Segmental arterial mediolysis with accompanying venous angiopathy: a clinical pathologic review, report of 3 new cases, and comments on the role of endothelin-1 in its pathogenesis.

PubMed

Slavin, Richard E; Inada, Kiyoshi

2007-04-01

The authors review 20 cases of segmental arterial mediolysis (SAM) including 3 newly reported cases. SAM developed in areas of vascular distention in 2 of the latter cases: 1 in utero in the heart of a recipient of a twin transfusion syndrome and the other in the jejunum secondary to partial venous obstruction. In the third case, it occurred in a patient with Raynaud disease. Characterizing SAM are injurious and reparative lesions that occur in the media and/or at the adventitial medial junction. Four distinctive alterations are recognized: (1) mediolysis, (2) a tearing separation of the outer media from adventitia, (3) arterial gaps, and (4) a florid reparative response that replaces zones of mediolysis and fills areas of medial adventitial separation. The repair can transform SAM into lesions indistinguishable from common types of fibromuscular dysplasia (FMD.) A venous angiopathy involving large and medium-sized veins accompanies SAM. It features medial muscle vacuolar change with lysis leading to apparent separation of residual muscle bundles. Immunostaining shows endothelin-1 (ET-1) decorating adventitial capillaries in SAM and neighboring arteries, in capillaries of adjoining tissues, and outlining smooth muscle cell membranes in adjacent veins including those of the venous angiopathy. The significance of these changes is uncertain. Vasospasm is believed to cause SAM, but ET-1 is not the direct pressor agent responsible for this condition. The reason(s) for synthesis and release of ET-1 in SAM are still hypothetical, but local perturbations in vascular tone may be an important factor. ET-1 may be indirectly play a role in SAM by cross-talking and potentiating the activities of other vasoconstrictors such as norepinephrine and by orchestrating its reparative phase.

SAMS Acceleration Measurement on Mir From March to September 1996

NASA Technical Reports Server (NTRS)

Moskowitz, Milton E.; Hrovat, Ken; Truong, Duc; Reckart, Timothy

1997-01-01

During NASA Increment 2 (March to September 1996), over 15 gigabytes of acceleration data were collected by the Space Acceleration Measurement System (SAMS) onboard the Russian Space Station, Mir. The data were recorded on 55 optical disks and were returned to Earth on STS-79. During this time, SAMS data were collected in the Kristall and Kvant modules, and in the Priroda module to support the following experiments: the Queen's University Experiments in Liquid Diffusion (QUELD), the Technological Evaluation of the MIM (TEM), the Forced Flow Flame Spreading Test (FFFT), and Candle Flames in Microgravity (CFM). This report points out some of the salient features of the microgravity environment to which these experiments were exposed. Also documented are mission events of interest such as the docked phase of STS-76 operations, an extravehicular activity (EVA) to install and deploy solar panels on the Kvant module, a Progress engine burn to raise Mir's altitude, and an on-orbit SAMS calibration procedure. Also included are a description of the Mir module orientations, and the panel notations within the modules. This report presents an overview of the SAMS acceleration measurements recorded by 10 Hz and 100 Hz sensor heads. Variations in the acceleration environment caused by unique activities such as crew exercise and life-support fans are presented. The analyses included herein complement those presented in previous mission summary reports published by the Principal Investigator Microgravity Services (PIMS) group.

Modulator for tone and binary signals. [phase of modulation of tone and binary signals on carrier waves in communication systems

NASA Technical Reports Server (NTRS)

Mcchesney, J. R.; Lerner, T.; Fitch, E. J. (Inventor)

1975-01-01

Tones and binary information are transmitted as phase variations on a carrier wave of constant amplitude and frequency. The carrier and tones are applied to a balanced modulator for deriving an output signal including a pair of sidebands relative to the carrier. The carrier is phase modulated by a digital signal so that it is + or - 90 deg out of phase with the predetermined phase of the carrier. The carrier is combined in an algebraic summing device with the phase modulated signal and the balanced modulator output signal. The output of the algebraic summing device is hard limited to derive a constant amplitude and frequency signal having very narrow bandwidth requirements. At a receiver, the tones and binary data are detected with a phase locked loop having a voltage controlled oscillator driving a pair of orthogonal detection channels.

Phonological awareness and sinusoidal amplitude modulation in phonological dislexia.

PubMed

Peñaloza-López, Yolanda; Herrera-Rangel, Aline; Pérez-Ruiz, Santiago J; Poblano, Adrián

2016-04-01

Dyslexia is the difficulty of children in learning to read and write as results of neurological deficiencies. The objective was to test the Phonological awareness (PA) and Sinusoidal amplitude modulation (SAM) threshold in children with Phonological dyslexia (PD). We performed a case-control, analytic, cross sectional study. We studied 14 children with PD and 14 control children from 7 to 11 years of age, by means of PA measurement and by SAM test. The mean age of dyslexic children was 8.39 years and in the control group was 8.15. Children with PD exhibited inadequate skills in PA, and SAM. We found significant correlations between PA and SAM at 4 Hertz frequency, and calculated regression equations that predicts between one-fourth and one-third of variance of measurements. Alterations in PA and SAM found can help to explain basis of deficient language processing exhibited by children with PD.

Increased dynamic regulation of postural tone through Alexander Technique training

PubMed Central

Cacciatore, TW; Gurfinkel, VS; Horak, FB; Cordo, PJ; Ames, KE

2010-01-01

Gurfinkel and colleagues (2006) recently found that healthy adults dynamically modulate postural muscle tone in the body axis during anti-gravity postural maintenance and that this modulation is inversely correlated with axial stiffness. Our objective in the present study was to investigate whether dynamic modulation of axial postural tone can change through training. We examined whether teachers of the Alexander Technique (AT), who undergo “long-term” (3-year) training, have greater modulation of axial postural tone than matched control subjects. In addition, we performed a longitudinal study on the effect of “short-term” (10-week) AT training on the axial postural tone of individuals with low back pain (LBP), since short term AT training has previously been shown to reduce LBP. Axial postural tone was quantified by measuring the resistance of the neck, trunk and hips to small (±10°), slow (1°/s) torsional rotation during stance. Modulation of tone was determined by the torsional resistance to rotation (peak-to-peak, phase-advance, and variability of torque) and axial muscle activity (EMG). Peak-to-peak torque was lower (~50%), while phase-advance and cycle-to-cycle variability were enhanced for AT teachers compared to matched control subjects at all levels of the axis. In addition, LBP subjects decreased trunk and hip stiffness following short-term AT training compared to a control intervention. While changes in static levels of postural tone may have contributed to the reduced stiffness observed with the AT, our results suggest that dynamic modulation of postural tone can be enhanced through long-term training in the AT, which may constitute an important direction for therapeutic intervention. PMID:21185100

Increased dynamic regulation of postural tone through Alexander Technique training.

PubMed

Cacciatore, T W; Gurfinkel, V S; Horak, F B; Cordo, P J; Ames, K E

2011-02-01

Gurfinkel and colleagues (2006) recently found that healthy adults dynamically modulate postural muscle tone in the body axis during anti-gravity postural maintenance and that this modulation is inversely correlated with axial stiffness. Our objective in the present study was to investigate whether dynamic modulation of axial postural tone can change through training. We examined whether teachers of the Alexander Technique (AT), who undergo "long-term" (3-year) training, have greater modulation of axial postural tone than matched control subjects. In addition, we performed a longitudinal study on the effect of "short-term" (10-week) AT training on the axial postural tone of individuals with low back pain (LBP), since short term AT training has previously been shown to reduce LBP. Axial postural tone was quantified by measuring the resistance of the neck, trunk and hips to small (±10°), slow (1°/s) torsional rotation during stance. Modulation of tone was determined by the torsional resistance to rotation (peak-to-peak, phase-advance, and variability of torque) and axial muscle activity (EMG). Peak-to-peak torque was lower (∼50%), while phase-advance and cycle-to-cycle variability were enhanced for AT teachers compared to matched control subjects at all levels of the axis. In addition, LBP subjects decreased trunk and hip stiffness following short-term AT training compared to a control intervention. While changes in static levels of postural tone may have contributed to the reduced stiffness observed with the AT, our results suggest that dynamic modulation of postural tone can be enhanced through long-term training in the AT, which may constitute an important direction for therapeutic intervention. Copyright © 2010 Elsevier B.V. All rights reserved.

Feasibility and validity of the structured attention module among economically disadvantaged preschool-age children.

PubMed

Bush, Hillary H; Eisenhower, Abbey; Briggs-Gowan, Margaret; Carter, Alice S

2015-01-01

Rooted in the theory of attention put forth by Mirsky, Anthony, Duncan, Ahearn, and Kellam (1991), the Structured Attention Module (SAM) is a developmentally sensitive, computer-based performance task designed specifically to assess sustained selective attention among 3- to 6-year-old children. The current study addressed the feasibility and validity of the SAM among 64 economically disadvantaged preschool-age children (mean age = 58 months; 55% female); a population known to be at risk for attention problems and adverse math performance outcomes. Feasibility was demonstrated by high completion rates and strong associations between SAM performance and age. Principal Factor Analysis with rotation produced robust support for a three-factor model (Accuracy, Speed, and Endurance) of SAM performance, which largely corresponded with existing theorized models of selective and sustained attention. Construct validity was evidenced by positive correlations between SAM Composite scores and all three SAM factors and IQ, and between SAM Accuracy and sequential memory. Value-added predictive validity was not confirmed through main effects of SAM on math performance above and beyond age and IQ; however, significant interactions by child sex were observed: Accuracy and Endurance both interacted with child sex to predict math performance. In both cases, the SAM factors predicted math performance more strongly for girls than for boys. There were no overall sex differences in SAM performance. In sum, the current findings suggest that interindividual variation in sustained selective attention, and potentially other aspects of attention and executive function, among young, high-risk children can be captured validly with developmentally sensitive measures.

Injection-modulated polarity conversion by charge carrier density control via a self-assembled monolayer for all-solution-processed organic field-effect transistors

NASA Astrophysics Data System (ADS)

Roh, Jeongkyun; Lee, Taesoo; Kang, Chan-Mo; Kwak, Jeonghun; Lang, Philippe; Horowitz, Gilles; Kim, Hyeok; Lee, Changhee

2017-04-01

We demonstrated modulation of charge carrier densities in all-solution-processed organic field-effect transistors (OFETs) by modifying the injection properties with self-assembled monolayers (SAMs). The all-solution-processed OFETs based on an n-type polymer with inkjet-printed Ag electrodes were fabricated as a test platform, and the injection properties were modified by the SAMs. Two types of SAMs with different dipole direction, thiophenol (TP) and pentafluorobenzene thiol (PFBT) were employed, modifying the work function of the inkjet-printed Ag (4.9 eV) to 4.66 eV and 5.24 eV with TP and PFBT treatments, respectively. The charge carrier densities were controlled by the SAM treatment in both dominant and non-dominant carrier-channel regimes. This work demonstrates that control of the charge carrier densities can be efficiently achieved by modifying the injection property with SAM treatment; thus, this approach can achieve polarity conversion of the OFETs.

Amplitude modulation reduces loudness adaptation to high-frequency tones.

PubMed

Wynne, Dwight P; George, Sahara E; Zeng, Fan-Gang

2015-07-01

Long-term loudness perception of a sound has been presumed to depend on the spatial distribution of activated auditory nerve fibers as well as their temporal firing pattern. The relative contributions of those two factors were investigated by measuring loudness adaptation to sinusoidally amplitude-modulated 12-kHz tones. The tones had a total duration of 180 s and were either unmodulated or 100%-modulated at one of three frequencies (4, 20, or 100 Hz), and additionally varied in modulation depth from 0% to 100% at the 4-Hz frequency only. Every 30 s, normal-hearing subjects estimated the loudness of one of the stimuli played at 15 dB above threshold in random order. Without any amplitude modulation, the loudness of the unmodulated tone after 180 s was only 20% of the loudness at the onset of the stimulus. Amplitude modulation systematically reduced the amount of loudness adaptation, with the 100%-modulated stimuli, regardless of modulation frequency, maintaining on average 55%-80% of the loudness at onset after 180 s. Because the present low-frequency amplitude modulation produced minimal changes in long-term spectral cues affecting the spatial distribution of excitation produced by a 12-kHz pure tone, the present result indicates that neural synchronization is critical to maintaining loudness perception over time.

Status Report on NEAMS System Analysis Module Development

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

Hu, R.; Fanning, T. H.; Sumner, T.

2015-12-01

Under the Reactor Product Line (RPL) of DOE-NE’s Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, an advanced SFR System Analysis Module (SAM) is being developed at Argonne National Laboratory. The goal of the SAM development is to provide fast-running, improved-fidelity, whole-plant transient analyses capabilities. SAM utilizes an object-oriented application framework MOOSE), and its underlying meshing and finite-element library libMesh, as well as linear and non-linear solvers PETSc, to leverage modern advanced software environments and numerical methods. It also incorporates advances in physical and empirical models and seeks closure models based on information from high-fidelity simulations and experiments. This reportmore » provides an update on the SAM development, and summarizes the activities performed in FY15 and the first quarter of FY16. The tasks include: (1) implement the support of 2nd-order finite elements in SAM components for improved accuracy and computational efficiency; (2) improve the conjugate heat transfer modeling and develop pseudo 3-D full-core reactor heat transfer capabilities; (3) perform verification and validation tests as well as demonstration simulations; (4) develop the coupling requirements for SAS4A/SASSYS-1 and SAM integration.« less

The molecular basis of the genesis of basal tone in internal anal sphincter

PubMed Central

Zhang, Cheng-Hai; Wang, Pei; Liu, Dong-Hai; Chen, Cai-Ping; Zhao, Wei; Chen, Xin; Chen, Chen; He, Wei-Qi; Qiao, Yan-Ning; Tao, Tao; Sun, Jie; Peng, Ya-Jing; Lu, Ping; Zheng, Kaizhi; Craige, Siobhan M.; Lifshitz, Lawrence M.; Keaney Jr, John F.; Fogarty, Kevin E.; ZhuGe, Ronghua; Zhu, Min-Sheng

2016-01-01

Smooth muscle sphincters exhibit basal tone and control passage of contents through organs such as the gastrointestinal tract; loss of this tone leads to disorders such as faecal incontinence. However, the molecular mechanisms underlying this tone remain unknown. Here, we show that deletion of myosin light-chain kinases (MLCK) in the smooth muscle cells from internal anal sphincter (IAS-SMCs) abolishes basal tone, impairing defecation. Pharmacological regulation of ryanodine receptors (RyRs), L-type voltage-dependent Ca2+ channels (VDCCs) or TMEM16A Ca2+-activated Cl− channels significantly changes global cytosolic Ca2+ concentration ([Ca2+]i) and the tone. TMEM16A deletion in IAS-SMCs abolishes the effects of modulators for TMEM16A or VDCCs on a RyR-mediated rise in global [Ca2+]i and impairs the tone and defecation. Hence, MLCK activation in IAS-SMCs caused by a global rise in [Ca2+]i via a RyR-TMEM16A-VDCC signalling module sets the basal tone. Targeting this module may lead to new treatments for diseases like faecal incontinence. PMID:27101932

Damage detection and locating using tone burst and continuous excitation modulation method

NASA Astrophysics Data System (ADS)

Li, Zheng; Wang, Zhi; Xiao, Li; Qu, Wenzhong

2014-03-01

Among structural health monitoring techniques, nonlinear ultrasonic spectroscopy methods are found to be effective diagnostic approach to detecting nonlinear damage such as fatigue crack, due to their sensitivity to incipient structural changes. In this paper, a nonlinear ultrasonic modulation method was developed to detect and locate a fatigue crack on an aluminum plate. The method is different with nonlinear wave modulation method which recognizes the modulation of low-frequency vibration and high-frequency ultrasonic wave; it recognizes the modulation of tone burst and high-frequency ultrasonic wave. In the experiment, a Hanning window modulated sinusoidal tone burst and a continuous sinusoidal excitation were simultaneously imposed on the PZT array which was bonded on the surface of an aluminum plate. The modulations of tone burst and continuous sinusoidal excitation was observed in different actuator-sensor paths, indicating the presence and location of fatigue crack. The results of experiments show that the proposed method is capable of detecting and locating the fatigue crack successfully.

Expanding the Chemistry of the Class C Radical SAM Methyltransferase NosN by Using an Allyl Analogue of SAM.

PubMed

Ji, Xinjian; Mandalapu, Dhanaraju; Cheng, Jinduo; Ding, Wei; Zhang, Qi

2018-03-30

The radical S-adenosylmethionine (SAM) superfamily enzymes cleave SAM reductively to generate a highly reactive 5'-deoxyadenosyl (dAdo) radical, which initiates remarkably diverse reactions. Unlike most radical SAM enzymes, the class C radical SAM methyltransferase NosN binds two SAMs in the active site, using one SAM to produce a dAdo radical and the second as a methyl donor. Here, we report a mechanistic investigation of NosN in which an allyl analogue of SAM (allyl-SAM) was used. We show that NosN cleaves allyl-SAM efficiently and the resulting dAdo radical can be captured by the olefin moieties of allyl-SAM or 5'-allylthioadenosine (ATA), the latter being a derivative of allyl-SAM. Remarkably, we found that NosN produced two distinct sets of products in the presence and absence of the methyl acceptor substrate, thus suggesting substrate-triggered production of ATA from allyl-SAM. We also show that NosN produces S-adenosylhomocysteine from 5'-thioadenosine and homoserine lactone. These results support the idea that 5'-methylthioadenosine is the direct methyl donor in NosN reactions, and demonstrate great potential to modulate radical SAM enzymes for novel catalytic activities. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of modulation phase on profile analysis in normal-hearing and hearing-impaired listeners

NASA Astrophysics Data System (ADS)

Rogers, Deanna; Lentz, Jennifer

2003-04-01

The ability to discriminate between sounds with different spectral shapes in the presence of amplitude modulation was measured in normal-hearing and hearing-impaired listeners. The standard stimulus was the sum of equal-amplitude modulated tones, and the signal stimulus was generated by increasing the level of half the tones (up components) and decreasing the level of half the tones (down components). The down components had the same modulation phase, and a phase shift was applied to the up components to encourage segregation from the down tones. The same phase shift was used in both standard and signal stimuli. Profile-analysis thresholds were measured as a function of the phase shift between up and down components. The phase shifts were 0, 30, 45, 60, 90, and 180 deg. As expected, thresholds were lowest when all tones had the same modulation phase and increased somewhat with increasing phase disparity. This small increase in thresholds was similar for both groups. These results suggest that hearing-impaired listeners are able to use modulation phase to group sounds in a manner similar to that of normal listeners. [Work supported by NIH (DC 05835).

Asymmetry of perceived key movement in chorale sequences: converging evidence from a probe-tone analysis.

PubMed

Cuddy, L L; Thompson, W F

1992-01-01

In a probe-tone experiment, two groups of listeners--one trained, the other untrained, in traditional music theory--rated the goodness of fit of each of the 12 notes of the chromatic scale to four-voice harmonic sequences. Sequences were 12 simplified excerpts from Bach chorales, 4 nonmodulating, and 8 modulating. Modulations occurred either one or two steps in either the clockwise or the counterclockwise direction on the cycle of fifths. A consistent pattern of probe-tone ratings was obtained for each sequence, with no significant differences between listener groups. Two methods of analysis (Fourier analysis and regression analysis) revealed a directional asymmetry in the perceived key movement conveyed by modulating sequences. For a given modulation distance, modulations in the counterclockwise direction effected a clearer shift in tonal organization toward the final key than did clockwise modulations. The nature of the directional asymmetry was consistent with results reported for identification and rating of key change in the sequences (Thompson & Cuddy, 1989a). Further, according to the multiple-regression analysis, probe-tone ratings did not merely reflect the distribution of tones in the sequence. Rather, ratings were sensitive to the temporal structure of the tonal organization in the sequence.

Four-amplitude shift keying-single sideband millimeter-wave signal generation with frequency sextupling based on optical phase modulation

NASA Astrophysics Data System (ADS)

Wu, Peng; Ma, Jianxin

2017-03-01

We have proposed and demonstrated a scheme to generate a frequency-sextupling amplitude shift keying (ASK)-single sideband optical millimeter (mm)-wave signal with high dispersion tolerance based on an optical phase modulator (PM) by ably using the-4th-order and +2nd-order sidebands of the optical modulation. The ASK radio frequency signal, superposed by a local oscillator with the same frequency, modulates the lightwave via an optical PM with proper voltage amplitudes, the +2nd-order sideband carries the ASK signal with a constant slope while the -4th-order sideband maintains constant amplitude. These two sidebands can be abstracted by a wavelength selective switch to form a dual-tone optical mm-wave with only one tone carrying the ASK signal. As only one tone bears the ASK signal while the other tone is unmodulated, the generated dual-tone optical mm-wave signal has high dispersion tolerance.

Benchmark Simulation of Natural Circulation Cooling System with Salt Working Fluid Using SAM

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

Ahmed, K. K.; Scarlat, R. O.; Hu, R.

Liquid salt-cooled reactors, such as the Fluoride Salt-Cooled High-Temperature Reactor (FHR), offer passive decay heat removal through natural circulation using Direct Reactor Auxiliary Cooling System (DRACS) loops. The behavior of such systems should be well-understood through performance analysis. The advanced system thermal-hydraulics tool System Analysis Module (SAM) from Argonne National Laboratory has been selected for this purpose. The work presented here is part of a larger study in which SAM modeling capabilities are being enhanced for the system analyses of FHR or Molten Salt Reactors (MSR). Liquid salt thermophysical properties have been implemented in SAM, as well as properties ofmore » Dowtherm A, which is used as a simulant fluid for scaled experiments, for future code validation studies. Additional physics modules to represent phenomena specific to salt-cooled reactors, such as freezing of coolant, are being implemented in SAM. This study presents a useful first benchmark for the applicability of SAM to liquid salt-cooled reactors: it provides steady-state and transient comparisons for a salt reactor system. A RELAP5-3D model of the Mark-1 Pebble-Bed FHR (Mk1 PB-FHR), and in particular its DRACS loop for emergency heat removal, provides steady state and transient results for flow rates and temperatures in the system that are used here for code-to-code comparison with SAM. The transient studied is a loss of forced circulation with SCRAM event. To the knowledge of the authors, this is the first application of SAM to FHR or any other molten salt reactors. While building these models in SAM, any gaps in the code’s capability to simulate such systems are identified and addressed immediately, or listed as future improvements to the code.« less

Human polyhomeotic homolog 3 (PHC3) sterile alpha motif (SAM) linker allows open-ended polymerization of PHC3 SAM.

PubMed

Robinson, Angela K; Leal, Belinda Z; Nanyes, David R; Kaur, Yogeet; Ilangovan, Udayar; Schirf, Virgil; Hinck, Andrew P; Demeler, Borries; Kim, Chongwoo A

2012-07-10

Sterile alpha motifs (SAMs) are frequently found in eukaryotic genomes. An intriguing property of many SAMs is their ability to self-associate, forming an open-ended polymer structure whose formation has been shown to be essential for the function of the protein. What remains largely unresolved is how polymerization is controlled. Previously, we had determined that the stretch of unstructured residues N-terminal to the SAM of a Drosophila protein called polyhomeotic (Ph), a member of the polycomb group (PcG) of gene silencers, plays a key role in controlling Ph SAM polymerization. Ph SAM with its native linker created shorter polymers compared to Ph SAM attached to either a random linker or no linker. Here, we show that the SAM linker for the human Ph ortholog, polyhomeotic homolog 3 (PHC3), also controls PHC3 SAM polymerization but does so in the opposite fashion. PHC3 SAM with its native linker allows longer polymers to form compared to when attached to a random linker. Attaching the PHC3 SAM linker to Ph SAM also resulted in extending Ph SAM polymerization. Moreover, in the context of full-length Ph protein, replacing the SAM linker with PHC3 SAM linker, intended to create longer polymers, resulted in greater repressive ability for the chimera compared to wild-type Ph. These findings show that polymeric SAM linkers evolved to modulate a wide dynamic range of SAM polymerization abilities and suggest that rationally manipulating the function of SAM containing proteins through controlling their SAM polymerization may be possible.

The SAM-responsive SMK box is a reversible riboswitch

PubMed Central

Smith, Angela M.; Fuchs, Ryan T.; Grundy, Frank J.; Henkin, Tina M.

2010-01-01

The SMK (SAM-III) box is an S-adenosylmethionine (SAM)-responsive riboswitch found in the 5′ untranslated region of metK genes, encoding SAM synthetase, in many members of the Lactobacillales. SAM binding causes a structural rearrangement in the RNA that sequesters the Shine-Dalgarno (SD) sequence by pairing with a complementary anti-SD (ASD) sequence; sequestration of the SD sequence inhibits binding of the 30S ribosomal subunit and prevents translation initiation. We observed a slight increase in the half-life of the metK transcript in vivo when Enterococcus faecalis cells were depleted for SAM, but no significant change in overall transcript abundance, consistent with the model that this riboswitch regulates at the level of translation initiation. The half-life of the SAM-SMK box RNA complex in vitro is shorter than that of the metK transcript in vivo, raising the possibility of reversible binding of SAM. We used a fluorescence assay to directly visualize reversible switching between the SAM-free and SAM-bound conformations. We propose that the SMK box riboswitch can make multiple SAM-dependent regulatory decisions during the lifetime of the transcript in vivo, acting as a reversible switch that allows the cell to respond rapidly to fluctuations in SAM pools by modulating expression of the SAM synthetase gene. PMID:21143313

SAMS Acceleration Measurements on MIR

NASA Technical Reports Server (NTRS)

Moskowitz, Milton E.; Hrovat, Kenneth; Finkelstein, Robert; Reckart, Timothy

1997-01-01

During NASA Increment 3 (September 1996 to January 1997), about 5 gigabytes of acceleration data were collected by the Space Acceleration Measurement System (SAMS) onboard the Russian Space Station, Mir. The data were recorded on 11 optical disks and were returned to Earth on STS-81. During this time, SAMS data were collected in the Priroda module to support the following experiments: the Mir Structural Dynamics Experiment (MiSDE) and Binary Colloidal Alloy Tests (BCAT). This report points out some of the salient features of the microgravity environment to which these experiments were exposed. Also documented are mission events of interest such as the docked phase of STS-81 operations, a Progress engine burn, attitude control thruster operation, and crew exercise. Also included are a description of the Mir module orientations, and the panel notations within the modules. This report presents an overview of the SAMS acceleration measurements recorded by 10 Hz and 100 Hz sensor heads. Variations in the acceleration environment caused by unique activities such as crew exercise and life-support fans are presented. The analyses included herein complement those presented in previous mission summary reports published by the Principal Investigator Microgravity Services (PIMS) group.

Familiarity-Based Stimulus Generalization of Conditioned Suppression

PubMed Central

2017-01-01

We report that stimulus novelty/familiarity is able to modulate stimulus generalization and discuss the theoretical implications of novelty/familiarity coding. Rats in Skinner boxes received clicker → shock pairings before generalization testing to a tone. Before clicker training, different groups of rats received preexposure treatments designed to systematically modulate the clicker and the tone’s novelty and familiarity. Rats whose preexposure matched novelty/familiarity (i.e., either both or neither clicker and tone were preexposed) showed enhanced suppression to the tone relative to rats whose preexposure mixed novelty/familiarity (i.e., only clicker or tone was preexposed). This was not the result of sensory preconditioning to clicker and tone. PMID:28383938

Increasing faculty participation in resident education and providing cost-effective self-assessment module credit to faculty through resident-generated didactics.

PubMed

Kim, Hyun; Malatesta, Theresa M; Anné, Pramila R; McAna, John; Bar-Ad, Voichita; Dicker, Adam P; Den, Robert B

Board certified radiation oncologists and medical physicists are required to earn self-assessment module (SAM) continuing medical education (CME) credit, which may require travel costs or usage fees. Data indicate that faculty participation in resident teaching activities is beneficial to resident education. Our hypothesis was that providing the opportunity to earn SAM credit in resident didactics would increase faculty participation in and improve resident education. SAM applications, comprising CME certified category 1 resident didactic lectures and faculty-generated questions with respective answers, rationales, and references, were submitted to the American Board of Radiology for formal review. Surveys were distributed to assess main academic campus physician, affiliate campus physician, physicist, and radiation oncology resident impressions regarding the quality of the lectures. Survey responses were designed in Likert-scale format. Sign-test was performed with P < .05 considered statistically different from neutral. First submission SAM approval was obtained for 9 of 9 lectures to date. A total of 52 SAM credits have been awarded to 4 physicists and 7 attending physicians. Main academic campus physician and affiliate campus physician attendance increased from 20% and 0%, respectively, over the 12 months preceding CME/SAM lectures, to 55.6% and 20%, respectively. Survey results indicated that the change to SAM lectures increased the quality of resident lectures (P = .001), attending physician participation in resident education (P < .0001), physicist involvement in medical resident education (P = .0006), and faculty motivation to attend resident didactics (P = .004). Residents reported an increased amount of time required to prepare lectures (P = .008). We are the first department, to our knowledge, to offer SAM credit to clinical faculty for participation in resident-generated didactics. Offering SAM credit at resident lectures is a cost-effective alternative to purchasing SAM resources, increases faculty attendance, and may improve the quality of radiation oncology resident education. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Human neuromagnetic steady-state responses to amplitude-modulated tones, speech, and music.

PubMed

Lamminmäki, Satu; Parkkonen, Lauri; Hari, Riitta

2014-01-01

Auditory steady-state responses that can be elicited by various periodic sounds inform about subcortical and early cortical auditory processing. Steady-state responses to amplitude-modulated pure tones have been used to scrutinize binaural interaction by frequency-tagging the two ears' inputs at different frequencies. Unlike pure tones, speech and music are physically very complex, as they include many frequency components, pauses, and large temporal variations. To examine the utility of magnetoencephalographic (MEG) steady-state fields (SSFs) in the study of early cortical processing of complex natural sounds, the authors tested the extent to which amplitude-modulated speech and music can elicit reliable SSFs. MEG responses were recorded to 90-s-long binaural tones, speech, and music, amplitude-modulated at 41.1 Hz at four different depths (25, 50, 75, and 100%). The subjects were 11 healthy, normal-hearing adults. MEG signals were averaged in phase with the modulation frequency, and the sources of the resulting SSFs were modeled by current dipoles. After the MEG recording, intelligibility of the speech, musical quality of the music stimuli, naturalness of music and speech stimuli, and the perceived deterioration caused by the modulation were evaluated on visual analog scales. The perceived quality of the stimuli decreased as a function of increasing modulation depth, more strongly for music than speech; yet, all subjects considered the speech intelligible even at the 100% modulation. SSFs were the strongest to tones and the weakest to speech stimuli; the amplitudes increased with increasing modulation depth for all stimuli. SSFs to tones were reliably detectable at all modulation depths (in all subjects in the right hemisphere, in 9 subjects in the left hemisphere) and to music stimuli at 50 to 100% depths, whereas speech usually elicited clear SSFs only at 100% depth.The hemispheric balance of SSFs was toward the right hemisphere for tones and speech, whereas SSFs to music showed no lateralization. In addition, the right lateralization of SSFs to the speech stimuli decreased with decreasing modulation depth. The results showed that SSFs can be reliably measured to amplitude-modulated natural sounds, with slightly different hemispheric lateralization for different carrier sounds. With speech stimuli, modulation at 100% depth is required, whereas for music the 75% or even 50% modulation depths provide a reasonable compromise between the signal-to-noise ratio of SSFs and sound quality or perceptual requirements. SSF recordings thus seem feasible for assessing the early cortical processing of natural sounds.

S-adenosylmethionine regulates thiopurine methyltransferase activity and decreases 6-mercaptopurine cytotoxicity in MOLT lymphoblasts.

PubMed

Milek, Miha; Karas Kuzelicki, Natasa; Smid, Alenka; Mlinaric-Rascan, Irena

2009-06-15

Six-mercaptopurine (6-MP) is a pro-drug widely used in treatment of various diseases, including acute lymphoblastic leukaemia (ALL). Side-effects of thiopurine therapy have been correlated with thiopurine methyltransferase (TPMT) activity. We propose a novel TPMT-mediated mechanism of S-adenosylmethionine (SAM)-specific effects on 6-mercaptopurine (6-MP) induced cytotoxicity in a model cell line for acute lymphoblastic leukemia (MOLT). Our results show that exogenous SAM (10-50microM) rescues cells from the toxic effects of 6-MP (5microM) by delaying the onset of apoptosis. We prove that the extent of methylthioinosine monophosphate (MeTIMP) induced inhibition of de novo purine synthesis (DNPS) determines the concentrations of intracellular ATP, and consequently SAM, which acts as a positive modulator of TPMT activity. This leads to a greater conversion of 6-MP to inactive 6-methylmercaptopurine, and thus lower availability of thioinosine monophosphate for the biotransformation to cytotoxic thioguanine nucleotides (TGNs) and MeTIMP. We further show that the addition of exogenous SAM to 6-MP treated cells maintains intracellular SAM levels, TPMT activity and protein levels, all of which are diminished in cells incubated with 6-MP. Since TPMT mRNA levels remained unaltered, the effect of SAM appears to be restricted to protein stabilisation rather than an increase of TPMT expression. We thus propose that SAM reverses the extent of 6-MP cytotoxicity, by acting as a TPMT-stabilizing factor. This study provides new insights into the pharmacogenetics of thiopurine drugs. Identification of SAM as critical modulator of TPMT activity and consequently thiopurine toxicity may set novel grounds for the rationalization of thiopurine therapy.

Colibactin assembly line enzymes use S-adenosylmethionine to build a cyclopropane ring

PubMed Central

Zha, Li; Jiang, Yindi; Henke, Matthew T.; Wilson, Matthew R.; Wang, Jennifer X.; Kelleher, Neil L.; Balskus, Emily P.

2017-01-01

Despite containing an α-amino acid, the versatile cofactor S-adenosylmethionine (SAM) is not a known building block for non-ribosomal peptide synthetase (NRPS) assembly lines. Here we report an unusual NRPS module from colibactin biosynthesis that uses SAM for amide bond formation and subsequent cyclopropanation. Our findings showcase a new use for SAM and reveal a novel biosynthetic route to a functional group that likely mediates colibactin’s genotoxicity. PMID:28805802

Trellis Tone Modulation Multiple-Access for Peer Discovery in D2D Networks

PubMed Central

Lim, Chiwoo; Kim, Sang-Hyo

2018-01-01

In this paper, a new non-orthogonal multiple-access scheme, trellis tone modulation multiple-access (TTMMA), is proposed for peer discovery of distributed device-to-device (D2D) communication. The range and capacity of discovery are important performance metrics in peer discovery. The proposed trellis tone modulation uses single-tone transmission and achieves a long discovery range due to its low Peak-to-Average Power Ratio (PAPR). The TTMMA also exploits non-orthogonal resource assignment to increase the discovery capacity. For the multi-user detection of superposed multiple-access signals, a message-passing algorithm with supplementary schemes are proposed. With TTMMA and its message-passing demodulation, approximately 1.5 times the number of devices are discovered compared to the conventional frequency division multiple-access (FDMA)-based discovery. PMID:29673167

Trellis Tone Modulation Multiple-Access for Peer Discovery in D2D Networks.

PubMed

Lim, Chiwoo; Jang, Min; Kim, Sang-Hyo

2018-04-17

In this paper, a new non-orthogonal multiple-access scheme, trellis tone modulation multiple-access (TTMMA), is proposed for peer discovery of distributed device-to-device (D2D) communication. The range and capacity of discovery are important performance metrics in peer discovery. The proposed trellis tone modulation uses single-tone transmission and achieves a long discovery range due to its low Peak-to-Average Power Ratio (PAPR). The TTMMA also exploits non-orthogonal resource assignment to increase the discovery capacity. For the multi-user detection of superposed multiple-access signals, a message-passing algorithm with supplementary schemes are proposed. With TTMMA and its message-passing demodulation, approximately 1.5 times the number of devices are discovered compared to the conventional frequency division multiple-access (FDMA)-based discovery.

Synthesis, characterization, and relative stabilities of self-assembled monolayers on gold generated from bidentate n-alkyl xanthic acids.

PubMed

Moore, H Justin; Colorado, Ramon; Lee, Han Ju; Jamison, Andrew C; Lee, T Randall

2013-08-27

A series of self-assembled monolayers (SAMs) on gold were generated by the adsorption of n-alkyl xanthic acids (NAXAs) having the general formula CH3(CH2)nOCS2H (n = 12-15). The structural features of these SAMs were characterized by optical ellipsometry, contact angle goniometry, polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS), and X-ray photoelectron spectroscopy (XPS). This series of xanthate SAMs were compared to SAMs generated from the corresponding n-alkanethiols and aliphatic dithiocarboxylic acids (ADTCAs). The collected data indicate that the NAXAs generate densely packed and well-ordered monolayers. The contact angles of hexadecane on the xanthate monolayers exhibited a large "odd-even" effect similar to that produced by the ADTCA SAMs. The relative stability of these bidentate xanthate SAMs was evaluated by monitoring the changes in ellipsometric thicknesses and wettability as a function of time under various conditions. The results demonstrate that SAMs formed from NAXAs are much less stable than analogous n-alkanethiolate and ADTCA SAMs.

Tone signal generator for producing multioperator tone signals using an operator circuit including a waveform generator, a selector and an enveloper

DOEpatents

Dong, Qiujie; Jenkins, Michael V.; Bernadas, Salvador R.

1997-01-01

A frequency modulation (FM) tone signal generator for generating a FM tone signal is disclosed. The tone signal generator includes a waveform generator having a plurality of wave tables, a selector and an enveloper. The waveform generator furnishes a waveform signal in response to a phase angle address signal. Each wave table stores a different waveform. The selector selects one of the wave tables in response to a plurality of selection signals such that the selected wave table largely provides the waveform signal upon being addressed largely by the phase angle address signal. Selection of the selected wave table varies with each selection signal. The enveloper impresses an envelope signal on the waveform signal. The envelope signal is used as a carrier or modulator for generating the FM tone signal.

Targeting EphA2-Sam and Its Interactome: Design and Evaluation of Helical Peptides Enriched in Charged Residues.

PubMed

Mercurio, Flavia A; Marasco, Daniela; Di Natale, Concetta; Pirone, Luciano; Costantini, Susan; Pedone, Emilia M; Leone, Marilisa

2016-11-17

The EphA2 receptor controls diverse physiological and pathological conditions and its levels are often upregulated in cancer. Targeting receptor overexpression, through modulation of endocytosis and consequent degradation, appears to be an appealing strategy for attacking tumor malignancy. In this scenario, the Sam domain of EphA2 plays a pivotal role because it is the site where protein regulators of endocytosis and stability are recruited by means of heterotypic Sam-Sam interactions. Because EphA2-Sam heterotypic complexes are largely based on electrostatic contacts, we have investigated the possibility of attacking these interactions with helical peptides enriched in charged residues. Several peptide sequences with high predicted helical propensities were designed, and detailed conformational analyses were conducted by diverse techniques including NMR, CD, and molecular dynamics (MD) simulations. Interaction studies were also performed by NMR, surface plasmon resonance (SPR), and microscale thermophoresis (MST) and led to the identification of two peptides capable of binding to the first Sam domain of Odin. These molecules represent early candidates for the generation of efficient Sam domain binders and antagonists of Sam-Sam interactions involving EphA2. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells

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

Lawrence, Paul; Schafer, Elizabeth A.; Rieder, Elizabeth, E-mail: elizabeth.rieder@ars.usda.gov

2012-03-30

Picornavirus infection can lead to disruption of nuclear pore traffic, shut-off of cell translation machinery, and cleavage of proteins involved in cellular signal transduction and the innate response to infection. Here, we demonstrated that the FMDV 3C{sup pro} induced the cleavage of nuclear RNA-binding protein Sam68 C-terminus containing the nuclear localization sequence (NLS). Consequently, it stimulated the redistribution of Sam68 to the cytoplasm. The siRNA knockdown of Sam68 resulted in a 1000-fold reduction in viral titers, which prompted us to study the effect of Sam68 on FMDV post-entry events. Interestingly, Sam68 interacts with the internal ribosomal entry site within themore » 5 Prime non-translated region of the FMDV genome, and Sam68 knockdown decreased FMDV IRES-driven activity in vitro suggesting that it could modulate translation of the viral genome. The results uncover a novel role for Sam68 in the context of picornaviruses and the proteolysis of a new cellular target of the FMDV 3C{sup pro}.« less

System Advisor Model, SAM 2014.1.14: General Description

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

Blair, Nate; Dobos, Aron P.; Freeman, Janine

2014-02-01

This document describes the capabilities of the U.S. Department of Energy and National Renewable Energy Laboratory's System Advisor Model (SAM), Version 2013.9.20, released on September 9, 2013. SAM is a computer model that calculates performance and financial metrics of renewable energy systems. Project developers, policy makers, equipment manufacturers, and researchers use graphs and tables of SAM results in the process of evaluating financial, technology, and incentive options for renewable energy projects. SAM simulates the performance of photovoltaic, concentrating solar power, solar water heating, wind, geothermal, biomass, and conventional power systems. The financial model can represent financial structures for projects thatmore » either buy and sell electricity at retail rates (residential and commercial) or sell electricity at a price determined in a power purchase agreement (utility). SAM's advanced simulation options facilitate parametric and sensitivity analyses, and statistical analysis capabilities are available for Monte Carlo simulation and weather variability (P50/P90) studies. SAM can also read input variables from Microsoft Excel worksheets. For software developers, the SAM software development kit (SDK) makes it possible to use SAM simulation modules in their applications written in C/C++, C#, Java, Python, and MATLAB. NREL provides both SAM and the SDK as free downloads at http://sam.nrel.gov. Technical support and more information about the software are available on the website.« less

Tone signal generator for producing multioperator tone signals using an operator circuit including a waveform generator, a selector and an enveloper

DOEpatents

Dong, Q.; Jenkins, M.V.; Bernadas, S.R.

1997-09-09

A frequency modulation (FM) tone signal generator for generating a FM tone signal is disclosed. The tone signal generator includes a waveform generator having a plurality of wave tables, a selector and an enveloper. The waveform generator furnishes a waveform signal in response to a phase angle address signal. Each wave table stores a different waveform. The selector selects one of the wave tables in response to a plurality of selection signals such that the selected wave table largely provides the waveform signal upon being addressed largely by the phase angle address signal. Selection of the selected wave table varies with each selection signal. The enveloper impresses an envelope signal on the waveform signal. The envelope signal is used as a carrier or modulator for generating the FM tone signal. 17 figs.

The SAM domains of Anks family proteins are critically involved in modulating the degradation of EphA receptors.

PubMed

Kim, Jieun; Lee, Haeryung; Kim, Yujin; Yoo, Sooyeon; Park, Eunjeong; Park, Soochul

2010-04-01

We recently reported that the phosphotyrosine-binding (PTB) domain of Anks family proteins binds to EphA8, thereby positively regulating EphA8-mediated signaling pathways. In the current study, we identified a potential role for the SAM domains of Anks family proteins in EphA signaling. We found that SAM domains of Anks family proteins directly bind to ubiquitin, suggesting that Anks proteins regulate the degradation of ubiquitinated EphA receptors. Consistent with the role of Cbl ubiquitin ligases in the degradation of Eph receptors, our results revealed that the ubiquitin ligase c-Cbl induced the ubiquitination and degradation of EphA8 upon ligand binding. Ubiquitinated EphA8 also bound to the SAM domains of Odin, a member of the Anks family proteins. More importantly, the overexpression of wild-type Odin protected EphA8 and EphA2 from undergoing degradation following ligand stimulation and promoted EphA-mediated inhibition of cell migration. In contrast, a SAM domain deletion mutant of Odin strongly impaired the function of endogenous Odin, suggesting that the mutant functions in a dominant-negative manner. An analysis of Odin-deficient primary embryonic fibroblasts indicated that Odin levels play a critical role in regulating the stability of EphA2 in response to ligand stimulation. Taken together, our studies suggest that the SAM domains of Anks family proteins play a pivotal role in enhancing the stability of EphA receptors by modulating the ubiquitination process.

CD and NMR conformational studies of a peptide encompassing the Mid Loop interface of Ship2-Sam.

PubMed

Mercurio, Flavia A; Scognamiglio, Pasqualina L; Di Natale, Concetta; Marasco, Daniela; Pellecchia, Maurizio; Leone, Marilisa

2014-11-01

The lipid phosphatase Ship2 is a protein that intervenes in several diseases such as diabetes, cancer, neurodegeneration, and atherosclerosis. It is made up of a catalytic domain and several protein docking modules such as a C-terminal Sam (Sterile alpha motif) domain. The Sam domain of Ship2 (Ship2-Sam) binds to the Sam domains of the EphA2 receptor (EphA2-Sam) and the PI3K effector protein Arap3 (Arap3-Sam). These heterotypic Sam-Sam interactions occur through formation of dimers presenting the canonical "Mid Loop/End Helix" binding mode. The central region of Ship2-Sam, spanning the C-terminal end of α2, the α3 and α4 helices together with the α2α3 and α3α4 interhelical loops, forms the Mid Loop surface that is needed to bind partners Sam domains. A peptide encompassing most of the Ship2-Sam Mid Loop interface (Shiptide) capable of binding to both EphA2-Sam and Arap3-Sam, was previously identified. Here we investigated the conformational features of this peptide, through solution CD and NMR studies in different conditions. These studies reveal that the peptide is highly flexible in aqueous buffer, while it adopts a helical conformation in presence of 2,2,2-trifluoroethanol. The discovered structural insights and in particular the identification of a helical motif, may lead to the design of more constrained and possibly cell permeable Shiptide analogs that could work as efficient antagonists of Ship2-Sam heterotypic interactions and embrace therapeutic applications. © 2014 Wiley Periodicals, Inc.

Conformational heterogeneity of the SAM-I riboswitch transcriptional ON state: a chaperone-like role for S-adenosyl methionine.

PubMed

Huang, Wei; Kim, Joohyun; Jha, Shantenu; Aboul-Ela, Fareed

2012-05-18

Riboswitches are promising targets for the design of novel antibiotics and engineering of portable genetic regulatory elements. There is evidence that variability in riboswitch properties allows tuning of expression for genes involved in different stages of biosynthetic pathways by mechanisms that are not currently understood. Here, we explore the mechanism for tuning of S-adenosyl methionine (SAM)-I riboswitch folding. Most SAM-I riboswitches function at the transcriptional level by sensing the cognate ligand SAM. SAM-I riboswitches orchestrate the biosynthetic pathways of cysteine, methionine, SAM, and so forth. We use base-pair probability predictions to examine the secondary-structure folding landscape of several SAM-I riboswitch sequences. We predict different folding behaviors for different SAM-I riboswitch sequences. We identify several "decoy" base-pairing interactions involving 5' riboswitch residues that can compete with the formation of a P1 helix, a component of the ligand-bound "transcription OFF" state, in the absence of SAM. We hypothesize that blockage of these interactions through SAM contacts contributes to stabilization of the OFF state in the presence of ligand. We also probe folding patterns for a SAM-I riboswitch RNA using constructs with different 3' truncation points experimentally. Folding was monitored through fluorescence, susceptibility to base-catalyzed cleavage, nuclear magnetic resonance, and indirectly through SAM binding. We identify key decision windows at which SAM can affect the folding pathway towards the OFF state. The presence of decoy conformations and differential sensitivities to SAM at different transcript lengths is crucial for SAM-I riboswitches to modulate gene expression in the context of global cellular metabolism. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sensitivity to Envelope Interaural Time Differences at High Modulation Rates

PubMed Central

Bleeck, Stefan; McAlpine, David

2015-01-01

Sensitivity to interaural time differences (ITDs) conveyed in the temporal fine structure of low-frequency tones and the modulated envelopes of high-frequency sounds are considered comparable, particularly for envelopes shaped to transmit similar fidelity of temporal information normally present for low-frequency sounds. Nevertheless, discrimination performance for envelope modulation rates above a few hundred Hertz is reported to be poor—to the point of discrimination thresholds being unattainable—compared with the much higher (>1,000 Hz) limit for low-frequency ITD sensitivity, suggesting the presence of a low-pass filter in the envelope domain. Further, performance for identical modulation rates appears to decline with increasing carrier frequency, supporting the view that the low-pass characteristics observed for envelope ITD processing is carrier-frequency dependent. Here, we assessed listeners’ sensitivity to ITDs conveyed in pure tones and in the modulated envelopes of high-frequency tones. ITD discrimination for the modulated high-frequency tones was measured as a function of both modulation rate and carrier frequency. Some well-trained listeners appear able to discriminate ITDs extremely well, even at modulation rates well beyond 500 Hz, for 4-kHz carriers. For one listener, thresholds were even obtained for a modulation rate of 800 Hz. The highest modulation rate for which thresholds could be obtained declined with increasing carrier frequency for all listeners. At 10 kHz, the highest modulation rate at which thresholds could be obtained was 600 Hz. The upper limit of sensitivity to ITDs conveyed in the envelope of high-frequency modulated sounds appears to be higher than previously considered. PMID:26721926

S-Adenosylmethionine Attenuates Oxidative Stress and Neuroinflammation Induced by Amyloid-β Through Modulation of Glutathione Metabolism.

PubMed

Li, Qian; Cui, Jing; Fang, Chen; Liu, Min; Min, Guowen; Li, Liang

2017-01-01

Oxidative stress and neuroinflammation are mainly involved in the pathogenic mechanisms of Alzheimer's disease (AD). Amyloid-β (Aβ), the main component of senile plaques, is a kind of strong inducer of oxidative stress. Glutathione is an endogenous antioxidant protecting cells from oxidative injury. S-adenosylmethionine (SAM) produced in the methionine cycle is the primary methyl donor and the precursor of glutathione. In this study, the Aβ intrahippocampal injection rat model and cultured SH-SY5Y cells were used to explore the neuroprotective effect of SAM. We found that SAM could protect cells against Aβ-induced cellular injury by inhibition of oxidative stress and neuroinflammation. SAM administration could increase the endogenous antioxidant glutathione and potentiate the antioxidant enzymes activities. SAM might act as an antioxidant and be a potential candidate therapy for AD patients.

The Growth-Suppressive Function of the Polycomb Group Protein Polyhomeotic Is Mediated by Polymerization of Its Sterile Alpha Motif (SAM) Domain*

PubMed Central

Robinson, Angela K.; Leal, Belinda Z.; Chadwell, Linda V.; Wang, Renjing; Ilangovan, Udayar; Kaur, Yogeet; Junco, Sarah E.; Schirf, Virgil; Osmulski, Pawel A.; Gaczynska, Maria; Hinck, Andrew P.; Demeler, Borries; McEwen, Donald G.; Kim, Chongwoo A.

2012-01-01

Polyhomeotic (Ph), a member of the Polycomb Group (PcG), is a gene silencer critical for proper development. We present a previously unrecognized way of controlling Ph function through modulation of its sterile alpha motif (SAM) polymerization leading to the identification of a novel target for tuning the activities of proteins. SAM domain containing proteins have been shown to require SAM polymerization for proper function. However, the role of the Ph SAM polymer in PcG-mediated gene silencing was uncertain. Here, we first show that Ph SAM polymerization is indeed required for its gene silencing function. Interestingly, the unstructured linker sequence N-terminal to Ph SAM can shorten the length of polymers compared with when Ph SAM is individually isolated. Substituting the native linker with a random, unstructured sequence (RLink) can still limit polymerization, but not as well as the native linker. Consequently, the increased polymeric Ph RLink exhibits better gene silencing ability. In the Drosophila wing disc, Ph RLink expression suppresses growth compared with no effect for wild-type Ph, and opposite to the overgrowth phenotype observed for polymer-deficient Ph mutants. These data provide the first demonstration that the inherent activity of a protein containing a polymeric SAM can be enhanced by increasing SAM polymerization. Because the SAM linker had not been previously considered important for the function of SAM-containing proteins, our finding opens numerous opportunities to manipulate linker sequences of hundreds of polymeric SAM proteins to regulate a diverse array of intracellular functions. PMID:22275371

Ablation of the Sam68 RNA Binding Protein Protects Mice from Age-Related Bone Loss

PubMed Central

Richard, Stéphane; Torabi, Nazi; Franco, Gladys Valverde; Tremblay, Guy A; Chen, Taiping; Vogel, Gillian; Morel, Mélanie; Cléroux, Patrick; Forget-Richard, Alexandre; Komarova, Svetlana; Tremblay, Michel L; Li, Wei; Li, Ailian; Gao, Yun Jing; Henderson, Janet E

2005-01-01

The Src substrate associated in mitosis of 68 kDa (Sam68) is a KH-type RNA binding protein that has been shown to regulate several aspects of RNA metabolism; however, its physiologic role has remained elusive. Herein we report the generation of Sam68-null mice by homologous recombination. Aged Sam68−/− mice preserved their bone mass, in sharp contrast with 12-month-old wild-type littermates in which bone mass was decreased up to approximately 75%. In fact, the bone volume of the 12-month-old Sam68−/− mice was virtually indistinguishable from that of 4-month-old wild-type or Sam68−/− mice. Sam68−/− bone marrow stromal cells had a differentiation advantage for the osteogenic pathway. Moreover, the knockdown of Sam68 using short hairpin RNA in the embryonic mesenchymal multipotential progenitor C3H10T1/2 cells resulted in more pronounced expression of the mature osteoblast marker osteocalcin when differentiation was induced with bone morphogenetic protein-2. Cultures of mouse embryo fibroblasts generated from Sam68+/+ and Sam68−/− littermates were induced to differentiate into adipocytes with culture medium containing pioglitazone and the Sam68−/− mouse embryo fibroblasts shown to have impaired adipocyte differentiation. Furthermore, in vivo it was shown that sections of bone from 12-month-old Sam68−/− mice had few marrow adipocytes compared with their age-matched wild-type littermate controls, which exhibited fatty bone marrow. Our findings identify endogenous Sam68 as a positive regulator of adipocyte differentiation and a negative regulator of osteoblast differentiation, which is consistent with Sam68 being a modulator of bone marrow mesenchymal cell differentiation, and hence bone metabolism, in aged mice. PMID:16362077

Modulation of the Seasonal Cycle of Antarctic Sea Ice Extent Related to the Southern Annular Mode

NASA Astrophysics Data System (ADS)

Doddridge, Edward W.; Marshall, John

2017-10-01

Through analysis of remotely sensed sea surface temperature (SST) and sea ice concentration data, we investigate the impact of winds related to the Southern Annular Mode (SAM) on sea ice extent around Antarctica. We show that positive SAM anomalies in the austral summer are associated with anomalously cold SSTs that persist and lead to anomalous ice growth in the following autumn, while negative SAM anomalies precede warm SSTs and a reduction in sea ice extent during autumn. The largest effect occurs in April, when a unit change in the detrended summertime SAM is followed by a 1.8±0.6 ×105 km2 change in detrended sea ice extent. We find no evidence that sea ice extent anomalies related to the summertime SAM affect the wintertime sea ice extent maximum. Our analysis shows that the wind anomalies related to the negative SAM during the 2016/2017 austral summer contributed to the record minimum Antarctic sea ice extent observed in March 2017.

Structure-guided discovery of the metabolite carboxy-SAM that modulates tRNA function.

PubMed

Kim, Jungwook; Xiao, Hui; Bonanno, Jeffrey B; Kalyanaraman, Chakrapani; Brown, Shoshana; Tang, Xiangying; Al-Obaidi, Nawar F; Patskovsky, Yury; Babbitt, Patricia C; Jacobson, Matthew P; Lee, Young-Sam; Almo, Steven C

2013-06-06

The identification of novel metabolites and the characterization of their biological functions are major challenges in biology. X-ray crystallography can reveal unanticipated ligands that persist through purification and crystallization. These adventitious protein-ligand complexes provide insights into new activities, pathways and regulatory mechanisms. We describe a new metabolite, carboxy-S-adenosyl-l-methionine (Cx-SAM), its biosynthetic pathway and its role in transfer RNA modification. The structure of CmoA, a member of the SAM-dependent methyltransferase superfamily, revealed a ligand consistent with Cx-SAM in the catalytic site. Mechanistic analyses showed an unprecedented role for prephenate as the carboxyl donor and the involvement of a unique ylide intermediate as the carboxyl acceptor in the CmoA-mediated conversion of SAM to Cx-SAM. A second member of the SAM-dependent methyltransferase superfamily, CmoB, recognizes Cx-SAM and acts as a carboxymethyltransferase to convert 5-hydroxyuridine into 5-oxyacetyl uridine at the wobble position of multiple tRNAs in Gram-negative bacteria, resulting in expanded codon-recognition properties. CmoA and CmoB represent the first documented synthase and transferase for Cx-SAM. These findings reveal new functional diversity in the SAM-dependent methyltransferase superfamily and expand the metabolic and biological contributions of SAM-based biochemistry. These discoveries highlight the value of structural genomics approaches in identifying ligands within the context of their physiologically relevant macromolecular binding partners, and in revealing their functions.

Steady-state MEG responses elicited by a sequence of amplitude-modulated short tones of different carrier frequencies.

PubMed

Kuriki, Shinya; Kobayashi, Yusuke; Kobayashi, Takanari; Tanaka, Keita; Uchikawa, Yoshinori

2013-02-01

The auditory steady-state response (ASSR) is a weak potential or magnetic response elicited by periodic acoustic stimuli with a maximum response at about a 40-Hz periodicity. In most previous studies using amplitude-modulated (AM) tones of stimulus sound, long lasting tones of more than 10 s in length were used. However, characteristics of the ASSR elicited by short AM tones have remained unclear. In this study, we examined magnetoencephalographic (MEG) ASSR using a sequence of sinusoidal AM tones of 0.78 s in length with various tone frequencies of 440-990 Hz in about one octave variation. It was found that the amplitude of the ASSR was invariant with tone frequencies when the level of sound pressure was adjusted along an equal-loudness curve. The amplitude also did not depend on the existence of preceding tone or difference in frequency of the preceding tone. When the sound level of AM tones was changed with tone frequencies in the same range of 440-990 Hz, the amplitude of ASSR varied in a proportional manner to the sound level. These characteristics are favorable for the use of ASSR in studying temporal processing of auditory information in the auditory cortex. The lack of adaptation in the ASSR elicited by a sequence of short tones may be ascribed to the neural activity of widely accepted generator of magnetic ASSR in the primary auditory cortex. Copyright © 2012 Elsevier B.V. All rights reserved.

Summary report of mission acceleration measurements for Spacehab-01, STS-57 launched 21 June 1993

NASA Technical Reports Server (NTRS)

Finley, Brian; Grodsinsky, Carlos; Delombard, Richard

1994-01-01

The maiden voyage of the commercial Spacehab laboratory module onboard the STS-57 mission was integrated with several accelerometer packages, one of which was the Space Acceleration Measurement System (SAMS). The June 21st 1993, launch was the seventh successful mission for the Office of Life and Microgravity Sciences and Application's (OLMSA) SAMS unit. This flight was also complemented by a second accelerometer system. The Three Dimensional Microgravity Accelerometer (3-DMA), a Code C funded acceleration measurement system, offering an on-orbit residual calibration as a reference for the unit's four triaxial accelerometers. The SAMS accelerometer unit utilized three remote triaxial sensor heads mounted on the forward Spacehab module bulkhead and on one centrally located experiment locker door. These triaxial heads had filter cut-offs set to 5, 50, and 1000 Hz. The mission also included other experiment specific accelerometer packages in various locations.

Auditory fear conditioning modifies steady-state evoked potentials in the rat inferior colliculus.

PubMed

Lockmann, André Luiz Vieira; Mourão, Flávio Afonso Gonçalves; Moraes, Marcio Flávio Dutra

2017-08-01

The rat inferior colliculus (IC) is a major midbrain relay for ascending inputs from the auditory brain stem and has been suggested to play a key role in the processing of aversive sounds. Previous studies have demonstrated that auditory fear conditioning (AFC) potentiates transient responses to brief tones in the IC, but it remains unexplored whether AFC modifies responses to sustained periodic acoustic stimulation-a type of response called the steady-state evoked potential (SSEP). Here we used an amplitude-modulated tone-a 10-kHz tone with a sinusoidal amplitude modulation of 53.7 Hz-as the conditioning stimulus (CS) in an AFC protocol (5 CSs per day in 3 consecutive days) while recording local field potentials (LFPs) from the IC. In the preconditioning session ( day 1 ), the CS elicited prominent 53.7-Hz SSEPs. In the training session ( day 2 ), foot shocks occurred at the end of each CS (paired group) or randomized in the inter-CS interval (unpaired group). In the test session ( day 3 ), SSEPs markedly differed from preconditioning in the paired group: in the first two trials the phase to which the SSEP coupled to the CS amplitude envelope shifted ~90°; in the last two trials the SSEP power and the coherence of SSEP with the CS amplitude envelope increased. LFP power decreased in frequency bands other than 53.7 Hz. In the unpaired group, SSEPs did not change in the test compared with preconditioning. Our results show that AFC causes dissociated changes in the phase and power of SSEP in the IC. NEW & NOTEWORTHY Local field potential oscillations in the inferior colliculus follow the amplitude envelope of an amplitude-modulated tone, originating a neural response called the steady-state evoked potential. We show that auditory fear conditioning of an amplitude-modulated tone modifies two parameters of the steady-state evoked potentials in the inferior colliculus: first the phase to which the evoked oscillation couples to the amplitude-modulated tone shifts; subsequently, the evoked oscillation power increases along with its coherence with the amplitude-modulated tone. Copyright © 2017 the American Physiological Society.

Optimization of pentacene double floating gate memories based on charge injection regulated by SAM functionalization

NASA Astrophysics Data System (ADS)

Li, S.; Guérin, D.; Lenfant, S.; Lmimouni, K.

2018-02-01

Pentacene based double nano-floating gate memories (NFGM) by using gold nanoparticles (Au NPs) and reduced graphene oxide (rGO) sheets as charge trapping layers are prepared and demonstrated. Particularly, the NFGM chemically treated by 2,3,4,5,6-pentafluorobenzenethiol (PFBT) self-assembled monolayers (SAM) exhibits excellent memory performances, including high mobility of 0.23 cm2V-1s-1, the large memory window of 51 V, and the stable retention property more than 108 s. Comparing the performances of NFGM without treating with PFBT SAM, the improving performances of the memory devices by SAM modification are explained by the increase of charge injection, which could be further investigated by XPS and UPS. In particular, the results highlight the utility of SAM modulations and controlling of charge transport in the development of organic transistor memories.

Sam68 Allows Selective Targeting of Human Cancer Stem Cells.

PubMed

Benoit, Yannick D; Mitchell, Ryan R; Risueño, Ruth M; Orlando, Luca; Tanasijevic, Borko; Boyd, Allison L; Aslostovar, Lili; Salci, Kyle R; Shapovalova, Zoya; Russell, Jennifer; Eguchi, Masakatsu; Golubeva, Diana; Graham, Monica; Xenocostas, Anargyros; Trus, Michael R; Foley, Ronan; Leber, Brian; Collins, Tony J; Bhatia, Mickie

2017-07-20

Targeting of human cancer stem cells (CSCs) requires the identification of vulnerabilities unique to CSCs versus healthy resident stem cells (SCs). Unfortunately, dysregulated pathways that support transformed CSCs, such as Wnt/β-catenin signaling, are also critical regulators of healthy SCs. Using the ICG-001 and CWP family of small molecules, we reveal Sam68 as a previously unappreciated modulator of Wnt/β-catenin signaling within CSCs. Disruption of CBP-β-catenin interaction via ICG-001/CWP induces the formation of a Sam68-CBP complex in CSCs that alters Wnt signaling toward apoptosis and differentiation induction. Our study identifies Sam68 as a regulator of human CSC vulnerability. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Modulation Detection Interference for Asynchronous Presentation of Masker and Target in Listeners with Normal and Impaired Hearing

ERIC Educational Resources Information Center

Koopman, Jan; Houtgast, Tammo; Dreschler, Wouter A.

2008-01-01

Purpose: The sensitivity to sinusoidal amplitude modulations (SAMs) is reduced when other modulated maskers are presented simultaneously at a distant frequency (also referred to as "modulation detection interference" [MDI]). This article describes the results of onset differences between masker and target as a parameter. Method: Carrier…

SAMS Acceleration Measurements on Mir (NASA Increment 4)

NASA Technical Reports Server (NTRS)

DeLombard, Richard

1998-01-01

During NASA Increment 4 (January to May 1997), about 5 gigabytes of acceleration data were collected by the Space Acceleration Measurements System (SAMS) onboard the Russian Space Station, Mir. The data were recorded on 28 optical disks which were returned to Earth on STS-84. During this increment, SAMS data were collected in the Priroda module to support the Mir Structural Dynamics Experiment (MiSDE), the Binary Colloidal Alloy Tests (BCAT), Angular Liquid Bridge (ALB), Candle Flames in Microgravity (CFM), Diffusion Controlled Apparatus Module (DCAM), Enhanced Dynamic Load Sensors (EDLS), Forced Flow Flame Spreading Test (FFFr), Liquid Metal Diffusion (LMD), Protein Crystal Growth in Dewar (PCG/Dewar), Queen's University Experiments in Liquid Diffusion (QUELD), and Technical Evaluation of MIM (TEM). This report points out some of the salient features of the microgravity environment to which these experiments were exposed. Also documented are mission events of interest such as the docked phase of STS-84 operations, a Progress engine bum, Soyuz vehicle docking and undocking, and Progress vehicle docking. This report presents an overview of the SAMS acceleration measurements recorded by 10 Hz and 100 Hz sensor heads. The analyses included herein complement those presented in previous summary reports prepared by the Principal Investigator Microgravity Services (PIMS) group.

Sam68 promotes Schwann cell proliferation by enhancing the PI3K/Akt pathway and acts on regeneration after sciatic nerve crush

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

Wu, Weijie, E-mail: 459586768@qq.com; Liu, Yuxi, E-mail: 924013616@qq.com; Wang, Youhua, E-mail: wyouhua1516@163.com

Sam68 (Src-associated in mitosis of 68 kD), a KH domain RNA-binding protein, is not only important in signaling transduction cascades, but crucial in a variety of cellular processes. Sam68 is reported to be involved in the phospoinositide3-kinase (PI3K) and nuclear factor-kappa B (NF-κB) signaling pathways, and it is closely associated with cell proliferation, RNA metabolism, and tumor progression. However, we know little about the role of Sam68 during peripheral nervous system injury and regeneration. In this study, we investigated the expression of Sam68 and its biological significances in sciatic nerve crush. Interestingly, we found Sam68 had a co-localization with S100 (Schwannmore » cell marker). Moreover, after crush, Sam68 had a spatiotemporal protein expression, which was in parallel with proliferation cell nuclear antigen (PCNA). In vitro, we also observed increased expression of Sam68 during the process of TNF-α-induced Schwann cell proliferation model. Besides, flow cytometry analyses, CCK-8, and EDU were all performed with the purpose of investigating the role of Sam68 in the regulation of Schwann cell proliferation. Even more importantly, we discovered that Sam68 could enhance the phosphorylation of Akt while LY294002 (a PI3K inhibitor) obviously reversed Sam68-induced cell proliferation. Finally, we detected the variance during regeneration progress through the rat walk footprint test. In summary, all these evidences demonstrated that Sam68 might participate in Schwann cell proliferation partially via PI3K/Akt pathway and also regulate regeneration after sciatic nerve crush. -- Highlights: •The dynamic changes and location of Sam68 after sciatic nerve crush. •Sam68 promoted Schwann cell proliferation via PI3K/Akt pathway. •Sam68 modulated functional recovery after sciatic nerve crush.« less

Cholinergic Modulation of the Hippocampus during Encoding and Retrieval of Tone/Shock-Induced Fear Conditioning

ERIC Educational Resources Information Center

Rogers, Jason L.; Kesner, Raymond P.

2004-01-01

We investigated the role of acetylcholine (ACh) during encoding and retrieval of tone/shock-induced fear conditioning with the aim of testing Hasselmo's cholinergic modulation model of encoding and retrieval using a task sensitive to hippocampal disruption. Lesions of the hippocampus impair acquisition and retention of contextual conditioning with…

14 CFR 171.265 - Glide path performance requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... depth of modulation of the radio frequency carrier due to each of the 90 Hz and 150 Hz tones must be 40... tone, which is the time average equivalent to amplitude modulation. The pattern must be arranged to... 5220 MHz to 5250 MHz. The frequency tolerance may not exceed ±0.0001 percent. (f) The emission from the...

System Advisor Model (SAM) General Description (Version 2017.9.5)

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

Freeman, Janine M; DiOrio, Nicholas A; Blair, Nathan J

This document describes the capabilities of the System Advisor Model (SAM) developed and distributed by the U.S. Department of Energy's National Renewable Energy Laboratory. The document is for potential users and others wanting to learn about the model's capabilities. SAM is a techno-economic computer model that calculates performance and financial metrics of renewable energy projects. Project developers, policy makers, equipment manufacturers, and researchers use graphs and tables of SAM results in the process of evaluating financial, technology, and incentive options for renewable energy projects. SAM simulates the performance of photovoltaic, concentrating solar power, solar water heating, wind, geothermal, biomass, andmore » conventional power systems. The financial models are for projects that either buy and sell electricity at retail rates (residential and commercial) or sell electricity at a price determined in a power purchase agreement (PPA). SAM's simulation tools facilitate parametric and sensitivity analyses, Monte Carlo simulation and weather variability (P50/P90) studies. SAM can also read input variables from Microsoft Excel worksheets. For software developers, the SAM software development kit (SDK) makes it possible to use SAM simulation modules in their applications written in C/C plus plus, C sharp, Java, Python, MATLAB, and other languages. NREL provides both SAM and the SDK as free downloads at https://sam.nrel.gov. SAM is an open source project, so its source code is available to the public. Researchers can study the code to understand the model algorithms, and software programmers can contribute their own models and enhancements to the project. Technical support and more information about the software are available on the website.« less

Modulating Tone to Promote Motor Development Using a Neurofacilitation of Developmental Reaction (NFDR) Approach in Children with Neurodevelopmental Delay

PubMed Central

Batra, Vijay; Batra, Meenakshi; Pandey, Ravindra Mohan; Sharma, Vijai Prakash; Agarwal, Girdhar Gopal

2015-01-01

Objective To compare the efficacy of a Neurofacilitation of Developmental Reaction (NFDR) approach with that of a Conventional approach in the modulation of tone in children with neurodevelopmental delay. Methods Experimental control design. A total of 30 spastic children ranging in age from 4 to 7 years with neurodevelopmental delay were included. Baseline evaluations of muscle tone and gross motor functional performance abilities were performed. The children were allocated into two intervention groups of 15 subjects each. In groups A and B, the NFDR and conventional approaches were applied, respectively, for 3 months and were followed by subsequent re-evaluations. Results Between group analyses were performed using independent t test for tone and primitive reflex intensity and a Mann-Whitney U test for gross motor functional ability. For the within-group analyses, paired t tests were used for tone and primitive reflex intensity, and a Wilcoxon signed-rank test was used for gross motor functional ability. Conclusion The NFDR approach/technique prepares the muscle to undergo tonal modulation and thereby enhances motor development and improves the motor functional performance abilities of the children with neurodevelopmental delay. PMID:28239268

Simulation of different types of ENSO impacts on South Asian Monsoon in CCSM4

NASA Astrophysics Data System (ADS)

Islam, Siraj ul; Tang, Youmin

2017-02-01

It has been found in observation that there are different types of influences of El Nino Southern Oscillation (ENSO) on the South Asian Monsoon (SAM). A correct description and representation of these teleconnections is critical for climate models to simulate and predict SAM. In this study, we examine these teleconnections in NCAR CAM4 and CCSM4 models, including the strength and weakness of these models in preserving different types of ENSO-SAM relationships. By using observational and simulation dataset, the composite analysis, based on specific selection criteria, is performed for both SAM rainfall and the eastern equatorial Pacific sea surface temperature (SST) anomalies. Anomalous SAM rainfall is characterized in three different types i.e. the indirect influence of the SST anomalies of preceding winter (DJF-only), direct influence of the SST anomalies of concurrent summer (JJAS-only) and the combined influence of both preceding winter and concurrent summer (DJF&JJAS). The analysis reveals that CAM4 uncoupled simulation can reasonably well reproduce the anomalous SAM rainfall in DJF-only and DJF&JJAS types whereas the model fails to simulate the anomalous rainfall in the JJAS-only type. The better performance of CAM4, particularly in DJF&JJAS type, comes from its realistic simulation of moisture content and thermal contrast. Its failure to preserve the ENSO-SAM relationship of JJAS-only type is due to the absence of ENSO induced warming in Northern Indian Ocean via atmospheric circulation which is indirectly linked to the lack of air-sea coupling. The role of Indian Ocean in controlling the ENSO-SAM teleconnections of the DJF&JJAS type is further investigated using CAM4 sensitivity experiments. It is found that in absence of Indian Ocean SST, the anomalous SAM summer rainfall suppresses in the DJF&JJAS type, suggesting the important modulation by Indian Ocean SST probably through the preceding winter equatorial Pacific SST forcing and the atmospheric circulations. On the other hand, CCSM4 shows large systematical errors in DJF-only and DJF&JJAS types and reproduce weak anomalous SAM rainfall. The failure of CCSM4 in simulating DJF-only and DJF&JJAS types is found mainly due to the errors in its SST simulation. The JJAS-only type is better reproduced in the CCSM4 simulation as compared to CAM4 and observation composites. Strong convergence over the SAM region which intensifies the anomalous SAM is seen to be responsible for its better simulation in this type. It is found that the atmospheric circulations in CCSM4 contribute more than the thermal contrast in modulating the intensity of anomalous rainfall in JJAS-only type. This study suggests that, although air-sea coupling is important for better SAM simulation and its relationship with ENSO, the SST bias in coupled model can significantly degrade ENSO-SAM relationship.

Characterization of the near native conformational states of the SAM domain of Ste11 protein by NMR spectroscopy.

PubMed

Gupta, Sebanti; Bhattacharjya, Surajit

2014-11-01

The sterile alpha motif or SAM domain is one of the most frequently present protein interaction modules with diverse functional attributions. SAM domain of the Ste11 protein of budding yeast plays important roles in mitogen-activated protein kinase cascades. In the current study, urea-induced, at subdenaturing concentrations, structural, and dynamical changes in the Ste11 SAM domain have been investigated by nuclear magnetic resonance spectroscopy. Our study revealed that a number of residues from Helix 1 and Helix 5 of the Ste11 SAM domain display plausible alternate conformational states and largest chemical shift perturbations at low urea concentrations. Amide proton (H/D) exchange experiments indicated that Helix 1, loop, and Helix 5 become more susceptible to solvent exchange with increased concentrations of urea. Notably, Helix 1 and Helix 5 are directly involved in binding interactions of the Ste11 SAM domain. Our data further demonstrate that the existence of alternate conformational states around the regions involved in dimeric interactions in native or near native conditions. © 2014 Wiley Periodicals, Inc.

Centennial-scale solar forcing of the South American Monsoon System recorded in stalagmites.

PubMed

Novello, Valdir F; Vuille, Mathias; Cruz, Francisco W; Stríkis, Nicolás M; de Paula, Marcos Saito; Edwards, R Lawrence; Cheng, Hai; Karmann, Ivo; Jaqueto, Plínio F; Trindade, Ricardo I F; Hartmann, Gelvam A; Moquet, Jean S

2016-04-21

The South American Monsoon System (SAMS) is generally considered to be highly sensitive to Northern Hemisphere (NH) temperature variations on multi-centennial timescales. The direct influence of solar forcing on moisture convergence in global monsoon systems on the other hand, while well explored in modeling studies, has hitherto not been documented in proxy data from the SAMS region. Hence little is known about the sensitivity of the SAMS to solar forcing over the past millennium and how it might compete or constructively interfere with NH temperature variations that occurred primarily in response to volcanic forcing. Here we present a new annually-resolved oxygen isotope record from a 1500-year long stalagmite recording past changes in precipitation in the hitherto unsampled core region of the SAMS. This record details how solar variability consistently modulated the strength of the SAMS on centennial time scales during the past 1500 years. Solar forcing, besides the previously recognized influence from NH temperature changes and associated Intertropical Convergence Zone (ITCZ) shifts, appears as a major driver affecting SAMS intensity at centennial time scales.

Sample Analysis at Mars Instrument Simulator

NASA Technical Reports Server (NTRS)

Benna, Mehdi; Nolan, Tom

2013-01-01

The Sample Analysis at Mars Instrument Simulator (SAMSIM) is a numerical model dedicated to plan and validate operations of the Sample Analysis at Mars (SAM) instrument on the surface of Mars. The SAM instrument suite, currently operating on the Mars Science Laboratory (MSL), is an analytical laboratory designed to investigate the chemical and isotopic composition of the atmosphere and volatiles extracted from solid samples. SAMSIM was developed using Matlab and Simulink libraries of MathWorks Inc. to provide MSL mission planners with accurate predictions of the instrument electrical, thermal, mechanical, and fluid responses to scripted commands. This tool is a first example of a multi-purpose, full-scale numerical modeling of a flight instrument with the purpose of supplementing or even eliminating entirely the need for a hardware engineer model during instrument development and operation. SAMSIM simulates the complex interactions that occur between the instrument Command and Data Handling unit (C&DH) and all subsystems during the execution of experiment sequences. A typical SAM experiment takes many hours to complete and involves hundreds of components. During the simulation, the electrical, mechanical, thermal, and gas dynamics states of each hardware component are accurately modeled and propagated within the simulation environment at faster than real time. This allows the simulation, in just a few minutes, of experiment sequences that takes many hours to execute on the real instrument. The SAMSIM model is divided into five distinct but interacting modules: software, mechanical, thermal, gas flow, and electrical modules. The software module simulates the instrument C&DH by executing a customized version of the instrument flight software in a Matlab environment. The inputs and outputs to this synthetic C&DH are mapped to virtual sensors and command lines that mimic in their structure and connectivity the layout of the instrument harnesses. This module executes, and thus validates, complex command scripts prior to their up-linking to the SAM instrument. As an output, this module generates synthetic data and message logs at a rate that is similar to the actual instrument.

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

PubMed

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

2017-11-01

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

Antimultipath communication by injecting tone into null in signal spectrum

NASA Technical Reports Server (NTRS)

Davarian, Faramaz (Inventor)

1987-01-01

A transmitter for digital radio communication creates a null by balanced encoding of data modulated on an RF carrier, and inserts a calibration tone within the null. This is accomplished by having the calibration tone coincide in phase and frequency with the transmitted radio frequency output, for coherent demodulation of data at the receiver where the tone calibration signal is extracted and used for multipath fading compensation.

Systematic approach to study of thinly and thickly sectioned melanoma tissues with scanning acoustic microscopy

NASA Astrophysics Data System (ADS)

Miyasaka, C.; Tittmann, B. R.; Tutwiler, R.; Tian, Y.; Maeva, E.; Shum, D.

2010-03-01

The present study is to investigate the feasibility of applying in-vivo acoustic microscopy to the analysis of cancerous tissue. The study was implemented with mechanical scanning reflection acoustic microscope (SAM) by the following procedures. First, we ultrasonically visualized thick sections of normal and tumor tissues to determine the lowest transducer frequency required for cellular imaging. We used skin for normal tissue and the tumor was a malignant melanoma. Thin sections of the tissue were also studied with the optical and high-frequency-ultrasonic imaging for pathological evaluation. Secondly, we ultrasonically visualized subsurface cellular details of thin tissue specimens with different modes (i.e., pulse and tone-burst wave modes) to obtain the highest quality ultrasonic images. The objective is to select the best mode for the future design of a future SAM for in-vivo examination. Thirdly, we developed a mathematical modeling technique based on an angular spectrum approach for improving image processing and comparing numerical to experimental results.

Teleconnection stationarity, variability and trends of the Southern Annular Mode (SAM) during the last millennium

NASA Astrophysics Data System (ADS)

Dätwyler, Christoph; Neukom, Raphael; Abram, Nerilie J.; Gallant, Ailie J. E.; Grosjean, Martin; Jacques-Coper, Martín; Karoly, David J.; Villalba, Ricardo

2017-11-01

The Southern Annular Mode (SAM) is the leading mode of atmospheric interannual variability in the Southern Hemisphere (SH) extra-tropics. Here, we assess the stationarity of SAM spatial correlations with instrumental and paleoclimate proxy data for the past millennium. The instrumental period shows that temporal non-stationarities in SAM teleconnections are not consistent across the SH land areas. This suggests that the influence of the SAM index is modulated by regional effects. However, within key-regions with good proxy data coverage (South America, Tasmania, New Zealand), teleconnections are mostly stationary over the instrumental period. Using different stationarity criteria for proxy record selection, we provide new austral summer and annual mean SAM index reconstructions over the last millennium. Our summer SAM reconstructions are very robust to changes in proxy record selection and the selection of the calibration period, particularly on the multi-decadal timescale. In contrast, the weaker performance and lower agreement in the annual mean SAM reconstructions point towards changing teleconnection patterns that may be particularly important outside the summer months. Our results clearly portend that the temporal stationarity of the proxy-climate relationships should be taken into account in the design of comprehensive regional and hemispherical climate reconstructions. The summer SAM reconstructions show no significant relationship to solar, greenhouse gas and volcanic forcing, with the exception of an extremely strong negative anomaly following the AD 1257 Samalas eruption. Furthermore, reconstructed pre-industrial summer SAM trends are very similar to trends obtained by model control simulations. We find that recent trends in the summer SAM lie outside the 5-95% range of pre-industrial natural variability.

Structural investigation of a C-terminal EphA2 receptor mutant: Does mutation affect the structure and interaction properties of the Sam domain?

PubMed

Mercurio, Flavia A; Costantini, Susan; Di Natale, Concetta; Pirone, Luciano; Guariniello, Stefano; Scognamiglio, Pasqualina L; Marasco, Daniela; Pedone, Emilia M; Leone, Marilisa

2017-09-01

Ephrin A2 receptor (EphA2) plays a key role in cancer, it is up-regulated in several types of tumors and the process of ligand-induced receptor endocytosis, followed by degradation, is considered as a potential path to diminish tumor malignancy. Protein modulators of this mechanism are recruited at the cytosolic Sterile alpha motif (Sam) domain of EphA2 (EphA2-Sam) through heterotypic Sam-Sam associations. These interactions engage the C-terminal helix of EphA2 and close loop regions (the so called End Helix side). In addition, several studies report on destabilizing mutations in EphA2 related to cataract formation and located in/or close to the Sam domain. Herein, we analyzed from a structural point of view, one of these mutants characterized by the insertion of a novel 39 residue long polypeptide at the C-terminus of EphA2-Sam. A 3D structural model was built by computational methods and revealed partial disorder in the acquired C-terminal tail and a few residues participating in an α-helix and two short β-strands. We investigated by CD and NMR studies the conformational properties in solution of two peptides encompassing the whole C-terminal tail and its predicted helical region, respectively. NMR binding experiments demonstrated that these peptides do not interact relevantly with either EphA2-Sam or its interactor Ship2-Sam. Molecular dynamics (MD) simulations further indicated that the EphA2 mutant could be represented only through a conformational ensemble and that the C-terminal tail should not largely wrap the EphA2-Sam End-Helix interface and affect binding to other Sam domains. Copyright © 2017 Elsevier B.V. All rights reserved.

S-Adenosylmethionine attenuates bile duct early warm ischemia reperfusion injury after rat liver transplantation.

PubMed

Tang, Yong; Chu, Hongpeng; Cao, Guojun; Du, Xiaolong; Min, Xiaobo; Wan, Chidan

2018-03-01

Warm ischemia reperfusion injury (IRI) plays a key role in biliary complication, which is a substantial vulnerability of liver transplantation. The early pathophysiological changes of IRI are characterized by an excessive inflammatory response. S-Adenosylmethionine (SAM) is an important metabolic intermediate that modulates inflammatory reactions; however, its role in bile duct warm IRI is not known. In this study, male rats were treated with or without SAM (170 μmol/kg body weight) after orthotopic autologous liver transplantation. The histopathological observations showed that bile duct injury in the IRI group was more serious than in the SAM group. The alanine aminotransferase (ALT), alkaline phosphatase (ALP) and direct bilirubin (DBIL) levels in the serum of the IRI group were significantly increased compared to the SAM group (P < .05). Simultaneously, SAM effectively improved the survival of the transplant recipients. Furthermore, the H 2 O 2 and malondialdehyde (MDA) of the IRI group were much higher compared to the SAM group (P < .05). The GSH/GSSG ratio in the SAM group was significantly increased by SAM treatment compared to the IRI group (P < .05). SAM administration significantly inhibited macrophage infiltration in liver and bile duct tissues, down-regulated TNF-α levels and up-regulated IL-10 expression in bile duct tissues compared to the IRI group (P < .05). The number of apoptotic biliary epithelial cells and caspase-3-positive cells in IRI rat livers were much higher compared to those in SAM-treated rats at 24 h after liver transplantation (P < .05). These data suggested that SAM protected bile ducts against warm IRI by suppressing oxidative stress, inflammatory reactions and apoptosis of biliary epithelial cells after liver transplantation.α. Copyright © 2018 Elsevier Ltd. All rights reserved.

Progress & Frontiers in PV Performance

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

Deline, Chris; DiOrio, Nick; Jordan, Dirk

2016-09-12

PowerPoint slides for a presentation given at Solar Power International 2016. Presentation includes System Advisor Model (SAM) introduction and battery modeling, bifacial PV modules and modeling, shade modeling and module level power electronics (MLPE), degradation rates, and PVWatts updates and validation.

Synthesis and characterization of self-assembled monolayers on gold generated from partially fluorinated alkanethiols and aliphatic dithiocarboxylic acids

NASA Astrophysics Data System (ADS)

Colorado, Ramon, Jr.

The formation of novel self-assembled monolayers (SAMs) on gold from the adsorption of four distinct series of partially fluorinated alkanethiols (PFAs) and one series of chelating aliphatic dithiocarboxylic acids (ADTCAs) is reported. The SAMs were characterized by optical ellipsometry, contact angle goniometry, polarization modulation infrared absorption spectroscopy (PM-IRRAS), and X-ray photoelectron spectroscopy (XPS). The results for the PFA SAMs provided evidence for both the importance of oriented surface dipoles in influencing interfacial wettabilities and the significance of the degree of fluorination of the PFAs in determining the dispersive interfacial energies of the films. In addition, a series of PFA SAMs was used to demonstrate that the attenuation lengths of photoelectrons in fluorocarbon films are indistinguishable from those in hydrocarbon films. The results for the ADTCA SAMs demonstrated that the use of a chelating headgroup induces structural changes within the monolayers that influence the interfacial properties of the films.

The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis.

PubMed

Bielli, Pamela; Busà, Roberta; Di Stasi, Savino M; Munoz, Manuel J; Botti, Flavia; Kornblihtt, Alberto R; Sette, Claudio

2014-04-01

Alternative splicing (AS) is tightly coupled to transcription for the majority of human genes. However, how these two processes are linked is not well understood. Here, we unveil a direct role for the transcription factor FBI-1 in the regulation of AS. FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA. This, in turn, results in the selection of the proximal 5' splice site in BCL-X exon 2, thereby favoring the anti-apoptotic BCL-XL variant and counteracting SAM68-mediated apoptosis. Conversely, depletion of FBI-1, or expression of a SAM68 mutant lacking the FBI-1 binding region, restores the ability of SAM68 to induce BCL-XS splicing and apoptosis. FBI-1's role in splicing requires the activity of histone deacetylases, whose pharmacological inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modulation with a direct impact on cell survival.

The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis

PubMed Central

Bielli, Pamela; Busà, Roberta; Di Stasi, Savino M; Munoz, Manuel J; Botti, Flavia; Kornblihtt, Alberto R; Sette, Claudio

2014-01-01

Alternative splicing (AS) is tightly coupled to transcription for the majority of human genes. However, how these two processes are linked is not well understood. Here, we unveil a direct role for the transcription factor FBI-1 in the regulation of AS. FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA. This, in turn, results in the selection of the proximal 5′ splice site in BCL-X exon 2, thereby favoring the anti-apoptotic BCL-XL variant and counteracting SAM68-mediated apoptosis. Conversely, depletion of FBI-1, or expression of a SAM68 mutant lacking the FBI-1 binding region, restores the ability of SAM68 to induce BCL-XS splicing and apoptosis. FBI-1's role in splicing requires the activity of histone deacetylases, whose pharmacological inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modulation with a direct impact on cell survival. PMID:24514149

Supra-physiological folic acid concentrations induce aberrant DNA methylation in normal human cells in vitro.

PubMed

Charles, Michelle A; Johnson, Ian T; Belshaw, Nigel J

2012-07-01

The micronutrients folate and selenium may modulate DNA methylation patterns by affecting intracellular levels of the methyl donor S-adenosylmethionine (SAM) and/or the product of methylation reactions S-adenosylhomocysteine (SAH). WI-38 fibroblasts and FHC colon epithelial cells were cultured in the presence of two forms of folate or four forms of selenium at physiologically-relevant doses, and their effects on LINE-1 methylation, gene-specific CpG island (CGI) methylation and intracellular SAM:SAH were determined. At physiologically-relevant doses the forms of folate or selenium had no effect on LINE-1 or CGI methylation, nor on intracellular SAM:SAH. However the commercial cell culture media used for the selenium studies, containing supra-physiological concentrations of folic acid, induced LINE-1 hypomethylation, CGI hypermethylation and decreased intracellular SAM:SAH in both cell lines. We conclude that the exposure of normal human cells to supra-physiological folic acid concentrations present in commercial cell culture media perturbs the intracellular SAM:SAH ratio and induces aberrant DNA methylation.

Microgravity acceleration measurement and environment characterization science (17-IML-1)

NASA Technical Reports Server (NTRS)

1992-01-01

The Space Acceleration Measurement System (SAMS) is a general purpose instrumentation system designed to measure the accelerations onboard the Shuttle Orbiter and Shuttle/Spacelab vehicles. These measurements are used to support microgravity experiments and investigation into the microgravity environment of the vehicle. Acceleration measurements can be made at locations remote from the SAMS main instrumentation unit by the use of up to three remote triaxial sensor heads. The prime objective for SAMS on the International Microgravity Lab (IML-1) mission will be to measure the accelerations experienced by the Fluid Experiment System (FES). The SAMS acceleration measurements for FES will be complemented by low level, low frequency acceleration measurements made by the Orbital Acceleration Research Experiment (OARE) installed on the shuttle. Secondary objectives for SAMS will be to measure accelerations at several specific locations to enable the acceleration transfer function of the Spacelab module to be analyzed. This analysis effort will be in conjunction with similar measurements analyses on other Spacelab missions.

Photoinduced work function changes by isomerization of a densely packed azobenzene-based SAM on Au: a joint experimental and theoretical study.

PubMed

Crivillers, N; Liscio, A; Di Stasio, F; Van Dyck, C; Osella, S; Cornil, D; Mian, S; Lazzerini, G M; Fenwick, O; Orgiu, E; Reinders, F; Braun, S; Fahlman, M; Mayor, M; Cornil, J; Palermo, V; Cacialli, F; Samorì, P

2011-08-28

Responsive monolayers are key building blocks for future applications in organic and molecular electronics in particular because they hold potential for tuning the physico-chemical properties of interfaces, including their energetics. Here we study a photochromic SAM based on a conjugated azobenzene derivative and its influence on the gold work function (Φ(Au)) when chemisorbed on its surface. In particular we show that the Φ(Au) can be modulated with external stimuli by controlling the azobenzene trans/cis isomerization process. This phenomenon is characterized experimentally by four different techniques, kelvin probe, kelvin probe force microscopy, electroabsorption spectroscopy and ultraviolet photoelectron spectroscopy. The use of different techniques implies exposing the SAM to different measurement conditions and different preparation methods, which, remarkably, do not alter the observed work function change (Φ(trans)-Φ(cis)). Theoretical calculations provided a complementary insight crucial to attain a deeper knowledge on the origin of the work function photo-modulation.

Combination of binaural and harmonic masking release effects in the detection of a single component in complex tones.

PubMed

Klein-Hennig, Martin; Dietz, Mathias; Hohmann, Volker

2018-03-01

Both harmonic and binaural signal properties are relevant for auditory processing. To investigate how these cues combine in the auditory system, detection thresholds for an 800-Hz tone masked by a diotic (i.e., identical between the ears) harmonic complex tone were measured in six normal-hearing subjects. The target tone was presented either diotically or with an interaural phase difference (IPD) of 180° and in either harmonic or "mistuned" relationship to the diotic masker. Three different maskers were used, a resolved and an unresolved complex tone (fundamental frequency: 160 and 40 Hz) with four components below and above the target frequency and a broadband unresolved complex tone with 12 additional components. The target IPD provided release from masking in most masker conditions, whereas mistuning led to a significant release from masking only in the diotic conditions with the resolved and the narrowband unresolved maskers. A significant effect of mistuning was neither found in the diotic condition with the wideband unresolved masker nor in any of the dichotic conditions. An auditory model with a single analysis frequency band and different binaural processing schemes was employed to predict the data of the unresolved masker conditions. Sensitivity to modulation cues was achieved by including an auditory-motivated modulation filter in the processing pathway. The predictions of the diotic data were in line with the experimental results and literature data in the narrowband condition, but not in the broadband condition, suggesting that across-frequency processing is involved in processing modulation information. The experimental and model results in the dichotic conditions show that the binaural processor cannot exploit modulation information in binaurally unmasked conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Principal pitch of frequency-modulated tones with asymmetrical modulation waveform: a comparison of models.

PubMed

Etchemendy, Pablo E; Eguia, Manuel C; Mesz, Bruno

2014-03-01

In this work, the overall perceived pitch (principal pitch) of pure tones modulated in frequency with an asymmetric waveform is studied. The dependence of the principal pitch on the degree of asymmetric modulation was obtained from a psychophysical experiment. The modulation waveform consisted of a flat portion of constant frequency and two linear segments forming a peak. Consistent with previous results, significant pitch shifts with respect to the time-averaged geometric mean were observed. The direction of the shifts was always toward the flat portion of the modulation. The results from the psychophysical experiment, along with those obtained from previously reported studies, were compared with the predictions of six models of pitch perception proposed in the literature. Even though no single model was able to predict accurately the perceived pitch for all experiments, there were two models that give robust predictions that are within the range of acceptable tuning of modulated tones for almost all the cases. Both models point to the existence of an underlying "stability sensitive" mechanism for the computation of pitch that gives more weight to the portion of the stimuli where the frequency is changing more slowly.

SAMS Acceleration Measurements on Mir from May 1997 to June 1998 (NASA Increments 5, 6, and 7)

NASA Technical Reports Server (NTRS)

DeLombard, Richard

1999-01-01

During NASA Increments 5, 6, and 7 (May 1997 to June 1998), about eight gigabytes of acceleration data were collected by the Space Acceleration Measurement System (SAMS) onboard the Russian Space Station Mir. The data were recorded on twenty-seven optical disks which were returned to Earth on Orbiter missions STS-86, STS-89, and STS-91. During these increments, SAMS data were collected in the Priroda module to support various microgravity experiments. This report points out some of the salient features of the microgravity acceleration environment to which the experiments were exposed. This report presents an overview of the SAMS acceleration measurements recorded by 10 Hz and 100 Hz sensor heads. The analyses included herein complement those presented in previous Mir increment summary reports prepared by the Principal Investigator Microgravity Services project.

SAMS Acceleration Measurements on Mir From January to May 1997 (NASA Increment 4)

NASA Technical Reports Server (NTRS)

DeLombard, Richard

1998-01-01

During NASA Increment 4 (January to May 1997), about 5 gigabytes of acceleration data were collected by the Space Acceleration Measurements System (SAMS) onboard the Russian Space Station, Mir. The data were recorded on 28 optical disks which were returned to Earth on STS-84. During this increment, SAMS data were collected in the Priroda module to support the Mir Structural Dynamics Experiment (MiSDE), the Binary Colloidal Alloy Tests (BCAT), Angular Liquid Bridge (ALB), Candle Flames in Microgravity (CFM), Diffusion Controlled Apparatus Module (DCAM), Enhanced Dynamic Load Sensors (EDLS), Forced Flow Flame Spreading Test (FFFT), Liquid Metal Diffusion (LMD), Protein Crystal Growth in Dewar (PCG/Dewar), Queen's University Experiments in Liquid Diffusion (QUELD), and Technical Evaluation of MIM (TEM). This report points out some of the salient features of the microgravity environment to which these experiments were exposed. Also documented are mission events of interest such as the docked phase of STS-84 operations, a Progress engine burn, Soyuz vehicle docking and undocking, and Progress vehicle docking. This report presents an overview of the SAMS acceleration measurements recorded by 10 Hz and 100 Hz sensor heads. The analyses included herein complement those presented in previous summary reports prepared by the Principal Investigator Microgravity Services (PIMS) group.

Modulating protein behaviors on responsive surface by external electric fields: A molecular dynamics study

NASA Astrophysics Data System (ADS)

Xie, Yun; Pan, Yufang; Zhang, Rong; Liang, Ying; Li, Zhanchao

2015-01-01

Molecular dynamics simulations were employed to investigate the modulation of protein behaviors on the electrically responsive zwitterionic phosphorylcholine self-assembled monolayers (PC-SAMs). Results show that PC-SAMs could sensitively respond to the applied electric fields and exhibit three states with different charge distributions, namely both the negatively charged phosphate groups and the positively charged choline groups are exposed to the solution in the absence of electric fields (state 1), phosphate groups exposed in the presence of positive electric fields (state 2), and choline groups exposed in the presence of negative electric fields (state 3). Under state 1, the adsorption of Cyt c on the PC-SAM is reversible and the orientations of Cyt c are randomly distributed. Under state 2, the adsorption of Cyt c is enhanced due to the electrostatic attractions between the exposed phosphate groups and the positively charged protein; when adsorbed on the PC-SAMs, Cyt c tends to adopt the orientation with the heme plane perpendicular to the surface plane, and the percentage of this orientation increases as the field strength rises up. Under state 3, the adsorption of Cyt c is retarded because of the electrostatic repulsions between the exposed choline groups and the protein; however, if the gaps between PC chains are large enough, Cyt c could insert into the PC-SAM and access the phosphate groups after overcoming a slight energy barrier. Under three states, the basic backbone structures of Cyt c are well kept within the simulation time since the conformation of Cyt c is mainly affected by the surface-generated electric fields, whose strengths are modulated by the external electric fields and are not strong enough to deform protein. The results indicate the possibility of regulating protein behaviors, including promoting or retarding protein adsorption and regulating protein orientations, on responsive surfaces by applying electric fields on the surfaces without worrying protein deformation, which may be helpful in the applications of protein separation and controlled drug delivery.

Tonal noise of a controlled-diffusion airfoil at low angle of attack and Reynolds number.

PubMed

Padois, Thomas; Laffay, Paul; Idier, Alexandre; Moreau, Stéphane

2016-07-01

The acoustic signature of a controlled-diffusion airfoil immersed in a flow is experimentally characterized. Acoustic measurements have been carried out in an anechoic open-jet-wind-tunnel for low Reynolds numbers (from 5 × 10(4) to 4.3 × 10(5)) and several angles of attack. As with the NACA0012, the acoustic spectrum is dominated by discrete tones. These tonal behaviors are divided into three different regimes. The first one is characterized by a dominant primary tone which is steady over time, surrounded by secondary peaks. The second consists of two unsteady primary tones associated with secondary peaks and the third consists of a hump dominated by several small peaks. A wavelet study allows one to identify an amplitude modulation of the acoustic signal mainly for the unsteady tonal regime. This amplitude modulation is equal to the frequency interval between two successive tones. Finally, a bispectral analysis explains the presence of tones at higher frequencies.

4-Mercaptophenylboronic acid SAMs on gold: comparison with SAMs derived from thiophenol, 4-mercaptophenol, and 4-mercaptobenzoic acid.

PubMed

Barriet, David; Yam, Chi Ming; Shmakova, Olga E; Jamison, Andrew C; Lee, T Randall

2007-08-14

We report the formation and characterization of self-assembled monolayers (SAMs) derived from the adsorption of 4-mercaptophenylboronic acid (MPBA) on gold. For comparison, SAMs derived from the adsorption of thiophenol (TP), 4-mercaptophenol (MP), and 4-mercaptobenzoic acid (MBA) were also examined. The structure and properties of the SAMs were evaluated by ellipsometry, contact-angle goniometry, polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS), and X-ray photoelectron spectroscopy (XPS). Specifically, ellipsometry was used to assess the formation of monolayer films, and contact angle measurements were used to determine the surface hydrophilicity and homogeneity. Separately, PM-IRRAS was used to evaluate the molecular composition and orientation as well as the intermolecular hydrogen bonding within the SAMs. Finally, XPS was used to evaluate the film composition and surface coverage (i.e., packing density), which was observed to increase in the following order: TP < MP < MPBA < MBA. A rationalization for the observed packing differences is presented. The XPS data indicate further that ultrahigh vacuum conditions induce the partial dehydration of MPBA SAMs with the concomitant formation of surface boronic anhydride species. Overall, the analytical data collectively show that the MPBA moieties in the SAMs exist in the acid form rather than the anhydride form under ambient laboratory conditions. Furthermore, stability studies find that MPBA SAMs are surprisingly labile in basic solution, where the terminal B-C bonds are cleaved by the attack of hydroxide ion and strongly basic amine nucleophiles. The unanticipated lability observed here should be considered by those wishing to use MPBA moieties in carbohydrate-sensing applications.

Ka-Band Transponder for Deep-Space Radio Science

NASA Technical Reports Server (NTRS)

Dennis, Matthew S.; Mysoor, Narayan R.; Folkner, William M.; Mendoza, Ricardo; Venkatesan, Jaikrishna

2008-01-01

A one-page document describes a Ka-band transponder being developed for use in deep-space radio science. The transponder receives in the Deep Space Network (DSN) uplink frequency band of 34.2 to 34.7 GHz, transmits in the 31.8- to 32.3 GHz DSN downlink band, and performs regenerative ranging on a DSN standard 4-MHz ranging tone subcarrier phase-modulated onto the uplink carrier signal. A primary consideration in this development is reduction in size, relative to other such transponders. The transponder design is all-analog, chosen to minimize not only the size but also the number of parts and the design time and, thus, the cost. The receiver features two stages of frequency down-conversion. The receiver locks onto the uplink carrier signal. The exciter signal for the transmitter is derived from the same source as that used to generate the first-stage local-oscillator signal. The ranging-tone subcarrier is down-converted along with the carrier to the second intermediate frequency, where the 4-MHz tone is demodulated from the composite signal and fed into a ranging-tone-tracking loop, which regenerates the tone. The regenerated tone is linearly phase-modulated onto the downlink carrier.

Predictions of psychophysical measurements for sinusoidal amplitude modulated (SAM) pulse-train stimuli from a stochastic model.

PubMed

Xu, Yifang; Collins, Leslie M

2007-08-01

Two approaches have been proposed to reduce the synchrony of the neural response to electrical stimuli in cochlear implants. One approach involves adding noise to the pulse-train stimulus, and the other is based on using a high-rate pulse-train carrier. Hypotheses regarding the efficacy of the two approaches can be tested using computational models of neural responsiveness prior to time-intensive psychophysical studies. In our previous work, we have used such models to examine the effects of noise on several psychophysical measures important to speech recognition. However, to date there has been no parallel analytic solution investigating the neural response to the high-rate pulse-train stimuli and their effect on psychophysical measures. This work investigates the properties of the neural response to high-rate pulse-train stimuli with amplitude modulated envelopes using a stochastic auditory nerve model. The statistics governing the neural response to each pulse are derived using a recursive method. The agreement between the theoretical predictions and model simulations is demonstrated for sinusoidal amplitude modulated (SAM) high rate pulse-train stimuli. With our approach, predicting the neural response in modern implant devices becomes tractable. Psychophysical measurements are also predicted using the stochastic auditory nerve model for SAM high-rate pulse-train stimuli. Changes in dynamic range (DR) and intensity discrimination are compared with that observed for noise-modulated pulse-train stimuli. Modulation frequency discrimination is also studied as a function of stimulus level and pulse rate. Results suggest that high rate carriers may positively impact such psychophysical measures.

Influence of Threonine Metabolism on S-adenosyl-methionine and Histone Methylation

PubMed Central

Shyh-Chang, Ng; Locasale, Jason W.; Lyssiotis, Costas A.; Zheng, Yuxiang; Teo, Ren Yi; Ratanasirintrawoot, Sutheera; Zhang, Jin; Onder, Tamer; Unternaehrer, Juli J.; Zhu, Hao; Asara, John M.; Daley, George Q.; Cantley, Lewis C.

2013-01-01

Threonine is the only amino acid critically required for the pluripotency of mouse embryonic stem cells (mESCs) but the detailed mechanism remains unclear. We found that threonine (Thr) and S-adenosyl-methionine (SAM) metabolism are coupled in pluripotent stem cells, resulting in regulation of histone methylation. Isotope labeling of mESCs revealed that Thr provides a substantial fraction of both the cellular glycine (Gly) and the acetyl-coenzyme A (CoA) needed for SAM synthesis. Depletion of Thr from the culture medium or threonine dehydrogenase (Tdh) from mESCs decreased accumulation of SAM and decreased tri-methylation of histone H3 lysine-4 (H3K4me3), leading to slowed growth, and increased differentiation. Thus abundance of SAM appears to influence H3K4me3, providing a possible mechanism by which modulation of a metabolic pathway might influence stem cell fate. PMID:23118012

Specificity of the Human Frequency Following Response for Carrier and Modulation Frequency Assessed Using Adaptation.

PubMed

Gockel, Hedwig E; Krugliak, Alexandra; Plack, Christopher J; Carlyon, Robert P

2015-12-01

The frequency following response (FFR) is a scalp-recorded measure of phase-locked brainstem activity to stimulus-related periodicities. Three experiments investigated the specificity of the FFR for carrier and modulation frequency using adaptation. FFR waveforms evoked by alternating-polarity stimuli were averaged for each polarity and added, to enhance envelope, or subtracted, to enhance temporal fine structure information. The first experiment investigated peristimulus adaptation of the FFR for pure and complex tones as a function of stimulus frequency and fundamental frequency (F0). It showed more adaptation of the FFR in response to sounds with higher frequencies or F0s than to sounds with lower frequency or F0s. The second experiment investigated tuning to modulation rate in the FFR. The FFR to a complex tone with a modulation rate of 213 Hz was not reduced more by an adaptor that had the same modulation rate than by an adaptor with a different modulation rate (90 or 504 Hz), thus providing no evidence that the FFR originates mainly from neurons that respond selectively to the modulation rate of the stimulus. The third experiment investigated tuning to audio frequency in the FFR using pure tones. An adaptor that had the same frequency as the target (213 or 504 Hz) did not generally reduce the FFR to the target more than an adaptor that differed in frequency (by 1.24 octaves). Thus, there was no evidence that the FFR originated mainly from neurons tuned to the frequency of the target. Instead, the results are consistent with the suggestion that the FFR for low-frequency pure tones at medium to high levels mainly originates from neurons tuned to higher frequencies. Implications for the use and interpretation of the FFR are discussed.

Tone-activated, remote, alert communication system

NASA Technical Reports Server (NTRS)

Baker, C. D.; Couvillon, L. A.; Hubbard, W. P.; Kollar, F. J.; Postal, R. B.; Tegnelia, C. R.

1971-01-01

Pocket sized transmitter, frequency modulated by crystal derived tones, with integral loop antenna provides police with easy operating alert signal communicator which uses patrol car radio to relay signal. Communication channels are time shared by several patrol units.

SAM68 is a physiological regulator of SMN2 splicing in spinal muscular atrophy

PubMed Central

Pagliarini, Vittoria; Pelosi, Laura; Bustamante, Maria Blaire; Nobili, Annalisa; Berardinelli, Maria Grazia; D’Amelio, Marcello; Musarò, Antonio

2015-01-01

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by loss of motor neurons in patients with null mutations in the SMN1 gene. The almost identical SMN2 gene is unable to compensate for this deficiency because of the skipping of exon 7 during pre–messenger RNA (mRNA) processing. Although several splicing factors can modulate SMN2 splicing in vitro, the physiological regulators of this disease-causing event are unknown. We found that knockout of the splicing factor SAM68 partially rescued body weight and viability of SMAΔ7 mice. Ablation of SAM68 function promoted SMN2 splicing and expression in SMAΔ7 mice, correlating with amelioration of SMA-related defects in motor neurons and skeletal muscles. Mechanistically, SAM68 binds to SMN2 pre-mRNA, favoring recruitment of the splicing repressor hnRNP A1 and interfering with that of U2AF65 at the 3′ splice site of exon 7. These findings identify SAM68 as the first physiological regulator of SMN2 splicing in an SMA mouse model. PMID:26438828

Information System through ANIS at CeSAM

NASA Astrophysics Data System (ADS)

Moreau, C.; Agneray, F.; Gimenez, S.

2015-09-01

ANIS (AstroNomical Information System) is a web generic tool developed at CeSAM to facilitate and standardize the implementation of astronomical data of various kinds through private and/or public dedicated Information Systems. The architecture of ANIS is composed of a database server which contains the project data, a web user interface template which provides high level services (search, extract and display imaging and spectroscopic data using a combination of criteria, an object list, a sql query module or a cone search interfaces), a framework composed of several packages, and a metadata database managed by a web administration entity. The process to implement a new ANIS instance at CeSAM is easy and fast : the scientific project has to submit data or a data secure access, the CeSAM team installs the new instance (web interface template and the metadata database), and the project administrator can configure the instance with the web ANIS-administration entity. Currently, the CeSAM offers through ANIS a web access to VO compliant Information Systems for different projects (HeDaM, HST-COSMOS, CFHTLS-ZPhots, ExoDAT,...).

Unpredicted Pitch Modulates Beta Oscillatory Power during Rhythmic Entrainment to a Tone Sequence.

PubMed

Chang, Andrew; Bosnyak, Dan J; Trainor, Laurel J

2016-01-01

Extracting temporal regularities in external stimuli in order to predict upcoming events is an essential aspect of perception. Fluctuations in induced power of beta band (15-25 Hz) oscillations in auditory cortex are involved in predictive timing during rhythmic entrainment, but whether such fluctuations are affected by prediction in the spectral (frequency/pitch) domain remains unclear. We tested whether unpredicted (i.e., unexpected) pitches in a rhythmic tone sequence modulate beta band activity by recording EEG while participants passively listened to isochronous auditory oddball sequences with occasional unpredicted deviant pitches at two different presentation rates. The results showed that the power in low-beta (15-20 Hz) was larger around 200-300 ms following deviant tones compared to standard tones, and this effect was larger when the deviant tones were less predicted. Our results suggest that the induced beta power activities in auditory cortex are consistent with a role in sensory prediction of both "when" (timing) upcoming sounds will occur as well as the prediction precision error of "what" (spectral content in this case). We suggest, further, that both timing and content predictions may co-modulate beta oscillations via attention. These findings extend earlier work on neural oscillations by investigating the functional significance of beta oscillations for sensory prediction. The findings help elucidate the functional significance of beta oscillations in perception.

Unpredicted Pitch Modulates Beta Oscillatory Power during Rhythmic Entrainment to a Tone Sequence

PubMed Central

Chang, Andrew; Bosnyak, Dan J.; Trainor, Laurel J.

2016-01-01

Extracting temporal regularities in external stimuli in order to predict upcoming events is an essential aspect of perception. Fluctuations in induced power of beta band (15–25 Hz) oscillations in auditory cortex are involved in predictive timing during rhythmic entrainment, but whether such fluctuations are affected by prediction in the spectral (frequency/pitch) domain remains unclear. We tested whether unpredicted (i.e., unexpected) pitches in a rhythmic tone sequence modulate beta band activity by recording EEG while participants passively listened to isochronous auditory oddball sequences with occasional unpredicted deviant pitches at two different presentation rates. The results showed that the power in low-beta (15–20 Hz) was larger around 200–300 ms following deviant tones compared to standard tones, and this effect was larger when the deviant tones were less predicted. Our results suggest that the induced beta power activities in auditory cortex are consistent with a role in sensory prediction of both “when” (timing) upcoming sounds will occur as well as the prediction precision error of “what” (spectral content in this case). We suggest, further, that both timing and content predictions may co-modulate beta oscillations via attention. These findings extend earlier work on neural oscillations by investigating the functional significance of beta oscillations for sensory prediction. The findings help elucidate the functional significance of beta oscillations in perception. PMID:27014138

Titanium-silicon oxide film structures for polarization-modulated infrared reflection absorption spectroscopy

PubMed Central

Dunlop, Iain E.; Zorn, Stefan; Richter, Gunther; Srot, Vesna; Kelsch, Marion; van Aken, Peter A.; Skoda, Maximilian; Gerlach, Alexander; Spatz, Joachim P.; Schreiber, Frank

2010-01-01

We present a titanium-silicon oxide film structure that permits polarization modulated infrared reflection absorption spectroscopy on silicon oxide surfaces. The structure consists of a ~6 nm sputtered silicon oxide film on a ~200 nm sputtered titanium film. Characterization using conventional and scanning transmission electron microscopy, electron energy loss spectroscopy, X-ray photoelectron spectroscopy and X-ray reflectometry is presented. We demonstrate the use of this structure to investigate a selectively protein-resistant self-assembled monolayer (SAM) consisting of silane-anchored, biotin-terminated poly(ethylene glycol) (PEG). PEG-associated IR bands were observed. Measurements of protein-characteristic band intensities showed that this SAM adsorbed streptavidin whereas it repelled bovine serum albumin, as had been expected from its structure. PMID:20418963

Coupling the System Analysis Module with SAS4A/SASSYS-1

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

Fanning, T. H.; Hu, R.

2016-09-30

SAS4A/SASSYS-1 is a simulation tool used to perform deterministic analysis of anticipated events as well as design basis and beyond design basis accidents for advanced reactors, with an emphasis on sodium fast reactors. SAS4A/SASSYS-1 has been under development and in active use for nearly forty-five years, and is currently maintained by the U.S. Department of Energy under the Office of Advanced Reactor Technology. Although SAS4A/SASSYS-1 contains a very capable primary and intermediate system modeling component, PRIMAR-4, it also has some shortcomings: outdated data management and code structure makes extension of the PRIMAR-4 module somewhat difficult. The user input format formore » PRIMAR-4 also limits the number of volumes and segments that can be used to describe a given system. The System Analysis Module (SAM) is a fairly new code development effort being carried out under the U.S. DOE Nuclear Energy Advanced Modeling and Simulation (NEAMS) program. SAM is being developed with advanced physical models, numerical methods, and software engineering practices; however, it is currently somewhat limited in the system components and phenomena that can be represented. For example, component models for electromagnetic pumps and multi-layer stratified volumes have not yet been developed. Nor is there support for a balance of plant model. Similarly, system-level phenomena such as control-rod driveline expansion and vessel elongation are not represented. This report documents fiscal year 2016 work that was carried out to couple the transient safety analysis capabilities of SAS4A/SASSYS-1 with the system modeling capabilities of SAM under the joint support of the ART and NEAMS programs. The coupling effort was successful and is demonstrated by evaluating an unprotected loss of flow transient for the Advanced Burner Test Reactor (ABTR) design. There are differences between the stand-alone SAS4A/SASSYS-1 simulations and the coupled SAS/SAM simulations, but these are mainly attributed to the limited maturity of the SAM development effort. The severe accident modeling capabilities in SAS4A/SASSYS-1 (sodium boiling, fuel melting and relocation) will continue to play a vital role for a long time. Therefore, the SAS4A/SASSYS-1 modernization effort should remain a high priority task under the ART program to ensure continued participation in domestic and international SFR safety collaborations and design optimizations. On the other hand, SAM provides an advanced system analysis tool, with improved numerical solution schemes, data management, code flexibility, and accuracy. SAM is still in early stages of development and will require continued support from NEAMS to fulfill its potential and to mature into a production tool for advanced reactor safety analysis. The effort to couple SAS4A/SASSYS-1 and SAM is the first step on the integration of these modeling capabilities.« less

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

Llave, Ezequiel de la; Herrera, Santiago E.; Adam, Catherine

The molecular and electronic structure of Os(II) complexes covalently bonded to self-assembled monolayers (SAMs) on Au(111) surfaces was studied by means of polarization modulation infrared reflection absorption spectroscopy, photoelectron spectroscopies, scanning tunneling microscopy, scanning tunneling spectroscopy, and density functional theory calculations. Attachment of the Os complex to the SAM proceeds via an amide covalent bond with the SAM alkyl chain 40° tilted with respect to the surface normal and a total thickness of 26 Å. The highest occupied molecular orbital of the Os complex is mainly based on the Os(II) center located 2.2 eV below the Fermi edge and themore » LUMO molecular orbital is mainly based on the bipyridine ligands located 1.5 eV above the Fermi edge.« less

An Objective Measurement of the Build-Up of Auditory Streaming and of Its Modulation by Attention

ERIC Educational Resources Information Center

Thompson, Sarah K.; Carlyon, Robert P.; Cusack, Rhodri

2011-01-01

Three experiments studied auditory streaming using sequences of alternating "ABA" triplets, where "A" and "B" were 50-ms tones differing in frequency by [delta]f semitones and separated by 75-ms gaps. Experiment 1 showed that detection of a short increase in the gap between a B tone and the preceding A tone, imposed on one ABA triplet, was better…

Polarization-interleave-multiplexed discrete multi-tone modulation with direct detection utilizing MIMO equalization.

PubMed

Zhou, Xian; Zhong, Kangping; Gao, Yuliang; Sui, Qi; Dong, Zhenghua; Yuan, Jinhui; Wang, Liang; Long, Keping; Lau, Alan Pak Tao; Lu, Chao

2015-04-06

Discrete multi-tone (DMT) modulation is an attractive modulation format for short-reach applications to achieve the best use of available channel bandwidth and signal noise ratio (SNR). In order to realize polarization-multiplexed DMT modulation with direct detection, we derive an analytical transmission model for dual polarizations with intensity modulation and direct diction (IM-DD) in this paper. Based on the model, we propose a novel polarization-interleave-multiplexed DMT modulation with direct diction (PIM-DMT-DD) transmission system, where the polarization de-multiplexing can be achieved by using a simple multiple-input-multiple-output (MIMO) equalizer and the transmission performance is optimized over two distinct received polarization states to eliminate the singularity issue of MIMO demultiplexing algorithms. The feasibility and effectiveness of the proposed PIM-DMT-DD system are investigated via theoretical analyses and simulation studies.

Divided attention modulates semantic activation: evidence from a nonletter-level prime task.

PubMed

Otsuka, Sachio; Kawaguchi, Jun

2007-12-01

Research has recently shown that semantic activation is modulated in proportion to the amount of attention required for letter-level processing of the prime (the attention modulation hypothesis; Smith, Bentin, & Spalek, 2001). In this study, we examined this hypothesis with an auditory divided-attention task. Participants were asked to decide whether the pitch of a probe tone presented with the prime word was higher or lower than the basic tone presented with the fixation cross. Their target task was lexical decision to the target word. Experiment 1 showed that semantic priming was modulated by the amount of attentional resources. Moreover, in Experiment 2, this modulation was also found in a situation that eliminated the possibility of participants' response strategies. Yet, Experiment 3 showed repetition priming to be unaffected. These results support an amended attention modulation hypothesis in which modulation is not limited to letter-level processing.

Modulation of Conformational Equilibria in the S-Adenosylmethionine (SAM) II Riboswitch by SAM, Mg(2+), and Trimethylamine N-Oxide.

PubMed

McPhie, Peter; Brown, Patrick; Chen, Bin; Dayie, Theodore K; Minton, Allen P

2016-09-13

The dependence of the conformation of the S-adenosylmethionine (SAM) II riboswitch on the concentration of added Mg(2+) ions and SAM, individually and in mixtures, was monitored by circular dichroism (CD) spectroscopy and by measurement of the diffusion coefficient. The results are analyzed in the context of two complementary quantitative models, both of which are consistent with a single underlying physical model. Magnesium binding sites in the open state have an affinity on average higher than the affinity of those in the compact state, but formation of the compact state is accompanied by an increase in the number of binding sites. Consequently, at low Mg(2+) concentrations, Mg(2+) binds preferentially to the open state, favoring its formation, but at high concentrations, Mg(2+) binds preferentially to the compact state. The affinity of the riboswitch for SAM increases drastically with an increased level of binding of Mg(2+) to the compact pseudoknot conformation. The effect of increasing concentrations of trimethylamine N-oxide (TMAO), a well-studied molecular crowding agent, on the conformation of the riboswitch and its affinity for SAM were also monitored by CD spectroscopy and measurement of diffusion. In the absence of added Mg(2+), high concentrations of TMAO were found to induce a conformational change compatible with the formation of the pseudoknot form but have only a small effect on the affinity of the RNA for SAM.

Responses to amplitude modulated infrared stimuli in the guinea pig inferior colliculus

NASA Astrophysics Data System (ADS)

Richter, Claus-Peter; Young, Hunter

2013-03-01

Responses of units in the central nucleus of the inferior colliculus of the guinea pig were recorded with tungsten electrodes. The set of data presented here is limited to high stimulus levels. The effect of changing the modulation frequency and the modulation depth was explored for acoustic and laser stimuli. The selected units responded to sinusoidal amplitude modulated (AM) tones, AM trains of clicks, and AM trains of laser pulses with a modulation of their spike discharge. At modulation frequencies of 20 Hz, some units tended to respond with 40 Hz to the acoustic stimuli, but only at 20 Hz for the trains of laser pulses. For all modes of stimulation the responses revealed a dominant response to the first cycle of the modulation, with decreasing number of action potential during successive cycles. While amplitude modulated tone bursts and amplitude modulated trains of acoustic clicks showed similar patterns, the response to trains of laser pulses was different.

Pre-attentive, context-specific representation of fear memory in the auditory cortex of rat.

PubMed

Funamizu, Akihiro; Kanzaki, Ryohei; Takahashi, Hirokazu

2013-01-01

Neural representation in the auditory cortex is rapidly modulated by both top-down attention and bottom-up stimulus properties, in order to improve perception in a given context. Learning-induced, pre-attentive, map plasticity has been also studied in the anesthetized cortex; however, little attention has been paid to rapid, context-dependent modulation. We hypothesize that context-specific learning leads to pre-attentively modulated, multiplex representation in the auditory cortex. Here, we investigate map plasticity in the auditory cortices of anesthetized rats conditioned in a context-dependent manner, such that a conditioned stimulus (CS) of a 20-kHz tone and an unconditioned stimulus (US) of a mild electrical shock were associated only under a noisy auditory context, but not in silence. After the conditioning, although no distinct plasticity was found in the tonotopic map, tone-evoked responses were more noise-resistive than pre-conditioning. Yet, the conditioned group showed a reduced spread of activation to each tone with noise, but not with silence, associated with a sharpening of frequency tuning. The encoding accuracy index of neurons showed that conditioning deteriorated the accuracy of tone-frequency representations in noisy condition at off-CS regions, but not at CS regions, suggesting that arbitrary tones around the frequency of the CS were more likely perceived as the CS in a specific context, where CS was associated with US. These results together demonstrate that learning-induced plasticity in the auditory cortex occurs in a context-dependent manner.

Neural Representation of Scale Illusion: Magnetoencephalographic Study on the Auditory Illusion Induced by Distinctive Tone Sequences in the Two Ears

PubMed Central

Kuriki, Shinya; Yokosawa, Koichi; Takahashi, Makoto

2013-01-01

The auditory illusory perception “scale illusion” occurs when a tone of ascending scale is presented in one ear, a tone of descending scale is presented simultaneously in the other ear, and vice versa. Most listeners hear illusory percepts of smooth pitch contours of the higher half of the scale in the right ear and the lower half in the left ear. Little is known about neural processes underlying the scale illusion. In this magnetoencephalographic study, we recorded steady-state responses to amplitude-modulated short tones having illusion-inducing pitch sequences, where the sound level of the modulated tones was manipulated to decrease monotonically with increase in pitch. The steady-state responses were decomposed into right- and left-sound components by means of separate modulation frequencies. It was found that the time course of the magnitude of response components of illusion-perceiving listeners was significantly correlated with smooth pitch contour of illusory percepts and that the time course of response components of stimulus-perceiving listeners was significantly correlated with discontinuous pitch contour of stimulus percepts in addition to the contour of illusory percepts. The results suggest that the percept of illusory pitch sequence was represented in the neural activity in or near the primary auditory cortex, i.e., the site of generation of auditory steady-state response, and that perception of scale illusion is maintained by automatic low-level processing. PMID:24086676

A diverse and intricate signalling network regulates stem cell fate in the shoot apical meristem.

PubMed

Dodsworth, Steven

2009-12-01

At the shoot apex of plants is a small region known as the shoot apical meristem (SAM) that maintains a population of undifferentiated (stem) cells whilst providing cells for developing lateral organs and the stem. All aerial structures of the plant develop from the SAM post-embryogenesis, enabling plants to grow in a characteristic modular fashion with great phenotypic and developmental plasticity throughout their lifetime. The maintenance of the stem cell population is intimately balanced with cell recruitment into differentiating tissues through intercellular communication involving a complex signalling network. Recent studies have shown that diverse regulators function in SAM maintenance, many of which converge on the WUSCHEL (WUS) gene. In this review the diverse regulatory modules that function in SAM maintenance are discussed: transcriptional and epigenetic control, hormonal regulation, and the balance with organogenesis. The central role of WUS as an integrator of multiple signals is highlighted; in addition, accessory feedback loops emerge as a feature enabling dynamic regulation of the stem cell niche.

Neural Substrates of Auditory Emotion Recognition Deficits in Schizophrenia.

PubMed

Kantrowitz, Joshua T; Hoptman, Matthew J; Leitman, David I; Moreno-Ortega, Marta; Lehrfeld, Jonathan M; Dias, Elisa; Sehatpour, Pejman; Laukka, Petri; Silipo, Gail; Javitt, Daniel C

2015-11-04

Deficits in auditory emotion recognition (AER) are a core feature of schizophrenia and a key component of social cognitive impairment. AER deficits are tied behaviorally to impaired ability to interpret tonal ("prosodic") features of speech that normally convey emotion, such as modulations in base pitch (F0M) and pitch variability (F0SD). These modulations can be recreated using synthetic frequency modulated (FM) tones that mimic the prosodic contours of specific emotional stimuli. The present study investigates neural mechanisms underlying impaired AER using a combined event-related potential/resting-state functional connectivity (rsfMRI) approach in 84 schizophrenia/schizoaffective disorder patients and 66 healthy comparison subjects. Mismatch negativity (MMN) to FM tones was assessed in 43 patients/36 controls. rsfMRI between auditory cortex and medial temporal (insula) regions was assessed in 55 patients/51 controls. The relationship between AER, MMN to FM tones, and rsfMRI was assessed in the subset who performed all assessments (14 patients, 21 controls). As predicted, patients showed robust reductions in MMN across FM stimulus type (p = 0.005), particularly to modulations in F0M, along with impairments in AER and FM tone discrimination. MMN source analysis indicated dipoles in both auditory cortex and anterior insula, whereas rsfMRI analyses showed reduced auditory-insula connectivity. MMN to FM tones and functional connectivity together accounted for ∼50% of the variance in AER performance across individuals. These findings demonstrate that impaired preattentive processing of tonal information and reduced auditory-insula connectivity are critical determinants of social cognitive dysfunction in schizophrenia, and thus represent key targets for future research and clinical intervention. Schizophrenia patients show deficits in the ability to infer emotion based upon tone of voice [auditory emotion recognition (AER)] that drive impairments in social cognition and global functional outcome. This study evaluated neural substrates of impaired AER in schizophrenia using a combined event-related potential/resting-state fMRI approach. Patients showed impaired mismatch negativity response to emotionally relevant frequency modulated tones along with impaired functional connectivity between auditory and medial temporal (anterior insula) cortex. These deficits contributed in parallel to impaired AER and accounted for ∼50% of variance in AER performance. Overall, these findings demonstrate the importance of both auditory-level dysfunction and impaired auditory/insula connectivity in the pathophysiology of social cognitive dysfunction in schizophrenia. Copyright © 2015 the authors 0270-6474/15/3514910-13$15.00/0.

Identification of cyst nematode B-type CLE peptides and modulation of the vascular stem cell pathway for feeding cell formation

USDA-ARS?s Scientific Manuscript database

Stem cells are important in the continuous formation of various tissues during postembryonic organogenesis. Stem cell pools in the SAM (shoot apical meristem), RAM (root apical meristem) and vascular procambium/cambium are regulated by CLE-receptor kinase-WOX signaling modules. Previous data showed ...

The mechanisms of the SAMS experiment flown on Nimbus 7 with particular reference to the 2 axis scanning mirror. [infrared radiometer for stratospheric and mesospheric investigations

NASA Technical Reports Server (NTRS)

Hadley, H.

1980-01-01

The stratospheric and mesospheric sounder (SAMS) experiment on Nimbus 7 includes a 2 axis scanning mirror and 7 pressure modulator cells. The SAMS experiment is a limb sounding instrument to measure the temperature profile and minor constituents of the atmosphere. The limb scan requires small mirror steps over a 3 deg range, while the scan in azimuth is in larger steps over a 15 deg range. The mirror is plane, 20 cm in diameter, and of zero expansion glass-ceramic. It is supported on two tilt tables, fitted one on the other, with the axes at right angles. The angle of tilt is adjusted by means of recirculating ball screws which are ion plated with lead for lubrication and driven by stepper motors. The seven gas filled cells are each pressure modulated by a 3 cm diameter, 0.3 cm stroke piston which is supported by diaphragm springs and driven electromagnetically at the system's mechanical resonant frequency. The mean pressure of the filling gas, which is the atmospheric constituent being measured, is changed by varying the temperature of a suitable molecular sieve.

High-dynamic range imaging techniques based on both color-separation algorithms used in conventional graphic arts and the human visual perception modeling

NASA Astrophysics Data System (ADS)

Lo, Mei-Chun; Hsieh, Tsung-Hsien; Perng, Ruey-Kuen; Chen, Jiong-Qiao

2010-01-01

The aim of this research is to derive illuminant-independent type of HDR imaging modules which can optimally multispectrally reconstruct of every color concerned in high-dynamic-range of original images for preferable cross-media color reproduction applications. Each module, based on either of broadband and multispectral approach, would be incorporated models of perceptual HDR tone-mapping, device characterization. In this study, an xvYCC format of HDR digital camera was used to capture HDR scene images for test. A tone-mapping module was derived based on a multiscale representation of the human visual system and used equations similar to a photoreceptor adaptation equation, proposed by Michaelis-Menten. Additionally, an adaptive bilateral type of gamut mapping algorithm, using approach of a multiple conversing-points (previously derived), was incorporated with or without adaptive Un-sharp Masking (USM) to carry out the optimization of HDR image rendering. An LCD with standard color space of Adobe RGB (D65) was used as a soft-proofing platform to display/represent HDR original RGB images, and also evaluate both renditionquality and prediction-performance of modules derived. Also, another LCD with standard color space of sRGB was used to test gamut-mapping algorithms, used to be integrated with tone-mapping module derived.

Impact of infrasound on the human cochlea.

PubMed

Hensel, Johannes; Scholz, Günther; Hurttig, Ulrike; Mrowinski, Dieter; Janssen, Thomas

2007-11-01

Low-frequency tones were reported to modulate the amplitude of distortion product otoacoustic emissions (DPOAEs) indicating periodic changes of the operating point of the cochlear amplifier. The present study investigates potential differences between infrasound and low-frequency sounds in their ability to modulate human DPOAEs. DPOAEs were recorded in 12 normally hearing subjects in the presence of a biasing tone with f(B)=6Hz and a level L(B)=130dB SPL. Primary frequencies were fixed at f(1)=1.6 and f(2)=2.0kHz with fixed levels L(1)=51 and L(2)=30dB SPL. A new measure, the modulation index (MI), was devised to characterise the degree of DPOAE modulation. In subsequent measurements with biasing tones of f(B) = 12, 24 and 50Hz, L(B) was adjusted to maintain the MI as obtained individually at 6Hz. Modulation patterns lagged with increasing f(B). The necessary L(B) decreased by 12dB/octave with increasing f(B) and ran almost parallel to the published infrasound detection threshold. No signs of an abrupt change in transmission into the cochlea were found between infra- and low-frequency sounds. The results show clearly that infrasound enters the inner ear, and can alter cochlear processing.

A laryngographic and laryngoscopic study of Northern Vietnamese tones.

PubMed

Brunelle, Marc; Nguyên, Duy Duong; Nguyên, Khac Hùng

2010-01-01

A laryngographic and laryngoscopic study of tone production in Northern Vietnamese, a language whose tones combine both fundamental frequency (f0) modulations and voice qualities (phonation types), was conducted with 5 male and 5 female speakers. Results show that the f0 contours of Northern Vietnamese tones are not only attributable to changes in vocal fold length and tension (partly through changes in larynx height), but that f0 drops are also largely caused by the glottal configurations responsible for the contrastive voice qualities associated with some of the tones. We also find that voice quality contrasts are mostly due to glottal constriction: they occasionally involve additional ventricular fold incursion and epiglottal constriction, but these articulations are usually absent. Copyright © 2010 S. Karger AG, Basel.

47 CFR 90.647 - Station identification.

Code of Federal Regulations, 2010 CFR

2010-10-01

... minute and by means of tone modulation of the transmitter, the tone frequency being between 800 and 1000... MOBILE RADIO SERVICES Regulations Governing Licensing and Use of Frequencies in the 806-824, 851-869, 896-901, and 935-940 MHz Bands Technical Regulations Regarding the Use of Frequencies in the 806-824 Mhz...

Attention-driven auditory cortex short-term plasticity helps segregate relevant sounds from noise.

PubMed

Ahveninen, Jyrki; Hämäläinen, Matti; Jääskeläinen, Iiro P; Ahlfors, Seppo P; Huang, Samantha; Lin, Fa-Hsuan; Raij, Tommi; Sams, Mikko; Vasios, Christos E; Belliveau, John W

2011-03-08

How can we concentrate on relevant sounds in noisy environments? A "gain model" suggests that auditory attention simply amplifies relevant and suppresses irrelevant afferent inputs. However, it is unclear whether this suffices when attended and ignored features overlap to stimulate the same neuronal receptive fields. A "tuning model" suggests that, in addition to gain, attention modulates feature selectivity of auditory neurons. We recorded magnetoencephalography, EEG, and functional MRI (fMRI) while subjects attended to tones delivered to one ear and ignored opposite-ear inputs. The attended ear was switched every 30 s to quantify how quickly the effects evolve. To produce overlapping inputs, the tones were presented alone vs. during white-noise masking notch-filtered ±1/6 octaves around the tone center frequencies. Amplitude modulation (39 vs. 41 Hz in opposite ears) was applied for "frequency tagging" of attention effects on maskers. Noise masking reduced early (50-150 ms; N1) auditory responses to unattended tones. In support of the tuning model, selective attention canceled out this attenuating effect but did not modulate the gain of 50-150 ms activity to nonmasked tones or steady-state responses to the maskers themselves. These tuning effects originated at nonprimary auditory cortices, purportedly occupied by neurons that, without attention, have wider frequency tuning than ±1/6 octaves. The attentional tuning evolved rapidly, during the first few seconds after attention switching, and correlated with behavioral discrimination performance. In conclusion, a simple gain model alone cannot explain auditory selective attention. In nonprimary auditory cortices, attention-driven short-term plasticity retunes neurons to segregate relevant sounds from noise.

A role for acoustic distortion in novel rapid frequency modulation behaviour in free-flying male mosquitoes.

PubMed

Simões, Patrício M V; Ingham, Robert A; Gibson, Gabriella; Russell, Ian J

2016-07-01

We describe a new stereotypical acoustic behaviour by male mosquitoes in response to the fundamental frequency of female flight tones during mating sequences. This male-specific free-flight behaviour consists of phonotactic flight beginning with a steep increase in wing-beat frequency (WBF) followed by rapid frequency modulation (RFM) of WBF in the lead up to copula formation. Male RFM behaviour involves remarkably fast changes in WBF and can be elicited without acoustic feedback or physical presence of the female. RFM features are highly consistent, even in response to artificial tones that do not carry the multi-harmonic components of natural female flight tones. Comparison between audiograms of the robust RFM behaviour and the electrical responses of the auditory Johnston's organ (JO) reveals that the male JO is tuned not to the female WBF per se but, remarkably, to the difference between the male and female WBFs. This difference is generated in the JO responses as a result of intermodulation distortion products (DPs) caused by non-linear interaction between male-female flight tones in the vibrations of the antenna. We propose that male mosquitoes rely on their own flight tones in making use of DPs to acoustically detect, locate and orientate towards flying females. We argue that the previously documented flight-tone harmonic convergence of flying male and female mosquitoes could be a consequence of WBF adjustments so that DPs generated through flight-tone interaction fall within the optimal frequency ranges for JO detection. © 2016. Published by The Company of Biologists Ltd.

Dual-tone optical vector millimeter wave signal generated by frequency-nonupling the radio frequency 16-star quadrature-amplitude-modulation signal

NASA Astrophysics Data System (ADS)

Wu, Tonggen; Ma, Jianxin

2017-12-01

This paper proposes an original scheme to generate the photonic dual-tone optical millimeter wave (MMW) carrying the 16-star quadrature-amplitude-modulation (QAM) signal via an optical phase modulator (PM) and an interleaver with adaptive photonic frequency-nonupling without phase precoding. To enable the generated optical vector MMW signal to resist the power fading effect caused by the fiber chromatic dispersion, the modulated -5th- and +4th-order sidebands are selected from the output of the PM, which is driven by the precoding 16-star QAM signal. The modulation index of the PM is optimized to gain the maximum opto-electrical conversion efficiency. A radio over fiber link is built by simulation, and the simulated constellations and the bit error rate graph demonstrate that the frequency-nonupling 16-star QAM MMW signal has good transmission performance. The simulation results agree well with our theoretical results.

The PRIDE (Partnership to Improve Diabetes Education) Toolkit: Development and Evaluation of Novel Literacy and Culturally Sensitive Diabetes Education Materials.

PubMed

Wolff, Kathleen; Chambers, Laura; Bumol, Stefan; White, Richard O; Gregory, Becky Pratt; Davis, Dianne; Rothman, Russell L

2016-02-01

Patients with low literacy, low numeracy, and/or linguistic needs can experience challenges understanding diabetes information and applying concepts to their self-management. The authors designed a toolkit of education materials that are sensitive to patients' literacy and numeracy levels, language preferences, and cultural norms and that encourage shared goal setting to improve diabetes self-management and health outcomes. The Partnership to Improve Diabetes Education (PRIDE) toolkit was developed to facilitate diabetes self-management education and support. The PRIDE toolkit includes a comprehensive set of 30 interactive education modules in English and Spanish to support diabetes self-management activities. The toolkit builds upon the authors' previously validated Diabetes Literacy and Numeracy Education Toolkit (DLNET) by adding a focus on shared goal setting, addressing the needs of Spanish-speaking patients, and including a broader range of diabetes management topics. Each PRIDE module was evaluated using the Suitability Assessment of Materials (SAM) instrument to determine the material's cultural appropriateness and its sensitivity to the needs of patients with low literacy and low numeracy. Reading grade level was also assessed using the Automated Readability Index (ARI), Coleman-Liau, Flesch-Kincaid, Fry, and SMOG formulas. The average reading grade level of the materials was 5.3 (SD 1.0), with a mean SAM of 91.2 (SD 5.4). All of the 30 modules received a "superior" score (SAM >70%) when evaluated by 2 independent raters. The PRIDE toolkit modules can be used by all members of a multidisciplinary team to assist patients with low literacy and low numeracy in managing their diabetes. © 2015 The Author(s).

Benzodiazepine temazepam suppresses the transient auditory 40-Hz response amplitude in humans.

PubMed

Jääskeläinen, I P; Hirvonen, J; Saher, M; Pekkonen, E; Sillanaukee, P; Näätänen, R; Tiitinen, H

1999-06-18

To discern the role of the GABA(A) receptors in the generation and attentive modulation of the transient auditory 40-Hz response, the effects of the benzodiazepine temazepam (10 mg) were studied in 10 healthy social drinkers, using a double-blind placebo-controlled design. Three hundred Hertz standard and 330 Hz rare deviant tones were presented to the left, and 1000 Hz standards and 1100 Hz deviants to the right ear of the subjects. Subjects attended to a designated ear and were to detect deviants therein while ignoring tones to the other. Temazepam significantly suppressed the amplitude of the 40-Hz response, the effect being equal for attended and non-attended tone responses. This suggests involvement of GABA(A) receptors in transient auditory 40-Hz response generation, however, not in the attentive modulation of the 40-Hz response.

Prosodic Transfer: From Chinese Lexical Tone to English Pitch Accent

ERIC Educational Resources Information Center

Ploquin, Marie

2013-01-01

Chinese tones are associated with a syllable to convey meaning, English pitch accents are prominence markers associated with stressed syllables. As both are created by pitch modulation, their pitch contours can be quite similar. The experiment reported here examines whether native speakers of Chinese produce, when speaking English, the Chinese…

TauG-guidance of transients in expressive musical performance.

PubMed

Schogler, Benjaman; Pepping, Gert-Jan; Lee, David N

2008-08-01

The sounds in expressive musical performance, and the movements that produce them, offer insight into temporal patterns in the brain that generate expression. To gain understanding of these brain patterns, we analyzed two types of transient sounds, and the movements that produced them, during a vocal duet and a bass solo. The transient sounds studied were inter-tone f (0)(t)-glides (the continuous change in fundamental frequency, f (0)(t), when gliding from one tone to the next), and attack intensity-glides (the continuous rise in sound intensity when attacking, or initiating, a tone). The temporal patterns of the inter-tone f (0)(t)-glides and attack intensity-glides, and of the movements producing them, all conformed to the mathematical function, tau (G)(t) (called tauG), predicted by General Tau Theory, and assumed to be generated in the brain. The values of the parameters of the tau (G)(t) function were modulated by the performers when they modulated musical expression. Thus the tau (G)(t) function appears to be a fundamental of brain activity entailed in the generation of expressive temporal patterns of movement and sound.

Detecting temporal changes in acoustic scenes: The variable benefit of selective attention.

PubMed

Demany, Laurent; Bayle, Yann; Puginier, Emilie; Semal, Catherine

2017-09-01

Four experiments investigated change detection in acoustic scenes consisting of a sum of five amplitude-modulated pure tones. As the tones were about 0.7 octave apart and were amplitude-modulated with different frequencies (in the range 2-32 Hz), they were perceived as separate streams. Listeners had to detect a change in the frequency (experiments 1 and 2) or the shape (experiments 3 and 4) of the modulation of one of the five tones, in the presence of an informative cue orienting selective attention either before the scene (pre-cue) or after it (post-cue). The changes left intensity unchanged and were not detectable in the spectral (tonotopic) domain. Performance was much better with pre-cues than with post-cues. Thus, change deafness was manifest in the absence of an appropriate focusing of attention when the change occurred, even though the streams and the changes to be detected were acoustically very simple (in contrast to the conditions used in previous demonstrations of change deafness). In one case, the results were consistent with a model based on the assumption that change detection was possible if and only if attention was endogenously focused on a single tone. However, it was also found that changes resulting in a steepening of amplitude rises were to some extent able to draw attention exogenously. Change detection was not markedly facilitated when the change produced a discontinuity in the modulation domain, contrary to what could be expected from the perspective of predictive coding. Copyright © 2017 Elsevier B.V. All rights reserved.

Pitch processing of dynamic lexical tones in the auditory cortex is influenced by sensory and extrasensory processes

PubMed Central

Krishnan, Ananthanarayan; Gandour, Jackson T.; Suresh, Chandan H.

2015-01-01

The aim is to evaluate how language experience (Chinese, English) shapes processing of pitch contours as reflected in the amplitude of cortical pitch response components. Responses were elicited from three dynamic, curvilinear, nonspeech stimuli varying in pitch direction and location of peak acceleration: Mandarin lexical Tone2 (rising) and Tone4 (falling); and a flipped variant of Tone2, Tone2′ (nonnative). At temporal sites (T7/T8), Chinese Na-Pb response amplitude to Tones 2 & 4 was greater than English in the right hemisphere only; a rightward asymmetry for Tones 2 & 4 was restricted to the Chinese group. In common to both Fz-to-linked T7/T8 and T7/T8 electrode sites, the stimulus pattern (Tones 2 & 4 > Tone2′) was found in the Chinese group only. As reflected by Pb-Nb at Fz, Chinese amplitude was larger than English in response to Tones 2 & 4; and Tones 2 & 4 were larger than Tone2′; whereas for English, Tone2 was larger than Tone2′ and Tone4. At frontal electrode sites (F3/F4), regardless of component or hemisphere, Chinese responses were larger in amplitude than English across stimuli. For either group, responses to Tones 2 & 4 were larger than Tone2′. No hemispheric asymmetry was observed at the frontal electrode sites. These findings highlight that cortical pitch response components are differentially modulated by experience-dependent, temporally distinct but functionally overlapping weighting of sensory and extrasensory effects on pitch processing of lexical tones in the right temporal lobe and, more broadly, are consistent with a distributed hierarchical predictive coding process. PMID:25943576

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

PubMed Central

Tykocki, Nathan R.; Boerman, Erika M.; Jackson, William F.

2017-01-01

Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes. PMID:28333380

Neurometric amplitude-modulation detection threshold in the guinea-pig ventral cochlear nucleus

PubMed Central

Sayles, Mark; Füllgrabe, Christian; Winter, Ian M

2013-01-01

Amplitude modulation (AM) is a pervasive feature of natural sounds. Neural detection and processing of modulation cues is behaviourally important across species. Although most ecologically relevant sounds are not fully modulated, physiological studies have usually concentrated on fully modulated (100% modulation depth) signals. Psychoacoustic experiments mainly operate at low modulation depths, around detection threshold (∼5% AM). We presented sinusoidal amplitude-modulated tones, systematically varying modulation depth between zero and 100%, at a range of modulation frequencies, to anaesthetised guinea-pigs while recording spikes from neurons in the ventral cochlear nucleus (VCN). The cochlear nucleus is the site of the first synapse in the central auditory system. At this locus significant signal processing occurs with respect to representation of AM signals. Spike trains were analysed in terms of the vector strength of spike synchrony to the amplitude envelope. Neurons showed either low-pass or band-pass temporal modulation transfer functions, with the proportion of band-pass responses increasing with increasing sound level. The proportion of units showing a band-pass response varies with unit type: sustained chopper (CS) > transient chopper (CT) > primary-like (PL). Spike synchrony increased with increasing modulation depth. At the lowest modulation depth (6%), significant spike synchrony was only observed near to the unit's best modulation frequency for all unit types tested. Modulation tuning therefore became sharper with decreasing modulation depth. AM detection threshold was calculated for each individual unit as a function of modulation frequency. Chopper units have significantly better AM detection thresholds than do primary-like units. AM detection threshold is significantly worse at 40 dB vs. 10 dB above pure-tone spike rate threshold. Mean modulation detection thresholds for sounds 10 dB above pure-tone spike rate threshold at best modulation frequency are (95% CI) 11.6% (10.0–13.1) for PL units, 9.8% (8.2–11.5) for CT units, and 10.8% (8.4–13.2) for CS units. The most sensitive guinea-pig VCN single unit AM detection thresholds are similar to human psychophysical performance (∼3% AM), while the mean neurometric thresholds approach whole animal behavioural performance (∼10% AM). PMID:23629508

A unifying view of the broad-spectrum antiviral activity of RSAD2 (viperin) based on its radical-SAM chemistry.

PubMed

Honarmand Ebrahimi, Kourosh

2018-04-25

RSAD2 (cig-5), also known as viperin (virus inhibitory protein, endoplasmic reticulum associated, interferon inducible), is a member of the radical S-adenosylmethionine (SAM) superfamily of enzymes. Since the discovery of this enzyme more than a decade ago, numerous studies have shown that it exhibits antiviral activity against a wide range of viruses. However, there is no clear picture demonstrating the mechanism by which RSAD2 restricts the replication process of different viruses, largely because there is no direct evidence describing its in vivo enzymatic activity. As a result, a multifunctionality model has emerged. According to this model the mechanism by which RSAD2 restricts replication of different viruses varies and in many cases is not dependent on the radical-SAM chemistry of RSAD2. If the radical-SAM activity of RSAD2 is not required for its antiviral function, the question worth asking is: why does the cellular defence mechanism induce the expression of the radical-SAM enzyme RSAD2, which is metabolically expensive due to the requirement for a [4Fe-4S] cluster and usage of SAM? Here, in contrast to the multifunctionality view, I put forward a unifying model. I postulate that the radical-SAM activity of RSAD2 modulates cellular metabolic pathways essential for viral replication and/or cell proliferation and survival. As a result, its catalytic activity restricts the replication of a wide range of viruses via a common cellular function. This view is based on recent discoveries hinting towards possible substrates of RSAD2, re-evaluation of previous studies regarding the antiviral activity of RSAD2, and accumulating evidence suggesting a role of human RSAD2 in the metabolic reprogramming of cells.

Activated Cdc42-associated kinase 1 (ACK1) binds the sterile α motif (SAM) domain of the adaptor SLP-76 and phosphorylates proximal tyrosines.

PubMed

Thaker, Youg R; Recino, Asha; Raab, Monika; Jabeen, Asma; Wallberg, Maja; Fernandez, Nelson; Rudd, Christopher E

2017-04-14

The adaptor protein Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) plays a crucial role in T cell activation by linking antigen receptor (T cell receptor, TCR) signals to downstream pathways. At its N terminus, SLP-76 has three key tyrosines (Tyr-113, Tyr-128, and Tyr-145, "3Y") as well as a sterile α motif (SAM) domain whose function is unclear. We showed previously that the SAM domain has two binding regions that mediate dimer and oligomer formation. In this study, we have identified SAM domain-carrying non-receptor tyrosine kinase, activated Cdc42-associated tyrosine kinase 1 (ACK1; also known as Tnk2, tyrosine kinase non-receptor 2) as a novel binding partner of SLP-76. Co-precipitation, laser-scanning confocal microscopy, and in situ proximity analysis confirmed the binding of ACK1 to SLP-76. Further, the interaction was induced in response to the anti-TCR ligation and abrogated by the deletion of SLP-76 SAM domain (ΔSAM) or mutation of Tyr-113, Tyr-128, and Tyr-145 to phenylalanine (3Y3F). ACK1 induced phosphorylation of the SLP-76 N-terminal tyrosines (3Y) dependent on the SAM domain. Further, ACK1 promoted calcium flux and NFAT-AP1 promoter activity and decreased the motility of murine CD4 + primary T cells on ICAM-1-coated plates, an event reversed by a small molecule inhibitor of ACK1 (AIM-100). These findings identify ACK1 as a novel SLP-76-associated protein-tyrosine kinase that modulates early activation events in T cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Activated Cdc42-associated kinase 1 (ACK1) binds the sterile α motif (SAM) domain of the adaptor SLP-76 and phosphorylates proximal tyrosines

PubMed Central

Thaker, Youg R.; Recino, Asha; Raab, Monika; Jabeen, Asma; Wallberg, Maja; Fernandez, Nelson; Rudd, Christopher E.

2017-01-01

The adaptor protein Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) plays a crucial role in T cell activation by linking antigen receptor (T cell receptor, TCR) signals to downstream pathways. At its N terminus, SLP-76 has three key tyrosines (Tyr-113, Tyr-128, and Tyr-145, “3Y”) as well as a sterile α motif (SAM) domain whose function is unclear. We showed previously that the SAM domain has two binding regions that mediate dimer and oligomer formation. In this study, we have identified SAM domain-carrying non-receptor tyrosine kinase, activated Cdc42-associated tyrosine kinase 1 (ACK1; also known as Tnk2, tyrosine kinase non-receptor 2) as a novel binding partner of SLP-76. Co-precipitation, laser-scanning confocal microscopy, and in situ proximity analysis confirmed the binding of ACK1 to SLP-76. Further, the interaction was induced in response to the anti-TCR ligation and abrogated by the deletion of SLP-76 SAM domain (ΔSAM) or mutation of Tyr-113, Tyr-128, and Tyr-145 to phenylalanine (3Y3F). ACK1 induced phosphorylation of the SLP-76 N-terminal tyrosines (3Y) dependent on the SAM domain. Further, ACK1 promoted calcium flux and NFAT-AP1 promoter activity and decreased the motility of murine CD4+ primary T cells on ICAM-1-coated plates, an event reversed by a small molecule inhibitor of ACK1 (AIM-100). These findings identify ACK1 as a novel SLP-76-associated protein-tyrosine kinase that modulates early activation events in T cells. PMID:28188290

Data handling with SAM and art at the NO vA experiment

DOE PAGES

Aurisano, A.; Backhouse, C.; Davies, G. S.; ...

2015-12-23

During operations, NOvA produces between 5,000 and 7,000 raw files per day with peaks in excess of 12,000. These files must be processed in several stages to produce fully calibrated and reconstructed analysis files. In addition, many simulated neutrino interactions must be produced and processed through the same stages as data. To accommodate the large volume of data and Monte Carlo, production must be possible both on the Fermilab grid and on off-site farms, such as the ones accessible through the Open Science Grid. To handle the challenge of cataloging these files and to facilitate their off-line processing, we havemore » adopted the SAM system developed at Fermilab. SAM indexes files according to metadata, keeps track of each file's physical locations, provides dataset management facilities, and facilitates data transfer to off-site grids. To integrate SAM with Fermilab's art software framework and the NOvA production workflow, we have developed methods to embed metadata into our configuration files, art files, and standalone ROOT files. A module in the art framework propagates the embedded information from configuration files into art files, and from input art files to output art files, allowing us to maintain a complete processing history within our files. Embedding metadata in configuration files also allows configuration files indexed in SAM to be used as inputs to Monte Carlo production jobs. Further, SAM keeps track of the input files used to create each output file. Parentage information enables the construction of self-draining datasets which have become the primary production paradigm used at NOvA. In this study we will present an overview of SAM at NOvA and how it has transformed the file production framework used by the experiment.« less

SAM Theory Manual

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

Hu, Rui

The System Analysis Module (SAM) is an advanced and modern system analysis tool being developed at Argonne National Laboratory under the U.S. DOE Office of Nuclear Energy’s Nuclear Energy Advanced Modeling and Simulation (NEAMS) program. SAM development aims for advances in physical modeling, numerical methods, and software engineering to enhance its user experience and usability for reactor transient analyses. To facilitate the code development, SAM utilizes an object-oriented application framework (MOOSE), and its underlying meshing and finite-element library (libMesh) and linear and non-linear solvers (PETSc), to leverage modern advanced software environments and numerical methods. SAM focuses on modeling advanced reactormore » concepts such as SFRs (sodium fast reactors), LFRs (lead-cooled fast reactors), and FHRs (fluoride-salt-cooled high temperature reactors) or MSRs (molten salt reactors). These advanced concepts are distinguished from light-water reactors in their use of single-phase, low-pressure, high-temperature, and low Prandtl number (sodium and lead) coolants. As a new code development, the initial effort has been focused on modeling and simulation capabilities of heat transfer and single-phase fluid dynamics responses in Sodium-cooled Fast Reactor (SFR) systems. The system-level simulation capabilities of fluid flow and heat transfer in general engineering systems and typical SFRs have been verified and validated. This document provides the theoretical and technical basis of the code to help users understand the underlying physical models (such as governing equations, closure models, and component models), system modeling approaches, numerical discretization and solution methods, and the overall capabilities in SAM. As the code is still under ongoing development, this SAM Theory Manual will be updated periodically to keep it consistent with the state of the development.« less

The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea

PubMed Central

Horner, Richard L

2001-01-01

Obstructive sleep apnoea is a common and serious breathing problem that is caused by effects of sleep on pharyngeal muscle tone in individuals with narrow upper airways. There has been increasing focus on delineating the brain mechanisms that modulate pharyngeal muscle activity in the awake and asleep states in order to understand the pathogenesis of obstructive apnoeas and to develop novel neurochemical treatments. Although initial clinical studies have met with only limited success, it is proposed that more rational and realistic approaches may be devised for neurochemical modulation of pharyngeal muscle tone as the relevant neurotransmitters and receptors that are involved in sleep-dependent modulation are identified following basic experiments. PMID:11686898

Attention-driven auditory cortex short-term plasticity helps segregate relevant sounds from noise

PubMed Central

Ahveninen, Jyrki; Hämäläinen, Matti; Jääskeläinen, Iiro P.; Ahlfors, Seppo P.; Huang, Samantha; Raij, Tommi; Sams, Mikko; Vasios, Christos E.; Belliveau, John W.

2011-01-01

How can we concentrate on relevant sounds in noisy environments? A “gain model” suggests that auditory attention simply amplifies relevant and suppresses irrelevant afferent inputs. However, it is unclear whether this suffices when attended and ignored features overlap to stimulate the same neuronal receptive fields. A “tuning model” suggests that, in addition to gain, attention modulates feature selectivity of auditory neurons. We recorded magnetoencephalography, EEG, and functional MRI (fMRI) while subjects attended to tones delivered to one ear and ignored opposite-ear inputs. The attended ear was switched every 30 s to quantify how quickly the effects evolve. To produce overlapping inputs, the tones were presented alone vs. during white-noise masking notch-filtered ±1/6 octaves around the tone center frequencies. Amplitude modulation (39 vs. 41 Hz in opposite ears) was applied for “frequency tagging” of attention effects on maskers. Noise masking reduced early (50–150 ms; N1) auditory responses to unattended tones. In support of the tuning model, selective attention canceled out this attenuating effect but did not modulate the gain of 50–150 ms activity to nonmasked tones or steady-state responses to the maskers themselves. These tuning effects originated at nonprimary auditory cortices, purportedly occupied by neurons that, without attention, have wider frequency tuning than ±1/6 octaves. The attentional tuning evolved rapidly, during the first few seconds after attention switching, and correlated with behavioral discrimination performance. In conclusion, a simple gain model alone cannot explain auditory selective attention. In nonprimary auditory cortices, attention-driven short-term plasticity retunes neurons to segregate relevant sounds from noise. PMID:21368107

Autonomic nervous system profile in fibromyalgia patients and its modulation by exercise: a mini review.

PubMed

Kulshreshtha, Poorvi; Deepak, Kishore K

2013-03-01

This review imparts an impressionistic tone to our current understanding of autonomic nervous system abnormalities in fibromyalgia. In the wake of symptoms present in patients with fibromyalgia (FM), autonomic dysfunction seems plausible in fibromyalgia. A popular notion is that of a relentless sympathetic hyperactivity and hyporeactivity based on heart rate variability (HRV) analyses and responses to various physiological stimuli. However, some exactly opposite findings suggesting normal/hypersympathetic reactivity in patients with fibromyalgia do exist. This heterogeneous picture along with multiple comorbidities accounts for the quantitative and qualitative differences in the degree of dysautonomia present in patients with FM. We contend that HRV changes in fibromyalgia may not actually represent increased cardiac sympathetic tone. Normal muscle sympathetic nerve activity (MSNA) and normal autonomic reactivity tests in patients with fibromyalgia suggest defective vascular end organ in fibromyalgia. Previously, we proposed a model linking deconditioning with physical inactivity resulting from widespread pain in patients with fibromyalgia. Deconditioning also modulates the autonomic nervous system (high sympathetic tone and a low parasympathetic tone). A high peripheral sympathetic tone causes regional ischaemia, which in turn results in widespread pain. Thus, vascular dysregulation and hypoperfusion in patients with FM give rise to ischaemic pain leading to physical inactivity. Microvascular abnormalities are also found in patients with FM. Therapeutic interventions (e.g. exercise) that result in vasodilatation and favourable autonomic alterations have proven to be effective. In this review, we focus on the vascular end organ in patients with fibromyalgia in particular and its modulation by exercise in general. © 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Technical Note: A fast online adaptive replanning method for VMAT using flattening filter free beams

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

Ates, Ozgur; Ahunbay, Ergun E.; Li, X. Allen, E-mail: ali@mcw.edu

Purpose: To develop a fast replanning algorithm based on segment aperture morphing (SAM) for online replanning of volumetric modulated arc therapy (VMAT) with flattening filter free (FFF) beams. Methods: A software tool was developed to interface with a VMAT research planning system, which enables the input and output of beam and machine parameters of VMAT plans. The SAM algorithm was used to modify multileaf collimator positions for each segment aperture based on the changes of the target from the planning (CT/MR) to daily image [CT/CBCT/magnetic resonance imaging (MRI)]. The leaf travel distance was controlled for large shifts to prevent themore » increase of VMAT delivery time. The SAM algorithm was tested for 11 patient cases including prostate, pancreatic, and lung cancers. For each daily image set, three types of VMAT plans, image-guided radiation therapy (IGRT) repositioning, SAM adaptive, and full-scope reoptimization plans, were generated and compared. Results: The SAM adaptive plans were found to have improved the plan quality in target and/or critical organs when compared to the IGRT repositioning plans and were comparable to the reoptimization plans based on the data of planning target volume (PTV)-V100 (volume covered by 100% of prescription dose). For the cases studied, the average PTV-V100 was 98.85% ± 1.13%, 97.61% ± 1.45%, and 92.84% ± 1.61% with FFF beams for the reoptimization, SAM adaptive, and repositioning plans, respectively. The execution of the SAM algorithm takes less than 10 s using 16-CPU (2.6 GHz dual core) hardware. Conclusions: The SAM algorithm can generate adaptive VMAT plans using FFF beams with comparable plan qualities as those from the full-scope reoptimization plans based on daily CT/CBCT/MRI and can be used for online replanning to address interfractional variations.« less

Monitoring machining conditions by infrared images

NASA Astrophysics Data System (ADS)

Borelli, Joao E.; Gonzaga Trabasso, Luis; Gonzaga, Adilson; Coelho, Reginaldo T.

2001-03-01

During machining process the knowledge of the temperature is the most important factor in tool analysis. It allows to control main factors that influence tool use, life time and waste. The temperature in the contact area between the piece and the tool is resulting from the material removal in cutting operation and it is too difficult to be obtained because the tool and the work piece are in motion. One way to measure the temperature in this situation is detecting the infrared radiation. This work presents a new methodology for diagnosis and monitoring of machining processes with the use of infrared images. The infrared image provides a map in gray tones of the elements in the process: tool, work piece and chips. Each gray tone in the image corresponds to a certain temperature for each one of those materials and the relationship between the gray tones and the temperature is gotten by the previous of infrared camera calibration. The system developed in this work uses an infrared camera, a frame grabber board and a software composed of three modules. The first module makes the image acquisition and processing. The second module makes the feature image extraction and performs the feature vector. Finally, the third module uses fuzzy logic to evaluate the feature vector and supplies the tool state diagnostic as output.

Improved electro-transformation of highly DNA-restrictive corynebacteria with DNA extracted from starved Escherichia coli.

PubMed

Ankri, S; Reyes, O; Leblon, G

1996-07-01

Differences of up to 33 000-fold in electro-transformability of highly DNA restrictive corynebacteria are observed in the DNA of a shuttle plasmid extracted from Escherichia coli hosts propagated in different nutritional conditions. Growth of the host in minimal medium increases plasmid transformability, whereas growth on rich media decreases it. In the E. coli DH5 alpha host, the starvation-dependent increase DNA transformability is reverted by supplementing with methionine, an obligate 5-adenosyl-methionine (SAM) precursor. This suggests that an E. coli nutritionally modulated SAM-dependent DNA-methyltransferase may be involved in this phenomenon.

Lexical Encoding of L2 Tones: The Role of L1 Stress, Pitch Accent and Intonation

ERIC Educational Resources Information Center

Braun, Bettina; Galts, Tobias; Kabak, Baris

2014-01-01

Native language prosodic structure is known to modulate the processing of non-native suprasegmental information. It has been shown that native speakers of French, a language without lexical stress, have difficulties storing non-native stress contrasts. We investigated whether the ability to store lexical tone (as in Mandarin Chinese) also depends…

Musical duplex perception: perception of figurally good chords with subliminal distinguishing tones.

PubMed

Hall, M D; Pastore, R E

1992-08-01

In a variant of duplex perception with speech, phoneme perception is maintained when distinguishing components are presented below intensities required for separate detection, forming the basis for the claim that a phonetic module takes precedence over nonspeech processing. This finding is replicated with music chords (C major and minor) created by mixing a piano fifth with a sinusoidal distinguishing tone (E or E flat). Individual threshold intensities for detecting E or E flat in the context of the fixed piano tones are established. Chord discrimination thresholds defined by distinguishing tone intensity were determined. Experiment 2 verified masked detection thresholds and subliminal chord identification for experienced musicians. Accurate chord perception was maintained at distinguishing tone intensities nearly 20 dB below the threshold for separate detection. Speech and music findings are argued to demonstrate general perceptual principles.

Are lexical tones musical? Native language's influence on neural response to pitch in different domains.

PubMed

Chen, Ao; Peter, Varghese; Wijnen, Frank; Schnack, Hugo; Burnham, Denis

2018-04-21

Language experience shapes musical and speech pitch processing. We investigated whether speaking a lexical tone language natively modulates neural processing of pitch in language and music as well as their correlation. We tested tone language (Mandarin Chinese), and non-tone language (Dutch) listeners in a passive oddball paradigm measuring mismatch negativity (MMN) for (i) Chinese lexical tones and (ii) three-note musical melodies with similar pitch contours. For lexical tones, Chinese listeners showed a later MMN peak than the non-tone language listeners, whereas for MMN amplitude there were no significant differences between groups. Dutch participants also showed a late discriminative negativity (LDN). In the music condition two MMNs, corresponding to the two notes that differed between the standard and the deviant were found for both groups, and an LDN were found for both the Dutch and the Chinese listeners. The music MMNs were significantly right lateralized. Importantly, significant correlations were found between the lexical tone and the music MMNs for the Dutch but not the Chinese participants. The results suggest that speaking a tone language natively does not necessarily enhance neural responses to pitch either in language or in music, but that it does change the nature of neural pitch processing: non-tone language speakers appear to perceive lexical tones as musical, whereas for tone language speakers, lexical tones and music may activate different neural networks. Neural resources seem to be assigned differently for the lexical tones and for musical melodies, presumably depending on the presence or absence of long-term phonological memory traces. Copyright © 2018 Elsevier Inc. All rights reserved.

Sound source localization identification accuracy: Envelope dependencies.

PubMed

Yost, William A

2017-07-01

Sound source localization accuracy as measured in an identification procedure in a front azimuth sound field was studied for click trains, modulated noises, and a modulated tonal carrier. Sound source localization accuracy was determined as a function of the number of clicks in a 64 Hz click train and click rate for a 500 ms duration click train. The clicks were either broadband or high-pass filtered. Sound source localization accuracy was also measured for a single broadband filtered click and compared to a similar broadband filtered, short-duration noise. Sound source localization accuracy was determined as a function of sinusoidal amplitude modulation and the "transposed" process of modulation of filtered noises and a 4 kHz tone. Different rates (16 to 512 Hz) of modulation (including unmodulated conditions) were used. Providing modulation for filtered click stimuli, filtered noises, and the 4 kHz tone had, at most, a very small effect on sound source localization accuracy. These data suggest that amplitude modulation, while providing information about interaural time differences in headphone studies, does not have much influence on sound source localization accuracy in a sound field.

Human Cataract Mutations in EPHA2 SAM Domain Alter Receptor Stability and Function

PubMed Central

Park, Jeong Eun; Son, Alexander I.; Hua, Rui; Wang, Lianqing; Zhang, Xue; Zhou, Renping

2012-01-01

The cellular and molecular mechanisms underlying the pathogenesis of cataracts leading to visual impairment remain poorly understood. In recent studies, several mutations in the cytoplasmic sterile-α-motif (SAM) domain of human EPHA2 on chromosome 1p36 have been associated with hereditary cataracts in several families. Here, we have investigated how these SAM domain mutations affect EPHA2 activity. We showed that the SAM domain mutations dramatically destabilized the EPHA2 protein in a proteasome-dependent pathway, as evidenced by the increase of EPHA2 receptor levels in the presence of the proteasome inhibitor MG132. In addition, the expression of wild-type EPHA2 promoted the migration of the mouse lens epithelial αTN4-1 cells in the absence of ligand stimulation, whereas the mutants exhibited significantly reduced activity. In contrast, stimulation of EPHA2 with its ligand ephrin-A5 eradicates the enhancement of cell migration accompanied by Akt activation. Taken together, our studies suggest that the SAM domain of the EPHA2 protein plays critical roles in enhancing the stability of EPHA2 by modulating the proteasome-dependent process. Furthermore, activation of Akt switches EPHA2 from promoting to inhibiting cell migration upon ephrin-A5 binding. Our results provide the first report of multiple EPHA2 cataract mutations contributing to the destabilization of the receptor and causing the loss of cell migration activity. PMID:22570727

Ear Advantage for Musical Location and Relative Pitch: Effects of Musical Training and Attention.

PubMed

Hutchison, Joanna L; Hubbard, Timothy L; Hubbard, Nicholas A; Rypma, Bart

2017-06-01

Trained musicians have been found to exhibit a right-ear advantage for high tones and a left-ear advantage for low tones. We investigated whether this right/high, left/low pattern of musical processing advantage exists in listeners who had varying levels of musical experience, and whether such a pattern might be modulated by attentional strategy. A dichotic listening paradigm was used in which different melodic sequences were presented to each ear, and listeners attended to (a) the left ear or the right ear or (b) the higher pitched tones or the lower pitched tones. Listeners judged whether tone-to-tone transitions within each melodic sequence moved upward or downward in pitch. Only musically experienced listeners could adequately judge the direction of successive pitch transitions when attending to a specific ear; however, all listeners could judge the direction of successive pitch transitions within a high-tone stream or a low-tone stream. Overall, listeners exhibited greater accuracy when attending to relatively higher pitches, but there was no evidence to support a right/high, left/low bias. Results were consistent with effects of attentional strategy rather than an ear advantage for high or low tones. Implications for a potential performer/audience paradox in listening space are considered.

Defining efficient enzyme-cofactor pairs for bioorthogonal profiling of protein methylation

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

Islam, Kabirul; Chen, Yuling; Wu, Hong

2013-11-18

Protein methyltransferase (PMT)-mediated posttranslational modification of histone and nonhistone substrates modulates stability, localization, and interacting partners of target proteins in diverse cellular contexts. These events play critical roles in normal biological processes and are frequently deregulated in human diseases. In the course of identifying substrates of individual PMTs, bioorthogonal profiling of protein methylation (BPPM) has demonstrated its merits. In this approach, specific PMTs are engineered to process S-adenosyl-L-methionine (SAM) analogs as cofactor surrogates and label their substrates with distinct chemical modifications for target elucidation. Despite the proof-of-concept advancement of BPPM, few efforts have been made to explore its generality. Withmore » two cancer-relevant PMTs, EuHMT1 (GLP1/KMT1D) and EuHMT2 (G9a/KMT1C), as models, we defined the key structural features of engineered PMTs and matched SAM analogs that can render the orthogonal enzyme–cofactor pairs for efficient catalysis. Here we have demonstrated that the presence of sulfonium-β-sp 2 carbon and flexible, medium-sized sulfonium-δ-substituents are crucial for SAM analogs as BPPM reagents. The bulky cofactors can be accommodated by tailoring the conserved Y1211/Y1154 residues and nearby hydrophobic cavities of EuHMT1/2. Profiling proteome-wide substrates with BPPM allowed identification of >500 targets of EuHMT1/2 with representative targets validated using native EuHMT1/2 and SAM. This finding indicates that EuHMT1/2 may regulate many cellular events previously unrecognized to be modulated by methylation. The present work, therefore, paves the way to a broader application of the BPPM technology to profile methylomes of diverse PMTs and elucidate their downstream functions.« less

Gamma-band activation predicts both associative memory and cortical plasticity

PubMed Central

Headley, Drew B.; Weinberger, Norman M.

2011-01-01

Gamma-band oscillations are a ubiquitous phenomenon in the nervous system and have been implicated in multiple aspects of cognition. In particular, the strength of gamma oscillations at the time a stimulus is encoded predicts its subsequent retrieval, suggesting that gamma may reflect enhanced mnemonic processing. Likewise, activity in the gamma-band can modulate plasticity in vitro. However, it is unclear whether experience-dependent plasticity in vivo is also related to gamma-band activation. The aim of the present study is to determine whether gamma activation in primary auditory cortex modulates both the associative memory for an auditory stimulus during classical conditioning and its accompanying specific receptive field plasticity. Rats received multiple daily sessions of single tone/shock trace and two-tone discrimination conditioning, during which local field potentials and multiunit discharges were recorded from chronically implanted electrodes. We found that the strength of tone-induced gamma predicted the acquisition of associative memory 24 h later, and ceased to predict subsequent performance once asymptote was reached. Gamma activation also predicted receptive field plasticity that specifically enhanced representation of the signal tone. This concordance provides a long-sought link between gamma oscillations, cortical plasticity and the formation of new memories. PMID:21900554

The perception of FM sweeps by Chinese and English listeners.

PubMed

Luo, Huan; Boemio, Anthony; Gordon, Michael; Poeppel, David

2007-02-01

Frequency-modulated (FM) signals are an integral acoustic component of ecologically natural sounds and are analyzed effectively in the auditory systems of humans and animals. Linearly frequency-modulated tone sweeps were used here to evaluate two questions. First, how rapid a sweep can listeners accurately perceive? Second, is there an effect of native language insofar as the language (phonology) is differentially associated with processing of FM signals? Speakers of English and Mandarin Chinese were tested to evaluate whether being a speaker of a tone language altered the perceptual identification of non-speech tone sweeps. In two psychophysical studies, we demonstrate that Chinese subjects perform better than English subjects in FM direction identification, but not in an FM discrimination task, in which English and Chinese speakers show similar detection thresholds of approximately 20 ms duration. We suggest that the better FM direction identification in Chinese subjects is related to their experience with FM direction analysis in the tone-language environment, even though supra-segmental tonal variation occurs over a longer time scale. Furthermore, the observed common discrimination temporal threshold across two language groups supports the conjecture that processing auditory signals at durations of approximately 20 ms constitutes a fundamental auditory perceptual threshold.

Vocal fold vibration and voice source aperiodicity in 'dist' tones: a study of a timbral ornament in rock singing.

PubMed

Borch, D Zangger; Sundberg, J; Lindestad, P A; Thalén, M

2004-01-01

The acoustic characteristics of so-called 'dist' tones, commonly used in singing rock music, are analyzed in a case study. In an initial experiment a professional rock singer produced examples of 'dist' tones. The tones were found to contain aperiodicity, SPL at 0.3 m varied between 90 and 96 dB, and subglottal pressure varied in the range of 20-43 cm H2O, a doubling yielding, on average, an SPL increase of 2.3 dB. In a second experiment, the associated vocal fold vibration patterns were recorded by digital high-speed imaging of the same singer. Inverse filtering of the simultaneously recorded audio signal showed that the aperiodicity was caused by a low frequency modulation of the flow glottogram pulse amplitude. This modulation was produced by an aperiodic or periodic vibration of the supraglottic mucosa. This vibration reduced the pulse amplitude by obstructing the airway for some of the pulses produced by the apparently periodically vibrating vocal folds. The supraglottic mucosa vibration can be assumed to be driven by the high airflow produced by the elevated subglottal pressure.

Musical experience facilitates lexical tone processing among Mandarin speakers: Behavioral and neural evidence.

PubMed

Tang, Wei; Xiong, Wen; Zhang, Yu-Xuan; Dong, Qi; Nan, Yun

2016-10-01

Music and speech share many sound attributes. Pitch, as the percept of fundamental frequency, often occupies the center of researchers' attention in studies on the relationship between music and speech. One widely held assumption is that music experience may confer an advantage in speech tone processing. The cross-domain effects of musical training on non-tonal language speakers' linguistic pitch processing have been relatively well established. However, it remains unclear whether musical experience improves the processing of lexical tone for native tone language speakers who actually use lexical tones in their daily communication. Using a passive oddball paradigm, the present study revealed that among Mandarin speakers, musicians demonstrated enlarged electrical responses to lexical tone changes as reflected by the increased mismatch negativity (MMN) amplitudes, as well as faster behavioral discrimination performance compared with age- and IQ-matched nonmusicians. The current results suggest that in spite of the preexisting long-term experience with lexical tones in both musicians and nonmusicians, musical experience can still modulate the cortical plasticity of linguistic tone processing and is associated with enhanced neural processing of speech tones. Our current results thus provide the first electrophysiological evidence supporting the notion that pitch expertise in the music domain may indeed be transferable to the speech domain even for native tone language speakers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Targeting S-adenosylmethionine biosynthesis with a novel allosteric inhibitor of Mat2A

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

Quinlan, Casey L.; Kaiser, Stephen E.; Bolaños, Ben

S-Adenosyl-L-methionine (SAM) is an enzyme cofactor used in methyl transfer reactions and polyamine biosynthesis. The biosynthesis of SAM from ATP and L-methionine is performed by the methionine adenosyltransferase enzyme family (Mat; EC 2.5.1.6). Human methionine adenosyltransferase 2A (Mat2A), the extrahepatic isoform, is often deregulated in cancer. We identified a Mat2A inhibitor, PF-9366, that binds an allosteric site on Mat2A that overlaps with the binding site for the Mat2A regulator, Mat2B. Studies exploiting PF-9366 suggested a general mode of Mat2A allosteric regulation. Allosteric binding of PF-9366 or Mat2B altered the Mat2A active site, resulting in increased substrate affinity and decreased enzymemore » turnover. These data support a model whereby Mat2B functions as an inhibitor of Mat2A activity when methionine or SAM levels are high, yet functions as an activator of Mat2A when methionine or SAM levels are low. The ramification of Mat2A activity modulation in cancer cells is also described.« less

Intermodulation and harmonic distortion in slow light Microwave Photonic phase shifters based on Coherent Population Oscillations in SOAs.

PubMed

Gasulla, Ivana; Sancho, Juan; Capmany, José; Lloret, Juan; Sales, Salvador

2010-12-06

We theoretically and experimentally evaluate the propagation, generation and amplification of signal, harmonic and intermodulation distortion terms inside a Semiconductor Optical Amplifier (SOA) under Coherent Population Oscillation (CPO) regime. For that purpose, we present a general optical field model, valid for any arbitrarily-spaced radiofrequency tones, which is necessary to correctly describe the operation of CPO based slow light Microwave Photonic phase shifters which comprise an electrooptic modulator and a SOA followed by an optical filter and supplements another recently published for true time delay operation based on the propagation of optical intensities. The phase shifter performance has been evaluated in terms of the nonlinear distortion up to 3rd order, for a modulating signal constituted of two tones, in function of the electrooptic modulator input RF power and the SOA input optical power, obtaining a very good agreement between theoretical and experimental results. A complete theoretical spectral analysis is also presented which shows that under small signal operation conditions, the 3rd order intermodulation products at 2Ω1 + Ω2 and 2Ω2 + Ω1 experience a power dip/phase transition characteristic of the fundamental tones phase shifting operation.

Spectral and Temporal Processing in Rat Posterior Auditory Cortex

PubMed Central

Pandya, Pritesh K.; Rathbun, Daniel L.; Moucha, Raluca; Engineer, Navzer D.; Kilgard, Michael P.

2009-01-01

The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing between these areas. To determine the filter properties of rat posterior auditory field (PAF) neurons, we compared neurophysiological responses to simple tones, frequency modulated (FM) sweeps, and amplitude modulated noise and tones with responses of primary auditory cortex (A1) neurons. PAF neurons have excitatory receptive fields that are on average 65% broader than A1 neurons. The broader receptive fields of PAF neurons result in responses to narrow and broadband inputs that are stronger than A1. In contrast to A1, we found little evidence for an orderly topographic gradient in PAF based on frequency. These neurons exhibit latencies that are twice as long as A1. In response to modulated tones and noise, PAF neurons adapt to repeated stimuli at significantly slower rates. Unlike A1, neurons in PAF rarely exhibit facilitation to rapidly repeated sounds. Neurons in PAF do not exhibit strong selectivity for rate or direction of narrowband one octave FM sweeps. These results indicate that PAF, like nonprimary visual fields, processes sensory information on larger spectral and longer temporal scales than primary cortex. PMID:17615251

Sympathetic control of bone mass regulated by osteopontin

PubMed Central

Nagao, Masashi; Feinstein, Timothy N.; Ezura, Yoichi; Hayata, Tadayoshi; Notomi, Takuya; Saita, Yoshitomo; Hanyu, Ryo; Hemmi, Hiroaki; Izu, Yayoi; Takeda, Shu; Wang, Kathryn; Rittling, Susan; Nakamoto, Tetsuya; Kaneko, Kazuo; Kurosawa, Hisashi; Karsenty, Gerard; Denhardt, David T.; Vilardaga, Jean-Pierre; Noda, Masaki

2011-01-01

The sympathetic nervous system suppresses bone mass by mechanisms that remain incompletely elucidated. Using cell-based and murine genetics approaches, we show that this activity of the sympathetic nervous system requires osteopontin (OPN), a cytokine and one of the major members of the noncollagenous extracellular matrix proteins of bone. In this work, we found that the stimulation of the sympathetic tone by isoproterenol increased the level of OPN expression in the plasma and bone and that mice lacking OPN (OPN-KO) suppressed the isoproterenol-induced bone loss by preventing reduced osteoblastic and enhanced osteoclastic activities. In addition, we found that OPN is necessary for changes in the expression of genes related to bone resorption and bone formation that are induced by activation of the sympathetic tone. At the cellular level, we showed that intracellular OPN modulated the capacity of the β2-adrenergic receptor to generate cAMP with a corresponding modulation of cAMP-response element binding (CREB) phosphorylation and associated transcriptional events inside the cell. Our results indicate that OPN plays a critical role in sympathetic tone regulation of bone mass and that this OPN regulation is taking place through modulation of the β2-adrenergic receptor/cAMP signaling system. PMID:21990347

Underwater sound pressure variation and bottlenose dolphin (Tursiops truncatus) hearing thresholds in a small pool.

PubMed

Finneran, James J; Schlundt, Carolyn E

2007-07-01

Studies of underwater hearing are often hampered by the behavior of sound waves in small experimental tanks. At lower frequencies, tank dimensions are often not sufficient for free field conditions, resulting in large spatial variations of sound pressure. These effects may be mitigated somewhat by increasing the frequency bandwidth of the sound stimulus, so effects of multipath interference average out over many frequencies. In this study, acoustic fields and bottlenose dolphin (Tursiops truncatus) hearing thresholds were compared for pure tone and frequency modulated signals. Experiments were conducted in a vinyl-walled, seawater-filled pool approximately 3.7 x 6 x 1.5 m. Acoustic signals were pure tone and linear and sinusoidal frequency modulated tones with bandwidths/modulation depths of 1%, 2%, 5%, 10%, and 20%. Thirteen center frequencies were tested between 1 and 100 kHz. Acoustic fields were measured (without the dolphin present) at three water depths over a 60 x 65 cm grid with a 5-cm spacing. Hearing thresholds were measured using a behavioral response paradigm and up/down staircase technique. The use of FM signals significantly improved the sound field without substantially affecting the measured hearing thresholds.

Assessment of frequency specific auditory steady-state response using amplitude modulation with 2-order exponential envelope.

PubMed

Cevallos-Larrea, Pablo; Pereira, Thobias; Santos, Wagner; Frota, Silvana M; Infantosi, Antonio F; Ichinose, Roberto M; Tierra-Criollo, Carlos

2016-08-01

This study investigated the performance of Frequency Specific Auditory Steady-State Response (FS-ASSR) detection elicited by the amplitude modulated tone with 2-order exponential envelope (AM2), using objective response detection (ORD) techniques of Spectral F-Test (SFT) and Magnitude Squared Coherence (MSC). ASSRs from 24 normal hearing adults were obtained during binaural multi-tone stimulation of amplitude-modulation (AM) and AM2 at intensities of 60, 45 and 30 dBSPL. The carrier frequencies were 500, 1000, 2000, and 4000 Hz, modulated between 77 and 105 Hz. AM2 achieve FS-ASSR amplitudes higher than AM by 16%, 18% and 12% at 60, 45 and 30 dBSPL, respectively, with a major increase at 500 Hz (22.5%). AMS2PL increased the Detection Rate (DR) up to 8.3% at 500 Hz for 30 dBSPL, which is particularly beneficial for FS-ASSR detection near the hearing threshold. In addition, responses in 1000 and 4000 Hz were consistently increased. The MSC and SFT presented no differences in Detection Rate (DR). False Detection Rate (FDR) was close to 5% for both techniques and tones. Detection times to reach DR over 90% were 3.5 and 4.9 min at 60 and 45 dBSPL, respectively. Further investigation concerning efficient multiple FS-ASSR is still necessary, such as testing subjects with hearing loss.

Effect of Time and Deposition Method on Quality of Phosphonic Acid Modifier Self-Assembled Monolayers on Indium Zinc Oxide

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

Sang, Lingzi; Knesting, Kristina M.; Bulusu, Anuradha

Phosphonic acid (PA) self-assembled monolayers (SAMs) are utilized at critical interfaces between transparent conductive oxides (TCO) and organic active layers in organic photovoltaic devices (OPVs). The effects of PA deposition method and time on the formation of close-packed, high-quality monolayers is investigated here for SAMs fabricated by solution deposition, micro-contact printing, and spray coating. The solution deposition isotherm for pentafluorinated benzylphosphonic acid (F5BnPA) on indium-doped zinc oxide (IZO) is studied using polarization modulation-infrared reflection-absorption spectroscopy (PM-IRRAS) at room temperature as a model PA/IZO system. Fast surface adsorption occurs within the first min; however, well-oriented high-quality SAMs are reached only aftermore » -48 h, presumably through a continual process of molecular adsorption/desorption and monolayer filling accompanied by molecular reorientation. Two other rapid, soak-free deposition techniques, micro-contact printing and spray coating, are also explored. SAM quality is compared for deposition of phenyl phosphonic acid (PPA), F13-octylphosphonic acid (F13OPA), and pentafluorinated benzyl phosphonic acid (F5BnPA) by solution deposition, micro-contact printing and spray coating using PM-IRRAS. In contrast to micro-contact printing and spray coating techniques, 48-168 h solution deposition at both room temperature and 70 degrees C result in contamination- and surface etch-free close-packed monolayers with good reproducibility. SAMs fabricated by micro-contact printing and spray coating are much less well ordered.« less

Leptin modulates enteric neurotransmission in the rat proximal colon: an in vitro study.

PubMed

Florian, Voinot; Caroline, Fischer; Francis, Crenner; Camille, Schmidt; Fabielle, Angel

2013-08-10

Leptin has been shown to modulate gastrointestinal functions including nutrient absorption, growth, and inflammation and to display complex effects on gut motility. Leptin receptors have also been identified within the enteric nervous system (ENS), which plays a crucial role in digestive functions. Although leptin has recently been shown to activate neurons in the ENS, the precise mechanisms involved are so far unknown. Therefore, the aim of the present study was to determine the effects of leptin on rat proximal colon smooth muscle and enteric neuron activities. The effects of exogenous leptin on tone and on responses to transmural nerve stimulation (TNS) of isolated circular smooth muscle of proximal colon in rats were investigated using an organ bath technique. The effects of a physiological concentration (0.1 μM) of leptin were also studied on tone and TNS-induced relaxation in the presence of atropine, hexamethonium, L-N(G)-nitroarginine methyl ester (L-NAME) and capsazepine. Leptin caused a slight but significant decrease in tone, TNS-induced relaxation and contraction in a concentration-dependent manner in colonic preparations. Cholinergic antagonists abolished the effects of 0.1 μM leptin on TNS-induced relaxation. This concentration of leptin had no further effect on relaxation in the presence of L-NAME. In the presence of capsazepine, leptin had no further effect either on tone or relaxation compared to the drug alone. In conclusion, leptin modulates the activity of enteric inhibitory and excitatory neurons in proximal colon. These effects may be mediated through nitrergic neurons. Intrinsic primary afferent neurons may be involved. © 2013.

Light and heavy touch reduces postural sway and modifies axial tone in Parkinson’s disease

PubMed Central

Franzén, Erika; Paquette, Caroline; Gurfinkel, Victor; Horak, Fay

2014-01-01

Background Light touch with a stable object reduces postural sway by increasing axial postural tone in healthy subjects. However, it is unknown whether subjects with Parkinson’s disease (PD), who have more postural sway and higher axial postural tone than healthy subjects, can benefit from haptic touch. Objective To investigate the effect of light and heavy touch on postural stability and hip tone in subjects with PD. Methods Fourteen subjects with mid-stage PD, and 14 healthy control subjects were evaluated during quiet standing with eyes closed with their arms: 1) crossed, 2) lightly touching a fixed rigid bar in front of them and 3) firmly gripping the bar. Postural sway was measured with a forceplate and axial hip tone was quantified using a unique device that measures the resistance of the hips to yaw rotation while maintaining active stance. Results Subjects with PD significantly decreased their postural sway with light or heavy touch (p<0.001 vs. arms crossed), similarly as control subjects. Without touch, hip tone was larger in PD subjects. With touch, however, tone values were similar in both groups. This change in hip tone with touch was highly correlated with the initial amount of tone (PD: r=− 0.72 to −0.95 and controls: r=−0.74 to−0.85). Conclusions We showed, for the first time, that subjects with PD benefit from touch similarly to control subjects and that despite higher axial postural tone, PD subjects are able to modulate their tone with touch. Future studies should investigate the complex relationship between touch and postural tone. PMID:22415944

Summary Report of Mission Acceleration Measurements for STS-65, Launched 8 July 1994

NASA Technical Reports Server (NTRS)

Rogers, Melissa J. B.; Delombard, Richard

1995-01-01

The second flight of the International Microgravity Laboratory (IML-2) payload on board the STS-65 mission was supported by three accelerometer instruments: The Orbital Acceleration Research Experiment (OARE) located close to the orbiter center of mass; the Quasi-Steady Acceleration Measurement experiment, and the Space Acceleration Measurement System (SAMS), both in the Spacelab module. A fourth accelerometer, the Microgravity Measuring Device recorded data in the middeck in support of exercise isolation tests.Data collected by OARE and SAMS during IML-2 are displayed in this report. The OARE data represent the microgravity environment below 1 Hz. The SAMS data represent the environment in the 0.01 Hz to 100 Hz range. Variations in the environment caused by unique activities are presented. Specific events addressed are: crew activity, crew exercise, experiment component mixing activities, experiment centrifuge operations, refrigerator/freezer operations and circulation pump operations. The analyses included in this report complement analyses presented in other mission summary reports.

Molecular oxygen detection using frequency modulation diode laser spectroscopy

NASA Technical Reports Server (NTRS)

Wang, Liang-Guo; Sachse, Glen

1990-01-01

A high-sensitivity spectroscopic measurement of O2 using two-tone frequency modulation spectroscopy with a GaAlAs diode laser is presented. An oxygen sensor based on this technique would be non-intrusive, compact and possess high sensitivity and fast time response.

Neurophysiological Modulations of Non-Verbal and Verbal Dual-Tasks Interference during Word Planning.

PubMed

Fargier, Raphaël; Laganaro, Marina

2016-01-01

Running a concurrent task while speaking clearly interferes with speech planning, but whether verbal vs. non-verbal tasks interfere with the same processes is virtually unknown. We investigated the neural dynamics of dual-task interference on word production using event-related potentials (ERPs) with either tones or syllables as concurrent stimuli. Participants produced words from pictures in three conditions: without distractors, while passively listening to distractors and during a distractor detection task. Production latencies increased for tasks with higher attentional demand and were longer for syllables relative to tones. ERP analyses revealed common modulations by dual-task for verbal and non-verbal stimuli around 240 ms, likely corresponding to lexical selection. Modulations starting around 350 ms prior to vocal onset were only observed when verbal stimuli were involved. These later modulations, likely reflecting interference with phonological-phonetic encoding, were observed only when overlap between tasks was maximal and the same underlying neural circuits were engaged (cross-talk).

Time-Dependent Traveling Wave Tube Model for Intersymbol Interference Investigations

DTIC Science & Technology

2001-06-01

band is 5.7 degrees. C. Differences between broadband and single-tone excitations The TWT characteristics are compared when excited by single-tones...direct description of the effects of the TWT on modulated digital signals. The TWT model comprehensively takes into account the effects of frequency...of the high power amplifier and the operational digital signal. This method promises superior predictive fidelity compared to methods using TWT

Factors affecting sensitivity to frequency change in school-age children and adults.

PubMed

Buss, Emily; Taylor, Crystal N; Leibold, Lori J

2014-10-01

The factors affecting frequency discrimination in school-age children are poorly understood. The goal of the present study was to evaluate developmental effects related to memory for pitch and the utilization of temporal fine structure. Listeners were 5.1- to 13.6-year-olds and adults, all with normal hearing. A subgroup of children had musical training. The task was a 3-alternative forced choice in which listeners identified the interval with the higher frequency tone or the tone characterized by frequency modulation (FM). The standard was 500 or 5000 Hz, and the FM rate was either 2 or 20 Hz. Thresholds tended to be higher for younger children than for older children and adults for all conditions, although this age effect was smaller for FM detection than for pure-tone frequency discrimination. Neither standard frequency nor modulation rate affected the child/adult difference FM thresholds. Children with musical training performed better than their peers on pure-tone frequency discrimination at 500 Hz. Testing frequency discrimination using a low-rate FM detection task may minimize effects related to cognitive factors like memory for pitch or training effects. Maturation of frequency discrimination does not appear to differ across conditions in which listeners are hypothesized to rely on temporal cues and place cues.

Methylenetetrahydrofolate Reductase Modulates Methyl Metabolism and Lignin Monomer Methylation in Maize.

PubMed

Wu, Zhenying; Ren, Hao; Xiong, Wangdan; Roje, Sanja; Liu, Yuchen; Su, Kunlong; Fu, Chunxiang

2018-05-30

The brown midrib2 (bm2) mutant of maize, with a modified lignin composition, contains a mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. We here show that a MITE transposon insertion caused downregulation of MTHFR with accompanying decrease in 5-methyl-THF and increase in 5, 10-methylene-THF and THF in the bm2 mutant. Furthermore, MTHFR mutation did not change the content of SAM, the methyl group donor involved in the biosynthesis of guaiacyl (G) and syringyl (S) lignins, but increased the level of S-adenosyl homocysteine (SAH), the de-methylation product of SAM. Moreover, competitive inhibition of the maize caffeoyl CoA O-methyltransferase (CCoAOMT) and caffeic acid O-methyltransferase (COMT) enzyme activities by SAH was found, suggesting that SAH/SAM ratio rather than SAM concentration regulates the transmethylation reactions of lignin intermediates. Phenolic profiling revealed that caffeoyl alcohol glucose derivatives accumulated in the mutant, indicating impaired 3-O-methylation of monolignols. A remarkable increase in the unusual catechyl (C) lignin determined in the mutant demonstrates that MTHFR downregulation mainly affects G lignin biosynthesis, consistent with the observation that CCoAOMT is more sensitive to SAH inhibition than COMT. This study which uncovered a novel regulatory mechanism in lignin biosynthesis and may offer an effective approach to utilize lignocellulosic feedstocks in future.

Generating Data Flow Programs from Nonprocedural Specifications.

DTIC Science & Technology

1983-03-01

With the I-structures, Gajski points out, it is difficult to know ahead of time the optimal memory allocation scheme to pertition large arrays. amory...contention problems may occur for frequently accessed elements stored in the sam memory module. Gajski observes that these are the same problem which

Understanding the physiology of mindfulness: aortic hemodynamics and heart rate variability.

PubMed

May, Ross W; Bamber, Mandy; Seibert, Gregory S; Sanchez-Gonzalez, Marcos A; Leonard, Joseph T; Salsbury, Rebecca A; Fincham, Frank D

2016-01-01

Data were collected to examine autonomic and hemodynamic cardiovascular modulation underlying mindfulness from two independent samples. An initial sample (N = 185) underwent laboratory assessments of central aortic blood pressure and myocardial functioning to investigated the association between mindfulness and cardiac functioning. Controlling for religiosity, mindfulness demonstrated a strong negative relationship with myocardial oxygen consumption and left ventricular work but not heart rate or blood pressure. A second sample (N = 124) underwent a brief (15 min) mindfulness inducing intervention to examine the influence of mindfulness on cardiovascular autonomic modulation via blood pressure variability and heart rate variability. The intervention had a strong positive effect on cardiovascular modulation by decreasing cardiac sympathovagal tone, vasomotor tone, vascular resistance and ventricular workload. This research establishes a link between mindfulness and cardiovascular functioning via correlational and experimental methodologies in samples of mostly female undergraduates. Future directions for research are outlined.

Fast Interrogation of Fiber Bragg Gratings with Electro-Optical Dual Optical Frequency Combs

PubMed Central

Posada-Roman, Julio E.; Garcia-Souto, Jose A.; Poiana, Dragos A.; Acedo, Pablo

2016-01-01

Optical frequency combs (OFC) generated by electro-optic modulation of continuous-wave lasers provide broadband coherent sources with high power per line and independent control of line spacing and the number of lines. In addition to their application in spectroscopy, they offer flexible and optimized sources for the interrogation of other sensors based on wavelength change or wavelength filtering, such as fiber Bragg grating (FBG) sensors. In this paper, a dual-OFC FBG interrogation system based on a single laser and two optical-phase modulators is presented. This architecture allows for the configuration of multimode optical source parameters such as the number of modes and their position within the reflected spectrum of the FBG. A direct read-out is obtained by mapping the optical spectrum onto the radio-frequency spectrum output of the dual-comb. This interrogation scheme is proposed for measuring fast phenomena such as vibrations and ultrasounds. Results are presented for dual-comb operation under optimized control. The optical modes are mapped onto detectable tones that are multiples of 0.5 MHz around a center radiofrequency tone (40 MHz). Measurements of ultrasounds (40 kHz and 120 kHz) are demonstrated with this sensing system. Ultrasounds induce dynamic strain onto the fiber, which generates changes in the reflected Bragg wavelength and, hence, modulates the amplitude of the OFC modes within the reflected spectrum. The amplitude modulation of two counterphase tones is detected to obtain a differential measurement proportional to the ultrasound signal. PMID:27898043

Fast Interrogation of Fiber Bragg Gratings with Electro-Optical Dual Optical Frequency Combs.

PubMed

Posada-Roman, Julio E; Garcia-Souto, Jose A; Poiana, Dragos A; Acedo, Pablo

2016-11-26

Optical frequency combs (OFC) generated by electro-optic modulation of continuous-wave lasers provide broadband coherent sources with high power per line and independent control of line spacing and the number of lines. In addition to their application in spectroscopy, they offer flexible and optimized sources for the interrogation of other sensors based on wavelength change or wavelength filtering, such as fiber Bragg grating (FBG) sensors. In this paper, a dual-OFC FBG interrogation system based on a single laser and two optical-phase modulators is presented. This architecture allows for the configuration of multimode optical source parameters such as the number of modes and their position within the reflected spectrum of the FBG. A direct read-out is obtained by mapping the optical spectrum onto the radio-frequency spectrum output of the dual-comb. This interrogation scheme is proposed for measuring fast phenomena such as vibrations and ultrasounds. Results are presented for dual-comb operation under optimized control. The optical modes are mapped onto detectable tones that are multiples of 0.5 MHz around a center radiofrequency tone (40 MHz). Measurements of ultrasounds (40 kHz and 120 kHz) are demonstrated with this sensing system. Ultrasounds induce dynamic strain onto the fiber, which generates changes in the reflected Bragg wavelength and, hence, modulates the amplitude of the OFC modes within the reflected spectrum. The amplitude modulation of two counterphase tones is detected to obtain a differential measurement proportional to the ultrasound signal.

A direct link between chorus emissions and pulsating aurora on timescales from milliseconds to minutes: A case study at subauroral latitudes

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

Ozaki, Mitsunori; Yagitani, Satoshi; Sawai, Kaoru

A correlation was observed between chorus emissions and pulsating aurora (PA) from observations at Athabasca (L ≈ 4.3) in Canada at 9:00–9:20 UT on 7 February 2013, using an electron multiplying charge-coupled device camera and a VLF loop antenna with sampling rates of 110 Hz and 100 kHz, respectively. Pulsating aurora having a quasiperiodic variation in luminosity and a few hertz modulation was observed together with chorus emissions consisting of a group of successive rising-tone elements. The repetition period and modulation frequency of the PA are in good agreement with those of the modulated chorus. After 9:11 UT, the temporalmore » features of the aurora became aperiodic PA of indistinct modulation. Simultaneously, the rising-tone chorus turned into chorus emissions consisting of numerous rising-tone elements. The equatorial geomagnetic field inhomogeneity calculated using the Tsyganenko 2002 model shows a decreasing trend during the period. This result is consistent with nonlinear wave growth theory having a small geomagnetic field inhomogeneity, which contributes to a decrease in the threshold amplitude to trigger discrete chorus elements. As a result, these observations show a close connection between chorus emissions and PA on timescales from milliseconds for generation of discrete chorus elements on the microphysics of wave-particle interaction to minutes for the variations of the geomagnetic field inhomogeneity related with the substorm activity.« less

A direct link between chorus emissions and pulsating aurora on timescales from milliseconds to minutes: A case study at subauroral latitudes

DOE PAGES

Ozaki, Mitsunori; Yagitani, Satoshi; Sawai, Kaoru; ...

2015-11-27

A correlation was observed between chorus emissions and pulsating aurora (PA) from observations at Athabasca (L ≈ 4.3) in Canada at 9:00–9:20 UT on 7 February 2013, using an electron multiplying charge-coupled device camera and a VLF loop antenna with sampling rates of 110 Hz and 100 kHz, respectively. Pulsating aurora having a quasiperiodic variation in luminosity and a few hertz modulation was observed together with chorus emissions consisting of a group of successive rising-tone elements. The repetition period and modulation frequency of the PA are in good agreement with those of the modulated chorus. After 9:11 UT, the temporalmore » features of the aurora became aperiodic PA of indistinct modulation. Simultaneously, the rising-tone chorus turned into chorus emissions consisting of numerous rising-tone elements. The equatorial geomagnetic field inhomogeneity calculated using the Tsyganenko 2002 model shows a decreasing trend during the period. This result is consistent with nonlinear wave growth theory having a small geomagnetic field inhomogeneity, which contributes to a decrease in the threshold amplitude to trigger discrete chorus elements. As a result, these observations show a close connection between chorus emissions and PA on timescales from milliseconds for generation of discrete chorus elements on the microphysics of wave-particle interaction to minutes for the variations of the geomagnetic field inhomogeneity related with the substorm activity.« less

Development of ROACH firmware for microwave multiplexed X-ray TES microcalorimeters

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

Madden, T. J.; Cecil, T. W.; Gades, L. M.

We are developing room temperature electronics based upon the ROACH platform for reading out microwave multiplexed X-ray TES. ROACH is an open-source hardware and software platform featuring a large Xilinx Field Programmable Gate Array (FPGA), Power PC processor, several 10GB Ethernet SFP+ interfaces, and a collection of daughter boards for analog signal generation and acquisition. The combination of a ROACH board, ADC/DAC conversion daughter boards, and hardware for RF mixing allows for the generation and capture of multiple RF tones for reading out microwave multiplexed x-ray TES microcalorimeters. The FPGA is used to generate multiple tones in base band, frommore » 10MHz to 250MHz, which are subsequently mixed to RF in the multiple GHz range and sent through the microwave multiplexer. The tones are generated in the FPGA by storing a large lookup table in Quad Data Rate (QDR) SRAM modules and playing out the waveform to a DAC board. Once the signal has been modulated to RF, passed through the microwave multiplexer, and has been modulated back to base band, the signal is digitized by an ADC board. The tones are modulated to 0Hz by using a FPGA circuit consisting of a polyphase filter bank, several Xilinx FFT blocks, Xilinx CORDIC blocks (for converting to magnitude and phase), and special phase accumulator circuit for mixing to exactly 0Hz. Upwards of 256 channels can be simultaneously captured and written into a bank of 256 First-In-First-Out (FIFO) memories, with each FIFO corresponding to a channel. Individual channel data can be further processed in the FPGA before being streamed through a 10GB Ethernet fiber-optic interface to a Linux system. The Linux system runs software written in Python and QT C++ for controlling the ROACH system, capturing data, and processing data.« less

The auditory enhancement effect is not reflected in the 80-Hz auditory steady-state response.

PubMed

Carcagno, Samuele; Plack, Christopher J; Portron, Arthur; Semal, Catherine; Demany, Laurent

2014-08-01

The perceptual salience of a target tone presented in a multitone background is increased by the presentation of a precursor sound consisting of the multitone background alone. It has been proposed that this "enhancement" phenomenon results from an effective amplification of the neural response to the target tone. In this study, we tested this hypothesis in humans, by comparing the auditory steady-state response (ASSR) to a target tone that was enhanced by a precursor sound with the ASSR to a target tone that was not enhanced. In order to record neural responses originating in the brainstem, the ASSR was elicited by amplitude modulating the target tone at a frequency close to 80 Hz. The results did not show evidence of an amplified neural response to enhanced tones. In a control condition, we measured the ASSR to a target tone that, instead of being perceptually enhanced by a precursor sound, was acoustically increased in level. This level increase matched the magnitude of enhancement estimated psychophysically with a forward masking paradigm in a previous experimental phase. We found that the ASSR to the tone acoustically increased in level was significantly greater than the ASSR to the tone enhanced by the precursor sound. Overall, our results suggest that the enhancement effect cannot be explained by an amplified neural response at the level of the brainstem. However, an alternative possibility is that brainstem neurons with enhanced responses do not contribute to the scalp-recorded ASSR.

Directional Selectivity for FM Sweeps in the Suprageniculate Nucleus of the Mustached Bat Medial Geniculate Body

PubMed Central

O’NEILL, WILLIAM E.; BRIMIJOIN, W. OWEN

2014-01-01

Mustached bats emit echolocation and communication calls containing both constant frequency (CF) and frequency-modulated (FM) components. Previously we found that 86% of neurons in the ventral division of the external nucleus of the inferior colliculus (ICXv) were directionally selective for linear FM sweeps and that selectivity was dependent on sweep rate. The ICXv projects to the suprageniculate nucleus (Sg) of the medial geniculate body. In this study, we isolated 37 single units in the Sg and measured their responses to best excitatory frequency (BEF) tones and linear 12-kHz upward and downward FM sweeps centered on the BEF. Sweeps were presented at durations of 30, 12, and 4 ms, yielding modulation rates of 400, 1,000, and 3,000 kHz/s. Spike count versus level functions were obtained at each modulation rate and compared with BEF controls. Sg units responded well to both tones and FM sweeps. BEFs clustered at 58 kHz, corresponding to the dominant CF component of the sonar signal. Spike count functions for both tones and sweeps were predominantly non-monotonic. FM directional selectivity was significant in 53–78% of the units, depending on modulation rate and level. Units were classified as up-selective (52%), down-selective (24%), or bi-directional (non-selective, 16%); a few units (8%) showed preferences that were either rate- or level-dependent. Most units showed consistent directional preferences at all SPLs and modulation rates tested, but typically showed stronger selectivity at lower sweep rates. Directional preferences were attributable to suppression of activity by sweeps in the non-preferred direction (~80% of units) and/or facilitation by sweeps in the preferred direction (~20–30%). Latencies for BEF tones ranged from 4.9 to 25.7 ms. Latencies for FM sweeps typically varied linearly with sweep duration. Most FM latency-duration functions had slopes ranging from 0.4 to 0.6, suggesting that the responses were triggered by the BEF. Latencies for BEF tones and FM sweeps were significantly correlated in most Sg units, i.e., the response to FM was temporally related to the occurrence of the BEF in the FM sweep. FM latency declined relative to BEF latency as modulation rate increased, suggesting that at higher rates response is triggered by frequencies in the sweep preceding the BEF. We conclude that Sg and ICXv units have similar, though not identical, response properties. Sg units are predominantly upsweep selective and could respond to either or both the CF and FM components in biosonar signals in a number of echolocation scenarios, as well as to a variety of communication sounds. PMID:12091543

PC-PLC/sphingomyelin synthase activity plays a central role in the development of myogenic tone in murine resistance arteries

PubMed Central

Zacharia, Joseph; Fairfax, Seth; Wier, Withrow Gil

2015-01-01

Myogenic tone is an intrinsic property of the vasculature that contributes to blood pressure control and tissue perfusion. Earlier investigations assigned a key role in myogenic tone to phospholipase C (PLC) and its products, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Here, we used the PLC inhibitor, U-73122, and two other, specific inhibitors of PLC subtypes (PI-PLC and PC-PLC) to delineate the role of PLC in myogenic tone of pressurized murine mesenteric arteries. U-73122 inhibited depolarization-induced contractions (high external K+ concentration), thus confirming reports of nonspecific actions of U-73122 and its limited utility for studies of myogenic tone. Edelfosine, a specific inhibitor of PI-PLC, did not affect depolarization-induced contractions but modulated myogenic tone. Because PI-PLC produces IP3, we investigated the effect of blocking IP3 receptor-mediated Ca2+ release on myogenic tone. Incubation of arteries with xestospongin C did not affect tone, consistent with the virtual absence of Ca2+ waves in arteries with myogenic tone. D-609, an inhibitor of PC-PLC and sphingomyelin synthase, strongly inhibited myogenic tone and had no effect on depolarization-induced contraction. D-609 appeared to act by lowering cytoplasmic Ca2+ concentration to levels below those that activate contraction. Importantly, incubation of pressurized arteries with a membrane-permeable analog of DAG induced vasoconstriction. The results therefore mandate a reexamination of the signaling pathways activated by the Bayliss mechanism. Our results suggest that PI-PLC and IP3 are not required in maintaining myogenic tone, but DAG, produced by PC-PLC and/or SM synthase, is likely through multiple mechanisms to increase Ca2+ entry and promote vasoconstriction. PMID:25888510

Enhanced resistance to soybean cyst nematode Heterodera glycines in transgenic soybean by silencing putative CLE receptors

USDA-ARS?s Scientific Manuscript database

CLE peptides are small extracellular proteins important in regulating plant meristematic activity through the CLE-receptor kinase-WOX signaling module. Stem cell pools in the SAM (shoot apical meristem), RAM (root apical meristem), and vascular cambium are tightly controlled by CLE signaling pathway...

Maintenance of certification: current attitudes of members of the American Society of Neuroradiology.

PubMed

Yousem, D M

2008-02-01

The maintenance of certification (MOC) process has begun in radiology, and many physicians will be affected by it. We sought to assess the compliance with and knowledge of the MOC steps by American Society of Neuroradiology (ASNR) members. An on-line survey was distributed via e-mail to the members of the ASNR for whom e-mail addresses were available. The survey addressed 3 components of the MOC currently implemented: 1) MOC cognitive examinations, 2) self-assessment modules (SAMs), and 3) continuing medical education (CME) credits. The response rate was 1020/2662 (38.3%). Of those responding, 11% stated that they either do not support the MOC examination (8%) or were unaware of it (3%), 21.4% of respondents have completed an SAM module, but >30% were unaware that they had to complete SAMs or did not know where they were offered. Many members will receive most of their 25 required CME hours for 2007 from sources besides the ASNR annual meeting. Of the small proportion of respondents who made comments (247/1020, 24.2%), those about the MOC process were favorable in 6.1% (15/247), unfavorable in 46.6% (115/247), and neutral in 47.4% (117/247). The MOC process remains poorly understood, with limited compliance. The radiology societies should spend additional effort publicizing the requirements and offering support and products aimed at allowing their members to achieve compliance in a reasonable cost-effective fashion.

Survey view of EXPRESS Rack 4 in the JPM during Expedition 22

NASA Image and Video Library

2009-12-30

iss022e015852 (12/30/2009) --- The image shows a front view of EXpedite the PRocessing of Experiments to Space Station EXPRESS Rack 4 (Rack 4,JPM/1F5) in the Japanese Experiment Module (JEM) Japanese Pressurized Module (JPM). Equipment visible in the EXPRESS Rack includes the Biotechnology Specimen Temperature Controller (BSTC) and the Gas Supply Module (GSM) support hardware for the CBOSS (Cellular Biotechnology Operations Support Systems) investigations, and the Device for the Study of Critical Liquids and Crystallization (DECLIC). Also visible is the Space Acceleration Measurement System (SAMS) II.

Potentials evoked by chirp-modulated tones: a new technique to evaluate oscillatory activity in the auditory pathway.

PubMed

Artieda, J; Valencia, M; Alegre, M; Olaziregi, O; Urrestarazu, E; Iriarte, J

2004-03-01

Steady-state potentials are oscillatory responses generated by a rhythmic stimulation of a sensory pathway. The frequency of the response, which follows the frequency of stimulation, is maximal at a stimulus rate of 40 Hz for auditory stimuli. The exact cause of these maximal responses is not known, although some authors have suggested that they might be related to the 'working frequency' of the auditory cortex. Testing of the responses to different frequencies of stimulation may be lengthy if a single frequency is studied at a time. Our aim was to develop a fast technique to explore the oscillatory response to auditory stimuli, using a tone modulated in amplitude by a sinusoid whose frequency increases linearly in frequency ('chirp') from 1 to 120 Hz. Time-frequency transforms were used for the analysis of the evoked responses in 10 subjects. Also, we analyzed whether the peaks in these responses were due to increases of amplitude or to phase-locking phenomena, using single-sweep time-frequency transforms and inter-trial phase analysis. The pattern observed in the time-frequency transform of the chirp-evoked potential was very similar in all subjects: a diagonal band of energy was observed, corresponding to the frequency of modulation at each time instant. Two components were present in the band, one around 45 Hz (30-60 Hz) and a smaller one between 80 and 120 Hz. Inter-trial phase analysis showed that these components were mainly due to phase locking phenomena. A simultaneous testing of the amplitude-modulation-following oscillatory responses to auditory stimulation is feasible using a tone modulated in amplitude at increasing frequencies. The maximal energies found at stimulation frequencies around 40 Hz are probably due to increased phase-locking of the individual responses.

Physiological correlates of comodulation masking release in the mammalian ventral cochlear nucleus.

PubMed

Pressnitzer, D; Meddis, R; Delahaye, R; Winter, I M

2001-08-15

Comodulation masking release (CMR) enhances the detection of signals embedded in wideband, amplitude-modulated maskers. At least part of the CMR is attributable to across-frequency processing, however, the relative contribution of different stages in the auditory system to across-frequency processing is unknown. We have measured the responses of single units from one of the earliest stages in the ascending auditory pathway, the ventral cochlear nucleus, where across frequency processing may take place. A sinusoidally amplitude-modulated tone at the best frequency of each unit was used as a masker. A pure tone signal was added in the dips of the masker modulation (reference condition). Flanking components (FCs) were then added at frequencies remote from the unit best frequency. The FCs were pure tones amplitude modulated either in phase (comodulated) or out of phase (codeviant) with the on-frequency component. Psychophysically, this CMR paradigm reduces within-channel cues while producing an advantage of approximately 10 dB for the comodulated condition in comparison with the reference condition. Some of the recorded units showed responses consistent with perceptual CMR. The addition of the comodulated FCs produced a strong reduction in the response to the masker modulation, making the signal more salient in the poststimulus time histograms. A decision statistic based on d' showed that threshold was reached at lower signal levels for the comodulated condition than for reference or codeviant conditions. The neurons that exhibited such a behavior were mainly transient chopper or primary-like units. The results obtained from a subpopulation of transient chopper units are consistent with a possible circuit in the cochlear nucleus consisting of a wideband inhibitor contacting a narrowband cell. A computational model was used to confirm the feasibility of such a circuit.

Mandarin Chinese Tone Identification in Cochlear Implants: Predictions from Acoustic Models

PubMed Central

Morton, Kenneth D.; Torrione, Peter A.; Throckmorton, Chandra S.; Collins, Leslie M.

2015-01-01

It has been established that current cochlear implants do not supply adequate spectral information for perception of tonal languages. Comprehension of a tonal language, such as Mandarin Chinese, requires recognition of lexical tones. New strategies of cochlear stimulation such as variable stimulation rate and current steering may provide the means of delivering more spectral information and thus may provide the auditory fine structure required for tone recognition. Several cochlear implant signal processing strategies are examined in this study, the continuous interleaved sampling (CIS) algorithm, the frequency amplitude modulation encoding (FAME) algorithm, and the multiple carrier frequency algorithm (MCFA). These strategies provide different types and amounts of spectral information. Pattern recognition techniques can be applied to data from Mandarin Chinese tone recognition tasks using acoustic models as a means of testing the abilities of these algorithms to transmit the changes in fundamental frequency indicative of the four lexical tones. The ability of processed Mandarin Chinese tones to be correctly classified may predict trends in the effectiveness of different signal processing algorithms in cochlear implants. The proposed techniques can predict trends in performance of the signal processing techniques in quiet conditions but fail to do so in noise. PMID:18706497

Framing topographic Rossby waves in the Southern Adriatic Sea

NASA Astrophysics Data System (ADS)

Bonaldo, Davide; Orlic, Mirko; Bergamasco, Andrea; Benetazzo, Alvise; Carniel, Sandro

2017-04-01

Topographic Rossby Waves (TRWs) are oscillatory phenomena associated with modulations induced by seabed morphology in the potential vorticity field. These features could be confined to a single layer or could involve the whole water column, and they are controlled by a combination of the bathymetric gradient and the uniform rotation in the same way as planetary Rossby waves are controlled by the meridional modulation of the Coriolis parameter. In terms of deep-sea circulation, TRWs provide a fundamental contribution by radiating large amounts of energy along and off a continental shelf. Under favorable conditions TRWs can be triggered by a number of factors, such as intense vorticity injections from the wind or the bathymetric perturbations - e.g., a promontory or a canyon crossing the path of a current. In this work we combine observational data and numerical model fields for detecting the presence of TRWs along the Southern Adriatic Margin (SAM, Eastern Mediterranean Sea) and investigating their dynamics during an episode of dense water downflow in spring 2012. Starting from the observation of high-intensity velocity pulses with a period of approximately 2 days, we carry out a sequence of operations on the results of a high-resolution, ocean currents-waves coupled numerical modelling experiment aiming to reproduce dense water formation and migration in the Adriatic Sea in winter-spring 2012. First, we apply a wavelet analysis to modelled velocity time series at several locations off the Italian coast and along the SAM in order to identify the spatial and temporal extent of the pulsing episodes. Then, the properties of the oscillations are assessed via rotary analysis; the propagation of the band-filtered signal along the continental margin is characterized by extracting wave length and propagation velocity, therefore allowing the comparison against theoretical dispersion relations associated with the bathymetry of the SAM. Our results show that the observed modulation was indeed related to a perturbation system propagating south-eastward along the Italian coast and amplified as a train of TRWs along the shelf break and on the continental slope, thus providing, to the best of our knowledge, the first evidence of the existence of such waves on the SAM. This work paves the way to further investigations of these waves and their implications on dense water dynamics and related impacts on the benthic environments.

Babies in traffic: infant vocalizations and listener sex modulate auditory motion perception.

PubMed

Neuhoff, John G; Hamilton, Grace R; Gittleson, Amanda L; Mejia, Adolfo

2014-04-01

Infant vocalizations and "looming sounds" are classes of environmental stimuli that are critically important to survival but can have dramatically different emotional valences. Here, we simultaneously presented listeners with a stationary infant vocalization and a 3D virtual looming tone for which listeners made auditory time-to-arrival judgments. Negatively valenced infant cries produced more cautious (anticipatory) estimates of auditory arrival time of the tone over a no-vocalization control. Positively valenced laughs had the opposite effect, and across all conditions, men showed smaller anticipatory biases than women. In Experiment 2, vocalization-matched vocoded noise stimuli did not influence concurrent auditory time-to-arrival estimates compared with a control condition. In Experiment 3, listeners estimated the egocentric distance of a looming tone that stopped before arriving. For distant stopping points, women estimated the stopping point as closer when the tone was presented with an infant cry than when it was presented with a laugh. For near stopping points, women showed no differential effect of vocalization type. Men did not show differential effects of vocalization type at either distance. Our results support the idea that both the sex of the listener and the emotional valence of infant vocalizations can influence auditory motion perception and can modulate motor responses to other behaviorally relevant environmental sounds. We also find support for previous work that shows sex differences in emotion processing are diminished under conditions of higher stress.

Neurobiology of hedonic tone: the relationship between treatment-resistant depression, attention-deficit hyperactivity disorder, and substance abuse

PubMed Central

Sternat, Tia; Katzman, Martin A

2016-01-01

Anhedonia, defined as the state of reduced ability to experience feelings of pleasure, is one of the hallmarks of depression. Hedonic tone is the trait underlying one’s characteristic ability to feel pleasure. Low hedonic tone represents a reduced capacity to experience pleasure, thus increasing the likelihood of experiencing anhedonia. Low hedonic tone has been associated with several psychopathologies, including major depressive disorder (MDD), substance use, and attention-deficit hyperactivity disorder (ADHD). The main neural pathway that modulates emotional affect comprises the limbic–cortical–striatal–pallidal–thalamic circuits. The activity of various components of the limbic–cortical–striatal–pallidal–thalamic pathway is correlated with hedonic tone in healthy individuals and is altered in MDD. Dysfunction of these circuits has also been implicated in the relative ineffectiveness of selective serotonin reuptake inhibitors used to treat anxiety and depression in patients with low hedonic tone. Mood disorders such as MDD, ADHD, and substance abuse share low hedonic tone as well as altered activation of brain regions involved in reward processing and monoamine signaling as their features. Given the common features of these disorders, it is not surprising that they have high levels of comorbidities. The purpose of this article is to review the neurobiology of hedonic tone as it pertains to depression, ADHD, and the potential for substance abuse. We propose that, since low hedonic tone is a shared feature of MDD, ADHD, and substance abuse, evaluation of hedonic tone may become a diagnostic feature used to predict subtypes of MDD, such as treatment-resistant depression, as well as comorbidities of these disorders. PMID:27601909

What do Westerly Wind Reconstructions from Fiordland, New Zealand, say about Southern Hemisphere Paleoclimatic Mechanisms?

NASA Astrophysics Data System (ADS)

Knudson, K. P.; Hendy, I. L.; Neil, H.

2010-12-01

The Southern Hemisphere westerly winds (SWW) have a major influence over deep ocean ventilation around Antarctica and are modulated by inter-annual and decadal climate variability, such as El Niño-Southern Oscillation (ENSO), Inter-decadal Pacific Oscillation (IPO), and Southern Annular Mode (SAM). Fiordland, New Zealand (44.5-46.5°S), is optimally located for reconstructing the SWW, since the fjord sediments record changes in precipitation dependent on the strength and position of the SWW. Here we present a multi-proxy precipitation reconstruction from three New Zealand fjords, demonstrating SWW variability during the late-Holocene, and compare our results to other climate records from New Zealand, Patagonia, and Antarctica. Our fjord sediment analysis uses bulk sediment δ13C and organic C/N ratios to determine the relative contributions of terrestrial organic matter (TOM) versus marine suspended organic matter (SPOM), indicative of terrestrial runoff due to precipitation. Our data indicate dry conditions in Fiordland at 1500-1100 and 750-150 yr B.P., with a reversal at 400 years B.P., and wet conditions at 2300-1600 and 1100-750 yr B.P., with short reversals around 1900 and 900 yr B.P. Our precipitation reconstruction linked to SWW variability provides significant implications for interpreting other Southern Hemisphere climate records and better understanding Pacific basin-wide SWW behavior. Locally, wet periods are likely associated with intervals of increased westerly flow over Fiordland, such as -SAM, El Niño, and/or +IPO, while dry periods may be associated with +SAM, La Niña, and/or -IPO. Comparison of our New Zealand record with Patagonian precipitation records shows differences, which may be attributed to regional variations of the expression of SAM, ENSO, and IPO. In contrast, Fiordland precipitation records appear to correlate to West Antarctic ice cores suggesting a linkage via SAM. Finally, Fiordland precipitation may be modulated by the position of the Subtropical Convergence Zone (STCZ) in the Tasman Sea, which has control over the moisture sources within the SWW path. Therefore, wet periods in Fiordland may be amplified by a southern position of the STCZ that caused the SWW to encounter a warm moisture source before reaching Fiordland.

Responses of auditory-cortex neurons to structural features of natural sounds.

PubMed

Nelken, I; Rotman, Y; Bar Yosef, O

1999-01-14

Sound-processing strategies that use the highly non-random structure of natural sounds may confer evolutionary advantage to many species. Auditory processing of natural sounds has been studied almost exclusively in the context of species-specific vocalizations, although these form only a small part of the acoustic biotope. To study the relationships between properties of natural soundscapes and neuronal processing mechanisms in the auditory system, we analysed sound from a range of different environments. Here we show that for many non-animal sounds and background mixtures of animal sounds, energy in different frequency bands is coherently modulated. Co-modulation of different frequency bands in background noise facilitates the detection of tones in noise by humans, a phenomenon known as co-modulation masking release (CMR). We show that co-modulation also improves the ability of auditory-cortex neurons to detect tones in noise, and we propose that this property of auditory neurons may underlie behavioural CMR. This correspondence may represent an adaptation of the auditory system for the use of an attribute of natural sounds to facilitate real-world processing tasks.

Rate change detection of frequency modulated signals: developmental trends.

PubMed

Cohen-Mimran, Ravit; Sapir, Shimon

2011-08-26

The aim of this study was to examine developmental trends in rate change detection of auditory rhythmic signals (repetitive sinusoidally frequency modulated tones). Two groups of children (9-10 years old and 11-12 years old) and one group of young adults performed a rate change detection (RCD) task using three types of stimuli. The rate of stimulus modulation was either constant (CR), raised by 1 Hz in the middle of the stimulus (RR1) or raised by 2 Hz in the middle of the stimulus (RR2). Performance on the RCD task significantly improved with age. Also, the different stimuli showed different developmental trajectories. When the RR2 stimulus was used, results showed adult-like performance by the age of 10 years but when the RR1 stimulus was used performance continued to improve beyond 12 years of age. Rate change detection of repetitive sinusoidally frequency modulated tones show protracted development beyond the age of 12 years. Given evidence for abnormal processing of auditory rhythmic signals in neurodevelopmental conditions, such as dyslexia, the present methodology might help delineate the nature of these conditions.

Modulation of high frequency noise by engine tones of small boats.

PubMed

Pollara, Alexander; Sutin, Alexander; Salloum, Hady

2017-07-01

The effect of modulation of high frequency ship noise by propeller rotation frequencies is well known. This modulation is observed with the Detection of Envelope Modulation on Noise (DEMON) algorithm. Analysis of the DEMON spectrum allows the revolutions per minute and number of blades of the propeller to be determined. This work shows that the high frequency noise of a small boat can also be modulated by engine frequencies. Prior studies have not reported high frequency noise amplitude modulated at engine frequencies. This modulation is likely produced by bubbles from the engine exhaust system.

TH-E-BRE-04: An Online Replanning Algorithm for VMAT

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

Ahunbay, E; Li, X; Moreau, M

2014-06-15

Purpose: To develop a fast replanning algorithm based on segment aperture morphing (SAM) for online replanning of volumetric modulated arc therapy (VMAT) with flattening filtered (FF) and flattening filter free (FFF) beams. Methods: A software tool was developed to interface with a VMAT planning system ((Monaco, Elekta), enabling the output of detailed beam/machine parameters of original VMAT plans generated based on planning CTs for FF or FFF beams. A SAM algorithm, previously developed for fixed-beam IMRT, was modified to allow the algorithm to correct for interfractional variations (e.g., setup error, organ motion and deformation) by morphing apertures based on themore » geometric relationship between the beam's eye view of the anatomy from the planning CT and that from the daily CT for each control point. The algorithm was tested using daily CTs acquired using an in-room CT during daily IGRT for representative prostate cancer cases along with their planning CTs. The algorithm allows for restricted MLC leaf travel distance between control points of the VMAT delivery to prevent SAM from increasing leaf travel, and therefore treatment delivery time. Results: The VMAT plans adapted to the daily CT by SAM were found to improve the dosimetry relative to the IGRT repositioning plans for both FF and FFF beams. For the adaptive plans, the changes in leaf travel distance between control points were < 1cm for 80% of the control points with no restriction. When restricted to the original plans' maximum travel distance, the dosimetric effect was minimal. The adaptive plans were delivered successfully with similar delivery times as the original plans. The execution of the SAM algorithm was < 10 seconds. Conclusion: The SAM algorithm can quickly generate deliverable online-adaptive VMAT plans based on the anatomy of the day for both FF and FFF beams.« less

Potential impact of the May Southern Hemisphere annular mode on the Indian summer monsoon rainfall

NASA Astrophysics Data System (ADS)

Dou, Juan; Wu, Zhiwei; Zhou, Yefan

2017-04-01

El Niño-Southern Oscillation (ENSO) is probably a most important external forcing to Indian summer monsoon (ISM) rainfall (ISMR), yet the observed ENSO-ISMR relationship has become weak in recent years. It's essential to explore other predominant modes of variability which can contribute to the ISMR. As the leading mode of the variability in Southern Hemisphere (SH) extratropical atmospheric circulation, the SH annular mode (SAM) has potential influence both on the northern and southern hemispheric climate. The present study investigates the relationship between the SAM and ISMR. It is found that the May SAM exhibits a significant positive correlation with the monsoon precipitation over the Indian sub-continent and the adjacent areas in JunetJuly (JJ). Observational and numerical evidences indicate that the May SAM anomaly can trigger a South Indian Ocean dipole (SIOD) sea surface temperature anomaly (SSTA) through air-sea interactions. The SIOD SSTA persisting into the following months of JJ excites abnormal meridional circulation and modulates the low-level cross-equatorial flow. Accordingly, the ascending (or descending) motion and water vapor transportation are enhanced (or suppressed), which favors more (or less) precipitation over the Indian sub-continent and the adjacent areas. In fact, the SIOD SSTA plays an "ocean bridge" role to "prolong" the influence of the May SAM to the subsequent season and in turn impacts on the ISMR. Moreover, an empirical model is established to forecast the JJ ISMR strength based on the ENSO, Indian Ocean Dipole (IOD) and May SAM. The hindcast is carried out for the period 1979-2014, and performs better than the multimodel ensemble mean (MME) obtained from the Development of a European MME system for seasonal to interannual prediction (DEMETER) project. Since all these predictors can be monitored in real time before the early boreal summer, the empirical model might provide a practical real-time forecast tool for predicting ISMR variations.

Potential impact of the May Southern Hemisphere annular mode on the Indian summer monsoon rainfall

NASA Astrophysics Data System (ADS)

Dou, Juan; Wu, Zhiwei; Zhou, Yefan

2017-08-01

El Niño-Southern Oscillation (ENSO) is probably a most important external forcing to Indian summer monsoon (ISM) rainfall (ISMR), yet the observed ENSO-ISMR relationship has become weak in recent years. It's essential to explore other predominant modes of variability which can contribute to the ISMR. As the leading mode of the variability in Southern Hemisphere (SH) extratropical atmospheric circulation, the SH annular mode (SAM) has potential influence both on the northern and southern hemispheric climate. The present study investigates the relationship between the SAM and ISMR. It is found that the May SAM exhibits a significant positive correlation with the monsoon precipitation over the Indian sub-continent and the adjacent areas in June-July (JJ). Observational and numerical evidences indicate that the May SAM anomaly can trigger a South Indian Ocean dipole (SIOD) sea surface temperature anomaly (SSTA) through air-sea interactions. The SIOD SSTA persisting into the following months of JJ excites abnormal meridional circulation and modulates the low-level cross-equatorial flow. Accordingly, the ascending (or descending) motion and water vapor transportation are enhanced (or suppressed), which favors more (or less) precipitation over the Indian sub-continent and the adjacent areas. In fact, the SIOD SSTA plays an "ocean bridge" role to "prolong" the influence of the May SAM to the subsequent season and in turn impacts on the ISMR. Moreover, an empirical model is established to forecast the JJ ISMR strength based on the ENSO, Indian Ocean Dipole and May SAM. The hindcast is carried out for the period 1979-2014, and performs better than the multimodel ensemble mean (MME) obtained from the Development of a European MME system for seasonal to interannual prediction (DEMETER) project. Since all these predictors can be monitored in real time before the early boreal summer, the empirical model might provide a practical real-time forecast tool for predicting ISMR variations.

GPER modulates tone and coronary vascular reactivity in male and female rats.

PubMed

Debortoli, Angelina Rafaela; Rouver, Wender do Nascimento; Delgado, Nathalie Tristão Banhos; Mengal, Vinicius; Claudio, Erick Roberto Gonçalves; Pernomian, Laena; Bendhack, Lusiane Maria; Moysés, Margareth Ribeiro; Santos, Roger Lyrio Dos

2017-08-01

Compared with age-matched men, premenopausal women are largely protected from coronary artery disease, a difference that is lost after menopause. The effects of oestrogens are mediated by the activation of nuclear receptors (ERα and ERβ) and by the G protein-coupled oestrogen receptor (GPER). This study aims to evaluate the potential role of GPER in coronary circulation in female and male rats. The baseline coronary perfusion pressure (CPP) and the concentration-response curve with a GPER agonist (G-1) were evaluated in isolated hearts before and after the blockade of GPER. GPER, superoxide dismutase (SOD-2), catalase and gp91phox protein expression were assessed by Western blotting. Superoxide production was evaluated ' in situ ' via dihydroethidium fluorescence (DHE). GPER blockade significantly increased the CPP in both groups, demonstrating the modulation of coronary tone by GPER. G-1 causes relaxation of the coronary bed in a concentration-dependent manner and was significantly higher in female rats. No differences were detected in GPER, SOD-2 and catalase protein expression. However, gp91phox expression and DHE fluorescence were higher in male rats, indicating elevated superoxide production. Therefore, GPER plays an important role in modulating coronary tone and reactivity in female and male rats. The observed differences in vascular reactivity may be related to the higher superoxide production in male rats. These findings help to elucidate the role of GPER-modulating coronary circulation, providing new information to develop a potential therapeutic target for the treatment of coronary heart disease. © 2017 Society for Endocrinology.

Poly(L-lysine) Interfaces via Dual Click Reactions on Surface-Bound Custom-Designed Dithiol Adsorbates.

PubMed

Shakiba, Amin; Jamison, Andrew C; Lee, T Randall

2015-06-09

Surfaces modified with poly(L-lysine) can be used to immobilize selected biomolecules electrostatically. This report describes the preparation of a set of self-assembled monolayers (SAMs) from three different azide-terminated adsorbates as platforms for performing controlled surface attachments and as a means of determining the parameters that afford stable poly(L-lysine)-modified SAM surfaces having controlled packing densities. A maleimide-terminated alkyne linker was "clicked" to the azide-terminated surfaces via a copper-catalyzed cycloaddition reaction to produce the attachment sites for the polypeptides. A thiol-Michael addition was then used to immobilize cysteine-terminated poly(L-lysine) moieties on the gold surface, avoiding adsorbate self-reactions with this two-step procedure. Each step in this process was analyzed by ellipsometry, X-ray photoelectron spectroscopy, polarization modulation infrared reflection-absorption spectroscopy, and contact angle goniometry to determine which adsorbate structure most effectively produced the targeted polypeptide interface. Additionally, a series of mixed SAMs using an azidoalkanethiol in combination with a normal alkanethiol having an equivalent alkyl chain were prepared to provide data to determine how dilution of the azide reactive site on the SAM surface influences the initial click reaction. Overall, the collected data demonstrate the advantages of an appropriately designed bidentate absorbate and its potential to form effective platforms for biomolecule surface attachment via click reactions.

The Achievement Gap between White and Non-White Students

ERIC Educational Resources Information Center

Rojas-LeBouef, Ana; Slate, John R.

2012-01-01

This Collection contains three seminal modules by Authors Ana Rojas-LeBouef and John R. Slate, professors and researchers from Sam Houston State University in Texas. They are nationally recognized scholars in the area of the academic inequity between White and Non-White students. This paper is divided into three chapters. Chapter 1--The…

Glutamate spillover drives endocannabinoid production and inhibits GABAergic transmission in the Substantia Nigra pars compacta.

PubMed

Freestone, Peter S; Guatteo, Ezia; Piscitelli, Fabiana; di Marzo, Vincenzo; Lipski, Janusz; Mercuri, Nicola B

2014-04-01

Endocannabinoids (eCBs) modulate synaptic transmission in the brain, but little is known of their regulatory role in nigral dopaminergic neurons, and whether transmission to these neurons is tonically inhibited by eCBs as seen in some other brain regions. Using whole-cell recording in midbrain slices, we observed potentiation of evoked IPSCs (eIPSCs) in these neurons after blocking CB1 receptors with rimonabant or LY-320,135, indicating the presence of an eCB tone reducing inhibitory synaptic transmission. Increased postsynaptic calcium buffering and block of mGluR1 or postsynaptic G-protein coupled receptors prevented this potentiation. Increasing spillover of endogenous glutamate by inhibiting uptake attenuated eIPSC amplitude, while enhancing the potentiation by rimonabant. Group I mGluR activation transiently inhibited eIPSCs, which could be prevented by GDP-β-S, increased calcium buffering or rimonabant. We explored the possibility that the dopamine-derived eCB N-arachidonoyl dopamine (NADA) is involved. The eCB tone was abolished by preventing dopamine synthesis, and enhanced by l-DOPA. It was not detected in adjacent non-dopaminergic neurons. Preventing 2-AG synthesis did not affect the tone, while inhibition of NADA production abolished it. Quantification of ventral midbrain NADA suggested a basal level that increased following prolonged depolarization or mGluR activation. Since block of the tone was not always accompanied by attenuation of depolarization-induced suppression of inhibition (DSI) and vice versa, our results indicate DSI and the eCB tone are mediated by distinct eCBs. This study provides evidence that dopamine modulates the activity of SNc neurons not only by conventional dopamine receptors, but also by CB1 receptors, potentially via NADA. Copyright © 2013 Elsevier Ltd. All rights reserved.

Investigation of fiber dispersion impairment in 400GbE discrete multi-tone system for reach enhancement up to 40 km

NASA Astrophysics Data System (ADS)

Okabe, Ryo; Tanaka, Toshiki; Nishihara, Masato; Kai, Yutaka; Takahara, Tomoo; Chen, Hao; Yan, Weizhen; Tao, Zhenning; Rasmussen, Jens C.

2015-01-01

Discrete multi-tone (DMT) technology is an attractive modulation technique for short reach optical transmission system. One of the main factors that limit system performance is fiber dispersion, which is strongly influenced by the chirp characteristics of transmitters. We investigated the fiber dispersion impairment in a 400GbE (4 × 116.1-Gb/s) DMT system on LAN-WDM grid for reach enhancement up to 40 km through experiments and numerical simulations.

An additional study and implementation of tone calibrated technique of modulation

NASA Technical Reports Server (NTRS)

Rafferty, W.; Bechtel, L. K.; Lay, N. E.

1985-01-01

The Tone Calibrated Technique (TCT) was shown to be theoretically free from an error floor, and is only limited, in practice, by implementation constraints. The concept of the TCT transmission scheme along with a baseband implementation of a suitable demodulator is introduced. Two techniques for the generation of the TCT signal are considered: a Manchester source encoding scheme (MTCT) and a subcarrier based technique (STCT). The results are summarized for the TCT link computer simulation. The hardware implementation of the MTCT system is addressed and the digital signal processing design considerations involved in satisfying the modulator/demodulator requirements are outlined. The program findings are discussed and future direction are suggested based on conclusions made regarding the suitability of the TCT system for the transmission channel presently under consideration.

Tone calibration technique: A digital signaling scheme for mobile applications

NASA Technical Reports Server (NTRS)

Davarian, F.

1986-01-01

Residual carrier modulation is conventionally used in a communication link to assist the receiver with signal demodulation and detection. Although suppressed carrier modulation has a slight power advantage over the residual carrier approach in systems enjoying a high level of stability, it lacks sufficient robustness to be used in channels severely contaminated by noise, interference and propagation effects. In mobile links, in particular, the vehicle motion and multipath waveform propagation affect the received carrier in an adverse fashion. A residual carrier scheme that uses a pilot carrier to calibrate a mobile channel against multipath fading anomalies is described. The benefits of this scheme, known as tone calibration technique, are described. A brief study of the system performance in the presence of implementation anomalies is also given.

Cantico Delle Creature: A microtonal original composition for soprano and string quartet to a text by St. Francis of Assisi, including analytical commentary

NASA Astrophysics Data System (ADS)

Sabol, Jason A.

Cantico delle Creature is an original piece of music for soprano and string quartet composed in 72 tone per octave equal temperament, dividing each semitone into six equal parts called twelfth-tones. This system of tuning makes it possible to combine just intonation and spectral principles based on the harmonic series with real imitation, modulation, and polyphony. Supplemental text discusses several aspects of microtonal structure and pedagogy, including the representation of the first 64 partials of the harmonic series in 72 tone equal temperament, performance of natural string harmonics, the relationship between interval size and vibration ratio, pitch to frequency conversion, and analysis of several passages in the musical score.

Parabolic Trough Collector Cost Update for the System Advisor Model (SAM)

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

Kurup, Parthiv; Turchi, Craig S.

2015-11-01

This report updates the baseline cost for parabolic trough solar fields in the United States within NREL's System Advisor Model (SAM). SAM, available at no cost at https://sam.nrel.gov/, is a performance and financial model designed to facilitate decision making for people involved in the renewable energy industry. SAM is the primary tool used by NREL and the U.S. Department of Energy (DOE) for estimating the performance and cost of concentrating solar power (CSP) technologies and projects. The study performed a bottom-up build and cost estimate for two state-of-the-art parabolic trough designs -- the SkyTrough and the Ultimate Trough. The SkyTroughmore » analysis estimated the potential installed cost for a solar field of 1500 SCAs as $170/m 2 +/- $6/m 2. The investigation found that SkyTrough installed costs were sensitive to factors such as raw aluminum alloy cost and production volume. For example, in the case of the SkyTrough, the installed cost would rise to nearly $210/m 2 if the aluminum alloy cost was $1.70/lb instead of $1.03/lb. Accordingly, one must be aware of fluctuations in the relevant commodities markets to track system cost over time. The estimated installed cost for the Ultimate Trough was only slightly higher at $178/m 2, which includes an assembly facility of $11.6 million amortized over the required production volume. Considering the size and overall cost of a 700 SCA Ultimate Trough solar field, two parallel production lines in a fully covered assembly facility, each with the specific torque box, module and mirror jigs, would be justified for a full CSP plant.« less

Transient Delivery of Adenosine as a Novel Therapy to Prevent Epileptogenesis

DTIC Science & Technology

2013-08-01

rats characterized by the development of SRS triggered by systemic kainic acid–induced (KA-induced) status epilepticus (SE) (Figure 3A). Using...to modulate DNA methylation status , have not been studied to date. Based on ADO’s role as an obligatory end product of DNA methylation, we...1E). Together, these findings show that modulating ADO tone either directly or via modulation of ADK expression can affect DNA methylation status in

Estradiol selectively enhances auditory function in avian forebrain neurons

PubMed Central

Caras, Melissa L.; O’Brien, Matthew; Brenowitz, Eliot A.; Rubel, Edwin W

2012-01-01

Sex steroids modulate vertebrate sensory processing, but the impact of circulating hormone levels on forebrain function remains unclear. We tested the hypothesis that circulating sex steroids modulate single-unit responses in the avian telencephalic auditory nucleus, field L. We mimicked breeding or non-breeding conditions by manipulating plasma 17β-estradiol levels in wild-caught female Gambel’s white-crowned sparrows (Zonotrichia leucophrys gambelii). Extracellular responses of single neurons to tones and conspecific songs presented over a range of intensities revealed that estradiol selectively enhanced auditory function in cells that exhibited monotonic rate-level functions to pure tones. In these cells, estradiol treatment increased spontaneous and maximum evoked firing rates, increased pure tone response strengths and sensitivity, and expanded the range of intensities over which conspecific song stimuli elicited significant responses. Estradiol did not significantly alter the sensitivity or dynamic ranges of cells that exhibited non-monotonic rate-level functions. Notably, there was a robust correlation between plasma estradiol concentrations in individual birds and physiological response properties in monotonic, but not non-monotonic neurons. These findings demonstrate that functionally distinct classes of anatomically overlapping forebrain neurons are differentially regulated by sex steroid hormones in a dose-dependent manner. PMID:23223283

Method to Measure Tone of Axial and Proximal Muscle

PubMed Central

Gurfinkel, Victor S.; Cacciatore, Timothy W.; Cordo, Paul J.; Horak, Fay B.

2011-01-01

The control of tonic muscular activity remains poorly understood. While abnormal tone is commonly assessed clinically by measuring the passive resistance of relaxed limbs1, no systems are available to study tonic muscle control in a natural, active state of antigravity support. We have developed a device (Twister) to study tonic regulation of axial and proximal muscles during active postural maintenance (i.e. postural tone). Twister rotates axial body regions relative to each other about the vertical axis during stance, so as to twist the neck, trunk or hip regions. This twisting imposes length changes on axial muscles without changing the body's relationship to gravity. Because Twister does not provide postural support, tone must be regulated to counteract gravitational torques. We quantify this tonic regulation by the restive torque to twisting, which reflects the state of all muscles undergoing length changes, as well as by electromyography of relevant muscles. Because tone is characterized by long-lasting low-level muscle activity, tonic control is studied with slow movements that produce "tonic" changes in muscle length, without evoking fast "phasic" responses. Twister can be reconfigured to study various aspects of muscle tone, such as co-contraction, tonic modulation to postural changes, tonic interactions across body segments, as well as perceptual thresholds to slow axial rotation. Twister can also be used to provide a quantitative measurement of the effects of disease on axial and proximal postural tone and assess the efficacy of intervention. PMID:22214974

Naturally together: pitch-height and brightness as coupled factors for eliciting the SMARC effect in non-musicians.

PubMed

Pitteri, Marco; Marchetti, Mauro; Priftis, Konstantinos; Grassi, Massimo

2017-01-01

Pitch-height is often labeled spatially (i.e., low or high) as a function of the fundamental frequency of the tone. This correspondence is highlighted by the so-called Spatial-Musical Association of Response Codes (SMARC) effect. However, the literature suggests that the brightness of the tone's timbre might contribute to this spatial association. We investigated the SMARC effect in a group of non-musicians by disentangling the role of pitch-height and the role of tone-brightness. In three experimental conditions, participants were asked to judge whether the tone they were listening to was (or was not) modulated in amplitude (i.e., vibrato). Participants were required to make their response in both the horizontal and the vertical axes. In a first condition, tones varied coherently in pitch (i.e., manipulation of the tone's F0) and brightness (i.e., manipulation of the tone's spectral centroid); in a second condition, pitch-height varied whereas brightness was fixed; in a third condition, pitch-height was fixed whereas brightness varied. We found the SMARC effect only in the first condition and only in the vertical axis. In contrast, we did not observe the effect in any of the remaining conditions. The present results suggest that, in non-musicians, the SMARC effect is not due to the manipulation of the pitch-height alone, but arises because of a coherent change of pitch-height and brightness; this effect emerges along the vertical axis only.

BPSK optical mm-wave signal generation by septupling frequency via a single optical phase modulator

NASA Astrophysics Data System (ADS)

Wu, Peng; Ma, Jianxin

2016-09-01

In this paper, we have proposed a novel and simple scheme to generate the BPSK optical millimeter wave (MMW) signal with frequency septupling by using an optical phase modulator (PM) and a wavelength selective switch (WSS). In this scheme, the PM is driven by a radio frequency (RF) BPSK signal at the optimized modulation index of 4.89 to assure the 4th and 3rd-order sidebands have equal amplitudes. An wavelength selective switch (WSS) is used to abstract the -4th and +3rd-order sidebands from the spectrum generated by RF BPSK signal modulating the lightwave to form the BPSK optical MMW signal with frequency septupling the driving RF signal. In these two tones, only the +3rd-order sideband bears the BPSK signal while the -4th-order sideband is unmodulated since the phase information is canceled by the even times multiplication of the phase of BPSK signal. The MMW signal can avoid the pulse walk-off effect and the amplitude fading effect caused by the fiber chromatic dispersion. By adjusting the modulation index to assure the two tones have equal amplitude, the generated optical MMW signal has the maximal opto-electrical conversion efficiency and good transmission performance.

Heterotypic Sam-Sam association between Odin-Sam1 and Arap3-Sam: binding affinity and structural insights.

PubMed

Mercurio, Flavia A; Marasco, Daniela; Pirone, Luciano; Scognamiglio, Pasqualina L; Pedone, Emilia M; Pellecchia, Maurizio; Leone, Marilisa

2013-01-02

Arap3 is a phosphatidylinositol 3 kinase effector protein that plays a role as GTPase activator (GAP) for Arf6 and RhoA. Arap3 contains a sterile alpha motif (Sam) domain that has high sequence homology with the Sam domain of the EphA2-receptor (EphA2-Sam). Both Arap3-Sam and EphA2-Sam are able to associate with the Sam domain of the lipid phosphatase Ship2 (Ship2-Sam). Recently, we reported a novel interaction between the first Sam domain of Odin (Odin-Sam1), a protein belonging to the ANKS (ANKyrin repeat and Sam domain containing) family, and EphA2-Sam. In our latest work, we applied NMR spectroscopy, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) to characterize the association between Arap3-Sam and Odin-Sam1. We show that these two Sam domains interact with low micromolar affinity. Moreover, by means of molecular docking techniques, supported by NMR data, we demonstrate that Odin-Sam1 and Arap3-Sam might bind with a topology that is common to several Sam-Sam complexes. The revealed structural details form the basis for the design of potential peptide antagonists that could be used as chemical tools to investigate functional aspects related to heterotypic Arap3-Sam associations. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Laser color recording unit

NASA Astrophysics Data System (ADS)

Jung, E.

1984-05-01

A color recording unit was designed for output and control of digitized picture data within computer controlled reproduction and picture processing systems. In order to get a color proof picture of high quality similar to a color print, together with reduced time and material consumption, a photographic color film material was exposed pixelwise by modulated laser beams of three wavelengths for red, green and blue light. Components of different manufacturers for lasers, acousto-optic modulators and polygon mirrors were tested, also different recording methods as (continuous tone mode or screened mode and with a drum or flatbed recording principle). Besides the application for the graphic arts - the proof recorder CPR 403 with continuous tone color recording with a drum scanner - such a color hardcopy peripheral unit with large picture formats and high resolution can be used in medicine, communication, and satellite picture processing.

Photonics-based microwave frequency measurement using a double-sideband suppressed-carrier modulation and an InP integrated ring-assisted Mach-Zehnder interferometer filter.

PubMed

Fandiño, Javier S; Muñoz, Pascual

2013-11-01

A photonic system capable of estimating the unknown frequency of a CW microwave tone is presented. The core of the system is a complementary optical filter monolithically integrated in InP, consisting of a ring-assisted Mach-Zehnder interferometer with a second-order elliptic response. By simultaneously measuring the different optical powers produced by a double-sideband suppressed-carrier modulation at the outputs of the photonic integrated circuit, an amplitude comparison function that depends on the input tone frequency is obtained. Using this technique, a frequency measurement range of 10 GHz (5-15 GHz) with a root mean square value of frequency error lower than 200 MHz is experimentally demonstrated. Moreover, simulations showing the impact of a residual optical carrier on system performance are also provided.

Potassium Channels and Uterine Vascular Adaptation to Pregnancy and Chronic Hypoxia

PubMed Central

Zhu, Ronghui; Xiao, DaLiao; Zhang, Lubo

2014-01-01

During a normal course of pregnancy, uterine vascular tone is significantly decreased resulting in a striking increase in uterine blood flow, which is essential for fetal development and fetal growth. Chronic hypoxia during gestation may adversely affect the normal adaptation of uterine vascular tone and increase the risk of preeclampsia and fetal intrauterine growth restriction. In this review, we present evidence that the regulation of K+ channels is an important mechanism in the adaptation of uterine vascular tone to pregnancy and hypoxia. There are four types of K+ channels identified in arterial smooth muscle cells: 1) voltage-dependent K+ (Kv) channels, 2) Ca2+-activated K+ (KCa) channels, 3) inward rectifier K+ (KIR) channels, and 4) ATP-sensitive K+ (KATP) channels. Pregnancy differentially augments the expression and activity of K+ channels via downregulation of protein kinase C signaling in uterine and other vascular beds, leading to decreased uterine vascular tone and increased uterine blood flow. Sex steroid hormones play an important role in the pregnancy-mediated alteration of K+ channels in the uterine vasculature. In addition, chronic hypoxia alters uterine vascular K+ channels expression and activities via modulation of steroid hormones/receptors-mediated signaling, resulting in increased uterine vascular tone during pregnancy. PMID:24063385

Auditory evoked potentials to abrupt pitch and timbre change of complex tones: electrophysiological evidence of 'streaming'?

PubMed

Jones, S J; Longe, O; Vaz Pato, M

1998-03-01

Examination of the cortical auditory evoked potentials to complex tones changing in pitch and timbre suggests a useful new method for investigating higher auditory processes, in particular those concerned with 'streaming' and auditory object formation. The main conclusions were: (i) the N1 evoked by a sudden change in pitch or timbre was more posteriorly distributed than the N1 at the onset of the tone, indicating at least partial segregation of the neuronal populations responsive to sound onset and spectral change; (ii) the T-complex was consistently larger over the right hemisphere, consistent with clinical and PET evidence for particular involvement of the right temporal lobe in the processing of timbral and musical material; (iii) responses to timbral change were relatively unaffected by increasing the rate of interspersed changes in pitch, suggesting a mechanism for detecting the onset of a new voice in a constantly modulated sound stream; (iv) responses to onset, offset and pitch change of complex tones were relatively unaffected by interfering tones when the latter were of a different timbre, suggesting these responses must be generated subsequent to auditory stream segregation.

Influence of the May Southern annular mode on the South China Sea summer monsoon

NASA Astrophysics Data System (ADS)

Liu, Ting; Li, Jianping; Li, YanJie; Zhao, Sen; Zheng, Fei; Zheng, Jiayu; Yao, Zhixiong

2017-07-01

The possible impact of the May Southern Hemisphere (SH) annular mode (SAM) on the following South China Sea (SCS) summer monsoon (SCSSM) is examined. A close inverse relationship between the two is revealed in the observations. The simultaneous South Pacific dipole (SPD), a dipole-like sea surface temperature anomaly pattern in the South Pacific, acts as the "oceanic bridge" to preserve the May SAM signal and prolong it into June-September. Observational evidence and numerical simulations both demonstrate that the SPD communicates its large thermal inertia signal to the atmosphere, regulating the Southern Pacific Subtropical Jet (SPSJ) variability over eastern Australia. Corresponding to the adjustment of circulation associated with the SPSJ is a prominent tripolar cross-Pacific teleconnection pattern stretching from the SH middle-high latitudes into the NH East Asia coastal region, referred to as the South-North Pacific (SNP) teleconnection pattern. Wave ray tracing analysis manifests that the SNP acts as the "atmospheric bridge" to propagate the related wave energy across the equator and into the Maritime Continent and SCS monsoon region, modulating the vertical motion and middle-lower tropospheric flows, and favoring the out-of-phase variation of the SCSSM. Therefore, the "coupled oceanic-atmospheric bridge" process and the related Rossby wave energy transmission are possible mechanisms for the significant influence of the May SAM on the variability of the following SCSSM. Therefore, the May SAM provides a fresh insight into the prediction of the SCSSM from the perspective of the SH high latitudes.

Tribological properties of self-assembled monolayers of catecholic imidazolium and the spin-coated films of ionic liquids.

PubMed

Liu, Jianxi; Li, Jinlong; Yu, Bo; Ma, Baodong; Zhu, Yangwen; Song, Xinwang; Cao, Xulong; Yang, Wu; Zhou, Feng

2011-09-20

A novel compound of an imidazolium type of ionic liquid (IL) containing a biomimetic catecholic functional group normally seen in mussel adhesive proteins was synthesized. The IL can be immobilized on a silicon surface and a variety of other engineering material surfaces via the catecholic anchor, allowing the tribological protection of these substrates for engineering applications. The surface wetting and adhesive properties and the tribological property of the synthesized self-assembled monolayers (SAMs) are successfully modulated by altering the counteranions. The chemical composition and wettability of the IL SAMs were characterized by means of X-ray photoelectron spectroscopy (XPS) and contact angle (CA) measurements. The adhesive and friction forces were measured with an atomic force microscope (AFM) on the nanometer scale. IL composite films were prepared by spin coating thin IL films on top of the SAMs. The macrotribological properties of these IL composite films were investigated with a pin-on-disk tribometer. The results indicate that the presence of IL SAMs on a surface can improve the wettability of spin-coated ionic liquids and thus the film quality and the tribological properties. These films registered a reduced friction coefficient and a significantly enhanced durability and load-carrying capacity. The tribological properties of the composite films are better than those of pure IL films because the presence of the monolayers improves the adhesion and compatibility of spin-coated IL films with substrates. © 2011 American Chemical Society

Sam37 is crucial for formation of the mitochondrial TOM-SAM supercomplex, thereby promoting β-barrel biogenesis.

PubMed

Wenz, Lena-Sophie; Ellenrieder, Lars; Qiu, Jian; Bohnert, Maria; Zufall, Nicole; van der Laan, Martin; Pfanner, Nikolaus; Wiedemann, Nils; Becker, Thomas

2015-09-28

Biogenesis of mitochondrial β-barrel proteins requires two preprotein translocases, the general translocase of the outer membrane (TOM) and the sorting and assembly machinery (SAM). TOM and SAM form a supercomplex that promotes transfer of β-barrel precursors. The SAM core complex contains the channel protein Sam50, which cooperates with Sam35 in precursor recognition, and the peripheral membrane protein Sam37. The molecular function of Sam37 has been unknown. We report that Sam37 is crucial for formation of the TOM-SAM supercomplex. Sam37 interacts with the receptor domain of Tom22 on the cytosolic side of the mitochondrial outer membrane and links TOM and SAM complexes. Sam37 thus promotes efficient transfer of β-barrel precursors to the SAM complex. We conclude that Sam37 functions as a coupling factor of the translocase supercomplex of the mitochondrial outer membrane. © 2015 Wenz et al.

Endogenous cholinergic tone modulates spontaneous network level neuronal activity in primary cortical cultures grown on multi-electrode arrays.

PubMed

Hammond, Mark W; Xydas, Dimitris; Downes, Julia H; Bucci, Giovanna; Becerra, Victor; Warwick, Kevin; Constanti, Andrew; Nasuto, Slawomir J; Whalley, Benjamin J

2013-03-26

Cortical cultures grown long-term on multi-electrode arrays (MEAs) are frequently and extensively used as models of cortical networks in studies of neuronal firing activity, neuropharmacology, toxicology and mechanisms underlying synaptic plasticity. However, in contrast to the predominantly asynchronous neuronal firing activity exhibited by intact cortex, electrophysiological activity of mature cortical cultures is dominated by spontaneous epileptiform-like global burst events which hinders their effective use in network-level studies, particularly for neurally-controlled animat ('artificial animal') applications. Thus, the identification of culture features that can be exploited to produce neuronal activity more representative of that seen in vivo could increase the utility and relevance of studies that employ these preparations. Acetylcholine has a recognised neuromodulatory role affecting excitability, rhythmicity, plasticity and information flow in vivo although its endogenous production by cortical cultures and subsequent functional influence upon neuronal excitability remains unknown. Consequently, using MEA electrophysiological recording supported by immunohistochemical and RT-qPCR methods, we demonstrate for the first time, the presence of intrinsic cholinergic neurons and significant, endogenous cholinergic tone in cortical cultures with a characterisation of the muscarinic and nicotinic components that underlie modulation of spontaneous neuronal activity. We found that tonic muscarinic ACh receptor (mAChR) activation affects global excitability and burst event regularity in a culture age-dependent manner whilst, in contrast, tonic nicotinic ACh receptor (nAChR) activation can modulate burst duration and the proportion of spikes occurring within bursts in a spatio-temporal fashion. We suggest that the presence of significant endogenous cholinergic tone in cortical cultures and the comparability of its modulatory effects to those seen in intact brain tissues support emerging, exploitable commonalities between in vivo and in vitro preparations. We conclude that experimental manipulation of endogenous cholinergic tone could offer a novel opportunity to improve the use of cortical cultures for studies of network-level mechanisms in a manner that remains largely consistent with its functional role.

First results from SAM-FP: Fabry-Perot observations with ground-layer adaptive optics - the structure and kinematics of the core of 30 Doradus

NASA Astrophysics Data System (ADS)

Mendes de Oliveira, C.; Amram, P.; Quint, Bruno C.; Torres-Flores, S.; Barbá, R.; Andrade, D.

2017-08-01

The aim of this paper is to present the first data set obtained with SOAR Adaptive Module-Fabry-Parot (SAM-FP), a Fabry-Perot instrument mounted inside the SOAR telescope Adaptive-Optics Module. This is the only existing imaging Fabry-Perot interferometer using laser-assisted ground-layer adaptive optics. SAM-FP was used to observe the ionized gas, traced by Hα, in the centre of the 30 Doradus starburst (the Tarantula Nebula) in the Large Magellanic Cloud, with high spatial (˜0.6 arcsec, or 0.15 pc) and spectral (R ≃ 11 200) resolution. Radial velocity, velocity dispersion and monochromatic maps were derived. The region displays a mix of narrow, σ ˜ 20 km s-1 profiles and multiple broader profiles with σ ˜ 70-80 km s-1, indicating the complex nature of the nebula kinematics. A comparison with previously obtained VLT/FLAMES spectroscopy demonstrates that the data agree well in the regions of overlap, but the Fabry-Perot data are superior in spatial coverage. A preliminary analysis of the observations finds a new expanding bubble south of R136, with a projected radius of r = 5.6 pc and an expansion velocity of 29 ± 4 km s-1. In addition, the first-time detailed kinematic maps derived here for several complexes and filaments of 30 Doradus allow identification of kinematically independent structures. These data exemplify the power of the combination of a high-order Fabry-Perot with a wide-field imager (3 × 3 arcmin2 GLAO-corrected field of view) for high-resolution spatial and spectral studies. In particular, SAM-FP data cubes are highly advantageous over multifibre or long-slit data sets for nebula structure studies and to search for small-scale bubbles, given their greatly improved spatial coverage. For reference, this paper also presents two appendices with detailed descriptions of the usage of Fabry-Perot devices, including formulae and explanations for understanding Fabry-Perot observations.

Differential phase acoustic microscope for micro-NDE

NASA Technical Reports Server (NTRS)

Waters, David D.; Pusateri, T. L.; Huang, S. R.

1992-01-01

A differential phase scanning acoustic microscope (DP-SAM) was developed, fabricated, and tested in this project. This includes the acoustic lens and transducers, driving and receiving electronics, scanning stage, scanning software, and display software. This DP-SAM can produce mechanically raster-scanned acoustic microscopic images of differential phase, differential amplitude, or amplitude of the time gated returned echoes of the samples. The differential phase and differential amplitude images provide better image contrast over the conventional amplitude images. A specially designed miniature dual beam lens was used to form two foci to obtain the differential phase and amplitude information of the echoes. High image resolution (1 micron) was achieved by applying high frequency (around 1 GHz) acoustic signals to the samples and placing two foci close to each other (1 micron). Tone burst was used in this system to obtain a good estimation of the phase differences between echoes from the two adjacent foci. The system can also be used to extract the V(z) acoustic signature. Since two acoustic beams and four receiving modes are available, there are 12 possible combinations to produce an image or a V(z) scan. This provides a unique feature of this system that none of the existing acoustic microscopic systems can provide for the micro-nondestructive evaluation applications. The entire system, including the lens, electronics, and scanning control software, has made a competitive industrial product for nondestructive material inspection and evaluation and has attracted interest from existing acoustic microscope manufacturers.

Conformational order of n-dodecanethiol and n-dodecaneselenol monolayers on polycrystalline copper investigated by PM-IRRAS and SFG spectroscopy

NASA Astrophysics Data System (ADS)

Fonder, G.; Cecchet, F.; Peremans, A.; Thiry, P. A.; Delhalle, J.; Mekhalif, Z.

2009-08-01

Self-assembled monolayers (SAMs) of n-dodecanethiol (C 12H 25SH) and n-dodecaneselenol (C 12H 25SeH) on polycrystalline copper have been elaborated with the purpose of achieving densely packed and crystalline-like assemblies. By combining the surface sensitivity of polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) and sum-frequency generation spectroscopy (SFG), the effect of the self-assembly time (15 min, 30 min, 1 h, 2 h and 24 h) on the formation of n-dodecanethiol and n-dodecaneselenol monolayers on untreated and electrochemically reduced polycrystalline copper has been investigated. On electrochemically reduced copper, PM-IRRAS spectroscopy shows that both molecules are able to form well organized layers. SFG spectroscopy indicates that the C 12H 25SeH SAMs are slightly better ordered than those achieved with C 12H 25SH. On untreated copper, the two molecules lead to different film organizations. Both PM-IRRAS and SFG indicate that C 12H 25SH SAMs are of the same film quality as those obtained on electrochemically reduced copper. On the contrary, C 12H 25SeH monolayers are invariably poorly organized at the molecular level.

Immobilization of Protein A on SAMs for the elaboration of immunosensors.

PubMed

Briand, Elisabeth; Salmain, Michèle; Compère, Chantal; Pradier, Claire-Marie

2006-12-01

Binary mixtures of 11-mercaptoundecanoic acid (MUA) and other thiols of various lengths and terminal functions were chemisorbed on gold-coated surfaces via S-Au bonds to form mixed self-assembled monolayers (SAMs). Several values of the mole fraction of MUA in the thiol mixtures were tested and the structure and composition of the resulted thin films were characterized by X-ray photoelectron spectroscopy (XPS) and polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS). The results made it clear that co-adsorption of MUA with thiols of similar chain length led to well-ordered monolayers whereas the co-adsorption of MUA with shorter thiols yielded less crystalline-like thin films, but with more reactive carboxylic acid terminal groups. This criterion appeared decisive for efficient covalent binding of Staphylococcus aureus Protein A (PrA), a protein that displays high affinity for the constant fragment (Fc) of antibodies of the IgG type from various mammal species. The ability of immobilized Protein A to recognize and bind a model IgG appeared to be optimal for the mixed SAM of MUA and the short-chain, omega-hydroxythiol 6-mercaptohexanol in the proportion 1-3.

Linkages between the South and East Asian summer monsoons: a review and revisit

NASA Astrophysics Data System (ADS)

Ha, Kyung-Ja; Seo, Ye-Won; Lee, June-Yi; Kripalani, R. H.; Yun, Kyung-Sook

2017-07-01

The relationship between the South Asia monsoon (SAM) and the East Asia monsoon (EAM) possibly modulated by both external forcings and internal dynamics has been a long-standing and controversial issue in climate sciences. This study reviews their linkages as revealed in modern records and model simulations during the past, present and future, and provides a comprehensive explanation of the key mechanisms controlling the diversity of the SAM-EAM relationship. Particular attention is paid to several external forcings that modulate the relationship, including El Niño and Southern Oscillation, Indian Ocean Dipole mode (IODM), boreal summer teleconnections, and Eurasian snow extent on intraseasonal to interdecadal timescales. The major focus is placed on two integral views of the inter-connection between the two monsoon systems: one is the positive inter-correlation, which is associated with decaying El Niño and developing Indian Ocean sea surface temperature (SST) warming anomalies; the other is the negative inter-correlation, resulting from developing El Niño and western Pacific SST cooling. The IODM mode also has a delayed impact on the negative connection by modulating Eurasian snow cover. The observed evidence reveals that the recent intensification of the negative relationship is attributable to the strengthening of the zonal SST gradient along the Indian Ocean, western Pacific, and eastern Pacific. Analysis of experiments in the fifth phase of the Coupled Model Intercomparison Project further indicates a possibility for the negative linkage to be further enhanced under anthropogenic global warming with considerable interdecadal modulation in mid and late twenty-first century.

Electric-acoustic pitch comparisons in single-sided-deaf cochlear implant users: frequency-place functions and rate pitch.

PubMed

Schatzer, Reinhold; Vermeire, Katrien; Visser, Daniel; Krenmayr, Andreas; Kals, Mathias; Voormolen, Maurits; Van de Heyning, Paul; Zierhofer, Clemens

2014-03-01

Eight cochlear implant users with near-normal hearing in their non-implanted ear compared pitch percepts for pulsatile electric and acoustic pure-tone stimuli presented to the two ears. Six subjects were implanted with a 31-mm MED-EL FLEX(SOFT) electrode, and two with a 24-mm medium (M) electrode, with insertion angles of the most apical contacts ranging from 565° to 758°. In the first experiment, frequency-place functions were derived from pure-tone matches to 1500-pps unmodulated pulse trains presented to individual electrodes and compared to Greenwood's frequency position map along the organ of Corti. While the overall median downward shift of the obtained frequency-place functions (-0.16 octaves re. Greenwood) and the mean shifts in the basal (<240°; -0.33 octaves) and middle (-0.35 octaves) regions were statistically significant, the shift in the apical region (>480°; 0.26 octaves) was not. Standard deviations of frequency-place functions were approximately half an octave at electrode insertion angles below 480°, increasing to an octave at higher angular locations while individual functions were gradually leveling off. In a second experiment, subjects matched the rates of unmodulated pulse trains presented to individual electrodes in the apical half of the array to low-frequency pure tones between 100 Hz and 450 Hz. The aim was to investigate the influence of electrode place on the salience of temporal pitch cues, for coding strategies that present temporal fine structure information via rate modulations on select apical channels. Most subjects achieved reliable matches to tone frequencies from 100 Hz to 300 Hz only on electrodes at angular insertion depths beyond 360°, while rate-matches to 450-Hz tones were primarily achieved on electrodes at shallower insertion angles. Only for electrodes in the second turn the average slopes of rate-pitch functions did not differ significantly from the pure-tone references, suggesting their use for the encoding of within-channel fine frequency information via rate modulations in temporal fine structure stimulation strategies. Copyright © 2013 Elsevier B.V. All rights reserved.

Distributional Learning of Lexical Tones: A Comparison of Attended vs. Unattended Listening.

PubMed

Ong, Jia Hoong; Burnham, Denis; Escudero, Paola

2015-01-01

This study examines whether non-tone language listeners can acquire lexical tone categories distributionally and whether attention in the training phase modulates the effect of distributional learning. Native Australian English listeners were trained on a Thai lexical tone minimal pair and their performance was assessed using a discrimination task before and after training. During Training, participants either heard a Unimodal distribution that would induce a single central category, which should hinder their discrimination of that minimal pair, or a Bimodal distribution that would induce two separate categories that should facilitate their discrimination. The participants either heard the distribution passively (Experiments 1A and 1B) or performed a cover task during training designed to encourage auditory attention to the entire distribution (Experiment 2). In passive listening (Experiments 1A and 1B), results indicated no effect of distributional learning: the Bimodal group did not outperform the Unimodal group in discriminating the Thai tone minimal pairs. Moreover, both Unimodal and Bimodal groups improved above chance on most test aspects from Pretest to Posttest. However, when participants' auditory attention was encouraged using the cover task (Experiment 2), distributional learning was found: the Bimodal group outperformed the Unimodal group on a novel test syllable minimal pair at Posttest relative to at Pretest. Furthermore, the Bimodal group showed above-chance improvement from Pretest to Posttest on three test aspects, while the Unimodal group only showed above-chance improvement on one test aspect. These results suggest that non-tone language listeners are able to learn lexical tones distributionally but only when auditory attention is encouraged in the acquisition phase. This implies that distributional learning of lexical tones is more readily induced when participants attend carefully during training, presumably because they are better able to compute the relevant statistics of the distribution.

Distributional Learning of Lexical Tones: A Comparison of Attended vs. Unattended Listening

PubMed Central

Ong, Jia Hoong; Burnham, Denis; Escudero, Paola

2015-01-01

This study examines whether non-tone language listeners can acquire lexical tone categories distributionally and whether attention in the training phase modulates the effect of distributional learning. Native Australian English listeners were trained on a Thai lexical tone minimal pair and their performance was assessed using a discrimination task before and after training. During Training, participants either heard a Unimodal distribution that would induce a single central category, which should hinder their discrimination of that minimal pair, or a Bimodal distribution that would induce two separate categories that should facilitate their discrimination. The participants either heard the distribution passively (Experiments 1A and 1B) or performed a cover task during training designed to encourage auditory attention to the entire distribution (Experiment 2). In passive listening (Experiments 1A and 1B), results indicated no effect of distributional learning: the Bimodal group did not outperform the Unimodal group in discriminating the Thai tone minimal pairs. Moreover, both Unimodal and Bimodal groups improved above chance on most test aspects from Pretest to Posttest. However, when participants’ auditory attention was encouraged using the cover task (Experiment 2), distributional learning was found: the Bimodal group outperformed the Unimodal group on a novel test syllable minimal pair at Posttest relative to at Pretest. Furthermore, the Bimodal group showed above-chance improvement from Pretest to Posttest on three test aspects, while the Unimodal group only showed above-chance improvement on one test aspect. These results suggest that non-tone language listeners are able to learn lexical tones distributionally but only when auditory attention is encouraged in the acquisition phase. This implies that distributional learning of lexical tones is more readily induced when participants attend carefully during training, presumably because they are better able to compute the relevant statistics of the distribution. PMID:26214002

Module 1: Text Versions | State, Local, and Tribal Governments | NREL

Science.gov Websites

local government solar project portal. The link is there on the right, and you can see a screen shot , when we talk about SAM, we're really talking about combining two different things together - one is a power, biomass, combustion power, and solar water heating - so, that's one that comes along with these

Educational Software for Interactive Training of Students on the Theme "Mutual Intersecting of Pyramids and Prisms in Axonometry"

ERIC Educational Resources Information Center

Karaibryamov, Samet; Tsareva, Bistra; Zlatanov, Boyan

2012-01-01

This work acquaints with the program Sam for interactive computer training of students on the theme "Mutual intersecting of pyramids and prisms in axonometry". The program containing three modules--teacher, student and autopilot--allows for briefest time to teach and study the whole variety of the tasks on this theme. A classification of…

Striding Towards Better Physical Therapy

NASA Technical Reports Server (NTRS)

2003-01-01

This paper presents a discussion on a new rehabilitative device that promises to improve physical therapy for patients working to regain the ability to walk after facing traumatic injuries or a degenerative illness. Produced by Enduro Medical Technology, of East Hartford, Connecticut, the Secure Ambulation Module (S.A.M.) creates a stable and secure environment for patients as they stand during ambulation therapy.

Multiple polymer architectures of human Polyhomeotic homolog 3 (PHC3) SAM

PubMed Central

Nanyes, David R.; Junco, Sarah E.; Taylor, Alexander B.; Robinson, Angela K.; Patterson, Nicolle L.; Shivarajpur, Ambika; Halloran, Jonathan; Hale, Seth M.; Kaur, Yogeet; Hart, P. John; Kim, Chongwoo A.

2014-01-01

The self-association of sterile alpha motifs (SAMs) into a helical polymer architecture is a critical functional component of many different and diverse array of proteins. For the Drosophila Polycomb group (PcG) protein Polyhomeotic (Ph), its SAM polymerization serves as the structural foundation to cluster multiple PcG complexes, helping to maintain a silenced chromatin state. Ph SAM shares 64% sequence identity with its human ortholog, PHC3 SAM, and both SAMs polymerize. However, in the context of their larger protein regions, PHC3 SAM forms longer polymers compared to Ph SAM. Motivated to establish the precise structural basis for the differences, if any, between Ph and PHC3 SAM, we determined the crystal structure of the PHC3 SAM polymer. PHC3 SAM utilizes the same SAM-SAM interaction as the Ph SAM six-fold repeat polymer. Yet, PHC3 SAM polymerizes utilizing just five SAMs per turn of the helical polymer rather than the typical six per turn observed for all SAM polymers reported to date. Structural analysis suggested that malleability of the PHC3 SAM would allow formation of not just the five-fold repeat structure but possibly others. Indeed, a second PHC3 SAM polymer in a different crystal form forms a six-fold repeat polymer. These results suggest that the polymers formed by PHC3 SAM, and likely others, are quite dynamic. The functional consequence of the variable PHC3 SAM polymers may be to create different chromatin architectures. PMID:25044168

The Sam Domain of EphA2 Receptor and its Relevance to Cancer: A Novel Challenge for Drug Discovery?

PubMed

Mercurio, Flavia A; Leone, Marilisa

2016-01-01

Eph receptors play important functions in developmental processes and diseases and among them EphA2 is well known for its controversial role in cancer. Drug discovery strategies are mainly centered on EphA2 extracellular ligand-binding domain however, the receptor also contains a largely unexplored cytosolic Sam (Sterile alpha motif) domain at the C-terminus. EphA2-Sam binds the Sam domain from the lipid phosphatase Ship2 and the first Sam domain of Odin. Sam-Sam interactions may be important to regulate ligand-induced receptor endocytosis and degradation i.e., processes that could be engaged against tumor malignancy. We critically analyzed literature related to a) Eph receptors with particular emphasis on EphA2 and its role in cancer, b) Sam domains, c) heterotypic Sam-Sam interactions involving EphA2-Sam. While literature data indicate that binding of EphA2-Sam to Ship2-Sam should largely generate pro-oncogenic effects in cancer cells, the correlation between EphA2- Sam/Odin-Sam1 complex and the disease is unclear. Recently a few linear peptides encompassing binding interfaces from either Ship2-Sam and Odin-Sam1 have been characterized but failed to efficiently block heterotypic Sam-Sam interactions involving EphA2-Sam due to the lack of a native like fold. Molecule antagonists of heterotypic EphA2-Sam associations could work as potential anticancer agents or be implemented as tools to further clarify receptor functions and eventually validate its role as a novel target in the field of anti-cancer drug discovery. Due to the failure of linear peptides there is a crucial need for novel approaches, based on cyclic or helical molecules, to target Sam-Sam interfaces.

Is a High Tone Pointy? Speakers of Different Languages Match Mandarin Chinese Tones to Visual Shapes Differently

PubMed Central

Shang, Nan; Styles, Suzy J.

2017-01-01

Studies investigating cross-modal correspondences between auditory pitch and visual shapes have shown children and adults consistently match high pitch to pointy shapes and low pitch to curvy shapes, yet no studies have investigated linguistic-uses of pitch. In the present study, we used a bouba/kiki style task to investigate the sound/shape mappings for Tones of Mandarin Chinese, for three groups of participants with different language backgrounds. We recorded the vowels [i] and [u] articulated in each of the four tones of Mandarin Chinese. In Study 1 a single auditory stimulus was presented with two images (one curvy, one spiky). In Study 2 a single image was presented with two auditory stimuli differing only in tone. Participants were asked to select the best match in an online ‘Quiz.’ Across both studies, we replicated the previously observed ‘u-curvy, i-pointy’ sound/shape cross-modal correspondence in all groups. However, Tones were mapped differently by people with different language backgrounds: speakers of Mandarin Chinese classified as Chinese-dominant systematically matched Tone 1 (high, steady) to the curvy shape and Tone 4 (falling) to the pointy shape, while English speakers with no knowledge of Chinese preferred to match Tone 1 (high, steady) to the pointy shape and Tone 3 (low, dipping) to the curvy shape. These effects were observed most clearly in Study 2 where tone-pairs were contrasted explicitly. These findings are in line with the dominant patterns of linguistic pitch perception for speakers of these languages (pitch-change, and pitch height, respectively). Chinese English balanced bilinguals showed a bivalent pattern, swapping between the Chinese pitch-change pattern and the English pitch-height pattern depending on the task. These findings show for that the supposedly universal pattern of mapping linguistic sounds to shape is modulated by the sensory properties of a speaker’s language system, and that people with high functioning in more than one language can dynamically shift between patterns. PMID:29270147

Sex-dependent hemispheric asymmetries for processing frequency-modulated sounds in the primary auditory cortex of the mustached bat

PubMed Central

Washington, Stuart D.

2012-01-01

Species-specific vocalizations of mammals, including humans, contain slow and fast frequency modulations (FMs) as well as tone and noise bursts. In this study, we established sex-specific hemispheric differences in the tonal and FM response characteristics of neurons in the Doppler-shifted constant-frequency processing area in the mustached bat's primary auditory cortex (A1). We recorded single-unit cortical activity from the right and left A1 in awake bats in response to the presentation of tone bursts and linear FM sweeps that are contained within their echolocation and/or communication sounds. Peak response latencies to neurons' preferred or best FMs were significantly longer on the right compared with the left in both sexes, and in males this right-left difference was also present for the most excitatory tone burst. Based on peak response magnitudes, right hemispheric A1 neurons in males preferred low-rate, narrowband FMs, whereas those on the left were less selective, responding to FMs with a variety of rates and bandwidths. The distributions of parameters for best FMs in females were similar on the two sides. Together, our data provide the first strong physiological support of a sex-specific, spectrotemporal hemispheric asymmetry for the representation of tones and FMs in a nonhuman mammal. Specifically, our results demonstrate a left hemispheric bias in males for the representation of a diverse array of FMs differing in rate and bandwidth. We propose that these asymmetries underlie lateralized processing of communication sounds and are common to species as divergent as bats and humans. PMID:22649207

Toward transparent and self-activated graphene harmonic transponder sensors

NASA Astrophysics Data System (ADS)

Huang, Haiyu Harry; Sakhdari, Maryam; Hajizadegan, Mehdi; Shahini, Ali; Akinwande, Deji; Chen, Pai-Yen

2016-04-01

We propose the concept and design of a transparent, flexible, and self-powered wireless sensor comprising a graphene-based sensor/frequency-modulator circuitry and a graphene antenna. In this all-graphene device, the multilayered-graphene antenna receives the fundamental tone at C band and retransmits the frequency-modulated sensed signal (harmonic tone) at X band. The frequency orthogonality between the received/re-transmitted signals may enable high-performance sensing in severe interference/clutter background. Here, a fully passive, quad-ring frequency multiplier is proposed using graphene field-effect transistors, of which the unique ambipolar charge transports render a frequency doubling effect with conversion gain being chemically sensitive to exposed gas/molecular/chemical/infectious agents. This transparent, light-weight, and self-powered system may potentially benefit a number of wireless sensing and diagnosis applications, particularly for smart contact lenses/glasses and microscope slides that require high optical transparency.

Dimming-discrete-multi-tone (DMT) for simultaneous color control and high speed visible light communication.

PubMed

Sung, Jiun-Yu; Chow, Chi-Wai; Yeh, Chien-Hung

2014-04-07

Visible light communication (VLC) using LEDs has attracted significant attention recently for the future secure, license-free and electromagnetic-interference (EMI)-free optical wireless communication. Dimming technique in LED lamp is advantageous for energy efficiency. Color control can be performed in the red-green-blue (RGB) LEDs by using dimming technique. It is highly desirable to employ dimming technique to provide simultaneous color and dimming control and high speed VLC. Here, we proposed and demonstrated a LED dimming control using dimming-discrete-multi-tone (DMT) modulation. High speed DMT-based VLC with simultaneous color and dimming control is demonstrated for the first time to the best of our knowledge. Demonstration and analyses for several modulation conditions and transmission distances are performed, for instance, demonstrating the data rate of 103.5 Mb/s (using RGB LED) with fast Fourier transform (FFT) size of 512.

100 Gb/s optical discrete multi-tone transceivers for intra- and inter-datacenter networks

NASA Astrophysics Data System (ADS)

Okabe, Ryo; Tanaka, Toshiki; Nishihara, Masato; Kai, Yutaka; Takahara, Tomoo; Liu, Bo; Li, Lei; Tao, Zhenning; Rasmussen, Jens C.

2016-03-01

Discrete multi-tone (DMT) technology is an attractive modulation technology for short-reach application due to its high spectral efficiency and simple configuration. In this paper, we first explain the features of DMT technology then discuss the impact of fiber dispersion and chirp on the frequency responses of the DMT signal and the importance in the relationship between chirp and the optical transmission band. Next, we explain our experiments of 100-Gb/s DMT transmission of 10 km in the O-band using directly modulated lasers for low-cost application. In an inter-datacenter network of more than several tens of kilometers, fiber dispersion mainly limits system performance. We also discuss our experiment of 100-Gb/s DMT transmission up to 100 km in the C-band without a dispersion compensator by using vestigial sideband spectrum shaping and nonlinear compensation.

Doppler compensation by shifting transmitted object frequency within limits

NASA Technical Reports Server (NTRS)

Laughlin, C. R., Jr.; Hollenbaugh, R. C.; Allen, W. K. (Inventor)

1973-01-01

A system and method are disclosed for position locating, deriving centralized air traffic control data, and communicating via voice and digital signals between a multiplicity of remote aircraft, including supersonic transports, and a central station. Such communication takes place through a synchronous satellite relay station. Side tone ranging patterns, as well as the digital and voice signals, are modulated on a carrier transmitted from the central station and received on all of the supersonic transports. Each aircraft communicates with the ground stations via a different frequency multiplexed spectrum. Supersonic transport position is derived from a computer at the central station and supplied to a local air traffic controller. Position is determined in response to variable phase information imposed on the side tones at the aircrafts. Common to all of the side tone techniques is Doppler compensation for the supersonic transport velocity.

Cortical evoked potentials to an auditory illusion: binaural beats.

PubMed

Pratt, Hillel; Starr, Arnold; Michalewski, Henry J; Dimitrijevic, Andrew; Bleich, Naomi; Mittelman, Nomi

2009-08-01

To define brain activity corresponding to an auditory illusion of 3 and 6Hz binaural beats in 250Hz or 1000Hz base frequencies, and compare it to the sound onset response. Event-Related Potentials (ERPs) were recorded in response to unmodulated tones of 250 or 1000Hz to one ear and 3 or 6Hz higher to the other, creating an illusion of amplitude modulations (beats) of 3Hz and 6Hz, in base frequencies of 250Hz and 1000Hz. Tones were 2000ms in duration and presented with approximately 1s intervals. Latency, amplitude and source current density estimates of ERP components to tone onset and subsequent beats-evoked oscillations were determined and compared across beat frequencies with both base frequencies. All stimuli evoked tone-onset P(50), N(100) and P(200) components followed by oscillations corresponding to the beat frequency, and a subsequent tone-offset complex. Beats-evoked oscillations were higher in amplitude with the low base frequency and to the low beat frequency. Sources of the beats-evoked oscillations across all stimulus conditions located mostly to left lateral and inferior temporal lobe areas in all stimulus conditions. Onset-evoked components were not different across stimulus conditions; P(50) had significantly different sources than the beats-evoked oscillations; and N(100) and P(200) sources located to the same temporal lobe regions as beats-evoked oscillations, but were bilateral and also included frontal and parietal contributions. Neural activity with slightly different volley frequencies from left and right ear converges and interacts in the central auditory brainstem pathways to generate beats of neural activity to modulate activities in the left temporal lobe, giving rise to the illusion of binaural beats. Cortical potentials recorded to binaural beats are distinct from onset responses. Brain activity corresponding to an auditory illusion of low frequency beats can be recorded from the scalp.

Cortical Evoked Potentials to an Auditory Illusion: Binaural Beats

PubMed Central

Pratt, Hillel; Starr, Arnold; Michalewski, Henry J.; Dimitrijevic, Andrew; Bleich, Naomi; Mittelman, Nomi

2009-01-01

Objective: To define brain activity corresponding to an auditory illusion of 3 and 6 Hz binaural beats in 250 Hz or 1,000 Hz base frequencies, and compare it to the sound onset response. Methods: Event-Related Potentials (ERPs) were recorded in response to unmodulated tones of 250 or 1000 Hz to one ear and 3 or 6 Hz higher to the other, creating an illusion of amplitude modulations (beats) of 3 Hz and 6 Hz, in base frequencies of 250 Hz and 1000 Hz. Tones were 2,000 ms in duration and presented with approximately 1 s intervals. Latency, amplitude and source current density estimates of ERP components to tone onset and subsequent beats-evoked oscillations were determined and compared across beat frequencies with both base frequencies. Results: All stimuli evoked tone-onset P50, N100 and P200 components followed by oscillations corresponding to the beat frequency, and a subsequent tone-offset complex. Beats-evoked oscillations were higher in amplitude with the low base frequency and to the low beat frequency. Sources of the beats-evoked oscillations across all stimulus conditions located mostly to left lateral and inferior temporal lobe areas in all stimulus conditions. Onset-evoked components were not different across stimulus conditions; P50 had significantly different sources than the beats-evoked oscillations; and N100 and P200 sources located to the same temporal lobe regions as beats-evoked oscillations, but were bilateral and also included frontal and parietal contributions. Conclusions: Neural activity with slightly different volley frequencies from left and right ear converges and interacts in the central auditory brainstem pathways to generate beats of neural activity to modulate activities in the left temporal lobe, giving rise to the illusion of binaural beats. Cortical potentials recorded to binaural beats are distinct from onset responses. Significance: Brain activity corresponding to an auditory illusion of low frequency beats can be recorded from the scalp. PMID:19616993

Altered active but not passive properties of mesenteric resistance arteries from the vitamin E-deprived rat

PubMed Central

Davidge, Sandra T; Gandley, Robin E; McLaughlin, Margaret K

1998-01-01

We tested the hypothesis that lowering antioxidant protection through dietary vitamin E deprivation would alter active and passive mechanical properties in resistance arteries of the rat. Specifically, we hypothesized that vascular tone in isolated mesenteric arteries of the vitamin E-deprived rats would be altered due to impaired endothelial influences of nitric oxide and/or prostaglandins.Lumen diameter and wall thickness were measured in pressurized arteries (≈amp;250 μm diameter) from control (n=9) and vitamin E deprived (n=9) Sprague-Dawley female rats by use of a dimension analysing system.Treatment with a cyclo-oxygenase inhibitor (meclofenamate) did not affect the basal vascular tone in either group. Treatment with a nitric oxide synthase inhibitor (NG-methyl-L-arginine) caused a significant increase in basal tone only in the vitamin E-deprived rats (% tone: 6.2±1.1 vs 1.2±0.3%; P<0.05). When tone was induced to 25% of the initial diameter with phenylephrine, treatment with the nitric oxide synthase inhibitor resulted in a greater potentiated tone in the vitamin E-deprived rats compared to the controls (26.5±2.7 vs 16.4±3.4%; P<0.05); suggesting a greater nitric oxide affect in the vessels from the vitamin E-deprived rats. Meclofenamate treatment in the induced tone arteries significantly relaxed (−17.4±4.0%; P<0.05) only the arteries from the vitamin E-deprived rats, indicating that a vasoconstrictor was modifying tone. The passive characteristics of distensibility and stress-strain relationship were not different between the two groups of rats.In summary, vitamin E deprivation in the rat enhanced the modulation of vascular tone by both the nitric oxide and cyclo-oxygenase pathways but did not alter passive characteristics of mesenteric arteries. PMID:9489616

Neural coding of time-varying interaural time differences and time-varying amplitude in the inferior colliculus

PubMed Central

2017-01-01

Binaural cues occurring in natural environments are frequently time varying, either from the motion of a sound source or through interactions between the cues produced by multiple sources. Yet, a broad understanding of how the auditory system processes dynamic binaural cues is still lacking. In the current study, we directly compared neural responses in the inferior colliculus (IC) of unanesthetized rabbits to broadband noise with time-varying interaural time differences (ITD) with responses to noise with sinusoidal amplitude modulation (SAM) over a wide range of modulation frequencies. On the basis of prior research, we hypothesized that the IC, one of the first stages to exhibit tuning of firing rate to modulation frequency, might use a common mechanism to encode time-varying information in general. Instead, we found weaker temporal coding for dynamic ITD compared with amplitude modulation and stronger effects of adaptation for amplitude modulation. The differences in temporal coding of dynamic ITD compared with SAM at the single-neuron level could be a neural correlate of “binaural sluggishness,” the inability to perceive fluctuations in time-varying binaural cues at high modulation frequencies, for which a physiological explanation has so far remained elusive. At ITD-variation frequencies of 64 Hz and above, where a temporal code was less effective, noise with a dynamic ITD could still be distinguished from noise with a constant ITD through differences in average firing rate in many neurons, suggesting a frequency-dependent tradeoff between rate and temporal coding of time-varying binaural information. NEW & NOTEWORTHY Humans use time-varying binaural cues to parse auditory scenes comprising multiple sound sources and reverberation. However, the neural mechanisms for doing so are poorly understood. Our results demonstrate a potential neural correlate for the reduced detectability of fluctuations in time-varying binaural information at high speeds, as occurs in reverberation. The results also suggest that the neural mechanisms for processing time-varying binaural and monaural cues are largely distinct. PMID:28381487

Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions

PubMed Central

Intskirveli, Irakli

2017-01-01

Abstract Nicotine enhances sensory and cognitive processing via actions at nicotinic acetylcholine receptors (nAChRs), yet the precise circuit- and systems-level mechanisms remain unclear. In sensory cortex, nicotinic modulation of receptive fields (RFs) provides a model to probe mechanisms by which nAChRs regulate cortical circuits. Here, we examine RF modulation in mouse primary auditory cortex (A1) using a novel electrophysiological approach: current-source density (CSD) analysis of responses to tone-in-notched-noise (TINN) acoustic stimuli. TINN stimuli consist of a tone at the characteristic frequency (CF) of the recording site embedded within a white noise stimulus filtered to create a spectral “notch” of variable width centered on CF. Systemic nicotine (2.1 mg/kg) enhanced responses to the CF tone and to narrow-notch stimuli, yet reduced the response to wider-notch stimuli, indicating increased response gain within a narrowed RF. Subsequent manipulations showed that modulation of cortical RFs by systemic nicotine reflected effects at several levels in the auditory pathway: nicotine suppressed responses in the auditory midbrain and thalamus, with suppression increasing with spectral distance from CF so that RFs became narrower, and facilitated responses in the thalamocortical pathway, while nicotinic actions within A1 further contributed to both suppression and facilitation. Thus, multiple effects of systemic nicotine integrate along the ascending auditory pathway. These actions at nAChRs in cortical and subcortical circuits, which mimic effects of auditory attention, likely contribute to nicotinic enhancement of sensory and cognitive processing. PMID:28660244

Systemic Nicotine Increases Gain and Narrows Receptive Fields in A1 via Integrated Cortical and Subcortical Actions.

PubMed

Askew, Caitlin; Intskirveli, Irakli; Metherate, Raju

2017-01-01

Nicotine enhances sensory and cognitive processing via actions at nicotinic acetylcholine receptors (nAChRs), yet the precise circuit- and systems-level mechanisms remain unclear. In sensory cortex, nicotinic modulation of receptive fields (RFs) provides a model to probe mechanisms by which nAChRs regulate cortical circuits. Here, we examine RF modulation in mouse primary auditory cortex (A1) using a novel electrophysiological approach: current-source density (CSD) analysis of responses to tone-in-notched-noise (TINN) acoustic stimuli. TINN stimuli consist of a tone at the characteristic frequency (CF) of the recording site embedded within a white noise stimulus filtered to create a spectral "notch" of variable width centered on CF. Systemic nicotine (2.1 mg/kg) enhanced responses to the CF tone and to narrow-notch stimuli, yet reduced the response to wider-notch stimuli, indicating increased response gain within a narrowed RF. Subsequent manipulations showed that modulation of cortical RFs by systemic nicotine reflected effects at several levels in the auditory pathway: nicotine suppressed responses in the auditory midbrain and thalamus, with suppression increasing with spectral distance from CF so that RFs became narrower, and facilitated responses in the thalamocortical pathway, while nicotinic actions within A1 further contributed to both suppression and facilitation. Thus, multiple effects of systemic nicotine integrate along the ascending auditory pathway. These actions at nAChRs in cortical and subcortical circuits, which mimic effects of auditory attention, likely contribute to nicotinic enhancement of sensory and cognitive processing.

The influence of tone inventory on ERP without focal attention: a cross-language study.

PubMed

Zheng, Hong-Ying; Peng, Gang; Chen, Jian-Yong; Zhang, Caicai; Minett, James W; Wang, William S-Y

2014-01-01

This study investigates the effect of tone inventories on brain activities underlying pitch without focal attention. We find that the electrophysiological responses to across-category stimuli are larger than those to within-category stimuli when the pitch contours are superimposed on nonspeech stimuli; however, there is no electrophysiological response difference associated with category status in speech stimuli. Moreover, this category effect in nonspeech stimuli is stronger for Cantonese speakers. Results of previous and present studies lead us to conclude that brain activities to the same native lexical tone contrasts are modulated by speakers' language experiences not only in active phonological processing but also in automatic feature detection without focal attention. In contrast to the condition with focal attention, where phonological processing is stronger for speech stimuli, the feature detection (pitch contours in this study) without focal attention as shaped by language background is superior in relatively regular stimuli, that is, the nonspeech stimuli. The results suggest that Cantonese listeners outperform Mandarin listeners in automatic detection of pitch features because of the denser Cantonese tone system.

Results using the OPAL strategy in Mandarin speaking cochlear implant recipients.

PubMed

Vandali, Andrew E; Dawson, Pam W; Arora, Komal

2017-01-01

To evaluate the effectiveness of an experimental pitch-coding strategy for improving recognition of Mandarin lexical tone in cochlear implant (CI) recipients. Adult CI recipients were tested on recognition of Mandarin tones in quiet and speech-shaped noise at a signal-to-noise ratio of +10 dB; Mandarin sentence speech-reception threshold (SRT) in speech-shaped noise; and pitch discrimination of synthetic complex-harmonic tones in quiet. Two versions of the experimental strategy were examined: (OPAL) linear (1:1) mapping of fundamental frequency (F0) to the coded modulation rate; and (OPAL+) transposed mapping of high F0s to a lower coded rate. Outcomes were compared to results using the clinical ACE™ strategy. Five Mandarin speaking users of Nucleus® cochlear implants. A small but significant benefit in recognition of lexical tones was observed using OPAL compared to ACE in noise, but not in quiet, and not for OPAL+ compared to ACE or OPAL in quiet or noise. Sentence SRTs were significantly better using OPAL+ and comparable using OPAL to those using ACE. No differences in pitch discrimination thresholds were observed across strategies. OPAL can provide benefits to Mandarin lexical tone recognition in moderately noisy conditions and preserve perception of Mandarin sentences in challenging noise conditions.

Effects of Posture and Stimulus Spectral Composition on Peripheral Physiological Responses to Loud Sounds

PubMed Central

Koch, Jennifer; Flemming, Jan; Zeffiro, Thomas; Rufer, Michael; Orr, Scott P.; Mueller-Pfeiffer, Christoph

2016-01-01

In the “loud-tone” procedure, a series of brief, loud, pure-tone stimuli are presented in a task-free situation. It is an established paradigm for measuring autonomic sensitization in posttraumatic stress disorder (PTSD). Successful use of this procedure during fMRI requires elicitation of brain responses that have sufficient signal-noise ratios when recorded in a supine, rather than sitting, position. We investigated the modulating effects of posture and stimulus spectral composition on peripheral psychophysiological responses to loud sounds. Healthy subjects (N = 24) weekly engaged in a loud-tone-like procedure that presented 500 msec, 95 dB sound pressure level, pure-tone or white-noise stimuli, either while sitting or supine and while peripheral physiological responses were recorded. Heart rate, skin conductance, and eye blink electromyographic responses were larger to white-noise than pure-tone stimuli (p’s < 0.001, generalized eta squared 0.073–0.076). Psychophysiological responses to the stimuli were similar in the sitting and supine position (p’s ≥ 0.082). Presenting white noise, rather than pure-tone, stimuli may improve the detection sensitivity of the neural concomitants of heightened autonomic responses by generating larger responses. Recording in the supine position appears to have little or no impact on psychophysiological response magnitudes to the auditory stimuli. PMID:27583659

MO-F-16A-03: AAPM Online Learning Support of New ABR MOC Requirements

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

Bloch, C; Ogburn, J; Woodward, M

2014-06-15

In 2002 the American Board of Radiology (ABR) discontinued issuing lifetime board certification. After that time diplomates received a timelimited certificate and must participate in the Maintenance of Certification (MOC) program in order to maintain their certification. Initially certificates were issued with a 10 year expiration period and the MOC had requirements to be met over that 10 year period. The goal was to demonstrate continuous maintenance of clinical competency, however some diplomates were attempting to fulfill most or all of the requirements near the end of the 10 year period. This failed to meet the continuous aspect of themore » goal and so the ABR changed to a sliding 3-year window. This was done to recognize that not every year would be the same, but that diplomates should be able to maintain a reasonable average over any 3 year period.A second significant change occurred in 2013. The initial requirements included 20 selfassessment modules (SAMs) over the original 10 year term. SAMs are a special type of continuing education (CE) credit that were an addition to the 250 standard CE credits required over the 10 year period. In 2013, however, the new requirement is 75 CE credits over the previous 3 years, of which 25 must include self-assessment. Effectively this raised the self-assessment requirement from 20 in 10 years to 25 in 3 years. Previously SAMs were an interactive presentation available in limited quantities at live meetings. However, the new requirement is not for SAMs but CE-SA which includes SAMs, but also includes the online quizzes provided at the AAPM online learning center. All credits earned at the AAPM online learning center fulfill the ABR SA requirement.This talk will be an interactive demonstration of the AAPM online learning center along with a discussion of the MOC requirements.« less

ELF/VLF Wave Generation via HF Modulation of the Equatorial Electrojet at Arecibo Observatory

NASA Astrophysics Data System (ADS)

Flint, Q. A.; Moore, R. C.; Burch, H.; Erdman, A.; Wilkes, R.

2017-12-01

In this work we generate ELF/VLF waves by modulating the conductivity of the lower ionosphere using the HF heater at Arecibo. For many years, researchers have generated ELF/VLF waves using the powerful HF transmitters at HAARP, but few have attempted to do the same in the mid- to low- latitude region. While HAARP users have benefitted from the auroral electrojet, we attempt to exploit the equatorial electrojet to generate radio waves. On 31 July 2017, we transmitted at an HF frequency of 5.1 MHz (X-Mode) applying sinusoidal amplitude modulation in a step-like fashion from 0-5 kHz in 200 Hz steps over 10 seconds at 100% peak power to approximate a linear frequency ramp. We also transmitted 10-second-long fixed frequency tones spaced from 1 to 5 kHz. The frequency sweep is a helpful visual tool to identify generated waves, but is also used to determine optimal modulation frequencies for future campaigns. The tones allow us to perform higher SNR analysis. Ground-based B-field VLF receivers recorded the amplitude and phase of the generated radio waves. We employ time-of-arrival techniques to determine the altitude of the ELF/VLF signal source. In this paper, we present the initial analysis of these experimental results.

DNA adenine methylation of sams1 gene in symbiont-bearing Amoeba proteus.

PubMed

Jeon, Taeck J

2008-10-01

The expression of amoeba sams genes is switched from sams1 to sams2 when amoebae are infected with Legionella jeonii. To elucidate the mechanism for the inactivation of host sams1 gene by endosymbiotic bacteria, methylation states of the sams1 gene of D and xD amoebae was compared in this study. The sams1 gene of amoebae was methylated at an internal adenine residue of GATC site in symbiont-bearing xD amoebae but not in symbiont-free D amoebae, suggesting that the modification might have caused the inactivation of sams1 in xD amoebae. The sams1 gene of xD amoebae was inactivated at the transcriptional level. Analysis of DNA showed that adenine residues in L. jeonii sams were also methylated, implying that L. jeonii bacteria belong to a Dam methylase-positive strain. In addition, both SAM and Met appeared to act as negative regulators for the expression of sams1 whereas the expression of sams2 was not affected in amoebae.

Atomic-level insights into metabolite recognition and specificity of the SAM-II riboswitch.

PubMed

Doshi, Urmi; Kelley, Jennifer M; Hamelberg, Donald

2012-02-01

Although S-adenosylhomocysteine (SAH), a metabolic by-product of S-adenosylmethionine (SAM), differs from SAM only by a single methyl group and an overall positive charge, SAH binds the SAM-II riboswitch with more than 1000-fold less affinity than SAM. Using atomistic molecular dynamics simulations, we investigated the molecular basis of such high selectivity in ligand recognition by SAM-II riboswitch. The biosynthesis of SAM exclusively generates the (S,S) stereoisomer, and (S,S)-SAM can spontaneously convert to the (R,S) form. We, therefore, also examined the effects of (R,S)-SAM binding to SAM-II and its potential biological function. We find that the unfavorable loss in entropy in SAM-II binding is greater for (S,S)- and (R,S)-SAM than SAH, which is compensated by stabilizing electrostatic interactions with the riboswitch. The positively charged sulfonium moiety on SAM acts as the crucial anchor point responsible for the formation of key ionic interactions as it fits favorably in the negatively charged binding pocket. In contrast, SAH, with its lone pair of electrons on the sulfur, experiences repulsion in the binding pocket of SAM-II and is enthalpically destabilized. In the presence of SAH, similar to the unbound riboswitch, the pseudoknot structure of SAM-II is not completely formed, thus exposing the Shine-Dalgarno sequence. Unlike SAM, this may further facilitate ribosomal assembly and translation initiation. Our analysis of the conformational ensemble sampled by SAM-II in the absence of ligands and when bound to SAM or SAH reveals that ligand binding follows a combination of conformational selection and induced-fit mechanisms.

Interface engineering of semiconductor/dielectric heterojunctions toward functional organic thin-film transistors.

PubMed

Zhang, Hongtao; Guo, Xuefeng; Hui, Jingshu; Hu, Shuxin; Xu, Wei; Zhu, Daoben

2011-11-09

Interface modification is an effective and promising route for developing functional organic field-effect transistors (OFETs). In this context, however, researchers have not created a reliable method of functionalizing the interfaces existing in OFETs, although this has been crucial for the technological development of high-performance CMOS circuits. Here, we demonstrate a novel approach that enables us to reversibly photocontrol the carrier density at the interface by using photochromic spiropyran (SP) self-assembled monolayers (SAMs) sandwiched between active semiconductors and gate insulators. Reversible changes in dipole moment of SPs in SAMs triggered by lights with different wavelengths produce two distinct built-in electric fields on the OFET that can modulate the channel conductance and consequently threshold voltage values, thus leading to a low-cost noninvasive memory device. This concept of interface functionalization offers attractive new prospects for the development of organic electronic devices with tailored electronic and other properties.

75 FR 56147 - Notice of Permits Issued Under the Antarctic Conservation Act of 1978

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-15

... received. Permits were issued on September 9, 2010 to: Sam Feola Permit No. 2011-009. Sam Feola Permit No. 2011-010. Sam Feola Permit No. 2011-011. Sam Feola Permit No. 2011-012. Sam Feola Permit No. 2011-013. Sam Feola Permit No. 2011-014. Sam Feola Permit No. 2011-015. Nadene G. Kennedy, Permit Officer. [FR...

Effects of sound intensity on temporal properties of inhibition in the pallid bat auditory cortex.

PubMed

Razak, Khaleel A

2013-01-01

Auditory neurons in bats that use frequency modulated (FM) sweeps for echolocation are selective for the behaviorally-relevant rates and direction of frequency change. Such selectivity arises through spectrotemporal interactions between excitatory and inhibitory components of the receptive field. In the pallid bat auditory system, the relationship between FM sweep direction/rate selectivity and spectral and temporal properties of sideband inhibition have been characterized. Of note is the temporal asymmetry in sideband inhibition, with low-frequency inhibition (LFI) exhibiting faster arrival times compared to high-frequency inhibition (HFI). Using the two-tone inhibition over time (TTI) stimulus paradigm, this study investigated the interactions between two sound parameters in shaping sideband inhibition: intensity and time. Specifically, the impact of changing relative intensities of the excitatory and inhibitory tones on arrival time of inhibition was studied. Using this stimulation paradigm, single unit data from the auditory cortex of pentobarbital-anesthetized cortex show that the threshold for LFI is on average ~8 dB lower than HFI. For equal intensity tones near threshold, LFI is stronger than HFI. When the inhibitory tone intensity is increased further from threshold, the strength asymmetry decreased. The temporal asymmetry in LFI vs. HFI arrival time is strongest when the excitatory and inhibitory tones are of equal intensities or if excitatory tone is louder. As inhibitory tone intensity is increased, temporal asymmetry decreased suggesting that the relative magnitude of excitatory and inhibitory inputs shape arrival time of inhibition and FM sweep rate and direction selectivity. Given that most FM bats use downward sweeps as echolocation calls, a similar asymmetry in threshold and strength of LFI vs. HFI may be a general adaptation to enhance direction selectivity while maintaining sweep-rate selective responses to downward sweeps.

Effects of nifedipine on anorectal smooth muscle in vitro.

PubMed

Cook, T A; Brading, A F; Mortensen, N J

1999-06-01

Glyceryl trinitrate reduces anal resting pressure and aids the healing of anal fissures. However, some patients develop tachyphylaxis and the fissure fails to heal, suggesting that other agents are needed. This study assesses the effects of nifedipine (a calcium channel antagonist) in modulating resting tone and agonist-induced contractions in human internal anal sphincter (IAS) and rectal circular muscle. Smooth muscle strips from the IAS and rectal circular muscle from ten patients undergoing surgical resection were mounted for isometric tension recording in a superfusion organ bath. The effects of noradrenaline and carbachol were assessed in the presence of various perfusates. LAS strips developed tone and spontaneous activity. Noradrenaline produced dose-dependent contractions. In calcium-free Krebs solution, tone and activity were abolished and no contractions were elicited in response to noradrenaline. Nifedipine also abolished tone and spontaneous activity, but contractions to noradrenaline were only slightly attenuated. In contrast, rectal smooth muscle strips developed spontaneous activity but no resting tone and contracted in response to carbachol. In calcium-free Krebs solution, the spontaneous activity and carbachol contractions were abolished. Addition of nifedipine to the perfusate abolished spontaneous activity and greatly reduced contractions. These data suggest that spontaneous activity and resting tone are dependent on extracellular calcium and flux across the cells. Agonist-induced contraction in the IAS is attributable mainly to the release of calcium from intracellular stores, whereas rectal circular smooth muscle depends principally on extracellular calcium entering the cell for contraction. The attenuation of contractions in both tissues and the abolition of resting tone in the IAS suggest that nifedipine may be useful in the management of patients with anorectal disorders.

Atomic-level insights into metabolite recognition and specificity of the SAM-II riboswitch

PubMed Central

Doshi, Urmi; Kelley, Jennifer M.; Hamelberg, Donald

2012-01-01

Although S-adenosylhomocysteine (SAH), a metabolic by-product of S-adenosylmethionine (SAM), differs from SAM only by a single methyl group and an overall positive charge, SAH binds the SAM-II riboswitch with more than 1000-fold less affinity than SAM. Using atomistic molecular dynamics simulations, we investigated the molecular basis of such high selectivity in ligand recognition by SAM-II riboswitch. The biosynthesis of SAM exclusively generates the (S,S) stereoisomer, and (S,S)-SAM can spontaneously convert to the (R,S) form. We, therefore, also examined the effects of (R,S)-SAM binding to SAM-II and its potential biological function. We find that the unfavorable loss in entropy in SAM-II binding is greater for (S,S)- and (R,S)-SAM than SAH, which is compensated by stabilizing electrostatic interactions with the riboswitch. The positively charged sulfonium moiety on SAM acts as the crucial anchor point responsible for the formation of key ionic interactions as it fits favorably in the negatively charged binding pocket. In contrast, SAH, with its lone pair of electrons on the sulfur, experiences repulsion in the binding pocket of SAM-II and is enthalpically destabilized. In the presence of SAH, similar to the unbound riboswitch, the pseudoknot structure of SAM-II is not completely formed, thus exposing the Shine-Dalgarno sequence. Unlike SAM, this may further facilitate ribosomal assembly and translation initiation. Our analysis of the conformational ensemble sampled by SAM-II in the absence of ligands and when bound to SAM or SAH reveals that ligand binding follows a combination of conformational selection and induced-fit mechanisms. PMID:22194311

Some considerations on the vibrational environment of the DSC-DCMIX1 experiment onboard ISS

NASA Astrophysics Data System (ADS)

Jurado, R.; Gavaldà, Jna.; Simón, M. J.; Pallarés, J.; Laverón-Simavilla, A.; Ruiz, X.; Shevtsova, V.

2016-12-01

The present work attempts to characterize the accelerometric environment of the DSC-DCMIX1 thermodiffusion experiment carried out in the International Space Station, from November 7th 2011 until January 16th 2012. Quasi-steady and vibrational/transient data coming from MAMS and SAMS2 sensors have been downloaded from the database of the PIMS NASA website. To be as exhaustive as possible, simultaneous digital signals coming from different SAMS2 sensors located in the Destiny and Columbus modules have also been considered. In order to detect orbital adjustments, dockings, undockings, as well as, quiescent periods, when the experiment runs were active, we have used the quasi-steady eight hours averaged (XA, YA and ZA) acceleration functions as well as the eight hours RMS ones. To determine the spectral contents of the different signals the Thomson multitaper and Welch methods have been used. On the other hand, to suppress the high levels of noise always existing in the raw SAMS2 signals, denoising techniques have been preferred for comparative reboostings considerations. Finally, the RMS values for specific 1/3 octave frequency bands showed that the International Space Station vibratory limit requirements have not been totally accomplished during both quiescent periods and strong disturbances, specially in the low frequency range.

The effect of synesthetic associations between the visual and auditory modalities on the Colavita effect.

PubMed

Stekelenburg, Jeroen J; Keetels, Mirjam

2016-05-01

The Colavita effect refers to the phenomenon that when confronted with an audiovisual stimulus, observers report more often to have perceived the visual than the auditory component. The Colavita effect depends on low-level stimulus factors such as spatial and temporal proximity between the unimodal signals. Here, we examined whether the Colavita effect is modulated by synesthetic congruency between visual size and auditory pitch. If the Colavita effect depends on synesthetic congruency, we expect a larger Colavita effect for synesthetically congruent size/pitch (large visual stimulus/low-pitched tone; small visual stimulus/high-pitched tone) than synesthetically incongruent (large visual stimulus/high-pitched tone; small visual stimulus/low-pitched tone) combinations. Participants had to identify stimulus type (visual, auditory or audiovisual). The study replicated the Colavita effect because participants reported more often the visual than auditory component of the audiovisual stimuli. Synesthetic congruency had, however, no effect on the magnitude of the Colavita effect. EEG recordings to congruent and incongruent audiovisual pairings showed a late frontal congruency effect at 400-550 ms and an occipitoparietal effect at 690-800 ms with neural sources in the anterior cingulate and premotor cortex for the 400- to 550-ms window and premotor cortex, inferior parietal lobule and the posterior middle temporal gyrus for the 690- to 800-ms window. The electrophysiological data show that synesthetic congruency was probably detected in a processing stage subsequent to the Colavita effect. We conclude that-in a modality detection task-the Colavita effect can be modulated by low-level structural factors but not by higher-order associations between auditory and visual inputs.

Characterization of sams genes of Amoeba proteus and the endosymbiotic X-bacteria.

PubMed

Jeon, Taeck J; Jeon, Kwang W

2003-01-01

As a result of harboring obligatory bacterial endosymbionts, the xD strain of Amoeba proteus no longer produces its own S-adenosylmethionine synthetase (SAMS). When symbiont-free D amoebae are infected with symbionts (X-bacteria), the amount of amoeba SAMS decreases to a negligible level within four weeks, but about 47% of the SAMS activity, which apparently comes from another source, is still detected. Complete nucleotide sequences of sams genes of D and xD amoebae are presented and show that there are no differences between the two. Long-established xD amoebae contain an intact sams gene and thus the loss of xD amoeba's SAMS is not due to the loss of the gene itself. The open reading frame of the amoeba's sams gene has 1,281 nucleotides, encoding SAMS of 426 amino acids with a mass of 48 kDa and pI of 6.5. The amino acid sequence of amoeba SAMS is longer than the SAMS of other organisms by having an extra internal stretch of 28 amino acids. The 5'-flanking region of amoeba sams contains consensus-binding sites for several transcription factors that are related to the regulation of sams genes in E. coli and yeast. The complete nucleotide sequence of the symbiont's sams gene is also presented. The open reading frame of X-bacteria sams is 1,146 nucleotides long, encoding SAMS of 381 amino acids with a mass of 41 kDa and pI of 6.0. The X-bacteria SAMS has 45% sequence identity with that of A. proteus.

The Sam-Sam interaction between Ship2 and the EphA2 receptor: design and analysis of peptide inhibitors.

PubMed

Mercurio, Flavia Anna; Di Natale, Concetta; Pirone, Luciano; Iannitti, Roberta; Marasco, Daniela; Pedone, Emilia Maria; Palumbo, Rosanna; Leone, Marilisa

2017-12-12

The lipid phosphatase Ship2 represents a drug discovery target for the treatment of different diseases, including cancer. Its C-terminal sterile alpha motif domain (Ship2-Sam) associates with the Sam domain from the EphA2 receptor (EphA2-Sam). This interaction is expected to mainly induce pro-oncogenic effects in cells therefore, inhibition of the Ship2-Sam/EphA2-Sam complex may represent an innovative route to discover anti-cancer therapeutics. In the present work, we designed and analyzed several peptide sequences encompassing the interaction interface of EphA2-Sam for Ship2-Sam. Peptide conformational analyses and interaction assays with Ship2-Sam conducted through diverse techniques (CD, NMR, SPR and MST), identified a positively charged penta-amino acid native motif in EphA2-Sam, that once repeated three times in tandem, binds Ship2-Sam. NMR experiments show that the peptide targets the negatively charged binding site of Ship2-Sam for EphA2-Sam. Preliminary in vitro cell-based assays indicate that -at 50 µM concentration- it induces necrosis of PC-3 prostate cancer cells with more cytotoxic effect on cancer cells than on normal dermal fibroblasts. This work represents a pioneering study that opens further opportunities for the development of inhibitors of the Ship2-Sam/EphA2-Sam complex for therapeutic applications.

Self-Encoded Spread Spectrum Modulation for Robust Anti-Jamming Communication

DTIC Science & Technology

2009-06-30

experience in both theoretical and experimental aspects of RF and optical communications, multi-user CDMA systems, transmitter precoding and code...the performance of DS - and FH-SESS modulation in the presence of worst-case jamming, develop innovative SESS schemes that further exploit time and...Determine BER and AJ performance of the feedback and iterative detectors in DS -SESS under pulsed-noise and multi-tone jamming • Task 2: Develop a scheme

A health literate approach to the prevention of childhood overweight and obesity

PubMed Central

White, Richard O.; Thompson, Jessica R.; Rothman, Russell L.; Scott, Amanda M. McDougald; Heerman, William J.; Sommer, Evan C.; Barkin, Shari L.

2013-01-01

Objective To describe a systematic assessment of patient educational materials for the Growing Right Onto Wellness (GROW) trial, a childhood obesity prevention study targeting a low health literate population. Methods Process included: (1) expert review of educational content, (2) assessment of the quality of materials including use of the Suitability Assessment of Materials (SAM) tool, and (3) material review and revision with target population. Results 12 core modules were developed and assessed in an iterative process. Average readability was at the 6th grade reading level (SMOG Index 5.63 ± 0.76, and Fry graph 6.0 ± 0.85). SAM evaluation resulted in adjustments to literacy demand, layout & typography, and learning stimulation & motivation. Cognitive interviews with target population revealed additional changes incorporated to enhance participant's perception of acceptability and feasibility for behavior change. Conclusion The GROW modules are a collection of evidence-based materials appropriate for parents with low health literacy and their preschool aged children, that target the prevention of childhood overweight/obesity. Practice implications Most trials addressing the treatment or prevention of childhood obesity use written materials. Due to the ubiquitous prevalence of limited health literacy, our described methods may assist researchers in ensuring their content is both understood and actionable. PMID:24001660

A health literate approach to the prevention of childhood overweight and obesity.

PubMed

White, Richard O; Thompson, Jessica R; Rothman, Russell L; McDougald Scott, Amanda M; Heerman, William J; Sommer, Evan C; Barkin, Shari L

2013-12-01

To describe a systematic assessment of patient educational materials for the Growing Right Onto Wellness (GROW) trial, a childhood obesity prevention study targeting a low health literate population. Process included: (1) expert review of educational content, (2) assessment of the quality of materials including use of the Suitability Assessment of Materials (SAM) tool, and (3) material review and revision with target population. 12 core modules were developed and assessed in an iterative process. Average readability was at the 6th grade reading level (SMOG Index 5.63 ± 0.76, and Fry graph 6.0 ± 0.85). SAM evaluation resulted in adjustments to literacy demand, layout & typography, and learning stimulation & motivation. Cognitive interviews with target population revealed additional changes incorporated to enhance participant's perception of acceptability and feasibility for behavior change. The GROW modules are a collection of evidence-based materials appropriate for parents with low health literacy and their preschool aged children, that target the prevention of childhood overweight/obesity. Most trials addressing the treatment or prevention of childhood obesity use written materials. Due to the ubiquitous prevalence of limited health literacy, our described methods may assist researchers in ensuring their content is both understood and actionable. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Millimeter-Wave Localizers for Aircraft-to-Aircraft Approach Navigation

NASA Technical Reports Server (NTRS)

Tang, Adrian J.

2013-01-01

Aerial refueling technology for both manned and unmanned aircraft is critical for operations where extended aircraft flight time is required. Existing refueling assets are typically manned aircraft, which couple to a second aircraft through the use of a refueling boom. Alignment and mating of the two aircraft continues to rely on human control with use of high-resolution cameras. With the recent advances in unmanned aircraft, it would be highly advantageous to remove/reduce human control from the refueling process, simplifying the amount of remote mission management and enabling new operational scenarios. Existing aerial refueling uses a camera, making it non-autonomous and prone to human error. Existing commercial localizer technology has proven robust and reliable, but not suited for aircraft-to-aircraft approaches like in aerial refueling scenarios since the resolution is too coarse (approximately one meter). A localizer approach system for aircraft-to-aircraft docking can be constructed using the same modulation with a millimeterwave carrier to provide high resolution. One technology used to remotely align commercial aircraft on approach to a runway are ILS (instrument landing systems). ILS have been in service within the U.S. for almost 50 years. In a commercial ILS, two partially overlapping beams of UHF (109 to 126 MHz) are broadcast from an antenna array so that their overlapping region defines the centerline of the runway. This is called a localizer system and is responsible for horizontal alignment of the approach. One beam is modulated with a 150-Hz tone, while the other with a 90-Hz tone. Through comparison of the modulation depths of both tones, an autopilot system aligns the approaching aircraft with the runway centerline. A similar system called a glide-slope (GS) exists in the 320-to-330MHz band for vertical alignment of the approach. While this technology has been proven reliable for millions of commercial flights annually, its UHF nature limits its ability to operate beyond the 1-to-2-meter precisions associated with commercial runway width. A prototype ILS-type system operates at millimeter-wave frequencies to provide automatic and robust approach control for aerial refueling. The system allows for the coupling process to remain completely autonomous, as a boom operator is no longer required. Operating beyond 100 GHz provides enough resolution and a narrow enough beamwidth that an approach corridor of centimeter scales can be maintained. Two modules were used to accomplish this task. The first module is a localizer/glide-slope module that can be fitted on a refueling aircraft. This module provides the navigation beams for aligning the approaching aircraft. The second module is navigational receiver fitted onto the approaching aircraft to be re fueled that can detect the approach beams. Since unmanned aircraft have a limited payload size and limited electrical power, the receiver portion was implemented in CMOS (complementary metal oxide semiconductor) technology based on a super-regenerative receiver (SRR) architecture. The SRR achieves mW-level power consumption and chip sizes less than l mm2. While super-regenerative techniques have small bandwidths that limit use in communication systems, their advantages of high sensitivity, low complexity, and low power make them ideal in this situation where modulating tones of less than 1 kHz are used.

Single-sideband modulator for frequency domain multiplexing of superconducting qubit readout

NASA Astrophysics Data System (ADS)

Chapman, Benjamin J.; Rosenthal, Eric I.; Kerckhoff, Joseph; Vale, Leila R.; Hilton, Gene C.; Lehnert, K. W.

2017-04-01

We introduce and experimentally characterize a superconducting single-sideband modulator compatible with cryogenic microwave circuits and propose its use for frequency domain multiplexing of superconducting qubit readout. The monolithic double-balanced modulators that comprise the device are formed with purely reactive elements (capacitors and Josephson junction inductors) and require no microwave-frequency control tones. Microwave signals in the 4 to 8 GHz band, with power up to -85 dBm, are converted up or down in frequency by as much as 120 MHz. Spurious harmonics in the device can be suppressed by up to 25 dB for select probe and modulation frequencies.

Impact of Game-Inspired Infographics on User Engagement and Information Processing in an eHealth Program

PubMed Central

Qian, Xiaokun; Deal, Allison M; Ribisl, Kurt M; Linnan, Laura A; Tate, Deborah F

2016-01-01

Background Online interventions providing individual health behavior assessment should deliver feedback in a way that is both understandable and engaging. This study focused on the potential for infographics inspired by the aesthetics of game design to contribute to these goals. Objective We conducted formative research to test game-inspired infographics against more traditional displays (eg, text-only, column chart) for conveying a behavioral goal and an individual’s behavior relative to the goal. We explored the extent to which the display type would influence levels of engagement and information processing. Methods Between-participants experiments compared game-inspired infographics with traditional formats in terms of outcomes related to information processing (eg, comprehension, cognitive load) and engagement (eg, attitudes toward the information, emotional tone). We randomly assigned participants (N=1162) to an experiment in 1 of 6 modules (tobacco use, alcohol use, vegetable consumption, fruit consumption, physical activity, and weight management). Results In the tobacco module, a game-inspired format (scorecard) was compared with text-only; there were no differences in attitudes and emotional tone, but the scorecard outperformed text-only on comprehension (P=.004) and decreased cognitive load (P=.006). For the other behaviors, we tested 2 game-inspired formats (scorecard, progress bar) and a traditional column chart; there were no differences in comprehension, but the progress bar outperformed the other formats on attitudes and emotional tone (P<.001 for all contrasts). Conclusions Across modules, a game-inspired infographic showed potential to outperform a traditional format for some study outcomes while not underperforming on other outcomes. Overall, findings support the use of game-inspired infographics in behavioral assessment feedback to enhance comprehension and engagement, which may lead to greater behavior change. PMID:27658469

Impact of Game-Inspired Infographics on User Engagement and Information Processing in an eHealth Program.

PubMed

Comello, Maria Leonora G; Qian, Xiaokun; Deal, Allison M; Ribisl, Kurt M; Linnan, Laura A; Tate, Deborah F

2016-09-22

Online interventions providing individual health behavior assessment should deliver feedback in a way that is both understandable and engaging. This study focused on the potential for infographics inspired by the aesthetics of game design to contribute to these goals. We conducted formative research to test game-inspired infographics against more traditional displays (eg, text-only, column chart) for conveying a behavioral goal and an individual's behavior relative to the goal. We explored the extent to which the display type would influence levels of engagement and information processing. Between-participants experiments compared game-inspired infographics with traditional formats in terms of outcomes related to information processing (eg, comprehension, cognitive load) and engagement (eg, attitudes toward the information, emotional tone). We randomly assigned participants (N=1162) to an experiment in 1 of 6 modules (tobacco use, alcohol use, vegetable consumption, fruit consumption, physical activity, and weight management). In the tobacco module, a game-inspired format (scorecard) was compared with text-only; there were no differences in attitudes and emotional tone, but the scorecard outperformed text-only on comprehension (P=.004) and decreased cognitive load (P=.006). For the other behaviors, we tested 2 game-inspired formats (scorecard, progress bar) and a traditional column chart; there were no differences in comprehension, but the progress bar outperformed the other formats on attitudes and emotional tone (P<.001 for all contrasts). Across modules, a game-inspired infographic showed potential to outperform a traditional format for some study outcomes while not underperforming on other outcomes. Overall, findings support the use of game-inspired infographics in behavioral assessment feedback to enhance comprehension and engagement, which may lead to greater behavior change.

Risk Factors for Hearing Loss in Patients Treated With Intensity-Modulated Radiotherapy for Head-and-Neck Tumors

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

Zuur, Charlotte L.; Simis, Yvonne J.; Lamers, Emmy A.

2009-06-01

Purpose: Radiotherapy (RT) is a common treatment of head-and-neck carcinoma. The objective of this study was to perform a prospective multivariate assessment of the dose-effect relationship between intensity-modulated RT and hearing loss. Methods and Materials: Pure tone audiometry at 0.250-16 kHz was obtained before and after treatment in 101 patients (202 ears). All patients received full-course intensity-modulated RT (range, 56-70 Gy), with a median cochlear dose of 11.4 Gy (range, 0.2-69.7). Results: Audiometry was performed 1 week before and a median of 9 weeks (range, 1-112) after treatment. The mean hearing deterioration at pure tone average air-conduction 1-2-4 kHz wasmore » small (from 28.6 dB HL to 30.1 dB HL). However, individual patients showed clinically significant hearing loss, with 10-dB threshold shift incidences of 13% and 18% at pure tone averages air-conduction 1-2-4 kHz and 8-10-12.5 kHz, respectively. Post-treatment hearing capability was unfavorable in the case of greater inner ear radiation doses (p <0.0001), unfavorable baseline hearing capability (p <0.0001), green-eyed patients (p <0.0001), and older age (p <0.0001). Using multivariate analysis, a prediction of individual hearing capabiltity after treatment was made. Conclusion: RT-induced hearing loss in the mean population is modest. However, clinically significant hearing loss was observed in older patients with green eyes and unfavorable pretreatment hearing. In these patients, the intended radiation dose may be adjusted according to the proposed predictive model, aiming to decrease the risk of ototoxicity.« less

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

PubMed

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

2016-09-01

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

Auditory-visual integration modulates location-specific repetition suppression of auditory responses.

PubMed

Shrem, Talia; Murray, Micah M; Deouell, Leon Y

2017-11-01

Space is a dimension shared by different modalities, but at what stage spatial encoding is affected by multisensory processes is unclear. Early studies observed attenuation of N1/P2 auditory evoked responses following repetition of sounds from the same location. Here, we asked whether this effect is modulated by audiovisual interactions. In two experiments, using a repetition-suppression paradigm, we presented pairs of tones in free field, where the test stimulus was a tone presented at a fixed lateral location. Experiment 1 established a neural index of auditory spatial sensitivity, by comparing the degree of attenuation of the response to test stimuli when they were preceded by an adapter sound at the same location versus 30° or 60° away. We found that the degree of attenuation at the P2 latency was inversely related to the spatial distance between the test stimulus and the adapter stimulus. In Experiment 2, the adapter stimulus was a tone presented from the same location or a more medial location than the test stimulus. The adapter stimulus was accompanied by a simultaneous flash displayed orthogonally from one of the two locations. Sound-flash incongruence reduced accuracy in a same-different location discrimination task (i.e., the ventriloquism effect) and reduced the location-specific repetition-suppression at the P2 latency. Importantly, this multisensory effect included topographic modulations, indicative of changes in the relative contribution of underlying sources across conditions. Our findings suggest that the auditory response at the P2 latency is affected by spatially selective brain activity, which is affected crossmodally by visual information. © 2017 Society for Psychophysiological Research.

Vagal afferent fibres determine the oxytocin-induced modulation of gastric tone

PubMed Central

Holmes, Gregory M; Browning, Kirsteen N; Babic, Tanja; Fortna, Samuel R; Coleman, F Holly; Travagli, R Alberto

2013-01-01

Oxytocin (OXT) inputs to the dorsal vagal complex (DVC; nucleus of the tractus solitarius (NTS) dorsal motor nucleus of the vagus (DMV) and area postrema) decrease gastric tone and motility. Our first aim was to investigate the mechanism(s) of OXT-induced gastric relaxation. We demonstrated recently that vagal afferent inputs modulate NTS–DMV synapses involved in gastric and pancreatic reflexes via group II metabotropic glutamate receptors (mGluRs). Our second aim was to investigate whether group II mGluRs similarly influence the response of vagal motoneurons to OXT. Microinjection of OXT in the DVC decreased gastric tone in a dose-dependent manner. The OXT-induced gastric relaxation was enhanced following bethanechol and reduced by l-NAME administration, suggesting a nitrergic mechanism of gastroinhibition. DVC application of the group II mGluR antagonist EGLU induced a gastroinhibition that was not dose dependent and shifted the gastric effects of OXT to a cholinergic-mediated mechanism. Evoked and miniature GABAergic synaptic currents between NTS and identified gastric-projecting DMV neurones were not affected by OXT in any neurones tested, unless the brainstem slice was (a) pretreated with EGLU or (b) derived from rats that had earlier received a surgical vagal deafferentation. Conversely, OXT inhibited glutamatergic currents even in naive slices, but their responses were unaffected by EGLU pretreatment. These results suggest that the OXT-induced gastroinhibition is mediated by activation of the NANC pathway. Inhibition of brainstem group II mGluRs, however, uncovers the ability of OXT to modulate GABAergic transmission between the NTS and DMV, resulting in the engagement of an otherwise silent cholinergic vagal neurocircuit. PMID:23587885

A New Test of Attention in Listening (TAIL) Predicts Auditory Performance

PubMed Central

Zhang, Yu-Xuan; Barry, Johanna G.; Moore, David R.; Amitay, Sygal

2012-01-01

Attention modulates auditory perception, but there are currently no simple tests that specifically quantify this modulation. To fill the gap, we developed a new, easy-to-use test of attention in listening (TAIL) based on reaction time. On each trial, two clearly audible tones were presented sequentially, either at the same or different ears. The frequency of the tones was also either the same or different (by at least two critical bands). When the task required same/different frequency judgments, presentation at the same ear significantly speeded responses and reduced errors. A same/different ear (location) judgment was likewise facilitated by keeping tone frequency constant. Perception was thus influenced by involuntary orienting of attention along the task-irrelevant dimension. When information in the two stimulus dimensions were congruent (same-frequency same-ear, or different-frequency different-ear), response was faster and more accurate than when they were incongruent (same-frequency different-ear, or different-frequency same-ear), suggesting the involvement of executive control to resolve conflicts. In total, the TAIL yielded five independent outcome measures: (1) baseline reaction time, indicating information processing efficiency, (2) involuntary orienting of attention to frequency and (3) location, and (4) conflict resolution for frequency and (5) location. Processing efficiency and conflict resolution accounted for up to 45% of individual variances in the low- and high-threshold variants of three psychoacoustic tasks assessing temporal and spectral processing. Involuntary orientation of attention to the irrelevant dimension did not correlate with perceptual performance on these tasks. Given that TAIL measures are unlikely to be limited by perceptual sensitivity, we suggest that the correlations reflect modulation of perceptual performance by attention. The TAIL thus has the power to identify and separate contributions of different components of attention to auditory perception. PMID:23300934

Optical subcarrier processing for Nyquist SCM signals via coherent spectrum overlapping in four-wave mixing with coherent multi-tone pump.

PubMed

Lu, Guo-Wei; Luís, Ruben S; Mendinueta, José Manuel Delgado; Sakamoto, Takahide; Yamamoto, Naokatsu

2018-01-22

As one of the promising multiplexing and multicarrier modulation technologies, Nyquist subcarrier multiplexing (Nyquist SCM) has recently attracted research attention to realize ultra-fast and ultra-spectral-efficient optical networks. In this paper, we propose and experimentally demonstrate optical subcarrier processing technologies for Nyquist SCM signals such as frequency conversion, multicast and data aggregation of subcarriers, through the coherent spectrum overlapping between subcarriers in four-wave mixing (FWM) with coherent multi-tone pump. The data aggregation is realized by coherently superposing or combining low-level subcarriers to yield high-level subcarriers in the optical field. Moreover, multiple replicas of the data-aggregated subcarriers and the subcarriers carrying the original data are obtained. In the experiment, two 5 Gbps quadrature phase-shift keying (QPSK) subcarriers are coherently combined to generate a 10 Gbps 16 quadrature amplitude modulation (QAM) subcarrier with frequency conversions through the FWM with coherent multi-tone pump. Less than 1 dB optical signal-to-noise ratio (OSNR) penalty variation is observed for the synthesized 16QAM subcarriers after the data aggregation. In addition, some subcarriers are kept in the original formats, QPSK, with a power penalty of less than 0.4 dB with respect to the original input subcarriers. The proposed subcarrier processing technology enables flexibility for spectral management in future dynamic optical networks.

A comparison of auditory evoked potentials to acoustic beats and to binaural beats.

PubMed

Pratt, Hillel; Starr, Arnold; Michalewski, Henry J; Dimitrijevic, Andrew; Bleich, Naomi; Mittelman, Nomi

2010-04-01

The purpose of this study was to compare cortical brain responses evoked by amplitude modulated acoustic beats of 3 and 6 Hz in tones of 250 and 1000 Hz with those evoked by their binaural beats counterparts in unmodulated tones to indicate whether the cortical processes involved differ. Event-related potentials (ERPs) were recorded to 3- and 6-Hz acoustic and binaural beats in 2000 ms duration 250 and 1000 Hz tones presented with approximately 1 s intervals. Latency, amplitude and source current density estimates of ERP components to beats-evoked oscillations were determined and compared across beat types, beat frequencies and base (carrier) frequencies. All stimuli evoked tone-onset components followed by oscillations corresponding to the beat frequency, and a subsequent tone-offset complex. Beats-evoked oscillations were higher in amplitude in response to acoustic than to binaural beats, to 250 than to 1000 Hz base frequency and to 3 Hz than to 6 Hz beat frequency. Sources of the beats-evoked oscillations across all stimulus conditions located mostly to left temporal lobe areas. Differences between estimated sources of potentials to acoustic and binaural beats were not significant. The perceptions of binaural beats involve cortical activity that is not different than acoustic beats in distribution and in the effects of beat- and base frequency, indicating similar cortical processing. Copyright 2010 Elsevier B.V. All rights reserved.

Probing the nature and resistance of the molecule-electrode contact in SAM-based junctions.

PubMed

Sangeeth, C S Suchand; Wan, Albert; Nijhuis, Christian A

2015-07-28

It is challenging to quantify the contact resistance and to determine the nature of the molecule-electrode contacts in molecular two-terminal junctions. Here we show that potentiodynamic and temperature dependent impedance measurements give insights into the nature of the SAM-electrode interface and other bottlenecks of charge transport (the capacitance of the SAM (C(SAM)) and the resistance of the SAM (R(SAM))), unlike DC methods, independently of each other. We found that the resistance of the top-electrode-SAM contact for junctions with the form of Ag(TS)-SC(n)//GaO(x)/EGaIn with n = 10, 12, 14, 16 or 18 is bias and temperature independent and hence Ohmic (non-rectifying) in nature, and is orders of magnitude smaller than R(SAM). The C(SAM) and R(SAM) are independent of the temperature, indicating that the mechanism of charge transport in these SAM-based junctions is coherent tunneling and the charge carrier trapping at the interfaces is negligible.

Structural basis for diversity in the SAM clan of riboswitches.

PubMed

Trausch, Jeremiah J; Xu, Zhenjiang; Edwards, Andrea L; Reyes, Francis E; Ross, Phillip E; Knight, Rob; Batey, Robert T

2014-05-06

In bacteria, sulfur metabolism is regulated in part by seven known families of riboswitches that bind S-adenosyl-l-methionine (SAM). Direct binding of SAM to these mRNA regulatory elements governs a downstream secondary structural switch that communicates with the transcriptional and/or translational expression machinery. The most widely distributed SAM-binding riboswitches belong to the SAM clan, comprising three families that share a common SAM-binding core but differ radically in their peripheral architecture. Although the structure of the SAM-I member of this clan has been extensively studied, how the alternative peripheral architecture of the other families supports the common SAM-binding core remains unknown. We have therefore solved the X-ray structure of a member of the SAM-I/IV family containing the alternative "PK-2" subdomain shared with the SAM-IV family. This structure reveals that this subdomain forms extensive interactions with the helix housing the SAM-binding pocket, including a highly unusual mode of helix packing in which two helices pack in a perpendicular fashion. Biochemical and genetic analysis of this RNA reveals that SAM binding induces many of these interactions, including stabilization of a pseudoknot that is part of the regulatory switch. Despite strong structural similarity between the cores of SAM-I and SAM-I/IV members, a phylogenetic analysis of sequences does not indicate that they derive from a common ancestor.

Two-Stage Processing of Sounds Explains Behavioral Performance Variations due to Changes in Stimulus Contrast and Selective Attention: An MEG Study

PubMed Central

Kauramäki, Jaakko; Jääskeläinen, Iiro P.; Hänninen, Jarno L.; Auranen, Toni; Nummenmaa, Aapo; Lampinen, Jouko; Sams, Mikko

2012-01-01

Selectively attending to task-relevant sounds whilst ignoring background noise is one of the most amazing feats performed by the human brain. Here, we studied the underlying neural mechanisms by recording magnetoencephalographic (MEG) responses of 14 healthy human subjects while they performed a near-threshold auditory discrimination task vs. a visual control task of similar difficulty. The auditory stimuli consisted of notch-filtered continuous noise masker sounds, and of 1020-Hz target tones occasionally () replacing 1000-Hz standard tones of 300-ms duration that were embedded at the center of the notches, the widths of which were parametrically varied. As a control for masker effects, tone-evoked responses were additionally recorded without masker sound. Selective attention to tones significantly increased the amplitude of the onset M100 response at 100 ms to the standard tones during presence of the masker sounds especially with notches narrower than the critical band. Further, attention modulated sustained response most clearly at 300–400 ms time range from sound onset, with narrower notches than in case of the M100, thus selectively reducing the masker-induced suppression of the tone-evoked response. Our results show evidence of a multiple-stage filtering mechanism of sensory input in the human auditory cortex: 1) one at early (100 ms) latencies bilaterally in posterior parts of the secondary auditory areas, and 2) adaptive filtering of attended sounds from task-irrelevant background masker at longer latency (300 ms) in more medial auditory cortical regions, predominantly in the left hemisphere, enhancing processing of near-threshold sounds. PMID:23071654

A novel speech processing algorithm based on harmonicity cues in cochlear implant

NASA Astrophysics Data System (ADS)

Wang, Jian; Chen, Yousheng; Zhang, Zongping; Chen, Yan; Zhang, Weifeng

2017-08-01

This paper proposed a novel speech processing algorithm in cochlear implant, which used harmonicity cues to enhance tonal information in Mandarin Chinese speech recognition. The input speech was filtered by a 4-channel band-pass filter bank. The frequency ranges for the four bands were: 300-621, 621-1285, 1285-2657, and 2657-5499 Hz. In each pass band, temporal envelope and periodicity cues (TEPCs) below 400 Hz were extracted by full wave rectification and low-pass filtering. The TEPCs were modulated by a sinusoidal carrier, the frequency of which was fundamental frequency (F0) and its harmonics most close to the center frequency of each band. Signals from each band were combined together to obtain an output speech. Mandarin tone, word, and sentence recognition in quiet listening conditions were tested for the extensively used continuous interleaved sampling (CIS) strategy and the novel F0-harmonic algorithm. Results found that the F0-harmonic algorithm performed consistently better than CIS strategy in Mandarin tone, word, and sentence recognition. In addition, sentence recognition rate was higher than word recognition rate, as a result of contextual information in the sentence. Moreover, tone 3 and 4 performed better than tone 1 and tone 2, due to the easily identified features of the former. In conclusion, the F0-harmonic algorithm could enhance tonal information in cochlear implant speech processing due to the use of harmonicity cues, thereby improving Mandarin tone, word, and sentence recognition. Further study will focus on the test of the F0-harmonic algorithm in noisy listening conditions.

Heme oxygenase-1 upregulation modulates tone and fibroelastic properties of internal anal sphincter

PubMed Central

Krishna, Chadalavada Vijay; Singh, Jagmohan; Kumar, Sumit

2014-01-01

A compromise in the internal anal sphincter (IAS) tone and fibroelastic properties (FEP) plays an important role in rectoanal incontinence. Herein, we examined the effects of heme oxygenase (HO)-1 upregulation on these IAS characteristics in young rats. We determined the effect of HO-1 upregulator hemin on HO-1 mRNA and protein expressions and on basal IAS tone and its FEP before and after HO-1 inhibitor tin protoporphyrin IX. For FEP, we determined the kinetics of the IAS smooth muscle responses, by the velocities of relaxation, and recovery of the IAS tone following 0 Ca2+ and electrical field stimulation. To characterize the underlying signal transduction for these changes, we determined the effects of hemin on RhoA-associated kinase (RhoA)/Rho kinase (ROCK) II, myosin-binding subunit of myosin light chain phosphatase 1, fibronectin, and elastin expression levels. Hemin increased HO-1 mRNA and protein similar to the increases in the basal tone, and in the FEP of the IAS. Underlying mechanisms in the IAS characteristics are associated with increases in the genetic and translational expressions of RhoA/ROCKII, and elastin. Fibronectin expression levels on the other hand were found to be decreased following HO-1 upregulation. The results of our study show that the hemin/HO-1 system regulates the tone and FEP of IAS. The hemin/HO-1 system thus provides a potential target for the development of new interventions aimed at treatment of gastrointestinal motility disorders, specifically the age-related IAS dysfunction. PMID:25035109

Reprint of: Initial uncertainty impacts statistical learning in sound sequence processing.

PubMed

Todd, Juanita; Provost, Alexander; Whitson, Lisa; Mullens, Daniel

2018-05-18

This paper features two studies confirming a lasting impact of first learning on how subsequent experience is weighted in early relevance-filtering processes. In both studies participants were exposed to sequences of sound that contained a regular pattern on two different timescales. Regular patterning in sound is readily detected by the auditory system and used to form "prediction models" that define the most likely properties of sound to be encountered in a given context. The presence and strength of these prediction models is inferred from changes in automatically elicited components of auditory evoked potentials. Both studies employed sound sequences that contained both a local and longer-term pattern. The local pattern was defined by a regular repeating pure tone occasionally interrupted by a rare deviating tone (p=0.125) that was physically different (a 30msvs. 60ms duration difference in one condition and a 1000Hz vs. 1500Hz frequency difference in the other). The longer-term pattern was defined by the rate at which the two tones alternated probabilities (i.e., the tone that was first rare became common and the tone that was first common became rare). There was no task related to the tones and participants were asked to ignore them while focussing attention on a movie with subtitles. Auditory-evoked potentials revealed long lasting modulatory influences based on whether the tone was initially encountered as rare and unpredictable or common and predictable. The results are interpreted as evidence that probability (or indeed predictability) assigns a differential information-value to the two tones that in turn affects the extent to which prediction models are updated and imposed. These effects are exposed for both common and rare occurrences of the tones. The studies contribute to a body of work that reveals that probabilistic information is not faithfully represented in these early evoked potentials and instead exposes that predictability (or conversely uncertainty) may trigger value-based learning modulations even in task-irrelevant incidental learning. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Summary Report of Mission Acceleration Measurements for STS-79. Launched 16 Sep. 1996

NASA Technical Reports Server (NTRS)

Rogers, Melissa J. B.; Moskowitz, Milton E.; Hrovat, Kenneth; Reckart, Timothy A.

1997-01-01

The Space Acceleration Measurement System (SAMS) collected acceleration data in support of the Mechanics of Granular Materials experiment during the STS-79 Mir docking mission, September 1996. STS-79 was the first opportunity to record SAMS data on an Orbiter while it was docked to Mir. Crew exercise activities in the Atlantis middeck and the Mir base module are apparent in the data. The acceleration signals related to the Enhanced Orbiter Refrigerator Freezer had different characteristics when comparing the data recorded on Atlantis on STS-79 with the data recorded on Mir during STS-74. This is probably due, at least in part, to different transmission paths and SAMS sensor head mounting mechanisms. Data collected on Atlantis during the STS-79 docking indicate that accelerations due to vehicle and solar array structural modes from Mir transfer to Atlantis and that the structural modes of the Atlantis-Mir complex are different from those of either vehicle independently. A 0.18 Hz component of the SAMS data, present while the two vehicles were docked, was probably caused by the Mir solar arrays. Compared to Atlantis structural modes of about 3.9 and 4.9 Hz, the Atlantis-Mir complex has structural components of about 4.5 and 5.1 Hz. After docking, apparent structural modes appeared in the data at about 0.8 and 1.8 Hz. The appearance, disappearance, and change in the structural modes during the docking and undocking phases of the joint Atlantis-Mir operations indicates that the structural modes of the two spacecraft have an effect on the microgravity environment of each other. The transfer of structural and equipment related accelerations between vehicles is something that should be considered in the International Space Station era.

Creatine supplementation prevents fatty liver in rats fed choline-deficient diet: a burden of one-carbon and fatty acid metabolism.

PubMed

Deminice, Rafael; de Castro, Gabriela Salim Ferreira; Francisco, Lucas Vieira; da Silva, Lilian Eslaine Costa Mendes; Cardoso, João Felipe Rito; Frajacomo, Fernando Tadeu Trevisan; Teodoro, Bruno Gonzaga; Dos Reis Silveira, Leonardo; Jordao, Alceu Afonso

2015-04-01

To examine the effects of creatine (Cr) supplementation on liver fat accumulation in rats fed a choline-deficient diet. Twenty-four rats were divided into 3 groups of 8 based on 4 weeks of feeding an AIN-93 control diet (C), a choline-deficient diet (CDD) or a CDD supplemented with 2% Cr. The CDD diet was AIN-93 without choline. The CDD significantly increased plasma homocysteine and TNFα concentration, as well as ALT activity. In liver, the CDD enhanced concentrations of total fat (55%), cholesterol (25%), triglycerides (87%), MDA (30%), TNFα (241%) and decreased SAM concentrations (25%) and the SAM/SAH ratio (33%). Cr supplementation prevented all these metabolic changes, except for hepatic SAM and the SAM/SAH ratio. However, no changes in PEMT gene expression or liver phosphatidylcholine levels were observed among the three experimental groups, and there were no changes in hepatic triglyceride transfer protein (MTP) mRNA level. On the contrary, Cr supplementation normalized expression of the transcription factors PPARα and PPARγ that were altered by the CDD. Further, the downstream targets and fatty acids metabolism genes, UCP2, LCAD and CPT1a, were also normalized in the Cr group as compared to CDD-fed rats. Cr supplementation prevented fat liver accumulation and hepatic injures in rats fed with a CDD for 4 weeks. Our results demonstrated that one-carbon metabolism may have a small role in mitigating hepatic fat accumulation by Cr supplementation. The modulation of key genes related to fatty acid oxidation pathway suggests a new mechanism by which Cr prevents liver fat accumulation. Copyright © 2015 Elsevier Inc. All rights reserved.

Analysis of the liver mitochondrial proteome in response to ethanol and S-adenosylmethionine treatments: novel molecular targets of disease and hepatoprotection.

PubMed

Andringa, Kelly K; King, Adrienne L; Eccleston, Heather B; Mantena, Sudheer K; Landar, Aimee; Jhala, Nirag C; Dickinson, Dale A; Squadrito, Giuseppe L; Bailey, Shannon M

2010-05-01

S-adenosylmethionine (SAM) minimizes alcohol hepatotoxicity; however, the molecular mechanisms responsible for SAM hepatoprotection remain unknown. Herein, we use proteomics to determine whether the hepatoprotective action of SAM against early-stage alcoholic liver disease is linked to alterations in the mitochondrial proteome. For this, male rats were fed control or ethanol-containing liquid diets +/- SAM and liver mitochondria were prepared for proteomic analysis. Two-dimensional isoelectric focusing (2D IEF/SDS-PAGE) and blue native gel electrophoresis (BN-PAGE) were used to determine changes in matrix and oxidative phosphorylation (OxPhos) proteins, respectively. SAM coadministration minimized alcohol-dependent inflammation and preserved mitochondrial respiration. SAM supplementation preserved liver SAM levels in ethanol-fed rats; however, mitochondrial SAM levels were increased by ethanol and SAM treatments. With use of 2D IEF/SDS-PAGE, 30 proteins showed significant changes in abundance in response to ethanol, SAM, or both. Classes of proteins affected by ethanol and SAM treatments were chaperones, beta oxidation proteins, sulfur metabolism proteins, and dehydrogenase enzymes involved in methionine, glycine, and choline metabolism. BN-PAGE revealed novel changes in the levels of 19 OxPhos proteins in response to ethanol, SAM, or both. Ethanol- and SAM-dependent alterations in the proteome were not linked to corresponding changes in gene expression. In conclusion, ethanol and SAM treatment led to multiple changes in the liver mitochondrial proteome. The protective effects of SAM against alcohol toxicity are mediated, in part, through maintenance of proteins involved in key mitochondrial energy conserving and biosynthetic pathways. This study demonstrates that SAM may be a promising candidate for treatment of alcoholic liver disease.

Ozone-Induced Pulmonary Injury and Inflammation are Modulated by Adrenal-Derived Stress Hormones

EPA Science Inventory

Ozone exposure promotes pulmonary injury and inflammation. Previously we have characterized systemic changes that occur immediately after acute ozone exposure and are mediated by neuro-hormonal stress response pathway. Both HPA axis and sympathetic tone alterations induce the rel...

Electrophysiological evidence for a general auditory prediction deficit in adults who stutter

PubMed Central

Daliri, Ayoub; Max, Ludo

2015-01-01

We previously found that stuttering individuals do not show the typical auditory modulation observed during speech planning in nonstuttering individuals. In this follow-up study, we further elucidate this difference by investigating whether stuttering speakers’ atypical auditory modulation is observed only when sensory predictions are based on movement planning or also when predictable auditory input is not a consequence of one’s own actions. We recorded 10 stuttering and 10 nonstuttering adults’ auditory evoked potentials in response to random probe tones delivered while anticipating either speaking aloud or hearing one’s own speech played back and in a control condition without auditory input (besides probe tones). N1 amplitude of nonstuttering speakers was reduced prior to both speaking and hearing versus the control condition. Stuttering speakers, however, showed no N1 amplitude reduction in either the speaking or hearing condition as compared with control. Thus, findings suggest that stuttering speakers have general auditory prediction difficulties. PMID:26335995

Nondegenerate parametric oscillations in a tunable superconducting resonator

NASA Astrophysics Data System (ADS)

Bengtsson, Andreas; Krantz, Philip; Simoen, Michaël; Svensson, Ida-Maria; Schneider, Ben; Shumeiko, Vitaly; Delsing, Per; Bylander, Jonas

2018-04-01

We investigate nondegenerate parametric oscillations in a superconducting microwave multimode resonator that is terminated by a superconducting quantum interference device (SQUID). The parametric effect is achieved by modulating magnetic flux through the SQUID at a frequency close to the sum of two resonator-mode frequencies. For modulation amplitudes exceeding an instability threshold, self-sustained oscillations are observed in both modes. The amplitudes of these oscillations show good quantitative agreement with a theoretical model. The oscillation phases are found to be correlated and exhibit strong fluctuations which broaden the oscillation spectral linewidths. These linewidths are significantly reduced by applying a weak on-resonant tone, which also suppresses the phase fluctuations. When the weak tone is detuned, we observe synchronization of the oscillation frequency with the frequency of the input. For the detuned input, we also observe an emergence of three idlers in the output. This observation is in agreement with theory indicating four-mode amplification and squeezing of a coherent input.

The acoustical bright spot and mislocalization of tones by human listeners.

PubMed

Macaulay, Eric J; Hartmann, William M; Rakerd, Brad

2010-03-01

Listeners attempted to localize 1500-Hz sine tones presented in free field from a loudspeaker array, spanning azimuths from 0 degrees (straight ahead) to 90 degrees (extreme right). During this task, the tone levels and phases were measured in the listeners' ear canals. Because of the acoustical bright spot, measured interaural level differences (ILD) were non-monotonic functions of azimuth with a maximum near 55 degrees . In a source-identification task, listeners' localization decisions closely tracked the non-monotonic ILD, and thus became inaccurate at large azimuths. When listeners received training and feedback, their accuracy improved only slightly. In an azimuth-discrimination task, listeners decided whether a first sound was to the left or to the right of a second. The discrimination results also reflected the confusion caused by the non-monotonic ILD, and they could be predicted approximately by a listener's identification results. When the sine tones were amplitude modulated or replaced by narrow bands of noise, interaural time difference (ITD) cues greatly reduced the confusion for most listeners, but not for all. Recognizing the important role of the bright spot requires a reevaluation of the transition between the low-frequency region for localization (mainly ITD) and the high-frequency region (mainly ILD).

Improving methionine and ATP availability by MET6 and SAM2 co-expression combined with sodium citrate feeding enhanced SAM accumulation in Saccharomyces cerevisiae.

PubMed

Chen, Hailong; Wang, Zhou; Wang, Zhilai; Dou, Jie; Zhou, Changlin

2016-04-01

S-adenosyl-L-methionine (SAM), biosynthesized from methionine and ATP, exhibited diverse pharmaceutical applications. To enhance SAM accumulation in S. cerevisiae CGMCC 2842 (wild type), improvement of methionine and ATP availability through MET6 and SAM2 co-expression combined with sodium citrate feeding was investigated here. Feeding 6 g/L methionine at 12 h into medium was found to increase SAM accumulation by 38 % in wild type strain. Based on this result, MET6, encoding methionine synthase, was overexpressed, which caused a 59 % increase of SAM. To redirect intracellular methionine into SAM, MET6 and SAM2 (encoding methionine adenosyltransferase) were co-expressed to obtain the recombinant strain YGSPM in which the SAM accumulation was 2.34-fold of wild type strain. The data obtained showed that co-expression of MET6 and SAM2 improved intracellular methionine availability and redirected the methionine to SAM biosynthesis. To elevate intracellular ATP levels, 6 g/L sodium citrate, used as an auxiliary energy substrate, was fed into the batch fermentation medium, and an additional 19 % increase of SAM was observed after sodium citrate addition. Meanwhile, it was found that addition of sodium citrate improved the isocitrate dehydrogenase activity which was associated with the intracellular ATP levels. The results demonstrated that addition of sodium citrate improved intracellular ATP levels which promoted conversion of methionine into SAM. This study presented a feasible approach with considerable potential for developing highly SAM-productive strains based on improving methionine and ATP availability.

Molecular Level Understanding of Interfaces and Excited State Electronic Structure in Organic Solar Cells Using Soft X-ray Techniques

NASA Astrophysics Data System (ADS)

Gliboff, Matthew

Transparent conductive oxides like indium tin oxide (ITO) are common substrates for optoelectronic devices, including organic light emitting diodes and organic solar cells. Tailoring the interface between the oxide and the active layer by adjusting the work function or wettability of the oxide can improve the performance of these devices in both emissive and photovoltaic applications. Molecular design of self-assembled monolayers (SAMs) allows for a range of surface properties using the same oxide material. The molecular ordering and conformation adopted by the SAMs determine properties such as work function and wettability at these critical interfaces. I use angle-dependent near edge x-ray absorption fine structure (NEXAFS) spectroscopy, to determine the molecular orientations of a variety of dipolar phosphonic acid surface modifiers. For a model system, phenylphosphonic acid on indium zinc oxide, the SAMs prove to be surprisingly well-oriented, with the phenyl ring adopting a well-defined tilt angle of 12-16° from the surface normal. The NEXAFS results agree with polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS) results and orientations calculated from density functional theory (DFT). These results not only provide a detailed picture of the molecular structure of a technologically important class of SAMs, but they also resolve a long-standing ambiguity regarding the vibrational-mode assignments for phosphonic acids on oxide surfaces, thus improving the utility of PM-IRRAS for future studies. The effect of fluorination on the orientation of these phosponic-acid SAMs is non-trivial, due to the combined effects of the fluorination on binding mode and steric packing. The latter effects are found to be more dominant in aliphatic SAMs, leading to a more upright orientation in the fluorinated SAM. In the aromatic case, the fluorinated SAM adopted a less upright orientation which I attribute to changes in binding mode. The relationship between structure and performance in active layer polymers for organic electronics is not yet well understood. To gain insight into the effect of the excited state electronic structure on device performance, we examine two similar donor-acceptor polymers: PCPDTBT and PCDTBT, which produce devices with internal quantum efficiency (IQE) of 70% and 100% respectively. We use time-dependent density functional theory (TD-DFT) in combination with near edge x-ray absorption fine structure (NEXAFS) and resonant Auger spectroscopy to predict the electronic structure of the lowest unoccupied molecular orbital (LUMO). The resonant Auger results are found to be independent of film morphology and likely dominated by monomer structure. We show that the degree of LUMO localization onto the benzothiadiazole acceptor group in each polymer is similar, indicating that that the differences in IQE between these two polymers are driven by larger-scale morphology and not explained by the electronic structure of the excited state.

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

None

Module-level power electronics, such as DC power optimizers, microinverters, and those found in AC modules, are increasing in popularity in smaller-scale photovoltaic (PV) systems as their prices continue to decline. Therefore, it is important to provide PV modelers with guidelines about how to model these distributed power electronics appropriately in PV modeling software. This paper extends the work completed at NREL that provided recommendations to model the performance of distributed power electronics in NREL’s popular PVWatts calculator [1], to provide similar guidelines for modeling these technologies in NREL's more complex System Advisor Model (SAM). Module-level power electronics - such asmore » DC power optimizers, microinverters, and those found in AC modules-- are increasing in popularity in smaller-scale photovoltaic (PV) systems as their prices continue to decline. Therefore, it is important to provide PV modelers with guidelines about how to model these distributed power electronics appropriately in PV modeling software.« less

Peptide Fragments of Odin-Sam1: Conformational Analysis and Interaction Studies with EphA2-Sam.

PubMed

Mercurio, Flavia A; Di Natale, Concetta; Pirone, Luciano; Scognamiglio, Pasqualina L; Marasco, Daniela; Pedone, Emilia M; Saviano, Michele; Leone, Marilisa

2015-07-27

Odin is a protein belonging to the ANKS family, and has two tandem Sam domains. The first, Odin-Sam1, binds to the Sam domain of the EphA2 receptor (EphA2-Sam); this interaction could be crucial for the regulation of receptor endocytosis and might have an impact on cancer. Odin-Sam1 associates with EphA2-Sam by adopting a "mid-loop/end-helix" model. In this study three peptide sequences, encompassing the mid-loop interacting portion of Odin-Sam1 and its C-terminal α5 helix, were designed. Their conformational properties were analyzed by CD and NMR. In addition, their abilities to interact with EphA2-Sam were investigated by SPR studies. The peptides adopt a predominantly disordered state in aqueous buffer, but a higher helical content is evident in the presence of the cosolvent trifluoroethanol. Dissociation constants towards EphA2-Sam were in the high micromolar range. The structural findings suggest further routes for the design of potential anti-cancer therapeutics as inhibitors of EphA2-Sam heterotypic interactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Redox Behavior of the S-Adenosylmethionine (SAM)-Binding Fe-S Cluster in Methylthiotransferase RimO, toward Understanding Dual SAM Activity.

PubMed

Molle, Thibaut; Moreau, Yohann; Clemancey, Martin; Forouhar, Farhad; Ravanat, Jean-Luc; Duraffourg, Nicolas; Fourmond, Vincent; Latour, Jean-Marc; Gambarelli, Serge; Mulliez, Etienne; Atta, Mohamed

2016-10-18

RimO, a radical-S-adenosylmethionine (SAM) enzyme, catalyzes the specific C 3 methylthiolation of the D89 residue in the ribosomal S 12 protein. Two intact iron-sulfur clusters and two SAM cofactors both are required for catalysis. By using electron paramagnetic resonance, Mössbauer spectroscopies, and site-directed mutagenesis, we show how two SAM molecules sequentially bind to the unique iron site of the radical-SAM cluster for two distinct chemical reactions in RimO. Our data establish that the two SAM molecules bind the radical-SAM cluster to the unique iron site, and spectroscopic evidence obtained under strongly reducing conditions supports a mechanism in which the first molecule of SAM causes the reoxidation of the reduced radical-SAM cluster, impeding reductive cleavage of SAM to occur and allowing SAM to methylate a HS - ligand bound to the additional cluster. Furthermore, by using density functional theory-based methods, we provide a description of the reaction mechanism that predicts the attack of the carbon radical substrate on the methylthio group attached to the additional [4Fe-4S] cluster.

Improving the productivity of S-adenosyl-l-methionine by metabolic engineering in an industrial Saccharomyces cerevisiae strain.

PubMed

Zhao, Weijun; Hang, Baojian; Zhu, Xiangcheng; Wang, Ri; Shen, Minjie; Huang, Lei; Xu, Zhinan

2016-10-20

S-Adenosyl-l-methionine (SAM) is an important metabolite having prominent roles in treating various diseases. In order to improve the production of SAM, the regulation of three metabolic pathways involved in SAM biosynthesis were investigated in an industrial yeast strain ZJU001. GLC3 encoded glycogen-branching enzyme (GBE), SPE2 encoded SAM decarboxylase, as well as ERG4 and ERG6 encoded key enzymes in ergosterol biosynthesis, were knocked out in ZJU001 accordingly. The results indicated that blocking of either glycogen pathway or SAM decarboxylation pathway could improve the SAM accumulation significantly in ZJU001, while single disruption of either ERG4 or ERG6 gene had no obvious effect on SAM production. Moreover, the double mutant ZJU001-GS with deletion of both GLC3 and SPE2 genes was also constructed, which showed further improvement of SAM accumulation. Finally, SAM2 was overexpressed in ZJU001-GS to give the best SAM-producing recombinant strain ZJU001-GS-SAM2, in which 12.47g/L SAM was produced by following our developed pseudo-exponential fed-batch cultivation strategy, about 81.0% increase comparing to its parent strain ZJU001. The present work laid a solid base for large-scale SAM production with the industrial Saccharomyces cerevisiae strain. Copyright © 2016 Elsevier B.V. All rights reserved.

Adsorption of hydrophobin on different self-assembled monolayers: the role of the hydrophobic dipole and the electric dipole.

PubMed

Peng, Chunwang; Liu, Jie; Zhao, Daohui; Zhou, Jian

2014-09-30

In this work, the adsorptions of hydrophobin (HFBI) on four different self-assembled monolayers (SAMs) (i.e., CH3-SAM, OH-SAM, COOH-SAM, and NH2-SAM) were investigated by parallel tempering Monte Carlo and molecular dynamics simulations. Simulation results indicate that the orientation of HFBI adsorbed on neutral surfaces is dominated by a hydrophobic dipole. HFBI adsorbs on the hydrophobic CH3-SAM through its hydrophobic patch and adopts a nearly vertical hydrophobic dipole relative to the surface, while it is nearly horizontal when adsorbed on the hydrophilic OH-SAM. For charged SAM surfaces, HFBI adopts a nearly vertical electric dipole relative to the surface. HFBI has the narrowest orientation distribution on the CH3-SAM, and thus can form an ordered monolayer and reverse the wettability of the surface. For HFBI adsorption on charged SAMs, the adsorption strength weakens as the surface charge density increases. Compared with those on other SAMs, a larger area of the hydrophobic patch is exposed to the solution when HFBI adsorbs on the NH2-SAM. This leads to an increase of the hydrophobicity of the surface, which is consistent with the experimental results. The binding of HFBI to the CH3-SAM is mainly through hydrophobic interactions, while it is mediated through a hydration water layer near the surface for the OH-SAM. For the charged SAM surfaces, the adsorption is mainly induced by electrostatic interactions between the charged surfaces and the oppositely charged residues. The effect of a hydrophobic dipole on protein adsorption onto hydrophobic surfaces is similar to that of an electric dipole for charged surfaces. Therefore, the hydrophobic dipole may be applied to predict the probable orientations of protein adsorbed on hydrophobic surfaces.

Space acceleration measurement system description and operations on the First Spacelab Life Sciences Mission

NASA Technical Reports Server (NTRS)

Delombard, Richard; Finley, Brian D.

1991-01-01

The Space Acceleration Measurement System (SAMS) project and flight units are briefly described. The SAMS operations during the STS-40 mission are summarized, and a preliminary look at some of the acceleration data from that mission are provided. The background and rationale for the SAMS project is described to better illustrate its goals. The functions and capabilities of each SAMS flight unit are first explained, then the STS-40 mission, the SAMS's function for that mission, and the preparation of the SAMS are described. Observations about the SAMS operations during the first SAMS mission are then discussed. Some sample data are presented illustrating several aspects of the mission's microgravity environment.

Specific Eph receptor-cytoplasmic effector signaling mediated by SAM-SAM domain interactions.

PubMed

Wang, Yue; Shang, Yuan; Li, Jianchao; Chen, Weidi; Li, Gang; Wan, Jun; Liu, Wei; Zhang, Mingjie

2018-05-11

The Eph receptor tyrosine kinase (RTK) family is the largest subfamily of RTKs playing critical roles in many developmental processes such as tissue patterning, neurogenesis and neuronal circuit formation, angiogenesis, etc. How the 14 Eph proteins, via their highly similar cytoplasmic domains, can transmit diverse and sometimes opposite cellular signals upon engaging ephrins is a major unresolved question. Here we systematically investigated the bindings of each SAM domain of Eph receptors to the SAM domains from SHIP2 and Odin, and uncover a highly specific SAM-SAM interaction-mediated cytoplasmic Eph-effector binding pattern. Comparative X-ray crystallographic studies of several SAM-SAM heterodimer complexes, together with biochemical and cell biology experiments, not only revealed the exquisite specificity code governing Eph/effector interactions but also allowed us to identify SAMD5 as a new Eph binding partner. Finally, these Eph/effector SAM heterodimer structures can explain many Eph SAM mutations identified in patients suffering from cancers and other diseases. © 2018, Wang et al.

SAM-VI RNAs selectively bind S-adenosylmethionine and exhibit similarities to SAM-III riboswitches.

PubMed

Mirihana Arachchilage, Gayan; Sherlock, Madeline E; Weinberg, Zasha; Breaker, Ronald R

2018-03-04

Five distinct riboswitch classes that regulate gene expression in response to the cofactor S-adenosylmethionine (SAM) or its metabolic breakdown product S-adenosylhomocysteine (SAH) have been reported previously. Collectively, these SAM- or SAH-sensing RNAs constitute the most abundant collection of riboswitches, and are found in nearly every major bacterial lineage. Here, we report a potential sixth member of this pervasive riboswitch family, called SAM-VI, which is predominantly found in Bifidobacterium species. SAM-VI aptamers selectively bind the cofactor SAM and strongly discriminate against SAH. The consensus sequence and structural model for SAM-VI share some features with the consensus model for the SAM-III riboswitch class, whose members are mainly found in lactic acid bacteria. However, there are sufficient differences between the two classes such that current bioinformatics methods separately cluster representatives of the two motifs. These findings highlight the abundance of RNA structures that can form to selectively recognize SAM, and showcase the ability of RNA to utilize diverse strategies to perform similar biological functions.

Alzheimer Abeta(1-42) monomer adsorbed on the self-assembled monolayers.

PubMed

Wang, Qiuming; Zhao, Jun; Yu, Xiang; Zhao, Chao; Li, Lingyan; Zheng, Jie

2010-08-03

Amyloid-beta (Abeta) peptide aggregation on the cell membranes is a key pathological event responsible for neuron cell death in Alzheimer's disease (AD). We present a collection of molecular docking and molecular dynamics simulations to study the conformational dynamics and adsorption behavior of Abeta monomer on the self-assembled monolayer (SAM), in comparison to Abeta structure in bulk solution. Two distinct Abeta conformations (i.e., alpha-helix and beta-hairpin) are selected as initial structures to mimic different adsorption states, whereas four SAM surfaces with different end groups in hydrophobicity and charge distribution are used to examine the effect of surface chemistry on Abeta structure and adsorption. Simulation results show that alpha-helical monomer displays higher structural stability than beta-hairpin monomer on all SAMs, suggesting that the preferential conformation of Abeta monomer could be alpha-helical or random structure when bound to surfaces. Structural stability and adsorption behavior of Abeta monomer on the SAMs originates from competitive interactions between Abeta and SAM and between SAM and interfacial water, which involve the conformation of Abeta, the surface chemistry of SAM, and the structure and dynamics of interfacial waters. The relative net binding affinity of Abeta with the SAMs is in the favorable order of COOH-SAM > NH(2)-SAM > CH(3)-SAM > OH-SAM, highlighting the importance of electrostatic and hydrophobic interactions for driving Abeta adsorption at the SAMs, but both interactions contribute differently to each Abeta-SAM complex. This work provides parallel insights into the understanding of Abeta structure and aggregation on cell membrane.

7 CFR 1739.10 - Eligible applicant.

Code of Federal Regulations, 2014 CFR

2014-01-01

...'s number. (d) Register in the System for Award Management (SAM) (formerly Central Contractor... paper, must be registered in the SAM prior to submitting an application. Applicants may register for the SAM at https://www.sam.gov/. (2) The SAM registration must remain active, with current information, at...

SAM Photovoltaic Model Technical Reference

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

Gilman, P.

2015-05-27

This manual describes the photovoltaic performance model in the System Advisor Model (SAM). The U.S. Department of Energy’s National Renewable Energy Laboratory maintains and distributes SAM, which is available as a free download from https://sam.nrel.gov. These descriptions are based on SAM 2015.1.30 (SSC 41).

SAM International Case Studies: DPV Analysis in Mexico

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

McCall, James D

Presentation demonstrates the use of the System Advisor Model (SAM) in international analyses, specifically Mexico. Two analyses are discussed with relation to SAM modelling efforts: 1) Customer impacts from changes to net metering and billing agreements and 2) Potential benefits of PV for Mexican solar customers, the Mexican Treasury, and the environment. Along with the SAM analyses, integration of the International Utility Rate Database (I-URDB) with SAM and future international SAM work are discussed. Presentation was created for the International Solar Energy Society's (ISES) webinar titled 'International use of the NREL System Advisor Model (SAM) with case studies'.

Structural Basis for Methyl Transfer by a Radical SAM Enzyme

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

Boal, Amie K.; Grove, Tyler L.; McLaughlin, Monica I.

2014-10-02

The radical S-adenosyl-l-methionine (SAM) enzymes RlmN and Cfr methylate 23S ribosomal RNA, modifying the C2 or C8 position of adenosine 2503. The methyl groups are installed by a two-step sequence involving initial methylation of a conserved Cys residue (RlmN Cys{sup 355}) by SAM. Methyl transfer to the substrate requires reductive cleavage of a second equivalent of SAM. Crystal structures of RlmN and RlmN with SAM show that a single molecule of SAM coordinates the [4Fe-4S] cluster. Residue Cys{sup 355} is S-methylated and located proximal to the SAM methyl group, suggesting the SAM that is involved in the initial methyl transfermore » binds at the same site. Thus, RlmN accomplishes its complex reaction with structural economy, harnessing the two most important reactivities of SAM within a single site.« less

Mice heterozygous for the Mdr2 gene demonstrate decreased PEMT activity and diminished steatohepatitis on the MCD diet.

PubMed

Igolnikov, Alexander C; Green, Richard M

2006-03-01

The administration of a methionine and choline deficient (MCD) diet to mice serves as an animal model of NASH. The multidrug resistant 2 (Mdr2) P-glycoprotein encodes for the canalicular phospholipid transporter, and Mdr2 (+/-) mice secrete 40% less phosphatidylcholine than wild-type mice. We have hypothesized that phosphatidylethanolamine-N-methyl transferase (PEMT) up-regulation is a consequence of MCD diet administration, and is important for the pathogenesis of steatohepatitis in this model. However, the effect of decreased phosphatidylcholine secretion and modulation of PEMT on the development of diet-induced steatohepatitis in Mdr2 (+/-) mice has not been explored. Thus, the purpose of the study is to examine the effects of the MCD diet on Mdr2 (+/-) mice. Mdr2 (+/-) and Mdr2 (+/+) mice were treated with an MCD or control diet for up to 30 days, and the severity of steatohepatitis, PEMT activity and hepatic S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) levels were measured. Serum ALT levels, hepatic inflammation, and PEMT activity were significantly lower, and hepatic SAM:SAH ratios were significantly higher in Mdr2 (+/-) mice at 7 and 30 days on the MCD diet. Mdr2 (+/-) mice have diminished susceptibility to MCD diet-induced NASH, which is associated with a relative decrease in PEMT activity and increased SAM:SAH ratios.

The role of surface electrostatics on the stability, function and regulation of human cystathionine β-synthase, a complex multidomain and oligomeric protein.

PubMed

Pey, Angel L; Majtan, Tomas; Kraus, Jan P

2014-09-01

Human cystathionine β-synthase (hCBS) is a key enzyme of sulfur amino acid metabolism, controlling the commitment of homocysteine to the transsulfuration pathway and antioxidant defense. Mutations in hCBS cause inherited homocystinuria (HCU), a rare inborn error of metabolism characterized by accumulation of toxic homocysteine in blood and urine. hCBS is a complex multidomain and oligomeric protein whose activity and stability are independently regulated by the binding of S-adenosyl-methionine (SAM) to two different types of sites at its C-terminal regulatory domain. Here we study the role of surface electrostatics on the complex regulation and stability of hCBS using biophysical and biochemical procedures. We show that the kinetic stability of the catalytic and regulatory domains is significantly affected by the modulation of surface electrostatics through noticeable structural and energetic changes along their denaturation pathways. We also show that surface electrostatics strongly affect SAM binding properties to those sites responsible for either enzyme activation or kinetic stabilization. Our results provide new insight into the regulation of hCBS activity and stability in vivo with implications for understanding HCU as a conformational disease. We also lend experimental support to the role of electrostatic interactions in the recently proposed binding modes of SAM leading to hCBS activation and kinetic stabilization. Copyright © 2014 Elsevier B.V. All rights reserved.

Investigation of gas surface interactions at self-assembled silicon surfaces acting as gas sensors

NASA Astrophysics Data System (ADS)

Narducci, Dario; Bernardinello, Patrizia; Oldani, Matteo

2003-05-01

This paper reports the results of an investigation aimed at using self-assembled monolayers to modify the supramolecular interactions between Si surfaces and gaseous molecules. The specific goal is that of employing molecularly imprinted silicon surfaces to develop a new class of chemical sensors capable to detect species with enhanced selectivity. Single-crystal p-type (0 0 1) silicon has been modified by grafting organic molecules onto its surface by using wet chemistry synthetic methods. Silicon has been activated toward nucleophilic attack by brominating its surface using a modified version of the purple etch, and aromatic fragments have been bonded through the formation of direct Si-C bonds onto it using Grignard reagents or lithium aryl species. Formation of self-assembled monolayers (SAMs) was verified by using vibrational spectroscopy. Porous metal-SAM-Si diodes have been successfully tested as resistive chemical sensors toward NO x, SO x, CO, NH 3 and methane. Current-voltage characteristics measured at different gas compositions showed that the mechanism of surface electron density modulation involves a modification of the junction barrier height upon gas adsorption. Quantum-mechanical simulations of the interaction mechanism were carried out using different computational methods to support such an interaction mechanism. The results obtained appear to open up new relevant applications of the SAM techniques in the area of gas sensing.

Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall

PubMed Central

Liu, Xiaoping; El-Mahdy, Mohamed A.; Boslett, James; Varadharaj, Saradhadevi; Hemann, Craig; Abdelghany, Tamer M.; Ismail, Raed S.; Little, Sean C.; Zhou, Danlei; Thuy, Le Thi Thanh; Kawada, Norifumi; Zweier, Jay L.

2017-01-01

The identity of the specific nitric oxide dioxygenase (NOD) that serves as the main in vivo regulator of O2-dependent NO degradation in smooth muscle remains elusive. Cytoglobin (Cygb) is a recently discovered globin expressed in fibroblasts and smooth muscle cells with unknown function. Cygb, coupled with a cellular reducing system, efficiently regulates the rate of NO consumption by metabolizing NO in an O2-dependent manner with decreased NO consumption in physiological hypoxia. Here we show that Cygb is a major regulator of NO degradation and cardiovascular tone. Knockout of Cygb greatly prolongs NO decay, increases vascular relaxation, and lowers blood pressure and systemic vascular resistance. We further demonstrate that downregulation of Cygb prevents angiotensin-mediated hypertension. Thus, Cygb has a critical role in the regulation of vascular tone and disease. We suggest that modulation of the expression and NOD activity of Cygb represents a strategy for the treatment of cardiovascular disease. PMID:28393874

Pitch Perception in Tone Language-Speaking Adults With and Without Autism Spectrum Disorders

PubMed Central

Cheng, Stella T. T.; Lam, Gary Y. H.

2017-01-01

Enhanced low-level pitch perception has been universally reported in autism spectrum disorders (ASD). This study examined whether tone language speakers with ASD exhibit this advantage. The pitch perception skill of 20 Cantonese-speaking adults with ASD was compared with that of 20 neurotypical individuals. Participants discriminated pairs of real syllable, pseudo-syllable (syllables that do not conform the phonotactic rules or are accidental gaps), and non-speech (syllables with attenuated high-frequency segmental content) stimuli contrasting pitch levels. The results revealed significantly higher discrimination ability in both groups for the non-speech stimuli than for the pseudo-syllables with one semitone difference. No significant group differences were noted. Different from previous findings, post hoc analysis found that enhanced pitch perception was observed in a subgroup of participants with ASD showing no history of delayed speech onset. The tone language experience may have modulated the pitch processing mechanism in the speakers in both ASD and non-ASD groups. PMID:28616150

Auditory memory for timbre.

PubMed

McKeown, Denis; Wellsted, David

2009-06-01

Psychophysical studies are reported examining how the context of recent auditory stimulation may modulate the processing of new sounds. The question posed is how recent tone stimulation may affect ongoing performance in a discrimination task. In the task, two complex sounds occurred in successive intervals. A single target component of one complex was decreased (Experiments 1 and 2) or increased (Experiments 3, 4, and 5) in intensity on half of trials: The task was simply to identify those trials. Prior to each trial, a pure tone inducer was introduced either at the same frequency as the target component or at the frequency of a different component of the complex. Consistent with a frequency-specific form of disruption, discrimination performance was impaired when the inducing tone matched the frequency of the following decrement or increment. A timbre memory model (TMM) is proposed incorporating channel-specific interference allied to inhibition of attending in the coding of sounds in the context of memory traces of recent sounds. (c) 2009 APA, all rights reserved.

Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall

NASA Astrophysics Data System (ADS)

Liu, Xiaoping; El-Mahdy, Mohamed A.; Boslett, James; Varadharaj, Saradhadevi; Hemann, Craig; Abdelghany, Tamer M.; Ismail, Raed S.; Little, Sean C.; Zhou, Danlei; Thuy, Le Thi Thanh; Kawada, Norifumi; Zweier, Jay L.

2017-04-01

The identity of the specific nitric oxide dioxygenase (NOD) that serves as the main in vivo regulator of O2-dependent NO degradation in smooth muscle remains elusive. Cytoglobin (Cygb) is a recently discovered globin expressed in fibroblasts and smooth muscle cells with unknown function. Cygb, coupled with a cellular reducing system, efficiently regulates the rate of NO consumption by metabolizing NO in an O2-dependent manner with decreased NO consumption in physiological hypoxia. Here we show that Cygb is a major regulator of NO degradation and cardiovascular tone. Knockout of Cygb greatly prolongs NO decay, increases vascular relaxation, and lowers blood pressure and systemic vascular resistance. We further demonstrate that downregulation of Cygb prevents angiotensin-mediated hypertension. Thus, Cygb has a critical role in the regulation of vascular tone and disease. We suggest that modulation of the expression and NOD activity of Cygb represents a strategy for the treatment of cardiovascular disease.

Auditory Memory for Timbre

ERIC Educational Resources Information Center

McKeown, Denis; Wellsted, David

2009-01-01

Psychophysical studies are reported examining how the context of recent auditory stimulation may modulate the processing of new sounds. The question posed is how recent tone stimulation may affect ongoing performance in a discrimination task. In the task, two complex sounds occurred in successive intervals. A single target component of one complex…

Central Cannabinoid Receptors Modulate Acquisition of Eyeblink Conditioning

ERIC Educational Resources Information Center

Steinmetz, Adam B.; Freeman, John H.

2010-01-01

Delay eyeblink conditioning is established by paired presentations of a conditioned stimulus (CS) such as a tone or light, and an unconditioned stimulus (US) that elicits the blink reflex. Conditioned stimulus information is projected from the basilar pontine nuclei to the cerebellar interpositus nucleus and cortex. The cerebellar cortex,…

Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3.

PubMed

Leettola, Catherine N; Knight, Mary Jane; Cascio, Duilio; Hoffman, Sigrid; Bowie, James U

2014-07-07

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure in humans. In the PKD/Mhm(cy/+) rat model of ADPKD, the point mutation R823W in the sterile alpha motif (SAM) domain of the protein ANKS6 is responsible for disease. SAM domains are known protein-protein interaction domains, capable of binding each other to form polymers and heterodimers. Despite its physiological importance, little is known about the function of ANKS6 and how the R823W point mutation leads to PKD. Recent work has revealed that ANKS6 interacts with a related protein called ANKS3. Both ANKS6 and ANKS3 have a similar domain structure, with ankyrin repeats at the N-terminus and a SAM domain at the C-terminus. The SAM domain of ANKS3 is identified as a direct binding partner of the ANKS6 SAM domain. We find that ANKS3-SAM polymerizes and ANKS6-SAM can bind to one end of the polymer. We present crystal structures of both the ANKS3-SAM polymer and the ANKS3-SAM/ANKS6-SAM complex, revealing the molecular details of their association. We also learn how the R823W mutation disrupts ANKS6 function by dramatically destabilizing the SAM domain such that the interaction with ANKS3-SAM is lost. ANKS3 is a direct interacting partner of ANKS6. By structurally and biochemically characterizing the interaction between the ANKS3 and ANKS6 SAM domains, our work provides a basis for future investigation of how the interaction between these proteins mediates kidney function.

Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3

PubMed Central

2014-01-01

Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure in humans. In the PKD/Mhm(cy/+) rat model of ADPKD, the point mutation R823W in the sterile alpha motif (SAM) domain of the protein ANKS6 is responsible for disease. SAM domains are known protein-protein interaction domains, capable of binding each other to form polymers and heterodimers. Despite its physiological importance, little is known about the function of ANKS6 and how the R823W point mutation leads to PKD. Recent work has revealed that ANKS6 interacts with a related protein called ANKS3. Both ANKS6 and ANKS3 have a similar domain structure, with ankyrin repeats at the N-terminus and a SAM domain at the C-terminus. Results The SAM domain of ANKS3 is identified as a direct binding partner of the ANKS6 SAM domain. We find that ANKS3-SAM polymerizes and ANKS6-SAM can bind to one end of the polymer. We present crystal structures of both the ANKS3-SAM polymer and the ANKS3-SAM/ANKS6-SAM complex, revealing the molecular details of their association. We also learn how the R823W mutation disrupts ANKS6 function by dramatically destabilizing the SAM domain such that the interaction with ANKS3-SAM is lost. Conclusions ANKS3 is a direct interacting partner of ANKS6. By structurally and biochemically characterizing the interaction between the ANKS3 and ANKS6 SAM domains, our work provides a basis for future investigation of how the interaction between these proteins mediates kidney function. PMID:24998259

Molecular dynamics simulations of low-ordered alzheimer β-amyloid oligomers from dimer to hexamer on self-assembled monolayers.

PubMed

Zhao, Jun; Wang, Qiuming; Liang, Guizhao; Zheng, Jie

2011-12-20

Accumulation of small soluble oligomers of amyloid-β (Aβ) in the human brain is thought to play an important pathological role in Alzheimer's disease. The interaction of these Aβ oligomers with cell membrane and other artificial surfaces is important for the understanding of Aβ aggregation and toxicity mechanisms. Here, we present a series of exploratory molecular dynamics (MD) simulations to study the early adsorption and conformational change of Aβ oligomers from dimer to hexamer on three different self-assembled monolayers (SAMs) terminated with CH(3), OH, and COOH groups. Within the time scale of MD simulations, the conformation, orientation, and adsorption of Aβ oligomers on the SAMs is determined by complex interplay among the size of Aβ oligomers, the surface chemistry of the SAMs, and the structure and dynamics of interfacial waters. Energetic analysis of Aβ adsorption on the SAMs reveals that Aβ adsorption on the SAMs is a net outcome of different competitions between dominant hydrophobic Aβ-CH(3)-SAM interactions and weak CH(3)-SAM-water interactions, between dominant electrostatic Aβ-COOH-SAM interactions and strong COOH-SAM-water interactions, and between comparable hydrophobic and electrostatic Aβ-OH-SAM interactions and strong OH-SAM-water interactions. Atomic force microscopy images also confirm that all of three SAMs can induce the adsorption and polymerization of Aβ oligomers. Structural analysis of Aβ oligomers on the SAMs shows a dramatic increase in structural stability and β-sheet content from dimer to trimer, suggesting that Aβ trimer could act as seeds for Aβ polymerization on the SAMs. This work provides atomic-level understanding of Aβ peptides at interface. © 2011 American Chemical Society

Edge-to-edge repair for prevention and treatment of mitral valve systolic anterior motion.

PubMed

Myers, Patrick O; Khalpey, Zain; Maloney, Ann M; Brinster, Derek R; D'Ambra, Michael N; Cohn, Lawrence H

2013-10-01

The edge-to-edge technique has been proposed to prevent systolic anterior motion (SAM) of the mitral valve. There is limited clinical data available on outcomes of this technique for this indication. We reviewed the midterm results of this technique for SAM prevention and treatment. A total of 2226 patients had mitral valve repair between 2000 and 2011, 1148 of which were for myxomatous mitral regurgitation. Beginning in 2000, predictability of postrepair SAM based on the prebypass, intraoperative transesophageal echocardiogram arose in our program. The edge-to-edge technique was used in 65 patients (5.7%) for SAM management, in 53 patients preemptively for transesophageal echocardiogram-based SAM prediction, and in 12 patients for postrepair SAM treatment. There was no operative mortality. Postoperative mitral regurgitation was significantly improved in all patients compared with the preoperative grade (P < .001). SAM was completely eliminated, the mean mitral regurgitation grade in the postoperative period was 0.7 ± 0.9, and the mean transmitral gradient was 1.3 ± 2.2 mm Hg. During a mean follow-up of 26 months, 1 patient in the SAM treatment group presented late recurrence of SAM and no patients developed mitral stenosis (mean transmitral gradient, 2.0 ± 2.6 mm Hg; P = .12). Without SAM prediction and preemptive edge-to-edge technique, the expected rate of SAM would have been 5.7%; however, the observed rate was 1% (12 of 1148 patients). Initiating an expectation for prebypass SAM prediction, combined with a surgical SAM prevention strategy, resulted in a reduced prevalence of SAM compared with our model of observed to-expected-ratios and to published norms. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

RAWINPROC: Computer program for decommutating, interpreting, and interpolating Rawinsonde meteorological balloon sounding data

NASA Technical Reports Server (NTRS)

Staffanson, F. L.

1981-01-01

The FORTRAN computer program RAWINPROC accepts output from NASA Wallops computer program METPASS1; and produces input for NASA computer program 3.0.0700 (ECC-PRD). The three parts together form a software system for the completely automatic reduction of standard RAWINSONDE sounding data. RAWINPROC pre-edits the 0.1-second data, including time-of-day, azimuth, elevation, and sonde-modulated tone frequency, condenses the data according to successive dwells of the tone frequency, decommutates the condensed data into the proper channels (temperature, relative humidity, high and low references), determines the running baroswitch contact number and computes the associated pressure altitudes, and interpolates the data appropriate for input to ACC-PRD.

Using Sarcasm to Compliment: Context, Intonation, and the Perception of Statements with a Negative Literal Meaning.

PubMed

Voyer, Daniel; Vu, Janie P

2016-06-01

The present study extended findings of contrast effects in an auditory sarcasm perception task manipulating context and tone of voice. In contrast to previous research that had used sarcastic and sincere statements with a positive literal meaning, the present experiment examined how statements with a negative literal meaning would affect the results. Eighty-four undergraduate students completed a task in which an ambiguous, positive, or negative computer-generated context spoken in a flat emotional tone was followed by a statement with a negative literal meaning spoken in a sincere or sarcastic tone of voice. Results for both the proportion of sarcastic responses and response time showed a significant context by tone interaction, reflecting relatively fast sarcastic responses for the situation in which sarcasm would turn the statement into a compliment (positive context, sarcastic intonation) and fast sincere responses when the literal insult was emphasized (negative context, sincere intonation). However, the ambiguous context produced a pattern of results modulated by the tone of voice that was similar to that observed when the context/intonation pairing could not be interpreted as a compliment or an insult (negative context/sarcastic intonation or positive context/sincere intonation). These findings add to the body of literature suggesting that situational contrast, context, and intonation influence how sarcasm is perceived while demonstrating the importance of the literal meaning in sarcasm perception. They can be interpreted in the context of models of sarcasm comprehension that postulate two stages of processing.

S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells

PubMed Central

Wang, Yan; Sun, ZhongSheng; Szyf, Moshe

2017-01-01

S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM is unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and are downregulated by SAM. Analysis of the methylome using bisulfite mapping of captured promoters and enhancers reveals that SAM hyper-methylates and downregulates genes in pathways of growth and metastasis that are upregulated in liver cancer cells. Depletion of two SAM downregulated genes STMN1 and TAF15 reduces cellular transformation and invasiveness, providing evidence that SAM targets are genes important for cancer growth and invasiveness. Taken together these data provide a molecular rationale for SAM as an anticancer agent. PMID:29340097

S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells.

PubMed

Wang, Yan; Sun, ZhongSheng; Szyf, Moshe

2017-12-19

S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to have chemo- protective activity against liver cancer, however the molecular footprint of SAM is unknown. We show here that SAM selectively inhibits growth, transformation and invasiveness of hepatocellular carcinoma cell lines but not normal primary liver cells. Analysis of the transcriptome of SAM treated and untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells reveals pathways involved in cancer and metastasis that are upregulated in cancer cells and are downregulated by SAM. Analysis of the methylome using bisulfite mapping of captured promoters and enhancers reveals that SAM hyper-methylates and downregulates genes in pathways of growth and metastasis that are upregulated in liver cancer cells. Depletion of two SAM downregulated genes STMN1 and TAF15 reduces cellular transformation and invasiveness, providing evidence that SAM targets are genes important for cancer growth and invasiveness. Taken together these data provide a molecular rationale for SAM as an anticancer agent.

Fetal auditory evoked responses to onset of amplitude modulated sounds. A fetal magnetoencephalography (fMEG) study.

PubMed

Draganova, R; Schollbach, A; Schleger, F; Braendle, J; Brucker, S; Abele, H; Kagan, K O; Wallwiener, D; Fritsche, A; Eswaran, H; Preissl, H

2018-06-01

The human fetal auditory system is functional around the 25th week of gestational age when the thalamocortical connections are established. Fetal magnetoencephalography (fMEG) provides evidence for fetal auditory brain responses to pure tones and syllables. Fifty-five pregnant women between 31 and 40 weeks of gestation were included in the study. Fetal MEG was recorded during the presentation of an amplitude modulated tone (AM) with a carrier frequency of 500 Hz to the maternal abdomen modulated by low modulation rates (MRs) - 2/s and 4/s, middle MR - 8/s and high MRs - 27/s, 42/s, 78/s and 91/s. The aim was to determine whether the fetal brain responds differently to envelope slopes and intensity change at the onset of the AM sounds. A significant decrease of the response latencies of transient event-related responses (ERR) to high and middle MRs in comparison to the low MRs was observed. The highest fetal response rate was achieved by modulation rates of 2/s, 4/s and 27/s (70%, 57%, and 86%, respectively). Additionally, a maturation effect of the ERR (response latency vs. gestational age) was observed only for 4/s MR. The significant difference between the response latencies to low, middle, and high MRs suggests that still before birth the fetal brain processes the sound slopes at the onset in different integration time-windows, depending on the time for the intensity increase or stimulus power density at the onset, which is a prerequisite for language acquisition. Copyright © 2018 Elsevier B.V. All rights reserved.

The use of alkanethiol self-assembled monolayers on 316L stainless steel for coronary artery stent nanomedicine applications: an oxidative and in vitro stability study.

PubMed

Mahapatro, Anil; Johnson, Dave M; Patel, Devang N; Feldman, Marc D; Ayon, Arturo A; Agrawal, C Mauli

2006-09-01

The use of self-assembled monolayers (SAMs) on medical devices offers a methodology for the incorporation of nanotechnology into medicine. SAMs are highly ordered nanosized molecular coatings, adding 1 to 10 nm thickness to a surface. This work is part of an overall goal to deliver therapeutic drugs from the surface of metal coronary stents using SAMs. In this study the oxidative and in vitro stability of functional alkylthiol SAMs on 316L stainless steel (SS) has been demonstrated. SAMs of 11-mercaptoundecanoic acid (-COOH SAM) and 11-mercapto-1-undecanol (-OH SAM) were formed on 316L SS. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and contact angle (CA) measurements collectively confirmed the formation of functional alkylthiol SAMs on 316L SS. Well-formed SAMs (CA: 82 deg +/- 9 deg) were achieved within 48 hours of immersion in ethanolic solutions, after which no significant improvement in CA was observed. The ratio of the thiolate peak (163.5 eV) to the oxidized sulfur (sulfonates) peak (166.5 eV) gives us an indication of the percentage SAMs that would bind to the metal and serve as a drug reservoir in vivo; which in turn represents the stability and viability of these SAMs, keeping in mind the cardiovascular application under consideration. Oxidative and in vitro stability studies showed that alkanethiol SAMs oxidized completely within 14 days. The SAMs tend to desorb and leave the metal surface after longer time periods (21 days) in phosphate-buffered saline (PBS) immersion, whereas for oxidative exposure the SAMs continue to remain on the metal surface in the form of sulfonates. Although the chemistry of bonding of alkylthiol with the 316L SS is not well understood, the nanosized alkylthiol SAMs demonstrate sufficient stability to justify further study on these systems for potential in vivo drug delivery in the chosen coronary artery stent applications.

Standardized added metabolic activity (SAM): a partial volume independent marker of total lesion glycolysis in liver metastases.

PubMed

Mertens, Jeroen; Dobbeleir, André; Ham, Hamphrey; D'Asseler, Yves; Goethals, Ingeborg; Van de Wiele, Christophe

2012-09-01

The standardized added metabolic activity (SAM) is a new marker of total lesion glycolysis that avoids partial volume effect (PVE) and thresholding. SAM is calculated by drawing a volume of interest (VOI(1)) around the tumour and a larger VOI (VOI(2)) around VOI(1). Subtracting the background activity in VOI(2)-VOI(1) from VOI(1) yields SAM. If VOI(1) is set at a reasonable distance from the tumour, PVE are avoided. Phantom and initial clinical validation data are presented. Spheres of a Jaszczak phantom were filled with a 5.4, 3.64 and 2.0 times higher concentration relative to background activity and positron emission tomography (PET) data were acquired during 10 min. SAM of all spheres was expressed as a percentage of the expected value (the actual activity ratio minus 1). In 15 patients a 10-min list-mode acquisition PET study centred on their primary squamous cell carcinoma (PSCC) was performed and images of 1-10 min reconstructed. SAM1-9min values of PSCC were expressed as a percentage of SAM10min. Nineteen patients suffering from liver metastases treated with chemotherapy underwent PET/CT prior to (scan 1) and after 3-6 cycles of chemotherapy (scan 2). SAM and maximum standardized uptake values (SUV(max)) of the liver lesions on scan 1 (SAM1 and SUV(max)1) and the percentage reduction between both ΔSAM and ΔSUV(max) were related to Response Evaluation Criteria in Solid Tumors (RECIST) response. For the phantom acquisitions, the mean normalized SAM/sphere volume calculated was 94.9 % (SD 5.9 %) of the expected value. In the PSCC patients, the mean difference between SAM1min and SAM10min was only 4 % (SD 5 %). SUV(max)1min and SUV(max)10min proved to be not significantly different, but the variability was slightly larger than that of SAM (SD 6.4 %). SAM1 and ΔSAM values for responders versus non-responders were, respectively, 57 (SD 119) versus 297 (SD 625) for SAM1 (p = 0.2) and 99 % (SD 3 %) versus 32 % (SD 44 %) for ΔSAM (p = 0.001). SUV(max)1 and ΔSUV(max) values in responders versus non-responders were, respectively, 3.9 (SD 2.4) versus 6.3 (SD 3.1) for SUV(max)1 (p = 0.08) and 94 % (SD 17) versus 7 % (SD 40 %) for ΔSUV(max) (p = 0.0001). The AUC of ΔSAM and ΔSUV(max) were not significantly different on receiver-operating characteristic (ROC) analysis (AUC 1.0 and 0.99, respectively, p = 0.6). SAM is a promising parameter for tumour response assessment of liver metastases by means of (18)F-fluorodeoxyglucose PET.

Sympathovagal response to orthostatism in overt and in subclinical hyperthyroidism.

PubMed

Goichot, B; Brandenberger, G; Vinzio, S; Perrin, A E; Geny, B; Schlienger, J L; Simon, C

2004-04-01

Heart rate variability (HRV) is a measure of the physiological variation of R-R intervals, reflecting the sympathovagal balance. In both overt and subclinical hyperthyroidism, a relative increase in sympathetic activity has been demonstrated, mainly due to a decrease in vagal activity. The modifications of HRV during orthostatism in normal subjects resemble those seen in hyperthyroidism. We have studied the response of 19 patients with overt hyperthyroidism and 12 with subclinical hyperthyroidism during orthostatism using HRV and compared the results to those of 32 healthy controls. In the three groups, the R-R intervals decreased in the same proportion after orthostatism. The low frequency power (LF)/[LF + high frequency power (HF)] ratio, which reflects the sympathetic tone, also increased in the same proportion in the three groups. However, the mechanisms of the modulation of the sympathovagal balance during orthostatism were different among the three groups. In controls, the relative increase of sympathetic tone after orthostatism was due principally to a decrease in vagal tone (reflected by decreased power in the HF band), while in overt hyperthyroidism, where the power in the HF band was already minimal in the lying position, there was a clear increase in the LF band power during orthostatism. The results were intermediate in the subclinical hyperthyroidism group, reflecting a continuum of effects of the thyroid hormone excess on the autonomic nervous system. Our study shows that despite an apparent normal cardiovascular adaptation to orthostatism in hyperthyroidism, the modulation of the autonomic nervous system is profoundly modified.

A simulation framework for auditory discrimination experiments: Revealing the importance of across-frequency processing in speech perception.

PubMed

Schädler, Marc René; Warzybok, Anna; Ewert, Stephan D; Kollmeier, Birger

2016-05-01

A framework for simulating auditory discrimination experiments, based on an approach from Schädler, Warzybok, Hochmuth, and Kollmeier [(2015). Int. J. Audiol. 54, 100-107] which was originally designed to predict speech recognition thresholds, is extended to also predict psychoacoustic thresholds. The proposed framework is used to assess the suitability of different auditory-inspired feature sets for a range of auditory discrimination experiments that included psychoacoustic as well as speech recognition experiments in noise. The considered experiments were 2 kHz tone-in-broadband-noise simultaneous masking depending on the tone length, spectral masking with simultaneously presented tone signals and narrow-band noise maskers, and German Matrix sentence test reception threshold in stationary and modulated noise. The employed feature sets included spectro-temporal Gabor filter bank features, Mel-frequency cepstral coefficients, logarithmically scaled Mel-spectrograms, and the internal representation of the Perception Model from Dau, Kollmeier, and Kohlrausch [(1997). J. Acoust. Soc. Am. 102(5), 2892-2905]. The proposed framework was successfully employed to simulate all experiments with a common parameter set and obtain objective thresholds with less assumptions compared to traditional modeling approaches. Depending on the feature set, the simulated reference-free thresholds were found to agree with-and hence to predict-empirical data from the literature. Across-frequency processing was found to be crucial to accurately model the lower speech reception threshold in modulated noise conditions than in stationary noise conditions.

The monaural temporal window based on masking period pattern data in school-aged children and adults.

PubMed

Buss, Emily; He, Shuman; Grose, John H; Hall, Joseph W

2013-03-01

Several lines of evidence indicate that auditory temporal resolution improves over childhood, whereas other data implicate the development of processing efficiency. The present study used the masking period pattern paradigm to examine the maturation of temporal processing in normal-hearing children (4.8 to 10.7 yrs) compared to adults. Thresholds for a brief tone were measured at 6 temporal positions relative to the period of a 5-Hz quasi-square-wave masker envelope, with a 20-dB modulation depth, as well as in 2 steady maskers. The signal was a pure tone at either 1000 or 6500 Hz, and the masker was a band of noise, either spectrally wide or narrow (21.3 and 1.4 equivalent rectangular bandwidths, respectively). Masker modulation improved thresholds more for wide than narrow bandwidths, and adults tended to receive more benefit from modulation than young children. Fits to data for the wide maskers indicated a change in window symmetry with development, reflecting relatively greater backward masking for the youngest listeners. Data for children >6.5 yrs of age appeared more adult-like for the 6500- than the 1000-Hz signal. Differences in temporal window asymmetry with listener age cannot be entirely explained as a consequence of a higher criterion for detection in children, a form of inefficiency.

Auditory Selective Attention to Speech Modulates Activity in the Visual Word Form Area

PubMed Central

Yoncheva, Yuliya N.; Zevin, Jason D.; Maurer, Urs

2010-01-01

Selective attention to speech versus nonspeech signals in complex auditory input could produce top-down modulation of cortical regions previously linked to perception of spoken, and even visual, words. To isolate such top-down attentional effects, we contrasted 2 equally challenging active listening tasks, performed on the same complex auditory stimuli (words overlaid with a series of 3 tones). Instructions required selectively attending to either the speech signals (in service of rhyme judgment) or the melodic signals (tone-triplet matching). Selective attention to speech, relative to attention to melody, was associated with blood oxygenation level–dependent (BOLD) increases during functional magnetic resonance imaging (fMRI) in left inferior frontal gyrus, temporal regions, and the visual word form area (VWFA). Further investigation of the activity in visual regions revealed overall deactivation relative to baseline rest for both attention conditions. Topographic analysis demonstrated that while attending to melody drove deactivation equivalently across all fusiform regions of interest examined, attending to speech produced a regionally specific modulation: deactivation of all fusiform regions, except the VWFA. Results indicate that selective attention to speech can topographically tune extrastriate cortex, leading to increased activity in VWFA relative to surrounding regions, in line with the well-established connectivity between areas related to spoken and visual word perception in skilled readers. PMID:19571269

Modulatory compartments in cortex and local regulation of cholinergic tone.

PubMed

Coppola, Jennifer J; Ward, Nicholas J; Jadi, Monika P; Disney, Anita A

2016-09-01

Neuromodulatory signaling is generally considered broad in its impact across cortex. However, variations in the characteristics of cortical circuits may introduce regionally-specific responses to diffuse modulatory signals. Features such as patterns of axonal innervation, tissue tortuosity and molecular diffusion, effectiveness of degradation pathways, subcellular receptor localization, and patterns of receptor expression can lead to local modification of modulatory inputs. We propose that modulatory compartments exist in cortex and can be defined by variation in structural features of local circuits. Further, we argue that these compartments are responsible for local regulation of neuromodulatory tone. For the cholinergic system, these modulatory compartments are regions of cortical tissue within which signaling conditions for acetylcholine are relatively uniform, but between which signaling can vary profoundly. In the visual system, evidence for the existence of compartments indicates that cholinergic modulation likely differs across the visual pathway. We argue that the existence of these compartments calls for thinking about cholinergic modulation in terms of finer-grained control of local cortical circuits than is implied by the traditional view of this system as a diffuse modulator. Further, an understanding of modulatory compartments provides an opportunity to better understand and perhaps correct signal modifications that lead to pathological states. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of level discrimination, increment detection, and comodulation masking release in the audio- and envelope-frequency domains

PubMed Central

Nelson, Paul C.; Ewert, Stephan D.; Carney, Laurel H.; Dau, Torsten

2008-01-01

In general, the temporal structure of stimuli must be considered to account for certain observations made in detection and masking experiments in the audio-frequency domain. Two such phenomena are (1) a heightened sensitivity to amplitude increments with a temporal fringe compared to gated level discrimination performance and (2) lower tone-in-noise detection thresholds using a modulated masker compared to those using an unmodulated masker. In the current study, translations of these two experiments were carried out to test the hypothesis that analogous cues might be used in the envelope-frequency domain. Pure-tone carrier amplitude-modulation (AM) depth-discrimination thresholds were found to be similar using both traditional gated stimuli and using a temporally modulated fringe for a fixed standard depth (ms=0.25) and a range of AM frequencies (4-64 Hz). In a second experiment, masked sinusoidal AM detection thresholds were compared in conditions with and without slow and regular fluctuations imposed on the instantaneous masker AM depth. Release from masking was obtained only for very slow masker fluctuations (less than 2 Hz). A physiologically motivated model that effectively acts as a first-order envelope change detector accounted for several, but not all, of the key aspects of the data. PMID:17471731

Sub-nanometer Resolution Imaging with Amplitude-modulation Atomic Force Microscopy in Liquid

PubMed Central

Farokh Payam, Amir; Piantanida, Luca; Cafolla, Clodomiro; Voïtchovsky, Kislon

2016-01-01

Atomic force microscopy (AFM) has become a well-established technique for nanoscale imaging of samples in air and in liquid. Recent studies have shown that when operated in amplitude-modulation (tapping) mode, atomic or molecular-level resolution images can be achieved over a wide range of soft and hard samples in liquid. In these situations, small oscillation amplitudes (SAM-AFM) enhance the resolution by exploiting the solvated liquid at the surface of the sample. Although the technique has been successfully applied across fields as diverse as materials science, biology and biophysics and surface chemistry, obtaining high-resolution images in liquid can still remain challenging for novice users. This is partly due to the large number of variables to control and optimize such as the choice of cantilever, the sample preparation, and the correct manipulation of the imaging parameters. Here, we present a protocol for achieving high-resolution images of hard and soft samples in fluid using SAM-AFM on a commercial instrument. Our goal is to provide a step-by-step practical guide to achieving high-resolution images, including the cleaning and preparation of the apparatus and the sample, the choice of cantilever and optimization of the imaging parameters. For each step, we explain the scientific rationale behind our choices to facilitate the adaptation of the methodology to every user's specific system. PMID:28060262

Gene switching in Amoeba proteus caused by endosymbiotic bacteria.

PubMed

Jeon, Taeck J; Jeon, Kwang W

2004-02-01

The expression of genes for S-adenosylmethionine synthetase (SAMS), which catalyzes the synthesis of S-adenosylmethionine (AdoMet), a major methyl donor in cells, was studied in symbiont-free (D) and symbiont-bearing (xD) amoeba strains to determine the effect of bacterial endosymbionts. The symbionts suppressed the expression of the gene in host xD amoebae, but amoebae still exhibited about half the enzyme activity found in symbiont-free D amoebae. The study was aimed at elucidating mechanisms of the suppression of the amoeba's gene and determining the alternative source for the gene product. Unexpectedly, we found a second sams (sams2) gene in amoebae, which encoded 390 amino acids. Results of experiments measuring SAMS activities and amounts of AdoMet in D and xD amoebae showed that the half SAMS activity found in xD amoebae came from the amoeba's SAMS2 and not from their endosymbionts. The expression of amoeba sams genes was switched from sams1 to sams2 as a result of infection with X-bacteria, raising the possibility that the switch in the expression of sams genes by bacteria plays a role in the development of symbiosis and the host-pathogen interactions. This is the first report showing such a switch in the expression of host sams genes by infecting bacteria.

78 FR 80369 - Federal Acquisition Regulation; Service Contracts Reporting Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-31

...-and- materials, and labor-hour contracts and orders above the simplified acquisition threshold (SAT... thresholds established in FAR 4.1703 (e.g., above the SAT for cost-reimbursement, time-and-materials, and... reporting will be made at www.sam.gov (See section 3.10 of the SAM User Guide at https://www.sam.gov/sam/SAM...

Unanticipated coordination of tris buffer to the Radical SAM cluster of the RimO methylthiotransferase.

PubMed

Molle, Thibaut; Clémancey, Martin; Latour, Jean-Marc; Kathirvelu, Velavan; Sicoli, Giuseppe; Forouhar, Farhad; Mulliez, Etienne; Gambarelli, Serge; Atta, Mohamed

2016-07-01

Radical SAM enzymes generally contain a [4Fe-4S](2+/1+) (RS cluster) cluster bound to the protein via the three cysteines of a canonical motif CxxxCxxC. The non-cysteinyl iron is used to coordinate SAM via its amino-carboxylate moiety. The coordination-induced proximity between the cluster acting as an electron donor and the adenosyl-sulfonium bond of SAM allows for the homolytic cleavage of the latter leading to the formation of the reactive 5'-deoxyadenosyl radical used for substrate activation. Most of the structures of Radical SAM enzymes have been obtained in the presence of SAM, and therefore, little is known about the situation when SAM is not present. In this report, we show that RimO, a methylthiotransferase belonging to the radical SAM superfamily, binds a Tris molecule in the absence of SAM leading to specific spectroscopic signatures both in Mössbauer and pulsed EPR spectroscopies. These data provide a cautionary note for researchers who work with coordinative unsaturated iron sulfur clusters.

Self-Assembled Monolayers of Dithiophosphinic Acids on Gold

NASA Astrophysics Data System (ADS)

San Juan, Ronan Roca

This dissertation reports the synthesis of derivatives of dithiophosphinic acids (R1R2DTPAs), and the formation and characterization of DTPA SAMs on gold to build a knowledge base on their nature of binding, organization of the alkyl chains and electrochemical barrier properties. The binding of DTPA molecules on gold depends on the morphology of the gold film: They bind in a mixed monodentate and bidentate modes on standard as-deposited (As-Dep) gold, while they fully chelate on smoother template-stripped (TS) gold. Chapter 2 focuses on van der Waals interactions of various alkyl chain lengths of symmetrical R2DTPA SAMs, which increase with increasing chain lengths similar to those of the analogous n-alkanethiol SAMs, but with alkyl chains that are generally less dense than those of n-alkanethiol SAMs. Chapter 3 addresses why the DTPA compounds do not chelate on the standard As-Dep gold by comparing (C16)2DTPA SAM to (C16 )2DDP SAM. Here, side chain crystallinity stabilizes DTPA SAM structure at the expense of chelation of the DTPA molecules, which leads to a mixture of bidentate and monodentate DTPA molecules, whereas the increased flexibility of the chains in DDP due to the oxygen atoms retains chelation of the DDP molecules. Chapter 4 focuses on the SAMs formed from RlongRshort DTPAs, which shows that the length of the short chain spacer affects SAM packing density and thickness. The SAMs of these molecules also show homogeneous mixing of Rlong and Rshort chains. Chapter 5 investigates PhRDTPA SAMs in preparation for molecular junction studies. The chelation of PhRDTPA molecules on TS gold allows the PhRDTPAs to act as molecular alligator clips. The length of the alkyl chains controls the density of the phenyl group and they fill in the voids between adsorbates to prevent electrical shorting. Finally, Chapter 6 incorporates OH tail group(s) to control the wettability of DTPA SAMs. The presence of OH groups in DTPAs forms hydrophilic SAMs. The symmetrical OH-terminated DTPA forms a SAM with similar packing density to that of an analogous CH3-terminated DTPA SAM, while the OH/CH 3-terminated DTPA forms a thin SAM with low molecular packing, however, the chains of this SAM are homogeneously mixed.

Serum S-adenosylmethionine, but not methionine, increases in response to overfeeding in humans.

PubMed

Elshorbagy, A K; Jernerén, F; Samocha-Bonet, D; Refsum, H; Heilbronn, L K

2016-01-25

Plasma concentration of the methyl donor S-adenosylmethionine (SAM) is linearly associated with body mass index (BMI) and fat mass. As SAM is a high-energy compound and a sensor of cellular nutrient status, we hypothesized that SAM would increase with overfeeding. Forty normal to overweight men and women were overfed by 1250 kcal per day for 28 days. Serum SAM increased from 106 to 130 nmol/l (P=0.006). In stratified analysis, only those with weight gain above the median (high-weight gainers; average weight gain 3.9±0.3 kg) had increased SAM (+42%, P=0.001), whereas low-weight gainers (weight gain 1.5±0.2 kg) did not (Pinteraction=0.018). Overfeeding did not alter serum concentrations of the SAM precursor, methionine or the products, S-adenosyl-homocysteine and homocysteine. The SAM/SAH (S-adenosylhomocysteine) ratio was unchanged in the total population, but increased in high-weight gainers (+52%, P=0.006, Pinteraction =0.005). Change in SAM correlated positively with change in weight (r=0.33, P=0.041) and fat mass (r=0.44, P=0.009), but not with change in protein intake or plasma methionine, glucose, insulin or low-density lipoprotein (LDL)-cholesterol. Overfeeding raised serum SAM in proportion to the fat mass gained. The increase in SAM may help stabilize methionine levels, and denotes a responsiveness of SAM to nutrient state in humans. The role of SAM in human energy metabolism deserves further attention.

Predicting depressed patients with suicidal ideation from ECG recordings.

PubMed

Khandoker, A H; Luthra, V; Abouallaban, Y; Saha, S; Ahmed, K I; Mostafa, R; Chowdhury, N; Jelinek, H F

2017-05-01

Globally suicidal behavior is the third most common cause of death among patients with major depressive disorder (MDD). This study presents multi-lag tone-entropy (T-E) analysis of heart rate variability (HRV) as a screening tool for identifying MDD patients with suicidal ideation. Sixty-one ECG recordings (10 min) were acquired and analyzed from control subjects (29 CONT), 16 MDD subjects with (MDDSI+) and 16 without suicidal ideation (MDDSI-). After ECG preprocessing, tone and entropy values were calculated for multiple lags (m: 1-10). The MDDSI+ group was found to have a higher mean tone value compared to that of the MDDSI- group for lags 1-8, whereas the mean entropy value was lower in MDDSI+ than that in CONT group at all lags (1-10). Leave-one-out cross-validation tests, using a classification and regression tree (CART), obtained 94.83 % accuracy in predicting MDDSI+ subjects by using a combination of tone and entropy values at all lags and including demographic factors (age, BMI and waist circumference) compared to results with time and frequency domain HRV analysis. The results of this pilot study demonstrate the usefulness of multi-lag T-E analysis in identifying MDD patients with suicidal ideation and highlight the change in autonomic nervous system modulation of the heart rate associated with depression and suicidal ideation.

Physiological correlates of memory recall in infancy: vagal tone, cortisol, and imitation in preterm and full-term infants at 6 months.

PubMed

Haley, David W; Grunau, Ruth E; Weinberg, Joanne; Keidar, Adi; Oberlander, Tim F

2010-04-01

We examined the role of physiological regulation (heart rate, vagal tone, and salivary cortisol) in short-term memory in preterm and full-term 6-month-old infants. Using a deferred imitation task to evaluate social learning and memory recall, an experimenter modeled three novel behaviors (removing, shaking, and replacing a glove) on a puppet. Infants were tested immediately after being shown the behaviors as well as following a 10-min delay. We found that greater suppression of vagal tone was related to better memory recall in full-term infants tested immediately after the demonstration as well as in preterm infants tested later after a 10-min delay. We also found that preterm infants showed greater coordination of physiology (i.e., tighter coupling of vagal tone, heart rate, and cortisol) at rest and during retrieval than full-term infants. These findings provide new evidence of the important links between changes in autonomic activity and memory recall in infancy. They also raise the intriguing possibility that social learning, imitation behavior, and the formation of new memories are modulated by autonomic activity that is coordinated differently in preterm and full-term infants. Copyright 2009 Elsevier Inc. All rights reserved.

The acoustical bright spot and mislocalization of tones by human listeners

PubMed Central

Macaulay, Eric J.; Hartmann, William M.; Rakerd, Brad

2010-01-01

Listeners attempted to localize 1500-Hz sine tones presented in free field from a loudspeaker array, spanning azimuths from 0° (straight ahead) to 90° (extreme right). During this task, the tone levels and phases were measured in the listeners’ ear canals. Because of the acoustical bright spot, measured interaural level differences (ILD) were non-monotonic functions of azimuth with a maximum near 55°. In a source-identification task, listeners’ localization decisions closely tracked the non-monotonic ILD, and thus became inaccurate at large azimuths. When listeners received training and feedback, their accuracy improved only slightly. In an azimuth-discrimination task, listeners decided whether a first sound was to the left or to the right of a second. The discrimination results also reflected the confusion caused by the non-monotonic ILD, and they could be predicted approximately by a listener’s identification results. When the sine tones were amplitude modulated or replaced by narrow bands of noise, interaural time difference (ITD) cues greatly reduced the confusion for most listeners, but not for all. Recognizing the important role of the bright spot requires a reevaluation of the transition between the low-frequency region for localization (mainly ITD) and the high-frequency region (mainly ILD). PMID:20329844

Modulations of neural activity in auditory streaming caused by spectral and temporal alternation in subsequent stimuli: a magnetoencephalographic study.

PubMed

Chakalov, Ivan; Draganova, Rossitza; Wollbrink, Andreas; Preissl, Hubert; Pantev, Christo

2012-06-20

The aim of the present study was to identify a specific neuronal correlate underlying the pre-attentive auditory stream segregation of subsequent sound patterns alternating in spectral or temporal cues. Fifteen participants with normal hearing were presented with series' of two consecutive ABA auditory tone-triplet sequences, the initial triplets being the Adaptation sequence and the subsequent triplets being the Test sequence. In the first experiment, the frequency separation (delta-f) between A and B tones in the sequences was varied by 2, 4 and 10 semitones. In the second experiment, a constant delta-f of 6 semitones was maintained but the Inter-Stimulus Intervals (ISIs) between A and B tones were varied. Auditory evoked magnetic fields (AEFs) were recorded using magnetoencephalography (MEG). Participants watched a muted video of their choice and ignored the auditory stimuli. In a subsequent behavioral study both MEG experiments were replicated to provide information about the participants' perceptual state. MEG measurements showed a significant increase in the amplitude of the B-tone related P1 component of the AEFs as delta-f increased. This effect was seen predominantly in the left hemisphere. A significant increase in the amplitude of the N1 component was only obtained for a Test sequence delta-f of 10 semitones with a prior Adaptation sequence of 2 semitones. This effect was more pronounced in the right hemisphere. The additional behavioral data indicated an increased probability of two-stream perception for delta-f = 4 and delta-f = 10 semitones with a preceding Adaptation sequence of 2 semitones. However, neither the neural activity nor the perception of the successive streaming sequences were modulated when the ISIs were alternated. Our MEG experiment demonstrated differences in the behavior of P1 and N1 components during the automatic segregation of sounds when induced by an initial Adaptation sequence. The P1 component appeared enhanced in all Test-conditions and thus demonstrates the preceding context effect, whereas N1 was specifically modulated only by large delta-f Test sequences induced by a preceding small delta-f Adaptation sequence. These results suggest that P1 and N1 components represent at least partially-different systems that underlie the neural representation of auditory streaming.

The spatio-temporal dynamics of deviance and target detection in the passive and active auditory oddball paradigm: a sLORETA study.

PubMed

Justen, Christoph; Herbert, Cornelia

2018-04-19

Numerous studies have investigated the neural underpinnings of passive and active deviance and target detection in the well-known auditory oddball paradigm by means of event-related potentials (ERPs) or functional magnetic resonance imaging (fMRI). The present auditory oddball study investigates the spatio-temporal dynamics of passive versus active deviance and target detection by analyzing amplitude modulations of early and late ERPs while at the same time exploring the neural sources underling this modulation with standardized low-resolution brain electromagnetic tomography (sLORETA) . A 64-channel EEG was recorded from twelve healthy right-handed participants while listening to 'standards' and 'deviants' (500 vs. 1000 Hz pure tones) during a passive (block 1) and an active (block 2) listening condition. During passive listening, participants had to simply listen to the tones. During active listening they had to attend and press a key in response to the deviant tones. Passive and active listening elicited an N1 component, a mismatch negativity (MMN) as difference potential (whose amplitudes were temporally overlapping with the N1) and a P3 component. N1/MMN and P3 amplitudes were significantly more pronounced for deviants as compared to standards during both listening conditions. Active listening augmented P3 modulation to deviants significantly compared to passive listening, whereas deviance detection as indexed by N1/MMN modulation was unaffected by the task. During passive listening, sLORETA contrasts (deviants > standards) revealed significant activations in the right superior temporal gyrus (STG) and the lingual gyri bilaterally (N1/MMN) as well as in the left and right insulae (P3). During active listening, significant activations were found for the N1/MMN in the right inferior parietal lobule (IPL) and for the P3 in multiple cortical regions (e.g., precuneus). The results provide evidence for the hypothesis that passive as well as active deviance and target detection elicit cortical activations in spatially distributed brain regions and neural networks including the ventral attention network (VAN), dorsal attention network (DAN) and salience network (SN). Based on the temporal activation of the neural sources underlying ERP modulations, a neurophysiological model of passive and active deviance and target detection is proposed which can be tested in future studies.

Effects of the swimming exercise on the consolidation and persistence of auditory and contextual fear memory.

PubMed

Faria, Rodolfo Souza; Gutierres, Luís Felipe Soares; Sobrinho, Fernando César Faria; Miranda, Iris do Vale; Reis, Júlia Dos; Dias, Elayne Vieira; Sartori, Cesar Renato; Moreira, Dalmo Antonio Ribeiro

2016-08-15

Exposure to negative environmental events triggers defensive behavior and leads to the formation of aversive associative memory. Cellular and molecular changes in the central nervous system underlie this memory formation, as well as the associated behavioral changes. In general, memory process is established in distinct phases such as acquisition, consolidation, evocation, persistence, and extinction of the acquired information. After exposure to a particular event, early changes in involved neural circuits support the memory consolidation, which corresponds to the short-term memory. Re-exposure to previously memorized events evokes the original memory, a process that is considered essential for the reactivation and consequent persistence of memory, ensuring that long-term memory is established. Different environmental stimuli may modulate the memory formation process, as well as their distinct phases. Among the different environmental stimuli able of modulating memory formation is the physical exercise which is a potent modulator of neuronal activity. There are many studies showing that physical exercise modulates learning and memory processes, mainly in the consolidation phase of the explicit memory. However, there are few reports in the literature regarding the role of physical exercise in implicit aversive associative memory, especially at the persistence phase. Thus, the present study aimed to investigate the relationship between swimming exercise and the consolidation and persistence of contextual and auditory-cued fear memory. Male Wistar rats were submitted to sessions of swimming exercise five times a week, over six weeks. After that, the rats were submitted to classical aversive conditioning training by a pairing tone/foot shock paradigm. Finally, rats were evaluated for consolidation and persistence of fear memory to both auditory and contextual cues. Our results demonstrate that classical aversive conditioning with tone/foot shock pairing induced consolidation as well as persistence of conditioned fear memory. In addition, rats submitted to swimming exercise over six weeks showed an improved performance in the test of auditory-cued fear memory persistence, but not in the test of contextual fear memory persistence. Moreover, no significant effect from swimming exercise was observed on consolidation of both contextual and auditory fear memory. So, our study, revealing the effect of the swimming exercise on different stages of implicit memory of tone/foot shock conditioning, contributes to and complements the current knowledge about the environmental modulation of memory process. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PWZ-029, A COMPOUND WITH MODERATE INVERSE AGONIST FUNCTIONAL SELECTIVITY AT GABAA RECEPTORS CONTAINING α5 SUBUNITS, IMPROVES PASSIVE, BUT NOT ACTIVE, AVOIDANCE LEARNING IN RATS

PubMed Central

Savić, Miroslav M.; Clayton, Terry; Furtmüller, Roman; Gavrilović, Ivana; Samardžić, Janko; Savić, Snežana; Huck, Sigismund; Sieghart, Werner; Cook, James M.

2008-01-01

Benzodiazepine (BZ) site ligands affect vigilance, anxiety, memory processes, muscle tone and epileptogenic propensity through modulation of neurotransmission at GABAA receptors containing α1, α2, α3 or α5 subunits, and may have numerous experimental and clinical applications. The ability of nonselective BZ site inverse agonists to enhance cognition, documented in animal models and human studies, is clinically not feasible due to potentially unacceptable psychomotor effects. Most investigations to date have proposed the α1 and/or α5 subunit-containing GABAA receptors as comprising the memory-modulating population of these receptors. The novel ligand PWZ-029, which we synthesised and characterized electrophysiologically, possesses in vitro binding selectivity and moderate inverse agonist functional selectivity at α5-containing GABAA receptors. This ligand has also been examined in rats in the passive and active avoidance, spontaneous locomotor activity, elevated plus maze and grip strength tests, primarily predictive of the effects on the memory acquisition, basal locomotor activity, anxiety level and muscle tone, respectively. The improvement of task learning was detected at the dose of 5 mg/kg in the passive, but not active avoidance test. The inverse agonist PWZ-029 had no effect on anxiety or muscle tone, whereas at higher doses (10 and 20 mg/kg) it decreased locomotor activity. This effect was antagonized by flumazenil and also by the lower (but not the higher) dose of an agonist (SH-053-R-CH3-2’F) selective for GABAA receptors containing the α5 subunit. The hypolocomotor effect of PWZ-029 was not antagonized by the antagonist β-CCt exhibiting a preferential affinity for α1-subunit containing receptors. These data suggest that moderate negative modulation at GABAA receptors containing the α5 subunit is a sufficient condition for eliciting enhanced encoding/consolidation of declarative memory, while the influence of higher doses of modulators at these receptors on motor activity shows an intricate pattern whose relevance and mechanism await to be defined. PMID:18394590

Inhibition of angiogenesis by S-adenosylmethionine

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

Sahin, Mehmet, E-mail: msahin@akdeniz.edu.tr; Sahin, Emel; Guemueslue, Saadet

2011-04-29

Highlights: {yields} Effects of S-adenosylmethionine (SAM) were investigated in endothelial cells. {yields} Our results showed that SAM decreased proliferation of endothelial cells. {yields} SAM influentially inhibited the percentage of cell migration. {yields} SAM probably stopped migration as independent from its effects on proliferation. {yields} SAM was shown to suppress in vitro angiogenesis. -- Abstract: Metastasis is a leading cause of mortality and morbidity in cancer. One of the steps in metastasis process is the formation of new blood vessels. Aberrant DNA methylation patterns are common in cancer cells. In recent studies, S-adenosylmethionine (SAM), which is a DNA methylating agent, hasmore » been found to have inhibitory effects on some carcinoma cells in vivo and in vitro. In the present study, we have used SAM to investigate whether it is effective against angiogenesis in vitro. Our results have shown that SAM can reduce the formation and organization of capillary-like structures of endothelial cells in tumoral environment. Besides, we have found SAM can block endothelial cell proliferation and the migration of cells towards growth factors-rich media. In conclusion, our study suggests that SAM may be used against angiogenesis as a natural bio-product.« less

Selection and Characteristics of Fermented Salted Seafood (jeotgal)-Originated Strains with Excellent S-adenosyl-L-methionine (SAM) Production and Probiotics Efficacy.

PubMed

Kim, Min-Jeong; Park, Sunhyun; Lee, Ran-Sook; Lim, Sang-Dong; Kim, Hyo Jin; Lee, Myung-Ki

2014-01-01

This study is executed to develop probiotics which produce S-adenosyl-L-methionine (SAM), a methyl group donor of the 5-methyltetrahydrofolate methylation reaction within the animal cell. SAM is an essential substance for the synthesis, activation, and metabolism of hormones, neurotransmitters, nucleic acids, phospholipids, and cell membranes of animals. The SAM is also known as a nutritional supplement to improve brain functions of the human. In this study, the SAM-producing strains are identified in 18 types of salted fish, and then, the strains with excellent SAM productions are being identified, with 1 strain in the Enterococcus genus and 9 strains in the Bacillus genus. Strains with a large amount of SAM production include the lactic acid bacteria such as En. faecium and En. durans, En. sanguinicola, as well as various strains in the Bacil-lus genus. The SAM-overproducing strains show antibacterial activities with certain harmful microbes in addition to the weak acid resistances and strong bile resistances, indicating characteristics of probiotics. It is possible that the jeotgal-originated beneficial strains with overproducing SAM can be commercially utilized in order to manufacture SAM enriched foods.

The Improvement of SAM Accumulation by Integrating the Endogenous Methionine Adenosyltransferase Gene SAM2 in Genome of the Industrial Saccharomyces cerevisiae Strain.

PubMed

Zhao, Weijun; Shi, Feng; Hang, Baojian; Huang, Lei; Cai, Jin; Xu, Zhinan

2016-03-01

S-Adenosyl-L-methionine (SAM) plays important roles in trans-methylation, trans-sulfuration, and polyamine synthesis in all living cells, and it is also an effective cure for liver disease, depressive syndromes, and osteoarthritis. The increased demands of SAM in pharmaceuticals industry have aroused lots of attempts to improve its production. In this study, a multiple-copy integrative plasmid pYMIKP-SAM2 was introduced into the chromosome of wild-type Saccharomyces cerevisiae strain ZJU001 to construct the recombined strain R1-ZJU001. Further studies showed that the recombinant yeast exhibited higher enzymatic activity of methionine adenosyltransferase and improved its SAM biosynthesis. With a three-phase fed-batch strategy in 15-liter bench-top fermentor, 8.81 g/L SAM was achieved after 52 h cultivation of R1-ZJU001, about 27.1 % increase over its parent strain ZJU001, whereas the SAM content was also improved from 64.6 mg/g DCW to 91.0 mg/g DCW. Our results shall provide insights into the metabolic engineering of SAM pathway in yeast for improved productivity of SAM and subsequent industrial applications.

Frequency comb generation in a silicon ring resonator modulator.

PubMed

Demirtzioglou, Iosif; Lacava, Cosimo; Bottrill, Kyle R H; Thomson, David J; Reed, Graham T; Richardson, David J; Petropoulos, Periklis

2018-01-22

We report on the generation of an optical comb of highly uniform in power frequency lines (variation less than 0.7 dB) using a silicon ring resonator modulator. A characterization involving the measurement of the complex transfer function of the ring is presented and five frequency tones with a 10-GHz spacing are produced using a dual-frequency electrical input at 10 and 20 GHz. A comb shape comparison is conducted for different modulator bias voltages, indicating optimum operation at a small forward-bias voltage. A time-domain measurement confirmed that the comb signal was highly coherent, forming 20.3-ps-long pulses.

Aberrant Splicing Induced by Dysregulated Rbfox2 Produces Enhanced Function of CaV1.2 Calcium Channel and Vascular Myogenic Tone in Hypertension.

PubMed

Zhou, Yingying; Fan, Jia; Zhu, Huayuan; Ji, Li; Fan, Wenyong; Kapoor, Isha; Wang, Yue; Wang, Yuan; Zhu, Guoqing; Wang, Juejin

2017-12-01

Calcium influx from activated voltage-gated calcium channel Ca V 1.2 in vascular smooth muscle cells is indispensable for maintaining myogenic tone and blood pressure. The function of Ca V 1.2 channel can be optimized by alternative splicing, one of post-transcriptional modification mechanisms. The splicing factor Rbfox2 is known to regulate the Ca V 1.2 pre-mRNA alternative splicing events during neuronal development. However, Rbfox2's roles in modulating the key function of vascular Ca V 1.2 channel and in the pathogenesis of hypertension remain elusive. Here, we report that the proportion of Ca V 1.2 channels with alternative exon 9* is increased by 10.3%, whereas that with alternative exon 33 is decreased by 10.5% in hypertensive arteries. Surprisingly, the expression level of Rbfox2 is increased ≈3-folds, presumably because of the upregulation of a dominant-negative isoform of Rbfox2. In vascular smooth muscle cells, we find that knockdown of Rbfox2 dynamically increases alternative exon 9*, whereas decreases exon 33 inclusion of Ca V 1.2 channels. By patch-clamp studies, we show that diminished Rbfox2-induced alternative splicing shifts the steady-state activation and inactivation curves of vascular Ca V 1.2 calcium channel to hyperpolarization, which makes the window current potential to more negative. Moreover, siRNA-mediated knockdown of Rbfox2 increases the pressure-induced vascular myogenic tone of rat mesenteric artery. Taken together, our data indicate that Rbfox2 modulates the functions of vascular Ca V 1.2 calcium channel by dynamically regulating the expressions of alternative exons 9* and 33, which in turn affects the vascular myogenic tone. Therefore, our work suggests a key role for Rbfox2 in hypertension, which provides a rational basis for designing antihypertensive therapies. © 2017 American Heart Association, Inc.

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

Shi, Zhiwei; Walker, Amy V., E-mail: amy.walker@utdallas.edu

The room temperature atomic layerlike deposition (ALLD) of ZnS on functionalized self-assembled monolayers (SAMs) was investigated, using diethyl zinc (DEZ) and in situ generated H{sub 2}S as reactants. Depositions on SAMs with three different terminal groups, –CH{sub 3,} –OH, and –COOH, were studied. It was found that the reaction of DEZ with the SAM terminal group is critical in determining the film growth rate. Little or no deposition is observed on –CH{sub 3} terminated SAMs because DEZ does not react with the methyl terminal group. ZnS does deposit on both –OH and –COOH terminated SAMs, but the grow rate onmore » –COOH terminated SAMs is ∼10% lower per cycle than on –OH terminated SAMs. DEZ reacts with the hydroxyl group on –OH terminated SAMs, while on –COOH terminated SAMs it reacts with both the hydroxyl and carbonyl bonds of the terminal groups. The carbonyl reaction is found to lead to the formation of ketones rather than deposition of ZnS, lowering the growth rate on –COOH terminated SAMs. SIMS spectra show that both –OH and –COOH terminated SAMs are covered by the deposited ZnS layer after five ALLD cycles. In contrast to ZnO ALLD where the composition of the film differs for the first few layers on –COOH and –OH terminated SAMs, the deposited film composition is the same for both –COOH and –OH terminated SAMs. The deposited film is found to be Zn-rich, suggesting that the reaction of H{sub 2}S with the Zn-surface adduct may be incomplete.« less

Plasticity of vagal brainstem circuits in the control of gastric function

PubMed Central

Browning, Kirsteen N.; Travagli, R. Alberto

2010-01-01

Background Sensory information from the viscera, including the gastrointestinal (GI) tract, is transmitted through the afferent vagus via a glutamatergic synapse to neurons of the nucleus tractus solitarius (NTS), which integrate this sensory information to regulate autonomic functions and homeostasis. The integrated response is conveyed to, amongst other nuclei, the preganglionic neurons of the dorsal motor nucleus of the vagus (DMV) using mainly GABA, glutamate and catecholamines as neurotransmitters. Despite being modulated by almost all the neurotransmitters tested so far, the glutamatergic synapse between NTS and DMV does not appear to be tonically active in the control of gastric motility and tone. Conversely, tonic inhibitory GABAergic neurotransmission from the NTS to the DMV appears critical in setting gastric tone and motility, yet, under basal conditions, this synapse appears resistant to modulation. Purpose Here, we review the available evidence suggesting that vagal efferent output to the GI tract is regulated, perhaps even controlled, in an “on-demand” and efficient manner in response to ever-changing homeostatic conditions. The focus of this review is on the plasticity induced by variations in the levels of second messengers in the brainstem neurons that form vago-vagal reflex circuits. Emphasis is placed upon the modulation of GABAergic transmission to DMV neurons and the modulation of afferent input from the GI tract by neurohormones/neurotransmitters and macronutrients. Derangement of this “on-demand” organization of brainstem vagal circuits may be one of the factors underlying the pathophysiological changes observed in functional dyspepsia or hyperglycemic gastroparesis. PMID:20804520

Ectopic shoot meristem generation in monocotyledonous rpk1 mutants is linked to SAM loss and altered seedling morphology.

PubMed

Fiesselmann, Birgit S; Luichtl, Miriam; Yang, Xiaomeng; Matthes, Michaela; Peis, Ottilie; Torres-Ruiz, Ramon A

2015-07-07

In dicot Arabidopsis thaliana embryos two cotyledons develop largely autonomously from the shoot apical meristem (SAM). Recessive mutations in the Arabidopsis receptor-like kinase RPK1 lead to monocotyledonous seedlings, with low (10 %) penetrance due to complex functional redundancy. In strong rpk1 alleles, about 10 % of these (i. e. 1 % of all homozygotes) did not develop a SAM. We wondered whether RPK1 might also control SAM gene expression and SAM generation in addition to its known stochastic impact on cell division and PINFORMED1 (PIN1) polarity in the epidermis. SAM-less seedlings developed a simple morphology with a straight and continuous hypocotyl-cotyledon structure lacking a recognizable epicotyl. According to rpk1's auxin-related PIN1 defect, the seedlings displayed defects in the vascular tissue. Surprisingly, SAM-less seedlings variably expressed essential SAM specific genes along the hypocotyl-cotyledon structure up into the cotyledon lamina. Few were even capable of developing an ectopic shoot meristem (eSM) on top of the cotyledon. The results highlight the developmental autonomy of the SAM vs. cotyledons and suggest that the primary rpk1 defect does not lie in the seedling's ability to express SAM genes or to develop a shoot meristem. Rather, rpk1's known defects in cell division and auxin homeostasis, by disturbed PIN1 polarity, impact on SAM and organ generation. In early embryo stages this failure generates a simplified monocotyledonous morphology. Once generated, this likely entails a loss of positional information that in turn affects the spatiotemporal development of the SAM. SAM-bearing and SAM-less monocotyledonous phenotypes show morphological similarities either to real monocots or to dicot species, which only develop one cotyledon. The specific cotyledon defect in rpk1 mutants thus sheds light upon the developmental implications of the transition from two cotyledons to one.

Variable sequences outside the SAM-binding core critically influence the conformational dynamics of the SAM-III/SMK box riboswitch

PubMed Central

Lu, Changrui; Smith, Angela M; Ding, Fang; Chowdhury, Anirban; Henkin, Tina M; Ke, Ailong

2012-01-01

The SMK box (SAM-III) translational riboswitches were identified in S-adenosyl-L-methionine (SAM) synthetase metK genes in members of the Lactobacillales. This riboswitch switches between two alternative conformations in response to the intracellular SAM concentration and controls metK expression at the level of translation initiation. We previously reported the crystal structure of the SAM-bound SMK box riboswitch. In this study we combined SHAPE chemical probing with mutagenesis to probe the ligand-induced conformational switching mechanism. We revealed that while the majority of the apo SMK box RNA molecules exist in an alternatively base paired (ON) conformation, a subset of them pre-organize into a SAM-bound-like (READY) conformation, which upon SAM exposure is selectively stabilized into the SAM-bound (OFF) conformation through an induced-fit mechanism. Mutagenesis showed that the ON state is only slightly more stable than the READY state, as several single-nucleotide substitutions in a hypervariable region outside the SAM-binding core can alter the folding landscape to favor the READY state. Such SMK variants display a “constitutively-OFF” behavior both in vitro and in vivo. Time-resolved and temperature-dependent SHAPE analyses revealed adaptation of the SMK box RNA to its mesothermal working environment. The latter analysis revealed that the SAM-bound SMK box RNA follows a two-step folding/unfolding process. PMID:21549712

Infrared spectroscopy of large scale single layer graphene on self assembled organic monolayer

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

Woo Kim, Nak; Youn Kim, Joo; Lee, Chul

2014-01-27

We study the effect of self-assembled monolayer (SAM) organic molecule substrate on large scale single layer graphene using infrared transmission measurement on Graphene/SAM/SiO{sub 2}/Si composite samples. From the Drude weight of the chemically inert CH{sub 3}-SAM, the electron-donating NH{sub 2}-SAM, and the SAM-less graphene, we determine the carrier density doped into graphene by the three sources—the SiO{sub 2} substrate, the gas-adsorption, and the functional group of the SAM's—separately. The SAM-treatment leads to the low carrier density N ∼ 4 × 10{sup 11} cm{sup −2} by blocking the dominant SiO{sub 2}- driven doping. The carrier scattering increases by the SAM-treatment rather than decreases. However, the transportmore » mobility is nevertheless improved due to the reduced carrier doping.« less

Segment Alignment Maintenance System for the Hobby-Eberly Telescope

NASA Technical Reports Server (NTRS)

Rakoczy, John; Burdine, Robert (Technical Monitor)

2001-01-01

NASA's Marshall Space Flight Center, in collaboration with Blue Line Engineering of Colorado Springs, Colorado, is developing a Segment Alignment Maintenance System (SAMS) for McDonald Observatory's Hobby-Eberly Telescope (HET). The SAMS shall sense motions of the 91 primary mirror segments and send corrections to HET's primary mirror controller as the mirror segments misalign due to thermo -elastic deformations of the mirror support structure. The SAMS consists of inductive edge sensors. All measurements are sent to the SAMS computer where mirror motion corrections are calculated. In October 2000, a prototype SAMS was installed on a seven-segment cluster of the HET. Subsequent testing has shown that the SAMS concept and architecture are a viable practical approach to maintaining HET's primary mirror figure, or the figure of any large segmented telescope. This paper gives a functional description of the SAMS sub-array components and presents test data to characterize the performance of the subarray SAMS.

Immunoassay of S-adenosylmethionine and S-adenosylhomocysteine: the methylation index as a biomarker for disease and health status.

PubMed

Hao, Xiujuan; Huang, Yan; Qiu, Ming; Yin, Chunlin; Ren, Huiming; Gan, Hongjie; Li, Huijun; Zhou, Yaxia; Xia, Jiazhi; Li, Wenting; Guo, Lijuan; Angres, Isaac A

2016-11-28

S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are relevant to a variety of diseases. Previous reports that quantified SAM and SAH were based on HPLC or LC-MS/MS. No antibody against SAM has been generated, and the antibody against SAH cannot be used with blood samples. Immunoassays have not been used to measure SAM and SAH. In this study, ELISA was used to measure blood SAM and SAH levels. Specific antibodies against SAM were produced for the first time using a stable analog as the antigen. The monoclonal antibodies against SAM and SAH were characterized. No cross-reactivity was detected for the analyzed analogs. For the anti-SAM antibodies, the ELISA sensitivity was ~2 nM, and the affinity was 7.29 × 10 10 L/mol. For the anti-SAH antibodies, the sensitivity was ~15 nM, and the affinity was 2.79 × 10 8 L/mol. Using high-quality antibodies against SAM and SAH, immunoassays for the detection of SAM and SAH levels in blood and tissue samples were developed. Clinical investigations using immunoassays to measure SAM, SAH and the methylation index (MI) in normal and diseased samples indicated that (1) the SAM level is age and gender dependent; (2) the SAM level is associated with the severity of liver diseases, inflammatory reactions and other diseases; and (3) the methylation index (MI) is significantly reduced in many diseases and may serve as a screening biomarker to identify potentially unfavorable health conditions. It is possible to generate antibodies against active small biomolecules with weak immunogenicity, such as SAM and SAH, using traditional hybridoma technology. The antigens and antibodies described here will contribute to the development of immunoassays to measure SAM, SAH and related molecules. These assays enable the MI to be measured specifically, accurately, easily and quickly without costly equipment. This preliminary study indicates that the MI could be an effective indicator of general health, except under conditions that may alter the value of the MI, such as special diets and medications.

Jeffries Matusita-Spectral Angle Mapper (JM-SAM) spectral matching for species level mapping at Bhitarkanika, Muthupet and Pichavaram mangroves

NASA Astrophysics Data System (ADS)

Padma, S.; Sanjeevi, S.

2014-12-01

This paper proposes a novel hyperspectral matching algorithm by integrating the stochastic Jeffries-Matusita measure (JM) and the deterministic Spectral Angle Mapper (SAM), to accurately map the species and the associated landcover types of the mangroves of east coast of India using hyperspectral satellite images. The JM-SAM algorithm signifies the combination of a qualitative distance measure (JM) and a quantitative angle measure (SAM). The spectral capabilities of both the measures are orthogonally projected using the tangent and sine functions to result in the combined algorithm. The developed JM-SAM algorithm is implemented to discriminate the mangrove species and the landcover classes of Pichavaram (Tamil Nadu), Muthupet (Tamil Nadu) and Bhitarkanika (Odisha) mangrove forests along the Eastern Indian coast using the Hyperion image dat asets that contain 242 bands. The developed algorithm is extended in a supervised framework for accurate classification of the Hyperion image. The pixel-level matching performance of the developed algorithm is assessed by the Relative Spectral Discriminatory Probability (RSDPB) and Relative Spectral Discriminatory Entropy (RSDE) measures. From the values of RSDPB and RSDE, it is inferred that hybrid JM-SAM matching measure results in improved discriminability of the mangrove species and the associated landcover types than the individual SAM and JM algorithms. This performance is reflected in the classification accuracies of species and landcover map of Pichavaram mangrove ecosystem. Thus, the JM-SAM (TAN) matching algorithm yielded an accuracy better than SAM and JM measures at an average difference of 13.49 %, 7.21 % respectively, followed by JM-SAM (SIN) at 12.06%, 5.78% respectively. Similarly, in the case of Muthupet, JM-SAM (TAN) yielded an increased accuracy than SAM and JM measures at an average difference of 12.5 %, 9.72 % respectively, followed by JM-SAM (SIN) at 8.34 %, 5.55% respectively. For Bhitarkanika, the combined JM-SAM (TAN) and (SIN) measures improved the performance of individual SAM by (16.1 %, 15%) and of JM by (10.3%, 9.2%) respectively.

47 CFR 73.128 - AM stereophonic broadcasting.

Code of Federal Regulations, 2013 CFR

2013-10-01

... negative peaks of 100%. (ii) Stereophonic (L−R) modulated with audio tones of the same amplitude at the... characteristics: (1) The audio response of the main (L+R) channel shall conform to the requirements of the ANSI... (NRSC-1). (2) The left and right channel audio signals shall conform to frequency response limitations...

CCSDS - SFCG Efficient Modulation Methods Study at NASA/JPL - Phase 4: Interference Susceptibility

NASA Technical Reports Server (NTRS)

Martin, W.; Yan, T. Y.; Gray, A.; Lee, D.

1999-01-01

Susceptibility to two types of interfering signals was requested by the SFCG: a pure carrier (single frequency tone)and wide-band RFI (characteristics unspecified). Selecting a broad-band interfering signal is diffuclt because it should represent the types of interference to be found in the space science service bands.

14 CFR 171.261 - Localizer performance requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Hz and 150 Hz wave form, the modulation tones must be phase-locked so that within the half course sector, the demodulated 90 Hz and 150 Hz wave forms pass through zero in the same direction within 20... runway and approach direction, on the same radio frequency carrier, as used for the localizer function...

Laminar-specific Scaling Down of Balanced Excitation and Inhibition in Auditory Cortex by Active Behavioral States

PubMed Central

Zhou, Mu; Liang, Feixue; Xiong, Xiaorui R.; Li, Lu; Li, Haifu; Xiao, Zhongju; Tao, Huizhong W.; Zhang, Li I.

2014-01-01

Cortical sensory processing is modulated by behavioral and cognitive states. How the modulation is achieved through impacting synaptic circuits remains largely unknown. In awake mouse auditory cortex, we reported that sensory-evoked spike responses of layer 2/3 (L2/3) excitatory cells were scaled down with preserved sensory tuning when animals transitioned from quiescence to active behaviors, while L4 and thalamic responses were unchanged. Whole-cell voltage-clamp recordings further revealed that tone-evoked synaptic excitation and inhibition exhibited a robust functional balance. Changes of behavioral state caused scaling down of excitation and inhibition at an approximately equal level in L2/3 cells, but no synaptic changes in L4 cells. This laminar-specific gain control could be attributed to an enhancement of L1–mediated inhibitory tone, with L2/3 parvalbumin inhibitory neurons suppressed as well. Thus, L2/3 circuits can adjust the salience of output in accordance with momentary behavioral demands while maintaining the sensitivity and quality of sensory processing. PMID:24747575

The effect of narrow-band noise maskers on increment detection1

PubMed Central

Messersmith, Jessica J.; Patra, Harisadhan; Jesteadt, Walt

2010-01-01

It is often assumed that listeners detect an increment in the intensity of a pure tone by detecting an increase in the energy falling within the critical band centered on the signal frequency. A noise masker can be used to limit the use of signal energy falling outside of the critical band, but facets of the noise may impact increment detection beyond this intended purpose. The current study evaluated the impact of envelope fluctuation in a noise masker on thresholds for detection of an increment. Thresholds were obtained for detection of an increment in the intensity of a 0.25- or 4-kHz pedestal in quiet and in the presence of noise of varying bandwidth. Results indicate that thresholds for detection of an increment in the intensity of a pure tone increase with increasing bandwidth for an on-frequency noise masker, but are unchanged by an off-frequency noise masker. Neither a model that includes a modulation-filter-bank analysis of envelope modulation nor a model based on discrimination of spectral patterns can account for all aspects of the observed data. PMID:21110593

Giant Shoot Apical Meristems in Cacti Have Ordinary Leaf Primordia but Altered Phyllotaxy and Shoot Diameter

PubMed Central

MAUSETH, JAMES D.

2004-01-01

• Background and Aims Shoot apical meristems (SAMs) in most seed plants are quite uniform in size and zonation, and molecular genetic studies of Arabidopsis and other model plants are revealing details of SAM morphogenesis. Some cacti have SAMs much larger than those of A. thaliana and other seed plants. This study examined how SAM size affects leaf primordium (LP) size, phyllotaxy and shoot diameter. • Methods. Apices from 183 species of cacti were fixed, microtomed and studied by light microscopy. • Key Results Cactus SAM diameter varies from 93 to 2565 µm, the latter being 36 times wider than SAMs of A. thaliana and having a volume 45 thousand times larger. Phyllotaxy ranges from distichous to having 56 rows of leaves and is not restricted to Fibonacci numbers. Leaf primordium diameter ranges from 44 to 402 µm, each encompassing many more cells than do LP of other plants. Species with high phyllotaxy have smaller LP, although the correlation is weak. There is almost no correlation between SAM diameter and LP size, but SAM diameter is strongly correlated with shoot diameter, with shoots being about 189·5 times wider than SAMs. • Conclusions Presumably, genes such as SHOOT‐MERISTEMLESS, WUSCHEL and CLAVATA must control much larger volumes of SAM tissue in cacti than they do in A. thaliana, and genes such as PERIANTHIA might establish much more extensive fields of inhibition around LP. These giant SAMs should make it possible to more accurately map gene expression patterns relative to SAM zonation and LP sites. PMID:15145794

Differences in reporting of perceived acute effects of alcohol use, marijuana use, and simultaneous alcohol and marijuana use.

PubMed

Lee, Christine M; Cadigan, Jennifer M; Patrick, Megan E

2017-11-01

Although there are serious negative harms associated with simultaneous alcohol and marijuana (SAM) use, little is known about the self-reported acute effects of SAM use and how they may be similar to or different than effects experienced when using alcohol or marijuana only. The current study examines the perceived acute effects of SAM use, compared to using alcohol or marijuana only, as well as demographic and substance use predictors of overall SAM effects. Participants were a community sample of young adults ages 18-23 participating in a longitudinal study on social role transitions and substance use during young adulthood. Young adults who reported SAM use at least once in their lifetime were selected for the present analyses (N=315; mean age=21.42; 58% female) and reported the effects they experienced from typical alcohol use, marijuana use, and SAM use. There were significant differences in the extent to which young adults perceived the effects depending on the substances used. Most effects (i.e., clumsy, confused, dizzy, difficulty concentrating) were rated strongest when engaging in SAM use, compared to typical alcohol or marijuana use alone. Feeling high and feeling marijuana effects were rated strongest when engaging in marijuana use alone compared to SAM use, but feeling drunk was greater during SAM use compared to alcohol use alone. Greater alcohol use and increased time spent high during typical SAM use were associated with greater overall SAM effects. When young adults engage in SAM use they report experiencing greater negative physiological and cognitive effects. Copyright © 2017 Elsevier B.V. All rights reserved.

SAM/SAH Analogs as Versatile Tools for SAM-Dependent Methyltransferases.

PubMed

Zhang, Jing; Zheng, Yujun George

2016-03-18

S-Adenosyl-L-methionine (SAM) is a sulfonium molecule with a structural hybrid of methionine and adenosine. As the second largest cofactor in the human body, its major function is to serve as methyl donor for SAM-dependent methyltransferases (MTases). The resultant transmethylation of biomolecules constitutes a significant biochemical mechanism in epigenetic regulation, cellular signaling, and metabolite degradation. Recently, numerous SAM analogs have been developed as synthetic cofactors to transfer the activated groups on MTase substrates for downstream ligation and identification. Meanwhile, new compounds built upon or derived from the SAM scaffold have been designed and tested as selective inhibitors for important MTase targets. Here, we summarized the recent development and application of SAM analogs as chemical biology tools for MTases.

Noncanonical Radical SAM Enzyme Chemistry Learned from Diphthamide Biosynthesis.

PubMed

Dong, Min; Zhang, Yugang; Lin, Hening

2018-05-10

Radical S-adenosylmethionine (SAM) enzymes are a superfamily of enzymes that use SAM and reduced [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical to catalyze numerous challenging reactions. We have reported a type of noncanonical radical SAM enzymes in the diphthamide biosynthesis pathway. These enzymes also use SAM and reduced [4Fe-4S] clusters, but generate a 3-amino-3-carboxypropyl (ACP) radical to modify the substrate protein, translation elongation factor 2. The regioselective cleavage of a different C-S bond of the sulfonium center of SAM in these enzymes comparing to canonical radical SAM enzymes is intriguing. Here, we highlight some recent findings in the mechanism of these types of enzymes, showing that the diphthamide biosynthetic radial SAM enzymes bound SAM with a distinct geometry. In this way, the unique iron of the [4Fe-4S] cluster in the enzyme can only attack the carbon on the ACP group to form an organometallic intermediate. The homolysis of the organometallic intermediate releases the ACP radical and generates the EF2 radial.

Crystal structures of the SAM-III/SMK riboswitch reveal the SAM-dependent translation inhibition mechanism

PubMed Central

Lu, Changrui; Smith, Angela M; Fuchs, Ryan T; Ding, Fang; Rajashankar, Kanagalaghatta; Henkin, Tina M; Ke, Ailong

2011-01-01

Three distinct classes of S-adenosyl-l-methionine (SAM)-responsive riboswitches have been identified that regulate bacterial gene expression at the levels of transcription attenuation or translation inhibition. The SMK box (SAM-III) translational riboswitch has been identified in the SAM synthetase gene in members of the Lactobacillales. Here we report the 2.2-Å crystal structure of the Enterococcus faecalis SMK box riboswitch. The Y-shaped riboswitch organizes its conserved nucleotides around a three-way junction for SAM recognition. The Shine-Dalgarno sequence, which is sequestered by base-pairing with the anti–Shine-Dalgarno sequence in response to SAM binding, also directly participates in SAM recognition. The riboswitch makes extensive interactions with the adenosine and sulfonium moieties of SAM but does not appear to recognize the tail of the methionine moiety. We captured a structural snapshot of the SMK box riboswitch sampling the near-cognate ligand S-adenosyl-l-homocysteine (SAH) in which SAH was found to adopt an alternative conformation and fails to make several key interactions. PMID:18806797

Crystal structures of the SAM-III/S[subscript MK] riboswitch reveal the SAM-dependent translation inhibition mechanism

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

Lu, C.; Smith, A.M.; Fuchs, R.T.

2010-01-07

Three distinct classes of S-adenosyl-L-methionine (SAM)-responsive riboswitches have been identified that regulate bacterial gene expression at the levels of transcription attenuation or translation inhibition. The SMK box (SAM-III) translational riboswitch has been identified in the SAM synthetase gene in members of the Lactobacillales. Here we report the 2.2-{angstrom} crystal structure of the Enterococcus faecalis SMK box riboswitch. The Y-shaped riboswitch organizes its conserved nucleotides around a three-way junction for SAM recognition. The Shine-Dalgarno sequence, which is sequestered by base-pairing with the anti-Shine-Dalgarno sequence in response to SAM binding, also directly participates in SAM recognition. The riboswitch makes extensive interactions withmore » the adenosine and sulfonium moieties of SAM but does not appear to recognize the tail of the methionine moiety. We captured a structural snapshot of the SMK box riboswitch sampling the near-cognate ligand S-adenosyl-L-homocysteine (SAH) in which SAH was found to adopt an alternative conformation and fails to make several key interactions.« less

Successful microscopic renal autotransplantation for left renal aneurysm associated with segmental arterial mediolysis.

PubMed

Yoshioka, Takashi; Araki, Motoo; Ariyoshi, Yuichi; Wada, Koichiro; Tanaka, Noriyuki; Nasu, Yasutomo

2017-07-01

Segmental arterial mediolysis (SAM) is an uncommon, nonarteriosclerotic vascular disease. SAM is characterized by lysis of arterial media and can lead to aneurysm formation. The renal arteries are the third most common arteries associated with SAM. We report the case of a 32-year-old man with left renal artery aneurysm associated with SAM. We successfully performed left renal autotransplantation using microscopic vascular reconstruction. SAM is characterized by vascular fragility; therefore, microscopic surgery is favorable for treating aneurysms associated with SAM. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

ER residency of the ceramide phosphoethanolamine synthase SMSr relies on homotypic oligomerization mediated by its SAM domain.

PubMed

Cabukusta, Birol; Kol, Matthijs; Kneller, Laura; Hilderink, Angelika; Bickert, Andreas; Mina, John G M; Korneev, Sergei; Holthuis, Joost C M

2017-01-25

SMSr/SAMD8 is an ER-resident ceramide phosphoethanolamine synthase with a critical role in controlling ER ceramides and suppressing ceramide-induced apoptosis in cultured cells. SMSr-mediated ceramide homeostasis relies on the enzyme's catalytic activity as well as on its N-terminal sterile α-motif or SAM domain. Here we report that SMSr-SAM is structurally and functionally related to the SAM domain of diacylglycerol kinase DGKδ, a central regulator of lipid signaling at the plasma membrane. Native gel electrophoresis indicates that both SAM domains form homotypic oligomers. Chemical crosslinking studies show that SMSr self-associates into ER-resident trimers and hexamers that resemble the helical oligomers formed by DGKδ-SAM. Residues critical for DGKδ-SAM oligomerization are conserved in SMSr-SAM and their substitution causes a dissociation of SMSr oligomers as well as a partial redistribution of the enzyme to the Golgi. Conversely, treatment of cells with curcumin, a drug disrupting ceramide and Ca 2+ homeostasis in the ER, stabilizes SMSr oligomers and promotes retention of the enzyme in the ER. Our data provide first demonstration of a multi-pass membrane protein that undergoes homotypic oligomerization via its SAM domain and indicate that SAM-mediated self-assembly of SMSr is required for efficient retention of the enzyme in the ER.

S-adenosylmethionine directly inhibits binding of 30S ribosomal subunits to the SMK box translational riboswitch RNA

PubMed Central

Fuchs, Ryan T.; Grundy, Frank J.; Henkin, Tina M.

2007-01-01

The SMK box is a conserved riboswitch motif found in the 5′ untranslated region of metK genes [encoding S-adenosylmethionine (SAM) synthetase] in lactic acid bacteria, including Enterococcus, Streptococcus, and Lactococcus sp. Previous studies showed that this RNA element binds SAM in vitro, and SAM binding causes a structural rearrangement that sequesters the Shine–Dalgarno (SD) sequence by pairing with an anti-SD (ASD) element. A model was proposed in which SAM binding inhibits metK translation by preventing binding of the ribosome to the SD region of the mRNA. In the current work, the addition of SAM was shown to inhibit binding of 30S ribosomal subunits to SMK box RNA; in contrast, the addition of S-adenosylhomocysteine (SAH) had no effect. A mutant RNA, which has a disrupted SD-ASD pairing, was defective in SAM binding and showed no reduction of ribosome binding in the presence of SAM, whereas a compensatory mutation that restored SD-ASD pairing restored the response to SAM. Primer extension inhibition assays provided further evidence for SD-ASD pairing in the presence of SAM. These results strongly support the model that SMK box translational repression operates through occlusion of the ribosome binding site and that SAM binding requires the SD-ASD pairing. PMID:17360376

Optical multi-point measurements of the acoustic particle velocity with frequency modulated Doppler global velocimetry.

PubMed

Fischer, Andreas; König, Jörg; Haufe, Daniel; Schlüssler, Raimund; Büttner, Lars; Czarske, Jürgen

2013-08-01

To reduce the noise of machines such as aircraft engines, the development and propagation of sound has to be investigated. Since the applicability of microphones is limited due to their intrusiveness, contactless measurement techniques are required. For this reason, the present study describes an optical method based on the Doppler effect and its application for acoustic particle velocity (APV) measurements. While former APV measurements with Doppler techniques are point measurements, the applied system is capable of simultaneous measurements at multiple points. In its current state, the system provides linear array measurements of one component of the APV demonstrated by multi-tone experiments with tones up to 17 kHz for the first time.

Systematic biochemical characterization of the SAM domains in Eph receptor family from Mus Musculus.

PubMed

Wang, Yue; Li, Qingxia; Zheng, Yunhua; Li, Gang; Liu, Wei

2016-05-13

The Eph receptor family is the largest subfamily of receptor tyrosine kinases and well-known for their pivotal roles in axon guidance, synaptogenesis, artery/venous differentiation and tumorigenesis, etc. Activation of the Eph receptor needs multimerization of the receptors. The intracellular C-terminal SAM domain of Eph receptor was reported to mediate self-association of Eph receptors via the homo SAM-SAM interaction. In this study, we systematically expressed and purified the SAM domain proteins of all fourteen Eph receptors of Mus musculus in Escherichia coli. The FPLC (fast protein liquid chromatography) results showed the recombinant SAM domains were highly homogeneous. Using CD (circular dichroism) spectrometry, we found that the secondary structure of all the SAM domains was typically alpha helical folded and remarkably similar. The thermo-stability tests showed that they were quite stable in solution. SEC-MALS (size exclusion chromatography coupled with multiple angle light scattering) results illustrated 200 μM Eph SAM domains behaved as good monomers in the size-exclusion chromatography. More importantly, DLS (dynamic light scattering) results revealed the overwhelming majority of SAM domains was not multimerized in solution either at 200 μM or 2000 μM protein concentration, which indicating the SAM domain alone was not sufficient to mediate the polymerization of Eph receptor. In summary, our studies provided the systematic biochemical characterizations of the Eph receptor SAM domains and implied their roles in Eph receptor mediated signaling pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

Microdissection of Shoot Meristem Functional Domains

USDA-ARS?s Scientific Manuscript database

The shoot apical meristem (SAM) maintains a pool of indeterminate cells within the SAM proper, while lateral organs are initiated from the SAM periphery. Laser microdissection–microarray technology was used to compare transcriptional profiles within these SAM domains to identify novel maize genes th...

Placebo-controlled vagus nerve stimulation paired with tones in a patient with refractory tinnitus: a case report.

PubMed

De Ridder, Dirk; Kilgard, Michael; Engineer, Navzer; Vanneste, Sven

2015-04-01

Classical neuromodulation consists of applying electrical or magnetic stimuli to the nervous system to modulate ongoing activity and connectivity. However, recently, an exciting novel neuromodulation technique was developed in which stimulation of the vagal nerve was paired with simultaneous presentation of tones, demonstrating that it reverses a tinnitus percept in noise-exposed rats. To determine whether this therapy could also be effective in humans, we delivered a similar therapy in a patient with chronic tinnitus unresponsive to previous therapies. In this report, we describe the case of a 59-year-old man who suffered from bilateral tinnitus for 14 years that arose after a cervical fusion operation. Pharmacotherapy, transcranial magnetic stimulation, transcranial direct current stimulation, neurofeedback, and bilateral auditory cortex stimulation via implanted electrodes did not improve the tinnitus. After implanting the vagal nerve stimulator, the patient received daily vagus nerve stimulation tone pairings for 4 weeks in a non-placebo-controlled way. At the end of therapy, the patient experienced a significant reduction in tinnitus symptoms that lasted for 2 months after treatment. Tinnitus Handicap Inventory and Tinnitus Reaction Questionnaire were reduced by 48% and 68%, respectively. Symptoms of depression were also improved by 40%, as quantified by the Beck Depression Inventory. Three months after ending therapy, placebo stimulation was performed consisting of only tone presentation without the simultaneous electrical stimuli. This resulted in further continuation of the gradual relapse to the baseline state, without renewed improvement. Our results suggest that vagus nerve stimulation paired with tones could become an effective therapy for the treatment of tinnitus.

Basis for ligand discrimination between ON and OFF state riboswitch conformations: The case of the SAM-I riboswitch

PubMed Central

Boyapati, Vamsi Krishna; Huang, Wei; Spedale, Jessica; Aboul-ela, Fareed

2012-01-01

Riboswitches are RNA elements that bind to effector ligands and control gene expression. Most consist of two domains. S-Adenosyl Methionine (SAM) binds the aptamer domain of the SAM-I riboswitch and induces conformational changes in the expression domain to form an intrinsic terminator (transcription OFF state). Without SAM the riboswitch forms the transcription ON state, allowing read-through transcription. The mechanistic link between the SAM/aptamer recognition event and subsequent secondary structure rearrangement by the riboswitch is unclear. We probed for those structural features of the Bacillus subtilis yitJ SAM-I riboswitch responsible for discrimination between the ON and OFF states by SAM. We designed SAM-I riboswitch RNA segments forming “hybrid” structures of the ON and OFF states. The choice of segment constrains the formation of a partial P1 helix, characteristic of the OFF state, together with a partial antiterminator (AT) helix, characteristic of the ON state. For most choices of P1 vs. AT helix lengths, SAM binds with micromolar affinity according to equilibrium dialysis. Mutational analysis and in-line probing confirm that the mode of SAM binding by hybrid structures is similar to that of the aptamer. Altogether, binding measurements and in-line probing are consistent with the hypothesis that when SAM is present, stacking interactions with the AT helix stabilize a partially formed P1 helix in the hybrids. Molecular modeling indicates that continuous stacking between the P1 and the AT helices is plausible with SAM bound. Our findings raise the possibility that conformational intermediates may play a role in ligand-induced aptamer folding. PMID:22543867

Defects in subventricular zone pigmented epithelium-derived factor niche signaling in the senescence-accelerated mouse prone-8.

PubMed

Castro-Garcia, Paola; Díaz-Moreno, María; Gil-Gas, Carmen; Fernández-Gómez, Francisco J; Honrubia-Gómez, Paloma; Álvarez-Simón, Carmen Belén; Sánchez-Sánchez, Francisco; Cano, Juan Carlos Castillo; Almeida, Francisco; Blanco, Vicente; Jordán, Joaquín; Mira, Helena; Ramírez-Castillejo, Carmen

2015-04-01

We studied potential changes in the subventricular zone (SVZ) stem cell niche of the senescence-accelerated mouse prone-8 (SAM-P8) aging model. Bromodeoxyuridine (BrdU) assays with longtime survival revealed a lower number of label-retaining stem cells in the SAM-P8 SVZ compared with the SAM-Resistant 1 (SAM-R1) control strain. We also found that in SAM-P8 niche signaling is attenuated and the stem cell pool is less responsive to the self-renewal niche factor pigmented epithelium-derived factor (PEDF). Protein analysis demonstrated stable amounts of the PEDF ligand in the SAM-P8 SVZ niche; however, SAM-P8 stem cells present a significant expression decrease of patatin-like phospholipase domain containing 2, a receptor for PEDF (PNPLA2-PEDF) receptor, but not of laminin receptor (LR), a receptor for PEDF (LR-PEDF) receptor. We observed changes in self-renewal related genes (hairy and enhancer of split 1 (Hes1), hairy and enhancer of split 1 (Hes5), Sox2] and report that although these genes are down-regulated in SAM-P8, differentiation genes (Pax6) are up-regulated and neurogenesis is increased. Finally, sheltering mammalian telomere complexes might be also involved given a down-regulation of telomeric repeat binding factor 1 (Terf1) expression was observed in SAM-P8 at young age periods. Differences between these 2 models, SAM-P8 and SAM-R1 controls, have been previously detected at more advanced ages. We now describe alterations in the PEDF signaling pathway and stem cell self-renewal at a very young age, which could be involved in the premature senescence observed in the SAM-P8 model. © FASEB.

Basis for ligand discrimination between ON and OFF state riboswitch conformations: the case of the SAM-I riboswitch.

PubMed

Boyapati, Vamsi Krishna; Huang, Wei; Spedale, Jessica; Aboul-Ela, Fareed

2012-06-01

Riboswitches are RNA elements that bind to effector ligands and control gene expression. Most consist of two domains. S-Adenosyl Methionine (SAM) binds the aptamer domain of the SAM-I riboswitch and induces conformational changes in the expression domain to form an intrinsic terminator (transcription OFF state). Without SAM the riboswitch forms the transcription ON state, allowing read-through transcription. The mechanistic link between the SAM/aptamer recognition event and subsequent secondary structure rearrangement by the riboswitch is unclear. We probed for those structural features of the Bacillus subtilis yitJ SAM-I riboswitch responsible for discrimination between the ON and OFF states by SAM. We designed SAM-I riboswitch RNA segments forming "hybrid" structures of the ON and OFF states. The choice of segment constrains the formation of a partial P1 helix, characteristic of the OFF state, together with a partial antiterminator (AT) helix, characteristic of the ON state. For most choices of P1 vs. AT helix lengths, SAM binds with micromolar affinity according to equilibrium dialysis. Mutational analysis and in-line probing confirm that the mode of SAM binding by hybrid structures is similar to that of the aptamer. Altogether, binding measurements and in-line probing are consistent with the hypothesis that when SAM is present, stacking interactions with the AT helix stabilize a partially formed P1 helix in the hybrids. Molecular modeling indicates that continuous stacking between the P1 and the AT helices is plausible with SAM bound. Our findings raise the possibility that conformational intermediates may play a role in ligand-induced aptamer folding.

Functionalization and Characterization of Gold Nanoparticles

NASA Astrophysics Data System (ADS)

Techane, Sirnegeda D.

2011-12-01

Surface characterization of gold nanoparticles (AuNPs) is necessary to obtain a thorough understanding of the AuNP properties and ultimately realize their full potential in applications. The work described in this dissertation strives to the structure and composition of AuNPs using highly surface sensitive techniques such as X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) in addition to the more widely used characterization techniques such as transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR) and UV-VIS spectroscopy. Self-assembled monolayers (SAMs) of alkanethiols were used to modify AuNPs surfaces to create positively and negatively charged surfaces. Functionalization with carboxylic acid terminated alkanethiol SAMs (COON-SAMs) was first optimized to produce clean and stable negatively charged AuNPs. Using 14nm and 40nm diameter AuNPs in combination with C11 and C16 chain length COOH-SAMs, it was found that addition of NH4OH during functionalization coupled with dialysis purification produced AuNPs that did not aggregate and did not have unbound thiols. Effects of AuNP size and COOH-SAM chain lengths were studied using 14, 25 and 40nm average diameter AuNPs functionalized with C6, C8, C11 and C16 COOH-SAMs. Flat Au surfaces were also functionalized with the COOH-SAMs for comparison. It was shown that the 14nm AuNPs with C16 COOH-SAMs were the most stable and had crystalline-like, well-ordered SAM structures. The SAMs on the 40nm AuNPs had similar surface chemistry as the SAMs on the flat Au surfaces. The effective photoelectron take-off angle of the C16 COOH-SAM decreased when the size of the AuNP increased. It was also shown that when using Kratos AxisUltra DLD XPS instrument in the hybrid mode, it was important to consider effects of both the hybrid mode and the AuNPs curvature when calculating overlayer thickness of the SAMs on AuNPs. Using the Kratos in the electrostatic mode, the overlayer thickness of C16 COON-SAM was 21A on a flat Au surface, which was comparable with previously reported values. However, the apparent thickness of the same SAM on the 14nm AuNPs was 31A, indicating the curvature of the AuNPs had an effect on the XPS measurements. To produce the positively charged AuNP surfaces, amine terminated alkanethiols (NH2 -thiols) with a C2 chain length were used in one-step AuNP synthesis and functionalization process followed by a ligand-exchange reaction with C11 chain length NH2-thiols. It was found that 14 days were needed for the ligand-exchange to be complete. After the ligand-exchange, it was found that the AuNPs with C11 NH2-SAMs were stable and could be purified, unlike AuNPs with C2 NH2-SAMs which aggregated upon purification. The C11 NH2-SAMs had both unbound and oxidized sulfur, which could be removed/converted after hydrochloric acid treatment. SESSA (simulation of electron spectra for surface analysis) allowed better interpretation of the XPS data of SAMs on AuNPs and flat Au. Comparing SESSA and experimental XPS data, it was found that C16 COON-SAM on a flat Au surface was 20A thick with a 1.5A hydrocarbon contamination overlayer and 1.05 relative surface roughness. After geometric weighing of angle-resolved XPS and SESSA data, it was found that C16 COOH-SAMs on 14nm AuNPs were 17A thick with a 1.5A hydrocarbon contamination. The decreased SAM thickness on the AuNPs is likely due to an increased tilt angle of the alkane chains or increased disorder in the SAM.

Development of a Reduced-Order Three-Dimensional Flow Model for Thermal Mixing and Stratification Simulation during Reactor Transients

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

Hu, Rui

2017-09-03

Mixing, thermal-stratification, and mass transport phenomena in large pools or enclosures play major roles for the safety of reactor systems. Depending on the fidelity requirement and computational resources, various modeling methods, from the 0-D perfect mixing model to 3-D Computational Fluid Dynamics (CFD) models, are available. Each is associated with its own advantages and shortcomings. It is very desirable to develop an advanced and efficient thermal mixing and stratification modeling capability embedded in a modern system analysis code to improve the accuracy of reactor safety analyses and to reduce modeling uncertainties. An advanced system analysis tool, SAM, is being developedmore » at Argonne National Laboratory for advanced non-LWR reactor safety analysis. While SAM is being developed as a system-level modeling and simulation tool, a reduced-order three-dimensional module is under development to model the multi-dimensional flow and thermal mixing and stratification in large enclosures of reactor systems. This paper provides an overview of the three-dimensional finite element flow model in SAM, including the governing equations, stabilization scheme, and solution methods. Additionally, several verification and validation tests are presented, including lid-driven cavity flow, natural convection inside a cavity, laminar flow in a channel of parallel plates. Based on the comparisons with the analytical solutions and experimental results, it is demonstrated that the developed 3-D fluid model can perform very well for a wide range of flow problems.« less

Structure-guided design of fluorescent S-adenosylmethionine analogs for a high-throughput screen to target SAM-I riboswitch RNAs.

PubMed

Hickey, Scott F; Hammond, Ming C

2014-03-20

Many classes of S-adenosylmethionine (SAM)-binding RNAs and proteins are of interest as potential drug targets in diverse therapeutic areas, from infectious diseases to cancer. In the former case, the SAM-I riboswitch is an attractive target because this structured RNA element is found only in bacterial mRNAs and regulates multiple genes in several human pathogens. Here, we describe the synthesis of stable and fluorescent analogs of SAM in which the fluorophore is introduced through a functionalizable linker to the ribose. A Cy5-labeled SAM analog was shown to bind several SAM-I riboswitches via in-line probing and fluorescence polarization assays, including one from Staphylococcus aureus that controls the expression of SAM synthetase in this organism. A fluorescent ligand displacement assay was developed and validated for high-throughput screening of compounds to target the SAM-I riboswitch class. Copyright © 2014 Elsevier Ltd. All rights reserved.

Single-molecule FRET reveals the energy landscape of the full-length SAM-I riboswitch.

PubMed

Manz, Christoph; Kobitski, Andrei Yu; Samanta, Ayan; Keller, Bettina G; Jäschke, Andres; Nienhaus, G Ulrich

2017-11-01

S-adenosyl-L-methionine (SAM) ligand binding induces major structural changes in SAM-I riboswitches, through which gene expression is regulated via transcription termination. Little is known about the conformations and motions governing the function of the full-length Bacillus subtilis yitJ SAM-I riboswitch. Therefore, we have explored its conformational energy landscape as a function of Mg 2+ and SAM ligand concentrations using single-molecule Förster resonance energy transfer (smFRET) microscopy and hidden Markov modeling analysis. We resolved four conformational states both in the presence and the absence of SAM and determined their Mg 2+ -dependent fractional populations and conformational dynamics, including state lifetimes, interconversion rate coefficients and equilibration timescales. Riboswitches with terminator and antiterminator folds coexist, and SAM binding only gradually shifts the populations toward terminator states. We observed a pronounced acceleration of conformational transitions upon SAM binding, which may be crucial for off-switching during the brief decision window before expression of the downstream gene.

System Advisor Model, SAM 2011.12.2: General Description

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

Gilman, P.; Dobos, A.

2012-02-01

This document describes the capabilities of the U.S. Department of Energy and National Renewable Energy Laboratory's System Advisor Model (SAM), Version 2011.12.2, released on December 2, 2011. SAM is software that models the cost and performance of renewable energy systems. Project developers, policy makers, equipment manufacturers, and researchers use graphs and tables of SAM results in the process of evaluating financial, technology, and incentive options for renewable energy projects. SAM simulates the performance of solar, wind, geothermal, biomass, and conventional power systems. The financial model can represent financing structures for projects that either buy and sell electricity at retail ratesmore » (residential and commercial) or sell electricity at a price determined in a power purchase agreement (utility). Advanced analysis options facilitate parametric, sensitivity, and statistical analyses, and allow for interfacing SAM with Microsoft Excel or with other computer programs. SAM is available as a free download at http://sam.nrel.gov. Technical support and more information about the software are available on the website.« less

Structural analysis of a putative SAM-dependent methyltransferase, YtqB, from Bacillus subtilis.

PubMed

Park, Sun Cheol; Song, Wan Seok; Yoon, Sung-il

2014-04-18

S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTases) methylate diverse biological molecules using a SAM cofactor. The ytqB gene of Bacillus subtilis encodes a putative MTase and its biological function has never been characterized. To reveal the structural features and the cofactor binding mode of YtqB, we have determined the crystal structures of YtqB alone and in complex with its cofactor, SAM, at 1.9 Å and 2.2 Å resolutions, respectively. YtqB folds into a β-sheet sandwiched by two α-helical layers, and assembles into a dimeric form. Each YtqB monomer contains one SAM binding site, which shapes SAM into a slightly curved conformation and exposes the reactive methyl group of SAM potentially to a substrate. Our comparative structural analysis of YtqB and its homologues indicates that YtqB is a SAM-dependent class I MTase, and provides insights into the substrate binding site of YtqB. Copyright © 2014 Elsevier Inc. All rights reserved.

Demonstration of a Segment Alignment Maintenance System on a Seven-Segment Sub-Array of the Hobby-Eberly Telescope

NASA Technical Reports Server (NTRS)

Rakoczy, John; Whitaker, Ann F. (Technical Monitor)

2001-01-01

NASA's Marshall Space Flight Center, in collaboration with Blue Line Engineering of Colorado Springs, Colorado, is developing a Segment Alignment Maintenance System (SAMS) for McDonald Observatory's Hobby-Eberly Telescope (HET). The SAMS shall sense motions of the 91 primary mirror segments and send corrections to HET's primary mirror controller as the mirror segments misalign due to thermo-elastic deformations of the mirror support structure. The SAMS consists of inductive edge sensors supplemented by inclinometers for global radius of curvature sensing. All measurements are sent to the SAMS computer where mirror motion corrections are calculated. In October 2000, a prototype SAMS was installed on a seven-segment cluster of the HET. Subsequent testing has shown that the SAMS concept and architecture are a viable practical approach to maintaining HET's primary mirror figure, or the figure of any large segmented telescope. This paper gives a functional description of the SAMS sub-array components and presents test data to characterize the performance of the sub-array SAMS.

Sorcin modulation of Ca2+ sparks in rat vascular smooth muscle cells

PubMed Central

Rueda, Angélica; Song, Ming; Toro, Ligia; Stefani, Enrico; Valdivia, Héctor H

2006-01-01

Spontaneous, local Ca2+ release events or Ca2+ sparks by ryanodine receptors (RyRs) are important determinants of vascular tone and arteriolar resistance, but the mechanisms that modulate their properties in smooth muscle are poorly understood. Sorcin, a Ca2+-binding protein that associates with cardiac RyRs and quickly stops Ca2+ release in the heart, provides a potential mechanism to modulate Ca2+ sparks in vascular smooth muscle, but little is known about the functional role of sorcin in this tissue. In this work, we characterized the expression and intracellular location of sorcin in aorta and cerebral artery and gained mechanistic insights into its functional role as a modulator of Ca2+ sparks. Sorcin is present in endothelial and smooth muscle cells, as assessed by immunocytochemical and Western blot analyses. Smooth muscle sorcin translocates from cytosolic to membranous compartments in a Ca2+-dependent manner and associates with RyRs, as shown by coimmunoprecipitation and immunostaining experiments. Ca2+ sparks recorded in saponin-permeabilized vascular myocytes have increased frequency, duration and spatial spread but reduced amplitude with respect to Ca2+ sparks in intact cells, suggesting that permeabilization disrupts the normal organization of RyRs and releases diffusible substances that control Ca2+ spark properties. Perfusion of 2 μm sorcin onto permeabilized myocytes reduced the amplitude, duration and spatial spread of Ca2+ sparks, demonstrating that sorcin effectively regulates Ca2+ signalling in vascular smooth muscle. Together with a dense distribution in the perimeter of the cell along a pool of RyRs, these properties make sorcin a viable candidate to modulate vascular tone in smooth muscle. PMID:16931553

Voluntary control of breathing does not alter vagal modulation of heart rate

NASA Technical Reports Server (NTRS)

Patwardhan, A. R.; Evans, J. M.; Bruce, E. N.; Eckberg, D. L.; Knapp, C. F.

1995-01-01

Variations in respiratory pattern influence the heart rate spectrum. It has been suggested, hence, that metronomic respiration should be used to correctly assess vagal modulation of heart rate by using spectral analysis. On the other hand, breathing to a metronome has been reported to increase heart rate spectral power in the high- or respiratory frequency region; this finding has led to the suggestion that metronomic respiration enhances vagal tone or alters vagal modulation of heart rate. To investigate whether metronomic breathing complicates the interpretation of heart rate spectra by altering vagal modulation, we recorded the electrocardiogram and respiration from eight volunteers during three breathing trials of 10 min each: 1) spontaneous breathing (mean rate of 14.4 breaths/min); 2) breathing to a metronome at the rate of 15, 18, and 21 breaths/min for 2, 6, and 2 min, respectively; and 3) breathing to a metronome at the rate of 18 breaths/min for 10 min. Data were also collected from eight volunteers who breathed spontaneously for 20 min and breathed metronomically at each subject's mean spontaneous breathing frequency for 20 min. Results from the three 10-min breathing trials showed that heart rate power in the respiratory frequency region was smaller during metronomic breathing than during spontaneous breathing. This decrease could be explained fully by the higher breathing frequencies used during trials 2 and 3 of metronomic breathing. When the subjects breathed metronomically at each subject's mean breathing frequency, the heart rate powers during metronomic breathing were similar to those during spontaneous breathing. Our results suggest that vagal modulation of heart rate is not altered and vagal tone is not enhanced during metronomic breathing.

Interaural time sensitivity of high-frequency neurons in the inferior colliculus.

PubMed

Yin, T C; Kuwada, S; Sujaku, Y

1984-11-01

Recent psychoacoustic experiments have shown that interaural time differences provide adequate cues for lateralizing high-frequency sounds, provided the stimuli are complex and not pure tones. We present here physiological evidence in support of these findings. Neurons of high best frequency in the cat inferior colliculus respond to interaural phase differences of amplitude modulated waveforms, and this response depends upon preservation of phase information of the modulating signal. Interaural phase differences were introduced in two ways: by interaural delays of the entire waveform and by binaural beats in which there was an interaural frequency difference in the modulating waveform. Results obtained with these two methods are similar. Our results show that high-frequency cells can respond to interaural time differences of amplitude modulated signals and that they do so by a sensitivity to interaural phase differences of the modulating waveform.

Common themes and differences in SAM recognition among SAM riboswitches

PubMed Central

Price, Ian R.; Grigg, Jason C.; Ke, Ailong

2014-01-01

The recent discovery of short cis-acting RNA elements termed riboswitches has caused a paradigm shift in our understanding of genetic regulatory mechanisms. The three distinct superfamilies of S-adenosyl-L-methionine (SAM) riboswitches are the most commonly found riboswitch classes in nature. These RNAs represent three independent evolutionary solutions to achieve specific SAM recognition. This review summarizes research on 1) modes of gene regulatory mechanisms, 2) common themes and differences in ligand recognition, and 3) ligand-induced conformational dynamics among SAM riboswitch families. The body of work on the SAM riboswitch families constitutes a useful primer to the topic of gene regulatory RNAs as a whole. PMID:24863160

Evaluating SAMS in Hong Kong Schools.

ERIC Educational Resources Information Center

Kwok, Lam-for; Lau, Chi-kuen; Fung, Sun-wai

1999-01-01

Describes the School Administration and Management Systems (SAMS) that was developed to support elementary and secondary schools in Hong Kong in administrative and managerial tasks. Reports results of a survey that investigated the impact of SAMS, evaluated its effectiveness, and identified possible areas of improvement to SAMS operation.…

ER residency of the ceramide phosphoethanolamine synthase SMSr relies on homotypic oligomerization mediated by its SAM domain

PubMed Central

Cabukusta, Birol; Kol, Matthijs; Kneller, Laura; Hilderink, Angelika; Bickert, Andreas; Mina, John G. M.; Korneev, Sergei; Holthuis, Joost C. M.

2017-01-01

SMSr/SAMD8 is an ER-resident ceramide phosphoethanolamine synthase with a critical role in controlling ER ceramides and suppressing ceramide-induced apoptosis in cultured cells. SMSr-mediated ceramide homeostasis relies on the enzyme’s catalytic activity as well as on its N-terminal sterile α-motif or SAM domain. Here we report that SMSr-SAM is structurally and functionally related to the SAM domain of diacylglycerol kinase DGKδ, a central regulator of lipid signaling at the plasma membrane. Native gel electrophoresis indicates that both SAM domains form homotypic oligomers. Chemical crosslinking studies show that SMSr self-associates into ER-resident trimers and hexamers that resemble the helical oligomers formed by DGKδ-SAM. Residues critical for DGKδ-SAM oligomerization are conserved in SMSr-SAM and their substitution causes a dissociation of SMSr oligomers as well as a partial redistribution of the enzyme to the Golgi. Conversely, treatment of cells with curcumin, a drug disrupting ceramide and Ca2+ homeostasis in the ER, stabilizes SMSr oligomers and promotes retention of the enzyme in the ER. Our data provide first demonstration of a multi-pass membrane protein that undergoes homotypic oligomerization via its SAM domain and indicate that SAM-mediated self-assembly of SMSr is required for efficient retention of the enzyme in the ER. PMID:28120887

Stress Response and Cognitive Performance Modulation in Classroom versus Natural Environments: A Quasi-Experimental Pilot Study with Children.

PubMed

Mygind, Lærke; Stevenson, Matt P; Liebst, Lasse S; Konvalinka, Ivana; Bentsen, Peter

2018-05-28

Stress during childhood can have mental and somatic health influences that track throughout life. Previous research attributes stress-reducing effects to natural environments, but has mainly focused on adults and often following leisurely relaxation in natural environments. This pilot study explores the impact of natural environments on stress response during rest and mental load and cognitive performance in 47 children aged 10⁻12 years in a school context. Heart rate variability measures indexing tonic, event, and phasic vagal tone and attention scores were compared across classroom and natural environments. Tonic vagal tone was higher in the natural environment than the classrooms, but no differences were found in event or phasic vagal tone or cognitive performance measures. These findings suggest a situational aspect of the conditions under which natural environments may give rise to stress-buffering influences. Further research is warranted to understand the potential benefits in a real-life context, in particular with respect to the underpinning mechanisms and effects of accumulated exposure over time in settings where children spend large proportions of time in natural environments.

Identifying increased risk of post-infarct people with diabetes using multi-lag Tone-Entropy analysis.

PubMed

Karmakar, Chandan; Jelinek, Herbert; Khandoker, Ahsan; Tulppo, Mikko; Makikallio, Timo; Kiviniemi, Antti; Huikuri, Heikki; Palaniswami, Marimuthu

2012-01-01

Diabetes mellitus is associated with multi-organ system dysfunction. One of the key causative factors is the increased blood sugar level that leads to an increase in free radical activity and organ damage including the cardiovascular and nervous system. Heart rhythm is extrinsically modulated by the autonomic nervous system and cardiac autonomic neuropathy or dysautonomia has been shown to lead to sudden cardiac death in people with diabetes due to the decrease in heart rate variability (HRV). Current algorithms for determining HRV describe only beat-to-beat variation and therefore do not consider the ability of a heart beat to influence a train of succeeding beats. Therefore mortality risk analysis based on HRV has often not been able to discern the presence of an increased risk. This study used a novel innovation of the tone-entropy algorithm by incorporating increased lag intervals and found that both the sympatho-vagal balance and total activity changed at larger lag intervals. Tone-Entropy was found to be better risk identifier of cardiac mortality in people with diabetes at lags higher than one and best at lag seven.

Forward and backward tone mapping of high dynamic range images based on subband architecture

NASA Astrophysics Data System (ADS)

Bouzidi, Ines; Ouled Zaid, Azza

2015-01-01

This paper presents a novel High Dynamic Range (HDR) tone mapping (TM) system based on sub-band architecture. Standard wavelet filters of Daubechies, Symlets, Coiflets and Biorthogonal were used to estimate the proposed system performance in terms of Low Dynamic Range (LDR) image quality and reconstructed HDR image fidelity. During TM stage, the HDR image is firstly decomposed in sub-bands using symmetrical analysis-synthesis filter bank. The transform coefficients are then rescaled using a predefined gain map. The inverse Tone Mapping (iTM) stage is straightforward. Indeed, the LDR image passes through the same sub-band architecture. But, instead of reducing the dynamic range, the LDR content is boosted to an HDR representation. Moreover, in our TM sheme, we included an optimization module to select the gain map components that minimize the reconstruction error, and consequently resulting in high fidelity HDR content. Comparisons with recent state-of-the-art methods have shown that our method provides better results in terms of visual quality and HDR reconstruction fidelity using objective and subjective evaluations.

Learning-dependent plasticity in human auditory cortex during appetitive operant conditioning.

PubMed

Puschmann, Sebastian; Brechmann, André; Thiel, Christiane M

2013-11-01

Animal experiments provide evidence that learning to associate an auditory stimulus with a reward causes representational changes in auditory cortex. However, most studies did not investigate the temporal formation of learning-dependent plasticity during the task but rather compared auditory cortex receptive fields before and after conditioning. We here present a functional magnetic resonance imaging study on learning-related plasticity in the human auditory cortex during operant appetitive conditioning. Participants had to learn to associate a specific category of frequency-modulated tones with a reward. Only participants who learned this association developed learning-dependent plasticity in left auditory cortex over the course of the experiment. No differential responses to reward predicting and nonreward predicting tones were found in auditory cortex in nonlearners. In addition, learners showed similar learning-induced differential responses to reward-predicting and nonreward-predicting tones in the ventral tegmental area and the nucleus accumbens, two core regions of the dopaminergic neurotransmitter system. This may indicate a dopaminergic influence on the formation of learning-dependent plasticity in auditory cortex, as it has been suggested by previous animal studies. Copyright © 2012 Wiley Periodicals, Inc.

Effect of S-adenosyl-L-methionine (SAM), an allosteric activator of cystathionine-β-synthase (CBS) on colorectal cancer cell proliferation and bioenergetics in vitro.

PubMed

Módis, Katalin; Coletta, Ciro; Asimakopoulou, Antonia; Szczesny, Bartosz; Chao, Celia; Papapetropoulos, Andreas; Hellmich, Mark R; Szabo, Csaba

2014-09-15

Recent data show that colon cancer cells selectively overexpress cystathionine-β-synthase (CBS), which produces hydrogen sulfide (H2S), to maintain cellular bioenergetics, support tumor growth and stimulate angiogenesis and vasorelaxation in the tumor microenvironment. The purpose of the current study was to investigate the effect of the allosteric CBS activator S-adenosyl-L-methionine (SAM) on the proliferation and bioenergetics of the CBS-expressing colon cancer cell line HCT116. The non-transformed, non-tumorigenic colon epithelial cell line NCM356 was used as control. For assessment of cell proliferation, the xCELLigence system was used. Bioenergetic function was measured by Extracellular Flux Analysis. Experiments using human recombinant CBS or HCT116 homogenates complemented the cell-based studies. SAM markedly enhanced CBS-mediated H2S production in vitro, especially when a combination of cysteine and homocysteine was used as substrates. Addition of SAM (0.1-3 mM) to HCT116 cells induced a concentration-dependent increase H2S production. SAM exerted time- and concentration-dependent modulatory effects on cell proliferation. At 0.1-1 mM SAM increased HCT116 proliferation between 0 and 12 h, while the highest SAM concentration (3 mM) inhibited proliferation. Over a longer time period (12-24 h), only the lowest concentration of SAM used (0.1 mM) stimulated cell proliferation; higher SAM concentrations produced a concentration-dependent inhibition. The short-term stimulatory effects of SAM were attenuated by the CBS inhibitor aminooxyacetic acid (AOAA) or by stable silencing of CBS. In contrast, the inhibitory effects of SAM on cell proliferation was unaffected by CBS inhibition or CBS silencing. In contrast to HCT116 cells, the lower rate of proliferation of the low-CBS expressor NCM356 cells was unaffected by SAM. Short-term (1 h) exposure of HCT116 cells to SAM induced a concentration-dependent increase in oxygen consumption and bioenergetic function at 0.1-1 mM, while 3 mM was inhibitory. Longer-term (72 h) exposure of HCT116 cells to all concentrations of SAM tested suppressed mitochondrial oxygen consumption rate, cellular ATP content and cell viability. The stimulatory effect of SAM on bioenergetics was attenuated in cells with stable CBS silencing, while the inhibitory effects were unaffected. In NCM356 cells SAM exerted smaller effects on cellular bioenergetics than in HCT116 cells. We have also observed a downregulation of CBS in response to prolonged exposure of SAM both in HCT116 and NCM356 cells. Taken together, the results demonstrate that H2S production in HCT116 cells is stimulated by the allosteric CBS activator, SAM. At low-to intermediate levels and early time periods the resulting H2S serves as an endogenous cancer cell growth and bioenergetic factor. In contrast, the inhibition of cell proliferation and bioenergetic function by SAM does not appear to relate to adverse autocrine effects of H2S resulting from CBS over-stimulation but, rather to CBS-independent pharmacological effects. Copyright © 2014 Elsevier Inc. All rights reserved.

48 CFR 4.1102 - Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SAM database prior to award of a contract or agreement, except for— (1) Purchases under the micro... registration in the SAM database, or use of SAM data, could compromise the safeguarding of classified... (a)(3) of this section to require SAM registration. (c)(1)(i) If a contractor has legally changed its...

78 FR 62627 - Sam Rayburn Dam Rate

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

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Infant & Toddlers: How to Calm an Exuberant Baby

ERIC Educational Resources Information Center

Honig, Alice Sterling

2006-01-01

It is important to understand that babies differ in temperament. Some are sensationally exuberant and loud. Others are more withdrawn and quiet. Babies also differ in tempo and style. Some eat with gusto. Others deliberately scoop a bit of cooked cereal onto a spoon and slowly munch on their food. Helping a baby learn to modulate voice tones means…

Human Factors Engineering Bibliographic Series. Volume 2: 1960-1964 Literature

DTIC Science & Technology

1966-10-01

flutter discrimination, melodic and temporal) binaural vs. monaural equipment and methods (e.g., anechoic chambers, audiometric devices, communication...brightness, duration, timbre, vocality) stimulus mixtures (e.g., harmonics, beats , combination tones, modulations) thresholds training, nonverbal--see Training...scales and aids) Beats --see Audition (stimulus mixtures) Bells--see Auditory (displays, nonverbal) Belts, Harnesses, and other Restraining Devices--see

49.6 Gb/s direct detection DMT transmission over 40 km single mode fibre using an electrically packaged silicon photonic modulator.

PubMed

Lacava, C; Cardea, I; Demirtzioglou, I; Khoja, A E; Ke, Li; Thomson, D J; Ruan, X; Zhang, F; Reed, G T; Richardson, D J; Petropoulos, P

2017-11-27

We present the characterization of a silicon Mach-Zehnder modulator with electrical packaging and show that it exhibits a large third-order intermodulation spurious-free dynamic range (> 100 dB Hz 2/3 ). This characteristic renders the modulator particularly suitable for the generation of high spectral efficiency discrete multi-tone signals and we experimentally demonstrate a single-channel, direct detection transmission system operating at 49.6 Gb/s, exhibiting a baseband spectral efficiency of 5 b/s/Hz. Successful transmission is demonstrated over various lengths of single mode fibre up to 40 km, without the need of any amplification or dispersion compensation.

Optical frequency comb generation with high tone-to-noise ratio for large-capacity wavelength division multiplexed passive optical network

NASA Astrophysics Data System (ADS)

Ullah, Rahat; Liu, Bo; Zhang, Qi; Tian, Qinghua; Tian, Feng; Qu, Zhaowei; Yan, Cheng; Khan, Muhammad Saad; Ahmad, Ibrar; Xin, Xiangjun

2015-11-01

We propose a technique for the generation of optical frequency comb from a single source, which reduces the costs of optical access networks. Two Mach-Zehnder modulators are cascaded with one phase modulator driven by radiofrequency signals. With 10-GHz frequency spacing, the generated 40 optical multicarriers have good tone-to-noise ratio with least excursions in their comb lines. The laser array at the optical line terminal of the conventional wavelength division multiplexed passive optical network (WDM-PON) system has been replaced with optical frequency comb generator (OFCG), which may result in cost-effective optical line terminal (OLT) supporting a large-capacity WDM-PON system. Of 40 carriers generated, each carrier carries 10 Gbps data based on differential phase-shift keying. Four hundred Gbps multiplexed data from all channels are successfully transmitted through a fiber span of 25 km with negligible power penalties. Part of the downlink signal is used in uplink transmission at optical network unit where intensity-modulated on-off keying is deployed for remodulation. Theoretical analysis of the proposed WDM-PON system based on OFCG are in good agreement with simulation results. The metrics considered for the analysis of the proposed OFCG in a WDM-PON system are power penalties of the full-duplex transmission, eye diagrams, and bit error rate.

A neural network model of normal and abnormal auditory information processing.

PubMed

Du, X; Jansen, B H

2011-08-01

The ability of the brain to attenuate the response to irrelevant sensory stimulation is referred to as sensory gating. A gating deficiency has been reported in schizophrenia. To study the neural mechanisms underlying sensory gating, a neuroanatomically inspired model of auditory information processing has been developed. The mathematical model consists of lumped parameter modules representing the thalamus (TH), the thalamic reticular nucleus (TRN), auditory cortex (AC), and prefrontal cortex (PC). It was found that the membrane potential of the pyramidal cells in the PC module replicated auditory evoked potentials, recorded from the scalp of healthy individuals, in response to pure tones. Also, the model produced substantial attenuation of the response to the second of a pair of identical stimuli, just as seen in actual human experiments. We also tested the viewpoint that schizophrenia is associated with a deficit in prefrontal dopamine (DA) activity, which would lower the excitatory and inhibitory feedback gains in the AC and PC modules. Lowering these gains by less than 10% resulted in model behavior resembling the brain activity seen in schizophrenia patients, and replicated the reported gating deficits. The model suggests that the TRN plays a critical role in sensory gating, with the smaller response to a second tone arising from a reduction in inhibition of TH by the TRN. Copyright © 2011 Elsevier Ltd. All rights reserved.

Agmatine suppresses peripheral sympathetic tone by inhibiting N-type Ca(2+) channel activity via imidazoline I2 receptor activation.

PubMed

Kim, Young-Hwan; Jeong, Ji-Hyun; Ahn, Duck-Sun; Chung, Seungsoo

2016-08-26

Agmatine, a putative endogenous ligand of imidazoline receptors, suppresses cardiovascular function by inhibiting peripheral sympathetic tone. However, the molecular identity of imidazoline receptor subtypes and its cellular mechanism underlying the agmatine-induced sympathetic suppression remains unknown. Meanwhile, N-type Ca(2+) channels are important for the regulation of NA release in the peripheral sympathetic nervous system. Therefore, it is possible that agmatine suppresses NA release in peripheral sympathetic nerve terminals by inhibiting Ca(2+) influx through N-type Ca(2+) channels. We tested this hypothesis by investigating agmatine effect on electrical field stimulation (EFS)-evoked contraction and NA release in endothelium-denuded rat superior mesenteric arterial strips. We also investigated the effect of agmatine on the N-type Ca(2+) current in superior cervical ganglion (SCG) neurons in rats. Our study demonstrates that agmatine suppresses peripheral sympathetic outflow via the imidazoline I2 receptor in rat mesenteric arteries. In addition, the agmatine-induced suppression of peripheral vascular sympathetic tone is mediated by modulating voltage-dependent N-type Ca(2+) channels in sympathetic nerve terminals. These results suggest a potential cellular mechanism for the agmatine-induced suppression of peripheral sympathetic tone. Furthermore, they provide basic and theoretical information regarding the development of new agents to treat hypertension. Copyright © 2016 Elsevier Inc. All rights reserved.

Crystal structure of SAM-dependent methyltransferase from Pyrococcus horikoshii.

PubMed

Pampa, K J; Madan Kumar, S; Hema, M K; Kumara, Karthik; Naveen, S; Kunishima, Naoki; Lokanath, N K

2017-12-01

Methyltransferases (MTs) are enzymes involved in methylation that are needed to perform cellular processes such as biosynthesis, metabolism, gene expression, protein trafficking and signal transduction. The cofactor S-adenosyl-L-methionine (SAM) is used for catalysis by SAM-dependent methyltransferases (SAM-MTs). The crystal structure of Pyrococcus horikoshii SAM-MT was determined to a resolution of 2.1 Å using X-ray diffraction. The monomeric structure consists of a Rossmann-like fold (domain I) and a substrate-binding domain (domain II). The cofactor (SAM) molecule binds at the interface between adjacent subunits, presumably near to the active site(s) of the enzyme. The observed dimeric state might be important for the catalytic function of the enzyme.

SAMS-II Requirements and Operations

NASA Technical Reports Server (NTRS)

Wald, Lawrence W.

1998-01-01

The Space Acceleration Measurements System (SAMS) II is the primary instrument for the measurement, storage, and communication of the microgravity environment aboard the International Space Station (ISS). SAMS-II is being developed by the NASA Lewis Research Center Microgravity Science Division to primarily support the Office of Life and Microgravity Science and Applications (OLMSA) Microgravity Science and Applications Division (MSAD) payloads aboard the ISS. The SAMS-II is currently in the test and verification phase at NASA LeRC, prior to its first hardware delivery scheduled for July 1998. This paper will provide an overview of the SAMS-II instrument, including the system requirements and topology, physical and electrical characteristics, and the Concept of Operations for SAMS-II aboard the ISS.

Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase.

PubMed

Fenwick, Michael K; Mehta, Angad P; Zhang, Yang; Abdelwahed, Sameh H; Begley, Tadhg P; Ealick, Steven E

2015-03-27

Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical. Canonical radical SAM enzymes are characterized by a β-barrel-like fold and SAM anchors to the differentiated iron of the cluster, which is located near the amino terminus and within the β-barrel, through its amino and carboxylate groups. Here we show that ThiC, the thiamin pyrimidine synthase in plants and bacteria, contains a tethered cluster-binding domain at its carboxy terminus that moves in and out of the active site during catalysis. In contrast to canonical radical SAM enzymes, we predict that SAM anchors to an additional active site metal through its amino and carboxylate groups. Superimposition of the catalytic domains of ThiC and glutamate mutase shows that these two enzymes share similar active site architectures, thus providing strong evidence for an evolutionary link between the radical SAM and adenosylcobalamin-dependent enzyme superfamilies.

SAM Companion Documents

EPA Pesticide Factsheets

SAM Companion Documents and Sample Collection Procedures provide information intended to complement the analytical methods listed in Selected Analytical Methods for Environmental Remediation and Recovery (SAM).

S-adenosyl methionine (SAM) attenuates the development of tolerance to analgesic activity of morphine in rats.

PubMed

Katyal, Jatinder; Kumar, Hemant; Joshi, Dinesh; Gupta, Yogendra Kumar

2017-04-03

Development of tolerance to analgesic effect, on chronic administration of morphine, limits its clinical usefulness in pain management. S-adenosyl methionine (SAM) used for arthritis and approved as a supplement in many countries including United States was evaluated for reducing morphine tolerance. Male 'Wistar' rats were used. The analgesic activity was determined using tail flick analgesiometer (Columbus Instruments, USA). Rats given morphine (7mg/kg), intraperitoneally (i.p.), once daily for 5days developed tolerance to analgesic effect. To evaluate the effect of SAM on morphine tolerance, SAM 800mg/kg was administered orally (p.o.), 45min prior to each dose of morphine. The analgesic activity of SAM and opioidergic component in its activity was also evaluated. Co-administration of morphine and SAM reversed morphine tolerance. SAM exhibited analgesic effect after repeated administration which was reversed by naloxone administration. Since safety of SAM on chronic use is documented it can be a good option in morphine tolerance. Role in drug addiction and withdrawal should also be evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

Expanding Radical SAM Chemistry by Using Radical Addition Reactions and SAM Analogues.

PubMed

Ji, Xinjian; Li, Yongzhen; Xie, Liqi; Lu, Haojie; Ding, Wei; Zhang, Qi

2016-09-19

Radical S-adenosyl-l-methionine (SAM) enzymes utilize a [4Fe-4S] cluster to bind SAM and reductively cleave its carbon-sulfur bond to produce a highly reactive 5'-deoxyadenosyl (dAdo) radical. In almost all cases, the dAdo radical abstracts a hydrogen atom from the substrates or from enzymes, thereby initiating a highly diverse array of reactions. Herein, we report a change of the dAdo radical-based chemistry from hydrogen abstraction to radical addition in the reaction of the radical SAM enzyme NosL. This change was achieved by using a substrate analogue containing an olefin moiety. We also showed that two SAM analogues containing different nucleoside functionalities initiate the radical-based reactions with high efficiencies. The radical adduct with the olefin produced in the reaction was found to undergo two divergent reactions, and the mechanistic insights into this process were investigated in detail. Our study demonstrates a promising strategy in expanding radical SAM chemistry, providing an effective way to access nucleoside-containing compounds by using radical SAM-dependent reactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Crystal Structure of Bicc1 SAM Polymer and Mapping of Interactions between the Ciliopathy-Associated Proteins Bicc1, ANKS3, and ANKS6.

PubMed

Rothé, Benjamin; Leettola, Catherine N; Leal-Esteban, Lucia; Cascio, Duilio; Fortier, Simon; Isenschmid, Manuela; Bowie, James U; Constam, Daniel B

2018-02-06

Head-to-tail polymers of sterile alpha motifs (SAM) can scaffold large macromolecular complexes. Several SAM-domain proteins that bind each other are mutated in patients with cystic kidneys or laterality defects, including the Ankyrin (ANK) and SAM domain-containing proteins ANKS6 and ANKS3, and the RNA-binding protein Bicc1. To address how their interactions are regulated, we first determined a high-resolution crystal structure of a Bicc1-SAM polymer, revealing a canonical SAM polymer with a high degree of flexibility in the subunit interface orientations. We further mapped interactions between full-length and distinct domains of Bicc1, ANKS3, and ANKS6. Neither ANKS3 nor ANKS6 alone formed macroscopic homopolymers in vivo. However, ANKS3 recruited ANKS6 to Bicc1, and the three proteins together cooperatively generated giant macromolecular complexes. Thus, the giant assemblies are shaped by SAM domains, their flanking sequences, and SAM-independent protein-protein and protein-mRNA interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bulk Hydrogen Content OF High-Silica Rocks in Gale Crater With the Active Dynamic Albedo of Neutrons Experiment

NASA Technical Reports Server (NTRS)

Gabriel, T. S. J.; Hardgrove, C.; Litvak, M.; Mitrofanov, I.; Boynton, W. V.; Fedosov, F.; Golovin, D.; Jun, I.; Mischna, M.; Tate, C. G.;

Square Wave Voltammetry of TNT at Gold Electrodes Modified with Self-Assembled Monolayers Containing Aromatic Structures

PubMed Central

Trammell, Scott A.; Zabetakis, Dan; Moore, Martin; Verbarg, Jasenka; Stenger, David A.

2014-01-01

Square wave voltammetry for the reduction of 2,4,6-trinitrotoluene (TNT) was measured in 100 mM potassium phosphate buffer (pH 8) at gold electrodes modified with self-assembled monolayers (SAMs) containing either an alkane thiol or aromatic ring thiol structures. At 15 Hz, the electrochemical sensitivity (µA/ppm) was similar for all SAMs tested. However, at 60 Hz, the SAMs containing aromatic structures had a greater sensitivity than the alkane thiol SAM. In fact, the alkane thiol SAM had a decrease in sensitivity at the higher frequency. When comparing the electrochemical response between simulations and experimental data, a general trend was observed in which most of the SAMs had similar heterogeneous rate constants within experimental error for the reduction of TNT. This most likely describes a rate limiting step for the reduction of TNT. However, in the case of the alkane SAM at higher frequency, the decrease in sensitivity suggests that the rate limiting step in this case may be electron tunneling through the SAM. Our results show that SAMs containing aromatic rings increased the sensitivity for the reduction of TNT when higher frequencies were employed and at the same time suppressed the electrochemical reduction of dissolved oxygen. PMID:25549081

Motor coordination defects in mice deficient for the Sam68 RNA-binding protein.

PubMed

Lukong, Kiven E; Richard, Stéphane

2008-06-03

The role of RNA-binding proteins in the central nervous system and more specifically their role in motor coordination and learning are poorly understood. We previously reported that ablation of RNA-binding protein Sam68 in mice results in male sterility and delayed mammary gland development and protection against osteoporosis in females. Sam68 however is highly expressed in most regions of the brain especially the cerebellum and thus we investigated the cerebellar-related manifestations in Sam68-null mice. We analyzed the mice for motor function, sensory function, and learning and memory abilities. Herein, we report that Sam68-null mice have motor coordination defects as assessed by beam walking and rotorod performance. Forty-week-old Sam68-null mice (n=12) were compared to their wild-type littermates (n=12). The Sam68-null mice exhibited more hindpaw faults in beam walking tests and fell from the rotating drum at lower speeds and prematurely compared to the wild-type controls. The Sam68-null mice were, however, normal for forelimb strength, tail-hang reflex, balance test, grid walking, the Morris water task, recognition memory, visual discrimination, auditory stimulation and conditional taste aversion. Our findings support a role for Sam68 in the central nervous system in the regulation of motor coordination.

Cooperation between Magnesium and Metabolite Controls Collapse of the SAM-I Riboswitch.

PubMed

Roy, Susmita; Onuchic, José N; Sanbonmatsu, Karissa Y

2017-07-25

The S-adenosylmethionine (SAM)-I riboswitch is a noncoding RNA that regulates the transcription termination process in response to metabolite (SAM) binding. The aptamer portion of the riboswitch may adopt an open or closed state depending on the presence of metabolite. Although the transition between the open and closed states is critical for the switching process, its atomistic details are not well understood. Using atomistic simulations, we calculate the effect of SAM and magnesium ions on the folding free energy landscape of the SAM-I riboswitch. These molecular simulation results are consistent with our previous wetlab experiments and aid in interpreting the SHAPE probing measurements. Here, molecular dynamics simulations explicitly identify target RNA motifs sensitive to magnesium ions and SAM. In the simulations, we observe that, whereas the metabolite mostly stabilizes the P1 and P3 helices, magnesium serves an important role in stabilizing a pseudoknot interaction between the P2 and P4 helices, even at high metabolite concentrations. The pseudoknot stabilization by magnesium, in combination with P1 stabilization by SAM, explains the requirement of both SAM and magnesium to form the fully collapsed metabolite-bound closed state of the SAM-I riboswitch. In the absence of SAM, frequent open-to-closed conformational transitions of the pseudoknot occur, akin to breathing. These pseudoknot fluctuations disrupt the binding site by facilitating fluctuations in the 5'-end of helix P1. Magnesium biases the landscape toward a collapsed state (preorganization) by coordinating pseudoknot and 5'-P1 fluctuations. The cooperation between SAM and magnesium in stabilizing important tertiary interactions elucidates their functional significance in transcription regulation. Published by Elsevier Inc.

Allosteric monofunctional aspartate kinases from Arabidopsis.

PubMed

Curien, Gilles; Laurencin, Mathieu; Robert-Genthon, Mylène; Dumas, Renaud

2007-01-01

Plant monofunctional aspartate kinase is unique among all aspartate kinases, showing synergistic inhibition by lysine and S-adenosyl-l-methionine (SAM). The Arabidopsis genome contains three genes for monofunctional aspartate kinases. We show that aspartate kinase 2 and aspartate kinase 3 are inhibited only by lysine, and that aspartate kinase 1 is inhibited in a synergistic manner by lysine and SAM. In the absence of SAM, aspartate kinase 1 displayed low apparent affinity for lysine compared to aspartate kinase 2 and aspartate kinase 3. In the presence of SAM, the apparent affinity of aspartate kinase 1 for lysine increased considerably, with K(0.5) values for lysine inhibition similar to those of aspartate kinase 2 and aspartate kinase 3. For all three enzymes, the inhibition resulted from an increase in the apparent K(m) values for the substrates ATP and aspartate. The mechanism of aspartate kinase 1 synergistic inhibition was characterized. Inhibition by lysine alone was fast, whereas synergistic inhibition by lysine plus SAM was very slow. SAM by itself had no effect on the enzyme activity, in accordance with equilibrium binding analyses indicating that SAM binding to aspartate kinase 1 requires prior binding of lysine. The three-dimensional structure of the aspartate kinase 1-Lys-SAM complex has been solved [Mas-Droux C, Curien G, Robert-Genthon M, Laurencin M, Ferrer JL & Dumas R (2006) Plant Cell18, 1681-1692]. Taken together, the data suggest that, upon binding to the inactive aspartate kinase 1-Lys complex, SAM promotes a slow conformational transition leading to formation of a stable aspartate kinase 1-Lys-SAM complex. The increase in aspartate kinase 1 apparent affinity for lysine in the presence of SAM thus results from the displacement of the unfavorable equilibrium between aspartate kinase 1 and aspartate kinase 1-Lys towards the inactive form.

Electroactive Self-Assembled Monolayers Detect Micelle Formation.

PubMed

Dionne, Eric R; Badia, Antonella

2017-02-15

The interfacial electrochemistry of self-assembled monolayers (SAMs) of ferrocenyldodecanethiolate on gold (FcC 12 SAu) electrodes is applied to detect the micellization of some common anionic surfactants, sodium n-alkyl sulfates, sodium n-alkyl sulfonates, sodium diamyl sulfosuccinate, and sodium dodecanoate, in aqueous solution by cyclic voltammetry. The apparent formal redox potential (E°' SAM ) of the FcC 12 SAu SAM is used to track changes in the concentration of the unaggregated surfactant anions and determine the critical micelle concentration (cmc). The effect of added salt (NaF) on the sodium alkyl sulfate concentration dependence of E°' SAM is also investigated. Weakly hydrated anions, such as ClO 4 - , pair with the electrogenerated SAM-bound ferroceniums to neutralize the excess positive charge created at the SAM/electrolyte solution interface and stabilize the oxidized cations. E°' SAM exhibits a Nernstian-type dependence on the anion activity in solution. Aggregation of the surfactant anions into micelles above the cmc causes the free surfactant anion activity to deviate from the molar concentration of added surfactant, resulting in a break in the plot of E°' SAM versus the logarithm of the concentration of anionic surfactant. The concentration at which this deviation occurs is in good agreement with literature or experimentally determined values of the cmc. The effects of Ohmic potential drop, liquid junction potential, and surfactant adsorption behavior on E°' SAM are addressed. Ultimately, the E°' SAM response as a function of the anionic surfactant concentration exhibits the same features reported using potentiometry and surfactant ion-selective electrodes, which provide a direct measure of the free surfactant anion activity, thus making FcC 12 SAu SAM electrodes useful for the detection of surfactant aggregation and micelle formation.

Fragmentation and reactivity in collisions of protonated diglycine with chemically modified perfluorinated alkylthiolate-self-assembled monolayer surfaces

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

Barnes, George L.; Yang Li; Hase, William L.

2011-03-07

Direct dynamics simulations are reported for quantum mechanical (QM)/molecular mechanical (MM) trajectories of N-protonated diglycine (gly{sub 2}-H{sup +}) colliding with chemically modified perfluorinated octanethiolate self-assembled monolayer (SAM) surfaces. The RM1 semiempirical theory is used for the QM component of the trajectories. RM1 activation and reaction energies were compared with those determined from higher-level ab initio theories. Two chemical modifications are considered in which a head group (-COCl or -CHO) is substituted on the terminal carbon of a single chain of the SAM. These surfaces are designated as the COCl-SAM and CHO-SAM, respectively. Fragmentation, peptide reaction with the SAM, and covalentmore » linkage of the peptide or its fragments with the SAM surface are observed. Peptide fragmentation via concerted CH{sub 2}-CO bond breakage is the dominant pathway for both surfaces. HCl formation is the dominant species produced by reaction with the COCl-SAM, while for the CHO-SAM a concerted H-atom transfer from the CHO-SAM to the peptide combined with either a H-atom or radical transfer from the peptide to the surface to form singlet reaction products is the dominant pathway. A strong collision energy dependence is found for the probability of peptide fragmentation, its reactivity, and linkage with the SAM. Surface deposition, i.e., covalent linkage between the surface and the peptide, is compared to recent experimental observations of such bonding by Laskin and co-workers [Phys. Chem. Chem. Phys. 10, 1512 (2008)]. Qualitative differences in reactivity are seen between the COCl-SAM and CHO-SAM showing that chemical identity is important for surface reactivity. The probability of reactive surface deposition, which is most closely analogous to experimental observables, peaks at a value of around 20% for a collision energy of 50 eV.« less

Testing the validity, reliability and utility of the Self-Administration of Medication (SAM) tool in patients undergoing rehabilitation.

PubMed

Anderson, Jessica; Manias, Elizabeth; Kusljic, Snezana; Finch, Sue

2014-01-01

Determination of patients' ability to self-administer medications in the hospital has largely been determined using the subjective judgment of health professionals. To examine the validity, reliability and utility of the Self-Administration of Medication (SAM) tool as an objective means to determine patients' ability to self-administer in a rehabilitation unit of a public teaching hospital in Melbourne, Australia. To assess validity of the SAM tool, associations were examined between the total SAM tool score and of the patients' competence to self-administer from the perceptions of the tool administrator, patients and nurses. Validity also was determined from a principal component analysis. Pearson correlations were calculated for how SAM scores related to scores obtained from the Functional Independence Measure (FIM) and Barthel Score Index (BSI). To assess the SAM tool's reliability, a Cronbach's alpha coefficient was calculated. Utility of the SAM tool was evidenced by documenting its administration time. One hundred patients participated in this study. The SAM tool had a Cronbach's alpha coefficient of 0.75 and took a mean time of 5.36 min to complete. The capability to self-medicate section of the SAM tool had strong correlations with the FIM (r = 0.485) and BSI (r = 0.472) data, respectively, and the total SAM tool had moderate and strong correlations with the nurses' (r = 0.315) and tool administrator's (r = 0.632) perceptions of patients' ability to self-administer, respectively. Bland-Altman and ROC curve analyses showed poor agreement between the total SAM tool score and the nurses' perceptions. The SAM tool demonstrated acceptable overall internal consistency. It only requires a short time to be completed and is more objective than seeking out health professionals' perceptions. Additional research is needed to further validate this approach to determining patients' ability to self-medicate. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Efficacy of artemether-lumefantrine in relation to drug exposure in children with and without severe acute malnutrition: an open comparative intervention study in Mali and Niger.

PubMed

Denoeud-Ndam, Lise; Dicko, Alassane; Baudin, Elisabeth; Guindo, Ousmane; Grandesso, Francesco; Diawara, Halimatou; Sissoko, Sibiri; Sanogo, Koualy; Traoré, Seydou; Keita, Sekouba; Barry, Amadou; de Smet, Martin; Lasry, Estrella; Smit, Michiel; Wiesner, Lubbe; Barnes, Karen I; Djimde, Abdoulaye A; Guerin, Philippe J; Grais, Rebecca F; Doumbo, Ogobara K; Etard, Jean-François

2016-10-24

Severe acute malnutrition (SAM) affects almost all organs and has been associated with reduced intestinal absorption of medicines. However, very limited information is available on the pharmacokinetic properties of antimalarial drugs in this vulnerable population. We assessed artemether-lumefantrine (AL) clinical efficacy in children with SAM compared to those without. Children under 5 years of age with uncomplicated P. falciparum malaria were enrolled between November 2013 and January 2015 in Mali and Niger, one third with uncomplicated SAM and two thirds without. AL was administered under direct observation with a fat intake consisting of ready-to-use therapeutic food (RUTF - Plumpy'Nut®) in SAM children, twice daily during 3 days. Children were followed for 42 days, with PCR-corrected adequate clinical and parasitological response (ACPR) at day 28 as the primary outcome. Lumefantrine concentrations were assessed in a subset of participants at different time points, including systematic measurements on day 7. A total of 399 children (360 in Mali and 39 in Niger) were enrolled. Children with SAM were younger than their non-SAM counterparts (mean 17 vs. 28 months, P < 0.0001). PCR-corrected ACPR was 100 % (95 % CI, 96.8-100 %) in SAM at both day 28 and 42, versus 98.8 % (96.4-99.7 %) at day 28 and 98.3 % (95.6-99.4 %) at day 42 in non-SAM (P = 0.236 and 0.168, respectively). Compared to younger children, children older than 21 months experienced more reinfections and SAM was associated with a greater risk of reinfection until day 28 (adjusted hazard ratio = 2.10 (1.04-4.22), P = 0.038). Day 7 lumefantrine concentrations were significantly lower in SAM than non-SAM (median 251 vs. 365 ng/mL, P = 0.049). This study shows comparable therapeutic efficacy of AL in children without SAM and in those with SAM when given in combination with RUTF, but a higher risk of reinfection in older children suffering from SAM. This could be associated with poorer exposure to the antimalarials as documented by a lower lumefantrine concentration on day 7. ClinicalTrials.gov: NCT01958905 , registration date: October 7, 2013.

Calibration and Sequence Development Status for the Sample Analysis at Mars Investigation on the Mars Science Laboratory

NASA Technical Reports Server (NTRS)

Mahaffy, Paul R.

2012-01-01

The measurement goals of the Sample Analysis at Mars (SAM) instrument suite on the "Curiosity" Rover of the Mars Science Laboratory (MSL) include chemical and isotopic analysis of organic and inorganic volatiles for both atmospheric and solid samples [1,2]. SAM directly supports the ambitious goals of the MSL mission to provide a quantitative assessment of habitability and preservation in Gale crater by means of a range of chemical and geological measurements [3]. The SAM FM combined calibration and environmental testing took place primarily in 2010 with a limited set of tests implemented after integration into the rover in January 2011. The scope of SAM FM testing was limited both to preserve SAM consumables such as life time of its electromechanical elements and to minimize the level of terrestrial contamination in the SAM instrument. A more comprehensive calibration of a SAM-like suite of instruments will be implemented in 2012 with calibration runs planned for the SAM testbed. The SAM Testbed is nearly identical to the SAM FM and operates in a ambient pressure chamber. The SAM Instrument Suite: SAM's instruments are a Quadrupole Mass Spectrometer (QMS), a 6-column Gas Chromatograph (GC), and a 2-channel Tunable Laser Spectrometer (TLS). Gas Chromatography Mass Spectrometry is designed for identification of even trace organic compounds. The TLS [5] secures the C, H, and O isotopic composition in carbon dioxide, water, and methane. Sieved materials are delivered from the MSL sample acquisition and processing system to one of68 cups of the Sample Manipulation System (SMS). 59 of these cups are fabricated from inert quartz. After sample delivery, a cup is inserted into one of 2 ovens for evolved gas analysis (EGA ambient to >9500C) by the QMS and TLS. A portion of the gas released can be trapped and subsequently analyzed by GCMS. Nine sealed cups contain liquid solvents and chemical derivatization or thermochemolysis agents to extract and transform polar molecules such as amino acids, nucleobases, and carboxylic acids into compounds that are sufficiently volatile to transmit through the GC columns. The remaining 6 cups contain calibrants. SAM FM Calibration Overview: The SAM FM calibration in the Mars chamber employed a variety of pure gases, gas mixtures, and solid materials. Isotope calibration runs for the TLS utilized 13C enriched C02 standards and 0 enriched CH4. A variety of fluorocarbon compounds that spanned the entire mass range of the QMS as well as C3-C6 hydrocarbons were utilized for calibration of the GCMS. Solid samples consisting of a mixture of calcite, melanterite, and inert silica glass either doped or not with fluorocarbons were introduced into the SAM FM cups through the SAM inlet funnel/tube system.

On the benefit of DMT modulation in nonlinear VLC systems.

PubMed

Qian, Hua; Cai, Sunzeng; Yao, Saijie; Zhou, Ting; Yang, Yang; Wang, Xudong

2015-02-09

In a visible light communication (VLC) system, the nonlinear characteristic of the light emitting diode (LED) in transmitter is a limiting factor of system performance. Modern modulation signals with large peak-to-power-ratio (PAPR) suffers uneven distortion. The nonlinear response directly impacts the intensity modulation and direct detection VLC system with pulse-amplitude modulation (PAM). The amplitude of the PAM signal is distorted unevenly and large signal is vulnerable to noise. Orthogonal linear transformations, such as discrete multi-tone (DMT) modulation, can spread the nonlinear effects evenly to each data symbol, thus perform better than PAM signals. In this paper, we provide theoretical analysis on the benefit of DMT modulation in nonlinear VLC system. We show that the DMT modulation is a better choice than the PAM modulation for the VLC system as the DMT modulation is more robust against nonlinearity. We also show that the post-distortion nonlinear elimination method, which is applied at the receiver, can be a reliable solution to the nonlinear VLC system. Simulation results show that the post-distortion greatly improves the system performance for the DMT modulation.

Investigation of e-beam sensitive negative-tone chemically amplified resists for binary mask making

NASA Astrophysics Data System (ADS)

Irmscher, Mathias; Berger, Lothar; Beyer, Dirk; Butschke, Joerg; Dress, Peter; Hoffmann, Thomas; Hudek, Peter; Koepernik, Corinna; Tschinkl, Martin; Voehringer, Peter

2003-08-01

Negative-tone chemically amplified resists MES-EN1G (JSR), FEN-270 (Fujifilm ARCH), EN-024M (TOK) and NEB-22 (Sumitomo) were evaluated for binary mask making. The investigations were performed on an advanced tool set comprising a 50kV e-beam writer Leica SB350, a Steag Hamatech hot/cool plate module APB5000, a Steag Hamatech developer ASP5000, an UNAXIS MASK ETCHER III and a SEM LEO1560 with integrated CD measurement option. We investigated and compared the evaluated resists in terms of resolution, e-beam sensitivity, resist profile, post exposure bake sensitivity, CD-uniformity, line edge roughness, pattern fidelity and etch resistance. Furthermore, the influence of post coating delay and post exposure delay in vacuum and air was determined.

Arousal mechanisms related to posture and locomotion: 1. Descending modulation.

PubMed

Garcia-Rill, Edgar; Homma, Yutaka; Skinner, Robert D

2004-01-01

Much of the controversy surrounding the induction of locomotion following stimulation of mesopontine sites, including the pedunculopontine nucleus (PPN), appears based on procedural differences, including stimulus onset, delay preceding stepping, and frequency of stimuli. The results reviewed in this chapter address these issues and provide novel information suggesting that descending projections from the PPN may exert a frequency-dependent effect. Stimulation at approximately 60 Hz (which induces prolonged tonic firing) may exercise a "push" towards locomotion (activation of pontine interneurons) as well as a "pull" away from decreased muscle tone (inhibiting giant pontine reticulospinal cells). Higher frequencies of stimulation (> 100 Hz, which induces phasic burst-like activity) may "push" towards decreases in muscle tone, including the atonia of rapid eye movement sleep (activating giant pontine reticulospinal cells).

Identification of new ligands for the methionine biosynthesis transcriptional regulator (MetJ) by FAC-MS.

PubMed

Martí-Arbona, Ricardo; Teshima, Munehiro; Anderson, Penelope S; Nowak-Lovato, Kristy L; Hong-Geller, Elizabeth; Unkefer, Clifford J; Unkefer, Pat J

2012-01-01

We have developed a high-throughput approach using frontal affinity chromatography coupled to mass spectrometry (FAC-MS) for the identification and characterization of the small molecules that modulate transcriptional regulator (TR) binding to TR targets. We tested this approach using the methionine biosynthesis regulator (MetJ). We used effector mixtures containing S-adenosyl-L-methionine (SAM) and S-adenosyl derivatives as potential ligands for MetJ binding. The differences in the elution time of different compounds allowed us to rank the binding affinity of each compound. Consistent with previous results, FAC-MS showed that SAM binds to MetJ with the highest affinity. In addition, adenine and 5'-deoxy-5'-(methylthio)adenosine bind to the effector binding site on MetJ. Our experiments with MetJ demonstrate that FAC-MS is capable of screening complex mixtures of molecules and identifying high-affinity binders to TRs. In addition, FAC-MS experiments can be used to discriminate between specific and nonspecific binding of the effectors as well as to estimate the dissociation constant (K(d)) for effector-TR binding. Copyright © 2012 S. Karger AG, Basel.

75 FR 4579 - Certificate of Alternative Compliance for the Tugboat MR SAM

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-28

... Compliance for the Tugboat MR SAM AGENCY: Coast Guard, DHS. ACTION: Notice. SUMMARY: The Coast Guard announces that a Certificate of Alternative Compliance was issued for the tugboat MR SAM as required by 33 U... Title 33, Code of Federal Regulations, Parts 81 and 89, has been issued for the tugboat MR SAM, O.N...

Preparation for Analytical Measurements on Mars

NASA Image and Video Library

2015-03-31

A Sample Analysis at Mars (SAM) team member at NASA's Goddard Space Flight Center, Greenbelt, Maryland, prepares the SAM testbed for an experiment. This test copy of the SAM suite of instruments is inside a chamber that, when closed, can model the pressure and temperature environment that SAM sees inside NASA's Curiosity rover on Mars. Many weeks of testing are often needed to develop and refine sequences of operations that SAM uses for making specific measurements on Mars. This was the case with preparation to pull a volume of gas from the atmosphere and extract the heavy noble gas xenon. SAM's measurements of different types of xenon in the Martian atmosphere provide clues about the planet's history. http://photojournal.jpl.nasa.gov/catalog/PIA19149

The influence of midazolam on heart rate arises from cardiac autonomic tones alterations in Burmese pythons, Python molurus.

PubMed

Lopes, Ivã Guidini; Armelin, Vinicius Araújo; Braga, Victor Hugo da Silva; Florindo, Luiz Henrique

2017-12-01

The GABA A receptor agonist midazolam is a compound widely used as a tranquilizer and sedative in mammals and reptiles. It is already known that this benzodiazepine produces small to intermediate heart rate (HR) alterations in mammals, however, its influence on reptiles' HR remains unexplored. Thus, the present study sought to verify the effects of midazolam on HR and cardiac modulation in the snake Python molurus. To do so, the snakes' HR, cardiac autonomic tones, and HR variability were evaluated during four different experimental stages. The first stage consisted on the data acquisition of animals under untreated conditions, in which were then administered atropine (2.5mgkg -1 ; intraperitoneal), followed later by propranolol (3.5mgkg -1 ; intraperitoneal) (cardiac double autonomic blockade). The second stage focused on the data acquisition of animals under midazolam effect (1.0mgkg -1 ; intramuscular), which passed through the same autonomic blockade protocol of the first stage. The third and fourth stages consisted of the same protocol of stages one and two, respectively, with the exception that atropine and propranolol injections were reversed. By comparing the HR of animals that received midazolam (second and fourth stages) with those that did not (first and third stages), it could be observed that this benzodiazepine reduced the snakes' HR by ~60%. The calculated autonomic tones showed that such cardiac depression was elicited by an ~80% decrease in cardiac adrenergic tone and an ~620% increase in cardiac cholinergic tone - a finding that was further supported by the results of HR variability analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Cerebellum, temporal predictability and the updating of a mental model.

PubMed

Kotz, Sonja A; Stockert, Anika; Schwartze, Michael

2014-12-19

We live in a dynamic and changing environment, which necessitates that we adapt to and efficiently respond to changes of stimulus form ('what') and stimulus occurrence ('when'). Consequently, behaviour is optimal when we can anticipate both the 'what' and 'when' dimensions of a stimulus. For example, to perceive a temporally expected stimulus, a listener needs to establish a fairly precise internal representation of its external temporal structure, a function ascribed to classical sensorimotor areas such as the cerebellum. Here we investigated how patients with cerebellar lesions and healthy matched controls exploit temporal regularity during auditory deviance processing. We expected modulations of the N2b and P3b components of the event-related potential in response to deviant tones, and also a stronger P3b response when deviant tones are embedded in temporally regular compared to irregular tone sequences. We further tested to what degree structural damage to the cerebellar temporal processing system affects the N2b and P3b responses associated with voluntary attention to change detection and the predictive adaptation of a mental model of the environment, respectively. Results revealed that healthy controls and cerebellar patients display an increased N2b response to deviant tones independent of temporal context. However, while healthy controls showed the expected enhanced P3b response to deviant tones in temporally regular sequences, the P3b response in cerebellar patients was significantly smaller in these sequences. The current data provide evidence that structural damage to the cerebellum affects the predictive adaptation to the temporal structure of events and the updating of a mental model of the environment under voluntary attention. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Cerebellum, temporal predictability and the updating of a mental model

PubMed Central

Kotz, Sonja A.; Stockert, Anika; Schwartze, Michael

2014-01-01

We live in a dynamic and changing environment, which necessitates that we adapt to and efficiently respond to changes of stimulus form (‘what’) and stimulus occurrence (‘when’). Consequently, behaviour is optimal when we can anticipate both the ‘what’ and ‘when’ dimensions of a stimulus. For example, to perceive a temporally expected stimulus, a listener needs to establish a fairly precise internal representation of its external temporal structure, a function ascribed to classical sensorimotor areas such as the cerebellum. Here we investigated how patients with cerebellar lesions and healthy matched controls exploit temporal regularity during auditory deviance processing. We expected modulations of the N2b and P3b components of the event-related potential in response to deviant tones, and also a stronger P3b response when deviant tones are embedded in temporally regular compared to irregular tone sequences. We further tested to what degree structural damage to the cerebellar temporal processing system affects the N2b and P3b responses associated with voluntary attention to change detection and the predictive adaptation of a mental model of the environment, respectively. Results revealed that healthy controls and cerebellar patients display an increased N2b response to deviant tones independent of temporal context. However, while healthy controls showed the expected enhanced P3b response to deviant tones in temporally regular sequences, the P3b response in cerebellar patients was significantly smaller in these sequences. The current data provide evidence that structural damage to the cerebellum affects the predictive adaptation to the temporal structure of events and the updating of a mental model of the environment under voluntary attention. PMID:25385781

A pilot study investigating the feasibility of symptom assessment manager (SAM), a Web-based real-time tool for monitoring challenging behaviors.

PubMed

Loi, Samantha M; Wanasinghage, Sangeeth; Goh, Anita; Lautenschlager, Nicola T; Darby, David G; Velakoulis, Dennis

2018-04-01

Improving and minimizing challenging behaviors seen in psychiatric conditions, including behavioral and psychological symptoms of dementia are important in the care of people with these conditions. Yet there is a lack of systematic evaluation of these as a part of routine clinical care. The Neuropsychiatric Inventory is a validated and reliable tool for rating the severity and disruptiveness of challenging behaviors. We report on the evaluation of a Web-based symptom assessment manager (SAM), designed to address the limitation of previous tools using some of the Neuropsychiatric Inventory functions, to monitor behaviors by staff caring for people with dementia and other psychiatric conditions in inpatient and residential care settings. The SAM was piloted in an 8-bed inpatient neuropsychiatry unit over 5 months. Eleven nurses and 4 clinicians were trained in usage of SAM. Primary outcomes were usage of SAM and perceived usability, utility, and acceptance of SAM. Secondary outcomes were the frequencies of documented behavior. Usage data were analyzed using chi-square and logistic regression analyses. The SAM was used for all admitted patients regardless of diagnosis, with a usage rate of 64% for nurses regularly employed in the unit. Staff provided positive feedback regarding the utility of SAM. The SAM appeared to offer individualized behavior assessment by providing a quick, structured, and standardized platform for assessing behavior in a real-world setting. Further research would involve trialing SAM with more staff in alternative settings such as in home or residential care settings. Copyright © 2017 John Wiley & Sons, Ltd.

A Response to Sam McKegney's "Strategies for Ethical Engagement: An Open Letter Concerning Non-Native Scholars of Native Literatures"

ERIC Educational Resources Information Center

Appleford, Rob

2009-01-01

This article presents the author's response to Sam McKegney's "Strategies for Ethical Engagement: An Open Letter Concerning Non-Native Scholars of Native Literatures." In his response to Sam's diagnosis of the malaise currently afflicting non-Aboriginal critics of this literature, the author attempts to consider the "cure" Sam offers (albeit…

Walking with a Slower Friend

ERIC Educational Resources Information Center

Bailey, Herb; Kalman, Dan

2011-01-01

Fay and Sam go for a walk. Sam walks along the left side of the street while Fay, who walks faster, starts with Sam but walks to a point on the right side of the street and then returns to meet Sam to complete one segment of their journey. We determine Fay's optimal path minimizing segment length, and thus maximizing the number of times they meet…

Severe acute malnutrition.

PubMed

Nel, E D

2016-05-01

The mortality and morbidity associated with severe acute malnutrition (SAM) remain high. A summary of recent studies that are of interest to clinicians treating children with SAM is provided. Three important themes emerged in 2015: the use of anthropometry in the diagnosis of SAM and its correlation with body composition; the composition of ready-to-use therapeutic feeds (RUTF); and an improved understanding of the pathophysiology of SAM. Standard anthropometry does not accurately predict body composition and mid-upper arm circumference more accurately reflects fat mass in children. As single measure, mid-upper arm circumference identifies those children who are most likely to die from SAM and is not influenced by dehydration. However, a significant proportion of SAM children requiring treatment will not be detected. Present RUTF formulations are deficient in long chain polyunsaturated fatty acids. Current evidence suggests that preformed docosahexaenoic acid should be added and/or the content of linoleic acid reduced in RUTF. In contrast to an animal model, stabile children with SAM have the same cardiac index as children without SAM. The situation in haemodynamically unstable children is unknown, continued conservative use of intravenous fluids seems advisable. A reduction in variability of the faecal DNA virome may account for increased susceptibility to malnutrition in vulnerable children.

Ontogeny of the Maize Shoot Apical Meristem[W][OA

PubMed Central

Takacs, Elizabeth M.; Li, Jie; Du, Chuanlong; Ponnala, Lalit; Janick-Buckner, Diane; Yu, Jianming; Muehlbauer, Gary J.; Schnable, Patrick S.; Timmermans, Marja C.P.; Sun, Qi; Nettleton, Dan; Scanlon, Michael J.

2012-01-01

The maize (Zea mays) shoot apical meristem (SAM) arises early in embryogenesis and functions during stem cell maintenance and organogenesis to generate all the aboveground organs of the plant. Despite its integral role in maize shoot development, little is known about the molecular mechanisms of SAM initiation. Laser microdissection of apical domains from developing maize embryos and seedlings was combined with RNA sequencing for transcriptomic analyses of SAM ontogeny. Molecular markers of key events during maize embryogenesis are described, and comprehensive transcriptional data from six stages in maize shoot development are generated. Transcriptomic profiling before and after SAM initiation indicates that organogenesis precedes stem cell maintenance in maize; analyses of the first three lateral organs elaborated from maize embryos provides insight into their homology and to the identity of the single maize cotyledon. Compared with the newly initiated SAM, the mature SAM is enriched for transcripts that function in transcriptional regulation, hormonal signaling, and transport. Comparisons of shoot meristems initiating juvenile leaves, adult leaves, and husk leaves illustrate differences in phase-specific (juvenile versus adult) and meristem-specific (SAM versus lateral meristem) transcript accumulation during maize shoot development. This study provides insight into the molecular genetics of SAM initiation and function in maize. PMID:22911570

Threshold-Voltage Shifts in Organic Transistors Due to Self-Assembled Monolayers at the Dielectric: Evidence for Electronic Coupling and Dipolar Effects.

PubMed

Aghamohammadi, Mahdieh; Rödel, Reinhold; Zschieschang, Ute; Ocal, Carmen; Boschker, Hans; Weitz, R Thomas; Barrena, Esther; Klauk, Hagen

2015-10-21

The mechanisms behind the threshold-voltage shift in organic transistors due to functionalizing of the gate dielectric with self-assembled monolayers (SAMs) are still under debate. We address the mechanisms by which SAMs determine the threshold voltage, by analyzing whether the threshold voltage depends on the gate-dielectric capacitance. We have investigated transistors based on five oxide thicknesses and two SAMs with rather diverse chemical properties, using the benchmark organic semiconductor dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene. Unlike several previous studies, we have found that the dependence of the threshold voltage on the gate-dielectric capacitance is completely different for the two SAMs. In transistors with an alkyl SAM, the threshold voltage does not depend on the gate-dielectric capacitance and is determined mainly by the dipolar character of the SAM, whereas in transistors with a fluoroalkyl SAM the threshold voltages exhibit a linear dependence on the inverse of the gate-dielectric capacitance. Kelvin probe force microscopy measurements indicate this behavior is attributed to an electronic coupling between the fluoroalkyl SAM and the organic semiconductor.

(13)C-metabolic flux analysis in S-adenosyl-L-methionine production by Saccharomyces cerevisiae.

PubMed

Hayakawa, Kenshi; Kajihata, Shuichi; Matsuda, Fumio; Shimizu, Hiroshi

2015-11-01

S-Adenosyl-L-methionine (SAM) is a major biological methyl group donor, and is used as a nutritional supplement and prescription drug. Yeast is used for the industrial production of SAM owing to its high intracellular SAM concentrations. To determine the regulation mechanisms responsible for such high SAM production, (13)C-metabolic flux analysis ((13)C-MFA) was conducted to compare the flux distributions in the central metabolism between Kyokai no. 6 (high SAM-producing) and S288C (control) strains. (13)C-MFA showed that the levels of tricarboxylic acid (TCA) cycle flux in SAM-overproducing strain were considerably increased compared to those in the S228C strain. Analysis of ATP balance also showed that a larger amount of excess ATP was produced in the Kyokai 6 strain because of increased oxidative phosphorylation. These results suggest that high SAM production in Kyokai 6 strains could be attributed to enhanced ATP regeneration with high TCA cycle fluxes and respiration activity. Thus, maintaining high respiration efficiency during cultivation is important for improving SAM production. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Discrimination between Closely Related Cellular Metabolites by the SAM-I Riboswitch

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

Montange, R.; Mondragon, E; van Tyne, D

2010-01-01

The SAM-I riboswitch is a cis-acting element of genetic control found in bacterial mRNAs that specifically binds S-adenosylmethionine (SAM). We previously determined the 2.9-{angstrom} X-ray crystal structure of the effector-binding domain of this RNA element, revealing details of RNA-ligand recognition. To improve this structure, variations were made to the RNA sequence to alter lattice contacts, resulting in a 0.5-{angstrom} improvement in crystallographic resolution and allowing for a more accurate refinement of the crystallographic model. The basis for SAM specificity was addressed by a structural analysis of the RNA complexed to S-adenosylhomocysteine (SAH) and sinefungin and by measuring the affinity ofmore » SAM and SAH for a series of mutants using isothermal titration calorimetry. These data illustrate the importance of two universally conserved base pairs in the RNA that form electrostatic interactions with the positively charged sulfonium group of SAM, thereby providing a basis for discrimination between SAM and SAH.« less

The vesicle protein SAM-4 regulates the processivity of synaptic vesicle transport.

PubMed

Zheng, Qun; Ahlawat, Shikha; Schaefer, Anneliese; Mahoney, Tim; Koushika, Sandhya P; Nonet, Michael L

2014-10-01

Axonal transport of synaptic vesicles (SVs) is a KIF1A/UNC-104 mediated process critical for synapse development and maintenance yet little is known of how SV transport is regulated. Using C. elegans as an in vivo model, we identified SAM-4 as a novel conserved vesicular component regulating SV transport. Processivity, but not velocity, of SV transport was reduced in sam-4 mutants. sam-4 displayed strong genetic interactions with mutations in the cargo binding but not the motor domain of unc-104. Gain-of-function mutations in the unc-104 motor domain, identified in this study, suppress the sam-4 defects by increasing processivity of the SV transport. Genetic analyses suggest that SAM-4, SYD-2/liprin-α and the KIF1A/UNC-104 motor function in the same pathway to regulate SV transport. Our data support a model in which the SV protein SAM-4 regulates the processivity of SV transport.

The Vesicle Protein SAM-4 Regulates the Processivity of Synaptic Vesicle Transport

PubMed Central

Zheng, Qun; Ahlawat, Shikha; Schaefer, Anneliese; Mahoney, Tim; Koushika, Sandhya P.; Nonet, Michael L.

2014-01-01

Axonal transport of synaptic vesicles (SVs) is a KIF1A/UNC-104 mediated process critical for synapse development and maintenance yet little is known of how SV transport is regulated. Using C. elegans as an in vivo model, we identified SAM-4 as a novel conserved vesicular component regulating SV transport. Processivity, but not velocity, of SV transport was reduced in sam-4 mutants. sam-4 displayed strong genetic interactions with mutations in the cargo binding but not the motor domain of unc-104. Gain-of-function mutations in the unc-104 motor domain, identified in this study, suppress the sam-4 defects by increasing processivity of the SV transport. Genetic analyses suggest that SAM-4, SYD-2/liprin-α and the KIF1A/UNC-104 motor function in the same pathway to regulate SV transport. Our data support a model in which the SV protein SAM-4 regulates the processivity of SV transport. PMID:25329901

Non-canonical active site architecture of the radical SAM thiamin pyrimidine synthase

DOE PAGES

Fenwick, Michael K.; Mehta, Angad P.; Zhang, Yang; ...

2015-03-27

Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to generate a 5'-deoxyadenosyl radical. Canonical radical SAM enzymes are characterized by a β-barrel-like fold and SAM anchors to the differentiated iron of the cluster, which is located near the amino terminus and within the β-barrel, through its amino and carboxylate groups. Here we show that ThiC, the thiamin pyrimidine synthase in plants and bacteria, contains a tethered cluster-binding domain at its carboxy terminus that moves in and out of the active site during catalysis. In contrast to canonical radical SAM enzymes, we predict that SAM anchors to an additional active sitemore » metal through its amino and carboxylate groups. Superimposition of the catalytic domains of ThiC and glutamate mutase shows that these two enzymes share similar active site architectures, thus providing strong evidence for an evolutionary link between the radical SAM and adenosylcobalamin-dependent enzyme superfamilies.« less

10 Hz Amplitude Modulated Sounds Induce Short-Term Tinnitus Suppression

PubMed Central

Neff, Patrick; Michels, Jakob; Meyer, Martin; Schecklmann, Martin; Langguth, Berthold; Schlee, Winfried

2017-01-01

Objectives: Acoustic stimulation or sound therapy is proposed as a main treatment option for chronic subjective tinnitus. To further probe the field of acoustic stimulations for tinnitus therapy, this exploratory study compared 10 Hz amplitude modulated (AM) sounds (two pure tones, noise, music, and frequency modulated (FM) sounds) and unmodulated sounds (pure tone, noise) regarding their temporary suppression of tinnitus loudness. First, it was hypothesized that modulated sounds elicit larger temporary loudness suppression (residual inhibition) than unmodulated sounds. Second, with manipulation of stimulus loudness and duration of the modulated sounds weaker or stronger effects of loudness suppression were expected, respectively. Methods: We recruited 29 participants with chronic tonal tinnitus from the multidisciplinary Tinnitus Clinic of the University of Regensburg. Participants underwent audiometric, psychometric and tinnitus pitch matching assessments followed by an acoustic stimulation experiment with a tinnitus loudness growth paradigm. In a first block participants were stimulated with all of the sounds for 3 min each and rated their subjective tinnitus loudness to the pre-stimulus loudness every 30 s after stimulus offset. The same procedure was deployed in the second block with the pure tone AM stimuli matched to the tinnitus frequency, manipulated in length (6 min), and loudness (reduced by 30 dB and linear fade out). Repeated measures mixed model analyses of variance (ANOVA) were calculated to assess differences in loudness growth between the stimuli for each block separately. Results: First, we found that all sounds elicit a short-term suppression of tinnitus loudness (seconds to minutes) with strongest suppression right after stimulus offset [F(6, 1331) = 3.74, p < 0.01]. Second, similar to previous findings we found that AM sounds near the tinnitus frequency produce significantly stronger tinnitus loudness suppression than noise [vs. Pink noise: t(27) = −4.22, p < 0.0001]. Finally, variants of the AM sound matched to the tinnitus frequency reduced in sound level resulted in less suppression while there was no significant difference observed for a longer stimulation duration. Moreover, feasibility of the overall procedure could be confirmed as scores of both tinnitus loudness and questionnaires were lower after the experiment [tinnitus loudness: t(27) = 2.77, p < 0.01; Tinnitus Questionnaire: t(27) = 2.06, p < 0.05; Tinnitus Handicap Inventory: t(27) = 1.92, p = 0.065]. Conclusion: Taken together, these results imply that AM sounds, especially in or around the tinnitus frequency, may induce larger suppression than unmodulated sounds. Future studies should thus evaluate this approach in longitudinal studies and real life settings. Furthermore, the putative neural relation of these sound stimuli with a modulation rate in the EEG α band to the observed tinnitus suppression should be probed with respective neurophysiological methods. PMID:28579955

Binaural sluggishness in the perception of tone sequences and speech in noise.

PubMed

Culling, J F; Colburn, H S

2000-01-01

The binaural system is well-known for its sluggish response to changes in the interaural parameters to which it is sensitive. Theories of binaural unmasking have suggested that detection of signals in noise is mediated by detection of differences in interaural correlation. If these theories are correct, improvements in the intelligibility of speech in favorable binaural conditions is most likely mediated by spectro-temporal variations in interaural correlation of the stimulus which mirror the spectro-temporal amplitude modulations of the speech. However, binaural sluggishness should limit the temporal resolution of the representation of speech recovered by this means. The present study tested this prediction in two ways. First, listeners' masked discrimination thresholds for ascending vs descending pure-tone arpeggios were measured as a function of rate of frequency change in the NoSo and NoSpi binaural configurations. Three-tone arpeggios were presented repeatedly and continuously for 1.6 s, masked by a 1.6-s burst of noise. In a two-interval task, listeners determined the interval in which the arpeggios were ascending. The results showed a binaural advantage of 12-14 dB for NoSpi at 3.3 arpeggios per s (arp/s), which reduced to 3-5 dB at 10.4 arp/s. This outcome confirmed that the discrimination of spectro-temporal patterns in noise is susceptible to the effects of binaural sluggishness. Second, listeners' masked speech-reception thresholds were measured in speech-shaped noise using speech which was 1, 1.5, and 2 times the original articulation rate. The articulation rate was increased using a phase-vocoder technique which increased all the modulation frequencies in the speech without altering its pitch. Speech-reception thresholds were, on average, 5.2 dB lower for the NoSpi than for the NoSo configuration, at the original articulation rate. This binaural masking release was reduced to 2.8 dB when the articulation rate was doubled, but the most notable effect was a 6-8 dB increase in thresholds with articulation rate for both configurations. These results suggest that higher modulation frequencies in masked signals cannot be temporally resolved by the binaural system, but that the useful modulation frequencies in speech are sufficiently low (<5 Hz) that they are invulnerable to the effects of binaural sluggishness, even at elevated articulation rates.

The SAM Suite

NASA Image and Video Library

2013-04-08

This illustration shows the instruments and subsystems of the Sample Analysis at Mars SAM suite on the Curiosity Rover of NASA Mars Science Laboratory Project. SAM analyzes the gases in the Martian atmosphere.

Common themes and differences in SAM recognition among SAM riboswitches.

PubMed

Price, Ian R; Grigg, Jason C; Ke, Ailong

2014-10-01

The recent discovery of short cis-acting RNA elements termed riboswitches has caused a paradigm shift in our understanding of genetic regulatory mechanisms. The three distinct superfamilies of S-adenosyl-l-methionine (SAM) riboswitches are the most commonly found riboswitch classes in nature. These RNAs represent three independent evolutionary solutions to achieve specific SAM recognition. This review summarizes research on 1) modes of gene regulatory mechanisms, 2) common themes and differences in ligand recognition, and 3) ligand-induced conformational dynamics among SAM riboswitch families. The body of work on the SAM riboswitch families constitutes a useful primer to the topic of gene regulatory RNAs as a whole. This article is part of a Special Issue entitled: Riboswitches. Copyright © 2014 Elsevier B.V. All rights reserved.

Evolved Gas Analyses of Sedimentary Materials in Gale Crater, Mars: Results of the Curiosity Rover's Sample Analysis at Mars (SAM) Instrument from Yellowknife Bay to the Stimson Formation

NASA Technical Reports Server (NTRS)

Sutter, B.; McAdam, A. C.; Rampe, E. B.; Ming, D. W.; Mahaffy, P. R.; Navarro-Gonzalez, R.; Stern, J. C.; Eigenbrode, J. L.; Archer, P. D.

2016-01-01

The Sample Analysis at Mars (SAM) instrument aboard the Mars Science Laboratory rover has analyzed 10 samples from Gale Crater. All SAM evolved gas analyses have yielded a multitude of volatiles (e.g, H2O, SO2, H2S, CO2, CO, NO, O2, HC1). The objectives of this work are to 1) Characterize the evolved H2O, SO2, CO2, and O2 gas traces of sediments analyzed by SAM through sol 1178, 2) Constrain sediment mineralogy/composition based on SAM evolved gas analysis (SAM-EGA), and 3) Discuss the implications of these results releative to understanding the geochemical history of Gale Crater.

KSC-2010-5277

NASA Image and Video Library

2010-10-19

CAPE CANAVERAL, Fla. -- In the Training Auditorium at NASA's Kennedy Space Center in Florida, Professor Sam Ting talks to employees about the Alpha Magnetic Spectrometer-2 (AMS). Ting is the particle physics detector's principal investigator at the Massachusetts Institute of Technology. AMS is designed to operate as an external module on the International Space Station. It will use the unique environment of space to study the universe and its origin by searching for dark matter. AMS-2 will fly to the station aboard space shuttle Endeavour's STS-134 mission targeted to launch Feb. 27, 2011. Photo credit: NASA/Jim Grossmann

KSC-2010-5275

NASA Image and Video Library

2010-10-19

CAPE CANAVERAL, Fla. -- In the Training Auditorium at NASA's Kennedy Space Center in Florida, Professor Sam Ting talks to employees about the Alpha Magnetic Spectrometer-2 (AMS). Ting is the particle physics detector's principal investigator at the Massachusetts Institute of Technology. AMS is designed to operate as an external module on the International Space Station. It will use the unique environment of space to study the universe and its origin by searching for dark matter. AMS-2 will fly to the station aboard space shuttle Endeavour's STS-134 mission targeted to launch Feb. 27, 2011. Photo credit: NASA/Jim Grossmann

KSC-2010-5276

NASA Image and Video Library

2010-10-19

CAPE CANAVERAL, Fla. -- In the Training Auditorium at NASA's Kennedy Space Center in Florida, Professor Sam Ting talks to employees about the Alpha Magnetic Spectrometer-2 (AMS). Ting is the particle physics detector's principal investigator at the Massachusetts Institute of Technology. AMS is designed to operate as an external module on the International Space Station. It will use the unique environment of space to study the universe and its origin by searching for dark matter. AMS-2 will fly to the station aboard space shuttle Endeavour's STS-134 mission targeted to launch Feb. 27, 2011. Photo credit: NASA/Jim Grossmann

Fabrication and characteristics of MOSFET protein chip for detection of ribosomal protein.

PubMed

Park, Keun-Yong; Kim, Min-Suk; Choi, Sie-Young

2005-04-15

A metal oxide silicon field effect transistor (MOSFET) protein chip for the easy detection of protein was fabricated and its characteristics were investigated. Generally, the drain current of the MOSFET is varied by the gate potential. It is expected that the formation of an antibody-antigen complex on the gate of MOSFET would lead to a detectable change in the charge distribution and thus, directly modulate the drain current of MOSFET. As such, the drain current of the MOSFET protein chip can be varied by ribosomal proteins absorbed by the self-assembled monolayer (SAM) immobilized on the gate (Au) surface, as ribosomal protein has positive charge, and these current variations then used as the response of the protein chip. The gate of MOSFET protein chip is not directly biased by an external voltage source, so called open gate or floating gate MOSFET, but rather chemically modified by immobilized molecular receptors called self-assembled monolayer (SAM). In our experiments, the current variation in the proposed protein chip was about 8% with a protein concentration of 0.7 mM. As the protein concentration increased, the drain current also gradually increased. In addition, there were some drift of the drain current in the device. It is considered that these drift might be caused by the drift from the MOSFET itself or protein absorption procedures that are relied on the facile attachment of thiol (-S) ligands to the gate (Au) surface. We verified the formation of SAM on the gold surface and the absorption of protein through the surface plasmon resonance (SPR) measurement.

Low vitamin D does not predict statin associated muscle symptoms but is associated with transient increases in muscle damage and pain.

PubMed

Taylor, Beth A; Lorson, Lindsay; White, C Michael; Thompson, Paul D

2017-01-01

Low vitamin D (VITD) may contribute to statin-associated muscle symptoms (SAMS). We examined the influence of baseline and change in VITD in patients with verified SAMS. SAMS was verified in 120 patients with prior statin muscle complaints using 8-week randomized, double-blind crossover trials of simvastatin (SIMVA) 20 mg/d and placebo. 25 (OH)vitamin D was measured at each phase of the trial. Forty-three patients (35.8%) experienced muscle pain on SIMVA but not placebo, exhibiting confirmed SAMS. VITD (mean ± standard deviation) prior to SIMVA treatment was not different between patients who did (31.7 ± 12.1 ng/mL, n = 43) or did not (31.6 ± 10.3 ng/mL, n = 77) develop SAMS and did not predict SAMS (p = 0.96). The change in VITD with SIMVA treatment was not different between patients with and without SAMS (0.3 ± 5.9 vs. 0.2 ± 8.3 ng/mL, respectively) and did not predict SAMS (p = 0.96). The proportion of patients classified as VITD deficient (<20 ng/mL) did not differ between patients with (n = 16) and without (n = 10) SAMS (χ 2  = 1.45; p = 0.23), nor did the proportion of patients classified as VITD insufficient (<30 ng/mL) (n = 42 vs. 48; χ 2  < 0.01 and p = 0.94). Both baseline and on-statin VITD were inversely related to the change in creatine kinase (CK) with statin therapy (p = 0.01 and 0.02, respectively), independent of SAMS (p = 0.36 and 0.35). Baseline VITD, VITD deficiency/insufficiency and changes in VITD with statin therapy do not predict SAMS in patients with rigorously verified SAMS. However, low VITD may exacerbate statin-induced muscle injury and could contribute to SAMS development with a longer duration of statin treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Standardized added metabolic activity (SAM) IN ¹⁸F-FDG PET assessment of treatment response in colorectal liver metastases.

PubMed

Mertens, Jeroen; De Bruyne, S; Van Damme, N; Smeets, P; Ceelen, W; Troisi, R; Laurent, S; Geboes, K; Peeters, M; Goethals, I; Van de Wiele, C

2013-08-01

Standardized added metabolic activity (SAM) is a PET parameter for assessing the total metabolic load of malignant processes, avoiding partial volume effects and lesion segmentation. The potential role of this parameter in the assessment of response to chemotherapy and bevacizumab was tested in patients with metastatic colorectal cancer with potentially resectable liver metastases (mCRC). (18)F-FDG PET/CT was performed in 18 mCRC patients with liver metastases before treatment and after five cycles of FOLFOX/FOLFIRI and bevacizumab. Of the 18 patients, 16 subsequently underwent resection of liver metastases. Baseline and follow-up SUVmax, and SAM as well as reduction in SUVmax (∆SUVmax) and SAM (∆SAM) of all liver metastases were correlated with morphological response, and progression-free and overall survival (PFS and OS). A significant reduction in metabolic activity of the liver metastases was seen after chemotherapy with a median ∆SUVmax of 25.3% and ∆SAM of 94.5% (p = 0.033 and 0.003). Median baseline SUVmax and SAM values were significantly different between morphological responders and nonresponders (3.8 vs. 7.2, p = 0.021; and 34 vs. 211, p = 0.002, respectively), but neither baseline PET parameters nor morphological response was correlated with PFS or OS. Follow-up SUVmax and SAM as well as ∆SAM were found to be prognostic factors. The median PFS and OS in the patient group with a high follow-up SUVmax were 10.4 months and 32 months, compared to a median PFS of 14.7 months and a median OS which had not been reached in the group with a low follow-up SUVmax (p = 0.01 and 0.003, respectively). The patient group with a high follow-up SAM and a low ∆SAM had a median PFS and OS of 9.4 months and 32 months, whereas the other group had a median PFS of 14.7 months and a median OS which had not been reached (p = 0.002 for both PFS and OS). (18)F-FDG PET imaging is a useful tool to assess treatment response and predict clinical outcome in patients with mCRC who undergo chemotherapy before liver metastasectomy. Follow-up SUVmax, follow-up SAM and ∆SAM were found to be significant prognostic factors for PFS and OS.

Temporal resolution of the Florida manatee (Trichechus manatus latirostris) auditory system.

PubMed

Mann, David A; Colbert, Debborah E; Gaspard, Joseph C; Casper, Brandon M; Cook, Mandy L H; Reep, Roger L; Bauer, Gordon B

2005-10-01

Auditory evoked potential (AEP) measurements of two Florida manatees (Trichechus manatus latirostris) were measured in response to amplitude modulated tones. The AEP measurements showed weak responses to test stimuli from 4 kHz to 40 kHz. The manatee modulation rate transfer function (MRTF) is maximally sensitive to 150 and 600 Hz amplitude modulation (AM) rates. The 600 Hz AM rate is midway between the AM sensitivities of terrestrial mammals (chinchillas, gerbils, and humans) (80-150 Hz) and dolphins (1,000-1,200 Hz). Audiograms estimated from the input-output functions of the EPs greatly underestimate behavioral hearing thresholds measured in two other manatees. This underestimation is probably due to the electrodes being located several centimeters from the brain.

Metabolism of a 5HT6 antagonist, 2-methyl-1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-benzo[d]imidazole (SAM-760): impact of sulfonamide metabolism on diminution of a ketoconazole mediated clinical drug-drug interaction.

PubMed

Sawant-Basak, Aarti; Obach, R Scott; Doran, Angela C; Lockwood, Peter; Schildknegt, Klaas; Gao, Hongying; Mancuso, Jessica; Tse, Susanna; Comery, Tom

2018-04-25

SAM-760, (2-methyl-1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-benzo[d]imidazole), a 5HT 6 antagonist, was investigated in humans for the treatment of Alzheimer's dementia. In liver microsomes and recombinant CYP450 isozymes, SAM-760 was predominantly metabolized by CYP3A (~85%). Based on these observations and an expectation of 5-fold magnitude of interaction with moderate to strong CYP3A inhibitors, a clinical DDI study was performed. In presence of ketoconazole, mean C max and AUC 0-inf of SAM-760 showed only a modest increase by 30% and 38%, respectively. In vitro investigation of this unexpectedly low interaction was undertaken using [ 14 C]SAM-760. Radiometric profiling in human hepatocytes, confirmed all oxidative metabolites observed previously with unlabeled SAM-760; however the pre-dominant radiometric peak was an unexpected polar metabolite which was insensitive to pan-CYP inhibitor, 1-aminobenzotriazole. In human hepatocytes, radiometric integration attributed 43% of total metabolism of SAM-760 to this non-CYP pathway. Using an authentic standard, this predominant metabolite was confirmed as benzenesulfinic acid. Additional investigation revealed that the benzenesulfinic acid metabolite may be a novel, non-enzymatic, thiol mediated reductive cleavage of aryl sulfonamide group of SAM-760. We also determined the relative contribution of P450 to metabolism of SAM-760 in human hepatocytes, by following the rate of formation of oxidative metabolites in presence and absence of P450 isoform specific inhibitors. P450 mediated oxidative metabolism of SAM-760 was still primarily attributed to CYP3A (33%), with minor contributions from CYP isoforms 2C19 and 2D6. Thus, disposition of [ 14 C]SAM-760 in human hepatocytes via novel sulfonamide metabolism and CYP3A verified the lower than expected clinical DDI when SAM-760 was co-administered with ketoconazole. The American Society for Pharmacology and Experimental Therapeutics.

Membrane protein resistance of oligo(ethylene oxide) self-assembled monolayers.

PubMed

Vaish, Amit; Vanderah, David J; Vierling, Ryan; Crawshaw, Fay; Gallagher, D Travis; Walker, Marlon L

2014-10-01

As part of an effort to develop biointerfaces for structure-function studies of integral membrane proteins (IMPs) a series of oligo(ethylene oxide) self-assembled monolayers (OEO-SAMs) were evaluated for their resistance to protein adsorption (RPA) of IMPs on Au and Pt. Spectroscopic ellipsometry (SE) was used to determine SAM thicknesses and compare the RPA of HS(CH2)3O(CH2CH2O)6CH3 (1), HS(CH2)3O(CH2CH2O)6H (2), [HS(CH2)3]2CHO(CH2CH2O)6CH3 (3) and [HS(CH2)3]2CHO(CH2CH2O)6H (4), assembled from water. For both substrates, SAM thicknesses for 1 to 4 were found to be comparable indicating SAMs with similar surface coverages and OEO chain order and packing densities. Fibrinogen (Fb), a soluble plasma protein, and rhodopsin (Rd), an integral membrane G-protein coupled receptor, adsorbed to the SAMs of 1, as expected from previous reports, but not to the hydroxy-terminated SAMs of 2 and 4. The methoxy-terminated SAMs of 3 were resistant to Fb but, surprisingly, not to Rd. The stark difference between the adsorption of Rd to the SAMs of 3 and 4 clearly indicate that a hydroxy-terminus of the OEO chain is essential for high RPA of IMPs. The similar thicknesses and high RPA of the SAMs of 2 and 4 show the conditions of protein resistance (screening the underlying substrate, packing densities, SAM order, and conformational mobility of the OEO chains) defined from previous studies on Au are applicable to Pt. In addition, the SAMs of 4, exhibiting the highest resistance to Fb and Rd, were placed in contact with undiluted fetal bovine serum for 2h. Low protein adsorption (≈12.4ng/cm(2)), obtained under these more challenging conditions, denote a high potential of the SAMs of 4 for various applications requiring the suppression of non-specific protein adsorption. Published by Elsevier B.V.

Music-evoked incidental happiness modulates probability weighting during risky lottery choices.

PubMed

Schulreich, Stefan; Heussen, Yana G; Gerhardt, Holger; Mohr, Peter N C; Binkofski, Ferdinand C; Koelsch, Stefan; Heekeren, Hauke R

2014-01-07

We often make decisions with uncertain consequences. The outcomes of the choices we make are usually not perfectly predictable but probabilistic, and the probabilities can be known or unknown. Probability judgments, i.e., the assessment of unknown probabilities, can be influenced by evoked emotional states. This suggests that also the weighting of known probabilities in decision making under risk might be influenced by incidental emotions, i.e., emotions unrelated to the judgments and decisions at issue. Probability weighting describes the transformation of probabilities into subjective decision weights for outcomes and is one of the central components of cumulative prospect theory (CPT) that determine risk attitudes. We hypothesized that music-evoked emotions would modulate risk attitudes in the gain domain and in particular probability weighting. Our experiment featured a within-subject design consisting of four conditions in separate sessions. In each condition, the 41 participants listened to a different kind of music-happy, sad, or no music, or sequences of random tones-and performed a repeated pairwise lottery choice task. We found that participants chose the riskier lotteries significantly more often in the "happy" than in the "sad" and "random tones" conditions. Via structural regressions based on CPT, we found that the observed changes in participants' choices can be attributed to changes in the elevation parameter of the probability weighting function: in the "happy" condition, participants showed significantly higher decision weights associated with the larger payoffs than in the "sad" and "random tones" conditions. Moreover, elevation correlated positively with self-reported music-evoked happiness. Thus, our experimental results provide evidence in favor of a causal effect of incidental happiness on risk attitudes that can be explained by changes in probability weighting.

Generation of narrowband elastic waves with a fiber laser and its application to the imaging of defects in a plate.

PubMed

Hayashi, Takahiro; Ishihara, Ken

2017-05-01

Pulsed laser equipment can be used to generate elastic waves through the instantaneous reaction of thermal expansion or ablation of the material; however, we cannot control the waveform generated by the laser in the same manner that we can when piezoelectric transducers are used as exciters. This study investigates the generation of narrowband tone-burst waves using a fiber laser of the type that is widely used in laser beam machining. Fiber lasers can emit laser pulses with a high repetition rate on the order of MHz, and the laser pulses can be modulated to a burst train by external signals. As a consequence of the burst laser emission, a narrowband tone-burst elastic wave is generated. We experimentally confirmed that the elastic waves agreed well with the modulation signals in time domain waveforms and their frequency spectra, and that waveforms can be controlled by the generation technique. We also apply the generation technique to defect imaging with a scanning laser source. In the experiments, with small laser emission energy, we were not able to obtain defect images from the signal amplitude due to low signal-to-noise ratio, whereas using frequency spectrum peaks of the tone-burst signals gave clear defect images, which indicates that the signal-to-noise ratio is improved in the frequency domain by using this technique for the generation of narrowband elastic waves. Moreover, even for defect imaging at a single receiving point, defect images were enhanced by taking an average of distributions of frequency spectrum peaks at different frequencies. Copyright © 2017 Elsevier B.V. All rights reserved.

Future's operation areas: new-generation suppression enemy air defence (SEAD) elements

NASA Astrophysics Data System (ADS)

Hazinedar, Ä.°lker

2015-05-01

Since air vehicles took place in the theater of operations, they have become the indispensable elements and the strongest attack power of armed forces. In the following period, with technological development, supersonic aircrafts took place in the operation area and this increased effectiveness of air vehicles much more. Air forces have used these aircrafts during important missions like strategic attack and air defense operations. On the other hand, decision makers understood that it was not feasible to intercept fighter aircrafts by executing combat air patrol flight missions. Since there is not enough reaction time to intercept the high speed aircrafts, ground stationed Surface to Air Missiles (SAM) system requirement has emerged. Therefore, SAM systems took place in the operation scene as well. Due to the fact that SAM systems emerged against the attack power, the attack aircrafts are to keep away from the fire of the ground stationed SAM systems. Hence, the requirement of Suppression Enemy Air Defense (SEAD) arose. SEAD elements take under suppression the radar of the SAM systems. In this way, attack aircrafts are able to attack without the risk of SAM systems. The purpose of this study is to find new methods or concepts in order to protect friendly attack aircrafts against ground based surface to air missiles' fires. Modernization of SAM systems and new generation SAM system producing activities have proceeded with positive acceleration. So, current SEAD elements and concepts are not able to cover the requirements due to the increased SAM system ranges. According to the concepts, SEAD weapons` ranges must be longer than the SAM weapons' ranges to protect friendly aircrafts. In this study, new concept was offered to overcome the deficiencies of current SEAD concept. The elements of new concepts were put forward. Classic SEAD concept and new generation concepts were assessed by using SWOT analysis technique. As a result, this study has revealed that, air forces' effectiveness can be enhanced by using new generation SEAD concepts against enemy SAM systems.

The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI): Revision for Clinical Use, Content Validation, and Inter-rater Reliability.

PubMed

Rosenson, Robert S; Miller, Kate; Bayliss, Martha; Sanchez, Robert J; Baccara-Dinet, Marie T; Chibedi-De-Roche, Daniela; Taylor, Beth; Khan, Irfan; Manvelian, Garen; White, Michelle; Jacobson, Terry A

2017-04-01

The Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) is a method for assessing the likelihood that a patient's muscle symptoms (e.g., myalgia or myopathy) were caused or worsened by statin use. The objectives of this study were to prepare the SAMS-CI for clinical use, estimate its inter-rater reliability, and collect feedback from physicians on its practical application. For content validity, we conducted structured in-depth interviews with its original authors as well as with a panel of independent physicians. Estimation of inter-rater reliability involved an analysis of 30 written clinical cases which were scored by a sample of physicians. A separate group of physicians provided feedback on the clinical use of the SAMS-CI and its potential utility in practice. Qualitative interviews with providers supported the content validity of the SAMS-CI. Feedback on the clinical use of the SAMS-CI included several perceived benefits (such as brevity, clear wording, and simple scoring process) and some possible concerns (workflow issues and applicability in primary care). The inter-rater reliability of the SAMS-CI was estimated to be 0.77 (confidence interval 0.66-0.85), indicating high concordance between raters. With additional provider feedback, a revised SAMS-CI instrument was created suitable for further testing, both in the clinical setting and in prospective validation studies. With standardized questions, vetted language, easily interpreted scores, and demonstrated reliability, the SAMS aims to estimate the likelihood that a patient's muscle symptoms were attributable to statins. The SAMS-CI may support better detection of statin-associated muscle symptoms in clinical practice, optimize treatment for patients experiencing muscle symptoms, and provide a useful tool for further clinical research.

The senescence-accelerated mouse prone-8 (SAM-P8) oxidative stress is associated with upregulation of renal NADPH oxidase system.

PubMed

Baltanás, Ana; Solesio, Maria E; Zalba, Guillermo; Galindo, María F; Fortuño, Ana; Jordán, Joaquín

2013-12-01

Herein, we investigate whether the NADPH oxidase might be playing a key role in the degree of oxidative stress in the senescence-accelerated mouse prone-8 (SAM-P8). To this end, the activity and expression of the NADPH oxidase, the ratio of glutathione and glutathione disulfides (GSH/GSSG), and the levels of malonyl dialdehyde (MDA) and nitrotyrosine (NT) were determined in renal tissue from SAM-P8 mice at the age of 1 and 6 months. The senescence-accelerated-resistant mouse (SAM-R1) was used as control. At the age of 1 month, NADPH oxidase activity and Nox2 protein expression were higher in SAM-P8 than in SAM-R1 mice. However, we found no differences in the GSH/GSSG ratio, MDA, NT, and Nox4 levels between both groups of animals. At the age of 6 months, SAM-R1 mice in comparison to SAM-P8 mice showed an increase in NADPH oxidase activity, which is associated with higher levels of NT and increased Nox4 and Nox2 expression levels. Furthermore, we found oxidative stress hallmarks including depletion in GSH/GSSG ratio and increase in MDA levels in the kidney of SAM-P8 mice. Finally, NADPH oxidase activity positively correlated with Nox2 expression in all the animals (r = 0.382, P < 0.05). Taken together, our data allow us to suggest that an increase in NADPH oxidase activity might be an early hallmark to predict future oxidative stress in renal tissue during the aging process that takes place in SAM-P8 mice.

Semantic Indexing of Medical Learning Objects: Medical Students' Usage of a Semantic Network.

PubMed

Tix, Nadine; Gießler, Paul; Ohnesorge-Radtke, Ursula; Spreckelsen, Cord

2015-11-11

The Semantically Annotated Media (SAM) project aims to provide a flexible platform for searching, browsing, and indexing medical learning objects (MLOs) based on a semantic network derived from established classification systems. Primarily, SAM supports the Aachen emedia skills lab, but SAM is ready for indexing distributed content and the Simple Knowledge Organizing System standard provides a means for easily upgrading or even exchanging SAM's semantic network. There is a lack of research addressing the usability of MLO indexes or search portals like SAM and the user behavior with such platforms. The purpose of this study was to assess the usability of SAM by investigating characteristic user behavior of medical students accessing MLOs via SAM. In this study, we chose a mixed-methods approach. Lean usability testing was combined with usability inspection by having the participants complete four typical usage scenarios before filling out a questionnaire. The questionnaire was based on the IsoMetrics usability inventory. Direct user interaction with SAM (mouse clicks and pages accessed) was logged. The study analyzed the typical usage patterns and habits of students using a semantic network for accessing MLOs. Four scenarios capturing characteristics of typical tasks to be solved by using SAM yielded high ratings of usability items and showed good results concerning the consistency of indexing by different users. Long-tail phenomena emerge as they are typical for a collaborative Web 2.0 platform. Suitable but nonetheless rarely used keywords were assigned to MLOs by some users. It is possible to develop a Web-based tool with high usability and acceptance for indexing and retrieval of MLOs. SAM can be applied to indexing multicentered repositories of MLOs collaboratively.

Reaction-diffusion pattern in shoot apical meristem of plants.

PubMed

Fujita, Hironori; Toyokura, Koichi; Okada, Kiyotaka; Kawaguchi, Masayoshi

2011-03-29

A fundamental question in developmental biology is how spatial patterns are self-organized from homogeneous structures. In 1952, Turing proposed the reaction-diffusion model in order to explain this issue. Experimental evidence of reaction-diffusion patterns in living organisms was first provided by the pigmentation pattern on the skin of fishes in 1995. However, whether or not this mechanism plays an essential role in developmental events of living organisms remains elusive. Here we show that a reaction-diffusion model can successfully explain the shoot apical meristem (SAM) development of plants. SAM of plants resides in the top of each shoot and consists of a central zone (CZ) and a surrounding peripheral zone (PZ). SAM contains stem cells and continuously produces new organs throughout the lifespan. Molecular genetic studies using Arabidopsis thaliana revealed that the formation and maintenance of the SAM are essentially regulated by the feedback interaction between WUSHCEL (WUS) and CLAVATA (CLV). We developed a mathematical model of the SAM based on a reaction-diffusion dynamics of the WUS-CLV interaction, incorporating cell division and the spatial restriction of the dynamics. Our model explains the various SAM patterns observed in plants, for example, homeostatic control of SAM size in the wild type, enlarged or fasciated SAM in clv mutants, and initiation of ectopic secondary meristems from an initial flattened SAM in wus mutant. In addition, the model is supported by comparing its prediction with the expression pattern of WUS in the wus mutant. Furthermore, the model can account for many experimental results including reorganization processes caused by the CZ ablation and by incision through the meristem center. We thus conclude that the reaction-diffusion dynamics is probably indispensable for the SAM development of plants.

Reaction-Diffusion Pattern in Shoot Apical Meristem of Plants

PubMed Central

Fujita, Hironori; Toyokura, Koichi; Okada, Kiyotaka; Kawaguchi, Masayoshi

2011-01-01

A fundamental question in developmental biology is how spatial patterns are self-organized from homogeneous structures. In 1952, Turing proposed the reaction-diffusion model in order to explain this issue. Experimental evidence of reaction-diffusion patterns in living organisms was first provided by the pigmentation pattern on the skin of fishes in 1995. However, whether or not this mechanism plays an essential role in developmental events of living organisms remains elusive. Here we show that a reaction-diffusion model can successfully explain the shoot apical meristem (SAM) development of plants. SAM of plants resides in the top of each shoot and consists of a central zone (CZ) and a surrounding peripheral zone (PZ). SAM contains stem cells and continuously produces new organs throughout the lifespan. Molecular genetic studies using Arabidopsis thaliana revealed that the formation and maintenance of the SAM are essentially regulated by the feedback interaction between WUSHCEL (WUS) and CLAVATA (CLV). We developed a mathematical model of the SAM based on a reaction-diffusion dynamics of the WUS-CLV interaction, incorporating cell division and the spatial restriction of the dynamics. Our model explains the various SAM patterns observed in plants, for example, homeostatic control of SAM size in the wild type, enlarged or fasciated SAM in clv mutants, and initiation of ectopic secondary meristems from an initial flattened SAM in wus mutant. In addition, the model is supported by comparing its prediction with the expression pattern of WUS in the wus mutant. Furthermore, the model can account for many experimental results including reorganization processes caused by the CZ ablation and by incision through the meristem center. We thus conclude that the reaction-diffusion dynamics is probably indispensable for the SAM development of plants. PMID:21479227

Molecular interfaces for plasmonic hot electron photovoltaics

NASA Astrophysics Data System (ADS)

Pelayo García de Arquer, F.; Mihi, Agustín; Konstantatos, Gerasimos

2015-01-01

The use of self-assembled monolayers (SAMs) to improve and tailor the photovoltaic performance of plasmonic hot-electron Schottky solar cells is presented. SAMs allow the simultaneous control of open-circuit voltage, hot-electron injection and short-circuit current. To that end, a plurality of molecule structural parameters can be adjusted: SAM molecule's length can be adjusted to control plasmonic hot electron injection. Modifying SAMs dipole moment allows for a precise tuning of the open-circuit voltage. The functionalization of the SAM can also be selected to modify short-circuit current. This allows the simultaneous achievement of high open-circuit voltages (0.56 V) and fill-factors (0.58), IPCE above 5% at the plasmon resonance and maximum power-conversion efficiencies of 0.11%, record for this class of devices.The use of self-assembled monolayers (SAMs) to improve and tailor the photovoltaic performance of plasmonic hot-electron Schottky solar cells is presented. SAMs allow the simultaneous control of open-circuit voltage, hot-electron injection and short-circuit current. To that end, a plurality of molecule structural parameters can be adjusted: SAM molecule's length can be adjusted to control plasmonic hot electron injection. Modifying SAMs dipole moment allows for a precise tuning of the open-circuit voltage. The functionalization of the SAM can also be selected to modify short-circuit current. This allows the simultaneous achievement of high open-circuit voltages (0.56 V) and fill-factors (0.58), IPCE above 5% at the plasmon resonance and maximum power-conversion efficiencies of 0.11%, record for this class of devices. Electronic supplementary information (ESI) available: Contact-potential differentiometry measurements, FTIR characterization, performance statistics and gold devices. See DOI: 10.1039/c4nr06356b

Sam Donaldson: Tips From a Cancer Survivor

MedlinePlus

... Home Current Issue Past Issues Special Section Sam Donaldson: Tips From a Cancer Survivor Past Issues / Spring ... courtesy of ABC News For 40 years, Sam Donaldson has worked for ABC News, reporting from virtually ...

pH-Switchable Interaction of a Carboxybetaine Ester-Based SAM with DNA and Gold Nanoparticles.

PubMed

Filip, Jaroslav; Popelka, Anton; Bertok, Tomas; Holazova, Alena; Osicka, Josef; Kollar, Jozef; Ilcikova, Marketa; Tkac, Jan; Kasak, Peter

2017-07-11

We describe a self-assembled monolayer (SAM) on a gold surface with a carboxybetaine ester functionality to control the interaction between DNA and gold nanoparticles via pH. The negatively charged phosphate backbone of DNA interacts with and adsorbs to the positively charged carboxybetaine esters on the SAM. DNA release can be achieved by the hydrolysis of carboxybetaine ester (CBE) to a zwitterionic carboxybetaine state. Furthermore, the adsorption of negatively charged citrate-capped gold nanoparticles to a SAM-modified plain gold surface can be controlled by the pH. The SAM based on carboxybetaine ester allows for the homogeneous adsorption of particles, whereas the SAM after hydrolysis at high pH repels AuNP adsorption. The antifouling surface properties of the surface modified with carboxybetaine were investigated with protein samples.

Detection and Quantification of Nitrogen Compounds in the First Drilled Martian Solid Samples by the Sample Analysis at Mars (SAM) Instrument Suite on the Mars Science Laboratory (MSL)

NASA Technical Reports Server (NTRS)

Stern, Jennifer C.; Navarro-Gonzalez, Rafael; Freissinet, Caroline; McKay, Christopher P.; Archer, P. Douglas, Jr.; Buch, Arnaud; Coll, Patrice; Eigenbrode, Jennifer L.; Franz, Heather B.; Glavin, Daniel P.;

Chemical resistivity of self-assembled monolayer covalently attached to silicon substrate to hydrofluoric acid and ammonium fluoride

NASA Astrophysics Data System (ADS)

Saito, N.; Youda, S.; Hayashi, K.; Sugimura, H.; Takai, O.

2003-06-01

Self-assembled monolayers (SAMs) were prepared on hydrogen-terminated silicon substrates through chemical vapor deposition using 1-hexadecene (HD) as a precursor. The HD-SAMs prepared in an atmosphere under a reduced pressure (≈50 Pa) showed better chemical resistivities to hydrofluoric acid and ammonium fluoride (NH 4F) solutions than that of an organosilane SAM formed on oxide-covered silicon substrates. The surface covered with the HD-SAM was micro-patterned by vacuum ultraviolet photolithography and consequently divided into two areas terminated with HD-SAM or silicon dioxide. This micro-patterned sample was immersed in a 40 vol.% NH 4F aqueous solution. Surface images obtained by an optical microscopy clearly show that the micro-patterns of HD-SAM/silicon dioxide were successfully transferred into the silicon substrate.

A role of the SAM domain in EphA2 receptor activation.

PubMed

Shi, Xiaojun; Hapiak, Vera; Zheng, Ji; Muller-Greven, Jeannine; Bowman, Deanna; Lingerak, Ryan; Buck, Matthias; Wang, Bing-Cheng; Smith, Adam W

2017-03-24

Among the 20 subfamilies of protein receptor tyrosine kinases (RTKs), Eph receptors are unique in possessing a sterile alpha motif (SAM domain) at their C-terminal ends. However, the functions of SAM domains in Eph receptors remain elusive. Here we report on a combined cell biology and quantitative fluorescence study to investigate the role of the SAM domain in EphA2 function. We observed elevated tyrosine autophosphorylation levels upon deletion of the EphA2 SAM domain (EphA2ΔS) in DU145 and PC3 prostate cancer cells and a skin tumor cell line derived from EphA1/A2 knockout mice. These results suggest that SAM domain deletion induced constitutive activation of EphA2 kinase activity. In order to explain these effects, we applied fluorescence correlation spectroscopy to investigate the lateral molecular organization of EphA2. Our results indicate that SAM domain deletion (EphA2ΔS-GFP) increases oligomerization compared to the full length receptor (EphA2FL-GFP). Stimulation with ephrinA1, a ligand for EphA2, induced further oligomerization and activation of EphA2FL-GFP. The SAM domain deletion mutant, EphA2ΔS-GFP, also underwent further oligomerization upon ephrinA1 stimulation, but the oligomers were larger than those observed for EphA2FL-GFP. Based on these results, we conclude that the EphA2 SAM domain inhibits kinase activity by reducing receptor oligomerization.

Evaluating the effectiveness of self-administration of medication (SAM) schemes in the hospital setting: a systematic review of the literature.

PubMed

Richardson, Suzanna J; Brooks, Hannah L; Bramley, George; Coleman, Jamie J

2014-01-01

Self-administration of medicines is believed to increase patients' understanding about their medication and to promote their independence and autonomy in the hospital setting. The effect of inpatient self-administration of medication (SAM) schemes on patients, staff and institutions is currently unclear. To systematically review the literature relating to the effect of SAM schemes on the following outcomes: patient knowledge, patient compliance/medication errors, success in self-administration, patient satisfaction, staff satisfaction, staff workload, and costs. Keyword and text word searches of online databases were performed between January and March 2013. Included articles described and evaluated inpatient SAM schemes. Case studies and anecdotal studies were excluded. 43 papers were included for final analysis. Due to the heterogeneity of results and unclear findings it was not possible to perform a quantitative synthesis of results. Participation in SAM schemes often led to increased knowledge about drugs and drug regimens, but not side effects. However, the effect of SAM schemes on patient compliance/medication errors was inconclusive. Patients and staff were highly satisfied with their involvement in SAM schemes. SAM schemes appear to provide some benefits (e.g. increased patient knowledge), but their effect on other outcomes (e.g. compliance) is unclear. Few studies of high methodological quality using validated outcome measures exist. Inconsistencies in both measuring and reporting outcomes across studies make it challenging to compare results and draw substantive conclusions about the effectiveness of SAM schemes.

Sam2bam: High-Performance Framework for NGS Data Preprocessing Tools

PubMed Central

Cheng, Yinhe; Tzeng, Tzy-Hwa Kathy

2016-01-01

This paper introduces a high-throughput software tool framework called sam2bam that enables users to significantly speed up pre-processing for next-generation sequencing data. The sam2bam is especially efficient on single-node multi-core large-memory systems. It can reduce the runtime of data pre-processing in marking duplicate reads on a single node system by 156–186x compared with de facto standard tools. The sam2bam consists of parallel software components that can fully utilize multiple processors, available memory, high-bandwidth storage, and hardware compression accelerators, if available. The sam2bam provides file format conversion between well-known genome file formats, from SAM to BAM, as a basic feature. Additional features such as analyzing, filtering, and converting input data are provided by using plug-in tools, e.g., duplicate marking, which can be attached to sam2bam at runtime. We demonstrated that sam2bam could significantly reduce the runtime of next generation sequencing (NGS) data pre-processing from about two hours to about one minute for a whole-exome data set on a 16-core single-node system using up to 130 GB of memory. The sam2bam could reduce the runtime of NGS data pre-processing from about 20 hours to about nine minutes for a whole-genome sequencing data set on the same system using up to 711 GB of memory. PMID:27861637

Isolating spectral cues in amplitude and quasi-frequency modulation discrimination by reducing stimulus duration.

PubMed

Borucki, Ewa; Berg, Bruce G

2017-05-01

This study investigated the psychophysical effects of distortion products in a listening task traditionally used to estimate the bandwidth of phase sensitivity. For a 2000 Hz carrier, estimates of modulation depth necessary to discriminate amplitude modulated (AM) tones and quasi-frequency modulated (QFM) were measured in a two interval forced choice task as a function modulation frequency. Temporal modulation transfer functions were often non-monotonic at modulation frequencies above 300 Hz. This was likely to be due to a spectral cue arising from the interaction of auditory distortion products and the lower sideband of the stimulus complex. When the stimulus duration was decreased from 200 ms to 20 ms, thresholds for low-frequency modulators rose to near-chance levels, whereas thresholds in the region of non-monotonicities were less affected. The decrease in stimulus duration appears to hinder the listener's ability to use temporal cues in order to discriminate between AM and QFM, whereas spectral information derived from distortion product cues appears more resilient. Copyright © 2017. Published by Elsevier B.V.

Overnight Fasting Regulates Inhibitory Tone to Cholinergic Neurons of the Dorsomedial Nucleus of the Hypothalamus

PubMed Central

Groessl, Florian; Jeong, Jae Hoon; Talmage, David A.; Role, Lorna W.; Jo, Young-Hwan

2013-01-01

The dorsomedial nucleus of the hypothalamus (DMH) contributes to the regulation of overall energy homeostasis by modulating energy intake as well as energy expenditure. Despite the importance of the DMH in the control of energy balance, DMH-specific genetic markers or neuronal subtypes are poorly defined. Here we demonstrate the presence of cholinergic neurons in the DMH using genetically modified mice that express enhanced green florescent protein (eGFP) selectively in choline acetyltransferase (Chat)-neurons. Overnight food deprivation increases the activity of DMH cholinergic neurons, as shown by induction of fos protein and a significant shift in the baseline resting membrane potential. DMH cholinergic neurons receive both glutamatergic and GABAergic synaptic input, but the activation of these neurons by an overnight fast is due entirely to decreased inhibitory tone. The decreased inhibition is associated with decreased frequency and amplitude of GABAergic synaptic currents in the cholinergic DMH neurons, while glutamatergic synaptic transmission is not altered. As neither the frequency nor amplitude of miniature GABAergic or glutamatergic postsynaptic currents is affected by overnight food deprivation, the fasting-induced decrease in inhibitory tone to cholinergic neurons is dependent on superthreshold activity of GABAergic inputs. This study reveals that cholinergic neurons in the DMH readily sense the availability of nutrients and respond to overnight fasting via decreased GABAergic inhibitory tone. As such, altered synaptic as well as neuronal activity of DMH cholinergic neurons may play a critical role in the regulation of overall energy homeostasis. PMID:23585854

The lateralized arcuate fasciculus in developmental pitch disorders among mandarin amusics: left for speech and right for music.

PubMed

Chen, Xizhuo; Zhao, Yanxin; Zhong, Suyu; Cui, Zaixu; Li, Jiaqi; Gong, Gaolang; Dong, Qi; Nan, Yun

2018-05-01

The arcuate fasciculus (AF) is a neural fiber tract that is critical to speech and music development. Although the predominant role of the left AF in speech development is relatively clear, how the AF engages in music development is not understood. Congenital amusia is a special neurodevelopmental condition, which not only affects musical pitch but also speech tone processing. Using diffusion tensor tractography, we aimed at understanding the role of AF in music and speech processing by examining the neural connectivity characteristics of the bilateral AF among thirty Mandarin amusics. Compared to age- and intelligence quotient (IQ)-matched controls, amusics demonstrated increased connectivity as reflected by the increased fractional anisotropy in the right posterior AF but decreased connectivity as reflected by the decreased volume in the right anterior AF. Moreover, greater fractional anisotropy in the left direct AF was correlated with worse performance in speech tone perception among amusics. This study is the first to examine the neural connectivity of AF in the neurodevelopmental condition of amusia as a result of disrupted music pitch and speech tone processing. We found abnormal white matter structural connectivity in the right AF for the amusic individuals. Moreover, we demonstrated that the white matter microstructural properties of the left direct AF is modulated by lexical tone deficits among the amusic individuals. These data support the notion of distinctive pitch processing systems between music and speech.

Taking global scale data handling to the Fermilab intensity frontier

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

Lyon, Adam L.; Illingworth, Robert A.; Mengel, Marc

2012-01-01

SAM is a comprehensive data management system used by the Tevatron Run II experiments with great success. The newest experiments at Fermilab, the Intensity Frontier experiments, are currently lacking such a system. In these proceedings, the advantages of using SAM for these experiments is discussed. Two improvements to SAM, namely SAMWeb and SAMfs are described. These improvements will make SAM much easier to integrate, deploy, maintain, and use.

Structural insights into SAM domain-mediated tankyrase oligomerization.

PubMed

DaRosa, Paul A; Ovchinnikov, Sergey; Xu, Wenqing; Klevit, Rachel E

2016-09-01

Tankyrase 1 (TNKS1; a.k.a. ARTD5) and tankyrase 2 (TNKS2; a.k.a ARTD6) are highly homologous poly(ADP-ribose) polymerases (PARPs) that function in a wide variety of cellular processes including Wnt signaling, Src signaling, Akt signaling, Glut4 vesicle translocation, telomere length regulation, and centriole and spindle pole maturation. Tankyrase proteins include a sterile alpha motif (SAM) domain that undergoes oligomerization in vitro and in vivo. However, the SAM domains of TNKS1 and TNKS2 have not been structurally characterized and the mode of oligomerization is not yet defined. Here we model the SAM domain-mediated oligomerization of tankyrase. The structural model, supported by mutagenesis and NMR analysis, demonstrates a helical, homotypic head-to-tail polymer that facilitates TNKS self-association. Furthermore, we show that TNKS1 and TNKS2 can form (TNKS1 SAM-TNKS2 SAM) hetero-oligomeric structures mediated by their SAM domains. Though wild-type tankyrase proteins have very low solubility, model-based mutations of the SAM oligomerization interface residues allowed us to obtain soluble TNKS proteins. These structural insights will be invaluable for the functional and biophysical characterization of TNKS1/2, including the role of TNKS oligomerization in protein poly(ADP-ribosyl)ation (PARylation) and PARylation-dependent ubiquitylation. © 2016 The Protein Society.

Regulation of C. elegans presynaptic differentiation and neurite branching via a novel signaling pathway initiated by SAM-10

PubMed Central

Zheng, Qun; Schaefer, Anneliese M.; Nonet, Michael L.

2011-01-01

Little is known about transcriptional control of neurite branching or presynaptic differentiation, events that occur relatively late in neuronal development. Using the Caenorhabditis elegans mechanosensory circuit as an in vivo model, we show that SAM-10, an ortholog of mammalian single-stranded DNA-binding protein (SSDP), functions cell-autonomously in the nucleus to regulate synaptic differentiation, as well as positioning of, a single neurite branch. PLM mechanosensory neurons in sam-10 mutants exhibit abnormal placement of the neurite branch point, and defective synaptogenesis, characterized by an overextended synaptic varicosity, underdeveloped synaptic morphology and disrupted colocalization of active zone and synaptic vesicles. SAM-10 functions coordinately with Lim domain-binding protein 1 (LDB-1), demonstrated by our observations that: (1) mutations in either gene show similar defects in PLM neurons; and (2) LDB-1 is required for SAM-10 nuclear localization. SAM-10 regulates PLM synaptic differentiation by suppressing transcription of prk-2, which encodes an ortholog of the mammalian Pim kinase family. PRK-2-mediated activities of SAM-10 are specifically involved in PLM synaptic differentiation, but not other sam-10 phenotypes such as neurite branching. Thus, these data reveal a novel transcriptional signaling pathway that regulates neuronal specification of neurite branching and presynaptic differentiation. PMID:21115607

Regulation of C. elegans presynaptic differentiation and neurite branching via a novel signaling pathway initiated by SAM-10.

PubMed

Zheng, Qun; Schaefer, Anneliese M; Nonet, Michael L

2011-01-01

Little is known about transcriptional control of neurite branching or presynaptic differentiation, events that occur relatively late in neuronal development. Using the Caenorhabditis elegans mechanosensory circuit as an in vivo model, we show that SAM-10, an ortholog of mammalian single-stranded DNA-binding protein (SSDP), functions cell-autonomously in the nucleus to regulate synaptic differentiation, as well as positioning of, a single neurite branch. PLM mechanosensory neurons in sam-10 mutants exhibit abnormal placement of the neurite branch point, and defective synaptogenesis, characterized by an overextended synaptic varicosity, underdeveloped synaptic morphology and disrupted colocalization of active zone and synaptic vesicles. SAM-10 functions coordinately with Lim domain-binding protein 1 (LDB-1), demonstrated by our observations that: (1) mutations in either gene show similar defects in PLM neurons; and (2) LDB-1 is required for SAM-10 nuclear localization. SAM-10 regulates PLM synaptic differentiation by suppressing transcription of prk-2, which encodes an ortholog of the mammalian Pim kinase family. PRK-2-mediated activities of SAM-10 are specifically involved in PLM synaptic differentiation, but not other sam-10 phenotypes such as neurite branching. Thus, these data reveal a novel transcriptional signaling pathway that regulates neuronal specification of neurite branching and presynaptic differentiation.

Similar regulation patterns of choline monooxygenase, phosphoethanolamine N-methyltransferase and S-adenosyl-L-methionine synthetase in leaves of the halophyte Atriplex nummularia L.

PubMed

Tabuchi, Tomoki; Kawaguchi, Yusuke; Azuma, Tetsushi; Nanmori, Takashi; Yasuda, Takeshi

2005-03-01

Glycinebetaine (betaine) highly accumulates as a compatible solute in certain plants and has been considered to play a role in the protection from salt stress. The betaine biosynthesis pathway of betaine-accumulating plants involves choline monooxygenase (CMO) as the key enzyme and phosphoethanolamine N-methyltransferase (PEAMT), which require S-adenosyl-L-methionine (SAM) as a methyl donor. SAM is synthesized by SAM synthetase (SAMS), and is needed not only for betaine synthesis but also for the synthesis of other compounds, especially lignin. We cloned CMO, PEAMT and SAMS isogenes from a halophyte Atriplex nummularia L. (Chenopodiaceous). The transcript and protein levels of CMO were much higher in leaves and stems than in roots, suggesting that betaine is synthesized mainly in the shoot. The regulation patterns of transcripts for SAMS and PEAMT highly resembled that of CMO in the leaves during and after relief from salt stress, and on a diurnal rhythm. In the leaves, the betaine content was increased but the lignin content was not changed by salt stress. These results suggest that the transcript levels of SAMS are co-regulated with those of PEAMT and CMO to supply SAM for betaine synthesis in the leaves.

The SAM domain inhibits EphA2 interactions in the plasma membrane.

PubMed

Singh, Deo R; Ahmed, Fozia; Paul, Michael D; Gedam, Manasee; Pasquale, Elena B; Hristova, Kalina

2017-01-01

All members of the Eph receptor family of tyrosine kinases contain a SAM domain near the C terminus, which has been proposed to play a role in receptor homotypic interactions and/or interactions with binding partners. The SAM domain of EphA2 is known to be important for receptor function, but its contribution to EphA2 lateral interactions in the plasma membrane has not been determined. Here we use a FRET-based approach to directly measure the effect of the SAM domain on the stability of EphA2 dimers on the cell surface in the absence of ligand binding. We also investigate the functional consequences of EphA2 SAM domain deletion. Surprisingly, we find that the EphA2 SAM domain inhibits receptor dimerization and decreases EphA2 tyrosine phosphorylation. This role is dramatically different from the role of the SAM domain of the related EphA3 receptor, which we previously found to stabilize EphA3 dimers and increase EphA3 tyrosine phosphorylation in cells in the absence of ligand. Thus, the EphA2 SAM domain likely contributes to a unique mode of EphA2 interaction that leads to distinct signaling outputs. Copyright © 2016 Elsevier B.V. All rights reserved.

Laparoscopic transgastric circumferential stapler-assisted versus endoscopic esophageal mucosectomy in a porcine model

PubMed Central

Steinemann, Daniel C.; Zerz, Andreas; Müller, Philip C.; Sauer, Peter; Schaible, Anja; Lasitschka, Felix; Schwarz, Anne-Catherine; Müller-Stich, Beat P.; Linke, Georg R.

2018-01-01

Background and study aims Extensive endoscopic mucosal resection (EMR) for Barrett’s esophagus (BE) may lead to stenosis. Laparoscopic, transgastric, stapler-assisted mucosectomy (SAM) retrieving circumferential specimens is proposed. Methods SAM was evaluated in two phases. The feasibility of SAM and the quality of specimens was assessed in eight animals. The mucosal healing was evaluated in a 6-weeks survival experiment comparing SAM (n=6) and EMR (n=6). The ratio of the esophageal lumen width (REL) at the resection level measured in fluoroscopy after 6-weeks divided by the width immediately after resection was compared. Results In all animals a circular mucosectomy specimen was successfully obtained with an area of 492(426-573)mm2 and 941(813-1209)mm2 using a 21-mm and 25-mm stapler, respectively. In the survival experiments two animals developed symptomatic stenosis after EMR and none after SAM. The REL was 0.27[0.18-0.39] and 0.96[0.9-1.04] (p<0.0001) for EMR and SAM, respectively. Conclusions SAM provides a novel technique for en-bloc mucosectomy in BE. In contrast to EMR mucosal healing in SAM was not associated with stenosis up to six weeks after intervention. PMID:28301879

The SAM, not the electrodes, dominates charge transport in metal-monolayer//Ga2O3/gallium-indium eutectic junctions.

PubMed

Reus, William F; Thuo, Martin M; Shapiro, Nathan D; Nijhuis, Christian A; Whitesides, George M

2012-06-26

The liquid-metal eutectic of gallium and indium (EGaIn) is a useful electrode for making soft electrical contacts to self-assembled monolayers (SAMs). This electrode has, however, one feature whose effect on charge transport has been incompletely understood: a thin (approximately 0.7 nm) film-consisting primarily of Ga(2)O(3)-that covers its surface when in contact with air. SAMs that rectify current have been measured using this electrode in Ag(TS)-SAM//Ga(2)O(3)/EGaIn (where Ag(TS) = template-stripped Ag surface) junctions. This paper organizes evidence, both published and unpublished, showing that the molecular structure of the SAM (specifically, the presence of an accessible molecular orbital asymmetrically located within the SAM), not the difference between the electrodes or the characteristics of the Ga(2)O(3) film, causes the observed rectification. By examining and ruling out potential mechanisms of rectification that rely either on the Ga(2)O(3) film or on the asymmetry of the electrodes, this paper demonstrates that the structure of the SAM dominates charge transport through Ag(TS)-SAM//Ga(2)O(3)/EGaIn junctions, and that the electrical characteristics of the Ga(2)O(3) film have a negligible effect on these measurements.

Two-way satellite time transfer using low power CW tones

NASA Technical Reports Server (NTRS)

Costain, C. C.; Daams, H.; Boulanger, J. S.

1983-01-01

In the search for an economical means of precise time transfer, the NRC Time Laboratory decided to adapt the techniques used by radio astronomers in an experiment to compare the phases of the local oscillators at widely separated VLBI stations. The objective is to design a system which would use commercial satellites, and which would be of reasonable cost for the ground stations and for operations. Two satellite ground stations were installed at NRC about 100 m from the Time Laboratory. For the preliminary experiment, a channel on the Anik Al 6/4 GHz satellite was made available by TELESAT Canada. Two tones were transmitted + or - MHz from the suppressed carrier. The difference frequency of 32 MHz was recorded using narrow band receivers. A low level 1 MHz phase modulation was added to identify the 32 MHz cycle, giving 1 microsec ambiguity in the time transfer. With less than 1/4 W in each tone, the EIRP is 43 dB below that of a normal TV Earth station, and no frequency dispersion is required. The measurements taken each second for the 32 MHz have an rms scatter of 1 ns.

Acoustic structure of the five perceptual dimensions of timbre in orchestral instrument tones

PubMed Central

Elliott, Taffeta M.; Hamilton, Liberty S.; Theunissen, Frédéric E.

2013-01-01

Attempts to relate the perceptual dimensions of timbre to quantitative acoustical dimensions have been tenuous, leading to claims that timbre is an emergent property, if measurable at all. Here, a three-pronged analysis shows that the timbre space of sustained instrument tones occupies 5 dimensions and that a specific combination of acoustic properties uniquely determines gestalt perception of timbre. Firstly, multidimensional scaling (MDS) of dissimilarity judgments generated a perceptual timbre space in which 5 dimensions were cross-validated and selected by traditional model comparisons. Secondly, subjects rated tones on semantic scales. A discriminant function analysis (DFA) accounting for variance of these semantic ratings across instruments and between subjects also yielded 5 significant dimensions with similar stimulus ordination. The dimensions of timbre space were then interpreted semantically by rotational and reflectional projection of the MDS solution into two DFA dimensions. Thirdly, to relate this final space to acoustical structure, the perceptual MDS coordinates of each sound were regressed with its joint spectrotemporal modulation power spectrum. Sound structures correlated significantly with distances in perceptual timbre space. Contrary to previous studies, most perceptual timbre dimensions are not the result of purely temporal or spectral features but instead depend on signature spectrotemporal patterns. PMID:23297911

Social regulation of plasma estradiol concentration in a female anuran

PubMed Central

Lynch, Kathleen S.; Wilczynski, Walter

2008-01-01

The behavior of an individual within a social aggregation profoundly influences behavior and physiology of other animals within the aggregation in such a way that these social interactions can enhance reproductive success, survival and fitness. This phenomenon is particularly important during the breeding season when males and female must synchronize their reproductive efforts. We examined whether exposure to conspecific social cues can elevate sex steroid levels, specifically estradiol and androgens, in female túngara frogs (Physalaemus pustulosus). We compared plasma estradiol and androgen concentrations in wild-caught females before and after exposure to either natural mate choruses or random tones. After exposure to mate choruses for 10 consecutive nights, estradiol concentrations were significantly elevated whereas there was no significant elevation in estradiol concentrations in the group of females exposed to random tones for 10 nights. Plasma androgen concentrations were not significantly changed after exposure to either natural mate choruses or random tones for 10 consecutive nights. Social modulation of estradiol concentrations may be important in maintaining a female’s reproductive state while males are chorusing. To our knowledge, this is the first study to demonstrate social regulation of estradiol concentration in female anurans. PMID:16545384

Serotonin receptor 1A promoter polymorphism, rs6295, modulates human anxiety levels via altering parasympathetic nervous activity.

PubMed

Huang, J-H; Chang, H-A; Fang, W-H; Ho, P-S; Liu, Y-P; Wan, F-J; Tzeng, N-S; Shyu, J-F; Chang, C-C

2018-03-01

The G-allele of the -1019C/G (rs6295) promoter polymorphism of the serotonin receptor 1A (HTR1A) gene has been implicated in anxiety; however, the underlying neurophysiological processes are still not fully understood. Recent evidence indicates that low parasympathetic (vagal) tone is predictive of anxiety. We thus conducted a structural equation model (SEM) to examine whether the HTR1A rs6295 variant can affect anxiety by altering parasympathetic nervous activity. A sample of 1141 drug-free healthy Han Chinese was recruited for HTR1A genotyping. Autonomic nervous function was assessed by short-term spectral analysis of heart rate variability (HRV). Anxiety and stress levels were evaluated by the Beck Anxiety Inventory (BAI) and the Perceived Stress Scale (PSS) respectively. The number of the HTR1A G allele was inversely correlated with high-frequency power (HF), a parasympathetic index of HRV. The HF index was negatively associated with BAI scores. Furthermore, the good-fitting SEM, adjusting for confounding variables (e.g., age and PSS levels), revealed a significant pathway linking rs6295 variant to BAI scores via HF index modulation. These results are the first to show that HTR1A -1019C/G polymorphism influences anxiety levels by modulating parasympathetic tone, providing a neurophysiological insight into the role of HTR1A in human anxiety. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The cognitive loci of the display and task-relevant set size effects on distractor interference: Evidence from a dual-task paradigm.

PubMed

Park, Bo Youn; Kim, Sujin; Cho, Yang Seok

2018-02-01

The congruency effect of a task-irrelevant distractor has been found to be modulated by task-relevant set size and display set size. The present study used a psychological refractory period (PRP) paradigm to examine the cognitive loci of the display set size effect (dilution effect) and the task-relevant set size effect (perceptual load effect) on distractor interference. A tone discrimination task (Task 1), in which a response was made to the pitch of the target tone, was followed by a letter discrimination task (Task 2) in which different types of visual target display were used. In Experiment 1, in which display set size was manipulated to examine the nature of the display set size effect on distractor interference in Task 2, the modulation of the congruency effect by display set size was observed at both short and long stimulus-onset asynchronies (SOAs), indicating that the display set size effect occurred after the target was selected for processing in the focused attention stage. In Experiment 2, in which task-relevant set size was manipulated to examine the nature of the task-relevant set size effect on distractor interference in Task 2, the effects of task-relevant set size increased with SOA, suggesting that the target selection efficiency in the preattentive stage was impaired with increasing task-relevant set size. These results suggest that display set size and task-relevant set size modulate distractor processing in different ways.

48 CFR 4.1803 - Verifying CAGE codes prior to award.

Code of Federal Regulations, 2014 CFR

2014-10-01

... registration in the System for Award Management (SAM). Active registrations in SAM have had the associated CAGE codes verified. (b) For entities not required to be registered in SAM, the contracting officer shall...

Neuroendocrine abnormalities in hypothalamic amenorrhea: spectrum, stability, and response to neurotransmitter modulation.

PubMed

Perkins, R B; Hall, J E; Martin, K A

1999-06-01

To characterize the neuroendocrine patterns of abnormal GnRH secretion in hypothalamic amenorrhea (HA), 49 women with primary and secondary HA underwent frequent sampling of LH in a total of 72 baseline studies over 12-24 h. A subset of women participated in more than one study to address 1) the variability of LH pulse patterns over time; and 2) the impact of modulating opioid, dopaminergic, and adrenergic tone on LH secretory patterns. The frequency and amplitude of LH secretion was compared with that seen in the early follicular phase (EFP) of normally cycling women. The spectrum of abnormalities of LH pulses was 8% apulsatile, 27% low frequency/low amplitude, 8% low amplitude/normal frequency, 43% low frequency/normal amplitude, 14% normal frequency/normal amplitude. Of patients studied overnight, 45% demonstrated a pubertal pattern of augmented LH secretion during sleep. Of patients studied repeatedly, 75% demonstrated at least 2 different patterns of LH secretion, and 33% reverted at least once to a normal pattern of secretion. An increase in LH pulse frequency was seen in 12 of 15 subjects in response to naloxone (opioid receptor antagonist). Clonidine (alpha-2 adrenergic agonist) was associated with a decrease in mean LH in 3 of 3 subjects. An increase in LH pulse frequency was seen in 4 of 8 subjects in response to metoclopramide (dopamine receptor antagonist), but the response was not statistically significant. Baseline abnormalities in LH secretion did not appear to influence response to neurotransmitter modulation. 1) HA represents a spectrum of disordered GnRH secretion that can vary over time; 2) LH pulse patterns at baseline do not appear to influence the ability to respond to neurotransmitter modulation; 3) Opioid and adrenergic tone appear to influence the hypothalamic GnRH pulse generator in some individuals with HA.

Influence of the preceding austral summer Southern Hemisphere annular mode on the amplitude of ENSO decay

NASA Astrophysics Data System (ADS)

Zheng, Fei; Li, Jianping; Ding, Ruiqiang

2017-11-01

There is increasing evidence of the possible role of extratropical forcing in the evolution of ENSO. The Southern Hemisphere Annular Mode (SAM) is the dominant mode of atmospheric circulation in the Southern Hemisphere extratropics. This study shows that the austral summer (December-January-February; DJF) SAM may also influence the amplitude of ENSO decay during austral autumn (March-April-May; MAM). The mechanisms associated with this SAM-ENSO relationship can be briefly summarized as follows: The SAM is positively (negatively) correlated with SST in the Southern Hemisphere middle (high) latitudes. This dipole-like SST anomaly pattern is referred to as the Southern Ocean Dipole (SOD). The DJF SOD, caused by the DJF SAM, could persist until MAM and then influence atmospheric circulation, including trade winds, over the Niño3.4 area. Anomalous trade winds and SST anomalies over the Niño3.4 area related to the DJF SAM are further developed through the Bjerkness feedback, which eventually results in a cooling (warming) over the Niño3.4 area followed by the positive (negative) DJF SAM.

Hypovolemia induced systolic anterior motion of the mitral valve in two dogs.

PubMed

Hammes, K; Novo Matos, J; Baron Toaldo, M; Glaus, T

2016-12-01

Systolic anterior (septal) motion of the mitral valve (SAM) is a common secondary phenomenon in hypertrophic cardiomyopathy (HCM) in people and cats. In humans, it is increasingly recognized that SAM may be found in other cardiac and non-cardiac disease states. In small animal cardiology, SAM unassociated with HCM has been described in dogs with mitral valve dysplasia and right ventricular pressure overload. In this report, we describe two cases of dogs where transient SAM was caused by hypovolemia. When SAM was present both dogs showed pseudohypertrophy and tachycardia. Important factors in the genesis of SAM in this scenario are probably hypovolemia induced changes in left ventricular geometry affecting the orientation of the mitral valve apparatus combined with elevated catecholamine levels. SAM associated with increased wall thickness is not pathognomonic of HCM; this observation is of particular clinical importance when extrapolated to species where HCM is highly prevalent, e.g., cats. An echocardiographic diagnosis should always be evaluated together with full clinical assessment of history and physical examination. Copyright © 2016. Published by Elsevier B.V.

Utilizing self-assembled-monolayer-based gate dielectrics to fabricate molybdenum disulfide field-effect transistors

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

Kawanago, Takamasa, E-mail: kawanago.t.ab@m.titech.ac.jp; Oda, Shunri

In this study, we apply self-assembled-monolayer (SAM)-based gate dielectrics to the fabrication of molybdenum disulfide (MoS{sub 2}) field-effect transistors. A simple fabrication process involving the selective formation of a SAM on metal oxides in conjunction with the dry transfer of MoS{sub 2} flakes was established. A subthreshold slope (SS) of 69 mV/dec and no hysteresis were demonstrated with the ultrathin SAM-based gate dielectrics accompanied by a low gate leakage current. The small SS and no hysteresis indicate the superior interfacial properties of the MoS{sub 2}/SAM structure. Cross-sectional transmission electron microscopy revealed a sharp and abrupt interface of the MoS{sub 2}/SAM structure.more » The SAM-based gate dielectrics are found to be applicable to the fabrication of low-voltage MoS{sub 2} field-effect transistors and can also be extended to various layered semiconductor materials. This study opens up intriguing possibilities of SAM-based gate dielectrics in functional electronic devices.« less

Alternative function for the mitochondrial SAM complex in biogenesis of alpha-helical TOM proteins.

PubMed

Stojanovski, Diana; Guiard, Bernard; Kozjak-Pavlovic, Vera; Pfanner, Nikolaus; Meisinger, Chris

2007-12-03

The mitochondrial outer membrane contains two preprotein translocases: the general translocase of outer membrane (TOM) and the beta-barrel-specific sorting and assembly machinery (SAM). TOM functions as the central entry gate for nuclear-encoded proteins. The channel-forming Tom40 is a beta-barrel protein, whereas all Tom receptors and small Tom proteins are membrane anchored by a transmembrane alpha-helical segment in their N- or C-terminal portion. Synthesis of Tom precursors takes place in the cytosol, and their import occurs via preexisting TOM complexes. The precursor of Tom40 is then transferred to SAM for membrane insertion and assembly. Unexpectedly, we find that the biogenesis of alpha-helical Tom proteins with a membrane anchor in the C-terminal portion is SAM dependent. Each SAM protein is necessary for efficient membrane integration of the receptor Tom22, whereas assembly of the small Tom proteins depends on Sam37. Thus, the substrate specificity of SAM is not restricted to beta-barrel proteins but also includes the majority of alpha-helical Tom proteins.

Maturity Assessment of Space Plug-and-Play Architecture

DTIC Science & Technology

2013-03-01

SSM SPA Service Module SRL System Readiness Level TAT Time-at-Tone TRA Technology Readiness Assessment TRL Technology Readiness Level USB Universal...maturity assessment—the Technology Readiness Level (TRL) process, the Integration Readiness Level (IRL) process, and the System Readiness Level ( SRL ...is an important hallmark of the SPA concept, and makes possible the composability and scalability of system designs that employ it. 14 4. SPA

An Evaluation of Bioregulators/Modulators as Terrorism and Warfare Agents

DTIC Science & Technology

2003-07-01

such as bronchial and vascular tone and muscle contraction . This opens an unprecedented possibility to use toxic substances that could not be...bronchial smooth muscles and also in the intestines and the uterus bradykinin leads to muscle contraction . Bradykinin is also one the most potent...gout. Bradykinin has a powerful influence in stimulating smooth muscle contraction , inducing hypotension, increasing blood flow and permeability of

Characterization of self assembly layers of octadecanephosphonic acid by polarisation modulation FT-IRRA spectroscopy mapping

NASA Astrophysics Data System (ADS)

Steiner, G.; Sablinskas, V.; Savchuk, O.; Bariseviciute, R.; Jähne, E.; Adler, H. J.; Salzer, R.

2003-12-01

Self assembly layers were studied by a polarization modulation FT-spectroscopy mapping technique. The optical lay out is based on polarization modulation FT infrared reflection absorption spectroscopy (PM-FT-IRRAS). Here we report for the first time on a PM-FT-IRRAS mapping instrument. Octadecanephosphonic acid adsorbed on a patterned aluminum/gold surface was investigated. The nature of chemical bonding at particular surface areas was evaluated by principal component analysis. The most prominent features of the PM-FT-IRRA spectra are the P-O and PO stretching vibrations. It is shown that octadecanephosphonic acid is adsorbed both on Al 2O 3 and on Au. Moreover, PM-FT-IRRAS maps reveal areas of non-equivalent structural features. Lateral dimensions of these areas are in the micrometer range. Such non-equivalencies may control the inhibition potential of SAMs on ignoble metals, hence become crucial to the quality of products as biosensors or microelectronic components.

Korean Affairs Report, No. 315.

DTIC Science & Technology

1983-10-24

assuming the connection with Kim Yong -sam forces, reacted with an unexpectedly resolute stance, aiming its resolute response toward the Kim Yong -sam... Kim Yong -sam, former president of the now-defunct New Democratic Party, to a 10-day detention yesterday. Chon Hong-ki, 31, a member of the Minju...Democratic) Alpine Club, had stood before a summary court on 28 June for having spread printed material on the hunger strike of Kim Yong -sam. He was

Radical SAM catalysis via an organometallic intermediate with an Fe-[5'-C]-deoxyadenosyl bond.

PubMed

Horitani, Masaki; Shisler, Krista; Broderick, William E; Hutcheson, Rachel U; Duschene, Kaitlin S; Marts, Amy R; Hoffman, Brian M; Broderick, Joan B

2016-05-13

Radical S-adenosylmethionine (SAM) enzymes use a [4Fe-4S] cluster to cleave SAM to initiate diverse radical reactions. These reactions are thought to involve the 5'-deoxyadenosyl radical intermediate, which has not yet been detected. We used rapid freeze-quenching to trap a catalytically competent intermediate in the reaction catalyzed by the radical SAM enzyme pyruvate formate-lyase activating enzyme. Characterization of the intermediate by electron paramagnetic resonance and (13)C, (57)Fe electron nuclear double-resonance spectroscopies reveals that it contains an organometallic center in which the 5' carbon of a SAM-derived deoxyadenosyl moiety forms a bond with the unique iron site of the [4Fe-4S] cluster. Discovery of this intermediate extends the list of enzymatic bioorganometallic centers to the radical SAM enzymes, the largest enzyme superfamily known, and reveals intriguing parallels to B12 radical enzymes. Copyright © 2016, American Association for the Advancement of Science.

Effect of molecular desorption on the electronic properties of self-assembled polarizable molecular monolayers.

PubMed

Wang, Gunuk; Jeong, Hyunhak; Ku, Jamin; Na, Seok-In; Kang, Hungu; Ito, Eisuke; Jang, Yun Hee; Noh, Jaegeun; Lee, Takhee

2014-04-01

We investigated the interfacial electronic properties of self-assembled monolayers (SAM)-modified Au metal surface at elevated temperatures. We observed that the work functions of the Au metal surfaces modified with SAMs changed differently under elevated-temperature conditions based on the type of SAMs categorized by three different features based on chemical anchoring group, molecular backbone structure, and the direction of the dipole moment. The temperature-dependent work function of the SAM-modified Au metal could be explained in terms of the molecular binding energy and the thermal stability of the SAMs, which were investigated with thermal desorption spectroscopic measurements and were explained with molecular modeling. Our study will aid in understanding the electronic properties at the interface between SAMs and metals in organic electronic devices if an annealing treatment is applied. Copyright © 2013 Elsevier Inc. All rights reserved.

Emerging roles for Sam68 in adipogenesis and neuronal development.

PubMed

Vogel, Gillian; Richard, Stéphane

2012-09-01

Sam68, the Src-associated substrate during mitosis of 68 kDa, belongs to the large class of heteronuclear ribonucleoprotein particle K (hnRNP K) homology (KH) domain family of RNA-binding proteins. Sam68 contains a single KH domain harboring conserved N- and C-terminal sequences required for RNA binding and homodimerization. The KH domain is one of the most prevalent RNA binding domains that directly contacts single-stranded RNA. Sam68 has been implicated in numerous aspects of RNA metabolism including alternative splicing and polysomal recruitment of mRNAs. Studies in mice have revealed physiological roles linking Sam68 to osteoporosis, obesity, cancer, infertility and ataxia. Recent publications have greatly enhanced our understanding of Sam68 mechanism of action in addition to its cellular role. Herein, we will discuss the latest advances in the literature pertaining to obesity and neuronal development.