominant mechanisms, both external and internal to the magnetosphere, that cause radiation-belt electron non-adiabatic changes during the passage of these fascinating solar wind structures.

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.

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.

Determination of PM mass emissions from an aircraft turbine engine using particle effective density

NASA Astrophysics Data System (ADS)

Durdina, L.; Brem, B. T.; Abegglen, M.; Lobo, P.; Rindlisbacher, T.; Thomson, K. A.; Smallwood, G. J.; Hagen, D. E.; Sierau, B.; Wang, J.

2014-12-01

Inventories of particulate matter (PM) emissions from civil aviation and air quality models need to be validated using up-to-date measurement data corrected for sampling artifacts. We compared the measured black carbon (BC) mass and the total PM mass determined from particle size distributions (PSD) and effective density for a commercial turbofan engine CFM56-7B26/3. The effective density was then used to calculate the PM mass losses in the sampling system. The effective density was determined using a differential mobility analyzer and a centrifugal particle mass analyzer, and increased from engine idle to take-off by up to 60%. The determined mass-mobility exponents ranged from 2.37 to 2.64. The mean effective density determined by weighting the effective density distributions by PM volume was within 10% of the unit density (1000 kg/m3) that is widely assumed in aircraft PM studies. We found ratios close to unity between the PM mass determined by the integrated PSD method and the real-time BC mass measurements. The integrated PSD method achieved higher precision at ultra-low PM concentrations at which current mass instruments reach their detection limit. The line loss model predicted ∼60% PM mass loss at engine idle, decreasing to ∼27% at high thrust. Replacing the effective density distributions with unit density lead to comparable estimates that were within 20% and 5% at engine idle and high thrust, respectively. These results could be used for the development of a robust method for sampling loss correction of the future PM emissions database from commercial aircraft engines.

Egr-1 antisense oligodeoxynucleotide administration into the olfactory bulb impairs olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx.

PubMed

Ganesh, Ambigapathy; Bogdanowicz, Wieslaw; Balamurugan, Krishnaswamy; Ragu Varman, Durairaj; Rajan, Koilmani Emmanuvel

2012-08-30

Postsynaptic densities (PSDs) contain proteins that regulate synaptic transmission. We examined two important examples of these, calcium/calmodulin-dependent protein kinase II (CaMKII) and PSD-95, in regard to the functional role of early growth response gene-1 (egr-1) in regulation of olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx (family Pteropodidae). To test whether activation of egr-1 in the olfactory bulb (OB) is required for olfactory memory of these bats, bilaterally canulated individuals were infused with antisense (AS) or non-sense (NS)-oligodeoxynucleotides (ODN) of egr-1, or with phosphate buffer saline (PBS), 2h before the olfactory training. Our results showed that behavioral training significantly up-regulates immediate early gene (IEG) EGR-1 and key synaptic proteins Synaptotagmin-1(SYT-1), CaMKII and PSD-95, and phosphorylation of CaMKII in the OB at the protein level per se. Subsequently, we observed that egr-1 antisense-ODN infusion in the OB impaired olfactory memory and down regulates the expression of CaMKII and PSD-95, and the phosphorylation of CaMKII but not SYT-1. In contrast, NS-ODN or PBS had no effect on the expression of the PSDs CaMKII or PSD-95, or on the phosphorylation of CaMKII. When the egr-1 NS-ODN was infused in the OB after training for the novel odor there was no effect on olfactory memory. These findings suggest that egr-1 control the activation of CaMKII and PSD-95 during the process of olfactory memory formation. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Random Process Simulation for stochastic fatigue analysis. Ph.D. Thesis - Rice Univ., Houston, Tex.

NASA Technical Reports Server (NTRS)

Larsen, Curtis E.

1988-01-01

A simulation technique is described which directly synthesizes the extrema of a random process and is more efficient than the Gaussian simulation method. Such a technique is particularly useful in stochastic fatigue analysis because the required stress range moment E(R sup m), is a function only of the extrema of the random stress process. The family of autoregressive moving average (ARMA) models is reviewed and an autoregressive model is presented for modeling the extrema of any random process which has a unimodal power spectral density (psd). The proposed autoregressive technique is found to produce rainflow stress range moments which compare favorably with those computed by the Gaussian technique and to average 11.7 times faster than the Gaussian technique. The autoregressive technique is also adapted for processes having bimodal psd's. The adaptation involves using two autoregressive processes to simulate the extrema due to each mode and the superposition of these two extrema sequences. The proposed autoregressive superposition technique is 9 to 13 times faster than the Gaussian technique and produces comparable values for E(R sup m) for bimodal psd's having the frequency of one mode at least 2.5 times that of the other mode.

Differentiation and Characterization of Excitatory and Inhibitory Synapses by Cryo-electron Tomography and Correlative Microscopy

PubMed Central

Sun, Rong; Zhang, Bin; Qi, Lei; Shivakoti, Sakar; Tian, Chong-Li; Lau, Pak-Ming

2018-01-01

As key functional units in neural circuits, different types of neuronal synapses play distinct roles in brain information processing, learning, and memory. Synaptic abnormalities are believed to underlie various neurological and psychiatric disorders. Here, by combining cryo-electron tomography and cryo-correlative light and electron microscopy, we distinguished intact excitatory and inhibitory synapses of cultured hippocampal neurons, and visualized the in situ 3D organization of synaptic organelles and macromolecules in their native state. Quantitative analyses of >100 synaptic tomograms reveal that excitatory synapses contain a mesh-like postsynaptic density (PSD) with thickness ranging from 20 to 50 nm. In contrast, the PSD in inhibitory synapses assumes a thin sheet-like structure ∼12 nm from the postsynaptic membrane. On the presynaptic side, spherical synaptic vesicles (SVs) of 25–60 nm diameter and discus-shaped ellipsoidal SVs of various sizes coexist in both synaptic types, with more ellipsoidal ones in inhibitory synapses. High-resolution tomograms obtained using a Volta phase plate and electron filtering and counting reveal glutamate receptor-like and GABAA receptor-like structures that interact with putative scaffolding and adhesion molecules, reflecting details of receptor anchoring and PSD organization. These results provide an updated view of the ultrastructure of excitatory and inhibitory synapses, and demonstrate the potential of our approach to gain insight into the organizational principles of cellular architecture underlying distinct synaptic functions. SIGNIFICANCE STATEMENT To understand functional properties of neuronal synapses, it is desirable to analyze their structure at molecular resolution. We have developed an integrative approach combining cryo-electron tomography and correlative fluorescence microscopy to visualize 3D ultrastructural features of intact excitatory and inhibitory synapses in their native state. Our approach shows that inhibitory synapses contain uniform thin sheet-like postsynaptic densities (PSDs), while excitatory synapses contain previously known mesh-like PSDs. We discovered “discus-shaped” ellipsoidal synaptic vesicles, and their distributions along with regular spherical vesicles in synaptic types are characterized. High-resolution tomograms further allowed identification of putative neurotransmitter receptors and their heterogeneous interaction with synaptic scaffolding proteins. The specificity and resolution of our approach enables precise in situ analysis of ultrastructural organization underlying distinct synaptic functions. PMID:29311144

An Investigation of the Overlap Between the Statistical Discrete Gust and the Power Spectral Density Analysis Methods

NASA Technical Reports Server (NTRS)

Perry, Boyd, III; Pototzky, Anthony S.; Woods, Jessica A.

1989-01-01

The results of a NASA investigation of a claimed Overlap between two gust response analysis methods: the Statistical Discrete Gust (SDG) Method and the Power Spectral Density (PSD) Method are presented. The claim is that the ratio of an SDG response to the corresponding PSD response is 10.4. Analytical results presented for several different airplanes at several different flight conditions indicate that such an Overlap does appear to exist. However, the claim was not met precisely: a scatter of up to about 10 percent about the 10.4 factor can be expected.

[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.

Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein-Protein Interactions.

PubMed

Pedersen, Søren W; Albertsen, Louise; Moran, Griffin E; Levesque, Brié; Pedersen, Stine B; Bartels, Lina; Wapenaar, Hannah; Ye, Fei; Zhang, Mingjie; Bowen, Mark E; Strømgaard, Kristian

2017-09-15

The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effect of phosphorylation on PSD-95, we used semisynthetic strategies to introduce phosphorylated amino acids at four positions within the PDZ domains and examined the effects on interactions with a large set of binding partners. We observed complex effects on affinity. Most notably, phosphorylation at Y397 induced a significant increase in affinity for stargazin, as confirmed by NMR and single molecule FRET. Additionally, we compared the effects of phosphorylation to phosphomimetic mutations, which revealed that phosphomimetics are ineffective substitutes for tyrosine phosphorylation. Our strategy to generate site-specifically phosphorylated PDZ domains provides a detailed understanding of the role of phosphorylation in the regulation of PSD-95 interactions.

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

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.

A Review of Spectral Methods for Variable Amplitude Fatigue Prediction and New Results

NASA Technical Reports Server (NTRS)

Larsen, Curtis E.; Irvine, Tom

2013-01-01

A comprehensive review of the available methods for estimating fatigue damage from variable amplitude loading is presented. The dependence of fatigue damage accumulation on power spectral density (psd) is investigated for random processes relevant to real structures such as in offshore or aerospace applications. Beginning with the Rayleigh (or narrow band) approximation, attempts at improved approximations or corrections to the Rayleigh approximation are examined by comparison to rainflow analysis of time histories simulated from psd functions representative of simple theoretical and real world applications. Spectral methods investigated include corrections by Wirsching and Light, Ortiz and Chen, the Dirlik formula, and the Single-Moment method, among other more recent proposed methods. Good agreement is obtained between the spectral methods and the time-domain rainflow identification for most cases, with some limitations. Guidelines are given for using the several spectral methods to increase confidence in the damage estimate.

Evolution of complexity in the zebrafish synapse proteome

PubMed Central

Bayés, Àlex; Collins, Mark O.; Reig-Viader, Rita; Gou, Gemma; Goulding, David; Izquierdo, Abril; Choudhary, Jyoti S.; Emes, Richard D.; Grant, Seth G. N.

2017-01-01

The proteome of human brain synapses is highly complex and is mutated in over 130 diseases. This complexity arose from two whole-genome duplications early in the vertebrate lineage. Zebrafish are used in modelling human diseases; however, its synapse proteome is uncharacterized, and whether the teleost-specific genome duplication (TSGD) influenced complexity is unknown. We report the characterization of the proteomes and ultrastructure of central synapses in zebrafish and analyse the importance of the TSGD. While the TSGD increases overall synapse proteome complexity, the postsynaptic density (PSD) proteome of zebrafish has lower complexity than mammals. A highly conserved set of ∼1,000 proteins is shared across vertebrates. PSD ultrastructural features are also conserved. Lineage-specific proteome differences indicate that vertebrate species evolved distinct synapse types and functions. The data sets are a resource for a wide range of studies and have important implications for the use of zebrafish in modelling human synaptic diseases. PMID:28252024

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.

Absolute Power Spectral Density Changes in the Magnetoencephalographic Activity During the Transition from Childhood to Adulthood.

PubMed

Gómez, Carlos M; Rodríguez-Martínez, Elena I; Fernández, Alberto; Maestú, Fernando; Poza, Jesús; Gómez, Carlos

2017-01-01

The aim of this study was to define the pattern of reduction in absolute power spectral density (PSD) of magnetoencephalography (MEG) signals throughout development. Specifically, we wanted to explore whether the human skull's high permeability for electromagnetic fields would allow us to question whether the pattern of absolute PSD reduction observed in the human electroencephalogram is due to an increase in the skull's resistive properties with age. Furthermore, the topography of the MEG signals during maturation was explored, providing additional insights about the areas and brain rhythms related to late maturation in the human brain. To attain these goals, spontaneous MEG activity was recorded from 148 sensors in a sample of 59 subjects divided into three age groups: children/adolescents (7-14 years), young adults (17-20 years) and adults (21-26 years). Statistical testing was carried out by means of an analysis of variance (ANOVA), with "age group" as between-subject factor and "sensor group" as within-subject factor. Additionally, correlations of absolute PSD with age were computed to assess the influence of age on the spectral content of MEG signals. Results showed a broadband PSD decrease in frontal areas, which suggests the late maturation of this region, but also a mild increase in high frequency PSD with age in posterior areas. These findings suggest that the intensity of the neural sources during spontaneous brain activity decreases with age, which may be related to synaptic pruning.

Origin of low-frequency noise in pentacene field-effect transistors

NASA Astrophysics Data System (ADS)

Xu, Yong; Minari, Takeo; Tsukagoshi, Kazuhito; Chroboczek, Jan; Balestra, Francis; Ghibaudo, Gerard

2011-07-01

Measurements of power spectral density (PSD) of low-frequency noise (LFN) in pentacene field-effect transistors reveal the preponderance of a 1/ f-type PSD behavior with the amplitude varying as the squared transistor gain and increasing as the inverse of the gate surface area. Such features impose an interpretation of LFN by carrier number fluctuations model involving capture/release of charges on traps uniformly distributed over the gate surface. The surface slow trap density extracted by the noise analysis is close to the surface states density deduced independently from static I(V) data, which confirms the validity of the proposed LFN interpretation. Further, we found that the trap densities in bottom-contact (BC) devices were higher than in their top-contact (TC) counterparts, in agreement with observations of a poorer crystal structure of BC devices, in the contact regions in particular. At the highest bias the noise originating from the contact resistance is also shown to be a dominant component in the PSD, and it is well explained by the noise originating from a gate-voltage dependent contact resistance. A gate area scaling was also performed, and the good scaling and the dispersion at the highest bias confirm the validity of the applied carrier number fluctuations model and the predominant contact noise at high current intensities.

Amyloid beta protein-induced zinc sequestration leads to synaptic loss via dysregulation of the ProSAP2/Shank3 scaffold

PubMed Central

2011-01-01

Background Memory deficits in Alzheimer's disease (AD) manifest together with the loss of synapses caused by the disruption of the postsynaptic density (PSD), a network of scaffold proteins located in dendritic spines. However, the underlying molecular mechanisms remain elusive. Since it was shown that ProSAP2/Shank3 scaffold assembly within the PSD is Zn2+-dependent and that the amyloid beta protein (Aβ) is able to bind Zn2+, we hypothesize that sequestration of Zn2+ ions by Aβ contributes to ProSAP/Shank platform malformation. Results To test this hypothesis, we designed multiple in vitro and in vivo assays demonstrating ProSAP/Shank dysregulation in rat hippocampal cultures following Aβ oligomer accumulation. These changes were independent from alterations on ProSAP/Shank transcriptional level. However, application of soluble Aβ prevented association of Zn2+ ions with ProSAP2/Shank3 in a cell-based assay and decreased the concentration of Zn2+ clusters within dendrites. Zn2+ supplementation or saturation of Aβ with Zn2+ ions prior to cell treatment was able to counter the effects induced by Aβ on synapse density and ProSAP2/Shank3 levels at the PSD. Interestingly, intracellular Zn2+ levels in APP-PS1 mice and human AD hippocampus are reduced along with a reduction in synapse density and synaptic ProSAP2/Shank3 and Shank1 protein levels. Conclusions We conclude that sequestration of Zn2+ ions by Aβ significantly contributes to changes in ProSAP2/Shank3 platforms. These changes in turn lead to less consolidated (mature) synapses reflected by a decrease in Shank1 protein levels at the PSD and decreased synapse density in hippocampal neurons. PMID:21939532

Enhanced Characterization of Niobium Surface Topography

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

Chen Xu, Hui Tian, Charles Reece, Michael Kelley

2011-12-01

Surface topography characterization is a continuing issue for the Superconducting Radio Frequency (SRF) particle accelerator community. Efforts are underway to both to improve surface topography, and its characterization and analysis using various techniques. In measurement of topography, Power Spectral Density (PSD) is a promising method to quantify typical surface parameters and develop scale-specific interpretations. PSD can also be used to indicate how chemical processes modifiesy the roughnesstopography at different scales. However, generating an accurate and meaningful topographic PSD of an SRF surface requires careful analysis and optimization. In this report, polycrystalline surfaces with different process histories are sampled with AFMmore » and stylus/white light interferometer profilometryers and analyzed to indicate trace topography evolution at different scales. evolving during etching or polishing. Moreover, Aan optimized PSD analysis protocol will be offered to serve the SRF surface characterization needs is presented.« less

A Search for Quasi-periodic Oscillations in the Blazar 1ES 1959+650

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

Li, Xiao-Pan; Luo, Yu-Hui; Yang, Hai-Yan

We have searched quasi-periodic oscillations (QPOs) in the 15 GHz light curve of the BL Lac object 1ES 1959+650 monitored by the Owens Valley Radio Observatory 40 m telescope during the period from 2008 January to 2016 February, using the Lomb–Scargle Periodogram, power spectral density (PSD), discrete autocorrelation function, and phase dispersion minimization (PDM) techniques. The red noise background has been established via the PSD method, and no QPO can be derived at the 3 σ confidence level accounting for the impact of the red noise variability. We conclude that the light curve of 1ES 1959+650 can be explained bymore » a stochastic red noise process that contributes greatly to the total observed variability amplitude, dominates the power spectrum, causes spurious bumps and wiggles in the autocorrelation function and can result in the variance of the folded light curve decreasing toward lower temporal frequencies when few-cycle, sinusoid-like patterns are present. Moreover, many early supposed periodicity claims for blazar light curves need to be reevaluated assuming red noise.« less

Using Elman recurrent neural networks with conjugate gradient algorithm in determining the anesthetic the amount of anesthetic medicine to be applied.

PubMed

Güntürkün, Rüştü

2010-08-01

In this study, Elman recurrent neural networks have been defined by using conjugate gradient algorithm in order to determine the depth of anesthesia in the continuation stage of the anesthesia and to estimate the amount of medicine to be applied at that moment. The feed forward neural networks are also used for comparison. The conjugate gradient algorithm is compared with back propagation (BP) for training of the neural Networks. The applied artificial neural network is composed of three layers, namely the input layer, the hidden layer and the output layer. The nonlinear activation function sigmoid (sigmoid function) has been used in the hidden layer and the output layer. EEG data has been recorded with Nihon Kohden 9200 brand 22-channel EEG device. The international 8-channel bipolar 10-20 montage system (8 TB-b system) has been used in assembling the recording electrodes. EEG data have been recorded by being sampled once in every 2 milliseconds. The artificial neural network has been designed so as to have 60 neurons in the input layer, 30 neurons in the hidden layer and 1 neuron in the output layer. The values of the power spectral density (PSD) of 10-second EEG segments which correspond to the 1-50 Hz frequency range; the ratio of the total power of PSD values of the EEG segment at that moment in the same range to the total of PSD values of EEG segment taken prior to the anesthesia.

A New Statistical Model of Electroencephalogram Noise Spectra for Real-Time Brain-Computer Interfaces.

PubMed

Paris, Alan; Atia, George K; Vosoughi, Azadeh; Berman, Stephen A

2017-08-01

A characteristic of neurological signal processing is high levels of noise from subcellular ion channels up to whole-brain processes. In this paper, we propose a new model of electroencephalogram (EEG) background periodograms, based on a family of functions which we call generalized van der Ziel-McWhorter (GVZM) power spectral densities (PSDs). To the best of our knowledge, the GVZM PSD function is the only EEG noise model that has relatively few parameters, matches recorded EEG PSD's with high accuracy from 0 to over 30 Hz, and has approximately 1/f θ behavior in the midfrequencies without infinities. We validate this model using three approaches. First, we show how GVZM PSDs can arise in a population of ion channels at maximum entropy equilibrium. Second, we present a class of mixed autoregressive models, which simulate brain background noise and whose periodograms are asymptotic to the GVZM PSD. Third, we present two real-time estimation algorithms for steady-state visual evoked potential (SSVEP) frequencies, and analyze their performance statistically. In pairwise comparisons, the GVZM-based algorithms showed statistically significant accuracy improvement over two well-known and widely used SSVEP estimators. The GVZM noise model can be a useful and reliable technique for EEG signal processing. Understanding EEG noise is essential for EEG-based neurology and applications such as real-time brain-computer interfaces, which must make accurate control decisions from very short data epochs. The GVZM approach represents a successful new paradigm for understanding and managing this neurological noise.

Computational nanometrology of line-edge roughness: noise effects, cross-line correlations and the role of etch transfer

NASA Astrophysics Data System (ADS)

Constantoudis, Vassilios; Papavieros, George; Lorusso, Gian; Rutigliani, Vito; Van Roey, Frieda; Gogolides, Evangelos

2018-03-01

The aim of this paper is to investigate the role of etch transfer in two challenges of LER metrology raised by recent evolutions in lithography: the effects of SEM noise and the cross-line and edge correlations. The first comes from the ongoing scaling down of linewidths, which dictates SEM imaging with less scanning frames to reduce specimen damage and hence with more noise. During the last decade, it has been shown that image noise can be an important budget of the measured LER while systematically affects and alter the PSD curve of LER at high frequencies. A recent method for unbiased LER measurement is based on the systematic Fourier or correlation analysis to decompose the effects of noise from true LER (Fourier-Correlation filtering method). The success of the method depends on the PSD and HHCF curve. Previous experimental and model works have revealed that etch transfer affects the PSD of LER reducing its high frequency values. In this work, we estimate the noise contribution to the biased LER through PSD flat floor at high frequencies and relate it with the differences between the PSDs of lithography and etched LER. Based on this comparison, we propose an improvement of the PSD/HHCF-based method for noise-free LER measurement to include the missed high frequency real LER. The second issue is related with the increased density of lithographic patterns and the special characteristics of DSA and MP lithography patterns exhibits. In a previous work, we presented an enlarged LER characterization methodology for such patterns, which includes updated versions of the old metrics along with new metrics defined and developed to capture cross-edge and cross-line correlations. The fundamental concept has been the Line Center Roughness (LCR), the edge c-factor and the line c-factor correlation function and length quantifying the line fluctuations and the extent of cross-edge and cross-line correlations. In this work, we focus on the role of etch steps on cross-edge and line correlation metrics in SAQP data. We find that the spacer etch steps reduce edge correlations while etch steps with pattern transfer increase these. Furthermore, the density doubling and quadrupling increase edge correlations as well as cross-line correlations.

An investigation of the 'Overlap' between the Statistical-Discrete-Gust and the Power-Spectral-Density analysis methods

NASA Technical Reports Server (NTRS)

Perry, Boyd, III; Pototzky, Anthony S.; Woods, Jessica A.

1989-01-01

This paper presents the results of a NASA investigation of a claimed 'Overlap' between two gust response analysis methods: the Statistical Discrete Gust (SDG) method and the Power Spectral Density (PSD) method. The claim is that the ratio of an SDG response to the corresponding PSD response is 10.4. Analytical results presented in this paper for several different airplanes at several different flight conditions indicate that such an 'Overlap' does appear to exist. However, the claim was not met precisely: a scatter of up to about 10 percent about the 10.4 factor can be expected.

A Comparison of PSD Enveloping Methods for Nonstationary Vibration

NASA Technical Reports Server (NTRS)

Irvine, Tom

2015-01-01

There is a need to derive a power spectral density (PSD) envelope for nonstationary acceleration time histories, including launch vehicle data, so that components can be designed and tested accordingly. This paper presents the results of the three methods for an actual flight accelerometer record. Guidelines are given for the application of each method to nonstationary data. The method can be extended to other scenarios, including transportation vibration.

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.

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

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.

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

Spectral Study of Measles Epidemics: The Dependence of Spectral Gradient on the Population Size of the Community

NASA Astrophysics Data System (ADS)

Sumi, Ayako; Olsen, Lars Folke; Ohtomo, Norio; Tanaka, Yukio; Sawamura, Sadashi

2003-02-01

We have carried out spectral analysis of measles notifications in several communities in Denmark, UK and USA. The results confirm that each power spectral density (PSD) shows exponential characteristics, which are universally observed in the PSD for time series generated from nonlinear dynamical system. The exponential gradient increases with the population size. For almost all communities, many spectral lines observed in each PSD can be fully assigned to linear combinations of several fundamental periods, suggesting that the measles data are substantially noise-free. The optimum least squares fitting curve calculated using these fundamental periods essentially reproduces an underlying variation of the measles data, and an extension of the curve can be used to predict measles epidemics. For the communities with large population sizes, some PSD patterns obtained from segment time series analysis show a close resemblance to the PSD patterns at the initial stages of a period-doubling bifurcation process for the so-called susceptible/exposed/infectious/recovered (SEIR) model with seasonal forcing. The meaning of the relationship between the exponential gradient and the population size is discussed.

Age-Associated Changes in the Spectral and Statistical Parameters of Surface Electromyogram of Tibialis Anterior.

PubMed

Siddiqi, Ariba; Arjunan, Sridhar Poosapadi; Kumar, Dinesh Kant

2016-01-01

Age-related neuromuscular change of Tibialis Anterior (TA) is a leading cause of muscle strength decline among the elderly. This study has established the baseline for age-associated changes in sEMG of TA at different levels of voluntary contraction. We have investigated the use of Gaussianity and maximal power of the power spectral density (PSD) as suitable features to identify age-associated changes in the surface electromyogram (sEMG). Eighteen younger (20-30 years) and 18 older (60-85 years) cohorts completed two trials of isometric dorsiflexion at four different force levels between 10% and 50% of the maximal voluntary contraction. Gaussianity and maximal power of the PSD of sEMG were determined. Results show a significant increase in sEMG's maximal power of the PSD and Gaussianity with increase in force for both cohorts. It was also observed that older cohorts had higher maximal power of the PSD and lower Gaussianity. These age-related differences observed in the PSD and Gaussianity could be due to motor unit remodelling. This can be useful for noninvasive tracking of age-associated neuromuscular changes.

Power-law statistics of neurophysiological processes analyzed using short signals

NASA Astrophysics Data System (ADS)

Pavlova, Olga N.; Runnova, Anastasiya E.; Pavlov, Alexey N.

2018-04-01

We discuss the problem of quantifying power-law statistics of complex processes from short signals. Based on the analysis of electroencephalograms (EEG) we compare three interrelated approaches which enable characterization of the power spectral density (PSD) and show that an application of the detrended fluctuation analysis (DFA) or the wavelet-transform modulus maxima (WTMM) method represents a useful way of indirect characterization of the PSD features from short data sets. We conclude that despite DFA- and WTMM-based measures can be obtained from the estimated PSD, these tools outperform the standard spectral analysis when characterization of the analyzed regime should be provided based on a very limited amount of data.

Cdk5-dependent phosphorylation of liprinα1 mediates neuronal activity-dependent synapse development

PubMed Central

Huang, Huiqian; Lin, Xiaochen; Liang, Zhuoyi; Zhao, Teng; Du, Shengwang; Loy, Michael M. T.; Lai, Kwok-On; Fu, Amy K. Y.

2017-01-01

The experience-dependent modulation of brain circuitry depends on dynamic changes in synaptic connections that are guided by neuronal activity. In particular, postsynaptic maturation requires changes in dendritic spine morphology, the targeting of postsynaptic proteins, and the insertion of synaptic neurotransmitter receptors. Thus, it is critical to understand how neuronal activity controls postsynaptic maturation. Here we report that the scaffold protein liprinα1 and its phosphorylation by cyclin-dependent kinase 5 (Cdk5) are critical for the maturation of excitatory synapses through regulation of the synaptic localization of the major postsynaptic organizer postsynaptic density (PSD)-95. Whereas Cdk5 phosphorylates liprinα1 at Thr701, this phosphorylation decreases in neurons in response to neuronal activity. Blockade of liprinα1 phosphorylation enhances the structural and functional maturation of excitatory synapses. Nanoscale superresolution imaging reveals that inhibition of liprinα1 phosphorylation increases the colocalization of liprinα1 with PSD-95. Furthermore, disruption of liprinα1 phosphorylation by a small interfering peptide, siLIP, promotes the synaptic localization of PSD-95 and enhances synaptic strength in vivo. Our findings collectively demonstrate that the Cdk5-dependent phosphorylation of liprinα1 is important for the postsynaptic organization during activity-dependent synapse development. PMID:28760951

Standard deviation of the mean and other time series properties of voltages measured with a digital lock-in amplifier

NASA Astrophysics Data System (ADS)

Witt, Thomas J.; Fletcher, N. E.

2010-10-01

We investigate some statistical properties of ac voltages from a white noise source measured with a digital lock-in amplifier equipped with finite impulse response output filters which introduce correlations between successive voltage values. The main goal of this work is to propose simple solutions to account for correlations when calculating the standard deviation of the mean (SDM) for a sequence of measurement data acquired using such an instrument. The problem is treated by time series analysis based on a moving average model of the filtering process. Theoretical expressions are derived for the power spectral density (PSD), the autocorrelation function, the equivalent noise bandwidth and the Allan variance; all are related to the SDM. At most three parameters suffice to specify any of the above quantities: the filter time constant, the time between successive measurements (both set by the lock-in operator) and the PSD of the white noise input, h0. Our white noise source is a resistor so that the PSD is easily calculated; there are no free parameters. Theoretical expressions are checked against their respective sample estimates and, with the exception of two of the bandwidth estimates, agreement to within 11% or better is found.

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

An investigation of wing buffeting response at subsonic and transonic speeds. Phase 2: F-111A flight data analysis. Volume 3: Tabulated power spectra

NASA Technical Reports Server (NTRS)

Benepe, D. B.; Cunningham, A. M., Jr.; Traylor, S., Jr.; Dunmyer, W. D.

1978-01-01

Power spectral density (PSD) data for all of the flight points examined during the Phase 2 flight data analysis are presented in tabular form. Detailed descriptions of the aircraft, the flight instrumentation and the analysis techniques are given. Measured and calculated vibration mode frequencies are also presented to assist in further interpretation of the PSD data.

A Software Toolbox for Systematic Evaluation of Seismometer-Digitizer System Responses

DTIC Science & Technology

2010-09-01

characteristics (e.g., borehole vs. surface installation) than the actual seismic noise characteristics. These results suggest that our best results of NOISETRAN...Award No. DE-FG02-09ER85548/Phase_I ABSTRACT Measurement of the absolute amplitudes of a seismic signal requires accurate knowledge of...power spectral density (PSD) estimator for background noise spectra at a seismic station. SACPSD differs from the current PSD used by NEIC and IRIS

In-Flight Vibration Environment of the NASA F-15B Flight Test Fixture

NASA Technical Reports Server (NTRS)

Corda, Stephen; Franz, Russell J.; Blanton, James N.; Vachon, M. Jake; DeBoer, James B.

2002-01-01

Flight vibration data are analyzed for the NASA F-15B/Flight Test Fixture II test bed. Understanding the in-flight vibration environment benefits design and integration of experiments on the test bed. The power spectral density (PSD) of accelerometer flight data is analyzed to quantify the in-flight vibration environment from a frequency of 15 Hz to 1325 Hz. These accelerometer data are analyzed for typical flight conditions and maneuvers. The vibration data are compared to flight-qualification random vibration test standards. The PSD levels in the lateral axis generally are greater than in the longitudinal and vertical axes and decrease with increasing frequency. At frequencies less than approximately 40 Hz, the highest PSD levels occur during takeoff and landing. Peaks in the PSD data for the test fixture occur at approximately 65, 85, 105-110, 200, 500, and 1000 Hz. The pitch-pulse and 2-g turn maneuvers produce PSD peaks at 115 Hz. For cruise conditions, the PSD level of the 85-Hz peak is greatest for transonic flight at Mach 0.9. From 400 Hz to 1325 Hz, the takeoff phase has the highest random vibration levels. The flight-measured vibration levels generally are substantially lower than the random vibration test curve.

Increased Excitatory Synaptic Transmission of Dentate Granule Neurons in Mice Lacking PSD-95-Interacting Adhesion Molecule Neph2/Kirrel3 during the Early Postnatal Period.

PubMed

Roh, Junyeop D; Choi, Su-Yeon; Cho, Yi Sul; Choi, Tae-Yong; Park, Jong-Sil; Cutforth, Tyler; Chung, Woosuk; Park, Hanwool; Lee, Dongsoo; Kim, Myeong-Heui; Lee, Yeunkum; Mo, Seojung; Rhee, Jeong-Seop; Kim, Hyun; Ko, Jaewon; Choi, Se-Young; Bae, Yong Chul; Shen, Kang; Kim, Eunjoon; Han, Kihoon

2017-01-01

Copy number variants and point mutations of NEPH2 (also called KIRREL3 ) gene encoding an immunoglobulin (Ig) superfamily adhesion molecule have been linked to autism spectrum disorders, intellectual disability and neurocognitive delay associated with Jacobsen syndrome, but the physiological roles of Neph2 in the mammalian brain remain largely unknown. Neph2 is highly expressed in the dentate granule (DG) neurons of the hippocampus and is localized in both dendrites and axons. It was recently shown that Neph2 is required for the formation of mossy fiber filopodia, the axon terminal structure of DG neurons forming synapses with GABAergic neurons of CA3. In contrast, however, it is unknown whether Neph2 also has any roles in the postsynaptic compartments of DG neurons. We here report that, through its C-terminal PDZ domain-binding motif, Neph2 directly interacts with postsynaptic density (PSD)-95, an abundant excitatory postsynaptic scaffolding protein. Moreover, Neph2 protein is detected in the brain PSD fraction and interacts with PSD-95 in synaptosomal lysates. Functionally, loss of Neph2 in mice leads to age-specific defects in the synaptic connectivity of DG neurons. Specifically, Neph2 -/- mice show significantly increased spontaneous excitatory synaptic events in DG neurons at postnatal week 2 when the endogenous Neph2 protein expression peaks, but show normal excitatory synaptic transmission at postnatal week 3. The evoked excitatory synaptic transmission and synaptic plasticity of medial perforant pathway (MPP)-DG synapses are also normal in Neph2 -/- mice at postnatal week 3, further confirming the age-specific synaptic defects. Together, our results provide some evidence for the postsynaptic function of Neph2 in DG neurons during the early postnatal period, which might be implicated in neurodevelopmental and cognitive disorders caused by NEPH2 mutations.

Population-Specific Haplotype Association of the Postsynaptic Density Gene DLG4 with Schizophrenia, in Family-Based Association Studies

PubMed Central

Balan, Shabeesh; Yamada, Kazuo; Hattori, Eiji; Iwayama, Yoshimi; Toyota, Tomoko; Ohnishi, Tetsuo; Maekawa, Motoko; Toyoshima, Manabu; Iwata, Yasuhide; Suzuki, Katsuaki; Kikuchi, Mitsuru; Yoshikawa, Takeo

2013-01-01

The post-synaptic density (PSD) of glutamatergic synapses harbors a multitude of proteins critical for maintaining synaptic dynamics. Alteration of protein expression levels in this matrix is a marked phenomenon of neuropsychiatric disorders including schizophrenia, where cognitive functions are impaired. To investigate the genetic relationship of genes expressed in the PSD with schizophrenia, a family-based association analysis of genetic variants in PSD genes such as DLG4, DLG1, PICK1 and MDM2, was performed, using Japanese samples (124 pedigrees, n = 376 subjects). Results showed a significant association of the rs17203281 variant from the DLG4 gene, with preferential transmission of the C allele (p = 0.02), although significance disappeared after correction for multiple testing. Replication analysis of this variant, found no association in a Chinese schizophrenia cohort (293 pedigrees, n = 1163 subjects) or in a Japanese case-control sample (n = 4182 subjects). The DLG4 expression levels between postmortem brain samples from schizophrenia patients showed no significant changes from controls. Interestingly, a five marker haplotype in DLG4, involving rs2242449, rs17203281, rs390200, rs222853 and rs222837, was enriched in a population specific manner, where the sequences A-C-C-C-A and G-C-C-C-A accumulated in Japanese (p = 0.0009) and Chinese (p = 0.0007) schizophrenia pedigree samples, respectively. However, this could not be replicated in case-control samples. None of the variants in other examined candidate genes showed any significant association in these samples. The current study highlights a putative role for DLG4 in schizophrenia pathogenesis, evidenced by haplotype association, and warrants further dense screening for variants within these haplotypes. PMID:23936182

Comparison of oscillations of skin blood flow and deoxygenation in vastus lateralis in light exercise.

PubMed

Yano, T; Lian, C-S; Afroundeh, R; Shirakawa, K; Yunoki, T

2014-03-01

The purpose of the present study was to compare oscillation of skin blood flow with that of deoxygenation in muscle during light exercise in order to determine the physiological significance of oscillations in deoxygenation. Prolonged exercise with 50% of peak oxygen uptake was performed for 60 min. Skin blood flow (SBF) was measured using a laser blood flow meter on the right vastus lateralis muscle. Deoxygenated haemoglobin/myoglobin (DHb/Mb) concentration in the left vastus lateralis were measured using a near-infrared spectroscopy system. SBF and DHb/Mb during exercise were analysed by fast Fourier transform. We classified frequency bands according to previous studies (Kvernmo et al. 1999, Kvandal et al. 2006) into phase I (0.005-0.0095 and 0.0095-0.02 Hz), phase II (0.02-0.06 Hz: phase II) and phase III (0.06-0.16 Hz). The first peak of power spectra density (PSD) in SBF appeared at 0.0078 Hz in phase I. The second peak of PSD in SBF appeared at 0.035 Hz. The third peak of PSD in SBF appeared at 0.078 Hz. The first peak of PSD in DHb/Mb appeared at 0.0039 Hz, which was out of phase I. The second peak of PSD in DHb/Mb appeared at 0.016 Hz. The third peak of PSD in DHb/Mb appeared at 0.035 Hz. The coefficient of cross correlation was very low. Cross power spectra density showed peaks of 0.0039, 0.016 and 0.035 Hz. It is concluded that a peak of 0.016 Hz in oscillations of DHb/Mb observed in muscle during exercise is associated with endothelium-dependent vasodilation (phase I) and that a peak of 0.035 Hz in DHb/Mb is associated with sympathetic nerve activity (phase II). It is also confirmed that each peak of SBF oscillations is observed in each phase.

Spectral density measurements of gyro noise

NASA Technical Reports Server (NTRS)

Truncale, A.; Koenigsberg, W.; Harris, R.

1972-01-01

Power spectral density (PSD) was used to analyze the outputs of several gyros in the frequency range from 0.01 to 200 Hz. Data were accumulated on eight inertial quality instruments. The results are described in terms of input angle noise (arcsec 2/Hz) and are presented on log-log plots of PSD. These data show that the standard deviation of measurement noise was 0.01 arcsec or less for some gyros in the passband from 1 Hz down 10 0.01 Hz and probably down to 0.001 Hz for at least one gyro. For the passband between 1 and 100 Hz, uncertainties in the 0.01 and 0.05 arcsec region were observed.

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

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.

Differentiation and Characterization of Excitatory and Inhibitory Synapses by Cryo-electron Tomography and Correlative Microscopy.

PubMed

Tao, Chang-Lu; Liu, Yun-Tao; Sun, Rong; Zhang, Bin; Qi, Lei; Shivakoti, Sakar; Tian, Chong-Li; Zhang, Peijun; Lau, Pak-Ming; Zhou, Z Hong; Bi, Guo-Qiang

2018-02-07

As key functional units in neural circuits, different types of neuronal synapses play distinct roles in brain information processing, learning, and memory. Synaptic abnormalities are believed to underlie various neurological and psychiatric disorders. Here, by combining cryo-electron tomography and cryo-correlative light and electron microscopy, we distinguished intact excitatory and inhibitory synapses of cultured hippocampal neurons, and visualized the in situ 3D organization of synaptic organelles and macromolecules in their native state. Quantitative analyses of >100 synaptic tomograms reveal that excitatory synapses contain a mesh-like postsynaptic density (PSD) with thickness ranging from 20 to 50 nm. In contrast, the PSD in inhibitory synapses assumes a thin sheet-like structure ∼12 nm from the postsynaptic membrane. On the presynaptic side, spherical synaptic vesicles (SVs) of 25-60 nm diameter and discus-shaped ellipsoidal SVs of various sizes coexist in both synaptic types, with more ellipsoidal ones in inhibitory synapses. High-resolution tomograms obtained using a Volta phase plate and electron filtering and counting reveal glutamate receptor-like and GABA A receptor-like structures that interact with putative scaffolding and adhesion molecules, reflecting details of receptor anchoring and PSD organization. These results provide an updated view of the ultrastructure of excitatory and inhibitory synapses, and demonstrate the potential of our approach to gain insight into the organizational principles of cellular architecture underlying distinct synaptic functions. SIGNIFICANCE STATEMENT To understand functional properties of neuronal synapses, it is desirable to analyze their structure at molecular resolution. We have developed an integrative approach combining cryo-electron tomography and correlative fluorescence microscopy to visualize 3D ultrastructural features of intact excitatory and inhibitory synapses in their native state. Our approach shows that inhibitory synapses contain uniform thin sheet-like postsynaptic densities (PSDs), while excitatory synapses contain previously known mesh-like PSDs. We discovered "discus-shaped" ellipsoidal synaptic vesicles, and their distributions along with regular spherical vesicles in synaptic types are characterized. High-resolution tomograms further allowed identification of putative neurotransmitter receptors and their heterogeneous interaction with synaptic scaffolding proteins. The specificity and resolution of our approach enables precise in situ analysis of ultrastructural organization underlying distinct synaptic functions. Copyright © 2018 Tao, Liu et al.

Comparison of Fatigue Life Estimation Using Equivalent Linearization and Time Domain Simulation Methods

NASA Technical Reports Server (NTRS)

Mei, Chuh; Dhainaut, Jean-Michel

2000-01-01

The Monte Carlo simulation method in conjunction with the finite element large deflection modal formulation are used to estimate fatigue life of aircraft panels subjected to stationary Gaussian band-limited white-noise excitations. Ten loading cases varying from 106 dB to 160 dB OASPL with bandwidth 1024 Hz are considered. For each load case, response statistics are obtained from an ensemble of 10 response time histories. The finite element nonlinear modal procedure yields time histories, probability density functions (PDF), power spectral densities and higher statistical moments of the maximum deflection and stress/strain. The method of moments of PSD with Dirlik's approach is employed to estimate the panel fatigue life.

Spatial and temporal variation in proportional stock density and relative weight of smallmouth bass in a reservoir

USGS Publications Warehouse

Mesa, Matthew G.; Duke, S.D.; Ward, David L.

1990-01-01

Population data for smallmouth bass Micropterus dolomieui in 20,235 ha John Day Reservoir on the Columbia River were used to (1) determine whether Proportional Stock Density (PSD) and Relative Weight (Wr) varied spatially and temporally in two areas of the reservoir with established smallmouth bass fisheries; (2) explore possible causes of any observed variation; and (3) discuss some management implications and recommendations. Both PSD and Wr varied spatially and monthly in all years examined. On an annual basis, PSD varied at one area but not at the other, whereas Wr showed little variation. Possible explanations for the variation in PSD and Wr are differences in growth, mortality, recruitment, and exploitation. Our data suggested that regulations established or changed on a reservoir-wide basis may have different effects on the fishery, depending on location in the reservoir. Also, pooling data from various areas within a reservoir to yield point estimates of structural indices may not represent the variation present in the population as a whole. The significant temporal variability reflects the importance of determining the proper time to sample fish to yield representative estimates of the variable of interest. In areas with valuable fisheries or markedly different population structures, we suggest that an area-specific approach be made to reservoir fishery management, and that efforts be made toward effecting consistent harvest regulations in interstate waters.

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.

The evolution of the disc variability along the hard state of the black hole transient GX 339-4

NASA Astrophysics Data System (ADS)

De Marco, B.; Ponti, G.; Muñoz-Darias, T.; Nandra, K.

2015-12-01

We report on the analysis of hard-state power spectral density function (PSD) of GX 339-4 down to the soft X-ray band, where the disc significantly contributes to the total emission. At any luminosity probed, the disc in the hard state is intrinsically more variable than in the soft state. However, the fast decrease of disc variability as a function of luminosity, combined with the increase of disc intensity, causes a net drop of fractional variability at high luminosities and low energies, which reminds the well-known behaviour of disc-dominated energy bands in the soft state. The peak frequency of the high-frequency Lorentzian (likely corresponding to the high-frequency break seen in active galactic nuclei, AGN) scales with luminosity, but we do not find evidence for a linear scaling. In addition, we observe that this characteristic frequency is energy dependent. We find that the normalization of the PSD at the peak of the high-frequency Lorentzian decreases with luminosity at all energies, though in the soft band this trend is steeper. Together with the frequency shift, this yields quasi-constant high-frequency (5-20 Hz) fractional rms at high energies, with less than 10 per cent scatter. This reinforces previous claims suggesting that the high-frequency PSD solely scales with black hole mass. On the other hand, this constancy breaks down in the soft band (where the scatter increases to ˜30 per cent). This is a consequence of the additional contribution from the disc component, and resembles the behaviour of optical variability in AGN.

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.

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.

Dysregulated post-synaptic density and endocytic zone in the amygdala of human heroin and cocaine abusers

PubMed Central

Ökvist, Anna; Fagergren, Pernilla; Whittard, John; Garcia-Osta, Ana; Drakenberg, Katarina; Horvath, Monika Cs.; Schmidt, Carl J.; Keller, Eva; Bannon, Michael J.; Hurd, Yasmin L.

2010-01-01

Background Glutamatergic transmission in the amygdala is hypothesized as an important mediator of stimulus-reward associations contributing to drug-seeking behavior and relapse. Insight is, however, lacking regarding the amygdala glutamatergic system in human drug abusers. Methods We examined glutamate receptors and scaffolding proteins associated with the post-synaptic density (PSD) of excitatory synapses in the human post-mortem amygdala. mRNA or protein levels were studied in a multi-drug (7 heroin, 8 cocaine, 7 heroin/cocaine and 7 control) or predominant heroin (29 heroin and 15 control) population of subjects. Results The amygdala of drug abusers was characterized by a striking positive correlation (r > 0.8) between AMPA GluA1 and post-synaptic protein-95 (PSD-95) mRNA levels, which was not evident in controls. Structural equation multi-group analysis of protein correlations also identified the relationship between GluA1 and PSD-95 protein levels as the distinguishing feature of abusers. In line with the GluA1—PSD-95 implications of enhanced synaptic plasticity, Homer 1b/c protein expression was significantly increased in both heroin and cocaine users as was its binding partner dynamin-3, localized to the endocytic zone. Furthermore, there was a positive relationship between Homer 1b/c and dynamin-3 in drug abusers that reflected an increase in the direct physical coupling between the proteins. A noted age-related decline of Homer 1b/c—dynamin-3 interactions, as well as GluA1 levels, was blunted in abusers. Conclusions Impairment of key components of the amygdala PSD and coupling to the endocytic zone, critical for the regulation of glutamate receptor cycling, may underlie heightened synaptic plasticity in human drug abusers. PMID:21126734

Disrupting nNOS-PSD-95 coupling in the hippocampal dentate gyrus promotes extinction memory retrieval.

PubMed

Li, Jun; Han, Zhou; Cao, Bo; Cai, Cheng-Yun; Lin, Yu-Hui; Li, Fei; Wu, Hai-Ying; Chang, Lei; Luo, Chun-Xia; Zhu, Dong-Ya

2017-11-04

Granule cells in the dentate gyrus regenerate constantly in adult hippocampus and then integrate into neural circuits in the hippocampus thereby providing the neural basis for learning and memory. Promoting the neurogenesis in the hippocampus facilitates learning and memory such as spatial learning, object identification, and extinction learning. The interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein-95 (PSD-95) is reported to negatively regulate neurogenesis in brain, so we hypothesized that disrupting this interaction might facilitate the neurogenesis in the dentate gyrus (DG) and thus enhance the extinction memory retrieval of fear learning. We found that uncoupling the nNOS-PSD-95 complex in remote contextual fear condition promoted both neuronal proliferation and survival in the DG, contributing to an enhanced retrieval of the extinction memory. Moreover, the nNOS-PSD-95 uncoupling-induced neurogenesis may be mediated by the extracellular signal-regulated kinase (ERK) as the phosphorylation level of ERK1/2 was increased after uncoupling. These findings suggest that the nNOS-PSD-95 complex may serve as a novel target for the treatment of post-traumatic stress disorder (PTSD). Copyright © 2017 Elsevier Inc. All rights reserved.

Age-Associated Changes in the Spectral and Statistical Parameters of Surface Electromyogram of Tibialis Anterior

PubMed Central

2016-01-01

Age-related neuromuscular change of Tibialis Anterior (TA) is a leading cause of muscle strength decline among the elderly. This study has established the baseline for age-associated changes in sEMG of TA at different levels of voluntary contraction. We have investigated the use of Gaussianity and maximal power of the power spectral density (PSD) as suitable features to identify age-associated changes in the surface electromyogram (sEMG). Eighteen younger (20–30 years) and 18 older (60–85 years) cohorts completed two trials of isometric dorsiflexion at four different force levels between 10% and 50% of the maximal voluntary contraction. Gaussianity and maximal power of the PSD of sEMG were determined. Results show a significant increase in sEMG's maximal power of the PSD and Gaussianity with increase in force for both cohorts. It was also observed that older cohorts had higher maximal power of the PSD and lower Gaussianity. These age-related differences observed in the PSD and Gaussianity could be due to motor unit remodelling. This can be useful for noninvasive tracking of age-associated neuromuscular changes. PMID:27610379

PDZ Ligand Binding-Induced Conformational Coupling of the PDZ-SH3-GK Tandems in PSD-95 Family MAGUKs.

PubMed

Zeng, Menglong; Ye, Fei; Xu, Jia; Zhang, Mingjie

2018-01-05

Discs large (DLG) MAGUKs are abundantly expressed in glutamatergic synapses, crucial for synaptic transmission, and plasticity by anchoring various postsynaptic components including glutamate receptors, downstream scaffold proteins and signaling enzymes. Different DLG members have shared structures and functions, but also contain unique features. How DLG family proteins function individually and cooperatively is largely unknown. Here, we report that PSD-95 PDZ3 directly couples with SH3-GK tandem in a PDZ ligand binding-dependent manner, and the coupling can promote PSD-95 dimerization and multimerization. Aided by sortase-mediated protein ligation and selectively labeling, we elucidated the PDZ3/SH3-GK conformational coupling mechanism using NMR spectroscopy. We further demonstrated that PSD-93, but not SAP102, can also undergo PDZ3 ligand binding-induced conformational coupling with SH3-GK and form homo-oligomers. Interestingly, PSD-95 and PSD-93 can also form ligand binding-induced hetero-oligomers, suggesting a cooperative assembly mechanism for the mega-N-methyl-d-aspartate receptor synaptic signaling complex. Finally, we provide evidence showing that ligand binding-induced conformational coupling between PDZ and SH3-GK is a common feature for other MAGUKs including CASK and PALS1. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Characterization and extraction of the synaptic apposition surface for synaptic geometry analysis

PubMed Central

Morales, Juan; Rodríguez, Angel; Rodríguez, José-Rodrigo; DeFelipe, Javier; Merchán-Pérez, Angel

2013-01-01

Geometrical features of chemical synapses are relevant to their function. Two critical components of the synaptic junction are the active zone (AZ) and the postsynaptic density (PSD), as they are related to the probability of synaptic release and the number of postsynaptic receptors, respectively. Morphological studies of these structures are greatly facilitated by the use of recent electron microscopy techniques, such as combined focused ion beam milling and scanning electron microscopy (FIB/SEM), and software tools that permit reconstruction of large numbers of synapses in three dimensions. Since the AZ and the PSD are in close apposition and have a similar surface area, they can be represented by a single surface—the synaptic apposition surface (SAS). We have developed an efficient computational technique to automatically extract this surface from synaptic junctions that have previously been three-dimensionally reconstructed from actual tissue samples imaged by automated FIB/SEM. Given its relationship with the release probability and the number of postsynaptic receptors, the surface area of the SAS is a functionally relevant measure of the size of a synapse that can complement other geometrical features like the volume of the reconstructed synaptic junction, the equivalent ellipsoid size and the Feret's diameter. PMID:23847474

Real-time particle size analysis using focused beam reflectance measurement as a process analytical technology tool for a continuous granulation-drying-milling process.

PubMed

Kumar, Vijay; Taylor, Michael K; Mehrotra, Amit; Stagner, William C

2013-06-01

Focused beam reflectance measurement (FBRM) was used as a process analytical technology tool to perform inline real-time particle size analysis of a proprietary granulation manufactured using a continuous twin-screw granulation-drying-milling process. A significant relationship between D20, D50, and D80 length-weighted chord length and sieve particle size was observed with a p value of <0.0001 and R(2) of 0.886. A central composite response surface statistical design was used to evaluate the effect of granulator screw speed and Comil® impeller speed on the length-weighted chord length distribution (CLD) and particle size distribution (PSD) determined by FBRM and nested sieve analysis, respectively. The effect of granulator speed and mill speed on bulk density, tapped density, Compressibility Index, and Flowability Index were also investigated. An inline FBRM probe placed below the Comil-generated chord lengths and CLD data at designated times. The collection of the milled samples for sieve analysis and PSD evaluation were coordinated with the timing of the FBRM determinations. Both FBRM and sieve analysis resulted in similar bimodal distributions for all ten manufactured batches studied. Within the experimental space studied, the granulator screw speed (650-850 rpm) and Comil® impeller speed (1,000-2,000 rpm) did not have a significant effect on CLD, PSD, bulk density, tapped density, Compressibility Index, and Flowability Index (p value > 0.05).

PSD Applicability: TEX-USS High Density Polyethylene Plant

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Postural control during quiet bipedal standing in rats

PubMed Central

Sato, Yota; Fujiki, Soichiro; Sato, Yamato; Aoi, Shinya; Tsuchiya, Kazuo; Yanagihara, Dai

2017-01-01

The control of bipedal posture in humans is subject to non-ideal conditions such as delayed sensation and heartbeat noise. However, the controller achieves a high level of functionality by utilizing body dynamics dexterously. In order to elucidate the neural mechanism responsible for postural control, the present study made use of an experimental setup involving rats because they have more accessible neural structures. The experimental design requires rats to stand bipedally in order to obtain a water reward placed in a water supplier above them. Their motions can be measured in detail using a motion capture system and a force plate. Rats have the ability to stand bipedally for long durations (over 200 s), allowing for the construction of an experimental environment in which the steady standing motion of rats could be measured. The characteristics of the measured motion were evaluated based on aspects of the rats’ intersegmental coordination and power spectrum density (PSD). These characteristics were compared with those of the human bipedal posture. The intersegmental coordination of the standing rats included two components that were similar to that of standing humans: center of mass and trunk motion. The rats’ PSD showed a peak at approximately 1.8 Hz and the pattern of the PSD under the peak frequency was similar to that of the human PSD. However, the frequencies were five times higher in rats than in humans. Based on the analysis of the rats’ bipedal standing motion, there were some common characteristics between rat and human standing motions. Thus, using standing rats is expected to be a powerful tool to reveal the neural basis of postural control. PMID:29244818

Development of Pseudorandom Binary Arrays for Calibration of Surface Profile Metrology Tools

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

Barber, S.K.; Takacs, P.; Soldate, P.

2009-12-01

Optical metrology tools, especially for short wavelengths (extreme ultraviolet and x-ray), must cover a wide range of spatial frequencies from the very low, which affects figure, to the important mid-spatial frequencies and the high spatial frequency range, which produces undesirable scattering. A major difficulty in using surface profilometers arises due to the unknown point-spread function (PSF) of the instruments [G. D. Boreman, Modulation Transfer Function in Optical and Electro-Optical Systems (SPIE, Bellingham, WA, 2001)] that is responsible for distortion of the measured surface profile. Generally, the distortion due to the PSF is difficult to account for because the PSF ismore » a complex function that comes to the measurement via the convolution operation, while the measured profile is described with a real function. Accounting for instrumental PSF becomes significantly simpler if the result of measurement of a profile is presented in the spatial frequency domain as a power spectral density (PSD) distribution [J. W. Goodman, Introduction to Fourier Optics, 3rd ed. (Roberts and Company, Englewood, CO, 2005)]. For example, measured PSD distributions provide a closed set of data necessary for three-dimensional calculations of scattering of light by the optical surfaces [E. L. Church et al., Opt. Eng. (Bellingham) 18, 125 (1979); J. C. Stover, Optical Scattering, 2nd ed. (SPIE Optical Engineering Press, Bellingham, WA, 1995)]. The distortion of the surface PSD distribution due to the PSF can be modeled with the modulation transfer function (MTF), which is defined over the spatial frequency bandwidth of the instrument. The measured PSD distribution can be presented as a product of the squared MTF and the ideal PSD distribution inherent for the system under test. Therefore, the instrumental MTF can be evaluated by comparing a measured PSD distribution of a known test surface with the corresponding ideal numerically simulated PSD. The square root of the ratio of the measured and simulated PSD distributions gives the MTF of the instrument. The applicability of the MTF concept to phase map measurements with optical interferometric microscopes needs to be experimentally verified as the optical tool and algorithms may introduce nonlinear artifacts into the process. In previous work [V. V. Yashchuk et al., Proc. SPIE 6704, 670408 (2007); Valeriy V. Yashchuk et al., Opt. Eng. (Bellingham) 47, 073602 (2008)] the instrumental MTF of a surface profiler was precisely measured using reference test surfaces based on binary pseudorandom (BPR) gratings. Here, the authors present results of fabricating and using two-dimensional (2D) BPR arrays that allow for a direct 2D calibration of the instrumental MTF. BPR sequences are widely used in engineering and communication applications such as global position systems and wireless communication protocols. The ideal BPR pattern has a flat 'white noise' response over the entire range of spatial frequencies of interest. The BPR array used here is based on the uniformly redundant array (URA) prescription [E. E. Fenimore and T. M. Cannon, Appl. Opt. 17, 337 (1978)] initially used for x-ray and gamma ray astronomy applications. The URA's superior imaging capability originates from the fact that its cyclical autocorrelation function very closely approximates a delta function, which produces a flat PSD. Three different size BPR array patterns were fabricated by electron beam lithography and induction coupled plasma etching of silicon. The basic size units were 200, 400, and 600 nm. Two different etch processes were used, CF{sub 4}/Ar and HBr, which resulted in undercut and vertical sidewall profiles, respectively. The 2D BPR arrays were used as standard test surfaces for MTF calibration of the MicroMap{trademark}-570 interferometric microscope using all available objectives. The MicroMap{trademark}-570 interferometric microscope uses incoherent illumination from a tungsten filament source and common path modulated phase shifting interference to produce a set of interferograms detected on a change coupled device. Mathematical algorithms applied to the datasets yield the surface phase map. The HBr etched two-dimensional BPR arrays have proven to be a very effective calibration standard making possible direct calibration corrections without the need of additional calculation considerations, while departures from the ideal vertical sidewall require an additional correction term for the CF{sub 4}/Ar etched samples [Samuel K. Barber et al., Abstract to Optics and Photonics 2009: Optical Engineering and Applications Symposium, San Diego, CA, 2-6 August 2009]. Initial surface roughness of low cost 'prime' wafers limits low magnification calibration but should not be a limitation if better polished samples are used.« less

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

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.

Understanding Effective Diameter and Its Application to Terrestrial Radiation in Ice Clouds

NASA Technical Reports Server (NTRS)

Mitchell, D. L.; Lawson, R. P.; Baker, B.

2011-01-01

The cloud property known as "effective diameter" or "effective radius", which in essence is the cloud particle size distribution (PSD) volume at bulk density divided by its projected area, is used extensively in atmospheric radiation transfer, climate modeling and remote sensing. This derives from the assumption that PSD optical properties can be uniquely described in terms of their effective diameter, D(sub e), and their cloud water content (CWC), henceforth referred to as the D(sub e)-CWC assumption. This study challenges this assumption, showing that while the D(sub e)-CWC assumption appears generally valid for liquid water clouds, it appears less valid for ice clouds in regions where (1) absorption is not primarily a function of either the PSD ice water content (IWC) or the PSD projected area, and (2) where wave resonance (i.e. photon tunneling) contributes significantly to absorption. These two regions often strongly coincide at terrestrial wavelengths when De less than 60 m, which is where this D(sub e)-CWC assumption appears poorest. Treating optical properties solely in terms of D(sub e) and IWC may lead to errors up to 24%, 26% and 20% for terrestrial radiation in the window region regarding the absorption and extinction coefficients and the single scattering albedo, respectively. Outside the window region, errors may reach 33% and 42% regarding absorption and extinction. The magnitude and sign of these errors can change rapidly with wavelength, which may produce significant errors in climate modeling, remote sensing and other applications concerned with the wavelength dependence of radiation. Where the D(sub e)-CWC assumption breaks down, ice cloud optical properties appear to depend on D(sub e), IWC and the PSD shape. Optical property parameterizations in climate models and remote sensing algorithms based on historical PSD measurements may exhibit errors due to previously unknown PSD errors (i.e. the presence of ice artifacts due to the shattering of larger ice particles on the probe inlet tube during sampling). More recently developed cloud probes are designed to mitigate this shattering problem. Using realistic PSD shapes for a given temperature (and/or IWC) and cloud type may minimize errors associated with PSD shape in ice optics parameterizations and remote sensing algorithms. While this topic was investigated using two ice optics schemes (the Yang et al., 2005 database and the modified anomalous diffraction approximation, or MADA), a physical understanding of the limitations of the D(sub e)-IWC assumption was made possible by using MADA. MADA allows one to approximate the contribution of photon tunneling to absorption relative to other optical processes, which reveals that part of the error regarding the D(sub e)-IWC assumption can be associated with tunneling. By relating the remaining error to the radiation penetration depth in bulk ice (DELTA L) due to absorption, the domain where the D(sub e)-IWC assumption is weakest was described in terms of D(sub e) and DELTA L.

Understanding effective diameter and its application to terrestrial radiation in ice clouds

NASA Astrophysics Data System (ADS)

Mitchell, D. L.; Lawson, R. P.; Baker, B.

2010-12-01

The cloud property known as "effective diameter" or "effective radius", which in essence is the cloud particle size distribution (PSD) volume at bulk density divided by its projected area, is used extensively in atmospheric radiation transfer, climate modeling and remote sensing. This derives from the assumption that PSD optical properties can be uniquely described in terms of their effective diameter, De, and their cloud water content (CWC), henceforth referred to as the De-CWC assumption. This study challenges this assumption, showing that while the De-CWC assumption appears generally valid for liquid water clouds, it appears less valid for ice clouds in regions where (1) absorption is not primarily a function of either the PSD ice water content (IWC) or the PSD projected area, and (2) where wave resonance (i.e. photon tunneling) contributes significantly to absorption. These two regions often strongly coincide at terrestrial wavelengths when De<∼60 μm, which is where this De-CWC assumption appears poorest. Treating optical properties solely in terms of De and IWC may lead to errors up to 24%, 26% and 20% for terrestrial radiation in the window region regarding the absorption and extinction coefficients and the single scattering albedo, respectively. Outside the window region, errors may reach 33% and 42% regarding absorption and extinction. The magnitude and sign of these errors can change rapidly with wavelength, which may produce significant errors in climate modeling, remote sensing and other applications concerned with the wavelength dependence of radiation. Where the De-CWC assumption breaks down, ice cloud optical properties appear to depend on De, IWC and the PSD shape. Optical property parameterizations in climate models and remote sensing algorithms based on historical PSD measurements may exhibit errors due to previously unknown PSD errors (i.e. the presence of ice artifacts due to the shattering of larger ice particles on the probe inlet tube during sampling). More recently developed cloud probes are designed to mitigate this shattering problem. Using realistic PSD shapes for a given temperature (and/or IWC) and cloud type may minimize errors associated with PSD shape in ice optics parameterizations and remote sensing algorithms. While this topic was investigated using two ice optics schemes (the Yang et al. (2005) database and the modified anomalous diffraction approximation, or MADA), a physical understanding of the limitations of the De-IWC assumption was made possible by using MADA. MADA allows one to separate the photon tunneling process from the other optical processes, which reveals that much of the error regarding the De-IWC assumption can be associated with tunneling. By relating the remaining error to the radiation penetration depth in bulk ice (ΔL) due to absorption, the domain where the De-IWC assumption is weakest was described in terms of De and ΔL.

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.

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.

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.

Rapid reversal of stress induced loss of synapses in CA3 of rat hippocampus following water maze training.

PubMed

Sandi, Carmen; Davies, Heather A; Cordero, M Isabel; Rodriguez, Jose J; Popov, Victor I; Stewart, Michael G

2003-06-01

The impact was examined of exposing rats to two life experiences of a very different nature (stress and learning) on synaptic structures in hippocampal area CA3. Rats were subjected to either (i) chronic restraint stress for 21 days, and/or (ii) spatial training in a Morris water maze. At the behavioural level, restraint stress induced an impairment of acquisition of the spatial response. Moreover, restraint stress and water maze training had contrasting impacts on CA3 synaptic morphometry. Chronic stress induced a loss of simple asymmetric synapses [those with an unperforated postsynaptic density (PSD)], whilst water maze learning reversed this effect, promoting a rapid recovery of stress-induced synaptic loss within 2-3 days following stress. In addition, in unstressed animals a correlation was found between learning efficiency and the density of synapses with an unperforated PSD: the better the performance in the water maze, the lower the synaptic density. Water maze training increased the number of perforated synapses (those with a segmented PSD) in CA3, both in stressed and, more notably, in unstressed rats. The distinct effects of stress and learning on CA3 synapses reported here provide a neuroanatomical basis for the reported divergent effects of these experiences on hippocampal synaptic activity, i.e. stress as a suppressor and learning as a promoter of synaptic plasticity.

How Far Is Quasar UV/Optical Variability from a Damped Random Walk at Low Frequency?

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

Guo Hengxiao; Wang Junxian; Cai Zhenyi

Studies have shown that UV/optical light curves of quasars can be described using the prevalent damped random walk (DRW) model, also known as the Ornstein–Uhlenbeck process. A white noise power spectral density (PSD) is expected at low frequency in this model; however, a direct observational constraint to the low-frequency PSD slope is difficult due to the limited lengths of the light curves available. Meanwhile, quasars show scatter in their DRW parameters that is too large to be attributed to uncertainties in the measurements and dependence on the variation of known physical factors. In this work we present simulations showing that,more » if the low-frequency PSD deviates from the DRW, the red noise leakage can naturally produce large scatter in the variation parameters measured from simulated light curves. The steeper the low-frequency PSD slope, the larger scatter we expect. Based on observations of SDSS Stripe 82 quasars, we find that the low-frequency PSD slope should be no steeper than −1.3. The actual slope could be flatter, which consequently requires that the quasar variabilities should be influenced by other unknown factors. We speculate that the magnetic field and/or metallicity could be such additional factors.« less

RXTE Observation of Cygnus X-1. Report 2; TIming Analysis

NASA Technical Reports Server (NTRS)

Nowak, Michael A.; Vaughan, Brian A.; Wilms, Joern; Dove, James B.; Begelman, Mitchell C.

1998-01-01

We present timing analysis for a Rossi X-ray Timing Explorer (RXTE) observation of Cygnus X-1 in its hard/low state. This was the first RXTE observation of Cyg X-1 taken after it transited back to this state from its soft/high state. RXTE's large effective area, superior timing capabilities, and ability to obtain long, uninterrupted observations have allowed us to obtain measurements of the power spectral density (PSD), coherence function, and Fourier time lags to a decade lower in frequency and half a decade higher in frequency than typically was achieved with previous instruments. Notable aspects of our observations include a weak 0.005 Hz feature in the PSD coincident with a coherence recovery; a 'hardening' of the high-frequency PSD with increasing energy; a broad frequency range measurement of the coherence function, revealing rollovers from unity coherence at both low and high frequency; and an accurate determination of the Fourier time lags over two and a half decades in frequency. As has been noted in previous similar observations, the time delay is approximately proportional to f(exp -0.7), and at a fixed Fourier frequency the time delay of the hard X-rays compared to the softest energy channel tends to increase logarithmically with energy. Curiously, the 0.01-0.2 Hz coherence between the highest and lowest energy bands is actually slightly greater than the coherence between the second highest and lowest energy bands. We carefully describe all of the analysis techniques used in this paper, and we make comparisons of the data to general theoretical expectations. In a companion paper, we make specific comparisons to a Compton corona model that we have successfully used to describe the energy spectral data from this observation.

Depression and Functional Status Among African American Stroke Survivors in Inpatient Rehabilitation.

PubMed

Harris, Gabrielle M; Collins-McNeil, Janice; Yang, Qing; Nguyen, Vu Q C; Hirsch, Mark A; Rhoads, Charles F; Guerrier, Tami; Thomas, J George; Pugh, Terrence M; Hamm, Deanna; Pereira, Carol; Prvu Bettger, Janet

2017-01-01

To examine the prevalence of poststroke depression (PSD) among African American stroke survivors and the association of depression with functional status at inpatient rehabilitation facility (IRF) discharge. Secondary data analysis was conducted of a patient cohort who received care at 3 IRFs in the United States from 2009 to 2011. Functional status was measured by the Functional Independence Measure (FIM). Multiple linear regression models were used to examine associations of PSD and FIM motor and cognitive scores. Of 458 African American stroke survivors, 48.5% were female, 84% had an ischemic stroke, and the mean age was 60.8 ± 13.6 years. Only 15.4% (n = 71) had documentation of PSD. Bivariate analyses to identify factors associated with depression identified a higher percentage of patients with depression than without who were retired due to disability (17.1% versus 11.6%) or employed (31.4% versus 19.6%) prestroke (P = .041). Dysphagia, cognitive deficits, and a lower admission motor FIM score were also significantly more common among those with depression. There was no significant relationship between depression and functional status after adjusting for patient characteristics. In this study, 15% of the African Americans who received rehabilitation after a stroke had documentation of PSD but this was not associated with functional status at discharge. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

[A study of complexity and power spectrum of cortical EEG and hippocampal potential in rats under different behavioral states].

PubMed

Feng, Zhou-yan; Zheng, Xiao-xiang

2002-08-01

Objective. To study the complexity and the power spectrum of cortical EEG and hippocampal potential in rats under waking and sleep states. Method. Cortical EEG and hippocampal potential were collected by implanted electrodes in freely moving rats. Algorithmic complexity (Kc), approximate entropy (ApEn), power spectral density (PSD) and gravity frequency of PSD of the potential waves were calculated. Result. The complexity of hippocampal potential was higher than that of cortical EEG under every state. The complexity of cortical EEG was lowest under the state of non rapid eye movement (NREM) sleep. The complexity of hippocampal potential was highest under waking state. The total power of both potentials in 0.5- 30 Hz frequency band showed their highest values under NREM state. Conclusion. The values of Kc and ApEn are closely related to the distributions of PSD. When there are evident peaks in PSD, the complexities of signals will decrease. The complexities may be used to distinguish the difference between cortical EEG and hippocampal potential, or large differences between the same kind of potentials under different behavioral states.

Spectral characterization of plastic scintillation detector response as a function of magnetic field strength

NASA Astrophysics Data System (ADS)

Simiele, E.; Kapsch, R.-P.; Ankerhold, U.; Culberson, W.; DeWerd, L.

2018-04-01

The purpose of this work was to characterize intensity and spectral response changes in a plastic scintillation detector (PSD) as a function of magnetic field strength. Spectra measurements as a function of magnetic field strength were performed using an optical spectrometer. The response of both a PSD and PMMA fiber were investigated to isolate the changes in response from the scintillator and the noise signal as a function of magnetic field strength. All irradiations were performed in water at a photon beam energy of 6 MV. Magnetic field strengths of (0, ±0.35, ±0.70, ±1.05, and  ±1.40) T were investigated. Four noise subtraction techniques were investigated to evaluate the impact on the resulting noise-subtracted scintillator response with magnetic field strength. The noise subtraction methods included direct spectral subtraction, the spectral method, and variants thereof. The PMMA fiber exhibited changes in response of up to 50% with magnetic field strength due to the directional light emission from \\breve{C} erenkov radiation. The PSD showed increases in response of up to 10% when not corrected for the noise signal, which agrees with previous investigations of scintillator response in magnetic fields. Decreases in the \\breve{C} erenkov light ratio with negative field strength were observed with a maximum change at  ‑1.40 T of 3.2% compared to 0 T. The change in the noise-subtracted PSD response as a function of magnetic field strength varied with the noise subtraction technique used. Even after noise subtraction, the PSD exhibited changes in response of up to 5.5% over the four noise subtraction methods investigated.

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

Impairment of TrkB-PSD-95 signaling in Angelman syndrome.

PubMed

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.

Expression of the postsynaptic scaffold PSD-95 and development of synaptic physiology during giant terminal formation in the auditory brainstem of the chicken.

PubMed

Goyer, David; Fensky, Luisa; Hilverling, Anna Maria; Kurth, Stefanie; Kuenzel, Thomas

2015-05-01

In the avian nucleus magnocellularis (NM) endbulb of Held giant synapses develop from temporary bouton terminals. The molecular regulation of this process is not well understood. Furthermore, it is unknown how the postsynaptic specialization of the endbulb synapses develops. We therefore analysed expression of the postsynaptic scaffold protein PSD-95 during the transition from bouton-to-endbulb synapses. PSD-95 has been implicated in the regulation of the strength of glutamatergic synapses and could accordingly be of functional relevance for giant synapse formation. PSD-95 protein was expressed at synaptic sites in embryonic chicken auditory brainstem and upregulated between embryonic days (E)12 and E16. We applied immunofluorescence staining and confocal microscopy to quantify pre-and postsynaptic protein signals during bouton-to-endbulb transition. Giant terminal formation progressed along the tonotopic axis in NM, but was absent in low-frequency NM. We found a tonotopic gradient of postsynaptic PSD-95 signals in NM. Furthermore, PSD-95 immunosignals showed the greatest increase between E12 and E15, temporally preceding the bouton-to-endbulb transition. We then applied whole-cell electrophysiology to measure synaptic currents elicited by synaptic terminals during bouton-to-endbulb transition. With progressing endbulb formation postsynaptic currents rose more rapidly and synapses were less susceptible to short-term depression, but currents were not different in amplitude or decay-time constant. We conclude that development of presynaptic specializations follows postsynaptic development and speculate that the early PSD-95 increase could play a functional role in endbulb formation. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Hypothyroidism in the adult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density.

PubMed

Cortés, Claudia; Eugenin, Eliseo; Aliaga, Esteban; Carreño, Leandro J; Bueno, Susan M; Gonzalez, Pablo A; Gayol, Silvina; Naranjo, David; Noches, Verónica; Marassi, Michelle P; Rosenthal, Doris; Jadue, Cindy; Ibarra, Paula; Keitel, Cecilia; Wohllk, Nelson; Court, Felipe; Kalergis, Alexis M; Riedel, Claudia A

2012-09-01

Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though tetra-iodothyronine (T(4)) treatment can overcome the hypothyroidism in the majority of cases, it cannot fully recover the patient's learning capacity and memory. In this work, we analyzed the cellular and molecular changes in the adult brain occurring with the development of experimental hypothyroidism. Adult male Sprague-Dawley rats were treated with 6-propyl-2-thiouracil (PTU) for 20 days to induce hypothyroidism. Neuronal and astrocyte apoptosis were analyzed in the hippocampus of control and hypothyroid adult rats by confocal microscopy. The content of brain-derived neurotrophic factor (BDNF) was analyzed using enzyme-linked immunosorbent assay (ELISA) and in situ hybridization. The glutamatergic synapse and the postsynaptic density (PSD) were analyzed by electron microscopy. The content of PSD proteins like tyrosine receptor kinase B (TrkB), p75, and N-methyl-D-aspartate receptor (NMDAr) were analyzed by immunoblot. We observed that the hippocampus of hypothyroid adult rats displayed increased apoptosis levels in neurons and astrocyte and reactive gliosis compared with controls. Moreover, we found that the amount of BDNF mRNA was higher in the hippocampus of hypothyroid rats and the content of TrkB, the receptor for BDNF, was reduced at the PSD of the CA3 region of hypothyroid rats, compared with controls. We also observed that the glutamatergic synapses from the stratum radiatum of CA3 from hypothyroid rats, contained thinner PSDs than control rats. This observation was in agreement with a reduced content of NMDAr subunits at the PSD in hypothyroid animals. Our data suggest that adult hypothyroidism affects the hippocampus by a mechanism that alters the composition of PSD, reduces neuronal and astrocyte survival, and alters the content of the signaling neurotrophic factors, such as BDNF.

Steroid Receptor Coactivator-1 Knockdown Decreases Synaptic Plasticity and Impairs Spatial Memory in the Hippocampus of Mice.

PubMed

Bian, Chen; Huang, Yan; Zhu, Haitao; Zhao, Yangang; Zhao, Jikai; Zhang, Jiqiang

2018-05-01

Steroids have been demonstrated to play profound roles in the regulation of hippocampal function by acting on their receptors, which need coactivators for their transcriptional activities. Previous studies have shown that steroid receptor coactivator-1 (SRC-1) is the predominant coactivator in the hippocampus, but its exact role and the underlying mechanisms remain unclear. In this study, we constructed SRC-1 RNA interference (RNAi) lentiviruses, injected them into the hippocampus of male mice, and then examined the changes in the expression of selected synaptic proteins, CA1 synapse density, postsynaptic density (PSD) thickness, and in vivo long-term potentiation (LTP). Spatial learning and memory behavior changes were investigated using the Morris water maze. We then transfected the lentiviruses into cultured hippocampal cells and examined the changes in synaptic protein and phospho-cyclic AMP response element-binding protein (pCREB) expression. The in vivo results showed that SRC-1 knockdown significantly decreased the expression of synaptic proteins and CA1 synapse density as well as PSD thickness; SRC-1 knockdown also significantly impaired in vivo LTP and disrupted spatial learning and memory. The in vitro results showed that while the expression of synaptic proteins was significantly decreased by SRC-1 knockdown, pCREB expression was also significantly decreased. The above results suggest a pivotal role of SRC-1 in the regulation of hippocampal synaptic plasticity and spatial learning and memory, strongly indicating SRC-1 may serve as a novel therapeutic target for hippocampus-dependent memory disorders. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

Fourier analysis of blazar variability

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

Finke, Justin D.; Becker, Peter A., E-mail: justin.finke@nrl.navy.mil

Blazars display strong variability on multiple timescales and in multiple radiation bands. Their variability is often characterized by power spectral densities (PSDs) and time lags plotted as functions of the Fourier frequency. We develop a new theoretical model based on the analysis of the electron transport (continuity) equation, carried out in the Fourier domain. The continuity equation includes electron cooling and escape, and a derivation of the emission properties includes light travel time effects associated with a radiating blob in a relativistic jet. The model successfully reproduces the general shapes of the observed PSDs and predicts specific PSD and timemore » lag behaviors associated with variability in the synchrotron, synchrotron self-Compton, and external Compton emission components, from submillimeter to γ-rays. We discuss applications to BL Lacertae objects and to flat-spectrum radio quasars (FSRQs), where there are hints that some of the predicted features have already been observed. We also find that FSRQs should have steeper γ-ray PSD power-law indices than BL Lac objects at Fourier frequencies ≲ 10{sup –4} Hz, in qualitative agreement with previously reported observations by the Fermi Large Area Telescope.« less

Dbo/Henji Modulates Synaptic dPAK to Gate Glutamate Receptor Abundance and Postsynaptic Response.

PubMed

Wang, Manyu; Chen, Pei-Yi; Wang, Chien-Hsiang; Lai, Tzu-Ting; Tsai, Pei-I; Cheng, Ying-Ju; Kao, Hsiu-Hua; Chien, Cheng-Ting

2016-10-01

In response to environmental and physiological changes, the synapse manifests plasticity while simultaneously maintains homeostasis. Here, we analyzed mutant synapses of henji, also known as dbo, at the Drosophila neuromuscular junction (NMJ). In henji mutants, NMJ growth is defective with appearance of satellite boutons. Transmission electron microscopy analysis indicates that the synaptic membrane region is expanded. The postsynaptic density (PSD) houses glutamate receptors GluRIIA and GluRIIB, which have distinct transmission properties. In henji mutants, GluRIIA abundance is upregulated but that of GluRIIB is not. Electrophysiological results also support a GluR compositional shift towards a higher IIA/IIB ratio at henji NMJs. Strikingly, dPAK, a positive regulator for GluRIIA synaptic localization, accumulates at the henji PSD. Reducing the dpak gene dosage suppresses satellite boutons and GluRIIA accumulation at henji NMJs. In addition, dPAK associated with Henji through the Kelch repeats which is the domain essential for Henji localization and function at postsynapses. We propose that Henji acts at postsynapses to restrict both presynaptic bouton growth and postsynaptic GluRIIA abundance by modulating dPAK.

Dbo/Henji Modulates Synaptic dPAK to Gate Glutamate Receptor Abundance and Postsynaptic Response

PubMed Central

Wang, Manyu; Chen, Pei-Yi; Wang, Chien-Hsiang; Lai, Tzu-Ting; Tsai, Pei-I; Cheng, Ying-Ju; Kao, Hsiu-Hua; Chien, Cheng-Ting

2016-01-01

In response to environmental and physiological changes, the synapse manifests plasticity while simultaneously maintains homeostasis. Here, we analyzed mutant synapses of henji, also known as dbo, at the Drosophila neuromuscular junction (NMJ). In henji mutants, NMJ growth is defective with appearance of satellite boutons. Transmission electron microscopy analysis indicates that the synaptic membrane region is expanded. The postsynaptic density (PSD) houses glutamate receptors GluRIIA and GluRIIB, which have distinct transmission properties. In henji mutants, GluRIIA abundance is upregulated but that of GluRIIB is not. Electrophysiological results also support a GluR compositional shift towards a higher IIA/IIB ratio at henji NMJs. Strikingly, dPAK, a positive regulator for GluRIIA synaptic localization, accumulates at the henji PSD. Reducing the dpak gene dosage suppresses satellite boutons and GluRIIA accumulation at henji NMJs. In addition, dPAK associated with Henji through the Kelch repeats which is the domain essential for Henji localization and function at postsynapses. We propose that Henji acts at postsynapses to restrict both presynaptic bouton growth and postsynaptic GluRIIA abundance by modulating dPAK. PMID:27736876

Traffic air pollution and risk of death from bladder cancer in Taiwan using petrol station density as a pollutant indicator.

PubMed

Ho, Chi-Kung; Peng, Chiung-Yu; Yang, Chun-Yuh

2010-01-01

To investigate the relationship between air pollution and risk of death from bladder cancer, a matched cancer case-control study was conducted using deaths that occurred in Taiwan from 1997 through 2006. Data for all eligible bladder cancer deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of individuals who died from causes other than cancer or diseases associated with genitourinary problems. The controls were pair matched to the cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data for the number of petrol stations in study municipalities were collected from the two major petroleum supply companies, Chinese Petroleum Corporation (CPC) and Formosa Petrochemical Corporation (FPCC). The petrol station density (per square kilometer) (PSD) for study municipalities was used as an indicator of a subject's exposure to benzene and other hydrocarbons present in ambient evaporative losses of petrol or to air emissions from motor vehicles. The subjects were divided into tertiles according to PSD in their residential municipality. The present study showed that individuals who resided in municipalities with high PSD levels were at an increased risk of death from bladder cancer compared to subjects living in municipalities with a low PSD level; however, the differences are not statistically significant. The findings of this study warrant further investigation of the role of vehicular air pollutant emissions in the etiology of bladder cancer development.

The LGI1–ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function

PubMed Central

Lovero, Kathryn L.; Fukata, Yuko; Granger, Adam J.; Fukata, Masaki; Nicoll, Roger A.

2015-01-01

Synapse development is coordinated by a number of transmembrane and secreted proteins that come together to form synaptic organizing complexes. Whereas a variety of synaptogenic proteins have been characterized, much less is understood about the molecular networks that support the maintenance and functional maturation of nascent synapses. Here, we demonstrate that leucine-rich, glioma-inactivated protein 1 (LGI1), a secreted protein previously shown to modulate synaptic AMPA receptors, is a paracrine signal released from pre- and postsynaptic neurons that acts specifically through a disintegrin and metalloproteinase protein 22 (ADAM22) to set postsynaptic strength. We go on to describe a novel role for ADAM22 in maintaining excitatory synapses through PSD-95/Dlg1/zo-1 (PDZ) domain interactions. Finally, we show that in the absence of LGI1, the mature synapse scaffolding protein PSD-95, but not the immature synapse scaffolding protein SAP102, is unable to modulate synaptic transmission. These results indicate that LGI1 and ADAM22 form an essential synaptic organizing complex that coordinates the maturation of excitatory synapses by regulating the functional incorporation of PSD-95. PMID:26178195

An operational modal analysis method in frequency and spatial domain

NASA Astrophysics Data System (ADS)

Wang, Tong; Zhang, Lingmi; Tamura, Yukio

2005-12-01

A frequency and spatial domain decomposition method (FSDD) for operational modal analysis (OMA) is presented in this paper, which is an extension of the complex mode indicator function (CMIF) method for experimental modal analysis (EMA). The theoretical background of the FSDD method is clarified. Singular value decomposition is adopted to separate the signal space from the noise space. Finally, an enhanced power spectrum density (PSD) is proposed to obtain more accurate modal parameters by curve fitting in the frequency domain. Moreover, a simulation case and an application case are used to validate this method.

Structural characteristics of gels prepared from sonohydrolysis and conventional hydrolysis of TEOS: an emphasis on the mass fractal as determined from the pore size distribution

NASA Astrophysics Data System (ADS)

Vollet, D. R.; Torres, R. R.; Donatti, D. A.; Ibañez Ruiz, A.

2005-11-01

Silica gels were preparated from fixed proportion mixtures of tetraethoxysilane, water and hydrocloric acid, using either ultrasound stimulation (US) or conventional method (CO) in the hydrolysis step of the process. Wet gels were obtained with the same silica volume concentration and density. According to small-angle X-ray scattering, the structure of the wet gels can be described as mass fractal structures with mass fractal dimension D = 2.20 in a length scale = 7.9 nm, in the case of wet gels US, and D = 2.26 in a length scale = 6.9 nm, in the case of wet gels CO. The mass fractal characteristics of the wet gels US and CO account for the different structures evolved in the drying of the gels US and CO in the obtaining of xerogels and aerogels. The pore structure of the dried gels was studied by nitrogen adsorption as a function of the temperature. Aerogels (US and CO) present high porosity with pore size distribution (PSD) curves in the mesopore region while xerogels (US and CO) present minor porosity with PSD curves mainly in the micropore region. The dried gels US (aerogels and xerogels) generally present pore volume and specific surface area greater than the dried gels CO. The mass fractal structure of the aerogels has been studied from an approach based on the PSD curves exclusively.

Characterization of nanoporous shales with gas sorption

NASA Astrophysics Data System (ADS)

Joewondo, N.; Prasad, M.

2017-12-01

The understanding of the fluid flow in porous media requires the knowledge of the pore system involved. Fluid flow in fine grained shales falls under different regime than transport regime in conventional reservoir due to the different average pore sizes in the two materials; the average pore diameter of conventional sandstones is on the micrometer scale, while of shales can be as small as several nanometers. Mercury intrusion porosimetry is normally used to characterize the pores of conventional reservoir, however with increasingly small pores, the injection pressure required to imbibe the pores becomes infinitely large due to surface tension. Characterization of pores can be expressed by a pore size distribution (PSD) plot, which reflects distribution of pore volume or surface area with respect to pore size. For the case of nanoporous materials, the surface area, which serves as the interface between the rock matrix and fluid, becomes increasingly large and important. Physisorption of gas has been extensively studied as a method of nanoporous solid characterization (particularly for the application of catalysis, metal organic frameworks, etc). The PSD is obtained by matching the experimental result to the calculated theoretical result (using Density Functional Theory (DFT), a quantum mechanics based modelling method for molecular scale interactions). We present the challenges and experimental result of Nitrogen and CO2 gas sorption on shales with various mineralogy and the interpreted PSD obtained by DFT method. Our result shows significant surface area contributed by the nanopores of shales, hence the importance of surface area measurements for the characterization of shales.

Influence of peri-implant artifacts on bone morphometric analysis with micro-computed tomography.

PubMed

Song, Jin Wook; Cha, Jung Yul; Bechtold, Till Edward; Park, Young Chel

2013-01-01

To determine the optimal dilation pixel size distance from the mini-implant interface needed to compensate for the metal artifact on micro-computed tomography (micro-CT) for bone morphometric analysis. A total of 72 self-drilling mini-implants were placed into the buccal alveolar bone of six male beagle dogs. After 12 weeks of orthodontic loading, specimens were harvested and scanned with micro-CT (Skyscan 1076) at a resolution of 9 μm. Using the reload plug-in and dilation procedure of CTAn, the percentage of bone-implant contact (BIC) and bone volume density (BV/TV, bone volume/total volume), respectively, were measured from one to seven pixels from the metal implant surface. Each pixel size of dilation (PSD) were compared with that of a ground histologic section, and the optimal PSD for bone morphometric analysis using micro-CT was determined. BIC values from micro-CT analysis decreased when the PSD increased (P < .05). BIC from micro-CT showed the highest correlation coefficient with BIC from histologic slides when the PSD was 5 to 7 (P < .05), whereas BV/TV from micro-CT showed a very high correlation with BV/TV from histologic slides in all ranges (P < .0001). To measure BIC and BV/TV using micro-CT, at least 5 PSD from the metal implant surface is needed.

Molecular organization of excitatory chemical synapses in the mammalian brain

NASA Astrophysics Data System (ADS)

Gundelfinger, E. D.; tom Dieck, S.

Chemical synapses are highly specialized cell-cell junctions designed for efficient signaling between nerve cells. Distinct cytoskeletal matrices are assembled at either side of the synaptic junction. The presynaptic cytomatrix at the active zone (CAZ) defines and organizes the site of neurotransmitter release from presynaptic nerve terminals. The postsynaptic density (PSD) tethers neurotransmitter receptors and the postsynaptic signal transduction machinery. Recent progress in the identification and characterization of novel CAZ and PSD components has revealed new insights into the molecular organization and assembly mechanisms of the synaptic neurotransmission apparatus. On the presynaptic side, Bassoon and Piccolo, two related giant proteins, are crucially involved in scaffolding the CAZ. On the postsynaptic side, two families of multi-domain adaptor proteins, the MAGuKs (membrane-associated guanylate kinase homologs) and the ProSAP (proline-rich synapse-associated protein, also termed Shank) family members are thought to be major organizing molecules of the PSD.

Development of a self-consistent free-form approach for studying the three-dimensional morphology of a thin film

NASA Astrophysics Data System (ADS)

Kozhevnikov, Igor V.; Peverini, Luca; Ziegler, Eric

2012-03-01

A method capable of extracting the depth distribution of the dielectric constant of a thin film deposited on a substrate and the three power spectral density (PSD) functions characterizing its roughness is presented. It is based on the concurrent analysis of x-ray reflectivity and scattering measurements obtained at different glancing angle values of the probe beam so that the effect of roughness is taken into account during reconstruction of the dielectric constant profile. Likewise, the latter is taken into account when determining the PSD functions describing the film roughness. This approach is using a numerical computation iterative procedure that demonstrated a rapid convergence for the overall set of data leading to a precise description of the three-dimensional morphology of a film. In the case of a tungsten thin film deposited by dc-magnetron sputtering onto a silicon substrate and characterized under vacuum, the analysis of the x-ray data showed the tungsten density to vary with depth from 95% of the bulk density at the top of the film to about 80% near the substrate, where the presence of an interlayer, estimated to be 0.7 nm thick, was evidenced. The latter may be due to diffusion and/or implantation of tungsten atoms into the silicon substrate. In the reconstruction of the depth profile, the resolution (minimum feature size correctly reconstructed) was estimated to be of the order of 0.4-0.5 nm. The depth distribution of the dielectric constant was shown to affect the roughness conformity coefficient extracted from the measured x-ray scattering distributions, while the deposition process increased the film roughness at high spatial frequency as compared to the virgin substrate. On the contrary, the roughness showed a weak influence on the dielectric constant depth profile extracted, as the sample used in our particular experiment was extremely smooth.

Properties of Particle Size Distribution from Milled White Nixtamalized Corn Kernels as a Function of Steeping Time

PubMed Central

Fernández-Muñoz, J. L.; Zapata-Torrez, M.; Márquez-Herrera, A.; Sánchez-Sinencio, F.; Mendoza-Álvarez, J. G.; Meléndez-Lira, M.; Zelaya-Ángel, O.

2016-01-01

This paper focuses on the particle size distribution (PSD) changes during nixtamalized corn kernels (NCK) as a function of the steeping time (ST). The process to obtain powder or corn flour from NCK was as follows: (i) the NCK with different STs were wet-milled in a stone mill, (ii) dehydrated by a Flash type dryer, and (iii) pulverized with a hammer mill and sieved with a 20 mesh. The powder was characterized by measuring the PSD percentage, calcium percentage (CP), peak viscosity at 90°C (PV), and crystallinity percentage (CP). The PSD of the powder as a function of ST was determined by sieving in Ro-TAP equipment. By sieving, five fractions of powder were obtained employing meshes 30, 40, 60, 80, and 100. The final weight of the PSD obtained from the sieving process follows a Gaussian profile with the maximum corresponding to the average particle obtained with mesh 60. The calcium percentage as a function of ST follows a behavior similar to the weight of the PSD. The study of crystallinity versus the mesh number shows that it decreases for smaller mesh number. A similar behavior is observed as steeping time increases, except around ST = 8 h where the gelatinization of starch is observed. The trend of increasing viscosity values of the powder samples occurs when increasing ST and decreasing particle size. The ST significantly changes the crystallinity and viscosity values of the powder and, in both cases, a minimum value is observed in the region 7–9 h. The experimental results show that the viscosity increases (decreases) if the particle size decreases (increases). PMID:27375921

Impact of Ocean Wave Climate on Double-Frequency Microseisms and Evaluation of Seismic Site Effect in Northern Mississippi, USA

NASA Astrophysics Data System (ADS)

Guo, Z.; Aydin, A.; Xue, M.

2017-12-01

This research presents the power spectral density (PSD) of double-frequency (DF) microseisms in both vertical (V) and resultant horizontal (H) directions and horizontal-to-vertical spectral ratios (HVSR) of 13 continuous single point long-term ambient noise recordings (LTR) at 5 inland and 2 coastal locations selected in Mississippi Embayment, and frequency value and PSD at DF peak (PSD@DF), predominant frequency (f0) and HVSR value at f0 (HVSR@f0) at 234 single point short-term ambient noise recordings (STR) over a large range of unconsolidated sediment thickness (UST) in Northern Mississippi. By correlating PSD of LTRs with the simultaneous ocean wave climate data of Atlantic Ocean and Gulf of Mexico, DF microseisms observed in Northern Mississippi were shown to be shaped by a combined impact of wave climates of both Atlantic Ocean and Gulf of Mexico. Polarization analysis conducted separately for LTRs and STRs strengthen this conclusion. The LTRs show stable estimates of f0, on the other hand, time-dependent variations on HVSR@f0 value. The plots of DFH-UST, rather than DFV-UST, coincide well with plots of f0-UST within area where UST is larger than 300 m, which indicates that the shear wave resonance in thick sediments modifies the DF microseisms more obviously in horizontal direction than in vertical direction. Transfer functions between HVSR@f0 and ocean data indicates that the variation of HVSR@f0 is caused by variations of source location and energy level of DF microseisms, i.e. ocean wave activities in Atlantic Ocean and Gulf of Mexico. Additionally, 3D microseism spectra of each LTR and those of all STRs within each 100 m-UST group are converted into spatial spectral vectors and projected on stereographic nets. Patterns of the clusters formed by these projections show that the HVSR@f0 values are related to both UST and vibration source location and energy level.

Wakefulness delta waves increase after cortical plasticity induction.

PubMed

Assenza, G; Pellegrino, G; Tombini, M; Di Pino, G; Di Lazzaro, V

2015-06-01

Delta waves (DW) are present both during sleep and in wakefulness. In the first case, DW are considered effectors of synaptic plasticity, while in wakefulness, when they appear in the case of brain lesions, their functional meaning is not unanimously recognized. To throw light on the latter, we aimed to investigate the impact on DW exerted by the cortical plasticity-inducing protocol of intermittent theta burst stimulation (iTBS). Twenty healthy subjects underwent iTBS (11 real iTBS and nine sham iTBS) on the left primary motor cortex with the aim of inducing long-term potentiation (LTP)-like phenomena. Five-minute resting open-eye 32-channel EEG, right opponens pollicis motor-evoked potentials (MEPs), and alertness behavioral scales were collected before and up to 30 min after the iTBS. Power spectral density (PSD), interhemispheric coherence between homologous sensorimotor regions, and intrahemispheric coherence were calculated for the frequency bands ranging from delta to beta. Real iTBS induced a significant increase of both MEP amplitude and DW PSD lasting up to 30 min after stimulation, while sham iTBS did not. The DW increase was evident over frontal areas ipsilateral and close to the stimulated cortex (electrode F3). Neither real nor sham iTBS induced significant modifications in the PSD of theta, alpha, and beta bands and in the interhemispheric coherence. Behavioral visuo-analogic scales score did not demonstrate changes in alertness after stimulations. No correlations were found between MEP amplitude and PSD changes in the delta band. Our data showed that LTP induction in the motor cortex during wakefulness, by means of iTBS, is accompanied by a large and enduring increase of DW over the ipsilateral frontal cortex. The present results are strongly in favor of a prominent role of DW in the neural plasticity processes taking place during the awake state. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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.

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.

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

D-Serine and Serine Racemase Are Associated with PSD-95 and Glutamatergic Synapse Stability

PubMed Central

Lin, Hong; Jacobi, Ariel A.; Anderson, Stewart A.; Lynch, David R.

2016-01-01

D-serine is an endogenous coagonist at the glycine site of synaptic NMDA receptors (NMDARs), synthesized by serine racemase (SR) through conversion of L-serine. It is crucial for synaptic plasticity and is implicated in schizophrenia. Our previous studies demonstrated specific loss of SR, D-serine-responsive synaptic NMDARs, and glutamatergic synapses in cortical neurons lacking α7 nicotinic acetylcholine receptors, which promotes glutamatergic synapse formation and maturation during development. We thus hypothesize that D-serine and SR (D-serine/SR) are associated with glutamatergic synaptic development. Using morphological and molecular studies in cortical neuronal cultures, we demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development. Endogenous D-serine and SR colocalize with PSD-95, but not presynaptic vesicular glutamate transporter 1 (VGLUT1), in glutamatergic synapses of cultured cortical neurons. Low-density astrocytes in cortical neuronal cultures lack SR expression but contain enriched D-serine in large vesicle-like structures, suggesting possible synthesis of D-serine in postsynaptic neurons and storage in astrocytes. More interestingly, endogenous D-serine and SR colocalize with PSD-95 in the postsynaptic terminals of glutamatergic synapses during early and late synaptic development, implicating involvement of D-serine/SR in glutamatergic synaptic development. Exogenous application of D-serine enhances the interactions of SR with PSD-95 and NR1, and increases the number of VGLUT1- and PSD-95-positive glutamatergic synapses, suggesting that exogenous D-serine enhances postsynaptic SR/PSD-95 signaling and stabilizes glutamatergic synapses during cortical synaptic development. This is blocked by NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5) and 7-chlorokynurenic acid (7-CK), a specific antagonist at the glycine site of NMDARs, demonstrating that D-serine effects are mediated through postsynaptic NMDARs. Conversely, exogenous application of glycine has no such effects, suggesting D-serine, rather than glycine, modulates postsynaptic events. Taken together, our findings demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development, implicating D-serine/SR as regulators of cortical synaptic and circuit development. PMID:26941605

D-Serine and Serine Racemase Are Associated with PSD-95 and Glutamatergic Synapse Stability.

PubMed

Lin, Hong; Jacobi, Ariel A; Anderson, Stewart A; Lynch, David R

2016-01-01

D-serine is an endogenous coagonist at the glycine site of synaptic NMDA receptors (NMDARs), synthesized by serine racemase (SR) through conversion of L-serine. It is crucial for synaptic plasticity and is implicated in schizophrenia. Our previous studies demonstrated specific loss of SR, D-serine-responsive synaptic NMDARs, and glutamatergic synapses in cortical neurons lacking α7 nicotinic acetylcholine receptors, which promotes glutamatergic synapse formation and maturation during development. We thus hypothesize that D-serine and SR (D-serine/SR) are associated with glutamatergic synaptic development. Using morphological and molecular studies in cortical neuronal cultures, we demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development. Endogenous D-serine and SR colocalize with PSD-95, but not presynaptic vesicular glutamate transporter 1 (VGLUT1), in glutamatergic synapses of cultured cortical neurons. Low-density astrocytes in cortical neuronal cultures lack SR expression but contain enriched D-serine in large vesicle-like structures, suggesting possible synthesis of D-serine in postsynaptic neurons and storage in astrocytes. More interestingly, endogenous D-serine and SR colocalize with PSD-95 in the postsynaptic terminals of glutamatergic synapses during early and late synaptic development, implicating involvement of D-serine/SR in glutamatergic synaptic development. Exogenous application of D-serine enhances the interactions of SR with PSD-95 and NR1, and increases the number of VGLUT1- and PSD-95-positive glutamatergic synapses, suggesting that exogenous D-serine enhances postsynaptic SR/PSD-95 signaling and stabilizes glutamatergic synapses during cortical synaptic development. This is blocked by NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5) and 7-chlorokynurenic acid (7-CK), a specific antagonist at the glycine site of NMDARs, demonstrating that D-serine effects are mediated through postsynaptic NMDARs. Conversely, exogenous application of glycine has no such effects, suggesting D-serine, rather than glycine, modulates postsynaptic events. Taken together, our findings demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development, implicating D-serine/SR as regulators of cortical synaptic and circuit development.

Ocular Dominance Plasticity after Stroke Was Preserved in PSD-95 Knockout Mice.

PubMed

Greifzu, Franziska; Parthier, Daniel; Goetze, Bianka; Schlüter, Oliver M; Löwel, Siegrid

2016-01-01

Neuronal plasticity is essential to enable rehabilitation when the brain suffers from injury, such as following a stroke. One of the most established models to study cortical plasticity is ocular dominance (OD) plasticity in the primary visual cortex (V1) of the mammalian brain induced by monocular deprivation (MD). We have previously shown that OD-plasticity in adult mouse V1 is absent after a photothrombotic (PT) stroke lesion in the adjacent primary somatosensory cortex (S1). Exposing lesioned mice to conditions which reduce the inhibitory tone in V1, such as raising animals in an enriched environment or short-term dark exposure, preserved OD-plasticity after an S1-lesion. Here we tested whether modification of excitatory circuits can also be beneficial for preserving V1-plasticity after stroke. Mice lacking postsynaptic density protein-95 (PSD-95), a signaling scaffold present at mature excitatory synapses, have lifelong juvenile-like OD-plasticity caused by an increased number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) -silent synapses in V1 but unaltered inhibitory tone. In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice after an S1-lesion but not in PSD-95 wildtype (WT)-mice. In addition, experience-enabled enhancement of the optomotor reflex of the open eye after MD was compromised in both lesioned PSD-95 KO and PSD-95 WT mice. Basic V1-activation and retinotopic map quality were, however, not different between lesioned PSD-95 KO mice and their WT littermates. The preserved OD-plasticity in the PSD-95 KO mice indicates that V1-plasticity after a distant stroke can be promoted by either changes in excitatory circuitry or by lowering the inhibitory tone in V1 as previously shown. Furthermore, the present data indicate that an increased number of AMPA-silent synapses preserves OD-plasticity not only in the healthy brain, but also in another experimental paradigm of cortical plasticity, namely the long-range influence on V1-plasticity after an S1-lesion.

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.

Comparisons of Particulate Size Distributions from Multiple Combustion Strategies

NASA Astrophysics Data System (ADS)

Zhang, Yizhou

In this study, a comparison of particle size distribution (PSD) measurements from eight different combustion strategies was conducted at four different load-speed points. The PSDs were measured using a scanning mobility particle sizer (SMPS) together with a condensation particle counter (CPC). To study the influence of volatile particles, PSD measurements were performed with and without a volatile particle remover (thermodenuder, TD) at both low and high dilution ratios. The common engine platform utilized in the experiment helps to eliminate the influence of background particulate and ensures similarity in dilution conditions. The results show a large number of volatile particles were present under LDR sample conditions for most of the operating conditions. The use of a TD, especially when coupled with HDR, was demonstrated to be effective at removing volatile particles and provided consistent measurements across all combustion strategies. The PSD comparison showed that gasoline premixed combustion strategies such as HCCI and GCI generally have low PSD magnitudes for particle sizes greater than the Particle Measurement Programme (PMP) cutoff diameter (23 nm), and the PSDs were highly nuclei-mode particle dominated. The strategies using diesel as the only fuel (DLTC and CDC) generally showed the highest particle number emissions for particles larger than 23 nm and had accumulation-mode particle dominated PSDs. A consistent correlation between the increase of the direct-injection of diesel fuel and a higher fraction of accumulation-mode particles was observed over all combustion strategies. A DI fuel substitution study and injector nozzle geometry study were conducted to better understand the correlation between PSD shape and DI fueling. It was found that DI fuel properties has a clear impact on PSD behavior for CDC and NG DPI. Fuel with lower density and lower sooting tendency led to a nuclei-mode particle dominated PSD shape. For NG RCCI, accumulation-mode particle concentration was found to be insensitive to DI fuel properties. Similar PSD behavior of increased nuclei-mode particle fraction was also observed when a smaller orifice nozzle was used for CDC and NG DPI operation. For NG DPI, a reduction of DI fuel fraction generally led to a reduction in accumulation-mode particles.

Ocular Dominance Plasticity after Stroke Was Preserved in PSD-95 Knockout Mice

PubMed Central

Greifzu, Franziska; Parthier, Daniel; Goetze, Bianka; Schlüter, Oliver M.; Löwel, Siegrid

2016-01-01

Neuronal plasticity is essential to enable rehabilitation when the brain suffers from injury, such as following a stroke. One of the most established models to study cortical plasticity is ocular dominance (OD) plasticity in the primary visual cortex (V1) of the mammalian brain induced by monocular deprivation (MD). We have previously shown that OD-plasticity in adult mouse V1 is absent after a photothrombotic (PT) stroke lesion in the adjacent primary somatosensory cortex (S1). Exposing lesioned mice to conditions which reduce the inhibitory tone in V1, such as raising animals in an enriched environment or short-term dark exposure, preserved OD-plasticity after an S1-lesion. Here we tested whether modification of excitatory circuits can also be beneficial for preserving V1-plasticity after stroke. Mice lacking postsynaptic density protein-95 (PSD-95), a signaling scaffold present at mature excitatory synapses, have lifelong juvenile-like OD-plasticity caused by an increased number of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) -silent synapses in V1 but unaltered inhibitory tone. In fact, using intrinsic signal optical imaging, we show here that OD-plasticity was preserved in V1 of adult PSD-95 KO mice after an S1-lesion but not in PSD-95 wildtype (WT)-mice. In addition, experience-enabled enhancement of the optomotor reflex of the open eye after MD was compromised in both lesioned PSD-95 KO and PSD-95 WT mice. Basic V1-activation and retinotopic map quality were, however, not different between lesioned PSD-95 KO mice and their WT littermates. The preserved OD-plasticity in the PSD-95 KO mice indicates that V1-plasticity after a distant stroke can be promoted by either changes in excitatory circuitry or by lowering the inhibitory tone in V1 as previously shown. Furthermore, the present data indicate that an increased number of AMPA-silent synapses preserves OD-plasticity not only in the healthy brain, but also in another experimental paradigm of cortical plasticity, namely the long-range influence on V1-plasticity after an S1-lesion. PMID:26930616

Interfering of the Reelin/ApoER2/PSD95 Signaling Axis Reactivates Dendritogenesis of Mature Hippocampal Neurons.

PubMed

Ampuero, Estibaliz; Jury, Nur; Härtel, Steffen; Marzolo, María-Paz; van Zundert, Brigitte

2017-05-01

Reelin, an extracellular glycoprotein secreted in embryonic and adult brain, participates in neuronal migration and neuronal plasticity. Extensive evidence shows that reelin via activation of the ApoER2 and VLDLR receptors promotes dendrite and spine formation during early development. Further evidence suggests that reelin signaling is needed to maintain a stable architecture in mature neurons, but, direct evidence is lacking. During activity-dependent maturation of the neuronal circuitry, the synaptic protein PSD95 is inserted into the postsynaptic membrane to induce structural refinement and stability of spines and dendrites. Given that ApoER2 interacts with PSD95, we tested if reelin signaling interference in adult neurons reactivates the dendritic architecture. Unlike findings in developing cultures, the presently obtained in vitro and in vivo data show, for the first time, that reelin signaling interference robustly increase dendritogenesis and reduce spine density in mature hippocampal neurons. In particular, the expression of a mutant ApoER2 form (ApoER2-tailless), which is unable to interact with PSD95 and hence cannot transduce reelin signaling, resulted in robust dendritogenesis in mature hippocampal neurons in vitro. These results indicate that reelin/ApoER2/PSD95 signaling is important for neuronal structure maintenance in mature neurons. Mechanistically, obtained immunofluorescent data indicate that reelin signaling impairment reduced synaptic PSD95 levels, consequently leading to synaptic re-insertion of NR2B-NMDARs. Our findings underscore the importance of reelin in maintaining adult network stability and reveal a new mode for reactivating dendritogenesis in neurological disorders where dendritic arbor complexity is limited, such as in depression, Alzheimer's disease, and stroke. J. Cell. Physiol. 232: 1187-1199, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Altered skin flowmotion in hypertensive humans

PubMed Central

Bruning, R.S.; Kenney, W.L.; Alexander, L.M.

2017-01-01

Essential hypertensive humans exhibit attenuated cutaneous nitric oxide (NO)-dependent vasodilation. Using spectral analysis (fast Fourier transformation) we aimed to characterize the skin flowmotion contained in the laser-Doppler flowmetry recordings during local heating-induced vasodilation before and after concurrent pharmacological inhibition of nitric oxide synthase (NOS) in hypertensive and age-matched normotensive men and women. We hypothesized that hypertensive subjects would have lower total power spectral densities (PSD), specifically in the frequency intervals associated with intrinsic endothelial and neurogenic control of the microvasculature. Furthermore, we hypothesized that NOS inhibition would attenuate the endothelial frequency interval. Laser-Doppler flowmetry recordings during local heating experiments from 18 hypertensive (MAP: 108±2mmHg) and 18 normotensive (MAP: 88±2mmHg) men and women were analyzed. Within site NO-dependent vasodilation was assessed by perfusion of a non-specific NOS inhibitor (NG-nitro-L-arginine methyl ester; L-NAME) through intradermal microdialysis during the heating-induced plateau in skin blood flow. Local heating-induced vasodilation increased total PSD for all frequency intervals (all p<0.001). Hypertensives had a lower total PSD (p=0.03) and absolute neurogenic frequency intervals (p<0.01) compared to the normotensives. When normalized as a percentage of total PSD, hypertensives had reduced neurogenic (p<0.001) and augmented myogenic contributions (p=0.04) to the total spectrum. NOS inhibition decreased total PSD (p<0.001) for both groups, but hypertensives exhibited lower absolute endothelial (p<0.01), neurogenic (p<0.05), and total PSD (p<0.001) frequency intervals compared to normotensives. These data suggest that essential hypertension results in altered neurogenic and NOS-dependent control of skin flowmotion and support the use of spectral analysis as a non-invasive technique to study vasoreactivity. PMID:24418051

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.

The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses

PubMed Central

Garcia, Rolando A. G.; Vasudevan, Kuzhalini; Buonanno, Andres

2000-01-01

Neuregulins regulate the expression of ligand- and voltage-gated channels in neurons and skeletal muscle by the activation of their cognate tyrosine kinase receptors, ErbB 1–4. The subcellular distribution and mechanisms that regulate the localization of ErbB receptors are unknown. We have found that ErbB receptors are present in brain subcellular fractions enriched for postsynaptic densities (PSD). The ErbB-4 receptor is unique among the ErbB proteins because its C-terminal tail (T-V-V) conforms to a sequence that binds to a protein motif known as the PDZ domain. Using the yeast two-hybrid system, we found that the C-terminal region of ErbB-4 interacts with the three related membrane-associated guanylate kinases (MAGUKs) PSD-95/SAP90, PSD-93/chapsyn-110, and SAP 102, which harbor three PDZ domains, as well as with β2-syntrophin, which has a single PDZ domain. As with N-methyl-d-aspartate (NMDA) receptors, ErbB4 interacts with the first two PDZ domains of PSD-95. Using coimmunoprecipitation assays, we confirmed the direct interactions between ErbB-4 and PSD-95 in transfected heterologous cells, as well as in vivo, where both proteins are coimmunoprecipitated from brain lysates. Moreover, evidence for colocalization of these proteins was also observed by immunofluorescence in cultured hippocampal neurons. ErbB-4 colocalizes with PSD-95 and NMDA receptors at a subset of excitatory synapses apposed to synaptophysin-positive presynaptic terminals. The capacity of ErbB receptors to interact with PDZ-domain proteins at cell junctions is conserved from invertebrates to mammals. As discussed, the interactions found between receptor tyrosine kinases and MAGUKs at neuronal synapses may have important implications for activity-dependent plasticity. PMID:10725395

New generation aircraft design problems relative to turbulence stability, aeroelastic loads and gust alleviation

NASA Technical Reports Server (NTRS)

Heimbaugh, Richard M.

1987-01-01

Past history, present status, and future of discrete gusts are schematically presented. It is shown that there are two approaches to the gust analysis: discrete and spectral density. The role of these two approaches to gust analysis are discussed. The idea of using power spectral density (PSD) in the analysis of gusts is especially detailed.

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.

Radial diffusion comparing a THEMIS statistical model with geosynchronous measurements as the outer boundary

NASA Astrophysics Data System (ADS)

Li, Z.; Hudson, M. K.; Chen, Y.

2013-12-01

The outer boundary energetic electron flux is used as a driver in radial diffusion calculations, and its precise determination is critical to the solution. A new model was proposed recently based on THEMIS measurements to express the boundary flux as three fit functions of solar wind parameters in a response window, that depend on energy and which solar parameter is used: speed, density, or both (Shin and Lee, 2013). The Dartmouth radial diffusion model has been run using LANL geosynchronous satellite measurements as the outer boundary for a one-month interval in July to August 2004 and the calculated phase space density (PSD) is compared with GPS measurements at the GPS orbit (L=4.16), at magnetic equatorial plane crossings, as a test of the model. We also used the outer boundary generated from the Shin and Lee model and examined this boundary condition by computing the error relative to the simulation using a LANL geosynchronous spacecraft data-driven outer boundary. The calculation shows that there is overestimation and underestimation at different times, however the new boundary condition can be used to drive the radial diffusion model generally, producing the phase space density increase and dropout during a storm with a relatively small error. Having this new method based on a solar wind parametrized data set, we can run the radial diffusion model for storms when particle measurements are not available at the outer boundary. We chose the Whole Heliosphere Interval (WHI) as an example and compared the result with MHD/test-particle simulations (Hudson et al., 2012), obtaining much better agreement with PSD based on GPS measurements at L=4.16 using the diffusion model, which incorporates atmospheric losses.

Overexpression of cypin alters dendrite morphology, single neuron activity, and network properties via distinct mechanisms

NASA Astrophysics Data System (ADS)

Rodríguez, Ana R.; O'Neill, Kate M.; Swiatkowski, Przemyslaw; Patel, Mihir V.; Firestein, Bonnie L.

2018-02-01

Objective. This study investigates the effect that overexpression of cytosolic PSD-95 interactor (cypin), a regulator of synaptic PSD-95 protein localization and a core regulator of dendrite branching, exerts on the electrical activity of rat hippocampal neurons and networks. Approach. We cultured rat hippocampal neurons and used lipid-mediated transfection and lentiviral gene transfer to achieve high levels of cypin or cypin mutant (cypinΔPDZ PSD-95 non-binding) expression cellularly and network-wide, respectively. Main results. Our analysis revealed that although overexpression of cypin and cypinΔPDZ increase dendrite numbers and decrease spine density, cypin and cypinΔPDZ distinctly regulate neuronal activity. At the single cell level, cypin promotes decreases in bursting activity while cypinΔPDZ reduces sEPSC frequency and further decreases bursting compared to cypin. At the network level, by using the Fano factor as a measure of spike count variability, cypin overexpression results in an increase in variability of spike count, and this effect is abolished when cypin cannot bind PSD-95. This variability is also dependent on baseline activity levels and on mean spike rate over time. Finally, our spike sorting data show that overexpression of cypin results in a more complex distribution of spike waveforms and that binding to PSD-95 is essential for this complexity. Significance. Our data suggest that dendrite morphology does not play a major role in cypin action on electrical activity.

How realistic is the pore size distribution calculated from adsorption isotherms if activated carbon is composed of fullerene-like fragments?

PubMed

Terzyk, Artur P; Furmaniak, Sylwester; Harris, Peter J F; Gauden, Piotr A; Włoch, Jerzy; Kowalczyk, Piotr; Rychlicki, Gerhard

2007-11-28

A plausible model for the structure of non-graphitizing carbon is one which consists of curved, fullerene-like fragments grouped together in a random arrangement. Although this model was proposed several years ago, there have been no attempts to calculate the properties of such a structure. Here, we determine the density, pore size distribution and adsorption properties of a model porous carbon constructed from fullerene-like elements. Using the method proposed recently by Bhattacharya and Gubbins (BG), which was tested in this study for ideal and defective carbon slits, the pore size distributions (PSDs) of the initial model and two related carbon models are calculated. The obtained PSD curves show that two structures are micro-mesoporous (with different ratio of micro/mesopores) and the third is strictly microporous. Using the grand canonical Monte Carlo (GCMC) method, adsorption isotherms of Ar (87 K) are simulated for all the structures. Finally PSD curves are calculated using the Horvath-Kawazoe, non-local density functional theory (NLDFT), Nguyen and Do, and Barrett-Joyner-Halenda (BJH) approaches, and compared with those predicted by the BG method. This is the first study in which different methods of calculation of PSDs for carbons from adsorption data can be really verified, since absolute (i.e. true) PSDs are obtained using the BG method. This is also the first study reporting the results of computer simulations of adsorption on fullerene-like carbon models.

An Integrated Nonlinear Analysis library - (INA) for solar system plasma turbulence

NASA Astrophysics Data System (ADS)

Munteanu, Costel; Kovacs, Peter; Echim, Marius; Koppan, Andras

2014-05-01

We present an integrated software library dedicated to the analysis of time series recorded in space and adapted to investigate turbulence, intermittency and multifractals. The library is written in MATLAB and provides a graphical user interface (GUI) customized for the analysis of space physics data available online like: Coordinated Data Analysis Web (CDAWeb), Automated Multi Dataset Analysis system (AMDA), Planetary Science Archive (PSA), World Data Center Kyoto (WDC), Ulysses Final Archive (UFA) and Cluster Active Archive (CAA). Three main modules are already implemented in INA : the Power Spectral Density (PSD) Analysis, the Wavelet and Intemittency Analysis and the Probability Density Functions (PDF) analysis.The layered structure of the software allows the user to easily switch between different modules/methods while retaining the same time interval for the analysis. The wavelet analysis module includes algorithms to compute and analyse the PSD, the Scalogram, the Local Intermittency Measure (LIM) or the Flatness parameter. The PDF analysis module includes algorithms for computing the PDFs for a range of scales and parameters fully customizable by the user; it also computes the Flatness parameter and enables fast comparison with standard PDF profiles like, for instance, the Gaussian PDF. The library has been already tested on Cluster and Venus Express data and we will show relevant examples. Research supported by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 313038/STORM, and a grant of the Romanian Ministry of National Education, CNCS UEFISCDI, project number PN-II-ID PCE-2012-4-0418.

Remodeling of the postsynaptic plasma membrane during neural development.

PubMed

Tulodziecka, Karolina; Diaz-Rohrer, Barbara B; Farley, Madeline M; Chan, Robin B; Di Paolo, Gilbert; Levental, Kandice R; Waxham, M Neal; Levental, Ilya

2016-11-07

Neuronal synapses are the fundamental units of neural signal transduction and must maintain exquisite signal fidelity while also accommodating the plasticity that underlies learning and development. To achieve these goals, the molecular composition and spatial organization of synaptic terminals must be tightly regulated; however, little is known about the regulation of lipid composition and organization in synaptic membranes. Here we quantify the comprehensive lipidome of rat synaptic membranes during postnatal development and observe dramatic developmental lipidomic remodeling during the first 60 postnatal days, including progressive accumulation of cholesterol, plasmalogens, and sphingolipids. Further analysis of membranes associated with isolated postsynaptic densities (PSDs) suggests the PSD-associated postsynaptic plasma membrane (PSD-PM) as one specific location of synaptic remodeling. We analyze the biophysical consequences of developmental remodeling in reconstituted synaptic membranes and observe remarkably stable microdomains, with the stability of domains increasing with developmental age. We rationalize the developmental accumulation of microdomain-forming lipids in synapses by proposing a mechanism by which palmitoylation of the immobilized scaffold protein PSD-95 nucleates domains at the postsynaptic plasma membrane. These results reveal developmental changes in lipid composition and palmitoylation that facilitate the formation of postsynaptic membrane microdomains, which may serve key roles in the function of the neuronal synapse. © 2016 Tulodziecka et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Anesthesia/Surgery Induces Cognitive Impairment in Female Alzheimer's Disease Transgenic Mice.

PubMed

Zhang, Ce; Zhang, Yiying; Shen, Yuan; Zhao, Guoqing; Xie, Zhongcong; Dong, Yuanlin

2017-01-01

Anesthesia and/or surgery may promote Alzheimer's disease (AD) by accelerating its neuropathogenesis. Other studies showed different findings. However, the potential sex difference among these studies has not been well considered, and it is unknown whether male or female AD patients are more vulnerable to develop postoperative cognitive dysfunction. We therefore set out to perform a proof of concept study to determine whether anesthesia and surgery can have different effects in male and female AD transgenic (Tg) mice, and in female AD Tg plus Cyclophilin D knockout (CypD KO) mice. The mice received an abdominal surgery under sevoflurane anesthesia (anesthesia/surgery). Fear Conditioning System (FCS) was used to assess the cognitive function. Hippocampal levels of synaptic marker postsynaptic density 95 (PSD-95) and synaptophysin (SVP) were measured using western blot analysis. Here we showed that the anesthesia/surgery decreased the freezing time in context test of FCS at 7 days after the anesthesia/surgery in female, but not male, mice. The anesthesia/surgery reduced hippocampus levels of synaptic marker PSD-95 and SVP in female, but not male, mice. The anesthesia/surgery induced neither reduction in freezing time in FCS nor decreased hippocampus levels of PSD-95 and SVP in the AD Tg plus CypD KO mice. These data suggest that the anesthesia/surgery induced a sex-dependent cognitive impairment and reduction in hippocampus levels of synaptic markers in AD Tg mice, potentially via a mitochondria-associated mechanism. These findings could promote clinical investigations to determine whether female AD patients are more vulnerable to the development of postoperative cognitive dysfunction.

Unimodular sequence design under frequency hopping communication compatibility requirements

NASA Astrophysics Data System (ADS)

Ge, Peng; Cui, Guolong; Kong, Lingjiang; Yang, Jianyu

2016-12-01

The integrated design for both radar and anonymous communication has drawn more attention recently since wireless communication system appeals to enhance security and reliability. Given the frequency hopping (FH) communication system, an effective way to realize integrated design is to meet the spectrum compatibility between these two systems. The paper deals with a unimodular sequence design technique which considers optimizing both the spectrum compatibility and peak sidelobes levels (PSL) of auto-correlation function (ACF). The spectrum compatibility requirement realizes anonymous communication for the FH system and provides this system lower probability of intercept (LPI) since the spectrum of the FH system is hidden in that of the radar system. The proposed algorithm, named generalized fitting template (GFT) technique, converts the sequence optimization design problem to a iterative fitting process. In this process, the power spectrum density (PSD) and PSL behaviors of the generated sequences fit both PSD and PSL templates progressively. Two templates are established based on the spectrum compatibility requirement and the expected PSL. As noted, in order to ensure the communication security and reliability, spectrum compatibility requirement is given a higher priority to achieve in the GFT algorithm. This algorithm realizes this point by adjusting the weight adaptively between these two terms during the iteration process. The simulation results are analyzed in terms of bit error rate (BER), PSD, PSL, and signal-interference rate (SIR) for both the radar and FH systems. The performance of GFT is compared with SCAN, CAN, FRE, CYC, and MAT algorithms in the above aspects, which shows its good effectiveness.

On the Compliance of Simbol-X Mirror Roughness with its Effective Area Requirements

NASA Astrophysics Data System (ADS)

Spiga, D.; Basso, S.; Cotroneo, V.; Pareschi, G.; Tagliaferri, G.

2009-05-01

Surface microroughness of X-ray mirrors is a key issue for the angular resolution of Simbol-X to comply with the required one (<20 arcsec at 30 keV). The maximum tolerable microroughness for Simbol-X mirrors, in order to satisfy the required imaging capability, has already been derived in terms of its PSD (Power Spectral Density). However, also the Effective Area of the telescope is affected by the mirror roughness. In this work we will show how the expected effective area of the Simbol-X mirror module can be computed from the roughness PSD tolerance, checking its compliance with the requirements.

Topological characterization of antireflective and hydrophobic rough surfaces: are random process theory and fractal modeling applicable?

NASA Astrophysics Data System (ADS)

Borri, Claudia; Paggi, Marco

2015-02-01

The random process theory (RPT) has been widely applied to predict the joint probability distribution functions (PDFs) of asperity heights and curvatures of rough surfaces. A check of the predictions of RPT against the actual statistics of numerically generated random fractal surfaces and of real rough surfaces has been only partially undertaken. The present experimental and numerical study provides a deep critical comparison on this matter, providing some insight into the capabilities and limitations in applying RPT and fractal modeling to antireflective and hydrophobic rough surfaces, two important types of textured surfaces. A multi-resolution experimental campaign using a confocal profilometer with different lenses is carried out and a comprehensive software for the statistical description of rough surfaces is developed. It is found that the topology of the analyzed textured surfaces cannot be fully described according to RPT and fractal modeling. The following complexities emerge: (i) the presence of cut-offs or bi-fractality in the power-law power-spectral density (PSD) functions; (ii) a more pronounced shift of the PSD by changing resolution as compared to what was expected from fractal modeling; (iii) inaccuracy of the RPT in describing the joint PDFs of asperity heights and curvatures of textured surfaces; (iv) lack of resolution-invariance of joint PDFs of textured surfaces in case of special surface treatments, not accounted for by fractal modeling.

X-Ray Variability Characteristics of the Seyfert 1 Galaxy NGC 3783

NASA Astrophysics Data System (ADS)

Markowitz, A.

2005-12-01

We have characterized the energy-dependent X-ray variability properties of the Seyfert 1 galaxy NGC 3783 using archival XMM-Newton and Rossi X-Ray Timing Explorer data. The high-frequency fluctuation power spectral density function (PSD) slope is consistent with flattening toward higher energies. Light-curve cross-correlation functions yield no significant lags, but peak coefficients generally decrease as energy separation of the bands increases on both short and long timescales. We have measured the coherence between various X-ray bands over the temporal frequency range of 6×10-8-1×10-4 Hz; this range includes the temporal frequency of the low-frequency PSD break tentatively detected by Markowitz et al. and includes the lowest temporal frequency over which coherence has been measured in any active galactic nucleus to date. Coherence is generally near unity at these temporal frequencies, although it decreases slightly as energy separation of the bands increases. Temporal frequency-dependent phase lags are detected on short timescales; phase lags are consistent with increasing as energy separation increases or as temporal frequency decreases. All of these results are similar to those obtained previously for several Seyfert galaxies and stellar mass black hole systems. Qualitatively, these results are consistent with the variability models of Kotov et al. and Lyubarskii, wherein the X-ray variability is due to inwardly propagating variations in the local mass accretion rate.

Analyzing coastal environments by means of functional data analysis

NASA Astrophysics Data System (ADS)

Sierra, Carlos; Flor-Blanco, Germán; Ordoñez, Celestino; Flor, Germán; Gallego, José R.

2017-07-01

Here we used Functional Data Analysis (FDA) to examine particle-size distributions (PSDs) in a beach/shallow marine sedimentary environment in Gijón Bay (NW Spain). The work involved both Functional Principal Components Analysis (FPCA) and Functional Cluster Analysis (FCA). The grainsize of the sand samples was characterized by means of laser dispersion spectroscopy. Within this framework, FPCA was used as a dimension reduction technique to explore and uncover patterns in grain-size frequency curves. This procedure proved useful to describe variability in the structure of the data set. Moreover, an alternative approach, FCA, was applied to identify clusters and to interpret their spatial distribution. Results obtained with this latter technique were compared with those obtained by means of two vector approaches that combine PCA with CA (Cluster Analysis). The first method, the point density function (PDF), was employed after adapting a log-normal distribution to each PSD and resuming each of the density functions by its mean, sorting, skewness and kurtosis. The second applied a centered-log-ratio (clr) to the original data. PCA was then applied to the transformed data, and finally CA to the retained principal component scores. The study revealed functional data analysis, specifically FPCA and FCA, as a suitable alternative with considerable advantages over traditional vector analysis techniques in sedimentary geology studies.

Recovery from Unrecognized Sleep Loss Accumulated in Daily Life Improved Mood Regulation via Prefrontal Suppression of Amygdala Activity

PubMed Central

Motomura, Yuki; Kitamura, Shingo; Nakazaki, Kyoko; Oba, Kentaro; Katsunuma, Ruri; Terasawa, Yuri; Hida, Akiko; Moriguchi, Yoshiya; Mishima, Kazuo

2017-01-01

Many modern people suffer from sleep debt that has accumulated in everyday life but is not subjectively noticed [potential sleep debt (PSD)]. Our hypothesis for this study was that resolution of PSD through sleep extension optimizes mood regulation by altering the functional connectivity between the amygdala and prefrontal cortex. Fifteen healthy male participants underwent an experiment consisting of a baseline (BL) evaluation followed by two successive interventions, namely, a 9-day sleep extension followed by one night of total sleep deprivation (TSD). Tests performed before and after the interventions included a questionnaire on negative mood and neuroimaging with arterial spin labeling MRI for evaluating regional cerebral blood flow (rCBF) and functional connectivity. Negative mood and amygdala rCBF were significantly reduced after sleep extension compared with BL. The amygdala had a significant negative functional connectivity with the medial prefrontal cortex (FCamg–MPFC), and this negative connectivity was greater after sleep extension than at BL. After TSD, these indices reverted to the same level as at BL. An additional path analysis with structural equation modeling showed that the FCamg–MPFC significantly explained the amygdala rCBF and that the amygdala rCBF significantly explained the negative mood. These findings suggest that the use of our sleep extension protocol normalized amygdala activity via negative amygdala–MPFC functional connectivity. The resolution of unnoticed PSD may improve mood by enhancing frontal suppression of hyperactivity in the amygdala caused by PSD accumulating in everyday life. PMID:28713328

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.

Fractal Theory and Field Cover Experiments: Implications for the Fractal Characteristics and Radon Diffusion Behavior of Soils and Rocks.

PubMed

Tan, Wanyu; Li, Yongmei; Tan, Kaixuan; Duan, Xianzhe; Liu, Dong; Liu, Zehua

2016-12-01

Radon diffusion and transport through different media is a complex process affected by many factors. In this study, the fractal theories and field covering experiments were used to study the fractal characteristics of particle size distribution (PSD) of six kinds of geotechnical materials (e.g., waste rock, sand, laterite, kaolin, mixture of sand and laterite, and mixture of waste rock and laterite) and their effects on radon diffusion. In addition, the radon diffusion coefficient and diffusion length were calculated. Moreover, new formulas for estimating diffusion coefficient and diffusion length functional of fractal dimension d of PSD were proposed. These results demonstrate the following points: (1) the fractal dimension d of the PSD can be used to characterize the property of soils and rocks in the studies of radon diffusion behavior; (2) the diffusion coefficient and diffusion length decrease with increasing fractal dimension of PSD; and (3) the effectiveness of final covers in reducing radon exhalation of uranium tailings impoundments can be evaluated on the basis of the fractal dimension of PSD of materials.

Neuroelectrical Correlates of Trustworthiness and Dominance Judgments Related to the Observation of Political Candidates

PubMed Central

Vecchiato, Giovanni; Toppi, Jlenia; Maglione, Anton Giulio; Olejarczyk, Elzbieta; Astolfi, Laura; Mattia, Donatella; Colosimo, Alfredo; Babiloni, Fabio

2014-01-01

The present research investigates the neurophysiological activity elicited by fast observations of faces of real candidates during simulated political elections. We used simultaneous recording of electroencephalographic (EEG) signals as well as galvanic skin response (GSR) and heart rate (HR) as measurements of central and autonomic nervous systems. Twenty healthy subjects were asked to give judgments on dominance, trustworthiness, and a preference of vote related to the politicians' faces. We used high-resolution EEG techniques to map statistical differences of power spectral density (PSD) cortical activity onto a realistic head model as well as partial directed coherence (PDC) and graph theory metrics to estimate the functional connectivity networks and investigate the role of cortical regions of interest (ROIs). Behavioral results revealed that judgment of dominance trait is the most predictive of the outcome of the simulated elections. Statistical comparisons related to PSD and PDC values highlighted an asymmetry in the activation of frontal cortical areas associated with the valence of the judged trait as well as to the probability to cast the vote. Overall, our results highlight the existence of cortical EEG features which are correlated with the prediction of vote and with the judgment of trustworthy and dominant faces. PMID:25214884

New general pore size distribution model by classical thermodynamics application: Activated carbon

USGS Publications Warehouse

Lordgooei, M.; Rood, M.J.; Rostam-Abadi, M.

2001-01-01

A model is developed using classical thermodynamics to characterize pore size distributions (PSDs) of materials containing micropores and mesopores. The thermal equation of equilibrium adsorption (TEEA) is used to provide thermodynamic properties and relate the relative pore filling pressure of vapors to the characteristic pore energies of the adsorbent/adsorbate system for micropore sizes. Pore characteristic energies are calculated by averaging of interaction energies between adsorbate molecules and adsorbent pore walls as well as considering adsorbate-adsorbate interactions. A modified Kelvin equation is used to characterize mesopore sizes by considering variation of the adsorbate surface tension and by excluding the adsorbed film layer for the pore size. The modified-Kelvin equation provides similar pore filling pressures as predicted by density functional theory. Combination of these models provides a complete PSD of the adsorbent for the micropores and mesopores. The resulting PSD is compared with the PSDs from Jaroniec and Choma and Horvath and Kawazoe models as well as a first-order approximation model using Polanyi theory. The major importance of this model is its basis on classical thermodynamic properties, less simplifying assumptions in its derivation compared to other methods, and ease of use.

Understanding the ion distributions near the boundaries of reconnection outflow region

NASA Astrophysics Data System (ADS)

Zhou, X.; Pan, D.; Angelopoulos, V.; Runov, A.; Zong, Q.; Pu, Z.

2016-12-01

An interesting signature observed shortly after the onset of magnetotail reconnection is the gradual appearance of a local peak of ion phase space density (PSD) in the duskward and downstream direction separated from the colder, nearly-isotropic ion population. Such characteristic ion distributions, well reproduced by a particle-tracing Liouville simulation, are found to appear only near the off-equatorial boundaries of the reconnection outflow region. Further analysis on ion trajectories suggests that the ions at the local peak and at the neighboring PSD cleft both belong to the outflowing population; they both meander across the neutral sheet to exhibit duskward velocities near the off-equatorial boundaries of their trajectories. The difference between them is that the local peak originates from ions previously constituting the pre-onset plasma sheet, whereas the cleft corresponds to the inflowing lobe ions before they are repelled in the downstream direction. As reconnection proceeds, the local PSD peak attenuates and then disappears, which indicates the eventual depletion of thermal ions in the pre-onset plasma sheet.

The radiation belts and ring current: the relationship between Dst and relativistic electron phase space density

NASA Astrophysics Data System (ADS)

Grande, M.; Carter, M.; Perry, C. H.

2002-03-01

We briefly review the radiation belts, before moving on to a more detailed examination of the relationship between the Disturbance Storm Time Index (Dst) and relativistic electron flux. We show that there is a strong correlation between the growth phase of storms, as represented by Dst, and dropouts in electron flux. Recovery is accompanied by growth of the electron flux. We calculate Electron Phase Space Density (PSD) as a function of adiabatic invariants using electron particle mesurements from the Imaging Electron Sensor (IES) and the High Sensitivity Telescope (HIST) on the CEPPAD experiment onboard POLAR. We present the time history of the phase space density through the year 1998 as L-sorted plots and look in detail at the May 98 storm. Comparison with the Tsyganenko 96 magnetic field model prediction for the last closed field line suggests that the loss of electrons may be directly caused by the opening of drift shells.

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.

Response of the Alliance 1 Proof-of-Concept Airplane Under Gust Loads

NASA Technical Reports Server (NTRS)

Naser, A. S.; Pototzky, A. S.; Spain, C. V.

2001-01-01

This report presents the work performed by Lockheed Martin's Langley Program Office in support of NASA's Environmental Research Aircraft and Sensor Technology (ERAST) program. The primary purpose of this work was to develop and demonstrate a gust analysis method which accounts for the span-wise variation of gust velocity. This is important because these unmanned aircraft having high aspect ratios and low wing loading are very flexible, and fly at low speeds. The main focus of the work was therefore to perform a two-dimensional Power Spectrum Density (PSD) analysis of the Alliance 1 Proof-of-Concept Unmanned Aircraft, As of this writing, none of the aircraft described in this report have been constructed. They are concepts represented by analytical models. The process first involved the development of suitable structural and aeroelastic Finite Element Models (FEM). This was followed by development of a one-dimensional PSD gust analysis, and then the two-dimensional (PSD) analysis of the Alliance 1. For further validation and comparison, two additional analyses were performed. A two-dimensional PSD gust analysis was performed on a simplet MSC/NASTRAN example problem. Finally a one-dimensional discrete gust analysis was performed on Alliance 1. This report describes this process, shows the relevant comparisons between analytical methods, and discusses the physical meanings of the results.

An innovative method for the preparation of high API-loaded hollow spherical granules for use in controlled-release formulation.

PubMed

Asada, Takumi; Kobiki, Mitsuaki; Ochiai, Yasushi; Iwao, Yasunori; Itai, Shigeru

2017-05-15

The aim of this study was to prepare controlled-release (CR) granules with suitable particle strength, flowability, particle size distribution (PSD) and density characteristics for blending with other excipients. We also wanted these CR granules to contain large quantities of active pharmaceutical ingredient (API). A high shear mixer was used to mix an API with various polymers at various feed ratios, and the resulting granulated materials were sprayed with solvent. The wet granules were dried using a fluidized bed dryer to give CR granules. The API content of the granules was determined to be 95wt%. The granules were found to be spherical in shape with smooth surfaces by scanning electron microscopy. The inner structure of each granule was determined to be hollow by X-ray computed tomography, highlighting the unusual mechanism of this granulation process. The PSD of the granules was found to be dependent on that of the constituent polymer, and a narrow PSD was obtained by adjusting the PSD of the polymer. The dissolution profile of the granules was also dependent on the constituent polymer. Taken together, these results show that we have successfully developed a new manufacturing technology for the simple and low-cost preparation of ideal CR granules. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Chronic alcoholism-mediated impairment in the medulla oblongata: a mechanism of alcohol-related mortality in traumatic brain injury?

PubMed

Lai, Xiao-ping; Yu, Xiao-jun; Qian, Hong; Wei, Lai; Lv, Jun-yao; Xu, Xiao-hu

2013-01-01

Alcohol-related traumatic brain injury (TBI) is a common condition in medical and forensic practice, and results in high prehospital mortality. We investigated the mechanism of chronic alcoholism-related mortality by examining the effects of alcohol on the synapses of the medulla oblongata in a rat model of TBI. Seventy adult male Sprague-Dawley rats were randomly assigned to either ethanol (EtOH) group, EtOH-TBI group, or control groups (water group, water-TBI group). To establish chronic alcoholism model, rats in the EtOH group were given EtOH twice daily (4 g/kg for 2 weeks and 6 g/kg for another 2 weeks). The rats also received a minor strike on the occipital tuberosity with an iron pendulum. Histopathologic and ultrastructure changes and the numerical density of the synapses in the medulla oblongata were examined. Expression of postsynaptic density-95 (PSD-95) in the medulla oblongata was measured by ELISA. Compared with rats in the control group, rats in the chronic alcoholism group showed: (1) minor axonal degeneration; (2) a significant decrease in the numerical density of synapses (p < 0.01); and (3) compensatory increase in PSD-95 expression (p < 0.01). Rats in the EtOH-TBI group showed: (1) high mortality (50%, p < 0.01); (2) inhibited respiration before death; (3) severe axonal injury; and (4) decrease in PSD-95 expression (p < 0.05). Chronic alcoholism induces significant synapse loss and axonal impairment in the medulla oblongata and renders the brain more susceptible to TBI. The combined effects of chronic alcoholism and TBI induce significant synapse and axon impairment and result in high mortality.

Self-crowding of AMPA receptors in the excitatory postsynaptic density can effectuate anomalous receptor sub-diffusion.

PubMed

Gupta, Rahul

2018-02-01

AMPA receptors (AMPARs) and their associations with auxiliary transmembrane proteins are bulky structures with large steric-exclusion volumes. Hence, self-crowding of AMPARs, depending on the local density, may affect their lateral diffusion in the postsynaptic membrane as well as in the highly crowded postsynaptic density (PSD) at excitatory synapses. Earlier theoretical studies considered only the roles of transmembrane obstacles and the AMPAR-binding submembranous scaffold proteins in shaping receptor diffusion within PSD. Using lattice model of diffusion, the present study investigates the additional impacts of self-crowding on the anomalousity and effective diffusion coefficient (Deff) of AMPAR diffusion. A recursive algorithm for avoiding false self-blocking during diffusion simulation is also proposed. The findings suggest that high density of AMPARs in the obstacle-free membrane itself engenders strongly anomalous diffusion and severe decline in Deff. Adding transmembrane obstacles to the membrane accentuates the anomalousity arising from self-crowding due to the reduced free diffusion space. Contrarily, enhanced AMPAR-scaffold binding, either through increase in binding strength or scaffold density or both, ameliorates the anomalousity resulting from self-crowding. However, binding has differential impacts on Deff depending on the receptor density. Increase in binding causes consistent decrease in Deff for low and moderate receptor density. For high density, binding increases Deff as long as it reduces anomalousity associated with intense self-crowding. Given a sufficiently strong binding condition when diffusion acquires normal behavior, further increase in binding causes decrease in Deff. Supporting earlier experimental observations are mentioned and implications of present findings to the experimental observations on AMPAR diffusion are also drawn.

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.

Predictivity of Early Depressive Symptoms for Post-Stroke Depression.

PubMed

Lewin-Richter, A; Volz, M; Jöbges, M; Werheid, K

2015-08-01

Depression is a frequent complication after stroke. However, little is known about the predictive value of early self-reported depressive symptoms (DS) for later development of post-stroke depression (PSD) 6 months after discharge. Using a prospective longitudinal design, we investigated the prevalence of DS and examined their predictive value for depressive disorders 6 months after stroke while statistically controlling major established PSD risk factors. During inpatient rehabilitation, 96 stroke patients were screened for DS. After 6 months, 71 patients were attainable for a follow-up. DS was assessed using the 15-item Geriatric Depression Scale (GDS-15). At follow-up a telephone interview that included the Structured Clinical Interview for Psychiatric Disorders (SCID), which is based on DSM-IV criteria, and the GDS-15 was conducted. Patients with major depression (MD) at the follow-up were considered to have PSD. Regression analyses were conducted to examine the influence of early DS on PSD after 6 months while controlling for age, premorbid depression, and functional and cognitive impairments. The percentage of patients who scored above the GDS-15 cut-off for clinically relevant DS increased significantly, from 37% to 44%, after 6 months. According to the SCID, 27% of stroke patients fulfilled the criteria for MD, and another 16% fulfilled those for minor depression. Logistic regression showed that DS at baseline significantly predicted PSD at follow-up (odds ratio: 1.43; 95% CI: 1.15-1.8). Self-reported DS during inpatient rehabilitation are predictive for PSD 6 months after discharge. Assessment of early DS contributes to identifying stroke patients at risk for PSD, thereby facilitating prevention and treatment.

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.

Protein ubiquitination in postsynaptic densities after hypoxia in rat neostriatum is blocked by hypothermia.

PubMed

Capani, Francisco; Saraceno, Gustavo Ezequiel; Botti, Valeria; Aon-Bertolino, Laura; de Oliveira, Diêgo Madureira; Barreto, George; Galeano, Pablo; Giraldez-Alvarez, Lisandro Diego; Coirini, Héctor

2009-10-01

Synaptic dysfunction has been associated with neuronal cell death following hypoxia. The lack of knowledge on the mechanisms underlying this dysfunction prompted us to investigate the morphological changes in the postsynaptic densities (PSDs) induced by hypoxia. The results presented here demonstrate that PSDs of the rat neostriatum are highly modified and ubiquitinated 6 months after induction of hypoxia in a model of perinatal asphyxia. Using both two dimensional (2D) and three dimensional (3D) electron microscopic analyses of synapses stained with ethanolic phosphotungstic acid (E-PTA), we observed an increment of PSD thickness dependent on the duration and severity of the hypoxic insult. The PSDs showed clear signs of damage and intense staining for ubiquitin. These morphological and molecular changes were effectively blocked by hypothermia treatment, one of the most effective strategies for hypoxia-induced brain injury available today. Our data suggest that synaptic dysfunction following hypoxia may be caused by long-term misfolding and aggregation of proteins in the PSD.

Several adaptor proteins promote intracellular localisation of the transporter MRP4/ABCC4 in platelets and haematopoietic cells.

PubMed

Schaletzki, Yvonne; Kromrey, Marie-Luise; Bröderdorf, Susanne; Hammer, Elke; Grube, Markus; Hagen, Paul; Sucic, Sonja; Freissmuth, Michael; Völker, Uwe; Greinacher, Andreas; Rauch, Bernhard H; Kroemer, Heyo K; Jedlitschky, Gabriele

2017-01-05

The multidrug resistance protein 4 (MRP4/ABCC4) has been identified as an important transporter for signalling molecules including cyclic nucleotides and several lipid mediators in platelets and may thus represent a novel target to interfere with platelet function. Besides its localisation in the plasma membrane, MRP4 has been also detected in the membrane of dense granules in resting platelets. In polarised cells it is localised at the basolateral or apical plasma membrane. To date, the mechanism of MRP4 trafficking has not been elucidated; protein interactions may regulate both the localisation and function of this transporter. We approached this issue by searching for interacting proteins by in vitro binding assays, followed by immunoblotting and mass spectrometry, and by visualising their co-localisation in platelets and haematopoietic cells. We identified the PDZ domain containing scaffold proteins ezrin-binding protein 50 (EBP50/NHERF1), postsynaptic density protein 95 (PSD95), and sorting nexin 27 (SNX27), but also the adaptor protein complex 3 subunit β3A (AP3B1) and the heat shock protein HSP90 as putative interaction partners of MRP4. The knock-down of SNX27, PSD95, and AP3B1 by siRNA in megakaryoblastic leukaemia cells led to a redistribution of MRP4 from intracellular structures to the plasma membrane. Inhibition of HSP90 led to a diminished expression and retention of MRP4 in the endoplasmic reticulum. These results indicate that MRP4 localisation and function are regulated by multiple protein interactions. Changes in the adaptor proteins can hence lead to altered localisation and function of the transporter.

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

Thein, Soe; Pham, Anna; Bayer, K. Ulrich

Highlights: • CYLD is phosphorylated by IKK in isolated PSDs in the absence of Ca{sup 2+}. • CYLD is phosphorylated by IKK at the PSDs of intact neurons in basal conditions. • Phosphorylation of CYLD by IKK increases its deubiquitinase activity. • The process is likely to influence protein trafficking at the PSD in basal conditions. - Abstract: K63-linked polyubiquitination of proteins regulates their trafficking into specific cellular pathways such as endocytosis and autophagy. CYLD, a deubiquitinase specific for K63-linked polyubiquitins, is present in high quantities at the postsynaptic density (PSD). It was previously shown that, under excitatory conditions, CaMKIImore » activates CYLD in a Ca{sup 2+}-dependent manner. The observation that CYLD can also be phosphorylated in the absence of Ca{sup 2+} in isolated PSDs led us to further explore the regulation of CYLD under basal conditions. A possible involvement of the autonomous form of CaMKII and IKK, both kinases known to be localized at the PSD, was examined. A CaMKII inhibitor CN21 had no effect on CYLD phosphorylation in the absence of Ca{sup 2+}, but two different IKK inhibitors, IKK16 and tatNEMO, inhibited its phosphorylation. Immuno-electron microscopy on hippocampal cultures, using an antibody for CYLD phosphorylated at S-418, revealed that the phosphorylated form of CYLD is present at the PSD under basal conditions. Phosphorylation of CYLD under basal conditions was inhibited by IKK16. NMDA treatment further promoted phosphorylation of CYLD at the PSD, but IKK16 failed to block the NMDA-induced effect. In vitro experiments using purified proteins demonstrated direct phosphorylation and activation of CYLD by the beta catalytic subunit of IKK. Activation of IKK in isolated PSDs also promoted phosphorylation of CYLD and an increase in endogenous deubiquitinase activity for K63-linked polyubiquitins. Altogether, the results suggest that in the absence of excitatory conditions, constitutive IKK activity at the PSD regulates CYLD and maintains basal levels of K63-linkage specific deubiquitination at the synapse.« less

MICOS and phospholipid transfer by Ups2-Mdm35 organize membrane lipid synthesis in mitochondria.

PubMed

Aaltonen, Mari J; Friedman, Jonathan R; Osman, Christof; Salin, Bénédicte; di Rago, Jean-Paul; Nunnari, Jodi; Langer, Thomas; Tatsuta, Takashi

2016-06-06

Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2-Mdm35 complexes (SLMO2-TRIAP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane. Second, Psd1 decarboxylates PS in the outer membrane in trans, independently of PS transfer by Ups2-Mdm35. This latter pathway requires close apposition between both mitochondrial membranes and the mitochondrial contact site and cristae organizing system (MICOS). In MICOS-deficient cells, limiting PS transfer by Ups2-Mdm35 and reducing mitochondrial PE accumulation preserves mitochondrial respiration and cristae formation. These results link mitochondrial PE metabolism to MICOS, combining functions in protein and lipid homeostasis to preserve mitochondrial structure and function. © 2016 Aaltonen et al.

Subunit- and pathway-specific localization of NMDA receptors and scaffolding proteins at ganglion cell synapses in rat retina

PubMed Central

Zhang, Jun; Diamond, Jeffrey S.

2014-01-01

Retinal ganglion cells (RGCs) receive excitatory glutamatergic input from ON and OFF bipolar cells in distinct sublaminae of the inner plexiform layer (IPL). AMPA and NMDA receptors (AMPARs and NMDARs) mediate excitatory inputs in both synaptic layers, but specific roles for NMDARs at RGC synapses remain unclear. NMDARs comprise NR1 and NR2 subunits and are anchored by membrane associated guanylate kinases (MAGUKs), but it is unknown whether particular NR2 subunits associate preferentially with particular NR1 splice variants and MAGUKs. Here, we used postembedding immunogold electron microscopy (EM) techniques to examine the subsynaptic localization of NMDAR subunits and MAGUKs at ON and OFF synapses onto rat RGCs. We found that the NR2A subunit, the NR1C2‘ splice variant and MAGUKs PSD-95 and PSD-93 are localized to the postsynaptic density (PSD), preferentially at OFF synapses, whereas the NR2B subunit, the NR1C2 splice variant and the MAGUK SAP102 are localized perisynaptically, with NR2B exhibiting a preference for ON synapses. Consistent with these anatomical data, spontaneous EPSCs (sEPSCs) recorded from OFF cells exhibited an NMDAR component that was insensitive to the NR2B antagonist Ro 25-6981. In ON cells, sEPSCs expressed an NMDAR component, partially sensitive to Ro 25-6981, only when glutamate transport was inhibited, indicating perisynaptic expression of NR2B NMDARs. These results provide the first evidence for preferential association of particular NR1 splice variants, NR2 subunits and MAGUKs at central synapses and suggest that different NMDAR subtypes may play specific roles at functionally distinct synapses in the retinal circuitry. PMID:19339621

Fatigue assessment of vibrating rail vehicle bogie components under non-Gaussian random excitations using power spectral densities

NASA Astrophysics Data System (ADS)

Wolfsteiner, Peter; Breuer, Werner

2013-10-01

The assessment of fatigue load under random vibrations is usually based on load spectra. Typically they are computed with counting methods (e.g. Rainflow) based on a time domain signal. Alternatively methods are available (e.g. Dirlik) enabling the estimation of load spectra directly from power spectral densities (PSDs) of the corresponding time signals; the knowledge of the time signal is then not necessary. These PSD based methods have the enormous advantage that if for example the signal to assess results from a finite element method based vibration analysis, the computation time of the simulation of PSDs in the frequency domain outmatches by far the simulation of time signals in the time domain. This is especially true for random vibrations with very long signals in the time domain. The disadvantage of the PSD based simulation of vibrations and also the PSD based load spectra estimation is their limitation to Gaussian distributed time signals. Deviations from this Gaussian distribution cause relevant deviations in the estimated load spectra. In these cases usually only computation time intensive time domain calculations produce accurate results. This paper presents a method dealing with non-Gaussian signals with real statistical properties that is still able to use the efficient PSD approach with its computation time advantages. Essentially it is based on a decomposition of the non-Gaussian signal in Gaussian distributed parts. The PSDs of these rearranged signals are then used to perform usual PSD analyses. In particular, detailed methods are described for the decomposition of time signals and the derivation of PSDs and cross power spectral densities (CPSDs) from multiple real measurements without using inaccurate standard procedures. Furthermore the basic intention is to design a general and integrated method that is not just able to analyse a certain single load case for a small time interval, but to generate representative PSD and CPSD spectra replacing extensive measured loads in time domain without losing the necessary accuracy for the fatigue load results. These long measurements may even represent the whole application range of the railway vehicle. The presented work demonstrates the application of this method to railway vehicle components subjected to random vibrations caused by the wheel rail contact. Extensive measurements of axle box accelerations have been used to verify the proposed procedure for this class of railway vehicle applications. The linearity is not a real limitation, because the structural vibrations caused by the random excitations are usually small for rail vehicle applications. The impact of nonlinearities is usually covered by separate nonlinear models and only needed for the deterministic part of the loads. Linear vibration systems subjected to Gaussian vibrations respond with vibrations having also a Gaussian distribution. A non-Gaussian distribution in the excitation signal produces also a non-Gaussian response with statistical properties different from these excitations. A drawback is the fact that there is no simple mathematical relation between excitation and response concerning these deviations from the Gaussian distribution (see e.g. Ito calculus [6], which is usually not part of commercial codes!). There are a couple of well-established procedures for the prediction of fatigue load spectra from PSDs designed for Gaussian loads (see [4]); the question of the impact of non-Gaussian distributions on the fatigue load prediction has been studied for decades (see e.g. [3,4,11-13]) and is still subject of the ongoing research; e.g. [13] proposed a procedure, capable of considering non-Gaussian broadbanded loads. It is based on the knowledge of the response PSD and some statistical data, defining the non-Gaussian character of the underlying time signal. As already described above, these statistical data are usually not available for a PSD vibration response that has been calculated in the frequency domain. Summarizing the above and considering the fact of having highly non-Gaussian excitations on railway vehicles caused by the wheel rail contact means that the fast PSD analysis in the frequency domain cannot be combined with load spectra prediction methods for PSDs.

Predicting available water of soil from particle-size distribution and bulk density in an oasis-desert transect in northwestern China

NASA Astrophysics Data System (ADS)

Li, Danfeng; Gao, Guangyao; Shao, Ming'an; Fu, Bojie

2016-07-01

A detailed understanding of soil hydraulic properties, particularly the available water content of soil, (AW, cm3 cm-3), is required for optimal water management. Direct measurement of soil hydraulic properties is impractical for large scale application, but routinely available soil particle-size distribution (PSD) and bulk density can be used as proxies to develop various prediction functions. In this study, we compared the performance of the Arya and Paris (AP) model, Mohammadi and Vanclooster (MV) model, Arya and Heitman (AH) model, and Rosetta program in predicting the soil water characteristic curve (SWCC) at 34 points with experimental SWCC data in an oasis-desert transect (20 × 5 km) in the middle reaches of the Heihe River basin, northwestern China. The idea of the three models emerges from the similarity of the shapes of the PSD and SWCC. The AP model, MV model, and Rosetta program performed better in predicting the SWCC than the AH model. The AW determined from the SWCCs predicted by the MV model agreed better with the experimental values than those derived from the AP model and Rosetta program. The fine-textured soils were characterized by higher AW values, while the sandy soils had lower AW values. The MV model has the advantages of having robust physical basis, being independent of database-related parameters, and involving subclasses of texture data. These features make it promising in predicting soil water retention at regional scales, serving for the application of hydrological models and the optimization of soil water management.

The efficacy and safety of Jiedu Tongluo granules for treating post-stroke depression with qi deficiency and blood stasis syndrome: study protocol for a randomized controlled trial.

PubMed

Zhao, Ai-Mei; Qiu, Wen-Ran; Mao, Li-Jun; Ren, Jun-Guo; Xu, Li; Yao, Ming-Jiang; Bilinksi, Kellie; Chang, Dennis; Liu, Jian-Xun

2018-05-10

Post-stroke depression (PSD) is the most common psychiatric complication after a stroke. The most frequently used antidepressants are selective serotonin receptor inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), however, these exhibit a series of side effects. Traditional Chinese medicine has been used to treat PSD with few side effects. The aim of this study is to evaluate the efficacy and safety of Jiedu Tongluo granules for treating PSD with qi deficiency and blood stasis syndrome. The planned study is a double-blind, randomized, placebo-controlled pilot trial. Eighty participants will be randomly assigned to receive either treatment or placebo. The treatment group will receive Jiedu Tongluo granules (JDTLG) with conventional treatment, and the placebo group will receive placebo with conventional treatment for 8 weeks. The primary outcome is the effectiveness of JDTLG on depression after 8 weeks treatment, which is defined as a decrease of 50% or more in 17-item Hamilton Depression Scale (HAMD-17) score or clinical recovery (score < 7). Secondary outcomes are improvement in neurological function, degree of independence, activities of daily living, and TCM syndrome at each visit, which will be measured with National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Barthel Index (BI) and TCM scale, respectively. Interleukin (IL)-6, IL-8, and small-molecule metabolites will be monitored to explore the mechanism of action of JDTLG on PSD. Safety measures include vital signs, results of electrocardiography, laboratory index (full blood count, kidney and liver function tests) and adverse events. The purpose of this trial is to evaluate the therapeutic effects and safety of JDTLG in individuals with PSD with concomitant qi deficiency and blood stasis syndrome. If successful, the outcome of this trial will provide a viable treatment option for PSD patients. ClinicalTrials.gov ID: NCT03147053 . Registered on 27 April 2017.

Characterization of perovskite film prepared by pulsed laser deposition on ferritic stainless steel using microscopic and optical methods

NASA Astrophysics Data System (ADS)

Durda, E.; Jaglarz, J.; Kąc, S.; Przybylski, K.; El Kouari, Y.

2016-06-01

The perovskite La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF48) film was deposited on Crofer 22 APU ferritic stainless steel by pulsed laser deposition (PLD). Morphological studies of the sample were performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Information about film thickness and surface topography of the film and the steel substrate were obtained using following optical methods: spectroscopic ellipsometry (SE), bidirectional reflection distribution function (BRDF) and total integrated reflectometry (TIS). In particular, the BRDF study, being complementary to atomic force microscopy, yielded information about surface topography. Using the previously mentioned methods, the following statistic surface parameters were determined: root-mean square (rms) roughness and autocorrelation length by determining the power spectral density (PSD) function of surface irregularities.

Childhood leukemia and traffic air pollution in Taiwan: petrol station density as an indicator.

PubMed

Weng, Hsu-Huei; Tsai, Shang-Shyue; Chiu, Hui-Fen; Wu, Trong-Neng; Yang, Chun-Yuh

2009-01-01

To investigate the relationship between traffic air pollution exposure and development of childhood leukemia (14 yr of age or younger), a matched case-control study was conducted using childhood deaths that occurred in Taiwan from 1996 through 2006. Data on all eligible childhood leukemia deaths were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. The control group consisted of children who died from causes other than neoplasms or diseases that were not associated with respiratory complications. The controls were pair matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on the number of petrol stations in study municipalities were collected from the two major petroleum supply companies, Chinese Petroleum Corporation (CPC) and Formosa Petrochemical Corporation (FPCC). The petrol station density (per square kilometer) (PSD) for study municipalities was used as an indicator of a subject's exposure to benzene and other hydrocarbons present in evaporative losses of petrol or to air emissions from motor vehicles. The subjects were divided into tertiles according to PSD in their residential municipality. The results showed that there was a significant exposure-response relationship between PSD and the risk of leukemia development in young children after controlling for possible confounders. The findings of this study warrant further investigation of the role of traffic air pollution exposure in the etiology of childhood leukemia.

Characteristics and mechanism of deep mesoscale variability south of the Kuroshio Extension

NASA Astrophysics Data System (ADS)

Miyamoto, Masatoshi; Oka, Eitarou; Yanagimoto, Daigo; Fujio, Shinzou; Mizuta, Genta; Imawaki, Shiro; Kurogi, Masao; Hasumi, Hiroyasu

2017-05-01

To clarify the characteristics and mechanism of mesoscale variability in the deep ocean, we analyzed historical mooring observations conducted at Site R (30°N, 147°E) south of the Kuroshio Extension during 1978-85 and the 10-year output of an eddy-resolving ocean general circulation model. The power spectral density (PSD) of current velocity at a depth of 5000 m had a peak at periods of 45-75 days at two mooring stations that were zonally 98 km apart and at 54 days at Site R in the model. In the model, the PSD at 54 days at 5000 m had a horizontal maximum 100 km north of Site R as well as in the Kuroshio Extension region 500 km north of Site R. Within the high-PSD region near Site R, variability in the velocity was coherent, and its phase propagation was characterized by zonal and meridional wavenumbers of -2.9×10-5 and 0.1×10-5 rad m-1, respectively, the former of which was comparable to the value of -2.6×10-5 rad m-1 obtained from the mooring observations. Such wavenumbers matched well with the dispersion relation of barotropic topographic Rossby waves (TRWs). Backward ray tracing and PSD distribution suggested that the barotropic TRWs at Site R were generated in the Kuroshio Extension region, and their energy propagated southward.

Line-width roughness of advanced semiconductor features by using FIB and planar-TEM as reference metrology

NASA Astrophysics Data System (ADS)

Takamasu, Kiyoshi; Takahashi, Satoru; Kawada, Hiroki; Ikota, Masami

2018-03-01

LER (Line Edge Roughness) and LWR (Line Width Roughness) of the semiconductor device are an important evaluation scale of the performance of the device. Conventionally, LER and LWR is evaluated from CD-SEM (Critical Dimension Scanning Electron Microscope) images. However, CD-SEM measurement has a problem that high frequency random noise is large, and resolution is not sufficiently high. For random noise of CD-SEM measurement, some techniques are proposed. In these methods, it is necessary to set parameters for model and processing, and it is necessary to verify the correctness of these parameters using reference metrology. We have already proposed a novel reference metrology using FIB (Focused Ion Beam) process and planar-TEM (Transmission Electron Microscope) method. In this study, we applied the proposed method to three new samples such as SAQP (Self-Aligned Quadruple Patterning) FinFET device, EUV (Extreme Ultraviolet Lithography) conventional resist, and EUV new material resist. LWR and PSD (Power Spectral Density) of LWR are calculated from the edge positions on planar-TEM images. We confirmed that LWR and PSD of LWR can be measured with high accuracy and evaluated the difference by the proposed method. Furthermore, from comparisons with PSD of the same sample by CD-SEM, the validity of measurement of PSD and LWR by CD-SEM can be verified.

Experimental Structural Dynamic Response of Plate Specimens Due to Sonic Loads in a Progressive Wave Tube

NASA Technical Reports Server (NTRS)

Betts, Juan F.

2001-01-01

The objective of the current study was to assess the repeatability of experiments at NASA Langley's Thermal Acoustic Fatigue Apparatus (TAFA) facility and to use these experiments to validate numerical models. Experiments show that power spectral density (PSD) curves were repeatable except at the resonant frequencies, which tended to vary between 5 Hz to 15 Hz. Results show that the thinner specimen had more variability in the resonant frequency location than the thicker sample, especially for modes higher than the first mode in the frequency range. Root Mean Square (RMS) tended to be more repeatable. The RMS behaved linearly through the SPL range of 135 to 153 dB. Standard Deviations (STDs) of the results tended to be relatively low constant up to about 147 dB. The RMS results were more repeatable than the PDS results. The STD results were less than 10% of the RMS results for both the 0.125 in (0.318 cm) and 0.062 in (0.1588 cm) thick plate. The STD of the PSD results were around 20% to 100% of the mean PSD results for non-resonant and resonant frequencies, respectively, for the 0.125 in (0.318 cm) thicker plate and between 25% to 125% of the mean PSD results, for nonresonant and resonant frequencies, respectively, for the thinner plate.

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

Isobe, Naoki; Sato, Ryosuke; Ueda, Yoshihiro

The archetypical very-high-energy γ-ray blazar Mrk 421 was monitored for more than three years with the Gas Slit Camera on board Monitor of All Sky X-ray Image (MAXI), and its long-term X-ray variability was investigated. The MAXI light curve in the 3-10 keV range was transformed into the periodogram in the frequency range f = 1 × 10{sup –8}-2 × 10{sup –6} Hz. The artifacts on the periodogram, resulting from data gaps in the observed light curve, were extensively simulated for variations with a power-law-like power spectrum density (PSD). By comparing the observed and simulated periodograms, the PSD index wasmore » evaluated as α = 1.60 ± 0.25. This index is smaller than that obtained in the higher-frequency range (f ≳ 1 × 10{sup –5} Hz), namely, α = 2.14 ± 0.06 in the 1998 ASCA observation of the object. The MAXI data impose a lower limit on the PSD break at f {sub b} = 5 × 10{sup –6} Hz, consistent with the break of f {sub b} = 9.5 × 10{sup –6} Hz suggested from the ASCA data. The low-frequency PSD index of Mrk 421 derived with MAXI falls well within the range of typical values among nearby Seyfert galaxies (α = 1-2). The physical implications from these results are briefly discussed.« less

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.

Advanced Microwave Radiometer (AMR) for SWOT mission

NASA Astrophysics Data System (ADS)

Chae, C. S.

2015-12-01

The objective of the SWOT (Surface Water & Ocean Topography) satellite mission is to measure wide-swath, high resolution ocean topography and terrestrial surface waters. Since main payload radar will use interferometric SAR technology, conventional microwave radiometer system which has single nadir look antenna beam (i.e., OSTM/Jason-2 AMR) is not ideally applicable for the mission for wet tropospheric delay correction. Therefore, SWOT AMR incorporates two antenna beams along cross track direction. In addition to the cross track design of the AMR radiometer, wet tropospheric error requirement is expressed in space frequency domain (in the sense of cy/km), in other words, power spectral density (PSD). Thus, instrument error allocation and design are being done in PSD which are not conventional approaches for microwave radiometer requirement allocation and design. A few of novel analyses include: 1. The effects of antenna beam size to PSD error and land/ocean contamination, 2. Receiver error allocation and the contributions of radiometric count averaging, NEDT, Gain variation, etc. 3. Effect of thermal design in the frequency domain. In the presentation, detailed AMR design and analyses results will be discussed.

Scale factor and noise performance tests of the Bendix Corporation Rate Gyro Assembly (RGA)

NASA Astrophysics Data System (ADS)

Kim, R.; Hoffman, J.

1980-08-01

Three Bendix Corporation gyroscopes in a Rate Gyro Assembly (RGA) were tested at the Central Inertial Guidance Test Facility (CIGTF), 6585th Test Group, Holloman Air Force Base, New Mexico, from 29 May through 19 June 1980, for the National Aeronautics and Space Administration (NASA), Marshall Space Flight Center (MSFC), Huntsville, Alabama. The purpose of the tests was to characterize the noise performance of each gyro in the RGA in the frequency range of 0.01 hertz to 20 hertz. Gyro noise performance was then compared with seismic activity and previous results from Bendix Corporation testing. Eight-point tests were performed to obtain scale factors which were used to scale the Power Spectral Density (PSD) data. The PSD test series consisted of 1, 2.5, 5, 40 and 180 minute tests under various operating conditions (wheels on and off, low and high rate modes, and horizontal and vertical output axis orientations). The data are presented as PSD plots in the frequency domain. These results show a negligible seismic contribution and are comparable with data obtained at the Bendix test facility.

Non-Stationarity and Power Spectral Shifts in EMG Activity Reflect Motor Unit Recruitment in Rat Diaphragm Muscle

PubMed Central

Seven, Yasin B.; Mantilla, Carlos B.; Zhan, Wen-Zhi; Sieck, Gary C.

2012-01-01

We hypothesized that diaphragm muscle (DIAm) by a shift in the EMG power spectral density (PSD) to higher frequencies reflects recruitment of more fatigable fast-twitch motor units and motor unit recruitment is reflected by EMG non-stationarity. DIAm EMG was recorded in anesthetized rats during eupnea, hypoxia-hypercapnia (10% O2-5% CO2), airway occlusion, and sneezing (maximal DIAm force). Although power in all frequency bands increased progressively across motor behaviors, PSD centroid frequency increased only during sneezing (p<0.05). The non-stationary period at the onset of EMG activity ranged from ~70 ms during airway occlusion to ~150 ms during eupnea. Within the initial non-stationary period of EMG activity 80–95% of motor units were recruited during different motor behaviors. Motor units augmented their discharge frequencies progressively beyond the non-stationary period; yet, EMG signal became stationary. In conclusion, non-stationarity of DIAm EMG reflects the period of motor unit recruitment, while a shift in the PSD towards higher frequencies reflects recruitment of more fatigable fast-twitch motor units. PMID:22986086

Structure of the PSD-95/MAP1A complex reveals a unique target recognition mode of the MAGUK GK domain.

PubMed

Xia, Yitian; Shang, Yuan; Zhang, Rongguang; Zhu, Jinwei

2017-08-10

The PSD-95 family of membrane-associated guanylate kinases (MAGUKs) are major synaptic scaffold proteins and play crucial roles in the dynamic regulation of dendritic remodelling, which is understood to be the foundation of synaptogenesis and synaptic plasticity. The guanylate kinase (GK) domain of MAGUK family proteins functions as a phosphor-peptide binding module. However, the GK domain of PSD-95 has been found to directly bind to a peptide sequence within the C-terminal region of neuronal-specific microtubule-associated protein 1A (MAP1A), although the detailed molecular mechanism governing this phosphorylation-independent interaction at the atomic level is missing. In the present study, we determine the crystal structure of PSD-95 GK in complex with the MAP1A peptide at 2.6-Å resolution. The complex structure reveals that, unlike a linear and elongated conformation in the phosphor-peptide/GK complexes, the MAP1A peptide adopts a unique conformation with a stretch of hydrophobic residues far from each other in the primary sequence clustering and interacting with the 'hydrophobic site' of PSD-95 GK and a highly conserved aspartic acid of MAP1A (D2117) mimicking the phosphor-serine/threonine in binding to the 'phosphor-site' of PSD-95 GK. We demonstrate that the MAP1A peptide may undergo a conformational transition upon binding to PSD-95 GK. Further structural comparison of known DLG GK-mediated complexes reveals the target recognition specificity and versatility of DLG GKs. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

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.

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

Ultrastructure of Dendritic Spines: Correlation Between Synaptic and Spine Morphologies

PubMed Central

Arellano, Jon I.; Benavides-Piccione, Ruth; DeFelipe, Javier; Yuste, Rafael

2007-01-01

Dendritic spines are critical elements of cortical circuits, since they establish most excitatory synapses. Recent studies have reported correlations between morphological and functional parameters of spines. Specifically, the spine head volume is correlated with the area of the postsynaptic density (PSD), the number of postsynaptic receptors and the ready-releasable pool of transmitter, whereas the length of the spine neck is proportional to the degree of biochemical and electrical isolation of the spine from its parent dendrite. Therefore, the morphology of a spine could determine its synaptic strength and learning rules. To better understand the natural variability of neocortical spine morphologies, we used a combination of gold-toned Golgi impregnations and serial thin-section electron microscopy and performed three-dimensional reconstructions of spines from layer 2/3 pyramidal cells from mouse visual cortex. We characterized the structure and synaptic features of 144 completed reconstructed spines, and analyzed their morphologies according to their positions. For all morphological parameters analyzed, spines exhibited a continuum of variability, without clearly distinguishable subtypes of spines or clear dependence of their morphologies on their distance to the soma. On average, the spine head volume was correlated strongly with PSD area and weakly with neck diameter, but not with neck length. The large morphological diversity suggests an equally large variability of synaptic strength and learning rules. PMID:18982124

Pitch Angle Dependence of Drift Resonant Ions Observed by the Van Allen Probes

NASA Astrophysics Data System (ADS)

Rankin, R.; Wang, C.; Wang, Y.; Zong, Q. G.; Zhou, X.

2017-12-01

Acceleration and modulation of ring current ions by poloidal mode ULF waves is investigated. A simplified MHD model of ULF waves in a dipole magnetic field is presented that includes phase mixing to perpendicular scales determined by the ionospheric Pedersen conductivity. The wave model is combined with a full Lorentz force test particle code to study drift and drift bounce resonance wave-particle interactions. Ion trajectories are traced backward-in-time to an assumed form of the distribution function, and Liouville's method is used to reconstruct the phase space density response (PSD) poloidal mode waves observed by the Van Allen Probes. In spite of its apparent simplicity, simulations using the wave and test particle models are able to explain the acceleration of ions and energy dispersion observed by the Van Allen Probes. The paper focuses on the pitch angle evolution of the initial PSD as it responds to the action of ULF waves. An interesting aspect of the study is the formation of butterfly ion distributions as ions make periodic radial oscillations across L. Ions become trapped in an effective potential well across a limited range of L and follow trajectories that cause them to surf along constant phase fronts. The impications of this new trapping mechanism for both ions and electrons is discussed.

An XMM-Newton Study of the Bright Narrow-Line Seyfert 1 Galaxy Arakelian 564

NASA Technical Reports Server (NTRS)

Brandt, Niel

2004-01-01

We report on two XMM-Newton observations of the bright Narrow-Line Seyfert 1 galaxy Ark 564 taken one year apart (2000 June and 2001 June). The 0.6-10 keV continuum is well described by a soft blackbody component (kT - 140-150 eV) plus a steep power law (Gamma - 2.50-2.55). No significant spectral changes are observed between the two observations, although the X-ray flux in the second observation is - 40-50 per cent lower. In both observations we detect a significant absorption edge at a rest-frame energy of - 0.73 keV, corresponding to 0 VII. The presence of the absorption feature is confirmed by a simultaneous Chandra grating observation in 2000 June, although the best-fitting edge threshold is at a slightly lower energy in the Chandra data, possibly because of a different parameterization of the underlying X-ray continuum. We find tentative evidence for a broad iron emission line in the 2000 June observation. The results from an analysis of the power spectral density (PSD) function are also presented. The present XMM-Newton data support the idea that the PSD shows two breaks, although the location of the high-frequency break requires further constraints.

Arakelian 564: An XMM-Newton View

NASA Technical Reports Server (NTRS)

Vignali, Cristian; Brandt, W. N.; Boller, Th.; Fabian, A. C.; Vaughan, Simon

2003-01-01

We report on two XMM-Newton observations of the bright narrow-line Seyfert 1 galaxy Ark 564 taken one year apart (2000 June and 2001 June). The 0.6-10 keV continuum is well described by a soft blackbody component (kTau approximately equal 140-150 eV) plus a steep power law (Tau approximately equal to 2.50-2.55). No significant spectral changes are observed between the two observations, although the X-ray flux in the second observation is approximately equal to 40-50 per cent lower. In both observations we detect a significant absorption edge at a rest-frame energy of approximately equal to 0.73 keV, corresponding to O VII. The presence of the absorption feature is confirmed by a simultaneous Chandra grating observation in 2000 June, although the best-fitting edge threshold is at a slightly lower energy in the Chandra data, possibly because of a different parameterization of the underlying X-ray continuum. We find tentative evidence for a broad iron emission line in the 2000 June observation. The results from an analysis of the power spectral density (PSD) function are also presented. The present XMM-Newton data support the idea that the PSD shown two breads, although the location of the high-frequency break requires further constraints.

The NR1-4 C-terminus interferes with N-methyl-D-aspartate receptor-mediated excitotoxicity: evidence against a typical T/SXV-PDZ interaction.

PubMed

Mattar, P A; Holmes, K D; Dekaban, G A

2005-01-01

The N-methyl-D-aspartate receptor (NMDAR) plays a key role in the neural plasticity that underlies learning and memory in vivo. The plasticity exhibited by NMDARs may also contribute to disease pathogenesis, as a number of disorders are caused or exacerbated by exaggerated NMDAR activity. The NMDAR is composed of two obligatory types of subunits, NR1 and NR2. These transmembrane proteins include large intracellular C-termini that have yet to be fully characterized. We have developed a three-color fluorescence system in order to visualize NMDAR expression in living cells. Using excitotoxicity as a proxy for exaggerated NMDAR activity, we analyzed the effect of over-expressing NR1-4 and NR2A C-terminal domains on exaggerated NMDAR function. We demonstrate that a determinant within the C-terminal domain of NR1-4 (C02') is important for NMDAR excitotoxicity, whereas no novel determinants were identified in the NR2A C-terminus. Through the use of heterologous cells, and by examining the interaction between the prototypical NMDAR-binding partner postsynaptic density-95 (PSD-95), we show that this effect is unlikely to be mediated through a classical interaction with PSD-95.

Jet flow issuing from an axisymmetric pipe-cavity-orifice nozzle

NASA Astrophysics Data System (ADS)

Broučková, Zuzana; Pušková, Pavlína; Trávníček, Zdeněk; Šafařík, Pavel

2016-03-01

An axisymmetric air jet flow is experimentally investigated under passive flow control. The jet issues from a pipe of the inner diameter and length of 10 mm and 150 mm which is equipped with an axisymmetric cavity at the pipe end. The cavity operates as a resonator creating self-sustained acoustic excitations of the jet flow. A mechanism of excitations is rather complex - in comparison with a common Helmholtz resonator. The experiments were performed using flow visualization, microphone measurements and time-mean velocity measurements by the Pitot probe. The power spectral density (PSD) and the sound pressure level (SPL) were evaluated from microphone measurements. The jet Reynolds number ranged Re = 1600-18 000. Distinguishable peaks in PSD indicated a function of the resonator. Because the most effective acoustic response was found at higher Re, a majority of experiments focused on higher Re regime. The results demonstrate effects of the passive control on the jet behavior. Fluid mixing and velocity decay along the axis is intensified. It causes shortening of the jet transition region. On the other hand, an inverse proportionality of the velocity decay (u ~ 1/x) in the fully developed region is not changed. The momentum and kinetic energy fluxes decrease more intensively in the controlled jets in comparison with common jets.

Interference tables: a useful model for interference analysis in asynchronous multicarrier transmission

NASA Astrophysics Data System (ADS)

Medjahdi, Yahia; Terré, Michel; Ruyet, Didier Le; Roviras, Daniel

2014-12-01

In this paper, we investigate the impact of timing asynchronism on the performance of multicarrier techniques in a spectrum coexistence context. Two multicarrier schemes are considered: cyclic prefix-based orthogonal frequency division multiplexing (CP-OFDM) with a rectangular pulse shape and filter bank-based multicarrier (FBMC) with physical layer for dynamic spectrum access and cognitive radio (PHYDYAS) and isotropic orthogonal transform algorithm (IOTA) waveforms. First, we present the general concept of the so-called power spectral density (PSD)-based interference tables which are commonly used for multicarrier interference characterization in spectrum sharing context. After highlighting the limits of this approach, we propose a new family of interference tables called `instantaneous interference tables'. The proposed tables give the interference power caused by a given interfering subcarrier on a victim one, not only as a function of the spectral distance separating both subcarriers but also with respect to the timing misalignment between the subcarrier holders. In contrast to the PSD-based interference tables, the accuracy of the proposed tables has been validated through different simulation results. Furthermore, due to the better frequency localization of both PHYDYAS and IOTA waveforms, FBMC technique is demonstrated to be more robust to timing asynchronism compared to OFDM one. Such a result makes FBMC a potential candidate for the physical layer of future cognitive radio systems.

Self-crowding of AMPA receptors in the excitatory postsynaptic density can effectuate anomalous receptor sub-diffusion

PubMed Central

Gupta, Rahul

2018-01-01

AMPA receptors (AMPARs) and their associations with auxiliary transmembrane proteins are bulky structures with large steric-exclusion volumes. Hence, self-crowding of AMPARs, depending on the local density, may affect their lateral diffusion in the postsynaptic membrane as well as in the highly crowded postsynaptic density (PSD) at excitatory synapses. Earlier theoretical studies considered only the roles of transmembrane obstacles and the AMPAR-binding submembranous scaffold proteins in shaping receptor diffusion within PSD. Using lattice model of diffusion, the present study investigates the additional impacts of self-crowding on the anomalousity and effective diffusion coefficient (Deff) of AMPAR diffusion. A recursive algorithm for avoiding false self-blocking during diffusion simulation is also proposed. The findings suggest that high density of AMPARs in the obstacle-free membrane itself engenders strongly anomalous diffusion and severe decline in Deff. Adding transmembrane obstacles to the membrane accentuates the anomalousity arising from self-crowding due to the reduced free diffusion space. Contrarily, enhanced AMPAR-scaffold binding, either through increase in binding strength or scaffold density or both, ameliorates the anomalousity resulting from self-crowding. However, binding has differential impacts on Deff depending on the receptor density. Increase in binding causes consistent decrease in Deff for low and moderate receptor density. For high density, binding increases Deff as long as it reduces anomalousity associated with intense self-crowding. Given a sufficiently strong binding condition when diffusion acquires normal behavior, further increase in binding causes decrease in Deff. Supporting earlier experimental observations are mentioned and implications of present findings to the experimental observations on AMPAR diffusion are also drawn. PMID:29444074

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...

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...

When can Empirical Green Functions be computed from Noise Cross-Correlations? Hints from different Geographical and Tectonic environments

NASA Astrophysics Data System (ADS)

Matos, Catarina; Silveira, Graça; Custódio, Susana; Domingues, Ana; Dias, Nuno; Fonseca, João F. B.; Matias, Luís; Krueger, Frank; Carrilho, Fernando

2014-05-01

Noise cross-correlations are now widely used to extract Green functions between station pairs. But, do all the cross-correlations routinely computed produce successful Green Functions? What is the relationship between noise recorded in a couple of stations and the cross-correlation between them? During the last decade, we have been involved in the deployment of several temporary dense broadband (BB) networks within the scope of both national projects and international collaborations. From 2000 to 2002, a pool of 8 BB stations continuously operated in the Azores in the scope of the Memorandum of Understanding COSEA (COordinated Seismic Experiment in the Azores). Thanks to the Project WILAS (West Iberia Lithosphere and Astenosphere Structure, PTDC/CTE-GIX/097946/2008) we temporarily increased the number of BB deployed in mainland Portugal to more than 50 (permanent + temporary) during the period 2010 - 2012. In 2011/12 a temporary pool of 12 seismometers continuously recorded BB data in the Madeira archipelago, as part of the DOCTAR (Deep Ocean Test Array Experiment) project. Project CV-PLUME (Investigation on the geometry and deep signature of the Cape Verde mantle plume, PTDC/CTE-GIN/64330/2006) covered the archipelago of Cape Verde, North Atlantic, with 40 temporary BB stations in 2007/08. Project MOZART (Mozambique African Rift Tomography, PTDC/CTE-GIX/103249/2008), covered Mozambique, East Africa, with 30 temporary BB stations in the period 2011 - 2013. These networks, located in very distinct geographical and tectonic environments, offer an interesting opportunity to study seasonal and spatial variations of noise sources and their impact on Empirical Green functions computed from noise cross-correlation. Seismic noise recorded at different seismic stations is evaluated by computation of the probability density functions of power spectral density (PSD) of continuous data. To assess seasonal variations of ambient noise sources in frequency content, time-series of PSD at different frequency bands have been computed. The influence of the spatial and seasonal variation is evaluated by analysis of the one-day length cross-correlations, stacked with a 30-day moving window and with an overlap of 30 days. To inspect the effects of frequency content variations, 30-day cross-correlograms have also been computed at different frequency bands. This work is supported by project QuakeLoc-PT (PTDC/GEO-FIQ/3522/2012) and a contribution to project AQUAREL (PTDC/CTE-GIX/116819/2010).

Correlation between Visual Field Index and Other Functional and Structural Measures in Glaucoma Patients and Suspects.

PubMed

Iutaka, Natalia A; Grochowski, Rubens A; Kasahara, Niro

2017-01-01

To evaluate the correlation between visual field index (VFI) and both structural and functional measures of the optic disc in primary open angle glaucoma patients and suspects. In this retrospective study, 162 glaucoma patients and suspects underwent standard automated perimetry (SAP), retinography, and retinal nerve fiber layer (RNFL) measurement. The optic disc was stratified according to the vertical cup/disc ratio (C/D) and sorted by the disc damage likelihood scale (DDLS). RNFL was measured with the optical coherence tomography. The VFI perimetry was correlated with the mean deviation (MD) and pattern standard deviation (PSD) obtained by SAP, and structural parameters by Pearson's correlation coefficients. VFI displayed strong correlation with MD ( R = 0.959) and PSD ( R = -0.744). The linear correlations between VFI and structural measures including C/D ( R = -0.179, P = 0.012), DDLS ( R = -0.214, P = 0.006), and RNFL ( R = 0.416, P < 0.001) were weak but statistically significant. VFI showed a strong correlation with MD and PSD but demonstrated a weak correlation with structural measures. It can possibly be used as a marker for functional impairment severity in patients with glaucoma.

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

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.

Modal parameter identification based on combining transmissibility functions and blind source separation techniques

NASA Astrophysics Data System (ADS)

Araújo, Iván Gómez; Sánchez, Jesús Antonio García; Andersen, Palle

2018-05-01

Transmissibility-based operational modal analysis is a recent and alternative approach used to identify the modal parameters of structures under operational conditions. This approach is advantageous compared with traditional operational modal analysis because it does not make any assumptions about the excitation spectrum (i.e., white noise with a flat spectrum). However, common methodologies do not include a procedure to extract closely spaced modes with low signal-to-noise ratios. This issue is relevant when considering that engineering structures generally have closely spaced modes and that their measured responses present high levels of noise. Therefore, to overcome these problems, a new combined method for modal parameter identification is proposed in this work. The proposed method combines blind source separation (BSS) techniques and transmissibility-based methods. Here, BSS techniques were used to recover source signals, and transmissibility-based methods were applied to estimate modal information from the recovered source signals. To achieve this combination, a new method to define a transmissibility function was proposed. The suggested transmissibility function is based on the relationship between the power spectral density (PSD) of mixed signals and the PSD of signals from a single source. The numerical responses of a truss structure with high levels of added noise and very closely spaced modes were processed using the proposed combined method to evaluate its ability to identify modal parameters in these conditions. Colored and white noise excitations were used for the numerical example. The proposed combined method was also used to evaluate the modal parameters of an experimental test on a structure containing closely spaced modes. The results showed that the proposed combined method is capable of identifying very closely spaced modes in the presence of noise and, thus, may be potentially applied to improve the identification of damping ratios.

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.

47 CFR 51.231 - Provision of information on advanced services deployment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... rejection; and (3) Information with respect to the number of loops using advanced services technology within... incumbent LEC information on the type of technology that the requesting carrier seeks to deploy. (1) Where... spectral density (PSD) mask, it also must provide Spectrum Class information for the technology. (2) Where...

Understanding the mechanisms of radiation belt dropouts observed by Van Allen Probes

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

Xiang, Zheng; Tu, Weichao; Li, Xinlin

To achieve a better understanding of the dominant loss mechanisms for the rapid dropouts of radiation belt electrons, three distinct radiation belt dropout events observed by Van Allen Probes are comprehensively investigated. For each event, observations of the pitch angle distribution of electron fluxes and electromagnetic ion cyclotron (EMIC) waves are analyzed to determine the effects of atmospheric precipitation loss due to pitch angle scattering induced by EMIC waves. Last closed drift shells (LCDS) and magnetopause standoff position are obtained to evaluate the effects of magnetopause shadowing loss. Evolution of electron phase space density (PSD) versus L* profiles and themore » μ and K (first and second adiabatic invariants) dependence of the electron PSD drops are calculated to further analyze the dominant loss mechanisms at different L*. Here, our findings suggest that these radiation belt dropouts can be classified into distinct classes in terms of dominant loss mechanisms: magnetopause shadowing dominant, EMIC wave scattering dominant, and combination of both mechanisms. Different from previous understanding, our results show that magnetopause shadowing can deplete electrons at L* < 4, while EMIC waves can efficiently scatter electrons at L* > 4. Compared to the magnetopause standoff position, it is more reliable to use LCDS to evaluate the impact of magnetopause shadowing. Finally, the evolution of electron PSD versus L* profile and the μ, K dependence of electron PSD drops can provide critical and credible clues regarding the mechanisms responsible for electron losses at different L* over the outer radiation belt.« less

Understanding the Mechanisms of Radiation Belt Dropouts Observed by Van Allen Probes

NASA Astrophysics Data System (ADS)

Xiang, Zheng; Tu, Weichao; Li, Xinlin; Ni, Binbin; Morley, S. K.; Baker, D. N.

2017-10-01

To achieve a better understanding of the dominant loss mechanisms for the rapid dropouts of radiation belt electrons, three distinct radiation belt dropout events observed by Van Allen Probes are comprehensively investigated. For each event, observations of the pitch angle distribution of electron fluxes and electromagnetic ion cyclotron (EMIC) waves are analyzed to determine the effects of atmospheric precipitation loss due to pitch angle scattering induced by EMIC waves. Last closed drift shells (LCDS) and magnetopause standoff position are obtained to evaluate the effects of magnetopause shadowing loss. Evolution of electron phase space density (PSD) versus L* profiles and the μ and K (first and second adiabatic invariants) dependence of the electron PSD drops are calculated to further analyze the dominant loss mechanisms at different L*. Our findings suggest that these radiation belt dropouts can be classified into distinct classes in terms of dominant loss mechanisms: magnetopause shadowing dominant, EMIC wave scattering dominant, and combination of both mechanisms. Different from previous understanding, our results show that magnetopause shadowing can deplete electrons at L* < 4, while EMIC waves can efficiently scatter electrons at L* > 4. Compared to the magnetopause standoff position, it is more reliable to use LCDS to evaluate the impact of magnetopause shadowing. The evolution of electron PSD versus L* profile and the μ, K dependence of electron PSD drops can provide critical and credible clues regarding the mechanisms responsible for electron losses at different L* over the outer radiation belt.

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.

Understanding the mechanisms of radiation belt dropouts observed by Van Allen Probes

DOE PAGES

Xiang, Zheng; Tu, Weichao; Li, Xinlin; ...

2017-08-30

To achieve a better understanding of the dominant loss mechanisms for the rapid dropouts of radiation belt electrons, three distinct radiation belt dropout events observed by Van Allen Probes are comprehensively investigated. For each event, observations of the pitch angle distribution of electron fluxes and electromagnetic ion cyclotron (EMIC) waves are analyzed to determine the effects of atmospheric precipitation loss due to pitch angle scattering induced by EMIC waves. Last closed drift shells (LCDS) and magnetopause standoff position are obtained to evaluate the effects of magnetopause shadowing loss. Evolution of electron phase space density (PSD) versus L* profiles and themore » μ and K (first and second adiabatic invariants) dependence of the electron PSD drops are calculated to further analyze the dominant loss mechanisms at different L*. Here, our findings suggest that these radiation belt dropouts can be classified into distinct classes in terms of dominant loss mechanisms: magnetopause shadowing dominant, EMIC wave scattering dominant, and combination of both mechanisms. Different from previous understanding, our results show that magnetopause shadowing can deplete electrons at L* < 4, while EMIC waves can efficiently scatter electrons at L* > 4. Compared to the magnetopause standoff position, it is more reliable to use LCDS to evaluate the impact of magnetopause shadowing. Finally, the evolution of electron PSD versus L* profile and the μ, K dependence of electron PSD drops can provide critical and credible clues regarding the mechanisms responsible for electron losses at different L* over the outer radiation belt.« less

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

Effects of the dimeric PSD-95 inhibitor UCCB01-144 on functional recovery after fimbria-fornix transection in rats.

PubMed

Sommer, Jens Bak; Bach, Anders; Malá, Hana; Strømgaard, Kristian; Mogensen, Jesper; Pickering, Darryl S

2017-10-01

Pharmacological inhibition of PSD-95 is a promising therapeutic strategy in the treatment of stroke, and positive effects of monomeric and dimeric PSD-95 inhibitors have been reported in numerous studies. However, whether therapeutic effects will generalize to other types of acute brain injury such as traumatic brain injury (TBI), which has pathophysiological mechanisms in common with stroke, is currently uncertain. We have previously found a lack of neuroprotective effects of dimeric PSD-95 inhibitors in the controlled cortical impact model of TBI in rats. However, as no single animal model is currently able to mimic the complex and heterogeneous pathophysiology of TBI, it is necessary to assess treatment effects across a range of models. In this preliminary study we investigated the neuroprotective abilities of the dimeric PSD-95 inhibitor UCCB01-144 after fimbria-fornix (FF) transection in rats. UCCB01-144 or saline was injected into the lateral tail vein of rats immediately after sham surgery or FF-transection, and effects on spatial delayed alternation in a T-maze were assessed over a 28-day period. Task acquisition was significantly impaired in FF-transected animals, but there were no significant effects of UCCB01-144 on spatial delayed alternation after FF-transection or sham surgery, although decelerated learning curves were seen after treatment with UCCB01-144 in FF-transected animals. The results of the present study are consistent with previous research showing a lack of neuroprotective effects of PSD-95 inhibition in experimental models of TBI. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae

PubMed Central

Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

2012-01-01

There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20–40 years) and a group of elderly women (n = 5, age: 70–95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (−2.374 vs. −2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. PMID:22946475

Age-dependence of power spectral density and fractal dimension of bone mineralized matrix in atomic force microscope topography images: potential correlates of bone tissue age and bone fragility in female femoral neck trabeculae.

PubMed

Milovanovic, Petar; Djuric, Marija; Rakocevic, Zlatko

2012-11-01

There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20-40 years) and a group of elderly women (n = 5, age: 70-95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (-2.374 vs. -2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. © 2012 The Authors Journal of Anatomy © 2012 Anatomical Society.

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

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

Petromagnetic Properties In The Naica Mining District, Chihuahua, Mexico: Searching For Source of Mineralization

NASA Astrophysics Data System (ADS)

Alva, L.; Gogichaishvili, A.; Urrutia, J.

Ore mineral and host lithologies have been sampled with 89 oriented samples from 14 sites in the Naica District, northern Mexico. Magnetic parameters permit to charac- terise samples: saturation magnetization, density, low- high-temperature magnetic sus- ceptibility, remanence intensity, Koenigsberger ratio, Curie temperature and hystere- sis parameters. Rock magnetic properties are controlled by variations in titanomag- netite content and hydrothermal alteration. Post-mineralization hydrothermal alter- ation seems the major event that affected the minerals and magnetic properties. Curie temperatures are characteristic of titanomagnetites or titanomaghemites. Hysteresis parameters indicate that most samples have pseudo-single domain (PSD) magnetic grains. Alternating filed (AF) demagnetization and isothermal remanence (IRM) ac- quisition both indicate that natural and laboratory remanences are carried by MD-PSD spinels in the host rocks. The trend of NRM intensity vs susceptibility suggests that the carrier of remanent and induced magnetization is the same in all cases (spinels). The Koenigsberger ratio range from 0.05 to 34.04, indicating the presence of MD and PSD magnetic grains. Constraints on the geometry of the intrusive source body devel- oped in the model of the magnetic anomaly are obtained by quantifying the relative contributions of induced and remanent magnetization components.

Understanding the ion distributions near the boundaries of reconnection outflow region

NASA Astrophysics Data System (ADS)

Zhou, Xu-Zhi; Pan, Dong-Xiao; Angelopoulos, Vassilis; Runov, Andrei; Zong, Qiu-Gang; Pu, Zu-Yin

2016-10-01

An interesting signature observed shortly after the onset of magnetotail reconnection is the gradual appearance of a local peak of ion phase space density (PSD) in the duskward and downstream direction separated from the colder, nearly isotropic ion population. Such a characteristic ion distribution, served as a diagnostic signature of magnetotail reconnection and well reproduced by a particle-tracing Liouville simulation, are found to appear only near the off-equatorial boundaries of the reconnection outflow region. Further analysis on ion trajectories suggests that the ions within the local peak and within the neighboring PSD cleft both belong to the outflowing population; on top of their outflowing motion, they both meander across the neutral sheet to exhibit duskward velocities near the off-equatorial edges of their trajectories. The difference between them is that the local peak originates from ions previously constituting the preonset plasma sheet, whereas the cleft corresponds to the inflowing lobe ions before they are repelled in the downstream direction. As reconnection proceeds, the local PSD peak gradually attenuates and then disappears, which is a signature of reconnection flushing effect that depletes the ions in the preonset plasma sheet and eventually replaces them by lobe ions.

Frequency Domain Analysis of Sensor Data for Event Classification in Real-Time Robot Assisted Deburring

PubMed Central

Pappachan, Bobby K; Caesarendra, Wahyu; Tjahjowidodo, Tegoeh; Wijaya, Tomi

2017-01-01

Process monitoring using indirect methods relies on the usage of sensors. Using sensors to acquire vital process related information also presents itself with the problem of big data management and analysis. Due to uncertainty in the frequency of events occurring, a higher sampling rate is often used in real-time monitoring applications to increase the chances of capturing and understanding all possible events related to the process. Advanced signal processing methods are used to further decipher meaningful information from the acquired data. In this research work, power spectrum density (PSD) of sensor data acquired at sampling rates between 40–51.2 kHz was calculated and the corelation between PSD and completed number of cycles/passes is presented. Here, the progress in number of cycles/passes is the event this research work intends to classify and the algorithm used to compute PSD is Welch’s estimate method. A comparison between Welch’s estimate method and statistical methods is also discussed. A clear co-relation was observed using Welch’s estimate to classify the number of cycles/passes. The paper also succeeds in classifying vibration signal generated by the spindle from the vibration signal acquired during finishing process. PMID:28556809

Non-stationarity and power spectral shifts in EMG activity reflect motor unit recruitment in rat diaphragm muscle.

PubMed

Seven, Yasin B; Mantilla, Carlos B; Zhan, Wen-Zhi; Sieck, Gary C

2013-01-15

We hypothesized that a shift in diaphragm muscle (DIAm) EMG power spectral density (PSD) to higher frequencies reflects recruitment of more fatigable fast-twitch motor units and motor unit recruitment is reflected by EMG non-stationarity. DIAm EMG was recorded in anesthetized rats during eupnea, hypoxia-hypercapnia (10% O(2)-5% CO(2)), airway occlusion, and sneezing (maximal DIAm force). Although power in all frequency bands increased progressively across motor behaviors, PSD centroid frequency increased only during sneezing (p<0.05). The non-stationary period at the onset of EMG activity ranged from ∼80 ms during airway occlusion to ∼150 ms during eupnea. Within the initial non-stationary period of EMG activity 80-95% of motor units were recruited during different motor behaviors. Motor units augmented their discharge frequencies progressively beyond the non-stationary period; yet, EMG signal became stationary. In conclusion, non-stationarity of DIAm EMG reflects the period of motor unit recruitment, while a shift in the PSD towards higher frequencies reflects recruitment of more fatigable fast-twitch motor units. Copyright © 2012 Elsevier B.V. All rights reserved.

Laser diffraction of acicular particles: practical applications

NASA Astrophysics Data System (ADS)

Scott, David M.; Matsuyama, Tatsushi

2014-08-01

Commercial laser diffraction instruments are widely used to measure particle size distribution (PSD), but the results are distorted for non-spherical (acicular) particles often encountered in practical applications. Consequently the distribution, which is reported in terms of equivalent spherical diameter, requires interpretation. For rod-like and plate-like particles, the PSD tends to be bi-modal, with the two modal sizes closely related to the median length and width, or width and thickness, of the particles. Furthermore, it is found that the bi-modal PSD for at least one instrument can typically be approximated by a bi-lognormal distribution. By fitting such a function to the reported distribution, one may extract quantitative information useful for process or product development. This approach is illustrated by examples of such measurement on industrial samples of polymer particles, crystals, bacteria, and clays.

Distributed Disdrometer and Rain Gauge Measurement Infrastructure Developed for GPM Ground Validation

NASA Technical Reports Server (NTRS)

Petersen, Walter A.; Bringi, V. N.; Gatlin, Patrick; Phillips, Dustin; Schwaller, Mathew; Tokay, Ali; Wingo, Mathew; Wolff, David

2010-01-01

Global Precipitation Mission (GPM)retrieval algorithm validation requires datasets characterizing the 4-D structure, variability, and correlation properties of hydrometeor particle size distributions (PSD) and accumulations over satellite fields of view (FOV;<10 km). Collection of this data provides a means to assess retrieval errors related to beam filling and algorithm PSD assumptions. Hence, GPM Ground Validation is developing a deployable network of precipitation gauges and disdrometers to provide fine-scale measurements of PSD and precipitation accumulation variability. These observations will be combined with dual-frequency, polarimetric, and profiling radar data in a bootstrapping fashion to extend validated PSD measurements to a large coverage domain. Accordingly, a total of 24 Parsivel disdrometers(PD), 5 3rd-generation 2D Video Disdrometers (2DVD), 70 tipping bucket rain gauges (TBRG),9 weighing gauges, 7 Hot-Plate precipitation sensors (HP), and 3 Micro Rain Radars (MRR) have been procured. In liquid precipitation the suite of TBRG, PD and 2DVD instruments will quantify a broad spectrum of rain rate and PSD variability at sub-kilometer scales. In the envisioned network configuration 5 2DVDs will act as reference points for 16 collocated PD and TBRG measurements. We find that PD measurements provide similar measures of the rain PSD as observed with collocated 2DVDs (e.g., D0, Nw) for rain rates less than 15 mm/hr. For heavier rain rates we will rely on 2DVDs for PSD information. For snowfall we will combine point-redundant observations of SWER distributed over three or more locations within a FOV. Each location will contain at least one fenced weighing gauge, one HP, two PDs, and a 2DVD. MRRs will also be located at each site to extend the measurement to the column. By collecting SWER measurements using different instrument types that employ different measurement techniques our objective is to separate measurement uncertainty from natural variability in SWER and PSD. As demonstrated using C3VP polarimetric radar, gauge, and 2DVD/PD datasets these measurements can be combined to bootstrap an area wide SWER estimate via constrained modification of density-diameter and radar reflectivity-snowfall relationships. These data will be combined with snowpack, airborne microphysics, radar, radiometer, and tropospheric sounding data to refine GPM snowfall retrievals. The gauge and disdrometer instruments are being developed to operate autonomously when necessary using solar power and wireless communications. These systems will be deployed in numerous field campaigns through 2016. Planned deployment of these systems include field campaigns in Finland (2010), Oklahoma (2011), Canada (2012) and North Carolina (2013). GPM will also deploy 20 pairs of TBRGs within a 25 km2 region along the Virginia coast under NASA NPOL radar coverage in order to quantify errors in point-area rainfall measurements.

Batch statistical process control of a fluid bed granulation process using in-line spatial filter velocimetry and product temperature measurements.

PubMed

Burggraeve, A; Van den Kerkhof, T; Hellings, M; Remon, J P; Vervaet, C; De Beer, T

2011-04-18

Fluid bed granulation is a batch process, which is characterized by the processing of raw materials for a predefined period of time, consisting of a fixed spraying phase and a subsequent drying period. The present study shows the multivariate statistical modeling and control of a fluid bed granulation process based on in-line particle size distribution (PSD) measurements (using spatial filter velocimetry) combined with continuous product temperature registration using a partial least squares (PLS) approach. Via the continuous in-line monitoring of the PSD and product temperature during granulation of various reference batches, a statistical batch model was developed allowing the real-time evaluation and acceptance or rejection of future batches. Continuously monitored PSD and product temperature process data of 10 reference batches (X-data) were used to develop a reference batch PLS model, regressing the X-data versus the batch process time (Y-data). Two PLS components captured 98.8% of the variation in the X-data block. Score control charts in which the average batch trajectory and upper and lower control limits are displayed were developed. Next, these control charts were used to monitor 4 new test batches in real-time and to immediately detect any deviations from the expected batch trajectory. By real-time evaluation of new batches using the developed control charts and by computation of contribution plots of deviating process behavior at a certain time point, batch losses or reprocessing can be prevented. Immediately after batch completion, all PSD and product temperature information (i.e., a batch progress fingerprint) was used to estimate some granule properties (density and flowability) at an early stage, which can improve batch release time. Individual PLS models relating the computed scores (X) of the reference PLS model (based on the 10 reference batches) and the density, respectively, flowabililty as Y-matrix, were developed. The scores of the 4 test batches were used to examine the predictive ability of the model. Copyright © 2011 Elsevier B.V. All rights reserved.

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

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.

Psychometric validation of the Psoriasis Symptom Diary using Phase III study data from patients with chronic plaque psoriasis.

PubMed

Strober, Bruce; Zhao, Yang; Tran, Mary Helen; Gnanasakthy, Ari; Nyirady, Judit; Papavassilis, Charis; Nelson, Lauren M; McLeod, Lori D; Mordin, Margaret; Gottlieb, Alice B; Elewski, Boni E; Lebwohl, Mark

2016-03-01

This analysis aimed to confirm the reliability, validity, and responsiveness of the Psoriasis Symptom Diary (PSD) using data from two Phase III studies in patients with moderate to severe chronic plaque psoriasis. Data from two randomized, double-blind, double-dummy, placebo-controlled, multicenter Phase III studies (n = 820) assessing the efficacy and safety of secukinumab were used. The PSD (24-h recall; 0-10 numeric rating scale) was electronically administered each evening. Test-retest reliability was determined using intraclass correlations. Construct validity hypotheses were evaluated via correlations with the Psoriasis Area and Severity Index (PASI), Investigator's Global Assessment (IGA), Dermatology Life Quality Index (DLQI), EuroQoL 5-Dimension Health Status Questionnaire, and Patient Global Impression of Change (PGIC). Discriminating ability and responsiveness were evaluated by estimating mean differences and effect sizes between known groups (using the PASI and IGA). Phase II-derived, anchor-based PGIC thresholds and cumulative distribution function (CDF) plots described meaningful change. Items on the PSD yielded high intraclass coefficients (>0.90). Correlations were in the anticipated direction and by week 12 were moderate to strong (0.41-0.73) in magnitude, demonstrating construct validity. Average PSD item scores differed predictably and significantly between known groups. Responsiveness effect size estimates were moderate to large (0.6-1.5), and CDF plots showed the percentage of responders to be consistently higher in treatment than in placebo arms across the range of change in PSD scores. The PSD is reliable, valid, and responsive, and represents a valid tool to enhance treatment decisions in patients with moderate to severe plaque psoriasis. © 2015 The International Society of Dermatology.

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.

Different effects of bisphenol-A on memory behavior and synaptic modification in intact and estrogen-deprived female mice.

PubMed

Xu, Xiaohong; Gu, Ting; Shen, Qiaoqiao

2015-03-01

Bisphenol-A (BPA) has the capability of interfering with the effects of estrogens on modulating brain function. The purpose of this study was to investigate the effects of BPA on memory and synaptic modification in the hippocampus of female mice under different levels of cycling estrogen. BPA exposure (40, 400 μg/kg/day) for 8 weeks did not affect spatial memory and passive avoidance task of gonadally intact mice but improved ovariectomy (Ovx)-induced memory impairment, whereas co-exposure of BPA with estradiol benzoate (EB) diminished the rescue effect of EB on memory behavior of Ovx mice. The results of morphometric measurement showed that BPA positively modified the synaptic interface structure and increased the synaptic density of CA1 pyramidal cell in the hippocampus of Ovx females, but inhibited the enhancement of EB on synaptic modification and synaptogenesis of Ovx mice. Furthermore, BPA up-regulated synaptic proteins synapsin I and PSD-95 and NMDA receptor NR2B but inhibited EB-induced increase in PSD-95 and NR2B in the hippocampus of Ovx mice. These results suggest that BPA interfered with normal hormonal regulation in synaptic plasticity and memory of female mice as a potent estrogen mimetic and as a disruptor of estrogen under various concentrations of cycling estrogen. © 2014 International Society for Neurochemistry.

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...

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...

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...

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...

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...

Decreased levels of PSD95 and two associated proteins and increased levels of BCl2 and caspase 3 in hippocampus from subjects with amnestic mild cognitive impairment: Insights into their potential roles for loss of synapses and memory, accumulation of Abeta, and neurodegeneration in a prodromal stage of Alzheimer's disease.

PubMed

Sultana, Rukhsana; Banks, William A; Butterfield, D Allan

2010-02-15

Alzheimer's disease (AD) is the most common form of dementia and is pathologically characterized by senile plaques, neurofibrillary tangles, synaptic disruption and loss, and progressive neuronal deficits. The exact mechanism(s) of AD pathogenesis largely remain unknown. With advances in technology diagnosis of a pre-AD stage referred to as amnestic mild cognitive impairment (MCI) has become possible. Amnestic MCI is characterized clinically by memory deficit, but normal activities of daily living and no dementia. In the present study, compared to controls, we observed in hippocampus from subjects with MCI a significantly decreased level of PSD95, a key synaptic protein, and also decreased levels of two proteins associated with PSD95, the N-methyl-D-aspartate receptor, subunit 2A (NR2A) and the low-density lipoprotein receptor-1 (LRP1). PSD95 and NR2A are involved in long-term potentiation, a key component of memory formation, and LRP1 is involved in efflux of amyloid beta-peptide (1-42). Abeta (1-42) conceivably is critical to the pathogenesis of MCI and AD, including the oxidative stress under which brain in both conditions exist. The data obtained from the current study suggest a possible involvement of these proteins in synaptic alterations, apoptosis and consequent decrements in learning and memory associated with the progression of MCI to AD. Copyright 2009 Wiley-Liss, Inc.

Postsynaptic density scaffold SAP102 regulates cortical synapse development through EphB and PAK signaling pathway

PubMed Central

Murata, Yasunobu; Constantine-Paton, Martha

2013-01-01

Membrane associated guanylate kinases (MAGUKs), including SAP102, PSD-95, PSD-93 and SAP97, are scaffolding proteins for ionotropic glutamate receptors at excitatory synapses. MAGUKs play critical roles in synaptic plasticity; however, details of signaling roles for each MAGUK remain largely unknown. Here we report that SAP102 regulates cortical synapse development through the EphB and PAK signaling pathways. Using lentivirus-delivered shRNAs, we found that SAP102 and PSD-95, but not PSD-93, are necessary for excitatory synapse formation and synaptic AMPA receptor localization in developing mouse cortical neurons. SAP102 knockdown (KD) increased numbers of elongated dendritic filopodia, which is often observed in mouse models and human patients with mental retardation. Further analysis revealed that SAP102 co-immunoprecipitated the receptor tyrosine kinase EphB2 and RacGEF Kalirin-7 in neonatal cortex, and SAP102 KD reduced surface expression and dendritic localization of EphB. Moreover, SAP102 KD prevented reorganization of actin filaments, synapse formation and synaptic AMPAR trafficking in response to EphB activation triggered by its ligand ephrinB. Lastly, p21-activated kinases (PAKs) were down-regulated in SAP102 KD neurons. These results demonstrate that SAP102 has unique roles in cortical synapse development by mediating EphB and its downstream PAK signaling pathway. Both SAP102 and PAKs are associated with X-linked mental retardation in humans; thus, synapse formation mediated by EphB/SAP102/PAK signaling in the early postnatal brain may be crucial for cognitive development. PMID:23486974

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.

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...

Contingency Plan for FGD Systems During Downtime as a Function of PSD

EPA Pesticide Factsheets

This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

Nicotine and caffeine modulate haloperidol-induced changes in postsynaptic density transcripts expression: Translational insights in psychosis therapy and treatment resistance.

PubMed

de Bartolomeis, Andrea; Iasevoli, Felice; Marmo, Federica; Buonaguro, Elisabetta Filomena; Avvisati, Livia; Latte, Gianmarco; Tomasetti, Carmine

2018-04-01

Caffeine and nicotine are widely used by schizophrenia patients and may worsen psychosis and affect antipsychotic therapies. However, they have also been accounted as augmentation strategies in treatment-resistant schizophrenia. Despite both substances are known to modulate dopamine and glutamate transmission, little is known about the molecular changes induced by these compounds in association to antipsychotics, mostly at the level of the postsynaptic density (PSD), a site of dopamine-glutamate interplay. Here we investigated whether caffeine and nicotine, alone or combined with haloperidol, elicited significant changes in the levels of both transcripts and proteins of the PSD members Homer1 and Arc, which have been implicated in synaptic plasticity, schizophrenia pathophysiology, and antipsychotics molecular action. Homer1a mRNA expression was significantly reduced by caffeine and nicotine, alone or combined with haloperidol, compared to haloperidol. Haloperidol induced significantly higher Arc mRNA levels than both caffeine and caffeine plus haloperidol in the striatum. Arc mRNA expression was significantly higher by nicotine plus haloperidol vs. haloperidol in the cortex, while in striatum gene expression by nicotine was significantly lower than that by both haloperidol and nicotine plus haloperidol. Both Homer1a and Arc protein levels were significantly increased by caffeine, nicotine, and nicotine plus haloperidol. Homer1b mRNA expression was significantly increased by nicotine and nicotine plus haloperidol, while protein levels were unaffected. Locomotor activity was not significantly affected by caffeine, while it was reduced by nicotine. These data indicate that both caffeine and nicotine trigger relevant molecular changes in PSD sites when given in association with haloperidol. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

PSD-95 expression controls l-DOPA dyskinesia through dopamine D1 receptor trafficking

PubMed Central

Porras, Gregory; Berthet, Amandine; Dehay, Benjamin; Li, Qin; Ladepeche, Laurent; Normand, Elisabeth; Dovero, Sandra; Martinez, Audrey; Doudnikoff, Evelyne; Martin-Négrier, Marie-Laure; Chuan, Qin; Bloch, Bertrand; Choquet, Daniel; Boué-Grabot, Eric; Groc, Laurent; Bezard, Erwan

2012-01-01

l-DOPA–induced dyskinesia (LID), a detrimental consequence of dopamine replacement therapy for Parkinson’s disease, is associated with an alteration in dopamine D1 receptor (D1R) and glutamate receptor interactions. We hypothesized that the synaptic scaffolding protein PSD-95 plays a pivotal role in this process, as it interacts with D1R, regulates its trafficking and function, and is overexpressed in LID. Here, we demonstrate in rat and macaque models that disrupting the interaction between D1R and PSD-95 in the striatum reduces LID development and severity. Single quantum dot imaging revealed that this benefit was achieved primarily by destabilizing D1R localization, via increased lateral diffusion followed by increased internalization and diminished surface expression. These findings indicate that altering D1R trafficking via synapse-associated scaffolding proteins may be useful in the treatment of dyskinesia in Parkinson’s patients. PMID:23041629

Players over the Surface: Unraveling the Role of Exopolysaccharides in Zinc Biosorption by Fluorescent Pseudomonas Strain Psd.

PubMed

Upadhyay, Anamika; Kochar, Mandira; Rajam, Manchikatla V; Srivastava, Sheela

2017-01-01

Fluorescent Pseudomonas strain Psd is a soil isolate, possessing multiple plant growth promoting (PGP) properties and biocontrol potential. In addition, the strain also possesses high Zn 2+ biosorption capability. In this study, we have investigated the role exopolysaccharides (EPS) play in Zn 2+ biosorption. We have identified that alginates are the prime components contributing to Zn 2+ biosorption. Deletion of the alg8 gene, which codes for a sub-unit of alginate polymerase, led to a significant reduction in EPS production by the organism. We have also demonstrated that the increased alginate production in response to Zn 2+ exposure leads to improved biofilm formation by the strain. In the alg8 deletion mutant, however, biofilm formation was severely compromised. Further, we have studied the functional implications of Zn 2+ biosorption by Pseudomonas strain Psd by demonstrating the effect on the PGP and biocontrol potential of the strain.

Players over the Surface: Unraveling the Role of Exopolysaccharides in Zinc Biosorption by Fluorescent Pseudomonas Strain Psd

PubMed Central

Upadhyay, Anamika; Kochar, Mandira; Rajam, Manchikatla V.; Srivastava, Sheela

2017-01-01

Fluorescent Pseudomonas strain Psd is a soil isolate, possessing multiple plant growth promoting (PGP) properties and biocontrol potential. In addition, the strain also possesses high Zn2+ biosorption capability. In this study, we have investigated the role exopolysaccharides (EPS) play in Zn2+ biosorption. We have identified that alginates are the prime components contributing to Zn2+ biosorption. Deletion of the alg8 gene, which codes for a sub-unit of alginate polymerase, led to a significant reduction in EPS production by the organism. We have also demonstrated that the increased alginate production in response to Zn2+ exposure leads to improved biofilm formation by the strain. In the alg8 deletion mutant, however, biofilm formation was severely compromised. Further, we have studied the functional implications of Zn2+ biosorption by Pseudomonas strain Psd by demonstrating the effect on the PGP and biocontrol potential of the strain. PMID:28286498

Prevention of poststroke depression: does prophylactic pharmacotherapy work?

PubMed

Salter, Katherine L; Foley, Norine C; Zhu, Lynn; Jutai, Jeffrey W; Teasell, Robert W

2013-11-01

Given the negative influence of poststroke depression (PSD) on functional recovery, cognition, social participation, quality of life, and risk for mortality, the early initiation of antidepressant therapy to prevent its development has been investigated; however, individual studies have offered conflicting evidence. The present systematic review and meta-analysis examined available evidence from published randomized controlled trials (RCTs) evaluating the effectiveness of pharmacotherapy for the prevention of PSD to provide updated pooled analyses. Literature searches of 6 databases were performed for the years 1990 to 2011. RCTs meeting study inclusion criteria were evaluated for methodologic quality. Data extracted included the antidepressant therapy used, treatment timing and duration, method(s) of assessment, and study results pertaining to the onset of PSD. Pooled analyses were conducted. Eight RCTs were identified for inclusion. Pooled analyses demonstrated reduced odds for the development of PSD associated with pharmacologic treatment (odds ratio [OR] 0.34; 95% confidence interval [CI] 0.22-0.53; P<.001), a treatment duration of 1 year (OR 0.31; 95% CI 0.18-0.56; P<.001), and the use of a selective serotonin reuptake inhibitor (OR 0.37; 95% CI 0.22-0.61; P<.001). The early initiation of antidepressant therapy, in nondepressed stroke patients, may reduce the odds for development of PSD. Optimum timing and duration for treatment and the identification of the most appropriate recipients for a program of indicated prevention require additional examination. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Test surfaces useful for calibration of surface profilometers

DOEpatents

Yashchuk, Valeriy V; McKinney, Wayne R; Takacs, Peter Z

2013-12-31

The present invention provides for test surfaces and methods for calibration of surface profilometers, including interferometric and atomic force microscopes. Calibration is performed using a specially designed test surface, or the Binary Pseudo-random (BPR) grating (array). Utilizing the BPR grating (array) to measure the power spectral density (PSD) spectrum, the profilometer is calibrated by determining the instrumental modulation transfer.

QEEG Spectral and Coherence Assessment of Autistic Children in Three Different Experimental Conditions

ERIC Educational Resources Information Center

Machado, Calixto; Estévez, Mario; Leisman, Gerry; Melillo, Robert; Rodríguez, Rafael; DeFina, Phillip; Hernández, Adrián; Pérez-Nellar, Jesús; Naranjo, Rolando; Chinchilla, Mauricio; Garófalo, Nicolás; Vargas, José; Beltrán, Carlos

2015-01-01

We studied autistics by quantitative EEG spectral and coherence analysis during three experimental conditions: basal, watching a cartoon with audio (V-A), and with muted audio band (VwA). Significant reductions were found for the absolute power spectral density (PSD) in the central region for delta and theta, and in the posterior region for sigma…

Pulsed plasma thruster by applied a high current hollow cathode discharge

NASA Astrophysics Data System (ADS)

Watanabe, Masayuki; N. Nogera Team; T. Kamada Team

2013-09-01

The pulsed plasma thruster applied by a high current hollow cathode discharge has been investigated. In this research, the pseudo-spark discharge (PSD), which is a one of a pulsed high current hollow cathode discharge, is applied to the plasma thruster. In PSD, the opposite surfaces of the anode and cathode have a small circular hole and the cathode has a cylindrical cavity behind the circular hole. To generate the high speed plasma flow, the diameter of the anode hole is enlarged as compared with that of the cathode hole. As a result, the plasma is accelerated by a combination of an electro-magnetic force and a thermo-dynamic force inside a cathode cavity. For the improvement of the plasma jet characteristic, the magnetic field is also applied to the plasma jet. To magnetize the plasma jet, the external magnetic field is directly induced nearby the electrode holes. Consequently, the plasma jet is accelerated with the self-azimuthal magnetic field. With the magnetic field, the temperature and the density of the plasma jet were around 5 eV and in the order of 10 19 m-3. The density increased several times as compared with that without the magnetic field.

Impact of the storm-time plasma sheet ion composition on the ring current energy density

NASA Astrophysics Data System (ADS)

Mouikis, C.; Kistler, L. M.; Petrinec, S. M.; Fuselier, S. A.; Cohen, I.

2017-12-01

The adiabatic inward transport of the night-side near-earth ( 6 Re) hot plasma sheet is the dominant contributor to the ring current pressure during storm times. During storm times, the plasma sheet composition in the 6 - 12 Re tail region changes due to O+ entry from the lobes (from the cusp) and the direct feeding from the night side auroral region. In addition, at substorm onset the plasma sheet O+ ions can be preferentially accelerated. We use MMS and observations during two magnetic storms, 5/8/2016 and 7/16/2017, to monitor the composition changes and energization in the 6 - 12 Re plasma sheet region. For both storms the MMS apogee was in the tail. In addition, we use subsequent Van Allen Probe observations (with apogee in the dawn and dusk respectively) to test if the 6-12 Re plasma sheet, observed by MMS, is a sufficient source of the O+ in the ring current. For this we will compare the phase space density (PSD) of the plasma sheet source population and the PSD of the inner magnetosphere at constant magnetic moment values as used in Kistler et al., [2016].

Monte Carlo Model Insights into the Lunar Sodium Exosphere

NASA Technical Reports Server (NTRS)

Hurley, Dana M.; Killen, R. M.; Sarantos, M.

2012-01-01

Sodium in the lunar exosphere is released from the lunar regolith by several mechanisms. These mechanisms include photon stimulated desorption (PSD), impact vaporization, electron stimulated desorption, and ion sputtering. Usually, PSD dominates; however, transient events can temporarily enhance other release mechanisms so that they are dominant. Examples of transient events include meteor showers and coronal mass ejections. The interaction between sodium and the regolith is important in determining the density and spatial distribution of sodium in the lunar exosphere. The temperature at which sodium sticks to the surface is one factor. In addition, the amount of thermal accommodation during the encounter between the sodium atom and the surface affects the exospheric distribution. Finally, the fraction of particles that are stuck when the surface is cold that are rereleased when the surface warms up also affects the exospheric density. In [1], we showed the "ambient" sodium exosphere from Monte Carlo modeling with a fixed source rate and fixed surface interaction parameters. We compared the enhancement when a CME passes the Moon to the ambient conditions. Here, we compare model results to data in order to determine the source rates and surface interaction parameters that provide the best fit of the model to the data.

Method development and validation for measuring the particle size distribution of pentaerythritol tetranitrate (PETN) powders.

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

Young, Sharissa Gay

2005-09-01

Currently, the critical particle properties of pentaerythritol tetranitrate (PETN) that influence deflagration-to-detonation time in exploding bridge wire detonators (EBW) are not known in sufficient detail to allow development of a predictive failure model. The specific surface area (SSA) of many PETN powders has been measured using both permeametry and gas absorption methods and has been found to have a critical effect on EBW detonator performance. The permeametry measure of SSA is a function of particle shape, packed bed pore geometry, and particle size distribution (PSD). Yet there is a general lack of agreement in PSD measurements between laboratories, raising concernsmore » regarding collaboration and complicating efforts to understand changes in EBW performance related to powder properties. Benchmarking of data between laboratories that routinely perform detailed PSD characterization of powder samples and the determination of the most appropriate method to measure each PETN powder are necessary to discern correlations between performance and powder properties and to collaborate with partnering laboratories. To this end, a comparison was made of the PSD measured by three laboratories using their own standard procedures for light scattering instruments. Three PETN powder samples with different surface areas and particle morphologies were characterized. Differences in bulk PSD data generated by each laboratory were found to result from variations in sonication of the samples during preparation. The effect of this sonication was found to depend on particle morphology of the PETN samples, being deleterious to some PETN samples and advantageous for others in moderation. Discrepancies in the submicron-sized particle characterization data were related to an instrument-specific artifact particular to one laboratory. The type of carrier fluid used by each laboratory to suspend the PETN particles for the light scattering measurement had no consistent effect on the resulting PSD data. Finally, the SSA of the three powders was measured using both permeametry and gas absorption methods, enabling the PSD to be linked to the SSA for these PETN powders. Consistent characterization of other PETN powders can be performed using the appropriate sample-specific preparation method, so that future studies can accurately identify the effect of changes in the PSD on the SSA and ultimately model EBW performance.« less

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...

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...

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...

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.

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.

Cortical compression rapidly trimmed transcallosal projections and altered axonal anterograde transport machinery.

PubMed

Chen, Li-Jin; Wang, Yueh-Jan; Tseng, Guo-Fang

2017-10-24

Trauma and tumor compressing the brain distort underlying cortical neurons. Compressed cortical neurons remodel their dendrites instantly. The effects on axons however remain unclear. Using a rat epidural bead implantation model, we studied the effects of unilateral somatosensory cortical compression on its transcallosal projection and the reversibility of the changes following decompression. Compression reduced the density, branching profuseness and boutons of the projection axons in the contralateral homotopic cortex 1week and 1month post-compression. Projection fiber density was higher 1-month than 1-week post-compression, suggesting adaptive temporal changes. Compression reduced contralateral cortical synaptophysin, vesicular glutamate transporter 1 (VGLUT1) and postsynaptic density protein-95 (PSD95) expressions in a week and the first two marker proteins further by 1month. βIII-tubulin and kinesin light chain (KLC) expressions in the corpus callosum (CC) where transcallosal axons traveled were also decreased. Kinesin heavy chain (KHC) level in CC was temporarily increased 1week after compression. Decompression increased transcallosal axon density and branching profuseness to higher than sham while bouton density returned to sham levels. This was accompanied by restoration of synaptophysin, VGLUT1 and PSD95 expressions in the contralateral cortex of the 1-week, but not the 1-month, compression rats. Decompression restored βIII-tubulin, but not KLC and KHC expressions in CC. However, KLC and KHC expressions in the cell bodies of the layer II/III pyramidal neurons partially recovered. Our results show cerebral compression compromised cortical axonal outputs and reduced transcallosal projection. Some of these changes did not recover in long-term decompression. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

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.

Proteomic comparison of two fractions derived from the transsynaptic scaffold.

PubMed

Phillips, Greg R; Florens, Laurence; Tanaka, Hidekazu; Khaing, Zin Z; Fidler, Lazar; Yates, John R; Colman, David R

2005-09-15

A fraction derived from presynaptic specializations (presynaptic particle fraction; PPF) can be separated from postsynaptic densities (PSD) by adjusting the pH of Triton X-100 (TX-100) extraction of isolated transsynaptic scaffolds. Solubilization of the PPF corresponds to disruption of the presynaptic specialization. We show that the PPF is insoluble to repeated TX-100 extraction at pH 6.0 but becomes soluble in detergent at pH 8.0. By immunolocalization, we find that the major proteins of the PPF, clathrin and dynamin, are concentrated in the presynaptic compartment. By using multidimensional protein identification technology, we compared the protein compositions of the PPF and the PSD fraction. We identified a total of 341 proteins, 50 of which were uniquely found in the PPF, 231 in the PSD fraction, and 60 in both fractions. Comparison of the two fractions revealed a relatively low proportion of actin and associated proteins and a high proportion of vesicle or intracellular compartment proteins in the PPF. We conclude that the PPF consists of presynaptic proteins not connected to the actin-based synaptic framework; its insolubility in pH 6 and solubility in pH 8 buffered detergent suggests that clathrin might be an anchorage scaffold for many proteins in the PPF. (c) 2005 Wiley-Liss, Inc.

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...

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...

Role of the DLGAP2 Gene Encoding the SAP90/PSD-95-Associated Protein 2 in Schizophrenia

PubMed Central

Li, Jun-Ming; Lu, Chao-Lin; Cheng, Min-Chih; Luu, Sy-Ueng; Hsu, Shih-Hsin; Hu, Tsung-Ming; Tsai, Hsin-Yao; Chen, Chia-Hsiang

2014-01-01

Aberrant synaptic dysfunction is implicated in the pathogenesis of schizophrenia. The DLGAP2 gene encoding the SAP90/PSD-95-associated protein 2 (SAPAP2) located at the post-synaptic density of neuronal cells is involved in the neuronal synaptic function. This study aimed to investigate whether the DLGAP2 gene is associated with schizophrenia. We resequenced the putative promoter region and all the exons of the DLGAP2 gene in 523 patients with schizophrenia and 596 non-psychotic controls from Taiwan and conducted a case-control association analysis. We identified 19 known SNPs in this sample. Association analysis of 9 SNPs with minor allele frequency greater than 5% showed no association with schizophrenia. However, we found a haplotype (CCACCAACT) significantly associated with schizophrenia (odds ratio:2.5, p<0.001). We also detected 16 missense mutations and 1 amino acid-insertion mutation in this sample. Bioinformatic analysis showed some of these mutations were damaging or pathological to the protein function, but we did not find increased burden of these mutations in the patient group. Notably, we identified 5 private rare variants in 5 unrelated patients, respectively, including c.−69+9C>T, c.−69+13C>T, c.−69+47C>T, c.−69+55C>T at intron 1 and c.−32A>G at untranslated exon 2 of the DLGAP2 gene. These rare variants were not detected in 559 control subjects. Further reporter gene assay of these rare variants except c.−69+13C>T showed significantly elevated promoter activity than the wild type, suggesting increased DLGAP2 gene expression may contribute to the pathogenesis of schizophrenia. Our results indicate that DLGAP2 is a susceptible gene of schizophrenia. PMID:24416398

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.

Structural and molecular remodeling of dendritic spine substructures during long-term potentiation

PubMed Central

Bosch, Miquel; Castro, Jorge; Saneyoshi, Takeo; Matsuno, Hitomi; Sur, Mriganka; Hayashi, Yasunori

2014-01-01

SUMMARY Synapses store information by long-lasting modifications of their structure and molecular composition, but the precise chronology of these changes has not been studied at single synapse resolution in real time. Here we describe the spatiotemporal reorganization of postsynaptic substructures during long-term potentiation (LTP) at individual dendritic spines. Proteins translocated to the spine in four distinct patterns through three sequential phases. In the initial phase, the actin cytoskeleton was rapidly remodeled while active cofilin was massively transported to the spine. In the stabilization phase, cofilin formed a stable complex with F-actin, was persistently retained at the spine, and consolidated spine expansion. In contrast, the postsynaptic density (PSD) was independently remodeled, as PSD scaffolding proteins did not change their amount and localization until a late protein synthesis-dependent third phase. Our findings show how and when spine substructures are remodeled during LTP and explain why synaptic plasticity rules change over time. PMID:24742465

Theory connecting nonlocal sediment transport, earth surface roughness, and the Sadler effect

NASA Astrophysics Data System (ADS)

Schumer, Rina; Taloni, Alessandro; Furbish, David Jon

2017-03-01

Earth surface evolution, like many natural phenomena typified by fluctuations on a wide range of scales and deterministic smoothing, results in a statistically rough surface. We present theory demonstrating that scaling exponents of topographic and stratigraphic statistics arise from long-time averaging of noisy surface evolution rather than specific landscape evolution processes. This is demonstrated through use of "elastic" Langevin equations that generically describe disturbance from a flat earth surface using a noise term that is smoothed deterministically via sediment transport. When smoothing due to transport is a local process, the geologic record self organizes such that a specific Sadler effect and topographic power spectral density (PSD) emerge. Variations in PSD slope reflect the presence or absence and character of nonlocality of sediment transport. The range of observed stratigraphic Sadler slopes captures the same smoothing feature combined with the presence of long-range spatial correlation in topographic disturbance.

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.

Broadening the optical bandwidth of quantum cascade lasers using RF noise current perturbations.

PubMed

Pinto, Tomás H P; Kirkbride, James M R; Ritchie, Grant A D

2018-04-15

We report on the broadening of the optical bandwidth of a distributed feedback quantum cascade laser (QCL) caused by the application of radio frequency (RF) noise to the injection current. The broadening is quantified both via Lamb-dip spectroscopy and the frequency noise power spectral density (PSD). The linewidth of the unperturbed QCL (emitting at ∼5.3  μm) determined by Lamb-dip spectroscopy is 680±170  kHz, and is in reasonable agreement with the linewidth of 460±40  kHz estimated by integrating the PSD measured under the same laser operating conditions. Measurements with both techniques reveal that by mixing the driving current with broadband RF noise the laser lineshape was reproducibly broadened up to ca 6 MHz with an increasing Gaussian contribution. The effects of linewidth broadening are then demonstrated in the two-color coherent transient spectra of nitric oxide.

Two-frequency /Delta k/ microwave scatterometer measurements of ocean wave spectra from an aircraft

NASA Technical Reports Server (NTRS)

Johnson, J. W.; Jones, W. L.; Weissman, D. E.

1981-01-01

A technique for remotely sensing the large-scale gravity wave spectrum on the ocean surface using a two frequency (Delta k) microwave scatterometer has been demonstrated from stationary platforms and proposed from moving platforms. This measurement takes advantage of Bragg type resonance matching between the electromagnetic wavelength at the difference frequency and the length of the large-scale surface waves. A prominent resonance appears in the cross product power spectral density (PSD) of the two backscattered signals. Ku-Band aircraft scatterometer measurements were conducted by NASA in the North Sea during the 1979 Maritime Remote Sensing (MARSEN) experiment. Typical examples of cross product PSD's computed from the MARSEN data are presented. They demonstrate strong resonances whose frequency and bandwidth agree with the surface characteristics and the theory. Directional modulation spectra of the surface reflectivity are compared to the gravity wave spectrum derived from surface truth measurements.

Method for calculating self-noise spectra and operating ranges for seismographic inertial sensors and recorders

USGS Publications Warehouse

Evans, John R.; Followill, F.; Hutt, Charles R.; Kromer, R.P.; Nigbor, R.L.; Ringler, A.T.; Steim, J.M.; Wielandt, E.

2010-01-01

Understanding the performance of sensors and recorders is prerequisite to making appropriate use of them in seismology and earthquake engineering. This paper explores a critical aspect of instrument performance, the “self” noise level of the device and the amplitude range it can usefully record. Self noise limits the smallest signals, while instrument clipping level creates the upper limit (above which it either cannot produce signals or becomes unacceptably nonlinear). Where these levels fall, and the “operating range” between them, determines much of the instrument's viability and the applications for which it is appropriate. The representation of seismic-instrument self-noise levels and their effective operating ranges (cf., dynamic range) for seismological inertial sensors, recorders (data acquisition units, or DAUs), and integrated systems of sensors and recorders (data acquisition systems, or DASs) forces one to address an unnatural comparison between transient finite-bandwidth signals, such as earthquake records, and the instrument's self noise, an effectively stationary signal of infinite duration. In addition to being transient, earthquakes and other records of interest are characterized by a peak amplitude and generally a narrow, peaked spectral shape. Unfortunately, any power spectrum computed for such transient signals is ill defined, since the maximum of that spectrum depends strongly upon signal and record durations. In contrast, the noise floor of an instrument is approximately stationary and properly described by a power spectral density (PSD) or its root (rPSD). Put another way, earthquake records have units of amplitude (e.g., m/s2) while PSDs have units of amplitude-squared per hertz (e.g., (m/s2)2/Hz) and the rPSD has units of amplitude per root of hertz (e.g., (m/s2)/Hz1/2). Thus, this incompatability is a conflict between earthquake (amplitude) and PSD (spectral density) units that requires one to make various assumptions before they can be compared. For purposes of instrument operational performance, we provide a means of evaluating signal and noise and the range between them in a manner representative of time-domain instrument performance. We call these “operating range diagrams” (ORDs), plots of instrument self noise and clipping level; the “operating range” is the range between these values. For frequency-domain performance we elect to show self noise as an rPSD that may be compared to another instrument's noise or to ambient Earth noise (e.g., Peterson 1993); however, to limit the number of arbitrary choices required to merge transient and stationary signals we do not compare the rPSD to transient signals in the frequency domain. Our solution for a time-domain comparison is not new but rather builds upon the consensus of the first and second Guidelines for Seismometer Testing workshops (Hutt et al. 2009) and long established practice in acoustics. We propose this method as a standard for characterizing seismic instruments, and it has been endorsed by the second workshop (Hutt et al. 2009, 2010) and the Advanced National Seismic System (ANSS) Working Group (2008) and recent ANSS procurement specifications.

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...

Kepler light-curve analysis of the blazar W2R 1926+42

NASA Astrophysics Data System (ADS)

Mohan, P.; Gupta, Alok C.; Bachev, Rumen; Strigachev, Anton

2016-02-01

We study the long term Kepler light curve of the blazar W2R 1926+42 (˜1.6 yr) which indicates a variety of variability properties during different intervals of observation. The normalized excess variance, Fvar ranges from 1.8 per cent in the quiescent phase and 43.3 per cent in the outburst phase. We find no significant deviation from linearity in the Fvar-flux relation. Time series analysis is conducted using the Fourier power spectrum and the wavelet analysis methods to study the power spectral density (PSD) shape, infer characteristic time-scales and statistically significant quasi-periodic oscillations (QPOs). A bending power law with an associated time-scale of T_B = 6.2^{+6.4}_{-3.1} hours is inferred in the PSD analysis. We obtain a black hole mass of M• = (1.5-5.9) × 107 M⊙ for the first time using Fvar and the bend time-scale for this source. From a mean outburst lifetime of days, we infer a distance from the jet base r ≤ 1.75 pc indicating that the outburst originates due to a shock. A possible QPO peaked at 9.1 d and lasting 3.4 cycles is inferred from the wavelet analysis. Assuming that the QPO is a true feature, r = (152-378)GM•/c2 and supported by the other timing analysis products such as a weighted mean PSD slope of -1.5 ± 0.2 from the PSD analysis, we argue that the observed variability and the weak and short duration QPO could be due to jet based processes including orbital features in a relativistic helical jet and others such as shocks and turbulence.

Adult Restoration of Shank3 Expression Rescues Selective Autistic-Like Phenotypes

PubMed Central

Mei, Yuan; Monteiro, Patricia; Zhou, Yang; Kim, Jin-Ah; Gao, Xian; Fu, Zhanyan; Feng, Guoping

2016-01-01

Because ASD is a neurodevelopmental disorder and patients typically display symptoms before the age of three1, one of the key questions in autism research is whether the pathology is reversible in adults. Here we investigated the developmental requirement of Shank3, one of the most prominent monogenic ASD genes that is estimated to contribute to ~1% of all ASD cases2–6. SHANK3 is a postsynaptic scaffold protein that regulates synaptic development, function and plasticity by orchestrating the assembly of postsynaptic density (PSD) macromolecular signaling complex7–9. Disruptions of the Shank3 gene in mouse models have resulted in synaptic defects and autistic-like behaviors including anxiety, social interaction deficits, and repetitive behavior10–13. We generated a novel Shank3 conditional knock-in mouse model and used it to demonstrate that re-expression of the Shank3 gene in adult led to improvements in synaptic protein composition, spine density and neural function in the striatum. We also provided behavioral evidence that certain behavioral abnormalities including social interaction deficit and repetitive grooming behavior could be rescued, while anxiety and motor coordination deficit could not be recovered in adulthood. Together, these results elucidate the profound impact of post-developmental activation of Shank3 expression on neural function and demonstrate certain degree of continued plasticity in the adult diseased brain. PMID:26886798

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.

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

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).

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

Smallwood, D.O.

It is recognized that some dynamic and noise environments are characterized by time histories which are not Gaussian. An example is high intensity acoustic noise. Another example is some transportation vibration. A better simulation of these environments can be generated if a zero mean non-Gaussian time history can be reproduced with a specified auto (or power) spectral density (ASD or PSD) and a specified probability density function (pdf). After the required time history is synthesized, the waveform can be used for simulation purposes. For example, modem waveform reproduction techniques can be used to reproduce the waveform on electrodynamic or electrohydraulicmore » shakers. Or the waveforms can be used in digital simulations. A method is presented for the generation of realizations of zero mean non-Gaussian random time histories with a specified ASD, and pdf. First a Gaussian time history with the specified auto (or power) spectral density (ASD) is generated. A monotonic nonlinear function relating the Gaussian waveform to the desired realization is then established based on the Cumulative Distribution Function (CDF) of the desired waveform and the known CDF of a Gaussian waveform. The established function is used to transform the Gaussian waveform to a realization of the desired waveform. Since the transformation preserves the zero-crossings and peaks of the original Gaussian waveform, and does not introduce any substantial discontinuities, the ASD is not substantially changed. Several methods are available to generate a realization of a Gaussian distributed waveform with a known ASD. The method of Smallwood and Paez (1993) is an example. However, the generation of random noise with a specified ASD but with a non-Gaussian distribution is less well known.« less

Phenology of particle size distributions and primary productivity in the North Pacific subtropical gyre (Station ALOHA)

PubMed Central

Letelier, Ricardo M.; Whitmire, Amanda L.; Barone, Benedetto; Bidigare, Robert R.; Church, Matthew J.; Karl, David M.

2015-01-01

Abstract The particle size distribution (PSD) is a critical aspect of the oceanic ecosystem. Local variability in the PSD can be indicative of shifts in microbial community structure and reveal patterns in cell growth and loss. The PSD also plays a central role in particle export by influencing settling speed. Satellite‐based models of primary productivity (PP) often rely on aspects of photophysiology that are directly related to community size structure. In an effort to better understand how variability in particle size relates to PP in an oligotrophic ecosystem, we collected laser diffraction‐based depth profiles of the PSD and pigment‐based classifications of phytoplankton functional types (PFTs) on an approximately monthly basis at the Hawaii Ocean Time‐series Station ALOHA, in the North Pacific subtropical gyre. We found a relatively stable PSD in the upper water column. However, clear seasonality is apparent in the vertical distribution of distinct particle size classes. Neither laser diffraction‐based estimations of relative particle size nor pigment‐based PFTs was found to be significantly related to the rate of 14C‐based PP in the light‐saturated upper euphotic zone. This finding indicates that satellite retrievals of particle size, based on particle scattering or ocean color would not improve parameterizations of present‐day bio‐optical PP models for this region. However, at depths of 100–125 m where irradiance exerts strong control on PP, we do observe a significant linear relationship between PP and the estimated carbon content of 2–20 μm particles. PMID:27812434

Phenology of particle size distributions and primary productivity in the North Pacific subtropical gyre (Station ALOHA).

PubMed

White, Angelicque E; Letelier, Ricardo M; Whitmire, Amanda L; Barone, Benedetto; Bidigare, Robert R; Church, Matthew J; Karl, David M

2015-11-01

The particle size distribution (PSD) is a critical aspect of the oceanic ecosystem. Local variability in the PSD can be indicative of shifts in microbial community structure and reveal patterns in cell growth and loss. The PSD also plays a central role in particle export by influencing settling speed. Satellite-based models of primary productivity (PP) often rely on aspects of photophysiology that are directly related to community size structure. In an effort to better understand how variability in particle size relates to PP in an oligotrophic ecosystem, we collected laser diffraction-based depth profiles of the PSD and pigment-based classifications of phytoplankton functional types (PFTs) on an approximately monthly basis at the Hawaii Ocean Time-series Station ALOHA, in the North Pacific subtropical gyre. We found a relatively stable PSD in the upper water column. However, clear seasonality is apparent in the vertical distribution of distinct particle size classes. Neither laser diffraction-based estimations of relative particle size nor pigment-based PFTs was found to be significantly related to the rate of 14 C-based PP in the light-saturated upper euphotic zone. This finding indicates that satellite retrievals of particle size, based on particle scattering or ocean color would not improve parameterizations of present-day bio-optical PP models for this region. However, at depths of 100-125 m where irradiance exerts strong control on PP, we do observe a significant linear relationship between PP and the estimated carbon content of 2-20 μm particles.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and post-stroke dementia: a hospital-based study from northern Iran.

PubMed

Rezaei, Sajjad; Asgari Mobarake, Karim; Saberi, Alia; Keshavarz, Parvaneh; Leili, Ehsan Kazemnejad

2016-06-01

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with functional and cognitive outcomes of stroke and plays a key role in preventing neuronal death. This study aimed to answer the following question: does BDNF Val66Met polymorphism prognosticate survival status and risk of post-stroke dementia (PSD)? In a retrospective cohort study, 206 patients with ischemic stroke (IS) entered the study. They were consecutively being admitted to the neurology clinic in Poursina Hospital (northern Iran) from 2012 to 2014. The diagnosis of PSD was based on DSM-5 criteria. The current and the premorbid cognitive statuses of the patients were respectively assessed through the third edition of Addenbrooke's Cognitive Examination and the Informant Questionnaire on Cognitive Decline in the Elderly. BDNF Val66Met gene polymorphism was determined by PCR-RFLP. On average, 48 patients (23.3 %) developed PSD 6 months after IS. Log-rank test showed that the survival rate of at least one Val-allele carriers was significantly lower than that of Met/Met homozygotes (P = 0.0005), and the former developed PSD sooner than the latter (375, 492 days, respectively). Cox model showed that heterozygous carriers of Val/Met were at greater risk of PSD over time (HR 2.280, 95 % CI 1.566-4.106, P = 0.006). However, the risk ratio of patients with PSD among different BDNF genotypes decreased after adjusting demographic, clinical, and vascular risk factors, and was no longer statistically significant (AHR 2.434, 95 % CI 0.597-9.926, P = 0.215). Val-allele carriers or Val/Met genotypes were more quickly diagnosed as having dementia after IS. However, this genetic vulnerability became more destructive when it was added to demographic, clinical, and vascular risk factors.

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...

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...

Immunotherapy alleviates amyloid-associated synaptic pathology in an Alzheimer’s disease mouse model

PubMed Central

Dorostkar, Mario M.; Burgold, Steffen; Filser, Severin; Barghorn, Stefan; Schmidt, Boris; Anumala, Upendra Rao; Hillen, Heinz; Klein, Corinna

2014-01-01

Cognitive decline in Alzheimer’s disease is attributed to loss of functional synapses, most likely caused by synaptotoxic, oligomeric forms of amyloid-β. Many treatment options aim at reducing amyloid-β levels in the brain, either by decreasing its production or by increasing its clearance. We quantified the effects of immunotherapy directed against oligomeric amyloid-β in Tg2576 mice, a mouse model of familial Alzheimer’s disease. Treatment of 12-month-old mice with oligomer-specific (A-887755) or conformation-unspecific (6G1) antibodies for 8 weeks did not affect fibrillar plaque density or growth. We also quantified densities of DLG4 (previously known as PSD95) expressing post-synapses and synapsin expressing presynapses immunohistochemically. We found that both pre- and post-synapses were strongly reduced in the vicinity of plaques, whereas distant from plaques, in the cortex and hippocampal CA1 field, only post-synapses were reduced. Immunotherapy alleviated this synapse loss. Synapse loss was completely abolished distant from plaques, whereas it was only attenuated in the vicinity of plaques. These results suggest that fibrillar plaques may act as reservoirs for synaptotoxic, oligomeric amyloid-β and that sequestering oligomers suffices to counteract synaptic pathology. Therefore, cognitive function may be improved by immunotherapy even when the load of fibrillar amyloid remains unchanged. PMID:25281869

Hetero-oligomeric Complex between the G Protein-coupled Estrogen Receptor 1 and the Plasma Membrane Ca2+-ATPase 4b*

PubMed Central

Tran, Quang-Kim; VerMeer, Mark; Burgard, Michelle A.; Hassan, Ali B.; Giles, Jennifer

2015-01-01

The new G protein-coupled estrogen receptor 1 (GPER/GPR30) plays important roles in many organ systems. The plasma membrane Ca2+-ATPase (PMCA) is essential for removal of cytoplasmic Ca2+ and for shaping the time courses of Ca2+-dependent activities. Here, we show that PMCA and GPER/GPR30 physically interact and functionally influence each other. In primary endothelial cells, GPER/GPR30 agonist G-1 decreases PMCA-mediated Ca2+ extrusion by promoting PMCA tyrosine phosphorylation. GPER/GPR30 overexpression decreases PMCA activity, and G-1 further potentiates this effect. GPER/GPR30 knockdown increases PMCA activity, whereas PMCA knockdown substantially reduces GPER/GPR30-mediated phosphorylation of the extracellular signal-related kinase (ERK1/2). GPER/GPR30 co-immunoprecipitates with PMCA with or without treatment with 17β-estradiol, thapsigargin, or G-1. Heterologously expressed GPER/GPR30 in HEK 293 cells co-localizes with PMCA4b, the main endothelial PMCA isoform. Endothelial cells robustly express the PDZ post-synaptic density protein (PSD)-95, whose knockdown reduces the association between GPER/GPR30 and PMCA. Additionally, the association between PMCA4b and GPER/GPR30 is substantially reduced by truncation of either or both of their C-terminal PDZ-binding motifs. Functionally, inhibition of PMCA activity is significantly reduced by truncation of GPER/GPR30's C-terminal PDZ-binding motif. These data strongly indicate that GPER/GPR30 and PMCA4b form a hetero-oligomeric complex in part via the anchoring action of PSD-95, in which they constitutively affect each other's function. Activation of GPER/GPR30 further inhibits PMCA activity through tyrosine phosphorylation of the pump. These interactions represent cross-talk between Ca2+ signaling and GPER/GPR30-mediated activities. PMID:25847233

Hetero-oligomeric Complex between the G Protein-coupled Estrogen Receptor 1 and the Plasma Membrane Ca2+-ATPase 4b.

PubMed

Tran, Quang-Kim; VerMeer, Mark; Burgard, Michelle A; Hassan, Ali B; Giles, Jennifer

2015-05-22

The new G protein-coupled estrogen receptor 1 (GPER/GPR30) plays important roles in many organ systems. The plasma membrane Ca(2+)-ATPase (PMCA) is essential for removal of cytoplasmic Ca(2+) and for shaping the time courses of Ca(2+)-dependent activities. Here, we show that PMCA and GPER/GPR30 physically interact and functionally influence each other. In primary endothelial cells, GPER/GPR30 agonist G-1 decreases PMCA-mediated Ca(2+) extrusion by promoting PMCA tyrosine phosphorylation. GPER/GPR30 overexpression decreases PMCA activity, and G-1 further potentiates this effect. GPER/GPR30 knockdown increases PMCA activity, whereas PMCA knockdown substantially reduces GPER/GPR30-mediated phosphorylation of the extracellular signal-related kinase (ERK1/2). GPER/GPR30 co-immunoprecipitates with PMCA with or without treatment with 17β-estradiol, thapsigargin, or G-1. Heterologously expressed GPER/GPR30 in HEK 293 cells co-localizes with PMCA4b, the main endothelial PMCA isoform. Endothelial cells robustly express the PDZ post-synaptic density protein (PSD)-95, whose knockdown reduces the association between GPER/GPR30 and PMCA. Additionally, the association between PMCA4b and GPER/GPR30 is substantially reduced by truncation of either or both of their C-terminal PDZ-binding motifs. Functionally, inhibition of PMCA activity is significantly reduced by truncation of GPER/GPR30's C-terminal PDZ-binding motif. These data strongly indicate that GPER/GPR30 and PMCA4b form a hetero-oligomeric complex in part via the anchoring action of PSD-95, in which they constitutively affect each other's function. Activation of GPER/GPR30 further inhibits PMCA activity through tyrosine phosphorylation of the pump. These interactions represent cross-talk between Ca(2+) signaling and GPER/GPR30-mediated activities. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Supervised segmentation of microelectrode recording artifacts using power spectral density.

PubMed

Bakstein, Eduard; Schneider, Jakub; Sieger, Tomas; Novak, Daniel; Wild, Jiri; Jech, Robert

2015-08-01

Appropriate detection of clean signal segments in extracellular microelectrode recordings (MER) is vital for maintaining high signal-to-noise ratio in MER studies. Existing alternatives to manual signal inspection are based on unsupervised change-point detection. We present a method of supervised MER artifact classification, based on power spectral density (PSD) and evaluate its performance on a database of 95 labelled MER signals. The proposed method yielded test-set accuracy of 90%, which was close to the accuracy of annotation (94%). The unsupervised methods achieved accuracy of about 77% on both training and testing data.

Environmental Assessment: Lake Yankton Fish Population Renovation Project Yankton County, South Dakota and Cedar County, Nebraska

DTIC Science & Technology

2014-08-01

2013 for largemouth bass only. Year Largemouth bass CPUE1 (Total no/hr) PSD2 RSD -P3 1994 61 80 43 1995 61 49 9 1996 84 57 17 1997 59 95 15 1998...of 50-80 for bass is desirable for a pond manager with trophy bass goals. 3 RSD (relative stock density) - The relative stock density is the...percentage of fish of any designated length-group in a sample of fish. Within that sample the RSD -P is the percentage of those fish that are of preferred

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.

Dynamic landscape of the local translation at activated synapses.

PubMed

Khlebodarova, T M; Kogai, V V; Trifonova, E A; Likhoshvai, V A

2018-01-01

The mammalian target of rapamycin (mTOR) signaling pathway is the central regulator of cap-dependent translation at the synapse. Disturbances in mTOR pathway have been associated with several neurological diseases, such as autism and epilepsy. RNA-binding protein FMRP, a negative regulator of translation initiation, is one of the key components of the local translation system. Activation and inactivation of FMRP occurs via phosphorylation by S6 kinase and dephosphorylation by PP2A phosphatase, respectively. S6 kinase and PP2A phosphatase are activated in response to mGluR receptor stimulation through different signaling pathways and at different rates. The dynamic aspects of this system are poorly understood. We developed a mathematical model of FMRP-dependent regulation of postsynaptic density (PSD) protein synthesis in response to mGluR receptor stimulation and conducted in silico experiments to study the regulatory circuit functioning. The modeling results revealed the possibility of generating oscillatory (cyclic and quasi-cyclic), chaotic and even hyperchaotic dynamics of postsynaptic protein synthesis as well as the presence of multiple attractors in a wide range of parameters of the local translation system. The results suggest that autistic disorders associated with mTOR pathway hyperactivation may be due to impaired proteome stability associated with the formation of complex dynamic regimes of PSD protein synthesis in response to stimulation of mGluR receptors on the postsynaptic membrane of excitatory synapses on pyramidal hippocampal cells.

Solar Wind Turbulence and Intermittency at 0.72 AU - Statistical Approach

NASA Astrophysics Data System (ADS)

Teodorescu, E.; Echim, M.; Munteanu, C.; Zhang, T.; Barabash, S. V.; Budnik, E.; Fedorov, A.

2014-12-01

Through this analysis we characterize the turbulent magnetic fluctuations by Venus Express Magnetometer, VEX-MAG in the solar wind during the last solar cycle minimum at a distance of 0.72 AU from the Sun. We analyze data recorded between 2007 and 2009 with time resolutions of 1 Hz and 32 Hz. In correlation with plasma data from the ASPERA instrument, Analyser of Space Plasma and Energetic Atoms, we identify 550 time intervals, at 1 Hz resolution, when VEX is in the solar wind and which satisfy selection criteria defined based on the amount and the continuity of the data. We identify 118 time intervals that correspond to fast solar wind. We compute the power spectral densities (PSD) for Bx, By, Bz, B, B2, B|| and B^. We perform a statistical analysis of the spectral indices computed for each of the PSD's and evidence a dependence of the spectral index on the solar wind velocity and a slight difference in power content between parallel and perpendicular components of the magnetic field. We also estimate the scale invariance of fluctuations by computing the Probability Distribution Functions (PDFs) for Bx, By, Bz, B and B2 time series and discuss the implications for intermittent turbulence. Research supported by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 313038/STORM, and a grant of the Romanian Ministry of National Education, CNCS - UEFISCDI, project number PN-II-ID-PCE-2012-4-0418.

Memantine mediates neuroprotection via regulating neurovascular unit in a mouse model of focal cerebral ischemia.

PubMed

Chen, Zheng-Zhen; Yang, Dan-Dan; Zhao, Zhan; Yan, Hui; Ji, Juan; Sun, Xiu-Lan

2016-04-01

Memantine is a low-moderate affinity and uncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist, which is also a potential neuroprotectant in acute ischemic stroke for its particular action profiles. The present study was to reveal the mechanisms involved in the neuroprotection of memantine. We used a mouse model of permanent focal cerebral ischemia via middle cerebral artery occlusion to verify our hypothesis. 2,3,5-Triphenyltetrazolium chloride staining was used to compare infarct size. The amount of astrocytes and the somal volume of the microglia cell body were analyzed by immunohistochemistry and stereological estimates. Western blotting was used to determine the protein expressions. Memantine prevented cerebral ischemia-induced brain infarct and neuronal injury, and reduced oxygen-glucose deprivation-induced cortical neuronal apoptosis. Moreover, memantine reduced the amount of the damaged astrocytes and over activated microglia after 24h of ischemia. In the early phase of ischemia, higher production of MMP-9 was observed, and thereby collagen IV was dramatically disrupted. Meanwhile, the post-synaptic density protein 95(PSD-95) was also severely cleavaged. Memantine decreased MMP-9 secretion, prevented the degradation of collagen IV in mouse brain. PSD-95 cleavage was also inhibited by memantine. These results suggested that memantine exerted neuroprotection effects in acute ischemic brain damage, partially via improving the functions of neurovascular unit. Taking all these findings together, we consider that memantine might be a promising protective agent against ischemic stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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

Archambault, L; Papaconstadopoulos, P; Seuntjens, J

Purpose: To study Cherenkov light emission in plastic scintillation detectors (PSDs) from a theoretical point of view to identify situations that may arise where the calibration coefficient obtained in one condition is not applicable to another condition. By identifying problematic situations, we hope to provide guidance on how to confidently use PSDs. Methods: Cherenkov light emission in PSD was modelled using basic physical principles. In particular, changes in refractive index as a function of wavelength were accounted for using the Sellmeier empirical equation. Both electron and photon beams were considered. For photons, realistic distributions of secondary charged particles were calculatedmore » using Klein-Nishina’s formula. Cherenkov production and collection in PSDs were studied for a range of parameters including beam energy, charged particle momentum distribution, detector orientation and material composition. Finally, experimental validation was made using a commercial plastic scintillation detector. Results: In specific situations, results show that the Cherenkov spectrum coupled in the PSD can deviate from its expected behaviour (i.e. one over the square of the wavelength). In these cases were the model is realistic it is possible to see a peak wavelength instead of a monotonically decreasing function. Consequences of this phenomenon are negligible when the momentum of charged particle is distributed randomly, but in some clinically relevant cases, such as an electron beam at depth close to R50 or for photon beams with minimal scatter component, the value of the calibration coefficient can be altered. Experimental tests with electron beams showed changes in the Cherenkov light ratio, the parameter used in the calibration of PSDs, up to 2–3% depending on the PSD orientation. Conclusion: This work is the first providing a physical explanation for apparent change in PSD calibration coefficient. With this new information at hand, it will be possible to better guide the clinical use of PSDs.« less

Fast convergent frequency-domain MIMO equalizer for few-mode fiber communication systems

NASA Astrophysics Data System (ADS)

He, Xuan; Weng, Yi; Wang, Junyi; Pan, Z.

2018-02-01

Space division multiplexing using few-mode fibers has been extensively explored to sustain the continuous traffic growth. In few-mode fiber optical systems, both spatial and polarization modes are exploited to transmit parallel channels, thus increasing the overall capacity. However, signals on spatial channels inevitably suffer from the intrinsic inter-modal coupling and large accumulated differential mode group delay (DMGD), which causes spatial modes de-multiplex even harder. Many research articles have demonstrated that frequency domain adaptive multi-input multi-output (MIMO) equalizer can effectively compensate the DMGD and demultiplex the spatial channels with digital signal processing (DSP). However, the large accumulated DMGD usually requires a large number of training blocks for the initial convergence of adaptive MIMO equalizers, which will decrease the overall system efficiency and even degrade the equalizer performance in fast-changing optical channels. Least mean square (LMS) algorithm is always used in MIMO equalization to dynamically demultiplex the spatial signals. We have proposed to use signal power spectral density (PSD) dependent method and noise PSD directed method to improve the convergence speed of adaptive frequency domain LMS algorithm. We also proposed frequency domain recursive least square (RLS) algorithm to further increase the convergence speed of MIMO equalizer at cost of greater hardware complexity. In this paper, we will compare the hardware complexity and convergence speed of signal PSD dependent and noise power directed algorithms against the conventional frequency domain LMS algorithm. In our numerical study of a three-mode 112 Gbit/s PDM-QPSK optical system with 3000 km transmission, the noise PSD directed and signal PSD dependent methods could improve the convergence speed by 48.3% and 36.1% respectively, at cost of 17.2% and 10.7% higher hardware complexity. We will also compare the frequency domain RLS algorithm against conventional frequency domain LMS algorithm. Our numerical study shows that, in a three-mode 224 Gbit/s PDM-16-QAM system with 3000 km transmission, the RLS algorithm could improve the convergence speed by 53.7% over conventional frequency domain LMS algorithm.

Influence of wind turbines on seismic stations in the upper rhine graben, SW Germany

NASA Astrophysics Data System (ADS)

Zieger, Toni; Ritter, Joachim R. R.

2018-01-01

By analysing long- and short-term seismological measurements at wind farms close to the town of Landau, SW Germany, we present new insights into ground motion signals from wind turbines (WTs) at local seismic stations. Because of their need to be located in similar regions with sparsely anthropogenic activities, wind turbines impact seismic stations and their recordings in a way that is not yet fully understood by researchers. To ensure the undisturbed recording tasks of a regional seismic array or a single station by a protected area around those endangered stations, it is very important to investigate the behavior of WTs as a seismic source. For that reason, we calculate averaged one-hour long spectra of the power spectral density (PSD) before and after the installation of a new wind farm within the investigated area. These PSD are ordered according to the rotation speed. We observe a clear increase of the PSD level after the WT installation in a frequency range of 0.5 to 10 Hz up to a distance of 5.5 km away from the WT. By analysing seismic borehole data, we also observe a decrease of the PSD of wind dependent signals with depth. The impact of wind-dependent signals is found to be much more pronounced for the shallower station (150 m depth) than for the deeper one (305 m depth). Using short-term profile measurements, we fit a power-law decay proportional to 1/ r b to the main WT-induced PSD peaks and differentiate between near-field and far-field effects of ground motions. For low frequencies in the range from 1 to 4 Hz, we determine a b value of 0.78 to 0.85 for the far field, which is consistent with surface waves. The b value increases (up to 1.59) with increasing frequencies (up to 5.5 Hz), which is obviously due to attenuating effects like scattering or anelasticity. These results give a better understanding of the seismic wavefield interactions between wind turbines (or wind farms) with nearby seismic stations, including borehole installations, in a sedimentary setting.

Recombinant probes for visualizing endogenous synaptic proteins in living neurons

PubMed Central

Gross, Garrett G.; Junge, Jason A.; Mora, Rudy J.; Kwon, Hyung-Bae; Olson, C. Anders; Takahashi, Terry T.; Liman, Emily R.; Ellis-Davies, Graham C.R.; McGee, Aaron W.; Sabatini, Bernardo L.; Roberts, Richard W.; Arnold, Don B.

2013-01-01

Summary The ability to visualize endogenous proteins in living neurons provides a powerful means to interrogate neuronal structure and function. Here we generate recombinant antibody-like proteins, termed FingRs (Fibronectin intrabodies generated with mRNA display), that bind endogenous neuronal proteins PSD-95 and Gephyrin with high affinity and which, when fused to GFP, allow excitatory and inhibitory synapses to be visualized in living neurons. Design of the FingR incorporates a novel transcriptional regulation system that ties FingR expression to the level of the target and reduces background fluorescence. In dissociated neurons and brain slices FingRs generated against PSD-95 and Gephyrin did not affect the expression patterns of their endogenous target proteins or the number or strength of synapses. Together, our data indicate that PSD-95 and Gephyrin FingRs can report the localization and amount of endogenous synaptic proteins in living neurons and thus may be used to study changes in synaptic strength in vivo. PMID:23791193

CDKL5 ensures excitatory synapse stability by reinforcing NGL-1-PSD95 interaction in the postsynaptic compartment and is impaired in patient iPSC-derived neurons.

PubMed

Ricciardi, Sara; Ungaro, Federica; Hambrock, Melanie; Rademacher, Nils; Stefanelli, Gilda; Brambilla, Dario; Sessa, Alessandro; Magagnotti, Cinzia; Bachi, Angela; Giarda, Elisa; Verpelli, Chiara; Kilstrup-Nielsen, Charlotte; Sala, Carlo; Kalscheuer, Vera M; Broccoli, Vania

2012-09-01

Mutations of the cyclin-dependent kinase-like 5 (CDKL5) and netrin-G1 (NTNG1) genes cause a severe neurodevelopmental disorder with clinical features that are closely related to Rett syndrome, including intellectual disability, early-onset intractable epilepsy and autism. We report here that CDKL5 is localized at excitatory synapses and contributes to correct dendritic spine structure and synapse activity. To exert this role, CDKL5 binds and phosphorylates the cell adhesion molecule NGL-1. This phosphorylation event ensures a stable association between NGL-1 and PSD95. Accordingly, phospho-mutant NGL-1 is unable to induce synaptic contacts whereas its phospho-mimetic form binds PSD95 more efficiently and partially rescues the CDKL5-specific spine defects. Interestingly, similarly to rodent neurons, iPSC-derived neurons from patients with CDKL5 mutations exhibit aberrant dendritic spines, thus suggesting a common function of CDKL5 in mice and humans.

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.

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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.

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.

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.

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.

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

Symmetric Positive 4th Order Tensors & Their Estimation from Diffusion Weighted MRI⋆

PubMed Central

Barmpoutis, Angelos; Jian, Bing; Vemuri, Baba C.; Shepherd, Timothy M.

2009-01-01

In Diffusion Weighted Magnetic Resonance Image (DW-MRI) processing a 2nd order tensor has been commonly used to approximate the diffusivity function at each lattice point of the DW-MRI data. It is now well known that this 2nd-order approximation fails to approximate complex local tissue structures, such as fibers crossings. In this paper we employ a 4th order symmetric positive semi-definite (PSD) tensor approximation to represent the diffusivity function and present a novel technique to estimate these tensors from the DW-MRI data guaranteeing the PSD property. There have been several published articles in literature on higher order tensor approximations of the diffusivity function but none of them guarantee the positive semi-definite constraint, which is a fundamental constraint since negative values of the diffusivity coefficients are not meaningful. In our methods, we parameterize the 4th order tensors as a sum of squares of quadratic forms by using the so called Gram matrix method from linear algebra and its relation to the Hilbert’s theorem on ternary quartics. This parametric representation is then used in a nonlinear-least squares formulation to estimate the PSD tensors of order 4 from the data. We define a metric for the higher-order tensors and employ it for regularization across the lattice. Finally, performance of this model is depicted on synthetic data as well as real DW-MRI from an isolated rat hippocampus. PMID:17633709

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

Comparative study of methods to calibrate the stiffness of a single-beam gradient-force optical tweezers over various laser trapping powers

PubMed Central

Sarshar, Mohammad; Wong, Winson T.; Anvari, Bahman

2014-01-01

Abstract. Optical tweezers have become an important instrument in force measurements associated with various physical, biological, and biophysical phenomena. Quantitative use of optical tweezers relies on accurate calibration of the stiffness of the optical trap. Using the same optical tweezers platform operating at 1064 nm and beads with two different diameters, we present a comparative study of viscous drag force, equipartition theorem, Boltzmann statistics, and power spectral density (PSD) as methods in calibrating the stiffness of a single beam gradient force optical trap at trapping laser powers in the range of 0.05 to 1.38 W at the focal plane. The equipartition theorem and Boltzmann statistic methods demonstrate a linear stiffness with trapping laser powers up to 355 mW, when used in conjunction with video position sensing means. The PSD of a trapped particle’s Brownian motion or measurements of the particle displacement against known viscous drag forces can be reliably used for stiffness calibration of an optical trap over a greater range of trapping laser powers. Viscous drag stiffness calibration method produces results relevant to applications where trapped particle undergoes large displacements, and at a given position sensing resolution, can be used for stiffness calibration at higher trapping laser powers than the PSD method. PMID:25375348

Combining optimization methods with response spectra curve-fitting toward improved damping ratio estimation

NASA Astrophysics Data System (ADS)

Brewick, Patrick T.; Smyth, Andrew W.

2016-12-01

The authors have previously shown that many traditional approaches to operational modal analysis (OMA) struggle to properly identify the modal damping ratios for bridges under traffic loading due to the interference caused by the driving frequencies of the traffic loads. This paper presents a novel methodology for modal parameter estimation in OMA that overcomes the problems presented by driving frequencies and significantly improves the damping estimates. This methodology is based on finding the power spectral density (PSD) of a given modal coordinate, and then dividing the modal PSD into separate regions, left- and right-side spectra. The modal coordinates were found using a blind source separation (BSS) algorithm and a curve-fitting technique was developed that uses optimization to find the modal parameters that best fit each side spectra of the PSD. Specifically, a pattern-search optimization method was combined with a clustering analysis algorithm and together they were employed in a series of stages in order to improve the estimates of the modal damping ratios. This method was used to estimate the damping ratios from a simulated bridge model subjected to moving traffic loads. The results of this method were compared to other established OMA methods, such as Frequency Domain Decomposition (FDD) and BSS methods, and they were found to be more accurate and more reliable, even for modes that had their PSDs distorted or altered by driving frequencies.

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.

A Presynaptic Function of Shank Protein in Drosophila.

PubMed

Wu, Song; Gan, Guangming; Zhang, Zhiping; Sun, Jie; Wang, Qifu; Gao, Zhongbao; Li, Meixiang; Jin, Shan; Huang, Juan; Thomas, Ulrich; Jiang, Yong-Hui; Li, Yan; Tian, Rui; Zhang, Yong Q

2017-11-29

Human genetic studies support that loss-of-function mutations in the SH 3 domain and ank yrin repeat containing family proteins (SHANK1-3), the large synaptic scaffolding proteins enriched at the postsynaptic density of excitatory synapses, are causative for autism spectrum disorder and other neuropsychiatric disorders in humans. To better understand the in vivo functions of Shank and facilitate dissection of neuropathology associated with SHANK mutations in human, we generated multiple mutations in the Shank gene, the only member of the SHANK family in Drosophila melanogaster Both male and female Shank null mutants were fully viable and fertile with no apparent morphological or developmental defects. Expression analysis revealed apparent enrichment of Shank in the neuropils of the CNS. Specifically, Shank coexpressed with another PSD scaffold protein, Homer, in the calyx of mushroom bodies in the brain. Consistent with high expression in mushroom body calyces, Shank mutants show an abnormal calyx structure and reduced olfactory acuity. These morphological and functional phenotypes were fully rescued by pan-neuronal reexpression of Shank, and only partially rescued by presynaptic but no rescue by postsynaptic reexpression of Shank. Our findings thus establish a previously unappreciated presynaptic function of Shank. SIGNIFICANCE STATEMENT Mutations in SHANK family genes are causative for idiopathic autism spectrum disorder. To understand the neural function of Shank, a large scaffolding protein enriched at the postsynaptic densities, we examined the role of Drosophila Shank in synapse development at the peripheral neuromuscular junctions and the central mushroom body calyx. Our results demonstrate that, in addition to its conventional postsynaptic function, Shank also acts presynaptically in synapse development in the brain. This study offers novel insights into the synaptic role of Shank. Copyright © 2017 the authors 0270-6474/17/3711592-13$15.00/0.

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.

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...

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...

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...

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...

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...

Insulation and wiring specificity of BceR-like response regulators and their target promoters in Bacillus subtilis.

PubMed

Fang, Chong; Nagy-Staroń, Anna; Grafe, Martin; Heermann, Ralf; Jung, Kirsten; Gebhard, Susanne; Mascher, Thorsten

2017-04-01

BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, P bceA or P psdA , resulting in a strong up-regulation of target gene expression and ultimately antibiotic resistance. Despite high sequence similarity between the RRs BceR and PsdR and their known binding sites, no cross-regulation has been observed between them. We therefore investigated the specificity determinants of P bceA and P psdA that ensure the insulation of these two paralogous pathways at the RR-promoter interface. In vivo and in vitro analyses demonstrate that the regulatory regions within these two promoters contain three important elements: in addition to the known (main) binding site, we identified a linker region and a secondary binding site that are crucial for functionality. Initial binding to the high-affinity, low-specificity main binding site is a prerequisite for the subsequent highly specific binding of a second RR dimer to the low-affinity secondary binding site. In addition to this hierarchical cooperative binding, discrimination requires a competition of the two RRs for their respective binding site mediated by only slight differences in binding affinities. © 2016 John Wiley & Sons Ltd.

Marshall Space Flight Center Propulsion Systems Department (PSD) KM Initiative

NASA Technical Reports Server (NTRS)

Caraccioli, Paul; Varnadoe, Tom; McCarter, Mike

2006-01-01

NASA Marshall Space Flight Center s Propulsion Systems Department (PSD) is four months into a fifteen month Knowledge Management (KM) initiative to support enhanced engineering decision making and analyses, faster resolution of anomalies (near-term) and effective, efficient knowledge infused engineering processes, reduced knowledge attrition, and reduced anomaly occurrences (long-term). The near-term objective of this initiative is developing a KM Pilot project, within the context of a 3-5 year KM strategy, to introduce and evaluate the use of KM within PSD. An internal NASA/MSFC PSD KM team was established early in project formulation to maintain a practitioner, user-centric focus throughout the conceptual development, planning and deployment of KM technologies and capabilities with in the PSD. The PSD internal team is supported by the University of Alabama's Aging Infrastructure Systems Center Of Excellence (AISCE), Intergraph Corporation, and The Knowledge Institute. The principle product of the initial four month effort has been strategic planning of PSD KM implementation by first determining the "as is" state of KM capabilities and developing, planning and documenting the roadmap to achieve the desired "to be" state. Activities undertaken to support the planning phase have included data gathering; cultural surveys, group work-sessions, interviews, documentation review, and independent research. Assessments and analyses have been performed including industry benchmarking, related local and Agency initiatives, specific tools and techniques used and strategies for leveraging existing resources, people and technology to achieve common KM goals. Key findings captured in the PSD KM Strategic Plan include the system vision, purpose, stakeholders, prioritized strategic objectives mapped to the top ten practitioner needs and analysis of current resource usage. Opportunities identified from research, analyses, cultural/KM surveys and practitioner interviews include: executive and senior management sponsorship, KM awareness, promotion and training, cultural change management, process improvement, leveraging existing resources and new innovative technologies to align with other NASA KM initiatives (convergence: the big picture). To enable results based incremental implementation and future growth of the KM initiative, key performance measures have been identified including stakeholder value, system utility, learning and growth (knowledge capture, sharing, reduced anomaly recurrence), cultural change, process improvement and return-on-investment. The next steps for the initial implementation spiral (focused on SSME Turbomachinery) have been identified, largely based on the organization and compilation of summary level engineering process models, data capture matrices, functional models and conceptual-level systems architecture. Key elements include detailed KM requirements definition, KM technology architecture assessment, evaluation and selection, deployable KM Pilot design, development, implementation and evaluation, and justifying full implementation (estimated Return-on-Investment). Features identified for the notional system architecture include the knowledge presentation layer (and its components), knowledge network layer (and its components), knowledge storage layer (and its components), User Interface and capabilities. This paper provides a snapshot of the progress to date, the near term planning for deploying the KM pilot project and a forward look at results based growth of KM capabilities with-in the MSFC PSD.

Marshall Space Flight Center Propulsion Systems Department (PSD) Knowledge Management (KM) Initiative

NASA Technical Reports Server (NTRS)

Caraccioli, Paul; Varnedoe, Tom; Smith, Randy; McCarter, Mike; Wilson, Barry; Porter, Richard

2006-01-01

NASA Marshall Space Flight Center's Propulsion Systems Department (PSD) is four months into a fifteen month Knowledge Management (KM) initiative to support enhanced engineering decision making and analyses, faster resolution of anomalies (near-term) and effective, efficient knowledge infused engineering processes, reduced knowledge attrition, and reduced anomaly occurrences (long-term). The near-term objective of this initiative is developing a KM Pilot project, within the context of a 3-5 year KM strategy, to introduce and evaluate the use of KM within PSD. An internal NASA/MSFC PSD KM team was established early in project formulation to maintain a practitioner, user-centric focus throughout the conceptual development, planning and deployment of KM technologies and capabilities within the PSD. The PSD internal team is supported by the University of Alabama's Aging Infrastructure Systems Center of Excellence (AISCE), lntergraph Corporation, and The Knowledge Institute. The principle product of the initial four month effort has been strategic planning of PSD KNI implementation by first determining the "as is" state of KM capabilities and developing, planning and documenting the roadmap to achieve the desired "to be" state. Activities undertaken to suppoth e planning phase have included data gathering; cultural surveys, group work-sessions, interviews, documentation review, and independent research. Assessments and analyses have beon pedormed including industry benchmarking, related local and Agency initiatives, specific tools and techniques used and strategies for leveraging existing resources, people and technology to achieve common KM goals. Key findings captured in the PSD KM Strategic Plan include the system vision, purpose, stakeholders, prioritized strategic objectives mapped to the top ten practitioner needs and analysis of current resource usage. Opportunities identified from research, analyses, cultural1KM surveys and practitioner interviews include: executive and senior management sponsorship, KM awareness, promotion and training, cultural change management, process improvement, leveraging existing resources and new innovative technologies to align with other NASA KM initiatives (convergence: the big picture). To enable results based incremental implementation and future growth of the KM initiative, key performance measures have been identified including stakeholder value, system utility, learning and growth (knowledge capture, sharing, reduced anomaly recurrence), cultural change, process improvement and return-on-investment. The next steps for the initial implementation spiral (focused on SSME Turbomachinery) have been identified, largely based on the organization and compilation of summary level engineering process models, data capture matrices, functional models and conceptual-level svstems architecture. Key elements include detailed KM requirements definition, KM technology architecture assessment, - evaluation and selection, deployable KM Pilot design, development, implementation and evaluation, and justifying full implementation (estimated Return-on-Investment). Features identified for the notional system architecture include the knowledge presentation layer (and its components), knowledge network layer (and its components), knowledge storage layer (and its components), User Interface and capabilities. This paper provides a snapshot of the progress to date, the near term planning for deploying the KM pilot project and a forward look at results based growth of KM capabilities with-in the MSFC PSD.

Analysis of longer period variation of the Kuroshio Current intrusion into the Luzon Strait using rectified wavelet power spectra

NASA Astrophysics Data System (ADS)

Yuan, Yaochu; Yang, Chenghao; Tseng, Yu-heng; Zhu, Xiao-Hua; Wang, Huiqun; Chen, Hong

2017-08-01

Longer period variation of the Kuroshio into the Luzon Strait (LS) was identified using acoustic Doppler current profiler (ADCP) observations as well as pressure and temperature time series data recorded by two TDs (manufactured by the RBR Ltd.) at mooring station N2 (20°40.441‧N, 120°38.324‧E). The ADCP was deployed at depths of 50-300 m between July 7, 2009 and April 10, 2011, and the TDs at around 340 and 365 m between July 9, 2009 and July 9, 2011. Observations provide strong evidence of longer period variation of the Kuroshio into the LS using the Vector rotary spectra (VRS) and Rectified wavelet power spectra analysis (RWPSA). RWPSA of the observations allowed the identification of two types of dominant periods. The first type, with the strongest power spectral density (PSD), had a dominant period of 112 d and was found throughout the upper 300 m. For example, the maximum PSD for western and northern velocity components time series were 3800 and 3550 at 50 m, respectively. The maximum power spectral density decrease with deeper depths, i.e., the depth dependence of maximum PSD. The 112 d period was also identified in the pressure and temperature time series data, at 340 m and 365 m. Combined RWPSA with VRS and mechanism analysis, it is clear that the occurrence of the most dominant period of 112 d in the upper 300 m is related to the clockwise meandering of the Kuroshio into the LS, which is caused by westward propagating stronger anticyclonic eddies from the interior ocean due to the interaction of Rossby eddies with the Kuroshio. The second type of dominant period, for example a 40 d period, is related to the anticlockwise meandering of the Kuroshio. The final dominant period of 14 d coincides with the fortnightly spring-neap tidal period.

Proteomic characterization of a mouse model of familial Danish dementia.

PubMed

Vitale, Monica; Renzone, Giovanni; Matsuda, Shuji; Scaloni, Andrea; D'Adamio, Luciano; Zambrano, Nicola

2012-01-01

A dominant mutation in the ITM2B/BRI2 gene causes familial Danish dementia (FDD) in humans. To model FDD in animal systems, a knock-in approach was recently implemented in mice expressing a wild-type and mutant allele, which bears the FDD-associated mutation. Since these FDD(KI) mice show behavioural alterations and impaired synaptic function, we characterized their synaptosomal proteome via two-dimensional differential in-gel electrophoresis. After identification by nanoliquid chromatography coupled to electrospray-linear ion trap tandem mass spectrometry, the differentially expressed proteins were classified according to their gene ontology descriptions and their predicted functional interactions. The Dlg4/Psd95 scaffold protein and additional signalling proteins, including protein phosphatases, were revealed by STRING analysis as potential players in the altered synaptic function of FDD(KI) mice. Immunoblotting analysis finally demonstrated the actual downregulation of the synaptosomal scaffold protein Dlg4/Psd95 and of the dual-specificity phosphatase Dusp3 in the synaptosomes of FDD(KI) mice.

Proteomic Characterization of a Mouse Model of Familial Danish Dementia

PubMed Central

Vitale, Monica; Renzone, Giovanni; Matsuda, Shuji; Scaloni, Andrea; D'Adamio, Luciano; Zambrano, Nicola

2012-01-01

A dominant mutation in the ITM2B/BRI2 gene causes familial Danish dementia (FDD) in humans. To model FDD in animal systems, a knock-in approach was recently implemented in mice expressing a wild-type and mutant allele, which bears the FDD-associated mutation. Since these FDDKI mice show behavioural alterations and impaired synaptic function, we characterized their synaptosomal proteome via two-dimensional differential in-gel electrophoresis. After identification by nanoliquid chromatography coupled to electrospray-linear ion trap tandem mass spectrometry, the differentially expressed proteins were classified according to their gene ontology descriptions and their predicted functional interactions. The Dlg4/Psd95 scaffold protein and additional signalling proteins, including protein phosphatases, were revealed by STRING analysis as potential players in the altered synaptic function of FDDKI mice. Immunoblotting analysis finally demonstrated the actual downregulation of the synaptosomal scaffold protein Dlg4/Psd95 and of the dual-specificity phosphatase Dusp3 in the synaptosomes of FDDKI mice. PMID:22619496

Long time scale hard X-ray variability in Seyfert 1 galaxies

NASA Astrophysics Data System (ADS)

Markowitz, Alex Gary

This dissertation examines the relationship between long-term X-ray variability characteristics, black hole mass, and luminosity of Seyfert 1 Active Galactic Nuclei. High dynamic range power spectral density functions (PSDs) have been constructed for six Seyfert 1 galaxies. These PSDs show "breaks" or characteristic time scales, typically on the order of a few days. There is resemblance to PSDs of lower-mass Galactic X-ray binaries (XRBs), with the ratios of putative black hole masses and variability time scales approximately the same (106--7) between the two classes of objects. The data are consistent with a linear correlation between Seyfert PSD break time scale and black hole mass estimate; the relation extrapolates reasonably well over 6--7 orders of magnitude to XRBs. All of this strengthens the case for a physical similarity between Seyfert galaxies and XRBs. The first six years of RXTE monitoring of Seyfert 1s have been systematically analyzed to probe hard X-ray variability on multiple time scales in a total of 19 Seyfert is in an expansion of the survey of Markowitz & Edelson (2001). Correlations between variability amplitude, luminosity, and black hole mass are explored, the data support the model of PSD movement with black hole mass suggested by the PSD survey. All of the continuum variability results are consistent with relatively more massive black holes hosting larger X-ray emission regions, resulting in 'slower' observed variability. Nearly all sources in the sample exhibit stronger variability towards softer energies, consistent with softening as they brighten. Direct time-resolved spectral fitting has been performed on continuous RXTE monitoring of seven Seyfert is to study long-term spectral variability and Fe Kalpha variability characteristics. The Fe Kalpha line displays a wide range of behavior but varies less strongly than the broadband continuum. Overall, however, there is no strong evidence for correlated variability between the line and continuum, severely challenging models in which the line tracks continuum variations modified only by a light-travel time delay. This experiment yields further support for spectral softening as continuum flux increases.

Subcellular Nanoparticle Distribution from Light Transmission Spectroscopy

NASA Astrophysics Data System (ADS)

Deatsch, Alison; Sun, Nan; Johnson, Jeffrey; Stack, Sharon; Tanner, Carol; Ruggiero, Steven

We have measured the particle-size distribution (PSD) of subcellular structures in plant and animal cells. We have employed a new technique developed by our group, Light Transmission Spectroscopy-combined with cell fractionation-to accurately measure PSDs over a wide size range: from 10 nm to 3000nm, which includes objects from the size of individual proteins to organelles. To date our experiments have included cultured human oral cells and spinach cells. These results show a power-law dependence of particle density with particle diameter, implying a universality of the packing distribution. We discuss modeling the cell as a self-similar (fractal) body comprised of spheres on all size scales. This goal of this work is to obtain a better understanding of the fundamental nature of particle packing within cells in order to enrich our knowledge of the structure, function, and interactions of sub-cellular nanostructures across cell types.