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Sample records for activation slow deactivation

  1. Voltage-induced slow activation and deactivation of mechanosensitive channels in Xenopus oocytes.

    PubMed Central

    Silberberg, S D; Magleby, K L

    1997-01-01

    1. The relationship between stretch and voltage activation of mechanosensitive (MS) channels from Xenopus oocytes was studied in excised patches of membrane using the patch clamp technique. 2. As is characteristic of MS channels to oocytes, stretching the membrane by applying negative pressure to the patch pipette at -50 mV activated the MS channels rapidly. The channels then deactivated rapidly when the stretch was removed. The stretch-activated MS channels entered a main conductance level (45 pS) and one or more subconductance levels in the range of about 75-90% of the main conductance level. 3. In the absence of stretch, a depolarizing step from -50 to +50 mV activated apparent MS channels after long delays of typically 1-20 s (range, 100 ms to 6 min). Upon repolarization, the channels deactivated slowly with a single exponential (mean time constant of 4 s) or double exponential (mean time constants of 0.8 and 3 s) time course. 4. Delayed activation with depolarization and slow deactivation upon repolarization were also observed for apparent MS channels in on-cell patches. 5. The voltage-activated channels were cation selective and had the same selectivity and conductance levels as the stretch activated MS channels. Applying stretch during voltage-induced channel activity did not activate any additional channels, and the same maximal number of channels were typically activated by either stretch or by voltage. These observations suggest that voltage activates the same MS channels that are activated by stretch. 6. The opening of MS channels following steps to +50 mV occurred in an apparently co-operative manner in 70% of the excised patches containing multiple MS channels. 7. In the absence of stretch, the opening frequency and open probability of MS channels increased with depolarization in the examined voltage range of -60 to -20 mV. 8. Applying a brief stretch during the delay to activation at +50 mV activated the MS channels rapidly, which then remained active

  2. Optical measurement of mGluR1 conformational changes reveals fast activation, slow deactivation, and sensitization

    PubMed Central

    Marcaggi, Païkan; Mutoh, Hiroki; Dimitrov, Dimitar; Beato, Marco; Knöpfel, Thomas

    2009-01-01

    Metabotropic glutamate receptor (mGluR) activation has been extensively studied under steady-state conditions. However, at central synapses, mGluRs are exposed to brief submillisecond glutamate transients and may not reach steady-state. The lack of information on the kinetics of mGluR activation impairs accurate predictions of their operation during synaptic transmission. Here, we report experiments designed to investigate mGluR kinetics in real-time. We inserted either CFP or YFP into the second intracellular loop of mGluR1β. When these constructs were coexpressed in PC12 cells, glutamate application induced a conformational change that could be monitored, using fluorescence resonance energy transfer (FRET), with an EC50 of 7.5 μM. The FRET response was mimicked by the agonist DHPG, abolished by the competitive antagonist MCPG, and partially inhibited by mGluR1-selective allosteric modulators. These results suggest that the FRET response reports active conformations of mGluR1 dimers. The solution exchange at the cell membrane was optimized for voltage-clamped cells by recording the current induced by co-application of 30 mM potassium. When glutamate was applied at increasing concentrations up to 2 mM, the activation time course decreased to a minimum of approximately 10 ms, whereas the deactivation time course remained constant (∼50 ms). During long-lasting applications, no desensitization was observed. In contrast, we observed a robust sensitization of the FRET response that developed over approximately 400 ms. Activation, deactivation, and sensitization time courses and amplitudes were used to derive a kinetic scheme and rate constants, from which we inferred the EC50 and frequency dependence of mGluR1 activation under non-steady-state conditions, as occurs during synaptic transmission. PMID:19549872

  3. Slowed N-Type Calcium Channel (CaV2.2) Deactivation by the Cyclin-Dependent Kinase Inhibitor Roscovitine

    PubMed Central

    Buraei, Zafir; Anghelescu, Mircea; Elmslie, Keith S.

    2005-01-01

    The lack of a calcium channel agonist (e.g., BayK8644) for CaV2 channels has impeded their investigation. Roscovitine, a potent inhibitor of cyclin-dependent kinases 1, 2, and 5, has recently been reported to slow the deactivation of P/Q-type calcium channels (CaV2.1). We show that roscovitine also slows deactivation (EC50 ∼53 μM) of N-type calcium channels (CaV2.2) and investigate gating alterations induced by roscovitine. The onset of slowed deactivation was rapid (∼2 s), which contrasts with a slower effect of roscovitine to inhibit N-current (EC50 ∼300 μM). Slow deactivation was specific to roscovitine, since it could not be induced by a closely related cyclin-dependent kinase inhibitor, olomoucine (300 μM). Intracellularly applied roscovitine failed to slow deactivation, which implies an extracellular binding site. The roscovitine-induced slow deactivation was accompanied by a slight left shift in the activation-voltage relationship, slower activation at negative potentials, and increased inactivation. Additional data showed that roscovitine preferentially binds to the open channel to slow deactivation. A model where roscovitine reduced a backward rate constant between two open states was able to reproduce the effect of roscovitine on both activation and deactivation. PMID:15951378

  4. Slow deactivation channels in UV-photoexcited adenine DNA.

    PubMed

    Chen, Xuebo; Fang, Weihai; Wang, Haobin

    2014-03-07

    The molecular mechanism for removing the excess energy in DNA bases is responsible for the high photostability of DNA and is thus the subject of intense theoretical/computational investigation. To understand why the excited state decay of the stacked bases is significantly longer than that of the monomers, we carried out electronic structure calculations on an adenine monomer and an aqueous (dA)5 oligonucleotide employing the CASPT2//CASSCF and CASPT2//CASSCF/AMBER levels of theory. The newly-found bright excited state pair Sstack1((1)ππ*) and Sstack2((1)ππ*) of d(A)5, originated from base stacking, is of intra-base charge transfer nature and occurs in different stacked bases with charge transfer along opposite directions. Two slow deactivation channels of d(A)5 were proposed as a result of the sizable barriers along the relaxation paths starting from the FC point of the Sstack1((1)ππ*) state. The SN1P((1)nπ*) state of d(A)5 serves as an intermediate state in one relaxation channel, to which a nonadiabatic decay from the Sstack1((1)ππ*) state occurs in an energy degeneracy region. A relatively high barrier in this state is found and attributed to the steric hindrance of the DNA environment due to the large NH2 group twisting, which gives a weak and red-shifted fluorescence. Another direct relaxation channel, induced by the C2-H2 bond twisting motion, is found to go through a conical intersection between the Sstack1((1)ππ*) and the ground state. The barrier found here enables fluorescence from the Sstack1((1)ππ*) state and may explain the bright state emission observed in the fluorescence upconversion measurements. The inter-molecular SCT((1)ππ*) state may be involved in the slow relaxation process of the photoexcited adenine oligomers through efficient internal conversion to the intra-base Sstack1((1)ππ*) state.

  5. On the CCN (de)activation nonlinearities

    NASA Astrophysics Data System (ADS)

    Arabas, Sylwester; Shima, Shin-ichiro

    2017-09-01

    We take into consideration the evolution of particle size in a monodisperse aerosol population during activation and deactivation of cloud condensation nuclei (CCN). Our analysis reveals that the system undergoes a saddle-node bifurcation and a cusp catastrophe. The control parameters chosen for the analysis are the relative humidity and the particle concentration. An analytical estimate of the activation timescale is derived through estimation of the time spent in the saddle-node bifurcation bottleneck. Numerical integration of the system coupled with a simple air-parcel cloud model portrays two types of activation/deactivation hystereses: one associated with the kinetic limitations on droplet growth when the system is far from equilibrium, and one occurring close to equilibrium and associated with the cusp catastrophe. We discuss the presented analyses in context of the development of particle-based models of aerosol-cloud interactions in which activation and deactivation impose stringent time-resolution constraints on numerical integration.

  6. Gating mechanisms underlying deactivation slowing by two KCNQ1 atrial fibrillation mutations

    PubMed Central

    Peng, Gary; Barro-Soria, Rene; Sampson, Kevin J.; Larsson, H. Peter; Kass, Robert S.

    2017-01-01

    KCNQ1 is a voltage-gated potassium channel that is modulated by the beta-subunit KCNE1 to generate IKs, the slow delayed rectifier current, which plays a critical role in repolarizing the cardiac action potential. Two KCNQ1 gain-of-function mutations that cause a genetic form of atrial fibrillation, S140G and V141M, drastically slow IKs deactivation. However, the underlying gating alterations remain unknown. Voltage clamp fluorometry (VCF) allows simultaneous measurement of voltage sensor movement and current through the channel pore. Here, we use VCF and kinetic modeling to determine the effects of mutations on channel voltage-dependent gating. We show that in the absence of KCNE1, S140G, but not V141M, directly slows voltage sensor movement, which indirectly slows current deactivation. In the presence of KCNE1, both S140G and V141M slow pore closing and alter voltage sensor-pore coupling, thereby slowing current deactivation. Our results suggest that KCNE1 can mediate changes in pore movement and voltage sensor-pore coupling to slow IKs deactivation and provide a key step toward developing mechanism-based therapies. PMID:28383569

  7. Temperature (de)activated patchy colloidal particles.

    PubMed

    de Las Heras, Daniel; da Gama, Margarida M Telo

    2016-06-22

    We present a new model of patchy particles in which the interaction sites can be activated or deactivated by varying the temperature of the system. We study the thermodynamics of the system by means of Wertheim's first order perturbation theory, and use Flory-Stockmayer theory of polymerization to analyse the percolation threshold. We find a very rich phase behaviour including lower critical points and reentrant percolation.

  8. 10 CFR 218.2 - Activation/Deactivation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Activation/Deactivation. 218.2 Section 218.2 Energy DEPARTMENT OF ENERGY OIL STANDBY MANDATORY INTERNATIONAL OIL ALLOCATION General Provisions § 218.2 Activation/Deactivation. (a) This rule shall take effect providing: (1) The International Energy Program has been...

  9. 10 CFR 218.2 - Activation/Deactivation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Activation/Deactivation. 218.2 Section 218.2 Energy DEPARTMENT OF ENERGY OIL STANDBY MANDATORY INTERNATIONAL OIL ALLOCATION General Provisions § 218.2 Activation/Deactivation. (a) This rule shall take effect providing: (1) The International Energy Program has been...

  10. 10 CFR 218.2 - Activation/Deactivation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Activation/Deactivation. 218.2 Section 218.2 Energy DEPARTMENT OF ENERGY OIL STANDBY MANDATORY INTERNATIONAL OIL ALLOCATION General Provisions § 218.2 Activation/Deactivation. (a) This rule shall take effect providing: (1) The International Energy Program has been...

  11. 10 CFR 218.2 - Activation/Deactivation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Activation/Deactivation. 218.2 Section 218.2 Energy DEPARTMENT OF ENERGY OIL STANDBY MANDATORY INTERNATIONAL OIL ALLOCATION General Provisions § 218.2 Activation/Deactivation. (a) This rule shall take effect providing: (1) The International Energy Program has been...

  12. 10 CFR 218.2 - Activation/Deactivation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Activation/Deactivation. 218.2 Section 218.2 Energy DEPARTMENT OF ENERGY OIL STANDBY MANDATORY INTERNATIONAL OIL ALLOCATION General Provisions § 218.2 Activation/Deactivation. (a) This rule shall take effect providing: (1) The International Energy Program has been...

  13. Activation-deactivation of self-healing in supramolecular rubbers

    NASA Astrophysics Data System (ADS)

    Corte, Laurent; Maes, Florine; Montarnal, Damien; Cantournet, Sabine; Tournilhac, Francois; Leibler, Ludwik; Mines-Paristech Cnrs (Umr7633) Team; Espci-Paristech Cnrs (Umr7167) Team

    2011-03-01

    Self-healing materials have the ability to restore autonomously their structural integrity after damage. Such a remarkable property was obtained recently in supramolecular rubbers formed by a network of small molecules associated via hydrogen bonds. Here we explore this self-healing through an original tack experiment where two parts of supramolecular rubber are brought into contact and then separated. These experiments reveal that a strong self-healing ability is activated by damage even though the surfaces of a molded part are weakly self-adhesive. In our testing conditions, a five minute contact between crack faces is sufficient to recover most mechanical properties of the bulk while days are required to obtain such adhesion levels with melt-pressed surfaces. We show that the deactivation of this self-healing ability seems unexpectedly slow as compared to the predicted dynamics of supramolecular networks. Fracture faces stored apart at room temperature still self-heal after days but are fully deactivated within hours by annealing. Combining these results with microstructural observations gives us a deeper insight into the mechanisms involved in this self-healing process.

  14. Pacemaker deactivation: withdrawal of support or active ending of life?

    PubMed

    Huddle, Thomas S; Amos Bailey, F

    2012-12-01

    In spite of ethical analyses assimilating the palliative deactivation of pacemakers to commonly accepted withdrawings of life-sustaining therapy, many clinicians remain ethically uncomfortable with pacemaker deactivation at the end of life. Various reasons have been posited for this discomfort. Some cardiologists have suggested that reluctance to deactivate pacemakers may stem from a sense that the pacemaker has become part of the patient's "self." The authors suggest that Daniel Sulmasy is correct to contend that any such identification of the pacemaker is misguided. The authors argue that clinicians uncomfortable with pacemaker deactivation are nevertheless correct to see it as incompatible with the traditional medical ethics of withdrawal of support. Traditional medical ethics is presently taken by many to sanction pacemaker deactivation when such deactivation honors the patient's right to refuse treatment. The authors suggest that the right to refuse treatment applies to treatments involving ongoing physician agency. This right cannot underwrite patient demands that physicians reverse the effects of treatments previously administered, in which ongoing physician agency is no longer implicated. The permanently indwelling pacemaker is best seen as such a treatment. As such, its deactivation in the pacemaker-dependent patient is best seen not as withdrawal of support but as active ending of life. That being the case, clinicians adhering to the usual ethical analysis of withdrawal of support are correct to be uncomfortable with pacemaker deactivation at the end of life.

  15. Automated Activation and Deactivation of a System Under Test

    NASA Technical Reports Server (NTRS)

    Poff, Mark A.

    2006-01-01

    The MPLM Automated Activation/Deactivation application (MPLM means Multi-Purpose Logistic Module) was created with a three-fold purpose in mind: 1. To reduce the possibility of human error in issuing commands to, or interpreting telemetry from, the MPLM power, computer, and environmental control systems; 2. To reduce the amount of test time required for the repetitive activation/deactivation processes; and 3. To reduce the number of on-console personnel required for activation/ deactivation. All of these have been demonstrated with the release of the software. While some degree of automated end-item commanding had previously been performed for space-station hardware in the test environment, none approached the functionality and flexibility of this application. For MPLM activation, it provides mouse-click selection of the hardware complement to be activated, activates the desired hardware and verifies proper feedbacks, and alerts the user when telemetry indicates an error condition or manual intervention is required. For MPLM deactivation, the product senses which end items are active and deactivates them in the proper sequence. For historical purposes, an on-line log is maintained of commands issued and telemetry points monitored. The benefits of the MPLM Automated Activation/ Deactivation application were demonstrated with its first use in December 2002, when it flawlessly performed MPLM activation in 8 minutes (versus as much as 2.4 hours for previous manual activations), and performed MPLM deactivation in 3 minutes (versus 66 minutes for previous manual deactivations). The number of test team members required has dropped from eight to four, and in actuality the software can be operated by a sole (knowledgeable) system engineer.

  16. Activated and deactivated functional brain areas in the Deqi state

    PubMed Central

    Huang, Yong; Zeng, Tongjun; Zhang, Guifeng; Li, Ganlong; Lu, Na; Lai, Xinsheng; Lu, Yangjia; Chen, Jiarong

    2012-01-01

    We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state, as reported by physicians and subjects during acupuncture. Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint. Real-time cerebral functional MRI showed that compared with non-sensation after sham needling, true needling activated Brodmann areas 3, 6, 8, 9, 10, 11, 13, 20, 21, 37, 39, 40, 43, and 47, the head of the caudate nucleus, the parahippocampal gyrus, thalamus and red nucleus. True needling also deactivated Brodmann areas 1, 2, 3, 4, 5, 6, 7, 9, 10, 18, 24, 31, 40 and 46. PMID:25538761

  17. The macrophage in HIV-1 infection: from activation to deactivation?

    PubMed

    Herbein, Georges; Varin, Audrey

    2010-04-09

    Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1) induced in particular by IFN-gamma display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2) induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM). Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease.

  18. Activation and deactivation of high concentration arsenic with some evidence of precipitation

    SciTech Connect

    Rousseau, P.M.; Griffin, P.B.; Plummer, J.D.; Carey, P.G.

    1992-12-29

    Using box-shaped profiles created by laser melt annealing, the authors investigate the kinetics of arsenic activation and deactivation. They find deactivation shows no history effects, which can be consistent either with clustering or precipitation for the cases considered. For activation, they notice it occurs on very short time scales, followed by a slower deactivation process. This is suggestive evidence that at least some precipitation occurs.

  19. Comparison of Methodologies of Activation Barrier Measurements for Reactions with Deactivation

    DOE PAGES

    Xie, Zhenhua; Yan, Binhang; Zhang, Li; ...

    2017-01-25

    In this work, methodologies of activation barrier measurements for reactions with deactivation were theoretically analyzed. Reforming of ethane with CO2 was introduced as an example for reactions with deactivation to experimentally evaluate these methodologies. Both the theoretical and experimental results showed that due to catalyst deactivation, the conventional method would inevitably lead to a much lower activation barrier, compared to the intrinsic value, even though heat and mass transport limitations were excluded. In this work, an optimal method was identified in order to provide a reliable and efficient activation barrier measurement for reactions with deactivation.

  20. Metabolic activation/deactivation reactions during perinatal development.

    PubMed Central

    Lucier, G W; Lui, E M; Lamartiniere, C A

    1979-01-01

    The role of metabolic activation/deactivation reactions during development is evaluated in relation to developmental pharmacology and toxicology. Enzyme systems evaluated include the mixed-function oxidases (aryl hydrocarbon hydroxylase and oxidative demethylation), epoxide hydration and conjugation (glutathione conjugation, sulfation, and glucuronidation). Placental transfer and milk secretion of chemicals are discussed in relation to maternal, placental, and fetal metabolism. Normal patterns of enzyme development can be modified in two ways: (1) enzyme induction and (2) enzyme imprinting. Postnatal induction of the mixed-function oxidases and glucuronyl-transferase following treatment of pregnant rats with TCDD is shown to be caused primarily by newborn exposure to TCDD in milk. Structure-activity relationship are defined for the perinatal induction of hepatic enzymes by the pure PCBs. PCBs are divided into two classes: P-450 inducers and P-448 inducers. Imprinting or programming of hepatic metabolism is a function of the sexual differentiation of enzyme activity; male and female activities are similar in prepubertal animals, whereas pronounced sex differences are evident in adults. Treatment of newborn rats (days 2--6) with diethystilbestrol or testosterone resulted in a feminization (decrease) of mixed-function oxidation and glucuronidation in adult males. No changes were seen in immature males or females or adult females. This effect appears to be irreversible and is under pituitary-hypothalamic-gonadal control. In addition to the feminization of enzyme activity, neonatal exposure to hormonally active chemicals also feminizes the hepatic response to cadmium in resultant adult animals. PMID:510244

  1. Force depression and relaxation kinetics after active shortening and deactivation in mouse soleus muscle.

    PubMed

    Van Noten, P; Van Leemputte, M

    2013-03-15

    After active shortening, isometric force production capacity of muscle is reduced (force depression, FD). The mechanism is incompletely understood but increasing cross-bridge detachment and/or decreasing attachment rate might be involved. Therefore we aimed to investigate the relation between work delivered during shortening (W), and change in half-relaxation time (Δ0.5RT) and change in the slow phase of muscle relaxation (Δkslow), considered as a marker for cross-bridge detachment rate, after shortening and after a short (0.7s) interruption of activation (deactivation). We hypothesized that shortening induces an accelerated relaxation related to W which is, similar to FD, largely abolished by a short deactivation. In 10 incubated supra-maximally stimulated mouse soleus muscles, we varied the amount of FD at L0 by varying shortening amplitude (0.6, 1.2 and 2.4mm). We found that W not only induces FD (R(2)=0.92) but also a dose dependent accelerated relaxation (R(2)=0.88 and R(2)=0.77 for respectively Δkslow and Δ0.5RT). In cyclic movements this is of functional significance, because the loss in force generating capacity might be (partially) compensated by faster relaxation. After a short deactivation, both FD and Δkslow were largely abolished but Δ0.5RT remained largely present. Under the assumption that Δkslow reflects a change in cross-bridge detachment rate, these results support the idea that FD is an intrinsic sarcomeric property originating from a work induced reduction of the number of force generating cross-bridges, however not via decreased attachment but via increased detachment rate.

  2. Attention, Emotion, and Deactivation of Default Activity in Inferior Medial Prefrontal Cortex

    ERIC Educational Resources Information Center

    Geday, Jacob; Gjedde, Albert

    2009-01-01

    Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC with positron emission tomography (PET) of labeled water…

  3. Attention, Emotion, and Deactivation of Default Activity in Inferior Medial Prefrontal Cortex

    ERIC Educational Resources Information Center

    Geday, Jacob; Gjedde, Albert

    2009-01-01

    Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC with positron emission tomography (PET) of labeled water…

  4. Flexural activation and de-activation responses of orthodontic wires in single-tooth, occlusogingival corrections.

    PubMed

    Nikolai, R J

    1989-09-01

    An experimental design was developed to simulate the processes of the activation in flexure of a wire segment to engage an occlusogingivally-malposed tooth and the correction of that malalignment. Independent, controlled parameters, clinically referred, were wire material, mesiodistal bracket width, and inter-bracket distance. Full-cycle, activation/de-activation diagrams were generated for 96 specimens. Each load-deflection diagram was in five segments. Slope discontinuities occurred at the states of disappearance and reappearance of "second-order" clearances at the support sites. Ratios of the slopes of the diagrams above these discontinuities to their counterparts beneath the discontinuities were typically between 2:1 and 4:1. A segment of the diagram was distinct at the initiation of de-activation, and was related to the reversal of frictional forces at the supports. Generalizing, in some cases activation may not eliminate the cited clearances; in others, clearances may be negligibly small in the passive states. Apparently, analyses should ordinarily recognize the segmented formats of the activation and de-activation plots. In comparisons of activation with de-activation plots within the individual diagrams, differences in quantified properties for the cobalt-chromium- and nickel-titanium-alloy wires were sufficient to suggest further study toward an objective of predicting de-activation behavior from outcomes of an activation analysis.

  5. PCG-STES, Rominger de-activates middeck experiment

    NASA Image and Video Library

    1997-08-27

    STS085-324-007 (7 - 19 August 1997) --- Astronaut Kent V. Rominger, pilot, uses a tool to deactivate the Protein Crystal Growth (PCG) experiment on the mid-deck of the Space Shuttle Discovery near the end of the 12-day STS-85 flight.

  6. Differences in Activation and Deactivation in Children with Sickle Cell Disease Compared with Demographically Matched Controls.

    PubMed

    Sun, B; Brown, R C; Burns, T G; Murdaugh, D; Palasis, S; Jones, R A

    2017-06-01

    Declines in both functional activation and functional connectivity have been reported in patients with sickle cell disease. In this study, we derived the functional and default mode responses to a word stem paradigm in age-, ethnicity-, and background-matched subjects with sickle cell disease and control groups, with the aim of testing whether both networks were similarly attenuated and whether the changes were related to physiologic parameters that characterize sickle cell disease. Both the functional and default mode responses were obtained from age- and background-matched controls and the sickle cell population by using a visually presented word stem paradigm on a 3T scanner. We observed an attenuated response to both activation and deactivation in the sickle cell disease group. There were no significant differences in the activation response between the 2 groups for the contrast control > sickle cell disease; however, significant differences were observed in the medial parietal cortex, the auditory cortex, and the angular gyrus for the default mode. For the sickle cell group, a significant correlation between the activation z scores and the physiologic parameters was observed; for the deactivation, the results were not significant but the trend was similar. The results indicate that the physiologic parameters modulate the activation in the expected fashion, but that the effect was weaker for deactivation. Given that significant differences between the 2 groups were only seen for deactivation, additional factors must modulate the deactivation in sickle cell disease. © 2017 by American Journal of Neuroradiology.

  7. Spread of activation and deactivation in the brain: does age matter?

    PubMed

    Gordon, Brian A; Tse, Chun-Yu; Gratton, Gabriele; Fabiani, Monica

    2014-01-01

    Cross-sectional aging functional MRI results are sometimes difficult to interpret, as standard measures of activation and deactivation may confound variations in signal amplitude and spread, which however, may be differentially affected by age-related changes in various anatomical and physiological factors. To disentangle these two types of measures, here we propose a novel method to obtain independent estimates of the peak amplitude and spread of the BOLD signal in areas activated (task-positive) and deactivated (task-negative) by a Sternberg task, in 14 younger and 28 older adults. The peak measures indicated that, compared to younger adults, older adults had increased activation of the task-positive network, but similar levels of deactivation in the task-negative network. Measures of signal spread revealed that older adults had an increased spread of activation in task-positive areas, but a starkly reduced spread of deactivation in task-negative areas. These effects were consistent across regions within each network. Further, there was greater variability in the anatomical localization of peak points in older adults, leading to reduced cross-subject overlap. These results reveal factors that may confound the interpretation of studies of aging. Additionally, spread measures may be linked to local connectivity phenomena and could be particularly useful to analyze age-related deactivation patterns, complementing the results obtained with standard peak and region of interest analyses.

  8. Spread of activation and deactivation in the brain: does age matter?

    PubMed Central

    Gordon, Brian A.; Tse, Chun-Yu; Gratton, Gabriele; Fabiani, Monica

    2014-01-01

    Cross-sectional aging functional MRI results are sometimes difficult to interpret, as standard measures of activation and deactivation may confound variations in signal amplitude and spread, which however, may be differentially affected by age-related changes in various anatomical and physiological factors. To disentangle these two types of measures, here we propose a novel method to obtain independent estimates of the peak amplitude and spread of the BOLD signal in areas activated (task-positive) and deactivated (task-negative) by a Sternberg task, in 14 younger and 28 older adults. The peak measures indicated that, compared to younger adults, older adults had increased activation of the task-positive network, but similar levels of deactivation in the task-negative network. Measures of signal spread revealed that older adults had an increased spread of activation in task-positive areas, but a starkly reduced spread of deactivation in task-negative areas. These effects were consistent across regions within each network. Further, there was greater variability in the anatomical localization of peak points in older adults, leading to reduced cross-subject overlap. These results reveal factors that may confound the interpretation of studies of aging. Additionally, spread measures may be linked to local connectivity phenomena and could be particularly useful to analyze age-related deactivation patterns, complementing the results obtained with standard peak and region of interest analyses. PMID:25360115

  9. Glut, war slow Mideast activity

    SciTech Connect

    Not Available

    1984-07-20

    Oilpatch activity in the Middle East has been on the slow side recently, and with a heated-up war between Iran and Iraq throwing off violent sparks around the Arabian Gulf, it's difficult to keep one's mind on business-as-usual. The article deals with the rising cost of insurance for shipping because of the war and the effects on drilling, production and the environment (oil spills). The development and production of offshore oil and gas in Egypt, Saudi Arabia, and the United Arab Emirates is also discussed.

  10. Decoupling HZSM-5 catalyst activity from deactivation during upgrading of pyrolysis oil vapors.

    PubMed

    Wan, Shaolong; Waters, Christopher; Stevens, Adam; Gumidyala, Abhishek; Jentoft, Rolf; Lobban, Lance; Resasco, Daniel; Mallinson, Richard; Crossley, Steven

    2015-02-01

    The independent evaluation of catalyst activity and stability during the catalytic pyrolysis of biomass is challenging because of the nature of the reaction system and rapid catalyst deactivation that force the use of excess catalyst. In this contribution we use a modified pyroprobe system in which pulses of pyrolysis vapors are converted over a series of HZSM-5 catalysts in a separate fixed-bed reactor controlled independently. Both the reactor-bed temperature and the Si/Al ratio of the zeolite are varied to evaluate catalyst activity and deactivation rates independently both on a constant surface area and constant acid site basis. Results show that there is an optimum catalyst-bed temperature for the production of aromatics, above which the production of light gases increases and that of aromatics decrease. Zeolites with lower Si/Al ratios give comparable initial rates for aromatics production, but far more rapid catalyst deactivation rates than those with higher Si/Al ratios.

  11. Stronger activation and deactivation in archery experts for differential cognitive strategy in visuospatial working memory processing.

    PubMed

    Seo, Jeehye; Kim, Yang-Tae; Song, Hui-Jin; Lee, Hui Joong; Lee, Jongmin; Jung, Tae-Du; Lee, Gunyoung; Kwon, Eunjin; Kim, Jin Gu; Chang, Yongmin

    2012-04-01

    It is well known that elite athletes have higher performance in perception, planning, and execution in sports activities relative to novices. It remains controversial, however, whether any differences in basic cognitive functions between experts and novices exist. Furthermore, few studies have directly used functional magnetic resonance imaging (fMRI) to investigate neural activation and deactivation differences between experts and novices while performing visuospatial working memory (WM) tasks. Therefore, the purpose of this study was to examine possible differences in neural activation and deactivation associated with working memory components in processing visuospatial information between archery experts and novices. To this end, we employed a judgment of line orientation (JLO) task, which has a strong WM component. With regard to brain activation, archery experts displayed higher activation in cortical areas associated with visuospatial attention and working memory, including the middle frontal cortex, supplemental motor area, and dorsolateral prefrontal cortex than that of the novices during the performance of the JLO task. With regard to brain deactivation, archery experts exhibited stronger task-related deactivation in cortical areas, such as the paracentral cortex/precuneus and the anterior and posterior cingulate cortex related to the default network, than that of the novices. These results suggest that the archery experts have a strategy that demands greater use of neural correlates associated with visuospatial working memory and attention in addition to greater use of DMN in visuospatial working memory task not directly tied to their domain of expertise.

  12. Deactivation model for the adsorption of trichloroethylene vapor on an activated carbon bed

    SciTech Connect

    Suyadal, Y.; Erol, M.; Oguz, H.

    2000-03-01

    In this work, the adsorption of trichloroethylene (TCE) vapor was investigated in a laboratory-scale packed-bed adsorber by using granular activated carbon (GAC) at constant pressure (101.3 kPa). The packed-bed adsorber (PBA) was operated batchwise with the charges of GAC particles in the ranges of 2.5--10.0 g for obtaining TCE breakthrough curves. Experiments were carried out at different temperatures (25.6 {le} T({degree}C) {le} 35.8) and TCE feedstock concentrations (6,350 {le} C (ppm TCE) {le} 7,950) within the range of space velocity (5,000 {le} {var_theta} (h{sup {minus}1}) {le} 17,000). The effects of TCE inlet concentration, operating temperature, and mass of adsorbent (m{sub Ads}) on the TCE breakthrough curves were investigated, respectively. The deactivation model (DM) was tested for these curves by using the analogy between the adsorption of TCE and the deactivation of catalyst particles. Observed adsorption rate constants (k{sub S}) and first-order deactivation rate constants (k{sub d}) were obtained from the model. It was found that the deactivation model describes the experimental breakthrough curves more accurately compared to the adsorption isotherms given in the literature.

  13. Recovery of Alkylation Activity in Deactivated USY Catalyst Using Supercritical Fluids: A Comparison of Light Hydrocarbons

    SciTech Connect

    Daniel M. Ginosar; David N. Thompson; Kyle C. Burch

    2004-05-01

    Off-line, in-situ alkylation activity recovery from a completely deactivated solid acid catalyst was examined in a continuous-flow reaction system employing supercritical fluids (SCF). A USY zeolite catalyst was initially deactivated during the liquid phase alkylation of butene with isobutane in a single-pass reactor and then varying amounts of alkylation activity were recovered by passing supercritical fluids over the catalyst bed. A comparison of reactivation fluids on catalyst activity recovery is reported. Fluids examined included helium, propane, n-butane, isobutane, n-pentane, and isopentane. Phases studied included gas, liquid, and supercritical. As much as 82% of the fresh catalyst activity was recovered when employing supercritical isobutane. The ability of the fluid to facilitate a hydride reaction with the adsorbed deactivating high-molecular weight carbocations was indicated as an important property necessary to attain high levels of catalyst activity recovery. Activity recovery utilizing supercritical fluids that enhance reactivation by both reacting with and desorbing fouling compounds appears to be a promising technique to advance solid catalyst alkylation.

  14. Activation and deactivation of vibronic channels in intact phycocyanin rods

    NASA Astrophysics Data System (ADS)

    Nganou, C.; David, L.; Meinke, R.; Adir, N.; Maultzsch, J.; Mkandawire, M.; Pouhè, D.; Thomsen, C.

    2014-02-01

    We investigated the excitation modes of the light-harvesting protein phycocyanin (PC) from Thermosynechococcus vulcanus in the crystalline state using UV and near-infrared Raman spectroscopy. The spectra revealed the absence of a hydrogen out-of-plane wagging (HOOP) mode in the PC trimer, which suggests that the HOOP mode is activated in the intact PC rod, while it is not active in the PC trimer. Furthermore, in the PC trimer an intense mode at 984 cm-1 is assigned to the C-C stretching vibration while the mode at 454 cm-1 is likely due to ethyl group torsion. In contrast, in the similar chromophore phytochromobilin the C5,10,15-D wag mode at 622 cm-1 does not come from a downshift of the HOOP. Additionally, the absence of modes between 1200 and 1300 cm-1 rules out functional monomerization. A correlation between phycocyanobilin (PCB) and phycoerythrobilin (PEB) suggests that the PCB cofactors of the PC trimer appear in a conformation similar to that of PEB. The conformation of the PC rod is consistent with that of the allophycocyanin (APC) trimer, and thus excitonic flow is facilitated between these two independent light-harvesting compounds. This excitonic flow from the PC rod to APC appears to be modulated by the vibration channels during HOOP wagging, C = C stretching, and the N-H rocking in-plan vibration.

  15. Activation and deactivation of vibronic channels in intact phycocyanin rods.

    PubMed

    Nganou, C; David, L; Meinke, R; Adir, N; Maultzsch, J; Mkandawire, M; Pouhè, D; Thomsen, C

    2014-02-28

    We investigated the excitation modes of the light-harvesting protein phycocyanin (PC) from Thermosynechococcus vulcanus in the crystalline state using UV and near-infrared Raman spectroscopy. The spectra revealed the absence of a hydrogen out-of-plane wagging (HOOP) mode in the PC trimer, which suggests that the HOOP mode is activated in the intact PC rod, while it is not active in the PC trimer. Furthermore, in the PC trimer an intense mode at 984 cm(-1) is assigned to the C-C stretching vibration while the mode at 454 cm(-1) is likely due to ethyl group torsion. In contrast, in the similar chromophore phytochromobilin the C5,10,15-D wag mode at 622 cm(-1) does not come from a downshift of the HOOP. Additionally, the absence of modes between 1200 and 1300 cm(-1) rules out functional monomerization. A correlation between phycocyanobilin (PCB) and phycoerythrobilin (PEB) suggests that the PCB cofactors of the PC trimer appear in a conformation similar to that of PEB. The conformation of the PC rod is consistent with that of the allophycocyanin (APC) trimer, and thus excitonic flow is facilitated between these two independent light-harvesting compounds. This excitonic flow from the PC rod to APC appears to be modulated by the vibration channels during HOOP wagging, C = C stretching, and the N-H rocking in-plan vibration.

  16. Probing activation/deactivation of the BRASSINOSTEROID INSENSITIVE1 receptor kinase by immunoprecipitation

    PubMed Central

    Martins, Sara; Vert, Grégory; Jaillais, Yvon

    2017-01-01

    Summary Brassinosteroids are plant sterol-derived hormones that control plant growth and development. The BR receptor complex is encoded by the BRASSINOSTEROID INSENSITIVE1 (BRI1) and members of the SOMATIC EMBRYOGENESIS RECEPTOR KINASE family. BR receptor complex activation and deactivation uses different post-translational modifications and recruitment of partner proteins. In this chapter, we describe optimized immunoprecipitation protocols and variants for biochemical analyses of BRI1 post-translational modification and protein-protein interaction. PMID:28124254

  17. Anterior Medial Prefrontal Cortex Exhibits Activation during Task Preparation but Deactivation during Task Execution

    PubMed Central

    Koshino, Hideya; Minamoto, Takehiro; Ikeda, Takashi; Osaka, Mariko; Otsuka, Yuki; Osaka, Naoyuki

    2011-01-01

    Background The anterior prefrontal cortex (PFC) exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN), which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC) is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task. Methodology/Principal Findings Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition) or to ignore them (No face memory condition), then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial. Conclusions/Significance The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing. PMID:21829668

  18. Activated and deactivated functional brain areas in the Deqi state: A functional MRI study.

    PubMed

    Huang, Yong; Zeng, Tongjun; Zhang, Guifeng; Li, Ganlong; Lu, Na; Lai, Xinsheng; Lu, Yangjia; Chen, Jiarong

    2012-10-25

    We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state, as reported by physicians and subjects during acupuncture. Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint. Real-time cerebral functional MRI showed that compared with non-sensation after sham needling, true needling activated Brodmann areas 3, 6, 8, 9, 10, 11, 13, 20, 21, 37, 39, 40, 43, and 47, the head of the caudate nucleus, the parahippocampal gyrus, thalamus and red nucleus. True needling also deactivated Brodmann areas 1, 2, 3, 4, 5, 6, 7, 9, 10, 18, 24, 31, 40 and 46.

  19. The transition between active and de-activated forms of NADH:ubiquinone oxidoreductase (Complex I) in the mitochondrial membrane of Neurospora crassa.

    PubMed Central

    Grivennikova, Vera G; Serebryanaya, Darya V; Isakova, Elena P; Belozerskaya, Tatyana A; Vinogradov, Andrei D

    2003-01-01

    The mammalian mitochondrial NADH:ubiquinone oxidoreductase (Complex I) has been shown to exist in two kinetically and structurally distinct slowly interconvertible forms, active (A) and de-activated (D) [Vinogradov and Grivennikova (2001) IUBMB Life 52, 129-134]. This work was undertaken to investigate the putative Complex I A-D transition in the mitochondrial membrane of the lower eukaryote Neurospora crassa and in plasma membrane of the prokaryote Paracoccus denitrificans, organisms that are eligible for molecular genetic manipulations. The potential interconversion between A and D forms was assessed by examination of the initial and steady-state rates of NADH oxidation catalysed by inside-out submitochondrial ( N. crassa ) and sub-bacterial ( P. denitrificans ) particles and their sensitivities to N -ethylmaleimide and Mg(2+). All diagnostic tests provide evidence that slow temperature- and turnover-dependent A-D transition is an explicit feature of eukaryotic N. crassa Complex I, whereas the phenomenon is not seen in the membranes of the prokaryote P. denitrificans. Significantly lower activation energy for A-to-D transition characterizes the N. crassa enzyme compared with that determined previously for the mammalian Complex I. Either a lag or a burst in the onset of the NADH oxidase assayed in the presence of Mg(2+) is seen when the reaction is initiated by the thermally de-activated or NADH-activated particles, whereas the delayed final activities of both preparations are the same. We conclude that continuous slow cycling between A and D forms occurs during the steady-state operation of Complex I in N. crassa mitochondria. PMID:12379145

  20. Neuroimaging of cerebral activations and deactivations associated with hypercapnia and hunger for air

    PubMed Central

    Brannan, Stephen; Liotti, Mario; Egan, Gary; Shade, Robert; Madden, Lisa; Robillard, Rachel; Abplanalp, Bart; Stofer, Katie; Denton, Derek; Fox, Peter T.

    2001-01-01

    There are defined medullary, mesencephalic, hypothalamic, and thalamic functions in regulation of respiration, but knowledge of cortical control and the elements subserving the consciousness of breathlessness and air hunger is limited. In nine young adults, air hunger was produced acutely by CO2 inhalation. Comparisons were made with inhalation of a N2/O2 gas mixture with the same apparatus, and also with paced breathing, and with eyes closed rest. A network of activations in pons, midbrain (mesencephalic tegmentum, parabrachial nucleus, and periaqueductal gray), hypothalamus, limbic and paralimbic areas (amygdala and periamygdalar region) cingulate, parahippocampal and fusiform gyrus, and anterior insula were seen along with caudate nuclei and pulvinar activations. Strong deactivations were seen in dorsal cingulate, posterior cingulate, and prefrontal cortex. The striking response of limbic and paralimbic regions points to these structures having a singular role in the affective sequelae entrained by disturbance of basic respiratory control whereby a process of which we are normally unaware becomes a salient element of consciousness. These activations and deactivations include phylogenetically ancient areas of allocortex and transitional cortex that together with the amygdalar/periamygdalar region may subserve functions of emotional representation and regulation of breathing. PMID:11172070

  1. SPM95 sensitivity to size, intensity and asymmetry of brain activation/deactivation patterns

    SciTech Connect

    Levy, A.V.; Volkow, N.D.; Alexoff, D.

    1996-05-01

    Statistical Parametric Mapping (Friston, SPM95), is used widely to ascertain the statistical significance between different brain patterns induced by functional activation, drug, effects or mental illness. Our purpose is to understand the limitations of applying the SPM95 methodology. We used a group of 8 FDG PET (CTI 931) studies from normal resting human subjects and via software we activated or deactivated the same specific pixel patterns (ROIs), across the group and observed if SPM95 performed correctly. A set of 6 experiments was designed with varying ROI intensities, (from +/-2% to +/-100% of original ROI value), varying ROI sizes, (from 76 to 656 mm{sup 2}) and different locations in the brain, (cortical and/or subcortical). In experiments where the selected activation pattern was spatially symmetric SPM95 identified correctly areas of activation for cortical ROIs as small as 76 mm{sup 2} having as low as a 10% activation with p<0.01; larger areas, 656 mm{sup 2} can be correctly identified even down to only 2%. In activation experiments with left/right cortical or anterior/posterior cortical asymmetry, SPM95 reported Type II errors for levels larger than +/-20% activation/deactivation. In experiments with left/right striatum asymmetry larger than +/-20% SPM95 reported Type I Errors. In experiments where the level of asymmetry was changes while keeping one ROI as a control at the same level of activation, SPM95 erroneously reported different p values for its statistical significance. One of the typical Type I Errors is shown in the figure as an ROI along the brain`s edge; this type of error has been previously observed to be caused by residual spatial registration errors that induce false activation signals. We conclude that while the statistical part of SPM95 performs correctly, the spatial registration method used in SPM95 has residual registration errors sensitive to the type of activation pattern.

  2. Deactivation of the inferior colliculus by cooling demonstrates intercollicular modulation of neuronal activity

    PubMed Central

    Orton, Llwyd D.; Poon, Paul W. F.; Rees, Adrian

    2012-01-01

    The auditory pathways coursing through the brainstem are organized bilaterally in mirror image about the midline and at several levels the two sides are interconnected. One of the most prominent points of interconnection is the commissure of the inferior colliculus (CoIC). Anatomical studies have revealed that these fibers make reciprocal connections which follow the tonotopic organization of the inferior colliculus (IC), and that the commissure contains both excitatory and, albeit fewer, inhibitory fibers. The role of these connections in sound processing is largely unknown. Here we describe a method to address this question in the anaesthetized guinea pig. We used a cryoloop placed on one IC to produce reversible deactivation while recording electrophysiological responses to sounds in both ICs. We recorded single units, multi-unit clusters and local field potentials (LFPs) before, during and after cooling. The degree and spread of cooling was measured with a thermocouple placed in the IC and other auditory structures. Cooling sufficient to eliminate firing was restricted to the IC contacted by the cryoloop. The temperature of other auditory brainstem structures, including the contralateral IC and the cochlea were minimally affected. Cooling below 20°C reduced or eliminated the firing of action potentials in frequency laminae at depths corresponding to characteristic frequencies up to ~8 kHz. Modulation of neural activity also occurred in the un-cooled IC with changes in single unit firing and LFPs. Components of LFPs signaling lemniscal afferent input to the IC showed little change in amplitude or latency with cooling, whereas the later components, which likely reflect inter- and intra-collicular processing, showed marked changes in form and amplitude. We conclude that the cryoloop is an effective method of selectively deactivating one IC in guinea pig, and demonstrate that auditory processing in the IC is strongly influenced by the other. PMID:23248587

  3. Galectin-1 Deactivates Classically-Activated Microglia and Protects from Inflammation-Induced Neurodegeneration

    PubMed Central

    Starossom, Sarah C.; Mascanfroni, Ivan D.; Imitola, Jaime; Cao, Li; Raddassi, Khadir; Hernandez, Silvia F.; Bassil, Ribal; Croci, Diego O.; Cerliani, Juan P.; Delacour, Delphine; Wang, Yue; Elyaman, Wassim; Khoury, Samia J.; Rabinovich, Gabriel A.

    2012-01-01

    SUMMARY Inflammation-mediated neurodegeneration occurs in the acute and the chronic phases of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Classically-activated (M1) microglia are key players mediating this process. Here we identified Galectin-1 (Gal1), an endogenous glycan-binding protein, as a pivotal regulator of M1 microglia activation, targeting the activation of p38MAPK-, CREB-, and NF-κB-dependent signaling pathways and hierarchically supressing downstream pro-inflammatory mediators such as iNOS, TNF and CCL2. Gal1 bound to core 2 O-glycans on CD45, favoring retention of this glycoprotein on the microglial cell surface and augmenting its phosphatase activity and inhibitory function. Gal1 was highly expressed in the acute phase of EAE and its targeted deletion resulted in pronounced inflammation-induced neurodegeneration. Adoptive transfer of Gal1-secreting astrocytes or administration of recombinant Gal1 suppressed EAE through mechanisms involving microglia de-activation. Thus, Gal1-glycan interactions are essential in tempering microglia activation, brain inflammation and neurodegeneration with critical therapeutic implications for MS. PMID:22884314

  4. One-colour control of activation, excitation and deactivation of a fluorescent diarylethene derivative in super-resolution microscopy.

    PubMed

    Arai, Yuhei; Ito, Syoji; Fujita, Hajime; Yoneda, Yusuke; Kaji, Takahiro; Takei, Satoshi; Kashihara, Ryota; Morimoto, Masakazu; Irie, Masahiro; Miyasaka, Hiroshi

    2017-02-28

    We demonstrated one-colour control of activation, excitation and deactivation of a fluorescent diarylethene derivative by using a 532 nm CW laser at a weak output power. This one-colour control method was applied to single-molecule tracking in polymer films over a total duration of a few hours at room temperature and PALM for the nanostructures of polymer systems.

  5. Caged Naloxone Reveals Opioid Signaling Deactivation Kinetics

    PubMed Central

    Banghart, Matthew R.; Shah, Ruchir C.; Lavis, Luke D.

    2013-01-01

    The spatiotemporal dynamics of opioid signaling in the brain remain poorly defined. Photoactivatable opioid ligands provide a means to quantitatively measure these dynamics and their underlying mechanisms in brain tissue. Although activation kinetics can be assessed using caged agonists, deactivation kinetics are obscured by slow clearance of agonist in tissue. To reveal deactivation kinetics of opioid signaling we developed a caged competitive antagonist that can be quickly photoreleased in sufficient concentrations to render agonist dissociation effectively irreversible. Carboxynitroveratryl-naloxone (CNV-NLX), a caged analog of the competitive opioid antagonist NLX, was readily synthesized from commercially available NLX in good yield and found to be devoid of antagonist activity at heterologously expressed opioid receptors. Photolysis in slices of rat locus coeruleus produced a rapid inhibition of the ionic currents evoked by multiple agonists of the μ-opioid receptor (MOR), but not of α-adrenergic receptors, which activate the same pool of ion channels. Using the high-affinity peptide agonist dermorphin, we established conditions under which light-driven deactivation rates are independent of agonist concentration and thus intrinsic to the agonist-receptor complex. Under these conditions, some MOR agonists yielded deactivation rates that are limited by G protein signaling, whereas others appeared limited by agonist dissociation. Therefore, the choice of agonist determines which feature of receptor signaling is unmasked by CNV-NLX photolysis. PMID:23960100

  6. Catalyst activation, deactivation, and degradation in palladium-mediated Negishi cross-coupling reactions.

    PubMed

    Böck, Katharina; Feil, Julia E; Karaghiosoff, Konstantin; Koszinowski, Konrad

    2015-03-27

    Pd-mediated Negishi cross-coupling reactions were studied by a combination of kinetic measurements, electrospray-ionization (ESI) mass spectrometry, (31)P NMR and UV/Vis spectroscopy. The kinetic measurements point to a rate-determining oxidative addition. Surprisingly, this step seems to involve not only the Pd catalyst and the aryl halide substrate, but also the organozinc reagent. In this context, the ESI-mass spectrometric observation of heterobimetallic Pd-Zn complexes [L2 PdZnR](+) (L=S-PHOS, R=Bu, Ph, Bn) is particularly revealing. The inferred presence of these and related neutral complexes with a direct Pd-Zn interaction in solution explains how the organozinc reagent can modulate the reactivity of the Pd catalyst. Previous theoretical calculations by González-Pérez et al. (Organometallics- 2012, 31, 2053) suggest that the complexation by the organozinc reagent lowers the activity of the Pd catalyst. Presumably, a similar effect also causes the rate decrease observed upon addition of ZnBr2 . In contrast, added LiBr apparently counteracts the formation of Pd-Zn complexes and restores the high activity of the Pd catalyst. At longer reaction times, deactivation processes due to degradation of the S-PHOS ligand and aggregation of the Pd catalyst come into play, thus further contributing to the appreciable complexity of the title reaction.

  7. β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle

    PubMed Central

    Nuber, Susanne; Zabel, Ulrike; Lorenz, Kristina; Nuber, Andreas; Milligan, Graeme; Tobin, Andrew B.; Lohse, Martin J.; Hoffmann, Carsten

    2016-01-01

    (β-)Arrestins are important regulators of G-protein-coupled receptors (GPCRs)1–3. They bind to active, phosphorylated GPCRs and thereby shut off ‘classical’ signalling to G proteins3,4, trigger internalization of GPCRs via interaction with the clathrin machinery5–7 and mediate signalling via ‘non-classical’ pathways1,2. In addition to two visual arrestins that bind to rod and cone photoreceptors (termed arrestin1 and arrestin4), there are only two (non-visual) β-arrestin proteins (β-arrestin1 and β-arrestin2, also termed arrestin2 and arrestin3), which regulate hundreds of different (non-visual) GPCRs. Binding of these proteins to GPCRs usually requires the active form of the receptors plus their phosphorylation by G-protein-coupled receptor kinases (GRKs)1,3,4. The binding of receptors or their carboxy terminus as well as certain truncations induce active conformations of (β-)arrestins that have recently been solved by X-ray crystallography8–10. Here we investigate both the interaction of β-arrestin with GPCRs, and the β-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET)-based β-arrestin2 biosensors. We observe receptor-specific patterns of conformational changes in β-arrestin2 that occur rapidly after the receptor–β-arrestin2 interaction. After agonist removal, these changes persist for longer than the direct receptor interaction. Our data indicate a rapid, receptor-type-specific, two-step binding and activation process between GPCRs and β-arrestins. They further indicate that β-arrestins remain active after dissociation from receptors, allowing them to remain at the cell surface and presumably signal independently. Thus, GPCRs trigger a rapid, receptor-specific activation/deactivation cycle of β-arrestins, which permits their active signalling. PMID:27007855

  8. Facilitation of epileptic activity during sleep is mediated by high amplitude slow waves.

    PubMed

    Frauscher, Birgit; von Ellenrieder, Nicolás; Ferrari-Marinho, Taissa; Avoli, Massimo; Dubeau, François; Gotman, Jean

    2015-06-01

    Epileptic discharges in focal epilepsy are frequently activated during non-rapid eye movement sleep. Sleep slow waves are present during this stage and have been shown to include a deactivated ('down', hyperpolarized) and an activated state ('up', depolarized). The 'up' state enhances physiological rhythms, and we hypothesize that sleep slow waves and particularly the 'up' state are the specific components of non-rapid eye movement sleep that mediate the activation of epileptic activity. We investigated eight patients with pharmaco-resistant focal epilepsies who underwent combined scalp-intracerebral electroencephalography for diagnostic evaluation. We analysed 259 frontal electroencephalographic channels, and manually marked 442 epileptic spikes and 8487 high frequency oscillations during high amplitude widespread slow waves, and during matched control segments with low amplitude widespread slow waves, non-widespread slow waves or no slow waves selected during the same sleep stages (total duration of slow wave and control segments: 49 min each). During the slow waves, spikes and high frequency oscillations were more frequent than during control segments (79% of spikes during slow waves and 65% of high frequency oscillations, both P ∼ 0). The spike and high frequency oscillation density also increased for higher amplitude slow waves. We compared the density of spikes and high frequency oscillations between the 'up' and 'down' states. Spike and high frequency oscillation density was highest during the transition from the 'up' to the 'down' state. Interestingly, high frequency oscillations in channels with normal activity expressed a different peak at the transition from the 'down' to the 'up' state. These results show that the apparent activation of epileptic discharges by non-rapid eye movement sleep is not a state-dependent phenomenon but is predominantly associated with specific events, the high amplitude widespread slow waves that are frequent, but not

  9. Facilitation of epileptic activity during sleep is mediated by high amplitude slow waves

    PubMed Central

    von Ellenrieder, Nicolás; Ferrari-Marinho, Taissa; Avoli, Massimo; Dubeau, François; Gotman, Jean

    2015-01-01

    Epileptic discharges in focal epilepsy are frequently activated during non-rapid eye movement sleep. Sleep slow waves are present during this stage and have been shown to include a deactivated (‘down’, hyperpolarized) and an activated state (‘up’, depolarized). The ‘up’ state enhances physiological rhythms, and we hypothesize that sleep slow waves and particularly the ‘up’ state are the specific components of non-rapid eye movement sleep that mediate the activation of epileptic activity. We investigated eight patients with pharmaco-resistant focal epilepsies who underwent combined scalp-intracerebral electroencephalography for diagnostic evaluation. We analysed 259 frontal electroencephalographic channels, and manually marked 442 epileptic spikes and 8487 high frequency oscillations during high amplitude widespread slow waves, and during matched control segments with low amplitude widespread slow waves, non-widespread slow waves or no slow waves selected during the same sleep stages (total duration of slow wave and control segments: 49 min each). During the slow waves, spikes and high frequency oscillations were more frequent than during control segments (79% of spikes during slow waves and 65% of high frequency oscillations, both P ∼ 0). The spike and high frequency oscillation density also increased for higher amplitude slow waves. We compared the density of spikes and high frequency oscillations between the ‘up’ and ‘down’ states. Spike and high frequency oscillation density was highest during the transition from the ‘up’ to the ‘down’ state. Interestingly, high frequency oscillations in channels with normal activity expressed a different peak at the transition from the ‘down’ to the ‘up’ state. These results show that the apparent activation of epileptic discharges by non-rapid eye movement sleep is not a state-dependent phenomenon but is predominantly associated with specific events, the high amplitude widespread slow

  10. Nonlinear analysis and modeling of cortical activation and deactivation patterns in the immature fetal electrocorticogram

    NASA Astrophysics Data System (ADS)

    Schwab, Karin; Groh, Tobias; Schwab, Matthias; Witte, Herbert

    2009-03-01

    An approach combining time-continuous nonlinear stability analysis and a parametric bispectral method was introduced to better describe cortical activation and deactivation patterns in the immature fetal electroencephalogram (EEG). Signal models and data-driven investigations were performed to find optimal parameters of the nonlinear methods and to confirm the occurrence of nonlinear sections in the fetal EEG. The resulting measures were applied to the in utero electrocorticogram (ECoG) of fetal sheep at 0.7 gestation when organized sleep states were not developed and compared to previous results at 0.9 gestation. Cycling of the nonlinear stability of the fetal ECoG occurred already at this early gestational age, suggesting the presence of premature sleep states. This was accompanied by cycling of the time-variant biamplitude which reflected ECoG synchronization effects during premature sleep states associated with nonrapid eye movement sleep later in gestation. Thus, the combined nonlinear and time-variant approach was able to provide important insights into the properties of the immature fetal ECoG.

  11. Deactivation of Building 7602

    SciTech Connect

    Yook, H.R.; Barnett, J.R.; Collins, T.L.

    1995-10-01

    The Department of Energy (DOE) has sponsored research and development programs in Building 7602 at Oak Ridge National Laboratory (ORNL) since 1984. This work focused on development of advanced technology for processing nuclear fuels. Building 7602 was used for engineering-scale tests using depleted and natural uranium to simulate the nuclear fuel. In April 1994 the DOE Office of Nuclear Energy (NE) sent supplemental FY 1994 guidance to ORNL stating that in FY 1995 and beyond, Building 7602 is considered surplus to NE programs and missions and shall be shut down (deactivated) and maintained in a radiologically and industrially safe condition with minimal surveillance and maintenance (S&M). DOE-NE subsequently provided FY 1995 funding to support the deactivation activities. Deactivation of Building 7602 was initiated on October 1, 1994. The principal activity during the first quarter of FY 1995 was removal of process materials (chemicals and uranium) from the systems. The process systems were operated to achieve chemical solution concentrations needed for reuse or disposal of the solutions prior to removal of the materials from the systems. During this phase of deactivation the process materials processed and removed were: (1) Uranyl nitrate solution 30,178 L containing 4490 kg of uranium; (2) Nitric acid (neutralized) 9850 L containing less than 0.013 kg of uranium; (3) Organic solution 3346 L containing 265 kg of uranium; (4) Uranium oxide powder 95 kg; and (5) Miscellaneous chemicals. At the end of December 1994, the process systems and control systems were shut down and deactivated. Disposition of the process materials removed from the process systems in Building 7602 proved to be the most difficult part of the deactivation. An operational stand down and funding reductions at Y-12 prevented planned conversion of the uranyl nitrate solution to depleted uranium oxide powder. This led to disposal of the uranyl nitrate solution as waste.

  12. Neurosteroid prolongs GABAA channel deactivation by altering kinetics of desensitized states.

    PubMed

    Zhu, W J; Vicini, S

    1997-06-01

    Fast applications of GABA (1 mM) to nucleated and outside-out patches excised from granule neurons in cerebellar slices from developing rats evoked currents with a double exponential time course reminiscent of that of IPSCs. A neurosteroid 3alpha, 21dihydroxy-5alpha-pregnan-20-one (THDOC) remarkably increased the slow deactivation time constant and slowed down recovery from desensitization, as estimated by paired-pulse GABA applications. THDOC also reduced the amplitude of GABA currents, whereas it failed to affect the fast deactivation component and its relative contribution to peak amplitude. The effects of THDOC on slow deactivation were greater in rats younger than postnatal day 13 (P13) as compared with rats at P30-P35. THDOC failed to alter deactivation of short responses induced by a less-potent agonist taurine at saturating doses. These responses had deactivation kinetics described by a fast single exponential decay, little desensitization, and quick recovery. However, THDOC slowed deactivation if taurine responses were long enough to allow consistent desensitization, suggesting that desensitized states are required for the neurosteroid to modulate GABA responses. In outside-out patches, just as desensitized states prolonged GABA responses by producing reopening of channels activated by brief GABA pulses, THDOC increased the channel open probability by further increasing the number of late channel openings, resulting in a prolongation of the slow deactivation. Our data suggest that neurosteroid potentiates the inhibitory postsynaptic transmission via the prolongation of the slow deactivation and that the alteration of kinetics of entry and exit from desensitized states underlies the allosteric modification of GABAA receptors by neurosteroids.

  13. Psychosocial versus physiological stress – meta-analyses on deactivations and activations of the neural correlates of stress reactions

    PubMed Central

    Kogler, Lydia; Mueller, Veronika I.; Chang, Amy; Eickhoff, Simon B.; Fox, Peter T.; Gur, Ruben C.; Derntl, Birgit

    2015-01-01

    Stress is present in everyday life in various forms and situations. Two stressors frequently investigated are physiological and psychosocial stress. Besides similar subjective and hormonal responses, it has been suggested that they also share common neural substrates. The current study used activation-likelihood-estimation meta-analysis to test this assumption by integrating results of previous neuroimaging studies on stress processing. Reported results are cluster-level FWE corrected. The inferior frontal gyrus (IFG) and the anterior insula (AI) were the only regions that demonstrated overlapping activation for both stressors. Analysis of physiological stress showed consistent activation of cognitive and affective components of pain processing such as the insula, striatum, or the middle cingulate cortex. Contrarily, analysis across psychosocial stress revealed consistent activation of the right superior temporal gyrus and deactivation of the striatum. Notably, parts of the striatum appeared to be functionally specified: the dorsal striatum was activated in physiological stress, whereas the ventral striatum was deactivated in psychosocial stress. Additional functional connectivity and decoding analyses further characterized this functional heterogeneity and revealed higher associations of the dorsal striatum with motor regions and of the ventral striatum with reward processing. Based on our meta-analytic approach, activation of the IFG and the AI seems to indicate a global neural stress reaction. While physiological stress activates a motoric fight-or-flight reaction, during psychosocial stress attention is shifted towards emotion regulation and goal-directed behavior, and reward processing is reduced. Our results show the significance of differentiating physiological and psychosocial stress in neural engagement. Furthermore, the assessment of deactivations in addition to activations in stress research is highly recommended. PMID:26123376

  14. Novel method demonstrates differential ligand activation and phosphatase-mediated deactivation of insulin receptor tyrosine-specific phosphorylation.

    PubMed

    Cieniewicz, Anne M; Cooper, Philip R; McGehee, Jennifer; Lingham, Russell B; Kihm, Anthony J

    2016-08-01

    Insulin receptor signaling is a complex cascade leading to a multitude of intracellular functional responses. Three natural ligands, insulin, IGF1 and IGF2, are each capable of binding with different affinities to the insulin receptor, and result in variable biological responses. However, it is likely these affinity differences alone cannot completely explain the myriad of diverse cellular outcomes. Ligand binding initiates activation of a signaling cascade resulting in phosphorylation of the IR itself and other intracellular proteins. The direct catalytic activity along with the temporally coordinated assembly of signaling proteins is critical for insulin receptor signaling. We hypothesized that determining differential phosphorylation among individual tyrosine sites activated by ligand binding or dephosphorylation by phosphatases could provide valuable insight into insulin receptor signaling. Here, we present a sensitive, novel immunoassay adapted from Meso Scale Discovery technology to quantitatively measure changes in site-specific phosphorylation levels on endogenous insulin receptors from HuH7 cells. We identified insulin receptor phosphorylation patterns generated upon differential ligand activation and phosphatase-mediated deactivation. The data demonstrate that insulin, IGF1 and IGF2 elicit different insulin receptor phosphorylation kinetics and potencies that translate to downstream signaling. Furthermore, we show that insulin receptor deactivation, regulated by tyrosine phosphatases, occurs distinctively across specific tyrosine residues. In summary, we present a novel, quantitative and high-throughput assay that has uncovered differential ligand activation and site-specific deactivation of the insulin receptor. These results may help elucidate some of the insulin signaling mechanisms, discriminate ligand activity and contribute to a better understanding of insulin receptor signaling. We propose this methodology as a powerful approach to characterize

  15. Patterns of activation and de-activation associated with cue-guided spatial navigation: A whole-brain, voxel-based study.

    PubMed

    Salgado-Pineda, Pilar; Landin-Romero, Ramón; Pomes, Ausias; Spanlang, Bernhard; Sarró, Salvador; Salvador, Raymond; Slater, Mel; McKenna, Peter J; Pomarol-Clotet, Edith

    2017-09-01

    Functional imaging studies have implicated the hippocampus and parahippocampal gyrus in cue-guided spatial navigation, but also many other regions. Furthermore, little is known about de-activations that take place during performance of navigation tasks, something that is of interest given that the hippocampus is a component of the default mode network, which de-activates during attention-demanding tasks. In this study 22 healthy subjects underwent whole-brain functional Magnetic Resonance Imaging (fMRI) while they navigated toward a previously learned goal in a virtual reality environment. At a threshold of p<0.05 corrected, the subjects showed a pattern of widespread cortical activations, including the parahippocampal and retrosplenial cortex and also parts of the frontal, temporal and occipital cortex. Hippocampal activation, however, was restricted to the posterior portion of the structure bilaterally. De-activations were seen in the medial frontal cortex and other regions of the default mode network, but not in the posterior cingulate cortex/precuneus. The findings support the involvement of the hippocampus in cue-guided navigation, but suggest that its posterior regions are particularly important. Cue-guided spatial navigation is associated with de-activation in some but not all parts of the default mode network. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Probing the Mechanism of the Double C—H (De)Activation Route of a Ru-Based Olefin Metathesis Catalyst

    NASA Astrophysics Data System (ADS)

    Poater, Albert; Cavallo, Luigi

    A theoretical study of a double C—H activation mechanism that deactivates a family of second generation Ru-based catalysts is presented. DFT calculations are used to rationalize the complex mechanistic pathway from the starting precatalyst to the experimentally characterized decomposition products. In particular, we show that all the intermediates proposed by Grubbs and coworkers are indeed possible intermediates in the deactivation pathway, although the sequence of steps is somewhat different

  17. Rationalizing current strategies to protect N-heterocyclic carbene-based ruthenium catalysts active in olefin metathesis from C-H (de)activation.

    PubMed

    Poater, Albert; Bahri-Laleh, Naeimeh; Cavallo, Luigi

    2011-06-21

    Defending second generation Ru-catalysts in olefin metathesis from C-H (de)activation reactions requires precise catalyst design strategies. Computer simulations are used here to rationalize precisely the role of the currently used catalyst structural modifications, and the way these modifications cooperate.

  18. The Orosomucoid 1 protein is involved in the vitamin D – mediated macrophage de-activation process

    SciTech Connect

    Gemelli, Claudia; Martello, Andrea; Montanari, Monica; Zanocco Marani, Tommaso; Salsi, Valentina; Zappavigna, Vincenzo; Parenti, Sandra; Vignudelli, Tatiana; Selmi, Tommaso; Ferrari, Sergio; Grande, Alexis

    2013-12-10

    Orosomucoid 1 (ORM1), also named Alpha 1 acid glycoprotein A (AGP-A), is an abundant plasma protein characterized by anti-inflammatory and immune-modulating properties. The present study was designed to identify a possible correlation between ORM1 and Vitamin D3 (1,25(OH)2D3), a hormone exerting a widespread effect on cell proliferation, differentiation and regulation of the immune system. In particular, the data described here indicated that ORM1 is a 1,25(OH)2D3 primary response gene, characterized by the presence of a VDRE element inside the 1 kb sequence of its proximal promoter region. This finding was demonstrated with gene expression studies, Chromatin Immunoprecipitation and luciferase transactivation experiments and confirmed by VDR full length and dominant negative over-expression. In addition, several experiments carried out in human normal monocytes demonstrated that the 1,25(OH)2D3 – VDR – ORM1 pathway plays a functional role inside the macrophage de-activation process and that ORM1 may be considered as a signaling molecule involved in the maintenance of tissue homeostasis and remodeling. - Highlights: • ORM1 is a Vitamin D primary response gene. • VD and its receptor VDR are involved in the de-activation process mediated by human resident macrophages. • The signaling pathway VD-VDR-ORM1 plays an important role in the control of macrophage de-activation process. • ORM1 may be defined as a signaling molecule implicated in the maintenance of tissue homeostasis and remodeling.

  19. Rac1 is deactivated at integrin activation sites through an IQGAP1–filamin-A–RacGAP1 pathway

    PubMed Central

    Jacquemet, Guillaume; Morgan, Mark R.; Byron, Adam; Humphries, Jonathan D.; Choi, Colin K.; Chen, Christopher S.; Caswell, Patrick T.; Humphries, Martin J.

    2013-01-01

    Summary Cell migration makes a fundamental contribution to both normal physiology and disease pathogenesis. Integrin engagement with extracellular ligands spatially controls, via the cyclical activation and deactivation of the small GTPase Rac1, the dynamic membrane protrusion and cytoskeletal reorganization events that are required for directional migration. Although the pathways that control integrin-mediated Rac1 activation are reasonably well defined, the mechanisms that are responsible for switching off activity are poorly understood. Here, proteomic analysis of activated integrin-associated complexes suggests filamin-A and IQ-motif-containing GTPase-activating protein 1 (IQGAP1) as candidates that link β1 integrin to Rac1. siRNA-mediated knockdown of either filamin-A or IQGAP1 induced high, dysregulated Rac1 activity during cell spreading on fibronectin. Using immunoprecipitation and immunocytochemistry, filamin-A and IQGAP1 were shown to be part of a complex that is recruited to active β1 integrin. Mass spectrometric analysis of individual filamin-A, IQGAP1 and Rac1 pull-downs and biochemical analysis, identified RacGAP1 as a novel IQGAP1 binding partner. Further immunoprecipitation and immunocytochemistry analyses demonstrated that RacGAP1 is recruited to IQGAP1 and active β1 integrin, and that suppression of RacGAP1 expression triggered elevated Rac1 activity during spreading on fibronectin. Consistent with these findings, reduced expression of filamin-A, IQGAP1 or RacGAP1 triggered unconstrained membrane protrusion and disrupted directional cell migration on fibrillar extracellular matrices. These findings suggest a model whereby integrin engagement, followed by filamin-A, IQGAP1 and RacGAP1 recruitment, deactivates Rac1 to constrain its activity spatially and thereby coordinate directional cell migration. PMID:23843620

  20. Photoluminescence study of time- and spatial-dependent light induced trap de-activation in CH3NH3PbI3 perovskite films.

    PubMed

    Fu, Xiao; Jacobs, Daniel A; Beck, Fiona J; Duong, The; Shen, Heping; Catchpole, Kylie R; White, Thomas P

    2016-08-10

    Organometal halide perovskite-based solar cells have rapidly achieved high efficiency in recent years. However, many fundamental recombination mechanisms underlying the excellent performance are still not well understood. Here we apply confocal photoluminescence microscopy to investigate the time and spatial characteristics of light-induced trap de-activation in CH3NH3PbI3 perovskite films. Trap de-activation is characterized by a dramatic increase in PL emission during continuous laser illumination accompanied by a lateral expansion of the PL enhancement far beyond the laser spot. These observations are attributed to an oxygen-assisted trap de-activation process associated with carrier diffusion. To model this effect, we add a trap de-activation term to the standard semiconductor carrier recombination and diffusion models. With this approach we are able to reproduce the observed temporal and spatial dependence of laser induced PL enhancement using realistic physical parameters. Furthermore, we experimentally investigate the role of trap diffusion in this process, and demonstrate that the trap de-activation is not permanent, with the traps appearing again once the illumination is turned off. This study provides new insights into recombination and trap dynamics in perovskite films that could offer a better understanding of perovskite solar cell performance.

  1. Can the use of deactivated glass fibre filters eliminate sorption artefacts associated with active air sampling of perfluorooctanoic acid?

    PubMed

    Johansson, Jana H; Berger, Urs; Cousins, Ian T

    2017-05-01

    Experimental work was undertaken to test whether gaseous perfluorooctanoic acid (PFOA) sorbs to glass fibre filters (GFFs) during air sampling, causing an incorrect measure of the gas-particle equilibrium distribution. Furthermore, tests were performed to investigate whether deactivation by siliconisation prevents sorption of gaseous PFOA to filter materials. An apparatus was constructed to closely simulate a high-volume air sampler, although with additional features allowing introduction of gaseous test compounds into an air stream stripped from particles. The set-up enabled investigation of the sorption of gaseous test compounds to filter media, eliminating any contribution from particles. Experiments were performed under ambient outdoor air conditions at environmentally relevant analyte concentrations. The results demonstrate that gaseous PFOA sorbs to GFFs, but that breakthrough of gaseous PFOA on the GFFs occurs at trace-level loadings. This indicates that during high volume air sampling, filters do not quantitatively capture all the PFOA in the sampled air. Experiments with siliconised GFFs showed that this filter pre-treatment reduced the sorption of gaseous PFOA, but that sorption still occurred at environmentally relevant air concentrations. We conclude that deactivation of GFFs does not allow for the separation of gaseous and particle bound perfluorinated carboxylic acids (PFCAs) during active air sampling. Consequently, the well-recognised theory that PFCAs do not prevail as gaseous species in the atmosphere may be based on biased measurements. Caution should be taken to ensure that this artefact will not bias the conclusions of future field studies.

  2. Rhodopsin-stimulated activation-deactivation cycle of transducin: kinetics of the intrinsic fluorescence response of the alpha subunit.

    PubMed

    Guy, P M; Koland, J G; Cerione, R A

    1990-07-31

    The intrinsic tryptophan fluorescence of the alpha subunit of transducin (alpha T) has been shown to be sensitive to the binding of guanine nucleotides, with the fluorescence being enhanced by as much as 2-fold upon the binding of GTP or nonhydrolyzable GTP analogues [cf. Phillips and Cerione (1988) J. Biol. Chem. 263, 15498-15505]. In this work, we have used these fluorescence changes to analyze the kinetics for the activation (GTP binding)-deactivation (GTPase) cycle of transducin in a well-defined reconstituted phospholipid vesicle system containing purified rhodopsin and the alpha T and beta gamma T subunits of the retinal GTP-binding protein. Both the rate and the extent of the GTP-induced fluorescence enhancement are dependent on [rhodopsin], while only the rate (and not the extent) of the GTP gamma S-induced enhancement is dependent on the levels of rhodopsin. Comparisons of the fluorescence enhancements elicited by GTP gamma S and GTP indicate that the GTP gamma S-induced enhancements directly reflect the GTP gamma S-binding event while the GTP-induced enhancements represent a composite of the GTP-binding and GTP hydrolysis events. At high [rhodopsin], the rates for GTP binding and GTPase are sufficiently different such that the GTP-induced enhancement essentially reflects GTP binding. A fluorescence decay, which always follows the GTP-induced enhancement, directly reflects the GTP hydrolytic event. The rate of the fluorescence decay matches the rate of [32P]Pi production due to [gamma-32P]GTP hydrolysis, and the decay is immediately reversed by rechallenging with GTP. The GTP-induced fluorescence changes (i.e., the enhancement and ensuing decay) could be fit to a simple model describing the activation-deactivation cycle of transducin. The results of this modeling suggest the following points: (1) the dependency of the activation-deactivation cycle on [rhodopsin] can be described by a simple dose response profile; (2) the rate of the rhodopsin

  3. Spontaneous neural activity during human slow wave sleep

    PubMed Central

    Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Albouy, Geneviève; Boly, Mélanie; Darsaud, Annabelle; Gais, Steffen; Rauchs, Géraldine; Sterpenich, Virginie; Vandewalle, Gilles; Carrier, Julie; Moonen, Gustave; Balteau, Evelyne; Degueldre, Christian; Luxen, André; Phillips, Christophe; Maquet, Pierre

    2008-01-01

    Slow wave sleep (SWS) is associated with spontaneous brain oscillations that are thought to participate in sleep homeostasis and to support the processing of information related to the experiences of the previous awake period. At the cellular level, during SWS, a slow oscillation (<1 Hz) synchronizes firing patterns in large neuronal populations and is reflected on electroencephalography (EEG) recordings as large-amplitude, low-frequency waves. By using simultaneous EEG and event-related functional magnetic resonance imaging (fMRI), we characterized the transient changes in brain activity consistently associated with slow waves (>140 μV) and delta waves (75–140 μV) during SWS in 14 non-sleep-deprived normal human volunteers. Significant increases in activity were associated with these waves in several cortical areas, including the inferior frontal, medial prefrontal, precuneus, and posterior cingulate areas. Compared with baseline activity, slow waves are associated with significant activity in the parahippocampal gyrus, cerebellum, and brainstem, whereas delta waves are related to frontal responses. No decrease in activity was observed. This study demonstrates that SWS is not a state of brain quiescence, but rather is an active state during which brain activity is consistently synchronized to the slow oscillation in specific cerebral regions. The partial overlap between the response pattern related to SWS waves and the waking default mode network is consistent with the fascinating hypothesis that brain responses synchronized by the slow oscillation restore microwake-like activity patterns that facilitate neuronal interactions. PMID:18815373

  4. Spontaneous neural activity during human slow wave sleep.

    PubMed

    Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Albouy, Geneviève; Boly, Mélanie; Darsaud, Annabelle; Gais, Steffen; Rauchs, Géraldine; Sterpenich, Virginie; Vandewalle, Gilles; Carrier, Julie; Moonen, Gustave; Balteau, Evelyne; Degueldre, Christian; Luxen, André; Phillips, Christophe; Maquet, Pierre

    2008-09-30

    Slow wave sleep (SWS) is associated with spontaneous brain oscillations that are thought to participate in sleep homeostasis and to support the processing of information related to the experiences of the previous awake period. At the cellular level, during SWS, a slow oscillation (<1 Hz) synchronizes firing patterns in large neuronal populations and is reflected on electroencephalography (EEG) recordings as large-amplitude, low-frequency waves. By using simultaneous EEG and event-related functional magnetic resonance imaging (fMRI), we characterized the transient changes in brain activity consistently associated with slow waves (>140 microV) and delta waves (75-140 microV) during SWS in 14 non-sleep-deprived normal human volunteers. Significant increases in activity were associated with these waves in several cortical areas, including the inferior frontal, medial prefrontal, precuneus, and posterior cingulate areas. Compared with baseline activity, slow waves are associated with significant activity in the parahippocampal gyrus, cerebellum, and brainstem, whereas delta waves are related to frontal responses. No decrease in activity was observed. This study demonstrates that SWS is not a state of brain quiescence, but rather is an active state during which brain activity is consistently synchronized to the slow oscillation in specific cerebral regions. The partial overlap between the response pattern related to SWS waves and the waking default mode network is consistent with the fascinating hypothesis that brain responses synchronized by the slow oscillation restore microwake-like activity patterns that facilitate neuronal interactions.

  5. GlialCAM, a CLC-2 Cl(-) channel subunit, activates the slow gate of CLC chloride channels.

    PubMed

    Jeworutzki, Elena; Lagostena, Laura; Elorza-Vidal, Xabier; López-Hernández, Tania; Estévez, Raúl; Pusch, Michael

    2014-09-02

    GlialCAM, a glial cell adhesion molecule mutated in megalencephalic leukoencephalopathy with subcortical cysts, targets the CLC-2 Cl(-) channel to cell contacts in glia and activates CLC-2 currents in vitro and in vivo. We found that GlialCAM clusters all CLC channels at cell contacts in vitro and thus studied GlialCAM interaction with CLC channels to investigate the mechanism of functional activation. GlialCAM slowed deactivation kinetics of CLC-Ka/barttin channels and increased CLC-0 currents opening the common gate and slowing its deactivation. No functional effect was seen for common gate deficient CLC-0 mutants. Similarly, GlialCAM targets the common gate deficient CLC-2 mutant E211V/H816A to cell contacts, without altering its function. Thus, GlialCAM is able to interact with all CLC channels tested, targeting them to cell junctions and activating them by stabilizing the open configuration of the common gate. These results are important to better understand the physiological role of GlialCAM/CLC-2 interaction.

  6. Rhodopsin-stimulated activation-deactivation cycle of transducin: Kinetics of the intrinsic fluorescence response of the alpha subunit

    SciTech Connect

    Guy, P.M.; Koland, J.G.; Cerione, R.A. )

    1990-07-31

    The intrinsic tryptophan fluorescence of the alpha subunit of transducin (alpha T) has been shown to be sensitive to the binding of guanine nucleotides, with the fluorescence being enhanced by as much as 2-fold upon the binding of GTP or nonhydrolyzable GTP analogues. In this work, we have used these fluorescence changes to analyze the kinetics for the activation (GTP binding)-deactivation (GTPase) cycle of transducin in a well-defined reconstituted phospholipid vesicle system containing purified rhodopsin and the alpha T and beta gamma T subunits of the retinal GTP-binding protein. Both the rate and the extent of the GTP-induced fluorescence enhancement are dependent on (rhodopsin), while only the rate (and not the extent) of the GTP gamma S-induced enhancement is dependent on the levels of rhodopsin. Comparisons of the fluorescence enhancements elicited by GTP gamma S and GTP indicate that the GTP gamma S-induced enhancements directly reflect the GTP gamma S-binding event while the GTP-induced enhancements represent a composite of the GTP-binding and GTP hydrolysis events. At high (rhodopsin), the rates for GTP binding and GTPase are sufficiently different such that the GTP-induced enhancement essentially reflects GTP binding. A fluorescence decay, which always follows the GTP-induced enhancement, directly reflects the GTP hydrolytic event. The rate of the fluorescence decay matches the rate of (32P)Pi production due to (gamma-32P)GTP hydrolysis, and the decay is immediately reversed by rechallenging with GTP. The GTP-induced fluorescence changes (i.e., the enhancement and ensuing decay) could be fit to a simple model describing the activation-deactivation cycle of transducin.

  7. Laminar analysis of slow wave activity in humans

    PubMed Central

    Csercsa, Richárd; Dombovári, Balázs; Fabó, Dániel; Wittner, Lucia; Erőss, Loránd; Entz, László; Sólyom, András; Rásonyi, György; Szűcs, Anna; Kelemen, Anna; Jakus, Rita; Juhos, Vera; Grand, László; Magony, Andor; Halász, Péter; Freund, Tamás F.; Maglóczky, Zsófia; Cash, Sydney S.; Papp, László; Karmos, György; Halgren, Eric

    2010-01-01

    Brain electrical activity is largely composed of oscillations at characteristic frequencies. These rhythms are hierarchically organized and are thought to perform important pathological and physiological functions. The slow wave is a fundamental cortical rhythm that emerges in deep non-rapid eye movement sleep. In animals, the slow wave modulates delta, theta, spindle, alpha, beta, gamma and ripple oscillations, thus orchestrating brain electrical rhythms in sleep. While slow wave activity can enhance epileptic manifestations, it is also thought to underlie essential restorative processes and facilitate the consolidation of declarative memories. Animal studies show that slow wave activity is composed of rhythmically recurring phases of widespread, increased cortical cellular and synaptic activity, referred to as active- or up-state, followed by cellular and synaptic inactivation, referred to as silent- or down-state. However, its neural mechanisms in humans are poorly understood, since the traditional intracellular techniques used in animals are inappropriate for investigating the cellular and synaptic/transmembrane events in humans. To elucidate the intracortical neuronal mechanisms of slow wave activity in humans, novel, laminar multichannel microelectrodes were chronically implanted into the cortex of patients with drug-resistant focal epilepsy undergoing cortical mapping for seizure focus localization. Intracortical laminar local field potential gradient, multiple-unit and single-unit activities were recorded during slow wave sleep, related to simultaneous electrocorticography, and analysed with current source density and spectral methods. We found that slow wave activity in humans reflects a rhythmic oscillation between widespread cortical activation and silence. Cortical activation was demonstrated as increased wideband (0.3–200 Hz) spectral power including virtually all bands of cortical oscillations, increased multiple- and single-unit activity and

  8. Interneuron-mediated inhibition synchronizes neuronal activity during slow oscillation

    PubMed Central

    Chen, Jen-Yung; Chauvette, Sylvain; Skorheim, Steven; Timofeev, Igor; Bazhenov, Maxim

    2012-01-01

    The signature of slow-wave sleep in the electroencephalogram (EEG) is large-amplitude fluctuation of the field potential, which reflects synchronous alternation of activity and silence across cortical neurons. While initiation of the active cortical states during sleep slow oscillation has been intensively studied, the biological mechanisms which drive the network transition from an active state to silence remain poorly understood. In the current study, using a combination of in vivo electrophysiology and thalamocortical network simulation, we explored the impact of intrinsic and synaptic inhibition on state transition during sleep slow oscillation. We found that in normal physiological conditions, synaptic inhibition controls the duration and the synchrony of active state termination. The decline of interneuron-mediated inhibition led to asynchronous downward transition across the cortical network and broke the regular slow oscillation pattern. Furthermore, in both in vivo experiment and computational modelling, we revealed that when the level of synaptic inhibition was reduced significantly, it led to a recovery of synchronized oscillations in the form of seizure-like bursting activity. In this condition, the fast active state termination was mediated by intrinsic hyperpolarizing conductances. Our study highlights the significance of both intrinsic and synaptic inhibition in manipulating sleep slow rhythms. PMID:22641778

  9. ND3, ND1 and 39 kDa subunits are more exposed in the de-active form of bovine mitochondrial complex I

    PubMed Central

    Babot, Marion; Labarbuta, Paola; Birch, Amanda; Kee, Sara; Fuszard, Matthew; Botting, Catherine H.; Wittig, Ilka; Heide, Heinrich; Galkin, Alexander

    2014-01-01

    An intriguing feature of mitochondrial complex I from several species is the so-called A/D transition, whereby the idle enzyme spontaneously converts from the active (A) form to the de-active (D) form. The A/D transition plays an important role in tissue response to the lack of oxygen and hypoxic deactivation of the enzyme is one of the key regulatory events that occur in mitochondria during ischaemia. We demonstrate for the first time that the A/D conformational change of complex I does not affect the macromolecular organisation of supercomplexes in vitro as revealed by two types of native electrophoresis. Cysteine 39 of the mitochondrially-encoded ND3 subunit is known to become exposed upon de-activation. Here we show that even if complex I is a constituent of the I + III2 + IV (S1) supercomplex, cysteine 39 is accessible for chemical modification in only the D-form. Using lysine-specific fluorescent labelling and a DIGE-like approach we further identified two new subunits involved in structural rearrangements during the A/D transition: ND1 (MT-ND1) and 39 kDa (NDUFA9). These results clearly show that structural rearrangements during de-activation of complex I include several subunits located at the junction between hydrophilic and hydrophobic domains, in the region of the quinone binding site. De-activation of mitochondrial complex I results in concerted structural rearrangement of membrane subunits which leads to the disruption of the sealed quinone chamber required for catalytic turnover. PMID:24560811

  10. Propagated infra-slow intrinsic brain activity reorganizes across wake and slow wave sleep

    PubMed Central

    Mitra, Anish; Snyder, Abraham Z; Tagliazucchi, Enzo; Laufs, Helmut; Raichle, Marcus E

    2015-01-01

    Propagation of slow intrinsic brain activity has been widely observed in electrophysiogical studies of slow wave sleep (SWS). However, in human resting state fMRI (rs-fMRI), intrinsic activity has been understood predominantly in terms of zero-lag temporal synchrony (functional connectivity) within systems known as resting state networks (RSNs). Prior rs-fMRI studies have found that RSNs are generally preserved across wake and sleep. Here, we use a recently developed analysis technique to study propagation of infra-slow intrinsic blood oxygen level dependent (BOLD) signals in normal adults during wake and SWS. This analysis reveals marked changes in propagation patterns in SWS vs. wake. Broadly, ordered propagation is preserved within traditionally defined RSNs but lost between RSNs. Additionally, propagation between cerebral cortex and subcortical structures reverses directions, and intra-cortical propagation becomes reorganized, especially in visual and sensorimotor cortices. These findings show that propagated rs-fMRI activity informs theoretical accounts of the neural functions of sleep. DOI: http://dx.doi.org/10.7554/eLife.10781.001 PMID:26551562

  11. Propagated infra-slow intrinsic brain activity reorganizes across wake and slow wave sleep.

    PubMed

    Mitra, Anish; Snyder, Abraham Z; Tagliazucchi, Enzo; Laufs, Helmut; Raichle, Marcus E

    2015-11-09

    Propagation of slow intrinsic brain activity has been widely observed in electrophysiogical studies of slow wave sleep (SWS). However, in human resting state fMRI (rs-fMRI), intrinsic activity has been understood predominantly in terms of zero-lag temporal synchrony (functional connectivity) within systems known as resting state networks (RSNs). Prior rs-fMRI studies have found that RSNs are generally preserved across wake and sleep. Here, we use a recently developed analysis technique to study propagation of infra-slow intrinsic blood oxygen level dependent (BOLD) signals in normal adults during wake and SWS. This analysis reveals marked changes in propagation patterns in SWS vs. wake. Broadly, ordered propagation is preserved within traditionally defined RSNs but lost between RSNs. Additionally, propagation between cerebral cortex and subcortical structures reverses directions, and intra-cortical propagation becomes reorganized, especially in visual and sensorimotor cortices. These findings show that propagated rs-fMRI activity informs theoretical accounts of the neural functions of sleep.

  12. L-364,373 fails to activate the slow delayed rectifier K+ current in canine ventricular cardiomyocytes.

    PubMed

    Magyar, János; Horváth, Balázs; Bányász, Tamás; Szentandrássy, Norbert; Birinyi, Péter; Varró, András; Szakonyi, Zsolt; Fülöp, Ferenc; Nánási, Péter P

    2006-04-01

    Activators of the slow delayed rectifier K+ current (I(Ks)) are promising tools to suppress ventricular arrhythmias originating from prolongation of action potentials. A recently synthesized compound, L-364,373, was shown to activate I(Ks) in ventricular cells isolated from guinea pigs and rabbits. Due to the interspecies differences known to exist in the properties of the delayed rectifier K+ currents, the effect of L-364,373 on I(Ks) was studied and compared with that of another I(Ks) activator mefenamic acid in canine ventricular myocytes. Mefenamic acid (100 microM) significantly increased the amplitude of the fully activated I(Ks) current, as well as the I(Ks) current tails, by shifting the voltage dependence of its activation towards negative voltages and increased the time constant for deactivation. In contrast, L-364,373, up to concentrations of 3 microM, failed to augment I(Ks) at any membrane potential studied, but slightly increased the time constant of deactivation. It is concluded that human studies are required to evaluate the therapeutically beneficial effects of I(Ks) activators. Rodent cardiac tissues are not suitable for this purpose.

  13. Rapid deactivation of NADPH oxidase in neutrophils: continuous replacement by newly activated enzyme sustains the respiratory burst.

    PubMed

    Akard, L P; English, D; Gabig, T G

    1988-07-01

    The cell-free system for activation of the neutrophil NADPH oxidase allowed us to examine activation of the oxidase in the absence of its NADPH-dependent turnover. The covalent sulfhydryl-modifying reagent N-ethylmaleimide completely inhibited the activation step (Ki = 40 mumol/L) in the cell-free system but had no effect on turnover of the preactivated particulate NADPH oxidase (up to 1 mmol/L). When N-ethylmaleimide was added to intact neutrophils during the period of maximal O2 generation in response to stimuli that activate the respiratory burst (phorbol myristate acetate, f-Met-Leu-Phe, opsonized zymosan, arachidonic acid), O2- generation ceased within seconds. Study of components of the cell-free activation system indicated that the cytosolic cofactor was irreversibly inhibited by N-ethylmaleimide whereas the N-ethylmaleimide-treated, membrane-associated oxidase could be activated by arachidonate and control cytosolic cofactor. Likewise, the cell-free system prepared from intact neutrophils that had been briefly exposed to N-ethylmaleimide and then washed reflected the effects of N-ethylmaleimide on the isolated cell-free components: cytosolic cofactor activity was absent, but the membrane oxidase remained fully activatable. Thus inhibition of oxidase activation by N-ethylamaleimide unmasked a rapid deactivation step that was operative in intact neutrophils but not in isolated particulate NADPH oxidase preparations. The demonstrated specificity of N-ethylmaleimide for oxidase activation and lack of effect on turnover of the NADPH oxidase suggested that sustained O2- generation by intact neutrophils was a result of continued replenishment of a small pool of active oxidase. The existence of an inactive pool of NADPH oxidase molecules in particulate preparations from stimulated neutrophils was supported more directly by activating these preparations again in the cell-free system.

  14. Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis.

    PubMed

    Takiar, Vinita; Nishio, Saori; Seo-Mayer, Patricia; King, J Darwin; Li, Hui; Zhang, Li; Karihaloo, Anil; Hallows, Kenneth R; Somlo, Stefan; Caplan, Michael J

    2011-02-08

    Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves both fluid secretion and abnormal proliferation of cyst-lining epithelial cells. The chloride channel of the cystic fibrosis transmembrane conductance regulator (CFTR) participates in secretion of cyst fluid, and the mammalian target of rapamycin (mTOR) pathway may drive proliferation of cyst epithelial cells. CFTR and mTOR are both negatively regulated by AMP-activated protein kinase (AMPK). Metformin, a drug in wide clinical use, is a pharmacological activator of AMPK. We find that metformin stimulates AMPK, resulting in inhibition of both CFTR and the mTOR pathways. Metformin induces significant arrest of cystic growth in both in vitro and ex vivo models of renal cystogenesis. In addition, metformin administration produces a significant decrease in the cystic index in two mouse models of ADPKD. Our results suggest a possible role for AMPK activation in slowing renal cystogenesis as well as the potential for therapeutic application of metformin in the context of ADPKD.

  15. Enhanced Sympathetic Arousal in Response to fMRI Scanning Correlates with Task Induced Activations and Deactivations

    PubMed Central

    Muehlhan, Markus; Lueken, Ulrike; Siegert, Jens; Wittchen, Hans-Ulrich; Smolka, Michael N.; Kirschbaum, Clemens

    2013-01-01

    It has been repeatedly shown that functional magnetic resonance imaging (fMRI) triggers distress and neuroendocrine response systems. Prior studies have revealed that sympathetic arousal increases, particularly at the beginning of the examination. Against this background it appears likely that those stress reactions during the scanning procedure may influence task performance and neural correlates. However, the question how sympathetic arousal elicited by the scanning procedure itself may act as a potential confounder of fMRI data remains unresolved today. Thirty-seven scanner naive healthy subjects performed a simple cued target detection task. Levels of salivary alpha amylase (sAA), as a biomarker for sympathetic activity, were assessed in samples obtained at several time points during the lab visit. SAA increased two times, immediately prior to scanning and at the end of the scanning procedure. Neural activation related to motor preparation and timing as well as task performance was positively correlated with the first increase. Furthermore, the first sAA increase was associated with task induced deactivation (TID) in frontal and parietal regions. However, these effects were restricted to the first part of the experiment. Consequently, this bias of scanner related sympathetic activation should be considered in future fMRI investigations. It is of particular importance for pharmacological investigations studying adrenergic agents and the comparison of groups with different stress vulnerabilities like patients and controls or adolescents and adults. PMID:23967320

  16. Cortical deactivation induced by subcortical network dysfunction in limbic seizures

    PubMed Central

    Englot, Dario J.; Modi, Badri; Mishra, Asht M.; DeSalvo, Matthew; Hyder, Fahmeed; Blumenfeld, Hal

    2009-01-01

    Normal human consciousness may be impaired by two possible routes: direct reduced function in widespread cortical regions, or indirect disruption of subcortical activating systems. The route through which temporal lobe limbic seizures impair consciousness is not known. We recently developed an animal model which, like human limbic seizures, exhibits neocortical deactivation including cortical slow waves and reduced cortical cerebral blood flow (CBF). We now find through functional MRI (fMRI) that electrically-stimulated hippocampal seizures in rats cause increased activity in subcortical structures including the septal area and mediodorsal thalamus, along with reduced activity in frontal, cingulate, and retrosplenial cortex. Direct recordings from the hippocampus, septum, and medial thalamus demonstrated fast poly-spike activity associated with increased neuronal firing and CBF, while frontal cortex showed slow oscillations with decreased neuronal firing and CBF. Stimulation of septal area, but not hippocampus or medial thalamus, in the absence of a seizure resulted in cortical deactivation with slow oscillations and behavioral arrest, resembling changes seen during limbic seizures. Transecting the fornix, the major route from hippocampus to subcortical structures, abolished the negative cortical and behavioral effects of seizures. Cortical slow oscillations and behavioral arrest could be reconstituted in fornix-lesioned animals by inducing synchronous activity in the hippocampus and septal area, implying involvement of a downstream region converged upon by both structures. These findings suggest that limbic seizures may cause neocortical deactivation indirectly, through impaired subcortical function. If confirmed, subcortical networks may represent a target for therapies aimed at preserving consciousness in human temporal lobe seizures. PMID:19828814

  17. Nanotube-assisted protein deactivation

    NASA Astrophysics Data System (ADS)

    Joshi, Amit; Punyani, Supriya; Bale, Shyam Sundhar; Yang, Hoichang; Borca-Tasciuc, Theodorian; Kane, Ravi S.

    2008-01-01

    Conjugating proteins onto carbon nanotubes has numerous applications in biosensing, imaging and cellular delivery. However, remotely controlling the activity of proteins in these conjugates has never been demonstrated. Here we show that upon near-infrared irradiation, carbon nanotubes mediate the selective deactivation of proteins in situ by photochemical effects. We designed nanotube-peptide conjugates to selectively destroy the anthrax toxin, and also optically transparent coatings that can self-clean following either visible or near-infrared irradiation. Nanotube-assisted protein deactivation may be broadly applicable to the selective destruction of pathogens and cells, and will have applications ranging from antifouling coatings to functional proteomics.

  18. Brain functional correlates of working memory: reduced load-modulated activation and deactivation in aging without hyperactivation or functional reorganization.

    PubMed

    Kaup, Allison R; Drummond, Sean P A; Eyler, Lisa T

    2014-10-01

    We aimed to identify brain functional correlates of working memory performance in aging, in hopes of facilitating understanding of mechanisms that promote better versus worse working memory in late-life. Among 64 healthy adults, aged 23 to 78, we examined the relationship between age, working memory performance, and brain functional response during task performance. We focused on the association between working memory load-modulated functional response and individual differences in performance and whether these function-performance relationships differed with age. As expected, older age was associated with poorer working memory performance. Older age was also associated with reduced load-modulated activation including in bilateral prefrontal and parietal regions and left caudate as well as reduced deactivation including in the medial prefrontal cortex. Contrary to findings of hyperactivation in aging, we found no evidence of increased activation with older age. Positive associations identified between brain response and performance did not differ with age. Our findings suggest that the neural mechanisms underlying better versus worse working memory performance are age-invariant across adulthood, and argue against a pattern of functional reorganization in aging. Results are discussed within the broader literature, in which significant heterogeneity in findings between studies has been common.

  19. Brain circuits for mating behavior in cats and brain activations and de-activations during sexual stimulation and ejaculation and orgasm in humans.

    PubMed

    Holstege, Gert; Huynh, Hieu K

    2011-05-01

    In cats, there exists a descending system that controls the posture necessary for mating behavior. A key role is played by the mesencephalic periaqueductal gray (PAG), which maintains strong specific projections to the nucleus retroambiguus located laterally in the most caudal medulla. The NRA, in turn, has direct access to motoneurons in the lumbosacral cord that produce the mating posture. This pathway is slightly different in males and females, but in females its strength fluctuates strongly depending on whether or not the cat is in heat. This way the PAG determines whether or not mating can take place. Via the PAG many other regions in the limbic system as well as in the prefrontal cortex and insula can influence mating behavior. In humans, the brain also controls responses to sexual stimulation as well as ejaculation in men and orgasm in women. Neuroimaging techniques show activations and de-activations but are not able to verify whether the PAG has a similar effect as in cats. PET-scanning results revealed that there is activation in the upper brainstem and cerebellum, as well as insula in men and in the somatomotor and somatosensory cortex in women. During sexual stimulation, but especially during ejaculation and orgasm there was strong de-activation mainly on the left side in the temporal lobe and ventral prefrontal cortex. These neuroimaging results show the importance of lowering the level of alertness regarding your immediate environment (left hemisphere) to have proper sexual behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Hydrogen sulfide and sodium nitroprusside compete to activate/deactivate MMPs in bone tissue homogenates.

    PubMed

    Vacek, Thomas P; Qipshidze, Natia; Tyagi, Suresh C

    2013-01-01

    Bone microvascular remodeling is the primary predictor of bone structure and function. Remodeling by its very nature implies synthesis and degradation of the extracellular matrix. Normally, 50% of total protein in the vessel wall is elastin. During remodeling, elastin is degraded by specialized matrix metalloproteinases (MMPs). Because the turnover of elastin is 1000-fold slower than that of collagen, most of the elastin is replaced by stiffer collagen. Stiffer vessels impose pressure on the aortic valve, causing regurgitation and increased pulse pressure. On the other hand, high MMP activity will cause vascular dilatation, leading to aneurysm. Therefore, balanced constitutive remodeling is necessary for adequate bone structure and function. Interestingly, collagen-degrading MMPs are involved in various pathological conditions, including osteoporosis, osteoarthritis, and cardiovascular disease. Sodium nitroprusside is a nitric oxide donor that could potentially alter MMP activity via vasodilation in vivo, but can also produce peroxynitrite, which activates MMPs by combining with superoxide. Moreover, hydrogen sulfide is a known antioxidant as well as a vasodilator, and is also speculated to contribute directly to MMP activity. We hypothesized that hydrogen sulfide reduced activity of MMP in ex vivo bone tissue homogenates and that sodium nitroprusside would increase MMP activity in vitro. We surgically removed the tibia and femur from anesthetized mice, and prepared bone tissue homogenates using a mortar and pestle, measured the protein concentration with a spectrophotometer, and detected MMP activity using gelatin gel zymography. Our data showed increased MMP activity at a sodium nitroprusside concentration of 1 μM, and MMP activity increased exponentially. There was a decrease in MMP activity with increasing hydrogen sulfide, beginning at 16 μM (P < 0.01) and continuing to 40 μM. Moreover, sodium nitroprusside 3 μM was able to overcome the decrease in MMP

  1. Activation and deactivation of a robust immobilized Cp*Ir-transfer hydrogenation catalyst: a multielement in situ X-ray absorption spectroscopy study.

    PubMed

    Sherborne, Grant J; Chapman, Michael R; Blacker, A John; Bourne, Richard A; Chamberlain, Thomas W; Crossley, Benjamin D; Lucas, Stephanie J; McGowan, Patrick C; Newton, Mark A; Screen, Thomas E O; Thompson, Paul; Willans, Charlotte E; Nguyen, Bao N

    2015-04-01

    A highly robust immobilized [Cp*IrCl2]2 precatalyst on Wang resin for transfer hydrogenation, which can be recycled up to 30 times, was studied using a novel combination of X-ray absorption spectroscopy (XAS) at Ir L3-edge, Cl K-edge, and K K-edge. These culminate in in situ XAS experiments that link structural changes of the Ir complex with its catalytic activity and its deactivation. Mercury poisoning and "hot filtration" experiments ruled out leached Ir as the active catalyst. Spectroscopic evidence indicates the exchange of one chloride ligand with an alkoxide to generate the active precatalyst. The exchange of the second chloride ligand, however, leads to a potassium alkoxide-iridate species as the deactivated form of this immobilized catalyst. These findings could be widely applicable to the many homogeneous transfer hydrogenation catalysts with Cp*IrCl substructure.

  2. Slow Magnetosonic Waves and Fast Flows in Active Region Loops

    NASA Technical Reports Server (NTRS)

    Ofman, L.; Wang, T. J.; Davila, J. M.

    2012-01-01

    Recent extreme ultraviolet spectroscopic observations indicate that slow magnetosonic waves are present in active region (AR) loops. Some of the spectral data were also interpreted as evidence of fast (approx 100-300 km/s) quasiperiodic flows. We have performed three-dimensional magnetohydrodynamic (3D MHD) modeling of a bipolar AR that contains impulsively generated waves and flows in coronal loops. The model AR is initiated with a dipole magnetic field and gravitationally stratified density, with an upflow-driven steadily or periodically in localized regions at the footpoints of magnetic loops. The resulting flows along the magnetic field lines of the AR produce higher density loops compared to the surrounding plasma by injection of material into the flux tubes and the establishment of siphon flow.We find that the impulsive onset of flows with subsonic speeds result in the excitation of damped slow magnetosonic waves that propagate along the loops and coupled nonlinearly driven fast-mode waves. The phase speed of the slow magnetosonic waves is close to the coronal sound speed. When the amplitude of the driving pulses is increased we find that slow shock-like wave trains are produced. When the upflows are driven periodically, undamped oscillations are produced with periods determined by the periodicity of the upflows. Based on the results of the 3D MHD model we suggest that the observed slow magnetosonic waves and persistent upflows may be produced by the same impulsive events at the bases of ARs.

  3. Enzyme activity of α-chymotrypsin: Deactivation by gold nano-cluster and reactivation by glutathione.

    PubMed

    Ghosh, Catherine; Mondal, Tridib; Bhattacharyya, Kankan

    2017-05-15

    Effect of gold nanoclusters (Au-NCs) on the circular dichroism (CD) spectra and enzymatic activity of α-chymotrypsin (ChT) (towards hydrolysis of a substrate, N-succinyl-l-phenylalanine p-nitroanilide) are studied. The CD spectra indicate that on binding to Au-NC, ChT is completely unfolded, resulting in nearly zero ellipticity. α-chymotrypsin (ChT) coated gold nano-clusters exhibit almost no enzymatic activity. Addition of glutathione (GSH) or oxidized glutathione (GSSG) restore the enzyme activity of α-chymotrypsin by 30-45%. ChT coated Au-NC exhibits two emission maxima-one at 480nm (corresponding to Au10) and one at 640nm (Au25). On addition of glutathione (GSH) or oxidized glutathione (GSSG) the emission peak at 640nm vanishes and only one peak at 480nm (Au10) remains. MALDI mass spectrometry studies suggest addition of glutathione (GSH) to α-chymotrypsin capped Au-NCs results in the formation of glutathione-capped Au-NCs and α-chymotrypsin is released from Au-NCs. CD spectroscopy indicates that the conformation of the released α-chymotrypsin is different from that of the native α-chymotrypsin.

  4. Intracellular Activation and Deactivation of Tasidotin, an Analog of Dolastatin 15: Correlation with Cytotoxicity

    PubMed Central

    Bai, Ruoli; Edler, Michael C.; Bonate, Peter L.; Copeland, Terry D.; Pettit, George R.; Ludueña, Richard F.; Hamel, Ernest

    2009-01-01

    Tasidotin, an oncolytic drug in phase II clinical trials, is a peptide analog of the antimitotic depsipeptide dolastatin 15. In tasidotin, the carboxyl-terminal ester group of dolastatin 15 has been replaced by a carboxy-terminal tert-butyl amide. As expected from studies with cemadotin, [3H]tasidotin, with the radiolabel in the second proline residue, was hydrolyzed intracellularly, with formation of N,N-dimethylvalyl-valyl-N-methylvalyl-prolyl-proline (P5), a pentapeptide also present in dolastatin 15 and cemadotin. P5 was more active as an inhibitor of tubulin polymerization and less active as a cytotoxic agent than tasidotin, cemadotin, and dolastatin 15. [3H]P5 was not the end product of tasidotin metabolism. Large amounts of [3H]proline were formed in every cell line studied, with proline ultimately becoming the major radiolabeled product. The putative second product of the hydrolysis of P5, N,N-dimethylvalyl-valyl-N-methylvalyl-proline (P4), had little activity as either an antitubulin or cytotoxic agent. In seven suspension cell lines, the cytotoxicity of tasidotin correlated with total cell uptake of the compound and was probably affected negatively by the extent of degradation of P5 to proline and, presumably, P4. The intracellular enzyme prolyl oligopeptidase probably degrades tasidotin to P5. When CCRF-CEM human leukemia cells were treated with N-benzyloxycarbonylprolylprolinal (BCPP), an inhibitor of prolyl oligopeptidase, there was a 30-fold increase in the IC50 of tasidotin and a marked increase in intracellular [3H]tasidotin. BCPP also caused a 4-fold increase in the IC50 of P5, so the enzyme probably does not convert P5 to P4. Inhibiting degradation of P5 should have led to a decrease in the IC50 obtained for P5 in the presence of BCPP. PMID:18927208

  5. Intracellular activation and deactivation of tasidotin, an analog of dolastatin 15: correlation with cytotoxicity.

    PubMed

    Bai, Ruoli; Edler, Michael C; Bonate, Peter L; Copeland, Terry D; Pettit, George R; Ludueña, Richard F; Hamel, Ernest

    2009-01-01

    Tasidotin, an oncolytic drug in phase II clinical trials, is a peptide analog of the antimitotic depsipeptide dolastatin 15. In tasidotin, the carboxyl-terminal ester group of dolastatin 15 has been replaced by a carboxy-terminal tert-butyl amide. As expected from studies with cemadotin, [(3)H]tasidotin, with the radiolabel in the second proline residue, was hydrolyzed intracellularly, with formation of N,N-dimethylvalyl-valyl-N-methylvalyl-prolyl-proline (P5), a pentapeptide also present in dolastatin 15 and cemadotin. P5 was more active as an inhibitor of tubulin polymerization and less active as a cytotoxic agent than tasidotin, cemadotin, and dolastatin 15. [(3)H]P5 was not the end product of tasidotin metabolism. Large amounts of [(3)H]proline were formed in every cell line studied, with proline ultimately becoming the major radiolabeled product. The putative second product of the hydrolysis of P5, N,N-dimethylvalyl-valyl-N-methylvalyl-proline (P4), had little activity as either an antitubulin or cytotoxic agent. In seven suspension cell lines, the cytotoxicity of tasidotin correlated with total cell uptake of the compound and was probably affected negatively by the extent of degradation of P5 to proline and, presumably, P4. The intracellular enzyme prolyl oligopeptidase probably degrades tasidotin to P5. When CCRF-CEM human leukemia cells were treated with N-benzyloxycarbonylprolylprolinal (BCPP), an inhibitor of prolyl oligopeptidase, there was a 30-fold increase in the IC(50) of tasidotin and a marked increase in intracellular [(3)H]tasidotin. BCPP also caused a 4-fold increase in the IC(50) of P5, so the enzyme probably does not convert P5 to P4. Inhibiting degradation of P5 should have led to a decrease in the IC(50) obtained for P5 in the presence of BCPP.

  6. An underwater superoleophobic surface that can be activated/deactivated via external triggers.

    PubMed

    Dunderdale, Gary J; Urata, Chihiro; Hozumi, Atsushi

    2014-11-11

    Poly[(2-dimethylamino)ethyl methacrylate] (pDMAEMA) brush surfaces were prepared using a facile aqueous Activators ReGenerated by Electron Transfer Atom Transfer Radical Polymerization (ARGET-ATRP) protocol at ambient temperature without any need to purge reaction solutions of oxygen. This produced underwater superoleophobic surfaces, which exhibited high advancing (θA, 164-166°) and receding (θR, 153-165°) contact angles (CAs) and low CA hysteresis (1-11°) with a variety of oils. Both in situ spectroscopic ellipsometry and dynamic CA measurements confirmed that pDMAEMA brush surfaces responded to three different external stimuli (pH, ionic strength, and temperature) by changing their thicknesses, degree of hydration, or their chemical composition. Increasing pH resulted in the largest decrease in hydration, followed by increasing temperature, and increasing ionic strength gave the smallest change in hydration. Coincident with these structural changes, stimulus-responsive dynamic dewetting behavior with various oils was observed. Increasing pH or ionic strength drastically reduced the θR values of oil drops and increased CA hysteresis, resulting in a sticky surface on which oil drops were pinned. No noticeable changes in dynamic oleophobicity were observed with increasing temperature. In addition, when oil drops impacted onto the brush surface instead of being gently placed, surfaces did not exhibit stimulus-responsive dewetting properties, being oleophobic under all conditions.

  7. Active vision system integrating fast and slow processes

    NASA Astrophysics Data System (ADS)

    Castrillon-Santana, Modesto; Guerra-Artal, C.; Hernandez-Sosa, J.; Dominguez-Brito, A.; Isern-Gonzalez, J.; Cabrera-Gamez, Jorge; Hernandez-Tejera, F. M.

    1998-10-01

    This paper describes an Active Vision System whose design assumes a distinction between fast or reactive and slow or background processes. Fast processes need to operate in cycles with critical timeouts that may affect system stability. While slow processes, though necessary, do not compromise system stability if its execution is delayed. Based on this simple taxonomy, a control architecture has been proposed and a prototype implemented that is able to track people in real-time with a robotic head while trying to identify the target. In this system, the tracking mobile is considered as the reactive part of the system while person identification is considered a background task. This demonstrator has been developed using a new generation DSP (TMS320C80) as a specialized coprocessor to deal with fast processes, and a commercial robotic head with a dedicated DSP-based motor controller. These subsystems are hosted by a standard Pentium-Pro PC running Windows NT where slow processes are executed. The flexibility achieved in the design phase and the preliminary results obtained so far seem to validate the approach followed to integrate time- critical and slow tasks on a heterogeneous hardware platform.

  8. Variance and Autocorrelation of the Spontaneous Slow Brain Activity

    PubMed Central

    Kaneoke, Yoshiki; Donishi, Tomohiro; Iwatani, Jun; Ukai, Satoshi; Shinosaki, Kazuhiro; Terada, Masaki

    2012-01-01

    Slow (<0.1 Hz) oscillatory activity in the human brain, as measured by functional magnetic imaging, has been used to identify neural networks and their dysfunction in specific brain diseases. Its intrinsic properties may also be useful to investigate brain functions. We investigated the two functional maps: variance and first order autocorrelation coefficient (r1). These two maps had distinct spatial distributions and the values were significantly different among the subdivisions of the precuneus and posterior cingulate cortex that were identified in functional connectivity (FC) studies. The results reinforce the functional segregation of these subdivisions and indicate that the intrinsic properties of the slow brain activity have physiological relevance. Further, we propose a sample size (degree of freedom) correction when assessing the statistical significance of FC strength with r1 values, which enables a better understanding of the network changes related to various brain diseases. PMID:22666461

  9. The slowed brain: cortical oscillatory activity in hepatic encephalopathy.

    PubMed

    Butz, Markus; May, Elisabeth S; Häussinger, Dieter; Schnitzler, Alfons

    2013-08-15

    Oscillatory activity of the human brain has received growing interest as a key mechanism of large-scale integration across different brain regions. Besides a crucial role of oscillatory activity in the emergence of other neurological and psychiatric diseases, recent evidence indicates a key role in the pathophysiology of hepatic encephalopathy (HE). This review summarizes the current knowledge on pathological alterations of oscillatory brain activity in association with liver dysfunction and HE in the context of spontaneous brain activity, motor symptoms, sensory processing, and attention. The existing literature demonstrates a prominent slowing of the frequency of oscillatory activity as shown for spontaneous brain activity at rest, with respect to deficits of motor behavior and motor symptoms, and in the context of visual attention processes. The observed slowing extends across different subsystems of the brain and has been confirmed across different frequency bands, providing evidence for ubiquitous changes of oscillatory activity in HE. For example, the frequency of cortico-muscular coherence in HE patients appears at the frequency of the mini-asterixis (⩽12Hz), while cirrhotics without overt signs of HE show coherence similar to healthy subjects, i.e. at 13-30Hz. Interestingly, the so-called critical flicker frequency (CFF) as a measure of the processing of an oscillating visual stimulus has emerged as a useful tool to quantify HE disease severity, correlating with behavioral and neurophysiological alterations. Moreover, the CFF reliably distinguishes patients with manifest HE from cirrhotics without any signs of HE and healthy controls using a cut-off frequency of 39Hz. In conclusion, oscillatory activity is globally slowed in HE in close association with HE symptoms and disease severity. Although the underlying causal mechanisms are not yet understood, these results indicate that pathological changes of oscillatory activity play an important role in the

  10. LBR deactivation information exchange

    SciTech Connect

    Guttenberg, S.

    1998-05-15

    This report contains vugraphs of presentations given at the meeting. The topics covered include the following: FFTF Deactivation Strategy; Sodium Drain and Disposition; Sodium Processing; and Fuel Storage and Disposition.

  11. Modeling place field activity with hierarchical slow feature analysis.

    PubMed

    Schönfeld, Fabian; Wiskott, Laurenz

    2015-01-01

    What are the computational laws of hippocampal activity? In this paper we argue for the slowness principle as a fundamental processing paradigm behind hippocampal place cell firing. We present six different studies from the experimental literature, performed with real-life rats, that we replicated in computer simulations. Each of the chosen studies allows rodents to develop stable place fields and then examines a distinct property of the established spatial encoding: adaptation to cue relocation and removal; directional dependent firing in the linear track and open field; and morphing and scaling the environment itself. Simulations are based on a hierarchical Slow Feature Analysis (SFA) network topped by a principal component analysis (ICA) output layer. The slowness principle is shown to account for the main findings of the presented experimental studies. The SFA network generates its responses using raw visual input only, which adds to its biological plausibility but requires experiments performed in light conditions. Future iterations of the model will thus have to incorporate additional information, such as path integration and grid cell activity, in order to be able to also replicate studies that take place during darkness.

  12. Modeling place field activity with hierarchical slow feature analysis

    PubMed Central

    Schönfeld, Fabian; Wiskott, Laurenz

    2015-01-01

    What are the computational laws of hippocampal activity? In this paper we argue for the slowness principle as a fundamental processing paradigm behind hippocampal place cell firing. We present six different studies from the experimental literature, performed with real-life rats, that we replicated in computer simulations. Each of the chosen studies allows rodents to develop stable place fields and then examines a distinct property of the established spatial encoding: adaptation to cue relocation and removal; directional dependent firing in the linear track and open field; and morphing and scaling the environment itself. Simulations are based on a hierarchical Slow Feature Analysis (SFA) network topped by a principal component analysis (ICA) output layer. The slowness principle is shown to account for the main findings of the presented experimental studies. The SFA network generates its responses using raw visual input only, which adds to its biological plausibility but requires experiments performed in light conditions. Future iterations of the model will thus have to incorporate additional information, such as path integration and grid cell activity, in order to be able to also replicate studies that take place during darkness. PMID:26052279

  13. Slow-light-enhanced gain in active photonic crystal waveguides

    NASA Astrophysics Data System (ADS)

    Ek, Sara; Lunnemann, Per; Chen, Yaohui; Semenova, Elizaveta; Yvind, Kresten; Mork, Jesper

    2014-09-01

    Passive photonic crystals have been shown to exhibit a multitude of interesting phenomena, including slow-light propagation in line-defect waveguides. It was suggested that by incorporating an active material in the waveguide, slow light could be used to enhance the effective gain of the material, which would have interesting application prospects, for example enabling ultra-compact optical amplifiers for integration in photonic chips. Here we experimentally investigate the gain of a photonic crystal membrane structure with embedded quantum wells. We find that by solely changing the photonic crystal structural parameters, the maximum value of the gain coefficient can be increased compared with a ridge waveguide structure and at the same time the spectral position of the peak gain be controlled. The experimental results are in qualitative agreement with theory and show that gain values similar to those realized in state-of-the-art semiconductor optical amplifiers should be attainable in compact photonic integrated amplifiers.

  14. Slow-light-enhanced gain in active photonic crystal waveguides.

    PubMed

    Ek, Sara; Lunnemann, Per; Chen, Yaohui; Semenova, Elizaveta; Yvind, Kresten; Mork, Jesper

    2014-09-30

    Passive photonic crystals have been shown to exhibit a multitude of interesting phenomena, including slow-light propagation in line-defect waveguides. It was suggested that by incorporating an active material in the waveguide, slow light could be used to enhance the effective gain of the material, which would have interesting application prospects, for example enabling ultra-compact optical amplifiers for integration in photonic chips. Here we experimentally investigate the gain of a photonic crystal membrane structure with embedded quantum wells. We find that by solely changing the photonic crystal structural parameters, the maximum value of the gain coefficient can be increased compared with a ridge waveguide structure and at the same time the spectral position of the peak gain be controlled. The experimental results are in qualitative agreement with theory and show that gain values similar to those realized in state-of-the-art semiconductor optical amplifiers should be attainable in compact photonic integrated amplifiers.

  15. PUREX Deactivation Health and Safety documentation

    SciTech Connect

    Dodd, E.N. III

    1995-01-01

    The purpose of the PUREX Deactivation Project is to establish a passively safe and environmentally secure configuration of PUREX at the Hanford Site, and to preserve that configuration for a 10-year horizon. The 10-year horizon is used to predict future maintenance requirements and represents they typical time duration expended to define, authorize, and initiate the follow-on Decontamination and Decommissioning (D&D) activities. This document was prepared to increase attention to worker safety issues during the deactivation project and, as such, identifies the documentation and programs associated with PUREX Deactivation Health and Safety.

  16. Report on First Activations with the Lead Slowing Down Spectrometer

    SciTech Connect

    Warren, Glen A.; Mace, Emily K.; Pratt, Sharon L.; Stave, Sean; Woodring, Mitchell L.

    2011-03-03

    On Feb. 17 and 18 2011, six items were irradiated with neutrons using the Lead Slowing Down Spectrometer. After irradiation, dose measurements and gamma-spectrometry measurements were completed on all of the samples. No contamination was found on the samples, and all but one provided no dose. Gamma-spectroscopy measurements qualitatively agreed with expectations based on the materials, with the exception of silver. We observed activation in the room in general, mostly due to 56Mn and 24Na. Most of the activation was short lived, with half-lives on the scale of hours, except for 198Au which has a half-life of 2.7 d.

  17. Early deactivation of slower muscle fibres at high movement frequencies.

    PubMed

    Blake, Ollie M; Wakeling, James M

    2014-10-01

    Animals produce rapid movements using fast cyclical muscle contractions. These types of movements are better suited to faster muscle fibres within muscles of mixed fibre types as they can shorten at faster velocities and achieve higher activation-deactivation rates than their slower counterparts. Preferential recruitment of faster muscle fibres has previously been shown during high velocity contractions. Additionally, muscle deactivation takes longer than activation and therefore may pose a limitation to fast cyclical contractions. It has been speculated that slower fibres may be deactivated before faster fibres to accommodate their longer deactivation time. This study aimed to test whether shifts in muscle fibre recruitment occur with derecruitment of slow fibres before faster fibres at high cycle frequencies. Electromyographic (EMG) signals were collected from the medial gastrocnemius at an extreme range of cycle frequencies and workloads. Wavelets were used to resolve the EMG signals into time and frequency space and the primary sources of variability within the EMG frequency spectra were identified through principal component analysis. Early derecruitment of slower fibres was evident at the end of muscle excitation at higher cycle frequencies, as determined by reduced low-frequency EMG content, and additional slower fibre recruitment was present at the highest cycle frequency. The duration of muscle excitation reached a minimum of about 150 ms and did not change for the three highest cycle frequencies, suggesting a duration limit for the medial gastrocnemius. This study provides further evidence of modifications of muscle fibre recruitment strategies to meet the mechanical demands of movement. © 2014. Published by The Company of Biologists Ltd.

  18. Environmental Assessment for Malmstrom Minuteman III Deactivation

    DTIC Science & Technology

    2007-05-01

    deactivation process is scheduled to be completed within a 2-year time period and would occur in three phases. Phase 1 involves the removal of the missiles...of deactivation activities, the LFs and MAFs would be subject to periodic drive-by inspections to identify vandalism, unauthorized entry, topside...flooding, or excessive weed growth. The Air Force would also conduct periodic surveys for erosion, noxious weeds, and liability hazards. Site

  19. Report on Second Activations with the Lead Slowing Down Spectrometer

    SciTech Connect

    Stave, Sean C.; Mace, Emily K.; Pratt, Sharon L.; Warren, Glen A.

    2012-04-27

    Summary On August 18 and 19 2011, five items were irradiated with neutrons using the Lead Slowing Down Spectrometer (LSDS). After irradiation, dose measurements and gamma-spectrometry measurements were completed on all of the samples. No contamination was found on the samples, and all but one provided no dose. Gamma-spectroscopy measurements qualitatively agreed with expectations based on the materials. As during the first activation run, we observed activation in the room in general, mostly due to 56Mn and 24Na. Most of the activation of the samples was short lived, with half-lives on the scale of hours to days, except for 60Co which has a half-life of 5.3 y.

  20. An active, general, and long-lived palladium catalyst for cross-couplings of deactivated (hetero)aryl chlorides and bromides with arylboronic acids.

    PubMed

    Hoshi, Takashi; Honma, Tomonobu; Mori, Ayako; Konishi, Maki; Sato, Tsutomu; Hagiwara, Hisahiro; Suzuki, Toshio

    2013-11-15

    An active, general, and long-lived palladium catalyst for Suzuki-Miyaura reactions of aryl and heteroaryl chlorides deactivated by steric hindrance, electron richness, and coordinating functional groups is reported. In reactions of arylbromide bearing two o-tert-butyl substituents, C(sp(3))-H arylation of the tert-butyl group, rather than the Suzuki-Miyaura reaction, proceeded in excellent yield. The key to the success of the reactions was the development of biphenylene-substituted dicyclohexylruthenocenylphosphine (CyR-Phos) as a supporting ligand.

  1. Influence of the Reaction Temperature on the Nature of the Active and Deactivating Species During Methanol-to-Olefins Conversion over H-SAPO-34

    PubMed Central

    2017-01-01

    The selectivity toward lower olefins during the methanol-to-olefins conversion over H-SAPO-34 at reaction temperatures between 573 and 773 K has been studied with a combination of operando UV–vis diffuse reflectance spectroscopy and online gas chromatography. It was found that the selectivity toward propylene increases in the temperature range of 573–623 K, while it decreases in the temperature range of 623–773 K. The high degree of incorporation of olefins, mainly propylene, into the hydrocarbon pool affects the product selectivity at lower reaction temperatures. The nature and dynamics of the active and deactivating hydrocarbon species with increasing reaction temperature were revealed by a non-negative matrix factorization of the time-resolved operando UV–vis diffuse reflectance spectra. The active hydrocarbon pool species consist of mainly highly methylated benzene carbocations at temperatures between 573 and 598 K, of both highly methylated benzene carbocations and methylated naphthalene carbocations at 623 K, and of only methylated naphthalene carbocations at temperatures between 673 and 773 K. The operando spectroscopy results suggest that the nature of the active species also influences the olefin selectivity. In fact, monoenylic and highly methylated benzene carbocations are more selective to the formation of propylene, whereas the formation of the group of low methylated benzene carbocations and methylated naphthalene carbocations at higher reaction temperatures (i.e., 673 and 773 K) favors the formation of ethylene. At reaction temperatures between 573 and 623 K, catalyst deactivation is caused by the gradual filling of the micropores with methylated naphthalene carbocations, while between 623 and 773 K the formation of neutral poly aromatics and phenanthrene/anthracene carbocations are mainly responsible for catalyst deactivation, their respective contribution increasing with increasing reaction temperature. Methanol pulse experiments at

  2. Influence of the Reaction Temperature on the Nature of the Active and Deactivating Species During Methanol-to-Olefins Conversion over H-SAPO-34.

    PubMed

    Borodina, E; Sharbini Harun Kamaluddin, H; Meirer, F; Mokhtar, M; Asiri, A M; Al-Thabaiti, S A; Basahel, S N; Ruiz-Martinez, J; Weckhuysen, B M

    2017-08-04

    The selectivity toward lower olefins during the methanol-to-olefins conversion over H-SAPO-34 at reaction temperatures between 573 and 773 K has been studied with a combination of operando UV-vis diffuse reflectance spectroscopy and online gas chromatography. It was found that the selectivity toward propylene increases in the temperature range of 573-623 K, while it decreases in the temperature range of 623-773 K. The high degree of incorporation of olefins, mainly propylene, into the hydrocarbon pool affects the product selectivity at lower reaction temperatures. The nature and dynamics of the active and deactivating hydrocarbon species with increasing reaction temperature were revealed by a non-negative matrix factorization of the time-resolved operando UV-vis diffuse reflectance spectra. The active hydrocarbon pool species consist of mainly highly methylated benzene carbocations at temperatures between 573 and 598 K, of both highly methylated benzene carbocations and methylated naphthalene carbocations at 623 K, and of only methylated naphthalene carbocations at temperatures between 673 and 773 K. The operando spectroscopy results suggest that the nature of the active species also influences the olefin selectivity. In fact, monoenylic and highly methylated benzene carbocations are more selective to the formation of propylene, whereas the formation of the group of low methylated benzene carbocations and methylated naphthalene carbocations at higher reaction temperatures (i.e., 673 and 773 K) favors the formation of ethylene. At reaction temperatures between 573 and 623 K, catalyst deactivation is caused by the gradual filling of the micropores with methylated naphthalene carbocations, while between 623 and 773 K the formation of neutral poly aromatics and phenanthrene/anthracene carbocations are mainly responsible for catalyst deactivation, their respective contribution increasing with increasing reaction temperature. Methanol pulse experiments at different

  3. Mission analysis report - deactivation facilities at Hanford

    SciTech Connect

    Lund, D.P.

    1996-09-27

    This document examines the portion of the Hanford Site Cleanup Mission that deals with facility deactivation. How facilities get identified for deactivation, how they enter EM-60 for deactivation, programmatic alternatives to perform facility deactivation, the deactivation process itself, key requirements and objectives associated with the deactivation process, and deactivation planning are discussed.

  4. Deactivating the Writing Program.

    ERIC Educational Resources Information Center

    Strickland, James

    A written language learner must be given an environment that enables or fosters writing development. Unfortunately, the typical system of education and the learning strategies that are taught are at times the very things that deactivate, frustrate, and even pervert the writing program. In fact, some of the rules that student writers respond to are…

  5. Changes in effective diffusivity for oxygen during neural activation and deactivation estimated from capillary diameter measured by two-photon laser microscope.

    PubMed

    Ito, Hiroshi; Takuwa, Hiroyuki; Tajima, Yosuke; Kawaguchi, Hiroshi; Urushihata, Takuya; Taniguchi, Junko; Ikoma, Yoko; Seki, Chie; Ibaraki, Masanobu; Masamoto, Kazuto; Kanno, Iwao

    2017-03-01

    The relation between cerebral blood flow (CBF) and cerebral oxygen extraction fraction (OEF) can be expressed using the effective diffusivity for oxygen in the capillary bed (D) as OEF = 1 - exp(-D/CBF). The D value is proportional to the microvessel blood volume. In this study, changes in D during neural activation and deactivation were estimated from changes in capillary and arteriole diameter measured by two-photon microscopy in awake mice. Capillary and arteriole vessel diameter in the somatosensory cortex and cerebellum were measured under neural activation (sensory stimulation) and neural deactivation [crossed cerebellar diaschisis (CCD)], respectively. Percentage changes in D during sensory stimulation and CCD were 10.3 ± 7.3 and -17.5 ± 5.3 % for capillary diameter of <6 μm, respectively. These values were closest to the percentage changes in D calculated from previously reported human positron emission tomography data. This may indicate that thinner capillaries might play the greatest role in oxygen transport from blood to brain tissue.

  6. Calculation of magnetic field-induced current densities for humans from EAS countertop activation/deactivation devices that use ferromagnetic cores

    NASA Astrophysics Data System (ADS)

    Li, Qingxiang; Gandhi, Om P.

    2005-01-01

    Compliance testing of electronic article surveillance (EAS) devices requires that induced current densities in central nervous system (CNS) tissues, i.e. brain and the spinal cord, be less than the prescribed safety limits. Even though ferromagnetic cores are mostly used for activation/deactivation of embedded magnetic tags, assumed equivalent air-core coils with guessed increased number of ampere turns have always been used to calculate the magnetic fields for the proximal region to which a customer is exposed. We show that at low frequencies up to several kilohertz, duality of electric and magnetic circuits may be exploited such that the shaped high reluctance core is modelled as though it was a higher conductivity electric circuit of the corresponding shape. The proposed procedure is tested by examples of two magnetic cores typical of countertop activation/deactivation devices. The equivalent exposure magnetic fields obtained from the dual electric fields are shown to be in excellent agreement (within ±5%) with those measured for these ferromagnetic EAS devices. The previously proposed impedance method is then used to calculate the induced current densities for a 1.974 × 1.974 × 2.93 mm resolution anatomic model of a human. For the two considered EAS systems using excitation currents of 5000 A turns at 200 Hz, the maximum 1 cm2 area-averaged induced current densities in the CNS tissues are calculated and found to be less than the ICNIRP safety limits.

  7. PFP deactivation project management plan

    SciTech Connect

    Bogen, D.M.

    1997-07-28

    This document identifies the overall approach for deactivation of the Plutonium Finishing Plant (PFP) Complex, excluding the vaults, and includes a draft set of End Point Criteria for all buildings being deactivated.

  8. A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel.

    PubMed

    Tang, Cheng; Zhou, Xi; Nguyen, Phuong Tran; Zhang, Yunxiao; Hu, Zhaotun; Zhang, Changxin; Yarov-Yarovoy, Vladimir; DeCaen, Paul G; Liang, Songping; Liu, Zhonghua

    2017-07-01

    Voltage-gated sodium channels (NaVs) are activated by transiting the voltage sensor from the deactivated to the activated state. The crystal structures of several bacterial NaVs have captured the voltage sensor module (VSM) in an activated state, but structure of the deactivated voltage sensor remains elusive. In this study, we sought to identify peptide toxins stabilizing the deactivated VSM of bacterial NaVs. We screened fractions from several venoms and characterized a cystine knot toxin called JZTx-27 from the venom of tarantula Chilobrachys jingzhao as a high-affinity antagonist of the prokaryotic NaVs NsVBa (nonselective voltage-gated Bacillus alcalophilus) and NaChBac (bacterial sodium channel from Bacillus halodurans) (IC50 = 112 nM and 30 nM, respectively). JZTx-27 was more efficacious at weaker depolarizing voltages and significantly slowed the activation but accelerated the deactivation of NsVBa, whereas the local anesthetic drug lidocaine was shown to antagonize NsVBa without affecting channel gating. Mutation analysis confirmed that JZTx-27 bound to S3-4 linker of NsVBa, with F98 being the critical residue in determining toxin affinity. All electrophysiological data and in silico analysis suggested that JZTx-27 trapped VSM of NsVBa in one of the deactivated states. In mammalian NaVs, JZTx-27 preferably inhibited the inactivation of NaV1.5 by targeting the fourth transmembrane domain. To our knowledge, this is the first report of peptide antagonist for prokaryotic NaVs. More important, we proposed that JZTx-27 stabilized the NsVBa VSM in the deactivated state and may be used as a probe to determine the structure of the deactivated VSM of NaVs.-Tang, C., Zhou, X., Nguyen, P. T., Zhang, Y., Hu, Z., Zhang, C., Yarov-Yarovoy, V., DeCaen, P. G., Liang, S., Liu, Z. A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel. © FASEB.

  9. Upper-crustal Stress Field Variations During the Building of the Central Andes: Constrains on the Activation/deactivation of Megadetachments

    NASA Astrophysics Data System (ADS)

    Giambiagi, L.; Tassara, A.; Mescua, J.; Suriano, J.; Mahoney, J. B.; Hoke, G. D.; Spagnotto, S. L.; Lossada, A. C.; Mardónez, D.; Mazzitelli, M.; Barrionuevo, M.

    2015-12-01

    Nowadays, it is broadly accepted that the Central Andes resulted largely from crustal shortening in the last ~45 Ma, driven by horizontal forces as a consequence of subduction of the Nazca plate beneath South America. However, the way this shortening is achieved is still a matter a debate. Structural, seismological, thermochronological, isotopical and sedimentological studies of the Central Andes, together with thermomechanical modeling, suggest that different megadetachments located shallow in the upper crust were active during the construction of the Andes. Constrains on changes in the state of stress in the crust gleaned from more than 1,500 fault-slip data in the arc region provide insights into how and when these megadetachments get activated or deactivated. We used a forward modeling procedure to examine five transects across the Central Andes, at 21.5°, 24°, 30°, 34° and 35°S, with particular emphasis on the relationship between deep and shallow structures. Our kinematic-thermomechanical models show that most of the upper-middle crust has a brittle-elastic behavior particularly for the cold and rigid forearc and foreland regions, and a ductile behavior below the thermally weakened arc region. Our models assume a shallow, sub-horizontal megadetachment located at the shallowest brittle-ductile transition, which concentrates the majority of the horizontal crustal shortening between the fore-arc and the South American craton. During this horizontal shortening, the crust gets thick and topography rises due to buoyancy of the crustal root. The threshold of this thickening is achieved when the bouyancy force equals the horizontal force. At this point, the megadetachment deactives and the crustal root widens eastwards in concert with ductile deformation in the lower crust and the generation of a new megadetachment. By studying changes in the paleostress fields along the arc region, from compression to strike-slip, and strike-slip to extension, associated with

  10. Role of N-Terminal Domain and Accessory Subunits in Controlling Deactivation-Inactivation Coupling of Kv4.2 Channels

    PubMed Central

    Barghaan, Jan; Tozakidou, Magdalini; Ehmke, Heimo; Bähring, Robert

    2008-01-01

    We examined the relationship between deactivation and inactivation in Kv4.2 channels. In particular, we were interested in the role of a Kv4.2 N-terminal domain and accessory subunits in controlling macroscopic gating kinetics and asked if the effects of N-terminal deletion and accessory subunit coexpression conform to a kinetic coupling of deactivation and inactivation. We expressed Kv4.2 wild-type channels and N-terminal deletion mutants in the absence and presence of Kv channel interacting proteins (KChIPs) and dipeptidyl aminopeptidase-like proteins (DPPs) in human embryonic kidney 293 cells. Kv4.2-mediated A-type currents at positive and deactivation tail currents at negative membrane potentials were recorded under whole-cell voltage-clamp and analyzed by multi-exponential fitting. The observed changes in Kv4.2 macroscopic inactivation kinetics caused by N-terminal deletion, accessory subunit coexpression, or a combination of the two maneuvers were compared with respective changes in deactivation kinetics. Extensive correlation analyses indicated that modulatory effects on deactivation closely parallel respective effects on inactivation, including both onset and recovery kinetics. Searching for the structural determinants, which control deactivation and inactivation, we found that in a Kv4.2Δ2–10 N-terminal deletion mutant both the initial rapid phase of macroscopic inactivation and tail current deactivation were slowed. On the other hand, the intermediate and slow phase of A-type current decay, recovery from inactivation, and tail current decay kinetics were accelerated in Kv4.2Δ2–10 by KChIP2 and DPPX. Thus, a Kv4.2 N-terminal domain, which may control both inactivation and deactivation, is not necessary for active modulation of current kinetics by accessory subunits. Our results further suggest distinct mechanisms for Kv4.2 gating modulation by KChIPs and DPPs. PMID:17981906

  11. N Reactor Deactivation Program Plan. Revision 4

    SciTech Connect

    Walsh, J.L.

    1993-12-01

    This N Reactor Deactivation Program Plan is structured to provide the basic methodology required to place N Reactor and supporting facilities {center_dot} in a radiologically and environmentally safe condition such that they can be decommissioned at a later date. Deactivation will be in accordance with facility transfer criteria specified in Department of Energy (DOE) and Westinghouse Hanford Company (WHC) guidance. Transition activities primarily involve shutdown and isolation of operational systems and buildings, radiological/hazardous waste cleanup, N Fuel Basin stabilization and environmental stabilization of the facilities. The N Reactor Deactivation Program covers the period FY 1992 through FY 1997. The directive to cease N Reactor preservation and prepare for decommissioning was issued by DOE to WHC on September 20, 1991. The work year and budget data supporting the Work Breakdown Structure in this document are found in the Activity Data Sheets (ADS) and the Environmental Restoration Program Baseline, that are prepared annually.

  12. Deriving stellar inclination of slow rotators using stellar activity signal

    NASA Astrophysics Data System (ADS)

    Dumusque, Xavier

    2015-01-01

    Stellar inclination is an important parameter for many astrophysical studies. In the context of exoplanets, this allows us to derive the true obliquity of a system if the projected stellar spin-planetary orbit angle can measured via the Rossiter-Mclaughlin effect. Although different techniques allow us to estimate stellar inclination for fast rotators, it becomes much more difficult when stars are rotating slower than 2-2.5 km.s-1. By using the new activity simulation SOAP 2.0 that can reproduce the photometric and spectroscopic variations induced by stellar activity, we are able to fit the activity variation of solar-type stars and derive their inclination. The case of the equator-on star HD189733 will be presented, as well as the case of Alpha Centauri B, which present an inclination of 45+9-19 degrees, implying that the earth-mass orbiting planet is not transiting if aligned with its host star. Other exemples will also demonstrate the power of the technique, that can infer a stellar inclination, even for slow rotators like Alpha Centauri B, that present a projected rotational velocity smaller than 1.15 km.s-1. In addition, the SOAP 2.0 simulation can be used to correct for the effect of activity when one major active region is dominating the RV signal. This could enhance the detection of small mass exoplanets orbiting slightly active stars.This project is funded by ETAEARTH (European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement n. 313014), a transnational collaboration between European countries and the US (the Swiss Space Office, the Harvard Origin of Life Initiative, the Scottish Universities Physics Alliance, the University of Geneva, the Smithsonian Astrophysical Observatory, the Italian National Astrophysical Institute, the University of St. Andrews, Queens University Belfast, and the University of Edinburgh) setup to optimize the synergy between space-and ground-based data whose scientific potential for the characterization of

  13. Catalyst deactivation in residue hydrocracking

    SciTech Connect

    Oballa, M.C.; Wong, C.; Krzywicki, A.

    1994-12-31

    The existence of a computer-controlled bench scale hydrocracking units at the authors site has made cheaper the non-stop running of experiments for long periods of time. It was, therefore possible to show, at minimal costs, when three hydrocracking catalysts in service reach their maximum lifetime. Different parameters which are helpful for catalyst life and activity predictions were calculated, e.g., relative catalyst age and the effectiveness factor. Experimental results compared well with model, giving them the minimum and maximum catalyst lifetime, as well as the deactivation profile with regard to sulfur and metals removal. Reaction rate constants for demetallization and desulfurization were also determined. Six commercial catalysts were evaluated at short term runs and the three most active were used for long term runs. Out of three catalysts tested for deactivation at long term runs, it was possible to choose one whose useful life was higher than the others. All runs were carried out in a Robinson-Mahoney continuous flow stirred tank reactor, using 50/50 volumetric mixture of Cold Lake/Lloydminster atmospheric residue and NiMo/Al{sub 2}O{sub 3} catalyst.

  14. Insights into the Activity and Deactivation of the Methanol-to-Olefins Process over Different Small-Pore Zeolites As Studied with Operando UV–vis Spectroscopy

    PubMed Central

    2017-01-01

    The nature and evolution of the hydrocarbon pool (HP) species during the Methanol-to-Olefins (MTO) process for three small-pore zeolite catalysts, with a different framework consisting of large cages interconnected by small eight-ring windows (CHA, DDR, and LEV) was studied at reaction temperatures between 350 and 450 °C using a combination of operando UV–vis spectroscopy and online gas chromatography. It was found that small differences in cage size, shape, and pore structure of the zeolite frameworks result in the generation of different hydrocarbon pool species. More specifically, it was found that the large cage of CHA results in the formation of a wide variety of hydrocarbon pool species, mostly alkylated benzenes and naphthalenes. In the DDR cage, 1-methylnaphthalene is preferentially formed, while the small LEV cage generally contains fewer hydrocarbon pool species. The nature and evolution of these hydrocarbon pool species was linked with the stage of the reaction using a multivariate analysis of the operando UV–vis spectra. In the 3-D pore network of CHA, the reaction temperature has only a minor effect on the performance of the MTO catalyst. However, for the 2-D pore networks of DDR and LEV, an increase in the applied reaction temperature resulted in a dramatic increase in catalytic activity. For all zeolites in this study, the role of the hydrocarbon species changes with reaction temperature. This effect is most clear in DDR, in which diamantane and 1-methylnaphthalene are deactivating species at a reaction temperature of 350 °C, whereas at higher temperatures diamantane formation is not observed and 1-methylnaphthalene is an active species. This results in a different amount and nature of coke species in the deactivated catalyst, depending on zeolite framework and reaction temperature. PMID:28603658

  15. Insights into the Activity and Deactivation of the Methanol-to-Olefins Process over Different Small-Pore Zeolites As Studied with Operando UV-vis Spectroscopy.

    PubMed

    Goetze, Joris; Meirer, Florian; Yarulina, Irina; Gascon, Jorge; Kapteijn, Freek; Ruiz-Martínez, Javier; Weckhuysen, Bert M

    2017-06-02

    The nature and evolution of the hydrocarbon pool (HP) species during the Methanol-to-Olefins (MTO) process for three small-pore zeolite catalysts, with a different framework consisting of large cages interconnected by small eight-ring windows (CHA, DDR, and LEV) was studied at reaction temperatures between 350 and 450 °C using a combination of operando UV-vis spectroscopy and online gas chromatography. It was found that small differences in cage size, shape, and pore structure of the zeolite frameworks result in the generation of different hydrocarbon pool species. More specifically, it was found that the large cage of CHA results in the formation of a wide variety of hydrocarbon pool species, mostly alkylated benzenes and naphthalenes. In the DDR cage, 1-methylnaphthalene is preferentially formed, while the small LEV cage generally contains fewer hydrocarbon pool species. The nature and evolution of these hydrocarbon pool species was linked with the stage of the reaction using a multivariate analysis of the operando UV-vis spectra. In the 3-D pore network of CHA, the reaction temperature has only a minor effect on the performance of the MTO catalyst. However, for the 2-D pore networks of DDR and LEV, an increase in the applied reaction temperature resulted in a dramatic increase in catalytic activity. For all zeolites in this study, the role of the hydrocarbon species changes with reaction temperature. This effect is most clear in DDR, in which diamantane and 1-methylnaphthalene are deactivating species at a reaction temperature of 350 °C, whereas at higher temperatures diamantane formation is not observed and 1-methylnaphthalene is an active species. This results in a different amount and nature of coke species in the deactivated catalyst, depending on zeolite framework and reaction temperature.

  16. Role of slow oscillatory activity and slow wave sleep in consolidation of episodic-like memory in rats.

    PubMed

    Oyanedel, Carlos N; Binder, Sonja; Kelemen, Eduard; Petersen, Kimberley; Born, Jan; Inostroza, Marion

    2014-12-15

    Our previous experiments showed that sleep in rats enhances consolidation of hippocampus dependent episodic-like memory, i.e. the ability to remember an event bound into specific spatio-temporal context. Here we tested the hypothesis that this enhancing effect of sleep is linked to the occurrence of slow oscillatory and spindle activity during slow wave sleep (SWS). Rats were tested on an episodic-like memory task and on three additional tasks covering separately the where (object place recognition), when (temporal memory), and what (novel object recognition) components of episodic memory. In each task, the sample phase (encoding) was followed by an 80-min retention interval that covered either a period of regular morning sleep or sleep deprivation. Memory during retrieval was tested using preferential exploration of novelty vs. familiarity. Consistent with previous findings, the rats which had slept during the retention interval showed significantly stronger episodic-like memory and spatial memory, and a trend of improved temporal memory (although not significant). Object recognition memory was similarly retained across sleep and sleep deprivation retention intervals. Recall of episodic-like memory was associated with increased slow oscillatory activity (0.85-2.0Hz) during SWS in the retention interval. Spatial memory was associated with increased proportions of SWS. Against our hypothesis, a relationship between spindle activity and episodic-like memory performance was not detected, but spindle activity was associated with object recognition memory. The results provide support for the role of SWS and slow oscillatory activity in consolidating hippocampus-dependent memory, the role of spindles in this process needs to be further examined.

  17. ACTIV: Sandwich Detector Activity from In-Pile Slowing-Down Spectra Experiment

    SciTech Connect

    2013-08-01

    ACTIV calculates the activities of a sandwich detector, to be used for in-pile measurements in slowing-down spectra below a few keV. The effect of scattering with energy degradation in the filter and in the detectors has been included to a first approximation.

  18. Slow wave activity and slow oscillations in sleepwalkers and controls: effects of 38 h of sleep deprivation.

    PubMed

    Perrault, Rosemarie; Carrier, Julie; Desautels, Alex; Montplaisir, Jacques; Zadra, Antonio

    2013-08-01

    Sleepwalkers have been shown to have an unusually high number of arousals from slow wave sleep and lower slow wave activity (SWA) power during the night than controls. Because sleep deprivation increases the frequency of slow wave sleep (SWS) arousals in sleepwalkers, it may also affect the expression of the homeostatic process to a greater extent than shown previously. We thus investigated SWA power as well as slow wave oscillation (SWO) density in 10 sleepwalkers and nine controls at baseline and following 38 h of sleep deprivation. There was a significant increase in SWA during participants' recovery sleep, especially during their second non-rapid eye movement (NREM) period. SWO density was similarly increased during recovery sleep's first two NREM periods. A fronto-central gradient in SWA and SWO was also present on both nights. However, no group differences were noted on any of the 2 nights on SWA or SWO. This unexpected result may be related to the heterogeneity of sleepwalkers as a population, as well as our small sample size. SWA pressure after extended sleep deprivation may also result in a ceiling effect in both sleepwalkers and controls.

  19. 340 Waste handling facility deactivation plan

    SciTech Connect

    Stordeur, R.T., Westinghouse Hanford

    1996-12-27

    This document provides an overview of both the present status of the 340 Complex (within Hanford`s 300 Area), and of tasks associated with the deactivation of segments associated with radioactive, mixed liquid waste receipt, storage, and shipping. The plan also describes activities that will allow portions of the 340 Complex to remain in service.

  20. Investigations on the mutagenicity of primary and secondary alpha-acetoxynitrosamines with Salmonella typhimurium: activation and deactivation of structurally related compounds by S-9.

    PubMed

    Pool, B L; Wiessler, M

    1981-01-01

    alpha-Acetoxynitrosamines may serve as model compounds to study mechanisms of action of N-nitrosamines. They are readily cleaved through hydrolysis, or by esterases, to yield the same ultimate, reactive species presumably also arising after metabolic activation of N-nitrosamines, Structure-activity investigations on alpha-acetoxynitrosamines promise to aid in elucidating mechanisms involved during the activation of N-nitrosamines. A series of alpha-acetoxyalkynitrosamines was therefore tested for mutagenicity with Salmonella typhimurium TA 1535. The compounds were readily cleaved, by hydrolysis, to mutagenic intermediates. When comparing compounds according to their proposed alkylating properties, unstable secondary alpha-acetates were considerably more mutagenic than the corresponding relatively stable primary alpha-acetates. Addition of S-9 mix caused both activation as well as deactivation in an unexpected structure-related pattern. This was so because an exactly opposite influence of S-9 components on the mutagenicity was observed for each pair of primary and secondary compounds containing the same alkylating spices. Furthermore, pairs of compounds with both methylating and ethylating properties were differently influenced by S-9 addition than those with propylating or butylating effects. This clearly demonstrates how different chemical properties of intermediate forms may strongly influence the biological activity of otherwise quite similar compounds.

  1. PUREX/UO{sub 3} deactivation project management plan

    SciTech Connect

    Washenfelder, D.J.

    1993-12-01

    From 1955 through 1990, the Plutonium-Uranium Extraction Plant (PUREX) provided the United States Department of Energy Hanford Site with nuclear fuel reprocessing capability. It operated in sequence with the Uranium Trioxide (UO{sub 3}) Plant, which converted the PUREX liquid uranium nitrate product to solid UO{sub 3} powder. Final UO{sub 3} Plant operation ended in 1993. In December 1992, planning was initiated for the deactivation of PUREX and UO{sub 3} Plant. The objective of deactivation planning was to identify the activities needed to establish a passively safe, environmentally secure configuration at both plants, and ensure that the configuration could be retained during the post-deactivation period. The PUREX/UO{sub 3} Deactivation Project management plan represents completion of the planning efforts. It presents the deactivation approach to be used for the two plants, and the supporting technical, cost, and schedule baselines. Deactivation activities concentrate on removal, reduction, and stabilization of the radioactive and chemical materials remaining at the plants, and the shutdown of the utilities and effluents. When deactivation is completed, the two plants will be left unoccupied and locked, pending eventual decontamination and decommissioning. Deactivation is expected to cost $233.8 million, require 5 years to complete, and yield $36 million in annual surveillance and maintenance cost savings.

  2. Inositol hexaphosphate represses telomerase activity and translocates TERT from the nucleus in mouse and human prostate cancer cells via the deactivation of Akt and PKC{alpha}

    SciTech Connect

    Jagadeesh, Shankar; Banerjee, Partha P. . E-mail: ppb@georgetown.edu

    2006-11-03

    Inositol hexaphosphate (IP6) has anti-proliferative effects on a variety of cancer cells, including prostate cancer. However, the molecular mechanism of anti-proliferative effects of IP6 is not entirely understood. Since the activation of telomerase is crucial for cells to gain immortality and proliferation ability, we examined the role of IP6 in the regulation of telomerase activity in prostate cancer cells. Here, we show that IP6 represses telomerase activity in mouse and human prostate cancer cells dose-dependently. In addition, IP6 prevents the translocation of TERT to the nucleus. Since phosphorylation of TERT by Akt and/or PKC{alpha} is necessary for nuclear translocation, we examined phosphorylation of Akt and PKC{alpha} after IP6 treatments. Our results show that IP6 inhibits phosphorylation of Akt and PKC{alpha}. These results show for the first time that IP6 represses telomerase activity in prostate cancer cells by posttranslational modification of TERT via the deactivation of Akt and PKC{alpha}.

  3. Inositol hexaphosphate represses telomerase activity and translocates TERT from the nucleus in mouse and human prostate cancer cells via the deactivation of Akt and PKCalpha.

    PubMed

    Jagadeesh, Shankar; Banerjee, Partha P

    2006-11-03

    Inositol hexaphosphate (IP6) has anti-proliferative effects on a variety of cancer cells, including prostate cancer. However, the molecular mechanism of anti-proliferative effects of IP6 is not entirely understood. Since the activation of telomerase is crucial for cells to gain immortality and proliferation ability, we examined the role of IP6 in the regulation of telomerase activity in prostate cancer cells. Here, we show that IP6 represses telomerase activity in mouse and human prostate cancer cells dose-dependently. In addition, IP6 prevents the translocation of TERT to the nucleus. Since phosphorylation of TERT by Akt and/or PKCalpha is necessary for nuclear translocation, we examined phosphorylation of Akt and PKCalpha after IP6 treatments. Our results show that IP6 inhibits phosphorylation of Akt and PKCalpha. These results show for the first time that IP6 represses telomerase activity in prostate cancer cells by posttranslational modification of TERT via the deactivation of Akt and PKCalpha.

  4. Deactivation of cellulases by phenols

    USDA-ARS?s Scientific Manuscript database

    Pretreatment of lignocellulosic materials may result in the release of inhibitors and deactivators of cellulose enzyme hydrolysis. We report the identification of phenols with major inhibition and/or deactivation effect on enzymes used for conversion of cellulose to ethanol. The inhibition effects w...

  5. Influence of explosive volcanic events on the activation versus de-activation of a modern turbidite system: the example of the Dohrn canyon-fan in the continental slope of the Campania volcanic district (Naples Bay, Italy - Western Mediterranean)

    NASA Astrophysics Data System (ADS)

    Roca, M.; Budillon, F.; Pappone, G.; Insinga, D.

    2015-12-01

    The interplay between volcanic activity, volcano-clastic yield and activation/deactivation of a turbidite system can be evaluated along the continental margin of Campania region (Tyrrhenian Sea - Italy), an active volcanic area, where three wide canyon-fans occur at short distances one to another. Actually, the Dohrn, Magnaghi and Cuma canyons cut the continental slope and shelf off Ischia and Procida volcanic islands and off the Campania Plain where Phlegraean Field and Mt. Vesuvius active vents are located. This research, partly supported by the Italian Flagship Project Ritmare, is based on single-channel, high-resolution seismic profiles (Sparker-One 16 kJ, 0.5 s twtt), swath-bathymetry and litho- and tephra-stratigraphy of gravity cores. We focused on the stratigraphic constraint of paleo-thalweg features and channel/levees deposits in seismics, debris flow, turbidites and hemipelagites in cores, to learn more on the activation/deactivation stages of the canyon Dohrn, in the frame of relative eustatic sea level variations over the Middle Pleistocene-Holocene time span.Preliminary outcomes suggest that even major volcanic events occurred in the last 300 ky, such as ignimbrite eruptions or large fallouts, have caused the infilling of the canyon head and the cover of pre-existing seabed morphology. As a consequence, the temporary deactivation of the turbidite system has occurred, despite the volcano-clastic overload in the coastal environment. Phases of renewed activities of the thalweg are observed to be in step with falling stages of sea level, which have driven the re-incision of canyon valleys through continuous volcano-clastic debris and turbidites down-flows. Since Holocene, the quiescence of the Dohrn Canyon has been documented, despite the intense volcano-tectonic activity in the area.

  6. Deactivation completed at historic Hanford Fuels Laboratory

    SciTech Connect

    Gerber, M.S.

    1994-03-01

    This report discusses deactivation work which was completed as of March 31, 1994 at the 308 Fuels Development Laboratory (FDL) at the Hanford Site near Richland, Washington. The decision to deactivate the structure, formerly known as the Plutonium Fabrication Pilot Plant (PFPP), was driven by a 1980s Department of Energy (DOE) decision that plutonium fuels should not be fabricated in areas near the Site`s boundaries, as well as by changing facility structural requirements. Inventory transfer has been followed by the cleanout and stabilization of plutonium oxide (PuO{sub 2}) and enriched uranium oxide (UO{sub 2}) residues and powders in the facility`s equipment and duct work. The Hanford Site, located in southeastern Washington state, was one of America`s primary arsenals of nuclear defense production for nearly 50 years beginning in World War II. Approximately 53 metric tons of weapons grade plutonium, over half of the national supply and about one quarter of the world`s supply, were produced at Hanford between 1944 and 1989. Today, many Site buildings are undergoing deactivation, a precursor phase to decontamination and decommissioning (D&D). The primary difference between the two activities is that equipment and structural items are not removed or torn down in deactivation. However, utilities are disconnected, and special nuclear materials (SNM) as well as hazardous and pyrophoric substances are removed from structures undergoing this process.

  7. The effect of temperature changes on in vitro slow wave activity in the equine ileum.

    PubMed

    Fintl, C; Hudson, N P H; Handel, I; Pearson, G T

    2016-03-01

    Slow waves are rhythmic pacemaker currents generated by the gastrointestinal pacemaker cells, the interstitial cells of Cajal, and represent the rate-limiting step for small intestinal smooth muscle contractions. Therefore, factors that affect slow wave activity may also influence contractile activity. It is not known how temperature changes may influence slow wave activity in the horse. This could be of relevance during colic surgery if cooling of exposed intestine resulted in reduced slow wave activity potentially exacerbating post operative ileus. To evaluate the effect of temperature changes on in vitro slow wave activity of normal equine ileum using intracellular recording techniques. In vitro experimental study. A segment of ileum was collected immediately following euthanasia from 9 horses for reasons unrelated to the gastrointestinal tract. Intracellular recordings of membrane potentials were made from individual smooth muscle cells. The temperature of the tissue bath was altered during the course of each experiment across a range of 27-41°C. All data were recorded and stored using a computer-interfaced acquisition system. A software package was used to analyse slow wave frequency, duration, amplitude and resting membrane potential. In all 9 horses, slow wave frequency was highly temperature sensitive and approximately linearly related to the temperature over the range studied, increasing by 0.5 cycles/min for each 1°C increase in temperature (P<0.001). The initial slow wave frequency resumed when the temperature was returned to 37°C. The recovery time appeared to be directly related to the duration for which the temperature had been changed. Slow wave frequency in the equine ileum is highly temperature sensitive. As post operative ileus is a major cause of morbidity and mortality in the horse, the negative effect of lower temperatures on slow waves, and therefore contractile activity, should be considered. © 2015 EVJ Ltd.

  8. A PROPOSED FRAMEWORK FOR PLANNING DEACTIVATION AND DECOMMISSIONING ENGINEERING AND DESIGN ACTIVITIES TO MEET THE REQUIREMENTS OF DOE ORDER 413.3A, PROGRAM AND PROJECT MANAGEMENT FOR THE ACQUISITION OF CAPITAL ASSETS

    SciTech Connect

    Santos, J; John Gladden, J

    2007-11-06

    This paper provides guidance in applying the requirements of DOE O 413.3A to Deactivation and Decommissioning (D&D) projects. A list of 41 engineering and design activities relevant to D&D projects was generated. For several activities in this list, examples of the level of development and/or types of deliverables that might be expected at the completion of the conceptual, preliminary and final project design phases described in the Order are provided.

  9. Design of new strategy for green algal photo-hydrogen production: spectral-selective photosystem I activation and photosystem II deactivation.

    PubMed

    Hoshino, Takanori; Johnson, Daniel J; Cuello, Joel L

    2012-09-01

    A new strategy in photosynthetic hydrogen (photo-H(2)) production from green algae was developed based on theory and successfully demonstrated. The new strategy applied a spectral-selective photosystem I (PSI) activating/photosystem II (PSII) deactivating radiation (or PSI light) that would drive a steady flow of electrons in the electron transport chain for delivery to hydrogenase for photo-H(2) production, but would reduce oxygen production through water photolysis below the respiratory oxygen consumption so that an anoxic condition would be maintained as required by hydrogenase. Implementing the strategy by using a PSI light (692 nm peak, 680-700 nm) on Chlamydomonas reinhardtii cells resulted in relatively sustained photo-H(2) production (total of 0.108 mL H(2)mg(-1)Chl, exceeding 0.066 mL H(2)mg(-1)Chl under white light). The strategy also proved successful and convenient in allowing cells to alternately switch between photo-H(2) production and a recovery period by simply turning on or off the PSI light. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Acute Cocaine Induces Fast Activation of D1R and Progressive Deactivation of D2R Striatal Neurons: In vivo Optical MicroProbe [Ca2+]i Imaging

    PubMed Central

    Luo, Zhongchi; Volkow, Nora D.; Heintz, Nathaniel; Pan, Yingtian; Du, Congwu

    2011-01-01

    Cocaine induces fast dopamine increases in brain striatal regions, which are recognized to underlie its rewarding effects. Both dopamine D1 and D2 receptors are involved in cocaine’s reward but the dynamic downstream consequences of cocaine effects in striatum are not fully understood. Here we used transgenic mice expressing EGFP under the control of either the D1 receptor (D1R) or the D2 receptor (D2R) gene and microprobe optical imaging to assess the dynamic changes in intracellular calcium ([Ca2+]i) responses (used as marker of neuronal activation) to acute cocaine in vivo separately for D1R versus D2R expressing neurons in striatum. Acute cocaine (8 mg/kg ip) rapidly increased [Ca2+]i in D1R expressing neurons (10.6±3.2%) in striatum within 8.3±2.3min after cocaine administration after which the increases plateaued; these fast [Ca2+]i increases were blocked by pretreatment with a D1R antagonist (SCH 23390). In contrast cocaine induced progressive decreases in [Ca2+]i in D2R expressing neurons (10.4±5.8%) continuously throughout the 30min that followed cocaine administration; these slower [Ca2+]i decreases were blocked by pretreatment with a D2R antagonist (raclopride). Since activation of striatal D1R expressing neurons (direct-pathway) enhances cocaine reward whereas activation of D2R expressing neurons suppresses it (indirect-pathway) (Lobo et al., 2010), this suggests that cocaine’s rewarding effects entail both its fast stimulation of D1R (resulting in abrupt activation of direct-pathway neurons) and a slower stimulation of D2R (resulting in longer lasting deactivation of indirect-pathway neurons). We also provide direct in-vivo evidence of D2R and D1R interactions in the striatal responses to acute cocaine administration. PMID:21917801

  11. The GTP binding protein-dependent activation and deactivation of cGMP phosphodiesterase in rod photoreceptors

    SciTech Connect

    Yamazaki, Akio.

    1989-01-01

    Cyclic GMP (cGMP) has a crucial role in visual transduction. Recent electrophysiological studies clearly indicate the existence of cGMP-activated conductance in photoreceptor plasma membranes. In darkness, Na{sup +}, Ca{sup ++}, and Mg{sup ++} enter rod outer segments (ROS) through cGMP-activated channels while light closes channels by lowering cGMP concentrations through activation of cGMP phosphodiesterase (PDE). Many excellent reviews reference the mechanism of PDE activation in photoreceptors. However, recent progress in understanding the mechanisms regulating cGMP hydrolysis has raised an important question in the PDE-regulation: how does the three-dimensional movement of a subunit of transducin (retinal G protein) relate to the PDE activation Associated with that question, the mechanism of PDE regulation appears to vary at different stages of evolution, for example, frog and bovine photoreceptors. This review examines recent progress of the cGMP hydrolysis mechanism by focusing on the subunit interactions between transducin and PDE. 36 refs., 2 figs.

  12. A computational method for the detection of activation/deactivation patterns in biological signals with three levels of electric intensity.

    PubMed

    Guerrero, J A; Macías-Díaz, J E

    2014-02-01

    In the present work, we develop a computational technique to approximate the changes of phase in temporal series associated to electric signals of muscles which perform activities at three different levels of intensity. We suppose that the temporal series are samples of independent, normally distributed random variables with mean equal to zero, and variance equal to one of three possible values, each of them associated to a certain degree of electric intensity. For example, these intensity levels may represent a leg muscle at rest, or active during a light activity (walking), or active during a highly demanding performance (jogging). The model is presented as a maximum likelihood problem involving discrete variables. In turn, this problem is transformed into a continuous one via the introduction of continuous variables with penalization parameters, and it is solved recursively through an iterative numerical method. An a posteriori treatment of the results is used in order to avoid the detection of relatively short periods of silence or activity. We perform simulations with synthetic data in order to assess the validity of our technique. Our computational results show that the method approximates well the occurrence of the change points in synthetic temporal series, even in the presence of autocorrelated sequences. In the way, we show that a generalization of a computational technique for the change-point detection of electric signals with two phases of activity (Esquivel-Frausto et al., 2010 [40]), may be inapplicable in cases of temporal series with three levels of intensity. In this sense, the method proposed in the present manuscript improves previous efforts of the authors.

  13. Heterogeneous activation of a slow myosin gene in proliferating myoblasts and differentiated single myofibers

    PubMed Central

    Wang, Jing-hua; Wang, Qiao-jing; Wang, Chao; Reinholt, Brad; Grant, Alan L; Gerrard, David E; Kuang, Shihuan

    2015-01-01

    Each skeletal muscle contains a fixed ratio of fast and slow myofibers that are distributed in a stereotyped pattern to achieve a specific motor function. How myofibers are specified during development and regeneration is poorly understood. Here we address this question using transgenic reporter mice that indelibly mark the myofiber lineages based on activation of fast or slow myosin. Lineage tracing indicates that during development all muscles have activated the fast myosin gene Myl1, but not the slow myosin gene Myh7, which is activated in all slow but a subset of fast myofibers. Similarly, most nascent myofibers do not activate Myh7 during fast muscle regeneration, but the ratio and pattern of fast and slow myofibers are restored at the completion of regeneration. At the single myofiber level, most mature fast myofibers are heterogeneous in nuclear composition, manifested by mosaic activation of Myh7. Strikingly, Myh7 is activated in a subpopulation of proliferating myoblasts that co-express the myogenic progenitor marker Pax7. When induced to differentiate, the Myh7-activated myoblasts differentiate more readily than the non-activated myoblasts, and have a higher tendency, but not restricted, to become slow myotubes. Together, our data reveal significant nuclear heterogeneity within a single myofiber, and challenge the conventional view that myosin genes are only expressed after myogenic differentiation. These results provide novel insights into the regulation of muscle fiber type specification. PMID:25794679

  14. Hysteresis of KcsA potassium channel's activation- deactivation gating is caused by structural changes at the channel's selectivity filter.

    PubMed

    Tilegenova, Cholpon; Cortes, D Marien; Cuello, Luis G

    2017-03-21

    Mode-shift or hysteresis has been reported in ion channels. Voltage-shift for gating currents is well documented for voltage-gated cation channels (VGCC), and it is considered a voltage-sensing domain's (VSD) intrinsic property. However, uncoupling the Shaker K(+) channel's pore domain (PD) from the VSD prevented the mode-shift of the gating currents. Consequently, it was proposed that an open-state stabilization of the PD imposes a mechanical load on the VSD, which causes its mode-shift. Furthermore, the mode-shift displayed by hyperpolarization-gated cation channels is likely caused by structural changes at the channel's PD similar to those underlying C-type inactivation. To demonstrate that the PD of VGCC undergoes hysteresis, it is imperative to study its gating process in the absence of the VSD. A back-door strategy is to use KcsA (a K(+) channel from the bacteria Streptomyces lividans) as a surrogate because it lacks a VSD and exhibits an activation coupled to C-type inactivation. By directly measuring KcsA's activation gate opening and closing in conditions that promote or halt C-type inactivation, we have found (i) that KcsA undergoes mode-shift of gating when having K(+) as the permeant ion; (ii) that Cs(+) or Rb(+), known to halt C-inactivation, prevented mode-shift of gating; and (iii) that, in the total absence of C-type inactivation, KcsA's mode-shift was prevented. Finally, our results demonstrate that an allosteric communication causes KcsA's activation gate to "remember" the conformation of the selectivity filter, and hence KcsA requires a different amount of energy for opening than for closing.

  15. [Deactivation of titania whiskers used for purification of drinking water].

    PubMed

    Wen, Gao-fei; Yang, Zhu-hong; Li, Wei; Feng, Xin; Lu, Xiao-hua

    2007-09-01

    The reason of deactivation of titania whiskers used for deep purification of drinking water and the corresponding regeneration methods were presented. AFM, XRD and ICP were carried out to characterize the titanium dioxide. The experimental results suggest that the main reason of deactivation of titania whiskers is the deposition of calcium carbonate on the catalyst surface. The surface of titania whiskers is covered by the insoluble carbonates generated from carbon dioxide produced during the degradation of organics and metal ions such as calcium in the tap water, and the activity of the titania whiskers decreases gradually till deactivation. After washing by 1 mol/L hydrochloric acid for four hours, the photocatalytic activity of the titania whiskers can achieve 95 percent of that before deactivation. The photocatalytic activity of the titania whiskers which regenerated for many times keeps steady.

  16. 340 waste handling complex: Deactivation project management plan

    SciTech Connect

    Stordeur, R.T.

    1998-06-25

    This document provides an overview of the strategy for deactivating the 340 Waste Handling Complex within Hanford`s 300 Area. The plan covers the period from the pending September 30, 1998 cessation of voluntary radioactive liquid waste (RLW) transfers to the 340 Complex, until such time that those portions of the 340 Complex that remain active beyond September 30, 1998, specifically, the Retention Process Sewer (RPS), can also be shut down and deactivated. Specific activities are detailed and divided into two phases. Phase 1 ends in 2001 after the core RLW systems have been deactivated. Phase 2 covers the subsequent interim surveillance of deactivated and stand-by components during the period of continued RPS operation, through the final transfer of the entire 340 Complex to the Environmental Restoration Contractor. One of several possible scenarios was postulated and developed as a budget and schedule planning case.

  17. The Deactive Form of Respiratory Complex I from Mammalian Mitochondria Is a Na+/H+ Antiporter*

    PubMed Central

    Roberts, Philippa G.; Hirst, Judy

    2012-01-01

    In mitochondria, complex I (NADH:ubiquinone oxidoreductase) uses the redox potential energy from NADH oxidation by ubiquinone to transport protons across the inner membrane, contributing to the proton-motive force. However, in some prokaryotes, complex I may transport sodium ions instead, and three subunits in the membrane domain of complex I are closely related to subunits from the Mrp family of Na+/H+ antiporters. Here, we define the relationship between complex I from Bos taurus heart mitochondria, a close model for the human enzyme, and sodium ion transport across the mitochondrial inner membrane. In accord with current consensus, we exclude the possibility of redox-coupled Na+ transport by B. taurus complex I. Instead, we show that the “deactive” form of complex I, which is formed spontaneously when enzyme turnover is precluded by lack of substrates, is a Na+/H+ antiporter. The antiporter activity is abolished upon reactivation by the addition of substrates and by the complex I inhibitor rotenone. It is specific for Na+ over K+, and it is not exhibited by complex I from the yeast Yarrowia lipolytica, which thus has a less extensive deactive transition. We propose that the functional connection between the redox and transporter modules of complex I is broken in the deactive state, allowing the transport module to assert its independent properties. The deactive state of complex I is formed during hypoxia, when respiratory chain turnover is slowed, and may contribute to determining the outcome of ischemia-reperfusion injury. PMID:22854968

  18. Origin and propagation of human gastric slow-wave activity defined by high-resolution mapping

    PubMed Central

    Du, Peng; Cheng, Leo K.; Egbuji, John U.; Lammers, Wim J. E. P.; Windsor, John A.; Pullan, Andrew J.

    2010-01-01

    Slow waves coordinate gastric motility, and abnormal slow-wave activity is thought to contribute to motility disorders. The current understanding of normal human gastric slow-wave activity is based on extrapolation from data derived from sparse electrode recordings and is therefore potentially incomplete. This study employed high-resolution (HR) mapping to reevaluate human gastric slow-wave activity. HR mapping was performed in 12 patients with normal stomachs undergoing upper abdominal surgery, using flexible printed circuit board (PCB) arrays (interelectrode distance 7.6 mm). Up to six PCBs (192 electrodes; 93 cm2) were used simultaneously. Slow-wave activity was characterized by spatiotemporal mapping, and regional frequencies, amplitudes, and velocities were defined and compared. Slow-wave activity in the pacemaker region (mid to upper corpus, greater curvature) was of greater amplitude (mean 0.57 mV) and higher velocity (8.0 mm/s) than the corpus (0.25 mV, 3.0 mm/s) (P < 0.001) and displayed isotropic propagation. A marked transition to higher amplitude and velocity activity occurred in the antrum (0.52 mV, 5.9 mm/s) (P < 0.001). Multiple (3–4) wavefronts were found to propagate simultaneously in the organoaxial direction. Frequencies were consistent between regions (2.83 ± 0.35 cycles per min). HR mapping has provided a more complete understanding of normal human gastric slow-wave activity. The pacemaker region is associated with high-amplitude, high-velocity activity, and multiple wavefronts propagate simultaneously. These data provide a baseline for future HR mapping studies in disease states and will inform noninvasive diagnostic strategies. PMID:20595620

  19. Slow State Transitions of Sustained Neural Oscillations by Activity-Dependent Modulation of Intrinsic Excitability

    PubMed Central

    Fröhlich, Flavio; Bazhenov, Maxim; Timofeev, Igor; Steriade, Mircea; Sejnowski, Terrence J.

    2010-01-01

    Little is known about the dynamics and mechanisms of transitions between tonic firing and bursting in cortical networks. Here, we use a computational model of a neocortical circuit with extracellular potassium dynamics to show that activity-dependent modulation of intrinsic excitability can lead to sustained oscillations with slow transitions between two distinct firing modes: fast run (tonic spiking or fast bursts with few spikes) and slow bursting. These transitions are caused by a bistability with hysteresis in a pyramidal cell model. Balanced excitation and inhibition stabilizes a network of pyramidal cells and inhibitory interneurons in the bistable region and causes sustained periodic alternations between distinct oscillatory states. During spike-wave seizures, neocortical paroxysmal activity exhibits qualitatively similar slow transitions between fast run and bursting. We therefore predict that extracellular potassium dynamics can cause alternating episodes of fast and slow oscillatory states in both normal and epileptic neocortical networks. PMID:16763023

  20. Deriving stellar inclination of slow rotators using stellar activity

    SciTech Connect

    Dumusque, X.

    2014-12-01

    Stellar inclination is an important parameter for many astrophysical studies. Although different techniques allow us to estimate stellar inclination for fast rotators, it becomes much more difficult when stars are rotating slower than ∼2-2.5 km s{sup –1}. By using the new activity simulation SOAP 2.0 which can reproduce the photometric and spectroscopic variations induced by stellar activity, we are able to fit observations of solar-type stars and derive their inclination. For HD 189733, we estimate the stellar inclination to be i=84{sub −20}{sup +6} deg, which implies a star-planet obliquity of ψ=4{sub −4}{sup +18} considering previous measurements of the spin-orbit angle. For α Cen B, we derive an inclination of i=45{sub −19}{sup +9}, which implies that the rotational spin of the star is not aligned with the orbital spin of the α Cen binary system. In addition, assuming that α Cen Bb is aligned with its host star, no transit would occur. The inclination of α Cen B can be measured using 40 radial-velocity measurements, which is remarkable given that the projected rotational velocity of the star is smaller than 1.15 km s{sup –1}.

  1. IH activity is increased in populations of slow versus fast motor axons of the rat

    PubMed Central

    Lorenz, Chad; Jones, Kelvin E.

    2014-01-01

    Much is known about the electrophysiological variation in motoneuron somata across different motor units. However, comparatively less is known about electrophysiological variation in motor axons and how this could impact function or electrodiagnosis in healthy or diseased states. We performed nerve excitability testing on two groups of motor axons in Sprague–Dawley rats that are known to differ significantly in their chronic daily activity patterns and in the relative proportion of motor unit types: one group innervating the soleus (“slow motor axons”) and the other group innervating the tibialis anterior (“fast motor axons”) muscles. We found that slow motor axons have significantly larger accommodation compared to fast motor axons upon application of a 100 ms hyperpolarizing conditioning stimulus that is 40% of axon threshold (Z = 3.24, p = 0.001) or 20% of axon threshold (Z = 2.67, p = 0.008). Slow motor axons had larger accommodation to hyperpolarizing currents in the current-threshold measurement (-80% Z = 3.07, p = 0.002; -90% Z = 2.98, p = 0.003). In addition, we found that slow motor axons have a significantly smaller rheobase than fast motor axons (Z = -1.99, p = 0.047) accompanied by a lower threshold in stimulus-response curves. The results provide evidence that slow motor axons have greater activity of the hyperpolarization-activated inwardly rectifying cation conductance (IH) than fast motor axons. It is possible that this difference between fast and slow axons is caused by an adaptation to their chronic differences in daily activity patterns, and that this adaptation might have a functional effect on the motor unit. Moreover, these findings indicate that slow and fast motor axons may react differently to pathological conditions. PMID:25309406

  2. Activity of Reticulitermes flavipes (Isoptera: Rhinotermitidae) Exposed to Nestmates Treated with Slow-Acting Nonrepellent Termiticides

    Treesearch

    J.E. Mulrooney; R. D. Hasse; T. L. Wagner; P. D. Gerard

    2007-01-01

    A 32-channel acoustical event detector was used to monitor termite activity in donor/recipient bioassays of slow-acting nonrepellent termiticides. Acoustical detection of termite activity illustrated termite mortality over time, attributed to termiticides moving from donors to recipients. In the first of two donor-recipient experiments, worker termites (donors) were...

  3. UVCS Observations of Slow Plasma Flow in the Corona Above Active Regions

    NASA Astrophysics Data System (ADS)

    Woo, R.; Habbal, S. R.

    2005-05-01

    The elusive source of slow solar wind has been the subject of ongoing discussion and debate. Observations of solar wind speed near the Earth orbit, first with IPS (interplanetary scintillation) and later with Ulysses in situ measurements, have suggested that some slow solar wind may be associated with active regions (Kojima & Kakinuma 1987; Woo, Habbal & Feldman 2004). The ability of SOHO UVCS Doppler dimming measurements to provide estimates of solar wind speed in the corona (Kohl et al. 1995) has made it possible to investigate the distribution of flow near the Sun. In this paper, we will present results confirming that active regions are one of the sources of slow wind. Insight into the relationship between coronal streamers, active regions and plasma flow will also be discussed.

  4. HEU Measurements of Holdup and Recovered Residue in the Deactivation and Decommissioning Activities of the 321-M Reactor Fuel Fabrication Facility at the Savannah River Site

    SciTech Connect

    DEWBERRY, RAYMOND; SALAYMEH, SALEEM R.; CASELLA, VITO R.; MOORE, FRANK S.

    2005-03-11

    This paper contains a summary of the holdup and material control and accountability (MC&A) assays conducted for the determination of highly enriched uranium (HEU) in the deactivation and decommissioning (D&D) of Building 321-M at the Savannah River Site (SRS). The 321-M facility was the Reactor Fuel Fabrication Facility at SRS and was used to fabricate HEU fuel assemblies, lithium-aluminum target tubes, neptunium assemblies, and miscellaneous components for the SRS production reactors. The facility operated for more than 35 years. During this time thousands of uranium-aluminum-alloy (U-Al) production reactor fuel tubes were produced. After the facility ceased operations in 1995, all of the easily accessible U-Al was removed from the building, and only residual amounts remained. The bulk of this residue was located in the equipment that generated and handled small U-Al particles and in the exhaust systems for this equipment (e.g., Chip compactor, casting furnaces, log saw, lathes A & B, cyclone separator, Freon{trademark} cart, riser crusher, ...etc). The D&D project is likely to represent an important example for D&D activities across SRS and across the Department of Energy weapons complex. The Savannah River National Laboratory was tasked to conduct holdup assays to quantify the amount of HEU on all components removed from the facility prior to placing in solid waste containers. The U-235 holdup in any single component of process equipment must not exceed 50 g in order to meet the container limit. This limit was imposed to meet criticality requirements of the low level solid waste storage vaults. Thus the holdup measurements were used as guidance to determine if further decontamination of equipment was needed to ensure that the quantity of U-235 did not exceed the 50 g limit and to ensure that the waste met the Waste Acceptance Criteria (WAC) of the solid waste storage vaults. Since HEU is an accountable nuclear material, the holdup assays and assays of recovered

  5. Fast and slow activation of voltage-dependent ion channels in radish vacuoles.

    PubMed Central

    Gambale, F; Cantu, A M; Carpaneto, A; Keller, B U

    1993-01-01

    The molecular processes associated with voltage-dependent opening and closing (gating) of ion channels were investigated using a new preparation from plant cells, i.e., voltage and calcium-activated ion channels in radish root vacuoles. These channels display a main single channel conductance of approximately 90 pS and are characterized by long activation times lasting several hundreds of milliseconds. Here, we demonstrate that these channels have a second kinetically distinct activation mode which is characterized by even longer activation times. Different membrane potential protocols allowed to switch between the fast and the slow mode in a controlled and reversible manner. At transmembrane potentials of -100 mV, the ratio between the fast and slow activation time constant was around 1:5. Correspondingly, activation times lasting several seconds were observed in the slow mode. The molecular process controlling fast and slow activation may represent an effective modulator of voltage-dependent gating of ion channels in other plant and animal systems. PMID:7507716

  6. Slow walking with turns” increases quadriceps and erector spinae muscle activity

    PubMed Central

    Araki, Mayumi; Hatamoto, Yoichi; Higaki, Yasuki; Tanaka, Hiroaki

    2017-01-01

    [Purpose] To maintain an independent lifestyle, older adults should improve muscle strength and mass, or aerobic capacity. A new exercise pattern, called slow walking with turns, which incorporates turning as an extra load additional to walking. The purpose of this study was to measure oxygen consumption during exercise and muscle activity while turning. [Subjects and Methods] Recreationally active volunteers participated. The participants performed 20 turns per minute while walking back and forth over distances of 1.5 to 3.5 m. We measured oxygen consumption, heart rate, and rating of perceived exertion and performed electromyography during the exercise. [Results] The metabolic equivalents of the exercise were 4.0 ± 0.4 to 6.3 ± 4.0 Mets. Activity was significantly greater in the vastus medialis, vastus lateralis, and erector spinae during the turn phase of slow walking with turns than during the stance phase of treadmill walking. [Conclusion] These findings suggest that slow walking with turns may help to preserve the muscle strength and mass of the trunk and lower limbs that are needed to maintain an independent lifestyle. Slow walking can be performed easily by older people, and in slow walking with turns, the exercise intensity can be adjusted as required for each individual. PMID:28356623

  7. Effects of environmental factors on the molluscicidal activities of slow-release hexabutyldistannoxane and copper sulfate*

    PubMed Central

    Chu, K. Y.

    1976-01-01

    Laboratory experiments were conducted to study the molluscicidal activities of slow-release hexabutyldistannoxane (TBTO) and copper sulfate under various environmental conditions. Organic materials such as mud and weeds reduced the molluscicidal efficacy of both chemicals. TBTO can be considered a good long-lasting molluscicide but, because of uncertainty as to its general toxic effects, it should not be used in field trials. The molluscicidal activity of slow-release copper sulfate was short-lived in plain lake water and was nil in the presence of mud or weeds at the concentration used. PMID:1088355

  8. Cross talk between activation and slow inactivation gates of Shaker potassium channels.

    PubMed

    Panyi, Gyorgy; Deutsch, Carol

    2006-11-01

    This study addresses the energetic coupling between the activation and slow inactivation gates of Shaker potassium channels. To track the status of the activation gate in inactivated channels that are nonconducting, we used two functional assays: the accessibility of a cysteine residue engineered into the protein lining the pore cavity (V474C) and the liberation by depolarization of a Cs(+) ion trapped behind the closed activation gate. We determined that the rate of activation gate movement depends on the state of the inactivation gate. A closed inactivation gate favors faster opening and slower closing of the activation gate. We also show that hyperpolarization closes the activation gate long before a channel recovers from inactivation. Because activation and slow inactivation are ubiquitous gating processes in potassium channels, the cross talk between them is likely to be a fundamental factor in controlling ion flux across membranes.

  9. Rotation sensing with Er3+-doped active ring resonator slow light structure

    NASA Astrophysics Data System (ADS)

    Gu, Hong; Liu, Xiaoqin

    2016-10-01

    An optical gyroscope, which is constituted by Er3+-doped active ring resonator (EDARR) slow light structure, is presented for the first time. The principle of improving the sensitivity of the detection of angular velocity is analysed in detail. The expression of the rotation phase difference of EDARR between the counter-propagating waves is derived and discussed. At the resonant frequency, the phase shift difference has the maximum value when the light power in the cavity is far greater than the input light power. We designed an experimental scheme of Er3+-doped active ring resonator slow light system. Two additional bias phases ϕb = ±π/2 were introduced in the optical path, by recording the light intensity difference ? and I0 at the resonant frequency ?, the input angular velocity can be obtained. The slow light structure based on EDARR can enhance the sensitivity of the detection of the angular velocity by three orders of magnitude.

  10. Family Mode Deactivation Therapy Results and Implications

    ERIC Educational Resources Information Center

    Apsche, Jack A.; Bass, Christopher K.

    2006-01-01

    This article highlights the inclusion of Mode Deactivation Therapy as a treatment modality for families in crisis. As an empirically validated treatment, Mode Deactivation Therapy has been effective in treating a wide variety of psychological issues. Mode Deactivation Therapy, (MDT) was developed to treat adolescents with disorders of conduct…

  11. Late feeding in the active period decreases slow-wave activity.

    PubMed

    Oura, Kanna; Otsuka, Airi; Shiuchi, Tetsuya; Chikahisa, Sachiko; Shimizu, Noriyuki; Séi, Hiroyoshi

    2016-09-01

    Sleep and feeding behaviors closely interact to maintain energy homeostasis. While it is known that sleep disorders can lead to various metabolic issues such as insulin resistance, the mechanism for this effect is poorly understood. We thus investigated whether different feeding rhythms during the active period affect sleep-wake regulation. For 2weeks, mice were randomly assigned to 1 of 3 feeding schedules as follows: free access to lab chow during the active period (ZT12-24, Ad-lib group), free access to lab chow during the first half of the active period (ZT12-18; Morning group), or free access to lab chow during the second half of the active period (ZT18-24, Evening group). Food intake, body weight, body temperature, locomotor activity, and sleep were evaluated. The hypothalamus and cerebral cortex were examined post-mortem. No alterations in food intake or body weight were observed among the 3 groups. The Evening group showed lower slow-wave activity (SWA) than the other 2 groups, in addition to higher expression of orexin mRNA in the hypothalamus and higher concentrations of dopamine and its metabolites in the cerebral cortex. AMPK phosphorylation was increased in the hypothalamus of mice in the Evening group; however, AMPK inhibition had no effect on SWA. We concluded that late feeding reduces SWA in NREM sleep via a mechanism that involves orexin-mediated arousal in the hypothalamus and elevated monoamines in the cerebral cortex. These data have important implications for the relationship between sleep-wake disturbances and metabolic disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Pharmaceutically active compounds: Their removal during slow sand filtration and their impact on slow sand filtration bacterial removal.

    PubMed

    D'Alessio, Matteo; Yoneyama, Bunnie; Kirs, Marek; Kisand, Veljo; Ray, Chittaranjan

    2015-08-15

    Slow sand filtration (SSF) has been widely used as a means of providing potable water due to its efficacy, low cost, and minimal maintenance. Advances in analytical instrumentation have revealed the occurrence of pharmaceutically active compounds (PhACs) in surface water as well as in groundwater. It is unclear if the presence of these compounds in the feed water can interfere with the performances of an SSF unit. The aim of this work was to examine i) the ability of two SSF units to remove six PhACs (caffeine, carbamazepine, 17-β estradiol [E2], estrone [E1], gemfibrozil, and phenazone), and ii) the impact of these PhACs on the removal of bacteria by two SSF units. The presence of PhACs in feed water for SSF can occur in surface waters impacted by wastewater or leakage from sewers and septic tanks, as well as in developing countries where unregulated use and improper disposal are prevalent. Two pilot-scale SSF units were used during the study. Unit B1 was fed with stream water with 1% of primary effluent added, while unit B2 was fed with stream water alone. Although limited removal (<10%) of carbamazepine, gemfibrozil, and phenazone occurred, the complete removal of caffeine, and the partial removal (11-92%) of E2 and E1 were observed in the two SSF units. The results of this study suggest that the occurrence of the selected PhACs, probably estrogens and caffeine, in the feed water at 50 μg L(-1) affected the ability of the schmutzdecke to remove total coliform and Escherichia coli. The bacterial removal achieved within the schmutzdecke dropped from 95% to less than 20% by the end of the study. This decrease in removal may be related to the change in the microbial community within the schmutzdecke. A diverse microbial community, including Bacteroidetes and several classes of Proteobacteria, was replaced by a microbial community in which Gammaproteobacteria was the predominant phylum (99%). Despite the low removal achieved within the schmutzdecke, removal of

  13. EEG sleep slow-wave activity as a mirror of cortical maturation.

    PubMed

    Buchmann, Andreas; Ringli, Maya; Kurth, Salomé; Schaerer, Margot; Geiger, Anja; Jenni, Oskar G; Huber, Reto

    2011-03-01

    Deep (slow wave) sleep shows extensive maturational changes from childhood through adolescence, which is reflected in a decrease of sleep depth measured as the activity of electroencephalographic (EEG) slow waves. This decrease in sleep depth is paralleled by massive synaptic remodeling during adolescence as observed in anatomical studies, which supports the notion that adolescence represents a sensitive period for cortical maturation. To assess the relationship between slow-wave activity (SWA) and cortical maturation, we acquired sleep EEG and magnetic resonance imaging data in children and adolescents between 8 and 19 years. We observed a tight relationship between sleep SWA and a variety of indexes of cortical maturation derived from magnetic resonance (MR) images. Specifically, gray matter volumes in regions correlating positively with the activity of slow waves largely overlapped with brain areas exhibiting an age-dependent decrease in gray matter. The positive relationship between SWA and cortical gray matter was present also for power in other frequency ranges (theta, alpha, sigma, and beta) and other vigilance states (theta during rapid eye movement sleep). Our findings indicate a strong relationship between sleep EEG activity and cortical maturation. We propose that in particular, sleep SWA represents a good marker for structural changes in neuronal networks reflecting cortical maturation during adolescence.

  14. Outcome of Children with Hyperventilation-Induced High-Amplitude Rhythmic Slow Activity with Altered Awareness

    ERIC Educational Resources Information Center

    Barker, Alexander; Ng, Joanne; Rittey, Christopher D. C.; Kandler, Rosalind H.; Mordekar, Santosh R.

    2012-01-01

    Hyperventilation-induced high-amplitude rhythmic slow activity with altered awareness (HIHARS) is increasingly being identified in children and is thought to be an age-related non-epileptic electrographic phenomenon. We retrospectively investigated the clinical outcome in 15 children (six males, nine females) with HIHARS (mean age 7y, SD 1y 11mo;…

  15. A distinctive subpopulation of medial septal slow-firing neurons promote hippocampal activation and theta oscillations

    PubMed Central

    Lin, Shih-Chieh; Nicolelis, Miguel A. L.

    2011-01-01

    The medial septum-vertical limb of the diagonal band of Broca (MSvDB) is important for normal hippocampal functions and theta oscillations. Although many previous studies have focused on understanding how MSVDB neurons fire rhythmic bursts to pace hippocampal theta oscillations, a significant portion of MSVDB neurons are slow-firing and thus do not pace theta oscillations. The function of these MSVDB neurons, especially their role in modulating hippocampal activity, remains unknown. We recorded MSVDB neuronal ensembles in behaving rats, and identified a distinct physiologically homogeneous subpopulation of slow-firing neurons (overall firing <4 Hz) that shared three features: 1) much higher firing rate during rapid eye movement sleep than during slow-wave (SW) sleep; 2) temporary activation associated with transient arousals during SW sleep; 3) brief responses (latency 15∼30 ms) to auditory stimuli. Analysis of the fine temporal relationship of their spiking and theta oscillations showed that unlike the theta-pacing neurons, the firing of these “pro-arousal” neurons follows theta oscillations. However, their activity precedes short-term increases in hippocampal oscillation power in the theta and gamma range lasting for a few seconds. Together, these results suggest that these pro-arousal slow-firing MSvDB neurons may function collectively to promote hippocampal activation. PMID:21865435

  16. Outcome of Children with Hyperventilation-Induced High-Amplitude Rhythmic Slow Activity with Altered Awareness

    ERIC Educational Resources Information Center

    Barker, Alexander; Ng, Joanne; Rittey, Christopher D. C.; Kandler, Rosalind H.; Mordekar, Santosh R.

    2012-01-01

    Hyperventilation-induced high-amplitude rhythmic slow activity with altered awareness (HIHARS) is increasingly being identified in children and is thought to be an age-related non-epileptic electrographic phenomenon. We retrospectively investigated the clinical outcome in 15 children (six males, nine females) with HIHARS (mean age 7y, SD 1y 11mo;…

  17. The activity of thalamus and cerebral cortex neurons in rabbits during "slow wave-spindle" EEG complexes.

    PubMed

    Burikov, A A; Bereshpolova YuI

    1999-01-01

    "Slow wave-spindle" complexes were studied during slow wave sleep in rabbits at the thalamic (medial thalamus) and cortical (upper and lower layers of the sensorimotor cortex) levels. Slow wave complexes are biphasic positive-negative complexes or triphasic complexes with a predominantly negative component. Spindles have characteristics close to those of spontaneous sleep spindles. Complexes arise singly, as though inserted into the rhythm of spontaneous sleep spindles, or in series with periods similar to the spindle rhythm. Medial thalamus neurons and some cortical neurons had the same activity during waves as during spindles: if the neuron decreased (increased) its spike frequency in a spindle, then decreases (increases) in frequency were also seen in slow waves; if the neuron produced trains of discharges during spindles, then trains of activity were also seen from the slow-wave part of "slow wave-spindle" complexes. The membrane potential changed in a similar fashion: on a background of hyperpolarization which started at the slow wave, individual depolarization oscillations appeared in the EEG wave rhythm; these oscillations were not always accompanied by spike trains. The slow wave mechanism, the rhythms of isolated complexes and simultaneous complexes and spontaneous sleep spindles may share a common underlying mechanism: slow, cyclical variations in excitability in thalamocortical neuronal networks, which have previously been demonstrated for spindle-like activity. The possibility that there are common mechanisms for slow waves in complexes and other EEG slow waves, particularly delta activity, remains hypothetical.

  18. Deactivation of Oxidation Catalysts

    DTIC Science & Technology

    1991-05-01

    the fresh catalyst . The loss in chromium may be related to the formation of volatile chromium oxychlorde which vaporizes from the catalyst . It is...CeO2 only marginally improved the thtrmal stability. The addition of 2% water vapor inhibited the oxidation of ethanol for all three copper catalysts ...original activity. Field tests of a copper chromite catalyst on process gas containing H2S, methyl mercaptan, n-aldehydes, and furfural showed

  19. Deactivation by carbon of iron catalysts for indirect liquefaction

    SciTech Connect

    Bartholomew, C H

    1991-02-14

    Progress is reported for a four-year fundamental investigation of carbon formation and its effects on the activity and selectivity of promoted iron catalysts for FT synthesis, the objectives of which were to (1) determine rates and mechanisms of carbon deactivation of unsupported Fe and Fe/K catalysts during CO hydrogenation and (2) model the global rates of deactivation at the surface of the catalyst for the same catalysts. A computer-automated reactor system to be used in the kinetic and deactivation studies was designed, constructed and tested. Kinetic data for CO hydrogenation on unsupported, unpromoted iron, 99% Fe/1% Al{sub 2}O{sub 3}, and K-promoted 99% Fe/1% Al{sub 2}O{sub 3} catalysts were obtained as functions of temperature, reactant particle pressures and time. The activity/selectivity and kinetic data are consistent with those previously reported for supported, unpromoted and promoted iron. Two kinds of deactivation were observed during FT synthesis on these samples: (1) loss of surface area after reduction of unsupported, unpromoted iron at 400{degree}C and (2) loss of activity with time due to carbon deposition, especially in the case of K-promoted 99% Fe/1% A1{sub 2}O{sub 3}. Deactivation rate data were obtained for CO hydrogenation on promoted Fe as a function of time, temperature, and H{sub 2}/CO ratio. 50 refs., 24 figs., 5 tabs.

  20. Slow oscillation electrical brain stimulation during waking promotes EEG theta activity and memory encoding.

    PubMed

    Kirov, Roumen; Weiss, Carsten; Siebner, Hartwig R; Born, Jan; Marshall, Lisa

    2009-09-08

    The application of transcranial slow oscillation stimulation (tSOS; 0.75 Hz) was previously shown to enhance widespread endogenous EEG slow oscillatory activity when applied during a sleep period characterized by emerging endogenous slow oscillatory activity. Processes of memory consolidation typically occurring during this state of sleep were also enhanced. Here, we show that the same tSOS applied in the waking brain also induced an increase in endogenous EEG slow oscillations (0.4-1.2 Hz), although in a topographically restricted fashion. Applied during wakefulness tSOS, additionally, resulted in a marked and widespread increase in EEG theta (4-8 Hz) activity. During wake, tSOS did not enhance consolidation of memories when applied after learning, but improved encoding of hippocampus-dependent memories when applied during learning. We conclude that the EEG frequency and related memory processes induced by tSOS critically depend on brain state. In response to tSOS during wakefulness the brain transposes stimulation by responding preferentially with theta oscillations and facilitated encoding.

  1. Social exclusion in middle childhood: rejection events, slow-wave neural activity, and ostracism distress.

    PubMed

    Crowley, Michael J; Wu, Jia; Molfese, Peter J; Mayes, Linda C

    2010-01-01

    This study examined neural activity with event-related potentials (ERPs) in middle childhood during a computer-simulated ball-toss game, Cyberball. After experiencing fair play initially, children were ultimately excluded by the other players. We focused specifically on “not my turn” events within fair play and rejection events within social exclusion. Dense-array ERPs revealed that rejection events are perceived rapidly. Condition differences (“not my turn” vs. rejection) were evident in a posterior ERP peaking at 420 ms consistent, with a larger P3 effect for rejection events indicating that in middle childhood rejection events are differentiated in <500 ms. Condition differences were evident for slow-wave activity (500-900 ms) in the medial frontal cortical region and the posterior occipital-parietal region, with rejection events more negative frontally and more positive posteriorly. Distress from the rejection experience was associated with a more negative frontal slow wave and a larger late positive slow wave, but only for rejection events. Source modeling with Geosouce software suggested that slow-wave neural activity in cortical regions previously identified in functional imaging studies of ostracism, including subgenual cortex, ventral anterior cingulate cortex, and insula, was greater for rejection events vs. “not my turn” events.

  2. Activation of very low frequency earthquakes by slow slip events in the Ryukyu Trench

    NASA Astrophysics Data System (ADS)

    Nakamura, Mamoru; Sunagawa, Naoya

    2015-02-01

    Long-term activity of shallow very low frequency earthquakes (VLFEs) in the Ryukyu Trench, unassociated with recent large thrust earthquakes, was analyzed using a broadband seismometer network. The distribution of shallow VLFEs was divided into three large clusters. The activity of the VLFEs is modulated by repetitive slow slip events, and the activity of these VLFEs increases to 2-3 times its ordinary rate at 10-20 days after the onset of the slow slip events. The activation of VLFEs could be generated by small increases on the order of approximately 0.1-0.5 kPa in Coulomb failure stress, suggesting that stress in the plate interface where the VLFEs occur is frequently released in small amounts. Moreover, the distribution of VLFEs is complementary to the historical tsunami source area and locked area. The distribution of the VLFEs indicates heterogeneity in interplate coupling along the trench.

  3. Enhanced Reactivity in Hydrogen Atom Transfer from Tertiary Sites of Cyclohexanes and Decalins via Strain Release: Equatorial C-H Activation vs Axial C-H Deactivation.

    PubMed

    Salamone, Michela; Ortega, Vanesa B; Bietti, Massimo

    2015-05-01

    Absolute rate constants for hydrogen atom transfer (HAT) from cycloalkanes and decalins to the cumyloxyl radical (CumO(•)) were measured by laser flash photolysis. Very similar reactivities were observed for the C-H bonds of cyclopentane and cyclohexane, while the tertiary C-H bond of methylcyclopentane was found to be 6 times more reactive than the tertiary axial C-H bond of methylcyclohexane, pointing toward a certain extent of tertiary axial C-H bond deactivation. Comparison between the cis and trans isomers of 1,2-dimethylcyclohexane, 1,4-dimethylcyclohexane and decalin provides a quantitative evaluation of the role played by strain release in these reactions. kH values for HAT from tertiary equatorial C-H bonds were found to be at least 1 order of magnitude higher than those for HAT from the corresponding tertiary axial C-H bonds (kH(eq)/kH(ax) = 10-14). The higher reactivity of tertiary equatorial C-H bonds was explained in terms of 1,3-diaxial strain release in the HAT transition state. Increase in torsional strain in the HAT transition state accounts instead for tertiary axial C-H bond deactivation. The results are compared with those obtained for the corresponding C-H functionalization reactions by dioxiranes and nonheme metal-oxo species indicating that CumO(•) can represent a convenient model for the reactivity patterns of these oxidants.

  4. Fluorescence-Tracking of Activation Gating in Human ERG Channels Reveals Rapid S4 Movement and Slow Pore Opening

    PubMed Central

    Xiong, Ping Yu; Robertson, Gail A.; Fedida, David

    2010-01-01

    Background hERG channels are physiologically important ion channels which mediate cardiac repolarization as a result of their unusual gating properties. These are very slow activation compared with other mammalian voltage-gated potassium channels, and extremely rapid inactivation. The mechanism of slow activation is not well understood and is investigated here using fluorescence as a direct measure of S4 movement and pore opening. Methods and Findings Tetramethylrhodamine-5-maleimide (TMRM) fluorescence at E519 has been used to track S4 voltage sensor movement, and channel opening and closing in hERG channels. Endogenous cysteines (C445 and C449) in the S1–S2 linker bound TMRM, which caused a 10 mV hyperpolarization of the V½ of activation to −27.5±2.0 mV, and showed voltage-dependent fluorescence signals. Substitution of S1–S2 linker cysteines with valines allowed unobstructed recording of S3–S4 linker E519C and L520C emission signals. Depolarization of E519C channels caused rapid initial fluorescence quenching, fit with a double Boltzmann relationship, F-VON, with V½,1 = −37.8±1.7 mV, and V½,2 = 43.5±7.9 mV. The first phase, V½,1, was ∼20 mV negative to the conductance-voltage relationship measured from ionic tail currents (G-V½ = −18.3±1.2 mV), and relatively unchanged in a non-inactivating E519C:S620T mutant (V½ = −34.4±1.5 mV), suggesting the fast initial fluorescence quenching tracked S4 voltage sensor movement. The second phase of rapid quenching was absent in the S620T mutant. The E519C fluorescence upon repolarization (V½ = −20.6±1.2, k = 11.4 mV) and L520C quenching during depolarization (V½ = −26.8±1.0, k = 13.3 mV) matched the respective voltage dependencies of hERG ionic tails, and deactivation time constants from −40 to −110 mV, suggesting they detected pore-S4 rearrangements related to ionic current flow during pore opening and closing. Conclusion The data indicate: 1) that rapid

  5. Repetitive activity slows axonal conduction velocity and concomitantly increases mechanical activation threshold in single axons of the rat cranial dura.

    PubMed

    De Col, Roberto; Messlinger, Karl; Carr, Richard W

    2012-02-15

    The passage of an action potential along a peripheral axon modulates the conduction velocity of subsequent action potentials. In C-neurones with unmyelinated axons repetitive activity progressively slows axonal conduction velocity and in microneurographic recordings from healthy human subjects the magnitude of this slowing can be used to predict the receptive properties of individual axons. Recently, a reduction in the number of available voltage-gated sodium channels (Na(V)) through inactivation has been implicated as the predominant factor responsible for the slowing of axonal conduction. Since Na(V)s are also responsible for the initiation of action potentials in sensory nerve terminals, changes in their availability may be expected to affect activation threshold for sensory stimuli. To examine this proposal, dynamic mechanical stimuli were used to make precise estimates of activation threshold in single unmyelinated axons innervating the rat cranial dura mater. Decreases in axonal conduction velocity induced by repetitive electrical stimulation were paralleled by an increase in mechanical activation threshold. Application of TTX (10-20 nM) also slowed axonal conduction velocity in all 11 fibres examined and in 9 of these this resulted in a parallel increase in mechanical activation threshold. We interpret this as indicating that a reduction in available Na(V) number contributes to both axonal conduction velocity slowing and the observed parallel increase in mechanical activation threshold. The slowing of axonal conduction velocity observed during repetitive activity thus represents a form of accommodation, i.e. self inhibition, which is likely to be decisive in limiting peripheral input to the spinal dorsal horn and thereby regulating processes that could otherwise lead to central sensitization.

  6. Solid-state enzyme deactivation in air and in organic solvents

    SciTech Connect

    Toscano, G.; Pirozzi, D.; Maremonti, M.; Greco, G. Jr. . Dipartimento di Ingegneria Chimica)

    1994-09-05

    Thermal deactivation of solid-state acid phosphatase is analyzed, both in the presence and in the absence of organic solvents. The thermal deactivation profile departs from first order kinetics and shows an unusual, temperature-dependent, asymptotic value of residual activity. The process is described by a phenomenological equation, whose theoretical implications are also discussed. The total amount of buffer salts in the enzyme powder dramatically affects enzyme stability in the range 70 to 105 C. The higher salt/protein ratio increases the rate of thermal deactivation. The deactivation rate is virtually unaffected by the presence of organic solvents, independent of their hydrophilicity.

  7. Slow sleep spindle activity, declarative memory, and general cognitive abilities in children.

    PubMed

    Hoedlmoser, Kerstin; Heib, Dominik P J; Roell, Judith; Peigneux, Philippe; Sadeh, Avi; Gruber, Georg; Schabus, Manuel

    2014-09-01

    Functional interactions between sleep spindle activity, declarative memory consolidation, and general cognitive abilities in school-aged children. Healthy, prepubertal children (n = 63; mean age 9.56 ± 0.76 y); ambulatory all-night polysomnography (2 nights); investigating the effect of prior learning (word pair association task; experimental night) versus nonlearning (baseline night) on sleep spindle activity; general cognitive abilities assessed using the Wechsler Intelligence Scale for Children-IV (WISC-IV). Analysis of spindle activity during nonrapid eye movement sleep (N2 and N3) evidenced predominant peaks in the slow (11-13 Hz) but not in the fast (13-15 Hz) sleep spindle frequency range (baseline and experimental night). Analyses were restricted to slow sleep spindles. Changes in spindle activity from the baseline to the experimental night were not associated with the overnight change in the number of recalled words reflecting declarative memory consolidation. Children with higher sleep spindle activity as measured at frontal, central, parietal, and occipital sites during both baseline and experimental nights exhibited higher general cognitive abilities (WISC-IV) and declarative learning efficiency (i.e., number of recalled words before and after sleep). Slow sleep spindles (11-13 Hz) in children age 8-11 y are associated with inter-individual differences in general cognitive abilities and learning efficiency. © 2014 Associated Professional Sleep Societies, LLC.

  8. Regeneration of a deactivated USY alkylation catalyst using supercritical isobutane

    SciTech Connect

    Daniel M. Ginosar; David N. Ghompson; Kyle C. Burch

    2005-01-01

    Off-line, in-situ alkylation activity recovery from a completely deactivated solid acid catalyst was examined in a continuous-flow reaction system employing supercritical isobutane. A USY zeolite catalyst was initially deactivated during the liquid phase alkylation of butene with isobutane in a single-pass reactor and then varying amounts of alkylation activity were recovered by passing supercritical isobutane over the catalyst bed at different reactivation conditions. Temperature, pressure and regeneration time were found to play important roles in the supercritical isobutane regeneration process when applied to a completely deactivated USY zeolite alkylation catalyst. Manipulation of the variables that influence solvent strength, diffusivity, surface desorption, hydride transfer rates, and coke aging, strongly influence regeneration effectiveness.

  9. Investigation of Slow-wave Activity Saturation during Surgical Anesthesia Reveals a Signature of Neural Inertia in Humans.

    PubMed

    Warnaby, Catherine E; Sleigh, Jamie W; Hight, Darren; Jbabdi, Saad; Tracey, Irene

    2017-10-01

    Previously, we showed experimentally that saturation of slow-wave activity provides a potentially individualized neurophysiologic endpoint for perception loss during anesthesia. Furthermore, it is clear that induction and emergence from anesthesia are not symmetrically reversible processes. The observed hysteresis is potentially underpinned by a neural inertia mechanism as proposed in animal studies. In an advanced secondary analysis of 393 individual electroencephalographic data sets, we used slow-wave activity dose-response relationships to parameterize slow-wave activity saturation during induction and emergence from surgical anesthesia. We determined whether neural inertia exists in humans by comparing slow-wave activity dose responses on induction and emergence. Slow-wave activity saturation occurs for different anesthetics and when opioids and muscle relaxants are used during surgery. There was wide interpatient variability in the hypnotic concentrations required to achieve slow-wave activity saturation. Age negatively correlated with power at slow-wave activity saturation. On emergence, we observed abrupt decreases in slow-wave activity dose responses coincident with recovery of behavioral responsiveness in ~33% individuals. These patients are more likely to have lower power at slow-wave activity saturation, be older, and suffer from short-term confusion on emergence. Slow-wave activity saturation during surgical anesthesia implies that large variability in dosing is required to achieve a targeted potential loss of perception in individual patients. A signature for neural inertia in humans is the maintenance of slow-wave activity even in the presence of very-low hypnotic concentrations during emergence from anesthesia.

  10. Slow expiration reduces sternocleidomastoid activity and increases transversus abdominis and internal oblique muscle activity during abdominal curl-up.

    PubMed

    Yoon, Tae-Lim; Kim, Ki-Song; Cynn, Heon-Seock

    2014-04-01

    The aim of this study was to investigate the effects of quiet inspiration versus slow expiration on sternocleidomastoid (SCM) and abdominal muscle activity during abdominal curl-up in healthy subjects. Twelve healthy subjects participated in this study. Surface electromyography (EMG) was used to collect activity of bilateral SCM, rectus abdominis (RA), external oblique (EO), and transversus abdominis/internal oblique (TrA/IO) muscles. A paired t-test was used to determine significant differences in the bilateral SCM, RF, EO, and TrA/IO muscles between abdominal curl-up with quiet inspiration and slow expiration. There were significantly lower EMG activity of both SCMs and greater EMG activity of both IOs during abdominal curl-up with slow expiration, compared with the EMG activity of both SCMs and IOs during abdominal curl-up with quiet inspiration (p<.05). The results of this study suggest that slow expiration would be recommended during abdominal curl-up for reduced SCM activation and selective activation of TrA/IO in healthy subjects compared with those in abdominal curl up with quiet inspiration.

  11. Impaired consciousness in temporal lobe seizures: role of cortical slow activity

    PubMed Central

    Englot, Dario J.; Yang, Li; Hamid, Hamada; Danielson, Nathan; Bai, Xiaoxiao; Marfeo, Anthony; Yu, Lissa; Gordon, Aliza; Purcaro, Michael J.; Motelow, Joshua E.; Agarwal, Ravi; Ellens, Damien J.; Golomb, Julie D.; Shamy, Michel C. F.; Zhang, Heping; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Vives, Kenneth; Spencer, Dennis D.; Spencer, Susan S.; Schevon, Catherine; Zaveri, Hitten P.

    2010-01-01

    Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a ‘network inhibition hypothesis’ in which temporal lobe seizures disrupt brainstem–diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1–2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure

  12. Slow Sleep Spindle Activity, Declarative Memory, and General Cognitive Abilities in Children

    PubMed Central

    Hoedlmoser, Kerstin; Heib, Dominik P.J.; Roell, Judith; Peigneux, Philippe; Sadeh, Avi; Gruber, Georg; Schabus, Manuel

    2014-01-01

    Study Objectives: Functional interactions between sleep spindle activity, declarative memory consolidation, and general cognitive abilities in school-aged children. Design: Healthy, prepubertal children (n = 63; mean age 9.56 ± 0.76 y); ambulatory all-night polysomnography (2 nights); investigating the effect of prior learning (word pair association task; experimental night) versus nonlearning (baseline night) on sleep spindle activity; general cognitive abilities assessed using the Wechsler Intelligence Scale for Children-IV (WISC-IV). Measurements and Results: Analysis of spindle activity during nonrapid eye movement sleep (N2 and N3) evidenced predominant peaks in the slow (11-13 Hz) but not in the fast (13-15 Hz) sleep spindle frequency range (baseline and experimental night). Analyses were restricted to slow sleep spindles. Changes in spindle activity from the baseline to the experimental night were not associated with the overnight change in the number of recalled words reflecting declarative memory consolidation. Children with higher sleep spindle activity as measured at frontal, central, parietal, and occipital sites during both baseline and experimental nights exhibited higher general cognitive abilities (WISC-IV) and declarative learning efficiency (i.e., number of recalled words before and after sleep). Conclusions: Slow sleep spindles (11-13 Hz) in children age 8–11 y are associated with inter-individual differences in general cognitive abilities and learning efficiency. Citation: Hoedlmoser K, Heib DPJ, Roell J, Peigneux P, Sadeh A, Gruber G, Schabus M. Slow sleep spindle activity, declarative memory, and general cognitive abilities in children. SLEEP 2014;37(9):1501-1512. PMID:25142558

  13. Characterization of Deactivated Bio-oil Hydrotreating Catalysts

    SciTech Connect

    Wang, Huamin; Wang, Yong

    2015-10-06

    Deactivation of bio-oil hydrotreating catalysts remains a significant challenge because of the poor quality of pyrolysis bio-oil input for hydrotreating and understanding their deactivation mode is critical to developing improved catalysts and processes. In this research, we developed an understanding of the deactivation of two-step bio-oil hydrotreating catalysts (sulfided Ru/C and sulfided CoMo/C) through detailed characterization of the catalysts using various complimentary analytical techniques. Severe fouling of both catalysts by carbonaceous species was the major form of deactivation, which is consistent with the significant loss of surface area and pore volume of both deactivated catalysts and the significant increase of the bulk density. Further analysis of the carbonaceous species by thermogravimetric analysis and x-ray photoelectron spectroscopy indicated that the carbonaceous species was formed by condensation reaction of active species such as sugars and sugar derivatives (aldehydes and ketones) in bio-oil feedstock during bio-oil hydrotreating under the conditions and catalysts used. Microscopy results did not show metal sintering of the Ru/C catalyst. However, X-ray diffraction indicated a probable transformation of the highly-active CoMoS phase in the sulfided CoMo/C catalyst to Co8S9 and MoS2 phase with low activity. Loss of the active site by transport of inorganic elements from the bio-oil and the reactor construction material onto the catalyst surface also might be a cause of deactivation as indicated by elemental analysis of spent catalysts.

  14. Acute sensitivity of FAST and SLOW mice to the effects of abused drugs on locomotor activity.

    PubMed

    Phillips, T J; Burkhart-Kasch, S; Gwiazdon, C C; Crabbe, J C

    1992-05-01

    The universal nature of the stimulant or euphoric effect of addictive drugs suggests that it may be an important predictor of a drug's addiction potential. Furthermore, assessment of stimulant sensitivity could be useful for predicting the liability of individuals to drug abuse. The stimulant actions of abused drugs from different pharmacological classes may share a common biological mechanism. We investigated this notion by assessing the drug responses relative to base-line locomotor activity of mice selectively bred for increased (FAST) and reduced (SLOW) sensitivity to ethanol-induced stimulation. FAST mice were more sensitive than SLOW mice to the stimulant effects of methanol (1.5-3.0 g/kg), t-butanol (0.2-0.6 g/kg), n-propanol (0.15-1.2 g/kg), pentobarbital (10-40 mg/kg) and phenobarbital (15-120 mg/kg). FAST and SLOW mice were similarly stimulated by d-amphetamine (1.25-10 mg/kg) and caffeine (2.5-20 mg/kg). The activity of FAST and SLOW mice was equally depressed by nicotine (0.5-2.0 mg/kg) and morphine (4-75 mg/kg). Finally, FAST mice were unaffected, whereas SLOW mice were depressed by diazepam (1-8 mg/kg). Selection for relative sensitivity to stimulation by ethanol has generalized to other alcohols and to barbiturates, but not to several other abused drugs, including amphetamine. The data presented here support a hypothesized common mechanism of stimulant action for alcohols and barbiturates, and suggest that differences in sensitivity to drug stimulant effects can be seen in the absence of dopamine system differences.

  15. Biodegradation of the cyanobacterial toxin microcystin LR in natural water and biologically active slow sand filters.

    PubMed

    Bourne, David G; Blakeley, Robert L; Riddles, Peter; Jones, Gary J

    2006-03-01

    A bacterium (MJ-PV) previously demonstrated to degrade the cyanobacterial toxin microcystin LR, was investigated for bioremediation applications in natural water microcosms and biologically active slow sand filters. Enhanced degradation of microcystin LR was observed with inoculated (1 x 10(6) cell/mL) treatments of river water dosed with microcystin LR (>80% degradation within 2 days) compared to uninoculated controls. Inoculation of MJ-PV at lower concentrations (1 x 10(2)-1 x 10(5) cells/mL) also demonstrated enhanced microcystin LR degradation over control treatments. Polymerase chain reactions (PCR) specifically targeting amplification of 16S rDNA of MJ-PV and the gene responsible for initial degradation of microcystin LR (mlrA) were successfully applied to monitor the presence of the bacterium in experimental trials. No amplified products indicative of an endemic MJ-PV population were observed in uninoculated treatments indicating other bacterial strains were active in degradation of microcystin LR. Pilot scale biologically active slow sand filters demonstrated degradation of microcystin LR irrespective of MJ-PV bacterial inoculation. PCR analysis detected the MJ-PV population at all locations within the sand filters where microcystin degradation was measured. Despite not observing enhanced degradation of microcystin LR in inoculated columns compared to uninoculated column, these studies demonstrate the effectiveness of a low-technology water treatment system like biologically active slow sand filters for removal of microcystins from reticulated water supplies.

  16. Ongoing slow oscillatory phase modulates speech intelligibility in cooperation with motor cortical activity.

    PubMed

    Onojima, Takayuki; Kitajo, Keiichi; Mizuhara, Hiroaki

    2017-01-01

    Neural oscillation is attracting attention as an underlying mechanism for speech recognition. Speech intelligibility is enhanced by the synchronization of speech rhythms and slow neural oscillation, which is typically observed as human scalp electroencephalography (EEG). In addition to the effect of neural oscillation, it has been proposed that speech recognition is enhanced by the identification of a speaker's motor signals, which are used for speech production. To verify the relationship between the effect of neural oscillation and motor cortical activity, we measured scalp EEG, and simultaneous EEG and functional magnetic resonance imaging (fMRI) during a speech recognition task in which participants were required to recognize spoken words embedded in noise sound. We proposed an index to quantitatively evaluate the EEG phase effect on behavioral performance. The results showed that the delta and theta EEG phase before speech inputs modulated the participant's response time when conducting speech recognition tasks. The simultaneous EEG-fMRI experiment showed that slow EEG activity was correlated with motor cortical activity. These results suggested that the effect of the slow oscillatory phase was associated with the activity of the motor cortex during speech recognition.

  17. Interstitial cells of Cajal integrate excitatory and inhibitory neurotransmission with intestinal slow-wave activity.

    PubMed

    Klein, Sabine; Seidler, Barbara; Kettenberger, Anna; Sibaev, Andrei; Rohn, Michael; Feil, Robert; Allescher, Hans-Dieter; Vanderwinden, Jean-Marie; Hofmann, Franz; Schemann, Michael; Rad, Roland; Storr, Martin A; Schmid, Roland M; Schneider, Günter; Saur, Dieter

    2013-01-01

    The enteric nervous system contains excitatory and inhibitory neurons, which control contraction and relaxation of smooth muscle cells as well as gastrointestinal motor activity. Little is known about the exact cellular mechanisms of neuronal signal transduction to smooth muscle cells in the gut. Here we generate a c-Kit(CreERT2) knock-in allele to target a distinct population of pacemaker cells called interstitial cells of Cajal. By genetic loss-of-function studies, we show that interstitial cells of Cajal, which generate spontaneous electrical slow waves and thus rhythmic contractions of the smooth musculature, are essential for transmission of signals from enteric neurons to gastrointestinal smooth muscle cells. Interstitial cells of Cajal, therefore, integrate excitatory and inhibitory neurotransmission with slow-wave activity to orchestrate peristaltic motor activity of the gut. Impairment of the function of interstitial cells of Cajal causes severe gastrointestinal motor disorders. The results of our study show at the genetic level that these disorders are not only due to loss of slow-wave activity but also due to disturbed neurotransmission.

  18. Intention Retrieval and Deactivation Following an Acute Psychosocial Stressor

    PubMed Central

    Walser, Moritz; Fischer, Rico; Goschke, Thomas; Kirschbaum, Clemens; Plessow, Franziska

    2013-01-01

    We often form intentions but have to postpone them until the appropriate situation for retrieval and execution has come, an ability also referred to as event-based prospective memory. After intention completion, our cognitive system has to deactivate no-more-relevant intention representations from memory to avoid interference with subsequent tasks. In everyday life, we frequently rely on these abilities also in stressful situations. Surprisingly, little is known about potential stress effects on these functions. Therefore, the present study aimed to examine the reliability of event-based prospective memory and of intention deactivation in conditions of acute psychosocial stress. To this aim, eighty-two participants underwent the Trier Social Stress Test, a standardized stress protocol, or a standardized control situation. Following this treatment, participants performed a computerized event-based prospective memory task with non-salient and focal prospective memory cues in order to assess prospective memory performance and deactivation of completed intentions. Although the stress group showed elevated levels of salivary cortisol as marker of a stress-related increase in hypothalamus-pituitary-adrenal axis activity throughout the cognitive testing period compared to the no-stress group, prospective memory performance and deactivation of completed intentions did not differ between groups. Findings indicate that cognitive control processes subserving intention retrieval and deactivation after completion may be mostly preserved even under conditions of acute stress. PMID:24386486

  19. Deactivation by carbon of iron catalysts for indirect liquefaction

    SciTech Connect

    Bartholomew, C.H.

    1991-01-10

    Although promoted cobalt and iron catalysts for Fischer-Tropsch (FT) synthesis of gasoline feedstock were first developed more than three decades ago, a major technical problem still limiting the commercial use of these catalysts today is carbon deactivation. This report describes recent progress in a fundamental, three-year investigation of carbon formation and its effects on the activity and selectivity of promoted iron catalysts for FT synthesis, the objectives of which are to: determine rates and mechanisms of carbon deactivation of unsupported Fe and Fe/K catalysts during CO hydrogenation over a range of CO concentrations, CO:H{sub 2} ratios, and temperatures; and model the rates of deactivation of the same catalysts in fixed-bed reactors. To accomplish the above objectives, the project is divided into the following tasks: (1) determine the kinetics of reaction and of carbon deactivation during CO hydrogenation on Fe and Fe/K catalysts coated on monolith bodies. (2) Determine the reactivities and types of carbon deposited during reaction on the same catalysts from temperature-programmed-surface-reaction spectroscopy (TPSR) and transmission electron microscopy (TEM). Determine the types of iron carbides formed at various temperatures and H{sub 2}/CO ratios using x-ray diffraction and Moessbauer spectroscopy. (3) Develop mathematical deactivation models which include heat and mass transport contributions for FT synthesis is packed-bed reactors. Progress to date is described. 48 refs., 3 figs., 1 tab.

  20. Oxidative Activation of Bacillus cereus Spores

    PubMed Central

    Cochran, Stuart A.; Ordal, Z. John

    1973-01-01

    A study was made of the activation of Bacillus cereus strain T spores by using the oxidizing agent sodium perborate. The degree of activation was measured with constant germination conditions by using L-alanine, inosine, adenosine, and L-alanine plus adenosine as germination stimulants. The germinal response following the various treatments was compared with the responses obtained with heat activation. It was concluded that the optimal time for activation with 30 mM sodium perborate at room temperature was about 4 hr. If the exposure time was greatly extended, the spores would germinate spontaneously. When the perborate treatment followed heat activation, the germinal response to L-alanine was stimulated, to inosine retarded and without apparent effect for adenosine or L-alanine plus adenosine. Results of experiments designed to demonstrate deactivation by slow oxidation showed that spores activated with sodium perborate were not deactivated by slow oxidation, whereas those activated by heat were. A deactivation study using mercaptoethanol as the deactivation agent showed that both methods of activation could be deactivated after a 24-hr exposure, but this deactivation was reversible by extending the exposure to mercaptoethanol. The results of heat-sensitivity studies revealed that about 70% of the sodium perborate-activated spores were heat sensitive after 60 min in a germination menstruum of L-alanine plus adenosine, whereas similarly treated heat-activated and nonactivated spores were about 99.99% heat sensitive, respectively. PMID:4632848

  1. Prolonged activity evokes potentiation and the "sag" phenomenon in slow motor units of rat soleus.

    PubMed

    Drzymała-Celichowska, Hanna; Raikova, Rositsa; Krutki, Piotr

    2016-01-01

    Slow motor units (MUs) have no sag in their unfused tetani. This study in anesthetized rats shows that the sag can be observed in slow soleus MUs after prolonged activity. Twitches and unfused tetanic contractions were recorded from male (n=35) and female (n=39) MUs before and after the four minutes of the fatigue test (trains of 13 pulses at 40 Hz repeated every second). After this activity twitch contractions potentiated and a shift in the steep part of the force-frequency curve towards lower frequencies was observed in both sexes. Initially no sag was visible in unfused tetani, but after the fatigue test the phenomenon was observed in 77% of male, while in 13% of female MUs, the result consistent with the previously reported higher content of IIa myosin and faster contraction of MUs in male soleus. The decomposition of tetani with sag into trains of twitch-shape responses to consecutive stimuli revealed higher forces of initial decomposed twitches than later. The revealed alterations the force development due to long-lasting activation of slow MUs were sex-related and more pronounced in male soleus.

  2. Physical activity monitoring: addressing the difficulties of accurately detecting slow walking speeds.

    PubMed

    Harrison, Samantha L; Horton, Elizabeth J; Smith, Robert; Sandland, Carolyn J; Steiner, Michael C; Morgan, Mike D L; Singh, Sally J

    2013-01-01

    To test the accuracy of a multi-sensor activity monitor (SWM) in detecting slow walking speeds in patients with chronic obstructive pulmonary disease (COPD). Concerns have been expressed regarding the use of pedometers in patient populations. Although activity monitors are more sophisticated devices, their accuracy at detecting slow walking speeds common in patients with COPD has yet to be proven. A prospective observational study design was employed. An incremental shuttle walk test (ISWT) was completed by 57 patients with COPD wearing an SWM. The ISWT was repeated by 20 patients wearing the same SWM. Differences were identified between metabolic equivalents (METS) and between step-count across five levels of the ISWT (p < 0.001). Good within monitor reproducibility between two ISWT was identified for total energy expenditure and step-count (p < 0.001). The SWM is able to detect slow (standardized) speeds of walking and is an acceptable method for measuring physical activity in individuals disabled by COPD. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. A System and Method for Online High-Resolution Mapping of Gastric Slow-Wave Activity

    PubMed Central

    Bull, Simon H.; O’Grady, Gregory; Du, Peng

    2015-01-01

    High-resolution (HR) mapping employs multielectrode arrays to achieve spatially detailed analyses of propagating bioelectrical events. A major current limitation is that spatial analyses must currently be performed “off-line” (after experiments), compromising timely recording feedback and restricting experimental interventions. These problems motivated development of a system and method for “online” HR mapping. HR gastric recordings were acquired and streamed to a novel software client. Algorithms were devised to filter data, identify slow-wave events, eliminate corrupt channels, and cluster activation events. A graphical user interface animated data and plotted electrograms and maps. Results were compared against off-line methods. The online system analyzed 256-channel serosal recordings with no unexpected system terminations with a mean delay 18 s. Activation time marking sensitivity was 0.92; positive predictive value was 0.93. Abnormal slow-wave patterns including conduction blocks, ectopic pacemaking, and colliding wave fronts were reliably identified. Compared to traditional analysis methods, online mapping had comparable results with equivalent coverage of 90% of electrodes, average RMS errors of less than 1 s, and CC of activation maps of 0.99. Accurate slow-wave mapping was achieved in near real-time, enabling monitoring of recording quality and experimental interventions targeted to dysrhythmic onset. This work also advances the translation of HR mapping toward real-time clinical application. PMID:24860024

  4. Antioxidant Deactivation on Graphenic Nanocarbon Surfaces

    SciTech Connect

    Liu, Xinyuan; Sen, Sujat; Liu, Jingyu; Kulaots, Indrek; Geohegan, David B; Kane, Agnes; Puretzky, Alexander A; Rouleau, Christopher M; More, Karren Leslie; Palmore, G. Tayhas R.; Hurt, Robert H.

    2011-01-01

    This article reports a direct chemical pathway for antioxidant deactivation on the surfaces of carbon nanomaterials. In the absence of cells, carbon nanotubes are shown to deplete the key physiological antioxidant glutathione (GSH) in a reaction involving dissolved dioxygen that yields the oxidized dimer, GSSG, as the primary product. In both chemical and electrochemical experiments, oxygen is only consumed at a significant steady-state rate in the presence of both nanotubes and GSH. GSH deactivation occurs for single- and multi-walled nanotubes, graphene oxide, nanohorns, and carbon black at varying rates that are characteristic of the material. The GSH depletion rates can be partially unified by surface area normalization, are accelerated by nitrogen doping, and suppressed by defect annealing or addition of proteins or surfactants. It is proposed that dioxygen reacts with active sites on graphenic carbon surfaces to produce surface-bound oxygen intermediates that react heterogeneously with glutathione to restore the carbon surface and complete a catalytic cycle. The direct catalytic reaction between nanomaterial surfaces and antioxidants may contribute to oxidative stress pathways in nanotoxicity, and the dependence on surface area and structural defects suggest strategies for safe material design.

  5. PUREX/UO{sub 3} facilities deactivation lessons learned: History

    SciTech Connect

    Gerber, M.S.

    1997-11-25

    In May 1997, a historic deactivation project at the PUREX (Plutonium URanium EXtraction) facility at the Hanford Site in south-central Washington State concluded its activities (Figure ES-1). The project work was finished at $78 million under its original budget of $222.5 million, and 16 months ahead of schedule. Closely watched throughout the US Department of Energy (DOE) complex and by the US Department of Defense for the value of its lessons learned, the PUREX Deactivation Project has become the national model for the safe transition of contaminated facilities to shut down status.

  6. Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen

    PubMed Central

    Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

    2016-01-01

    Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active

  7. Synaptic refinement during development and its effect on slow-wave activity: a computational study

    PubMed Central

    Hoel, Erik P.; Albantakis, Larissa; Cirelli, Chiara

    2016-01-01

    Recent evidence suggests that synaptic refinement, the reorganization of synapses and connections without significant change in their number or strength, is important for the development of the visual system of juvenile rodents. Other evidence in rodents and humans shows that there is a marked drop in sleep slow-wave activity (SWA) during adolescence. Slow waves reflect synchronous transitions of neuronal populations between active and inactive states, and the amount of SWA is influenced by the connection strength and organization of cortical neurons. In this study, we investigated whether synaptic refinement could account for the observed developmental drop in SWA. To this end, we employed a large-scale neural model of primary visual cortex and sections of the thalamus, capable of producing realistic slow waves. In this model, we reorganized intralaminar connections according to experimental data on synaptic refinement: during prerefinement, local connections between neurons were homogenous, whereas in postrefinement, neurons connected preferentially to neurons with similar receptive fields and preferred orientations. Synaptic refinement led to a drop in SWA and to changes in slow-wave morphology, consistent with experimental data. To test whether learning can induce synaptic refinement, intralaminar connections were equipped with spike timing-dependent plasticity. Oriented stimuli were presented during a learning period, followed by homeostatic synaptic renormalization. This led to activity-dependent refinement accompanied again by a decline in SWA. Together, these modeling results show that synaptic refinement can account for developmental changes in SWA. Thus sleep SWA may be used to track noninvasively the reorganization of cortical connections during development. PMID:26843602

  8. Synaptic refinement during development and its effect on slow-wave activity: a computational study.

    PubMed

    Hoel, Erik P; Albantakis, Larissa; Cirelli, Chiara; Tononi, Giulio

    2016-04-01

    Recent evidence suggests that synaptic refinement, the reorganization of synapses and connections without significant change in their number or strength, is important for the development of the visual system of juvenile rodents. Other evidence in rodents and humans shows that there is a marked drop in sleep slow-wave activity (SWA) during adolescence. Slow waves reflect synchronous transitions of neuronal populations between active and inactive states, and the amount of SWA is influenced by the connection strength and organization of cortical neurons. In this study, we investigated whether synaptic refinement could account for the observed developmental drop in SWA. To this end, we employed a large-scale neural model of primary visual cortex and sections of the thalamus, capable of producing realistic slow waves. In this model, we reorganized intralaminar connections according to experimental data on synaptic refinement: during prerefinement, local connections between neurons were homogenous, whereas in postrefinement, neurons connected preferentially to neurons with similar receptive fields and preferred orientations. Synaptic refinement led to a drop in SWA and to changes in slow-wave morphology, consistent with experimental data. To test whether learning can induce synaptic refinement, intralaminar connections were equipped with spike timing-dependent plasticity. Oriented stimuli were presented during a learning period, followed by homeostatic synaptic renormalization. This led to activity-dependent refinement accompanied again by a decline in SWA. Together, these modeling results show that synaptic refinement can account for developmental changes in SWA. Thus sleep SWA may be used to track noninvasively the reorganization of cortical connections during development. Copyright © 2016 the American Physiological Society.

  9. [Soil biological activities at maize seedling stage under application of slow/controlled release nitrogen fertilizers].

    PubMed

    Li, Dongpo; Wu, Zhijie; Chen, Lijun; Liang, Chenghua; Zhang, Lili; Wang, Weicheng; Yang, Defu

    2006-06-01

    With pot experiment and simulating field ecological environment, this paper studied the effects of different slow/ controlled release N fertilizers on the soil nitrate - reductase and urease activities and microbial biomass C and N at maize seedling stage. The results showed that granular urea amended with dicyandiamide (DCD) and N-(n-bultyl) thiophosphoric triamide (NBPT) induced the highest soil nitrate-reductase activity, granular urea brought about the highest soil urease activity and microbial biomass C and N, while starch acetate (SA)-coated granular urea, SA-coated granular urea amended with DCD, methyl methacrylate (MMA) -coated granular urea amended with DCD, and no N fertilization gave a higher soil urease activity. Soil microbial C and N had a similar variation trend after applying various kinds of test slow/controlled release N fertilizers, and were the lowest after applying SA-coated granular urea amended with DCD and NBPT. Coated granular urea amended with inhibitors had a stronger effect on soil biological activities than coated granular urea, and MMA-coating had a better effect than SA-coating.

  10. Safety Design Requirements for Active Hazard Mitigation Device (AHMD) Employed to Address Fast and Slow Cook-off Thermal Threats

    DTIC Science & Technology

    2014-12-18

    Hazard Mitigation Device (AHMD) Employed to Address Fast and Slow Cook -off Thermal Threats 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM...environments. 15. SUBJECT TERMS Active Hazard Mitigation Device insensitive munitions fast cook -off slow... cook -off 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT SAR 18. NUMBER OF PAGES 14 19a. NAME

  11. Inhibition of slow-wave repolarization and Ca(2+)-activated K+ channels by quaternary ammonium ions.

    PubMed

    Carl, A; Frey, B W; Ward, S M; Sanders, K M; Kenyon, J L

    1993-03-01

    We studied the effects of the K+ channel blocker tetrapentylammonium (TPeA) on the electrical activity of intact circular smooth muscle from canine colon. TPeA (10 and 20 microM) increased slow-wave duration and "locked" the membrane potential around -30 mV plateau potential after several minutes of application, suggesting that K+ channels are essential for termination of colonic slow waves. Repolarization and normal slow-wave activity resumed after 20-30 min of washout. The patch-clamp technique was used to study the block of large-conductance Ca(2+)-activated K+ channels (BK channels) by TPeA and tetraethylammonium (TEA) in excised and cell-attached patches from isolated colonic smooth muscle cells. Channel block was characterized by a voltage-dependent dissociation constant [Kd(V)] for the binding of TEA and TPeA to a blocking site located a fraction of the distance across the membrane field (delta). The extracellular TEA binding site had a Kd(0) of 0.33 mM and a delta of 0.23. The extracellular TPeA binding site had a Kd(0) of 2.2 mM but showed significantly less voltage dependence (delta = 0.02). The intracellular binding site for TEA was of low affinity [Kd(0) = 76 mM]. Intracellular TPeA was the most potent blocker of BK channel current [Kd(0) = 11.7 microM]. The voltage dependence of block by intracellular TPeA (delta = -0.21) was not significantly different from that of intracellular TEA (delta = -0.3). Internal TPeA (10 microM) also blocked a 70-pS K+ channel and a 23-pS K+ channel.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Catalyst deactivation model for residual oil hydrodesulfurization

    SciTech Connect

    Takatsuka, T.; Higasino, S.; Hirohama, S.

    1995-12-31

    Hydrodesulfurization process plays a dominant role in the modern refineries to upgrade residual oil either by removing heterogeneous atoms or by hydrocracking the bottom to distillates products. The practical model is proposed to predict a catalyst life which is the most concern in the process. The catalyst is deactivated in the early stage of the operation by coke deposition on the catalyst active site. The ultimate catalyst life is determined by pore mouth plugging depending on its metal capacity. The phenomena are mathematically described by losses of catalyst surface area and effective diffusivity of feedstock molecules in catalyst pore. The model parameters were collected through the pilot plant tests with different types of catalysts and feedstocks.

  13. Stimulating forebrain communications: Slow sinusoidal electric fields over frontal cortices dynamically modulate hippocampal activity and cortico-hippocampal interplay during slow-wave states.

    PubMed

    Greenberg, Anastasia; Whitten, Tara A; Dickson, Clayton T

    2016-06-01

    Slow-wave states are characterized by the most global physiological phenomenon in the mammalian brain, the large-amplitude slow oscillation (SO; ~1Hz) composed of alternating states of activity (ON/UP states) and silence (OFF/DOWN states) at the network and single cell levels. The SO is cortically generated and appears as a traveling wave that can propagate across the cortical surface and can invade the hippocampus. This cortical rhythm is thought to be imperative for sleep-dependent memory consolidation, potentially through increased interactions with the hippocampus. The SO is correlated with learning and its presumed enhancement via slow rhythmic electrical field stimulation improves subsequent mnemonic performance. However, the mechanism by which such field stimulation influences the dynamics of ongoing cortico-hippocampal communication is unknown. Here we show - using multi-site recordings in urethane-anesthetized rats - that sinusoidal electrical field stimulation applied to the frontal region of the cerebral cortex creates a platform for improved cortico-hippocampal communication. Moderate-intensity field stimulation entrained hippocampal slow activity (likely by way of the temporoammonic pathway) and also increased sharp-wave ripples, the signature memory replay events of the hippocampus, and further increased cortical spindles. Following cessation of high-intensity stimulation, SO interactions in the cortical-to-hippocampal direction were reduced, while the reversed hippocampal-to-cortical communication at both SO and gamma bandwidths was enhanced. Taken together, these findings suggest that cortical field stimulation may function to boost memory consolidation by strengthening cortico-hippocampal and hippocampo-cortical interplay at multiple nested frequencies in an intensity-dependent fashion.

  14. Patterns of Default Mode Network Deactivation in Obsessive Compulsive Disorder

    PubMed Central

    Gonçalves, Óscar F.; Soares, José Miguel; Carvalho, Sandra; Leite, Jorge; Ganho-Ávila, Ana; Fernandes-Gonçalves, Ana; Pocinho, Fernando; Carracedo, Angel; Sampaio, Adriana

    2017-01-01

    The objective of the present study was to research the patterns of Default Mode Network (DMN) deactivation in Obsessive Compulsive Disorder (OCD) in the transition between a resting and a non-rest emotional condition. Twenty-seven participants, 15 diagnosed with OCD and 12 healthy controls (HC), underwent a functional neuroimaging paradigm in which DMN brain activation in a resting condition was contrasted with activity during a non-rest condition consisting in the presentation of emotionally pleasant and unpleasant images. Results showed that HC, when compared with OCD, had a significant deactivation in two anterior nodes of the DMN (medial frontal and superior frontal) in the non-rest pleasant stimuli condition. Additional analysis for the whole brain, contrasting the resting condition with all the non-rest conditions grouped together, showed that, compared with OCD, HC had a significantly deactivation of a widespread brain network (superior frontal, insula, middle and superior temporal, putamen, lingual, cuneus, and cerebellum). Concluding, the present study found that OCD patients had difficulties with the deactivation of DMN even when the non-rest condition includes the presentation of emotional provoking stimuli, particularly evident for images with pleasant content. PMID:28287615

  15. "Stepping Up" Activity Poststroke: Ankle-Positioned Accelerometer Can Accurately Record Steps During Slow Walking.

    PubMed

    Klassen, Tara D; Simpson, Lisa A; Lim, Shannon B; Louie, Dennis R; Parappilly, Beena; Sakakibara, Brodie M; Zbogar, Dominik; Eng, Janice J

    2016-03-01

    As physical activity in people poststroke is low, devices that monitor and provide feedback of walking activity provide motivation to engage in exercise and may assist rehabilitation professionals in auditing walking activity. However, most feedback devices are not accurate at slow walking speeds. This study assessed the accuracy of one accelerometer to measure walking steps of community-dwelling individuals poststroke. This was a cross-sectional study. Two accelerometers were positioned on the nonparetic waist and ankle of participants (N=43), and walking steps from these devices were recorded at 7 speeds (0.3-0.9 m/s) and compared with video recordings (gold standard). When positioned at the waist, the accelerometer had more than 10% error at all speeds, except 0.8 and 0.9 m/s, and numerous participants recorded zero steps at 0.3 to 0.5 m/s. The device had 10% or less error when positioned at the ankle for all speeds between 0.4 and 0.9 m/s. Some participants were unable to complete the faster walking speeds due to their walking impairments and inability to maintain the requested walking speed. Although not recommended by the manufacturer, positioning the accelerometer at the ankle (compared with the waist) may fill a long-standing need for a readily available device that provides accurate feedback for the altered and slow walking patterns that occur with stroke. © 2016 American Physical Therapy Association.

  16. Signatures of Slow Solar Wind Streams from Active Regions in the Inner Corona

    NASA Astrophysics Data System (ADS)

    Slemzin, V.; Harra, L.; Urnov, A.; Kuzin, S.; Goryaev, F.; Berghmans, D.

    2013-08-01

    The identification of solar-wind sources is an important question in solar physics. The existing solar-wind models ( e.g., the Wang-Sheeley-Arge model) provide the approximate locations of the solar wind sources based on magnetic field extrapolations. It has been suggested recently that plasma outflows observed at the edges of active regions may be a source of the slow solar wind. To explore this we analyze an isolated active region (AR) adjacent to small coronal hole (CH) in July/August 2009. On 1 August, Hinode/EUV Imaging Spectrometer observations showed two compact outflow regions in the corona. Coronal rays were observed above the active-region coronal hole (ARCH) region on the eastern limb on 31 July by STEREO-A/EUVI and at the western limb on 7 August by CORONAS- Photon/TESIS telescopes. In both cases the coronal rays were co-aligned with open magnetic-field lines given by the potential field source surface model, which expanded into the streamer. The solar-wind parameters measured by STEREO-B, ACE, Wind, and STEREO-A confirmed the identification of the ARCH as a source region of the slow solar wind. The results of the study support the suggestion that coronal rays can represent signatures of outflows from ARs propagating in the inner corona along open field lines into the heliosphere.

  17. PUREX Plant deactivation mission analysis report

    SciTech Connect

    Lund, D.P.

    1995-05-24

    The purpose of the PUREX Deactivation Project mission analysis is to define the problem to be addressed by the PUREX mission, and to lay the ground work for further system definition. The mission analysis is an important first step in the System Engineering (SE) process. This report presents the results of the PUREX Deactivation Project mission analysis. The purpose of the PUREX Deactivation Project is to prepare PUREX for Decontamination and Decommissioning within a five year time frame. This will be accomplished by establishing a passively safe and environmentally secure configuration of the PUREX Plant, that can be preserved for a 10-year horizon. During deactivation, appropriate portions of the safety envelop will be maintained to ensure deactivation takes place in a safe and regulatory compliant manner.

  18. Origin of Active States in Local Neocortical Networks during Slow Sleep Oscillation

    PubMed Central

    Chauvette, Sylvain; Volgushev, Maxim

    2010-01-01

    Slow-wave sleep is characterized by spontaneous alternations of activity and silence in corticothalamic networks, but the causes of transition from silence to activity remain unknown. We investigated local mechanisms underlying initiation of activity, using simultaneous multisite field potential, multiunit recordings, and intracellular recordings from 2 to 4 nearby neurons in naturally sleeping or anesthetized cats. We demonstrate that activity may start in any neuron or recording location, with tens of milliseconds delay in other cells and sites. Typically, however, activity originated at deep locations, then involved some superficial cells, but appeared later in the middle of the cortex. Neuronal firing was also found to begin, after the onset of active states, at depths that correspond to cortical layer V. These results support the hypothesis that switch from silence to activity is mediated by spontaneous synaptic events, whereby any neuron may become active first. Due to probabilistic nature of activity onset, the large pyramidal cells from deep cortical layers, which are equipped with the most numerous synaptic inputs and large projection fields, are best suited for switching the whole network into active state. PMID:20200108

  19. Changes in contractile activation characteristics of rat fast and slow skeletal muscle fibres during regeneration

    PubMed Central

    Gregorevic, Paul; Plant, David R; Stupka, Nicole; Lynch, Gordon S

    2004-01-01

    Damaged skeletal muscle fibres are replaced with new contractile units via muscle regeneration. Regenerating muscle fibres synthesize functionally distinct isoforms of contractile and regulatory proteins but little is known of their functional properties during the regeneration process. An advantage of utilizing single muscle fibre preparations is that assessment of their function is based on the overall characteristics of the contractile apparatus and regulatory system and as such, these preparations are sensitive in revealing not only coarse, but also subtle functional differences between muscle fibres. We examined the Ca2+- and Sr2+-activated contractile characteristics of permeabilized fibres from rat fast-twitch (extensor digitorum longus) and slow-twitch (soleus) muscles at 7, 14 and 21 days following myotoxic injury, to test the hypothesis that fibres from regenerating fast and slow muscles have different functional characteristics to fibres from uninjured muscles. Regenerating muscle fibres had ∼10% of the maximal force producing capacity (Po) of control (uninjured) fibres, and an altered sensitivity to Ca2+ and Sr2+ at 7 days post-injury. Increased force production and a shift in Ca2+ sensitivity consistent with fibre maturation were observed during regeneration such that Po was restored to 36–45% of that in control fibres by 21 days, and sensitivity to Ca2+ and Sr2+ was similar to that of control (uninjured) fibres. The findings support the hypothesis that regenerating muscle fibres have different contractile activation characteristics compared with mature fibres, and that they adopt properties of mature fast- or slow-twitch muscle fibres in a progressive manner as the regeneration process is completed. PMID:15181161

  20. Hippocalcin gates the calcium activation of the slow afterhyperpolarization in hippocampal pyramidal cells.

    PubMed

    Tzingounis, Anastassios V; Kobayashi, Masaaki; Takamatsu, Ken; Nicoll, Roger A

    2007-02-15

    In the brain, calcium influx following a train of action potentials activates potassium channels that mediate a slow afterhyperpolarization current (I(sAHP)). The key steps between calcium influx and potassium channel activation remain unknown. Here we report that the key intermediate between calcium and the sAHP channels is the diffusible calcium sensor hippocalcin. Brief depolarizations sufficient to activate the I(sAHP) in wild-type mice do not elicit the I(sAHP) in hippocalcin knockout mice. Introduction of hippocalcin in cultured hippocampal neurons leads to a pronounced I(sAHP), while neurons expressing a hippocalcin mutant lacking N-terminal myristoylation exhibit a small I(sAHP) that is similar to that recorded in uninfected neurons. This implies that hippocalcin must bind to the plasma membrane to mediate its effects. These findings support a model in which the calcium sensor for the sAHP channels is not preassociated with the channel complex.

  1. Slow Conductances Could Underlie Intrinsic Phase-Maintaining Properties of Isolated Lobster (Panulirus interruptus) Pyloric Neurons

    PubMed Central

    Hooper, Scott L.; Buchman, Einat; Weaver, Adam L.; Thuma, Jeffrey B.; Hobbs, Kevin H.

    2009-01-01

    The rhythmic pyloric network of the lobster stomatogastric system approximately maintains phase (that is, the burst durations and durations between the bursts of its neurons change proportionally) when network cycle period is altered by current injection into the network pacemaker (Hooper, 1997a,b). When isolated from the network and driven by rhythmic hyperpolarizing current pulses, the delay to firing after each pulse of at least one network neuron type (Pyloric, PY) varies in a phase-maintaining manner when cycle period is varied (Hooper, 1998). These variations require PY neurons to have intrinsic mechanisms that respond to changes in neuron activity on time scales at least as long as two seconds. Slowly activating and deactivating conductances could provide such a mechanism. We tested this possibility by building models containing various slow conductances. This work showed that such conductances could indeed support intrinsic phase-maintenance and we show here results for one such conductance, a slow potassium conductance. These conductances supported phase maintenance because their mean activation level changed, hence altering neuron post-inhibition firing delay, when the rhythmic input to the neuron changed. Switching the sign of the dependence of slow conductance activation and deactivation on membrane potential resulted in neuron delays switching to change in an anti-phase maintaining manner. These data suggest that slow conductances or similar slow processes such as changes in intracellular Ca2+ concentration could underlie phase maintenance in pyloric network neurons. PMID:19211890

  2. EEG Σ and slow-wave activity during NREM sleep correlate with overnight declarative and procedural memory consolidation.

    PubMed

    Holz, Johannes; Piosczyk, Hannah; Feige, Bernd; Spiegelhalder, Kai; Baglioni, Chiara; Riemann, Dieter; Nissen, Christoph

    2012-12-01

    Previous studies suggest that sleep-specific brain activity patterns such as sleep spindles and electroencephalographic slow-wave activity contribute to the consolidation of novel memories. The generation of both sleep spindles and slow-wave activity relies on synchronized oscillations in a thalamo-cortical network that might be implicated in synaptic strengthening (spindles) and downscaling (slow-wave activity) during sleep. This study further examined the association between electroencephalographic power during non-rapid eye movement sleep in the spindle (sigma, 12-16 Hz) and slow-wave frequency range (0.1-3.5 Hz) and overnight memory consolidation in 20 healthy subjects (10 men, 27.1 ± 4.6 years). We found that both electroencephalographic sigma power and slow-wave activity were positively correlated with the pre-post-sleep consolidation of declarative (word list) and procedural (mirror-tracing) memories. These results, although only correlative in nature, are consistent with the view that processes of synaptic strengthening (sleep spindles) and synaptic downscaling (slow-wave activity) might act in concert to promote synaptic plasticity and the consolidation of both declarative and procedural memories during sleep.

  3. Hydrothermal activity at slow-spreading ridges: variability and importance of magmatic controls

    NASA Astrophysics Data System (ADS)

    Escartin, Javier

    2016-04-01

    Hydrothermal activity along mid-ocean ridge axes is ubiquitous, associated with mass, chemical, and heat exchanges between the deep lithosphere and the overlying envelopes, and sustaining chemiosynthetic ecosystems at the seafloor. Compared with hydrothermal fields at fast-spreading ridges, those at slow spreading ones show a large variability as their location and nature is controlled or influenced by several parameters that are inter-related: a) tectonic setting, ranging from 'volcanic systems' (along the rift valley floor, volcanic ridges, seamounts), to 'tectonic' ones (rift-bounding faults, oceanic detachment faults); b) the nature of the host rock, owing to compositional heterogeneity of slow-spreading lithosphere (basalt, gabbro, peridotite); c) the type of heat source (magmatic bodies at depth, hot lithosphere, serpentinization reactions); d) and the associated temperature of outflow fluids (high- vs.- low temperature venting and their relative proportion). A systematic review of the distribution and characteristics of hydrothermal fields along the slow-spreading Mid-Atlantic Ridge suggests that long-lived hydrothermal activity is concentrated either at oceanic detachment faults, or along volcanic segments with evidence of robust magma supply to the axis. A detailed study of the magmatically robust Lucky Strike segment suggests that all present and past hydrothermal activity is found at the center of the segment. The association of these fields to central volcanos, and the absence of indicators of hydrothermal activity along the remaining of the ridge segment, suggests that long-lived hydrothermal activity in these volcanic systems is maintained by the enhanced melt supply and the associated magma chamber(s) required to build these volcanic edifices. In this setting, hydrothermal outflow zones at the seafloor are systematically controlled by faults, indicating that hydrothermal fluids in the shallow crust exploit permeable fault zones to circulate. While

  4. Sacks-Evertson Borehole Strainmeters: New Designs, Volcanic Activity and Slow Earthquakes

    NASA Astrophysics Data System (ADS)

    Linde, A. T.; Sacks, S.

    2008-12-01

    The quality of borehole strain data depends on a variety of factors, perhaps the most important being the character of rock in the immediate vicinity of the instrument. In tectonically active areas it is often difficult to find sites that provide suitable geometry for studying the activity and also have strong competent rock with few or no fractures. We have tested new designs, for both dilatometers and 3 component Sacks-Evertson hydraulic strainmeters, and have found that, in sites we would previously have rejected because of rock quality, we now obtain reliable data. The approach depends on two factors: the sensing components of the instruments have always been ~3m in length so that they integrate over that vertical interval of rock and additionally we can now have a weak inclusion so that we minimize the mechanical impedance contrast between rock and cement plus instrument. Our current three component design is radically different from the modified Sakata-type used previously. Numerical modeling of the design shows that the response to strain change is essentially perfect; compared with earlier designs this gives better shear response and avoids strain concentrations in the rock wall. This design also provides good data from a site with very low rock quality. Data recorded in Taiwan from the 'weak' single component system have been critically important in allowing us to identify and model slow earthquakes triggered by typhoons. During a 5 year interval we have observed 20 slow earthquakes (durations of hours to days), 11 of which are coincident with typhoons (30 during that time span). This part of Taiwan (south east) experiences extremely high deformation rates but has a paucity of large earthquakes. Our data and modeling indicate that the stressed region is segmented by slow relief of stress, reducing the likelihood of seismic failure over extended fault lengths. Borehole strain recordings of volcanic activity in Montserrat and in Iceland have been critical in

  5. Acetylene is an active-site-directed, slow-binding, reversible inhibitor of Azotobacter vinelandii hydrogenase

    SciTech Connect

    Hyman, M.R.; Arp, D.J.

    1987-10-06

    The inhibition of purified and membrane-bound hydrogenase from Azotobacter vinelandii by dihydrogen-free acetylene was investigated. The inhibition was a time-dependent process which exhibited first-order kinetics. Both H/sub 2/ and CO protected against the inhibition by acetylene. K/sub protect(app)/ values of 0.41 and 24 ..mu..M were derived for these gases, respectively. Both H/sub 2/-oxidizing activity and the tritium exchange capacity of the purified enzyme were inhibited at the same rate by acetylene. Removal of acetylene reversed the inhibition for both the purified and the membrane-associated form of the enzyme. The purified hydrogenases from both Rhizobium japonicum and Alcaligenes eutrophus H16 were also inhibited by acetylene in a time-dependent fashion. These findings suggest that acetylene is an active-site-directed, slow-binding, reversible inhibitor of some membrane-bound hydrogenases from aerobic bacteria.

  6. Effects of Skilled Training on Sleep Slow Wave Activity and Cortical Gene Expression in the Rat

    PubMed Central

    Hanlon, Erin C.; Faraguna, Ugo; Vyazovskiy, Vladyslav V.; Tononi, Giulio; Cirelli, Chiara

    2009-01-01

    Study Objective: The best characterized marker of sleep homeostasis is the amount of slow wave activity (SWA, 0.5–4 Hz) during NREM sleep. SWA increases as a function of previous waking time and declines during sleep, but the underlying mechanisms remain unclear. We have suggested that SWA homeostasis is linked to synaptic potentiation associated with learning during wakefulness. Indeed, studies in rodents and humans found that SWA increases after manipulations that presumably enhance synaptic strength, but the evidence remains indirect. Here we trained rats in skilled reaching, a task known to elicit long-term potentiation in the trained motor cortex, and immediately after learning measured SWA and cortical protein levels of c-fos and Arc, 2 activity-dependent genes involved in motor learning. Design: Intracortical local field potential recordings and training on reaching task. Setting: Basic sleep research laboratory. Patients or Participants: Long Evans adult male rats. Interventions: N/A Measurements and Results: SWA increased post-training in the trained cortex (the frontal cortex contralateral to the limb used to learn the task), with smaller or no increase in other cortical areas. This increase was reversible within 1 hour, specific to NREM sleep, and positively correlated with changes in performance during the prior training session, suggesting that it reflects plasticity and not just motor activity. Fos and Arc levels were higher in the trained relative to untrained motor cortex immediately after training, but this asymmetry was no longer present after 1 hour of sleep. Conclusion: Learning to reach specifically affects gene expression in the trained motor cortex and, in the same area, increases sleep need as measured by a local change in SWA. Citation: Hanlon EC; Faraguna U; Vyazovskiy VV; Tononi G; Cirelli C. Effects of skilled training on sleep slow wave activity and cortical gene expression in the rat. SLEEP 2009;32(6):719-729. PMID:19544747

  7. Cytoplasm-to-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers

    NASA Technical Reports Server (NTRS)

    Tseng, B. S.; Kasper, C. E.; Edgerton, V. R.

    1994-01-01

    The relationship between myonuclear number, cellular size, succinate dehydrogenase activity, and myosin type was examined in single fiber segments (n = 54; 9 +/- 3 mm long) mechanically dissected from soleus and plantaris muscles of adult rats. One end of each fiber segment was stained for DNA before quantitative photometric analysis of succinate dehydrogenase activity; the other end was double immunolabeled with fast and slow myosin heavy chain monoclonal antibodies. Mean +/- S.D. cytoplasmic volume/myonucleus ratio was higher in fast and slow plantaris fibers (112 +/- 69 vs. 34 +/- 21 x 10(3) microns3) than fast and slow soleus fibers (40 +/- 20 vs. 30 +/- 14 x 10(3) microns3), respectively. Slow fibers always had small volumes/myonucleus, regardless of fiber diameter, succinate dehydrogenase activity, or muscle of origin. In contrast, smaller diameter (< 70 microns) fast soleus and plantaris fibers with high succinate dehydrogenase activity appeared to have low volumes/myonucleus while larger diameter (> 70 microns) fast fibers with low succinate dehydrogenase activity always had large volume/myonucleus. Slow soleus fibers had significantly greater numbers of myonuclei/mm than did either fast soleus or fast plantaris fibers (116 +/- 51 vs. 55 +/- 22 and 44 +/- 23), respectively. These data suggest that the myonuclear domain is more limited in slow than fast fibers and in the fibers with a high, compared to a low, oxidative metabolic capability.

  8. Leg kinematics and muscle activity during treadmill running in the cockroach, Blaberus discoidalis: I. Slow running.

    PubMed

    Watson, J T; Ritzmann, R E

    1998-01-01

    We have combined high-speed video motion analysis of leg movements with electromyogram (EMG) recordings from leg muscles in cockroaches running on a treadmill. The mesothoracic (T2) and metathoracic (T3) legs have different kinematics. While in each leg the coxa-femur (CF) joint moves in unison with the femurtibia (FT) joint, the relative joint excursions differ between T2 and T3 legs. In T3 legs, the two joints move through approximately the same excursion. In T2 legs, the FT joint moves through a narrower range of angles than the CF joint. In spite of these differences in motion, no differences between the T2 and T3 legs were seen in timing or qualitative patterns of depressor coxa and extensor tibia activity. The average firing frequencies of slow depressor coxa (Ds) and slow extensor tibia (SETi) motor neurons are directly proportional to the average angular velocity of their joints during stance. The average Ds and SETi firing frequency appears to be modulated on a cycle-by-cycle basis to control running speed and orientation. In contrast, while the frequency variations within Ds and SETi bursts were consistent across cycles, the variations within each burst did not parallel variations in the velocity of the relevant joints.

  9. Dense seismic networks as a tool to characterize active faulting in regions of slow deformation

    NASA Astrophysics Data System (ADS)

    Custódio, Susana; Arroucau, Pierre; Carrilho, Fernando; Cesca, Simone; Dias, Nuno; Matos, Catarina; Vales, Dina

    2016-04-01

    The theory of plate tectonics states that the relative motion between lithospheric plates is accommodated at plate boundaries, where earthquakes occur on long faults. However, earthquakes with a wide range of magnitudes also occur both off plate boundaries, in intra-plate settings, and along discontinuous, diffuse plate boundaries. These settings are characterized by low rates of lithospheric deformation. A fundamental limitation in the study of slowly deforming regions is the lack of high-quality observations. In these regions, earthquake catalogs have traditionally displayed diffuse seismicity patterns. The location, geometry and activity rate of faults - all basic parameters for understanding fault dynamics - are usually poorly known. The dense seismic networks deployed in the last years around the world have opened new windows in observational seismology. Although high-magnitude earthquakes are rare in regions of slow deformation, low-magnitude earthquakes are well observable on the time-scale of these deployments. In this presentation, we will show how data from dense seismic deployments can be used to characterize faulting in regions of slow deformation. In particular, we will present the case study of western Iberia, a region undergoing low-rate deformation and which has generated some of the largest earthquakes in Europe, both intraplate (mainland) and interplate (offshore). The methods that we employ include automated earthquake detection methods to lower the completeness magnitude of catalogs, earthquake relocations, focal mechanisms patterns, waveform similarity and clustering analysis.

  10. Nonvolcanic Tremor Activity is Highly Correlated With Slow Slip Events, Mexico

    NASA Astrophysics Data System (ADS)

    Kostoglodov, V.; Shapiro, N.; Larson, K. M.; Payero, J. S.; Husker, A.; Santiago, L. A.; Clayton, R. W.

    2008-12-01

    Significant activity of nonvolcanic tremor (NVT) has been observed in the central Mexico (Guerrero) subduction zone since 2001 when continuous seismic records became available. Although the quality of these records is poor, it is possible to estimate a temporal variation of energy in the range of 1-2Hz (best signal/noise ratio for the NVT). These clearly indicate a maximum of NVT energy release (En) during the 2001-2002 and 2006 large aseismic slow slip events (SSE) registered by the Guerrero GPS network. In particular En is higher for the 2001-2002 SSE which had larger surface displacements and extension than the 2006 SSE. A more detailed and accurate study of NVT activity was carried out using the data collected during the MASE experiment in Mexico. MASE consisted of 100 broad band seismometers in operation for ~2.5 years (2005-2007) along the profile oriented SSW-NNE from Acapulco, and crossing over the subduction zone for a distance of ~500 km. Epicenters and depths of individual tremor events determined using the envelope cross-correlation technique have rather large uncertainties, partly originated from the essentially 2D geometry of the network. The 'energy' approach is more efficient in this case because it provides an average NVT activity evolution in time and space. The data processing consists of a band pass (1-2Hz) filter of the raw 100 Hz sampled N-S component records, application a 10 min-width median filter to eliminate the effect of local seismic events and noise, and integration of the energy and normalization of daily En using an average coda amplitude from several regional earthquakes of M~5. A time-space distribution of En reveals a strong correlation between NVT energy release and the 2006 SSE, which also replicates the two-phase character of this slow event and a migration of the slow slip maximum from North to South. There are also a few clear episodes of relatively high NVT energy release that do not correspond to any significant geodetic

  11. Can Co-Activation of Nrf2 and Neurotrophic Signaling Pathway Slow Alzheimer’s Disease?

    PubMed Central

    Murphy, Kelsey E.; Park, Joshua J.

    2017-01-01

    Alzheimer’s disease (AD) is a multifaceted disease that is hard to treat by single-modal treatment. AD starts with amyloid peptides, mitochondrial dysfunction, and oxidative stress and later is accompanied with chronic endoplasmic reticulum (ER) stress and autophagy dysfunction, resulting in more complicated pathogenesis. Currently, few treatments can modify the complicated pathogenic progress of AD. Compared to the treatment with exogenous antioxidants, the activation of global antioxidant defense system via Nrf2 looks more promising in attenuating oxidative stress in AD brains. Accompanying the activation of the Nrf2-mediated antioxidant defense system that reduce the AD-causative factor, oxidative stress, it is also necessary to activate the neurotrophic signaling pathway that replaces damaged organelles and molecules with new ones. Thus, the dual actions to activate both the Nrf2 antioxidant system and neurotrophic signaling pathway are expected to provide a better strategy to modify AD pathogenesis. Here, we review the current understanding of AD pathogenesis and neuronal defense systems and discuss a possible way to co-activate the Nrf2 antioxidant system and neurotrophic signaling pathway with the hope of helping to find a better strategy to slow AD. PMID:28561773

  12. The pattern of slow wave activity in spontaneously occurring long sleep.

    PubMed

    Kecklund; Åkerstedt

    1992-03-01

    The aim of the present study was to estimate the time course of slow wave activity (SWA) in naturally occurring long sleep episodes (ad lib). Sixteen male shift workers were subjected to 24 h ambulatory polysomnography in connection with an afternoon shift. The EEG was subjected to spectral analysis (FFT) as well as to traditional sleep stage scoring. SWA (0.5-4.5 Hz band, both nonREM and REM sleep) declined exponentially and reached an asymptote by the fifth or sixth sleep cycle. However, half the subjects showed a reduced SWA in the first cycle, with a subsequent recovery in the second cycle. The SWA reduction of the first cycle was associated with a reduced REM-latency and it was suggested that uncontrolled external influences of the real life settings may have affected SWA in the first cycle. It was concluded that the decline of SWA across time may deviate from an exponential shape under real life conditions.

  13. Slow potentials and spike unit activity of the cerebral cortex of rabbits exposed to microwaves

    SciTech Connect

    Chizhenkova, R.A.

    1988-01-01

    Unanesthetized rabbits exposed to 12.5-cm microwaves at a field intensity of 40 mW/cm/sup 2/ in the region of the head showed an increase in the number of slow waves and spindle-shaped firings in the EEG and a change in the discharge frequency of neurons in the visual cortex in 41-52% of the cases. An enhancement of the evoked response of visual cortex neurons to light was observed in 61% of the cases and a facilitation of the driving response in 80% of all cases. It is concluded that the evoked response is a more sensitive indicator of the microwave effect than background activity. The effects of the fields were most distinctly observed with the driving response.

  14. PUREX Plant deactivation function analysis report

    SciTech Connect

    Lund, D.P.; PUREX Working Group

    1995-09-01

    The document contains the functions, function definitions, function interfaces, function interface definitions, Input Computer Automated Manufacturing Definition (IDEFO) diagrams, and a function hierarchy chart that describe what needs to be performed to deactivate PUREX.

  15. Gamification of Learning Deactivates the Default Mode Network

    PubMed Central

    Howard-Jones, Paul A.; Jay, Tim; Mason, Alice; Jones, Harvey

    2016-01-01

    We hypothesized that embedding educational learning in a game would improve learning outcomes, with increased engagement and recruitment of cognitive resources evidenced by increased activation of working memory network (WMN) and deactivation of default mode network (DMN) regions. In an fMRI study, we compared activity during periods of learning in three conditions that were increasingly game-like: Study-only (when periods of learning were followed by an exemplar question together with its correct answer), Self-quizzing (when periods of learning were followed by a multiple choice question in return for a fixed number of points) and Game-based (when, following each period of learning, participants competed with a peer to answer the question for escalating, uncertain rewards). DMN hubs deactivated as conditions became more game-like, alongside greater self-reported engagement and, in the Game-based condition, higher learning scores. These changes did not occur with any detectable increase in WMN activity. Additionally, ventral striatal activation was associated with responding to questions and receiving positive question feedback. Results support the significance of DMN deactivation for educational learning, and are aligned with recent evidence suggesting DMN and WMN activity may not always be anti-correlated. PMID:26779054

  16. Gamification of Learning Deactivates the Default Mode Network.

    PubMed

    Howard-Jones, Paul A; Jay, Tim; Mason, Alice; Jones, Harvey

    2015-01-01

    We hypothesized that embedding educational learning in a game would improve learning outcomes, with increased engagement and recruitment of cognitive resources evidenced by increased activation of working memory network (WMN) and deactivation of default mode network (DMN) regions. In an fMRI study, we compared activity during periods of learning in three conditions that were increasingly game-like: Study-only (when periods of learning were followed by an exemplar question together with its correct answer), Self-quizzing (when periods of learning were followed by a multiple choice question in return for a fixed number of points) and Game-based (when, following each period of learning, participants competed with a peer to answer the question for escalating, uncertain rewards). DMN hubs deactivated as conditions became more game-like, alongside greater self-reported engagement and, in the Game-based condition, higher learning scores. These changes did not occur with any detectable increase in WMN activity. Additionally, ventral striatal activation was associated with responding to questions and receiving positive question feedback. Results support the significance of DMN deactivation for educational learning, and are aligned with recent evidence suggesting DMN and WMN activity may not always be anti-correlated.

  17. Deactivation of a silica-alumina catalyst by coke deposition

    SciTech Connect

    Garcia-Ochoa, F.; Santos, A. . Dept. de Ingenieria Quimica)

    1993-11-01

    Deactivation by fouling of a silica-alumina catalyst when it is used for cyclohexanol dehydration has been studied in a fixed bed laboratory reactor between 548 and 573 K. A kinetic model of the main reaction has been determined, corresponding to a mechanism in which the surface reaction in two active sites is the controlling step of the process rate. The deactivation rate has been determined from activity-time data, calculated from outlet conversion-time data. Coke precursor formation has been determined that occurs by reaction of three adsorbed molecules of reactant (cyclohexanol) or product (cyclohexene). A greater contribution (bigger parallel contribution) of coke formation from the reactant has been found. Also, the variation of different physical and chemical catalyst properties, such as surface, pore volume, acidity, and coke composition, have been measured at different coke contents, with the result that relationships between coke content and activity and between activity and acidity support the hypothesis of site coverage deactivation, at least for the coke level range achieved in this study (0--4.1 % (w/w), corresponding to an activity decay from 1 to 0.13); hence, the monolayer coke formation over the catalyst surface can be assumed. These results are confirmed by the nonvariation of physical properties.

  18. Experimental and Automated Analysis Techniques for High-resolution Electrical Mapping of Small Intestine Slow Wave Activity

    PubMed Central

    Angeli, Timothy R; O'Grady, Gregory; Paskaranandavadivel, Niranchan; Erickson, Jonathan C; Du, Peng; Pullan, Andrew J; Bissett, Ian P

    2013-01-01

    Background/Aims Small intestine motility is governed by an electrical slow wave activity, and abnormal slow wave events have been associated with intestinal dysmotility. High-resolution (HR) techniques are necessary to analyze slow wave propagation, but progress has been limited by few available electrode options and laborious manual analysis. This study presents novel methods for in vivo HR mapping of small intestine slow wave activity. Methods Recordings were obtained from along the porcine small intestine using flexible printed circuit board arrays (256 electrodes; 4 mm spacing). Filtering options were compared, and analysis was automated through adaptations of the falling-edge variable-threshold (FEVT) algorithm and graphical visualization tools. Results A Savitzky-Golay filter was chosen with polynomial-order 9 and window size 1.7 seconds, which maintained 94% of slow wave amplitude, 57% of gradient and achieved a noise correction ratio of 0.083. Optimized FEVT parameters achieved 87% sensitivity and 90% positive-predictive value. Automated activation mapping and animation successfully revealed slow wave propagation patterns, and frequency, velocity, and amplitude were calculated and compared at 5 locations along the intestine (16.4 ± 0.3 cpm, 13.4 ± 1.7 mm/sec, and 43 ± 6 µV, respectively, in the proximal jejunum). Conclusions The methods developed and validated here will greatly assist small intestine HR mapping, and will enable experimental and translational work to evaluate small intestine motility in health and disease. PMID:23667749

  19. Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases

    PubMed Central

    McCarty, Mark F.; DiNicolantonio, James

    2016-01-01

    Lysophosphatidic acid (LPA), generated in the microenvironment of cancer cells, can drive the proliferation, invasion, and migration of cancer cells by activating G protein-coupled LPA receptors. Moreover, in cancer cells that have metastasized to bone, LPA signaling can promote osteolysis by inducing cancer cell production of cytokines, such as IL-6 and IL-8, which can stimulate osteoblasts to secrete RANKL, a key promoter of osteoclastogenesis. Indeed, in cancers prone to metastasize to bone, LPA appears to be a major driver of the expansion of osteolytic bone metastases. Activation of NADPH oxidase has been shown to play a mediating role in the signaling pathways by which LPA, as well as RANKL, promote osteolysis. In addition, there is reason to suspect that Nox4 activation is a mediator of the feed-forward mechanism whereby release of TGF-beta from bone matrix by osteolysis promotes expression of PTHrP in cancer cells, and thereby induces further osteolysis. Hence, measures which can down-regulate NADPH oxidase activity may have potential for slowing the expansion of osteolytic bone metastases in cancer patients. Phycocyanin and high-dose statins may have utility in this regard, and could be contemplated as complements to bisphosphonates or denosumab for the prevention and control of osteolytic lesions. Ingestion of omega-3-rich flaxseed or fish oil may also have potential for controlling osteolysis in cancer patients. PMID:27571113

  20. Active region plasma outflows as sources of slow/intermediate solar wind

    NASA Astrophysics Data System (ADS)

    van Driel-Gesztelyi, Lidia M.

    2015-08-01

    L. van Driel-Gesztelyi (1,2,3), D. Baker (1), P. Démoulin (2), Culhane, J.L. (1), M.L. DeRosa (4) C.H. Mandrini (5,6), D.H. Brooks (7), A.N. Fazakerley (1), L.K. Harra (1), L. Zhao (7), T.H. Zurbuchen (7), F.A. Nuevo (5,6), A.M. Vásquez (5,6), G.D. Cristiani (5,6) M. Pick (2)1) UCL/MSSL, UK, (2) Paris Observatory, LESIA, CNRS, France, (3) Konkoly Observatory, Hungary, (4) Lockheed Martin Solar and Astrophysics Laboratory, USA, (5) IAFE, CONICET-UBA, Argentina (6) FCEN, UBA, Argentina (7) Dept. of Atmospheric, Oceanic and Earth Sciences, Univ. of Michigan, USAWe analyse plasma upflows of tens of km/s from the edges of solar active regions discovered by Hinode/EIS and investigate whether or not they become outflows, i.e. find their way into the solar wind. We analyse two magnetic configurations: bipolar and quadrupolar and find that the active region plasma may be directly channeled into the solar wind via interchange reconnection at a high-altitude null point above the active region especially when active regions are located besides coronal holes or in a more complex way via multiple reconnections even from under a closed helmet streamer. We relate the solar observations to in-situ slow/intermediate solar wind streams.

  1. Deactivating Cochlear Implant Electrodes Based on Pitch Information for Users of the ACE Strategy.

    PubMed

    Vickers, Deborah; Degun, Aneeka; Canas, Angela; Stainsby, Thomas; Vanpoucke, Filiep

    2016-01-01

    There is a wide range in performance for cochlear implant (CI) users and there is some evidence to suggest that implant fitting can be modified to improve performance if electrodes that do not provide distinct pitch information are de-activated. However, improvements in performance may not be the same for users of all CI devices; in particular for those with Cochlear devices using n-of-m strategies (ACE or SPEAK).The goal of this research was to determine for users of Cochlear devices (CP810 or CP900 series processors) if speech perception could be improved when indiscriminable electrodes were de-activated and this was also compared to when the same number of discriminable electrodes were de-activated.A cross-over study was conducted with 13 adult CI users who received experimental maps with de-activated channels for a minimum of 2 months and these were compared to optimised clinical maps.The findings showed that there were no significant benefits of electrode de-activation on speech perception and that there was a significant deterioration in spectro-temporal ripple perception when electrodes were switched off. There were no significant differences between de-activation of discriminable or indiscriminable electrodes.These findings suggest that electrode de-activation with n-of-m strategies may not be beneficial.

  2. Plasma flux-dependent lipid A deactivation

    NASA Astrophysics Data System (ADS)

    Chang, Hung-Wen; Hsu, Cheng-Che; Ahmed, Musahid; Liu, Suet Yi; Fang, Yigang; Seog, Joonil; Oehrlein, Gottlieb S.; Graves, David B.

    2014-06-01

    This paper reports the influence of gas plasma flux on endotoxin lipid A film deactivation. To study the effect of the flux magnitude of reactive species, a modified low-pressure inductively coupled plasma (ICP) with O radical flux ˜1016 cm-2 s-1 was used. After ICP exposures, it was observed that while the Fourier transform infrared absorbance of fatty chains responsible for the toxicity drops by 80% through the film, no obvious film endotoxin deactivation is seen. This is in contrast to that previously observed under low flux exposure conducted in a vacuum beam system: near-surface only loss of fatty chains led to significant film deactivation. Secondary ion mass spectrometry characterization of changes at the film surface did not appear to correlate with the degree of deactivation. Lipid A films need to be nearly completely removed in order to detect significant deactivation under high flux conditions. Additional high reactive species flux experiments were conducted using an atmospheric pressure helium plasma jet and a UV/ozone device. Exposure of lipid A films to reactive species with these devices showed similar deactivation behaviour. The causes for the difference between low and high flux exposures may be due to the nature of near-surface structural modifications as a function of the rate of film removal.

  3. Slowing of oscillatory brain activity is a stable characteristic of Parkinson's disease without dementia.

    PubMed

    Stoffers, D; Bosboom, J L W; Deijen, J B; Wolters, E C; Berendse, H W; Stam, C J

    2007-07-01

    Extensive changes in resting-state oscillatory brain activity have recently been demonstrated using magnetoencephalography (MEG) in moderately advanced, non-demented Parkinson's disease patients relative to age-matched controls. The aim of the present study was to determine the onset and evolution of these changes over the disease course and their relationship with clinical parameters. In addition, we evaluated the effects of dopaminomimetics on resting-state oscillatory brain activity in levodopa-treated patients. MEG background oscillatory activity was studied in a group of 70 Parkinson's disease patients with varying disease duration and severity (including 18 de novo patients) as well as in 21 controls that were age-matched to the de novo patients. Whole head 151-channel MEG recordings were obtained in an eyes-closed resting-state condition. Levodopa-treated patients (N = 37) were examined both in a practically defined 'OFF' as well as in the 'ON' state. Relative spectral power was calculated for delta, theta, low alpha, high alpha, beta and gamma frequency bands and averaged for 10 cortical regions of interest (ROIs). Additionally, extensive clinical and neuropsychological testing was performed in all subjects. De novo Parkinson's disease patients showed widespread slowing of background MEG activity relative to controls. Changes included a widespread increase in theta and low alpha power, as well as a loss of beta power over all but the frontal ROIs and a loss of gamma power over all but the right occipital ROI. Neuropsychological assessment revealed abnormal perseveration in de novo patients, which was associated with increased low alpha power in centroparietal ROIs. In the whole group of Parkinson's disease patients, longer disease duration was associated with reduced low alpha power in the right temporal and right occipital ROI, but not with any other spectral power measure. No association was found between spectral power and disease stage, disease severity

  4. Visualizing in situ translational activity for identifying and sorting slow-growing archaeal-bacterial consortia

    DOE PAGES

    Hatzenpichler, Roland; Connon, Stephanie A.; Goudeau, Danielle; ...

    2016-06-28

    To understand the biogeochemical roles of microorganisms in the environment, it is important to determine when and under which conditions they are metabolically active. Bioorthogonal noncanonical amino acid tagging (BONCAT) can reveal active cells by tracking the incorporation of synthetic amino acids into newly synthesized proteins. The phylogenetic identity of translationally active cells can be determined by combining BONCAT with rRNA-targeted fluorescence in situ hybridization (BONCAT-FISH). In theory, BONCAT-labeled cells could be isolated with fluorescence-activated cell sorting (BONCAT-FACS) for subsequent genetic analyses. Here, in the first application, to our knowledge, of BONCAT-FISH and BONCAT-FACS within an environmental context, we probemore » the translational activity of microbial consortia catalyzing the anaerobic oxidation of methane (AOM), a dominant sink of methane in the ocean. These consortia, which typically are composed of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria, have been difficult to study due to their slow in situ growth rates, and fundamental questions remain about their ecology and diversity of interactions occurring between ANME and associated partners. Our activity-correlated analyses of > 16,400 microbial aggregates provide the first evidence, to our knowledge, that AOM consortia affiliated with all five major ANME clades are concurrently active under controlled conditions. Surprisingly, sorting of individual BONCAT-labeled consortia followed by whole-genome amplification and 16S rRNA gene sequencing revealed previously unrecognized interactions of ANME with members of the poorly understood phylum Verrucomicrobia. This finding, together with our observation that ANME-associated Verrucomicrobia are found in a variety of geographically distinct methane seep environments, suggests a broader range of symbiotic relationships within AOM consortia than previously thought.« less

  5. Visualizing in situ translational activity for identifying and sorting slow-growing archaeal−bacterial consortia

    PubMed Central

    Hatzenpichler, Roland; Connon, Stephanie A.; Goudeau, Danielle; Malmstrom, Rex R.; Woyke, Tanja; Orphan, Victoria J.

    2016-01-01

    To understand the biogeochemical roles of microorganisms in the environment, it is important to determine when and under which conditions they are metabolically active. Bioorthogonal noncanonical amino acid tagging (BONCAT) can reveal active cells by tracking the incorporation of synthetic amino acids into newly synthesized proteins. The phylogenetic identity of translationally active cells can be determined by combining BONCAT with rRNA-targeted fluorescence in situ hybridization (BONCAT-FISH). In theory, BONCAT-labeled cells could be isolated with fluorescence-activated cell sorting (BONCAT-FACS) for subsequent genetic analyses. Here, in the first application, to our knowledge, of BONCAT-FISH and BONCAT-FACS within an environmental context, we probe the translational activity of microbial consortia catalyzing the anaerobic oxidation of methane (AOM), a dominant sink of methane in the ocean. These consortia, which typically are composed of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria, have been difficult to study due to their slow in situ growth rates, and fundamental questions remain about their ecology and diversity of interactions occurring between ANME and associated partners. Our activity-correlated analyses of >16,400 microbial aggregates provide the first evidence, to our knowledge, that AOM consortia affiliated with all five major ANME clades are concurrently active under controlled conditions. Surprisingly, sorting of individual BONCAT-labeled consortia followed by whole-genome amplification and 16S rRNA gene sequencing revealed previously unrecognized interactions of ANME with members of the poorly understood phylum Verrucomicrobia. This finding, together with our observation that ANME-associated Verrucomicrobia are found in a variety of geographically distinct methane seep environments, suggests a broader range of symbiotic relationships within AOM consortia than previously thought. PMID:27357680

  6. 42 CFR 424.540 - Deactivation of Medicare billing privileges.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Deactivation of Medicare billing privileges. 424... Establishing and Maintaining Medicare Billing Privileges § 424.540 Deactivation of Medicare billing privileges. (a) Reasons for deactivation. CMS may deactivate a provider or supplier's Medicare billing...

  7. 42 CFR 424.540 - Deactivation of Medicare billing privileges.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Deactivation of Medicare billing privileges. 424... Establishing and Maintaining Medicare Billing Privileges § 424.540 Deactivation of Medicare billing privileges. (a) Reasons for deactivation. CMS may deactivate a provider or supplier's Medicare billing...

  8. Effect of slow wave and REM sleep on thyropharyngeus and stylopharyngeus activity during induced central apneas.

    PubMed

    Feroah, T R; Forster, H V; Pan, L; Wenninger, J; Martino, P; Rice, T

    2001-01-01

    The pharyngeal constrictors have been hypothesized to play an important role in the regulation of upper airway (UAW) patency in patients with sleep apnea. However, little research has focused on the activation and control of muscles that determine the lateral and posterior wall of the retropalatal airway dimensions. Our aim was to investigate the effects of slow wave sleep (SWS) and rapid eye movement (REM) sleep on the activation of pharyngeal constrictor (thyropharyngeus; TP) and dilator (stylopharyngeus; SP) muscles during eupneic breathing and induced central apneas. In nine goats, we found that eupneic TP and SP activity progressively decreased from awake to SWS (57 and 56%, respectively; P<0.01) and further in REM (25.6 and 19.9%, respectively; P<0.01). In contrast, diaphragm activity decreased equally during SWS and REM (89.3 and 87.7%, respectively; P<0.01) compared to awake. Following induced apneas while SP activity was eliminated in every state, maximal TP activity was highest in awake state (318.6% of control; P<0.02), less in SWS (157.6%; P<0.02), and nearly absent in REM (117.3%; P>0.02). During the recovery from an induced apnea when diaphragm activity was at 95% of its' control, awake TP activity remained significantly elevated and SP reduced (P>0.02) while TP activity during SWS was elevated and SP had returned to control level. During REM, TP and SP activity were not different from their reduced controls (P>0.02). The data supports our hypotheses that SWS and REM sleep causes a reduction in the eupneic TP and SP activity, as well as a reduction in TP response to induced apneas. However, the relative imbalance in TP vs SP activity during the recovery from an apnea (awake and SWS) suggest that an imbalance of active neuromuscular forces may contribute to upper airway narrowing in mixed apneas, but not in central apnea during sleep.

  9. Neuronal networks in children with continuous spikes and waves during slow sleep.

    PubMed

    Siniatchkin, Michael; Groening, Kristina; Moehring, Jan; Moeller, Friederike; Boor, Rainer; Brodbeck, Verena; Michel, Christoph M; Rodionov, Roman; Lemieux, Louis; Stephani, Ulrich

    2010-09-01

    Epileptic encephalopathy with continuous spikes and waves during slow sleep is an age-related disorder characterized by the presence of interictal epileptiform discharges during at least >85% of sleep and cognitive deficits associated with this electroencephalography pattern. The pathophysiological mechanisms of continuous spikes and waves during slow sleep and neuropsychological deficits associated with this condition are still poorly understood. Here, we investigated the haemodynamic changes associated with epileptic activity using simultaneous acquisitions of electroencephalography and functional magnetic resonance imaging in 12 children with symptomatic and cryptogenic continuous spikes and waves during slow sleep. We compared the results of magnetic resonance to electric source analysis carried out using a distributed linear inverse solution at two time points of the averaged epileptic spike. All patients demonstrated highly significant spike-related positive (activations) and negative (deactivations) blood oxygenation-level-dependent changes (P < 0.05, family-wise error corrected). The activations involved bilateral perisylvian region and cingulate gyrus in all cases, bilateral frontal cortex in five, bilateral parietal cortex in one and thalamus in five cases. Electrical source analysis demonstrated a similar involvement of the perisylvian brain regions in all patients, independent of the area of spike generation. The spike-related deactivations were found in structures of the default mode network (precuneus, parietal cortex and medial frontal cortex) in all patients and in caudate nucleus in four. Group analyses emphasized the described individual differences. Despite aetiological heterogeneity, patients with continuous spikes and waves during slow sleep were characterized by activation of the similar neuronal network: perisylvian region, insula and cingulate gyrus. Comparison with the electrical source analysis results suggests that the activations

  10. Simplified greywater treatment systems: Slow filters of sand and slate waste followed by granular activated carbon.

    PubMed

    Zipf, Mariah Siebert; Pinheiro, Ivone Gohr; Conegero, Mariana Garcia

    2016-07-01

    One of the main actions of sustainability that is applicable to residential, commercial, and public buildings is the rational use of water that contemplates the reuse of greywater as one of the main options for reducing the consumption of drinking water. Therefore, this research aimed to study the efficiencies of simplified treatments for greywater reuse using slow sand and slow slate waste filtration, both followed by granular activated carbon filters. The system monitoring was conducted over 28 weeks, using analyses of the following parameters: pH, turbidity, apparent color, biochemical oxygen demand (BOD), chemical oxygen demand (COD), surfactants, total coliforms, and thermotolerant coliforms. The system was run at two different filtration rates: 6 and 2 m(3)/m(2)/day. Statistical analyses showed no significant differences in the majority of the results when filtration rate changed from 6 to 2 m(3)/m(2)/day. The average removal efficiencies with regard to the turbidity, apparent color, COD and BOD were 61, 54, 56, and 56%, respectively, for the sand filter, and 66, 61, 60, and 51%, respectively, for the slate waste filter. Both systems showed good efficiencies in removing surfactants, around 70%, while the pH reached values of around 7.80. The average removal efficiencies of the total and thermotolerant coliforms were of 61 and 90%, respectively, for the sand filter, and 67 and 80%, respectively, for the slate waste filter. The statistical analysis found no significant differences between the responses of the two systems, which attest to the fact that the slate waste can be a substitute for sand. The maximum levels of efficiency were high, indicating the potential of the systems, and suggesting their optimization in order to achieve much higher average efficiencies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Deactivation of metastable single-crystal silicon hyperdoped with sulfur

    SciTech Connect

    Simmons, C. B.; Akey, Austin J.; Sullivan, Joseph T.; Buonassisi, Tonio; Krich, Jacob J.; Recht, Daniel; Aziz, Michael J.

    2013-12-28

    Silicon supersaturated with sulfur by ion implantation and pulsed laser melting exhibits broadband optical absorption of photons with energies less than silicon's band gap. However, this metastable, hyperdoped material loses its ability to absorb sub-band gap light after subsequent thermal treatment. We explore this deactivation process through optical absorption and electronic transport measurements of sulfur-hyperdoped silicon subject to anneals at a range of durations and temperatures. The deactivation process is well described by the Johnson-Mehl-Avrami-Kolmogorov framework for the diffusion-mediated transformation of a metastable supersaturated solid solution, and we find that this transformation is characterized by an apparent activation energy of E{sub A}=1.7 ± 0.1 eV. Using this activation energy, the evolution of the optical and electronic properties for all anneal duration-temperature combinations collapse onto distinct curves as a function of the extent of reaction. We provide a mechanistic interpretation of this deactivation based on short-range thermally activated atomic movements of the dopants to form sulfur complexes.

  12. High-resolution Mapping of In Vivo Gastrointestinal Slow Wave Activity Using Flexible Printed Circuit Board Electrodes: Methodology and Validation

    PubMed Central

    DU, PENG; O'GRADY, G.; EGBUJI, J. U.; LAMMERS, W. J.; BUDGETT, D.; NIELSEN, P.; WINDSOR, J. A.; PULLAN, A. J.; CHENG, L. K.

    2014-01-01

    High-resolution, multi-electrode mapping is providing valuable new insights into the origin, propagation, and abnormalities of gastrointestinal (GI) slow wave activity. Construction of high-resolution mapping arrays has previously been a costly and time-consuming endeavor, and existing arrays are not well suited for human research as they cannot be reliably and repeatedly sterilized. The design and fabrication of a new flexible printed circuit board (PCB) multi-electrode array that is suitable for GI mapping is presented, together with its in vivo validation in a porcine model. A modified methodology for characterizing slow waves and forming spatiotemporal activation maps showing slow waves propagation is also demonstrated. The validation study found that flexible PCB electrode arrays are able to reliably record gastric slow wave activity with signal quality near that achieved by traditional epoxy resin-embedded silver electrode arrays. Flexible PCB electrode arrays provide a clinically viable alternative to previously published devices for the high-resolution mapping of GI slow wave activity. PCBs may be mass-produced at low cost, and are easily sterilized and potentially disposable, making them ideally suited to intra-operative human use. PMID:19224368

  13. High-resolution mapping of in vivo gastrointestinal slow wave activity using flexible printed circuit board electrodes: methodology and validation.

    PubMed

    Du, Peng; O'Grady, G; Egbuji, J U; Lammers, W J; Budgett, D; Nielsen, P; Windsor, J A; Pullan, A J; Cheng, L K

    2009-04-01

    High-resolution, multi-electrode mapping is providing valuable new insights into the origin, propagation, and abnormalities of gastrointestinal (GI) slow wave activity. Construction of high-resolution mapping arrays has previously been a costly and time-consuming endeavor, and existing arrays are not well suited for human research as they cannot be reliably and repeatedly sterilized. The design and fabrication of a new flexible printed circuit board (PCB) multi-electrode array that is suitable for GI mapping is presented, together with its in vivo validation in a porcine model. A modified methodology for characterizing slow waves and forming spatiotemporal activation maps showing slow waves propagation is also demonstrated. The validation study found that flexible PCB electrode arrays are able to reliably record gastric slow wave activity with signal quality near that achieved by traditional epoxy resin-embedded silver electrode arrays. Flexible PCB electrode arrays provide a clinically viable alternative to previously published devices for the high-resolution mapping of GI slow wave activity. PCBs may be mass-produced at low cost, and are easily sterilized and potentially disposable, making them ideally suited to intra-operative human use.

  14. Final deactivation project report on the Integrated Process Demonstration Facility, Building 7602 Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1997-09-01

    The purpose of this report is to document the condition of the Integrated Process Demonstration Facility (Building 7602) at Oak Ridge National Laboratory (ORNL) after completion of deactivation activities by the High Ranking Facilities Deactivation Project (HRFDP). This report identifies the activities conducted to place the facility in a safe and environmentally sound condition prior to transfer to the U.S. Department of Energy (DOE) Environmental Restoration EM-40 Program. This report provides a history and description of the facility prior to commencing deactivation activities and documents the condition of the building after completion of all deactivation activities. Turnover items, such as the Post-Deactivation Surveillance and Maintenance (S&M) Plan, remaining hazardous and radioactive materials inventory, radiological controls, Safeguards and Security, and supporting documentation provided in the Office of Nuclear Material and Facility Stabilization Program (EM-60) Turnover package are discussed.

  15. Slow active potentials in ventral inhibitory motor neurons of the nematode Ascaris.

    PubMed

    Angstadt, J D; Stretton, A O

    1989-12-01

    The ability of ventral inhibitory motor neurons of the nematode Ascaris to generate slow depolarizing potentials was investigated using intracellular recording and current injection. In quiescent cells, regenerative depolarizations with peak amplitudes of approximately 20 mV and durations of several 100 ms were evoked in response to brief depolarizing current pulses. Repetitive slow potentials were produced in response to sustained depolarizing currents in a threshold-dependent manner. Repetitive slow potentials also occurred spontaneously, exhibiting cycle periods of about 700 ms. The ability of inhibitory motor neurons to generate slow potentials was blocked by addition of Co++, Cd++, or other Ca-channel blockers to the saline but not by TTX or substitution of Na+ with Tris. The amplitude and duration of slow potentials were increased in the presence of Ba++, Sr++, and TEA. Spontaneous slow potentials exhibited characteristics expected of intrinsically generated oscillations, including frequency modulation by injection of prolonged offset currents, phase resetting by brief current pulses, and suppression by strong hyperpolarization. Slow potentials appear to be generated in the ventral nerve cord processes and/or cell body of the motor neuron, and they produce rhythmic inhibitory postsynaptic potentials in ventral muscle cells. Slow potentials may therefore contribute to locomotory or other motor behaviors of the animal.

  16. Slow activator degradation reduces the robustness of a coupled feedback loop oscillator.

    PubMed

    Sayut, Daniel J; Sun, Lianhong

    2010-08-01

    Genetic circuits composed of coupled positive and negative feedback loops have been shown to occur as common motifs in natural oscillatory networks. Recent work in synthetic biology has begun to demonstrate how the properties and architectures of these circuits affect their behavior. Expanding on this work, we constructed a new implementation of a common coupled feedback loop architecture by incorporating the LuxR transcriptional activator as the positive feedback element. We found that the properties of the LuxR activator had a significant impact on the observed behavior of the coupled feedback loop circuit, as a slow degradation rate of LuxR led to its accumulation after initial circuit induction. Due to this accumulation, the presence of feedback on LuxR did not greatly alter the oscillatory behavior of the circuit from a control consisting of an independent negative feedback loop, with both systems showing oscillatory responses in 30-40% of the measured cells and highly variable periods. While the oscillatory properties of individual cells were not influenced by induction levels, the percentage of cells that demonstrated oscillations was. Slight improvements to the initial responses of the coupled feedback loop circuit were also obtained by coexpression of the GroE chaperones due to improved LuxR folding. These findings illustrate the importance that positive feedback has on the tunability and robustness of coupled feedback loop oscillators, and improve our understanding of how the behavior of these systems is impacted upon by their components' properties.

  17. Sustained increase in hippocampal sharp-wave ripple activity during slow-wave sleep after learning

    PubMed Central

    Eschenko, Oxana; Ramadan, Wiâm; Mölle, Matthias; Born, Jan; Sara, Susan J.

    2008-01-01

    High-frequency oscillations, known as sharp-wave/ripple (SPW-R) complexes occurring in hippocampus during slow-wave sleep (SWS), have been proposed to promote synaptic plasticity necessary for memory consolidation. We recorded sleep for 3 h after rats were trained on an odor-reward association task. Learning resulted in an increased number SPW-Rs during the first hour of post-learning SWS. The magnitude of ripple events and their duration were also elevated for up to 2 h after the newly formed memory. Rats that did not learn the discrimination during the training session did not show any change in SPW-Rs. Successful retrieval from remote memory was likewise accompanied by an increase in SPW-R density and magnitude, relative to the previously recorded baseline, but the effects were much shorter lasting and did not include increases in ripple duration and amplitude. A short-lasting increase of ripple activity was also observed when rats were rewarded for performing a motor component of the task only. There were no increases in ripple activity after habituation to the experimental environment. These experiments show that the characteristics of hippocampal high-frequency oscillations during SWS are affected by prior behavioral experience. Associative learning induces robust and sustained (up to 2 h) changes in several SPW-R characteristics, while after retrieval from remote memory or performance of a well-trained procedural aspect of the task, only transient changes in ripple density were induced. PMID:18385477

  18. Anthropogenically-Induced Superficial Seismic Activity Modulated By Slow-Slip Events in Guerrero, Mexico

    NASA Astrophysics Data System (ADS)

    Frank, W.; Shapiro, N.; Husker, A. L.; Kostoglodov, V.; Campillo, M.

    2014-12-01

    We use the data of the MASE seismic experiment operated during 2.5 years in Guerrero, Mexico to create a large catalog of seismic multiplets. This catalog is dominated by families of Low-Frequency Earthquakes (LFE) occurring in vicinity of the main subduction interface. In addition to more than one thousand LFE families, we detected nine repeating seismic event families that are located in the upper crust and are anthropogenically induced (AI) by mining blasts. Analysis of the recurrence of these AI events in time shows that their activity significantly increases during the strong Slow-Slip Event (SSE) in 2006. Modeled static stress perturbations induced by the SSE at the surface are ~5 kPa that is on the same order of magnitude as dynamic stress perturbations observed to trigger other low stress drop phenomena, such as tectonic tremor. We propose therefore that strong SSEs in Guerrero impose an extensional regime throughout the continental crust, modifying the stress field near the surface and increasing AI activity. This modulation of the recurrence of the crustal seismic events by the SSE-induced stress might be related to another recent observation: the SSE-induced reduction of seismic velocities linked to nonlinear elastic effects caused by opening of cracks (Rivet et al., 2011, 2014).

  19. The dynamics of spindles and EEG slow-wave activity in NREM sleep in mice.

    PubMed

    Vyazovskiy, V V; Achermann, P; Borbély, A A; Tobler, I

    2004-07-01

    A quantitative analysis of spindles and spindle-related EEG activity was performed in C57BL/6 mice. The hypothesis that spindles are involved in sleep regulatory mechanisms was tested by investigating their occurrence during 24 h and after 6 h sleep deprivation (SD; n = 7). In the frontal derivation distinct spindle events were characterized as EEG oscillations with a dominant frequency approximately at 11 Hz. Spindles were most prominent during NREM sleep and increased before NREM-REM sleep transitions. Whereas spindles increased concomitantly with slow wave activity (SWA, EEG power between 0.5 and 4.0 Hz) at the beginning of the NREM sleep episode, these measures showed an opposite evolution prior to the transition to REM sleep. The 24-h time course of spindles showed a maximum at the end of the 12-h light period, and was a mirror image of SWA in NREM sleep. After 6 h SD the spindles in NREM sleep were initially suppressed, and showed a delayed rebound. In contrast, spindles occurring immediately before the transition to REM sleep were enhanced during the first 2 h of recovery. The data suggest that spindles in NREM sleep may be involved in sleep maintenance, while spindles heralding the transition to REM sleep may be related to mechanisms of REM sleep initiation.

  20. UO3 deactivation end point criteria

    SciTech Connect

    Stefanski, L.D.

    1994-10-01

    The UO{sub 3} Deactivation End Point Criteria are necessary to facilitate the transfer of the UO{sub 3} Facility from the Office of Facility Transition and Management (EM-60) to the office of Environmental Restoration (EM-40). The criteria were derived from a logical process for determining end points for the systems and spaces at the UO{sub 3}, Facility based on the objectives, tasks, and expected future uses pertinent to that system or space. Furthermore, the established criteria meets the intent and supports the draft guidance for acceptance criteria prepared by EM-40, {open_quotes}U.S. Department of Energy office of Environmental Restoration (EM-40) Decontamination and Decommissioning Guidance Document (Draft).{close_quotes} For the UO{sub 3} Facility, the overall objective of deactivation is to achieve a safe, stable and environmentally sound condition, suitable for an extended period, as quickly and economically as possible. Once deactivated, the facility is kept in its stable condition by means of a methodical surveillance and maintenance (S&M) program, pending ultimate decontamination and decommissioning (D&D). Deactivation work involves a range of tasks, such as removal of hazardous material, elimination or shielding of radiation fields, partial decontamination to permit access for inspection, installation of monitors and alarms, etc. it is important that the end point of each of these tasks be established clearly and in advance, for the following reasons: (1) End points must be such that the central element of the deactivation objective - to achieve stability - is unquestionably achieved. (2) Much of the deactivation work involves worker exposure to radiation or dangerous materials. This can be minimized by avoiding unnecessary work. (3) Each task is, in effect, competing for resources with other deactivation tasks and other facilities. By assuring that each task is appropriately bounded, DOE`s overall resources can be used most fully and effectively.

  1. Visinin-like neuronal calcium sensor proteins regulate the slow calcium-activated afterhyperpolarizing current in the rat cerebral cortex

    PubMed Central

    Villalobos, Claudio; Andrade, Rodrigo

    2010-01-01

    Many neurons in the nervous systems express afterhyperpolarizations that are mediated by a slow calcium-activated potassium current. This current shapes neuronal firing and is inhibited by neuromodulators, suggesting an important role in the regulation of neuronal function. Surprisingly, very little is currently known about the molecular basis for this current or how it is gated by calcium. Recently, the neuronal calcium sensor protein hippocalcin was identified as a calcium sensor for the slow afterhyperpolarizing current in the hippocampus. However, while hippocalcin is very strongly expressed in the hippocampus, this protein shows a relatively restricted distribution in the brain. Furthermore, the genetic deletion of this protein only partly reduces the slow hyperpolarizing current in hippocampus. These considerations question whether hippocalcin can be the sole calcium sensor for the slow afterhyperpolarizing current. Here we use loss of function and overexpression strategies to show that hippocalcin functions as a calcium sensor for the slow afterhyperpolarizing current in the cerebral cortex, an area where hippocalcin is expressed at much lower levels than in hippocampus. In addition we show that neurocalcin δ, but not VILIP-2, can also act as a calcium sensor for the slow afterhyperpolarizing current. Finally we show that hippocalcin and neurocalcin δ both increase the calcium sensitivity of the afterhyperpolarizing current but do not alter its sensitivity to inhibition by carbachol acting through the Gαq-11-PLCβ signaling cascade. These results point to a general role for a subgroup of visinin-like neuronal calcium sensor proteins in the activation of the slow calcium-activated afterhyperpolarizing current. PMID:20980592

  2. The interaction of a metal deactivator with metal surfaces

    SciTech Connect

    Schreifels, J.A. ); Morris, R.E.; Turner, N.H.; Mowery, R.L. )

    1990-01-01

    In modern aircraft fuel systems, the fuel is used as a heat transfer medium to dissipate heat from the avionics and hydraulic systems. Under these conditions, the fuel can undergo autooxidations. Autooxidations of net fuel can result in the formation of insoluble gum and sediment which can impair operation of the jet engine. Metal deactivator additives (MDA) were developed to counteract the catalytic activity of dissolved metals. The authors have directed their efforts at ascertaining the various mechanisms by which MDA can act, particularly in accelerated stability testing. One objective of this study was to determine to what extent interactions with metal surfaces of the test apparent govern the effectiveness of metal deactivators. This paper describes an examination of metal surfaces exposed to MDA solutions to determine under what, if any, conditions metal passivation can occur.

  3. Conversion of Biomass-Derived Small Oxygenates over HZSM-5 and its Deactivation Mechanism

    SciTech Connect

    Ramasamy, Karthikeyan K.; Gerber, Mark A.; Flake, Matthew D.; Zhang, He; Wang, Yong

    2014-02-28

    HZSM-5 catalyst deactivation was studied using aqueous feed mixtures containing ethanol, ethanol+ acetic acid, ethanol+ethyl acetate, or ethanol+acetaldehyde in a fixed bed reactor at 360°C and 300psig. Compared to ethanol alone experiment, addition of other oxygenates reduced catalyst life in the order of: ethyl acetatedeactivate the catalyst through a pore-blocking mechanism. Acetic acid deactivates the catalyst through an active site poisoning mechanism or strong adsorption of acetate intermediates on the active sites (hydroxyl groups). Ethanol deactivates the catalyst primarily through its pore-blocking mechanism, but the rate of ethanol deactivation is orders of magnitude slower than that of acetaldehyde. Ethyl acetate hydrolyzes to form acetic acid and ethanol which deactivate the catalyst through its respective mechanisms. In addition, each functional group of oxygenates requires different active sites/catalysts and different operating conditions due to competitive adsorptions on active sites for their conversion to the desired products. Therefore, it is necessary to pre-treat the mixture of oxygenates to produce a feed stream containing the same or similar functional group compounds before converting the feed stream to hydrocarbon compounds over HZSM-5 catalyst.

  4. Electrical slow waves in the mouse oviduct are dependent upon a calcium activated chloride conductance encoded by Tmem16a.

    PubMed

    Dixon, Rose Ellen; Hennig, Grant W; Baker, Salah A; Britton, Fiona C; Harfe, Brian D; Rock, Jason R; Sanders, Kenton M; Ward, Sean M

    2012-01-01

    Myosalpinx contractions are critical for oocyte transport along the oviduct. A specialized population of pacemaker cells-oviduct interstitial cells of Cajal-generate slow waves, the electrical events underlying myosalpinx contractions. The ionic basis of oviduct pacemaker activity is unknown. We examined the role of a new class of Ca(2+)-activated Cl(-) channels (CaCCs)-anoctamin 1, encoded by Tmem16a-in oviduct slow wave generation. RT-PCR revealed the transcriptional expression of Tmem16a-encoded CaCCs in the myosalpinx. Intracellular microelectrode recordings were performed in the presence of two pharmacologically distinct Cl(-) channel antagonists, anthracene-9-carboxylic acid and niflumic acid. Both of these inhibitors caused membrane hyperpolarization, reduced the duration of slow waves, and ultimately inhibited pacemaker activity. Niflumic acid also inhibited propagating calcium waves within the myosalpinx. Slow waves were present at birth in wild-type and heterozygous oviducts but failed to develop by birth in mice homozygous for a null allele of Tmem16a (Tmem16a(tm1Bdh/tm1Bdh)). These data suggest that Tmem16a-encoded CaCCs contribute to membrane potential and are responsible for the upstroke and plateau phases of oviduct slow waves.

  5. The slow Ca(2+)-activated K+ current, IAHP, in the rat sympathetic neurone.

    PubMed Central

    Sacchi, O; Rossi, M L; Canella, R

    1995-01-01

    1. Adult and intact sympathetic neurones of the rat superior cervical ganglion maintained in vitro at 37 degrees C were analysed using the two-electrode voltage-clamp technique in order to investigate the slow component of the Ca(2+)-dependent K+ current, IAHP. 2. The relationship between the after-hyperpolarization (AHP) conductance, gAHP, and estimated Ca2+ influx resulting from short-duration calcium currents evoked at various voltages proved to be linear over a wide range of injected Ca2+ charge. An inflow of about 1.7 x 10(7) Ca2+ ions was required before significant activation of gAHP occurred. After priming, the gAHP sensitivity was about 0.3 nS pC-1 of Ca2+ inward charge. 3. IAHP was repeatedly measured at different membrane potentials; its amplitude decreased linearly with membrane hyperpolarization and was mostly abolished close to the K+ reversal potential, EK (-93 mV). The monoexponential decay rate of IAHP was a linear function of total Ca2+ entry and was not significantly altered by membrane potential in the -40 to -80 mV range. 4. Voltage-clamp tracings of IAHP could be modelled as a difference between two exponentials with tau on approximately 5 ms and tau off = 50-250 ms. 5. Sympathetic neurones discharged only once at the onset of a long-lasting depolarizing step. If IAHP was selectively blocked by apamin or D-tubocurarine treatments, accommodation was abolished and an unusual repetitive firing appeared. 6. Summation of IAHP was demonstrated under voltage-clamp conditions when the depolarizing steps were repeated sufficiently close to one another. Under current-clamp conditions the threshold depolarizing charge for action potential discharge significantly increased with progressive pulse numbers in the train, suggesting that an opposing conductance was accumulating with repetitive firing. This frequency-dependent spike firing ability was eliminated by pharmacological inhibition of the slow IAHP. 7. The IAHP was significantly activated by a single

  6. Deactivation by carbon of iron catalysts for indirect liquefaction

    SciTech Connect

    Bartholomew, C.H.

    1990-10-11

    This report describes recent progress in a fundamental, three-year investigation of carbon formation and its effects on the activity and selectivity of promoted iron catalysts for Fischer-Tropsch (FT) synthesis, the objectives of which are: determine rates and mechanisms of carbon deactivation of unsupported Fe and Fe/K catalysts during CO hydrogenation over a range of CO concentrations, CO:H{sub 2} ratios, and temperatures; model the rates of deactivation of the same catalysts in fixed-bed reactors. During the thirteenth quarter design of software for a computer-automated reactor system to be used in the kinetic and deactivation studies was continued. Further progress was made toward the completion of the control language, control routines, and software for operating this system. Progress was also made on the testing of the system hardware and software. H{sub 2} chemisorption capacities and activity selectivity data were also measured for three iron catalysts promoted with 1% alumina. 47 refs., 8 figs., 1 tab.

  7. Allosteric effects of permeating cations on gating currents during K+ channel deactivation.

    PubMed

    Chen, F S; Steele, D; Fedida, D

    1997-08-01

    K+ channel gating currents are usually measured in the absence of permeating ions, when a common feature of channel closing is a rising phase of off-gating current and slow subsequent decay. Current models of gating invoke a concerted rearrangement of subunits just before the open state to explain this very slow charge return from opening potentials. We have measured gating currents from the voltage-gated K+ channel, Kv1.5, highly overexpressed in human embryonic kidney cells. In the presence of permeating K+ or Cs+, we show, by comparison with data obtained in the absence of permeant ions, that there is a rapid return of charge after depolarizations. Measurement of off-gating currents on repolarization before and after K+ dialysis from cells allowed a comparison of off-gating current amplitudes and time course in the same cells. Parallel experiments utilizing the low permeability of Cs+ through Kv1.5 revealed similar rapid charge return during measurements of off-gating currents at ECs. Such effects could not be reproduced in a nonconducting mutant (W472F) of Kv1.5, in which, by definition, ion permeation was macroscopically absent. This preservation of a fast kinetic structure of off-gating currents on return from potentials at which channels open suggests an allosteric modulation by permeant cations. This may arise from a direct action on a slow step late in the activation pathway, or via a retardation in the rate of C-type inactivation. The activation energy barrier for K+ channel closing is reduced, which may be important during repetitive action potential spiking where ion channels characteristically undergo continuous cyclical activation and deactivation.

  8. Collisional deactivation of highly vibrationally excited pyrazine

    NASA Astrophysics Data System (ADS)

    Miller, Laurie A.; Barker, John R.

    1996-07-01

    The collisional deactivation of vibrationally excited pyrazine (C4N2H4) in the electronic ground state by 19 collider gases was studied using the time-resolved infrared fluorescence (IRF) technique. The pyrazine was photoexcited with a 308 nm laser and its vibrational deactivation was monitored following rapid radiationless transitions to produce vibrationally excited molecules in the electronic ground state. The IRF data were analyzed by a simple approximate inversion method, as well as with full collisional master equation simulations. The average energies transferred in deactivating collisions (<ΔE>d) exhibit a near-linear dependence on vibrational energy at lower energies and less dependence at higher energies. The deactivation of ground state pyrazine was found to be similar to that of ground state benzene [J. R. Barker and B. M. Toselli, Int. Rev. Phys. Chem. 12, 305 (1990)], but it is strikingly different from the deactivation of triplet state pyrazine [T. J. Bevilacqua and R. B. Weisman, J. Chem. Phys. 98, 6316 (1993)].

  9. Developmental changes in the activation properties and ultrastructure of fast- and slow-twitch muscles from fetal sheep.

    PubMed

    West, J M; Barclay, C J; Luff, A R; Walker, D W

    1999-04-01

    At early stages of muscle development, skeletal muscles contract and relax slowly, regardless of whether they are destined to become fast- or slow-twitch. In this study, we have characterised the activation profiles of developing fast- and slow-twitch muscles from a precocial species, the sheep, to determine if the activation profiles of the muscles are characteristically slow when both the fast- and slow-twitch muscles have slow isometric contraction profiles. Single skinned muscle fibres from the fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus muscles from fetal (gestational ages 70, 90, 120 and 140 days; term 147 days) and neonatal (8 weeks old) sheep were used to determine the isometric force-pCa (pCa = -log10[Ca2+]) and force-pSr relations during development. Fast-twitch mammalian muscles generally have a greatly different sensitivity to Ca2+ and Sr2+ whereas slow-twitch muscles have a similar sensitivity to these divalent cations. At all ages studied, the force-pCa and force-pSr relations of the FDL muscle were widely separated. The mean separation of the mid-point of the curves (pCa50-pSr50) was approximately 1.1. This is typical of adult fast-twitch muscle. The force-pCa and force-pSr curves for soleus muscle were also widely separated at 70 and 90 days gestation (pCa50-pSr50 approximately 0.75); between 90 days and 140 days this separation decreased significantly to approximately 0.2. This leads to a paradoxical situation whereby at early stages of muscle development the fast muscles have contraction dynamics of slow muscles but the slow muscles have activation profiles more characteristic of fast muscles. The time course for development of the FDL and soleus is different, based on sarcomere structure with the soleus muscle developing clearly defined sarcomere structure earlier in gestation than the FDL. At 70 days gestation the FDL muscle had no clearly defined sarcomeres. Force (N cm-2) increased almost linearly between 70 and 140 days

  10. Object category classification of fMRI data using support vector machine combined with deactivation voxel selection

    NASA Astrophysics Data System (ADS)

    Yan, Caifeng; Song, Sutao; Li, Yao; Guo, Xiaojuan

    2012-03-01

    Support Vector Machine (SVM) is an accurate pattern recognition method which has been widely used in functional MRI (fMRI) data classification. Voxel selection is a very important part in classification. In general, voxel selection is based on brain regions associated with activation caused by different experiment conditions or stimulations. However, negative blood oxygenation level-dependent responses (deactivation) which have also been found in humans or animals contribute to the classification of different cognitive tasks. Different from traditional studies which focused merely on the activation voxel selection methods, our aim is to investigate the deactivation voxel selection methods in the classification of fMRI data using SVM. In this study, three different voxel selection methods (deactivation, activation, the combination of deactivation and activation) are applied to decide which voxel is included in SVM classifier with linear kernel in classifying 4-category objects on fMRI data. The average accuracies of deactivation classification were 73.36%(house vs. face), 60.34%(house vs. car), 60.94%(house vs. cat), 71.43%(face vs. car), 63.17%(face vs. cat) and 61.61%(car vs. cat). The classification results of deactivation were significantly above the chance level which implies the deactivation is informative. The accuracies of combination of activation and deactivation method were close to that of activation method, and it was even better for some representative subjects. These results suggest deactivation provides useful information in the object category classification on fMRI data and the method of voxel selection based on both activation and deactivation will be a significant method in classification in the future.

  11. Small Coronal Holes Near Active Regions as Sources of Slow Solar Wind

    NASA Astrophysics Data System (ADS)

    Wang, Y.-M.

    2017-06-01

    We discuss the nature of the small areas of rapidly diverging, open magnetic flux that form in the strong unipolar fields at the peripheries of active regions (ARs), according to coronal extrapolations of photospheric field measurements. Because such regions usually have dark counterparts in extreme-ultraviolet (EUV) images, we refer to them as coronal holes, even when they appear as narrow lanes or contain sunspots. Revisiting previously identified “AR sources” of slow solar wind from 1998 and 1999, we find that they are all associated with EUV coronal holes; the absence of well-defined He i 1083.0 nm counterparts to some of these holes is attributed to the large flux of photoionizing radiation from neighboring AR loops. Examining a number of AR-associated EUV holes during the 2014 activity maximum, we confirm that they are characterized by wind speeds of ˜300-450 km s-1, O7+/O6+ ratios of ˜0.05-0.4, and footpoint field strengths typically of order 30 G. The close spacing between ARs at sunspot maximum limits the widths of unipolar regions and their embedded holes, while the continual emergence of new flux leads to rapid changes in the hole boundaries. Because of the highly nonradial nature of AR fields, the smaller EUV holes are often masked by the overlying canopy of loops, and may be more visible toward one solar limb than at central meridian. As sunspot activity declines, the AR remnants merge to form much larger, weaker, and longer-lived unipolar regions, which harbor the “classical” coronal holes that produce recurrent high-speed streams.

  12. Regulation of GIRK channel deactivation by Galpha(q) and Galpha(i/o) pathways.

    PubMed

    Mark, M D; Ruppersberg, J P; Herlitze, S

    2000-09-01

    G protein regulated inward rectifying potassium channels (GIRKs) are activated by G protein coupled receptors (GPCRs) via the G protein betagamma subunits. However, little is known about the effects of different GPCRs on the deactivation kinetics of transmitter-mediated GIRK currents. In the present study we investigated the influence of different GPCRs in the presence and absence of RGS proteins on the deactivation kinetics of GIRK channels by coexpressing the recombinant protein subunits in Xenopus oocytes. The stimulation of both G(i/o)- and G(q)-coupled pathways accelerated GIRK deactivation. GIRK currents deactivated faster upon stimulation of G(i/o)- and G(q)-coupled pathways by P(2)Y(2) receptors (P(2)Y(2)Rs) than upon activation of the G(i/o)-coupled pathway alone via muscarinic acetylcholine receptor M2 (M(2) mAChRs). This acceleration was found to be dependent on phospholipase C (PLC) and protein kinase C (PKC) activities and intracellular calcium. With the assumption that RGS2 has a higher affinity for Galpha(q) than Galpha(i/o), we demonstrated that the deactivation kinetics of GIRK channels can be differentially regulated by the relative amount of RGS proteins. These data indicate that transmitter-mediated deactivation of GIRK currents is modulated by crosstalk between G(i/o)- and G(q)-coupled pathways.

  13. Targeting Mortalin by Embelin Causes Activation of Tumor Suppressor p53 and Deactivation of Metastatic Signaling in Human Breast Cancer Cells

    PubMed Central

    Nigam, Nupur; Grover, Abhinav; Goyal, Sukriti; Katiyar, Shashank P.; Bhargava, Priyanshu; Wang, Pi-Chao; Sundar, Durai; Kaul, Sunil C.; Wadhwa, Renu

    2015-01-01

    Embelin, a natural quinone found in the fruits of Embelia ribes, is commonly used in Ayurvedic home medicine for a variety of therapeutic potentials including anti-inflammation, anti-fever, anti-bacteria and anti-cancer. Molecular mechanisms of these activities and cellular targets have not been clarified to-date. We demonstrate that the embelin inhibits mortalin-p53 interactions, and activates p53 protein in tumor cells. We provide bioinformatics, molecular docking and experimental evidence to the binding affinity of embelin with mortalin and p53. Binding of embelin with mortalin/p53 abrogates their complex resulted in nuclear translocation and transcriptional activation function of p53 causing growth arrest in cancer cells. Furthermore, analyses of growth factors and metastatic signaling using antibody membrane array revealed their downregulation in embelin-treated cells. We also found that the embelin causes transcriptional attenuation of mortalin and several other proteins involved in metastatic signaling in cancer cells. Based on these molecular dynamics and experimental data, it is concluded that the anticancer activity of embelin involves targeting of mortalin, activation of p53 and inactivation of metastatic signaling. PMID:26376435

  14. Dopamine Transporters in Striatum Correlated with Deactivation in the Default Mode Network during Visuospatial Attention

    SciTech Connect

    Tomasi, D.; Fowler, J.; Tomasi, D.; Volkow, N.D.; Wang, R.L.; Telang, F.; Wang, Chang, L.; Ernst, T.; /Fowler, J.S.

    2009-06-01

    Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task. For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [{sup 11}C]cocaine used as DAT radiotracer) and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus. These findings provide evidence that dopamine transporters modulate neural activity in the DMN and anterior cingulate gyrus during visuospatial attention. Our findings suggest that dopamine modulates attention in part by regulating neuronal activity in posterior parietal cortex including precuneus (region involved in alertness) and cingulate gyrus (region deactivated in proportion to emotional interference). These findings suggest that the beneficial effects of stimulant medications (increase dopamine by blocking DAT) in inattention reflect in part their ability to facilitate the deactivation of the DMN.

  15. Enhancing influence of intranasal interleukin-6 on slow-wave activity and memory consolidation during sleep.

    PubMed

    Benedict, Christian; Scheller, Jürgen; Rose-John, Stefan; Born, Jan; Marshall, Lisa

    2009-10-01

    The cytokine IL-6 has been considered to exert neuromodulating influences on the brain, with promoting influences on sleep. Sleep enhances the consolidation of memories, and, in particular, late nocturnal sleep also represents a period of enhanced IL-6 signaling, due to a distinctly enhanced availability of soluble IL-6 receptors during this period, enabling trans-signaling of IL-6 to neurons. Thus, a contribution of IL-6 to sleep-dependent memory consolidation is hypothesized. To test this hypothesis, we compared effects of intranasally administered IL-6 (vs. placebo) on sleep-dependent consolidation of declarative (neutral and emotional texts, 2-dimensional object location) and procedural (finger sequence tapping) memories in 17 healthy young men. IL-6 distinctly improved the sleep-related consolidation of emotional text material (P<0.03), which benefits mostly from sleep in the second night-half, in which rapid eye movement sleep (REM) dominates the non-REM-REM sleep cycle. During this second night-half, the amount of electroencephalogram slow-wave activity (0.5-4 Hz) distinctly increased after IL-6 (P<0.01). Other types of memory were not affected. The ability of IL-6 to enhance sleep-associated emotional memory consolidation highlights an example of a functional interaction between the central nervous and immune system.

  16. Altered slow wave activity in major depressive disorder with hypersomnia: a high density EEG pilot study.

    PubMed

    Plante, David T; Landsness, Eric C; Peterson, Michael J; Goldstein, Michael R; Wanger, Tim; Guokas, Jeff J; Tononi, Giulio; Benca, Ruth M

    2012-03-31

    Hypersomnolence in major depressive disorder (MDD) plays an important role in the natural history of the disorder, but the basis of hypersomnia in MDD is poorly understood. Slow wave activity (SWA) has been associated with sleep homeostasis, as well as sleep restoration and maintenance, and may be altered in MDD. Therefore, we conducted a post-hoc study that utilized high density electroencephalography (hdEEG) to test the hypothesis that MDD subjects with hypersomnia (HYS+) would have decreased SWA relative to age- and sex-matched MDD subjects without hypersomnia (HYS-) and healthy controls (n=7 for each group). After correction for multiple comparisons using statistical non-parametric mapping, HYS+ subjects demonstrated significantly reduced parieto-occipital all-night SWA relative to HYS- subjects. Our results suggest hypersomnolence may be associated with topographic reductions in SWA in MDD. Further research using an adequately powered prospective design is indicated to confirm these findings. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Increased frontal sleep slow wave activity in adolescents with major depression

    PubMed Central

    Tesler, Noemi; Gerstenberg, Miriam; Franscini, Maurizia; Jenni, Oskar G.; Walitza, Susanne; Huber, Reto

    2015-01-01

    Sleep slow wave activity (SWA), the major electrophysiological characteristic of deep sleep, mirrors both cortical restructuring and functioning. The incidence of Major Depressive Disorder (MDD) substantially rises during the vulnerable developmental phase of adolescence, where essential cortical restructuring is taking place. The goal of this study was to assess characteristics of SWA topography in adolescents with MDD, in order to assess abnormalities in both cortical restructuring and functioning on a local level. All night high-density EEG was recorded in 15 patients meeting DSM-5 criteria for MDD and 15 sex- and age-matched healthy controls. The actual symptom severity was assessed using the Children's Depression Rating Scale—Revised (CDRS-R). Topographical power maps were calculated based on the average SWA of the first non-rapid eye movement (NREM) sleep episode. Depressed adolescents exhibited significantly more SWA in a cluster of frontal electrodes compared to controls. SWA over frontal brain regions correlated positively with the CDRS-R subscore “morbid thoughts”. Self-reported sleep latency was significantly higher in depressed adolescents compared to controls whereas sleep architecture did not differ between the groups. Higher frontal SWA in depressed adolescents may represent a promising biomarker tracing cortical regions of intense use and/or restructuring. PMID:26870661

  18. Slow acting protein extract from fruit pulp of Momordica charantia with insulin secretagogue and insulinomimetic activities.

    PubMed

    Yibchok-anun, Sirintorn; Adisakwattana, Sirichai; Yao, Cheng Yu; Sangvanich, Polkit; Roengsumran, Sophon; Hsu, Walter Haw

    2006-06-01

    The protein from Thai bitter gourd (Momordica charantia) fruit pulp was extracted and studied for its hypoglycemic effect. Subcutaneous administration of the protein extract (5, 10 mg/kg) significantly and markedly decreased plasma glucose concentrations in both normal and streptozotocin-induced diabetic rats in a dose-dependent manner. The onset of the protein extract-induced antihyperglycemia/hypoglycemia was observed at 4 and 6 h in diabetic and normal rats, respectively. This protein extract also raised plasma insulin concentrations by 2 fold 4 h following subcutaneous administration. In perfused rat pancreas, the protein extract (10 microg/ml) increased insulin secretion, but not glucagon secretion. The increase in insulin secretion was apparent within 5 min of administration and was persistent during 30 min of administration. Furthermore, the protein extract enhanced glucose uptake into C2C12 myocytes and 3T3-L1 adipocytes. Time course experiments performed in rat adipocytes revealed that M. charantia protein extract significantly increased glucose uptake after 4 and 6 h of incubation. Thus, the M. charantia protein extract, a slow acting chemical, exerted both insulin secretagogue and insulinomimetic activities to lower blood glucose concentrations in vivo.

  19. Fast and slow spreading ridges - Structure and hydrothermal activity, ultramafic topographic highs, and CH4 output

    NASA Astrophysics Data System (ADS)

    Bougault, Henri; Charlou, Jean-Luc; Fouquet, Yves; Needham, Hubert D.; Vaslet, Nathalie; Appriou, Pierre; Baptiste, Philippe J.; Rona, Peter A.; Dmitriev, Leonid; Silant'ev, Sergej

    1993-06-01

    Different parts of the world ridge system have quite different morphologies, which reflect different constructional processes. It appears that hydrothermal circulation at all spreading centers is an important exchange process between the ocean and the newly formed oceanic crust. This hydrothermal circulation may vary according to morphology and crustal composition and may also affect ridge constructional processes. The TAG and Snake Pit hydrothermal sites on the Mid-Atlantic Ridge (MAR) display Mn/CH4 ratios in overlying seawater similar to those of nonsedimented East Pacific Rise sites, i.e., about 0.2 mol/L. In contrast, large methane anomalies with very low Mn/CH4 ratios of 0.005 mol/L are associated with ultramafic topographic highs near 15 deg N, close to the axis and on ultramafic walls of the rift valley. The association of ultramafic bodies and CH4 anomalies in seawater indicates active serpentinization processes. CH4 is produced during serpentinization according to the Fisher-Tropsch reaction. Changes of mechanical properties and of density of uplifted deep material in the accreting plate boundary zone caused by serpentinization may play an important role in the construction of slow spreading ridges.

  20. A non-mitotic CENP-E homolog in Dictyostelium discoideum with slow motor activity.

    PubMed

    Kösem, Süleyman; Ökten, Zeynep; Ho, Thi-Hieu; Trommler, Gudrun; Koonce, Michael P; Samereier, Matthias; Müller-Taubenberger, Annette

    2013-02-15

    Kinesins are ATP-dependent molecular motors that mediate unidirectional intracellular transport along microtubules. Dictyostelium discoideum has 13 different kinesin isoforms including two members of the kinesin-7 family, Kif4 and Kif11. While Kif4 is structurally and functionally related to centromere-associated CENP-E proteins involved in the transport of chromosomes to the poles during mitosis, the function of the unusually short CENP-E variant Kif11 is unclear. Here we show that orthologs of short CENP-E variants are present in plants and fungi, and analyze functional properties of the Dictyostelium CENP-E version, Kif11. Gene knockout mutants reveal that Kif11 is not required for mitosis or development. Imaging of GFP-labeled Kif11 expressing Dictyostelium cells indicates that Kif11 is a plus-end directed motor that accumulates at microtubule plus ends. By multiple motor gliding assays, we show that Kif11 moves with an average velocity of 38nm/s, thus defining Kif11 as a very slow motor. The activity of the Kif11 motor appears to be modulated via interactions with the non-catalytic tail region. Our work highlights a subclass of kinesin-7-like motors that function outside of a role in mitosis.

  1. Vitamin E and antioxidant activity; its role in slow coronary flow

    PubMed Central

    Kenan Celik, Veysel; Eken, İmge Ezgi; Aydin, Hüseyin; Yildiz, Gürsel; Birhan Yilmaz, Mehmet; Gurlek, Ahmet

    2013-01-01

    Summary Aim Oxidative stress, which is widely recognised as an important feature of many diseases, can be defined as an increased formation of reactive oxygen species or decreased antioxidant defense. In this study we measured plasma vitamin E levels and total antioxidant activity (AOA) in patients with slow coronary flow (SCF). Methods The plasma vitamin E levels and AOA were measured in 40 patients with angiographically diagnosed SCF. Forty subjects with normal coronary flow (NCF) served as the control group. SCF and NCF were analysed, and blood samples were taken for plasma vitamin E levels and AOA. Plasma vitamin E levels and AOA in patients with SCF were evaluated and compared to those of patients with NCF. Results There was no significant difference between the two groups in terms of plasma AOA, lipid profile and C-reactive protein (CRP) levels but there was a significant difference in vitamin E levels between the two groups (p = 0.001). Conclusion Vitamin E levels were found to be lowered in patients with SCF compared to the NCF group. The association between smoking and vitamin E levels is worth further investigating in larger samples. PMID:24337212

  2. Increased frontal sleep slow wave activity in adolescents with major depression.

    PubMed

    Tesler, Noemi; Gerstenberg, Miriam; Franscini, Maurizia; Jenni, Oskar G; Walitza, Susanne; Huber, Reto

    2016-01-01

    Sleep slow wave activity (SWA), the major electrophysiological characteristic of deep sleep, mirrors both cortical restructuring and functioning. The incidence of Major Depressive Disorder (MDD) substantially rises during the vulnerable developmental phase of adolescence, where essential cortical restructuring is taking place. The goal of this study was to assess characteristics of SWA topography in adolescents with MDD, in order to assess abnormalities in both cortical restructuring and functioning on a local level. All night high-density EEG was recorded in 15 patients meeting DSM-5 criteria for MDD and 15 sex- and age-matched healthy controls. The actual symptom severity was assessed using the Children's Depression Rating Scale-Revised (CDRS-R). Topographical power maps were calculated based on the average SWA of the first non-rapid eye movement (NREM) sleep episode. Depressed adolescents exhibited significantly more SWA in a cluster of frontal electrodes compared to controls. SWA over frontal brain regions correlated positively with the CDRS-R subscore "morbid thoughts". Self-reported sleep latency was significantly higher in depressed adolescents compared to controls whereas sleep architecture did not differ between the groups. Higher frontal SWA in depressed adolescents may represent a promising biomarker tracing cortical regions of intense use and/or restructuring.

  3. SCN10A Mutation in a Patient with Erythromelalgia Enhances C-Fiber Activity Dependent Slowing.

    PubMed

    Kist, Andreas M; Sagafos, Dagrun; Rush, Anthony M; Neacsu, Cristian; Eberhardt, Esther; Schmidt, Roland; Lunden, Lars Kristian; Ørstavik, Kristin; Kaluza, Luisa; Meents, Jannis; Zhang, Zhiping; Carr, Thomas Hedley; Salter, Hugh; Malinowsky, David; Wollberg, Patrik; Krupp, Johannes; Kleggetveit, Inge Petter; Schmelz, Martin; Jørum, Ellen; Lampert, Angelika; Namer, Barbara

    2016-01-01

    Gain-of-function mutations in the tetrodotoxin (TTX) sensitive voltage-gated sodium channel (Nav) Nav1.7 have been identified as a key mechanism underlying chronic pain in inherited erythromelalgia. Mutations in TTX resistant channels, such as Nav1.8 or Nav1.9, were recently connected with inherited chronic pain syndromes. Here, we investigated the effects of the p.M650K mutation in Nav1.8 in a 53 year old patient with erythromelalgia by microneurography and patch-clamp techniques. Recordings of the patient's peripheral nerve fibers showed increased activity dependent slowing (ADS) in CMi and less spontaneous firing compared to a control group of erythromelalgia patients without Nav mutations. To evaluate the impact of the p.M650K mutation on neuronal firing and channel gating, we performed current and voltage-clamp recordings on transfected sensory neurons (DRGs) and neuroblastoma cells. The p.M650K mutation shifted steady-state fast inactivation of Nav1.8 to more hyperpolarized potentials and did not significantly alter any other tested gating behaviors. The AP half-width was significantly broader and the stimulated action potential firing rate was reduced for M650K transfected DRGs compared to WT. We discuss the potential link between enhanced steady state fast inactivation, broader action potential width and the potential physiological consequences.

  4. SCN10A Mutation in a Patient with Erythromelalgia Enhances C-Fiber Activity Dependent Slowing

    PubMed Central

    Neacsu, Cristian; Eberhardt, Esther; Schmidt, Roland; Lunden, Lars Kristian; Ørstavik, Kristin; Kaluza, Luisa; Meents, Jannis; Zhang, Zhiping; Carr, Thomas Hedley; Salter, Hugh; Malinowsky, David; Wollberg, Patrik; Krupp, Johannes; Kleggetveit, Inge Petter; Schmelz, Martin; Jørum, Ellen; Namer, Barbara

    2016-01-01

    Gain-of-function mutations in the tetrodotoxin (TTX) sensitive voltage-gated sodium channel (Nav) Nav1.7 have been identified as a key mechanism underlying chronic pain in inherited erythromelalgia. Mutations in TTX resistant channels, such as Nav1.8 or Nav1.9, were recently connected with inherited chronic pain syndromes. Here, we investigated the effects of the p.M650K mutation in Nav1.8 in a 53 year old patient with erythromelalgia by microneurography and patch-clamp techniques. Recordings of the patient’s peripheral nerve fibers showed increased activity dependent slowing (ADS) in CMi and less spontaneous firing compared to a control group of erythromelalgia patients without Nav mutations. To evaluate the impact of the p.M650K mutation on neuronal firing and channel gating, we performed current and voltage-clamp recordings on transfected sensory neurons (DRGs) and neuroblastoma cells. The p.M650K mutation shifted steady-state fast inactivation of Nav1.8 to more hyperpolarized potentials and did not significantly alter any other tested gating behaviors. The AP half-width was significantly broader and the stimulated action potential firing rate was reduced for M650K transfected DRGs compared to WT. We discuss the potential link between enhanced steady state fast inactivation, broader action potential width and the potential physiological consequences. PMID:27598514

  5. Lipoprotein lipase and hydrofluoric acid deactivate both bacterial lipoproteins and lipoteichoic acids, but platelet-activating factor-acetylhydrolase degrades only lipoteichoic acids.

    PubMed

    Seo, Ho Seong; Nahm, Moon H

    2009-08-01

    To identify the Toll-like receptor 2 ligand critically involved in infections with gram-positive bacteria, lipoprotein lipase (LPL) or hydrogen peroxide (H(2)O(2)) is often used to selectively inactivate lipoproteins, and hydrofluoric acid (HF) or platelet-activating factor-acetylhydrolase (PAF-AH) is used to selectively inactivate lipoteichoic acid (LTA). However, the specificities of these chemical reactions are unknown. We investigated the reaction specificities by using two synthetic lipoproteins (Pam(3)CSK(4) and FSL-1) and LTAs from pneumococci and staphylococci. Changes in the structures of the two synthetic proteins and the LTAs were monitored by mass spectrometry, and biological activity changes were evaluated by measuring tumor necrosis factor alpha production by mouse macrophage cells (RAW 264.7) following stimulation. PAF-AH inactivated LTA without reducing the biological activities of Pam(3)CSK(4) and FSL-1. Mass spectroscopy confirmed that PAF-AH monodeacylated pneumococcal LTA but did not alter the structure of either Pam(3)CSK(4) or FSL-1. As expected, HF treatment reduced the biological activity of LTA by more than 80% and degraded LTA. HF treatment not only deacylated Pam(3)CSK(4) and FSL-1 but also reduced the activities of the lipoproteins by more than 60%. Treatment with LPL decreased the biological activities by more than 80%. LPL also removed an acyl chain from the LTA and reduced its activity. Our results indicate that treatment with 1% H(2)O(2) for 6 h at 37 degrees C inactivates Pam(3)CSK(4), FSL-1, and LTA by more than 80%. Although HF, LPL, and H(2)O(2) treatments degrade and inactivate both lipopeptides and LTA, PAF-AH selectively inactivated LTA with no effect on the biological and structural properties of the two lipopeptides. Also, the ability of PAF-AH to reduce the inflammatory activities of cell wall extracts from gram-positive bacteria suggests LTA to be essential in inflammatory responses to gram-positive bacteria.

  6. Participation of fast-activating, voltage-dependent K currents in electrical slow waves of colonic circular muscle.

    PubMed

    Thornbury, K D; Ward, S M; Sanders, K M

    1992-07-01

    The plateau phase of electrical slow waves in phasic gastrointestinal muscles is critical for excitation-contraction coupling. The plateau appears to depend upon a balance between inward Ca2+ current and outward K+ currents that is sustained for several seconds. Voltage-dependent, non-Ca(2+)-dependent K currents were studied in canine colonic circular muscle cells using the whole cell patch-clamp technique. At room temperature, depolarization activated a slow outward current that showed little inactivation during 500 ms. Increasing the temperature to 37 degrees C significantly increased the rate of activation of voltage-dependent outward current. The onset of the outward current overlapped the transient inward Ca2+ current, suggesting that this K current may act as a brake on the upstroke depolarization of electrical slow waves in intact muscles. Voltage-dependent outward current was sustained for the duration of test pulses. This current balanced the sustained inward current that was also activated at physiological test potentials. The outward current evoked by test pulses positive to -20 mV inactivated by at least 50% within 500 ms. Half inactivation occurred at -36 mV. Voltage-dependent K current was reduced by 4-aminopyridine (4-AP; 1-5 mM), but difference currents obtained by subtracting currents elicited from holding potentials of -45 mV from currents obtained from holding potentials of -100 mV were not affected by 4-AP (1 mM). Studies were also performed on intact muscles to test the effects of 4-AP on electrical slow waves. 4-AP increased the amplitude and rate of rise of the upstroke potential and increased the amplitude and prolonged the plateau phase of slow waves. These data suggest that a rapidly activating, inactivating, voltage-dependent K current participates in electrical slow waves of colonic circular smooth muscles.

  7. An active learning mammalian skeletal muscle lab demonstrating contractile and kinetic properties of fast- and slow-twitch muscle.

    PubMed

    Head, S I; Arber, M B

    2013-12-01

    The fact that humans possess fast- and slow-twitch muscle in the ratio of ∼50% has profound implications for designing exercise training strategies for power and endurance activities. With the growth of exercise and sport science courses, we have seen the need to develop an undergraduate student laboratory that demonstrates the basic properties of fast- and slow-twitch mammalian skeletal muscle. This laboratory illustrates the major differences in contractile properties and fatigue profiles exhibited by the two muscle types. Students compare and contrast twitch kinetics, fused tetanus characteristics, force-frequency relationships, and fatigue properties of fast- and slow-twitch muscles. Examples of results collected by students during class are used to illustrate the type of data collected and analysis performed. During the laboratory, students are encouraged to connect factual information from their skeletal muscle lectures to their laboratory findings. This enables student learning in an active fashion; in particular, the isolated muscle preparation demonstrates that much of what makes muscle fast or slow is myogenic and not the product of the nervous or circulatory systems. This has far-reaching implications for motor control and exercise behavior and therefore is a crucial element in exercise science, with its focus on power and endurance sport activities. To measure student satisfaction with this active learning technique, a questionnaire was administered after the laboratory; 96% of the comments were positive in their support of active versus passive learning strategies.

  8. Lignocellulosic hydrolysate inhibitors selectively inhibit/deactivate cellulase performance.

    PubMed

    Mhlongo, Sizwe I; den Haan, Riaan; Viljoen-Bloom, Marinda; van Zyl, Willem H

    2015-12-01

    In this study, we monitored the inhibition and deactivation effects of various compounds associated with lignocellulosic hydrolysates on individual and combinations of cellulases. Tannic acid representing polymeric lignin residues strongly inhibited cellobiohydrolase 1 (CBH1) and β-glucosidase 1 (BGL1), but had a moderate inhibitory effect on endoglucanase 2 (EG2). Individual monomeric lignin residues had little or no inhibitory effect on hydrolytic enzymes. However, coniferyl aldehyde and syringaldehyde substantially decreased the activity of CBH1 and deactivated BGL1. Acetic and formic acids also showed strong inhibition of BGL1 but not CBH1 and EG2, whereas tannic, acetic and formic acid strongly inhibited a combination of CBH1 and EG2 during Avicel hydrolysis. Diminishing enzymatic hydrolysis is largely a function of inhibitor concentration and the enzyme-inhibitor relationship, rather than contact time during the hydrolysis process (i.e. deactivation). This suggests that decreased rates of hydrolysis during the enzymatic depolymerisation of lignocellulosic hydrolysates may be imparted by other factors related to substrate crystallinity and accessibility.

  9. Characterization of a heat-resistant extracellular protease from Pseudomonas fluorescens 07A shows that low temperature treatments are more effective in deactivating its proteolytic activity.

    PubMed

    Alves, Maura P; Salgado, Rafael L; Eller, Monique R; Vidigal, Pedro Marcus P; Fernandes de Carvalho, Antonio

    2016-10-01

    This work discusses the biological and biochemical characterization of an extracellular protease produced by Pseudomonas fluorescens. The enzyme has a molecular weight of 49.486 kDa and hydrolyzes gelatin, casein, and azocasein, but not BSA. Its maximum activity is found at 37°C and pH 7.5, but it retained almost 70% activity at pH 10.0. It was shown to be a metalloprotease inhibited by Cu(2+), Ni(2+), Zn(2+), Hg(2+), Fe(2+), and Mg(2+), but induced by Mn(2+). After incubation at 100°C for 5min, the enzyme presented over 40% activity, but only 14 to 30% when submitted to milder heat treatments. This behavior may cause significant problems under conditions commonly used for the processing and storage of milk and dairy products, particularly UHT milk. A specific peptide sequenced by mass spectrometer analysis allowed the identification of gene that encodes this extracellular protease in the genome of Pseudomonas fluorescens 07A strain. The enzyme has 477 AA and highly conserved Ca(2+)- and Zn(2+)-binding domains, indicating that Ca(2+), the main ion in milk, is also a cofactor. This work contributes to the understanding of the biochemical aspects of enzyme activity and associates them with its sequence and structure. These findings are essential for the full understanding and control of these enzymes and the technological problems they cause in the dairy industry. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  10. Anti-HSV Activity of Kuwanon X from Mulberry Leaves with Genes Expression Inhibitory and HSV-1 Induced NF-κB Deactivated Properties.

    PubMed

    Ma, Fang; Shen, Wenwei; Zhang, Xiaoqi; Li, Manmei; Wang, Yifei; Zou, Yuxiao; Li, Yaolan; Wang, Hui

    2016-01-01

    Six stilbene derivatives isolated from Mulberry leaves including Kuwanon X, Mulberrofuran C, Mulberrofuran G, Moracin C, Moracin M 3'-O-b-glucopyranoside and Moracin M were found to have antiviral effects against herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) at different potencies except for Mulberrofuran G. Kuwanon X exhibited the greatest activity against HSV-1 15577 and clinical strains and HSV-2 strain 333 with IC50 values of 2.2, 1.5 and 2.5 µg/mL, respectively. Further study revealed that Kuwanon X did not inactivate cell-free HSV-1 particles, but inhibited cellular adsorption and penetration of HSV-1 viral particles. Following viral penetration, Kuwanon X reduced the expression of HSV-1 IE and L genes, and decreased the synthesis of HSV-1 DNA. Furthermore, it was demonstrated that Kuwanon X inhibited the HSV-1-induced nuclear factor (NF)-κB activation through blocking the nuclear translocation and DNA binding of NF-κB. These results suggest that Kuwanon X exerts anti-HSV activity through multiple modes and could be a potential candidate for the therapy of HSV infection.

  11. Deactivation of the TiO2 photocatalyst by coupling with WO3 and the electrochemically assisted high photocatalytic activity of WO3.

    PubMed

    Tada, Hiroaki; Kokubu, Akio; Iwasaki, Mitsunobu; Ito, Seisihro

    2004-05-25

    Patterned TiO2 stripes were formed on a sol-gel crystalline WO3 film by using a chemically modified sol-gel method (pat-TiO2/WO3), and the coupling effect on the photocatalytic activity was studied. Although the photoinduced electron transfer from TiO2 to WO3 was confirmed by labeling and visualization of the reduction sites with Ag particles, the photocatalytic activities of TiO2 for both the gas-phase oxidation of CH3CHO and the liquid-phase oxidation of 2-naphthol decreased significantly with the coupling. This finding was rationalized in terms of the decrease in the rate of the electron transfer from the semiconductor-(s) to 02 with the coupling, which was estimated from the kinetic analysis of the photopotential relaxation. When the excited electrons were removed by a SnO2 underlayer, the WO3 film exhibited a high photocatalytic activity exceeding that of TiO2 for the oxidation of 2-naphthol.

  12. Slow early growers have more muscle in relation to adult activity: Evidence from Cebu, Philippines

    PubMed Central

    Workman, Megan; McDade, Thomas W.; Adair, Linda S.; Kuzawa, Christopher W.

    2015-01-01

    Background/objectives Adult skeletal muscle mass (SMM) protects against type 2 diabetes but little is known about its developmental antecedents. We examined whether pace of early weight gain predicted adult SMM in a birth cohort from Cebu City, Philippines. Additionally, we examined whether increases in SMM associated with adult muscle-building exercise varied according to early growth. Subjects/methods Data came from 1472 participants of the Cebu Longitudinal Health and Nutrition Survey. Weight was measured at birth and at 6-month intervals through age 24 months. Adult SMM was estimated from anthropometric measurements when participants were 20-22 years old. Interviews provided information on adult exercise/lifestyle habits. Results SMM (mean ± SD) was 20.8 ± 3.9 kg (men) and 13.6 ± 3.4 kg (women). Faster early weight gain predicted higher adult SMM. After adjustment for height and lifestyle factors, strongest associations with SMM were found for 6-12 months growth in men (β=0.17, p=0.001) and for birth weight in women (β=0.14, p=0.001). Individuals who had grown slowly displayed greater SMM in association with adult weight lifting, basketball playing, and physically demanding forms of employment (men) or household chores (women). Conclusions These results suggest heightened sensitivity of activity-induced muscle hypertrophy among adults who were born light or who gained weight slowly as infants. Future research should test this finding by comparing responses of muscle mass to an intervention in slow v. fast early growers. Findings suggest that adults who display reduced SMM following suboptimal early growth may be good candidates for new anti-diabetes interventions that promote muscle-building activities. PMID:25782430

  13. Slow early growers have more muscle in relation to adult activity: evidence from Cebu, Philippines.

    PubMed

    Workman, M; McDade, T W; Adair, L S; Kuzawa, C W

    2015-12-01

    Adult skeletal muscle mass (SMM) protects against type 2 diabetes, but little is known about its developmental antecedents. We examined whether pace of early weight gain predicted adult SMM in a birth cohort from Cebu City, Philippines. In addition, we examined whether increases in SMM associated with adult muscle-building exercise varied according to the early growth. Data came from 1472 participants of the Cebu Longitudinal Health and Nutrition Survey. Weight was measured at birth and at 6-month intervals through the age of 24 months. Adult SMM was estimated from anthropometric measurements when participants were 20-22-years old. Interviews provided the information on adult exercise/lifestyle habits. SMM (mean ± s.d.) was 20.8 ± 3.9 kg (men) and 13.6 ± 3.4 kg (women). Faster early weight gain predicted a higher adult SMM. After adjustment for height and lifestyle factors, strongest associations with SMM were found for 6-12 months growth in men (β=0.17, P=0.001) and for birth weight in women (β=0.14, P=0.001). Individuals who had grown slowly displayed greater SMM in association with adult weightlifting, basketball playing and physically demanding forms of employment (men) or household chores (women). These results suggest heightened sensitivity of activity-induced muscle hypertrophy among the adults who were born light or who gained weight slowly as infants. Future research should test this finding by comparing responses of muscle mass to an intervention in slow vs fast early growers. Findings suggest that adults who display a reduced SMM following suboptimal early growth may be good candidates for new anti-diabetes interventions that promote muscle-building activities.

  14. Spontaneous slow and fast MEG activity in male schizophrenics treated with clozapine.

    PubMed

    Sperling, W; Vieth, J; Martus, M; Demling, J; Barocka, A

    1999-03-01

    The atypical neuroleptic clozapine induces specific electroencephalogram changes, which have not been investigated using the technique of magnetoencephalography (MEG). The present study investigated whether spontaneous magnetoencephalographic (MEG) activity in patients treated with clozapine differs from that in patients treated with haloperidol and untreated control subjects. A 2 x 37 channel biomagnetic system was used to record spontaneous magnetic activity for the frequency ranges (2-6 Hz), (7.5-12 Hz), (12.5-30 Hz) in schizophrenic patients and controls in two trials within 3 weeks. After data acquisition, the processed data were digitally filtered and the spatial distribution of dipoles was determined by a 3-D convolution with a Gaussian envelope. The dipole localisation was calculated by the dipole density plot and the principal component analysis. The target parameters were absolute dipole values and the dipole localisations. The relationship between absolute dipole values, dipole localisations and psychopathological findings (documented by the use of the PANSS, BPRS-scale) during a 3 week period with constant doses of clozapine and haloperidol was investigated using correlation analysis. Our results lend strong support to the assumption of a significant elevation of absolute dipole values [dipole density maximum (Dmax), dipole number (Dtotal), absolute and relative dipole density] in the fast frequency range (12.5-30 Hz) over the left hemisphere, especially in the temporoparietal region by clozapine. In this area, we found a dipole concentration effect only in patients treated with the atypical neuroleptic, whereas the dipole distribution in patients treated with haloperidol and healthy controls was concentrated in the central region. With regard to the absolute dipole values in the frequency ranges 2-6 Hz (delta, theta) and 7.5-12 Hz (alpha), we found no statistically significant differences between the groups investigated. In the slow frequency range (2

  15. An Active Learning Mammalian Skeletal Muscle Lab Demonstrating Contractile and Kinetic Properties of Fast- and Slow-Twitch Muscle

    ERIC Educational Resources Information Center

    Head, S. I.; Arber, M. B.

    2013-01-01

    The fact that humans possess fast and slow-twitch muscle in the ratio of approximately 50% has profound implications for designing exercise training strategies for power and endurance activities. With the growth of exercise and sport science courses, we have seen the need to develop an undergraduate student laboratory that demonstrates the basic…

  16. Using Hilbert-Huang Transform to assess EEG slow wave activity during anesthesia in post-cardiac arrest patients.

    PubMed

    Kortelainen, Jukka; Vayrynen, Eero; Huuskonen, Usko; Laurila, Jouko; Koskenkari, Juha; Backman, Janne T; Alahuhta, Seppo; Seppanen, Tapio; Ala-Kokko, Tero

    2016-08-01

    Hypoxic ischemic encephalopathy (HIE) is a severe consequence of cardiac arrest (CA) representing a substantial diagnostic challenge. We have recently designed a novel method for the assessment of HIE after CA. The method is based on estimating the severity of the brain injury by analyzing changes in the electroencephalogram (EEG) slow wave activity while the patient is exposed to an anesthetic drug propofol in a controlled manner. In this paper, Hilbert-Huang Transform (HHT) was used to analyze EEG slow wave activity during anesthesia in ten post-CA patients. The recordings were made in the intensive care unit 36-48 hours after the CA in an experiment, during which the propofol infusion rate was incrementally decreased to determine the drug-induced changes in the EEG at different anesthetic levels. HHT was shown to successfully capture the changes in the slow wave activity to the behavior of intrinsic mode functions (IMFs). While, in patients with good neurological outcome defined after a six-month control period, propofol induced a significant increase in the amplitude of IMFs representing the slow wave activity, the patients with poor neurological outcome were unable to produce such a response. Consequently, the proposed method offer substantial prognostic potential by providing a novel approach for early estimation of HIE after CA.

  17. An Active Learning Mammalian Skeletal Muscle Lab Demonstrating Contractile and Kinetic Properties of Fast- and Slow-Twitch Muscle

    ERIC Educational Resources Information Center

    Head, S. I.; Arber, M. B.

    2013-01-01

    The fact that humans possess fast and slow-twitch muscle in the ratio of approximately 50% has profound implications for designing exercise training strategies for power and endurance activities. With the growth of exercise and sport science courses, we have seen the need to develop an undergraduate student laboratory that demonstrates the basic…

  18. Metal-deactivating additives for liquid fuels

    SciTech Connect

    Boneva, M.I.; Ivanov, S.K.; Kalitchin, Z.D.; Tanielyan, S.K.; Terebenina, A.; Todorova, O.I.

    1995-05-01

    The metal-deactivating and the antioxidant properties of 1-phenyl-3-methylpyrazolone-5 derivatives have been investigated both in the model reaction of low temperature oxidation of ethylbenzene and in gasoline oxidation. The study of the ability of these derivatives to reduce the catalytic effect of copper naphthenate demonstrates that they are promising as metal deactivating additives for light fuels. Some of the pyrazolone compounds appear to be of special interest for the long-term storage of liquid fuels due to their action as multifunctional inhibitors.

  19. Effects of minimal exposures to atmospheric pressure plasma on the activity of Salmonella Typhimurium: Deactivation of bacterial motility and suppression of host-cell invasion.

    PubMed

    Park, Jin-Sung; Kim, Kijung; Han, Je-Hyun; Gweon, Bomi; Ko, Ung Hyun; Yoo, Suk Jae; Choe, Wonho; Shin, Jennifer H

    2016-09-01

    Atmospheric pressure plasma (APP) has been shown effective in sterilization by reducing the number of viable microbes during surface cleaning, food processing, or human tissue treatment. For safe conduct, the majority of previous research focused on complete abolition of microbes, which may require severe treatments. Our aim is to investigate the minimal treatment conditions necessary for effective inactivation of bacteria in such a manner that the APP treated bacteria would not be able to harm the host cells. For this, we ought to identify the objective criteria to make the bacteria dysfunctional. We choose the motile properties and the host-cell invasion capability as two measures to quantify the pathogenic state of bacteria. In this paper, we investigated how the APP treatment in a minimal dosage affects the activity of Salmonella Typhimurium. At 100 W and 15 kHz for 20 s, the APP treatment effectively suppressed active "run and tumble" type motility and induced formation of abnormally long structures. With 20 s exposure, the bacterial cells failed to cause pyroptosis in the host cells with >90% survival after 12 h of co-incubation. Our results suggest novel measures to evaluate the functional pathogenic state for identifying safe APP treatment conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Deactivation of photocatalytically active ZnO nanoparticle and enhancement of its compatibility with organic compounds by surface-capping with organically modified silica

    NASA Astrophysics Data System (ADS)

    Cao, Zhi; Zhang, Zhijun

    2011-02-01

    Tetraethyl orthosilicate (TEOS) and dimethyldiethoxysilane (DEDMS) were used as co-precursors to prepare organically modified silica (ormosil) via sol-gel process. The resultant ormosil was adopted for surface-capping of ZnO nanoparticle, where methyl (organic functional group) and silica (inorganic component) were simultaneously introduced onto the surface of the nanoparticles for realizing dual surface-modification. The ormosil-capped ZnO nanoparticle showed strong hydrophobicity and good compatibility with organic phases, as well as effectively decreased photocatalytic activity and almost unchanged ultraviolet (UV)-shielding ability. More importantly, the comprehensive properties of ormosil-capped ZnO nanoparticle could be manipulated by adjusting the molar ratio of TEOS to DEDMS during sol-gel process. This should help to open a wider window to better utilizing the unique and highly attractive properties such as high UV-shielding ability and high-visible light transparency of ZnO nanoparticle in sunscreen cosmetics.

  1. Slow temporal filtering may largely explain the transformation of stick insect (Carausius morosus) extensor motor neuron activity into muscle movement.

    PubMed

    Hooper, Scott L; Guschlbauer, Christoph; von Uckermann, Géraldine; Büschges, Ansgar

    2007-09-01

    Understanding how nervous systems generate behavior requires understanding how muscles transform neural input into movement. The stick insect extensor tibiae muscle is an excellent system in which to study this issue because extensor motor neuron activity is highly variable during single leg walking and extensor muscles driven with this activity produce highly variable movements. We showed earlier that spike number, not frequency, codes for extensor amplitude during contraction rises, which implies the muscle acts as a slow filter on the time scale of burst interspike intervals (5-10 ms). We examine here muscle response to spiking variation over entire bursts, a time scale of hundreds of milliseconds, and directly measure muscle time constants. Muscle time constants differ during contraction and relaxation, and contraction time constants, although variable, are always extremely slow (200-700 ms). Models using these data show that extremely slow temporal filtering alone can explain much of the observed transform properties. This work also revealed an unexpected (to us) ability of slow filtering to transform steadily declining inputs into constant amplitude outputs. Examination of the effects of time constant variability on model output showed that variation within an SD primarily altered output amplitude, but variation across the entire range also altered contraction shape. These substantial changes suggest that understanding the basis of this variation is central to predicting extensor activity and that the animal could theoretically vary muscle time constant to match extensor response to changing behavioral need.

  2. Integrin activation by P-Rex1 is required for selectin-mediated slow leukocyte rolling and intravascular crawling.

    PubMed

    Herter, Jan M; Rossaint, Jan; Block, Helena; Welch, Heidi; Zarbock, Alexander

    2013-03-21

    Integrin activation is essential for the function of leukocytes. Impaired integrin activation on leukocytes is the hallmark of the leukocyte adhesion deficiency syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. In inflammation, leukocytes collect different signals during the contact with the microvasculature, which activate signaling pathways leading to integrin activation and leukocyte recruitment. We report the role of P-Rex1, a Rac-specific guanine nucleotide exchanging factor, in integrin activation and leukocyte recruitment. We find that P-Rex1 is required for inducing selectin-mediated lymphocyte function-associated antigen-1 (LFA-1) extension that corresponds to intermediate affinity and induces slow leukocyte rolling, whereas P-Rex1 is not involved in the induction of the high-affinity conformation of LFA-1 obligatory for leukocyte arrest. Furthermore, we demonstrate that P-Rex1 is involved in Mac-1-dependent intravascular crawling. In vivo, both LFA-1-dependent slow rolling and Mac-1-dependent crawling are defective in P-Rex1(-/-) leukocytes, whereas chemokine-induced arrest and postadhesion strengthening remain intact in P-Rex1-deficient leukocytes. Rac1 is involved in E-selectin-mediated slow rolling and crawling. In vivo, in an ischemia-reperfusion-induced model of acute kidney injury, abolished selectin-mediated integrin activation contributed to decreased neutrophil recruitment and reduced kidney damage in P-Rex1-deficient mice. We conclude that P-Rex1 serves distinct functions in LFA-1 and Mac-1 activation.

  3. Biomagnetic and bioelectric detection of gastric slow wave activity in normal human subjects--a correlation study.

    PubMed

    Somarajan, S; Muszynski, N D; Obioha, C; Richards, W O; Bradshaw, L A

    2012-07-01

    We measured gastric slow wave activity simultaneously with a Superconducting Quantum Interference Device (SQUID) magnetometer, mucosal electrodes and cutaneous electrodes in 18 normal human subjects (11 women and 7 men). We processed signals with Fourier spectral analysis and SOBI blind-source separation techniques. We observed a high waveform correlation between the mucosal electromyogram (EMG) and multichannel SQUID magnetogastrogram (MGG). There was a lower waveform correlation between the mucosal EMG and cutaneous electrogastrogram (EGG), but the correlation improved with the application of SOBI. There was also a high correlation between the frequency of the electrical activity recorded in the MGG and in mucosal electrodes (r = 0.97). We concluded that SQUID magnetometers noninvasively record gastric slow wave activity that is highly correlated with the activity recorded by invasive mucosal electrodes.

  4. Biomagnetic and bioelectric detection of gastric slow wave activity in normal human subjects – a correlation study

    PubMed Central

    Somarajan, S; Muszynski, ND; Obioha, C; Richards, WO; Bradshaw, LA

    2012-01-01

    We measured gastric slow wave activity simultaneously with a Superconducting Quantum Interference Device (SQUID) magnetometer, mucosal electrodes, and cutaneous electrodes in 18 normal human subjects (11 women and 7 men). We processed signals with Fourier spectral analysis and SOBI blind-source separation techniques. We observed a high waveform correlation between mucosal electromyogram (EMG) and multichannel SQUID magnetogastrogram (MGG). There was a lower waveform correlation between mucosal EMG and cutaneous electrogastrogram (EGG), but the correlation improved with application of SOBI. There was also a high correlation between the frequency of the electrical activity recorded in MGG and in mucosal electrodes (r =0.97). We concluded that SQUID magnetometers noninvasively record gastric slow wave activity that is highly correlated with the activity recorded by invasive mucosal electrodes. PMID:22735166

  5. Inhibition modifies the effects of slow calcium-activated potassium channels on epileptiform activity in a neuronal network model.

    PubMed

    Yang, K-H; Franaszczuk, Piotr J; Bergey, Gregory K

    2005-02-01

    Generation of epileptiform activity typically results from a change in the balance between network excitation and inhibition. Experimental evidence indicates that alterations of either synaptic activity or intrinsic membrane properties can produce increased network excitation. The slow Ca(2+)-activated K(+) currents (sI(AHP)) are important modulators of neuronal firing rate and excitability and have important established and potential roles in epileptogenesis. While the effects of changes in sI(AHP) on individual neuronal excitability are readily studied and well established, the effects of such changes on network behavior are less well known. The experiments here utilize a defined small network model of multicompartment pyramidal cells and an inhibitory interneuron to study the effects of changes in sI(AHP) on network behavior. The benefits of this model system include the ability to observe activity in all cells in a network and the effects of interactions of multiple simultaneous influences. In the model with no inhibitory interneuron, increasing sI(AHP) results in progressively decreasing burst activity. Adding an inhibitory interneuron changes the observed effects; at modest inhibitory strengths, increasing sI(AHP) in all network neurons actually results in increased network bursting (except at very high values). The duration of the burst activity is influenced by the length of delay in a feedback loop, with longer loops resulting in more prolonged bursting. These observations illustrate that the study of potential antiepileptogenic membrane effects must be extended to realistic networks. Network inhibition can dramatically alter the observations seen in pure excitatory networks.

  6. Intracellular Ca2+ release from endoplasmic reticulum regulates slow wave currents and pacemaker activity of interstitial cells of Cajal

    PubMed Central

    Zhu, Mei Hong; Sung, Tae Sik; O'Driscoll, Kate; Koh, Sang Don

    2015-01-01

    Interstitial cells of Cajal (ICC) provide pacemaker activity in gastrointestinal muscles that underlies segmental and peristaltic contractions. ICC generate electrical slow waves that are due to large-amplitude inward currents resulting from anoctamin 1 (ANO1) channels, which are Ca2+-activated Cl− channels. We investigated the hypothesis that the Ca2+ responsible for the stochastic activation of ANO1 channels during spontaneous transient inward currents (STICs) and synchronized activation of ANO1 channels during slow wave currents comes from intracellular Ca2+ stores. ICC, obtained from the small intestine of Kit+/copGFP mice, were studied under voltage and current clamp to determine the effects of blocking Ca2+ uptake into stores and release of Ca2+ via inositol 1,4,5-trisphosphate (IP3)-dependent and ryanodine-sensitive channels. Cyclocpiazonic acid, thapsigargin, 2-APB, and xestospongin C inhibited STICs and slow wave currents. Ryanodine and tetracaine also inhibited STICs and slow wave currents. Store-active compounds had no direct effects on ANO1 channels expressed in human embryonic kidney-293 cells. Under current clamp, store-active drugs caused significant depolarization of ICC and reduced spontaneous transient depolarizations (STDs). After block of ryanodine receptors with ryanodine and tetracaine, repolarization did not restore STDs. ANO1 expressed in ICC has limited access to cytoplasmic Ca2+ concentration, suggesting that pacemaker activity depends on Ca2+ dynamics in restricted microdomains. Our data from studies of isolated ICC differ somewhat from studies on intact muscles and suggest that release of Ca2+ from both IP3 and ryanodine receptors is important in generating pacemaker activity in ICC. PMID:25631870

  7. Every slow-wave impulse is associated with motor activity of the human stomach.

    PubMed

    Hocke, Michael; Schöne, Ulrike; Richert, Hendryk; Görnert, Peter; Keller, Jutta; Layer, Peter; Stallmach, Andreas

    2009-04-01

    Using a newly developed high-resolution three-dimensional magnetic detector system (3D-MAGMA), we observed periodical movements of a small magnetic marker in the human stomach at the typical gastric slow-wave frequency, that is 3 min(-1). Thus we hypothesized that each gastric slow wave induces a motor response that is not strong enough to be detected by conventional methods. Electrogastrographies (EGG, Medtronic, Minneapolis, MN) for measurement of gastric slow waves and 3D-MAGMA (Innovent, Jena, Germany) measurements were simultaneously performed in 21 healthy volunteers (10 men, 40.4+/-13.6 yr; 11 women, 35.8+/-11.6 yr). The 3D-MAGMA system contains 27 highly sensitive magnetic field sensors that are able to locate a magnetic pill inside a human body with an accuracy of +/-5 mm or less in position and +/-2 degrees in orientation at a frequency of 50 Hz. Gastric transit time of the magnetic marker ranged from 19 to 154 min. The mean dominant EGG frequency while the marker was in the stomach was 2.87+/-0.15 cpm. The mean dominant 3D-MAGMA frequency during this interval was nearly identical; that is, 2.85+/-0.15 movements per minute. We observed a strong linear correlation between individual dominant EGG and 3D-MAGMA frequency (R=0.66, P=0.0011). Our findings suggest that each gastric slow wave induces a minute contraction that is too small to be detected by conventional motility investigations but can be recorded by the 3D-MAGMA system. The present slow-wave theory that assumes that the slow wave is a pure electrical signal should be reconsidered.

  8. The Approach of Emotional Deactivation of Prejudice

    ERIC Educational Resources Information Center

    Boucher, Jean-Nil

    2011-01-01

    The aim of the approach of emotional deactivation is to help students reduce the prejudice they may feel towards diverse social groups. Be those groups homosexuals, people living with a disability or immigrants, the victims of prejudice are invited to come into classrooms and to confront the preconceptions that students have in their respect.…

  9. The Approach of Emotional Deactivation of Prejudice

    ERIC Educational Resources Information Center

    Boucher, Jean-Nil

    2011-01-01

    The aim of the approach of emotional deactivation is to help students reduce the prejudice they may feel towards diverse social groups. Be those groups homosexuals, people living with a disability or immigrants, the victims of prejudice are invited to come into classrooms and to confront the preconceptions that students have in their respect.…

  10. 309 Building deactivation mission analysis report

    SciTech Connect

    Lund, D.P.

    1995-05-24

    This report presents the results of the 309 Building (Plutonium Fuels Utilization Program) Deactivation Project mission analysis. Hanford systems engineering (SE) procedures call for a mission analysis. The mission analysis is an important first step in the SE process. The functions and requirements to successfully accomplish this mission, the selected alternatives and products will later be defined using the SE process.

  11. Frontal slow-wave activity as a predictor of negative symptoms, cognition and functional capacity in schizophrenia

    PubMed Central

    Chen, Yu-Han; Stone-Howell, Breannan; Edgar, J. Christopher; Huang, Mingxiong; Wootton, Cassandra; Hunter, Michael A.; Lu, Brett Y.; Sadek, Joseph R.; Miller, Gregory A.; Cañive, José M.

    2016-01-01

    Background Increased temporal and frontal slow-wave delta (1–4 Hz) and theta (4–7 Hz) activities are the most consistent resting-state neural abnormalities reported in schizophrenia. The frontal lobe is associated with negative symptoms and cognitive abilities such as attention, with negative symptoms and impaired attention associated with poor functional capacity. Aims To establish whether frontal dysfunction, as indexed by slowing, would be associated with functional impairments. Method Eyes-closed magnetoencephalography data were collected in 41 participants with schizophrenia and 37 healthy controls, and frequency-domain source imaging localised delta and theta activity. Results Elevated delta and theta activity in right frontal and right temporoparietal regions was observed in the schizophrenia v. control group. In schizophrenia, right-frontal delta activity was uniquely associated with negative but not positive symptoms. In the full sample, increased right-frontal delta activity predicted poorer attention and functional capacity. Conclusions Our findings suggest that treatment-associated decreases in slow-wave activity could be accompanied by improved functional outcome and thus better prognosis. PMID:26206861

  12. Membrane stretch accelerates activation and slow inactivation in Shaker channels with S3-S4 linker deletions.

    PubMed Central

    Tabarean, Iustin V; Morris, Catherine E

    2002-01-01

    At low P(open)(V) Shaker exhibits pronounced stretch-activation. Possible explanations for Shaker's sensitivity to tension include 1) Shaker channels are sufficiently distensible that stretch produces novel channel states and 2) Shaker channels expand in the plane of the membrane during voltage gating. For channels expressed in oocytes, we compared effects of patch stretch on Shaker and mutants that retain their voltage-gating ability but activate sluggishly because all or most of the S3-S4 linker has been deleted. Deletants had 10, 5, or 0 amino acid (aa) linkers, whereas wild-type is 31 aa. In deletants, though activation is exceptionally slow, slow inactivation is exceptionally quick; the resulting kinetic match was a bonus that allowed effects of stretch to be followed simultaneously in both processes. With the intact linker, an approximately 3 orders of magnitude mismatch in the two processes makes this impracticable. Standard stretch stimuli increased the rates and extent of activation by about the same degree in wild type and deletants, with effects especially pronounced near the foot of G(V). In deletants (where slow inactivation is strongly coupled to activation) stretch also accelerated slow inactivation. Maximum conductances were unaffected by stretch in all variants. In ramp clamp dose experiments, near-lytic patch stretch acted, for all variants, like a approximately 10 mV hyperpolarizing shift. These results suggested that, whether basal rates were high (wild type) or low (deletants), stretch acted by facilitating voltage-dependent activation. Channel activity was therefore simulated with/without "tension," tension being simulated via rate changes at voltage-dependent closed-closed transitions that might involve in-plane expansion (explanation 2). Simulated Delta P(open) arising from approximately 2 kT of "mechanical gating energy" mimicked experimental effects seen with comfortably sub-lytic stretch. PMID:12023221

  13. Nuclear fuel reprocessing deactivation plan for the Idaho Chemical Processing Plant, Revision 1

    SciTech Connect

    Patterson, M.W.

    1994-10-01

    The decision was announced on April 28, 1992 to cease all United States Department of Energy (DOE) reprocessing of nuclear fuels. This decision leads to the deactivation of all fuels dissolution, solvent extraction, krypton gas recovery operations, and product denitration at the Idaho Chemical Processing Plant (ICPP). The reprocessing facilities will be converted to a safe and stable shutdown condition awaiting future alternate uses or decontamination and decommissioning (D&D). This ICPP Deactivation Plan includes the scope of work, schedule, costs, and associated staffing levels necessary to achieve a safe and orderly deactivation of reprocessing activities and the Waste Calcining Facility (WCF). Deactivation activities primarily involve shutdown of operating systems and buildings, fissile and hazardous material removal, and related activities. A minimum required level of continued surveillance and maintenance is planned for each facility/process system to ensure necessary environmental, health, and safety margins are maintained and to support ongoing operations for ICPP facilities that are not being deactivated. Management of the ICPP was transferred from Westinghouse Idaho Nuclear Company, Inc. (WINCO) to Lockheed Idaho Technologies Company (LITCO) on October 1, 1994 as part of the INEL consolidated contract. This revision of the deactivation plan (formerly the Nuclear Fuel Reprocessing Phaseout Plan for the ICPP) is being published during the consolidation of the INEL site-wide contract and the information presented here is current as of October 31, 1994. LITCO has adopted the existing plans for the deactivation of ICPP reprocessing facilities and the plans developed under WINCO are still being actively pursued, although the change in management may result in changes which have not yet been identified. Accordingly, the contents of this plan are subject to revision.

  14. Acute Cocaine Induces Fast Activation of D1 Receptor and Progressive Deactivation of D2 Receptor Strial Neurons: In Vivo Optical Microprobe [Ca(superscript)2+]subscript)i Imaging

    SciTech Connect

    Du, C.; Luo, Z.; Volkow, N.D.; Heintz, N.; Pan, Y.; Du, C.

    2011-09-14

    Cocaine induces fast dopamine increases in brain striatal regions, which are recognized to underlie its rewarding effects. Both dopamine D1 and D2 receptors are involved in cocaine's reward but the dynamic downstream consequences of cocaine effects in striatum are not fully understood. Here we used transgenic mice expressing EGFP under the control of either the D1 receptor (D1R) or the D2 receptor (D2R) gene and microprobe optical imaging to assess the dynamic changes in intracellular calcium ([Ca{sup 2+}]{sub i} ) responses (used as marker of neuronal activation) to acute cocaine in vivo separately for D1R- versus D2R-expressing neurons in striatum. Acute cocaine (8 mg/kg, i.p.) rapidly increased [Ca{sup 2+}]{sub i} in D1R-expressing neurons (10.6 {+-} 3.2%) in striatum within 8.3 {+-} 2.3 min after cocaine administration after which the increases plateaued; these fast [Ca{sup 2+}]{sub i} increases were blocked by pretreatment with a D1R antagonist (SCH23390). In contrast, cocaine induced progressive decreases in [Ca{sup 2+}]{sub i} in D2R-expressing neurons (10.4 {+-} 5.8%) continuously throughout the 30 min that followed cocaine administration; these slower [Ca{sup 2+}]{sub i} decreases were blocked by pretreatment with a D2R antagonist (raclopride). Since activation of striatal D1R-expressing neurons (direct-pathway) enhances cocaine reward, whereas activation of D2R expressing neurons suppresses it (indirect-pathway) (Lobo et al., 2010), this suggests that cocaine's rewarding effects entail both its fast stimulation ofD1R (resulting in abrupt activation of direct-pathway neurons) and a slower stimulation of D2R (resulting in longer-lasting deactivation of indirect-pathway neurons). We also provide direct in vivo evidence of D2R and D1R interactions in the striatal responses to acute cocaine administration.

  15. Ionic mechanism of the slow afterdepolarization induced by muscarinic receptor activation in rat prefrontal cortex.

    PubMed

    Haj-Dahmane, S; Andrade, R

    1998-09-01

    The mammalian prefrontal cortex receives a dense cholinergic innervation from subcortical regions. We previously have shown that cholinergic stimulation of layer V pyramidal neurons of the rat prefrontal cortex results in a depolarization and the appearance of a slow afterdepolarization (sADP). In the current report we examine the mechanism underlying the sADP with the use of sharp microelectrode and whole cell recording techniques in in vitro brain slices. The ability of acetylcholine (ACh) and carbachol to induce the appearance of an sADP in pyramidal cells of layer V of prefrontal cortex is antagonized in a surmountable manner by atropine and is mimicked by application of muscarine or oxotremorine. These results indicate that ACh acts on muscarinic receptors to induce the sADP. In many cell types afterpotentials are triggered by calcium influx into the cell. Therefore we examined the possibility that calcium influx might be the trigger for the generation of the sADP. Consistent with this possibility, buffering intracellular calcium reduced or abolished the sADP but had little effect on the direct muscarinic receptor-induced depolarization also seen in these cells. These results, coupled to the previous observation that calcium channel blockers inhibit the sADP, indicated that the sADP results from a rise in intracellular calcium secondary to calcium influx into the cell. The ionic basis for the current underlying the sADP (IsADP) was examined with the use of ion substitution experiments. The amplitude of IsADP was found to be reduced in a graded fashion by replacement of extracellular sodium with N-methyl-D-glucamine (NMDG). In contrast no clear evidence for the involvement of potassium or chloride channels in the generation of the sADP or IsADP could be found. This result indicated that IsADP is carried by sodium ions flowing into the cell. However, the dependence of IsADP on extracellular sodium was less pronounced than expected for a pure sodium current. We

  16. Purification and characterization of a lipid thiobis ester from human neutrophil cytosol that reversibly deactivates the O2- -generating NADPH oxidase.

    PubMed

    Eklund, E A; Gabig, T G

    1990-05-25

    Intact neutrophils possess a cellular mechanism that efficiently deactivates the microbicidal O2-generating NADPH oxidase during the respiratory burst (Akard, L. P., English, D., and Gabig, T. G. (1988) Blood 72, 322-327). The present studies directed at identifying the molecular mechanism(s) involved in NADPH oxidase deactivation showed that a heat- and trypsin-insensitive species in the cytosolic fraction from normal unstimulated neutrophils was capable of deactivating the membrane-associated NADPH oxidase isolated from opsonized zymosan- or phorbol 12-myristate 13-acetate-stimulated neutrophils. This cytosolic species also deactivated the cell-free-activated oxidase. Deactivation by this cytosolic species occurred in the absence of NADPH-dependent catalytic turnover and was reversible, since NADPH oxidase activity could be subsequently reactivated in the cell-free system. The sedimentable particulate fraction from unstimulated neutrophils did not demonstrate deactivator activity. Deactivator activity was demonstrated in the neutral lipid fraction of neutrophil cytosol extracted with chloroform:methanol. Following complete purification of cytosolic deactivator activity by thin layer chromatography and reversed phase high performance liquid chromatography, the deactivator species was shown to be a lipid thiobis ester compound by mass spectroscopy. Cellular metabolism of this compound in human neutrophils may reveal a unique mechanism for enzymatic control of the NADPH oxidase system and thereby play an important role in regulation of the inflammatory response.

  17. Activation of Hindbrain Neurons Is Mediated by Portal-Mesenteric Vein Glucosensors During Slow-Onset Hypoglycemia

    PubMed Central

    Bohland, MaryAnn; Matveyenko, Aleksey V.; Saberi, Maziyar; Khan, Arshad M.; Watts, Alan G.

    2014-01-01

    Hypoglycemic detection at the portal-mesenteric vein (PMV) appears mediated by spinal afferents and is critical for the counter-regulatory response (CRR) to slow-onset, but not rapid-onset, hypoglycemia. Since rapid-onset hypoglycemia induces Fos protein expression in discrete brain regions, we hypothesized that denervation of the PMV or lesioning spinal afferents would suppress Fos expression in the dorsal medulla during slow-onset hypoglycemia, revealing a central nervous system reliance on PMV glucosensors. Rats undergoing PMV deafferentation via capsaicin, celiac-superior mesenteric ganglionectomy (CSMG), or total subdiaphragmatic vagotomy (TSV) were exposed to hyperinsulinemic–hypoglycemic clamps where glycemia was lowered slowly over 60–75 min. In response to hypoglycemia, control animals demonstrated a robust CRR along with marked Fos expression in the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus. Fos expression was suppressed by 65–92% in capsaicin-treated animals, as was epinephrine (74%), norepinephrine (33%), and glucagon (47%). CSMG also suppressed Fos expression and CRR during slow-onset hypoglycemia, whereas TSV failed to impact either. In contrast, CSMG failed to impact upon Fos expression or the CRR during rapid-onset hypoglycemia. Peripheral glucosensory input from the PMV is therefore required for activation of hindbrain neurons and the full CRR during slow-onset hypoglycemia. PMID:24727435

  18. The role of non-rapid eye movement slow-wave activity in prefrontal metabolism across young and middle-aged adults.

    PubMed

    Wilckens, Kristine A; Aizenstein, Howard J; Nofzinger, Eric A; James, Jeffrey A; Hasler, Brant P; Rosario-Rivera, Bedda L; Franzen, Peter L; Germain, Anne; Hall, Martica H; Kupfer, David J; Price, Julie C; Siegle, Greg J; Buysse, Daniel J

    2016-06-01

    Electroencephalographic slow-wave activity (0.5-4 Hz) during non-rapid eye movement (NREM) sleep is a marker for cortical reorganization, particularly within the prefrontal cortex. Greater slow wave activity during sleep may promote greater waking prefrontal metabolic rate and, in turn, executive function. However, this process may be affected by age. Here we examined whether greater NREM slow wave activity was associated with higher prefrontal metabolism during wakefulness and whether this relationship interacted with age. Fifty-two participants aged 25-61 years were enrolled into studies that included polysomnography and a (18) [F]-fluoro-deoxy-glucose positron emission tomography scan during wakefulness. Absolute and relative measures of NREM slow wave activity were assessed. Semiquantitative and relative measures of cerebral metabolism were collected to assess whole brain and regional metabolism, focusing on two regions of interest: the dorsolateral prefrontal cortex and the orbitofrontal cortex. Greater relative slow wave activity was associated with greater dorsolateral prefrontal metabolism. Age and slow wave activity interacted significantly in predicting semiquantitative whole brain metabolism and outside regions of interest in the posterior cingulate, middle temporal gyrus and the medial frontal gyrus, such that greater slow-wave activity was associated with lower metabolism in the younger participants and greater metabolism in the older participants. These results suggest that slow-wave activity is associated with cerebral metabolism during wakefulness across the adult lifespan within regions important for executive function. © 2016 European Sleep Research Society.

  19. Novel method of determination of the internal enzyme distribution within porous solid supports and the deactivation rate constant

    SciTech Connect

    Do, D.D.; Hossain, M.M.

    1986-04-01

    This article presents a method for determining the rate constant for deactivation and the internal distribution of immobilized enzyme. This method makes use of the parallel deactivation process in a diffusion-controlled regime, in which the internal activity profile behaves like a penetration front. This front basically traces through the initial active enzymatic profile, and one can determine the internal profile and the rate constant for deactivation from the experimentally observable bulk concentration versus time. This method is applied to the experimental data of the system of hydrogen peroxide-immobilized catalase on controlled pore glas and Si-Al particles. 26 references.

  20. Threshold of Geomorphic Detectability Estimated from Geologic Observations of Active Slow-Slipping Strike-Slip Faults

    NASA Astrophysics Data System (ADS)

    Kaneda, H.

    2002-12-01

    Sources of catastrophic earthquakes include not only major active faults, but also slow-slipping ones. However, geomorphic characteristics and long-term seismic behavior of slow-slipping faults have not been well understood, although intensive paleoseismic studies were carried out after the unexpected 1992 Landers and 1999 Hector Mine earthquakes. Two Japanese surface faulting earthquakes on slow-slipping strike-slip faults (the 1927 Mw=7.0 Kita-Tango and 1943 Mw=7.0 Tottori earthquakes) provided good opportunity to examine these problems. Analysis of coseismic surface slip, cumulative geomorphic expressions, and paleoseismicity for these two events not only supports a characteristic-slip behavior for these faults, but also suggests a concept of threshold of geomorphic detectability for intramontane strike-slip faults, which must be exceeded in order that progressive coseismic surface offsets can be preserved against surface processes as detectable systematic deflections of channels and ridge crests. The determined threshold slip rates for these examples are in the range of 0.06-0.13 mm/yr, which can be a quantitative explanation for an extremely small number of mapped active faults with slip rates of less than 0.1 mm/yr in Japan islands. On the contrary, the threshold of geomorphic detectability is probably negligible in arid regions where denudation rate would be extremely low. To date, the issue of geomorphologically undetectable active faults has been that of blind thrust faults buried beneath thick sediments, but another type of blind active faults or fault segments can exist in humid and mountainous regions. In spite of their low slip rates and long recurrence intervals, their potential presence must be considered, especially in regions under the tectonically undeveloped regime, where regional strain is accommodated by many scattered slow-slipping faults.

  1. Frequency of slow oscillations in arterial pressure and R-R intervals during muscle metaboreflex activation.

    PubMed

    Kiviniemi, Antti M; Tiinanen, Suvi; Hautala, Arto J; Seppänen, Tapio; Mäkikallio, Timo H; Huikuri, Heikki V; Tulppo, Mikko P

    2010-01-15

    Altered frequency of slow (0.04-0.15Hz) arterial pressure and R-R interval oscillations has been observed in various diseases but the mechanisms for this frequency shift are unclear. The median (Med) frequencies of slow R-R interval and blood pressure (BP) oscillations were recorded in 11 healthy subjects with paced breathing (0.25Hz) during muscle metaboreflex and baroreflex mediated sympathetic stimuli: 1) handgrip exercise (HG) followed by post-exercise circulatory occlusion (PECO), 2) handgrip exercise during ischemia by circulatory occlusion (IHG) and 3) passive head-up tilt (TILT). Med(BP) shifted to the higher frequency during HG, PECO and IHG (from 0.070+/-0.009Hz to 0.088+/-0.013, 0.085+/-0.015 and 0.099+/-0.013Hz, respectively, p<0.01 for all) but not during TILT (0.078+/-0.012Hz). Similarly, Med(R-R) shifted to the higher frequency during HG, PECO and IHG (from 0.072+/-0.009Hz to 0.085+/-0.014, 0.085+/-0.016 and 0.095+/-0.015Hz, respectively, p<0.01 for all) but not during TILT (0.075+/-0.012Hz). Med(BP) and Med(R-R) were higher during IHG compared to HG and lower during TILT compared to both HG and IHG (p<0.01 for all). We conclude that the sympathetic stimulus induced by muscle metaboreflex is an important mechanism increasing the frequency of slow oscillations in arterial pressure and R-R intervals. The present results give new insight to understand the physiology underlying the frequency of slow arterial pressure and R-R interval oscillations.

  2. Odors enhance slow-wave activity in non-rapid eye movement sleep.

    PubMed

    Perl, Ofer; Arzi, Anat; Sela, Lee; Secundo, Lavi; Holtzman, Yael; Samnon, Perry; Oksenberg, Arie; Sobel, Noam; Hairston, Ilana S

    2016-05-01

    Most forms of suprathreshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep-protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive KCs. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 women, 15 men; mean age 26.5 ± 2.5 yr) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single night. Each participant was exposed to one of four odorants, lavender oil (n = 13), vetiver oil (n = 5), vanillin (n = 12), or ammonium sulfide (n = 4), for durations of 5, 10, and 20 s every 9-15 min. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5-4 Hz) and slow spindle (9-12 Hz) frequencies during non-rapid eye movement sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow-frequency oscillations. Copyright © 2016 the American Physiological Society.

  3. Odors enhance slow-wave activity in non-rapid eye movement sleep

    PubMed Central

    Perl, Ofer; Arzi, Anat; Sela, Lee; Secundo, Lavi; Holtzman, Yael; Samnon, Perry; Oksenberg, Arie; Sobel, Noam

    2016-01-01

    Most forms of suprathreshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep-protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive KCs. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 women, 15 men; mean age 26.5 ± 2.5 yr) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single night. Each participant was exposed to one of four odorants, lavender oil (n = 13), vetiver oil (n = 5), vanillin (n = 12), or ammonium sulfide (n = 4), for durations of 5, 10, and 20 s every 9–15 min. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5–4 Hz) and slow spindle (9–12 Hz) frequencies during non-rapid eye movement sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow-frequency oscillations. PMID:26888107

  4. Time scale bridging in atomistic simulation of slow dynamics: viscous relaxation and defect activation

    NASA Astrophysics Data System (ADS)

    Kushima, A.; Eapen, J.; Li, Ju; Yip, S.; Zhu, T.

    2011-08-01

    Atomistic simulation methods are known for timescale limitations in resolving slow dynamical processes. Two well-known scenarios of slow dynamics are viscous relaxation in supercooled liquids and creep deformation in stressed solids. In both phenomena the challenge to theory and simulation is to sample the transition state pathways efficiently and follow the dynamical processes on long timescales. We present a perspective based on the biased molecular simulation methods such as metadynamics, autonomous basin climbing (ABC), strain-boost and adaptive boost simulations. Such algorithms can enable an atomic-level explanation of the temperature variation of the shear viscosity of glassy liquids, and the relaxation behavior in solids undergoing creep deformation. By discussing the dynamics of slow relaxation in two quite different areas of condensed matter science, we hope to draw attention to other complex problems where anthropological or geological-scale time behavior can be simulated at atomic resolution and understood in terms of micro-scale processes of molecular rearrangements and collective interactions. As examples of a class of phenomena that can be broadly classified as materials ageing, we point to stress corrosion cracking and cement setting as opportunities for atomistic modeling and simulations.

  5. Lanthanum-mediated modification of GABAA receptor deactivation, desensitization and inhibitory synaptic currents in rat cerebellar neurons.

    PubMed

    Zhu, W J; Wang, J F; Corsi, L; Vicini, S

    1998-09-15

    1. We investigated La3+ effects on recombinant and native gamma-aminobutyric acid A (GABAA) receptors using rapid agonist applications and on inhibitory synaptic currents (IPSCs) in granule and stellate neurons of rat cerebellar slices. 2. Rapid desensitization of currents elicited by 200 ms pulses of 1 mM GABA to small lifted cells transfected with alpha1beta3gamma2 cDNAs was greatly decreased by the coapplication of 100 microM LaCl3. 3. GABA responses were unaffected when coapplication lasted only 2 ms. In contrast, with LaCl3 pre-perfusion, a significant slowing of deactivation in response to 2 ms applications was observed. LaCl3 pre-perfusion also prolonged the duration of responses to 20 mM taurine. 4. Outside-out patches excised from cells transfected with alpha1beta3gamma2 subunit cDNAs were briefly exposed to a saturating concentration of GABA, eliciting a transient activation of single channel currents with a main conductance of 30 pS. Opening and burst durations increased by pre-equilibration of patches with LaCl3. 5. LaCl3 depressed the peak amplitude without affecting the slow deactivation and desensitization of GABA responses in cells transfected with alpha6beta3gamma2 and alpha6beta3delta cDNAs. No significant difference in La3+ modulation of GABA-gated currents was observed between alpha1beta3gamma2 and alpha1beta3delta receptors. 6. The effects of LaCl3 on deactivation and desensitization of GABA responses observed in nucleated patches excised from rat cerebellar granule and stellate neurons were comparable to those in the cells transfected with alpha1beta3gamma2 cDNAs. In addition, La3+ clearly prolonged the spontaneous IPSC time course without changing the amplitude. 7. Our results indicate that La3+ has a dual action on GABA-gated currents: it decreases desensitization and increases channel opening duration. These actions depend on receptor subunit composition and contribute to the prolongation of IPSCs.

  6. Routes for deactivation of different autothermal reforming catalysts

    NASA Astrophysics Data System (ADS)

    Pasel, Joachim; Wohlrab, Sebastian; Kreft, Stefanie; Rotov, Mikhail; Löhken, Katrin; Peters, Ralf; Stolten, Detlef

    2016-09-01

    Fuel cell systems with integrated autothermal reforming units require active and robust catalysts for H2 production. In pursuit of this, an experimental screening of catalysts utilized in the autothermal reforming of commercial diesel fuels is performed. The catalysts incorporate a monolithic cordierite substrate, an oxide support (γ-Al2O3, La-Al2O3, CeO2, Gd-CeO2, ZrO2, Y-ZrO2) and Rh as the active phase. Experiments are run by widely varying the O2/C and H2O/C molar ratios at different gas hourly space velocities. In most cases, this provokes accelerated catalyst deactivation and permits an informative comparison of the catalysts. Fresh and aged catalysts are characterized by temperature-programmed methods, thermogravimetry and transmission electron microscopy to find correlations with catalytic activity and stability. Using this approach, routes for catalyst deactivation are identified, together with causes of different catalytic activities. Suitable reaction conditions can be derived from our results for the operation of reactors for autothermal reforming at steady-state and under transient reaction conditions, which helps improve the efficiency and the stability of fuel cell systems.

  7. Characteristics of hydrothermal convection in inclined layers: implications for hydrothermal activity at slow-spreading axis.

    NASA Astrophysics Data System (ADS)

    Fontaine, F. J.; Cannat, M.; Escartin, J.; Dusunur, D.

    2006-12-01

    The thermal structure of segments along (slow-spreading) mid-ocean ridges is likely to be a key parameter controlling the distribution, dynamics and geometry of hydrothermal systems. It is usually considered that the depth of penetration of hydrothermal fluids at the ridge axis is a function of the depth to the brittle-ductile transition. At slow-spreading axis, it is likely that this depth varies both along- and across-axis, with a deepening of several kilometers from the segment center towards its ends [e.g., Hooft et al., 2000]. This geometry is a consequence of focused melt supply to the segment center, resulting in the episodic and localized injection of magma bodies in the crust, as observed at the Lucky Strike segment of the Mid-Atlantic ridge [Singh et al., 2005]. In order to study the effect of such slopes of the basal temperature on the dynamics of slow-spreading axis hydrothermal systems, we ran a series of two-dimensional numerical models of hydrothermal convection. As a first approximation and following previous studies [e.g., Rabinowicz et al., 1999], we assume that these systems can be represented as rectangular and inclined permeable layers. The models are single-phase and incorporate realistic fluid properties and permeabilities. We have explored the cases of slopes ranging from 0 to 15°, aspect ratios from 1 to 16, and permeabilities up to 10^{-14} m2. The basal slope controls the number of convective cells. As the slope increases, the ratio of the size of the downflow and upflow areas increases. Above a critical slope the circulation is uni-cellular and composed of a broad recharge zone and a focused discharge zone, and encompassing the whole length of the segment. We will present the implication of our models for the distribution of vent sites along slow-spreading ridge segments. The segment-scale circulation and focused outflow obtained could also explain the elevated heat flux at some of the main sites found along slow-spreading ridges like

  8. Final Deactivation Project report on the Alpha Powder Facility, Building 3028, at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1997-04-01

    This report documents the condition of the Alpha Powder Facility (APF), Building 3028, after completion of deactivation activities. Activities conducted to place the facility in a safe and environmentally sound condition for transfer to the U.S. Department of Energy (DOE) Office of Environmental Restoration (EM-40) program are outlined. A history and profile of the facility prior to commencing deactivation activities and a profile of the building after completion of deactivation activities are provided. Turnover items, such as the post-deactivation surveillance and maintenance (S&M) plan, remaining hazardous materials, radiological controls, safeguards and security, quality assurance, facility operations, and supporting documentation provided for in the DOE Nuclear Materials and Facility Stabilization Program (EM-60) turnover package are discussed.

  9. Deactivation and poisoning of fuel cell catalysts

    NASA Astrophysics Data System (ADS)

    Ross, P. N., Jr.

    1985-06-01

    The deactivation and poisoning phenomena reviewed are: the poisoning of anode (fuel electrode) catalyst by carbon monoxide and hydrogen sulfide; the deactivation of the cathode (air electrode) catalyst by sintering; and the deactivation of the cathode by corrosion of the support. The anode catalyst is Pt supported on a conductive, high area carbon black, usually at a loading of 10 w/o. This catalyst is tolerant to some level of carbon monoxide or hydrogen sulfide or both in combination, the level depending on temperature and pressure. Much less is known about hydrogen sulfide poisoning. Typical tolerance levels are 2% CO, and 10 ppM H2S. The cathode catalyst is typically Pt supported on a raphitic carbon black, usually a furnace black heat-treated to 2700 C. The Pt loading is typically 10 w/o, and the dispersion (or percent exposed) as-prepared is typically 30%. The loss of dispersion in use depends on the operational parameters, most especially the cathode potential history, i.e., higher potentials cause more rapid decrease in dispersion. The mechanism of loss of dispersion is not well known. The graphitic carbon support corrodes at a finite rate that is also potential dependent. Support corrosion causes thickening of the electrolyte film between the gas pores and the catalyst particles, which in turn causes increased diffusional resistance and performance loss.

  10. Photophysical deactivation pathways in adenine oligonucleotides.

    PubMed

    Spata, Vincent A; Matsika, Spiridoula

    2015-12-14

    In this work we study deactivation processes in adenine oligomers after absorption of UV radiation using Quantum Mechanics combined with Molecular Mechanics (QM/MM). Correlated electronic structure methods appropriate for describing the excited states are used to describe a π-stacked dimer of adenine bases incorporated into (dA)20(dT)20. The results of these calculations reveal three different types of excited state minima which play a role in deactivation processes. Within this set of minima there are minima where the excited state is localized on one adenine (monomer-like) as well as minima where the excited state is delocalized on two adenines, forming different types of excimers and bonded excimers of varying but inter-related character. The proximity of their energies reveals that the minima can decay into one another along a flat potential energy surface dependent on the interbase separation. Additionally, analysis of the emissive energies and other physical properties, including theoretical anisotropy calculations, and comparison with fluorescence experiments, provides evidence that excimers play an important role in long-lived signals in adenine oligonucleotides while the subpicosecond decay is attributed to monomer-like minima. The necessity for a close approach of the nucleobases reveals that the deactivation mechanism is tied to macro-molecular motion.

  11. Astrocytic glutamate uptake is slow and does not limit neuronal NMDA receptor activation in the neonatal neocortex.

    PubMed

    Hanson, Elizabeth; Armbruster, Moritz; Cantu, David; Andresen, Lauren; Taylor, Amaro; Danbolt, Niels Christian; Dulla, Chris G

    2015-10-01

    Glutamate uptake by astrocytes controls the time course of glutamate in the extracellular space and affects neurotransmission, synaptogenesis, and circuit development. Astrocytic glutamate uptake has been shown to undergo post-natal maturation in the hippocampus, but has been largely unexplored in other brain regions. Notably, glutamate uptake has never been examined in the developing neocortex. In these studies, we investigated the development of astrocytic glutamate transport, intrinsic membrane properties, and control of neuronal NMDA receptor activation in the developing neocortex. Using astrocytic and neuronal electrophysiology, immunofluorescence, and Western blot analysis we show that: (1) glutamate uptake in the neonatal neocortex is slow relative to neonatal hippocampus; (2) astrocytes in the neonatal neocortex undergo a significant maturation of intrinsic membrane properties; (3) slow glutamate uptake is accompanied by lower expression of both GLT-1 and GLAST; (4) glutamate uptake is less dependent on GLT-1 in neonatal neocortex than in neonatal hippocampus; and (5) the slow glutamate uptake we report in the neonatal neocortex corresponds to minimal astrocytic control of neuronal NMDA receptor activation. Taken together, our results clearly show fundamental differences between astrocytic maturation in the developing neocortex and hippocampus, and corresponding changes in how astrocytes control glutamate signaling.

  12. Deactivation of Ni2P/SiO2 catalyst in hydrodechlorination of chlorobenzene

    NASA Astrophysics Data System (ADS)

    Chen, Jixiang; Ci, Donghui; Yang, Qing; Li, Kelun

    2014-11-01

    The deactivation of the Ni2P/SiO2 catalyst in the hydrodechlorination of chlorobenzene was studied. To better illuminate the reasons for the deactivation, the effect of HCl on the structure and activity of Ni2P/SiO2 was investigated. For comparison, the deactivation of the Ni/SiO2 catalyst was also involved. It was found that the Ni2P particles possessed good resistance to HCl poison and to sintering, which is ascribed to the electron-deficiency of Niδ+(0 < δ < 1) site in Ni2P. Acted as the Lewis and Brönsted acid site, the Niδ+ site and the Psbnd OH group on Ni2P/SiO2 catalyzed the formation of the carbonaceous deposit that was difficultly eliminated by hydrogenation. The carbonaceous deposit covered the active sites and might also induce a decrease in the Ni2P crystallinity, subsequently leading to the Ni2P/SiO2 deactivation. Different from Ni2P/SiO2, Ni/SiO2 was mainly deactivated by the chlorine poison and the sintering of nickel crystallites.

  13. Development of deactivation of the default-mode network during episodic memory formation

    PubMed Central

    Chai, Xiaoqian J.; Ofen, Noa; Gabrieli, John D. E.; Whitfield-Gabrieli, Susan

    2014-01-01

    Task-induced deactivation of the default-mode network (DMN) has been associated in adults with successful episodic memory formation, possibly as a mechanism to focus allocation of mental resources for successful encoding of external stimuli. We investigated developmental changes of deactivation of the DMN (posterior cingulate, medial prefrontal, and bilateral lateral parietal cortices) during episodic memory formation in children, adolescents, and young adults (ages 8–24), who studied scenes during functional magnetic resonance imaging (fMRI). Recognition memory improved with age. We defined DMN regions of interest from a different sample of participants with the same age range, using resting-state fMRI. In adults, there was greater deactivation of the DMN for scenes that were later remembered than scenes that were later forgotten. In children, deactivation of the default-network did not differ reliably between scenes that were later remembered or forgotten. Adolescents exhibited a pattern of activation intermediate to that of children and adults. The hippocampal region, often considered part of the DMN, showed a functional dissociation with the rest of the DMN by exhibiting increased activation for later remembered than later forgotten scene that was similar across age groups. These findings suggest that development of memory ability from childhood through adulthood may involve increased deactivation of the neocortical DMN during learning. PMID:24064072

  14. The slow relaxation dynamics in active pharmaceutical ingredients studied by DSC and TSDC: Voriconazole, miconazole and itraconazole.

    PubMed

    Ramos, Joaquim J Moura; Diogo, Hermínio P

    2016-03-30

    The slow molecular mobility of three active pharmaceutical drugs (voriconazole, miconazole and itraconazole) has been studied by differential scanning calorimetry (DSC) and thermally stimulated depolarization currents (TSDC). This study yielded the main kinetic features of the secondary relaxations and of the main (glass transition) relaxation, in particular their distribution of relaxation times. The dynamic fragility of the three glass formers was determined from DSC data (using two different procedures) and from TSDC data. According to our results voriconazole behaves as a relatively strong liquid, while miconazole is moderately fragile and itraconazole is a very fragile liquid. There are no studies in this area published in the literature relating to voriconazole. Also not available in the literature is a slow mobility study by dielectric relaxation spectroscopy in the amorphous miconazole. Apart from that, the results obtained are in reasonable agreement with published works using different experimental techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Separate activation of fast and slow inhibitory postsynaptic potentials in rat neocortex in vitro.

    PubMed Central

    Benardo, L S

    1994-01-01

    Synaptic inhibition was investigated by stimulating inhibitory neurones with focal microapplications of glutamate, while recording from layer V pyramidal neurones of rat somatosensory cortical slices. One class of inhibitory postsynaptic potentials (IPSPs) thus elicited was characterized as a fast, chloride-mediated, GABAA IPSP in part by its fast time-to-peak (mean 2.5 ms) and brief duration, but primarily on the basis of its reversal potential at -68 mV, and its blockade by picrotoxin. The average peak amplitude for these fast IPSPs was -1.5 mV, measured at -60 mV. The peak conductance calculated for these events was about 10 nS. The conductance change associated with the maximal fast inhibitory postsynaptic potential resulting from electrical stimulation of afferent pathways ranged up to 116 nS. A second class of IPSP was encountered much less frequently. These glutamate-triggered events were characterized as slow, potassium-mediated GABAB IPSPs partly because of their longer times-to-peak (mean, 45 ms) and duration, but especially because of their extrapolated equilibrium potential at about -89 mV and blockade by 2-hydroxysaclofen. The average peak amplitude for these slow IPSPs was -2.3 mV, measured at -60 mV. The peak conductance for these events was about 8 nS. IPSPs resulting from the excitation of individual inhibitory interneurones were elicited by glutamate microapplication at particular locations relative to recording sites. Both fast and slow IPSPs were generated, but these occurred as separate events, and mixed responses were never seen. Thus, the two mechanistically distinct types of IPSPs which result from GABA interaction at GABAA and GABAB receptors on neocortical neurones may be mediated by separate classes of inhibitory neurones. PMID:7913968

  16. Rundown of the hyperpolarization-activated KAT1 channel involves slowing of the opening transitions regulated by phosphorylation.

    PubMed Central

    Tang, X D; Hoshi, T

    1999-01-01

    Disappearance of the functional activity or rundown of ion channels upon patch excision in many cells involves a decrease in the number of channels available to open. A variety of cellular and biophysical mechanisms have been shown to be involved in the rundown of different ion channels. We examined the rundown process of the plant hyperpolarization-activated KAT1 K+ channel expressed in Xenopus oocytes. The decrease in the KAT1 channel activity on patch excision was accompanied by progressive slowing of the activation time course, and it was caused by a shift in the voltage dependence of the channel without any change in the single-channel amplitude. The single-channel analysis showed that patch excision alters only the transitions leading up to the burst states of the channel. Patch cramming or concurrent application of protein kinase A (PKA) and ATP restored the channel activity. In contrast, nonspecific alkaline phosphatase (ALP) accelerated the rundown time course. Low internal pH, which inhibits ALP activity, slowed the KAT1 rundown time course. The results show that the opening transitions of the KAT1 channel are enhanced not only by hyperpolarization but also by PKA-mediated phosphorylation. PMID:10354434

  17. Brain activity modeling in general anesthesia: Enhancing local mean-field models using a slow adaptive firing rate

    NASA Astrophysics Data System (ADS)

    Molaee-Ardekani, B.; Senhadji, L.; Shamsollahi, M. B.; Vosoughi-Vahdat, B.; Wodey, E.

    2007-10-01

    In this paper, an enhanced local mean-field model that is suitable for simulating the electroencephalogram (EEG) in different depths of anesthesia is presented. The main building elements of the model (e.g., excitatory and inhibitory populations) are taken from Steyn-Ross [M. L. Steyn-Ross , Phys. Rev. E 64, 011917 (2001), D. A. Steyn-Ross , Phys. Rev. E 64, 011918 (2001)] and Bojak and Liley [I. Bojak and D. T. Liley, Phys. Rev. E 71, 041902 (2005)] mean-field models and a new slow ionic mechanism is included in the main model. Generally, in mean-field models, some sigmoid-shape functions determine firing rates of neural populations according to their mean membrane potentials. In the enhanced model, the sigmoid function corresponding to excitatory population is redefined to be also a function of the slow ionic mechanism. This modification adapts the firing rate of neural populations to slow ionic activities of the brain. When an anesthetic drug is administered, the slow mechanism may induce neural cells to alternate between two levels of activity referred to as up and down states. Basically, the frequency of up-down switching is in the delta band (0-4Hz) and this is the main reason behind high amplitude, low frequency fluctuations of EEG signals in anesthesia. Our analyses show that the enhanced model may have different working states driven by anesthetic drug concentration. The model is settled in the up state in the waking period, it may switch to up and down states in moderate anesthesia while in deep anesthesia it remains in the down state.

  18. Large Scale Cortical Functional Networks Associated with Slow-Wave and Spindle-Burst-Related Spontaneous Activity

    PubMed Central

    McVea, David A.; Murphy, Timothy H.; Mohajerani, Majid H.

    2016-01-01

    Cortical sensory systems are active with rich patterns of activity during sleep and under light anesthesia. Remarkably, this activity shares many characteristics with those present when the awake brain responds to sensory stimuli. We review two specific forms of such activity: slow-wave activity (SWA) in the adult brain and spindle bursts in developing brain. SWA is composed of 0.5–4 Hz resting potential fluctuations. Although these fluctuations synchronize wide regions of cortex, recent large-scale imaging has shown spatial details of their distribution that reflect underlying cortical structural projections and networks. These networks are regulated, as prior awake experiences alter both the spatial and temporal features of SWA in subsequent sleep. Activity patterns of the immature brain, however, are very different from those of the adult. SWA is absent, and the dominant pattern is spindle bursts, intermittent high frequency oscillations superimposed on slower depolarizations within sensory cortices. These bursts are driven by intrinsic brain activity, which act to generate peripheral inputs, for example via limb twitches. They are present within developing sensory cortex before they are mature enough to exhibit directed movements and respond to external stimuli. Like in the adult, these patterns resemble those evoked by sensory stimulation when awake. It is suggested that spindle-burst activity is generated purposefully by the developing nervous system as a proxy for true external stimuli. While the sleep-related functions of both slow-wave and spindle-burst activity may not be entirely clear, they reflect robust regulated phenomena which can engage select wide-spread cortical circuits. These circuits are similar to those activated during sensory processing and volitional events. We highlight these two patterns of brain activity because both are prominent and well-studied forms of spontaneous activity that will yield valuable insights into brain function in

  19. Reflections of hunger and satiation in the structure of temporal organization of slow electrical and spike activities of fundal and antral stomach muscles in rabbits.

    PubMed

    Kromin, A A; Zenina, O Yu

    2012-11-01

    Manifestations of hunger and satiation in myoelectric activity patterns in different portions of the stomach were studied in chronic experiments. The state of hunger manifested in the structure of temporal organization of slow electric activity of muscles in the stomach body and antrum in the form of bimodal distributions of slow electric wave periods, while satiation as unimodal distribution. In hunger-specific bimodal distribution of slow electric wave periods generated by muscles of the stomach body and antrum, the position of the first maximum carries the information about oncoming food reinforcement, since this particular range of slow wave fluctuations determines temporal parameters of slow electric activity of muscles in all stomach regions in the course of subsequent successive food-procuring behavior. Under conditions of hunger, the pacemaker features of muscles in the lesser curvature are realized incompletely. Complete realization is achieved in the course of food intake and at the state of satiation.

  20. Final deactivation report on the radioisotope area services, Building 3034, at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1997-09-01

    The purpose of this report is to document the condition of Bldg. 3034, after completion of deactivation activities as outlined by the Department of Energy Office of Nuclear Materials and Facility Stabilization Program (EM-60) guidance documentation. This report outlines the activities conducted to place the facility in a safe and environmentally sound condition for transfer to the Department of Energy Office of Environmental Restoration (EM-40) Program. This report provides a history and profile of Bldg. 3034 before commencement of deactivation activities and a profile of the building after completion of deactivation activities. Turnover, items, such as the Postdeactivation Surveillance & Maintenance Plan, remaining hazardous materials, radiological controls, Safeguards and Security, quality assurance, facility operations, an supporting documentation provided in the Office of Nuclear Materials and Facility Stabilization Program (EM-60) Turnover Package, are discussed. Building 3034 will require access to facilitate required surveillance and maintenance (S&M) activities to maintain the building safety envelope. Building 3034 was stabilized during deactivation so that when transferred to the EM-40 program, only a minimal S&M effort would be required to maintain the building safety envelope. In addition to the minimal S&M activities, the building will be occupied by the maintenance coordinator and the S&M supervisor for the Isotopes Facilities Deactivation Project. The exterior doors are locked when unoccupied to prevent unauthorized access. All materials have been removed from the building. Piping and alarms have been deactivated.

  1. Premature deactivation of soleus during the propulsive phase of cat jumping.

    PubMed

    Kaya, Motoshi; Leonard, Tim R; Herzog, Walter

    2008-04-06

    It has been shown that cat soleus (SOL) forces remain nearly constant despite increases in electromyography (EMG) activity for increasing speeds of locomotion, while medial gastrocnemius (MG) forces and EMG activity increase in parallel. Furthermore, during jumping, average cat SOL forces decrease, while average EMG activity increases dramatically compared with walking conditions. Finally, during rapid paw-shake movements, SOL forces and EMG activities are nearly zero. Based on these results, we hypothesized that the SOL is deactivated, despite ankle extensor requirements, if the contractile conditions limit SOL force potential severely. The purposes of this study were to (i) investigate SOL EMG activity and force as a function of its contractile conditions during jumping, (ii) test whether SOL EMG activity is associated with SOL contractile conditions, and (iii) determine the functional implications of SOL EMG activity during jumping. It was found that the SOL was prematurely deactivated in two distinct phases during the propulsive phase of jumping, in which shortening speeds approached or even exceeded the maximal speed of muscle shortening. We concluded that the SOL was prematurely deactivated to save energy because its mechanical work output approached zero, and speculated that the first phase of deactivation might be caused by a decrease in group Ia firing associated with active shortening and the second by a pre-programmed response inherent to the central pattern generator.

  2. Reversible Deactivation of Enzymes by Redox-Responsive Nanogel Carriers.

    PubMed

    Peng, Huan; Rübsam, Kristin; Jakob, Felix; Pazdzior, Patrizia; Schwaneberg, Ulrich; Pich, Andrij

    2016-11-01

    Novel redox-responsive polymeric nanogels that allow highly efficient enzyme encapsulation and reversible modulation of enzyme activity are developed. The nanogel synthesis and encapsulation of enzyme are performed simultaneously via in situ crosslinking of pyridyldisulfide-functionalized water-soluble reactive copolymers, which are synthesized via reversible addition-fragmentation chain transfer copolymerization. Obtained nanogels with loaded cellulase demonstrate very good colloidal stability in aqueous solutions. The enzymatic activity of cellulase is greatly reduced when encapsulated in the nanogels and rapidly recovered in 10 × 10(-3) m dithiothreitol solution. Fluorescence resonance energy transfer (FRET)-based experiments indicate that the recovered enzymatic activity is mainly ascribed to the release of the enzyme due to the degradation of the disulfide crosslinking network after addition of dithiothreitol (DTT), instead of the enhanced substrate transport rate. The developed enzyme immobilization method opens new possibilities for reversible activation/deactivation of enzymes and opens up new directions for targeted protein therapy and biotechnology applications.

  3. Final deactivation report on the Radioisotope Production Lab-E, Building 3032, at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1997-09-01

    The purpose of this report is to document the condition of Bldg. 3032, after completion of deactivation activities as outlined by the Department of Energy (DOE) Office of Nuclear Materials and Facility Stabilization Program (EM-60) guidance documentation. This report outlines the activities conducted to place the facility in a safe and environmentally sound condition for transfer to the DOE Office of Environmental Restoration Program (EM-40). This report provides a history and profile of Bldg. 3032 prior to commencing deactivation activities and a profile of the building after completion of deactivation activities. Turnover items, such as the Postdeactivation Surveillance & Maintenance Plan, remaining hazardous materials, radiological controls, Safeguards and Security, quality assurance, facility operations, and supporting documentation provided in the EM-60 turnover package are discussed. Building 3032 will be used as the Health Physics Office for the Isotopes Facilities Deactivation Program area and will require access for these offices and to facilitate required surveillance and maintenance (S&M) activities to maintain the building safety envelope. Bldg. 3032 was stabilized during deactivation so that when transferred to the EM-40 program, only a minimal S&M effort would be required to maintain the building safety envelope. All materials have been removed from the building, and all utility systems, piping, and alarms have been deactivated except electricity and steam needed for the office areas.

  4. The role of fast and slow EEG activity during sleep in males and females with Major Depressive Disorder

    PubMed Central

    Cheng, Philip; Goldschmied, Jennifer; Deldin, Patricia; Hoffmann, Robert; Armitage, Roseanne

    2015-01-01

    Sleep difficulties are highly prevalent in depression, and appears to be a contributing factor in the development and maintenance of symptoms. However, despite the generally acknowledged relationship between sleep and depression, the neurophysiological substrates underlying this relationship still remain unclear. Two main hypotheses were tested in this study. The first hypothesis states that sleep in depression is characterized by inadequate generation of restorative sleep, as indexed by reduced amounts of slow-wave activity. Conversely, the second hypothesis states that poor sleep in depression is due to intrusions of fast-frequency activity that may be reflective of a hyperaroused central nervous system. This study aimed to test both hypotheses in a large sample of individuals with clinically validated depression, as well as examine sex as a moderator. Results suggest that depression is better characterized by an overall decrease in slow-wave activity, which is related to elevated anxious and depressed mood the following morning. Results also suggest that females may be more likely to experience fast frequency activity related to depression symptom severity. PMID:26175101

  5. PUREX/UO3 Facilities deactivation lessons learned history

    SciTech Connect

    Gerber, M.S.

    1996-09-19

    Disconnecting the criticality alarm permanently in June 1996 signified that the hazards in the PUREX (plutonium-uranium extraction) plant had been so removed and reduced that criticality was no longer a credible event. Turning off the PUREX criticality alarm also marked a salient point in a historic deactivation project, 1 year before its anticipated conclusion. The PUREX/UO3 Deactivation Project began in October 1993 as a 5-year, $222.5- million project. As a result of innovations implemented during 1994 and 1995, the project schedule was shortened by over a year, with concomitant savings. In 1994, the innovations included arranging to send contaminated nitric acid from the PUREX Plant to British Nuclear Fuels, Limited (BNFL) for reuse and sending metal solutions containing plutonium and uranium from PUREX to the Hanford Site tank farms. These two steps saved the project $36.9- million. In 1995, reductions in overhead rate, work scope, and budget, along with curtailed capital equipment expenditures, reduced the cost another $25.6 million. These savings were achieved by using activity-based cost estimating and applying technical schedule enhancements. In 1996, a series of changes brought about under the general concept of ``reengineering`` reduced the cost approximately another $15 million, and moved the completion date to May 1997. With the total savings projected at about $75 million, or 33.7 percent of the originally projected cost, understanding how the changes came about, what decisions were made, and why they were made becomes important. At the same time sweeping changes in the cultural of the Hanford Site were taking place. These changes included shifting employee relations and work structures, introducing new philosophies and methods in maintaining safety and complying with regulations, using electronic technology to manage information, and, adopting new methods and bases for evaluating progress. Because these changes helped generate cost savings and were

  6. Triggering slow waves during NREM sleep in the rat by intracortical electrical stimulation: effects of sleep/wake history and background activity.

    PubMed

    Vyazovskiy, Vladyslav V; Faraguna, Ugo; Cirelli, Chiara; Tononi, Giulio

    2009-04-01

    In humans, non-rapid eye movement (NREM) sleep slow waves occur not only spontaneously but can also be induced by transcranial magnetic stimulation. Here we investigated whether slow waves can also be induced by intracortical electrical stimulation during sleep in rats. Intracortical local field potential (LFP) recordings were obtained from several cortical locations while the frontal or the parietal area was stimulated intracortically with brief (0.1 ms) electrical pulses. Recordings were performed in early sleep (1st 2-3 h after light onset) and late sleep (6-8 h after light onset). The stimuli reliably triggered LFP potentials that were visually indistinguishable from naturally occurring slow waves. The induced slow waves shared the following features with spontaneous slow waves: they were followed by spindling activity in the same frequency range ( approximately 15 Hz) as spontaneously occurring sleep spindles; they propagated through the neocortex from the area of the stimulation; and compared with late sleep, waves triggered during early sleep were larger, had steeper slopes and fewer multipeaks. Peristimulus background spontaneous activity had a profound influence on the amplitude of the induced slow waves: they were virtually absent if the stimulus was delivered immediately after the spontaneous slow wave. These results show that in the rat a volley of electrical activity that is sufficiently strong to excite and recruit a large cortical neuronal population is capable of inducing slow waves during natural sleep.

  7. Slow activity transients’ in infant rat visual cortex: a spreading synchronous oscillation patterned by retinal waves

    PubMed Central

    Colonnese, Matthew T.; Khazipov, Rustem

    2010-01-01

    A primary feature of the preterm infant electroencephalogram is the presence of large infra-slow potentials containing rapid oscillations called Slow Activity Transients (SATs). Such activity has not been described in animal models, and their generative mechanisms are unknown. Here we use direct-current and multi-site extracellular, as well as whole-cell, recording in vivo to demonstrate the existence of regularly repeating SATs in the visual cortex of infant rats before eye-opening. Present only in absence of anesthesia, SATs at post-natal day 10-11 were identifiable as a separate group of long-duration (∼10s) events that consisted of large (>1 mV) negative local-field potentials produced by the summation of multiple bursts of rapid oscillatory activity (15-30 Hz). SATs synchronized the vast majority of neuronal activity (87%) in the visual cortex before eye-opening. Enucleation eliminated SATs, and their duration, inter-event interval and sub-burst structure matched those of phase III retinal waves recorded in vitro. Retinal waves, however, lacked rapid oscillations, suggesting they arise centrally. Multi-electrode recordings showed that SATs spread horizontally in cortex and synchronize activity at co-active locales via the rapid oscillations. SATs were clearly different from ongoing cortical activity, which was observable as a separate class of short bursts from P9. Together our data suggest that in vivo, early cortical activity is largely determined by peripheral inputs--retinal waves in visual cortex--which provide excitatory input, and by thalamocortical circuitry, which transforms this input to beta oscillations. We propose that the synchronous oscillations of SATs participate in the formation of visual circuitry. PMID:20335468

  8. Application, Deactivation, and Regeneration of Heterogeneous Catalysts in Bio-Oil Upgrading

    DOE PAGES

    Cheng, Shouyun; Wei, Lin; Zhao, Xianhui; ...

    2016-12-01

    The massive consumption of fossil fuels and associated environmental issues are leading to an increased interest in alternative resources such as biofuels. The renewable biofuels can be upgraded from bio-oils that are derived from biomass pyrolysis. Catalytic cracking and hydrodeoxygenation (HDO) are two of the most promising bio-oil upgrading processes for biofuel production. Heterogeneous catalysts are essential for upgrading bio-oil into hydrocarbon biofuel. Although advances have been achieved, the deactivation and regeneration of catalysts still remains a challenge. This review focuses on the current progress and challenges of heterogeneous catalyst application, deactivation, and regeneration. The technologies of catalysts deactivation, reduction,more » and regeneration for improving catalyst activity and stability are discussed. Some suggestions for future research including catalyst mechanism, catalyst development, process integration, and biomass modification for the production of hydrocarbon biofuels are provided.« less

  9. Application, Deactivation, and Regeneration of Heterogeneous Catalysts in Bio-Oil Upgrading

    SciTech Connect

    Cheng, Shouyun; Wei, Lin; Zhao, Xianhui; Julson, James

    2016-12-01

    The massive consumption of fossil fuels and associated environmental issues are leading to an increased interest in alternative resources such as biofuels. The renewable biofuels can be upgraded from bio-oils that are derived from biomass pyrolysis. Catalytic cracking and hydrodeoxygenation (HDO) are two of the most promising bio-oil upgrading processes for biofuel production. Heterogeneous catalysts are essential for upgrading bio-oil into hydrocarbon biofuel. Although advances have been achieved, the deactivation and regeneration of catalysts still remains a challenge. This review focuses on the current progress and challenges of heterogeneous catalyst application, deactivation, and regeneration. The technologies of catalysts deactivation, reduction, and regeneration for improving catalyst activity and stability are discussed. Some suggestions for future research including catalyst mechanism, catalyst development, process integration, and biomass modification for the production of hydrocarbon biofuels are provided.

  10. Effects of halothane on GABA(A) receptor kinetics: evidence for slowed agonist unbinding.

    PubMed

    Li, X; Pearce, R A

    2000-02-01

    Many anesthetics, including the volatile agent halothane, prolong the decay of GABA(A) receptor-mediated IPSCs at central synapses. This effect is thought to be a major factor in the production of anesthesia. A variety of different kinetic mechanisms have been proposed for several intravenous agents, but for volatile agents the kinetic mechanisms underlying this change remain unknown. To address this question, we used rapid solution exchange techniques to apply GABA to recombinant GABA(A) receptors (alpha(1)beta(2)gamma(2s)) expressed in HEK 293 cells, in the absence and presence of halothane. To differentiate between different microscopic kinetic steps that may be altered by the anesthetic, we studied a variety of measures, including peak concentration-response characteristics, macroscopic desensitization, recovery from desensitization, maximal current activation rates, and responses to the low-affinity agonist taurine. Experimentally observed alterations were compared with predictions based on a kinetic scheme that incorporated two agonist binding steps, and open and desensitized states. We found that, in addition to slowing deactivation after a brief pulse of GABA, halothane increased agonist sensitivity and slowed recovery from desensitization but did not alter macroscopic desensitization or maximal activation rate and only slightly slowed rapid deactivation after taurine application. This pattern of responses was found to be consistent with a reduction in the microscopic agonist unbinding rate (k(off)) but not with changes in channel gating steps, such as the channel opening rate (beta), closing rate (alpha), or microscopic desensitization. We conclude that halothane slows IPSC decay by slowing dissociation of agonist from the receptor.

  11. Epidemics with temporary link deactivation in scale-free networks

    PubMed Central

    Shkarayev, Maxim S.; Tunc, Ilker; Shaw, Leah B.

    2014-01-01

    During an epidemic, people may adapt or alter their social contacts to avoid infection. Various adaptation mechanisms have been studied previously. Recently, a new adaptation mechanism was presented in [1], where susceptible nodes temporarily deactivate their links to infected neighbors and reactivate when their neighbors recover. Considering the same adaptation mechanism on a scale-free network, we find that the topology of the subnetwork consisting of active links is fundamentally different from the original network topology. We predict the scaling exponent of the active degree distribution and derive mean-field equations by using improved moment closure approximations based on the conditional distribution of active degree given the total degree. These mean field equations show better agreement with numerical simulation results than the standard mean field equations based on a homogeneity assumption. PMID:25419231

  12. Mortality salience modulates cortical responses to painful somatosensory stimulation: Evidence from slow wave and delta band activity.

    PubMed

    Valentini, Elia; Koch, Katharina; Nicolardi, Valentina; Aglioti, Salvatore Maria

    2015-10-15

    Social psychology studies show that awareness of one's eventual death profoundly influences human cognition and behaviour by inducing defensive reactions against end-of-life-related anxiety. Much less is known about the impact of reminders of mortality on brain activity. Here we tested whether reminders of mortality can induce a modulation of the slow electroencephalographic activity triggered by somatosensory nociceptive or auditory threatening stimulation and if this modulation is related to mood and anxiety as well as personality traits. We found a specific slow wave (SW) modulation only for nociceptive stimulation and only following mortality salience induction (compared to reminders of an important failed exam). The enhancement of SW negativity at the scalp vertex was associated with increased state anxiety and negative mood, whereas higher self-esteem was associated with reduced SW amplitude. In addition, mortality salience was linked to an increased amplitude of frontal delta band, which was correlated also with increased positive mood and higher self-esteem. The results indicate that SW and delta spectral activity may represent both proximal and distal defences associated with reminders of death and that neurophysiological correlates of somatosensory representation of painful and threatening stimuli may be useful for existential neuroscience studies.

  13. Effects of slow-release urea fertilizers on urease activity, microbial biomass, and nematode communities in an aquic brown soil.

    PubMed

    Jiao, Xiaoguang; Liang, Wenju; Chen, Lijun; Zhang, Haijun; Li, Qi; Wang, Peng; Wen, Dazhong

    2005-05-01

    A field experiment was carried out at the Shenyang Experimental Station of Ecology (CAS) in order to study the effects of slow-release urea fertilizers high polymer-coated urea (SRU1), SRU1 mixed with dicyandiamide DCD (SRU2), and SRU1 mixed with calcium carbide CaC2 (SRU3) on urease activity, microbial biomass C and N, and nematode communities in an aquic brown soil during the maize growth period. The results demonstrated that the application of slow-release urea fertilizers inhibits soil urease activity and increases the soil NH4+-N content. Soil available N increment could promote its immobilization by microorganisms. Determination of soil microbial biomass N indicated that a combined application of coated urea and nitrification inhibitors increased the soil active N pool. The population of predators/omnivores indicated that treatment with SRU2 could provide enough soil NH4+-N to promote maize growth and increased the food resource for the soil fauna compared with the other treatments.

  14. Modulation of starch digestion for slow glucose release through "toggling" of activities of mucosal α-glucosidases.

    PubMed

    Lee, Byung-Hoo; Eskandari, Razieh; Jones, Kyra; Reddy, Kongara Ravinder; Quezada-Calvillo, Roberto; Nichols, Buford L; Rose, David R; Hamaker, Bruce R; Pinto, B Mario

    2012-09-14

    Starch digestion involves the breakdown by α-amylase to small linear and branched malto-oligosaccharides, which are in turn hydrolyzed to glucose by the mucosal α-glucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI). MGAM and SI are anchored to the small intestinal brush-border epithelial cells, and each contains a catalytic N- and C-terminal subunit. All four subunits have α-1,4-exohydrolytic glucosidase activity, and the SI N-terminal subunit has an additional exo-debranching activity on the α-1,6-linkage. Inhibition of α-amylase and/or α-glucosidases is a strategy for treatment of type 2 diabetes. We illustrate here the concept of "toggling": differential inhibition of subunits to examine more refined control of glucogenesis of the α-amylolyzed starch malto-oligosaccharides with the aim of slow glucose delivery. Recombinant MGAM and SI subunits were individually assayed with α-amylolyzed waxy corn starch, consisting mainly of maltose, maltotriose, and branched α-limit dextrins, as substrate in the presence of four different inhibitors: acarbose and three sulfonium ion compounds. The IC(50) values show that the four α-glucosidase subunits could be differentially inhibited. The results support the prospect of controlling starch digestion rates to induce slow glucose release through the toggling of activities of the mucosal α-glucosidases by selective enzyme inhibition. This approach could also be used to probe associated metabolic diseases.

  15. “Stepping Up” Activity Poststroke: Ankle-Positioned Accelerometer Can Accurately Record Steps During Slow Walking

    PubMed Central

    Klassen, Tara D.; Simpson, Lisa A.; Lim, Shannon B.; Louie, Dennis R.; Parappilly, Beena; Sakakibara, Brodie M.; Zbogar, Dominik

    2016-01-01

    Background As physical activity in people poststroke is low, devices that monitor and provide feedback of walking activity provide motivation to engage in exercise and may assist rehabilitation professionals in auditing walking activity. However, most feedback devices are not accurate at slow walking speeds. Objective This study assessed the accuracy of one accelerometer to measure walking steps of community-dwelling individuals poststroke. Design This was a cross-sectional study. Methods Two accelerometers were positioned on the nonparetic waist and ankle of participants (N=43), and walking steps from these devices were recorded at 7 speeds (0.3–0.9 m/s) and compared with video recordings (gold standard). Results When positioned at the waist, the accelerometer had more than 10% error at all speeds, except 0.8 and 0.9 m/s, and numerous participants recorded zero steps at 0.3 to 0.5 m/s. The device had 10% or less error when positioned at the ankle for all speeds between 0.4 and 0.9 m/s. Limitations Some participants were unable to complete the faster walking speeds due to their walking impairments and inability to maintain the requested walking speed. Conclusions Although not recommended by the manufacturer, positioning the accelerometer at the ankle (compared with the waist) may fill a long-standing need for a readily available device that provides accurate feedback for the altered and slow walking patterns that occur with stroke. PMID:26251478

  16. Influence of thigh activation on the VO₂ slow component in boys and men.

    PubMed

    Breese, Brynmor C; Barker, Alan R; Armstrong, Neil; Fulford, Jonathan; Williams, Craig A

    2014-11-01

    During constant work rate exercise above the lactate threshold (LT), the initial rapid phase of pulmonary oxygen uptake (VO₂) kinetics is supplemented by an additional VO₂ slow component (VO₂Sc) which reduces the efficiency of muscular work. The VO₂Sc amplitude has been shown to increase with maturation but the mechanisms are poorly understood. We utilized the transverse relaxation time (T₂) of muscle protons from magnetic resonance imaging (MRI) to test the hypothesis that a lower VO₂ slow component (VO₂Sc) amplitude in children would be associated with a reduced muscle recruitment compared to adults. Eight boys (mean age 11.4 ± 0.4) and eight men (mean age 25.3 ± 3.3 years) completed repeated step transitions of unloaded-to-very heavy-intensity (U → VH) exercise on a cycle ergometer. MRI scans of the thigh region were acquired at rest and after VH exercise up to the VO₂Sc time delay (ScTD) and after 6 min. T₂ for each of eight muscles was adjusted in relation to cross-sectional area and then summed to provide the area-weighted ΣT₂ as an index of thigh recruitment. There were no child/adult differences in the relative VO₂Sc amplitude [Boys 14 ± 7 vs. Men 18 ± 3 %, P = 0.15, effect size (ES) = 0.8] during which the change (∆) in area-weighted ΣT₂ between the ScTD and 6 min was not different between groups (Boys 1.6 ± 1.2 vs. Men 2.3 ± 1.1 ms, P = 0.27, ES = 0.6). A positive and strong correlation was found between the relative VO₂Sc amplitude and the magnitude of the area-weighted ∆ΣT₂ in men (r = 0.92, P = 0.001) but not in boys (r = 0.09, P = 0.84). This study provides evidence to show that progressive muscle recruitment (as inferred from T₂ changes) contributes to the development of the VO₂Sc during intense submaximal exercise independent of age.

  17. Effects of red light running camera systems installation and then deactivation on intersection safety.

    PubMed

    Ko, Myunghoon; Geedipally, Srinivas Reddy; Walden, Troy Duane; Wunderlich, Robert Carl

    2017-09-01

    The primary objective of this paper is to evaluate the safety impacts of red-light running camera (RLC) system installation and then deactivation at 48 intersections in Houston, Texas. The second objective is to evaluate the spillover effect at nearby non-treated intersections in Houston after the deactivation. To accomplish study objectives, an Empirical Bayes (EB) before-after analysis was used. The results indicate statistically significant collision reductions on all red-light running (RLR) crash types (37 percent) as well as right-angle RLR crashes (47 percent) at the treated intersections after RLC activation. By way of comparison, the RLC deactivation analysis indicated that crashes increased by 20 percent for all RLR crash types and by 23 percent in right-angle RLR crashes at the formerly treated intersections. After deactivation, all severity RLR crashes increased more than expected at nearby non-treated intersections, which indicates the possibility of an adverse spillover effect. However, fatal/injury crashes associated with rear-end decreased after deactivation at both formerly treated and non-treated intersections, although those rear-end crashes account for smaller proportions when compared to all crash types/right-angle crashes. Overall, removing RLC treatments results in a negative reaction to the safety benefits that the treatment provides when it is in place and actively working and to the nearby intersections where the treatment has not been implemented. This study helps define the effects that RLCs have on safety at signalized intersections after installation and deactivation. Copyright © 2017 National Safety Council and Elsevier Ltd. All rights reserved.

  18. Activity of the anticonvulsant lacosamide in experimental and human epilepsy via selective effects on slow Na(+) channel inactivation.

    PubMed

    Holtkamp, Dominik; Opitz, Thoralf; Niespodziany, Isabelle; Wolff, Christian; Beck, Heinz

    2017-01-01

    In human epilepsy, pharmacoresistance to antiepileptic drug therapy is a major problem affecting ~30% of patients with epilepsy. Many classical antiepileptic drugs target voltage-gated sodium channels, and their potent activity in inhibiting high-frequency firing has been attributed to their strong use-dependent blocking action. In chronic epilepsy, a loss of use-dependent block has emerged as a potential cellular mechanism of pharmacoresistance for anticonvulsants acting on voltage-gated sodium channels. The anticonvulsant drug lacosamide (LCM) also targets sodium channels, but has been shown to preferentially affect sodium channel slow inactivation processes, in contrast to most other anticonvulsants. We used whole-cell voltage clamp recordings in acutely isolated cells to investigate the effects of LCM on transient Na(+) currents. Furthermore, we used whole-cell current clamp recordings to assess effects on repetitive action potential firing in hippocampal slices. We show here that LCM exerts its effects primarily via shifting the slow inactivation voltage dependence to more hyperpolarized potentials in hippocampal dentate granule cells from control and epileptic rats, and from patients with epilepsy. It is important to note that this activity of LCM was maintained in chronic experimental and human epilepsy. Furthermore, we demonstrate that the efficacy of LCM in inhibiting high-frequency firing is undiminished in chronic experimental and human epilepsy. Taken together, these results show that LCM exhibits maintained efficacy in chronic epilepsy, in contrast to conventional use-dependent sodium channel blockers such as carbamazepine. They also establish that targeting slow inactivation may be a promising strategy for overcoming target mechanisms of pharmacoresistance. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  19. Salt reduction in slow fermented sausages affects the generation of aroma active compounds.

    PubMed

    Corral, Sara; Salvador, Ana; Flores, Mónica

    2013-03-01

    Slow fermented sausages with different salt content were manufactured: control (2.7% NaCl, S), 16% salt reduced (2.26% NaCl, RS) and 16% replaced by KCl (2.26% NaCl and 0.43% KCl, RSK). The effect of salt reduction on microbiology and chemical parameters, sensory characteristics, texture and volatile compounds was studied. The aroma compounds were identified by GC-MS and olfactometry analyses. Small salt reduction (16%) (RS) affected sausage quality producing a reduction in the acceptance of aroma, taste, juiciness and overall quality. The substitution by KCl (RSK) produced the same acceptability by consumers as for high salt (S) treatment except for the aroma that was not improved by KCl addition. The aroma was affected due to the reduction in sulfur and acids and the increase of aldehyde compounds. Aroma compounds that characterized the high salt treatment (S) were dimethyl trisulfide, 3-methyl thiophene, 2,3-butanedione, 2-nonanone and acetic acid.

  20. Characterization of K-Complexes and Slow Wave Activity in a Neural Mass Model

    PubMed Central

    Ngo, Hong-Viet Victor; Claussen, Jens Christian; Martinetz, Thomas

    2014-01-01

    NREM sleep is characterized by two hallmarks, namely K-complexes (KCs) during sleep stage N2 and cortical slow oscillations (SOs) during sleep stage N3. While the underlying dynamics on the neuronal level is well known and can be easily measured, the resulting behavior on the macroscopic population level remains unclear. On the basis of an extended neural mass model of the cortex, we suggest a new interpretation of the mechanisms responsible for the generation of KCs and SOs. As the cortex transitions from wake to deep sleep, in our model it approaches an oscillatory regime via a Hopf bifurcation. Importantly, there is a canard phenomenon arising from a homoclinic bifurcation, whose orbit determines the shape of large amplitude SOs. A KC corresponds to a single excursion along the homoclinic orbit, while SOs are noise-driven oscillations around a stable focus. The model generates both time series and spectra that strikingly resemble real electroencephalogram data and points out possible differences between the different stages of natural sleep. PMID:25392991

  1. A novel slow hyperpolarization-activated potassium current (IK(SHA)) from a mouse hippocampal cell line.

    PubMed Central

    Wischmeyer, E; Karschin, A

    1997-01-01

    1. A slow hyperpolarization-activated inwardly rectifying K+ current (IK(SHA)) with novel characteristics was identified from the mouse embryonic hippocampus x neuroblastoma cell line HN9.10e. 2. The non-inactivating current activated negative to a membrane potential of -80 mV with slow and complex activation kinetics (tau act approximately 1-7 s) and a characteristic delay of 1-10 s (-80 to -140 mV) that was linearly dependent on the membrane potential. 3. Tail currents and instantaneous open channel currents determined through fast voltage ramps reversed at the K+ equilibrium potential (EK) indicating that primarily K+, but not Na+, permeated the channels. 4. IK(SHA) was unaffected by altering the intracellular Ca2+ concentration between approximately 0 and 10 microM, but was susceptible to block by 5 mM extracellular Ca2+, Ba2+ (Ki = 0.42 mM), and Cs+ (Ki = 2.77 mM) 5. In cells stably transformed with M2 muscarinic receptors, IK(SHA) was rapidly, but reversibly, suppressed by application of micromolar concentrations of muscarine. 6. At the single channel level K(SHA) channel openings were observed with the characteristic delay upon membrane hyperpolarization. Analysis of unitary currents revealed an inwardly rectifying I-V profile and a channel slope conductance of 7 pS. Channel activity persisted in the inside-out configuration for many minutes. 7. It is concluded that IK(SHA) in HN9.10e cells represents a novel K+ current, which is activated upon membrane hyperpolarization. It is functionally different from both classic inwardly rectifying IKir currents and other cationic hyperpolarization-activated IH currents that have been previously described in neuronal or glial cells. Images Figure 1 Figure 2 Figure 6 Figure 7 Figure 8 PMID:9401967

  2. Importance of Counterion Reactivity on the Deactivation of Co-Salen Catalysts in the Hydrolytic Kinetic Resolution of Epichlorohydrin

    SciTech Connect

    Jain,S.; Zheng, X.; Jones, C.; Weck, M.; Davis, R.

    2007-01-01

    Possible modes of deactivation of Jacobsen's Co-salen catalyst during the hydrolytic kinetic resolution (HKR) of epichlorohydrin were explored by UV-vis spectroscopy, X-ray absorption spectroscopy, and electrospray ionization mass spectrometry, combined with recycling studies. Although an active Co(III)-salen catalyst deactivated substantially after multiple cycles without regeneration, the catalyst maintained its +3 oxidation state throughout the runs. Thus, deactivation of Co-salen during HKR was not the result of Co reduction. The mass spectrum of a deactivated material showed that catalyst dimerization does not account for the loss of activity. Results from various catalyst pretreatment tests, as well as from catalysts containing various counterions (acetate, tosylate, chloride, iodide) indicated that the rate of addition of the Co-salen counterions to epoxide forming Co-OH during the reaction correlated with deactivation. The extent of counterion addition to epoxide was influenced by the exposure time and the nucleophilicity of the counterion. An oligo(cyclooctene)-supported Co-OAc salen catalyst, which was 25 times more active than the standard Co-salen catalyst, was recycled multiple times with negligible deactivation.

  3. EDITORIAL: Slow light Slow light

    NASA Astrophysics Data System (ADS)

    Boyd, Robert; Hess, Ortwin; Denz, Cornelia; Paspalakis, Emmanuel

    2010-10-01

    Research into slow light began theoretically in 1880 with the paper [1] of H A Lorentz, who is best known for his work on relativity and the speed of light. Experimental work started some 60 years later with the work of S L McCall and E L Hahn [2] who explored non-linear self-induced transparency in ruby. This field of research has burgeoned in the last 10 years, starting with the work of L Vestergaard Hau and coworkers on slow light via electromagnetically induced transparency in a Bose-Einstein condensate [3]. Many groups are now able to slow light down to a few metres per second or even stop the motion of light entirely [4]. Today, slow light - or more often `slow and fast light' - has become its own vibrant field with a strongly increasing number of publications. In broad scope, slow light research can be categorized in terms of the sort of physical mechanism used to slow down the light. One sort of slow light makes use of material dispersion. This dispersion can be the natural dispersion of the ordinary refractive index or can be the frequency dependence of some nonlinear optical process, such as electromagnetically induced transparency, coherent population oscillations, stimulated light scattering, or four-wave mixing processes. The second sort of slow light makes use of the wavelength dependence of artificially structured materials, such as photonic crystals, optical waveguides, and collections of microresonators. Material systems in which slow light has been observed include metal vapours, rare-earth-doped materials, Raman and Brillioun gain media, photonic crystals, microresonators and, more recently, metamaterials. A common feature of all of these schemes is the presence of a sharp single resonance or multiple resonances produced by an atomic transition, a resonance in a photonic structure, or in a nonlinear optical process. Current applications of slow light include a series of attractive topics in optical information processing, such as optical data

  4. Calcium-activated force responses in fast- and slow-twitch skinned muscle fibres of the rat at different temperatures.

    PubMed Central

    Stephenson, D G; Williams, D A

    1981-01-01

    1. Force responses from mechanically skinned fibres of rat skeletal muscles (extensor digitorum longus and soleus) were measured at different temperatures in the range 3-35 degrees C following sudden changes in Ca2+ concentration in the preparations. 2. At all temperatures there were characteristic differences between the slow- and fast-twitch muscle fibres with respect to the relative steady-state force-[Ca2+] relation: such as a lower [Ca2+] threshold for activation and a less steep force-pCa curve in slow-twitch muscle fibres. 3. At 3-5 degrees C the force changes in both types of muscle fibres lagged considerably behind the estimated changes in [Ca2+] within the preparations and this enabled us to perform a comparative analysis of the Ca2+ kinetics in the process of force development in both muscle fibre types. This analysis suggest that two and six Ca2+ ions are involved in the regulatory unit for contraction of slow- and fast-twitch muscle fibres respectively. 4. The rate of relaxation following a sudden decrease in [Ca2+] was much lower in the slow-twitch than in the fast-twitch muscle at 5 degrees C, suggesting that properties of the contractile apparatus could play an essential role in determining the rate of relaxation in vivo. 5. There was substantial variation in Ca2+ sensitivity between muscle fibres of the same type from different animals at each temperature. However the steepness of the force-[Ca2+] relation was essentially the same for all fibres of the same type. 6. A change in temperature from 5 to 25 degrees C had a statistically significant effect on the sensitivity of the fast-twitch muscle fibres, rendering them less sensitive to Ca2+ by a factor of 2. However a further increase in temperature from 25 to 35 degrees C did not have any statistically significant effect on the force-[Ca2+] relation in fast-twitch muscle fibres. 7. The effect of temperature on the Ca2+ sensitivity of slow-twitch muscle fibres was not statistically significant

  5. Local increase of sleep slow wave activity after three weeks of working memory training in children and adolescents.

    PubMed

    Pugin, Fiona; Metz, Andreas J; Wolf, Martin; Achermann, Peter; Jenni, Oskar G; Huber, Reto

    2015-04-01

    Evidence is accumulating that electroencephalographic (EEG) sleep slow wave activity (SWA), the key characteristic of deep sleep, is regulated not only globally, but also locally. Several studies have shown local learning- and use-dependent changes in SWA. In vitro and in vivo animal experiments and studies in humans indicate that these local changes in SWA reflect synaptic plasticity. During maturation, when synaptic changes are most prominent, learning is of utmost importance. Thus, in this study, we aimed to examine whether intensive working memory training for 3 w would lead to a local increase of sleep SWA using high-density EEG recordings in children and young adolescents. Sleep laboratory at the University Children's Hospital Zurich. Fourteen healthy subjects between 10 and 16 y. Three weeks of intensive working memory training. After intensive working memory training, sleep SWA was increased in a small left frontoparietal cluster (11.06 ± 1.24%, mean ± standard error of the mean). In addition, the local increase correlated positively with increased working memory performance assessed immediately (r = 0.66) and 2 to 5 mo (r = 0.68) after the training. The increase in slow wave activity (SWA) correlates with cognitive training-induced plasticity in a region known to be involved in working memory performance. Thus, in future, the mapping of sleep SWA may be used to longitudinally monitor the effects of working memory training in children and adolescents with working memory deficiencies. © 2015 Associated Professional Sleep Societies, LLC.

  6. Deactivation processes of the lowest excited state of [UO2(H2O)5]2+ in aqueous solution.

    PubMed

    Formosinho, Sebastião J; Burrows, Hugh D; da Graça Miguel, Maria; Azenha, M Emília D G; Saraiva, Isabel M; Ribeiro, A Catarina D N; Khudyakov, Igor V; Gasanov, Rashid G; Bolte, Michèle; Sarakha, Mohamed

    2003-05-01

    A detailed analysis of the photophysical behaviour of uranyl ion in aqueous solutions at room temperature is given using literature data, together with results of new experimental and theoretical studies to see whether the decay mechanism of the lowest excited state involves physical deactivation by energy transfer or a chemical process through hydrogen atom abstraction. Comparison of the radiative lifetimes determined from quantum yield and lifetime data with that obtained from the Einstein relationship strongly suggests that the emitting state is identical to that observed in the lowest energy absorption band. From study of the experimental rate and that calculated theoretically, from deuterium isotope effects and the activation energy for decay support is given to a deactivation mechanism of hydrogen abstraction involving water clusters to give uranium(v) and hydroxyl radicals. Support for hydroxyl radical formation comes from electron spin resonance spectra observed in the presence of the spin traps 5,5-dimethyl-1-pyrroline N-oxide and tert-butyl-N-phenylnitrone and from literature results on photoinduced uranyl oxygen exchange and photoconductivity. It has previously been suggested that the uranyl emission above pH 1.5 may involve an exciplex between excited uranyl ion and uranium(v). Evidence against this mechanism is given on the basis of quenching of uranyl luminescence by uranium(v), together with other kinetic reasoning. No overall photochemical reaction is observed on excitation of aqueous uranyl solutions, and it is suggested that this is mainly due to reoxidation of UO2+ by hydroxyl radicals in a radical pair. An alternative process involving oxidation by molecular oxygen is analysed experimentally and theoretically, and is suggested to be too slow to be a major reoxidation pathway.

  7. Work plan for the Isotopes Facilities Deactivation Project at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1995-08-01

    The purpose of the Isotopes Facilities Deactivation Project (IFDP) is to place former isotopes production facilities at the Oak Ridge National Laboratory in a safe, stable, and environmentally sound condition; suitable for an extended period of minimum surveillance and maintenance (S and M) and as quickly and economical as possible. Implementation and completion of the deactivation project will further reduce the risks to the environment and to public safety and health. Furthermore, completion of the project will result in significant S and M cost savings in future years. The IFDP work plan defines the project schedule, the cost estimate, and the technical approach for the project. A companion document, the EFDP management plan, has been prepared to document the project objectives, define organizational relationships and responsibilities, and outline the management control systems to be employed in the management of the project. The project has adopted the strategy of deactivating the simple facilities first, to reduce the scope of the project and to gain experience before addressing more difficult facilities. A decision support system is being developed to identify the activities that best promote the project mission and result in the largest cost savings. This work plan will be reviewed and revised annually. Deactivation of EFDP Facilities was initiated in FY 1994 and will be completed in FY 2000. The schedule for deactivation of facilities is shown. The total cost of the project is estimated to be $51M. The costs are summarized. Upon completion of deactivation, annual S and M costs of these facilities will be reduced from the current level of $5M per year to less than $1M per year.

  8. Work plan for the Isotopes Facilities Deactivation Project at Oak Ridge National Laboratory

    SciTech Connect

    1995-05-01

    The purpose of the Isotopes Facilities Deactivation Project (IFDP) is to place former isotopes production facilities at the Oak Ridge National Laboratory in a safe, stable, and environmentally sound condition; suitable for an extended period of minimum surveillance and maintenance (S&M) and as quickly and economical as possible. Implementation and completion of the deactivation project will further reduce the risks to the environment and to public safety and health. Furthermore, completion of the project will result in significant S&M cost savings in future years. The IFDP work plan defines the project schedule, the cost estimate, and the technical approach for the project. A companion document, the IFDP management plan, has been prepared to document the project objectives, define organizational relationships and responsibilities, and outline the management control systems to be employed in the management of the project. The project has adopted the strategy of deactivating the simple facilities first, to reduce the scope of the project and to gain experience before addressing more difficult facilities. A decision support system is being developed to identify the activities that best promote the project mission and result in the largest cost savings. This work plan will be reviewed and revised annually. Deactivation of IFDP facilities was initiated in FY 1994 and will be completed in FY 1999. The schedule for deactivation of facilities is shown. The total cost of the project is estimated to be $36M. The costs are summarized. Upon completion of deactivation, annual S&M costs of these facilities will be reduced from the current level of $5M per year to less than $1M per year.

  9. Slow Wave Activity and Modulations in Mouse Jejunum Myenteric Plexus In Situ

    PubMed Central

    Cai, Ying; Tang, He; Jiang, Fan; Dong, Zhaojun

    2017-01-01

    Background/Aims Myenteric plexus interstitial cells of Cajal (ICC-MY) are involved in the generation of gut pacemaker activity and neuronal communication. We performed patch clamp on ICC-MY in situ to observe the changes of pacemaker activity in response to neural modulations. Methods A fresh longitudinal muscle with myenteric plexus (LMMP) from mouse jejunum was prepared. ICC-MY and ganglion neurons embedded in the layer of longitudinal muscles were targeted by patch clamping in whole-cell configuration in a model of current or voltage clamp. Neurogenic modulators were applied to evaluate their effects on ICC pacemaker activity. Results In situ ICC-MY showed spontaneous and rhythmical voltage oscillations with a frequency of 27.2 ± 3.9 cycles/min, amplitude of 32.6 ± 6.3 mV, and resting membrane potential of −62.2 ± 2.8 mV. In situ neurons showed electrically evocable action potential in single or multiple spikes. Pacemaker activity was modulated by neuronal activators through receiving a neuronal input. Application of tetrodotoxin depolarized pacemaker potentials in a dose dependent manner, and decreased the amplitude at tetrodotoxin 0.3 μM for about 40 ± 10%; capsaicin (1 μM) ameliorated ICC-MY K+ current for about 49 ± 14.8%; and, nitric oxide hyperpolarized pacemaker potential and decreased the amplitude and frequency. Conclusions The in situ preparation patch clamp study further demonstrates that the pacemaker activity is an intrinsic property of ICC. The neurogenic activators change and shape pacemaker potential and activity in situ. LMMP preparation in situ patch clamp provides an ideal platform to study the functional innervation of the ICC and the enteric neural system, thereby, for evaluating the neural regulation of pacemaker activity, especially in disorder models. PMID:27436346

  10. Quasi-Periodic Slow Earthquakes and Their Association With Magmatic Activity at Kilauea Volcano, Hawai`i

    NASA Astrophysics Data System (ADS)

    Brooks, B. A.; Foster, J. H.; Sandwell, D.; Poland, M.; Myer, D.; Wolfe, C.; Patrick, M.

    2007-12-01

    Since 1998 the mobile south flank of Kilauea volcano, Hawai`i, has been the site of multiple slow earthquake (SE) events recorded principally with continuous GPS. One spatially coincident family of these SEs exhibited a high degree of periodicity (774 +/- 7 days) from 1998 to 2005 suggesting the next SE would be in mid-March, 2007. In fact, no anomalous deformation occurred there until the June 17 Father's day dike intrusion that caused up to 1m of opening along Kilauea's east rift zone. We analyzed deformation related to the Father's day event using GPS, tilt, ALOS and Envisat interferometry, microseismicity, and elastic dislocation modeling. Our analysis reveals significant motions of far-field sites that cannot be explained by dike-related deformation and that are very similar to previous SE displacements of the same sites, strongly suggesting that a SE occurred. Inclusion of this event in the overall time series yields SE repeat times of 798 +/- 50 days, apparently maintaining the quasi- periodicity of the Kilauea events. Furthermore, the timing of dike- and SE-related deformation and stress modeling suggest the Father's day dike triggered the slow earthquake. We explore the connection between magmatism and SEs at Kilauea and find a potential correlation between SE-timing and eruptive activity since 2000. This suggests the possibility that a mechanistic understanding of Kilauea SEs may require consideration of magmatic processes in addition to fault zone processes.

  11. CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil

    NASA Astrophysics Data System (ADS)

    Almqvist, Helena; Axelsson, Hanna; Jafari, Rozbeh; Dan, Chen; Mateus, André; Haraldsson, Martin; Larsson, Andreas; Molina, Daniel Martinez; Artursson, Per; Lundbäck, Thomas; Nordlund, Pär

    2016-03-01

    Target engagement is a critical factor for therapeutic efficacy. Assessment of compound binding to native target proteins in live cells is therefore highly desirable in all stages of drug discovery. We report here the first compound library screen based on biophysical measurements of intracellular target binding, exemplified by human thymidylate synthase (TS). The screen selected accurately for all the tested known drugs acting on TS. We also identified TS inhibitors with novel chemistry and marketed drugs that were not previously known to target TS, including the DNA methyltransferase inhibitor decitabine. By following the cellular uptake and enzymatic conversion of known drugs we correlated the appearance of active metabolites over time with intracellular target engagement. These data distinguished a much slower activation of 5-fluorouracil when compared with nucleoside-based drugs. The approach establishes efficient means to associate drug uptake and activation with target binding during drug discovery.

  12. CETSA screening identifies known and novel thymidylate synthase inhibitors and slow intracellular activation of 5-fluorouracil

    PubMed Central

    Almqvist, Helena; Axelsson, Hanna; Jafari, Rozbeh; Dan, Chen; Mateus, André; Haraldsson, Martin; Larsson, Andreas; Molina, Daniel Martinez; Artursson, Per; Lundbäck, Thomas; Nordlund, Pär

    2016-01-01

    Target engagement is a critical factor for therapeutic efficacy. Assessment of compound binding to native target proteins in live cells is therefore highly desirable in all stages of drug discovery. We report here the first compound library screen based on biophysical measurements of intracellular target binding, exemplified by human thymidylate synthase (TS). The screen selected accurately for all the tested known drugs acting on TS. We also identified TS inhibitors with novel chemistry and marketed drugs that were not previously known to target TS, including the DNA methyltransferase inhibitor decitabine. By following the cellular uptake and enzymatic conversion of known drugs we correlated the appearance of active metabolites over time with intracellular target engagement. These data distinguished a much slower activation of 5-fluorouracil when compared with nucleoside-based drugs. The approach establishes efficient means to associate drug uptake and activation with target binding during drug discovery. PMID:27010513

  13. Concurrent fast and slow synchronized efferent phrenic activities in time and frequency domain.

    PubMed

    Schmid, K; Böhmer, G; Weichel, T

    1990-09-24

    In urethane-anesthetized or decerebrated vagotomized rabbits efferent multifiber activity of the phrenic nerve was investigated for synchronized activities both in time and frequency domains. When respiratory drive was steadily increased by either an elevation of end-tidal CO2 concentration or i.v. administration of 4-aminopyridine, medium-frequency oscillations (MFO) first increased, then decreased and finally became absent. The power of high-frequency oscillations (HFO) steadily rose with increasing respiratory drive. In contrast to HFO which revealed a unimodal spectral peak of mostly small bandwidth, the MFO spectrum in most cases consisted of a broad complex. This complex in some cases was composed of two distinct peaks, i.e. MFO were heterogenous. The low- and high-frequency fractions of the MFO complex were related predominantly to the first and last third of inspiration, respectively. Examination of the on-going multifiber activity of the phrenic nerve with an expanded time scale revealed that lower frequency MFO probably result from synchronized ramp-like wave activity during early and mid-inspiration. The duration of the observed ramps well matched the corresponding MFO frequency. We suggest that these ramps might result from propagated synchronized waves of high-threshold phrenic motoneurons. During the last part of inspiration, however, MFO, like HFO, resulted from burst-like synchronized discharge of phenic motoneurons. Thus HFO are superimposed on ramp-like and burst-like activity of the MFO. It is assumed that the decline of MFO at high respiratory drive may be due to the increasing strength of HFO bursts which interrupt ramp activity in the MFO range and thus let MFO appear 'invisible' to the recording electrode. Both MFO and HFO were visually detectable in postinspiration.

  14. Activated-Lignite-Based Super Large Granular Slow-Release Fertilizers Improve Apple Tree Growth: Synthesis, Characterizations, and Laboratory and Field Evaluations.

    PubMed

    Tang, Yafu; Wang, Xinying; Yang, Yuechao; Gao, Bin; Wan, Yongshan; Li, Yuncong C; Cheng, Dongdong

    2017-07-26

    In this work, lignite, a low-grade coal, was modified using the solid-phase activation method with the aid of a Pd/CeO2 nanoparticle catalyst to improve its pore structure and nutrient absorption. Results indicate that the adsorption ability of the activated lignite to NO3(-), NH4(+), H2PO4(-), and K(+) was significantly higher than that of raw lignite. The activated lignite was successfully combined with the polymeric slow-release fertilizer, which exhibits typical slow-release behavior, to prepare the super large granular activated lignite slow-release fertilizer (SAF). In addition to the slow-release ability, the SAF showed excellent water-retention capabilities. Soil column leaching experiments further confirmed the slow-release characteristics of the SAF with fertilizer nutrient loss greatly reduced in comparison to traditional and slow-release fertilizers. Furthermore, field tests of the SAF in an orchard showed that the novel SAF was better than other tested fertilizers in improve the growth of young apple trees. Findings from this study suggest that the newly developed SAF has great potential to be used in apple cultivation and production systems in the future.

  15. Blue light activates phase 2 response proteins and slows growth of a431 epidermoid carcinoma xenografts.

    PubMed

    Patel, Alpesh D; Rotenberg, Shaun; Messer, Regina L W; Wataha, John C; Ogbureke, Kalu U E; McCloud, Veronica V; Lockwood, Petra; Hsu, Stephen; Lewis, Jill B

    2014-11-01

    Recent studies suggest that light in the UVA range (320-400 nm) activates signaling pathways that are anti-inflammatory, antioxidative and play a critical role in protection against cancer. These effects have been attributed to NF-E2-related factor (NRF2)-mediated up-regulation of 'phase 2' genes that neutralize oxidative stress and metabolize electrophiles. We had previously shown that small doses of blue light (400-500 nm) had selective toxicity for cultured oral tumor cells and increased levels of peroxiredoxin phase 2 proteins, which led to our hypothesis that blue light activates NRF2 signaling. A431 epidermoid carcinoma cells were treated in culture and as nude mouse xenografts with doses of blue light. Cell lysates and tumor samples were tested for NRF2 activation, and for markers of proliferation and oxidative stress. Blue light activated the phase 2 response in cultured A431 cells and reduced their viability dose dependently. Light treatment of tumors reduced tumor growth, and levels of proliferating cell nuclear antigen (PCNA), and oxidized proteins. Cellular responses to these light energies are worth further study and may provide therapeutic interventions for inflammation and cancer. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Active cortical innervation protects striatal neurons from slow degeneration in culture.

    PubMed

    Fishbein, Ianai; Segal, Menahem

    2011-03-01

    Spiny striatal GABAergic neurons receive most of their excitatory input from the neocortex. In culture, striatal neurons form inhibitory connections, but the lack of intrinsic excitatory afferents prevents the development of spontaneous network activity. Addition of cortical neurons to the striatal culture provides the necessary excitatory input to the striatal neurons, and in the presence of these neurons, striatal cultures do express spontaneous network activity. We have confirmed that cortical neurons provide excitatory drive to striatal neurons in culture using paired recording from cortical and striatal neurons. In the presence of tetrodotoxin (TTX), which blocks action potential discharges, the connections between cortical and striatal neurons are still formed, and in fact synaptic currents generated between them when TTX is removed are far larger than in control, undrugged cultures. Interestingly, the continuous presence of TTX in the co-culture caused striatal cell death. These observations indicate that the mere presence of cortical neurons is not sufficient to preserve striatal neurons in culture, but their synchronous activity, triggered by cortical excitatory synapses, is critical for the maintenance of viability of striatal neurons. These results have important implications for understanding the role of activity in neurodegenerative diseases of the striatum.

  17. Deactivation of Multilayered MFI Nanosheet Zeolite during Upgrading of Biomass Pyrolysis Vapors

    DOE PAGES

    Xu, Mengze; Mukarakate, Calvin; Iisa, Kristiina; ...

    2017-05-02

    Here, the catalytic fast pyrolysis (CFP) of biomass is a promising technology for producing renewable transportation fuels and chemicals. MFI-type catalysts have shown promise for CFP because they produce gasoline range hydrocarbons from oxygenated pyrolysis compounds; however, rapid catalyst deactivation due to coking is one of the major technical barriers inhibiting the commercialization of this technology. Coke deposited on the surface of the catalysts blocks access to active sites in the micropores leading to rapid catalyst deactivation. Our strategy is to minimize rapid catalyst deactivation by adding mesoporosity through forming MFI nanosheet materials. The synthesized MFI nanosheet catalysts were fullymore » characterized and evaluated for cellulose pyrolysis vapor upgrading to produce olefins and aromatic hydrocarbons. The data obtained from pyrolysis-GCMS (py-GCMS), showed that fresh MFI nanosheets produced similar aromatic hydrocarbon and olefin yields compared to conventional HZSM-5. However, MFI nanosheets demonstrated a longer lifetime than HZSM-5 even though coke contents were also higher than for HZSM-5 because the mesopores enabled better accessibility to active acid sites. This conclusion was supported by results from post-reaction analysis of various spent catalysts collected at different points during the deactivation experiments.« less

  18. Deactivation of the EBR-II complex

    SciTech Connect

    Michelbacher, J.A.; Earle, O.K.; Henslee, S.P.

    1997-12-31

    In January of 1994, the Department of Energy mandated the termination of the Integral Fast Reactor (IFR) Program, effective October 1, 1994. To comply with this decision, Argonne National Laboratory-West (ANL-W) prepared a plan providing detailed requirements to place the Experimental Breeder Reactor-II (EBR-II) in a radiologically and industrially safe condition, including removal of all irradiated fuel assemblies from the reactor plant, and removal and stabilization of the primary and secondary sodium, a liquid metal used to transfer heat within the reactor plant. The ultimate goal of the deactivation process is to place the EBR-II complex in a stable condition until a decontamination and decommissioning (D&D) plan can be prepared, thereby minimizing requirements for maintenance and surveillance and maximizing the amount of time for radioactive decay. The final closure state will be achieved in full compliance with federal, state and local environmental, safety, and health regulations and requirements. The decision to delay the development of a detailed D&D plan has necessitated this current action. The EBR-II is a pool-type reactor. The primary system contains approximately 87,000 gallons of sodium, while the secondary system has 13,000 gallons. In order to properly dispose of the sodium in compliance with the Resource Conservation and Recovery Act (RCRA), a facility has been built to react the sodium to a dry carbonate powder in a two stage process. Deactivation of a liquid metal fast breeder reactor (LMFBR) presents unique concerns. Residual amounts of sodium remaining in the primary and secondary systems must be either reacted or inerted to preclude future concerns with sodium-air reactions that generate explosive mixtures of hydrogen and leave corrosive compounds. Residual amounts of sodium on components will effectively {open_quotes}solder{close_quotes} components in place, making future operation or removal unfeasible.

  19. Fast and slow transitions in frontal ensemble activity during flexible sensorimotor behavior

    PubMed Central

    Siniscalchi, Michael J.; Phoumthipphavong, Victoria; Ali, Farhan; Lozano, Marc; Kwan, Alex C.

    2016-01-01

    The ability to shift between repetitive and goal-directed actions is a hallmark of cognitive control. Previous studies have reported that adaptive shifts in behavior are accompanied by changes of neural activity in frontal cortex. However, neural and behavioral adaptations can occur at multiple time scales, and their relationship remains poorly defined. Here, we developed a novel adaptive sensorimotor decision-making task for head-fixed mice, requiring them to shift flexibly between multiple auditory-motor mappings. Two-photon calcium imaging of secondary motor cortex (M2) revealed different ensemble activity states for each mapping. Notably, when adapting to a conditional mapping, transitions in ensemble activity were abrupt and occurred before the recovery of behavioral performance. By contrast, gradual and delayed transitions accompanied shifts towards repetitive responding. These results demonstrate distinct ensemble signatures associated with the start versus end of sensory-guided behavior, and suggest that M2 leads in engaging goal-directed response strategies that require sensorimotor associations. PMID:27399844

  20. Block of human cardiac sodium channels by lacosamide: evidence for slow drug binding along the activation pathway.

    PubMed

    Wang, Ging Kuo; Wang, Sho-Ya

    2014-05-01

    Lacosamide is an anticonvulsant hypothesized to enhance slow inactivation of neuronal Na(+) channels for its therapeutic action. Cardiac Na(+) channels display less and incomplete slow inactivation, but their sensitivity toward lacosamide remains unknown. We therefore investigated the action of lacosamide in human cardiac Nav1.5 and Nav1.5-CW inactivation-deficient Na(+) channels. Lacosamide showed little effect on hNav1.5 Na(+) currents at 300 µM when cells were held at -140 mV. With 30-second conditioning pulses from -90 to -50 mV; however, hNav1.5 Na(+) channels became sensitive to lacosamide with IC50 (50% inhibitory concentration) around 70-80 µM. Higher IC50 values were found at -110 and -30 mV. The development of lacosamide block at -70 mV was slow in wild-type Na(+) channels (τ; 8.04 ± 0.39 seconds, n = 8). This time constant was significantly accelerated in hNav1.5-CW inactivation-deficient counterparts. The recovery from lacosamide block at -70 mV for 10 seconds was relatively rapid in wild-type Na(+) channels (τ; 639 ± 90 milliseconds, n = 8). This recovery was accelerated further in hNav1.5-CW counterparts. Unexpectedly, lacosamide elicited a time-dependent block of persistent hNav1.5-CW Na(+) currents with an IC50 of 242 ± 19 µM (n = 5). Furthermore, both hNav1.5-CW/F1760K mutant and batrachotoxin-activated hNav1.5 Na(+) channels became completely lacosamide resistant, indicating that the lacosamide receptor overlaps receptors for local anesthetics and batrachotoxin. Our results together suggest that lacosamide targets the intermediate preopen and open states of hNav1.5 Na(+) channels. Lacosamide may thus track closely the conformational changes at the hNav1.5-F1760 region along the activation pathway.

  1. Block of Human Cardiac Sodium Channels by Lacosamide: Evidence for Slow Drug Binding along the Activation Pathway

    PubMed Central

    Wang, Sho-Ya

    2014-01-01

    Lacosamide is an anticonvulsant hypothesized to enhance slow inactivation of neuronal Na+ channels for its therapeutic action. Cardiac Na+ channels display less and incomplete slow inactivation, but their sensitivity toward lacosamide remains unknown. We therefore investigated the action of lacosamide in human cardiac Nav1.5 and Nav1.5-CW inactivation-deficient Na+ channels. Lacosamide showed little effect on hNav1.5 Na+ currents at 300 µM when cells were held at −140 mV. With 30-second conditioning pulses from −90 to −50 mV; however, hNav1.5 Na+ channels became sensitive to lacosamide with IC50 (50% inhibitory concentration) around 70–80 µM. Higher IC50 values were found at −110 and −30 mV. The development of lacosamide block at −70 mV was slow in wild-type Na+ channels (τ; 8.04 ± 0.39 seconds, n = 8). This time constant was significantly accelerated in hNav1.5-CW inactivation-deficient counterparts. The recovery from lacosamide block at −70 mV for 10 seconds was relatively rapid in wild-type Na+ channels (τ; 639 ± 90 milliseconds, n = 8). This recovery was accelerated further in hNav1.5-CW counterparts. Unexpectedly, lacosamide elicited a time-dependent block of persistent hNav1.5-CW Na+ currents with an IC50 of 242 ± 19 µM (n = 5). Furthermore, both hNav1.5-CW/F1760K mutant and batrachotoxin-activated hNav1.5 Na+ channels became completely lacosamide resistant, indicating that the lacosamide receptor overlaps receptors for local anesthetics and batrachotoxin. Our results together suggest that lacosamide targets the intermediate preopen and open states of hNav1.5 Na+ channels. Lacosamide may thus track closely the conformational changes at the hNav1.5-F1760 region along the activation pathway. PMID:24563546

  2. Slow-wave activity in the spectral analysis of the electroencephalogram is associated with cortical dysfunctions in patients with Alzheimer's disease.

    PubMed

    Helkala, E L; Laulumaa, V; Soikkeli, R; Partanen, J; Soininen, H; Riekkinen, P J

    1991-06-01

    Cortical functions and slow-wave activity in the spectral analysis of the electroencephalogram (EEG) have been studied in 19 patients with Alzheimer's disease (AD), 18 patients with Parkinson's disease with dementia (PD), and 14 control subjects (C) to determine which functions are explained by their relationship of slow-wave activity. Multiple regression analyses revealed that a variance in visual functions, praxia of the hand, automatic speech, speech understanding, and retrieval from semantic memory were explained by their relationship with slow-wave activity in EEG in the AD group but not in the PD or C groups. The PD and AD groups exhibited equal cortical dysfunctions and mean amplitudes of delta activity in EEG. The cholinergic system, disrupted in AD, has been shown to be important in the regulation of neocortical electrical activity and may be associated with the processing of cortical functions.

  3. Slow recovery of tropical old-field rainforest regrowth and the value and limitations of active restoration.

    PubMed

    Shoo, Luke P; Freebody, Kylie; Kanowski, John; Catterall, Carla P

    2016-02-01

    There is current debate about the potential for secondary regrowth to rescue tropical forests from an otherwise inevitable cascade of biodiversity loss due to land clearing and scant evidence to test how well active restoration may accelerate recovery. We used site chronosequences to compare developmental trajectories of vegetation between self-organized (i.e., spontaneous) forest regrowth and biodiversity plantings (established for ecological restoration, with many locally native tree species at high density) in the Australian wet tropics uplands. Across 28 regrowth sites aged 1-59 years, some structural attributes reached reference rainforest levels within 40 years, whereas wood volume and most tested components of native plant species richness (classified by species' origins, family, and ecological functions) reached less than 50% of reference rainforest values. Development of native tree and shrub richness was particularly slow among species that were wind dispersed or animal dispersed with large (>10 mm) seeds. Many species with animal-dispersed seeds were from near-basal evolutionary lineages that contribute to recognized World Heritage values of the study region. Faster recovery was recorded in 25 biodiversity plantings of 1-25 years in which wood volume developed more rapidly; native woody plant species richness reached values similar to reference rainforest and was better represented across all dispersal modes; and species from near-basal plant families were better (although incompletely) represented. Plantings and regrowth showed slow recovery in species richness of vines and epiphytes and in overall resemblance to forest in species composition. Our results can inform decision making about when and where to invest in active restoration and provide strong evidence that protecting old-growth forest is crucially important for sustaining tropical biodiversity.

  4. Fewer active motors per vesicle may explain slowed vesicle transport in chick motoneurons after three days in vitro.

    PubMed

    Macosko, Jed C; Newbern, Jason M; Rockford, Jean; Chisena, Ernest N; Brown, Charlotte M; Holzwarth, George M; Milligan, Carol E

    2008-05-23

    Vesicle transport in cultured chick motoneurons was studied over a period of 3 days using motion-enhanced differential interference contrast (MEDIC) microscopy, an improved version of video-enhanced DIC. After 3 days in vitro (DIV), the average vesicle velocity was about 30% less than after 1 DIV. In observations at 1, 2 and 3 DIV, larger vesicles moved more slowly than small vesicles, and retrograde vesicles were larger than anterograde vesicles. The number of retrograde vesicles increased relative to anterograde vesicles after 3 DIV, but this fact alone could not explain the decrease in velocity, since the slowing of vesicle transport in maturing motoneurons was observed independently for both anterograde and retrograde vesicles. In order to better understand the slowing trend, the distance vs. time trajectories of individual vesicles were examined at a frame rate of 8.3/s. Qualitatively, these trajectories consisted of short (1-2 s) segments of constant velocity, and the changes in velocity between segments were abrupt (<0.2 s). The trajectories were therefore fit to a series of connected straight lines. Surprisingly, the slopes of theses lines, i.e. the vesicle velocities, were often found to be multiples of ~0.6 mum/s. The velocity histogram showed multiple peaks, which, when fit with Gaussians using a least squares minimization, yielded an average spacing of 0.57 mum/s (taken as the slope of a fit to peak position vs. peak number, R(2)=0.994). We propose that the abrupt velocity changes occur when 1 or 2 motors suddenly begin or cease actively participating in vesicle transport. Under this hypothesis, the decrease in average vesicle velocity observed for maturing motoneurons is due to a decrease in the average number of active motors per vesicle.

  5. Fewer active motors per vesicle may explain slowed vesicle transport in chick motoneurons after three days in vitro

    PubMed Central

    Macosko, Jed C.; Newbern, Jason M.; Rockford, Jean; Chisena, Ernest N.; Brown, Charlotte M.; Holzwarth, George M.; Milligan, Carol E.

    2008-01-01

    Vesicle transport in cultured chick motoneurons was studied over a period of 3 days using motion enhanced differential interference contrast (MEDIC) microscopy, an improved version of video-enhanced DIC. After 3 days in vitro (DIV), the average vesicle velocity was about 30% less than after 1 DIV. In observations at 1, 2 and 3 DIV, larger vesicles moved more slowly than small vesicles, and retrograde vesicles were larger than anterograde vesicles. The number of retrograde vesicles increased relative to anterograde vesicles after 3 DIV, but this fact alone could not explain the decrease in velocity, since the slowing of vesicle transport in maturing motoneurons was observed independently for both anterograde and retrograde vesicles. In order to better understand the slowing trend, the distance vs. time trajectories of individual vesicles were examined at a frame rate of 8.3/s. Qualitatively, these trajectories consisted of short (1–2 s) segments of constant velocity, and the changes in velocity between segments were abrupt (<0.2 s). The trajectories were therefore fit to a series of connected straight lines. Surprisingly, the slopes of theses lines, i.e. the vesicle velocities, were often found to be multiples of ~0.6 µm/s. The velocity histogram showed multiple peaks, which, when fit with Gaussians using a least squares minimization, yielded an average spacing of 0.57 µm/s (taken as the slope of a fit to peak position vs. peak number, R2 = 0.994). We propose that the abrupt velocity changes occur when 1 or 2 motors suddenly begin or cease actively participating in vesicle transport. Under this hypothesis, the decrease in average vesicle velocity observed for maturing motoneurons is due to a decrease in the average number of active motors per vesicle. PMID:18433736

  6. Regional differences in cortical electroencephalogram (EEG) slow wave activity and interhemispheric EEG asymmetry in the fur seal.

    PubMed

    Lyamin, Oleg I; Pavlova, Ivetta F; Kosenko, Peter O; Mukhametov, Lev M; Siegel, Jerome M

    2012-12-01

    Slow wave sleep (SWS) in the northern fur seal (Callorhinus ursinus) is characterized by a highly expressed interhemispheric electroencephalogram (EEG) asymmetry, called 'unihemispheric' or 'asymmetrical' SWS. The aim of this study was to examine the regional differences in slow wave activity (SWA; power in the range of 1.2-4.0 Hz) within one hemisphere and differences in the degree of interhemispheric EEG asymmetry within this species. Three seals were implanted with 10 EEG electrodes, positioned bilaterally (five in each hemisphere) over the frontal, occipital and parietal cortex. The expression of interhemispheric SWA asymmetry between symmetrical monopolar recordings was estimated based on the asymmetry index [AI = (L-R)/(L+R), where L and R are the power in the left and right hemispheres, respectively]. Our findings indicate an anterior-posterior gradient in SWA during asymmetrical SWS in fur seals, which is opposite to that described for other mammals, including humans, with a larger SWA recorded in the parietal and occipital cortex. Interhemispheric EEG asymmetry in fur seals was recorded across the entire dorsal cerebral cortex, including sensory (visual and somatosensory), motor and associative (parietal or suprasylvian) cortical areas. The expression of asymmetry was greatest in occipital-lateral and parietal derivations and smallest in frontal-medial derivations. Regardless of regional differences in SWA, the majority (90%) of SWS episodes with interhemispheric EEG asymmetry meet the criteria for 'unihemispheric SWS' (one hemisphere is asleep while the other is awake). The remaining episodes can be described as episodes of bilateral SWS with a local activation in one cerebral hemisphere.

  7. Slowing of Hippocampal Activity Correlates with Cognitive Decline in Early Onset Alzheimer's Disease. An MEG Study with Virtual Electrodes.

    PubMed

    Engels, Marjolein M A; Hillebrand, Arjan; van der Flier, Wiesje M; Stam, Cornelis J; Scheltens, Philip; van Straaten, Elisabeth C W

    2016-01-01

    Pathology in Alzheimer's disease (AD) starts in the entorhinal cortex and hippocampus. Because of their deep location, activity from these areas is difficult to record with conventional electro- or magnetoencephalography (EEG/MEG). The purpose of this study was to explore hippocampal activity in AD patients and healthy controls using "virtual MEG electrodes". We used resting-state MEG recordings from 27 early onset AD patients [age 60.6 ± 5.4, 12 females, mini-mental state examination (MMSE) range: 19-28] and 26 cognitively healthy age- and gender-matched controls (age 61.8 ± 5.5, 14 females). Activity was reconstructed using beamformer-based virtual electrodes for 78 cortical regions and 6 hippocampal regions. Group differences in peak frequency and relative power in six frequency bands were identified using permutation testing. For the patients, spearman correlations between the MMSE scores and peak frequency or relative power were calculated. Moreover, receiver operator characteristic curves were plotted to estimate the diagnostic accuracy. We found a lower hippocampal peak frequency in AD compared to controls, which, in the patients, correlated positively with MMSE [r(25) = 0.61; p < 0.01] whereas hippocampal relative theta power correlated negatively with MMSE [r(25) = -0.54; p < 0.01]. Cortical peak frequency was also lower in AD in association areas. Furthermore, cortical peak frequency correlated positively with MMSE [r(25) = 0.43; p < 0.05]. In line with this finding, relative theta power was higher in AD across the cortex, and relative alpha and beta power was lower in more circumscribed areas. The average cortical relative theta power was the best discriminator between AD and controls (sensitivity 82%; specificity 81%). Using beamformer-based virtual electrodes, we were able to detect hippocampal activity in AD. In AD, this hippocampal activity is slowed, and correlates better with cognition than the (slowed) activity in cortical areas. On the other

  8. A pilot study of active rehabilitation for adolescents who are slow to recover from sport-related concussion.

    PubMed

    Gagnon, I; Grilli, L; Friedman, D; Iverson, G L

    2016-03-01

    The purpose of this study was to examine the effectiveness of an active rehabilitation intervention for adolescents who are slow-to-recover after a sport-related concussion. Ten adolescents (three girls and seven boys) seen at the Montreal Children's Hospital Concussion Clinic participated in this case series. Adolescents who were symptomatic more than 4 weeks after the injury were provided with an active rehabilitation intervention (M = 7.9 weeks following injury; range = 3.7 to 26.2 weeks). The rehabilitation program includes gradual, closely monitored light aerobic exercise, general coordination exercises, mental imagery, as well as reassurance, normalization of recovery, and stress/anxiety reduction strategies. The program continued until complete symptom resolution and readiness to begin stepwise return to activities. The primary outcome of the study was evolution of post-concussion symptoms. Secondary outcomes included mood, energy, balance, and cognition. After the intervention, post-concussion symptoms significantly decreased for the group of participants. They also had decreased fatigue and improved mood after 6 weeks of initiating the rehabilitation intervention. This case series shows that postconcussive symptoms and functioning in adolescents following sports-related concussion can be improved after participation in an active rehabilitation intervention. The introduction of graded light intensity exercise in the post-acute period following concussion is safe, feasible and appears to have a positive impact on adolescents' functioning.

  9. Slow relaxation of the magnetization in non-linear optical active layered mixed metal oxalate chains.

    PubMed

    Cariati, Elena; Ugo, Renato; Santoro, Giuseppe; Tordin, Elisa; Sorace, Lorenzo; Caneschi, Andrea; Sironi, Angelo; Macchi, Piero; Casati, Nicola

    2010-12-06

    New Co(II) members of the family of multifunctional materials of general formula [DAMS](4)[M(2)Co(C(2)O(4))(6)]·2DAMBA·2H(2)O (M(III) = Rh, Fe, Cr; DAMBA = para-dimethylaminobenzaldehyde and [DAMS(+)] = trans-4-(4-dimethylaminostyryl)-1-methylpyridinium) have been isolated and characterized. Such new hybrid mixed metal oxalates are isostructural with the previously investigated containing Zn(II), Mn(II), and Ni(II). This allows to preserve the exceptional second harmonic generation (SHG) activity, due to both the large molecular quadratic hyperpolarizability of [DAMS(+)] and the efficiency of the crystalline network which organizes [DAMS(+)] into head-to-tail arranged J-type aggregates, and to further tune the magnetic properties. In particular, the magnetic data of the Rh(III) derivative demonstrate that high spin octacoordinated Co(II) centers behave very similarly to the hexacoordinated Co(II) ones, being dominated by a large orbital contribution. The Cr(III) derivative is characterized by ferromagnetic Cr(III)-Co(II) interactions. Most relevantly, the Fe(III) compound is characterized by a moderate antiferromagnetic interaction between Fe(III) and Co(II), resulting in a ferrimagnetic like structure. Its low temperature dynamic magnetic properties were found to follow a thermally activated behavior (τ(0) = 8.6 × 10(-11) s and ΔE = 21.4 K) and make this a candidate for the second oxalate-based single chain magnet (SCM) reported up to date, a property which in this case is coupled to the second order non linear optical (NLO) ones.

  10. Slow river incision and erosion strongly limit active uplift in southern Africa

    NASA Astrophysics Data System (ADS)

    Erlanger, E. D.; Granger, D. E.; Gibbon, R. J.

    2010-12-01

    The high topography of the southern African passive margin has been attributed to uplift since the 1950’s, when L.C. King associated widespread, deeply weathered surfaces to successive cycles of uplift and erosion. Since the time of King, others have attempted to identify a source for the high topography. Competing hypotheses include 1) uplift is recent and continuing due to mantle-driven dynamic topography, or 2) the high topography has been relict since at least the late Cretaceous, and any ongoing uplift is due solely to erosional isostasy. It has remained difficult to test these hypotheses because estimates of late Neogene uplift rates have been very poorly constrained, ranging from ~10-1000 m/My. To resolve whether uplift is active today, we determined modern erosion rates, paleo-erosion rates, and river incision rates in South Africa. River incision rates and paleo-erosion rates were calculated from a flight of terraces along the Sundays River Valley, located on the southeastern coast. This valley hosts the best preserved flight of strath terraces in southern Africa. We dated the river terraces with cosmogenic 26Al and 10Be in quartz sediment, using an isochron burial dating method. The ages of these terraces range from modern to ~4 Ma and vary in height from ~6-80 m above the present river level, providing an excellent opportunity to evaluate uplift rates over million-year timescales. From the terrace ages and heights, we calculated a long-term incision rate of 16 m/My for the Sundays River. The average paleo-erosion rate for the Sundays River is ~10 m/My, about equal in magnitude to the long-term incision rate. We measured modern erosion rates over a large part of South Africa, including several distinct geographic regions: the southeast coast, the Great escarpment, the Lesotho highlands, and the continental interior. Along the southeast coast, erosion rates vary from 4-10 m/My. The Great Escarpment is eroding the fastest at 30-60 m/My. Erosion rates in

  11. Temporal coordination of olfactory cortex sharp-wave activity with up- and downstates in the orbitofrontal cortex during slow-wave sleep.

    PubMed

    Onisawa, Naomi; Manabe, Hiroyuki; Mori, Kensaku

    2017-01-01

    During slow-wave sleep, interareal communications via coordinated, slow oscillatory activities occur in the large-scale networks of the mammalian neocortex. Because olfactory cortex (OC) areas, which belong to paleocortex, show characteristic sharp-wave (SPW) activity during slow-wave sleep, we examined whether OC SPWs in freely behaving rats occur in temporal coordination with up- and downstates of the orbitofrontal cortex (OFC) slow oscillation. Simultaneous recordings of local field potentials and spike activities in the OC and OFC showed that during the downstate in the OFC, the OC also exhibited downstate with greatly reduced neuronal activity and suppression of SPW generation. OC SPWs occurred during two distinct phases of the upstate of the OFC: early-phase SPWs occurred at the start of upstate shortly after the down-to-up transition in the OFC, whereas late-phase SPWs were generated at the end of upstate shortly before the up-to-down transition. Such temporal coordination between neocortical up- and downstates and olfactory system SPWs was observed between the prefrontal cortex areas (OFC and medial prefrontal cortex) and the OC areas (anterior piriform cortex and posterior piriform cortex). These results suggest that during slow-wave sleep, OC and OFC areas communicate preferentially in specific time windows shortly after the down-to-up transition and shortly before the up-to-down transition. Simultaneous recordings of local field potentials and spike activities in the anterior piriform cortex (APC) and orbitofrontal cortex (OFC) during slow-wave sleep showed that APC sharp waves tended to occur during two distinct phases of OFC upstate: early phase, shortly after the down-to-up transition, and late phase, shortly before the up-to-down transition, suggesting that during slow-wave sleep, olfactory cortex and OFC areas communicate preferentially in the specific time windows. Copyright © 2017 the American Physiological Society.

  12. New Observational Evidence of Active Asteroid P/2010 A2: Slow Rotation of the Largest Fragment

    NASA Astrophysics Data System (ADS)

    Kim, Yoonyoung; Ishiguro, Masateru; Lee, Myung Gyoon

    2017-06-01

    We report new observations of the active asteroid P/2010 A2 taken when it made its closest approach to Earth (1.06 au in 2017 January) after its first discovery in 2010. Despite a crucial role of the rotational period in clarifying its ejection mechanism, the rotational property of P/2010 A2 has not yet been studied due to the extreme faintness of this tiny object (∼120 m in diameter). Taking advantage of the best observing geometry since the discovery, we succeed in obtaining the rotational light curve of the largest fragment with Gemini/GMOS-N. We find that (1) the largest fragment has a double-peaked period of 11.36 ± 0.02 hr spinning much slower than its critical spin period; (2) the largest fragment is a highly elongated object (a/b ≥ 1.94) with an effective radius of {61.9}-9.2+16.8 m; (3) the size distribution of the ejecta follows a broken power law (the power indices of the cumulative size distributions of the dust and fragments are 2.5 ± 0.1 and 5.2 ± 0.1, respectively); (4) the mass ratio of the largest fragment to the total ejecta is around 0.8; and (5) the dust cloud morphology is in agreement with the anisotropic ejection model in Kim et al. These new characteristics of the ejecta obtained in this work are favorable to the impact shattering hypothesis.

  13. Active tectonics, paleoseismology and associated methodological challenges posed by the slow moving Alhama de Murcia fault (SE Iberia)

    NASA Astrophysics Data System (ADS)

    Ferrater, Marta; Ortuño, Maria; Masana, Eulàlia; Pallàs, Raimon; Perea, Hector; Baize, Stephane; García-Meléndez, Eduardo; Martínez-Díaz, José J.; Echeverria, Anna; Rockwell, Thomas; Sharp, Warren D.; Arrowsmith, Ramon; Medialdea, Alicia; Rhodes, Edward

    2016-04-01

    The Alhama de Murcia fault (AMF) is a 87 km-long left-lateral slow moving fault and is responsible for the 5.1 Mw 2011 Lorca earthquake. The characterization of the seismic potential of seismogenic strike-slip slow moving faults is necessary but raises huge methodological challenges, as most paleoseismological and active tectonic techniques have been designed on and for fast moving faults. The AMF is used here as a pilot study area to adapt the traditional geomorphological and trenching analyses, especially concerning the precise quantification of offset channels. We: 1) adapted methodologies to slow moving faults, 2) obtained, for the first time, the slip rate of the AMF, and 3) updated its recurrence period and maximum expected magnitude. Morphotectonic studies aim to use the measured tectonic offset of surface channels to calculate seismic parameters. However, these studies lack a standard criterion to score the analysed features. We improved this by differentiating between subjective and objective qualities, and determining up to three objective parameters (lithological changes, associated morphotectonics and shape, and three shape sub-parameters; all ranging from 0 to 1). By applying this methodology to the AMF, we identified and characterized 138 offset features that we mapped on a high-resolution (0.5 × 0.5 m pixel size) Digital Elevation Model (DEM) from a point cloud acquired in 2013 by airborne light detection and ranging (lidar). The identified offsets, together with the ongoing datings, are going to be used to calculate the lateral slip rate of the AMF. In three-dimensional trenches, we measured the offsets of a buried channel by projecting the far-field tendency of the channel onto the fault. This procedure is inspired by the widespread geomorphological procedure and aims to avoid the diffuse deformation in the fault zone associated with slow moving faults. The calculation of the 3D tendency of the channel and its projection onto the fault permitted

  14. Slow-Onset Inhibition of the FabI Enoyl Reductase from Francisella Tularensis: Residence Time and In Vivo Activity

    PubMed Central

    Lu, Hao; England, Kathleen; Ende, Christopher am; Truglio, James J.; Luckner, Sylvia; Reddy, B. Gopal; Marlenee, Nikki; Knudson, Susan E.; Knudson, Dennis L.; Bowen, Richard A.; Kisker, Caroline; Slayden, Richard A.; Tonge, Peter J.

    2009-01-01

    Francisella tularensis is a highly virulent and contagious gram-negative intracellular bacterium that causes the disease tularemia in mammals. The high infectivity and the ability of the bacterium to survive for weeks in a cool, moist environment have raised the possibility that this organism could be exploited deliberately as a potential biological weapon. Fatty acid biosynthesis (FAS-II) is essential for bacterial viability and has been validated as a target for the discovery of novel antibacterials. The FAS-II enoyl reductase ftuFabI has been cloned and expressed, and a series of diphenyl ethers have been identified that are subnanomolar inhibitors of the enzyme with MIC90 values as low as 0.00018 μg/ml. The existence of a linear correlation between the Ki and MIC values strongly suggests that the antibacterial activity of the diphenyl ethers results from direct inhibition of ftuFabI within the cell. The compounds are slow onset inhibitors of ftuFabI, and the residence time of the inhibitors on the enzyme correlates with their in vivo activity in a mouse model of tularemia infection. Significantly, the rate of breakdown of the enzyme-inhibitor complex is a better predictor of in vivo activity than the overall thermodynamic stability of the complex, a concept that has important implications for the discovery of novel chemotherapeutics that normally rely on equilibrium measurements of potency. PMID:19206187

  15. Slow-Onset Inhibition of the FabI Enoyl Reductase from Francisella tularensis: Residence Time and in Vivo Activity

    SciTech Connect

    Lu, H.; England, K; Ende, C; Truglio, J; Luckner, S; Reddy, B; Marlenee, N; Knudson, S; Knudson, D; et. al.

    2009-01-01

    Francisella tularensis is a highly virulent and contagious Gram-negative intracellular bacterium that causes the disease tularemia in mammals. The high infectivity and the ability of the bacterium to survive for weeks in a cool, moist environment have raised the possibility that this organism could be exploited deliberately as a potential biological weapon. Fatty acid biosynthesis (FAS-II) is essential for bacterial viability and has been validated as a target for the discovery of novel antibacterials. The FAS-II enoyl reductase ftuFabI has been cloned and expressed, and a series of diphenyl ethers have been identified that are subnanomolar inhibitors of the enzyme with MIC90 values as low as 0.00018 ?g mL-1. The existence of a linear correlation between the Ki and MIC values strongly suggests that the antibacterial activity of the diphenyl ethers results from direct inhibition of ftuFabI within the cell. The compounds are slow-onset inhibitors of ftuFabI, and the residence time of the inhibitors on the enzyme correlates with their in vivo activity in a mouse model of tularemia infection. Significantly, the rate of breakdown of the enzyme-inhibitor complex is a better predictor of in vivo activity than the overall thermodynamic stability of the complex, a concept that has important implications for the discovery of novel chemotherapeutics that normally rely on equilibrium measurements of potency.

  16. Active-Site pKa Determination for Photoactive Yellow Protein Rationalizes Slow Ground-State Recovery.

    PubMed

    Oktaviani, Nur Alia; Pool, Trijntje J; Yoshimura, Yuichi; Kamikubo, Hironari; Scheek, Ruud M; Kataoka, Mikio; Mulder, Frans A A

    2017-05-23

    The ability to avoid blue-light radiation is crucial for bacteria to survive. In Halorhodospira halophila, the putative receptor for this response is known as photoactive yellow protein (PYP). Its response to blue light is mediated by changes in the optical properties of the chromophore para-coumaric acid (pCA) in the protein active site. PYP displays photocycle kinetics with a strong pH dependence for ground-state recovery, which has remained enigmatic. To resolve this problem, a comprehensive pKa determination of the active-site residues of PYP is required. Herein, we show that Glu-46 stays protonated from pH 3.4 to pH 11.4 in the ground (pG) state. This conclusion is supported by the observed hydrogen-bonded protons between Glu-46 and pCA and Tyr-42 and pCA, which are persistent over the entire pH range. Our experimental results show that none of the active-site residues of PYP undergo pH-induced changes in the pG state. Ineluctably, the pH dependence of pG recovery is linked to conformational change that is dependent upon the population of the relevant protonation state of Glu-46 and the pCA chromophore in the excited state, collaterally explaining why pG recovery is slow. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  17. Replication Fork Slowing and Reversal upon DNA Damage Require PCNA Polyubiquitination and ZRANB3 DNA Translocase Activity.

    PubMed

    Vujanovic, Marko; Krietsch, Jana; Raso, Maria Chiara; Terraneo, Nastassja; Zellweger, Ralph; Schmid, Jonas A; Taglialatela, Angelo; Huang, Jen-Wei; Holland, Cory L; Zwicky, Katharina; Herrador, Raquel; Jacobs, Heinz; Cortez, David; Ciccia, Alberto; Penengo, Lorenza; Lopes, Massimo

    2017-09-07

    DNA damage tolerance during eukaryotic replication is orchestrated by PCNA ubiquitination. While monoubiquitination activates mutagenic translesion synthesis, polyubiquitination activates an error-free pathway, elusive in mammals, enabling damage bypass by template switching. Fork reversal is driven in vitro by multiple enzymes, including the DNA translocase ZRANB3, shown to bind polyubiquitinated PCNA. However, whether this interaction promotes fork remodeling and template switching in vivo was unknown. Here we show that damage-induced fork reversal in mammalian cells requires PCNA ubiquitination, UBC13, and K63-linked polyubiquitin chains, previously involved in error-free damage tolerance. Fork reversal in vivo also requires ZRANB3 translocase activity and its interaction with polyubiquitinated PCNA, pinpointing ZRANB3 as a key effector of error-free DNA damage tolerance. Mutations affecting fork reversal also induced unrestrained fork progression and chromosomal breakage, suggesting fork remodeling as a global fork slowing and protection mechanism. Targeting these fork protection systems represents a promising strategy to potentiate cancer chemotherapy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Active tectonics and rheology of slow-moving thrusts in the Tibetan foreland of peninsular India

    NASA Astrophysics Data System (ADS)

    Copley, Alex; Mitra, Supriyo; Sloan, Alastair; Gaonkar, Sharad; Avouac, Jean-Philippe; Hollingsworth, James

    2016-04-01

    Peninsular India is cut by active thrust faults that break in earthquakes in response to the compressive force exerted between India and the Tibetan Plateau. The rate of deformation is low, with 2 +/- 1 mm/yr of shortening being accommodated over the entire N-S extent of the Indian sub-continent. However, the large seismogenic thickness in the region (40-50 km), and the long faults, mean that the rare earthquakes that do occur can have magnitudes up to at least 8. This contribution describes studies of two large Indian earthquakes, and their rheological and hazard implications, using a range of techniques. First, the Mw 7.6 Bhuj (Gujarat) earthquake of 2001 is examined using a combination of seismology, InSAR, and levelling data. A slip model for the earthquake will be presented, which allows the material properties of the fault plane to be examined. Second, a Holocene-age earthquake rupture from central India will be discussed. Geomorphic analysis of the scarps produced by the event suggest a magnitude of 7.6 - 8.4. Both of these earthquakes had unusually large stress-drops, amongst the largest recorded for shallow earthquakes. The information provided by these two events will be combined with calculations for the total compressive force being transmitted through the Indian peninsular in order to suggest that the faults are characterised by a low coefficient of friction (approximately 0.1), and that the stress-drops in the earthquakes are close to complete. In turn, these results imply that the majority of the force being transmitted through the Indian plate is supported by the brittle crust. Finally, the along-strike continuation of the faults will be described, with implications for hazard assessment and material properties throughout India.

  19. Reduced Tonoplast Fast-Activating and Slow-Activating Channel Activity Is Essential for Conferring Salinity Tolerance in a Facultative Halophyte, Quinoa1[C][W][OA

    PubMed Central

    Bonales-Alatorre, Edgar; Shabala, Sergey; Chen, Zhong-Hua; Pottosin, Igor

    2013-01-01

    Halophyte species implement a “salt-including” strategy, sequestering significant amounts of Na+ to cell vacuoles. This requires a reduction of passive Na+ leak from the vacuole. In this work, we used quinoa (Chenopodium quinoa) to investigate the ability of halophytes to regulate Na+-permeable slow-activating (SV) and fast-activating (FV) tonoplast channels, linking it with Na+ accumulation in mesophyll cells and salt bladders as well as leaf photosynthetic efficiency under salt stress. Our data indicate that young leaves rely on Na+ exclusion to salt bladders, whereas old ones, possessing far fewer salt bladders, depend almost exclusively on Na+ sequestration to mesophyll vacuoles. Moreover, although old leaves accumulate more Na+, this does not compromise their leaf photochemistry. FV and SV channels are slightly more permeable for K+ than for Na+, and vacuoles in young leaves express less FV current and with a density unchanged in plants subjected to high (400 mm NaCl) salinity. In old leaves, with an intrinsically lower density of the FV current, FV channel density decreases about 2-fold in plants grown under high salinity. In contrast, intrinsic activity of SV channels in vacuoles from young leaves is unchanged under salt stress. In vacuoles of old leaves, however, it is 2- and 7-fold lower in older compared with young leaves in control- and salt-grown plants, respectively. We conclude that the negative control of SV and FV tonoplast channel activity in old leaves reduces Na+ leak, thus enabling efficient sequestration of Na+ to their vacuoles. This enables optimal photosynthetic performance, conferring salinity tolerance in quinoa species. PMID:23624857

  20. Reduced tonoplast fast-activating and slow-activating channel activity is essential for conferring salinity tolerance in a facultative halophyte, quinoa.

    PubMed

    Bonales-Alatorre, Edgar; Shabala, Sergey; Chen, Zhong-Hua; Pottosin, Igor

    2013-06-01

    Halophyte species implement a "salt-including" strategy, sequestering significant amounts of Na(+) to cell vacuoles. This requires a reduction of passive Na(+) leak from the vacuole. In this work, we used quinoa (Chenopodium quinoa) to investigate the ability of halophytes to regulate Na(+)-permeable slow-activating (SV) and fast-activating (FV) tonoplast channels, linking it with Na(+) accumulation in mesophyll cells and salt bladders as well as leaf photosynthetic efficiency under salt stress. Our data indicate that young leaves rely on Na(+) exclusion to salt bladders, whereas old ones, possessing far fewer salt bladders, depend almost exclusively on Na(+) sequestration to mesophyll vacuoles. Moreover, although old leaves accumulate more Na(+), this does not compromise their leaf photochemistry. FV and SV channels are slightly more permeable for K(+) than for Na(+), and vacuoles in young leaves express less FV current and with a density unchanged in plants subjected to high (400 mm NaCl) salinity. In old leaves, with an intrinsically lower density of the FV current, FV channel density decreases about 2-fold in plants grown under high salinity. In contrast, intrinsic activity of SV channels in vacuoles from young leaves is unchanged under salt stress. In vacuoles of old leaves, however, it is 2- and 7-fold lower in older compared with young leaves in control- and salt-grown plants, respectively. We conclude that the negative control of SV and FV tonoplast channel activity in old leaves reduces Na(+) leak, thus enabling efficient sequestration of Na(+) to their vacuoles. This enables optimal photosynthetic performance, conferring salinity tolerance in quinoa species.

  1. TiO2 Nanotubes with Open Channels as Deactivation-Resistant Photocatalyst for the Degradation of Volatile Organic Compounds.

    PubMed

    Weon, Seunghyun; Choi, Wonyong

    2016-03-01

    We synthesized ordered TiO2 nanotubes (TNT) and compared their photocatalytic activity with that of TiO2 nanoparticles (TNP) film during the repeated cycles of photocatalytic degradation of gaseous toluene and acetaldehyde to test the durability of TNT as an air-purifying photocatalyst. The photocatalytic activity of TNT showed only moderate reduction after the five cycles of toluene degradation, whereas TNP underwent rapid deactivation as the photocatalysis cycles were repeated. Dynamic SIMS analysis showed that carbonaceous deposits were formed on the surface of TNP during the photocatalytic degradation of toluene, which implies that the photocatalyst deactivation should be ascribed to the accumulation of recalcitrant degradation intermediates (carbonaceous residues). In more oxidizing atmosphere (100% O2 under which less carbonaceous residues should form), the photocatalytic activity of TNP still decreased with repeating cycles of toluene degradation, whereas TNT showed no sign of deactivation. Because TNT has a highly ordered open channel structure, O2 molecules can be more easily supplied to the active sites with less mass transfer limitation, which subsequently hinders the accumulation of carbonaceous residues on TNT surface. Contrary to the case of toluene degradation, both TNT and TNP did not exhibit any significant deactivation during the photocatalytic degradation of acetaldehyde, because the generation of recalcitrant intermediates from acetaldehyde degradation is insignificant. The structural characteristics of TNT is highly advantageous in preventing the catalyst deactivation during the photocatalytic degradation of aromatic compounds.

  2. Slow Active Intraplate Faults: The Paleoseismology Of The Irtysh Fault Zone, Eastern Kazakhstan

    NASA Astrophysics Data System (ADS)

    Baize, S.; Reicherter, K. R.; Avagyan, A.; Belyashov, A.; Pestov, E.; Eutizio, V.; Arakelyan, A.

    2016-12-01

    The Asian plate interiors are known to host strong earthquakes with magnitudes up to M 8, especially around the border area between Mongolia, Russia, Kazakhstan and China. Their recurrence times are long, because of the low slip rates of faults smaller than 1 mm/yr. Geodynamically, our study region in eastern Kazakhstan is set in the frame of the Indian-Eurasian collision zone situated on the Eurasian craton. Major plate tectonic forces are induced by the indentation of the Indian plate into Eurasia. As a consequence, in the foreland a set of very long and large strike-slip fault zones developed, the western of which all have in common a dextral sense of shear. The more than 250 km long Irtysh Fault Zone (IFZ) marks a major tectonic block boundary separating two different units with granitoid intrusions, Silurian-Devonian magmatic rocks, and, thick deposits of Late Paleozoic age with coal measures of the Carboniferous and Permian. The formation of the IFZ probably dates back into Paleozoic times, it was repeatedly reactivated in later times. The IFZ is one potential source of large earthquakes in easternmost Kazakhstan. Tectonic-morphological analyses revealed the occurrence of a set of lineaments offsetting or deflecting streamlets and lithology. Geophysical data (GPR and seismics) helped to identify fault strands and trenching sites. Across three main segments, all longer than 50 km, a series of paleoseismic trenches was excavated. Within the trenches, faulted Holocene-Late Pleistocene deposits with organic soils, loess layers and colluvium directly overlying the Paleozoic rocks were encountered and 14C-dated. Astonishingly, no older Pleistocene rocks have been found suggesting complete erosion during/after glacial periods. Our findings lead to the conclusions that the IFZ and all segments are clearly active during the Holocene with surface ruptures displacements of around 2.0±0.2 meters, suggesting events with a magnitude around M≈7 along the individual

  3. Mild Airflow Limitation during N2 Sleep Increases K-complex Frequency and Slows Electroencephalographic Activity.

    PubMed

    Nguyen, Chinh D; Wellman, Andrew; Jordan, Amy S; Eckert, Danny J

    2016-03-01

    To determine the effects of mild airflow limitation on K-complex frequency and morphology and electroencephalogram (EEG) spectral power. Transient reductions in continuous positive airway pressure (CPAP) during stable N2 sleep were performed to induce mild airflow limitation in 20 patients with obstructive sleep apnea (OSA) and 10 healthy controls aged 44 ± 13 y. EEG at C3 and airflow were measured in 1-min windows to quantify K-complex properties and EEG spectral power immediately before and during transient reductions in CPAP. The frequency and morphology (amplitude and latency of P200, N550 and N900 components) of K-complexes and EEG spectral power were compared between conditions. During mild airflow limitation (18% reduction in peak inspiratory airflow from baseline, 0.38 ± 0.11 versus 0.31 ± 0.1 L/sec) insufficient to cause American Academy of Sleep Medicine-defined cortical arousal, K-complex frequency (9.5 ± 4.5 versus 13.7 ± 6.4 per min, P < 0.01), N550 amplitude (25 ± 3 versus 27 ± 3 μV, P < 0.01) and EEG spectral power (delta: 147 ± 48 versus 230 ± 99 μV(2), P < 0.01 and theta bands: 31 ± 14 versus 34 ± 13 μV(2), P < 0.01) significantly increased whereas beta band power decreased (14 ± 5 versus 11 ± 4 μV(2), P < 0.01) compared to the preceding non flow-limited period on CPAP. K-complex frequency, morphology, and timing did not differ between patients and controls. Mild airflow limitation increases K-complex frequency, N550 amplitude, and spectral power of delta and theta bands. In addition to providing mechanistic insight into the role of mild airflow limitation on K-complex characteristics and EEG activity, these findings may have important implications for respiratory conditions in which airflow limitation during sleep is common (e.g., snoring and OSA). © 2016 Associated Professional Sleep Societies, LLC.

  4. Highly n -doped silicon: Deactivating defects of donors

    NASA Astrophysics Data System (ADS)

    Mueller, D. Christoph; Fichtner, Wolfgang

    2004-12-01

    We report insight into the deactivation mechanisms of group V donors in heavily doped silicon. Based on our ab initio calculations, we suggest a three step model for the donor deactivation. In highly n -type Si grown at low temperatures, in the absence of excess native point defects, the intrinsic limit to ne seems to rise in part by means of donor deactivating distortions of the silicon lattice in the proximity of two or more donor atoms that share close sites. Also, donor dimers play an important part in the deactivation at high doping concentrations. While the dimers constitute a stable or metastable inactive donor configuration, the lattice distortions lower the donor levels gradually below the impurity band in degenerate silicon. On the other hand, we find that, in general, none of the earlier proposed deactivating donor pair defects is stable at any position of the Fermi level. The lattice distortions may be viewed as a precursor to Frenkel pair generation and donor-vacancy clustering process (step 2) that account for deactivation at elevated temperature and longer annealing times. Ultimately, and most prominently in the case of the large Sb atoms, precipitation of the donor atoms may set in as the last step of the deactivation process chain.

  5. Slow fluctuations in eye position and resting-state functional magnetic resonance imaging brain activity during visual fixation.

    PubMed

    Fransson, Peter; Flodin, Pär; Seimyr, Gustaf Öqvist; Pansell, Tony

    2014-12-01

    The neuronal circuitry that supports voluntary changes in eye position in tasks that require attention-driven oculo-motor control is well known. However, less is known about the neuronal basis for eye control during visual fixation. This, together with the fact that visual fixation is one of the most commonly used baseline conditions in resting-state functional magnetic resonance imaging (fMRI) studies, prompted us to conduct a study in which we employed resting-state fMRI and concurrent recordings of eye gaze to investigate the relationship between spontaneous changes in eye position during passive visual fixation and intrinsic brain activity. As a control experiment, we recorded fMRI brain activity related to cued voluntary vertical and horizontal changes in eye position in a block-related task-evoked fMRI experiment. Our results for the voluntarily performed changes in eye position elicited brain activity in the bilateral occipitotemporal cortex, supplementary motor cortex and frontal eye fields. In contrast, we show that slow fluctuations in eye position during passive visual fixation are linked to intrinsic brain activity, foremost in midline cortical brain regions located in the posteromedial parietal cortex and the medial prefrontal cortex, brain regions that act as core cortical hubs in the brain's default mode network. Our results suggest that subconscious and sustained changes in behavior are tied to intrinsic brain activity on a moment-by-moment basis. © 2014 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  6. Structure-Activity Relationships of the Sustained Effects of Adenosine A2A Receptor Agonists Driven by Slow Dissociation Kinetics

    PubMed Central

    Hothersall, J. Daniel; Guo, Dong; Sarda, Sunil; Sheppard, Robert J.; Chen, Hongming; Keur, Wesley; Waring, Michael J.; IJzerman, Adriaan P.; Hill, Stephen J.; Dale, Ian L.

    2017-01-01

    The duration of action of adenosine A2A receptor (A2A) agonists is critical for their clinical efficacy, and we sought to better understand how this can be optimized. The in vitro temporal response profiles of a panel of A2A agonists were studied using cAMP assays in recombinantly (CHO) and endogenously (SH-SY5Y) expressing cells. Some agonists (e.g., 3cd; UK-432,097) but not others (e.g., 3ac; CGS-21680) demonstrated sustained wash-resistant agonism, where residual receptor activation continued after washout. The ability of an antagonist to reverse pre-established agonist responses was used as a surrogate read-out for agonist dissociation kinetics, and together with radioligand binding studies suggested a role for slow off-rate in driving sustained effects. One compound, 3ch, showed particularly marked sustained effects, with a reversal t1/2 > 6 hours and close to maximal effects that remained for at least 5 hours after washing. Based on the structure-activity relationship of these compounds, we suggest that lipophilic N6 and bulky C2 substituents can promote stable and long-lived binding events leading to sustained agonist responses, although a high compound logD is not necessary. This provides new insight into the binding interactions of these ligands and we anticipate that this information could facilitate the rational design of novel long-acting A2A agonists with improved clinical efficacy. PMID:27803241

  7. Synergistic activity of rifampicin and ethambutol against slow-growing nontuberculous mycobacteria is currently of questionable clinical significance.

    PubMed

    van Ingen, Jakko; Hoefsloot, Wouter; Mouton, Johan W; Boeree, Martin J; van Soolingen, Dick

    2013-07-01

    A key issue in the treatment of disease caused by slow-growing nontuberculous mycobacteria is the limited association between in vitro minimum inhibitory concentrations (MICs) of rifampicin and ethambutol alone and the in vivo outcome of treatment with these drugs. Combined susceptibility testing to rifampicin and ethambutol could provide a more realistic view of the efficacy of these drugs. In this study, Mycobacterium avium (n = 5), Mycobacterium chimaera (n = 6), Mycobacterium intracellulare (n = 4), Mycobacterium xenopi (n = 4), Mycobacterium malmoense (n = 3) and Mycobacterium simiae (n = 2) clinical isolates were selected and the MICs of rifampicin and ethambutol alone and in combination were measured using the Middlebrook 7H10 agar dilution method. Synergy was defined as a fractional inhibitory concentration index ≤ 0.5. Rifampicin and ethambutol showed synergistic activity against the majority of M. avium (4/5), M. chimaera (5/6) and M. intracellulare (3/4) isolates and 1 of 2 eligible M. malmoense isolates. No synergistic activity was measured against M. xenopi and M. simiae. Synergy was neither universal for all species nor for all isolates of one species; it thus needs to be tested for rather than assumed. Even if this synergy exists in vivo, it is questionable whether the MICs to the combined drugs can be overcome by the drug exposure attained by current regimens at the recommended dosages. New dosing strategies for rifampicin and ethambutol should be studied to increase the exposure to these drugs and thus maximise their impact.

  8. Planning for closure and deactivation of the EBR-II complex

    SciTech Connect

    Michelbacher, J.A.; Henslee, S.P.; Poland, H.F.; Wells, P.B.

    1997-07-01

    In January 1994, DOE terminated the Integral Fast Reactor (IFR) Program. Argonne National Laboratory-West (ANL-W) prepared a detailed plan to put Experimental Breeder Reactor-II (EBR-II) in a safe condition, including removal of irradiated fueled subassemblies from the plant, transfer of subassemblies, and removal and stabilization of primary and secondary sodium liquid heat transfer metal. The goal of deactivation is to stabilize the EBR-II complex until decontamination and decommissioning (D&D) is implemented, thereby minimizing maintenance and surveillance. Deactivation of a sodium cooled reactor presents unique concerns. Residual sodium in the primary and secondary systems must be either reacted or inerted to preclude concerns with explosive sodium-air reactions. Also, residual sodium on components will effectively solder these items in place, making removal unfeasible. Several special cases reside in the primary system, including primary cold traps, a cesium trap, a cover gas condenser, and systems containing sodium-potassium alloy. The sodium or sodium-potassium alloy in these components must be reacted in place or the components removed. The Sodium Components Maintenance Shop at ANL-W provides the capability for washing primary components, removing residual quantities of sodium while providing some decontamination capacity. Considerations need to be given to component removal necessary for providing access to primary tank internals for D&D activities, removal of hazardous materials, and removal of stored energy sources. ANL-W`s plan for the deactivation of EBR-II addresses these issues, providing for an industrially and radiologically safe complex, requiring minimal surveillance during the interim period between deactivation and D&D. Throughout the deactivation and closure of the EBR-II complex, federal environmental concerns will be addressed, including obtaining the proper permits for facility condition and waste processing and disposal. 2 figs.

  9. Implantable cardioverter defibrillator knowledge and end-of-life device deactivation: A cross-sectional survey.

    PubMed

    McEvedy, Samantha M; Cameron, Jan; Lugg, Eugene; Miller, Jennifer; Haedtke, Chris; Hammash, Muna; Biddle, Martha J; Lee, Kyoung Suk; Mariani, Justin A; Ski, Chantal F; Thompson, David R; Chung, Misook Lee; Moser, Debra K

    2017-06-01

    End-of-life implantable cardioverter defibrillator deactivation discussions should commence before device implantation and be ongoing, yet many implantable cardioverter defibrillators remain active in patients' last days. To examine associations among implantable cardioverter defibrillator knowledge, patient characteristics and attitudes to implantable cardioverter defibrillator deactivation. Cross-sectional survey using the Experiences, Attitudes and Knowledge of End-of-Life Issues in Implantable Cardioverter Defibrillator Patients Questionnaire. Participants were classified as insufficient or sufficient implantable cardioverter defibrillator knowledge and the two groups were compared. Implantable cardioverter defibrillator recipients ( n = 270, mean age 61 ± 14 years; 73% male) were recruited from cardiology and implantable cardioverter defibrillator clinics attached to two tertiary hospitals in Melbourne, Australia, and two in Kentucky, the United States. Participants with insufficient implantable cardioverter defibrillator knowledge ( n = 77, 29%) were significantly older (mean age 66 vs 60 years, p = 0.001), less likely to be Caucasian (77% vs 87%, p  = 0.047), less likely to have received implantable cardioverter defibrillator shocks (26% vs 40%, p = 0.031), and more likely to have indications of mild cognitive impairment (Montreal Cognitive Assessment score <24: 44% vs 16%, p < 0.001). Insufficient implantable cardioverter defibrillator knowledge was associated with attitudes suggesting unwillingness to discuss implantable cardioverter defibrillator deactivation, even during the last days towards end of life ( p < 0.05). Implantable cardioverter defibrillator recipients, especially those who are older or have mild cognitive impairment, often have limited knowledge about implantable cardioverter defibrillator deactivation. This study identified several potential teachable moments throughout the patients' treatment trajectory

  10. Deactivation of the EBR-II complex

    SciTech Connect

    Michelbacher, J A; Earle, O K; Henslee, S P; Wells, P B; Zahn, T P

    1996-01-01

    In January of 1994, the Department of Energy mandated the termination of the Integral Fast Reactor (IFR) Program, effective October 1, 1994. To comply with this decision, Argonne National Laboratory-West (ANL-W) prepared a plan providing detailed requirements to place the Experimental Breeder Reactor-II (EBR-II) in a radiologically and industrially safe condition, including removal of all irradiated fuel assemblies from the reactor plant, and removal and stabilization of the primary and secondary sodium, a liquid metal used to transfer heat within the reactor plant. The ultimate goal of the deactivation process is to place the EBR-II complex in a stable condition until a decontamination and decommissioning (D and D) plan can be prepared, thereby minimizing requirements for maintenance and surveillance and maximizing the amount of time for radioactive decay. The final closure state will be achieved in full compliance with federal, state and local environmental, safety, and health regulations and requirements. The decision to delay the development of a detailed D and D plan has necessitated this current action.

  11. Effect of age on the sleep EEG: slow-wave activity and spindle frequency activity in young and middle-aged men.

    PubMed

    Landolt, H P; Dijk, D J; Achermann, P; Borbély, A A

    1996-11-04

    The effect of age on sleep and the sleep EEG was investigated in middle-aged men (mean age: 62.0 years) and in young men (mean age: 22.4 years). Even though the older men reported a higher number of nocturnal awakenings, subjective sleep quality did not differ. Total sleep time, sleep efficiency, and slow wave sleep were lower in the middle-aged, while stage 1 and wakefulness after sleep onset were higher. The differences in wakefulness within nonREM-REM sleep cycles was most pronounced in the third and fourth cycle. In the older men, EEG power density in nonREM sleep was reduced in frequencies below 14.0 Hz, whereas in REM sleep age-related reductions were limited to he delta-theta (0.25-7.0 Hz) and low alpha (8.25-10.0 Hz) band. Slow-wave activity (SWA, power density in the 0.75-4.5 Hz range) decreased in the course of sleep in both age groups. The between-group difference in SWA diminished in the course of sleep, whereas the difference in activity in the frequency range of sleep spindles (12.25-14.0 Hz) increased. It is concluded that frequency and state specific changes occur as a function of age, and that sleep dependent decline in SWA and increase in sleep spindle activity are attenuated with age.

  12. Hydrogen peroxide modulates Ca2+-activation of single permeabilized fibres from fast- and slow-twitch skeletal muscles of rats.

    PubMed

    Plant, D R; Lynch, G S; Williams, D A

    2000-01-01

    We examined the effects of redox modulation on single membrane-permeabilized fibre segments from the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of adult rats to determine whether the contractile apparatus was the redox target responsible for the increased contractility of muscles exposed to low concentrations of H2O2. The effects of H2O2 on maximum Ca2+-activated force were dose-dependent with 30 min exposure to 5 mM H2O2 causing a progressive decrease by 22+/-3 and 13+/-2% in soleus and EDL permeabilized muscle fibres, respectively. Lower concentrations of exogenous H2O2 (100 microM and 1 mM) had no effect on maximum Ca2+-activated force. Subsequent exposure to the reductant dithiothreitol (DTT, 10 mM, 10 min) fully reversed the H2O2-induced depression of force in EDL, but not in soleus muscle fibres. Incubation with DTT alone for 10 min did not alter Ca2+-activated force in either soleus or EDL muscle fibres. The sensitivity of the contractile filaments to Ca2+ (pCa50) was not altered by exposure to any concentration of exogenous H2O2. However, all concentrations of H2O2 diminished the Hill coefficient in permeabilized fibres from the EDL muscle, indicating that the cooperativity of Ca2+ binding to troponin is altered. H2O2 (5 mM) did not affect rigor force, which indicates that the number of crossbridges participating in contraction was not reduced. In conclusion, H2O2 may reduce the maximum Ca2+ activated force production in skinned muscle fibres by decreasing the force per crossbridge.

  13. Deactivation and unfolding are uncoupled in a bacterial lipase exposed to heat, low pH and organic solvents.

    PubMed

    Invernizzi, Gaetano; Casiraghi, Laura; Grandori, Rita; Lotti, Marina

    2009-04-20

    The lipase from Burkholderia glumae (BGL) was incubated at variable temperature, pH and concentration of organic solvents, and the decrease of enzymatic activity was compared to changes in the molecular structure as monitored by ESI-mass spectrometry. We observed that deactivation is not strictly related to structural instability in the assay conditions, in fact (i) thermal deactivation preceded denaturation; (ii) acid-induced deactivation arose at higher pH than partial or global protein unfolding; and (iii) activity in most organic solvents decreased at solvent concentrations where conformation was fully retained. In particular, no denaturation at all could be elicited by dimethyl formamide (DMF), isopropanol, and dimethyl sulfoxide (DMSO) up to 80%, in spite of a reduction of enzyme activity to 60-75%.

  14. Electrical Slow Waves in the Mouse Oviduct Are Dependent upon a Calcium Activated Chloride Conductance Encoded by Tmem16a1

    PubMed Central

    Dixon, Rose Ellen; Hennig, Grant W.; Baker, Salah A.; Britton, Fiona C.; Harfe, Brian D.; Rock, Jason R.; Sanders, Kenton M.; Ward, Sean M.

    2011-01-01

    ABSTRACT Myosalpinx contractions are critical for oocyte transport along the oviduct. A specialized population of pacemaker cells—oviduct interstitial cells of Cajal—generate slow waves, the electrical events underlying myosalpinx contractions. The ionic basis of oviduct pacemaker activity is unknown. We examined the role of a new class of Ca2+-activated Cl− channels (CaCCs)—anoctamin 1, encoded by Tmem16a—in oviduct slow wave generation. RT-PCR revealed the transcriptional expression of Tmem16a-encoded CaCCs in the myosalpinx. Intracellular microelectrode recordings were performed in the presence of two pharmacologically distinct Cl− channel antagonists, anthracene-9-carboxylic acid and niflumic acid. Both of these inhibitors caused membrane hyperpolarization, reduced the duration of slow waves, and ultimately inhibited pacemaker activity. Niflumic acid also inhibited propagating calcium waves within the myosalpinx. Slow waves were present at birth in wild-type and heterozygous oviducts but failed to develop by birth in mice homozygous for a null allele of Tmem16a (Tmem16atm1Bdh/tm1Bdh). These data suggest that Tmem16a-encoded CaCCs contribute to membrane potential and are responsible for the upstroke and plateau phases of oviduct slow waves. PMID:21976594

  15. Voltage-clamp analysis of the potentiation of the slow Ca2+-activated K+ current in hippocampal pyramidal neurons.

    PubMed

    Borde, M; Bonansco, C; Fernández de Sevilla, D; Le Ray, D; Buño, W

    2000-01-01

    Exploring the principles that govern activity-dependent changes in excitability is an essential step to understand the function of the nervous system, because they act as a general postsynaptic control mechanism that modulates the flow of synaptic signals. We show an activity-dependent potentiation of the slow Ca2+-activated K+ current (sl(AHP)) which induces sustained decreases in the excitability in CA1 pyramidal neurons. We analyzed the sl(AHP) using the slice technique and voltage-clamp recordings with sharp or patch-electrodes. Using sharp electrodes-repeated activation with depolarizing pulses evoked a prolonged (8-min) potentiation of the amplitude (171%) and duration (208%) of the sl(AHP). Using patch electrodes, early after entering the whole-cell configuration (<20 min), responses were as those reported above. However, although the sl(AHP) remained unchanged, its potentiation was markedly reduced in later recordings, suggesting that the underlying mechanisms were rapidly eliminated by intracellular dialysis. Inhibition of L-type Ca2+ current by nifedipine (20 microM) markedly reduced the sl(AHP) (79%) and its potentiation (55%). Ryanodine (20 microM) that blocks the release of intracellular Ca2+ also reduced sl(AHP) (29%) and its potentiation (25%). The potentiation of the sl(AHP) induced a marked and prolonged (>50%; approximately equals 8 min) decrease in excitability. The results suggest that sl(AHP) is potentiated as a result of an increased intracellular Ca2+ concentration ([Ca2+]i) following activation of voltage-gated L-type Ca2+ channels, aided by the subsequent release of Ca2+ from intracellular stores. Another possibility is that repeated activation increases the Ca2+-binding capacity of the channels mediating the sl(AHP). This potentiation of the sl(AHP) could be relevant in hippocampal physiology, because the changes in excitability it causes may regulate the induction threshold of the long-term potentiation of synaptic efficacy. Moreover, the

  16. Design of waste deactivation systems for biopharmaceutical manufacturing facilities

    SciTech Connect

    Nghiem, N.P.

    1995-12-01

    Waste deactivation system is an essential part of any biopharmaceutical manufacturing facility. Regulations require that all genetically engineered bacteria or cells be killed before the waste can be discharged from the facility. This is typically accomplished by heat or chemicals. In a small facility, a batch heat kill system normally is used. In larger facilities, continuous systems are preferred. In both systems, the most critical parameters are capacity and cycle time. These parameters must be carefully determined when designing a heat kill system. Heat-deactivated wastes sometimes cause odor problems, especially in the case of a facility located near a residential area. These problems can be alleviated by using chemicals. Among these, ozone is the most promising one because it can be generated on-site when needed, is easy to handle, and leaves no residual in the deactivated wastes. Design of heat kill and ozone deactivation systems will be discussed.

  17. Deactivation of Pacemakers and Implantable Cardioverter-Defibrillators

    PubMed Central

    Kramer, Daniel B.; Mitchell, Susan L.; Brock, Dan W.

    2013-01-01

    Cardiac implantable electrical devices (CIEDs), including pacemakers (PMs) and implantable cardioverter-defibrillators (ICDs), are the most effective treatment for life-threatening arrhythmias. Patients or their surrogates may request device deactivation to avoid prolongation of the dying process or in other settings, such as after device-related complications or with changes in their health care goals. Despite published guidelines outlining theoretical and practical aspects of this common clinical scenario, significant uncertainty remains for both patients and health care providers regarding the ethical and legal status of CIED deactivation. This review outlines the ethical and legal principles supporting CIED deactivation at patients’ request, centered upon patient autonomy and authority over their own medical treatment. The empirical literature describing stakeholder views and experiences surrounding CIED deactivation is described, along with lessons for future research and practice guidance surrounding the care of patients with CIEDs. PMID:23217433

  18. 1997 project of the year, PUREX deactivation project

    SciTech Connect

    Bailey, R.W.

    1998-02-13

    At the end of 1992, the PUREX and UO{sub 3} plants were deemed no longer necessary for the defense needs of the United States. Although no longer necessary, they were very costly to maintain in their post-operation state. The DOE embarked on a deactivation strategy for these plants to reduce the costs of providing continuous surveillance of the facilities and their hazards. Deactivation of the PUREX and UO{sub 3} plants was estimated to take 5 years and cost $222.5 million and result in an annual surveillance and maintenance cost of $2 million. Deactivation of the PUREX/UO{sub 3} plants officially began on October 1, 1993. The deactivation was 15 months ahead of the original schedule and $75 million under the original cost estimate. The annual cost of surveillance and maintenance of the plants was reduced to less than $1 million.

  19. Substance P and the neurokinin-1 receptor regulate electroencephalogram non-rapid eye movement sleep slow-wave activity locally.

    PubMed

    Zielinski, M R; Karpova, S A; Yang, X; Gerashchenko, D

    2015-01-22

    The neuropeptide substance P is an excitatory neurotransmitter produced by various cells including neurons and microglia that is involved in regulating inflammation and cerebral blood flow--functions that affect sleep and slow-wave activity (SWA). Substance P is the major ligand for the neurokinin-1 receptor (NK-1R), which is found throughout the brain including the cortex. The NK-1R is found on sleep-active cortical neurons expressing neuronal nitric oxide synthase whose activity is associated with SWA. We determined the effects of local cortical administration of a NK-1R agonist (substance P-fragment 1, 7) and a NK-1R antagonist (CP96345) on sleep and SWA in mice. The NK-1R agonist significantly enhanced SWA for several hours when applied locally to the cortex of the ipsilateral hemisphere as the electroencephalogram (EEG) electrode but not after application to the contralateral hemisphere when compared to saline vehicle control injections. In addition, a significant compensatory reduction in SWA was found after the NK-1R agonist-induced enhancements in SWA. Conversely, injections of the NK-1R antagonist into the cortex of the ipsilateral hemisphere of the EEG electrode attenuated SWA compared to vehicle injections but this effect was not found after injections of the NK-1R antagonist into contralateral hemisphere as the EEG electrode. Non-rapid eye movement sleep and rapid eye movement sleep duration responses after NK-1R agonist and antagonist injections were not significantly different from the responses to the vehicle. Our findings indicate that the substance P and the NK-1R are involved in regulating SWA locally.

  20. Enhanced slow-wave EEG activity and thermoregulatory impairment following the inhibition of the lateral hypothalamus in the rat.

    PubMed

    Cerri, Matteo; Del Vecchio, Flavia; Mastrotto, Marco; Luppi, Marco; Martelli, Davide; Perez, Emanuele; Tupone, Domenico; Zamboni, Giovanni; Amici, Roberto

    2014-01-01

    Neurons within the lateral hypothalamus (LH) are thought to be able to evoke behavioural responses that are coordinated with an adequate level of autonomic activity. Recently, the acute pharmacological inhibition of LH has been shown to depress wakefulness and promote NREM sleep, while suppressing REM sleep. These effects have been suggested to be the consequence of the inhibition of specific neuronal populations within the LH, i.e. the orexin and the MCH neurons, respectively. However, the interpretation of these results is limited by the lack of quantitative analysis of the electroencephalographic (EEG) activity that is critical for the assessment of NREM sleep quality and the presence of aborted NREM-to-REM sleep transitions. Furthermore, the lack of evaluation of the autonomic and thermoregulatory effects of the treatment does not exclude the possibility that the wake-sleep changes are merely the consequence of the autonomic, in particular thermoregulatory, changes that may follow the inhibition of LH neurons. In the present study, the EEG and autonomic/thermoregulatory effects of a prolonged LH inhibition provoked by the repeated local delivery of the GABAA agonist muscimol were studied in rats kept at thermoneutral (24°C) and at a low (10°C) ambient temperature (Ta), a condition which is known to depress sleep occurrence. Here we show that: 1) at both Tas, LH inhibition promoted a peculiar and sustained bout of NREM sleep characterized by an enhancement of slow-wave activity with no NREM-to-REM sleep transitions; 2) LH inhibition caused a marked transitory decrease in brain temperature at Ta 10°C, but not at Ta 24°C, suggesting that sleep changes induced by LH inhibition at thermoneutrality are not caused by a thermoregulatory impairment. These changes are far different from those observed after the short-term selective inhibition of either orexin or MCH neurons, suggesting that other LH neurons are involved in sleep-wake modulation.

  1. Enhanced Slow-Wave EEG Activity and Thermoregulatory Impairment following the Inhibition of the Lateral Hypothalamus in the Rat

    PubMed Central

    Cerri, Matteo; Vecchio, Flavia Del; Mastrotto, Marco; Luppi, Marco; Martelli, Davide; Perez, Emanuele; Tupone, Domenico; Zamboni, Giovanni; Amici, Roberto

    2014-01-01

    Neurons within the lateral hypothalamus (LH) are thought to be able to evoke behavioural responses that are coordinated with an adequate level of autonomic activity. Recently, the acute pharmacological inhibition of LH has been shown to depress wakefulness and promote NREM sleep, while suppressing REM sleep. These effects have been suggested to be the consequence of the inhibition of specific neuronal populations within the LH, i.e. the orexin and the MCH neurons, respectively. However, the interpretation of these results is limited by the lack of quantitative analysis of the electroencephalographic (EEG) activity that is critical for the assessment of NREM sleep quality and the presence of aborted NREM-to-REM sleep transitions. Furthermore, the lack of evaluation of the autonomic and thermoregulatory effects of the treatment does not exclude the possibility that the wake-sleep changes are merely the consequence of the autonomic, in particular thermoregulatory, changes that may follow the inhibition of LH neurons. In the present study, the EEG and autonomic/thermoregulatory effects of a prolonged LH inhibition provoked by the repeated local delivery of the GABAA agonist muscimol were studied in rats kept at thermoneutral (24°C) and at a low (10°C) ambient temperature (Ta), a condition which is known to depress sleep occurrence. Here we show that: 1) at both Tas, LH inhibition promoted a peculiar and sustained bout of NREM sleep characterized by an enhancement of slow-wave activity with no NREM-to-REM sleep transitions; 2) LH inhibition caused a marked transitory decrease in brain temperature at Ta 10°C, but not at Ta 24°C, suggesting that sleep changes induced by LH inhibition at thermoneutrality are not caused by a thermoregulatory impairment. These changes are far different from those observed after the short-term selective inhibition of either orexin or MCH neurons, suggesting that other LH neurons are involved in sleep-wake modulation. PMID:25398141

  2. Isomerization of 1-butene on silica-alumina: Kinetic modeling and catalyst deactivation

    SciTech Connect

    Garcia-Ochoa, F.; Santos, A. . Dept. de Ingenieria Quimica)

    1995-02-01

    In the study of 1-butene isomerization on a silica-alumina catalyst 448--523 K, cis-2-butene and trans-2-butene are detected. Based on BSTR experimental data and zero-time prediction kinetic models using the Langmuir-Hinshelwood mechanism are assumed to develop kinetic equations for which a triangular reaction scheme is used. In four different mechanisms, one and two active sites take part in the surface reaction as the controlling step and then the deactivation rate determined considering two types of experimental data from BSTR and by measuring weight changes of a catalyst particle from coke deposition in an electrobalance. A coke precursor is assumed formed by reaction of adsorbed molecules (of any butene isomer) and gas-phase molecules. Activity and coke-content-time data allow one to choose a model whose activation energies of the deactivation kinetic parameter are closer in value. Coke is assumed deposited in a monolayer. The model chosen shows a triangular scheme, kinetic equations of the reaction for fresh catalyst with two active sites in the surface reaction, and the deactivation rate according to a coke formation mechanism in which a precursor is formed by reaction of 3 adsorbed molecules and 1 molecule in the gas phase. It accurately fits both BSTR conversion-time data and electrobalance coke-content data. The coke formation mechanism establishes relationships of activity vs. coke content and catalyst acidity which are supported by experimental results.

  3. Direct Interaction between the Voltage Sensors Produces Cooperative Sustained Deactivation in Voltage-gated H+ Channel Dimers*

    PubMed Central

    Okuda, Hiroko; Yonezawa, Yasushige; Takano, Yu; Okamura, Yasushi; Fujiwara, Yuichiro

    2016-01-01

    The voltage-gated H+ channel (Hv) is a voltage sensor domain-like protein consisting of four transmembrane segments (S1–S4). The native Hv structure is a homodimer, with the two channel subunits functioning cooperatively. Here we show that the two voltage sensor S4 helices within the dimer directly cooperate via a π-stacking interaction between Trp residues at the middle of each segment. Scanning mutagenesis showed that Trp situated around the original position provides the slow gating kinetics characteristic of the dimer's cooperativity. Analyses of the Trp mutation on the dimeric and monomeric channel backgrounds and analyses with tandem channel constructs suggested that the two Trp residues within the dimer are functionally coupled during Hv deactivation but are less so during activation. Molecular dynamics simulation also showed direct π-stacking of the two Trp residues. These results provide new insight into the cooperative function of voltage-gated channels, where adjacent voltage sensor helices make direct physical contact and work as a single unit according to the gating process. PMID:26755722

  4. Repetitive transcranial magnetic stimulation induced slow wave activity modification: A possible role in disorder of consciousness differential diagnosis?

    PubMed

    Pisani, Laura Rosa; Naro, Antonino; Leo, Antonino; Aricò, Irene; Pisani, Francesco; Silvestri, Rosalia; Bramanti, Placido; Calabrò, Rocco Salvatore

    2015-12-15

    Slow wave activity (SWA) generation depends on cortico-thalamo-cortical loops that are disrupted in patients with chronic Disorders of Consciousness (DOC), including the Unresponsive Wakefulness Syndrome (UWS) and the Minimally Conscious State (MCS). We hypothesized that the modulation of SWA by means of a repetitive transcranial magnetic stimulation (rTMS) could reveal residual patterns of connectivity, thus supporting the DOC clinical differential diagnosis. We enrolled 10 DOC individuals who underwent a 24hh polysomnography followed by a real or sham 5Hz-rTMS over left primary motor area, and a second polysomnographic recording. A preserved sleep-wake cycle, a standard temporal progression of sleep stages, and a SWA perturbation were found in all of the MCS patients and in none of the UWS individuals, only following the real-rTMS. In conclusion, our combined approach may improve the differential diagnosis between MCS patients, who show a partial preservation of cortical plasticity, and UWS individuals, who lack such properties.

  5. Developmental trajectories of EEG sleep slow wave activity as a marker for motor skill development during adolescence: a pilot study.

    PubMed

    Lustenberger, Caroline; Mouthon, Anne-Laure; Tesler, Noemi; Kurth, Salome; Ringli, Maya; Buchmann, Andreas; Jenni, Oskar G; Huber, Reto

    2017-01-01

    Reliable markers for brain maturation are important to identify neural deviations that eventually predict the development of mental illnesses. Recent studies have proposed topographical EEG-derived slow wave activity (SWA) during NREM sleep as a mirror of cortical development. However, studies about the longitudinal stability as well as the relationship with behavioral skills are needed before SWA topography may be considered such a reliable marker. We examined six subjects longitudinally (over 5.1 years) using high-density EEG and a visuomotor learning task. All subjects showed a steady increase of SWA at a frontal electrode and a decrease in central electrodes. Despite these large changes in EEG power, SWA topography was relatively stable within each subject during development indicating individual trait-like characteristics. Moreover, the SWA changes in the central cluster were related to the development of specific visuomotor skills. Taken together with the previous work in this domain, our results suggest that EEG sleep SWA represents a marker for motor skill development and further supports the idea that SWA mirrors cortical development during childhood and adolescence. © 2016 Wiley Periodicals, Inc.

  6. Some kinetic aspects of the processes accompanied by catalyst deactivation

    SciTech Connect

    Kumbilieva, K.; Petrov, L.; Kiperman, S.L.

    1995-01-01

    Continuing our previous works, we performed a general analysis of the joint effect of the catalyst deactivation and intraparticle diffusion resistance leading to a retardation of the reactions. A significant effect of the mechanism of model reactions under study on the character of changes in the rate and selectivity of deactivation processes is demonstrated, with a number of examples proving the fruitfulness of such an approach. The problems arising and the possibilities and prospects for further investigations are discussed.

  7. Reversible and rapid transfer-RNA deactivation as a mechanism of translational repression in stress.

    PubMed

    Czech, Andreas; Wende, Sandra; Mörl, Mario; Pan, Tao; Ignatova, Zoya

    2013-08-01

    Stress-induced changes of gene expression are crucial for survival of eukaryotic cells. Regulation at the level of translation provides the necessary plasticity for immediate changes of cellular activities and protein levels. In this study, we demonstrate that exposure to oxidative stress results in a quick repression of translation by deactivation of the aminoacyl-ends of all transfer-RNA (tRNA). An oxidative-stress activated nuclease, angiogenin, cleaves first within the conserved single-stranded 3'-CCA termini of all tRNAs, thereby blocking their use in translation. This CCA deactivation is reversible and quickly repairable by the CCA-adding enzyme [ATP(CTP):tRNA nucleotidyltransferase]. Through this mechanism the eukaryotic cell dynamically represses and reactivates translation at low metabolic costs.

  8. Reversible and Rapid Transfer-RNA Deactivation as a Mechanism of Translational Repression in Stress

    PubMed Central

    Czech, Andreas; Wende, Sandra; Mörl, Mario; Pan, Tao; Ignatova, Zoya

    2013-01-01

    Stress-induced changes of gene expression are crucial for survival of eukaryotic cells. Regulation at the level of translation provides the necessary plasticity for immediate changes of cellular activities and protein levels. In this study, we demonstrate that exposure to oxidative stress results in a quick repression of translation by deactivation of the aminoacyl-ends of all transfer-RNA (tRNA). An oxidative-stress activated nuclease, angiogenin, cleaves first within the conserved single-stranded 3′-CCA termini of all tRNAs, thereby blocking their use in translation. This CCA deactivation is reversible and quickly repairable by the CCA-adding enzyme [ATP(CTP):tRNA nucleotidyltransferase]. Through this mechanism the eukaryotic cell dynamically represses and reactivates translation at low metabolic costs. PMID:24009533

  9. Expertise-related deactivation of the right temporoparietal junction during musical improvisation.

    PubMed

    Berkowitz, Aaron L; Ansari, Daniel

    2010-01-01

    Musical training has been associated with structural changes in the brain as well as functional differences in brain activity when musicians are compared to nonmusicians on both perceptual and motor tasks. Previous neuroimaging comparisons of musicians and nonmusicians in the motor domain have used tasks involving prelearned motor sequences or synchronization with an auditorily presented sequence during the experiment. Here we use functional magnetic resonance imaging (fMRI) to examine expertise-related differences in brain activity between musicians and nonmusicians during improvisation--the generation of novel musical-motor sequences--using a paradigm that we previously used in musicians alone. Despite behaviorally matched performance, the two groups showed significant differences in functional brain activity during improvisation. Specifically, musicians deactivated the right temporoparietal junction (rTPJ) during melodic improvisation, while nonmusicians showed no change in activity in this region. The rTPJ is thought to be part of a ventral attentional network for bottom-up stimulus-driven processing, and it has been postulated that deactivation of this region occurs in order to inhibit attentional shifts toward task-irrelevant stimuli during top-down, goal-driven behavior. We propose that the musicians' deactivation of the rTPJ during melodic improvisation may represent a training-induced shift toward inhibition of stimulus-driven attention, allowing for a more goal-directed performance state that aids in creative thought.

  10. Final deactivation report on the Radioactive Gas Processing Facility, Building 3033, and the Actinide Fabrication Facility, Building 3033A, at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1997-09-01

    The purpose of this report is to document the condition of Buildings 3033 and 3033A, after completion of deactivation activities as outlined by the Department of Energy Office of Nuclear Materials and Facility Stabilization Program (EM-60) guidance documentation. This report outlines the activities conducted to place the facility in a safe and environmentally sound condition for transfer to the Department of Energy Office of Environmental Restoration Program (EM-40). This report provides a history and profile of Buildings 3033 and 3033A prior to commencing deactivation activities and a profile of the building after completion of deactivation activities. Turnover items, such as the Post-Deactivation Surveillance and Maintenance Plan, remaining hazardous materials, radiological controls, Safeguards and Security, quality assurance, facility operations, and supporting documentation provided in the Office of Nuclear Materials and Facility Stabilization Program (EM-60) Turnover package are discussed. Buildings 3033 and 3033A will require access to facilitate required S and M activities to maintain the building safety envelope. Buildings 3033 and 3033A were stabilized during deactivation so that when transferred to the EM-40 program, only a minimal S and M effort would be required to maintain the building safety envelope. Other than the minimal S and M activities the building will be unoccupied and the exterior doors locked to prevent unauthorized access. The building will be entered only to perform the required S and M. All materials have been removed from the building, and all utility systems, piping, and alarms have been deactivated.

  11. Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles.

    PubMed

    Hwang, Sung Jin; Blair, Peter J A; Britton, Fiona C; O'Driscoll, Kate E; Hennig, Grant; Bayguinov, Yulia R; Rock, Jason R; Harfe, Brian D; Sanders, Kenton M; Ward, Sean M

    2009-10-15

    Interstitial cells of Cajal (ICC) generate pacemaker activity (slow waves) in gastrointestinal (GI) smooth muscles, but the mechanism(s) of pacemaker activity are controversial. Several conductances, such as Ca(2+)-activated Cl() channels (CaCC) and non-selective cation channels (NSCC) have been suggested to be involved in slow wave depolarization. We investigated the expression and function of a new class of CaCC, anoctamin 1 (ANO1), encoded by Tmem16a, which was discovered to be highly expressed in ICC in a microarray screen. GI muscles express splice variants of the Tmem16a transcript in addition to other paralogues of the Tmem16a family. ANO1 protein is expressed abundantly and specifically in ICC in all regions of the murine, non-human primate (Macaca fascicularis) and human GI tracts. CaCC blocking drugs, niflumic acid and 4,4-diisothiocyano-2,2-stillbene-disulfonic acid (DIDS) reduced the frequency and blocked slow waves in murine, primate, human small intestine and stomach in a concentration-dependent manner. Unitary potentials, small stochastic membrane depolarizations thought to underlie slow waves, were insensitive to CaCC blockers. Slow waves failed to develop by birth in mice homozygous for a null allele of Tmem16a (Tmem16a(tm1Bdh)(/tm1Bdh)) and did not develop subsequent to birth in organ culture, as in wildtype and heterozygous muscles. Loss of function of ANO1 did not inhibit the development of ICC networks that appeared structurally normal as indicated by Kit antibodies. These data demonstrate the fundamental role of ANO1 in the generation of slow waves in GI ICC.

  12. Brief and Rare Mental "Breaks" Keep You Focused: Deactivation and Reactivation of Task Goals Preempt Vigilance Decrements

    ERIC Educational Resources Information Center

    Ariga, Atsunori; Lleras, Alejandro

    2011-01-01

    We newly propose that the vigilance decrement occurs because the cognitive control system fails to maintain active the goal of the vigilance task over prolonged periods of time (goal habituation). Further, we hypothesized that momentarily deactivating this goal (via a switch in tasks) would prevent the activation level of the vigilance goal from…

  13. Soluble inhibitors/deactivators of cellulase enzymes from lignocellulosic biomass.

    PubMed

    Kim, Youngmi; Ximenes, Eduardo; Mosier, Nathan S; Ladisch, Michael R

    2011-04-07

    Liquid hot water, steam explosion, and dilute acid pretreatments of lignocellulose generate soluble inhibitors which hamper enzymatic hydrolysis as well as fermentation of sugars to ethanol. Toxic and inhibitory compounds will vary with pretreatment and include soluble sugars, furan derivatives (hydroxymethyl fulfural, furfural), organic acids (acetic, formic and, levulinic acid), and phenolic compounds. Their effect is seen when an increase in the concentration of pretreated biomass in a hydrolysis slurry results in decreased cellulose conversion, even though the ratio of enzyme to cellulose is kept constant. We used lignin-free cellulose, Solka Floc, combined with mixtures of soluble components released during pretreatment of wood, to prove that the decrease in the rate and extent of cellulose hydrolysis is due to a combination of enzyme inhibition and deactivation. The causative agents were extracted from wood pretreatment liquid using PEG surfactant, activated charcoal or ethyl acetate and then desorbed, recovered, and added back to a mixture of enzyme and cellulose. At enzyme loadings of either 1 or 25mg protein/g glucan, the most inhibitory components, later identified as phenolics, decreased the rate and extent of cellulose hydrolysis by half due to both inhibition and precipitation of the enzymes. Full enzyme activity occurred when the phenols were removed. Hence detoxification of pretreated woods through phenol removal is expected to reduce enzyme loadings, and therefore reduce enzyme costs, for a given level of cellulose conversion. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Study of the scapular muscle latency and deactivation time in people with and without shoulder impingement.

    PubMed

    Phadke, Vandana; Ludewig, Paula M

    2013-04-01

    Changes in muscle activities are commonly associated with shoulder impingement and theoretically caused by changes in motor program strategies. The purpose of this study was to assess for differences in latencies and deactivation times of scapular muscles between subjects with and without shoulder impingement. Twenty-five healthy subjects and 24 subjects with impingement symptoms were recruited. Glenohumeral kinematic data and myoelectric activities using surface electrodes from upper trapezius (UT), lower trapezius (LT), serratus anterior (SA) and anterior fibers of deltoid were collected as subjects raised and lowered their arm in response to a visual cue. Data were collected during unloaded, loaded and after repetitive arm raising motion conditions. The variables were analyzed using 2 or 3 way mixed model ANOVAs. Subjects with impingement demonstrated significantly earlier contraction of UT while raising in the unloaded condition and an earlier deactivation of SA across all conditions during lowering of the arm. All subjects exhibited an earlier activation and delayed deactivation of LT and SA in conditions with a weight held in hand. The subjects with impingement showed some significant differences to indicate possible differences in motor control strategies. Rehabilitation measures should consider appropriate training measures to improve movement patterns and muscle control.

  15. Slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with chronic heart failure: from modeling to clinical application.

    PubMed

    Harada, Daisuke; Asanoi, Hidetsugu; Takagawa, Junya; Ishise, Hisanari; Ueno, Hiroshi; Oda, Yoshitaka; Goso, Yukiko; Joho, Shuji; Inoue, Hiroshi

    2014-10-15

    Influences of slow and deep respiration on steady-state sympathetic nerve activity remain controversial in humans and could vary depending on disease conditions and basal sympathetic nerve activity. To elucidate the respiratory modulation of steady-state sympathetic nerve activity, we modeled the dynamic nature of the relationship between lung inflation and muscle sympathetic nerve activity (MSNA) in 11 heart failure patients with exaggerated sympathetic outflow at rest. An autoregressive exogenous input model was utilized to simulate entire responses of MSNA to variable respiratory patterns. In another 18 patients, we determined the influence of increasing tidal volume and slowing respiratory frequency on MSNA; 10 patients underwent a 15-min device-guided slow respiration and the remaining 8 had no respiratory modification. The model predicted that a 1-liter, step increase of lung volume decreased MSNA dynamically; its nadir (-33 ± 22%) occurred at 2.4 s; and steady-state decrease (-15 ± 5%), at 6 s. Actually, in patients with the device-guided slow and deep respiration, respiratory frequency effectively fell from 16.4 ± 3.9 to 6.7 ± 2.8/min (P < 0.0001) with a concomitant increase in tidal volume from 499 ± 206 to 1,177 ± 497 ml (P < 0.001). Consequently, steady-state MSNA was decreased by 31% (P < 0.005). In patients without respiratory modulation, there were no significant changes in respiratory frequency, tidal volume, and steady-state MSNA. Thus slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with high levels of resting sympathetic tone as in heart failure.

  16. Kinetics of deactivation of catalysts for vinyl acetate synthesis in the fluidized-bed reactor: The optimal loading and distribution of zinc acetate in the porous structure of a support

    SciTech Connect

    Romanchuk, S.V.; Makhlin, V.A.

    1995-03-01

    The deactivation of a catalyst (zinc acetate on activated carbon) including a change of the phase state of the active component is considered. The mechanism and relevant kinetic model of the deactivation are presented. A degree of thermal decomposition of zinc acetate controls the deactivation rate, which depends on the loading and distribution of zinc acetate in the porous structure of a support. A modeling of the process in an industrial reactor is performed with regard to the deactivation, attrition, and loss of a catalyst. Each carbon support has an optimal loading of zinc acetate (equal to the critical value), which provides both a high activity and stability of catalyst operation. The reasons behind the fast deactivation of the commercial catalyst are revealed. The possibility is demonstrated of extending the life time of a catalyst on available carbon supports by a factor of {approximately}2.5, due to the optimal loading and distribution of the active component in the porous support structure.

  17. Redistribution of slow wave activity of sleep during pharmacological treatment of depression with paroxetine but not with nefazodone.

    PubMed

    Argyropoulos, Spilios V; Hicks, Jane A; Nash, John R; Bell, Caroline J; Rich, Anne S; Nutt, David J; Wilson, Sue

    2009-09-01

    It has been suggested that increase in delta sleep ratio (DSR), a marker for the relative distribution of slow wave activity (SWA) over night time, is associated with clinical response to antidepressant treatment. We examined this index and its relationship to rapid eye movement (REM) suppression before and during long-term treatment with nefazodone, which does not suppress REM sleep, and paroxetine which does. The effect of serotonin (5-HT(2A)) receptor blockade on the evolution of SWA during treatment was also investigated. In a double-blind, randomised, parallel group, 8-week study in 29 depressed patients, sleep electroencephalograms were performed at home at baseline, on night 3 and 10, and at 8 weeks of treatment with either paroxetine or nefazodone. SWA was automatically analysed and a modified DSR (mDSR) was derived, being the ratio of amount of SWA in the first 90 min of sleep to that in the second plus third 90-min periods. At baseline, the pattern of SWA over night time was similar to other reports of depressed patients. mDSR improved over the course of treatment; there was no difference between remitters and non-remitters but there was a significant drug effect and a significant drug x time effect with paroxetine patients having a much higher mDSR after treatment, regardless of clinical status. SWA and REM during antidepressant treatment appear to be interdependent and neither of them alone is likely to predict response to treatment. Higher mDSR did not predict therapeutic response. 5-HT(2A) blockade by nefazodone does not increase SWA above normal levels.

  18. Indigenous bacteria with antagonistic and plant-growth-promoting activities improve slow-filtration efficiency in soilless cultivation.

    PubMed

    Déniel, F; Rey, P; Chérif, M; Guillou, A; Tirilly, Y

    2004-07-01

    In tomato soilless culture, slow filtration allows one to control the development of diseases caused by pathogenic microorganisms. During the disinfecting process, microbial elimination is ensured by mechanical and biological factors. In this study, system efficacy was enhanced further to a biological activation of filter by inoculating the pozzolana grains contained in the filtering unit with 5 selected bacteria. Three strains identified as Pseudomonas putida and 2 as Bacillus cereus came from a filter whose high efficiency to eliminate pathogens has been proven over years. These 5 bacteria displayed either a plant growth promoting activity (P. putida strains) or antagonistic properties (B. cereus strains). Over the first months following their introduction in the filter, the bacterial colonisation of pozzolana grains was particularly high as compared to the one observed in the control filter. Conversely to Bacillus spp. populations, Pseudomonas spp. ones remained abundant throughout the whole cultural season. The biological activation of filter unit very significantly enhanced fungal elimination with respect to the one displayed by the control filter. Indeed, the 6-month period needed by the control filter to reach its best efficacy against Fusarium oxysporum was shortened for the bacteria-amended filter; in addition, a high efficacy filtration was got as soon as the first month. Fast colonization of pozzolana grains by selected bacteria and their subsequent interaction with F. oxysporum are likely responsible for filter efficiency. Our results suggest that Pseudomonas spp. act by competition for nutrients, and Bacillus spp. by antibiosis and (or) direct parasitism. Elimination of other fungal pathogens, i.e., Pythium spp., seems to differ from that of Fusarium since both filters demonstrated a high efficacy at the experiment start. Pythium spp. elimination appears to mainly rely on physical factors. It is worth noting that a certain percentage of the 5 pozzolana

  19. Kinetics of camptothecin deactivation determined by time evolution of fluorescence and absorption spectra

    NASA Astrophysics Data System (ADS)

    Ziomkowska, Blanka; Kruszewski, Stefan; Siuda, Ryszard; Cyrankiewicz, Michal

    2004-07-01

    Fluorescence and absorption spectra of camptothecin -- anticancer alkaloid, are analyzed in this paper. Camptothecin exists in two forms: lactone and carboxylate. Only lactone form is biologically active. In physiological fluids at pH 7.4 lactone form hydrolyses and converts into carboxylate form. There are some differences in shapes between fluorescence and absorption spectra of lactone and carboxylate form. In the deactivation process fluorescence and absorption spectra evaluate. Thanks to the factor analysis of series of spectra recorded during the process of hydrolysis one can follow the concentration of both forms in the solution. Described method could be useful in determining of kinetics of deactivation process and competitive with the HPLC method.

  20. Deactivation of Ceria Supported Palladium through C–C Scission during Transfer Hydrogenation of Phenol with Alcohols

    SciTech Connect

    Nelson, Nicholas C.; Manzano, J. Sebastián; Slowing, Igor I.

    2016-11-21

    The stability of palladium supported on ceria (Pd/CeO2) was studied during liquid flow transfer hydrogenation using primary and secondary alcohols as hydrogen donors. For primary alcohols, the ceria support was reduced to cerium hydroxy carbonate within 14 h and was a contributing factor toward catalyst deactivation. For secondary alcohols, cerium hydroxy carbonate was not observed during the same time period and the catalyst was stable upon prolonged reaction. Regeneration through oxidation/reduction does not restore initial activity likely due to irreversible catalyst restructuring. Lastly, a deactivation mechanism involving C–C scission of acyl and carboxylate intermediates is proposed.

  1. Deactivation of Ceria Supported Palladium through C–C Scission during Transfer Hydrogenation of Phenol with Alcohols

    DOE PAGES

    Nelson, Nicholas C.; Manzano, J. Sebastián; Slowing, Igor I.

    2016-11-21

    The stability of palladium supported on ceria (Pd/CeO2) was studied during liquid flow transfer hydrogenation using primary and secondary alcohols as hydrogen donors. For primary alcohols, the ceria support was reduced to cerium hydroxy carbonate within 14 h and was a contributing factor toward catalyst deactivation. For secondary alcohols, cerium hydroxy carbonate was not observed during the same time period and the catalyst was stable upon prolonged reaction. Regeneration through oxidation/reduction does not restore initial activity likely due to irreversible catalyst restructuring. Lastly, a deactivation mechanism involving C–C scission of acyl and carboxylate intermediates is proposed.

  2. Final deactivation report on the radioisotope production Lab-H, Building 3118, at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1997-08-01

    This report outlines the activities conducted to place the facility in a safe and environmentally sound condition for transfer to the DOE Office of Environmental Restoration Program (EM-40). This report provides a history and profile of Bldg. 3118 prior to and after deactivation. Turnover items (e.g. Surveillance & Maintenance Plant, remaining materials, etc.) are discussed. Building 3118 was stabilized during deactivation so that when transferred to the EM-40 program, only minimal S&M is required (other than that, the building will be unoccupied and the exterior doors locked).

  3. Psychomotor Slowing in Schizophrenia

    PubMed Central

    Morrens, Manuel; Hulstijn, Wouter; Sabbe, Bernard

    2007-01-01

    Psychomotor slowing (PS) is a cluster of symptoms that was already recognized in schizophrenia by its earliest investigators. Nevertheless, few studies have been dedicated to the clarification of the nature and the role of the phenomenon in this illness. Moreover, slowed psychomotor functioning is often not clearly delineated from reduced processing speed. The current, first review of all existing literature on the subject discusses the key findings. Firstly, PS is a clinically observable feature that is most frequently established by neuropsychological measures assessing speed of fine movements such as writing or tasks that require rapid fingertip manipulations or the maintenance of maximal speed over brief periods of time in manual activities. Moreover, the slowed performance on the various psychomotor measures has been demonstrated independent of medication and has also been found to be associated with negative symptoms and, to a lesser extent, with positive and depressive symptoms. Importantly, performance on the psychomotor tasks proved related to the patients' social, clinical, and functional outcomes. Several imaging studies showed slowed performance to coincide with dopaminergic striatal activity. Finally, conventional neuroleptics do not improve the patients' PS symptoms, in contrast to the atypical agents that do seem to produce modestly improving effects. PMID:17093141

  4. A graded approach to safety analysis for Rover Processing Facility deactivation

    SciTech Connect

    Henrikson, D.J.

    1997-08-01

    The Rover Fuels Processing Facility operated in the early 1980`s, recovering uranium from graphite fuels. In 1996 clean-out began of uranium bearing material remaining in the Rover cells where combustion processes had occurred. Success of the Rover Deactivation Project depends on the safe, timely, and cost-effective repackaging and removal of the uranium bearing material. Due to a number of issues which could not be resolved prior to clean-out, and consideration of cost and schedule objectives, a graded approach was taken to projected design and criticality safety analysis. The safety authorization basis was upgraded primarily by a specific Deactivation addendum, instead of being completely rewritten to current format and content standards. In place of having all design activities completed prior to the start of the Deactivation, the project design and accompanying safety documentation evolved as the project progressed. The Unreviewed Safety Question determination process was used to ensure that new project activities were within the safety envelope. This graded approach allowed operational flexibility while maintaining a critically safe work environment.

  5. Mathematics anxiety reduces default mode network deactivation in response to numerical tasks

    PubMed Central

    Pletzer, Belinda; Kronbichler, Martin; Nuerk, Hans-Christoph; Kerschbaum, Hubert H.

    2015-01-01

    Mathematics anxiety is negatively related to mathematics performance, thereby threatening the professional success. Preoccupation with the emotional content of the stimuli may consume working memory resources, which may be reflected in decreased deactivation of areas associated with the default mode network (DMN) activated during self-referential and emotional processing. The common problem is that math anxiety is usually associated with poor math performance, so that any group differences are difficult to interpret. Here we compared the BOLD-response of 18 participants with high (HMAs) and 18 participants with low mathematics anxiety (LMAs) matched for their mathematical performance to two numerical tasks (number comparison, number bisection). During both tasks, we found stronger deactivation within the DMN in LMAs compared to HMAs, while BOLD-response in task-related activation areas did not differ between HMAs and LMAs. The difference in DMN deactivation between the HMA and LMA group was more pronounced in stimuli with additional requirement on inhibitory functions, but did not differ between number magnitude processing and arithmetic fact retrieval. PMID:25954179

  6. Mathematics anxiety reduces default mode network deactivation in response to numerical tasks.

    PubMed

    Pletzer, Belinda; Kronbichler, Martin; Nuerk, Hans-Christoph; Kerschbaum, Hubert H

    2015-01-01

    Mathematics anxiety is negatively related to mathematics performance, thereby threatening the professional success. Preoccupation with the emotional content of the stimuli may consume working memory resources, which may be reflected in decreased deactivation of areas associated with the default mode network (DMN) activated during self-referential and emotional processing. The common problem is that math anxiety is usually associated with poor math performance, so that any group differences are difficult to interpret. Here we compared the BOLD-response of 18 participants with high (HMAs) and 18 participants with low mathematics anxiety (LMAs) matched for their mathematical performance to two numerical tasks (number comparison, number bisection). During both tasks, we found stronger deactivation within the DMN in LMAs compared to HMAs, while BOLD-response in task-related activation areas did not differ between HMAs and LMAs. The difference in DMN deactivation between the HMA and LMA group was more pronounced in stimuli with additional requirement on inhibitory functions, but did not differ between number magnitude processing and arithmetic fact retrieval.

  7. Treatment of a mobile intracardiac thrombus using ultra-slow low-dose tissue plasminogen activator in combination with heparin.

    PubMed

    Polen, C B; Mullins Busch, H N; Ratliff, P D

    2017-09-17

    Free-floating thrombi in the right heart occur in a subset of patients with pulmonary embolism with high rates of mortality if untreated. Treatment of choice is controversial and likely patient specific as studies have failed to consistently show a significant difference in mortality between options. We present a case of a 45-year-old female with a mobile right heart thrombus treated with ultra-slow, low-dose t-PA infusion in combination with heparin. Ultra-slow, low-dose infusion of t-PA may be an option for treatment of mobile intracardiac thrombi. © 2017 John Wiley & Sons Ltd.

  8. Inhibition of the ribonuclease H activity of HIV-1 reverse transcriptase by GSK5750 correlates with slow enzyme-inhibitor dissociation.

    PubMed

    Beilhartz, Greg L; Ngure, Marianne; Johns, Brian A; DeAnda, Felix; Gerondelis, Peter; Götte, Matthias

    2014-06-06

    Compounds that efficiently inhibit the ribonuclease (RNase) H activity of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have yet to be developed. Here, we demonstrate that GSK5750, a 1-hydroxy-pyridopyrimidinone analog, binds to the enzyme with an equilibrium dissociation constant (K(d)) of ~400 nM. Inhibition of HIV-1 RNase H is specific, as DNA synthesis is not affected. Moreover, GSK5750 does not inhibit the activity of Escherichia coli RNase H. Order-of-addition experiments show that GSK5750 binds to the free enzyme in an Mg(2+)-dependent fashion. However, as reported for other active site inhibitors, binding of GSK5750 to a preformed enzyme-substrate complex is severely compromised. The bound nucleic acid prevents access to the RNase H active site, which represents a possible biochemical hurdle in the development of potent RNase H inhibitors. Previous studies suggested that formation of a complex with the prototypic RNase H inhibitor β-thujaplicinol is slow, and, once formed, it dissociates rapidly. This unfavorable kinetic behavior can limit the potency of RNase H active site inhibitors. Although the association kinetics of GSK5750 remains slow, our data show that this compound forms a long lasting complex with HIV-1 RT. We conclude that slow dissociation of the inhibitor and HIV-1 RT improves RNase H active site inhibitors and may circumvent the obstacle posed by the inability of these compounds to bind to a preformed enzyme-substrate complex.

  9. Slow Pseudotachylites

    NASA Astrophysics Data System (ADS)

    Pec, M.; Stunitz, H.; Heilbronner, R.

    2011-12-01

    Tectonic pseudotachylites as solidified, friction induced melts are believed to be the only unequivocal evidence for paleo-earthquakes. Earthquakes occur when fast slip (1 - 3 m/s) propagates on a localized failure plane and are always related with stress drops. The mechanical work expended, together with the rock composition and the efficiency of thermal dissipation, controls whether the temperature increase on a localized slip plane will be sufficient to induce fusion. We report the formation of pseudotachylites during steady-state plastic flow at slow bulk shear strain rates (~10^-3 to ~10^-5 /s corresponding to slip rates of ~10^-6 to ~10^-8 m/s) in experiments performed at high confining pressures (500 MPa) and temperatures (300°C) corresponding to a depth of ~15 km. Crushed granitioid rock (Verzasca gneiss), grain size ≤ 200 μm, with 0.2 wt% water added was placed between alumina forcing blocks pre-cut at 45°, weld-sealed in platinum jackets and deformed with a constant displacement rate in a solid medium deformation apparatus (modified Griggs rig). Microstructural observations show the development of a S-C-C' fabric with C' slip zones being the dominant feature. Strain hardening in the beginning of the experiment is accompanied with compaction which is achieved by closely spaced R1 shears pervasively cutting the whole gouge zone and containing fine-grained material (d < 100 nm). The peak strength is achieved at γ ~ 2 at shear stress levels of 1350-1450 MPa when compaction ceases. During further deformation, large local displacements (γ > 10) are localized in less densely spaced, ~10 μm thick C'-C slip zones which develop predominantly in feldspars and often contain micas. In TEM, they appear to have no porosity consisting of partly amorphous material and small crystalline fragments with the average grain size of 20 nm. After the peak strength, the samples weaken by ~20 MPa and continue deforming up to γ ~ 4 without any stress drops. Strain

  10. A nuclear protein tyrosine phosphatase TC-PTP is a potential negative regulator of the PRL-mediated signaling pathway: dephosphorylation and deactivation of signal transducer and activator of transcription 5a and 5b by TC-PTP in nucleus.

    PubMed

    Aoki, Naohito; Matsuda, Tsukasa

    2002-01-01

    In the present study we examined involvement of nuclear protein tyrosine phosphatase TC-PTP in PRL-mediated signaling. TC-PTP could dephosphorylate signal transducer and activator of transcription 5a (STAT5a) and STAT5b, but the apparent dephosphorylation activity of TC-PTP was weaker than that of cytosolic PTP1B 30 min after PRL stimulation in transfected COS-7 cells, whereas both STAT5a and STAT5b were dephosphorylated to the same extent by recombinant TC-PTP and PTP1B in vitro. Tyrosine-phosphorylated STAT5 was coimmunoprecipitated with substrate trapping mutants of TC-PTP, suggesting that STAT5 is a specific substrate of TC-PTP. These observations were further extended in mammary epithelial COMMA-1D cells stably expressing TC-PTP. A time-course study revealed that dephosphorylation of STAT5 by TC-PTP was delayed compared with that by cytosolic PTP1B due to nuclear localization of TC-PTP throughout PRL stimulation in mammary epithelial cells. Endogenous beta-casein gene expression and beta-casein gene promoter activation in COS-7 cells were largely suppressed by TC-PTP wild type as well as catalytically inactive mutants, suggesting that stable complexes formed between STAT5 and TC-PTP in the nucleus. Taken together, we conclude that TC-PTP is catalytically competent with respect to dephosphorylation and deactivation of PRL-activated STAT5 in the nucleus.

  11. Final deactivation report on the radioisotope production Lab-D, Building 3031, at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1997-08-01

    The purpose of this report is to document the condition of Bldg. 3031 after completion of deactivation activities as outlined by the Department of Energy Office of Nuclear Materials and Facility Stabilization Program (EM-60) guidance documentation. This report outlines the activities conducted to place the facility in a safe and environmentally sound condition for transfer to the Department of Energy Office of Environmental Restoration (EM-40) Program. This report provides a profile of Bldg. 3031 before and after deactivation activities. Turnover items, such as the Postdeactivation Surveillance & Maintenance Plan, remaining hazardous materials, radiological controls, Safeguards and Security, quality assurance, facility operations, and supporting documentation provided in the Office of Nuclear Materials and Facility Stabilization Program (EM-60) Turnover package, are discussed. Building 3031 will require access to facilitate required surveillance and maintenance activities to maintain the building safety envelope. Building 3031 was stabilized during deactivation so that when transferred to the EM-40 program, only a minimal surveillance and maintenance effort would be required to maintain the building safety envelope. Other than the minimal surveillance and maintenance activities, the building will be unoccupied and the exterior doors locked to prevent unauthorized access. The building will be entered only to perform the required surveillance and maintenance. All materials have been removed from the building and the hot cell, and all utility systems, piping, and alarms have been deactivated.

  12. Age-Dependency of Location of Epileptic Foci in "Continuous Spike-and-Waves during Sleep": A Parallel to the Posterior-Anterior Trajectory of Slow Wave Activity.

    PubMed

    Heinzle, Bigna Katrin Bölsterli; Bast, Thomas; Critelli, Hanne; Huber, Reto; Schmitt, Bernhard

    2017-02-01

    Background Epileptic encephalopathy with continuous spike-and-waves during sleep (CSWS) occurs during childhood and is characterized by an activation of spike wave complexes during slow wave sleep. The location of epileptic foci is variable, as is etiology. A relationship between the epileptic focus and age has been shown in various focal epilepsies following a posterior-anterior trajectory, and a link to brain maturation has been proposed.We hypothesize that in CSWS, maximal spike wave activity, corresponding to the epileptic focus, is related to age and shows a posterior-anterior evolution. Findings In a retrospective cross-sectional study on CSWS (22 EEGs of 22 patients aged 3.1-13.5 years), the location of the epileptic focus is related to age and follows a posterior-anterior course. Younger patients are more likely to have posterior foci than older ones. Conclusions We propose that the posterior-anterior trajectory of maximal spike waves in CSWS might reflect maturational changes of maximal expression of sleep slow waves, which follow a comparable course. Epileptic spike waves, that is, "hyper-synchronized slow waves" may occur at the place where the highest and therefore most synchronized slow waves meet brain tissue with an increased susceptibility to synchronization.

  13. Diagnosis of industrial catalyst deactivation by surface characterization techniques

    SciTech Connect

    Menon, P.G. . Lab. voor Petrochemische Techniek Chalmers Univ. of Technology, Goeteborg . Dept. of Engineering Chemistry)

    1994-06-01

    The exact nature of the catalyst surface and the various ways of catalyst deactivation are subjects of great scientific interest and enormous economic importance. A brief review like the present one has to be very selective, giving only the underlying principles and representative examples. The focus of this review is on industrial catalysts, in particular, on the most commonly used supported metal and mixed-oxide type catalysts. Here again, only typical examples are chosen and cited to illustrate the specific types of problems involved in catalyst deactivation and how these problems wee diagnosed by a judicious application of the experimental techniques available today. Of the types of catalyst deactivation caused by coking, poisoning, and solid-state transformations, the emphasis in this review is on the last type. Changes in the chemical composition of the catalyst surface, restructuring or reconstruction of the surface, phase transformations, gradual enrichment/depletion of a particular catalyst component on/from the catalyst surface, these are the topics of prominence in this review. Even here, emphasis is on normally unexpected or unsuspected types of deactivation and the catalyst metamorphosis produced by the catalytic reaction itself, as distinct from the purely thermal effects at the reaction temperature. This review is aimed to provide some essential background information and possibly to serve as a reference guide for trouble-shooting when a catalyst is deactivated for rather mysterious reasons. 147 refs.

  14. Reactions of n-heptane and methylcyclopentane over an oxygen-modified molybdenum carbide catalyst. Study of coke formation, catalyst deactivation, and regeneration

    SciTech Connect

    Pham-Huu, C.; York, A.P.E.; Benaissa, M.; Del Gallo, P.; Ledoux, M.J.

    1995-04-01

    After an oxidative treatment, molybdenum carbide is an active and very selective catalyst for the isomerization of n-heptane. An important parameter in the choice of a catalyst for application in industry is its resistance to deactivation by coke formation, which can be caused by the presence of cyclic molecules. In this work, a study of the effect of methylcyclopentane (MCP) on the deactivation of the oxygen-modified molybdenum carbide catalyst has been performed. It has been found that the catalyst deactivates in the presence of pure MCP and that a lower activity for heptane isomerization is obtained after the reaction under MCP. TEM showed that coke formation is the cause of the deactivation. It has also been shown that increasing the total pressure when the MCP is reacted leads to a large decrease in the catalyst deactivation and that heptane isomerization can be carried out over this deactivated sample with only a small loss in activity. Further, the catalyst can be totally regenerated in air.

  15. Deactivation and desensitization of non-NMDA receptors in patches and the time course of EPSCs in rat cerebellar granule cells.

    PubMed Central

    Silver, R A; Colquhoun, D; Cull-Candy, S G; Edmonds, B

    1996-01-01

    1. Spontaneous and evoked non-NMDA receptor-mediated EPSCs were recorded from cerebellar granule cells in slices at approximately 24 and approximately 34 degrees C. The EPSC decay was fitted with the sum of two exponential functions. 2. The time courses of non-NMDA receptor deactivation and desensitization were determined with fast concentration jumps of glutamate onto patches from cultured granule cells. Deactivation (decay time constant tau = 0.6 ms at 24 degrees C) was substantially faster than desensitization (tau = 4 ms). Both processes were fitted by single exponential functions. 3. The decay of the fast component of the spontaneous EPSC (tau EPSCfast = 0.9 ms at 23 degrees C) was marginally slower than deactivation but too fast to be determined by desensitization. Our results suggest that the decay of this component is set by both the rate of decline of transmitter concentration and channel deactivation. 4. A simple diffusion model predicts that the time course of transmitter in the cleft declines slowly during the later stages of its action. The slow phase of transmitter removal could account for the time course of the slow component of the spontaneous EPSC (tau EPSCslow = 8 ms at 23 degrees C). PMID:8735702

  16. What Does Ipsilateral Delay Activity Reflect? Inferences from Slow Potentials in a Lateralized Visual Working Memory Task

    ERIC Educational Resources Information Center

    Arend, Anna M.; Zimmer, Hubert D.

    2011-01-01

    In the lateralized change detection task, two item arrays are presented, one on each side of the display. Participants have to remember the items in the relevant hemifield and ignore the items in the irrelevant hemifield. A difference wave between contralateral and ipsilateral slow potentials with respect to the relevant items, the contralateral…

  17. Attenuation of the slow component of delayed rectification, action potential prolongation, and triggered activity in mice expressing a dominant-negative Kv2 alpha subunit.

    PubMed

    Xu, H; Barry, D M; Li, H; Brunet, S; Guo, W; Nerbonne, J M

    1999-10-01

    An in vivo experimental strategy, involving cardiac-specific expression of a mutant Kv 2.1 subunit that functions as a dominant negative, was exploited in studies focused on exploring the role of members of the Kv2 subfamily of pore-forming (alpha) subunits in the generation of functional voltage-gated K(+) channels in the mammalian heart. A mutant Kv2.1 alpha subunit (Kv2.1N216) was designed to produce a truncated protein containing the intracellular N terminus, the S1 membrane-spanning domain, and a portion of the S1/S2 loop. The truncated Kv2.1N216 was epitope tagged at the C terminus with the 8-amino acid FLAG peptide to generate Kv2. 1N216FLAG. No ionic currents are detected on expression of Kv2. 1N216FLAG in HEK-293 cells, although coexpression of this construct with wild-type Kv2.1 markedly reduced the amplitudes of Kv2. 1-induced currents. Using the alpha-myosin heavy chain promoter to direct cardiac specific expression of the transgene, 2 lines of Kv2. 1N216FLAG-expressing transgenic mice were generated. Electrophysiological recordings from ventricular myocytes isolated from these animals revealed that I(K, slow) is selectively reduced. The attenuation of I(K, slow) is accompanied by marked action potential prolongation, and, occasionally, spontaneous triggered activity (apparently induced by early afterdepolarizations) is observed. The time constant of inactivation of I(K, slow) in Kv2. 1N216FLAG-expressing cells (mean+/-SEM=830+/-103 ms; n=17) is accelerated compared with the time constant of I(K, slow) inactivation (mean+/-SEM=1147+/-57 ms; n=25) in nontransgenic cells. In addition, unlike I(K, slow) in wild-type cells, the component of I(K, slow) remaining in the Kv2.1N216FLAG-expressing cells is insensitive to 25 mmol/L tetraethylammonium. Taken together, these observations suggest that there are 2 distinct components of I(K, slow) in mouse ventricular myocytes and that Kv2 alpha subunits underlie the more slowly inactivating, tetraethylammonium

  18. The ethics of unilateral implantable cardioverter defibrillators and cardiac resynchronization therapy with defibrillator deactivation: patient perspectives.

    PubMed

    Daeschler, Margaret; Verdino, Ralph J; Kirkpatrick, James N

    2017-08-01

    Decisions about deactivation of implantable cardioverter defibrillators (ICDs) are complicated. Unilateral do-not-resuscitate (DNR) orders (against patient/family wishes) have been ethically justified in cases of medical futility. Unilateral deactivation of ICDs may be seen as a logical extension of a unilateral DNR order. However, the ethical implications of unilateral ICD deactivation have not been explored. Sixty patients who had an ICD or cardiac resynchronization therapy with defibrillator (CRT-D) were interviewed at a quaternary medical centre outpatient electrophysiology practice. Survey questions addressed whether deactivation of defibrillator function was included in advanced directives, whether deactivation constitutes physician-assisted suicide, and whether unilateral deactivation can be ethically justified. Responses were elicited to scenarios in which defibrillation function was deactivated in different contexts (including patient request to deactivate, existing DNR, and unilateral deactivation). Only 15% of respondents had thought about device deactivation if they were to develop a serious illness from which they were not expected to recover. A majority (53%) had advance directives, but only one mentioned what to do with the device. However, a majority (78%) did not consider deactivation of an ICD shocking function against patients' wishes to be ethical or moral. Management of ICDs and CRT-Ds as patients near the end of their lives creates ethical dilemmas. Few patients consider device deactivation at end-of-life, although a large majority believes that unilateral deactivation is not ethical/moral, even in the setting of medical futility. Advance care planning for these patients should address device deactivation.

  19. [Slow activated voltage-dependent sodium current contribution in fast depolarization in the rabbit heart true pacemaker sinoatrial node].

    PubMed

    Golovko, V A

    2009-04-01

    The functional role of INa in initiation and conduction of cardiac true pacemaker activity remains uncertain. Therefore the goal of this work was to study the effects of Na+ substitution of action potentials parameters of the sinoatrial area cells. Transmembrane action potentials were recorded with 15 to 40 MOmega glass microelectrodes filled with 2.5 M KCl. The final preparations was about 5 x 3 mm in size, contained a portion sinoatrial node and the adjacent fragment of tissue of the right branch of the sinoatrial ring bundle and crista terminalis. All strips were allowed to beat spontaneously. We have registered that Na+ replacement of 50% in external solution causes an almost two-fold monotonous decrease of dV/dtmax and overshoot values of primary (3.2 V/s, n = 15), latent pacemaker (17 V/s, n = 16) and "conducting"-like cells (130 V/s, n = 16, control, 35 C) as compared with the control. Finally (at 30 min exposure) action potential frequency is slowed dowb by 20-30%. True pacemaker cells decreased action potential amplitude from 65 to 9 mV for 20-30 min 50% Na solution exposure. It should be noted that the cells of the "conducting"-like type demonstrated the generation block of action potential 30% Na exposure. At the same time dV/dtmax monotonously decreased from 3.1 to 1.5 V/s (true pacemaker) 16 vs 7 V/s (latent) and from 130 to 1.8 v/s ("conducting"). In our opinion, these facts deserve particular attention because it has been reported earlier that tetrodotoxin (20 mcM) addition in to the control solution caused the decrease of dV/dt from 100 to 4 V/s in latent pacemaker, whereas action potential amplitude is decreased by only some mV and the rate of beating by 1.5 times. As for true pacemaker cells, the TTX does not influence them.

  20. PUREX/UO{sub 3} facilities deactivation lessons learned history

    SciTech Connect

    Hamrick, D.G.; Gerber, M.S.

    1995-01-01

    The Plutonium-Uranium Extraction (PUREX) Facility operated from 1956-1972, from 1983-1988, and briefly during 1989-1990 to produce for national defense at the Hanford Site in Washington State. The Uranium Trioxide (UO{sub 3}) Facility operated at the Hanford Site from 1952-1972, 1984-1988, and briefly in 1993. Both plants were ordered to permanent shutdown by the U.S. Department of Energy (DOE) in December 1992, thus initiating their deactivation phase. Deactivation is that portion of a facility`s life cycle that occurs between operations and final decontamination and decommissioning (D&D). This document details the history of events, and the lessons learned, from the time of the PUREX Stabilization Campaign in 1989-1990, through the end of the first full fiscal year (FY) of the deactivation project (September 30, 1994).

  1. Age association of language task induced deactivation induced in a pediatric population.

    PubMed

    Sun, Binjian; Berl, Madison M; Burns, Thomas G; Gaillard, William D; Hayes, Laura; Adjouadi, Malek; Jones, Richard A

    2013-01-15

    Task-induced deactivation (TID) potentially reflects the interactions between the default mode and task specific networks, which are assumed to be age dependent. The study of the age association of such interactions provides insight about the maturation of neural networks, and lays out the groundwork for evaluating abnormal development of neural networks in neurological disorders. The current study analyzed the deactivations induced by language tasks in 45 right-handed normal controls aging from 6 to 22 years of age. Converging results from GLM, dual regression and ROI analyses showed a gradual reduction in both the spatial extent and the strength of the TID in the DMN cortices as the brain matured from kindergarten to early adulthood in the absence of any significant change in task performance. The results may be ascribed to maturation leading to either improved multi-tasking (i.e. reduced deactivation) or reduced cognitive demands due to greater experience (affects both control and active tasks but leads to reduced overall difference). However, other effects, such as changes in the DMN connectivity that were not included in this study may also have influenced the results. In light of this, researchers should be cautious when investigating the maturation of DMN using TID. With a GLM analysis using the concatenated fMRI data from several paradigms, this study additionally identified an age associated increase of TID in the STG (bilateral), possibly reflecting the role of this area in speech perception and phonological processing.

  2. Dorsolateral Prefrontal Cortex Deactivation in Monkeys Reduces Preparatory Beta and Gamma Power in the Superior Colliculus

    PubMed Central

    Chan, Jason L.; Koval, Michael J.; Womelsdorf, Thilo; Lomber, Stephen G.; Everling, Stefan

    2015-01-01

    Cognitive control requires the selection and maintenance of task-relevant stimulus–response associations, or rules. The dorsolateral prefrontal cortex (DLPFC) has been implicated by lesion, functional imaging, and neurophysiological studies to be involved in encoding rules, but the mechanisms by which it modulates other brain areas are poorly understood. Here, the functional relationship of the DLPFC with the superior colliculus (SC) was investigated by bilaterally deactivating the DLPFC while recording local field potentials (LFPs) in the SC in monkeys performing an interleaved pro- and antisaccade task. Event-related LFPs showed differences between pro- and antisaccades and responded prominently to stimulus presentation. LFP power after stimulus onset was higher for correct saccades than erroneous saccades. Deactivation of the DLPFC did not affect stimulus onset related LFP activity, but reduced high beta (20–30 Hz) and high gamma (60–150 Hz) power during the preparatory period for both pro- and antisaccades. Spike rate during the preparatory period was positively correlated with gamma power and this relationship was attenuated by DLPFC deactivation. These results suggest that top-down control of the SC by the DLPFC may be mediated by beta oscillations. PMID:25037923

  3. Tectonic and magmatic control of hydrothermal activity along the slow-spreading Central Indian Ridge, 8°S-17°S

    NASA Astrophysics Data System (ADS)

    Son, Juwon; Pak, Sang-Joon; Kim, Jonguk; Baker, Edward T.; You, Ok-Rye; Son, Seung-Kyu; Moon, Jai-Woon

    2014-05-01

    complex geology and expansive axial valleys typical of slow-spreading ridges makes evaluating their hydrothermal activity a challenge. This challenge has gone largely unmet, as the most undersampled MOR type for hydrothermal activity is slow spreading (20-55 mm/yr). Here we report the first systematic hydrothermal plume survey conducted on the Central Indian Ridge (CIR, 8°S-17°S), the most extensive such survey yet conducted on a slow-spreading ridge. Using a combined CTD/Miniature Autonomous Plume Recorder (MAPR) package, we used 118 vertical casts along seven segments of the CIR (˜700 km of ridge length) to estimate the frequency of hydrothermal activity. Evidence for hydrothermal activity (particle and methane plumes) was found on each of the seven spreading segments, with most plumes found between 3000 and 3500 m, generally <1000 m above bottom. We most commonly found plumes on asymmetric ridge sections where ultramafic massifs formed along one ridge flank near ridge-transform intersections or nontransform offsets. The estimated plume incidence (ph) for axial and wall casts (ph=0.30, 35 of 118 casts) is consistent with the existing global trend, indicating that the long-term magmatic budget on the CIR is the primary control on the spatial frequency of hydrothermal venting. Our results show that the tectonic fabric of the CIR strongly determines where hydrothermal venting is expressed, and that using only near-axial sampling might underestimate hydrothermal activity along slow-spreading and ultraslow-spreading ridges. Serpentinization is a minor contributor to the plume inventory, based on 15 profiles with methane anomalies only, predominantly at depths above the local valley walls.

  4. Robot Work Platform for Large Hot Cell Deactivation

    SciTech Connect

    BITTEN, E.J.

    2000-05-01

    The 324 Building, located at the Hanford Site near Richland, Washington, is being deactivated to meet state and federal cleanup commitments. The facility is currently in its third year of a nine-year project to complete deactivation and closure for long-term surveillance and maintenance. The 324 building contains large hot cells that were used for high-radiation, high-contamination chemical process development and demonstrations. A major obstacle for the 324 deactivation project is the inability to effectively perform deactivation tasks within highly radioactive, contaminated environments. Current strategies use inefficient, resource intensive technologies that significantly impact the cost and schedule for deactivation. To meet mandated cleanup commitments, there is a need to deploy rapid, more efficient remote/robot technologies to minimize worker exposure, accelerate work tasks, and eliminate the need for multiple specialized tool design and procurement efforts. This paper describes the functions and performance requirements for a crane-deployed remote/robot Work Platform possessing full access capabilities. The remote/robot Work Platform will deploy commercially available off-the-shelf tools and end effectors to support Project cleanup goals and reduce overall project risk and cost. The intent of this system is to maximize the use of off-the-shelf technologies that minimize additional new, unproven, or novel designs. This paper further describes procurement strategy, the selection process, the selected technology, and the current status of the procurement and lessons learned. Funding, in part, has been provided by the US Department of Energy, Office of Science and Technology, Deactivation and Decommissioning Focus Area.

  5. Cyclophilin-promoted folding of mouse dihydrofolate reductase does not include the slow conversion of the late-folding intermediate to the active enzyme.

    PubMed

    von Ahsen, O; Lim, J H; Caspers, P; Martin, F; Schönfeld, H J; Rassow, J; Pfanner, N

    2000-03-31

    Cyclophilins accelerate slow protein folding reactions in vitro by catalyzing the cis/trans isomerization of peptidyl-prolyl bonds. Cyclophilins were reported to be involved in a variety of cellular functions, including the promotion of protein folding by use of the substrate mouse dihydrofolate reductase (DHFR). The interaction of cyclophilin with DHFR has only been studied under limited conditions so far, not taking into account that native DHFR exists in equilibrium with a non-native late-folding intermediate. Here we report a systematic analysis of catalysis of DHFR folding by cyclophilins. The specific ligand methotrexate traps DHFR in its native state, permitting a specific analysis of the action of cyclophilin on both denatured DHFR with non-native prolyl bonds and denatured DHFR with all-native prolyl bonds. Cyclophilins from yeast and Neurospora crassa as well as the related prolyl isomerase b from Escherichia coli promote the folding of different forms of DHFR to the enzymatically active form, demonstrating the generality of cyclophilin-catalyzed folding of DHFR. The slow equilibrium between the late-folding intermediate and native DHFR suggests that prolyl isomerization may be required for this final phase of conversion to native DHFR. However, by reversible trapping of the intermediate, we analyze the slow interconversion between native and late-folding conformations in the backward and forward reactions and show a complete independence of cyclophilin. We conclude that cyclophilin catalyzes folding of DHFR, but surprisingly not in the last slow folding step. Copyright 2000 Academic Press.

  6. Systems and methods for deactivating a matrix converter

    SciTech Connect

    Ransom, Ray M.

    2013-04-02

    Systems and methods are provided for deactivating a matrix conversion module. An electrical system comprises an alternating current (AC) interface, a matrix conversion module coupled to the AC interface, an inductive element coupled between the AC interface and the matrix conversion module, and a control module. The control module is coupled to the matrix conversion module, and in response to a shutdown condition, the control module is configured to operate the matrix conversion module to deactivate the first conversion module when a magnitude of a current through the inductive element is less than a threshold value.

  7. Perovskite photovoltaics: Slow recombination unveiled

    NASA Astrophysics Data System (ADS)

    Moser, Jacques-E.

    2017-01-01

    One of the most salient features of hybrid lead halide perovskites is the extended lifetime of their photogenerated charge carriers. This property has now been shown experimentally to originate from a slow, thermally activated recombination process.

  8. Effects of electric stimulation of the hunger center in the lateral hypothalamus on slow electric activity and spike activity of fundal and antral stomach muscles in rabbits under conditions of hunger and satiation.

    PubMed

    Kromin, A A; Zenina, O Yu

    2013-09-01

    In chronic experiments on rabbits, the effect of electric stimulation of the hunger center in the lateral hypothalamus on myoelectric activity of the fundal and antral parts of the stomach was studied under conditions of hunger and satiation in the absence of food. Stimulation of the lateral hypothalamus in rabbits subjected to 24-h food deprivation and in previously fed rabbits produced incessant seeking behavior, which was followed by reorganization of the structure of temporal organization of slow wave electric activity of muscles of the stomach body and antrum specific for hungry and satiated animals. Increased hunger motivation during electric stimulation of the lateral hypothalamus manifested in the structure of temporal organization of slow wave electric activity of the stomach body and antrum muscles in rabbits subjected to 24-h food deprivation in the replacement of bimodal distribution of slow wave periods to a trimodal type typical of 2-day deprivation, while transition from satiation to hunger caused by electric stimulation of the lateral hypothalamus was associated with a shift from monomodal distributions of slow wave periods to a bimodal type typical of 24-h deprivation. Reorganization of the structure of temporal organization of slow wave electric activity of the stomach body and antrum muscles during electric stimulation of the lateral hypothalamus was determined by descending inhibitory influences of food motivational excitation on activity of the myogenic pacemaker of the lesser curvature of the stomach.

  9. Final deactivation project report on the High Radiation Level Analytical Facility, Building 3019B at Oak Ridge National Laboratory, Oak Ridge, Tennessee

    SciTech Connect

    1997-09-01

    The purpose of this report is to document the condition of the High Radiation Level Analytical Facility (Building 3019B) at Oak Ridge National Laboratory (ORNL) after completion of deactivation activities. This report identifies the activities conducted to place the facility in a safe and environmentally sound condition prior to transfer to the Environmental Restoration EM-40 Program. This document provides a history and description of the facility prior to the commencement of deactivation activities and documents the condition of the building after completion of all deactivation activities. Turnover items, such as the Post-Deactivation Surveillance and Maintenance (S&M) Plan, remaining hazardous materials inventory, radiological controls, safeguards and security, quality assurance, facility operations, and supporting documentation provided in the Nuclear Material and Facility Stabilization (EM-60) Turnover package are discussed. Building 3019B will require access to perform required S&M activities to maintain the building safety envelope. Building 3019B was stabilized during deactivation so that when transferred to the EM-40 Program, only a minimal S&M effort would be required to maintain the building safety envelope. Other than the minimal S&M activities the building will be unoccupied and the exterior doors locked to prevent unauthorized access. The building will be entered only to perform the required S&M until decommissioning activities begin.

  10. "Ectopic" theta oscillations and interictal activity during slow-wave state in the R6/1 mouse model of Huntington's disease.

    PubMed

    Pignatelli, Michele; Lebreton, Fanny; Cho, Yoon H; Leinekugel, Xavier

    2012-12-01

    The pathophysiology of Huntington's disease (HD) is primarily associated with striatal degeneration and a number of behavioral symptoms such as involuntary movements, cognitive decline, psychiatric disorders, and in the most juvenile-onset cases with epilepsy. In addition to several changes in cellular and synaptic properties previously reported in HD, attention was recently driven towards the potential relationships between cognitive deficits and sleep disturbances in patients and animal models of Huntington's disease. In the present study, we have investigated whether the population-activity patterns normally expressed by the hippocampal and neocortical circuits during active and slow-wave states are affected in R6/1 mice, a model of Huntington's disease. By performing electrophysiological recordings from the hippocampus and neocortex of R6/1 mice that were either freely moving, head restrained or anesthetized, we observed an altered segregation of active and slow wave brain states, in relation with an epileptic phenotype. Slow-wave state (SWS) in R6/1 was characterized by the intrusion of active-state features (increased 6-10 Hz theta power and depressed 2-3 Hz delta power) and transient, temporally misplaced ("ectopic") theta oscillations. The epileptic phenotype, in addition to previously reported occasional ictal seizures, was characterized by the systematic presence of interictal activity, confined to SWS. Ectopic theta episodes, which could be reversed by the cholinergic antagonist atropine, concentrated interictal spikes and phase-locked hippocampal sharp-wave-ripples. These results point to major alterations of neuronal activity during rest in R6/1 mice, potentially involving anomalous activation of the cholinergic system, which may contribute to the cognitive deficits observed in Huntington's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Movement - uncontrolled or slow

    MedlinePlus

    Dystonia; Involuntary slow and twisting movements; Choreoathetosis; Leg and arm movements - uncontrollable; Arm and leg movements - uncontrollable; Slow involuntary movements of large muscle groups; Athetoid movements

  12. A Summary of Published Mode Deactivation Therapy Articles

    ERIC Educational Resources Information Center

    Apsche, Jack A.

    2006-01-01

    This article summarizes all of the Mode Deactivation Therapy, (MDT) articles published to date. MDT has shown to be more effective than Cognitive Behavior Therapy, (CBT), Social Skills Training, (SST), and Dialectical Behavior Therapy, (DBT), Apsche, Bass, Jennings, Murphy, Hunter, and Siv, (2005); Apsche & Bass, (2005); Apsche, Bass & Murphy,…

  13. 200 Area Deactivation Project Facilities Authorization Envelope Document

    SciTech Connect

    DODD, E.N.

    2000-03-28

    Project facilities as required by HNF-PRO-2701, Authorization Envelope and Authorization Agreement. The Authorization Agreements (AA's) do not identify the specific set of environmental safety and health requirements that are applicable to the facility. Therefore, the facility Authorization Envelopes are defined here to identify the applicable requirements. This document identifies the authorization envelopes for the 200 Area Deactivation.

  14. Compassionate deactivation of ventricular assist devices in pediatric patients.

    PubMed

    Hollander, Seth A; Axelrod, David M; Bernstein, Daniel; Cohen, Harvey J; Sourkes, Barbara; Reddy, Sushma; Magnus, David; Rosenthal, David N; Kaufman, Beth D

    2016-05-01

    Despite greatly improved survival in pediatric patients with end-stage heart failure through the use of ventricular assist devices (VADs), heart failure ultimately remains a life-threatening disease with a significant symptom burden. With increased demand for donor o