Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca2+ spike frequency.

PubMed

Fahrion, Jennifer K; Komuro, Yutaro; Li, Ying; Ohno, Nobuhiko; Littner, Yoav; Raoult, Emilie; Galas, Ludovic; Vaudry, David; Komuro, Hitoshi

2012-03-27

In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development. The cerebellum is one of the most susceptible brain regions to MeHg exposure, and profound loss of cerebellar granule cells is detected in the brains of patients with FMD. We show that MeHg inhibits granule cell migration by reducing the frequency of somal Ca(2+) spikes through alterations in Ca(2+), cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the speed of granule cell migration in a dose-dependent manner, independent of the mode of migration. Second, MeHg reduces the frequency of spontaneous Ca(2+) spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo live-imaging system for cell migration reveals that reducing the inhibitory effects of MeHg on somal Ca(2+) spike frequency by stimulating internal Ca(2+) release and Ca(2+) influxes, inhibiting cAMP activity, or activating IGF1 receptors ameliorates the inhibitory effects of MeHg on granule cell migration. These results suggest that alteration of Ca(2+) spike frequency and Ca(2+), cAMP, and IGF1 signaling could be potential therapeutic targets for infants with MeHg intoxication.

Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca2+ spike frequency

PubMed Central

Fahrion, Jennifer K.; Ohno, Nobuhiko; Littner, Yoav; Raoult, Emilie; Galas, Ludovic; Vaudry, David; Komuro, Hitoshi

2012-01-01

In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development. The cerebellum is one of the most susceptible brain regions to MeHg exposure, and profound loss of cerebellar granule cells is detected in the brains of patients with FMD. We show that MeHg inhibits granule cell migration by reducing the frequency of somal Ca2+ spikes through alterations in Ca2+, cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the speed of granule cell migration in a dose-dependent manner, independent of the mode of migration. Second, MeHg reduces the frequency of spontaneous Ca2+ spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo live-imaging system for cell migration reveals that reducing the inhibitory effects of MeHg on somal Ca2+ spike frequency by stimulating internal Ca2+ release and Ca2+ influxes, inhibiting cAMP activity, or activating IGF1 receptors ameliorates the inhibitory effects of MeHg on granule cell migration. These results suggest that alteration of Ca2+ spike frequency and Ca2+, cAMP, and IGF1 signaling could be potential therapeutic targets for infants with MeHg intoxication. PMID:22411806

Surface Penetrating Radar Simulations for Europa

NASA Technical Reports Server (NTRS)

Markus, T.; Gogineni, S. P.; Green, J. L.; Fung, S. F.; Cooper, J. F.; Taylor, W. W. L.; Garcia, L.; Reinisch, B. W.; Song, P.; Benson, R. F.

2004-01-01

The space environment above the icy surface of Europa is a source of radio noise in this frequency range from natural sources in the Jovian magnetosphere. The ionospheric and magnetospheric plasma environment of Europa affects propagation of transmitted and return signals between the spacecraft and the solid surface in a frequency-dependent manner. The ultimate resolution of the subsurface sounding measurements will be determined, in part, by a capability to mitigate these effects. We discuss an integrated multi-frequency approach to active radio sounding of the Europa ionospheric and local magnetospheric environments, based on operational experience from the Radio Plasma Imaging @PI) experiment on the IMAGE spacecraft in Earth orbit, in support of the subsurface measurement objectives.

Cross-Linker Unbinding and Self-Similarity in Bundled Cytoskeletal Networks

NASA Astrophysics Data System (ADS)

Lieleg, O.; Bausch, A. R.

2007-10-01

The macromechanical properties of purely bundled in vitro actin networks are not only determined by the micromechanical properties of individual bundles but also by molecular unbinding events of the actin-binding protein (ABP) fascin. Under high mechanical load the network elasticity depends on the forced unbinding of individual ABPs in a rate dependent manner. Cross-linker unbinding in combination with the structural self-similarity of the network enables the introduction of a concentration-time superposition principle—broadening the mechanically accessible frequency range over 8 orders of magnitude.

Criteria for Handling Qualities of Military Aircraft.

DTIC Science & Technology

1982-06-01

loop precognitive manner. The pilot is able to apply discrete, step-like inputs which more or less exactly produce the desired aircraft response. Some...While closed loop operation depends upon the frequency domain response characteristics, successful precognitive control requires the time domain...represents the other extreme of the pilot task from the precognitive time response situation. Mich work was done in attempting to predict pilot opinion from

Retinohypothalamic Tract Synapses in the Rat Suprachiasmatic Nucleus Demonstrate Short-Term Synaptic Plasticity

PubMed Central

Moldavan, Mykhaylo G.

2010-01-01

The master circadian pacemaker located in the suprachiasmatic nucleus (SCN) is entrained by light intensity–dependent signals transmitted via the retinohypothalamic tract (RHT). Short-term plasticity at glutamatergic RHT–SCN synapses was studied using stimulus frequencies that simulated the firing of light sensitive retinal ganglion cells. The evoked excitatory postsynaptic current (eEPSC) was recorded from SCN neurons located in hypothalamic brain slices. The eEPSC amplitude was stable during 0.08 Hz stimulation and exhibited frequency-dependent short-term synaptic depression (SD) during 0.5 to 100 Hz stimulus trains in 95 of 99 (96%) recorded neurons. During SD the steady-state eEPSC amplitude decreased, whereas the cumulative charge transfer increased in a frequency-dependent manner and saturated at 20 Hz. SD was similar during subjective day and night and decreased with increasing temperature. Paired-pulse stimulation (PPS) and voltage-dependent Ca2+ channel (VDCC) blockers were used to characterize a presynaptic release mechanism. Facilitation was present in 30% and depression in 70% of studied neurons during PPS. Synaptic transmission was reduced by blocking both N- and P/Q-type presynaptic VDCCs, but only the N-type channel blocker significantly relieved SD. Aniracetam inhibited AMPA receptor desensitization but did not alter SD. Thus we concluded that SD is the principal form of short-term plasticity at RHT synapses, which presynaptically and frequency-dependently attenuates light-induced glutamatergic RHT synaptic transmission protecting SCN neurons against excessive excitation. PMID:20220078

Lateral separation of colloids or cells by dielectrophoresis augmented by AC electroosmosis.

PubMed

Zhou, Hao; White, Lee R; Tilton, Robert D

2005-05-01

Colloidal particles and biological cells are patterned and separated laterally adjacent to a micropatterned electrode array by applying AC electric fields that are principally oriented normally to the electrode array. This is demonstrated for yeast cells, red blood cells, and colloidal polystyrene particles of different sizes and zeta-potentials. The separation mechanism is observed experimentally to depend on the applied field frequency and voltage. At high frequencies, particles position themselves in a manner that is consistent with dielectrophoresis, while at low frequencies, the positioning is explained in terms of a strong coupling between gravity, the vertical component of the dielectrophoretic force, and the Stokes drag on particles induced by AC electroosmotic flow. Compared to high frequency dielectrophoretic separations, the low frequency separations are faster and require lower applied voltages. Furthermore, the AC electroosmosis coupling with dielectrophoresis may enable cell separations that are not feasible based on dielectrophoresis alone.

Manual control of yaw motion with combined visual and vestibular cues

NASA Technical Reports Server (NTRS)

Zacharias, G. L.; Young, L. R.

1977-01-01

Measurements are made of manual control performance in the closed-loop task of nulling perceived self-rotation velocity about an earth-vertical axis. Self-velocity estimation was modelled as a function of the simultaneous presentation of vestibular and peripheral visual field motion cues. Based on measured low-frequency operator behavior in three visual field environments, a parallel channel linear model is proposed which has separate visual and vestibular pathways summing in a complementary manner. A correction to the frequency responses is provided by a separate measurement of manual control performance in an analogous visual pursuit nulling task. The resulting dual-input describing function for motion perception dependence on combined cue presentation supports the complementary model, in which vestibular cues dominate sensation at frequencies above 0.05 Hz. The describing function model is extended by the proposal of a non-linear cue conflict model, in which cue weighting depends on the level of agreement between visual and vestibular cues.

Genotoxicity of dill (Anethum graveolens L.), peppermint (Menthaxpiperita L.) and pine (Pinus sylvestris L.) essential oils in human lymphocytes and Drosophila melanogaster.

PubMed

Lazutka, J R; Mierauskiene, J; Slapsyte, G; Dedonyte, V

2001-05-01

Genotoxic properties of the essential oils extracted from dill (Anethum graveolens L.) herb and seeds, peppermint (Menthaxpiperita L.) herb and pine (Pinus sylvestris L.) needles were studied using chromosome aberration (CA) and sister chromatid exchange (SCE) tests in human lymphocytes in vitro, and Drosophila melanogaster somatic mutation and recombination test (SMART) in vivo. In the CA test, the most active essential oil was from dill seeds, then followed essential oils from dill herb, peppermint herb and pine needles, respectively. In the SCE test, the most active essential oils were from dill herb and seeds followed by essential oils from pine needles and peppermint herb. Essential oils from dill herb and seeds and pine needles induced CA and SCE in a clear dose-dependent manner, while peppermint essential oil induced SCE in a dose-independent manner. All essential oils were cytotoxic for human lymphocytes. In the SMART test, a dose-dependent increase in mutation frequency was observed for essential oils from pine and dill herb. Peppermint essential oil induced mutations in a dose-independent manner. Essential oil from dill seeds was almost inactive in the SMART test.

Modulation of cell function by electric field: a high-resolution analysis

PubMed Central

Taghian, T.; Narmoneva, D. A.; Kogan, A. B.

2015-01-01

Regulation of cell function by a non-thermal, physiological-level electromagnetic field has potential for vascular tissue healing therapies and advancing hybrid bioelectronic technology. We have recently demonstrated that a physiological electric field (EF) applied wirelessly can regulate intracellular signalling and cell function in a frequency-dependent manner. However, the mechanism for such regulation is not well understood. Here, we present a systematic numerical study of a cell-field interaction following cell exposure to the external EF. We use a realistic experimental environment that also recapitulates the absence of a direct electric contact between the field-sourcing electrodes and the cells or the culture medium. We identify characteristic regimes and present their classification with respect to frequency, location, and the electrical properties of the model components. The results show a striking difference in the frequency dependence of EF penetration and cell response between cells suspended in an electrolyte and cells attached to a substrate. The EF structure in the cell is strongly inhomogeneous and is sensitive to the physical properties of the cell and its environment. These findings provide insight into the mechanisms for frequency-dependent cell responses to EF that regulate cell function, which may have important implications for EF-based therapies and biotechnology development. PMID:25994294

Model Equation for Acoustic Nonlinear Measurement of Dispersive Specimens at High Frequency

NASA Astrophysics Data System (ADS)

Zhang, Dong; Kushibiki, Junichi; Zou, Wei

2006-10-01

We present a theoretical model for acoustic nonlinearity measurement of dispersive specimens at high frequency. The nonlinear Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation governs the nonlinear propagation in the SiO2/specimen/SiO2 multi-layer medium. The dispersion effect is considered in a special manner by introducing the frequency-dependant sound velocity in the KZK equation. Simple analytic solutions are derived by applying the superposition technique of Gaussian beams. The solutions are used to correct the diffraction and dispersion effects in the measurement of acoustic nonlinearity of cottonseed oil in the frequency range of 33-96 MHz. Regarding two different ultrasonic devices, the accuracies of the measurements are improved to ±2.0% and ±1.3% in comparison with ±9.8% and ±2.9% obtained from the previous plane wave model.

Continuous- and discrete-time stimulus sequences for high stimulus rate paradigm in evoked potential studies.

PubMed

Wang, Tao; Huang, Jiang-hua; Lin, Lin; Zhan, Chang'an A

2013-01-01

To obtain reliable transient auditory evoked potentials (AEPs) from EEGs recorded using high stimulus rate (HSR) paradigm, it is critical to design the stimulus sequences of appropriate frequency properties. Traditionally, the individual stimulus events in a stimulus sequence occur only at discrete time points dependent on the sampling frequency of the recording system and the duration of stimulus sequence. This dependency likely causes the implementation of suboptimal stimulus sequences, sacrificing the reliability of resulting AEPs. In this paper, we explicate the use of continuous-time stimulus sequence for HSR paradigm, which is independent of the discrete electroencephalogram (EEG) recording system. We employ simulation studies to examine the applicability of the continuous-time stimulus sequences and the impacts of sampling frequency on AEPs in traditional studies using discrete-time design. Results from these studies show that the continuous-time sequences can offer better frequency properties and improve the reliability of recovered AEPs. Furthermore, we find that the errors in the recovered AEPs depend critically on the sampling frequencies of experimental systems, and their relationship can be fitted using a reciprocal function. As such, our study contributes to the literature by demonstrating the applicability and advantages of continuous-time stimulus sequences for HSR paradigm and by revealing the relationship between the reliability of AEPs and sampling frequencies of the experimental systems when discrete-time stimulus sequences are used in traditional manner for the HSR paradigm.

Rapid estimation of earthquake magnitude from the arrival time of the peak high‐frequency amplitude

USGS Publications Warehouse

Noda, Shunta; Yamamoto, Shunroku; Ellsworth, William L.

2016-01-01

We propose a simple approach to measure earthquake magnitude M using the time difference (Top) between the body‐wave onset and the arrival time of the peak high‐frequency amplitude in an accelerogram. Measured in this manner, we find that Mw is proportional to 2logTop for earthquakes 5≤Mw≤7, which is the theoretical proportionality if Top is proportional to source dimension and stress drop is scale invariant. Using high‐frequency (>2  Hz) data, the root mean square (rms) residual between Mw and MTop(M estimated from Top) is approximately 0.5 magnitude units. The rms residuals of the high‐frequency data in passbands between 2 and 16 Hz are uniformly smaller than those obtained from the lower‐frequency data. Top depends weakly on epicentral distance, and this dependence can be ignored for distances <200  km. Retrospective application of this algorithm to the 2011 Tohoku earthquake produces a final magnitude estimate of M 9.0 at 120 s after the origin time. We conclude that Top of high‐frequency (>2  Hz) accelerograms has value in the context of earthquake early warning for extremely large events.

The effects of experimentally induced conductive hearing loss on spectral and temporal aspects of sound transmission through the ear.

PubMed

Eric Lupo, J; Koka, Kanthaiah; Thornton, Jennifer L; Tollin, Daniel J

2011-02-01

Conductive hearing loss (CHL) is known to produce hearing deficits, including deficits in sound localization ability. The differences in sound intensities and timing experienced between the two tympanic membranes are important cues to sound localization (ILD and ITD, respectively). Although much is known about the effect of CHL on hearing levels, little investigation has been conducted into the actual impact of CHL on sound location cues. This study investigated effects of CHL induced by earplugs on cochlear microphonic (CM) amplitude and timing and their corresponding effect on the ILD and ITD location cues. Acoustic and CM measurements were made in 5 chinchillas before and after earplug insertion, and again after earplug removal using pure tones (500 Hz to 24 kHz). ILDs in the unoccluded condition demonstrated position and frequency dependence where peak far-lateral ILDs approached 30 dB for high frequencies. Unoccluded ear ITD cues demonstrated positional and frequency dependence with increased ITD cue for both decreasing frequency (±420 μs at 500 Hz, ±310 μs for 1-4 kHz) and increasingly lateral sound source locations. Occlusion of the ear canal with foam plugs resulted in a mild, frequency-dependent conductive hearing loss of 10-38 dB (mean 31 ± 3.9 dB) leading to a concomitant frequency dependent increase in ILDs at all source locations. The effective ITDs increased in a frequency dependent manner with ear occlusion as a direct result of the acoustic properties of the plugging material, the latter confirmed via acoustical measurements using a model ear canal with varying volumes of acoustic foam. Upon ear plugging with acoustic foam, a mild CHL is induced. Furthermore, the CHL induced by acoustic foam results in substantial changes in the magnitudes of both the ITD and ILD cues to sound location. Copyright © 2010 Elsevier B.V. All rights reserved.

The effects of experimentally induced conductive hearing loss on spectral and temporal aspects of sound transmission through the ear

PubMed Central

Lupo, J. Eric; Koka, Kanthaiah; Thornton, Jennifer L.; Tollin, Daniel J.

2010-01-01

Conductive hearing loss (CHL) is known to produce hearing deficits, including deficits in sound localization ability. The differences in sound intensities and timing experienced between the two tympanic membranes are important cues to sound localization (ILD and ITD, respectively). Although much is known about the effect of CHL on hearing levels, little investigation has been conducted into the actual impact of CHL on sound location cues. This study investigated effects of CHL induced by earplugs on cochlear microphonic (CM) amplitude and timing and their corresponding effect on the ILD and ITD location cues. Acoustic and CM measurements were made in 5 chinchillas before and after earplug insertion, and again after earplug removal using pure tones (500 Hz to 24 kHz). ILDs in the unoccluded condition demonstrated position and frequency dependence where peak far-lateral ILDs approached 30 dB for high frequencies. Unoccluded ear ITD cues demonstrated positional and frequency dependence with increased ITD cue for both decreasing frequency (± 420 µs at 500 Hz, ± 310 µs for 1–4 kHz ) and increasingly lateral sound source locations. Occlusion of the ear canal with foam plugs resulted in a mild, frequency-dependent conductive hearing loss of 10–38 dB (mean 31 ± 3.9 dB) leading to a concomitant frequency dependent increase in ILDs at all source locations. The effective ITDs increased in a frequency dependent manner with ear occlusion as a direct result of the acoustic properties of the plugging material, the latter confirmed via acoustical measurements using a model ear canal with varying volumes of acoustic foam. Upon ear plugging with acoustic foam, a mild CHL is induced. Furthermore, the CHL induced by acoustic foam results in substantial changes in the magnitudes of both the ITD and ILD cues to sound location. PMID:21073935

Efficacy and safety of tranexamic acid as an emetic in dogs.

PubMed

Kakiuchi, Hitoshi; Kawarai-Shimamura, Asako; Fujii, Yoko; Aoki, Takuma; Yoshiike, Masaki; Arai, Hayato; Nakamura, Atsushi; Orito, Kensuke

2014-12-01

To determine dose dependency of tranexamic acid-induced emesis and the time course of the antifibrinolytic potency of tranexamic acid in dogs. 10 Beagles. In a dose-escalating experiment, ascending doses of tranexamic acid (10, 20, and 30 mg/kg, IV) were administered at 5-minute intervals until vomiting was observed. In a separate single-dose experiment, ascending doses of tranexamic acid (20, 30, 40, and 50 mg/kg, IV) were administered at 1-week intervals until vomiting was observed. Time to onset of vomiting and number of vomiting episodes were measured in both experiments. In a coagulation experiment, a single 50 mg/kg bolus of tranexamic acid was administered, and blood was obtained 1 hour before and 20 minutes, 3 hours, and 24 hours after administration. Antifibrinolytic potency of tranexamic acid was evaluated by use of a modified rotational thromboelastography method. Tranexamic acid induced vomiting in a dose-dependent manner. Vomiting frequency was ≤ 2 episodes, and vomiting concluded ≤ 250 seconds after administration. Antifibrinolytic potency of tranexamic acid was significantly higher at 20 minutes following administration, but not different by 24 hours, when compared with the potency measured before administration. No adverse effects were observed in any experiment. IV administration of tranexamic acid induced emesis in a dose-dependent manner. The antifibrinolytic potency of tranexamic acid decreased in a time-dependent manner and was resolved ≤ 24 hours after administration. Further studies are warranted to investigate the emetic and other adverse effects of tranexamic acid in dogs of various breeds and ages.

Trigeminal induced arousals during human sleep.

PubMed

Heiser, Clemens; Baja, Jan; Lenz, Franziska; Sommer, J Ulrich; Hörmann, Karl; Herr, Raphael M; Stuck, Boris A

2015-05-01

Arousals caused by external stimuli during human sleep have been studied for most of the sensorial systems. It could be shown that a pure nasal trigeminal stimulus leads to arousals during sleep. The frequency of arousals increases dependent on the stimulus concentration. The aim of the study was to evaluate the influence of different stimulus durations on arousal frequency during different sleep stages. Ten young healthy volunteers with 20 nights of polysomnography were included in the study. Pure trigeminal stimulation with both different concentrations of CO2 (0, 10, 20, 40% v/v) and different stimulus durations (1, 3, 5, and 10 s) were applied during different sleep stages to the volunteers using an olfactometer. The application was performed during different sleep stages (light sleep, deep sleep, REM sleep). The number of arousals increased with rising stimulus duration and stimulus concentration during each sleep stage. Trigeminal stimuli during sleep led to arousals in dose- and time-dependent manner.

Electrophysiological effects of an anti-influenza drug oseltamivir on the guinea-pig atrium: comparison with those of pilsicainide.

PubMed

Takahara, Akira; Suzuki, Sanae; Hagiwara, Mihoko; Nozaki, Shuhei; Sugiyama, Atsushi

2013-01-01

We assessed the effects of oseltamivir on the conduction velocity and effective refractory period in the guinea-pig atrium in comparison with those of a class Ic antiarrhythmic drug pilsicainide. The recording and stimulating electrodes were attached on the epicardium close to the sinus nodal region and on the left atrial appendage. Oseltamivir (10-100 µM) as well as pilsicainide (1-10 µM) decreased the atrial conduction velocity in a frequency-dependent manner. Both drugs also increased the effective refractory period in both atria; but the frequency-dependent property of oseltamivir was lacking in the left atrium, and it was less obvious in the right atrium compared with that of pilsicainide. These results suggest that oseltamivir can directly modify the electrophysiological functions in the guinea-pig atrium possibly via combination of Na(+) and K(+) channel-blocking actions.

Electro-acupuncture stimulation acts on the basal ganglia output pathway to ameliorate motor impairment in Parkinsonian model rats.

PubMed

Jia, Jun; Li, Bo; Sun, Zuo-Li; Yu, Fen; Wang, Xuan; Wang, Xiao-Min

2010-04-01

The role of electro-acupuncture (EA) stimulation on motor symptoms in Parkinson's disease (PD) has not been well studied. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), EA stimulation improved motor impairment in a frequency-dependent manner. Whereas EA stimulation at a low frequency (2 Hz) had no effect, EA stimulation at a high frequency (100 Hz) significantly improved motor coordination. However, neither low nor high EA stimulation could significantly enhance dopamine levels in the striatum. EA stimulation at 100 Hz normalized the MFB lesion-induced increase in midbrain GABA content, but it had no effect on GABA content in the globus pallidus. These results suggest that high-frequency EA stimulation improves motor impairment in MFB-lesioned rats by increasing GABAergic inhibition in the output structure of the basal ganglia.

A "caliper" type of controlled-source, frequency-domain, electromagnetic sounding method

NASA Astrophysics Data System (ADS)

Zhang, W.; Lin, J.; Zhou, F.; Liu, C.; Chen, J.; Xue, K.; Liu, L.; Wu, Y.

2011-12-01

We developed a special measurement manner for controlled-source, frequency-domain, electromagnetic sounding method that can improve resolution and efficiency, called as "caliper". This manner is base on our array electromagnetic system DPS-I, which consists of 53 channels and can cover 2500 m survey line at one arrangement. There are several steps to apply this method. First, a rough measurement is carried out, using large dynamic range but sparse frequencies. The ratio of adjacent frequency is set to be 2 or 4. The frequency points cover the entire frequency band that is required according to the geological environment, and are almost equidistantly distributed at logarithmic axis. Receivers array are arranged in one or more survey lines to measure the amplitude and phase of electromagnetic field components simultaneously. After all frequency points for rough measurement are measured, data in each sub-receiver are transmitted to the controller and the apparent resistivity and phase are calculated in field quickly. Then the pseudo section diagrams of apparent resistivity and phase are drew. By the pseudo section we can roughly lock the abnormal zone and determine the frequency band required for detail investigation of abnormal zone. Next, the measurement using high density of frequencies in this frequency band is carried out, which we called "detailed measurement". The ratio of adjacent frequency in this time is m which lies between 1 and 2. The exact value of m will depend on how detailed that the user expected. After "detailed measurement" is finished, the pseudo section diagrams of apparent resistivity and phase are drew in the same way with the first step. We can see more detailed information about the abnormal zone and decide whether further measurement is necessary. If it is necessary, we can repeat the second step using smaller m until the resolution meet the requirements to distinguish the target. By simulation, we know that high density of frequencies really help us to improve resolution. But we also need to say that the improvement is limited and it will do no help to add frequencies if the frequency is already dense enough. This method not only improves efficiency, but also improves the ability to distinguish the abnormal body. This measurement mode consisting of rough measurement and detailed measurement is similar to the caliper measurement of length, so called "caliper" type. It is accurate and fast. It not only can be applied to frequency-domain sounding, such as controlled source audio -frequency magnetotelluric (CSAMT), but also can be extended to the spectral induced polarization method. By using this measurement manner, high resolution and high-efficiency can be expected.

Method of electric field flow fractionation wherein the polarity of the electric field is periodically reversed

DOEpatents

Stevens, Fred J.

1992-01-01

A novel method of electric field flow fractionation for separating solute molecules from a carrier solution is disclosed. The method of the invention utilizes an electric field that is periodically reversed in polarity, in a time-dependent, wave-like manner. The parameters of the waveform, including amplitude, frequency and wave shape may be varied to optimize separation of solute species. The waveform may further include discontinuities to enhance separation.

Eicosapentaenoic and docosahexaenoic acid ethyl esters differentially enhance B-cell activity in murine obesity[S

PubMed Central

Teague, Heather; Harris, Mitchel; Fenton, Jenifer; Lallemand, Perrine; Shewchuk, Brian M.; Shaikh, Saame Raza

2014-01-01

EPA and DHA are not biologically equivalent; however, their individual activity on B cells is unknown. We previously reported fish oil enhanced murine B-cell activity in obesity. To distinguish between the effects of EPA and DHA, we studied the ethyl esters of EPA and DHA on murine B-cell function as a function of time. We first demonstrate that EPA and DHA maintained the obese phenotype, with no improvements in fat mass, adipose inflammatory cytokines, fasting insulin, or glucose clearance. We then tested the hypothesis that EPA and DHA would increase the frequency of splenic B cells. EPA and DHA differentially enhanced the frequency and/or percentage of select B-cell subsets, correlating with increased natural serum IgM and cecal IgA. We next determined the activities of EPA and DHA on ex vivo production of cytokines upon lipopolysaccharide stimulation of B cells. EPA and DHA, in a time-dependent manner, enhanced B-cell cytokines with DHA notably increasing IL-10. At the molecular level, EPA and DHA differentially enhanced the formation of ordered microdomains but had no effect on Toll-like receptor 4 mobility. Overall, the results establish differential effects of EPA and DHA in a time-dependent manner on B-cell activity in obesity, which has implications for future clinical studies. PMID:24837990

How do the medial olivocochlear efferents influence the biomechanics of the outer hair cells and thereby the cochlear amplifier? Simulation results

NASA Astrophysics Data System (ADS)

Saremi, Amin; Stenfelt, Stefan; Verhulst, Sarah

2015-12-01

The bottom-up signal pathway, which starts from the outer ear and leads to the brain cortices, gives the classic image of the human sound perception. However, there have been growing evidences in the last six decades for existence of a functional descending network whereby the central auditory system can modulate the early auditory processing, in a top-down manner. The medial olivocochlear efferent fibers project from the superior olivary complex at the brainstem into the inner ear. They are linked to the basal poles of the hair cells by forming synaptic cisterns. This descending network can activate nicotinic cholinergic receptors (nAChR) that increase the membrane conductance of the outer hair cells and thereby modify the magnitude of the active force generated inside the cochlea. The aim of the presented work is to quantitatively investigate how the changes in the biomechanics of the outer hair cells, caused by the efferent activation, manipulate the cochlear responses. This is done by means of a frequency-domain biophysical model of the cochlea [12] where the parameters of the model convey physiological interpretations of the human cochlear structures. The simulations manifest that a doubling of the outer hair cell conductance, due to efferent activation, leads to a frequency-dependent gain reduction along the cochlear duct with its highest effect at frequencies between 1 kHz and 3.5 kHz and a maximum of approximately 10 dB gain reduction at 2 kHz. This amount of the gain inhibition and its frequency dependence reasonably agrees with the experimental data recorded from guinea pig, cat and human cochleae where the medial olivococlear efferents had been elicited by broad-band stimuli. The simulations also indicate that the efferent-induced increase of the outer hair cell conductance increases the best frequency of the cochlear responses, in the basal region. The presented simulations quantitatively confirm that activation of the medial olivocochlear efferents can biomechanically manipulate the cochlear responses, in a top-down manner, by inhibiting the gain of the cochlear amplifier as well as altering the frequency-position map (tuning pattern) of the cochlea.

Frequency dependence 3.0: an attempt at codifying the evolutionary ecology perspective.

PubMed

Metz, Johan A J; Geritz, Stefan A H

2016-03-01

The fitness concept and perforce the definition of frequency independent fitnesses from population genetics is closely tied to discrete time population models with non-overlapping generations. Evolutionary ecologists generally focus on trait evolution through repeated mutant substitutions in populations with complicated life histories. This goes with using the per capita invasion speed of mutants as their fitness. In this paper we develop a concept of frequency independence that attempts to capture the practical use of the term by ecologists, which although inspired by population genetics rarely fits its strict definition. We propose to call the invasion fitnesses of an eco-evolutionary model frequency independent when the phenotypes can be ranked by competitive strength, measured by who can invade whom. This is equivalent to the absence of weak priority effects, protected dimorphisms and rock-scissor-paper configurations. Our concept differs from that of Heino et al. (TREE 13:367-370, 1998) in that it is based only on the signs of the invasion fitnesses, whereas Heino et al. based their definitions on the structure of the feedback environment, summarising the effect of all direct and indirect interactions between individuals on fitness. As it turns out, according to our new definition an eco-evolutionary model has frequency independent fitnesses if and only if the effect of the feedback environment on the fitness signs can be summarised by a single scalar with monotonic effect. This may be compared with Heino et al.'s concept of trivial frequency dependence defined by the environmental feedback influencing fitness, and not just its sign, in a scalar manner, without any monotonicity restriction. As it turns out, absence of the latter restriction leaves room for rock-scissor-paper configurations. Since in 'realistic' (as opposed to toy) models frequency independence is exceedingly rare, we also define a concept of weak frequency dependence, which can be interpreted intuitively as almost frequency independence, and analyse in which sense and to what extent the restrictions on the potential model outcomes of the frequency independent case stay intact for models with weak frequency dependence.

Supramodal parametric working memory processing in humans.

PubMed

Spitzer, Bernhard; Blankenburg, Felix

2012-03-07

Previous studies of delayed-match-to-sample (DMTS) frequency discrimination in animals and humans have succeeded in delineating the neural signature of frequency processing in somatosensory working memory (WM). During retention of vibrotactile frequencies, stimulus-dependent single-cell and population activity in prefrontal cortex was found to reflect the task-relevant memory content, whereas increases in occipital alpha activity signaled the disengagement of areas not relevant for the tactile task. Here, we recorded EEG from human participants to determine the extent to which these mechanisms can be generalized to frequency retention in the visual and auditory domains. Subjects performed analogous variants of a DMTS frequency discrimination task, with the frequency information presented either visually, auditorily, or by vibrotactile stimulation. Examining oscillatory EEG activity during frequency retention, we found characteristic topographical distributions of alpha power over visual, auditory, and somatosensory cortices, indicating systematic patterns of inhibition and engagement of early sensory areas, depending on stimulus modality. The task-relevant frequency information, in contrast, was found to be represented in right prefrontal cortex, independent of presentation mode. In each of the three modality conditions, parametric modulations of prefrontal upper beta activity (20-30 Hz) emerged, in a very similar manner as recently found in vibrotactile tasks. Together, the findings corroborate a view of parametric WM as supramodal internal scaling of abstract quantity information and suggest strong relevance of previous evidence from vibrotactile work for a more general framework of quantity processing in human working memory.

Population receptive field (pRF) measurements of chromatic responses in human visual cortex using fMRI.

PubMed

Welbourne, Lauren E; Morland, Antony B; Wade, Alex R

2018-02-15

The spatial sensitivity of the human visual system depends on stimulus color: achromatic gratings can be resolved at relatively high spatial frequencies while sensitivity to isoluminant color contrast tends to be more low-pass. Models of early spatial vision often assume that the receptive field size of pattern-sensitive neurons is correlated with their spatial frequency sensitivity - larger receptive fields are typically associated with lower optimal spatial frequency. A strong prediction of this model is that neurons coding isoluminant chromatic patterns should have, on average, a larger receptive field size than neurons sensitive to achromatic patterns. Here, we test this assumption using functional magnetic resonance imaging (fMRI). We show that while spatial frequency sensitivity depends on chromaticity in the manner predicted by behavioral measurements, population receptive field (pRF) size measurements show no such dependency. At any given eccentricity, the mean pRF size for neuronal populations driven by luminance, opponent red/green and S-cone isolating contrast, are identical. Changes in pRF size (for example, an increase with eccentricity and visual area hierarchy) are also identical across the three chromatic conditions. These results suggest that fMRI measurements of receptive field size and spatial resolution can be decoupled under some circumstances - potentially reflecting a fundamental dissociation between these parameters at the level of neuronal populations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Ghrelin decreases firing activity of gonadotropin-releasing hormone (GnRH) neurons in an estrous cycle and endocannabinoid signaling dependent manner.

PubMed

Farkas, Imre; Vastagh, Csaba; Sárvári, Miklós; Liposits, Zsolt

2013-01-01

The orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R) in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca(2+)-imaging revealed a ghrelin-triggered increase of the Ca(2+)-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10 µM) suggesting direct action of ghrelin. Estradiol (1nM) eliminated the ghrelin-evoked rise of Ca(2+)-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40 nM-4 μM) administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1) antagonist AM251 (1µM) and the intracellularly applied DAG-lipase inhibitor THL (10 µM), indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner.

Electrohydrodynamic deposition of polymeric droplets under low-frequency pulsation.

PubMed

Xu, Lei; Wang, Xiang; Lei, Tingping; Sun, Daoheng; Lin, Liwei

2011-05-17

Circularly shaped polymeric droplets with diameter of about 20 μm have been intermittently ejected and deposited in an orderly manner on a collector from a syringe needle by means of near-field, electrohydrodynamic reactions using pulsating voltages at around 2.25 kV. The needle has an inner diameter of 100 μm and was placed 1 mm above a silicon conductor substrate to have location control for droplet depositions. Under low-frequency operation of less than 100 Hz, the deposition frequency of droplets, f(dep), has been observed to be equal to the frequency of the applied driving voltage divided by an integer, N, as small as 1. Furthermore, the diameter of the deposited droplets has been found to be linearly dependent on (Q/f(dep))(1/3), where Q is the polymer solution supply rate at around 30 nL/s. These experimentally observed droplet ejection rules under low-frequency pulsation provide useful design guidelines for controllable deposition of polymer droplets in various potential applications, including electrohydrodynamic printing.

Discomfort during lateral acceleration: influence of seat cushion and backrest.

PubMed

Beard, George F; Griffin, Michael J

2013-07-01

Lateral acceleration causes discomfort but how the discomfort depends on the frequency of acceleration or characteristics of seating is poorly understood. Using magnitude estimation, twelve male subjects rated the discomfort caused by lateral oscillation at eight frequencies (0.2-1.0 Hz) across four seating conditions (a rigid seat and a train seat, both with and without backrests). Discomfort increased with increasing frequency of lateral acceleration in a similar manner for all four seating conditions. However, at all frequencies and with both seats there was less discomfort when sitting with backrest support than without. Least discomfort occurred on the train seat with backrest and greatest discomfort on the rigid seat without backrest. Current standards predict an additive effect of backrest on vibration discomfort, but the findings show that low frequency lateral acceleration can cause less discomfort when sitting with a backrest than when sitting on the same seat without a backrest. Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.

2013 Workplace and Equal Opportunity Survey of Active Duty Members: Tabulations Responses

DTIC Science & Technology

2014-03-01

can be defined as the frequency which people in the workplace act in an angry or hostile manner toward personnel...angry or hostile manner toward personnel. Percent Responding Mean Max ME Workplace Hostility TOTAL DOD 96 ±1 1.9 ±0.1 Enlisted 96 ±1 2.0...be defined as the frequency which people in the workplace act in an angry or hostile manner toward personnel. Percent Responding Mean Max ME

Replication Rate, Framing, and Format Affect Attitudes and Decisions about Science Claims.

PubMed

Barnes, Ralph M; Tobin, Stephanie J; Johnston, Heather M; MacKenzie, Noah; Taglang, Chelsea M

2016-01-01

A series of five experiments examined how the evaluation of a scientific finding was influenced by information about the number of studies that had successfully replicated the initial finding. The experiments also tested the impact of frame (negative, positive) and numeric format (percentage, natural frequency) on the evaluation of scientific findings. In Experiments 1 through 4, an attitude difference score served as the dependent measure, while a measure of choice served as the dependent measure in Experiment 5. Results from a diverse sample of 188 non-institutionalized U.S. adults (Experiment 2) and 730 undergraduate college students (Experiments 1, 3, and 4) indicated that attitudes became more positive as the replication rate increased and attitudes were more positive when the replication information was framed positively. The results also indicate that the manner in which replication rate was framed had a greater impact on attitude than the replication rate itself. The large effect for frame was attenuated somewhat when information about replication was presented in the form of natural frequencies rather than percentages. A fifth study employing 662 undergraduate college students in a task in which choice served as the dependent measure confirmed the framing effect and replicated the replication rate effect in the positive frame condition, but provided no evidence that the use of natural frequencies diminished the effect.

Thresholding of auditory cortical representation by background noise

PubMed Central

Liang, Feixue; Bai, Lin; Tao, Huizhong W.; Zhang, Li I.; Xiao, Zhongju

2014-01-01

It is generally thought that background noise can mask auditory information. However, how the noise specifically transforms neuronal auditory processing in a level-dependent manner remains to be carefully determined. Here, with in vivo loose-patch cell-attached recordings in layer 4 of the rat primary auditory cortex (A1), we systematically examined how continuous wideband noise of different levels affected receptive field properties of individual neurons. We found that the background noise, when above a certain critical/effective level, resulted in an elevation of intensity threshold for tone-evoked responses. This increase of threshold was linearly dependent on the noise intensity above the critical level. As such, the tonal receptive field (TRF) of individual neurons was translated upward as an entirety toward high intensities along the intensity domain. This resulted in preserved preferred characteristic frequency (CF) and the overall shape of TRF, but reduced frequency responding range and an enhanced frequency selectivity for the same stimulus intensity. Such translational effects on intensity threshold were observed in both excitatory and fast-spiking inhibitory neurons, as well as in both monotonic and nonmonotonic (intensity-tuned) A1 neurons. Our results suggest that in a noise background, fundamental auditory representations are modulated through a background level-dependent linear shifting along intensity domain, which is equivalent to reducing stimulus intensity. PMID:25426029

Ptychodiscus brevis toxin enhances the frequency-dependent depression of the monosynaptic reflex in neonatal rat spinal cord in vitro.

PubMed

Deshpande, S B; Singh, J N; Das Gupta, S

2003-12-10

The involvement of frequency-dependent depression (FDD) of synaptic transmission for the depressant action of the Ptychodiscus brevis toxin (PbTx) was investigated in neonatal rat spinal cord in vitro. The stimulation of a dorsal root by train of pulses (five stimuli) at different frequencies evoked potentials in the ventral root (monosynaptic reflex, MSR). Amplitude of the fifth response as percent of first response at 0.1, 0.2, 0.5, 1.0 and 2.0 Hz were 90, 80, 75, 70 and 50%, respectively. In Mg2+-free medium, PbTx depressed the MSR and also enhanced the FDD in a concentration-dependent manner. Further, the PbTx-induced depression can well be correlated with the enhancement of FDD (r=0.98). In the presence of Mg2+ (1.3 mM), the FDD was greater than that in the absence of Mg2+. But in the presence of Mg2+ PbTx did not alter FDD, even though there was 25% depression at 28 microM (significantly lesser than in Mg2+-free medium). The results indicate that the Mg2+-sensitive component of PbTx-induced depression of MSR is mediated via the neuronal systems involving FDD.

40 CFR 141.204 - Tier 3 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.204 Tier 3 Public Notice—Form, manner, and frequency of notice. (a) Which... exemption granted under Section 1416 of the Safe Drinking Water Act; (4) Availability of unregulated...

40 CFR 141.204 - Tier 3 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.204 Tier 3 Public Notice—Form, manner, and frequency of notice. (a) Which... exemption granted under Section 1416 of the Safe Drinking Water Act; (4) Availability of unregulated...

40 CFR 141.204 - Tier 3 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.204 Tier 3 Public Notice—Form, manner, and frequency of notice. (a) Which... exemption granted under Section 1416 of the Safe Drinking Water Act; (4) Availability of unregulated...

40 CFR 141.204 - Tier 3 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.204 Tier 3 Public Notice—Form, manner, and frequency of notice. (a) Which... exemption granted under Section 1416 of the Safe Drinking Water Act; (4) Availability of unregulated...

40 CFR 141.204 - Tier 3 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2010 CFR

2010-07-01

... exemption granted under Section 1416 of the Safe Drinking Water Act; (4) Availability of unregulated... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.204 Tier 3 Public Notice—Form, manner, and frequency of notice. (a) Which...

Equivalent circuit for the characterization of the resonance mode in piezoelectric systems

NASA Astrophysics Data System (ADS)

Fernández-Afonso, Y.; García-Zaldívar, O.; Calderón-Piñar, F.

2015-12-01

The impedance properties in polarized piezoelectric can be described by electric equivalent circuits. The classic circuit used in the literature to describe real systems is formed by one resistor (R), one inductance (L) and one capacitance C connected in series and one capacity (C0) connected in parallel with the formers. Nevertheless, the equation that describe the resonance and anti-resonance frequencies depends on a complex manner of R, L, C and C0. In this work is proposed a simpler model formed by one inductance (L) and one capacity (C) in series; one capacity (C0) in parallel; one resistor (RP) in parallel and one resistor (RS) in series with other components. Unlike the traditional circuit, the equivalent circuit elements in the proposed model can be simply determined by knowing the experimental values of the resonance frequency fr, anti-resonance frequency fa, impedance module at resonance frequency |Zr|, impedance module at anti-resonance frequency |Za| and low frequency capacitance C0, without fitting the impedance experimental data to the obtained equation.

Time-dependent nonlinear Jaynes-Cummings dynamics of a trapped ion

NASA Astrophysics Data System (ADS)

Krumm, F.; Vogel, W.

2018-04-01

In quantum interaction problems with explicitly time-dependent interaction Hamiltonians, the time ordering plays a crucial role for describing the quantum evolution of the system under consideration. In such complex scenarios, exact solutions of the dynamics are rarely available. Here we study the nonlinear vibronic dynamics of a trapped ion, driven in the resolved sideband regime with some small frequency mismatch. By describing the pump field in a quantized manner, we are able to derive exact solutions for the dynamics of the system. This eventually allows us to provide analytical solutions for various types of time-dependent quantities. In particular, we study in some detail the electronic and the motional quantum dynamics of the ion, as well as the time evolution of the nonclassicality of the motional quantum state.

40 CFR 141.202 - Tier 1 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Detection of E. coli, enterococci, or coliphage in source water samples as specified in § 141.402(a) and... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.202 Tier 1 Public Notice—Form, manner, and frequency of notice. (a) Which...

CK-2127107 amplifies skeletal muscle response to nerve activation in humans.

PubMed

Andrews, Jinsy A; Miller, Timothy M; Vijayakumar, Vipin; Stoltz, Randall; James, Joyce K; Meng, Lisa; Wolff, Andrew A; Malik, Fady I

2018-05-01

Three studies evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of CK-2127107 (CK-107), a next-generation fast skeletal muscle troponin activator (FSTA), in healthy participants. We tested the hypothesis that CK-107 would amplify the force-frequency response of muscle in humans. To assess the force-frequency response, participants received single doses of CK-107 and placebo in a randomized, double-blind, 4-period, crossover study. The force-frequency response of foot dorsiflexion following stimulation of the deep fibular nerve to activate the tibialis anterior muscle was assessed. CK-107 significantly increased tibialis anterior muscle response with increasing dose and plasma concentration in a frequency-dependent manner; the largest increase in peak force was ∼60% at 10 Hz. CK-107 appears more potent and produced larger increases in force than tirasemtiv-a first-generation FSTA-in a similar pharmacodynamic study, thereby supporting its development for improvement of muscle function of patients. Muscle Nerve 57: 729-734, 2018. © 2017 The Authors. Muscle & Nerve published by Wiley Periodicals, Inc.

Numerical analysis of effects of transglottal pressure change on fundamental frequency of phonation.

PubMed

Deguchi, Shinji; Matsuzaki, Yuji; Ikeda, Tadashige

2007-02-01

In humans, a decrease in transglottal pressure (Pt) causes an increase in the fundamental frequency of phonation (F0) only at a specific voice pitch within the modal register, the mechanism of which remains unclear. In the present study, numerical analyses were performed to investigate the mechanism of the voice pitch-dependent positive change of F0 due to Pt decrease. The airflow and the airway, including the vocal folds, were modeled in terms of mechanics of fluid and structure. Simulations of phonation using the numerical model indicated that Pt affects both the average position and the average amplitude magnitude of vocal fold self-excited oscillation in a non-monotonous manner. This effect results in voice pitch-dependent responses of F0 to Pt decreases, including the positive response of F0 as actually observed in humans. The findings of the present study highlight the importance of considering self-excited oscillation of the vocal folds in elucidation of the phonation mechanism.

Coda Q and its Frequency Dependence in the Eastern Himalayan and Indo-Burman Plate Boundary Systems

NASA Astrophysics Data System (ADS)

Mitra, S.; Kumar, A.

2015-12-01

We use broadband waveform data for 305 local earthquakes from the Eastern Himalayan and Indo-Burman plate boundary systems, to model the seismic attenuation in NE India. We measure the decay in amplitude of coda waves at discreet frequencies (between 1 and 12Hz) to evaluate the quality factor (Qc) as a function of frequency. We combine these measurements to evaluate the frequency dependence of Qc of the form Qc(f)=Qof η, where Qo is the quality factor at 1Hz and η is the frequency dependence. Computed Qo values range from 80-360 and η ranges from 0.85-1.45. To study the lateral variation in Qo and η, we regionalise the Qc by combining all source-receiver measurements using a back-projection algorithm. For a single back scatter model, the coda waves sample an elliptical area with the epicenter and receiver at the two foci. We parameterize the region using square grids. The algorithm calculates the overlap in area and distributes Qc in the sampled grids using the average Qc as the boundary value. This is done in an iterative manner, by minimising the misfit between the observed and computed Qc within each grid. This process is repeated for all frequencies and η is computed for each grid by combining Qc for all frequencies. Our results reveal strong variation in Qo and η across NE India. The highest Qo are in the Bengal Basin (210-280) and the Indo-Burman subduction zone (300-360). The Shillong Plateau and Mikir Hills have intermediate Qo (~160) and the lowest Qo (~80) is observed in the Naga fold thrust belt. This variation in Qo demarcates the boundary between the continental crust beneath the Shillong Plateau and Mikir Hills and the transitional to oceanic crust beneath the Bengal Basin and Indo-Burman subduction zone. Thick pile of sedimentary strata in the Naga fold thrust belt results in the low Qo. Frequency dependence (η) of Qc across NE India is observed to be very high, with regions of high Qo being associated with relatively higher η.

Computational study of noise in a large signal transduction network.

PubMed

Intosalmi, Jukka; Manninen, Tiina; Ruohonen, Keijo; Linne, Marja-Leena

2011-06-21

Biochemical systems are inherently noisy due to the discrete reaction events that occur in a random manner. Although noise is often perceived as a disturbing factor, the system might actually benefit from it. In order to understand the role of noise better, its quality must be studied in a quantitative manner. Computational analysis and modeling play an essential role in this demanding endeavor. We implemented a large nonlinear signal transduction network combining protein kinase C, mitogen-activated protein kinase, phospholipase A2, and β isoform of phospholipase C networks. We simulated the network in 300 different cellular volumes using the exact Gillespie stochastic simulation algorithm and analyzed the results in both the time and frequency domain. In order to perform simulations in a reasonable time, we used modern parallel computing techniques. The analysis revealed that time and frequency domain characteristics depend on the system volume. The simulation results also indicated that there are several kinds of noise processes in the network, all of them representing different kinds of low-frequency fluctuations. In the simulations, the power of noise decreased on all frequencies when the system volume was increased. We concluded that basic frequency domain techniques can be applied to the analysis of simulation results produced by the Gillespie stochastic simulation algorithm. This approach is suited not only to the study of fluctuations but also to the study of pure noise processes. Noise seems to have an important role in biochemical systems and its properties can be numerically studied by simulating the reacting system in different cellular volumes. Parallel computing techniques make it possible to run massive simulations in hundreds of volumes and, as a result, accurate statistics can be obtained from computational studies. © 2011 Intosalmi et al; licensee BioMed Central Ltd.

Noise Trauma Induced Plastic Changes in Brain Regions outside the Classical Auditory Pathway

PubMed Central

Chen, Guang-Di; Sheppard, Adam; Salvi, Richard

2017-01-01

The effects of intense noise exposure on the classical auditory pathway have been extensively investigated; however, little is known about the effects of noise-induced hearing loss on non-classical auditory areas in the brain such as the lateral amygdala (LA) and striatum (Str). To address this issue, we compared the noise-induced changes in spontaneous and tone-evoked responses from multiunit clusters (MUC) in the LA and Str with those seen in auditory cortex (AC). High-frequency octave band noise (10–20 kHz) and narrow band noise (16–20 kHz) induced permanent thresho ld shifts (PTS) at high-frequencies within and above the noise band but not at low frequencies. While the noise trauma significantly elevated spontaneous discharge rate (SR) in the AC, SRs in the LA and Str were only slightly increased across all frequencies. The high-frequency noise trauma affected tone-evoked firing rates in frequency and time dependent manner and the changes appeared to be related to severity of noise trauma. In the LA, tone-evoked firing rates were reduced at the high-frequencies (trauma area) whereas firing rates were enhanced at the low-frequencies or at the edge-frequency dependent on severity of hearing loss at the high frequencies. The firing rate temporal profile changed from a broad plateau to one sharp, delayed peak. In the AC, tone-evoked firing rates were depressed at high frequencies and enhanced at the low frequencies while the firing rate temporal profiles became substantially broader. In contrast, firing rates in the Str were generally decreased and firing rate temporal profiles become more phasic and less prolonged. The altered firing rate and pattern at low frequencies induced by high frequency hearing loss could have perceptual consequences. The tone-evoked hyperactivity in low-frequency MUC could manifest as hyperacusis whereas the discharge pattern changes could affect temporal resolution and integration. PMID:26701290

40 CFR 141.202 - Tier 1 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., or coliphage in source water samples as specified in § 141.402(a) and § 141.402(b); (9) Other... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.202 Tier 1 Public Notice—Form, manner, and frequency of notice. (a) Which...

40 CFR 141.202 - Tier 1 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., or coliphage in source water samples as specified in § 141.402(a) and § 141.402(b); (9) Other... (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Public Notification of Drinking Water Violations § 141.202 Tier 1 Public Notice—Form, manner, and frequency of notice. (a) Which...

Metabolic gene regulation in a dynamically changing environment.

PubMed

Bennett, Matthew R; Pang, Wyming Lee; Ostroff, Natalie A; Baumgartner, Bridget L; Nayak, Sujata; Tsimring, Lev S; Hasty, Jeff

2008-08-28

Natural selection dictates that cells constantly adapt to dynamically changing environments in a context-dependent manner. Gene-regulatory networks often mediate the cellular response to perturbation, and an understanding of cellular adaptation will require experimental approaches aimed at subjecting cells to a dynamic environment that mimics their natural habitat. Here we monitor the response of Saccharomyces cerevisiae metabolic gene regulation to periodic changes in the external carbon source by using a microfluidic platform that allows precise, dynamic control over environmental conditions. We show that the metabolic system acts as a low-pass filter that reliably responds to a slowly changing environment, while effectively ignoring fast fluctuations. The sensitive low-frequency response was significantly faster than in predictions arising from our computational modelling, and this discrepancy was resolved by the discovery that two key galactose transcripts possess half-lives that depend on the carbon source. Finally, to explore how induction characteristics affect frequency response, we compare two S. cerevisiae strains and show that they have the same frequency response despite having markedly different induction properties. This suggests that although certain characteristics of the complex networks may differ when probed in a static environment, the system has been optimized for a robust response to a dynamically changing environment.

Dietary Phenethyl Isothiocyanate Protects Mice from Colitis Associated Colon Cancer.

PubMed

Liu, Yi; Dey, Moul

2017-09-06

We have previously reported alleviation of dextran sodium sulfate (DSS)-induced ulcerative colitis signs in phenethyl isothiocyanate (PEITC)-treated mice. Here we investigated chemoprotective activities of PEITC in mice with Azoxymethane-DSS induced colitis associated colon carcinogenesis. We also examined the molecular mediators associated with the PEITC effects using relevant cell lines. A 0.12% PEITC-enriched mouse-diet reduced mucosal and submucosal inflammation as well as glandular atypia by 12% and the frequency of adenocarcinoma by 17% with a concomitant improvement in overall disease activity indices compared to the diseased control group. Lipopolysaccharide-induced in vitro up-regulation of key mediators of inflammation, immune response, apoptosis, and cell proliferation were attenuated by 10 μM PEITC. Three of these mediators showed concentration-dependent reduction in respective mRNAs. Furthermore, PEITC inhibited Nuclear factor kappa B1 (NFκB1) proteins in a concentration-dependent manner. The NFκB1 mRNA expression inversely correlated ( r = −0.940, p = 0.013) with tri-methylation of lysine 27 on histone 3 near its promoter region in a time-dependent manner. These results indicate that PEITC may slow down the development of colon carcinogenesis in an inflammatory intestinal setting which is potentially associated with epigenetic modulation of NFκB1 signaling.

Frequency-dependent tACS modulation of BOLD signal during rhythmic visual stimulation.

PubMed

Chai, Yuhui; Sheng, Jingwei; Bandettini, Peter A; Gao, Jia-Hong

2018-05-01

Transcranial alternating current stimulation (tACS) has emerged as a promising tool for modulating cortical oscillations. In previous electroencephalogram (EEG) studies, tACS has been found to modulate brain oscillatory activity in a frequency-specific manner. However, the spatial distribution and hemodynamic response for this modulation remains poorly understood. Functional magnetic resonance imaging (fMRI) has the advantage of measuring neuronal activity in regions not only below the tACS electrodes but also across the whole brain with high spatial resolution. Here, we measured fMRI signal while applying tACS to modulate rhythmic visual activity. During fMRI acquisition, tACS at different frequencies (4, 8, 16, and 32 Hz) was applied along with visual flicker stimulation at 8 and 16 Hz. We analyzed the blood-oxygen-level-dependent (BOLD) signal difference between tACS-ON vs tACS-OFF, and different frequency combinations (e.g., 4 Hz tACS, 8 Hz flicker vs 8 Hz tACS, 8 Hz flicker). We observed significant tACS modulation effects on BOLD responses when the tACS frequency matched the visual flicker frequency or the second harmonic frequency. The main effects were predominantly seen in regions that were activated by the visual task and targeted by the tACS current distribution. These findings bridge different scientific domains of tACS research and demonstrate that fMRI could localize the tACS effect on stimulus-induced brain rhythms, which could lead to a new approach for understanding the high-level cognitive process shaped by the ongoing oscillatory signal. © 2018 Wiley Periodicals, Inc.

Restoration of middle-ear input in fluid-filled middle ears by controlled introduction of air or a novel air-filled implant.

PubMed

Ravicz, Michael E; Chien, Wade W; Rosowski, John J

2015-10-01

The effect of small amounts of air on sound-induced umbo velocity in an otherwise saline-filled middle ear (ME) was investigated to examine the efficacy of a novel balloon-like air-filled ME implant suitable for patients with chronically non-aerated MEs. In this study, air bubbles or air-filled implants were introduced into saline-filled human cadaveric MEs. Umbo velocity, a convenient measure of ME response, served as an indicator of hearing sensitivity. Filling the ME with saline reduced umbo velocity by 25-30 dB at low frequencies and more at high frequencies, consistent with earlier work (Ravicz et al., Hear. Res. 195: 103-130 (2004)). Small amounts of air (∼30 μl) in the otherwise saline-filled ME increased umbo velocity substantially, to levels only 10-15 dB lower than in the dry ME, in a frequency- and location-dependent manner: air in contact with the tympanic membrane (TM) increased umbo velocity at all frequencies, while air located away from the TM increased umbo velocity only below about 500 Hz. The air-filled implant also affected umbo velocity in a manner similar to an air bubble of equivalent compliance. Inserting additional implants into the ME had the same effect as increasing air volume. These results suggest these middle-ear implants would significantly reduce conductive hearing loss in patients with chronically fluid-filled MEs. Copyright © 2015 Elsevier B.V. All rights reserved.

Replication Rate, Framing, and Format Affect Attitudes and Decisions about Science Claims

PubMed Central

Barnes, Ralph M.; Tobin, Stephanie J.; Johnston, Heather M.; MacKenzie, Noah; Taglang, Chelsea M.

2016-01-01

A series of five experiments examined how the evaluation of a scientific finding was influenced by information about the number of studies that had successfully replicated the initial finding. The experiments also tested the impact of frame (negative, positive) and numeric format (percentage, natural frequency) on the evaluation of scientific findings. In Experiments 1 through 4, an attitude difference score served as the dependent measure, while a measure of choice served as the dependent measure in Experiment 5. Results from a diverse sample of 188 non-institutionalized U.S. adults (Experiment 2) and 730 undergraduate college students (Experiments 1, 3, and 4) indicated that attitudes became more positive as the replication rate increased and attitudes were more positive when the replication information was framed positively. The results also indicate that the manner in which replication rate was framed had a greater impact on attitude than the replication rate itself. The large effect for frame was attenuated somewhat when information about replication was presented in the form of natural frequencies rather than percentages. A fifth study employing 662 undergraduate college students in a task in which choice served as the dependent measure confirmed the framing effect and replicated the replication rate effect in the positive frame condition, but provided no evidence that the use of natural frequencies diminished the effect. PMID:27920743

Influence of combined visual and vestibular cues on human perception and control of horizontal rotation

NASA Technical Reports Server (NTRS)

Zacharias, G. L.; Young, L. R.

1981-01-01

Measurements are made of manual control performance in the closed-loop task of nulling perceived self-rotation velocity about an earth-vertical axis. Self-velocity estimation is modeled as a function of the simultaneous presentation of vestibular and peripheral visual field motion cues. Based on measured low-frequency operator behavior in three visual field environments, a parallel channel linear model is proposed which has separate visual and vestibular pathways summing in a complementary manner. A dual-input describing function analysis supports the complementary model; vestibular cues dominate sensation at higher frequencies. The describing function model is extended by the proposal of a nonlinear cue conflict model, in which cue weighting depends on the level of agreement between visual and vestibular cues.

Waveform selectivity at the same frequency.

PubMed

Wakatsuchi, Hiroki; Anzai, Daisuke; Rushton, Jeremiah J; Gao, Fei; Kim, Sanghoon; Sievenpiper, Daniel F

2015-04-13

Electromagnetic properties depend on the composition of materials, i.e. either angstrom scales of molecules or, for metamaterials, subwavelength periodic structures. Each material behaves differently in accordance with the frequency of an incoming electromagnetic wave due to the frequency dispersion or the resonance of the periodic structures. This indicates that if the frequency is fixed, the material always responds in the same manner unless it has nonlinearity. However, such nonlinearity is controlled by the magnitude of the incoming wave or other bias. Therefore, it is difficult to distinguish different incoming waves at the same frequency. Here we present a new concept of circuit-based metasurfaces to selectively absorb or transmit specific types of waveforms even at the same frequency. The metasurfaces, integrated with schottky diodes as well as either capacitors or inductors, selectively absorb short or long pulses, respectively. The two types of circuit elements are then combined to absorb or transmit specific waveforms in between. This waveform selectivity gives us another degree of freedom to control electromagnetic waves in various fields including wireless communications, as our simulation reveals that the metasurfaces are capable of varying bit error rates in response to different waveforms.

Dendritic small conductance calcium-activated potassium channels activated by action potentials suppress EPSPs and gate spike-timing dependent synaptic plasticity.

PubMed

Jones, Scott L; To, Minh-Son; Stuart, Greg J

2017-10-23

Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs). This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. In cortical pyramidal neurons EPSP suppression by preceding APs depended on their precise timing as well as the distance of activated synapses from the soma, was dendritic in origin, and involved SK-dependent suppression of NMDA receptor activation. As a result SK channel activation by backpropagating APs gated STDP induction during low-frequency AP-EPSP pairing, with both LTP and LTD absent under control conditions but present after SK channel block. These findings indicate that activation of SK channels in spines by backpropagating APs plays a key role in regulating both EPSP amplitude and STDP induction.

The interrelationship between disease severity, dynamic stability, and falls in cerebellar ataxia.

PubMed

Schniepp, Roman; Schlick, Cornelia; Pradhan, Cauchy; Dieterich, Marianne; Brandt, Thomas; Jahn, Klaus; Wuehr, Max

2016-07-01

Cerebellar ataxia (CA) results in discoordination of body movements (ataxia), a gait disorder, and falls. All three aspects appear to be obviously interrelated; however, experimental evidence is sparse. This study systematically correlated the clinical rating of the severity of ataxia with dynamic stability measures and the fall frequency in patients with CA. Clinical severity of CA in patients with sporadic (n = 34) and hereditary (n = 24) forms was assessed with the Scale for the Assessment and Rating of Ataxia (SARA). Gait performance was examined during slow, preferred, and maximally fast walking speeds. Spatiotemporal variability parameters in the fore-aft and medio-lateral directions were analyzed. The fall frequency was assessed using a standardized interview about fall events within the last 6 months. Fore-aft gait variability showed significant speed-dependent characteristics with highest magnitudes during slow and fast walking. The SARA score correlated positively with fore-aft gait variability, most prominently during fast walking. The fall frequency was significantly associated to fore-aft gait variability during slow walking. Severity of ataxia, dynamic stability, and the occurrence of falls were interrelated in a speed-dependent manner: (a) Severity of ataxia symptoms was closely related to instability during fast walking. (b) Fall frequency was associated with instability during slow walking. These findings suggest the presence of a speed-dependent, twofold cerebellar locomotor control. Assessment of gait performance during non-preferred, slow and fast walking speeds provides novel insights into the pathophysiology of cerebellar locomotor control and may become a useful approach in the clinical evaluation of patients with CA.

Difference and similarity of dielectric relaxation processes among polyols

NASA Astrophysics Data System (ADS)

Minoguchi, Ayumi; Kitai, Kei; Nozaki, Ryusuke

2003-09-01

Complex permittivity measurements were performed on sorbitol, xylitol, and sorbitol-xylitol mixture in the supercooled liquid state in an extremely wide frequency range from 10 μHz to 500 MHz at temperatures near and above the glass transition temperature. We determined detailed behavior of the relaxation parameters such as relaxation frequency and broadening against temperature not only for the α process but also for the β process above the glass transition temperature, to the best of our knowledge, for the first time. Since supercooled liquids are in the quasi-equilibrium state, the behavior of all the relaxation parameters for the β process can be compared among the polyols as well as those for the α process. The relaxation frequencies of the α processes follow the Vogel-Fulcher-Tammann manner and the loci in the Arrhenius diagram are different corresponding to the difference of the glass transition temperatures. On the other hand, the relaxation frequencies of the β processes, which are often called as the Johari-Goldstein processes, follow the Arrhenius-type temperature dependence. The relaxation parameters for the β process are quite similar among the polyols at temperatures below the αβ merging temperature, TM. However, they show anomalous behavior near TM, which depends on the molecular size of materials. These results suggest that the origin of the β process is essentially the same among the polyols.

State-dependent effects of transcranial oscillatory currents on the motor system: what you think matters.

PubMed

Feurra, Matteo; Pasqualetti, Patrizio; Bianco, Giovanni; Santarnecchi, Emiliano; Rossi, Alessandro; Rossi, Simone

2013-10-30

Imperceptible transcranial alternating current stimulation (tACS) changes the endogenous cortical oscillatory activity in a frequency-specific manner. In the human motor system, tACS coincident with the idling beta rhythm of the quiescent motor cortex increased the corticospinal output. We reasoned that changing the initial state of the brain (i.e., from quiescence to a motor imagery task that desynchronizes the local beta rhythm) might also change the susceptibility of the corticospinal system to resonance effects induced by beta-tACS. We tested this hypothesis by delivering tACS at different frequencies (theta, alpha, beta, and gamma) on the primary motor cortex at rest and during motor imagery. Motor-evoked potentials (MEPs) were obtained by transcranial magnetic stimulation (TMS) on the primary motor cortex with an online-navigated TMS-tACS setting. During motor imagery, the increase of corticospinal excitability was maximal with theta-tACS, likely reflecting a reinforcement of working memory processes required to mentally process and "execute" the cognitive task. As expected, the maximal MEPs increase with subjects at rest was instead obtained with beta-tACS, substantiating previous evidence. This dissociation provides new evidence of state and frequency dependency of tACS effects on the motor system and helps discern the functional role of different oscillatory frequencies of this brain region. These findings may be relevant for rehabilitative neuromodulatory interventions.

Shear wave anisotropy from aligned inclusions: ultrasonic frequency dependence of velocity and attenuation

NASA Astrophysics Data System (ADS)

de Figueiredo, J. J. S.; Schleicher, J.; Stewart, R. R.; Dayur, N.; Omoboya, B.; Wiley, R.; William, A.

2013-04-01

To understand their influence on elastic wave propagation, anisotropic cracked media have been widely investigated in many theoretical and experimental studies. In this work, we report on laboratory ultrasound measurements carried out to investigate the effect of source frequency on the elastic parameters (wave velocities and the Thomsen parameter γ) and shear wave attenuation) of fractured anisotropic media. Under controlled conditions, we prepared anisotropic model samples containing penny-shaped rubber inclusions in a solid epoxy resin matrix with crack densities ranging from 0 to 6.2 per cent. Two of the three cracked samples have 10 layers and one has 17 layers. The number of uniform rubber inclusions per layer ranges from 0 to 100. S-wave splitting measurements have shown that scattering effects are more prominent in samples where the seismic wavelength to crack aperture ratio ranges from 1.6 to 1.64 than in others where the ratio varied from 2.72 to 2.85. The sample with the largest cracks showed a magnitude of scattering attenuation three times higher compared with another sample that had small inclusions. Our S-wave ultrasound results demonstrate that elastic scattering, scattering and anelastic attenuation, velocity dispersion and crack size interfere directly in shear wave splitting in a source-frequency dependent manner, resulting in an increase of scattering attenuation and a reduction of shear wave anisotropy with increasing frequency.

Quasiparticle properties at microwave frequencies in the underdoped YBa2Cu3O7-δ thin films

NASA Astrophysics Data System (ADS)

Hsing, Lai

2004-03-01

Microstrip ring resonators with quality factor (Q) over 10^4 at temperature 5 K were fabricated using the double-side YBa_2Cu_3O_7-δ (YBCO) films deposited on LaAlO3 (LAO) substrates. By placing a narrow gap in the ring resonator, the original fundamental resonating mode (3.61 GHz) splits into two modes (1.80 GHz and 5.33 GHz) with distinct resonating frequencies. The samples allow us to determine the temperature and the frequency dependences of penetration depth and microwave conductivity for various underdoped-cuprates by using Drude formula and the modified two-fluid model. The natures of the order parameter of high-Tc superconductivity in the underdoped cases are shown to be of d-wave type in an exact manner. In particular, the Fermi-liquid correction factor α ^2 and the vertex correction factor β from the model, proposed by Wen and Lee, can be estimated that α ^2 is doping independent in the underdoped regime and β decreases as oxygen content is decreasing in our experiment data. All these results are independent of frequencies as well. The results reveal that the interaction between quasiparticles is insensitive dependence of the impurity concentrations due to oxygen deficiency on the CuO chain and the impurity potential for forward scattering approaches the same as back scattering with more oxygen deficiency.

The application of real-time model update by oblique ionospheric sounders to frequency sharing

NASA Astrophysics Data System (ADS)

Uffelman, D. R.; Harnish, L. O.; Goodman, J. M.

1983-03-01

Frequency management systems for the high frequencies (HF) currently in use by the US Department of Defense (DoD) rely heavily on manual selection of frequencies which were allocated on a circuit by circuit basis. There is no capability to anticipate frequency changes (QSY's) in advance in a manner such that a frequency being released by one user is utilized effectively and immediately by a second user. A scheme by which a small computer model of the maximum usage frequency (MUF) of the HF channel (MINIMUF 3.5) is made to perform very accurately to anticipate channel characteristics in a short term prediction mode was examined. It is proposed that this model be utilized to provide automated frequency management which would allow one to anticipate frequency availability and thereby sharing of frequencies between several users. Utilizing data obtained from an oblique sounder net on the East Coast of the United States, the manner in which this might be accomplished is demonstrated.

Review of measurements of the RF spectrum of radiation from lightning

NASA Technical Reports Server (NTRS)

Levine, D. M.

1986-01-01

Measurements reported in the literature of the spectrum of electromagnetic radiation from lightning in the frequency range from 1 kHz to 1 GHz are reviewed. Measurements have been made either by monitoring the power received at individual frequencies using a narrow bandwidth recording device tuned to the frequencies under investigation or by recording the transient (time dependent) radiation with a wide bandwidth device and then Fourier transforming the waveform to obtain a spectrum. Measurements of the first type were made extensively in the 1950's and 1960's and several composite spectra have been deduced by normalizing the data of different investigators to common units of bandwidth and distance. The composite spectra tend to peak near 5 kHz and then decrease roughly as (frequency) to the -1, up to nearly 100 MHz where scatter in the data make the behavior uncertain. Measurements of the second type have been reported for return strokes, the stepped leader and for some intracloud processes. The spectrum of first return strokes obtained in this manner is very similar to the composite spectra obtained from the narrow-band measurements.

Apoptotic effects on cultured cells of atmospheric-pressure plasma produced using various gases

NASA Astrophysics Data System (ADS)

Tominami, Kanako; Kanetaka, Hiroyasu; Kudo, Tada-aki; Sasaki, Shota; Kaneko, Toshiro

2016-01-01

This study investigated the effects of low-temperature atmospheric-pressure plasma on various cells such as rat fibroblastic Rat-1 cell line, rat neuroblastoma-like PC12 cell line, and rat macrophage-like NR8383 cell line. The plasma was irradiated directly to a culture medium containing plated cells for 0-20 s. The applied voltage, excitation frequency, and argon or helium gas flow were, respectively, 3-6 kV, 10 kHz, and 3 L/min. Cell viability and apoptotic activity were evaluated using annexin-V/propidium iodide staining. Results showed that the low-temperature atmospheric-pressure plasma irradiation promoted cell death in a discharge-voltage-dependent and irradiation-time-dependent manner. Furthermore, different effects are produced depending on the cell type. Moreover, entirely different mechanisms might be responsible for the induction of apoptosis in cells by helium and argon plasma.

Millimeter wave treatment induces apoptosis via activation of the mitochondrial-dependent pathway in human osteosarcoma cells.

PubMed

Wu, Guangwen; Chen, Xuzheng; Peng, Jun; Cai, Qiaoyan; Ye, Jinxia; Xu, Huifeng; Zheng, Chunsong; Li, Xihai; Ye, Hongzhi; Liu, Xianxiang

2012-05-01

Millimeter wave (MW) is an electromagnetic wave with a wavelength between 1 and 10 mm and a frequency of 30-300 GHz that causes multiple biological effects and has been used as a major component in physiotherapies for the clinical treatment of various types of diseases including cancers. However, the precise molecular mechanism of the anticancer activity of millimeter wave remains to be elucidated. In the present study, we investigated the cellular effects of the MW in the U-2OS human osteosarcoma cell line. Our results showed that MW induced cell morphological changes and reduced cell viability in a dose- and time-dependent manner suggesting that MW inhibited the growth of U-2OS cells as demonstrated. Hoechst 33258 staining and Annexin V/propidium iodide double staining exhibited the typical nuclear features of apoptosis and increased the proportion of apoptotic Annexin V-positive cells in a dose-dependent manner, respectively. In addition, MW treatment caused loss of plasma membrane asymmetry, release of cytochrome c, collapse of mitochondrial membrane potential, activation of caspase-9 and -3, and increase of the ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2. Taken together, the results indicate that the U-2OS cell growth inhibitory activity of MW was due to mitochondrial-mediated apoptosis, which may partly explain the anticancer activity of millimeter wave treatment.

Strain-Dependent Effects of Acute Alcohol on Synaptic Vesicle Recycling and Post-Tetanic Potentiation in Medial Glutamate Inputs to the Mouse Basolateral Amygdala.

PubMed

Gioia, Dominic A; McCool, Brian

2017-04-01

Inbred mouse strains are differentially sensitive to the acute effects of ethanol (EtOH) and are useful tools for examining how unique genomes differentially affect alcohol-related behaviors and physiology. DBA/2J mice have been shown to be sensitive to the acute anxiolytic effects of alcohol as well as the anxiogenic effects of withdrawal from chronic alcohol exposure, while B6 mice are resistant to both. Considering that the basolateral amygdala (BLA) is an important brain region for the acute and chronic effects of EtOH on fear and anxiety related behaviors, we hypothesized that there would be strain-dependent differences in the acute effects of EtOH in BLA slices. We utilized patch clamp electrophysiology in BLA coronal slices from 4 inbred mouse strains (A/J, BALBcJ, C57BL/6J, and DBA/2J) to examine how genetic background influences acute EtOH effects on synaptic vesicle recycling and post-tetanic potentiation (PTP) in response to low (2 Hz)- and high (40 Hz)-frequency stimulation. We found that EtOH inhibited synaptic vesicle recycling in a strain- and stimulation frequency-dependent manner. Vesicle recycling in DBA/2J and BALBcJ cells was inhibited by acute EtOH during both low- and high-frequency stimulation, while recycling measured from A/J cells was sensitive only during high-frequency stimulation. Recycling at C57BL/6J synapses was insensitive to EtOH regardless of stimulation frequency. We additionally found that cells from DBA/2J and BALBcJ mice were sensitive to EtOH-mediated inhibition of PTP. Acute EtOH application inhibited vesicle recycling and PTP at glutamatergic synapses in both a strain- and frequency-dependent fashion. Several presynaptic proteins that contribute to synaptic vesicle priming in addition to PTP have been implicated in alcohol-related behaviors, including Munc13, Munc18, and RIM proteins, making them potential candidates for the molecular mechanism controlling these effects. Copyright © 2017 by the Research Society on Alcoholism.

Lipid rafts sense and direct electric field-induced migration

PubMed Central

Lin, Bo-jian; Tsao, Shun-hao; Chen, Alex; Hu, Shu-Kai; Chao, Ling

2017-01-01

Endogenous electric fields (EFs) are involved in developmental regulation and wound healing. Although the phenomenon is known for more than a century, it is not clear how cells perceive the external EF. Membrane proteins, responding to electrophoretic and electroosmotic forces, have long been proposed as the sensing molecules. However, specific charge modification of surface proteins did not change cell migration motility nor directionality in EFs. Moreover, symmetric alternating current (AC) EF directs cell migration in a frequency-dependent manner. Due to their charge and ability to coalesce, glycolipids are therefore the likely primary EF sensor driving polarization of membrane proteins and intracellular signaling. We demonstrate that detergent-resistant membrane nanodomains, also known as lipid rafts, are the primary response element in EF sensing. The clustering and activation of caveolin and signaling proteins further stabilize raft structure and feed-forward downstream signaling events, such as rho and PI3K activation. Theoretical modeling supports the experimental results and predicts AC frequency-dependent cell and raft migration. Our results establish a fundamental mechanism for cell electrosensing and provide a role in lipid raft mechanotransduction. PMID:28739955

Lipid rafts sense and direct electric field-induced migration.

PubMed

Lin, Bo-Jian; Tsao, Shun-Hao; Chen, Alex; Hu, Shu-Kai; Chao, Ling; Chao, Pen-Hsiu Grace

2017-08-08

Endogenous electric fields (EFs) are involved in developmental regulation and wound healing. Although the phenomenon is known for more than a century, it is not clear how cells perceive the external EF. Membrane proteins, responding to electrophoretic and electroosmotic forces, have long been proposed as the sensing molecules. However, specific charge modification of surface proteins did not change cell migration motility nor directionality in EFs. Moreover, symmetric alternating current (AC) EF directs cell migration in a frequency-dependent manner. Due to their charge and ability to coalesce, glycolipids are therefore the likely primary EF sensor driving polarization of membrane proteins and intracellular signaling. We demonstrate that detergent-resistant membrane nanodomains, also known as lipid rafts, are the primary response element in EF sensing. The clustering and activation of caveolin and signaling proteins further stabilize raft structure and feed-forward downstream signaling events, such as rho and PI3K activation. Theoretical modeling supports the experimental results and predicts AC frequency-dependent cell and raft migration. Our results establish a fundamental mechanism for cell electrosensing and provide a role in lipid raft mechanotransduction.

Acoustic near-field characteristics of a conical, premixed flame

NASA Astrophysics Data System (ADS)

Lee, Doh-Hyoung; Lieuwen, Tim C.

2003-01-01

The occurrence of self-excited pressure oscillations routinely plagues the development of combustion systems. These oscillations are often driven by interactions between the flame and acoustic perturbations. This study was performed to characterize the structure of the acoustic field in the near field of the flame and the manner in which it is influenced by oscillation frequency, combustor geometry, flame length and temperature ratio. The results of these calculations indicate that the acoustic velocity has primarily one- and two-dimensional features near the flame tip and base, respectively. The magnitude of the radial velocity components increases with temperature ratio across the flame, while their axial extent increases with frequency. However, the acoustic pressure has primarily one-dimensional characteristics. They also show that the acoustic field structure exhibits only moderate dependencies upon area expansion and flame temperature ratio for values typical of practical systems. Finally, they show that the local characteristics of the acoustic field, as well as the overall plane-wave reflection coefficient, exhibit a decreasing dependence upon the flame length as the area expansion ratio increases.

Acoustic near-field characteristics of a conical, premixed flame.

PubMed

Lee, Doh-Hyoung; Lieuwen, Tim C

2003-01-01

The occurrence of self-excited pressure oscillations routinely plagues the development of combustion systems. These oscillations are often driven by interactions between the flame and acoustic perturbations. This study was performed to characterize the structure of the acoustic field in the near field of the flame and the manner in which it is influenced by oscillation frequency, combustor geometry, flame length and temperature ratio. The results of these calculations indicate that the acoustic velocity has primarily one- and two-dimensional features near the flame tip and base, respectively. The magnitude of the radial velocity components increases with temperature ratio across the flame, while their axial extent increases with frequency. However, the acoustic pressure has primarily one-dimensional characteristics. They also show that the acoustic field structure exhibits only moderate dependencies upon area expansion and flame temperature ratio for values typical of practical systems. Finally, they show that the local characteristics of the acoustic field, as well as the overall plane-wave reflection coefficient, exhibit a decreasing dependence upon the flame length as the area expansion ratio increases.

Enhancement of collective atomic recoil lasing due to pump phase modulation

NASA Astrophysics Data System (ADS)

Robb, G. R. M.; Burgess, R. T. L.; Firth, W. J.

2008-10-01

We investigate the effect of a phase-modulated pump beam on collective backscattering [also termed collective atomic recoil lasing (CARL)] by a cold, collisionless atomic gas. We show using a numerical analysis that different regimes can be identified in which the atomic dynamics evolves in a qualitatively different manner during the light-atom interaction, depending on the magnitude of the pump modulation frequency. Our results also demonstrate that phase-modulating the pump field can substantially enhance the backscattered field intensity relative to the case of a monochromatic pump which has been used in CARL experiments to date.

A numerical study of self-sustained oscillations in wind instruments

NASA Astrophysics Data System (ADS)

Rendon, Pablo L.; Velasco-Segura, Roberto

2017-11-01

The study of sustained notes in wind musical instruments in realistic conditions requires consideration of both excitation and propagation mechanisms, and the manner in which these two interact. Further, to model adequately acoustic propagation inside the instrument, a variety of competing effects must be taken into account, such as nonlinearity, thermoviscous attenuation and radiation at the open end. Physical solutions also involve some degree of feedback at the excitation end, and here we propose the simplest boundary conditions possible at this end, given by a simple harmonic oscillator with fixed stiffness. By feeding single-frequency acoustic waves into the system we are able to study the formation of self-sustained oscillations, which are stationary states associated with resonance frequencies, and also to observe transitory states. Visualizations are presented of waves traveling in both directions. As expected, resonance frequencies are dependent on the stiffness parameter, and this dependence is examined. The full-wave simulation is performed in the time domain over a 2D spatial domain assuming axial symmetry, and it is based on a previously validated open source code, using a finite volume method (FiVoNAGI) implemented in a GPU [Velasco-Segura & Rendn, 2015]. The authors acknowledge the financial support of DGAPA-UNAM through project PAPIIT IG100717.

Vibrational energy harvesting by exploring structural benefits and nonlinear characteristics

NASA Astrophysics Data System (ADS)

Wei, Chongfeng; Jing, Xingjian

2017-07-01

Traditional energy harvesters are often of low efficiency due to very limited energy harvesting bandwidth, which should also be enough close to the ambient excitation frequency. To overcome this difficulty, some attempts can be seen in the literature typically with the purposes of either increasing the energy harvesting bandwidth with a harvester array, or enhancing the energy harvesting bandwidth and peak with nonlinear coupling effect etc. This paper presents an alternative way which can achieve tuneable resonant frequency (from high frequency to ultralow frequency) and improved energy harvesting bandwidth and peak simultaneously by employing special structural benefits and advantageous displacement-dependent nonlinear damping property. The proposed energy harvesting system employs a lever systems combined with an X-shape supporting structure and demonstrates very adjustable stiffness and unique nonlinear damping characteristics which are very beneficial for energy harvesting. It is shown that the energy harvesting performance of the proposed system is directly determined by several easy-to-tune structural parameters and also by the relative displacement in a special nonlinear manner, which provides a great flexibility and/or a unique tool for tuning and improving energy harvesting efficiency via matching excitation frequencies and covering a broader frequency band. This study potentially provides a new insight into the design of energy harvesting systems by employing structural benefits and geometrical nonlinearities.

Differential effects of tactile high- and low-frequency stimulation on tactile discrimination in human subjects.

PubMed

Ragert, Patrick; Kalisch, Tobias; Bliem, Barbara; Franzkowiak, Stephanie; Dinse, Hubert R

2008-01-23

Long-term potentiation (LTP) and long-term depression (LTD) play important roles in mediating activity-dependent changes in synaptic transmission and are believed to be crucial mechanisms underlying learning and cortical plasticity. In human subjects, however, the lack of adequate input stimuli for the induction of LTP and LTD makes it difficult to study directly the impact of such protocols on behavior. Using tactile high- and low-frequency stimulation protocols in humans, we explored the potential of such protocols for the induction of perceptual changes. We delivered tactile high-frequency and low-frequency stimuli (t-HFS, t-LFS) to skin sites of approximately 50 mm2 on the tip of the index finger. As assessed by 2-point discrimination, we demonstrate that 20 minutes of t-HFS improved tactile discrimination, while t-LFS impaired performance. T-HFS-effects were stable for at least 24 hours whereas t-LFS-induced changes recovered faster. While t-HFS changes were spatially very specific with no changes on the neighboring fingers, impaired tactile performance after t-LFS was also observed on the right middle-finger. A central finding was that for both t-LFS and t-HFS perceptual changes were dependent on the size of the stimulated skin area. No changes were observed when the stimulated area was very small (< 1 mm2) indicating special requirements for spatial summation. Our results demonstrate differential effects of such protocols in a frequency specific manner that might be related to LTP- and LTD-like changes in human subjects.

Inhibition of cardiac sodium currents by toluene exposure

PubMed Central

Cruz, Silvia L; Orta-Salazar, Gerardo; Gauthereau, Marcia Y; Millan-Perez Peña, Lourdes; Salinas-Stefanón, Eduardo M

2003-01-01

Toluene is an industrial solvent widely used as a drug of abuse, which can produce sudden sniffing death due to cardiac arrhythmias. In this paper, we tested the hypothesis that toluene inhibits cardiac sodium channels in Xenopus laevis oocytes transfected with Nav1.5 cDNA and in isolated rat ventricular myocytes. In oocytes, toluene inhibited sodium currents (INa+) in a concentration-dependent manner, with an IC50 of 274 μM (confidence limits: 141–407μM). The inhibition was complete, voltage-independent, and slowly reversible. Toluene had no effect on: (i) the shape of the I–V curves; (ii) the reversal potential of Na+; and (iii) the steady-state inactivation. The slow recovery time constant from inactivation of INa+ decreased with toluene exposure, while the fast recovery time constant remained unchanged. Block of INa+ by toluene was use- and frequency-dependent. In rat cardiac myocytes, 300 μM toluene inhibited the sodium current (INa+) by 62%; this inhibition was voltage independent. These results suggest that toluene binds to cardiac Na+ channels in the open state and unbinds either when channels move between inactivated states or from an inactivated to a closed state. The use- and frequency-dependent block of INa+ by toluene might be responsible, at least in part, for its arrhythmogenic effect. PMID:14534149

Anomalous frequency and temperature-dependent scattering and Hund's coupling in the almost quantum critical heavy-fermion system CeFe2Ge2

NASA Astrophysics Data System (ADS)

Bossé, G.; Pan, LiDong; Li, Yize S.; Greene, L. H.; Eckstein, J.; Armitage, N. P.

2016-02-01

We present THz range optical conductivity data of a thin film of the near quantum critical heavy-fermion compound CeFe2Ge2 . Our complex conductivity measurements find a deviation from conventional Drude-like transport in a temperature range previously reported to exhibit unconventional behavior. We calculate the frequency-dependent effective mass and scattering rate using an extended Drude model analysis. We find the inelastic scattering rate can be described by a temperature-dependent power law ωn (T ), where n (T ) approaches ˜1.0 ±0.2 at 1.5 K. This is compared to the ρ ˜T1.5 behavior claimed in dc resistivity data and the ρ ˜T2 expected from Fermi-liquid theory. In addition to a low-temperature mass renormalization, we find an anomalous mass renormalization that persists to high temperature. We attribute this to a Hund's coupling in the Fe states in a manner similar to that recently proposed in the ferropnictides. CeFe2Ge2 appears to be a very interesting system where one may study the interplay between the usual 4 f lattice Kondo effect and this Hund's enhanced Kondo effect in the 3 d states.

Cardiomyocyte Ca2+ handling and structure is regulated by degree and duration of mechanical load variation.

PubMed

Ibrahim, Michael; Kukadia, Punam; Siedlecka, Urszula; Cartledge, James E; Navaratnarajah, Manoraj; Tokar, Sergiy; Van Doorn, Carin; Tsang, Victor T; Gorelik, Julia; Yacoub, Magdi H; Terracciano, Cesare M

2012-12-01

Cardiac transverse (t)-tubules are altered during disease and may be regulated by stretch-sensitive molecules. The relationship between variations in the degree and duration of load and t-tubule structure remains unknown, as well as its implications for local Ca(2+)-induced Ca(2+) release (CICR). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart-lung transplantation (HAHLT)] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR, cell and t-tubule structure were assessed using confocal-microscopy, patch-clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart-only transplantation (HAHT)]. Mechanical unloading reduced cardiomyocyte volume in a time-dependent manner. Ca(2+) release synchronicity was reduced at 8 weeks moderate unloading only. Ca(2+) sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t-tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t-tubule morphology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37% reduction in cell volume at 4 weeks compared to 56% reduction after severe mechanical unloading) and did not cause depression and delay of the Ca(2+) transient, increased Ca(2+) spark frequency or impaired t-tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t-tubule structure in a time- and degree-dependent manner, and that physiological states of increased and reduced cell size, without pathological changes are possible. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

47 CFR 74.803 - Frequency selection to avoid interference.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Frequency selection to avoid interference. 74... Power Auxiliary Stations § 74.803 Frequency selection to avoid interference. (a) Where two or more low... frequencies or schedule operation in such manner as to avoid mutual interference. If a mutually satisfactory...

47 CFR 74.403 - Frequency selection to avoid interference.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Frequency selection to avoid interference. 74... Pickup Broadcast Stations § 74.403 Frequency selection to avoid interference. (a) Where two or more... select frequencies or schedule operation in such manner as to avoid mutual interference. If mutual...

47 CFR 74.403 - Frequency selection to avoid interference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Frequency selection to avoid interference. 74... Pickup Broadcast Stations § 74.403 Frequency selection to avoid interference. (a) Where two or more... select frequencies or schedule operation in such manner as to avoid mutual interference. If mutual...

47 CFR 74.803 - Frequency selection to avoid interference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Frequency selection to avoid interference. 74... Power Auxiliary Stations § 74.803 Frequency selection to avoid interference. (a) Where two or more low... frequencies or schedule operation in such manner as to avoid mutual interference. If a mutually satisfactory...

Differential modulation of late sodium current by protein kinase A in R1623Q mutant of LQT3

PubMed Central

Tsurugi, Takuo; Nagatomo, Toshihisa; Abe, Haruhiko; Oginosawa, Yasushi; Takemasa, Hiroko; Kohno, Ritsuko; Makita, Naomasa; Makielski, Jonathan C.; Otsuji, Yutaka

2009-01-01

Aims In the type 3 long QT syndrome (LQT3), shortening of the QT interval by overdrive pacing is used to prevent life-threatening arrhythmias. However, it is unclear whether accelerated heart rate induced by β-adrenergic agents produces similar effects on the late sodium current (INa) to those by overdrive pacing therapy. We analyzed the β-adrenergic-like effects of protein kinase A and fluoride on INa in R1623Q mutant channels. Main methods cDNA encoding either wild-type (WT) or R1623Q mutant of hNav1.5 was stably transfected into HEK293 cells. INa was recorded using a whole-cell patch-clamp technique at 23 °C. Key findings In R1623Q channels, 2 mM pCPT-AMP and 120 mM fluoride significantly delayed macroscopic current decay and increased relative amplitude of the late INa in a time-dependent manner. Modulations of peak INa gating kinetics (activation, inactivation, recovery from inactivation) by fluoride were similar in WT and R1623Q channels. The effects of fluoride were almost completely abolished by concomitant dialysis with a protein kinase inhibitor. We also compared the effect of pacing with that of β-adrenergic stimulation by analyzing the frequency-dependence of the late INa. Fluoride augmented frequency-dependent reduction of the late INa, which was due to preferential delay of recovery of late INa. However, the increase in late INa by fluoride at steady-state was more potent than the frequency-dependent reduction of late INa. Significance Different basic mechanisms participate in the QT interval shortening by pacing and β-adrenergic stimulation in the LQT3. PMID:19167409

Bepridil differentially inhibits two delayed rectifier K+ currents, IKr and IKs, in guinea-pig ventricular myocytes

PubMed Central

Wang, Jin-Cheng; Kiyosue, Tatsuto; Kiriyama, Kuninori; Arita, Makoto

1999-01-01

We investigated the effects of bepridil on the two components of the delayed rectifier K+ current, i.e., the rapidly activating (IKr) and the slowly activating (IKs) currents using tight-seal whole-cell patch-clamp techniques in guinea-pig ventricular myocytes, under blockade of L-type Ca2+ current with nitrendipine (5 μM) or D600 (1 μM).Bepridil decreased IKs under blockade of IKr with E4031 (5 μM), in a concentration-dependent manner. The concentration-dependent inhibition of IKs by bepridil was fitted by a curve, assuming one-to-one interactions between the channel and the drug molecule. The concentration of half-maximal inhibition (IC50) was found to be 6.2 μM.The effect of bepridil on IKr was assessed using an envelope-of-tails test. In the control condition, a ratio of the tail current to the time-dependent current measured during depolarization was large (>1) at shorter pulses (<200 ms), and it decreased to a steady state value of ∼0.4 with increases in the pulse duration. Bepridil at a concentration of 2 μM did not decrease this ratio at shorter pulses.In a short-pulse (duration=50 ms) experiment that largely activates IKr, the drug was found to block IKr in a cooperative manner (Hill coefficient=3.03) and the IC50 was 13.2 μM.These results suggest that bepridil at a clinical therapeutic concentration (∼2 μM) selectively blocks IKs but does not inhibit IKr. This may relate to the characteristic frequency-dependent effects of bepridil on the action potential duration (APD), e.g., the non-reverse use-dependent prolongation of APD. PMID:10588929

Genotoxicity of municipal landfill leachate on root tips of Vicia faba.

PubMed

Sang, Nan; Li, Guangke

2004-06-13

The genotoxicity of municipal landfill leachate was studied using the Vicia faba root-tip cytogenetic bioassay. Results show that landfill leachates collected in different seasons decreased the mitotic index (MI) and caused significant increases of micronucleus (MN) frequencies and anaphase aberration (AA) frequencies in a concentration-dependent manner (concentration expressed as 'chemical oxygen demand' measured by the method of potassium dichromate oxidation (COD(Cr))). In addition, a seasonal difference in genotoxicity induced by leachate was observed. The results confirm that leachate is a genotoxic agent in plant cells and imply that exposure to leachate in the aquatic environment may pose a potential genotoxic risk to organisms. The results also show that the V. faba cytogenetic bioassay is efficient, simple and reproducible in genotoxicity studies of leachate, and that there is a correlation between the genotoxicity and the chemical measurement (COD(Cr)) of leachate.

Drug transport mechanism of oral antidiabetic nanomedicines.

PubMed

Gundogdu, Evren; Yurdasiper, Aysu

2014-01-01

Over the last few decades, extensive efforts have been made worldwide to develop nanomedicine delivery systems, especially via oral route for antidiabetic drugs. Absorption of insulin is hindered by epithelial cells of gastrointestinal tract, acidic gastric pH and digestive enzymes. Recent reports have identified and explained the beneficial role of several structural molecules like mucoadhesive polymers (polyacrylic acid, sodium alginate, chitosan) and other copolymers for the efficient transport and release of insulin to its receptors. Insulin nanomedicines based on alginate-dextran sulfate core with a chitosan-polyethylene glycol-albumin shell reduced glycaemia in a dose dependent manner. Orally available exendin-4 formulations exerted their effects in a time dependent manner. Insulin nanoparticles formed by using alginate and dextran sulfate nucleating around calcium and binding to poloxamer, stabilized by chitosan, and subsequently coated with albumin showed a threefold increase of the hypoglycemic effect in comparison to free insulin in animal models. Solid lipid nanoparticles showed an enhancement of the bioavailability of repaglinide (RG) within optimized solid lipid nanoparticle formulations when compared with RG alone. Nanoparticles represent multiparticulate delivery systems designed to obtain prolonged or controlled drug delivery and to improve bioavailability as well as stability. Nanoparticles can also offer advantages like limiting fluctuations within therapeutic range, reducing side effects, protecting drugs from degradation, decreasing dosing frequency, and improving patient compliance and convenience.

Quantum resonances in a single plaquette of Josephson junctions: excitations of Rabi oscillations

NASA Astrophysics Data System (ADS)

Fistul, M. V.

2002-03-01

We present a theoretical study of a quantum regime of the resistive (whirling) state of dc driven anisotropic single plaquette containing small Josephson junctions. The current-voltage characteristics of such systems display resonant steps that are due to the resonant interaction between the time dependent Josephson current and the excited electromagnetic oscillations (EOs). The voltage positions of the resonances are determined by the quantum interband transitions of EOs. We show that in the quantum regime as the system is driven on the resonance, coherent Rabi oscillations between the quantum levels of EOs occur. At variance with the classical regime the magnitude and the width of resonances are determined by the frequency of Rabi oscillations that in turn, depends in a peculiar manner on an externally applied magnetic field and the parameters of the system.

Creating diversified response profiles from a single quenchometric sensor element by using phase-resolved luminescence.

PubMed

Tehan, Elizabeth C; Bukowski, Rachel M; Chodavarapu, Vamsy P; Titus, Albert H; Cartwright, Alexander N; Bright, Frank V

2015-01-05

We report a new strategy for generating a continuum of response profiles from a single luminescence-based sensor element by using phase-resolved detection. This strategy yields reliable responses that depend in a predictable manner on changes in the luminescent reporter lifetime in the presence of the target analyte, the excitation modulation frequency, and the detector (lock-in amplifier) phase angle. In the traditional steady-state mode, the sensor that we evaluate exhibits a linear, positive going response to changes in the target analyte concentration. Under phase-resolved conditions the analyte-dependent response profiles: (i) can become highly non-linear; (ii) yield negative going responses; (iii) can be biphasic; and (iv) can exhibit super sensitivity (e.g., sensitivities up to 300 fold greater in comparison to steady-state conditions).

Transmission dynamics of two dengue serotypes with vaccination scenarios.

PubMed

González Morales, N L; Núñez-López, M; Ramos-Castañeda, J; Velasco-Hernández, J X

2017-05-01

In this work we present a mathematical model that incorporates two Dengue serotypes. The model has been constructed to study both the epidemiological trends of the disease and conditions that allow coexistence in competing strains under vaccination. We consider two viral strains and temporary cross-immunity with one vector mosquito population. Results suggest that vaccination scenarios will not only reduce disease incidence but will also modify the transmission dynamics. Indeed, vaccination and cross immunity period are seen to decrease the frequency and magnitude of outbreaks but in a differentiated manner with specific effects depending upon the interaction vaccine and strain type. Copyright © 2016 Elsevier Inc. All rights reserved.

Concentration-dependent activation of dopamine receptors differentially modulates GABA release onto orexin neurons

PubMed Central

Linehan, Victoria; Trask, Robert B.; Briggs, Chantalle; Rowe, Todd M.; Hirasawa, Michiru

2017-01-01

Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups, where orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying DA action on orexin neurons remain incompletely understood. Therefore, the effect of DA on inhibitory transmission to orexin neurons was investigated in rat brain slices using whole cell patch clamp technique. We found that DA modulated the frequency of spontaneous and miniature IPSCs (mIPSCs) in a concentration dependent, bidirectional manner. Low (1 μM) and high concentrations (100 μM) of DA decreased and increased IPSC frequency, respectively. These effects did not accompany a change in mIPSC amplitude and persisted in the presence of G protein signaling inhibitor GDPβS in the pipette, suggesting that DA acts presynaptically. The decrease in mIPSC frequency was mediated by D2 receptors, whereas the increase required co-activation of D1 and D2 receptors and subsequent activation of phospholipase C. In summary, our results suggest that DA has complex effects on GABAergic transmission to orexin neurons, involving cooperation of multiple receptor subtypes. The direction of dopaminergic influence on orexin neurons is dependent on the level of DA in the hypothalamus. At low levels DA disinhibits orexin neurons whereas at high levels it facilitates GABA release, which may act as negative feedback to curb the excitatory orexinergic output to DA neurons. These mechanisms may have implications for consummatory and motivated behaviours. PMID:26036709

Bone as an ion exchange system: evidence for a link between mechanotransduction and metabolic needs.

PubMed

Rubinacci, A; Covini, M; Bisogni, C; Villa, I; Galli, M; Palumbo, C; Ferretti, M; Muglia, M A; Marotti, G

2002-04-01

To detect whether the mutual interaction occurring between the osteocytes-bone lining cells system (OBLCS) and the bone extracellular fluid (BECF) is affected by load through a modification of the BECF-extracellular fluid (ECF; systemic extracellular fluid) gradient, mice metatarsal bones immersed in ECF were subjected ex vivo to a 2-min cyclic axial load of different amplitudes and frequencies. The electric (ionic) currents at the bone surface were measured by a vibrating probe after having exposed BECF to ECF through a transcortical hole. The application of different loads and different frequencies increased the ionic current in a dose-dependent manner. The postload current density subsequently decayed following an exponential pattern. Postload increment's amplitude and decay were dependent on bone viability. Dummy and static loads did not induce current density modifications. Because BECF is perturbed by loading, it is conceivable that OBLCS tends to restore BECF preload conditions by controlling ion fluxes at the bone-plasma interface to fulfill metabolic needs. Because the electric current reflects the integrated activity of OBLCS, its evaluation in transgenic mice engineered to possess genetic lesions in channels or matrix constituents could be helpful in the characterization of the mechanical and metabolic functions of bone.

Thalamic reticular cells firing modes and its dependency on the frequency and amplitude ranges of the current stimulus.

PubMed

Hernandez, Oscar; Hernandez, Lilibeth; Vera, David; Santander, Alcides; Zurek, Eduardo

2015-01-01

The neurons of the Thalamic Reticular Nucleus (TRNn) respond to inputs in two activity modes called burst and tonic firing and both can be observed in different physiological states. The functional states of the thalamus depend in part on the properties of synaptic transmission between the TRNn and the thalamocortical and corticothalamic neurons. A dendrite can receive inhibitory and excitatory postsynaptic potentials. The novelties presented in this paper can be summarized as follows: First, it shows, through a computational simulation, that the burst and tonic firings observed in the TRNn soma could be explained as a product of random synaptic inputs on the distal dendrites, the tonic firings are generated by random excitatory stimuli, and the burst firings are generated by two different types of stimuli: inhibitory random stimuli, and a combination of inhibitory (from TRNn) and excitatory (from corticothalamic and thalamocortical neurons) random stimuli; second, according to in vivo recordings, we have found that the burst observed in the TRNn soma has graduate properties that are proportional to the stimuli frequency; and third, a novel method for showing in a quantitative manner the accelerando-decelerando pattern is proposed.

Biochemical Frequency Control by Synchronisation of Coupled Repressilators: An In Silico Study of Modules for Circadian Clock Systems

PubMed Central

Hinze, Thomas; Schumann, Mathias; Bodenstein, Christian; Heiland, Ines; Schuster, Stefan

2011-01-01

Exploration of chronobiological systems emerges as a growing research field within bioinformatics focusing on various applications in medicine, agriculture, and material sciences. From a systems biological perspective, the question arises whether biological control systems for regulation of oscillatory signals and their technical counterparts utilise similar mechanisms. If so, modelling approaches and parameterisation adopted from building blocks can help to identify general components for frequency control in circadian clocks along with gaining insight into mechanisms of clock synchronisation to external stimuli like the daily rhythm of sunlight and darkness. Phase-locked loops could be an interesting candidate in this context. Both, biology and engineering, can benefit from a unified view resulting from systems modularisation. In a first experimental study, we analyse a model of coupled repressilators. We demonstrate its ability to synchronise clock signals in a monofrequential manner. Several oscillators initially deviate in phase difference and frequency with respect to explicit reaction and diffusion rates. Accordingly, the duration of the synchronisation process depends on dedicated reaction and diffusion parameters whose settings still lack to be sufficiently captured analytically. PMID:22046179

The trigger mechanism of low-frequency earthquakes on Montserrat

NASA Astrophysics Data System (ADS)

Neuberg, J. W.; Tuffen, H.; Collier, L.; Green, D.; Powell, T.; Dingwell, D.

2006-05-01

A careful analysis of low-frequency seismic events on Soufrièere Hills volcano, Montserrat, points to a source mechanism that is non-destructive, repetitive, and has a stationary source location. By combining these seismological clues with new field evidence and numerical magma flow modelling, we propose a seismic trigger model which is based on brittle failure of magma in the glass transition. Loss of heat and gas from the magma results in a strong viscosity gradient across a dyke or conduit. This leads to a build-up of shear stress near the conduit wall where magma can rupture in a brittle manner, as field evidence from a rhyolitic dyke demonstrates. This brittle failure provides seismic energy, the majority of which is trapped in the conduit or dyke forming the low-frequency coda of the observed seismic signal. The trigger source location marks the transition from ductile conduit flow to friction-controlled magma ascent. As the trigger mechanism is governed by the depth-dependent magma parameters, the source location remains fixed at a depth where the conditions allow brittle failure. This is reflected in the fixed seismic source locations.

Fluid mechanical model of the Helmholtz resonator

NASA Technical Reports Server (NTRS)

Hersh, A. S.; Walker, B.

1977-01-01

A semi-empirical fluid mechanical model of the acoustic behavior of Helmholtz resonators is presented which predicts impedance as a function of the amplitude and frequency of the incident sound pressure field and resonator geometry. The model assumes that the particle velocity approaches the orifice in a spherical manner. The incident and cavity sound fields are connected by solving the governing oscillating mass and momentum conservation equations. The model is in agreement with the Rayleigh slug-mass model at low values of incident sound pressure level. At high values, resistance is predicted to be independent of frequency, proportional to the square root of the amplitude of the incident sound pressure field, and virtually independent of resonator geometry. Reactance is predicted to depend in a very complicated way upon resonator geometry, incident sound pressure level, and frequency. Nondimensional parameters are defined that divide resonator impedance into three categories corresponding to low, moderately low, and intense incident sound pressure amplitudes. The two-microphone method was used to measure the impedance of a variety of resonators. The data were used to refine and verify the model.

A θ-γ oscillation code for neuronal coordination during motor behavior.

PubMed

Igarashi, Jun; Isomura, Yoshikazu; Arai, Kensuke; Harukuni, Rie; Fukai, Tomoki

2013-11-20

Sequential motor behavior requires a progression of discrete preparation and execution states. However, the organization of state-dependent activity in neuronal ensembles of motor cortex is poorly understood. Here, we recorded neuronal spiking and local field potential activity from rat motor cortex during reward-motivated movement and observed robust behavioral state-dependent coordination between neuronal spiking, γ oscillations, and θ oscillations. Slow and fast γ oscillations appeared during distinct movement states and entrained neuronal firing. γ oscillations, in turn, were coupled to θ oscillations, and neurons encoding different behavioral states fired at distinct phases of θ in a highly layer-dependent manner. These findings indicate that θ and nested dual band γ oscillations serve as the temporal structure for the selection of a conserved set of functional channels in motor cortical layer activity during animal movement. Furthermore, these results also suggest that cross-frequency couplings between oscillatory neuronal ensemble activities are part of the general coding mechanism in cortex.

Stability of horizontal viscous fluid layers in a vertical arbitrary time periodic electric field

NASA Astrophysics Data System (ADS)

Bandopadhyay, Aditya; Hardt, Steffen

2017-12-01

The stability of a horizontal interface between two viscous fluids, one of which is conducting and the other is dielectric, acted upon by a vertical time-periodic electric field is considered theoretically. The two fluids are bounded by electrodes separated by a finite distance. For an applied ac electric field, the unstable interface deforms in a time periodic manner, owing to the time dependent Maxwell stress, and is characterized by the oscillation frequency which may or may not be the same as the frequency of the ac electric field. The stability curve, which relates the critical voltage, manifested through the Mason number—the ratio of normal electric stress and viscous stress, and the instability wavenumber at the onset of the instability, is obtained by means of the Floquet theory for a general arbitrary time periodic electric field. The limit of vanishing viscosities is shown to be in excellent agreement with the marginal stability curves predicted by means of a Mathieu equation. The influence of finite viscosity and electrode separation is discussed in relation to the ideal case of inviscid fluids. The methodology to obtain the marginal stability curves developed here is applicable to any arbitrary but time periodic signal, as demonstrated for the case of a signal with two different frequencies, and four different frequencies with a dc offset. The mode coupling in the interfacial normal stress leads to appearance of harmonic and subharmonic modes, characterized by the frequency of the oscillating interface at an integral or half-integral multiple of the applied frequency, respectively. This is in contrast to the application of a voltage with a single frequency which always leads to a harmonic mode oscillation of the interface. Whether a harmonic or subharmonic mode is the most unstable one depends on details of the excitation signal.

Low-frequency ultrasound increases non-viral gene transfer to the mouse lung.

PubMed

Xenariou, Stefania; Liang, Hai-Dong; Griesenbach, Uta; Zhu, Jie; Farley, Raymond; Somerton, Lucinda; Singh, Charanjit; Jeffery, Peter K; Scheule, Ronald K; Cheng, Seng H; Geddes, Duncan M; Blomley, Martin; Alton, Eric W F W

2010-01-01

The aim of the study was to assess if low-frequency ultrasound (US), in the range of 30-35 kHz, increases non-viral gene transfer to the mouse lung. US is greatly attenuated in the lung due to large energy losses at the air/tissue interfaces. The advantages of low-frequency US, compared with high-frequency US are: (i) increased cavitation (responsible for the formation of transient pores in the cell membrane) and (ii) reduced energy losses during lung penetration. Cationic lipid GL67/plasmid DNA (pDNA), polyethylenimine (PEI)/pDNA and naked pDNA were delivered via intranasal instillation and the animals were then exposed to US (sonoporation) at 0.07 or 0.1 MPa for 10 min. Under these conditions, US did not enhance GL67 or PEI-mediated transfection. It did, however, increase naked pDNA gene transfer by approximately 4 folds. Importantly, this was achieved in the absence of microbubbles, which are crucial for the commonly used high-frequency (1 MHz) sonoporation but may not be able to withstand nebulization in a clinically relevant setup. Lung hemorrhage was also assessed and shown to increase with US pressure in a dose-dependent manner. We have thus, established that low-frequency US can enhance lung gene transfer with naked pDNA and this enhancement is more effective than the previously reported 1 MHz US.

Back extensor muscle fatigue at submaximal workloads assessed using frequency banding of the electromyographic signal.

PubMed

Cardozo, Adalgiso Coscrato; Gonçalves, Mauro; Dolan, Patricia

2011-12-01

Changes in the mean or median frequency of the electromyographic (EMG) power spectrum are often used to assess skeletal muscle fatigue. A more global analysis of the spectral changes using frequency banding may provide a more sensitive measure of fatigue than changes in mean or median frequency. So, the aim of the present study was to characterize changes in different power spectrum frequency bands and compare these with changes in median frequency. Twenty male subjects performed isometric contractions of the back muscles in an isometric dynamometer at 30%, 40%, 50% and 60% of maximum voluntary contraction. During each contraction, surface EMG signals were recorded from the right and left longissimus thoracis muscles, and endurance time was measured. The EMG power spectra were divided into four frequency bands (20-50 Hz; 50-80 Hz; 80-110 Hz; 110-140 Hz) and changes in power in each band with fatigue were compared with changes in median frequency. The percentage changes in 20-50 Hz band were greater than in all other and the rate of change in power, indicated by the slope, was also greatest in 20-50 Hz band. Also, 20-50 Hz band had a greater change in power than the median frequency. Power in the low frequency part of the EMG power spectrum increases with fatigue in a load-dependent manner. The rate of change in low frequency power may be a useful indicator of fatigue rate or "fatigability" in the back muscles. Also, changes in low frequency power are more evident than changes in the median frequency. Copyright © 2011 Elsevier Ltd. All rights reserved.

Revealing the Raft Domain Organization in the Plasma Membrane by Single-Molecule Imaging of Fluorescent Ganglioside Analogs.

PubMed

Suzuki, Kenichi G N; Ando, Hiromune; Komura, Naoko; Konishi, Miku; Imamura, Akihiro; Ishida, Hideharu; Kiso, Makoto; Fujiwara, Takahiro K; Kusumi, Akihiro

2018-01-01

Gangliosides have been implicated in a variety of physiological processes, particularly in the formation and function of raft domains in the plasma membrane. However, the scarcity of suitable fluorescent ganglioside analogs had long prevented us from determining exactly how gangliosides perform their functions in the live-cell plasma membrane. With the development of new fluorescent ganglioside analogs, as described by Komura et al. (2017), this barrier has been broken. We can now address the dynamic behaviors of gangliosides in the live-cell plasma membrane, using fluorescence microscopy, particularly by single-fluorescent molecule imaging and tracking. Single-molecule tracking of fluorescent GM1 and GM3 revealed that these molecules are transiently and dynamically recruited to monomers (monomer-associated rafts) and homodimer rafts of the raftophilic GPI-anchored protein CD59 in quiescent cells, with exponential residency times of 12 and 40ms, respectively, in a manner dependent on raft-lipid interactions. Upon CD59 stimulation, which induces CD59-cluster signaling rafts, the fluorescent GM1 and GM3 analogs were recruited to the signaling rafts, with a lifetime of 48ms. These results represent the first direct evidence that GPI-anchored receptors and gangliosides interact in a cholesterol-dependent manner. Furthermore, they show that gangliosides continually move in and out of rafts that contain CD59 in an extremely dynamic manner, with much higher frequency than expected previously. Such studies would not have been possible without fluorescent ganglioside probes, which exhibit native-like behavior and single-molecule tracking. In this chapter, we review the methods for single-molecule tracking of fluorescent ganglioside analogs and the results obtained by applying these methods. © 2018 Elsevier Inc. All rights reserved.

Endomorphin-2 is Released from Newborn Rat Primary Sensory Neurons in a Frequency- and Calcium- Dependent Manner

PubMed Central

Scanlin, Heather L.; Carroll, Elizabeth A.; Jenkins, Victoria K.; Balkowiec, Agnieszka

2008-01-01

Recent evidence indicates that endomorphins, endogenous mu-opioid receptor (MOR) agonists, modulate synaptic transmission in both somatic and visceral sensory pathways. Here we show that endomorphin-2 (END-2) is expressed in newborn rat dorsal root ganglion (DRG) and nodose-petrosal ganglion complex (NPG) neurons, and rarely co-localizes with brain-derived neurotrophic factor (BDNF). In order to examine activity-dependent release of END-2 from neurons, we established a model using dispersed cultures of DRG and NPG cells activated by patterned electrical field stimulation. To detect release of END-2, we developed a novel rapid capture ELISA, in which END-2 capture antibody was added to neuronal cultures shortly before their electrical stimulation. The conventional assay was effective at reliably detecting END-2 only when the cells were stimulated in the presence of CTAP, a MOR-selective antagonist. This suggests that the strength of the novel assay is related primarily to rapid capture of released END-2 before it binds to endogenous MORs. Using the rapid capture ELISA, we found that stimulation protocols known to induce plastic changes at sensory synapses were highly effective at releasing END-2. Removal of extracellular calcium or blocking voltage-activated calcium channels significantly reduced the release. Together, our data provide the first evidence that END-2 is expressed by newborn DRG neurons of all sizes found in this age group, and can be released from these, as well as from NPG neurons, in an activity-dependent manner. These results point to END-2 as a likely mediator of activity-dependent plasticity in sensory pathways. PMID:18513316

Time-dependent solutions for a stochastic model of gene expression with molecule production in the form of a compound Poisson process.

PubMed

Jędrak, Jakub; Ochab-Marcinek, Anna

2016-09-01

We study a stochastic model of gene expression, in which protein production has a form of random bursts whose size distribution is arbitrary, whereas protein decay is a first-order reaction. We find exact analytical expressions for the time evolution of the cumulant-generating function for the most general case when both the burst size probability distribution and the model parameters depend on time in an arbitrary (e.g., oscillatory) manner, and for arbitrary initial conditions. We show that in the case of periodic external activation and constant protein degradation rate, the response of the gene is analogous to the resistor-capacitor low-pass filter, where slow oscillations of the external driving have a greater effect on gene expression than the fast ones. We also demonstrate that the nth cumulant of the protein number distribution depends on the nth moment of the burst size distribution. We use these results to show that different measures of noise (coefficient of variation, Fano factor, fractional change of variance) may vary in time in a different manner. Therefore, any biological hypothesis of evolutionary optimization based on the nonmonotonic dependence of a chosen measure of noise on time must justify why it assumes that biological evolution quantifies noise in that particular way. Finally, we show that not only for exponentially distributed burst sizes but also for a wider class of burst size distributions (e.g., Dirac delta and gamma) the control of gene expression level by burst frequency modulation gives rise to proportional scaling of variance of the protein number distribution to its mean, whereas the control by amplitude modulation implies proportionality of protein number variance to the mean squared.

Model cerebellar granule cells can faithfully transmit modulated firing rate signals

PubMed Central

Rössert, Christian; Solinas, Sergio; D'Angelo, Egidio; Dean, Paul; Porrill, John

2014-01-01

A crucial assumption of many high-level system models of the cerebellum is that information in the granular layer is encoded in a linear manner. However, granule cells are known for their non-linear and resonant synaptic and intrinsic properties that could potentially impede linear signal transmission. In this modeling study we analyse how electrophysiological granule cell properties and spike sampling influence information coded by firing rate modulation, assuming no signal-related, i.e., uncorrelated inhibitory feedback (open-loop mode). A detailed one-compartment granule cell model was excited in simulation by either direct current or mossy-fiber synaptic inputs. Vestibular signals were represented as tonic inputs to the flocculus modulated at frequencies up to 20 Hz (approximate upper frequency limit of vestibular-ocular reflex, VOR). Model outputs were assessed using estimates of both the transfer function, and the fidelity of input-signal reconstruction measured as variance-accounted-for. The detailed granule cell model with realistic mossy-fiber synaptic inputs could transmit information faithfully and linearly in the frequency range of the vestibular-ocular reflex. This was achieved most simply if the model neurons had a firing rate at least twice the highest required frequency of modulation, but lower rates were also adequate provided a population of neurons was utilized, especially in combination with push-pull coding. The exact number of neurons required for faithful transmission depended on the precise values of firing rate and noise. The model neurons were also able to combine excitatory and inhibitory signals linearly, and could be replaced by a simpler (modified) integrate-and-fire neuron in the case of high tonic firing rates. These findings suggest that granule cells can in principle code modulated firing-rate inputs in a linear manner, and are thus consistent with the high-level adaptive-filter model of the cerebellar microcircuit. PMID:25352777

45 CFR 800.112 - Reporting requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) OPM specification of reporting requirements. OPM will specify the data and information that must be... specify the form, manner, processes, and frequency for the reporting of data and information. The Director... and administration of the MSPP in a manner similar to the FEHBP. (b) Quality and quality improvement...

45 CFR 800.112 - Reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) OPM specification of reporting requirements. OPM will specify the data and information that must be... specify the form, manner, processes, and frequency for the reporting of data and information. The Director... and administration of the MSPP in a manner similar to the FEHBP. (b) Quality and quality improvement...

A QCM-D study of the concentration- and time-dependent interactions of human LL37 with model mammalian lipid bilayers.

PubMed

Lozeau, Lindsay D; Rolle, Marsha W; Camesano, Terri A

2018-07-01

The human antimicrobial peptide LL37 is promising as an alternative to antibiotics due to its biophysical interactions with charged bacterial lipids. However, its clinical potential is limited due to its interactions with zwitterionic mammalian lipids leading to cytotoxicity. Mechanistic insight into the LL37 interactions with mammalian lipids may enable rational design of less toxic LL37-based therapeutics. To this end, we studied concentration- and time-dependent interactions of LL37 with zwitterionic model phosphatidylcholine (PC) bilayers with quartz crystal microbalance with dissipation (QCM-D). LL37 mass adsorption and PC bilayer viscoelasticity changes were monitored by measuring changes in frequency (Δf) and dissipation (ΔD), respectively. The Voigt-Kelvin viscoelastic model was applied to Δf and ΔD to study changes in bilayer thickness and density with LL37 concentration. At low concentrations (0.10-1.00 μM), LL37 adsorbed onto bilayers in a concentration-dependent manner. Further analyses of Δf, ΔD and thickness revealed that peptide saturation on the bilayers was a threshold for interactions observed above 2.00 μM, interactions that were rapid, multi-step, and reached equilibrium in a concentration- and time-dependent manner. Based on these data, we proposed a model of stable transmembrane pore formation at 2.00-10.0 μM, or transition from a primarily lipid to a primarily protein film with a transmembrane pore formation intermediate state at concentrations of LL37 > 10 μM. The concentration-dependent interactions between LL37 and PC bilayers correlated with the observed concentration-dependent biological activities of LL37 (antimicrobial, immunomodulatory and non-cytotoxic at 0.1-1.0 μM, hemolytic and some cytotoxicity at 2.0-13 μM and cytotoxic at >13 μM). Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of azelastine on sulphur dioxide induced impairment of ciliary motility in airway epithelium.

PubMed Central

Tamaoki, J; Chiyotani, A; Sakai, N; Takeyama, K; Konno, K

1993-01-01

OBJECTIVE--The effect of azelastine on airway mucociliary transport function was studied by measuring ciliary motility of human bronchial epithelium in vitro with a photoelectric method. METHOD--Bronchial epithelial cells were obtained by fibreoptic bronchoscopy, mounted in a Rose chamber, and perfused with Krebs-Henseleit solution. The preparations were placed on a microscope stage equipped with an illuminator, and the variations of light intensity caused by ciliary beating were detected by a photometer. RESULTS--The addition of azelastine to the perfusate increased ciliary beat frequency (CBF) in a dose dependent manner without ciliary discoordination. The mean (SE) maximal increase from the baseline value and the concentration required to produce a half maximal effect were 27.0 (4.2)% and 9.2 x 10(-6) mol/l, respectively. Exposure of the cells to the perfusate containing 3 ppm sulphur dioxide rapidly decreased CBF by 59.2 (5.0)%, and was accompanied by a reduction in intracellular cyclic AMP levels from 38.1 (4.3) to 10.1 (2.4) pmol/mg protein. This effect was prevented by pretreatment of cells with azelastine in a dose dependent manner. CONCLUSIONS--Azelastine not only stimulates ciliary motility of airway epithelium and hence mucociliary transport function, but may also protect against sulphur dioxide induced ciliary dysfunction, probably by inhibiting intracellular cyclic AMP loss. PMID:8322244

Drug Transport Mechanism of Oral Antidiabetic Nanomedicines

PubMed Central

Gundogdu, Evren; Yurdasiper, Aysu

2014-01-01

Context: Over the last few decades, extensive efforts have been made worldwide to develop nanomedicine delivery systems, especially via oral route for antidiabetic drugs. Absorption of insulin is hindered by epithelial cells of gastrointestinal tract, acidic gastric pH and digestive enzymes. Evidence Acquisition: Recent reports have identified and explained the beneficial role of several structural molecules like mucoadhesive polymers (polyacrylic acid, sodium alginate, chitosan) and other copolymers for the efficient transport and release of insulin to its receptors. Results: Insulin nanomedicines based on alginate-dextran sulfate core with a chitosan-polyethylene glycol-albumin shell reduced glycaemia in a dose dependent manner. Orally available exendin-4 formulations exerted their effects in a time dependent manner. Insulin nanoparticles formed by using alginate and dextran sulfate nucleating around calcium and binding to poloxamer, stabilized by chitosan, and subsequently coated with albumin showed a threefold increase of the hypoglycemic effect in comparison to free insulin in animal models. Solid lipid nanoparticles showed an enhancement of the bioavailability of repaglinide (RG) within optimized solid lipid nanoparticle formulations when compared with RG alone. Conclusions: Nanoparticles represent multiparticulate delivery systems designed to obtain prolonged or controlled drug delivery and to improve bioavailability as well as stability. Nanoparticles can also offer advantages like limiting fluctuations within therapeutic range, reducing side effects, protecting drugs from degradation, decreasing dosing frequency, and improving patient compliance and convenience PMID:24696697

Concentration-dependent activation of dopamine receptors differentially modulates GABA release onto orexin neurons.

PubMed

Linehan, Victoria; Trask, Robert B; Briggs, Chantalle; Rowe, Todd M; Hirasawa, Michiru

2015-08-01

Dopamine (DA) and orexin neurons play important roles in reward and food intake. There are anatomical and functional connections between these two cell groups: orexin peptides stimulate DA neurons in the ventral tegmental area and DA inhibits orexin neurons in the hypothalamus. However, the cellular mechanisms underlying the action of DA on orexin neurons remain incompletely understood. Therefore, the effect of DA on inhibitory transmission to orexin neurons was investigated in rat brain slices using the whole-cell patch-clamp technique. We found that DA modulated the frequency of spontaneous and miniature IPSCs (mIPSCs) in a concentration-dependent bidirectional manner. Low (1 μM) and high (100 μM) concentrations of DA decreased and increased IPSC frequency, respectively. These effects did not accompany a change in mIPSC amplitude and persisted in the presence of G-protein signaling inhibitor GDPβS in the pipette, suggesting that DA acts presynaptically. The decrease in mIPSC frequency was mediated by D2 receptors whereas the increase required co-activation of D1 and D2 receptors and subsequent activation of phospholipase C. In summary, our results suggest that DA has complex effects on GABAergic transmission to orexin neurons, involving cooperation of multiple receptor subtypes. The direction of dopaminergic influence on orexin neurons is dependent on the level of DA in the hypothalamus. At low levels DA disinhibits orexin neurons whereas at high levels it facilitates GABA release, which may act as negative feedback to curb the excitatory orexinergic output to DA neurons. These mechanisms may have implications for consummatory and motivated behaviours. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite.

PubMed

Saifullah, Bullo; Hussein, Mohd Zobir; Hussein-Al-Ali, Samer Hasan; Arulselvan, Palanisamy; Fakurazi, Sharida

2013-04-20

Tuberculosis (TB), is caused by the bacteria, Mycobacterium tuberculosis and its a threat to humans since centuries. Depending on the type of TB, its treatment can last for 6-24 months which is a major cause for patients non-compliance and treatment failure. Many adverse effects are associated with the currently available TB medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process.Development of the biocompatible nano drug delivery systems with the ability to minimize the side effects of the drugs, protection of the drug from enzymatic degradation. And most importantly the drug delivery systems which can deliver the drug at target site would increase the therapeutic efficacy. Nanovehicles with their tendency to release the drug in a sustained manner would result in the bioavalibilty of the drugs in the body for a longer period of time and this would reduce the dosing frequency in drug administration. The biocompatible nanovehicles with the properties like sustained release of drug of the target site, protection of the drug from physio-chemical degradation, reduction in dosing frequency, and prolong bioavailability of drug in the body would result in the shortening of the treatment duration. All of these factors would improve the patient compliance with chemotherapy of TB. An anti-tuberculosis drug, 4-amino salicylic acid (4-ASA) was successfully intercalated into the interlamellae of zinc layered hydroxide (ZLH) via direct reaction with zinc oxide suspension. The X-ray diffraction patterns and FTIR analyses indicate that the molecule was successfully intercalated into the ZLH interlayer space with an average basal spacing of 24 Å. Furthermore, TGA and DTG results show that the drug 4-ASA is stabilized in the interlayers by electrostatic interaction. The release of 4-ASA from the nanocomposite was found to be in a sustained manner. The nanocomposite treated with normal 3T3 cells shows it reduces cell viability in a dose- and time-dependent manner. Sustained release formulation of the nanocomposite, 4-ASA intercalated into zinc layered hydroxides, with its ease of preparation, sustained release of the active and less-toxic to the cell is a step forward for a more patient-friendly chemotherapy of Tuberculosis.

Sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite

PubMed Central

2013-01-01

Background Tuberculosis (TB), is caused by the bacteria, Mycobacterium tuberculosis and its a threat to humans since centuries. Depending on the type of TB, its treatment can last for 6–24 months which is a major cause for patients non-compliance and treatment failure. Many adverse effects are associated with the currently available TB medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process. Development of the biocompatible nano drug delivery systems with the ability to minimize the side effects of the drugs, protection of the drug from enzymatic degradation. And most importantly the drug delivery systems which can deliver the drug at target site would increase the therapeutic efficacy. Nanovehicles with their tendency to release the drug in a sustained manner would result in the bioavalibilty of the drugs in the body for a longer period of time and this would reduce the dosing frequency in drug administration. The biocompatible nanovehicles with the properties like sustained release of drug of the target site, protection of the drug from physio-chemical degradation, reduction in dosing frequency, and prolong bioavailability of drug in the body would result in the shortening of the treatment duration. All of these factors would improve the patient compliance with chemotherapy of TB. Result An anti-tuberculosis drug, 4-amino salicylic acid (4-ASA) was successfully intercalated into the interlamellae of zinc layered hydroxide (ZLH) via direct reaction with zinc oxide suspension. The X-ray diffraction patterns and FTIR analyses indicate that the molecule was successfully intercalated into the ZLH interlayer space with an average basal spacing of 24 Å. Furthermore, TGA and DTG results show that the drug 4-ASA is stabilized in the interlayers by electrostatic interaction. The release of 4-ASA from the nanocomposite was found to be in a sustained manner. The nanocomposite treated with normal 3T3 cells shows it reduces cell viability in a dose- and time-dependent manner. Conclusions Sustained release formulation of the nanocomposite, 4-ASA intercalated into zinc layered hydroxides, with its ease of preparation, sustained release of the active and less-toxic to the cell is a step forward for a more patient-friendly chemotherapy of Tuberculosis. PMID:23601852

Effects of mechanical vibration on proliferation and osteogenic differentiation of human periodontal ligament stem cells.

PubMed

Zhang, Chunxiang; Li, Ji; Zhang, Linkun; Zhou, Yi; Hou, Weiwei; Quan, Huixin; Li, Xiaoyu; Chen, Yangxi; Yu, Haiyang

2012-10-01

Paradental tissues (alveolar bone, periodontal ligament (PDL), and gingiva) have the capacity to adapt to their functional environment. The principal cellular elements of the PDL play an important role in normal function, regeneration of periodontal tissue and in orthodontic treatment. Recently, several studies have shown that low-magnitude, high-frequency (LMHF) mechanical vibration can positively influence bone homeostasis; however, the mechanism and optimal conditions for LMHF mechanical vibration have not been elucidated. It has been speculated that LMHF mechanical vibration stimulations have a favourable influence on osteocytes, osteoblasts and their precursors, thereby enhancing the expression of osteoblastic genes involved in bone formation and remodelling. The objective of this study was to test the effect of LMHF mechanical vibration on proliferation and osteogenic differentiation of human PDL stem cells (PDLSCs). Human PDLSCs were isolated from premolar teeth and randomized into vibration (magnitude: 0.3g; frequency: 10-180 Hz; 30 min/24h) and static cultures. The effect of vibration on PDLSC proliferation, differentiation and osteogenic potential was assessed at the genetic and protein level. After LMHF mechanical vibration, PDLSC proliferation was decreased; however, this was accompanied by increased markers of osteogenesis in a frequency-dependent manner. Specifically, alkaline phosphatase activity gradually increased with the frequency of vibration, to a peak at 50 Hz, and the level of osteocalcin was significantly higher than control following vibration at 40 Hz, 50 Hz, 60 Hz, 90 Hz and 120 Hz. Levels of Col-I, Runx2 and Osterix were significantly increased by LMHF mechanical vibration at frequencies of 40 Hz and 50 Hz. Our data demonstrates that LMHF mechanical vibration promotes PDLSC osteogenic differentiation and implies the existence of a frequency-dependent effect of vibration on determining PDLSC commitment to the osteoblast lineage. Copyright © 2012 Elsevier Ltd. All rights reserved.

The dynamics of mucosal-associated invariant T cells in multiple sclerosis.

PubMed

Sugimoto, Chie; Hirotani, Makoto; Yoshikiyo, Kazunori; Koshimizu, Uichi; Wakao, Rika; Horinouchi, Takahiro; Mazaki, Yuichi; Higashi, Tsunehiko; Fukazawa, Toshiyuki; Fujita, Hiroyoshi; Sasaki, Hidenao; Wakao, Hiroshi

2016-01-01

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination, gliosis and axonal loss in the Central Nervous System. Although the etiology of the disease has remained enigmatic, recent studies have suggested a role of the innate-like T cells, called Mucosal Associated Invariant T cells (MAITs) in the pathophysiology. In the present study, we have analyzed the relative frequency of MAITs and the expression of the cell surface antigens in MAITs to seek a possible link to the disease. There was little difference in the frequency of total MAITs between healthy donors (HDs) and untreated MS patients, whereas the latter harbored more CD8(lo/neg) (DN) MAITs concomitant with a decrease in CD8(high) MAITs and in CD4 MAITs compared with those in HDs. While the expression of CCR5, CCR6, CD95, CD127, and CD150 has increased in untreated subjects compared with that in HDs, CD45RO has declined in untreated subjects in both DN MAITs and CD8(hi) MAITs. FTY720 therapy has increased the relative frequency of total MAITs in a time-dependent fashion up to 2 years. Intriguingly, FTY720 therapy for 3 years reversed the above phenotype, engendering more CD8(high) MAITs accompanied with decreased DN MAITs. FTY720 therapy affected the cytokine production from CD4 T cells and also enhanced the relative frequency of cells producing both TNF-α and IFN-γ from MAITs, CD8 T cells, and CD4 T cells compared with that in untreated subjects. FTY 720 therapy enhanced the relative frequency of MAITs in MS patients in a time-dependent manner. Although the expression of CD8 in MAITs has been affected early by FTY720, longer treatment has reversed the phenotypic change. These data demonstrated that FTY720 induced dynamic change in the relative frequency and in the phenotype of MAITs in MS.

Frequency-dependent Alfvén-wave Propagation in the Solar Wind: Onset and Suppression of Parametric Decay Instability

NASA Astrophysics Data System (ADS)

Shoda, Munehito; Yokoyama, Takaaki; Suzuki, Takeru K.

2018-06-01

Using numerical simulations we investigate the onset and suppression of parametric decay instability (PDI) in the solar wind, focusing on the suppression effect by the wind acceleration and expansion. Wave propagation and dissipation from the coronal base to 1 au is solved numerically in a self-consistent manner; we take into account the feedback of wave energy and pressure in the background. Monochromatic waves with various injection frequencies, f 0, are injected to discuss the suppression of PDI, while broadband waves are applied to compare the numerical results with observation. We find that high-frequency ({f}0≳ {10}-3 {Hz}) Alfvén waves are subject to PDI. Meanwhile, the maximum growth rate of the PDI of low-frequency ({f}0≲ {10}-4 {Hz}) Alfvén waves becomes negative due to acceleration and expansion effects. Medium-frequency ({f}0≈ {10}-3.5 {Hz}) Alfvén waves have a positive growth rate but do not show the signature of PDI up to 1 au because the growth rate is too small. The medium-frequency waves experience neither PDI nor reflection so they propagate through the solar wind most efficiently. The solar wind is shown to possess a frequency-filtering mechanism with respect to Alfvén waves. The simulations with broadband waves indicate that the observed trend of the density fluctuation is well explained by the evolution of PDI while the observed cross-helicity evolution is in agreement with low-frequency wave propagation.

Modulation of human time processing by subthalamic deep brain stimulation.

PubMed

Wojtecki, Lars; Elben, Saskia; Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

2011-01-01

Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥ 130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥ 130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds.

Modulation of Human Time Processing by Subthalamic Deep Brain Stimulation

PubMed Central

Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

2011-01-01

Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds. PMID:21931767

Genotoxicity of fenpropathrin and fenitrothion on root tip cells of Vicia faba.

PubMed

Bu, N; Wang, S H; Yu, C M; Zhang, Y; Ma, C Y; Li, X M; Ma, L J

2011-11-01

The genotoxicity of fenpropathrin and fenitrothion on root tip cells of Vicia faba was studied. The symptoms were investigated about the mitotic index, the micronucleus frequency and chromosomal aberration frequency of root tip cells of Vicia faba which were induced by different concentrations of fenpropathrin and fenitrothion (1 × 10(-10)-1 × 10(-2) g L(-1)). Results showed that fenpropathrin and fenitrothion could induce the micronucleus of root tip cells of Vicia faba. It occurred in a dose-dependent manner. Peaks were observed at 1 × 10( -6) g L(-1) fenpropathrin and 1 × 10(-4) g L(-1) fenitrothion, and micronucleus frequency reached 14.587 ± 1.511‰ and 14.164 ± 1.623‰, respectively. From 1 × 10(-10) g L(-1) to 1 × 10( -6) g L(-1) fenpropathrin and 1 × 10(-4) g L(-1) fenitrothion, the micronucleus frequency increased with the increase of the concentrations, but beyond this range, the micronucleus frequency decreased with the further increase of the concentrations. A similar trend was observed for mitotic index. Moreover, fenpropathrin and fenitrothion could induce various types of chromosome aberration, such as lagging chromosomes, chromosome fragment, chromosome bridge, multipolar, nuclear buds, karyorrhexis, etc.

Multipath detection with the combination of SNR measurements - Example from urban environment

NASA Astrophysics Data System (ADS)

Špánik, Peter; Hefty, Ján

2017-12-01

Multipath is one of the most severe station-dependent error sources in both static and kinematic positioning. Relatively new and simple detection technique using the Signal-to-Noise (SNR) measurements on three frequencies will be presented based on idea of Strode and Groves. Exploitation of SNR measurements is benefi cial especially for their unambiguous character. Method is based on the fact that SNR values are closely linked with estimation of pseudo-ranges and phase measurements during signal correlation processing. Due to this connection, combination of SNR values can be used to detect anomalous behavior in received signal, however some kind of calibration in low multipath environment has to be done previously. In case of multipath, phase measurements on different frequencies will not be affected in the same manner. Specular multipath, e.g. from building wall introduces additional path delay which is interpreted differently on each of the used carrier, due to different wavelengths. Experimental results of multipath detection in urban environment will be presented. Originally proposed method is designed to work with three different frequencies in each epoch, thus only utilization of GPS Block II-F and Galileo satellites is possible. Simplification of detection statistics to use only two frequencies is made and results using GPS and GLONASS systems are presented along with results obtained using original formula.

Stimulus presentation order and the perception of lexical tones in Cantonese

NASA Astrophysics Data System (ADS)

Francis, Alexander L.; Ciocca, Valter

2003-09-01

Listeners' auditory discrimination of vowel sounds depends in part on the order in which stimuli are presented. Such presentation order effects have been argued to be language independent, and to result from psychophysical (not speech- or language-specific) factors such as the decay of memory traces over time or increased weighting of later-occurring stimuli. In the present study, native Cantonese speakers' discrimination of a linguistic tone continuum is shown to exhibit order of presentation effects similar to those shown for vowels in previous studies. When presented with two successive syllables differing in fundamental frequency by approximately 4 Hz, listeners were significantly more sensitive to this difference when the first syllable was higher in frequency than the second. However, American English-speaking listeners with no experience listening to Cantonese showed no such contrast effect when tested in the same manner using the same stimuli. Neither English nor Cantonese listeners showed any order of presentation effects in the discrimination of a nonspeech continuum in which tokens had the same fundamental frequencies as the Cantonese speech tokens but had a qualitatively non-speech-like timbre. These results suggest that tone presentation order effects, unlike vowel effects, may be language specific, possibly resulting from the need to compensate for utterance-related pitch declination when evaluating fundamental frequency for tone identification.

Frequency of sucrose exposure on the cariogenicity of a biofilm-caries model

PubMed Central

Díaz-Garrido, Natalia; Lozano, Carla; Giacaman, Rodrigo A.

2016-01-01

Objective: Although sucrose is considered the most cariogenic carbohydrate in the human diet, the question of how many exposures are needed to induce damage on the hard dental tissues remains unclear. To approach this question, different frequencies of daily sucrose exposure were tested on a relevant biological caries model. Materials and Methods: Biofilms of the Streptococcus mutans were formed on enamel slabs and exposed to cariogenic challenges with 10% sucrose for 5 min at 0, 1, 3, 5, 8, or 10 times per day. After 5 days, biofilms were retrieved to analyze biomass, protein content, viable bacteria, and polysaccharide formation. Enamel demineralization was evaluated by percentage of microhardness loss (percentage surface hardness loss [%SHL]). Results: Biomass, protein content, polysaccharide production, acidogenicity of the biofilm, and %SHL proportionally increased with the number of daily exposures to sucrose (P < 0.05). One daily sucrose exposure was enough to induce 20% more demineralization than the negative unexposed control. Higher frequencies induced greater demineralization and more virulent biofilms, but eight and ten exposures were not different between them in most of the analyzed variables (P > 0.05). Conclusions: Higher sucrose exposure seems to increase cariogenicity, in a frequency-dependent manner, by the modification of bacterial virulent properties. PMID:27403051

The Potential Effect of Sea Level Rise on Coastal Property Values

NASA Astrophysics Data System (ADS)

O'Donnell, J.

2015-12-01

It is well established that one consequence of increasing global sea level is that the frequency of flooding at low-lying coastal sites will increase. We review recent evidence that the effects coastal geometry will create substantial spatial variations in the changes in flooding frequency with scales of order 100km. Using a simple model of the evolution of coastal property values we demonstrate that a consequence of sea level rise is that the appreciation of coastal properties will peak, and then decline relative to higher properties. The time when the value reach a maximum is shown to depend upon the demand for the coastal property, and the local rate of change of flooding frequency due to sea level rise. The simple model is then extended to include, in an elementary manner, the effects on the value of adjacent but higher properties. We show that the effect of increased flooding frequency of the lower properties leads to an accelerated appreciation of the value of upland properties and an accelerated decline in the value of the coastal properties. We then provide some example calculations for selected sites. We conclude with a discussion of comparisons of the prediction of the analyses to recent data, and then comments on the impact of sea level rise on tax base of coastal communities.

Distributed friction damping of travelling wave vibration in rods.

PubMed

Tangpong, Xiangqing W; Wickert, Jonathan A; Akay, Adnan

2008-03-13

A ring damper can be affixed to a rotating base structure such as a gear, an automotive brake rotor or a gas turbine's labyrinth air seal. Depending on the frequency range, wavenumber and level of preload, vibration of the base structure can be effectively and passively attenuated by friction that develops along the interface between it and the damper. The assembly is modelled as two rods that couple in longitudinal vibration through spatially distributed hysteretic friction, with each rod having periodic boundary conditions in a manner analogous to an unwrapped ring and disc. As is representative of rotating machinery applications, the system is driven by a travelling wave disturbance, and for that form of excitation, the base structure's and the damper's responses are determined without the need for computationally intensive simulation. The damper's performance can be optimized with respect to normal preload, and its effectiveness is insensitive to variations in preload or the excitation's magnitude when its natural frequency is substantially lower than the base structure's in the absence of contact.

An evaluation of Space Shuttle STS-2 payload bay acoustic data and comparison with predictions

NASA Technical Reports Server (NTRS)

Wilby, J. F.; Piersol, A. G.; Wilby, E. G.

1982-01-01

Space average sound pressure levels computed from measurements at 18 locations in the payload bay of the Space Shuttle orbiter vehicle during the STS-2 launch were compared with predicted levels obtained using the PACES computer program. The comparisons were performed over the frequency range 12.5 Hz to 1000 Hz, since the test data at higher frequencies are contaminated by instrumentation background noise. In general the PACES computer program tends to overpredict the space average sound levels in the payload bay, although the magnitude of the discrepancy is usually small. Furthermore the discrepancy depends to some extent on the manner in which the payload is modeled analytically, and the method used to determine the "measured' space average sound pressure levels. Thus the difference between predicted and measured sound levels, averaged over the 20 one third octave bands from 12.5 Hz to 1000 Hz, varies from 1 dB to 3.5 dB.

Electrostatic ion-cyclotron waves in a nonuniform magnetic field

NASA Technical Reports Server (NTRS)

Cartier, S. L.; Dangelo, N.; Merlino, R. L.

1985-01-01

The properties of electrostatic ion-cyclotron waves excited in a single-ended cesium Q machine with a nonuniform magnetic field are described. The electrostatic ion-cyclotron waves are generated in the usual manner by drawing an electron current to a small exciter disk immersed in the plasma column. The parallel and perpendicular (to B) wavelengths and phase velocities are determined by mapping out two-dimensional wave phase contours. The wave frequency f depends on the location of the exciter disk in the nonuniform magnetic field, and propagating waves are only observed in the region where f is approximately greater than fci, where fci is the local ion-cyclotron frequency. The parallel phase velocity is in the direction of the electron drift. From measurements of the plasma properties along the axis, it is inferred that the electron drift velocity is not uniform along the entire current channel. The evidence suggests that the waves begin being excited at that axial position where the critical drift velocity is first exceeded, consistent with a current-driven excitation mechanism.

Depolarizing GABA/glycine synaptic events switch from excitation to inhibition during frequency increases

NASA Astrophysics Data System (ADS)

Branchereau, Pascal; Cattaert, Daniel; Delpy, Alain; Allain, Anne-Emilie; Martin, Elodie; Meyrand, Pierre

2016-02-01

By acting on their ionotropic chloride channel receptors, GABA and glycine represent the major inhibitory transmitters of the central nervous system. Nevertheless, in various brain structures, depolarizing GABAergic/glycinergic postsynaptic potentials (dGPSPs) lead to dual inhibitory (shunting) and excitatory components, the functional consequences of which remain poorly acknowledged. Indeed, the extent to which each component prevails during dGPSP is unclear. Understanding the mechanisms predicting the dGPSP outcome on neural network activity is therefore a major issue in neurobiology. By combining electrophysiological recordings of spinal embryonic mouse motoneurons and modelling study, we demonstrate that increasing the chloride conductance (gCl) favors inhibition either during a single dGPSP or during trains in which gCl summates. Finally, based on this summation mechanism, the excitatory effect of EPSPs is overcome by dGPSPs in a frequency-dependent manner. These results reveal an important mechanism by which dGPSPs protect against the overexcitation of neural excitatory circuits.

Do β3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?

PubMed Central

Afeli, Serge A. Y.; Hristov, Kiril L.

2012-01-01

In many species, β3-adrenergic receptors (β3-ARs) have been reported to play a primary role in pharmacologically induced detrusor smooth muscle (DSM) relaxation. However, their role in guinea pig DSM remains controversial. The aim of this study was to investigate whether β3-ARs are expressed in guinea pig DSM and to evaluate how BRL37344 and L-755,507, two selective β3-AR agonists, modulate guinea pig DSM excitability and contractility. We used a combined experimental approach including RT-PCR, patch-clamp electrophysiology, and isometric DSM tension recordings. β3-AR mRNA message was detected in freshly isolated guinea pig DSM single cells. BRL37344 but not L-755,507 caused a slight decrease in DSM spontaneous phasic contraction amplitude and frequency in a concentration-dependent manner. In the presence of atropine (1 μM), only the spontaneous phasic contractions frequency was inhibited by BRL37344 at higher concentrations. Both BRL37344 and L-755,507 significantly decreased DSM carbachol-induced phasic and tonic contractions in a concentration-dependent manner. However, only BRL37344 inhibitory effect was partially antagonized by SR59230A (10 μM), a β3-AR antagonist. In the presence of atropine, BRL37344 and L-755,507 had no inhibitory effect on electrical field stimulation-induced contractions. Patch-clamp experiments showed that BRL37344 (100 μM) did not affect the DSM cell resting membrane potential and K+ conductance. Although β3-ARs are expressed at the mRNA level, they play a minor to no role in guinea pig DSM spontaneous contractility without affecting cell excitability. However, BRL37344 and L-755,507 have pronounced inhibitory effects on guinea pig DSM carbachol-induced contractions. The study outlines important DSM β3-ARs species differences. PMID:21993887

Carrier-envelope phase effects for a dipolar molecule interacting with two-color pump-probe laser pulses

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

Cheng Taiwang; Brown, Alex

2004-12-01

The interaction of a two-level dipolar molecule with two laser pulses, where one laser's frequency is tuned to the energy level separation (pump laser) while the second laser's frequency is extremely small (probe laser), is investigated. A dipolar molecule is one with a nonzero difference between the permanent dipole moments of the molecular states. As shown previously [A. Brown, Phys. Rev. A 66, 053404 (2002)], the final population transfer between the two levels exhibits a dependence on the carrier-envelope phase of the probe laser. Based on the rotating-wave approximation (RWA), an effective Hamiltonian is derived to account for the basicmore » characteristics of the carrier-envelope phase dependence effect. By analysis of the effective Hamiltonian, scaling properties of the system are found with regard to field strengths, pulse durations, and frequencies. According to these scaling properties, the final-state population transfer can be controlled by varying the carrier-envelope phase of the probe laser field using lasers with weak field strengths (low intensities) and relatively long pulse durations. In order to examine the possible roles of background states, the investigation is extended to a three-level model. It is demonstrated that the carrier-envelope phase effect still persists in a well-defined manner even when neighboring energy levels are present. These results illustrate the potential of utilizing excitation in dipolar molecules as a means of measuring the carrier-envelope phase of a laser pulse or if one can manipulate the carrier envelope phase, as a method of controlling population transfer in dipolar molecules. The results also suggest that the carrier-envelope phases must be taken into account properly when performing calculations involving pump-probe excitation schemes with laser frequencies which differ widely in magnitude.« less

Are reconstruction filters necessary?

NASA Astrophysics Data System (ADS)

Holst, Gerald C.

2006-05-01

Shannon's sampling theorem (also called the Shannon-Whittaker-Kotel'nikov theorem) was developed for the digitization and reconstruction of sinusoids. Strict adherence is required when frequency preservation is important. Three conditions must be met to satisfy the sampling theorem: (1) The signal must be band-limited, (2) the digitizer must sample the signal at an adequate rate, and (3) a low-pass reconstruction filter must be present. In an imaging system, the signal is band-limited by the optics. For most imaging systems, the signal is not adequately sampled resulting in aliasing. While the aliasing seems excessive mathematically, it does not significantly affect the perceived image. The human visual system detects intensity differences, spatial differences (shapes), and color differences. The eye is less sensitive to frequency effects and therefore sampling artifacts have become quite acceptable. Indeed, we love our television even though it is significantly undersampled. The reconstruction filter, although absolutely essential, is rarely discussed. It converts digital data (which we cannot see) into a viewable analog signal. There are several reconstruction filters: electronic low-pass filters, the display media (monitor, laser printer), and your eye. These are often used in combination to create a perceived continuous image. Each filter modifies the MTF in a unique manner. Therefore image quality and system performance depends upon the reconstruction filter(s) used. The selection depends upon the application.

Physical properties of YBa 2Cu 3O 7- δ thin films using microstrip ring resonators technique

NASA Astrophysics Data System (ADS)

Lai, L. S.; Zeng, H. K.; Juang, J. Y.; Wu, K. H.; Uen, T. M.; Lin, J. Y.; Gou, Y. S.

2006-09-01

Microstrip ring resonators with quality factor ( Q) over 10 4 at temperature 5 K, were fabricated using the double-side YBa 2Cu 3O 7- δ (YBCO) epitaxial films deposited on LaAlO 3 (LAO) substrates. By placing a narrow gap in the ring resonator, we observed that the original fundamental resonating mode (resonance frequency f = 3.61 GHz) splits into a dual-mode with different resonating frequencies ( f = 1.80 GHz and f = 5.33 GHz). These two kinds of the resonator allow us to determine the temperature and frequency dependences of the magnetic penetration depth λ( T, f) and the surface loss. Several salient features of the above findings related to the nature of low-lying excitations for high- Tc superconductivity as a function of oxygen content will be elucidated. In particular, the current models, suggested by Wen and Lee, will be examined in a quantitative manner. It allows us to give a justification of quasiparticle as Fermi-liquid in the superconducting state. In addition, an equivalent inductance circuit model is suggested to account for the occurrence of the dual-mode resonance.

Within-host competitive interactions as a mechanism for the maintenance of parasite diversity

PubMed Central

Bashey, Farrah

2015-01-01

Variation among parasite strains can affect the progression of disease or the effectiveness of treatment. What maintains parasite diversity? Here I argue that competition among parasites within the host is a major cause of variation among parasites. The competitive environment within the host can vary depending on the parasite genotypes present. For example, parasite strategies that target specific competitors, such as bacteriocins, are dependent on the presence and susceptibility of those competitors for success. Accordingly, which parasite traits are favoured by within-host selection can vary from host to host. Given the fluctuating fitness landscape across hosts, genotype by genotype (G×G) interactions among parasites should be prevalent. Moreover, selection should vary in a frequency-dependent manner, as attacking genotypes select for resistance and genotypes producing public goods select for cheaters. I review competitive coexistence theory with regard to parasites and highlight a few key examples where within-host competition promotes diversity. Finally, I discuss how within-host competition affects host health and our ability to successfully treat infectious diseases. PMID:26150667

Effects of L-arabinose efflux on λ Red recombination-mediated gene knockout in multiple-antimicrobial-resistant Salmonella enterica serovar Choleraesuis.

PubMed

Liao, Shi-Wei; Lee, Jen-Jie; Ptak, Christopher P; Wu, Ying-Chen; Hsuan, Shih-Ling; Kuo, Chih-Jung; Chen, Ter-Hsin

2018-03-01

In this study, six swine-derived multiple-antimicrobial-resistant (MAR) strains of Salmonella Choleraesuis (S. Choleraesuis) were demonstrated to possess higher efflux pump activity than the wild-type (WT). L-Arabinose, a common inducer for gene expression, modulated S. Choleraesuis efflux pump activity in a dose-dependent manner. At low L-arabinose concentrations, increasing L-arabinose led to a corresponding increase in fluorophore efflux, while at higher L-arabinose concentrations, increasing L-arabinose decreased fluorophore efflux activity. The WT S. Choleraesuis that lacks TolC (ΔtolC), an efflux protein associated with bacterial antibiotic resistance and virulence, was demonstrated to possess a significantly reduced ability to extrude L-arabinose. Further, due to the rapid export of L-arabinose, an efficient method for recombination-mediated gene knockout, the L-arabinose-inducible bacteriophage λ Red recombinase system, has a reduced recombination frequency (~ 12.5%) in clinically isolated MAR Salmonella strains. An increased recombination frequency (up to 60%) can be achieved using a higher concentration of L-arabinose (fivefold) for genetic manipulation and functional analysis for MAR Salmonella using the λ Red system. The study suggests that L-arabinose serves not only as an inducer of the TolC-dependent efflux system but also acts as a competitive substrate of the efflux system. In addition, understanding the TolC-dependent efflux of L-arabinose should facilitate the optimization of L-arabinose induction in strains with high efflux activity.

Cumulative and Randomized Evaluation: Ascertaining Performance in Pharmacy Coursework in a Manner Congruent with Pharmacy Practice

ERIC Educational Resources Information Center

Bender, Kenneth J.; Purohit, Anal

1977-01-01

A testing mechanism that provides a closer approximation than traditional testing of the frequency and random manner with which disease state and therapeutic problems present in practice was developed with the initiation of self-directed study courses in pharmacy therapeutics. The rationales, construction, and application of this model for…

Vacuum tube operation analysis under multi-harmonic driving and heavy beam loading effect in J-PARC RCS

NASA Astrophysics Data System (ADS)

Yamamoto, M.; Nomura, M.; Shimada, T.; Tamura, F.; Hara, K.; Hasegawa, K.; Ohmori, C.; Toda, M.; Yoshii, M.; Schnase, A.

2016-11-01

An rf cavity in the J-PARC RCS not only covers the frequency range of a fundamental acceleration pattern but also generates multi-harmonic rf voltage because it has a broadband impedance. However, analyzing the vacuum tube operation in the case of multi-harmonics is very complicated because many variables must be solved in a self-consistent manner. We developed a method to analyze the vacuum tube operation using a well-known formula and which includes the dependence on anode current for some variables. The calculation method is verified with beam tests, and the results indicate that it is efficient under condition of multi-harmonics with a heavy beam loading effect.

The role of the sarcoplasmic reticulum in the generation of high heart rates and blood pressures in reptiles.

PubMed

Galli, Gina L J; Gesser, Hans; Taylor, Edwin W; Shiels, Holly A; Wang, Tobias

2006-05-01

The functional significance of the sarcoplasmic reticulum (SR) in the generation of high heart rates and blood pressures was investigated in four species of reptile; the turtle, Trachemys scripta; the python, Python regius, the tegu lizard, Tupinanvis merianae, and the varanid lizard, Varanus exanthematicus. Force-frequency trials and imposed pauses were performed on ventricular and atrial tissue from each species with and without the SR inhibitor ryanodine, and in the absence and presence of adrenaline. In all species, an imposed pause of 1 or 5 min caused a post-rest decay of force, and a negative force-frequency response was observed in all species within their in vivo frequency range of heart rates. These relationships were not affected by either ryanodine or adrenaline. In ventricular strips from varanid lizards and pythons, ryanodine caused significant reductions in twitch force within their physiologically relevant frequency range. In atrial tissue from the tegu and varanid lizards, SR inhibition reduced twitch force across the whole of their physiological frequency range. In contrast, in the more sedentary species, the turtle and the python, SR inhibition only decreased twitch force at stimulation frequencies above maximal in vivo heart rates. Adrenaline caused an increase in twitch force in all species studied. In ventricular tissue, this positive inotropic effect was sufficient to overcome the negative effects of ryanodine. In atrial tissue however, adrenaline could only ameliorate the negative effects of ryanodine at the lower pacing frequencies. Our results indicate that reptiles recruit Ca2+ from the SR for force development in a frequency and tissue dependent manner. This is discussed in the context of the development of high reptilian heart rates and blood pressures.

Not all reading disabilities are dyslexia: distinct neurobiology of specific comprehension deficits.

PubMed

Cutting, Laurie E; Clements-Stephens, Amy; Pugh, Kenneth R; Burns, Scott; Cao, Aize; Pekar, James J; Davis, Nicole; Rimrodt, Sheryl L

2013-01-01

Although an extensive literature exists on the neurobiological correlates of dyslexia (DYS), to date, no studies have examined the neurobiological profile of those who exhibit poor reading comprehension despite intact word-level abilities (specific reading comprehension deficits [S-RCD]). Here we investigated the word-level abilities of S-RCD as compared to typically developing readers (TD) and those with DYS by examining the blood oxygenation-level dependent response to words varying on frequency. Understanding whether S-RCD process words in the same manner as TD, or show alternate pathways to achieve normal word-reading abilities, may provide insights into the origin of this disorder. Results showed that as compared to TD, DYS showed abnormal covariance during word processing with right-hemisphere homologs of the left-hemisphere reading network in conjunction with left occipitotemporal underactivation. In contrast, S-RCD showed an intact neurobiological response to word stimuli in occipitotemporal regions (associated with fast and efficient word processing); however, inferior frontal gyrus (IFG) abnormalities were observed. Specifically, TD showed a higher-percent signal change within right IFG for low-versus-high frequency words as compared to both S-RCD and DYS. Using psychophysiological interaction analyses, a coupling-by-reading group interaction was found in right IFG for DYS, as indicated by a widespread greater covariance between right IFG and right occipitotemporal cortex/visual word-form areas, as well as bilateral medial frontal gyrus, as compared to TD. For S-RCD, the context-dependent functional interaction anomaly was most prominently seen in left IFG, which covaried to a greater extent with hippocampal, parahippocampal, and prefrontal areas than for TD for low- as compared to high-frequency words. Given the greater lexical access demands of low frequency as compared to high-frequency words, these results may suggest specific weaknesses in accessing lexical-semantic representations during word recognition. These novel findings provide foundational insights into the nature of S-RCD, and set the stage for future investigations of this common, but understudied, reading disorder.

Direct block of hERG potassium channels by the protein kinase C inhibitor bisindolylmaleimide I (GF109203X).

PubMed

Thomas, Dierk; Hammerling, Bettina C; Wimmer, Anna-Britt; Wu, Kezhong; Ficker, Eckhard; Kuryshev, Yuri A; Scherer, Daniel; Kiehn, Johann; Katus, Hugo A; Schoels, Wolfgang; Karle, Christoph A

2004-12-01

The human ether-a-go-go-related gene (hERG) encodes the rapid component of the cardiac repolarizing delayed rectifier potassium current, I(Kr). The direct interaction of the commonly used protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIM I) with hERG, KvLQT1/minK, and I(Kr) currents was investigated in this study. hERG and KvLQT1/minK channels were heterologously expressed in Xenopus laevis oocytes, and currents were measured using the two-microelectrode voltage clamp technique. In addition, hERG currents in stably transfected human embryonic kidney (HEK 293) cells, native I(Kr) currents and action potentials in isolated guinea pig ventricular cardiomyocytes were recorded using whole-cell patch clamp electrophysiology. Bisindolylmaleimide I blocked hERG currents in HEK 293 cells and Xenopus oocytes in a concentration-dependent manner with IC(50) values of 1.0 and 13.2 muM, respectively. hERG channels were primarily blocked in the open state in a frequency-independent manner. Analysis of the voltage-dependence of block revealed a reduction of inhibition at positive membrane potentials. BIM I caused a shift of -20.3 mV in the voltage-dependence of inactivation. The point mutations tyrosine 652 alanine (Y652A) and phenylalanine 656 alanine (F656A) attenuated hERG current blockade, indicating that BIM I binds to a common drug receptor within the pore region. KvLQT1/minK currents were not significantly altered by BIM I. Finally, 1 muM BIM I reduced native I(Kr) currents by 69.2% and lead to action potential prolongation. In summary, PKC-independent effects have to be carefully considered when using BIM I as PKC inhibitor in experimental models involving hERG channels and I(Kr) currents.

Paternal engagement during childbirth depending on the manner of their preparation.

PubMed

Sioma-Markowska, Urszula; Poręba, Ryszard; Machura, Mariola; Skrzypulec-Plinta, Violetta

2016-01-01

The analysis of the forms of paternal activity depending on the manner of their preparation, including stages of labor. A prospective survey-based study involved 250 fathers who participated in their child's birth. The fathers included in the study were present during all stages of family-assisted natural labor. The study was conducted one day after childbirth with the use of a survey prepared by the authors. Statistical calculations were conducted using the Statistica PL software. The frequency of individual qualitative features (non-measurable) was assessed by means of a non-parametric χ² (chi-squared) test. The statistical significance level was p < 0.05. A half of the fathers included in the study (52.4%) participated in childbirth with no prior preparation. The dominant form of preparation involved self-education from books, magazines and the Internet (24%). 23.6% of fathers participated in ante-natal classes. The study demonstrated that fathers prepared for childbirth in ante-natal classes more often engaged in the supportive role, provided nursing care and carried out instrumental monitoring during each stage of childbirth. The fathers prepared for childbirth in ante-natal classes more often engage in the supportive role, provide nursing care and carry out instrumental control during each stage of childbirth. Ante-natal classes should be promoted as an optimal form of preparation for active participation in childbirth. Moreover, other forms of paternal ante-natal education as well as continued education in a delivery room should be developed.

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

PubMed

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

2013-02-01

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

Substance P stimulates the opossum sphincter of Oddi in vitro.

PubMed

Parodi, J E; Cho, N; Zenilman, M E; Barteau, J A; Soper, N J; Becker, J M

1990-09-01

We have previously shown that substance P (SP) regulates sphincter of Oddi (SO) motility in vivo. However, its mechanism of action remains unclear. Our aim was to develop an in vitro model to measure spikeburst (SB) an contractile frequency (CMC) of the SO and to characterize further SP effects. In 16 opossums, SO rings were excised, mounted within a Kreb's tissue bath with bipolar electrodes and force transducers, allowed to equilibrate, and exposed to increasing SP concentrations with washout between each test solution. Spikeburst and CMC frequencies were recorded on a polygraph, quantitated, expressed as differences before and during SP, and statistically analyzed with Student's test. Although SP induced a significant concentration-dependent increase in phasic SB frequency and CMC, the amplitude of concentrations was not affected by SP. A close correlation was found between basal and SP-stimulated SB and CMC, suggesting myoelectric and mechanical coupling. Previous exposure of SO to SP antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP significantly decreased the response to SP. Tetrodotoxin (TTX), did not affect the delta CMC response to SP. In conclusion an in vitro preparation was developed to study the effect of SP on the SO. Substance P increased SB and CMC of the SO in a concentration-dependent fashion, thus acting as a stimulatory peptide. Perfusion of SO rings with SP antagonist had no effect on basal CMC but significantly inhibited the action of SP in a competitive manner. The effect of SP was not altered by TTX. These data suggest that the action of SP on the SO is primarily myogenic.

Cutting edge: double-stranded DNA breaks in the IgV region gene were detected at lower frequency in affinity-maturation impeded GANP-/- mice.

PubMed

Kawatani, Yousuke; Igarashi, Hideya; Matsui, Takeshi; Kuwahara, Kazuhiko; Fujimura, Satoru; Okamoto, Nobukazu; Takagi, Katsumasa; Sakaguchi, Nobuo

2005-11-01

Double-stranded DNA breaks (DSBs) at the IgV region (IgV) genes might be involved in somatic hypermutation and affinity-maturation of the B cell receptor in response to T cell-dependent Ag. By ligation-mediated PCR, we studied IgV DSBs that occurred in mature germinal center B cells in response to nitrophenyl-chicken gamma-globulin in a RAG1-independent, Ag-dependent, and IgV-selective manner. We quantified their levels in GANP-deficient B cells that have impaired generation of high-affinity Ab. GANP-/- B cells showed a decreased level of DSBs with blunt ends than control B cells and, on the contrary, the ganp gene transgenic (GANPTg) B cells showed an increased level. These results suggested that the level of IgV DSBs in germinal center B cells is associated with GANP expression, which is presumably required for B cell receptor affinity maturation.

Gap junction plasticity as a mechanism to regulate network-wide oscillations

PubMed Central

Nicola, Wilten; Clopath, Claudia

2018-01-01

Cortical oscillations are thought to be involved in many cognitive functions and processes. Several mechanisms have been proposed to regulate oscillations. One prominent but understudied mechanism is gap junction coupling. Gap junctions are ubiquitous in cortex between GABAergic interneurons. Moreover, recent experiments indicate their strength can be modified in an activity-dependent manner, similar to chemical synapses. We hypothesized that activity-dependent gap junction plasticity acts as a mechanism to regulate oscillations in the cortex. We developed a computational model of gap junction plasticity in a recurrent cortical network based on recent experimental findings. We showed that gap junction plasticity can serve as a homeostatic mechanism for oscillations by maintaining a tight balance between two network states: asynchronous irregular activity and synchronized oscillations. This homeostatic mechanism allows for robust communication between neuronal assemblies through two different mechanisms: transient oscillations and frequency modulation. This implies a direct functional role for gap junction plasticity in information transmission in cortex. PMID:29529034

DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition.

PubMed

Liu, Xiao; Dang, Yunkun; Matsu-Ura, Toru; He, Yubo; He, Qun; Hong, Christian I; Liu, Yi

2017-07-20

Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here, we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter. The FACT complex, known to be involved in histone disassembly/reassembly, is required for clock function and is recruited to the frq promoter in a replication-dependent manner to promote replacement of histone H2A.Z by H2A. Finally, deletion of H2A.Z uncoupled the dependence of the circadian clock on DNA replication. Together, these results establish circadian clock and cell cycle as interdependent coupled oscillators and identify DNA replication as a critical process in the circadian mechanism. Published by Elsevier Inc.

In vitro effect of the antimalarial drug proguanil hydrochloride on viability and DNA damage in human peripheral blood lymphocytes.

PubMed

Gajski, Goran; Dinter, Domagoj; Garaj-Vrhovac, Vera

2010-11-01

This study aimed to evaluate the effect of proguanil, a chemical substance used for treatment and prevention of malaria on viability and DNA integrity in human lymphocytes in vitro. Two different concentrations of proguanil obtained from the plasma concentrations were used: 130ng/ml used for prophylactic treatment and 520ng/ml used in treatment of malaria. Testing was done with and without metabolic activation. Viability of lymphocytes decreased in time and dose dependent manner. Comet assay parameters showed similar effects, indicating that some damage to DNA molecule can occur. Frequency of sister chromatid exchanges did not show significant deviation from the control samples. As for the proliferation kinetics no significant changes were noticed. Since majority of DNA damaging effect is induced after metabolic activation it is to be concluded that activity of proguanil is dependent upon the active metabolite cycloguanil and that monitoring should be conducted especially among frequent travellers. Copyright © 2010 Elsevier B.V. All rights reserved.

[Effects of nitrous oxide on electroencephalographic activity during sevoflurane anesthesia: a zero-crossing analysis].

PubMed

Kaneda, T; Ochiai, R; Takeda, J; Fukushima, K

1995-11-01

We have investigated the influence of nitrous oxide (N2O) on central nervous system (CNS) during sevoflurane anesthesia by using zero-crossing method of EEG in 31 patients. The study was divided into three parts: Study 1 (n = 18), Study 2 (n = 6) and Study 3 (n = 7). (Study 1) After induction of anesthesia, sevoflurane 1.0 % in oxygen (O2), and sevoflurane 1.0 % with 67 % N2O in O2 were given to the patients sequentially in a random fashion, and EEG was recorded. (Study 2) Sevoflurane 1.7 % in O2, and sevoflurane 0.7 % with 67 % N2O in O2, which were considered to be the same anesthetic depth (= sevoflurane 1 MAC), were inhaled, and EEG was recorded in the same manner as in the study 1. (Study 3) We compared the effects of N2O on EEG during intravenous administration of fentanyl and midazolam with 67 % N2O, and without N2O, and EEG was recorded in the same manner. In all studies, percentage of each frequency range (delta, theta, alpha, beta) and average frequency were calculated by zero-crossing method. During sevoflurane anesthesia, the EEG activity was decelerated with N2O, depending on minimum alveolar concentration (MAC). But there were no significant changes in EEG activity of the patient with and those without N2O during intravenous anesthesia. We concluded that the influences of N2O on CNS can be evaluated by quantitative analysis of EEG.

A Theory of Term Importance in Automatic Text Analysis.

ERIC Educational Resources Information Center

Salton, G.; And Others

Most existing automatic content analysis and indexing techniques are based on work frequency characteristics applied largely in an ad hoc manner. Contradictory requirements arise in this connection, in that terms exhibiting high occurrence frequencies in individual documents are often useful for high recall performance (to retrieve many relevant…

Determination of the hydrate structure of an isolated alcoholic OH in hydrophobic medium by infrared and near-infrared spectroscopy.

PubMed

Iwamoto, Reikichi; Kusanagi, Hiroshi

2009-05-07

This paper reports the structure of the hydrate complex of an isolated alcoholic OH, produced in a small amount in hydrophobic solution in heptane. The structure was determined from the changes, caused by hydration, in the infrared and near-infrared spectra of 2-nonanol in the solution. The changes were exhibited in the "difference" spectrum, in which the spectrum of the solution before hydration was subtracted from that after hydration. The difference spectrum showed a "plus" or "minus" peak at the frequency of the stretching band of a free OH, depending on whether the concentration was below or above about 2%(v/v), respectively. The plus peak appears because the OH stretching band of the isolated OH that acts as an acceptor does not change in frequency but significantly increases in intensity, in agreement with theoretical calculations. In contrast, the stretching band of an isolated OH that acts as a donor shifts downward. This shift decreases the intensity at the stretching frequency of a free OH, giving rise to a minus peak at the frequency in the difference spectrum. It was concluded that an isolated OH is hydrated in the manner as HO...HOH and OH...OH(2) at a concentration below and above about 2%, respectively, in the hydrophobic solution of 2-nonanol.

Kohn's theorem in a superfluid Fermi gas with a Feshbach resonance

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

Ohashi, Y.

2004-12-01

We investigate the dipole mode in a superfluid gas of Fermi atoms trapped in a harmonic potential. According to Kohn's theorem, the frequency of this collective mode is not affected by an interaction between the atoms and is always equal to the trap frequency. This remarkable property, however, does not necessarily hold in an approximate theory. We explicitly prove that the Hartree-Fock-Bogoliubov generalized random phase approximation (HFB-GRPA), including a coupling between fluctuations in the density and Cooper channels, is consistent with both Kohn's theorem as well as Goldstone's theorem. This proof can be immediately extended to the strong-coupling superfluid theorymore » developed by Nozieres and Schmitt-Rink (NSR), where the effect of superfluid fluctuations is included within the Gaussian level. As a result, the NSR-GRPA formalism can be used to study collective modes in the BCS-BEC crossover region in a manner which is consistent with Kohn's theorem. We also include the effect of a Feshbach resonance and a condensate of the associated molecular bound states. A detailed discussion is given of the unusual nature of the Kohn mode eigenfunctions in a Fermi superfluid, in the presence and absence of a Feshbach resonance. When the molecular bosons feel a different trap frequency from the Fermi atoms, the dipole frequency is shown to depend on the strength of effective interaction associated with the Feshbach resonance.« less

Oscillatory fluid flow induces the osteogenic lineage commitment of mesenchymal stem cells: The effect of shear stress magnitude, frequency, and duration.

PubMed

Stavenschi, Elena; Labour, Marie-Noelle; Hoey, David A

2017-04-11

A potent regulator of bone anabolism is physical loading. However, it is currently unclear whether physical stimuli such as fluid shear within the marrow cavity is sufficient to directly drive the osteogenic lineage commitment of resident mesenchymal stem cells (MSC). Therefore, the objective of the study is to employ a systematic analysis of oscillatory fluid flow (OFF) parameters predicted to occur in vivo on early MSC osteogenic responses and late stage lineage commitment. MSCs were exposed to OFF of 1Pa, 2Pa and 5Pa magnitudes at frequencies of 0.5Hz, 1Hz and 2Hz for 1h, 2h and 4h of stimulation. Our findings demonstrate that OFF elicits a positive osteogenic response in MSCs in a shear stress magnitude, frequency, and duration dependent manner that is gene specific. Based on the mRNA expression of osteogenic markers Cox2, Runx2 and Opn after short-term fluid flow stimulation, we identified that a regime of 2Pa shear magnitude and 2Hz frequency induces the most robust and reliable upregulation in osteogenic gene expression. Furthermore, long-term mechanical stimulation utilising this regime, elicits a significant increase in collagen and mineral deposition when compared to static control demonstrating that mechanical stimuli predicted within the marrow is sufficient to directly drive osteogenesis. Copyright © 2017. Published by Elsevier Ltd.

Heritable stress response dynamics revealed by single-cell genealogy

PubMed Central

2018-01-01

Cells often respond to environmental stimuli by activating specific transcription factors. Upon exposure to glucose limitation stress, it is known that yeast Saccharomyces cerevisiae cells dephosphorylate the general stress response factor Msn2, leading to its nuclear localization, which in turn activates the expression of many genes. However, the precise dynamics of Msn2 nucleocytoplasmic translocations and whether they are inherited over multiple generations in a stress-dependent manner are not well understood. Tracking Msn2 localization events in yeast lineages grown on a microfluidic chip, here we report how cells modulate the amplitude, duration, frequency, and dynamic pattern of the localization events in response to glucose limitation stress. Single yeast cells were found to modulate the amplitude and frequency of Msn2 nuclear localization, but not its duration. Moreover, the Msn2 localization frequency was epigenetically inherited in descendants of mother cells, leading to a decrease in cell-to-cell variation in localization frequency. An analysis of the time dynamic patterns of nuclear localizations between genealogically related cell pairs using an information theory approach found that the magnitude of pattern similarity increased with stress intensity and was strongly inherited by the descendant cells at the highest stress level. By dissecting how general stress response dynamics is contributed by different modulation schemes over long time scales, our work provides insight into which scheme evolution might have acted on to optimize fitness in stressful environments. PMID:29675464

Frequency-duration analysis of dissolved-oxygen concentrations in two southwestern Wisconsin streams

USGS Publications Warehouse

Greb, Steven R.; Graczyk, David J.

2007-01-01

Historically, dissolved-oxygen (DO) data have been collected in the same manner as other water-quality constituents, typically at infrequent intervals as a grab sample or an instantaneous meter reading. Recent years have seen an increase in continuous water-quality monitoring with electronic dataloggers. This new technique requires new approaches in the statistical analysis of the continuous record. This paper presents an application of frequency-duration analysis to the continuous DO records of a cold and a warm water stream in rural southwestern Wisconsin. This method offers a quick, concise way to summarize large time-series data bases in an easily interpretable manner. Even though the two streams had similar mean DO concentrations, frequency-duration analyses showed distinct differences in their DO-concentration regime. This type of analysis also may be useful in relating DO concentrations to biological effects and in predicting low DO occurrences.

Protective role of Delphinium denudatum (Jadwar) against morphine induced tolerance and dependence in mice.

PubMed

Zafar, S; Ahmad, M A; Siddiqui, T A

2001-11-01

Chronic treatment with Delphinium denudatum (Dd) (Jadwar) (family: Ranunculaceae, 200-1600 mg/kg) suppressed morphine withdrawal jumps in a dose-dependent manner, a sign of the development of dependence to opiate as assessed by naloxone (2 mg/kg) precipitation withdrawal on day 10 of testing in mice. Repeated administration of Dd (200-1600 mg/kg) for 9 days attenuated the development of tolerance to the analgesic effect of morphine (10 mg/kg), also produces significant change in tail-flick latency from the saline pretreated group in a dose-dependent manner.

Loss of CDKL5 in Glutamatergic Neurons Disrupts Hippocampal Microcircuitry and Leads to Memory Impairment in Mice

PubMed Central

Wang, I-Ting Judy; Yue, Cuiyong; Takano, Hajime; Terzic, Barbara

2017-01-01

Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal neurons lacking CDKL5 show decreased dendritic complexity but a trend toward increased spine density. This morphological change is accompanied by an increase in the frequency of spontaneous miniature EPSCs and interestingly, miniature IPSCs. Using voltage-sensitive dye imaging to interrogate the evoked response of the CA1 microcircuit, we find that CA1 pyramidal neurons lacking CDKL5 show hyperexcitability in their dendritic domain that is constrained by elevated inhibition in a spatially and temporally distinct manner. These results suggest a novel role for CDKL5 in the regulation of synaptic function and uncover an intriguing microcircuit mechanism underlying impaired learning and memory. SIGNIFICANCE STATEMENT Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a severe neurodevelopmental disorder caused by mutations in the CDKL5 gene. Although Cdkl5 constitutive knock-out mice have recapitulated key aspects of human symptomatology, the cellular origins of CDKL5 deficiency-related phenotypes are unknown. Here, using conditional knock-out mice, we show that hippocampal-dependent learning and memory deficits in CDKL5 deficiency have origins in glutamatergic neurons of the forebrain and that loss of CDKL5 results in the enhancement of synaptic transmission and disruptions in neural circuit dynamics in a spatially and temporally specific manner. Our findings demonstrate that CDKL5 is an important regulator of synaptic function in glutamatergic neurons and serves a critical role in learning and memory. PMID:28674172

Loss of CDKL5 in Glutamatergic Neurons Disrupts Hippocampal Microcircuitry and Leads to Memory Impairment in Mice.

PubMed

Tang, Sheng; Wang, I-Ting Judy; Yue, Cuiyong; Takano, Hajime; Terzic, Barbara; Pance, Katarina; Lee, Jun Y; Cui, Yue; Coulter, Douglas A; Zhou, Zhaolan

2017-08-02

Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal neurons lacking CDKL5 show decreased dendritic complexity but a trend toward increased spine density. This morphological change is accompanied by an increase in the frequency of spontaneous miniature EPSCs and interestingly, miniature IPSCs. Using voltage-sensitive dye imaging to interrogate the evoked response of the CA1 microcircuit, we find that CA1 pyramidal neurons lacking CDKL5 show hyperexcitability in their dendritic domain that is constrained by elevated inhibition in a spatially and temporally distinct manner. These results suggest a novel role for CDKL5 in the regulation of synaptic function and uncover an intriguing microcircuit mechanism underlying impaired learning and memory. SIGNIFICANCE STATEMENT Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a severe neurodevelopmental disorder caused by mutations in the CDKL5 gene. Although Cdkl5 constitutive knock-out mice have recapitulated key aspects of human symptomatology, the cellular origins of CDKL5 deficiency-related phenotypes are unknown. Here, using conditional knock-out mice, we show that hippocampal-dependent learning and memory deficits in CDKL5 deficiency have origins in glutamatergic neurons of the forebrain and that loss of CDKL5 results in the enhancement of synaptic transmission and disruptions in neural circuit dynamics in a spatially and temporally specific manner. Our findings demonstrate that CDKL5 is an important regulator of synaptic function in glutamatergic neurons and serves a critical role in learning and memory. Copyright © 2017 the authors 0270-6474/17/377420-18$15.00/0.

Achromatic phase-matching second harmonic generation for a tunable laser

DOEpatents

Jacobson, A.G.; Bisson, S.; Trebino, R.

1998-01-20

An optical system uses a nonlinear optical medium to alter the frequency of a relatively narrow band light source tunable over a plurality of different frequencies using an optical system for passively directing light to the nonlinear medium at a correct phase matching angle. In this manner, the light from the tunable light source can be efficiently frequency-doubled or frequency-tripled without the need of moving parts. An all prism design provides a system of optimal efficiency. 6 figs.

Achromatic phase-matching second harmonic generation for a tunable laser

DOEpatents

Jacobson, Alexander Gerson; Bisson, Scott; Trebino, Rick

1998-01-01

An optical system uses a nonlinear optical medium to alter the frequency of a relatively narrow band light source tunable over a plurality of different frequencies using an optical system for passively directing light to the nonlinear medium at a correct phase matching angle. In this manner, the light from the tunable light source can be efficiently frequency-doubled or frequency-tripled without the need of moving parts. An all prism design provides a system of optimal efficiency.

Are pacemaker properties required for respiratory rhythm generation in adult turtle brain stems in vitro?

PubMed

Johnson, Stephen M; Wiegel, Liana M; Majewski, David J

2007-08-01

The role of pacemaker properties in vertebrate respiratory rhythm generation is not well understood. To address this question from a comparative perspective, brain stems from adult turtles were isolated in vitro, and respiratory motor bursts were recorded on hypoglossal (XII) nerve rootlets. The goal was to test whether burst frequency could be altered by conditions known to alter respiratory pacemaker neuron activity in mammals (e.g., increased bath KCl or blockade of specific inward currents). While bathed in artificial cerebrospinal fluid (aCSF), respiratory burst frequency was not correlated with changes in bath KCl (0.5-10.0 mM). Riluzole (50 microM; persistent Na(+) channel blocker) increased burst frequency by 31 +/- 5% (P < 0.05) and decreased burst amplitude by 42 +/- 4% (P < 0.05). In contrast, flufenamic acid (FFA, 20-500 microM; Ca(2+)-activated cation channel blocker) reduced and abolished burst frequency in a dose- and time-dependent manner (P < 0.05). During synaptic inhibition blockade with bicuculline (50 microM; GABA(A) channel blocker) and strychnine (50 muM; glycine receptor blocker), rhythmic motor activity persisted, and burst frequency was directly correlated with extracellular KCl (0.5-10.0 mM; P = 0.005). During synaptic inhibition blockade, riluzole (50 microM) did not alter burst frequency, whereas FFA (100 microM) abolished burst frequency (P < 0.05). These data are most consistent with the hypothesis that turtle respiratory rhythm generation requires Ca(2+)-activated cation channels but not pacemaker neurons, which thereby favors the group-pacemaker model. During synaptic inhibition blockade, however, the rhythm generator appears to be transformed into a pacemaker-driven network that requires Ca(2+)-activated cation channels.

A refined protocol for coding nursing home residents' comments during satisfaction interviews.

PubMed

Levy-Storms, Lené; Simmons, Sandra F; Gutierrez, Veronica F; Miller-Martinez, Dana; Hickey, Kelly; Schnelle, John F

2005-11-01

This study's objective was to refine a method for coding nursing home (NH) residents' comments about their perceptions of care into unmet needs specific to the manner and frequency of care delivery. NH residents (N=69) were interviewed with both closed-ended (i.e., forced-choice) and open-ended (i.e., residents' own words) questions about their perceptions of care across eight care domains. Unmet needs included comments indicating that residents desired a change in staff- and non-staff-related care. Staff-related unmet needs were further coded into unmet emotional support (i.e., emotional support or manner of care delivery) and instrumental (i.e., instrumental support or frequency of care) needs. Of 66 residents who commented, 66% expressed at least one unmet need across eight care domains. Among these 44 residents, 52% and 84% had unmet emotional support and instrumental support needs, respectively (kappa=68 and.92). An additional 18% expressed both unmet emotional support and instrumental support needs. The refined method offers a systematic way to code residents' comments about their care into unmet needs related to the manner and frequency of care delivery. The findings have direct implications for the identification of care areas in need of improvement from the resident's perspective and the evaluation of improvement efforts.

Evaluation of the RBC Pig-a and PIGRET assays using single doses of hydroxyurea and melphalan in rats.

PubMed

Adachi, Hideki; Uematsu, Yasuaki; Yamada, Toru

2016-11-15

To evaluate the suitability of the rat Pig-a assay on reticulocytes (PIGRET assay) as a short-term test, red blood cell (RBC) Pig-a and PIGRET assays after single doses with hydroxyurea (HU) and melphalan (L-PAM) were conducted and the results of both assays were compared. HU was administered once orally to male SD rats at 250, 500 and 1000mg/kg, and both assays were conducted using peripheral blood withdrawn from the jugular vein at 1, 2 and 4 weeks after dosing. L-PAM was administered at 1.25, 2.5 and 5mg/kg in the same manner. L-PAM produced significant dose-dependent increases in mutant frequencies in the PIGRET assay after single oral doses, but did not produce dose-dependent increases in mutant frequencies in the RBC Pig-a assay. These results suggest that the PIGRET assay is more sensitive for the evaluation of the mutagenic potential of L-PAM than the RBC Pig-a assay. In contrast, HU, a clastogenic but not DNA-reactive compound, gave negative results in both assays. The results with these 2 chemicals indicate that the single-dose PIGRET assay in rats has the potential to properly detect DNA-reactive compounds that directly cause DNA damage in a short-term assay. Copyright © 2016 Elsevier B.V. All rights reserved.

Coalescence with Background and Balancing Selection in Systems with Bi- and Uniparental Reproduction: Contrasting Partial Asexuality and Selfing

PubMed Central

Agrawal, Aneil F.; Hartfield, Matthew

2016-01-01

Uniparental reproduction in diploids, via asexual reproduction or selfing, reduces the independence with which separate loci are transmitted across generations. This is expected to increase the extent to which a neutral marker is affected by selection elsewhere in the genome. Such effects have previously been quantified in coalescent models involving selfing. Here we examine the effects of background selection and balancing selection in diploids capable of both sexual and asexual reproduction (i.e., partial asexuality). We find that the effect of background selection on reducing coalescent time (and effective population size) can be orders of magnitude greater when rates of sex are low than when sex is common. This is because asexuality enhances the effects of background selection through both a recombination effect and a segregation effect. We show that there are several reasons that the strength of background selection differs between systems with partial asexuality and those with comparable levels of uniparental reproduction via selfing. Expectations for reductions in Ne via background selection have been verified using stochastic simulations. In contrast to background selection, balancing selection increases the coalescence time for a linked neutral site. With partial asexuality, the effect of balancing selection is somewhat dependent upon the mode of selection (e.g., heterozygote advantage vs. negative frequency-dependent selection) in a manner that does not apply to selfing. This is because the frequency of heterozygotes, which are required for recombination onto alternative genetic backgrounds, is more dependent on the pattern of selection with partial asexuality than with selfing. PMID:26584901

Coalescence with Background and Balancing Selection in Systems with Bi- and Uniparental Reproduction: Contrasting Partial Asexuality and Selfing.

PubMed

Agrawal, Aneil F; Hartfield, Matthew

2016-01-01

Uniparental reproduction in diploids, via asexual reproduction or selfing, reduces the independence with which separate loci are transmitted across generations. This is expected to increase the extent to which a neutral marker is affected by selection elsewhere in the genome. Such effects have previously been quantified in coalescent models involving selfing. Here we examine the effects of background selection and balancing selection in diploids capable of both sexual and asexual reproduction (i.e., partial asexuality). We find that the effect of background selection on reducing coalescent time (and effective population size) can be orders of magnitude greater when rates of sex are low than when sex is common. This is because asexuality enhances the effects of background selection through both a recombination effect and a segregation effect. We show that there are several reasons that the strength of background selection differs between systems with partial asexuality and those with comparable levels of uniparental reproduction via selfing. Expectations for reductions in Ne via background selection have been verified using stochastic simulations. In contrast to background selection, balancing selection increases the coalescence time for a linked neutral site. With partial asexuality, the effect of balancing selection is somewhat dependent upon the mode of selection (e.g., heterozygote advantage vs. negative frequency-dependent selection) in a manner that does not apply to selfing. This is because the frequency of heterozygotes, which are required for recombination onto alternative genetic backgrounds, is more dependent on the pattern of selection with partial asexuality than with selfing. Copyright © 2016 by the Genetics Society of America.

47 CFR 101.103 - Frequency coordination procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Assignment of frequencies will be made only in such a manner as to facilitate the rendition of communication...-point basis may not be extended or otherwise modified through the addition of point-to-point links. Such... modified through the addition of point-to-point links. Such operations licensed on a point-to-radius basis...

47 CFR 101.103 - Frequency coordination procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Assignment of frequencies will be made only in such a manner as to facilitate the rendition of communication...-point basis may not be extended or otherwise modified through the addition of point-to-point links. Such... modified through the addition of point-to-point links. Such operations licensed on a point-to-radius basis...

47 CFR 101.103 - Frequency coordination procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Assignment of frequencies will be made only in such a manner as to facilitate the rendition of communication...-point basis may not be extended or otherwise modified through the addition of point-to-point links. Such... modified through the addition of point-to-point links. Such operations licensed on a point-to-radius basis...

An Investigation of Primary School Science Teachers' Use of Computer Applications

ERIC Educational Resources Information Center

Ocak, Mehmet Akif; Akdemir, Omur

2008-01-01

This study investigated the level and frequency of science teachers' use of computer applications as an instructional tool in the classroom. The manner and frequency of science teachers' use of computer, their perceptions about integration of computer applications, and other factors contributed to changes in their computer literacy are…

Growth inhibition of malignant melanoma by intermediate frequency alternating electric fields, and the underlying mechanisms.

PubMed

Chen, H; Liu, R; Liu, J; Tang, J

2012-01-01

This study investigated the antitumour effects of intermediate frequency alternating electric fields (IF-AEF) in a murine melanoma cell line (B16F10) and a mouse tumour model. IF-AEF was applied at 100 kHz. Proliferation of B16F10 cells in vitro was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. IF-AEF was applied in vivo to mice bearing B16F10 tumours. Terminal deoxy nucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay for apoptosis, and immunohistochemical detection of CD34 and vascular endothelial growth factor (VEGF), were performed. IF-AEF inhibited the proliferation of B16F10 cells in an electrical intensity and time-dependent manner. Treatment with IF-AEF for 7 days significantly inhibited the growth of tumours compared with untreated controls. IF-AEF induced apoptosis in vivo and reduced CD34-positive cell numbers; CD34 is a special marker of microvessel density. IF-AEF reduced microvessel density related to tumour growth and may serve as a therapeutic strategy for cancer treatment.

Reanalysis of the occurrence of back pain among construction workers: modelling for the interdependent effects of heavy physical work, earlier back accidents, and aging.

PubMed

Nurminen, M

1997-11-01

To re-examine the relation between heavy physical work and the occurrence of sciatic pain among construction workers reported previously to be absent in an epidemiological study. METHODS-Poisson log linear regression was used to model for the frequency of sciatic pain among concrete reinforcement workers and maintenance house painters with adjustment for the interactive effects of earlier back accidents and aging that modified the relation. Concrete reinforcement work not only had a direct effect on the frequency of sciatic pain, but it also contributed significantly to the risk indirectly through earlier back accidents. The risk of sciatic pain increased from age 25 to 54 in a different manner for a worker depending on his occupational group and record of back accidents. Epidemiological studies on low back pain need to be analysed with sound methodology. This is important in view of future meta-analyses that will be performed for the purpose of providing guidelines on the prevention of back disorders in heavy physical work.

Glutamatergic postsynaptic block by Pamphobeteus spider venoms in crayfish.

PubMed

Araque, A; Ferreira, W; Lucas, S; Buño, W

1992-01-31

The effects of toxins from venom glands of two south american spiders (Pamphobeteus platyomma and P. soracabae) on glutamatergic excitatory synaptic transmission were studied in the neuromuscular junction of the opener muscle of crayfish. The toxins selectively and reversibly blocked both excitatory postsynaptic currents and potentials in a dose-dependent manner. They also reversibly abolished glutamate-induced postsynaptic membrane depolarization. They had no effect on resting postsynaptic membrane conductance nor on postsynaptic voltage-gated currents. The synaptic facilitation and the frequency of miniature postsynaptic potentials were unaffected by the toxins, indicating that presynaptic events were not modified. Picrotoxin, a selective antagonist of the gamma-aminobutyric acid (GABA)A receptor, did not modify toxin effects. We conclude that both toxins specifically block the postsynaptic glutamate receptor-channel complex.

Mechanically induced alterations in cultured skeletal muscle growth

NASA Technical Reports Server (NTRS)

Vandenburgh, H. H.; Hatfaludy, S.; Karlisch, P.; Shansky, J.

1991-01-01

Model systems are available for mechanically stimulating cultured skeletal muscle cells by passive tensile forces which simulate those found in vivo. When applied to embryonic muscle cells in vitro these forces induce tissue organogenesis, metabolic adaptations, and muscle cell growth. The mechanical stimulation of muscle cell growth correlates with stretch-induced increases in the efflux of prostaglandins PGE2 and PGF2(alpha) in a time and frequency dependent manner. These prostaglandins act as mechanical 'second messengers' regulating skeletal muscle protein turnover rates. Since they also effect bone remodelling in response to tissue loading and unloading, secreted prostaglandins may serve as paracrine growth factors, coordinating the growth rates of muscle and bone in response to external mechanical forces. Cell culture model systems will supplement other models in understanding mechanical transduction processes at the molecular level.

Ethanol produces corticotropin releasing factor receptor-dependent enhancement of spontaneous glutamatergic transmission in the mouse central amygdala

PubMed Central

Silberman, Yuval; Fetterly, Tracy L.; Awad, Elias K.; Milano, Elana J.; Usdin, Ted B.; Winder, Danny G.

2015-01-01

Background Ethanol modulation of Central Amygdala (CeA) neurocircuitry plays a key role in the development of alcoholism via activation of the corticotropin releasing factor (CRF) receptor system. Previous work has predominantly focused on ethanol/CRF interactions on the CeA GABA circuitry; however our lab recently showed that CRF enhances CeA glutamatergic transmission. Therefore, this study sought to determine if ethanol modulates CeA glutamate transmission via activation of CRF signaling. Methods The effects of ethanol on spontaneous excitatory postsynaptic currents (sEPSCs) and basal resting membrane potentials were examined via standard electrophysiology methods in adult male C57BL/6J mice. Local ablation of CeA CRF neurons (CRFCeAhDTR) was achieved by targeting the human diphtheria toxin receptor (hDTR) to CeA CRF neurons with an adeno-associated virus. Ablation was quantified post-hoc with confocal microscopy. Genetic targeting of the diphtheria toxin active subunit to CRF neurons (CRFDTA mice) ablated CRF neurons throughout the CNS, as assessed by qRT-PCR quantification of CRF mRNA. Results Acute bath application of ethanol significantly increased sEPSC frequency in a concentration dependent manner in CeA neurons, and this effect was blocked by pretreatment of co-applied CRF receptor 1 and CRF receptor 2 antagonists. In experiments utilizing a CRF-tomato reporter mouse, ethanol did not significantly alter the basal membrane potential of CeA CRF neurons. The ability of ethanol to enhance CeA sEPSC frequency was not altered in CRFCeAhDTR mice despite a ~78% reduction in CeA CRF cell counts. The ability of ethanol to enhance CeA sEPSC frequency was also not altered in the CRFDTA mice despite a three-fold reduction in CRF mRNA levels. Conclusion These findings demonstrate that ethanol enhances spontaneous glutamatergic transmission in the CeA via a CRF receptor dependent mechanism. Surprisingly, our data suggest that this action may not require endogenous CRF. PMID:26503065

Inward rectifier potassium current IKir promotes intrinsic pacemaker activity of thalamocortical neurons.

PubMed

Amarillo, Yimy; Tissone, Angela I; Mato, Germán; Nadal, Marcela S

2018-06-01

Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (<4 Hz), which are the physiological oscillations during non-rapid eye movement sleep or pathological oscillations during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that upregulation of the small and neglected inward rectifier potassium current I Kir induces repetitive burst firing at slow and delta frequency bands. We demonstrate this in mouse TC neurons in brain slices by manipulating the Kir maximum conductance with dynamic clamp. We also performed a thorough theoretical analysis that explains how the unique properties of I Kir enable this current to induce slow periodic bursting in TC neurons. We describe a new ionic mechanism based on the voltage- and time-dependent interaction of I Kir and hyperpolarization-activated cationic current I h that endows TC neurons with the ability to oscillate spontaneously at very low frequencies, even below 0.5 Hz. Bifurcation analysis of conductance-based models of increasing complexity demonstrates that I Kir induces bistability of the membrane potential at the same time that it induces sustained oscillations in combination with I h and increases the robustness of low threshold-activated calcium current I T -mediated oscillations. NEW & NOTEWORTHY The strong inwardly rectifying potassium current I Kir of thalamocortical neurons displays a region of negative slope conductance in the current-voltage relationship that generates potassium currents activated by hyperpolarization. Bifurcation analysis shows that I Kir induces bistability of the membrane potential; generates sustained subthreshold oscillations by interacting with the hyperpolarization-activated cationic current I h ; and increases the robustness of oscillations mediated by the low threshold-activated calcium current I T . Upregulation of I Kir in thalamocortical neurons induces repetitive burst firing at slow and delta frequency bands (<4 Hz).

From Experiment to Theory: What Can We Learn from Growth Curves?

PubMed

Kareva, Irina; Karev, Georgy

2018-01-01

Finding an appropriate functional form to describe population growth based on key properties of a described system allows making justified predictions about future population development. This information can be of vital importance in all areas of research, ranging from cell growth to global demography. Here, we use this connection between theory and observation to pose the following question: what can we infer about intrinsic properties of a population (i.e., degree of heterogeneity, or dependence on external resources) based on which growth function best fits its growth dynamics? We investigate several nonstandard classes of multi-phase growth curves that capture different stages of population growth; these models include hyperbolic-exponential, exponential-linear, exponential-linear-saturation growth patterns. The constructed models account explicitly for the process of natural selection within inhomogeneous populations. Based on the underlying hypotheses for each of the models, we identify whether the population that it best fits by a particular curve is more likely to be homogeneous or heterogeneous, grow in a density-dependent or frequency-dependent manner, and whether it depends on external resources during any or all stages of its development. We apply these predictions to cancer cell growth and demographic data obtained from the literature. Our theory, if confirmed, can provide an additional biomarker and a predictive tool to complement experimental research.

Interaction of plant chimeric calcium/calmodulin-dependent protein kinase with a homolog of eukaryotic elongation factor-1alpha

NASA Technical Reports Server (NTRS)

Wang, W.; Poovaiah, B. W.

1999-01-01

A chimeric Ca2+/calmodulin-dependent protein kinase (CCaMK) was previously cloned and characterized in this laboratory. To investigate the biological functions of CCaMK, the yeast two-hybrid system was used to isolate genes encoding proteins that interact with CCaMK. One of the cDNA clones obtained from the screening (LlEF-1alpha1) has high similarity with the eukaryotic elongation factor-1alpha (EF-1alpha). CCaMK phosphorylated LlEF-1alpha1 in a Ca2+/calmodulin-dependent manner. The phosphorylation site for CCaMK (Thr-257) was identified by site-directed mutagenesis. Interestingly, Thr-257 is located in the putative tRNA-binding region of LlEF-1alpha1. An isoform of Ca2+-dependent protein kinase (CDPK) phosphorylated multiple sites of LlEF-1alpha1 in a Ca2+-dependent but calmodulin-independent manner. Unlike CDPK, CCaMK phosphorylated only one site, and this site is different from CDPK phosphorylation sites. This suggests that the phosphorylation of EF-1alpha by these two kinases may have different functional significance. Although the phosphorylation of LlEF-1alpha1 by CCaMK is Ca2+/calmodulin-dependent, in vitro binding assays revealed that CCaMK binds to LlEF-1alpha1 in a Ca2+-independent manner. This was further substantiated by coimmunoprecipitation of CCaMK and EF-1alpha using the protein extract from lily anthers. Dissociation of CCaMK from EF-1alpha by Ca2+ and phosphorylation of EF-1alpha by CCaMK in a Ca2+/calmodulin-dependent manner suggests that these interactions may play a role in regulating the biological functions of EF-1alpha.

Phase-locked loop with controlled phase slippage

DOEpatents

Mestha, Lingappa K.

1994-01-01

A system for synchronizing a first subsystem controlled by a changing frequency sweeping from a first frequency to a second frequency, with a second subsystem operating at a steady state second frequency. Trip plan parameters are calculated in advance to determine the phase relationship between the frequencies of the first subsystem and second subsystem in order to obtain synchronism at the end of the frequency sweep of the first subsystem. During the time in which the frequency of the first subsystem is sweeping from the first frequency to the second frequency, the phase locked system compares the actual phase difference with the trip plan phase difference and incrementally changes the sweep frequency in a manner so that phase lock is achieved when the first subsystem reaches a frequency substantially identical to that of the second subsystem.

Prolonged exposure to WIN55,212-2 causes down-regulation of the CB1 receptor and the development of tolerance to its anticonvulsant effects in the hippocampal neuronal culture model of acquired epilepsy

PubMed Central

Blair, Robert E.; Deshpande, Laxmikant S.; Sombati, Sompong; Elphick, Maurice R.; Martin, Billy R.; DeLorenzo, Robert J.

2009-01-01

Summary Cannabinoids have been shown to cause CB1-receptor dependent anticonvulsant activity in both in vivo and in vitro models of status epilepticus (SE) and acquired epilepsy (AE). It has been further demonstrated in these models that the endocannabinoid system functions in a tonic manner to suppress seizure discharges through a CB1-receptor dependent pathway. Although acute cannabinoid treatment has anticonvulsant activity, little is known concerning the effects of prolonged exposure to CB1 agonists and development of tolerance on the epileptic phenotype. This study was carried out to evaluate the effects of prolonged exposure to the CB1 agonist WIN55,212-2 on seizure activity in a hippocampal neuronal culture model of low-Mg2+ induced spontaneous recurrent epileptiform discharges (SREDs). Following low-Mg2+ induced SREDs, cultures were returned to maintenance media containing 10, 100 or 1000 nM WIN55,212-2 from 4 to 24 hours. Whole-cell current-clamp analysis of WIN55,212-2 treated cultures revealed a concentration-dependent increase in SRED frequency. Immunocytochemical staining revealed that WIN55,212-2 treatment induced a concentration-dependent down-regulation of the CB1 receptor in neuronal processes and at both glutamatergic and GABAergic presynaptic terminals. Prolonged exposure to the inactive enantiomer WIN55,212-3 in low-Mg2+ treated cultures had no effect on the frequency of SREDs or CB1 receptor staining. The results from this study further substantiate a role for a tonic CB1 receptor-dependent endocannabinoid regulation of seizure discharge and suggest that prolonged exposure to cannabinoids results in the development of tolerance to the anticonvulsant effects of cannabinoids and an exacerbation of seizure activity in the epileptic phenotype. PMID:19540252

Cadmium induces histopathological injuries and ultrastructural changes in the liver of freshwater turtle (Chinemys reevesii).

PubMed

Huo, Junfeng; Dong, Aiguo; Wang, Yonghui; Lee, Shaochin; Ma, Cungen; Wang, Lan

2017-11-01

The study investigated the histopathological and ultrastructural lesions of liver of freshwater turtle Chinemys reevesii exposed to Cadmium (Cd). The animals were exposed to 0 mg kg -1 (0.85% normal saline (NS)), 7.5 mg kg -1 , 15 mg kg -1 , 30 mg kg -1 Cd chloride separately by intraperitoneal injection. Liver samples were collected for examination of lesions under light and electronic microscopes. Results showed that liver tissues from Cd -treated animals presented various degrees of histopathological lesions. Liver cells showed swollen, degeneration and necrosis with dose-dependent manner. Under electronic microscope, nucleus, mitochondria and rough endoplasmic reticulum presented various degrees of lesions with dose-dependent manner. In conclusion, Cd has significant toxicity on liver tissue of the freshwater turtle, which occurs in a dose-dependent manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

Device for frequency modulation of a laser output spectrum

DOEpatents

Beene, James R.; Bemis, Jr., Curtis E.

1986-01-01

A device is provided for fast frequency modulating the output spectrum of multimode lasers and single frequency lasers that are not actively stabilized. A piezoelectric transducer attached to a laser cavity mirror is driven in an unconventional manner to excite resonance vibration of the transducer to rapidly, cyclicly change the laser cavity length. The result is a cyclic sweeping of the output wavelength sufficient to fill the gaps in the laser output frequency spectrum. When such a laser is used to excite atoms or molecules, complete absorption line coverage is made possible.

Device for frequency modulation of a laser output spectrum

DOEpatents

Beene, J.R.; Bemis, C.E. Jr.

1984-07-17

A device is provided for fast frequency modulating the output spectrum of multimode lasers and single frequency lasers that are not actively stabilized. A piezoelectric transducer attached to a laser cavity mirror is driven in an unconventional manner to excite resonance vibration of the tranducer to rapidly, cyclicly change the laser cavity length. The result is a cyclic sweeping of the output wavelength sufficient to fill the gaps in the laser output frequency spectrum. When a laser is used to excite atoms or molecules, complete absorption line coverage is made possible.

Separation of circadian and wake duration-dependent modulation of EEG activation during wakefulness

NASA Technical Reports Server (NTRS)

Cajochen, C.; Wyatt, J. K.; Czeisler, C. A.; Dijk, D. J.

2002-01-01

The separate contribution of circadian rhythmicity and elapsed time awake on electroencephalographic (EEG) activity during wakefulness was assessed. Seven men lived in an environmental scheduling facility for 4 weeks and completed fourteen 42.85-h 'days', each consisting of an extended (28.57-h) wake episode and a 14.28-h sleep opportunity. The circadian rhythm of plasma melatonin desynchronized from the 42.85-h day. This allowed quantification of the separate contribution of circadian phase and elapsed time awake to variation in EEG power spectra (1-32 Hz). EEG activity during standardized behavioral conditions was markedly affected by both circadian phase and elapsed time awake in an EEG frequency- and derivation-specific manner. The nadir of the circadian rhythm in alpha (8-12 Hz) activity in both fronto-central and occipito-parietal derivations occurred during the biological night, close to the crest of the melatonin rhythm. The nadir of the circadian rhythm of theta (4.5-8 Hz) and beta (20-32 Hz) activity in the fronto-central derivation was located close to the onset of melatonin secretion, i.e. during the wake maintenance zone. As time awake progressed, delta frequency (1-4.5 Hz) and beta (20-32 Hz) activity rose monotonically in frontal derivations. The interaction between the circadian and wake-dependent increase in frontal delta was such that the intrusion of delta was minimal when sustained wakefulness coincided with the biological day, but pronounced during the biological night. Our data imply that the circadian pacemaker facilitates frontal EEG activation during the wake maintenance zone, by generating an arousal signal that prevents the intrusion of low-frequency EEG components, the propensity for which increases progressively during wakefulness.

Acetylcholine modulates gamma frequency oscillations in the hippocampus by activation of muscarinic M1 receptors.

PubMed

Betterton, Ruth T; Broad, Lisa M; Tsaneva-Atanasova, Krasimira; Mellor, Jack R

2017-06-01

Modulation of gamma oscillations is important for the processing of information and the disruption of gamma oscillations is a prominent feature of schizophrenia and Alzheimer's disease. Gamma oscillations are generated by the interaction of excitatory and inhibitory neurons where their precise frequency and amplitude are controlled by the balance of excitation and inhibition. Acetylcholine enhances the intrinsic excitability of pyramidal neurons and suppresses both excitatory and inhibitory synaptic transmission, but the net modulatory effect on gamma oscillations is not known. Here, we find that the power, but not frequency, of optogenetically induced gamma oscillations in the CA3 region of mouse hippocampal slices is enhanced by low concentrations of the broad-spectrum cholinergic agonist carbachol but reduced at higher concentrations. This bidirectional modulation of gamma oscillations is replicated within a mathematical model by neuronal depolarisation, but not by reducing synaptic conductances, mimicking the effects of muscarinic M1 receptor activation. The predicted role for M1 receptors was supported experimentally; bidirectional modulation of gamma oscillations by acetylcholine was replicated by a selective M1 receptor agonist and prevented by genetic deletion of M1 receptors. These results reveal that acetylcholine release in CA3 of the hippocampus modulates gamma oscillation power but not frequency in a bidirectional and dose-dependent manner by acting primarily through muscarinic M1 receptors. © 2017 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Noise-induced phase space transport in two-dimensional Hamiltonian systems.

PubMed

Pogorelov, I V; Kandrup, H E

1999-08-01

First passage time experiments were used to explore the effects of low amplitude noise as a source of accelerated phase space diffusion in two-dimensional Hamiltonian systems, and these effects were then compared with the effects of periodic driving. The objective was to quantify and understand the manner in which "sticky" chaotic orbits that, in the absence of perturbations, are confined near regular islands for very long times, can become "unstuck" much more quickly when subjected to even very weak perturbations. For both noise and periodic driving, the typical escape time scales logarithmically with the amplitude of the perturbation. For white noise, the details seem unimportant: Additive and multiplicative noise typically have very similar effects, and the presence or absence of a friction related to the noise by a fluctuation-dissipation theorem is also largely irrelevant. Allowing for colored noise can significantly decrease the efficacy of the perturbation, but only when the autocorrelation time, which vanishes for white noise, becomes so large that there is little power at frequencies comparable to the natural frequencies of the unperturbed orbit. Similarly, periodic driving is relatively inefficient when the driving frequency is not comparable to these natural frequencies. This suggests that noise-induced extrinsic diffusion, like modulational diffusion associated with periodic driving, is a resonance phenomenon. The logarithmic dependence of the escape time on amplitude reflects the fact that the time required for perturbed and unperturbed orbits to diverge a given distance scales logarithmically in the amplitude of the perturbation.

The effect of dopamine receptor blockade in the rodent nucleus accumbens on local field potential oscillations and motor activity in response to ketamine.

PubMed

Matulewicz, Pawel; Kasicki, Stefan; Hunt, Mark Jeremy

2010-12-17

Altered functioning of the nucleus accumbens (NAc) has been implicated in the psychotomimetic actions of NMDA receptor (NMDAR) antagonists and the pathophysiology of schizophrenia. We have shown previously that NMDAR antagonists enhance the power of high-frequency oscillations (HFO) in the NAc in a dose-dependent manner, as well as increase locomotor activity. Systemic administration of NMDAR antagonists is known to increase the release of dopamine in the NAc and dopamine antagonists can reduce ketamine-induced hyperactivity. In this study, we examined the effect of 0.5 μl intra-NAc infusion of 3.2 μg SCH23390 (D1 antagonist), 10 μg raclopride (D2 antagonist) and saline on ketamine-induced changes in motor and oscillatory activity. We found that local blockade of D1 receptors attenuated ketamine-induced increases in motor activity and blockade of D2 receptors produced a much weaker effect, with respect to saline-infused control groups. In contrast, none of the antagonists, infused separately or together, significantly modified the power or dominant frequency of ketamine-induced increases in HFO, but changes in delta and theta frequency bands were observed. Together, these findings suggest, that, in contrast to delta and theta frequency bands, the generation of ketamine enhanced-HFO in the NAc is not causally related to locomotor activation and occurs largely independently of local changes in dopamine receptor activation. Copyright © 2010 Elsevier B.V. All rights reserved.

Ranolazine improves abnormal repolarization and contraction in left ventricular myocytes of dogs with heart failure by inhibiting late sodium current

PubMed Central

Undrovinas, Albertas I.; Belardinelli, Luiz; Undrovinas, Nidas A.; Sabbah, Hani N.

2005-01-01

Background Ventricular repolarization and contractile function are frequently abnormal in ventricular myocytes from human failing hearts as well as canine hearts with experimentally induced heart failure (HF). These abnormalities have been attributed to dysfunction involving various steps of the excitation-contraction coupling process, leading to impaired intracellular sodium and calcium homeostasis. We previously reported that the slow inactivating component of the Na+ current (late INa) is augmented in myocytes from failing hearts, and this appears to play a significant role in abnormal ventricular myocytes repolarization and function. We tested the effect of ranolazine, a novel drug being developed to treat angina, on 1) action potential duration (APD), 2) peak transient and late INa (INaT and INaL respectively), 3) early afterdepolarizations (EADs), and 4) twitch contraction (TC) including aftercontractions and contracture. Methods: Myocytes were isolated from the left ventricle of normal dogs and of dogs with chronic HF caused by multiple sequential intracoronary microembolizations. INaT and INaL were recorded using conventional whole-cell patch-clamp techniques. APs were recorded using the β-escin perforated patch-clamp configuration at frequencies of 0.25 and 0.5 Hz. TCs were recorded using an edge movement detector at stimulation frequencies ranging from 0.5 to 2.0 Hz. Results Ranolazine significantly (p < 0.05) and reversibly shortened the APD of myocytes stimulated at either 0.5 or 0.25 Hz in a concentration-dependent manner. At a stimulation frequency of 0.5 Hz, 5, 10 and 20 μM ranolazine shortened the APD90 (APD measured at 90% repolarization) from 516 ± 51 to 304 ± 22, 212 ± 34 and 160 ± 11 ms, respectively, and markedly decreased beat-to-beat variability of APD90, EADs and dispersion of APDs. Ranolazine preferentially blocked INaL relative to INaT in a state-dependent manner; with a ~ 38-fold greater potency against INaL to produce tonic block (IC50 = 6.5 μ M) than INaT (IC50 =294 μM). When we evaluated inactivated state blockade of INaL from the steady-state inactivation mid-potential shift using a theoretical model, ranolazine was found to bind more tightly to the inactivated state than the resting state of the sodium channel underlying INaL, with apparent dissociation constants Kdr=7.47μ M and Kdi=1.71μ M, respectively. TCs of myocytes stimulated at 0.5 Hz were characterized by an initial spike followed by a dome-like aftercontraction, which was observed in75% of myocytes from failing hearts and coincided with the long AP plateau and EADs. Ranolazine at 5, and 10 μM reversibly shortened duration of TCs and abolished the aftercontraction. When the rate of myocyte stimulation was increased from 1.0 to 2.0 Hz, there was a progressive increase in diastolic “tension”, i.e., contracture. Ranolazine at 5, and 10 μM reversibly prevented this frequency-dependent contracture. PMID:16686675

Anti-inflammatory activity of 6-hydroxy-2,7-dimethoxy-1,4-henanthraquinone from tuberous roots of yam (Dioscorea batatas) through inhibition of prostaglandin D₂ and leukotriene C₄ production in mouse bone marrow-derived mast cells.

PubMed

Jin, Meihua; Lu, Yue; Yang, Ju Hye; Jo, Tae Hyung; Park, Young In; Lee, Chong-Kil; Park, Sang-Jo; Son, Kun Ho; Chang, Hyeun Wook

2011-09-01

6-Hydroxy-2,7-dimethoxy-1,4-phenanthraquinone (PAQ) isolated from the tuberous roots of Yam (Dioscorea batatas) inhibited cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) dependent prostaglandin D(2) (PGD(2)) generation in mouse bone marrow-derived mast cells in a concentration-dependent manner with IC(50) values of 0.08 μM and 0.27 μM, respectively. In the Western blotting with specific anti-COX-2 antibodies, the decrease of the quantity of PGD(2) was accompanied by a decrease in the COX-2 protein level. But PAQ did not affect COX-1 protein level. In addition, this compound inhibited 5-lipoxygenase (5-LOX) dependent production of leukotriene C(4) in a dose-dependent manner, with an IC(50) of 0.032 μM. These results demonstrate that PAQ has a dual COX-2/5-LOX inhibitory activity. This compound also inhibited the degranulation reaction in a dose-dependent manner with an IC(50) of 2.7 μM. Thus, these results suggest that PAQ may be useful in regulating mast cell-mediated inflammatory diseases.

Phase-locked loop with controlled phase slippage

DOEpatents

Mestha, L.K.

1994-03-29

A system for synchronizing a first subsystem controlled by a changing frequency sweeping from a first frequency to a second frequency, with a second subsystem operating at a steady state second frequency is described. Trip plan parameters are calculated in advance to determine the phase relationship between the frequencies of the first subsystem and second subsystem in order to obtain synchronism at the end of the frequency sweep of the first subsystem. During the time in which the frequency of the first subsystem is sweeping from the first frequency to the second frequency, the phase locked system compares the actual phase difference with the trip plan phase difference and incrementally changes the sweep frequency in a manner so that phase lock is achieved when the first subsystem reaches a frequency substantially identical to that of the second subsystem. 10 figures.

Tobacco components stimulate Akt-dependent proliferation and NFkappaB-dependent survival in lung cancer cells.

PubMed

Tsurutani, Junji; Castillo, S Sianna; Brognard, John; Granville, Courtney A; Zhang, Chunyu; Gills, Joell J; Sayyah, Jacqueline; Dennis, Phillip A

2005-07-01

Retrospective studies have shown that patients with tobacco-related cancers who continue to smoke after their diagnoses have lower response rates and shorter median survival compared with patients who stop smoking. To provide insight into the biologic basis for these clinical observations, we tested whether two tobacco components, nicotine or the tobacco-specific carcinogen, 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), could activate the Akt pathway and increase lung cancer cell proliferation and survival. Nicotine or NNK, rapidly and potently, activated Akt in non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) cells. Nicotinic activation of Akt increased phosphorylation of multiple downstream substrates of Akt in a time-dependent manner, including GSK-3, FKHR, tuberin, mTOR and S6K1. Since nicotine or NNK bind to cell surface nicotinic acetylcholine receptors (nAchR), we used RT-PCR to assess expression of nine alpha and three beta nAchR subunits in five NSCLC cell lines and two types of primary lung epithelial cells. NSCLC cells express multiple nAchR subunits in a cell line-specific manner. Agonists of alpha3/alpha4 or alpha7 subunits activated Akt in a time-dependent manner, suggesting that tobacco components utilize these subunits to activate Akt. Cellular outcomes after nicotine or NNK administration were also assessed. Nicotine or NNK increased proliferation of NSCLC cells in an Akt-dependent manner that was closely linked with changes in cyclin D1 expression. Despite similar induction of proliferation, only nicotine decreased apoptosis caused by serum deprivation and/or chemotherapy. Protection conferred by nicotine was NFkappaB-dependent. Collectively, these results identify tobacco component-induced, Akt-dependent proliferation and NFkappaB-dependent survival as cellular processes that could underlie the detrimental effects of smoking in cancer patients.

High efficiency laser spectrum conditioner

DOEpatents

Greiner, Norman R.

1980-01-01

A high efficiency laser spectrum conditioner for generating a collinear parallel output beam containing a predetermined set of frequencies from a multifrequency laser. A diffraction grating and spherical mirror are used in combination, to disperse the various frequencies of the input laser beam and direct these frequencies along various parallel lines spatially separated from one another to an apertured mask. Selection of the desired frequencies is accomplished by placement of apertures at locations on the mask where the desired frequencies intersect the mask. A recollimated parallel output beam with the desired set of frequencies is subsequently generated utilizing a mirror and grating matched and geometrically aligned in the same manner as the input grating and mirror.

Vocal learning beyond imitation: mechanisms of adaptive vocal development in songbirds and human infants

PubMed Central

Tchernichovski, Ofer; Marcus, Gary

2014-01-01

Studies of vocal learning in songbirds typically focus on the acquisition of sensory templates for song imitation and on the consequent process of matching song production to templates. However, functional vocal development also requires the capacity to adaptively diverge from sensory templates, and to flexibly assemble vocal units. Examples of adaptive divergence include the corrective imitation of abnormal songs, and the decreased tendency to copy overabundant syllables. Such frequency-dependent effects might mirror tradeoffs between the assimilation of group identity (culture) while establishing individual and flexibly expressive songs. Intriguingly, although the requirements for vocal plasticity vary across songbirds, and more so between birdsong and language, the capacity to flexibly assemble vocal sounds develops in a similar, stepwise manner across species. Therefore, universal features of vocal learning go well beyond the capacity to imitate. PMID:25005823

Appplications of the post-Tolman-Oppenheimer-Volkoff formalism

NASA Astrophysics Data System (ADS)

Silva, Hector O.; Glampedakis, Kostas; Pappas, George; Berti, Emanuele

2017-01-01

Besides their astrophysical interest, neutron stars are promising candidates for testing theories of gravity in the strong-field regime. It is known that, generically, modifications to general relativity affect the bulk properties of neutron stars, e.g. their masses and radii, in a way that depends on the specific choice of theory. In this presentation we review a theory-agnostic approach to model relativistic stars, called the post-Tolman-Oppenheimer-Volkoff formalism. Drawing inspiration from the parametrized post-Newtonian formalism, this framework allows us to describe perturbative deviations from general relativity in the structure of neutrons stars in a parametrized manner. We show that a variety of astrophysical observables (namely the surface redshift, the apparent radius, the Eddington luminosity and the orbital frequency of particles in geodesic motion around neutron stars) can be parametrized using only two parameters.

Not All Reading Disabilities Are Dyslexia: Distinct Neurobiology of Specific Comprehension Deficits

PubMed Central

Clements-Stephens, Amy; Pugh, Kenneth R.; Burns, Scott; Cao, Aize; Pekar, James J.; Davis, Nicole; Rimrodt, Sheryl L.

2013-01-01

Abstract Although an extensive literature exists on the neurobiological correlates of dyslexia (DYS), to date, no studies have examined the neurobiological profile of those who exhibit poor reading comprehension despite intact word-level abilities (specific reading comprehension deficits [S-RCD]). Here we investigated the word-level abilities of S-RCD as compared to typically developing readers (TD) and those with DYS by examining the blood oxygenation-level dependent response to words varying on frequency. Understanding whether S-RCD process words in the same manner as TD, or show alternate pathways to achieve normal word-reading abilities, may provide insights into the origin of this disorder. Results showed that as compared to TD, DYS showed abnormal covariance during word processing with right-hemisphere homologs of the left-hemisphere reading network in conjunction with left occipitotemporal underactivation. In contrast, S-RCD showed an intact neurobiological response to word stimuli in occipitotemporal regions (associated with fast and efficient word processing); however, inferior frontal gyrus (IFG) abnormalities were observed. Specifically, TD showed a higher-percent signal change within right IFG for low-versus-high frequency words as compared to both S-RCD and DYS. Using psychophysiological interaction analyses, a coupling-by-reading group interaction was found in right IFG for DYS, as indicated by a widespread greater covariance between right IFG and right occipitotemporal cortex/visual word-form areas, as well as bilateral medial frontal gyrus, as compared to TD. For S-RCD, the context-dependent functional interaction anomaly was most prominently seen in left IFG, which covaried to a greater extent with hippocampal, parahippocampal, and prefrontal areas than for TD for low- as compared to high-frequency words. Given the greater lexical access demands of low frequency as compared to high-frequency words, these results may suggest specific weaknesses in accessing lexical-semantic representations during word recognition. These novel findings provide foundational insights into the nature of S-RCD, and set the stage for future investigations of this common, but understudied, reading disorder. PMID:23273430

Power Scaling and Frequency Stabilization of an Injection-Locked Laser

DTIC Science & Technology

2000-05-01

In Chapter 4,1 alter the well -documented theory of locking a laser to a Fabry- Perot by performing the PDH error signal derivation in a new manner...the well -documented modulation transfer scheme to lock the frequency-doubled NPRO to a hyperfine component of an electronic transition in I2. 33 I...generally true at very low noise frequencies, well within the feedback loop bandwidth. However, when G0L(V„) « 1 and thus GCL(vn) « 1, Equation 3.9

Regulation of Local Ambient GABA Levels via Transporter-Mediated GABA Import and Export for Subliminal Learning.

PubMed

Hoshino, Osamu

2015-06-01

Perception of supraliminal stimuli might in general be reflected in bursts of action potentials (spikes), and their memory traces could be formed through spike-timing-dependent plasticity (STDP). Memory traces for subliminal stimuli might be formed in a different manner, because subliminal stimulation evokes a fraction (but not a burst) of spikes. Simulations of a cortical neural network model showed that a subliminal stimulus that was too brief (10 msec) to perceive transiently (more than about 500 msec) depolarized stimulus-relevant principal cells and hyperpolarized stimulus-irrelevant principal cells in a subthreshold manner. This led to a small increase or decrease in ongoing-spontaneous spiking activity frequency (less than 1 Hz). Synaptic modification based on STDP during this period effectively enhanced relevant synaptic weights, by which subliminal learning was improved. GABA transporters on GABAergic interneurons modulated local levels of ambient GABA. Ambient GABA molecules acted on extrasynaptic receptors, provided principal cells with tonic inhibitory currents, and contributed to achieving the subthreshold neuronal state. We suggest that ongoing-spontaneous synaptic alteration through STDP following subliminal stimulation may be a possible neuronal mechanism for leaving its memory trace in cortical circuitry. Regulation of local ambient GABA levels by transporter-mediated GABA import and export may be crucial for subliminal learning.

Robust random telegraph conductivity noise in single crystals of the ferromagnetic insulating manganite La0.86Ca0.14MnO3

NASA Astrophysics Data System (ADS)

Przybytek, J.; Fink-Finowicki, J.; Puźniak, R.; Shames, A.; Markovich, V.; Mogilyansky, D.; Jung, G.

2017-03-01

Robust random telegraph conductivity fluctuations have been observed in La0.86Ca0.14MnO3 manganite single crystals. At room temperatures, the spectra of conductivity fluctuations are featureless and follow a 1 /f shape in the entire experimental frequency and bias range. Upon lowering the temperature, clear Lorentzian bias-dependent excess noise appears on the 1 /f background and eventually dominates the spectral behavior. In the time domain, fully developed Lorentzian noise appears as pronounced two-level random telegraph noise with a thermally activated switching rate, which does not depend on bias current and applied magnetic field. The telegraph noise is very robust and persists in the exceptionally wide temperature range of more than 50 K. The amplitude of the telegraph noise decreases exponentially with increasing bias current in exactly the same manner as the sample resistance increases with the current, pointing out the dynamic current redistribution between percolation paths dominated by phase-separated clusters with different conductivity as a possible origin of two-level conductivity fluctuations.

Nonlinear viscoelastic characterization of polymer materials using a dynamic-mechanical methodology

NASA Technical Reports Server (NTRS)

Strganac, Thomas W.; Payne, Debbie Flowers; Biskup, Bruce A.; Letton, Alan

1995-01-01

Polymer materials retrieved from LDEF exhibit nonlinear constitutive behavior; thus the authors present a method to characterize nonlinear viscoelastic behavior using measurements from dynamic (oscillatory) mechanical tests. Frequency-derived measurements are transformed into time-domain properties providing the capability to predict long term material performance without a lengthy experimentation program. Results are presented for thin-film high-performance polymer materials used in the fabrication of high-altitude scientific balloons. Predictions based upon a linear test and analysis approach are shown to deteriorate for moderate to high stress levels expected for extended applications. Tests verify that nonlinear viscoelastic response is induced by large stresses. Hence, an approach is developed in which the stress-dependent behavior is examined in a manner analogous to modeling temperature-dependent behavior with time-temperature correspondence and superposition principles. The development leads to time-stress correspondence and superposition of measurements obtained through dynamic mechanical tests. Predictions of material behavior using measurements based upon linear and nonlinear approaches are compared with experimental results obtained from traditional creep tests. Excellent agreement is shown for the nonlinear model.

Disintegration of Nascent Replication Bubbles during Thymine Starvation Triggers RecA- and RecBCD-dependent Replication Origin Destruction*

PubMed Central

Kuong, Kawai J.; Kuzminov, Andrei

2012-01-01

Thymineless death strikes cells unable to synthesize DNA precursor dTTP, with the nature of chromosomal damage still unclear. Thymine starvation stalls replication forks, whereas accumulating evidence indicates the replication origin is also affected. Using a novel DNA labeling technique, here we show that replication slowly continues in thymine-starved cells, but the newly synthesized DNA becomes fragmented and degraded. This degradation apparently releases enough thymine to sustain initiation of new replication bubbles from the chromosomal origin, which destabilizes the origin in a RecA-dependent manner. Marker frequency analysis with gene arrays 1) reveals destruction of the origin-centered chromosomal segment in RecA+ cells; 2) confirms origin accumulation in the recA mutants; and 3) identifies the sites around the origin where destruction initiates in the recBCD mutants. We propose that thymineless cells convert persistent single-strand gaps behind replication forks into double-strand breaks, using the released thymine for new initiations, whereas subsequent disintegration of small replication bubbles causes replication origin destruction. PMID:22621921

Ethosuximide and Phenytoin Dose-Dependently Attenuate Acute Nonconvulsive Seizures after Traumatic Brain Injury in Rats

PubMed Central

Shear, Deborah A.; Potter, Brittney; Marcsisin, Sean R.; Sousa, Jason; Melendez, Victor; Tortella, Frank C.; Lu, Xi-Chun M.

2013-01-01

Abstract Acute seizures frequently occur following severe traumatic brain injury (TBI) and have been associated with poor patient prognosis. Silent or nonconvulsive seizures (NCS) manifest in the absence of motor convulsion, can only be detected via continuous electroencephalographic (EEG) recordings, and are often unidentified and untreated. Identification of effective anti-epileptic drugs (AED) against post-traumatic NCS remains crucial to improve neurological outcome. Here, we assessed the anti-seizure profile of ethosuximide (ETX, 12.5–187.5 mg/kg) and phenytoin (PHT, 5–30 mg/kg) in a spontaneously occurring NCS model associated with penetrating ballistic-like brain injury (PBBI). Rats were divided between two drug cohorts, PHT or ETX, and randomly assigned to one of four doses or vehicle within each cohort. Following PBBI, NCS were detected by continuous EEG monitoring for 72 h post-injury. Drug efficacy was evaluated on NCS parameters of incidence, frequency, episode duration, total duration, and onset latency. Both PHT and ETX attenuated NCS in a dose-dependent manner. In vehicle-treated animals, 69–73% experienced NCS (averaging 9–10 episodes/rat) with average onset of NCS occurring at 30 h post-injury. Compared with control treatment, the two highest PHT and ETX doses significantly reduced NCS incidence to 13–40%, reduced NCS frequency (1.8–6.2 episodes/rat), and delayed seizure onset: <20% of treated animals exhibited NCS within the first 48 h. NCS durations were also dose-dependently mitigated. For the first time, we demonstrate that ETX and PHT are effective against spontaneously occurring NCS following PBBI, and suggest that these AEDs may be effective at treating post-traumatic NCS. PMID:23822888

Ulex europaeus agglutinin II (UEA-II) is a novel, potent inhibitor of complement activation.

PubMed

Lekowski, R; Collard, C D; Reenstra, W R; Stahl, G L

2001-02-01

Complement is an important mediator of vascular injury following oxidative stress. We recently demonstrated that complement activation following endothelial oxidative stress is mediated by mannose-binding lectin (MBL) and activation of the lectin complement pathway. Here, we investigated whether nine plant lectins which have a binding profile similar to that of MBL competitively inhibit MBL deposition and subsequent complement activation following human umbilical vein endothelial cell (HUVEC) oxidative stress. HUVEC oxidative stress (1% O(2), 24 hr) significantly increased Ulex europaeus agglutinin II (UEA-II) binding by 72 +/- 9% compared to normoxic cells. UEA-II inhibited MBL binding to HUVEC in a concentration-dependent manner following oxidative stress. Further, MBL inhibited UEA-II binding to HUVEC in a concentration-dependent manner following oxidative stress, suggesting a common ligand. UEA-II (< or = 100 micromol/L) did not attenuate the hemolytic activity, nor did it inhibit C3a des Arg formation from alternative or classical complement pathway-specific hemolytic assays. C3 deposition (measured by ELISA) following HUVEC oxidative stress was inhibited by UEA-II in a concentration-dependent manner (IC(50) = 10 pmol/L). UEA-II inhibited C3 and MBL co-localization (confocal microscopy) in a concentration-dependent manner on HUVEC following oxidative stress (IC(50) approximately 1 pmol/L). Finally, UEA-II significantly inhibited complement-dependent neutrophil chemotaxis, but failed to inhibit fMLP-mediated chemotaxis, following endothelial oxidative stress. These data demonstrate that UEA-II is a novel, potent inhibitor of human MBL deposition and complement activation following human endothelial oxidative stress.

Ulex europaeus agglutinin II (UEA-II) is a novel, potent inhibitor of complement activation

PubMed Central

Lekowski, Robert; Collard, Charles D.; Reenstra, Wende R.; Stahl, Gregory L.

2001-01-01

Complement is an important mediator of vascular injury following oxidative stress. We recently demonstrated that complement activation following endothelial oxidative stress is mediated by mannose-binding lectin (MBL) and activation of the lectin complement pathway. Here, we investigated whether nine plant lectins which have a binding profile similar to that of MBL competitively inhibit MBL deposition and subsequent complement activation following human umbilical vein endothelial cell (HUVEC) oxidative stress. HUVEC oxidative stress (1% O2, 24 hr) significantly increased Ulex europaeus agglutinin II (UEA-II) binding by 72 ± 9% compared to normoxic cells. UEA-II inhibited MBL binding to HUVEC in a concentration-dependent manner following oxidative stress. Further, MBL inhibited UEA-II binding to HUVEC in a concentration-dependent manner following oxidative stress, suggesting a common ligand. UEA-II (≤ 100 μmol/L) did not attenuate the hemolytic activity, nor did it inhibit C3a des Arg formation from alternative or classical complement pathway-specific hemolytic assays. C3 deposition (measured by ELISA) following HUVEC oxidative stress was inhibited by UEA-II in a concentration-dependent manner (IC50 = 10 pmol/L). UEA-II inhibited C3 and MBL co-localization (confocal microscopy) in a concentration-dependent manner on HUVEC following oxidative stress (IC50 ≈ 1 pmol/L). Finally, UEA-II significantly inhibited complement-dependent neutrophil chemotaxis, but failed to inhibit fMLP-mediated chemotaxis, following endothelial oxidative stress. These data demonstrate that UEA-II is a novel, potent inhibitor of human MBL deposition and complement activation following human endothelial oxidative stress. PMID:11266613

Methods, computer readable media, and graphical user interfaces for analysis of frequency selective surfaces

DOEpatents

Kotter, Dale K [Shelley, ID; Rohrbaugh, David T [Idaho Falls, ID

2010-09-07

A frequency selective surface (FSS) and associated methods for modeling, analyzing and designing the FSS are disclosed. The FSS includes a pattern of conductive material formed on a substrate to form an array of resonance elements. At least one aspect of the frequency selective surface is determined by defining a frequency range including multiple frequency values, determining a frequency dependent permittivity across the frequency range for the substrate, determining a frequency dependent conductivity across the frequency range for the conductive material, and analyzing the frequency selective surface using a method of moments analysis at each of the multiple frequency values for an incident electromagnetic energy impinging on the frequency selective surface. The frequency dependent permittivity and the frequency dependent conductivity are included in the method of moments analysis.

The non-competitive acetylcholinesterase inhibitor APS12-2 is a potent antagonist of skeletal muscle nicotinic acetylcholine receptors

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

Grandič, Marjana; Aráoz, Romulo; Molgó, Jordi

APS12-2, a non-competitive acetylcholinesterase inhibitor, is one of the synthetic analogs of polymeric alkylpyridinium salts (poly-APS) isolated from the marine sponge Reniera sarai. In the present work the effects of APS12-2 were studied on isolated mouse phrenic nerve–hemidiaphragm muscle preparations, using twitch tension measurements and electrophysiological recordings. APS12-2 in a concentration-dependent manner blocked nerve-evoked isometric muscle contraction (IC{sub 50} = 0.74 μM), without affecting directly-elicited twitch tension up to 2.72 μM. The compound (0.007–3.40 μM) decreased the amplitude of miniature endplate potentials until a complete block by concentrations higher than 0.68 μM, without affecting their frequency. Full size endplate potentials,more » recorded after blocking voltage-gated muscle sodium channels, were inhibited by APS12-2 in a concentration-dependent manner (IC{sub 50} = 0.36 μM) without significant change in the resting membrane potential of the muscle fibers up to 3.40 μM. The compound also blocked acetylcholine-evoked inward currents in Xenopus oocytes in which Torpedo (α1{sub 2}β1γδ) muscle-type nicotinic acetylcholine receptors (nAChRs) have been incorporated (IC{sub 50} = 0.0005 μM), indicating a higher affinity of the compound for Torpedo (α1{sub 2}β1γδ) than for the mouse (α1{sub 2}β1γε) nAChR. Our data show for the first time that APS12-2 blocks neuromuscular transmission by a non-depolarizing mechanism through an action on postsynaptic nAChRs of the skeletal neuromuscular junction. -- Highlights: ► APS12-2 produces concentration-dependent inhibition of nerve-evoked muscle contraction in vitro. ► APS12-2 blocks MEPPs and EPPs at the neuromuscular junction. APS12-2 blocks ACh-activated current in Xenopus oocytes incorporated with Torpedo nAChRs.« less

Imaging density and seismic velocities in the Eastern Mediterranean

NASA Astrophysics Data System (ADS)

Fichtner, A.; Blom, N.; Gokhberg, A.

2017-12-01

The Mediterranean domain is a geologically complicated region, a result of its complex tectonic and geodynamic evolution. Our understanding of it draws from surface geology, modeling and imaging of the subsurface. Here, we present a seismic waveform tomography of the Eastern Mediterranean. While computationally more expensive than ray-based imaging methods, the advantage of waveform methods lies in their ability to incorporate in a consistent manner all the information in seismograms - not just the arrivals of certain, specified phases. As a result, body and multimode surface waves, source effects, frequency-dependence, wavefront healing, anisotropy and attenuation are naturally and coherently incorporated. This not only allows us to image P- and S-wave velocity jointly for the crust and mantle, but also makes it possible to put constraints on density that ray tomography cannot provide. This is of special interest because heterogeneities in density drive geodynamics, and the combined knowledge of all parameters can help to distinguish between thermal and compositional effect.Our tomography makes use of a multi-scale approach, initially using only the very lowest frequency signals with periods of 100-150 s. The low-frequency data is not only important in order to avoid local minima in the optimisation, also the recovery of density relies crucially on it. As the model is updated and more of the data is explained by it, higher-frequency data is added and more parts of the seismogram are included. Only those parts are used in which data and synthetics are similar enough to allow for meaningful comparison. Our aim is to go down to periods of 10 s, which corresponds to structures of 15 km size in the crust to 25 km in the mantle. Resolution of the final model is assessed using a resolution analysis strategy developed by Fichtner & van Leeuwen (JGR, 2015). This helps us to evaluate the effects of smearing and heterogeneous ray coverage in a quantitative manner and gives an indication of trade-offs between parameters. Our work aims to provide a coherent model for the crust and upper mantle in the Eastern Mediterranean that includes seismic velocities, anisotropy and density. Taken together, these parameters may help shed light on the nature of anomalies as slabs, thermal provinces or compositional heterogeneity.

Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety.

PubMed

Johanson, J F; Ueno, R

2007-06-01

Lubiprostone, a locally acting type-2 chloride channel activator, induces intestinal fluid secretion. To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation. A total of 129 patients with chronic constipation were randomized to receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous bowel movement (SBM) frequency, rescue medication use, symptom assessments and adverse events (AEs) were tracked. Over the double-blinded period, mean SBM frequencies were higher for lubiprostone groups (5.1-6.1) vs. placebo (3.8) and the overall difference was statistically significant (P = 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day (P < or = 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo (P < or = 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day (P < or = 0.009). The most common AEs were nausea, headache and diarrhoea. Lubiprostone improved SBM rates in a dose-dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk-to-benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.

Beta oscillations reflect supramodal information during perceptual judgment.

PubMed

Haegens, Saskia; Vergara, José; Rossi-Pool, Román; Lemus, Luis; Romo, Ranulfo

2017-12-26

Previous work on perceptual decision making in the sensorimotor system has shown population dynamics in the beta band, corresponding to the encoding of stimulus properties and the final decision outcome. Here, we asked how oscillatory dynamics in the medial premotor cortex (MPC) contribute to supramodal perceptual decision making. We recorded local field potentials (LFPs) and spikes in two monkeys trained to perform a tactile-acoustic frequency discrimination task, including both unimodal and crossmodal conditions. We studied the role of oscillatory activity as a function of stimulus properties (frequency and sensory modality), as well as decision outcome. We found that beta-band power correlated with relevant stimulus properties: there was a significant modulation by stimulus frequency during the working-memory (WM) retention interval, as well as modulation by stimulus modality-the latter was observed only in the case of a purely unimodal task, where modality information was relevant to prepare for the upcoming second stimulus. Furthermore, we found a significant modulation of beta power during the comparison and decision period, which was predictive of decision outcome. Finally, beta-band spike-field coherence (SFC) matched these LFP observations. In conclusion, we demonstrate that beta power in MPC is reflective of stimulus features in a supramodal, context-dependent manner, and additionally reflects the decision outcome. We propose that these beta modulations are a signature of the recruitment of functional neuronal ensembles, which encode task-relevant information.

Growth promotion effect of steelmaking slag on Spirulina platensis

NASA Astrophysics Data System (ADS)

Nogami, R.; Tam, L. T.; Anh, H. T. L.; Quynh, H. T. H.; Thom, L. T.; Nhat, P. V.; Thu, N. T. H.; Hong, D. D.; Wakisaka, M.

2016-04-01

A growth promotion effect of steelmaking slag on Spirulina platensis M135 was investigated. The growth promotion effect was obtained that was 1.27 times greater than that obtained by the control by adding 500 mg L-1 of steelmaking slag and culturing for 60 days. The lipid content decreased in a concentration-dependent manner with steelmaking slag, whereas the carbohydrate content remained constant. The protein content of S. platensis M135 increased in a concentration-dependent manner with steelmaking slag when cultured at day 45. The superoxide dismutase activity of S. platensis M135 exhibited a decreasing trend in a time-dependent manner and an increasing trend in the control. The superoxide dismutase activity was lower than that of the control at day 1 but was higher at day 30. No genetic damage was observed up to 500 mg L-1 of steelmaking slag at 30 days of culture. Recovery from genetic damage was observed at 1,000 mg L-1 of steelmaking slag but not at higher concentrations.

Geraniol attenuates α-synuclein expression and neuromuscular impairment through increase dopamine content in MPTP intoxicated mice by dose dependent manner.

PubMed

Rekha, Karamkolly R; Selvakumar, Govindasamy P; Santha, Karunanithi; Inmozhi Sivakamasundari, Ramu

2013-11-01

Parkinson's disease (PD) is characterized by progressive loss of dopamine (DA) neurons in the nigrostriatal system and by the presence of Lewy bodies (LB), proteinaceous inclusions mainly composed of filamentous α-synuclein (α-Syn) aggregates. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was adopted to generate PD models in C57BL/6 mice. In the present study, we investigated the effect of geraniol (GE) against α-Syn aggregation on MPTP induced mouse model of PD in dose dependant manner. When pretreatment of GE improved neuromuscular impairment, TH expressions and decreases α-Syn expressions in MPTP intoxicated PD mice by dose dependent manner. In addition, we confirmed that sub-chronic administration of MPTP in mice leads to permanent neuromuscular deficits and depletion of dopamine and its metabolites. Our results suggest that GE is beneficial for the treatment of PD associated with neuromuscular disability and LB aggregation. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions.

PubMed

Monticelli, Laurel A; Osborne, Lisa C; Noti, Mario; Tran, Sara V; Zaiss, Dietmar M W; Artis, David

2015-08-25

The barrier surfaces of the skin, lung, and intestine are constantly exposed to environmental stimuli that can result in inflammation and tissue damage. Interleukin (IL)-33-dependent group 2 innate lymphoid cells (ILC2s) are enriched at barrier surfaces and have been implicated in promoting inflammation; however, the mechanisms underlying the tissue-protective roles of IL-33 or ILC2s at surfaces such as the intestine remain poorly defined. Here we demonstrate that, following activation with IL-33, expression of the growth factor amphiregulin (AREG) is a dominant functional signature of gut-associated ILC2s. In the context of a murine model of intestinal damage and inflammation, the frequency and number of AREG-expressing ILC2s increases following intestinal injury and genetic disruption of the endogenous AREG-epidermal growth factor receptor (EGFR) pathway exacerbated disease. Administration of exogenous AREG limited intestinal inflammation and decreased disease severity in both lymphocyte-sufficient and lymphocyte-deficient mice, revealing a previously unrecognized innate immune mechanism of intestinal tissue protection. Furthermore, treatment with IL-33 or transfer of ILC2s ameliorated intestinal disease severity in an AREG-dependent manner. Collectively, these data reveal a critical feedback loop in which cytokine cues from damaged epithelia activate innate immune cells to express growth factors essential for ILC-dependent restoration of epithelial barrier function and maintenance of tissue homeostasis.

Use of an ultrasonic reflectance technique to examine bubble size changes in dough

NASA Astrophysics Data System (ADS)

Strybulevych, A.; Leroy, V.; Shum, A. L.; Koksel, H. F.; Scanlon, M. G.; Page, J. H.

2012-12-01

Bread quality largely depends on the manner in which bubbles are created and manipulated in the dough during processing. We have developed an ultrasonic reflectance technique to monitor bubbles in dough, even at high volume fractions, where near the bubble resonances it is difficult to make measurements using transmission techniques. A broadband transducer centred at 3.5 MHz in a normal incidence wave reflection set-up is used to measure longitudinal velocity and attenuation from acoustic impedance measurements. The technique is illustrated by examining changes in bubbles in dough due to two very different physical effects. In dough made without yeast, a peak in attenuation due to bubble resonance is observed at approximately 2 MHz. This peak diminishes rapidly and shifts to lower frequencies, indicative of Ostwald ripening of bubbles within the dough. The second effect involves the growth of bubble sizes due to gas generated by yeast during fermentation. This process is experimentally challenging to investigate with ultrasound because of very high attenuation. The reflectance technique allows the changes of the velocity and attenuation during fermentation to be measured as a function of frequency and time, indicating bubble growth effects that can be monitored even at high volume fractions of bubbles.

Evaluation of the cytotoxic and genotoxic potential of lecithin/chitosan nanoparticles

NASA Astrophysics Data System (ADS)

Taner, Gökçe; Yeşilöz, Recep; Özkan Vardar, Deniz; Şenyiğit, Taner; Özer, Özgen; Degen, Gisela H.; Başaran, Nurşen

2014-02-01

Nanoparticles-based drug targeting delivery systems have been introduced in the treatment for various diseases because of their effective properties, although there have been conflicting results on the toxicity of nanoparticles. In the present study, the aim was to evaluate the cytotoxicity and the genotoxicity of different concentrations of lecithin/chitosan nanoparticles with and without clobetasol-17-propionate (CP) by neutral red uptake (NRU) cytotoxicity assay and single cell gel electrophoresis (Comet) and cytokinesis-blocked micronucleus assays. The IC50 values of lecithin/chitosan nanoparticles with/without CP were found as 1.9 and 1.8 %, respectively, in the NRU cytotoxicity test. High concentrations of lecithin/chitosan nanoparticles induced DNA damage in human lymphocytes as evaluated by comet assay. The micronucleus frequency was increased by the lecithin/chitosan treatment in a dose-dependent manner. Also at the two highest concentrations, a significant increase in micronucleus formation was observed. Lecithin/chitosan nanoparticles with CP did not increase the frequency of micronucleus and also did not induce additional DNA damage when compared with lecithin/chitosan nanoparticles without CP; therefore, CP itself has not found to be genotoxic at the studied concentration.

Radioprotective effect of Haberlea rhodopensis (Friv.) leaf extract on gamma-radiation-induced DNA damage, lipid peroxidation and antioxidant levels in rabbit blood.

PubMed

Georgieva, Svetlana; Popov, Borislav; Bonev, Georgi

2013-01-01

Different concentrations of H. rhodopensis total extract (HRE; 0.03, 0.06 and 0.12 g/kg body weight) were injected im, into rabbits 2 h before collecting the blood samples. The whole blood samples were exposed in vitro to 2.0 Gy 60Co gamma-radiation. The radiation-induced changes were estimated by using the chromosome aberration test (CA) and cytokinesis blocked micronucleus assay (CBMN) in peripheral lymphocytes, and by determining the malondialdehyde levels (MDA) in blood plasma and the superoxide dismutase (SOD) and catalase (CAT) activity in erythrocytes. Radiation significantly increased the chromosome aberration and micronuclei frequencies as well as MDA levels and decreased the antioxidant enzyme activity. On the other hand, the HRE pretreatment significantly decreased the CA, MN frequencies and MDA levels and increased the SOD and CAT activity in a concentration dependent manner. The most effective was the highest concentration of HRE (0.12 g/kg body weight). The results suggest that HRE as a natural product with a nantioxidant capacity could play a modulatory role against the cellular damage induced by gamma-irradiation. The possible mechanism involved in the radioprotective potential of HRE is discussed.

Bioparticles assembled using low frequency vibration immune to evacuation drifts

NASA Astrophysics Data System (ADS)

Shao, Fenfen; Whitehill, James David; Ng, Tuck Wah

2012-08-01

The use of low frequency vibration on suspensions of glass beads in a droplet has been shown to develop a strong degree of patterning (to a ring) due to the manner with which the surface waves are modified. Functionalized glass beads that serve as bioparticles permit for sensitive readings when concentrated at specific locations. However, a time controlled exposure with analytes is desirable. The replacement of the liquid medium with analyte through extraction is needed to conserve time. Nevertheless, we show here that extraction with a porous media, which is simple and useable in the field, will strongly displace the patterned beads. The liquid removal was found to be dependent on two mechanisms that affect the shape of the droplet, one of contact hysteresis due to the outer edge pinning, and the other of liquid being drawn into the porous media. From this, we developed and demonstrated a modified well structure that prevented micro-bead displacement during evacuation. An added strong advantage with this approach lies with its ability to require only analytes to be dispensed at the location of aggregated particles, which minimizes analyte usage. This was analytically established here.

Fourier and Wavelet Analysis of Coronal Time Series

NASA Astrophysics Data System (ADS)

Auchère, F.; Froment, C.; Bocchialini, K.; Buchlin, E.; Solomon, J.

2016-10-01

Using Fourier and wavelet analysis, we critically re-assess the significance of our detection of periodic pulsations in coronal loops. We show that the proper identification of the frequency dependence and statistical properties of the different components of the power spectra provies a strong argument against the common practice of data detrending, which tends to produce spurious detections around the cut-off frequency of the filter. In addition, the white and red noise models built into the widely used wavelet code of Torrence & Compo cannot, in most cases, adequately represent the power spectra of coronal time series, thus also possibly causing false positives. Both effects suggest that several reports of periodic phenomena should be re-examined. The Torrence & Compo code nonetheless effectively computes rigorous confidence levels if provided with pertinent models of mean power spectra, and we describe the appropriate manner in which to call its core routines. We recall the meaning of the default confidence levels output from the code, and we propose new Monte-Carlo-derived levels that take into account the total number of degrees of freedom in the wavelet spectra. These improvements allow us to confirm that the power peaks that we detected have a very low probability of being caused by noise.

Octopamine and tyramine regulate the activity of reproductive visceral muscles in the adult female blood-feeding bug, Rhodnius prolixus.

PubMed

Hana, Sam; Lange, Angela B

2017-05-15

The role of octopamine and tyramine in regulating spontaneous contractions of reproductive tissues was examined in the female Rhodnius prolixus Octopamine decreased the amplitude of spontaneous contractions of the oviducts and reduced RhoprFIRFa-induced contractions in a dose-dependent manner, whereas tyramine only reduced the RhoprFIRFa-induced contractions. Both octopamine and tyramine decreased the frequency of spontaneous bursal contractions and completely abolished the contractions at 5×10 -7  mol l -1 and above. Phentolamine, an octopamine receptor antagonist, attenuated the inhibition induced by octopamine on the oviducts and the bursa. Octopamine also increased the levels of cAMP in the oviducts, and this effect was blocked by phentolamine. Dibutyryl cyclic AMP mimicked the effects of octopamine by reducing the frequency of bursal contractions, suggesting that the octopamine receptor may act by an Octβ receptor. The tyramine receptor antagonist yohimbine failed to block the inhibition of contractions induced by tyramine on the bursa, suggesting that tyramine may be acting on the Octβ receptor in the bursa. © 2017. Published by The Company of Biologists Ltd.

Functional Covariance Networks: Obtaining Resting-State Networks from Intersubject Variability

PubMed Central

Gohel, Suril; Di, Xin; Walter, Martin; Biswal, Bharat B.

2012-01-01

Abstract In this study, we investigate a new approach for examining the separation of the brain into resting-state networks (RSNs) on a group level using resting-state parameters (amplitude of low-frequency fluctuation [ALFF], fractional ALFF [fALFF], the Hurst exponent, and signal standard deviation). Spatial independent component analysis is used to reveal covariance patterns of the relevant resting-state parameters (not the time series) across subjects that are shown to be related to known, standard RSNs. As part of the analysis, nonresting state parameters are also investigated, such as mean of the blood oxygen level-dependent time series and gray matter volume from anatomical scans. We hypothesize that meaningful RSNs will primarily be elucidated by analysis of the resting-state functional connectivity (RSFC) parameters and not by non-RSFC parameters. First, this shows the presence of a common influence underlying individual RSFC networks revealed through low-frequency fluctation (LFF) parameter properties. Second, this suggests that the LFFs and RSFC networks have neurophysiological origins. Several of the components determined from resting-state parameters in this manner correlate strongly with known resting-state functional maps, and we term these “functional covariance networks”. PMID:22765879

[MAIT cells in autoimmunity].

PubMed

Miyake, Sachiko

2012-01-01

Mucosal associated invariant T (MAIT) cells are restricted by a nonpolymorphic MHC-related molecule-1 (MR1), and express an invariant TCRα chain: Vα7.2-Jα33 in humans and Vα19-Jα33 in mice. MAIT cells are selected in the thymus, but, interestingly, MAIT cells require B cells as well as commensal flora for their peripheral expansion. Bourhis et al demonstrated that MAIT cells display antimicrobial capacity. Both human and mouse MAIT cells have been shown to be activated by Escherichia coli-infected antigen presenting cells in an MR1-dependent manner. MAIT cells show a protective role against Mycobacteriu abscessus or E. coli infections in mice. Human MAIT cells are capable of producing IFNγ and IL-17 and are found in Mycobacterium tuberculosis-infected lung tissues. Thus, MAIT cells play an antimicrobial function under these infectious conditions. MAIT cells play a protective role against autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), whereas they play a pathogenic role in murine models of arthritis. In patients with autoimmune diseases, the frequency of MAIT cells in peripheral blood was significantly reduced. The frequency of MAIT cells reflected the disease activity in MS patients, suggesting the involvement of MAIT cells in the regulation of autoimmune diseases.

Differential regulation of NMDA receptors by d-serine and glycine in mammalian spinal locomotor networks

PubMed Central

Acton, David

2017-01-01

Activation of N-methyl-d-aspartate receptors (NMDARs) requires the binding of a coagonist, either d-serine or glycine, in addition to glutamate. Changes in occupancy of the coagonist binding site are proposed to modulate neural networks including those controlling swimming in frog tadpoles. Here, we characterize regulation of the NMDAR coagonist binding site in mammalian spinal locomotor networks. Blockade of NMDARs by d(−)-2-amino-5-phosphonopentanoic acid (d-APV) or 5,7-dichlorokynurenic acid reduced the frequency and amplitude of pharmacologically induced locomotor-related activity recorded from the ventral roots of spinal-cord preparations from neonatal mice. Furthermore, d-APV abolished synchronous activity induced by blockade of inhibitory transmission. These results demonstrate an important role for NMDARs in murine locomotor networks. Bath-applied d-serine enhanced the frequency of locomotor-related but not disinhibited bursting, indicating that coagonist binding sites are saturated during the latter but not the former mode of activity. Depletion of endogenous d-serine by d-amino acid oxidase or the serine-racemase inhibitor erythro-β-hydroxy-l-aspartic acid (HOAsp) increased the frequency of locomotor-related activity, whereas application of l-serine to enhance endogenous d-serine synthesis reduced burst frequency, suggesting a requirement for d-serine at a subset of synapses onto inhibitory interneurons. Consistent with this, HOAsp was ineffective during disinhibited activity. Bath-applied glycine (1–100 µM) failed to alter locomotor-related activity, whereas ALX 5407, a selective inhibitor of glycine transporter-1 (GlyT1), enhanced burst frequency, supporting a role for GlyT1 in NMDAR regulation. Together these findings indicate activity-dependent and synapse-specific regulation of the coagonist binding site within spinal locomotor networks, illustrating the importance of NMDAR regulation in shaping motor output. NEW & NOTEWORTHY We provide evidence that NMDARs within murine spinal locomotor networks determine the frequency and amplitude of ongoing locomotor-related activity in vitro and that NMDARs are regulated by d-serine and glycine in a synapse-specific and activity-dependent manner. In addition, glycine transporter-1 is shown to be an important regulator of NMDARs during locomotor-related activity. These results show how excitatory transmission can be tuned to diversify the output repertoire of spinal locomotor networks in mammals. PMID:28202572

Gravitational waves produced by compressible MHD turbulence from cosmological phase transitions

NASA Astrophysics Data System (ADS)

Peter, Niksa; Martin, Schlederer; Günter, Sigl

2018-07-01

We calculate the gravitational wave spectrum produced by magneto-hydrodynamic turbulence in a first order phase transitions. We focus in particular on the role of decorrelation of incompressible (solenoidal) homogeneous isotropic turbulence, which is dominated by the sweeping effect. The sweeping effect describes that turbulent decorrelation is primarily due to the small scale eddies being swept with by large scale eddies in a stochastic manner. This effect reduces the gravitational wave signal produced by incompressible MHD turbulence by around an order of magnitude compared to previous studies. Additionally, we find a more complicated dependence for the spectral shape of the gravitational wave spectrum on the energy density sourced by solenoidal modes (magnetic and kinetic). The high frequency tail follows either a k ‑5/3 or a k ‑8/3 power law for large and small solenoidal turbulence density parameter, respectively. Further, magnetic helicity tends to increase the gravitational wave energy at low frequencies. Moreover, we show how solenoidal modes might impact the gravitational wave spectrum from dilatational modes e.g. sound waves. We find that solenoidal modes greatly affect the shape of the gravitational wave spectrum due to the sweeping effect on the dilatational modes. For a high velocity flow, one expects a k ‑2 high frequency tail, due to sweeping. In contrast, for a low velocity flow and a sound wave dominated flow, we expect a k ‑3 high frequency tail. If neither of these limiting cases is realized, the gravitational wave spectrum may be a broken power law with index between  ‑2 and  ‑3, extending up to the frequency at which the source is damped by viscous dissipation.

Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors.

PubMed

Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Weng, Nan-Ping; Young, Lauren F; Shieh, Jae-Hung; Moore, Malcolm A; van den Brink, Marcel R M; Kusunoki, Yoichiro

2016-05-01

Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34+Lin-) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

X-ray-induced bystander responses reduce spontaneous mutations in V79 cells

PubMed Central

Maeda, Munetoshi; Kobayashi, Katsumi; Matsumoto, Hideki; Usami, Noriko; Tomita, Masanori

2013-01-01

The potential for carcinogenic risks is increased by radiation-induced bystander responses; these responses are the biological effects in unirradiated cells that receive signals from the neighboring irradiated cells. Bystander responses have attracted attention in modern radiobiology because they are characterized by non-linear responses to low-dose radiation. We used a synchrotron X-ray microbeam irradiation system developed at the Photon Factory, High Energy Accelerator Research Organization, KEK, and showed that nitric oxide (NO)-mediated bystander cell death increased biphasically in a dose-dependent manner. Here, we irradiated five cell nuclei using 10 × 10 µm2 5.35 keV X-ray beams and then measured the mutation frequency at the hypoxanthine-guanosine phosphoribosyl transferase (HPRT) locus in bystander cells. The mutation frequency with the null radiation dose was 2.6 × 10–5 (background level), and the frequency decreased to 5.3 × 10–6 with a dose of approximately 1 Gy (absorbed dose in the nucleus of irradiated cells). At high doses, the mutation frequency returned to the background level. A similar biphasic dose-response effect was observed for bystander cell death. Furthermore, we found that incubation with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a specific scavenger of NO, suppressed not only the biphasic increase in bystander cell death but also the biphasic reduction in mutation frequency of bystander cells. These results indicate that the increase in bystander cell death involves mechanisms that suppress mutagenesis. This study has thus shown that radiation-induced bystander responses could affect processes that protect the cell against naturally occurring alterations such as mutations. PMID:23660275

Loss of heterozygosity and methylation of multiple tumor suppressor genes on chromosome 3 in hepatocellular carcinoma.

PubMed

Zhang, Xiaoying; Li, Hiu Ming; Liu, Zhiyan; Zhou, Gengyin; Zhang, Qinghui; Zhang, Tingguo; Zhang, Jianping; Zhang, Cuijuan

2013-01-01

Genetic and epigenetic alterations are the two key mechanisms in the development of hepatocellular carcinoma (HCC). However, how they contribute to hepatocarcinogenesis and the correlation between them has not been fully elucidated. A total of 48 paired HCCs and noncancerous tissues were used to detect loss of heterozygosity (LOH) and the methylation profiles of five tumor suppressor genes (RASSF1A, BLU, FHIT, CRBP1, and HLTF) on chromosome 3 by using polymerase chain reaction (PCR) and methylation-specific PCR. Gene expression was analyzed by immunohistochemistry and reverse transcription (RT)-PCR. Sixteen of 48 (33.3 %) HCCs had LOH on at least one locus on chromosome 3, and two smallest common deleted regions (3p22.3-24.3 and 3p12.3-14.2) were identified. RASSF1A, BLU, and FHIT showed very high frequencies of methylation in HCCs (100, 81.3, and 64.6 %, respectively) and noncancerous tissues, but not in liver tissues from control patients. Well-differentiated HCCs showed high methylation frequencies of these genes but very low frequencies of LOH. Furthermore, BLU methylation was associated with an increased level of alpha-fetoprotein, and FHIT methylation was inversely correlated with HCC recurrence. In comparison, CRBP1 showed moderate frequencies of methylation, while HLTF showed low frequencies of methylation, and CRBP1 methylation occurred mainly in elderly patients. Treatment with 5-aza-2'-deoxycytidine demethylated at least one of these genes and restored their expression in a DNA methylation-dependent or -independent manner. Hypermethylation of RASSF1A, BLU, and FHIT is a common and very early event in hepatocarcinogenesis; CRBP1 methylation may also be involved in the later stage. Although LOH was not too frequent on chromosome 3, it may play a role as another mechanism in hepatocarcinogenesis.

Relationship between spontaneous γH2AX foci formation and progenitor functions in circulating hematopoietic stem and progenitor cells among atomic-bomb survivors

PubMed Central

Kajimura, Junko; Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Weng, Nan-ping; Young, Lauren F.; Shieh, Jae-Hung; Moore, Malcolm A.; van den Brink, Marcel R.M.; Kusunoki, Yoichiro

2016-01-01

Accumulated DNA damage in hematopoietic stem cells is a primary mechanism of aging-associated dysfunction in human hematopoiesis. About 70 years ago, atomic-bomb (A-bomb) radiation induced DNA damage and functional decreases in the hematopoietic system of A-bomb survivors in a radiation dose-dependent manner. The peripheral blood cell populations then recovered to a normal range, but accompanying cells derived from hematopoietic stem cells still remain that bear molecular changes possibly caused by past radiation exposure and aging. In the present study, we evaluated radiation-related changes in the frequency of phosphorylated (Ser-139) H2AX (γH2AX) foci formation in circulating CD34-positive/lineage marker-negative (CD34 + Lin−) hematopoietic stem and progenitor cells (HSPCs) among 226Hiroshima A-bomb survivors. An association between the frequency of γH2AX foci formation in HSPCs and the radiation dose was observed, but the γH2AX foci frequency was not significantly elevated by past radiation. We found a negative correlation between the frequency of γH2AX foci formation and the length of granulocyte telomeres. A negative interaction effect between the radiation dose and the frequency of γH2AX foci was suggested in a proportion of a subset of HSPCs as assessed by the cobblestone area-forming cell assay (CAFC), indicating that the self-renewability of HSPCs may decrease in survivors who were exposed to a higher radiation dose and who had more DNA damage in their HSPCs. Thus, although many years after radiation exposure and with advancing age, the effect of DNA damage on the self-renewability of HSPCs may be modified by A-bomb radiation exposure. PMID:27169377

Amino Acid Insertion Frequencies Arising from Photoproducts Generated Using Aliphatic Diazirines

NASA Astrophysics Data System (ADS)

Ziemianowicz, Daniel S.; Bomgarden, Ryan; Etienne, Chris; Schriemer, David C.

2017-10-01

Mapping proteins with chemical reagents and mass spectrometry can generate a measure of accessible surface area, which in turn can be used to support the modeling and refinement of protein structures. Photolytically generated carbenes are a promising class of reagent for this purpose. Substituent effects appear to influence surface mapping properties, allowing for a useful measure of design control. However, to use carbene labeling data in a quantitative manner for modeling activities, we require a better understanding of their inherent amino acid reactivity, so that incorporation data can be normalized. The current study presents an analysis of the amino acid insertion frequency of aliphatic carbenes generated by the photolysis of three different diazirines: 3,3'-azibutyl-1-ammonium, 3,3'-azibutan-1-ol, and 4,4'-azipentan-1-oate. Leveraging an improved photolysis system for single-shot labeling of sub-microliter frozen samples, we used EThCD to localize insertion products in a large population of labeled peptides. Counting statistics were drawn from data-dependent LC-MS2 experiments and used to estimate the frequencies of insertion as a function of amino acid. We observed labeling of all 20 amino acids over a remarkably narrow range of insertion frequencies. However, the nature of the substituent could influence relative insertion frequencies, within a general preference for larger polar amino acids. We confirm a large (6-fold) increase in labeling yield when carbenes were photogenerated in the solid phase (77 K) relative to the liquid phase (293 K), and we suggest that carbene labeling should always be conducted in the frozen state to avoid information loss in surface mapping experiments. [Figure not available: see fulltext.

Parameters affecting frequency of CRISPR/Cas9 mediated targeted mutagenesis in rice.

PubMed

Mikami, Masafumi; Toki, Seiichi; Endo, Masaki

2015-10-01

Frequency of CRISPR/Cas9-mediated targeted mutagenesis varies depending on Cas9 expression level and culture period of rice callus. Recent reports have demonstrated that the CRISPR/Cas9 system can function as a sequence-specific nuclease in various plant species. Induction of mutation in proliferating tissue during embryogenesis or in germline cells is a practical means of generating heritable mutations. In the case of plant species in which cultured cells are used for transformation, non-chimeric plants can be obtained when regeneration occurs from mutated cells. Since plantlets are regenerated from both mutated and non-mutated cells in a random manner, any increment in the proportion of mutated cells in Cas9- and guide RNA (gRNA)-expressing cells will help increase the number of plants containing heritable mutations. In this study, we examined factors affecting mutation frequency in rice calli. Following sequential transformation of rice calli with Cas9- and gRNA- expression constructs, the mutation frequency in independent Cas9 transgenic lines was analyzed. A positive correlation between Cas9 expression level and mutation frequency was found. This positive relationship was observed regardless of whether the transgene or an endogenous gene was used as the target for CRISPR/Cas9-mediated mutagenesis. Furthermore, we found that extending the culture period increased the proportion of mutated cells as well as the variety of mutations obtained. Because mutated and non-mutated cells might proliferate equally, these results suggest that a prolonged tissue culture period increases the chance of inducing de novo mutations in non-mutated cells. This fundamental knowledge will help improve systems for obtaining non-chimeric regenerated plants in many plant species.

Reminiscence therapy using odor in alcohol-dependent patients--psychophysiological evaluation and psychological evaluation; power spectral analysis of heart rate variability.

PubMed

Arizono, H; Morita, N; Iizuka, S; Satoh, S; Nakatani, Y

2000-12-01

This research was based on the hypothesis that when alcohol-dependent patients describe themselves, awakening of emotion by affirmative odor stimulation may facilitate memory reframing focusing on more affirmative emotion and memories. To prove the hypothesis, physiological changes accompanied by emotional awakening were evaluated by measuring the autonomic activity. In addition, subjective evaluation by a self-report manner was examined to investigate the effectiveness of Reminiscence Therapy (RT) using odor in alcohol-dependent patients. Thirty-four patients who met the DSM-IV criteria of alcohol-related disorders and were hospitalized in a ward specialized to alcohol dependence therapy. Each patient underwent a one-to-one interview twice. For counterbalance, one interview was performed with odor stimulation using an odor with a relaxing effect that recall pleasant emotion, and the other was without odor stimulation. As the evaluation indices of physiological changes accompanied by emotional awakening, index of autonomic function (HRV; Heart rate variability) for objective evaluation and psychological indices (STAI; State-Trait Anxiety Inventory VAS; Visual Analog Scale) for subjective evaluation were measured. 1) Objective evaluation: Regarding the evaluation index of the autonomic function, the sympathetic nervous system activity (LF/HF; low frequency component/high frequency component ratio) was significantly inhibited by odor stimulation (p < 0.05). 2) Subjective evaluation: Compared to the state prior to interview, state anxiety judged by STAI was significantly decreased after interview (p < 0.01). The VAS score was significantly decreased after interview regardless of the presence or absence of odor stimulation (p < 0.0001). A reduction in state anxiety was observed. The effect of odor was not significant on the subjective evaluation, but the objective evaluation suggested that the odor inhibited the sympathetic nervous system. Thus, it was suggested that odor can be used in RT, that is, emotional changes due to stimulation of odor may be applicable in RT.

Cocaine disinhibits dopamine neurons in the ventral tegmental area via use-dependent blockade of GABA neuron voltage-sensitive sodium channels

PubMed Central

Steffensen, Scott C.; Taylor, Seth R.; Horton, Malia L.; Barber, Elise N.; Lyle, Laura T.; Stobbs, Sarah H.; Allison, David W.

2010-01-01

The aim of this study was to evaluate the effects of cocaine on γ-aminobutyric acid (GABA) and dopamine (DA) neurons in the ventral tegmental area (VTA). Utilizing single-unit recordings in vivo, microelectrophoretic administration of DA enhanced the firing rate of VTA GABA neurons via D2/D3 DA receptor activation. Lower doses of intravenous cocaine (0.25–0.5 mg/kg), or the DA transporter (DAT) blocker methamphetamine, enhanced VTA GABA neuron firing rate via D2/D3 receptor activation. Higher doses of cocaine (1.0–2.0 mg/kg) inhibited their firing rate, which was not sensitive to the D2/D3 antagonist eticlopride. The voltage-sensitive sodium channel (VSSC) blocker lidocaine inhibited the firing rate of VTA GABA neurons at all doses tested (0.25–2.0 mg/kg). Cocaine or lidocaine reduced VTA GABA neuron spike discharges induced by stimulation of the internal capsule (ICPSDs) at dose levels 0.25–2 mg/kg (IC50 1.2 mg/kg). There was no effect of DA or methamphetamine on ICPSDs, or of DA antagonists on cocaine inhibition of ICPSDs. In VTA GABA neurons in vitro, cocaine reduced (IC50 13 μm) current-evoked spikes and TTX-sensitive sodium currents in a use-dependent manner. In VTA DA neurons, cocaine reduced IPSCs (IC50 13 μm), increased IPSC paired-pulse facilitation and decreased spontaneous IPSC frequency, without affecting miniature IPSC frequency or amplitude. These findings suggest that cocaine acts on GABA neurons to reduce activity-dependent GABA release on DA neurons in the VTA, and that cocaine's use-dependent blockade of VTA GABA neuron VSSCs may synergize with its DAT inhibiting properties to enhance mesolimbic DA transmission implicated in cocaine reinforcement. PMID:19046384

Frequency-Unspecific Effects of θ-tACS Related to a Visuospatial Working Memory Task

PubMed Central

Kleinert, Maria-Lisa; Szymanski, Caroline; Müller, Viktor

2017-01-01

Working memory (WM) is crucial for intelligent cognitive functioning, and synchronization phenomena in the fronto-parietal network have been suggested as an underlying neural mechanism. In an attempt to provide causal evidence for this assumption, we applied transcranial alternating current stimulation (tACS) at theta frequency over fronto-parietal sites during a visuospatial match-to-sample (MtS) task. Depending on the stimulation protocol, i.e., in-phase, anti-phase or sham, we anticipated a differential impact of tACS on behavioral WM performance as well as on the EEG (electroencephalography) during resting state before and after stimulation. We hypothesized that in-phase tACS of the fronto-parietal theta network (stimulation frequency: 5 Hz; intensity: 1 mA peak-to-peak) would result in performance enhancement, whereas anti-phase tACS would cause performance impairment. Eighteen participants (nine female) received in-phase, anti-phase, and sham stimulation in balanced order. While being stimulated, subjects performed the MtS task, which varied in executive demand (two levels: low and high). EEG analysis of power peaks within the delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), and beta (12–30 Hz) frequency bands was carried out. No significant differences were observed between in-phase and anti-phase stimulation regarding both behavioral and EEG measurements. Yet, with regard to the alpha frequency band, we observed a statistically significant drop of peak power from pre to post in the sham condition, whereas alpha power remained on a similar level in the actively stimulated conditions. Our results indicate a frequency-unspecific modulation of neuronal oscillations by tACS. However, the closer participants’ individual theta peak frequencies were to the stimulation frequency of 5 Hz after anti-phase tACS, the faster they responded in the MtS task. This effect did not reach statistical significance during in-phase tACS and was not present during sham. A lack of statistically significant behavioral results in the MtS task and frequency-unspecific effects on the electrophysiological level question the effectiveness of tACS in modulating cortical oscillations in a frequency-specific manner. PMID:28747881

Despite differences in cytosolic calcium regulation, lidocaine toxicity is similar in adult and neonatal rat dorsal root ganglia in vitro.

PubMed

Doan, Lisa V; Eydlin, Olga; Piskoun, Boris; Kline, Richard P; Recio-Pinto, Esperanza; Rosenberg, Andrew D; Blanck, Thomas J J; Xu, Fang

2014-01-01

Neuraxial local anesthetics may have neurological complications thought to be due to neurotoxicity. A primary site of action of local anesthetics is the dorsal root ganglia (DRG) neuron. Physiologic differences have been noted between young and adult DRG neurons; hence, the authors examined whether there were any differences in lidocaine-induced changes in calcium and lidocaine toxicity in neonatal and adult rat DRG neurons. DRG neurons were cultured from postnatal day 7 (P7) and adult rats. Lidocaine-induced changes in cytosolic calcium were examined with the calcium indicator Fluo-4. Cells were incubated with varying concentrations of lidocaine and examined for viability using calcein AM and ethidium homodimer-1 staining. Live imaging of caspase-3/7 activation was performed after incubation with lidocaine. The mean KCl-induced calcium transient was greater in P7 neurons (P < 0.05), and lidocaine significantly inhibited KCl-induced calcium responses in both ages (P < 0.05). Frequency distribution histograms of KCl-evoked calcium increases were more heterogeneous in P7 than in adult neurons. With lidocaine, KCl-induced calcium transients in both ages became more homogeneous but remained different between the groups. Interestingly, cell viability was decreased by lidocaine in a dose-dependent manner similarly in both ages. Lidocaine treatment also activated caspase-3/7 in a dose- and time-dependent manner similarly in both ages. Despite physiological differences in P7 and adult DRG neurons, lidocaine cytotoxicity is similar in P7 and adult DRG neurons in vitro. Differences in lidocaine- and KCl-evoked calcium responses suggest the similarity in lidocaine cytotoxicity involves other actions in addition to lidocaine-evoked effects on cytosolic calcium responses.

Despite Differences in Cytosolic Calcium Regulation, Lidocaine Toxicity Is Similar in Adult and Neonatal Rat Dorsal Root Ganglia in Vitro

PubMed Central

Doan, Lisa V.; Eydlin, Olga; Piskoun, Boris; Kline, Richard P; Recio-Pinto, Esperanza; Rosenberg, Andrew D; Blanck, Thomas JJ; Xu, Fang

2013-01-01

Background Neuraxial local anesthetics may have neurological complications thought to be due to neurotoxicity. A primary site of action for local anesthetics is the dorsal root ganglia (DRG) neuron. Physiologic differences have been noted between young and adult DRG neurons; hence, we examined whether there were differences in lidocaine-induced changes in calcium and lidocaine toxicity in neonatal and adult rat DRG neurons. Methods DRG neurons were cultured from postnatal day 7 (P7) and adult rats. Lidocaine-induced changes in cytosolic calcium were examined with the calcium indicator Fluo-4. Cells were incubated with varying concentrations of lidocaine and examined for viability using calcein AM and ethidium homodimer-1 staining. Live imaging of caspase-3/7 activation was performed after incubation with lidocaine. Results The mean KCl-induced calcium transient was greater in P7 neurons (p < 0.05), and lidocaine significantly inhibited KCl-induced calcium responses in both ages (p < 0.05). Frequency distribution histograms of KCl-evoked calcium increases were more heterogeneous in P7 than in adult neurons. With lidocaine, KCl-induced calcium transients in both ages became more homogeneous but remained different between the groups. Interestingly cell viability was decreased by lidocaine in a dose-dependent manner similarly in both ages. Lidocaine treatment also activated caspase-3/7 in a dose- and time-dependent manner similarly in both ages. Conclusions Despite physiological differences in P7 and adult DRG neurons, lidocaine cytotoxicity is similar in P7 and adult DRG neurons in vitro. Differences in lidocaine- and KCl-evoked calcium responses suggest the similarity in lidocaine cytotoxicity involves other actions in addition to lidocaine-evoked effects on cytosolic calcium responses. PMID:23851347

Influence of chemistry, interfacial width, and non-isothermal conditions on spatially heterogeneous activated relaxation and elasticity in glass-forming free standing films

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

Mirigian, Stephen; Schweizer, Kenneth S.

Here, we employ the Elastically Collective Nonlinear Langevin Equation (ECNLE) theory of activated relaxation to study several questions in free standing thin films of glass-forming molecular and polymer liquids. The influence of non-universal chemical aspects on dynamical confinement effects is found to be relatively weak, but with the caveat that for the systems examined, the bulk ECNLE polymer theory does not predict widely varying fragilities. Allowing the film model to have a realistic vapor interfacial width significantly enhances the reduction of the film-averaged glass transition temperature, T g, in a manner that depends on whether a dynamic or pseudo-thermodynamic averagingmore » of the spatial mobility gradient is adopted. The nature of film thickness effects on the spatial profiles of the alpha relaxation time and elastic modulus is studied under non-isothermal conditions and contrasted with the corresponding isothermal behavior. Modest differences are found if a film-thickness dependent T g is defined in a dynamical manner. But, adopting a pseudo-thermodynamic measure of T g leads to a qualitatively new form of the alpha relaxation time gradient where highly mobile layers near the film surface coexist with strongly vitrified regions in the film interior. Consequently, the film-averaged shear modulus can increase with decreasing film thickness, despite the T g reduction and presence of a mobile surface layer. Such a behavior stands in qualitative contrast to the predicted mechanical softening under isothermal conditions. Spatial gradients of the elastic modulus are studied as a function of temperature, film thickness, probing frequency, and experimental protocol, and a rich behavior is found.« less

Influence of chemistry, interfacial width, and non-isothermal conditions on spatially heterogeneous activated relaxation and elasticity in glass-forming free standing films

DOE PAGES

Mirigian, Stephen; Schweizer, Kenneth S.

2017-02-02

Here, we employ the Elastically Collective Nonlinear Langevin Equation (ECNLE) theory of activated relaxation to study several questions in free standing thin films of glass-forming molecular and polymer liquids. The influence of non-universal chemical aspects on dynamical confinement effects is found to be relatively weak, but with the caveat that for the systems examined, the bulk ECNLE polymer theory does not predict widely varying fragilities. Allowing the film model to have a realistic vapor interfacial width significantly enhances the reduction of the film-averaged glass transition temperature, T g, in a manner that depends on whether a dynamic or pseudo-thermodynamic averagingmore » of the spatial mobility gradient is adopted. The nature of film thickness effects on the spatial profiles of the alpha relaxation time and elastic modulus is studied under non-isothermal conditions and contrasted with the corresponding isothermal behavior. Modest differences are found if a film-thickness dependent T g is defined in a dynamical manner. But, adopting a pseudo-thermodynamic measure of T g leads to a qualitatively new form of the alpha relaxation time gradient where highly mobile layers near the film surface coexist with strongly vitrified regions in the film interior. Consequently, the film-averaged shear modulus can increase with decreasing film thickness, despite the T g reduction and presence of a mobile surface layer. Such a behavior stands in qualitative contrast to the predicted mechanical softening under isothermal conditions. Spatial gradients of the elastic modulus are studied as a function of temperature, film thickness, probing frequency, and experimental protocol, and a rich behavior is found.« less

Inhibitory effects of hesperetin on Kv1.5 potassium channels stably expressed in HEK 293 cells and ultra-rapid delayed rectifier K(+) current in human atrial myocytes.

PubMed

Wang, Huan; Wang, Hong-Fei; Wang, Chen; Chen, Yu-Fang; Ma, Rong; Xiang, Ji-Zhou; Du, Xin-Ling; Tang, Qiang

2016-10-15

In the present study, the inhibitory effects of hesperetin (HSP) on human cardiac Kv1.5 channels expressed in HEK 293 cells and the ultra-rapid delayed rectifier K(+) current (Ikur) in human atrial myocytes were examined by using the whole-cell configuration of the patch-clamp techniques. We found that hesperetin rapidly and reversibly suppressed human Kv1.5 current in a concentration dependent manner with a half-maximal inhibition (IC50) of 23.15 μΜ with a Hill coefficient of 0.89. The current was maximally diminished about 71.36% at a concentration of 300μM hesperetin. Hesperetin significantly positive shifted the steady-state activation curve of Kv1.5, while negative shifted the steady-state inactivation curve. Hesperetin also accelerated the inactivation and markedly slowed the recovery from the inactivation of Kv1.5 currents. Block of Kv1.5 currents by hesperetin was in a frequency dependent manner. However, inclusion of 30μM hesperetin in pipette solution produced no effect on Kv1.5 channel current, while the current were remarkable and reversibly inhibited by extracellular application of 30μM hesperetin. We also found that hesperetin potently and reversibly inhibited the ultra-repaid delayed K(+) current (Ikur) in human atrial myocytes, which is in consistent with the effects of hesperetin on Kv1.5 currents in HEK 293 cells. In conclusion, hesperetin is a potent inhibitor of Ikur (which is encoded by Kv1.5), with blockade probably due to blocking of both open state and inactivated state channels from outside of the cell. Copyright © 2016 Elsevier B.V. All rights reserved.

The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+)-dependence of a transient K+ current.

PubMed

Levic, Snezana; Lv, Ping; Yamoah, Ebenezer N

2011-01-01

Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+) current that regulates patterning of action potentials is I(A). This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A) are not normally classified as Ca(2+)-dependent, we demonstrate that throughout the development of chicken hair cells, I(A) is greatly reduced by acute alterations of intracellular Ca(2+). As determinants of spike timing and firing frequency, intracellular Ca(2+) buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A) are tightly regulated by intracellular Ca(2+). Such feedback mechanism between the functional expression of I(A) and intracellular Ca(2+) may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea. © 2011 Levic et al.

Bioreactor design for successive culture of anchorage-dependent cells operated in an automated manner.

PubMed

Kino-Oka, Masahiro; Ogawa, Natsuki; Umegaki, Ryota; Taya, Masahito

2005-01-01

A novel bioreactor system was designed to perform a series of batchwise cultures of anchorage-dependent cells by means of automated operations of medium change and passage for cell transfer. The experimental data on contamination frequency ensured the biological cleanliness in the bioreactor system, which facilitated the operations in a closed environment, as compared with that in flask culture system with manual handlings. In addition, the tools for growth prediction (based on growth kinetics) and real-time growth monitoring by measurement of medium components (based on small-volume analyzing machinery) were installed into the bioreactor system to schedule the operations of medium change and passage and to confirm that culture proceeds as scheduled, respectively. The successive culture of anchorage-dependent cells was conducted with the bioreactor running in an automated way. The automated bioreactor gave a successful culture performance with fair accordance to preset scheduling based on the information in the latest subculture, realizing 79- fold cell expansion for 169 h. In addition, the correlation factor between experimental data and scheduled values through the bioreactor performance was 0.998. It was concluded that the proposed bioreactor with the integration of the prediction and monitoring tools could offer a feasible system for the manufacturing process of cultured tissue products.

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

Onopiuk, Marta; Wierzbicka, Katarzyna; Brutkowski, Wojciech

Activation of T-cells triggers store-operated Ca{sup 2+} entry, which begins a signaling cascade leading to induction of appropriate gene expression and eventually lymphocyte proliferation and differentiation. The simultaneous enhancement of Fas ligand gene expression in activated cells allows the immune response to be limited by committing the activated cells to apoptosis. In apoptotic cells the store-operated calcium entry is significantly inhibited. It has been documented that moderate activation of Fas receptor may cause reversible inhibition of store-operated channels by ceramide released from hydrolyzed sphingomyelin. Here we show that activation of Fas receptor in T-cells results in caspase-dependent decrease of cellularmore » STIM1 and Orai1 protein content. This effect may be responsible for the substantial inhibition of Ca{sup 2+} entry into Jurkat cells undergoing apoptosis. In turn, this inhibition might prevent overloading of cells with calcium and protect them against necrosis. -- Research highlights: {yields} Fas activation reduces STIM1 and Orai1 protein content in caspase dependent manner. {yields} Fas activation partially reduces mitochondrial potential in caspase dependent manner. {yields} Fas stimulation inhibits of store-operated Ca{sup 2+} entry in caspase dependent manner. {yields} Inhibition of Ca{sup 2+} entry in apoptotic cells may protect them from secondary necrosis.« less

Rethinking cell-cycle-dependent gene expression in Schizosaccharomyces pombe.

PubMed

Cooper, Stephen

2017-11-01

Three studies of gene expression during the division cycle of Schizosaccharomyces pombe led to the proposal that a large number of genes are expressed at particular times during the S. pombe cell cycle. Yet only a small fraction of genes proposed to be expressed in a cell-cycle-dependent manner are reproducible in all three published studies. In addition to reproducibility problems, questions about expression amplitudes, cell-cycle timing of expression, synchronization artifacts, and the problem with methods for synchronizing cells must be considered. These problems and complications prompt the idea that caution should be used before accepting the conclusion that there are a large number of genes expressed in a cell-cycle-dependent manner in S. pombe.

Method for detection of a few pathogenic bacteria and determination of live versus dead cells

NASA Astrophysics Data System (ADS)

Horikawa, Shin; Chen, I.-Hsuan; Du, Songtao; Liu, Yuzhe; Wikle, Howard C.; Suh, Sang-Jin; Barbaree, James M.; Chin, Bryan A.

2016-05-01

This paper presents a method for detection of a few pathogenic bacteria and determination of live versus dead cells. The method combines wireless phage-coated magnetoelastic (ME) biosensors and a surface-scanning dectector, enabling real-time monitoring of the growth of specific bacteria in a nutrient broth. The ME biosensor used in this investigation is composed of a strip-shaped ME resonator upon which an engineered bacteriophage is coated to capture a pathogen of interest. E2 phage with high binding affinity for Salmonella Typhimurium was used as a model study. The specificity of E2 phage has been reported to be 1 in 105 background bacteria. The phage-coated ME biosensors were first exposed to a low-concentration Salmonella suspension to capture roughly 300 cells on the sensor surface. When the growth of Salmonella in the broth occurs, the mass of the biosensor increases, which results in a decrease in the biosensor's resonant frequency. Monitoring of this mass- induced resonant frequency change allows for real-time detection of the presence of Salmonella. Detection of a few bacteria is also possible by growing them to a sufficient number. The surface-scanning detector was used to measure resonant frequency changes of 25 biosensors sequentially in an automated manner as a function of time. This methodology offers direct, real-time detection, quantification, and viability determination of specific bacteria. The rate of the sensor's resonant frequency change was found to be largely dependent on the number of initially bound cells and the efficiency of cell growth.

Correlating Nitrile IR Frequencies to Local Electrostatics Quantifies Noncovalent Interactions of Peptides and Proteins.

PubMed

Deb, Pranab; Haldar, Tapas; Kashid, Somnath M; Banerjee, Subhrashis; Chakrabarty, Suman; Bagchi, Sayan

2016-05-05

Noncovalent interactions, in particular the hydrogen bonds and nonspecific long-range electrostatic interactions are fundamental to biomolecular functions. A molecular understanding of the local electrostatic environment, consistently for both specific (hydrogen-bonding) and nonspecific electrostatic (local polarity) interactions, is essential for a detailed understanding of these processes. Vibrational Stark Effect (VSE) has proven to be an extremely useful method to measure the local electric field using infrared spectroscopy of carbonyl and nitrile based probes. The nitrile chemical group would be an ideal choice because of its absorption in an infrared spectral window transparent to biomolecules, ease of site-specific incorporation into proteins, and common occurrence as a substituent in various drug molecules. However, the inability of VSE to describe the dependence of IR frequency on electric field for hydrogen-bonded nitriles to date has severely limited nitrile's utility to probe the noncovalent interactions. In this work, using infrared spectroscopy and atomistic molecular dynamics simulations, we have reported for the first time a linear correlation between nitrile frequencies and electric fields in a wide range of hydrogen-bonding environments that may bridge the existing gap between VSE and H-bonding interactions. We have demonstrated the robustness of this field-frequency correlation for both aromatic nitriles and sulfur-based nitriles in a wide range of molecules of varying size and compactness, including small molecules in complex solvation environments, an amino acid, disordered peptides, and structured proteins. This correlation, when coupled to VSE, can be used to quantify noncovalent interactions, specific or nonspecific, in a consistent manner.

Origami-based mechanical metamaterials with tunable frequency band structures (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yasuda, Hiromi; Pratt, Riley; Yang, Jinkyu

2017-04-01

We investigate wave dynamics in origami-based mechanical metamaterials composed of bellows-like origami structures, specifically the Tachi-Miura Polyhedron (TMP). One of the unique features of the TMP is that its structural deformations take place only along the crease lines, therefore the structure can be made of rigid plates and hinges. By utilizing this feature, we introduce linear torsional springs to model the crease lines and derive the force and displacement relationship of the TMP structure along the longitudinal direction. Our analysis shows strain softening/hardening behaviors in compression/tensile regions respectively, and the force-displacement curve can be manipulated by altering the initial configuration of the TMP (e.g., the initial folding angle). We also fabricate physical prototypes and measure the force-displacement behavior to verify our analytical model. Based on this static analysis on the TMP, we simplify the TMP structure into a linkage model, preserving the tunable strain softening/hardening behaviors. Dynamic analysis is also conducted numerically to analyze the frequency response of the simplified TMP unit cell under harmonic excitations. The simplified TMP exhibits a transition between linear and nonlinear behaviors, which depends on the amplitude of the excitation and the initial configuration. In addition, we design a 1D system composed of simplified TMP unit cells and analyze the relationship between frequency and wave number. If two different configurations of the unit cell (e.g., different initial folding angles) are connected in an alternating arrangement, the system develops frequency bandgaps. These unique static/dynamic behaviors can be exploited to design engineering devices which can handle vibrations and impact in an efficient manner.

Stability and bistability in a one-dimensional model of coastal foredune height

NASA Astrophysics Data System (ADS)

Goldstein, Evan B.; Moore, Laura J.

2016-05-01

On sandy coastlines, foredunes provide protection from coastal storms, potentially sheltering low areas—including human habitat—from elevated water level and wave erosion. In this contribution we develop and explore a one-dimensional model for coastal dune height based on an impulsive differential equation. In the model, coastal foredunes continuously grow in a logistic manner as the result of a biophysical feedback and they are destroyed by recurrent storm events that are discrete in time. Modeled dunes can be in one of two states: a high "resistant-dune" state or a low "overwash-flat" state. The number of stable states (equilibrium dune heights) depends on the value of two parameters, the nondimensional storm frequency (the ratio of storm frequency to the intrinsic growth rate of dunes) and nondimensional storm magnitude (the ratio of total water level during storms to the maximum theoretical dune height). Three regions of phase space exist (1) when nondimensional storm frequency is small, a single high resistant-dune attracting state exists; (2) when both the nondimensional storm frequency and magnitude are large, there is a single overwash-flat attracting state; (3) within a defined region of phase space model dunes exhibit bistable behavior—both the resistant-dune and the low overwash-flat states are stable. Comparisons to observational studies suggest that there is evidence for each state to exist independently, the coexistence of both states (i.e., segments of barrier islands consisting of overwash-flats and segments of islands having large dunes that resist erosion by storms), as well as transitions between states.

40 CFR 141.203 - Tier 2 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2012 CFR

2012-07-01

...., house renters, apartment dwellers, university students, nursing home patients, prison inmates, etc... private employers); posting in public places served by the system or on the Internet; or delivery to...

Inhibition of Estrogen-Induced Growth of Breast Cancer by Targeting Mitrochondrial Oxidants

DTIC Science & Technology

2007-04-01

expected estradiol induced oxidants production in MCF-7 cells in dose dependent manner (Fig. 1). 0 50 100 150 200 250 300 DMSO 100pg 10ng 100ng...dose dependent manner. This is in agreement with previous findings (Foster et al., 2001). 0 50 100 150 200 250 300 DMSO 100pg/ml 10ng/ml 100ng/ml C...significantly inhibited E2-induced cell growth by as much as 50 % after a 72 h treatment. The reduction of E2-induced cell growth observed with NAC and

Real-Time Frequency Response Estimation Using Joined-Wing SensorCraft Aeroelastic Wind-Tunnel Data

NASA Technical Reports Server (NTRS)

Grauer, Jared A; Heeg, Jennifer; Morelli, Eugene A

2012-01-01

A new method is presented for estimating frequency responses and their uncertainties from wind-tunnel data in real time. The method uses orthogonal phase-optimized multi- sine excitation inputs and a recursive Fourier transform with a least-squares estimator. The method was first demonstrated with an F-16 nonlinear flight simulation and results showed that accurate short period frequency responses were obtained within 10 seconds. The method was then applied to wind-tunnel data from a previous aeroelastic test of the Joined- Wing SensorCraft. Frequency responses describing bending strains from simultaneous control surface excitations were estimated in a time-efficient manner.

Effects of Loading Frequency on Fatigue Behavior, Residual Stress, and Microstructure of Deep-Rolled Stainless Steel AISI 304 at Elevated Temperatures

NASA Astrophysics Data System (ADS)

Nikitin, I.; Juijerm, P.

2018-02-01

The effects of loading frequency on the fatigue behavior of non-deep-rolled (NDR) and deep-rolled (DR) austenitic stainless steel AISI 304 were systematically clarified at elevated temperatures, especially at temperatures exhibiting the dynamic strain aging (DSA) phenomena. Tension-compression fatigue tests were performed isothermally at temperatures of 573 K and 773 K (300 °C and 500 °C) with different loading frequencies of 5, 0.5, 0.05, and 0.005 Hz. For the DR condition, the residual stresses and work-hardening states will be presented. It was found that DSA would be detected at appropriate temperatures and deformation rates. The cyclic deformation curves and the fatigue lives of the investigated austenitic stainless steel AISI 304 are considerably affected by the DSA, especially on the DR condition having high dislocation densities at the surface and in near-surface regions. In the temperature range of the DSA, residual stresses and work-hardening states of the DR condition seem to be stabilized. The microstructural alterations were investigated by transmission electron microscopy (TEM). At an appropriate temperature with low loading frequency, the plastic deformation mechanism shifted from a wavy slip manner to a planar slip manner in the DSA regimes, whereas the dislocation movements were obstructed.

Hippocampal-prefrontal input supports spatial encoding in working memory.

PubMed

Spellman, Timothy; Rigotti, Mattia; Ahmari, Susanne E; Fusi, Stefano; Gogos, Joseph A; Gordon, Joshua A

2015-06-18

Spatial working memory, the caching of behaviourally relevant spatial cues on a timescale of seconds, is a fundamental constituent of cognition. Although the prefrontal cortex and hippocampus are known to contribute jointly to successful spatial working memory, the anatomical pathway and temporal window for the interaction of these structures critical to spatial working memory has not yet been established. Here we find that direct hippocampal-prefrontal afferents are critical for encoding, but not for maintenance or retrieval, of spatial cues in mice. These cues are represented by the activity of individual prefrontal units in a manner that is dependent on hippocampal input only during the cue-encoding phase of a spatial working memory task. Successful encoding of these cues appears to be mediated by gamma-frequency synchrony between the two structures. These findings indicate a critical role for the direct hippocampal-prefrontal afferent pathway in the continuous updating of task-related spatial information during spatial working memory.

The critical dimensions of the response-reinforcer contingency.

PubMed

Williams, B A.

2001-05-03

Two major dimensions of any contingency of reinforcement are the temporal relation between a response and its reinforcer, and the relative frequency of the reinforcer given the response versus when the response has not occurred. Previous data demonstrate that time, per se, is not sufficient to explain the effects of delay-of-reinforcement procedures; needed in addition is some account of the events occurring in the delay interval. Moreover, the effects of the same absolute time values vary greatly across situations, such that any notion of a standard delay-of-reinforcement gradient is simplistic. The effects of reinforcers occurring in the absence of a response depend critically upon the stimulus conditions paired with those reinforcers, in much the same manner as has been shown with Pavlovian contingency effects. However, it is unclear whether the underlying basis of such effects is response competition or changes in the calculus of causation.

Pairwise amino acid secondary structural propensities

NASA Astrophysics Data System (ADS)

Chemmama, Ilan E.; Chapagain, Prem P.; Gerstman, Bernard S.

2015-04-01

We investigate the propensities for amino acids to form a specific secondary structure when they are paired with other amino acids. Our investigations use molecular dynamics (MD) computer simulations, and we compare the results to those from the Protein Data Bank (PDB). Proper comparison requires weighting of the MD results in a manner consistent with the relative frequency of appearance in the PDB of each possible pair of amino acids. We find that the propensity for an amino acid to assume a secondary structure varies dramatically depending on the amino acid that is before or after it in the primary sequence. This cooperative effect means that when selecting amino acids to facilitate the formation of a secondary structure in peptide engineering experiments, the adjacent amino acids must be considered. We also examine the preference for a secondary structure in bacterial proteins and compare the results to those of human proteins.

Modulatory effects of garlic extract against the cyclophosphamide induced genotoxicity in human lymphocytes in vitro.

PubMed

Sowjanya, B Lakshmi; Devi, K Rudrama; Madhavi, D

2009-09-01

Cyclophosphamide (CP) is a commonly used chemotherapeutic and immunosuppressive agent which is used in the treatment of wide range of cancers and autoimmune diseases. Besides that it is a well known carcinogen. In this study by using chromosomal aberrations (CA) and sister chromatid exchanges (SCE) assays method, the modulatory effects exerted by the extract of garlic against the CP induced genotoxicity in the human lymphocyte cultures in vitro were tested. Three different doses of garlic extract were tested for their modulatory capacity on the mutagenecity exerted by 100 microg ml(-1) of CR The results indicate a significant decrease in the frequency of CA and SCE suggesting that the garlic extract modulates the CP induced genotoxicity in a dose dependent manner. These findings provide the future directions for the research on design and development of possible modulatory drugs containing garlic extract.

Spin-current probe for phase transition in an insulator

DOE PAGES

Qiu, Zhiyong; Li, Jia; Hou, Dazhi; ...

2016-08-30

Spin fluctuation and transition have always been one of the central topics of magnetism and condensed matter science. Experimentally, the spin fluctuation is found transcribed onto scattering intensity in the neutron-scattering process, which is represented by dynamical magnetic susceptibility and maximized at phase transitions. Importantly, a neutron carries spin without electric charge, and therefore it can bring spin into a sample without being disturbed by electric energy. However, large facilities such as a nuclear reactor are necessary. Here we present that spin pumping, frequently used in nanoscale spintronic devices, provides a desktop microprobe for spin transition; spin current is amore » flux of spin without an electric charge and its transport reflects spin excitation. Additionally, we demonstrate detection of antiferromagnetic transition in ultra-thin CoO films via frequency-dependent spin-current transmission measurements, which provides a versatile probe for phase transition in an electric manner in minute devices.« less

Searching for topological defect dark matter via nongravitational signatures.

PubMed

Stadnik, Y V; Flambaum, V V

2014-10-10

We propose schemes for the detection of topological defect dark matter using pulsars and other luminous extraterrestrial systems via nongravitational signatures. The dark matter field, which makes up a defect, may interact with standard model particles, including quarks and the photon, resulting in the alteration of their masses. When a topological defect passes through a pulsar, its mass, radius, and internal structure may be altered, resulting in a pulsar "quake." A topological defect may also function as a cosmic dielectric material with a distinctive frequency-dependent index of refraction, which would give rise to the time delay of a periodic extraterrestrial light or radio signal, and the dispersion of a light or radio source in a manner distinct to a gravitational lens. A topological defect passing through Earth may alter Earth's period of rotation and give rise to temporary nonzero electric dipole moments for an electron, proton, neutron, nuclei and atoms.

A forskolin derivative, colforsin daropate hydrochloride, inhibits rat mesangial cell mitogenesis via the cyclic AMP pathway.

PubMed

Ogata, Junichi; Minami, Kouichiro; Segawa, Kayoko; Yamamoto, Chieko; Kim, Sung-Teh; Shigematsu, Akio

2003-11-01

A forskolin derivative, colforsin daropate hydrochloride (CDH), has been introduced as an inotropic agent that acts directly on adenylate cyclase to increase intracellular cyclic AMP (cAMP) levels and ventricular contractility, resulting in positive inotropic activity. We investigated the effects of CDH on rat mesangial cell (MC) proliferation. CDH (10(-7)-10(-5) mol/l) inhibited [(3)H]thymidine incorporation into cultured rat MCs in a concentration-dependent manner. CDH (10(-7)-10(-5) mol/l) also decreased cell numbers in a similar manner, and stimulated cAMP accumulation in MCs in a concentration-dependent manner. A protein kinase A inhibitor, H-89, abolished the inhibitory effects of CDH on MC mitogenesis. These findings suggest that CDH would inhibit the proliferation of rat MCs via the cAMP pathway. Copyright 2003 S. Karger AG, Basel

Engineering frequency-dependent superfluidity in Bose-Fermi mixtures

NASA Astrophysics Data System (ADS)

Arzamasovs, Maksims; Liu, Bo

2018-04-01

Unconventional superconductivity and superfluidity are among the most exciting and fascinating quantum phenomena in condensed-matter physics. Usually such states are characterized by nontrivial spin or spatial symmetry of the pairing order parameter, such as "spin triplet" or "p wave." However, besides spin and spatial dependence the order parameter may have unconventional frequency dependence which is also permitted by Fermi-Dirac statistics. Odd-frequency fermionic pairing is an exciting paradigm when discussing exotic superfluidity or superconductivity and is yet to be realized in experiments. In this paper we propose a symmetry-based method of controlling frequency dependence of the pairing order parameter via manipulating the inversion symmetry of the system. First, a toy model is introduced to illustrate that frequency dependence of the order parameter can be achieved through our proposed approach. Second, by taking advantage of recent rapid developments in producing spin-orbit-coupled dispersions in ultracold gases, we propose a Bose-Fermi mixture to realize such frequency-dependent superfluid. The key idea is introducing the frequency-dependent attraction between fermions mediated by Bogoliubov phonons with asymmetric dispersion. Our proposal should pave an alternative way for exploring frequency-dependent superfluids with cold atoms.

Antioxidant activities of saponins extracted from Radix Trichosanthis: an in vivo and in vitro evaluation

PubMed Central

2014-01-01

Background Radix Trichosanthis (RT), the dry root tuber of Trichosanthis kirilowii Maxim (Cucurbitaceae), is a traditional Chinese medicine. Although a wide range of saponin pharmacological properties has been identified, to our knowledge, this may be the first report to investigate the crude saponins from RT. The purpose of this study was to delineate the antioxidant activity both in vitro and in vivo by using ethyl acetate (EtOAc), n-butanol, and the mixture of n-butanol and EtOAc fractions. Methods In vitro antioxidant activity was detected by using DPPH free radical, hydrogen peroxide scavenging, and reducing power assays. After pretreatment with different fractions saponins at 2 mg/kg/d and 3 mg/kg/d of crude drug, respectively, an established CCl4 induced acute cytotoxicity model was used to evaluate the in vivo antioxidant potential by detection of superoxide dismutase (SOD), malonaldehyde (MDA), lactate dehydrogenase (LDH), and total antioxidant capacity (T-AOC) levels. Results The in vitro assay showed that the antioxidant activity of all the three fractions was promising. The reducing power of the EtOAc and the mixture of n-butanol and EtOAc extracts increased in a dose dependent manner. However, both the n-butanol and the mixture of n-butanol and EtOAc fractions in low dose exhibited in a time dependent manner with prolonged reaction time. As for hydrogen peroxide scavenging capability, the n-butanol fraction mainly demonstrated a time dependent manner, whereas EtOAc fraction showed a dose dependent manner. However, in case of in vivo assay, an increase of SOD and T-AOC and decrease of MDA and LDH levels were only observed in n-butanol (2 mg/kg/d of crude drug) extracts pretreatment group. Conclusions RT saponins in n-butanol fraction might be a potential antioxidant candidate, as CCl4-induced oxidative stress has been found to be alleviated, which may be associated with the time dependent manner of n-butanol saponins in a low dose. Further studies will be needed to investigate the active individual components in n-butanol extract, in vivo antioxidant activities and antioxidant mechanisms. PMID:24597831

40 CFR 141.203 - Tier 2 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2014 CFR

2014-07-01

... students, nursing home patients, prison inmates, etc.). Other methods may include: Publication in a local... others (e.g., apartment building owners or large private employers); posting in public places served by...

40 CFR 141.203 - Tier 2 Public Notice-Form, manner, and frequency of notice.

Code of Federal Regulations, 2013 CFR

2013-07-01

... students, nursing home patients, prison inmates, etc.). Other methods may include: Publication in a local... others (e.g., apartment building owners or large private employers); posting in public places served by...

Computational method for exact frequency-dependent rays on the basis of the solution of the Helmholtz equation

NASA Astrophysics Data System (ADS)

Protasov, M.; Gadylshin, K.

2017-07-01

A numerical method is proposed for the calculation of exact frequency-dependent rays when the solution of the Helmholtz equation is known. The properties of frequency-dependent rays are analysed and compared with classical ray theory and with the method of finite-difference modelling for the first time. In this paper, we study the dependence of these rays on the frequency of signals and show the convergence of the exact rays to the classical rays with increasing frequency. A number of numerical experiments demonstrate the distinctive features of exact frequency-dependent rays, in particular, their ability to penetrate into shadow zones that are impenetrable for classical rays.

CD86 and beta2-adrenergic receptor signaling pathways, respectively, increase Oct-2 and OCA-B Expression and binding to the 3'-IgH enhancer in B cells.

PubMed

Podojil, Joseph R; Kin, Nicholas W; Sanders, Virginia M

2004-05-28

Stimulation of CD86 (formerly known as B7-2) and/or the beta2-adrenergic receptor on a CD40 ligand/interleukin-4-activated B cell increased the rate of mature IgG1 transcription. To identify the mechanism responsible for this effect, we determined whether CD86 and/or beta2-adrenergic receptor stimulation regulated transcription factor expression and binding to the 3'-IgH enhancer in vitro and in vivo. We showed that CD86 stimulation increased the nuclear localization of NF-kappaB1 (p50) and phosphorylated RelA (p65) and increased Oct-2 expression and binding to the 3'-IgH enhancer, in a protein kinase C-dependent manner. These effects were lost when CD86-deficient or NF-kappaB1-deficient B cells were used. CD86 stimulation also increased the level of IkappaB-alpha phosphorylation but in a protein kinase C-independent manner. Beta2-adrenergic receptor stimulation increased CREB phosphorylation, OCA-B expression, and OCA-B binding to the 3'-IgH enhancer in a protein kinase A-dependent manner, an effect lost when beta2-adrenergic receptor-deficient B cells were used. Also, the beta2-adrenergic receptor-induced increase in the level of mature IgG1 transcript was lost when OCA-B-deficient B cells were used. These data are the first to show that CD86 stimulation up-regulates the expression of the transcription factor Oct-2 in a protein kinase C- and NF-kappaB1-dependent manner, and that beta2-adrenergic receptor stimulation up-regulates the expression of the coactivator OCA-B in a protein kinase A-dependent manner to cooperate with Oct-2 binding to the 3'-IgH enhancer.

Evidence for a possible neurotransmitter/neuromodulator role of tyramine on the locust oviducts.

PubMed

Donini, Andrew; Lange, Angela B

2004-04-01

Visualization of the tyraminergic innervation of the oviducts was demonstrated by immunohistochemistry, and the presence of tyramine was confirmed using high-performance liquid chromatography coupled to electrochemical detection. Oviducts incubated in high-potassium saline released tyramine in a calcium-dependent manner. Stimulation of the oviducal nerves also resulted in tyramine release, suggesting that tyramine might function as a neurotransmitter/neuromodulator at the locust oviducts. Tyramine decreased the basal tension, and also attenuated proctolin-induced contractions in a dose-dependent manner over a range of doses between 10(-7) and 10(-4) M. Low concentrations of tyramine attenuated forskolin-stimulated cyclic AMP levels in a dose-dependent manner. This effect was not blocked by yohimbine. High concentrations of tyramine increased basal cyclic AMP levels of locust oviducts in a dose-dependent manner; however, the increases in cyclic AMP were only evident at the highest concentrations tested, 5 x 10(-5) and 10(-4) M tyramine. The tyramine-induced increase in cyclic AMP shared a similar pharmacological profile with the octopamine-induced increase in cyclic AMP. Tyramine increased the amplitude of excitatory junction potentials at low concentrations while hyperpolarizing the membrane potential by 2-5 mV. A further increase in the amplitude of the excitatory junction potentials and the occurrence of an active response was seen upon washing tyramine from the preparation. These results suggest that tyramine can activate at least three different endogenous receptors on the locust oviducts a putative tyramine receptor at low concentrations, a different tyramine receptor to inhibit muscle contraction, and an octopamine receptor at high concentrations.

H. F. Frequency management by frequency sharing as assisted by models updated in real-time

NASA Astrophysics Data System (ADS)

Uffelman, D. R.; Harnish, L. O.; Goodman, J. M.

1984-03-01

Frequency management systems for the high frequencies (HF) currently in use by the U.S. Department of Defense (DoD) rely heavily on manual selection of frequencies which have been allocated on a circuit by circuit basis. There is no capability to anticipate frequency changes (QSY's) in advance in a manner such that a frequency being released by one user can be utilized effectively and immediately by a second user. NRL has been examining a scheme by which a small computer of the HF channel can be made to perform very accurately to anticipate channel characteristics in a short term prediction mode. It is proposed that this model be utilized to provide automated frequency management which would allow one to anticipate frequency availability and thereby allow sharing of frequencies between several users (frequency pooling). Utilizing data obtained from an oblique sounder net on the East Coast of the United States, this report suggests a method by which this may be accomplished.

Effect of ammonium metavanadate on the murine immune response

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

Cohen, M.D.; Wei, C.I.; Tan, H.

1986-01-01

Female B/sub 6/C/sub 3/F/sub 1/ mice were exposed to ammonium metavanadate (NH/sub 4/VO/sub 3/) by intraperitoneal injection every 3 d at 2.5, 5.0, or 10 mg V/kg for 3, 6, or 9 w and were then assayed for alterations in immunoresponsiveness. Resistance to Escherichia coli endotoxin lethality increased in a dose-dependent manner up to 6 w of exposure, while resistance to viable gram-positive Listeria lethality was depressed in a dose-dependent manner. Comparison of LD20 values indicated a 250-fold decrease in resistance to Listeria at the lowest vanadium exposure and a 40% increase in resistance to endotoxin after the highest vanadiummore » exposure. Peritoneal macrophage phagocytic capacities were decreased in a dose-dependent manner, but viabilities remained unaffected. Rosetting capacity of splenic lymphocytes was increased following vanadium exposure. Liver and splenic enlargement was observed, and examination of splenic tissue indicated enhanced formation of megakaryocytes and red blood cell precursors. Subchronic exposure to vanadium may thus disrupt the normal function of the immune system.« less

Antibodies enhance CXCL10 production during RSV infection of infant and adult immune cells.

PubMed

Vissers, Marloes; Schreurs, Inge; Jans, Jop; Heldens, Jacco; de Groot, Ronald; de Jonge, Marien I; Ferwerda, Gerben

2015-12-01

Respiratory syncytial virus (RSV) bronchiolitis is a major burden in infants below three months of age, when the primary immune response is mainly dependent on innate immunity and maternal antibodies. We investigated the influence of antibodies on innate immunity during RSV infection. PBMCs from infants and adults were stimulated with live RSV and inactivated RSV in combination with antibody-containing and antibody-depleted serum. The immune response was determined by transcriptome analysis and chemokine levels were measured using ELISA and flow cytometry. Microarray data showed that CXCL10 gene transcription was RSV dependent, whereas CXCL11 and IFNα were upregulated in an antibody-dependent manner. Although the presence of antibodies reduces RSV infection rate, it enhances the innate immune response. In adult immune cells, antibodies enhance CXCL10, CXCL11, IFNα and IFNγ production in response to RSV infection. Contrary, in infant immune cells only CXCL10 was enhanced in an antibody-dependent manner. Monocytes are the main source of CXCL10 and they produce CXCL10 in both an antibody- and virus-dependent manner. This study shows that antibodies enhance CXCL10 production in infant immune cells. CXCL10 has been implicated in exuberating the inflammatory response during viral infections and antibodies could therefore play a role in the pathogenesis of RSV infections. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phase difference of arrival geolocation

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

Mason, John J.; Romero, Louis

2017-05-16

Geolocation is performed by receiving, at a plurality of non-earthbound platforms each moving in a known manner within a spatial coordinate system, a radio frequency (RF) signal transmitted from a transmitter at an unknown location on earth within the spatial coordinate system. For each of the platforms, a phase change of the received frequency carrier is measured over the same duration of time. The measured phase changes are combined to determine the transmitter location.

Detection of aneugenic and clastogenic potential of X-rays, directly and indirectly acting chemicals in human hepatoma (Hep G2) and peripheral blood lymphocytes, using the micronucleus assay and fluorescent in situ hybridization with a DNA centromeric probe.

PubMed

Darroudi, F; Meijers, C M; Hadjidekova, V; Natarajan, A T

1996-09-01

In human hepatoma (Hep G2) cells and peripheral blood lymphocytes (HPBL) the cytokinesis-blocked micronuclei (MN) and fluorescent in situ hybridization (FISH) assays were applied to study aneugenic and clastogenic potentials of X-rays, directly and indirectly acting chemicals. Induction of MN was studied in vitro following treatment with X-rays, directly acting chemicals, such as methylmeth-anesulphonate (MMS), colchicine (COL), vincristine sulphate (VCS) and vinblastine sulphate (VBS), and indirectly acting agents, such as cyclophosphamide (CP), hexamethylphosphoramide (HMPA), 2-acetylaminofluorene (2-AAF) and 4-acetylaminofluorene (4-AAF). Depending on the presence of the fluorescent signal in the MN following FISH with a human DNA centromeric probe, MN in the binucleated Hep G2 cells and lymphocytes were scored as centromere-positive or centromere-negative, representing an aneugenic and clastogenic event respectively. In the controls approximately 50% of spontaneously occurring MN were centromere-positive. Treatment of human hepatoma cells and HPBL (in vitro) with potent aneugens such as COL, VCS and VBS increased the number of MN in a dose-dependent manner; of these 75-93% were centromere-positive. X-irradiation induced MN in a dose-related manner in binucleated Hep G2 cells and HPBL, of which 33-40% were centromere-positive, which demonstrates the significant aneugenic potentials of X-rays. Strong clastogenic activity was observed with MMS and frequency of centromere-positive MN was low: approximately 20 and 30% for HPBL and Hep G2 cells respectively. In Hep G2 cells significant aneugenic activity was found with indirectly acting promutagens/procarcinogens such as HMPA and 2-AAF, in contrast to CP, which came out as a potent clastogen. The non-carcinogen 4-AAF was not able to induce an increase in the frequency of MN in Hep G2 cells. All indirectly acting chemicals tested came out negative when HPBL were used as targets for DNA damage. The results presented correlate positively with data from in vivo assays and indicate that the Hep G2 cell system is a suitable bioactivation system (in vitro) for evaluating the clastogenic and aneugenic potentials of chemicals which require exogenous metabolic activations in order to exert their mutagenic potential.

Inhibition of gamma-radiation induced DNA damage in plasmid pBR322 by TMG, a water-soluble derivative of vitamin E.

PubMed

Rajagopalan, Rema; Wani, Khalida; Huilgol, Nagaraj G; Kagiya, Tsutomu V; Nair, Cherupally K Krishnan

2002-06-01

Alpha-tocopherol monoglucoside (TMG), a water-soluble derivative of alpha-tocopherol, has been examined for its ability to protect DNA against radiation-induced strand breaks. Gamma radiation, up to a dose of 6 Gy (dose rate, 0.7 Gy/minute), induced a dose-dependent increase in single strand breaks (SSBs) in plasmid pBR322 DNA. TMG inhibited the formation of gamma-radiation induced DNA single strand breaks (SSBs) in a concentration-dependent manner; 500 microM of TMG protected the single strand breaks completely. It also protected thymine glycol formation induced by gamma-radiation in a dose-dependent manner, based on an estimation of thymine glycol by HPLC.

Pedunculopontine Nucleus Gamma Band Activity-Preconscious Awareness, Waking, and REM Sleep

PubMed Central

Urbano, Francisco J.; D’Onofrio, Stasia M.; Luster, Brennon R.; Beck, Paige B.; Hyde, James Robert; Bisagno, Veronica; Garcia-Rill, Edgar

2014-01-01

The pedunculopontine nucleus (PPN) is a major component of the reticular activating system (RAS) that regulates waking and REM sleep, states of high-frequency EEG activity. Recently, we described the presence of high threshold, voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve gamma band oscillations in the mesopontine PPN, intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD). Cortical gamma band activity participates in sensory perception, problem solving, and memory. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. That is, the RAS may play an early permissive role in volition. Our latest results suggest that (1) the manifestation of gamma band activity during waking may employ a separate intracellular pathway compared to that during REM sleep, (2) neuronal calcium sensor (NCS-1) protein, which is over expressed in schizophrenia and bipolar disorder, modulates gamma band oscillations in the PPN in a concentration-dependent manner, (3) leptin, which undergoes resistance in obesity resulting in sleep dysregulation, decreases sodium currents in PPN neurons, accounting for its normal attenuation of waking, and (4) following our discovery of electrical coupling in the RAS, we hypothesize that there are cell clusters within the PPN that may act in concert. These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS. PMID:25368599

Hydralazine and Organic Nitrates Restore Impaired Excitation-Contraction Coupling by Reducing Calcium Leak Associated with Nitroso-Redox Imbalance*

PubMed Central

Dulce, Raul A.; Yiginer, Omer; Gonzalez, Daniel R.; Goss, Garrett; Feng, Ning; Zheng, Meizi; Hare, Joshua M.

2013-01-01

Although the combined use of hydralazine and isosorbide dinitrate confers important clinical benefits in patients with heart failure, the underlying mechanism of action is still controversial. We used two models of nitroso-redox imbalance, neuronal NO synthase-deficient (NOS1−/−) mice and spontaneously hypertensive heart failure rats, to test the hypothesis that hydralazine (HYD) alone or in combination with nitroglycerin (NTG) or isosorbide dinitrate restores Ca2+ cycling and contractile performance and controls superoxide production in isolated cardiomyocytes. The response to increased pacing frequency was depressed in NOS1−/− compared with wild type myocytes. Both sarcomere length shortening and intracellular Ca2+ transient (Δ[Ca2+]i) responses in NOS1−/− cardiomyocytes were augmented by HYD in a dose-dependent manner. NTG alone did not affect myocyte shortening but reduced Δ[Ca2+]i across the range of pacing frequencies and increased myofilament Ca2+ sensitivity thereby enhancing contractile efficiency. Similar results were seen in failing myocytes from the heart failure rat model. HYD alone or in combination with NTG reduced sarcoplasmic reticulum (SR) leak, improved SR Ca2+ reuptake, and restored SR Ca2+ content. HYD and NTG at low concentrations (1 μm), scavenged superoxide in isolated cardiomyocytes, whereas in cardiac homogenates, NTG inhibited xanthine oxidoreductase activity and scavenged NADPH oxidase-dependent superoxide more efficiently than HYD. Together, these results revealed that by reducing SR Ca2+ leak, HYD improves Ca2+ cycling and contractility impaired by nitroso-redox imbalance, and NTG enhanced contractile efficiency, restoring cardiac excitation-contraction coupling. PMID:23319593

Navigating the auditory scene: an expert role for the hippocampus.

PubMed

Teki, Sundeep; Kumar, Sukhbinder; von Kriegstein, Katharina; Stewart, Lauren; Lyness, C Rebecca; Moore, Brian C J; Capleton, Brian; Griffiths, Timothy D

2012-08-29

Over a typical career piano tuners spend tens of thousands of hours exploring a specialized acoustic environment. Tuning requires accurate perception and adjustment of beats in two-note chords that serve as a navigational device to move between points in previously learned acoustic scenes. It is a two-stage process that depends on the following: first, selective listening to beats within frequency windows, and, second, the subsequent use of those beats to navigate through a complex soundscape. The neuroanatomical substrates underlying brain specialization for such fundamental organization of sound scenes are unknown. Here, we demonstrate that professional piano tuners are significantly better than controls matched for age and musical ability on a psychophysical task simulating active listening to beats within frequency windows that is based on amplitude modulation rate discrimination. Tuners show a categorical increase in gray matter volume in the right frontal operculum and right superior temporal lobe. Tuners also show a striking enhancement of gray matter volume in the anterior hippocampus, parahippocampal gyrus, and superior temporal gyrus, and an increase in white matter volume in the posterior hippocampus as a function of years of tuning experience. The relationship with gray matter volume is sensitive to years of tuning experience and starting age but not actual age or level of musicality. Our findings support a role for a core set of regions in the hippocampus and superior temporal cortex in skilled exploration of complex sound scenes in which precise sound "templates" are encoded and consolidated into memory over time in an experience-dependent manner.

Thrust Measurement of Dielectric Barrier Discharge (DBD) Plasma Actuators

NASA Astrophysics Data System (ADS)

Ashpis, David E.; Laun, Matthew C.

2013-11-01

DBD plasma actuators generate a wall-jet that can be used for active flow control. We used an analytical balance to measure the thrust generated by the actuator, it is a common metric of its performance without external flow. We found that the measured force is afflicted by several problems; it drifts in time, not always repeatable, is unstable, and depends on the manner the voltage is applied. We report results of investigations of these issues. Tests were conducted on an actuator constructed of 1/4 inch thick high-density polyethylene (HDPE) dielectric with 100 mm long offset electrodes, with applied voltages up to 48 kV p-p and frequencies from 32 Hz to 2.5 kHz, and pure Sine and Trapezoidal waveforms. The relative humidity was in the range of 51-55%, corresponding to moisture range of 10,500 to13,000 ppm mass. Force readings were up to 500 mg, (approximately 50 mN/m). We found that the measured force is the net of the positive thrust generated by the wall-jet and an ``anti-thrust'' acting in the opposite direction. We propose a correction procedure that yields the plasma-generated thrust. The correction is based on voltage-dependent anti-thrust measured in the low frequency range of 20-40 Hz. We found that adjacent objects in a test setup affect the measured thrust, and verified it by comparing experiments with and without a metal enclosure, grounded and ungrounded. Uncorrected thrust varied by up to approximately +/-100%, and the corrected thrust variations were up to approximately 30%. Supported by NASA's FAP/Aerospace Sciences Project.

Pedunculopontine Nucleus Gamma Band Activity-Preconscious Awareness, Waking, and REM Sleep.

PubMed

Urbano, Francisco J; D'Onofrio, Stasia M; Luster, Brennon R; Beck, Paige B; Hyde, James Robert; Bisagno, Veronica; Garcia-Rill, Edgar

2014-01-01

The pedunculopontine nucleus (PPN) is a major component of the reticular activating system (RAS) that regulates waking and REM sleep, states of high-frequency EEG activity. Recently, we described the presence of high threshold, voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve gamma band oscillations in the mesopontine PPN, intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD). Cortical gamma band activity participates in sensory perception, problem solving, and memory. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. That is, the RAS may play an early permissive role in volition. Our latest results suggest that (1) the manifestation of gamma band activity during waking may employ a separate intracellular pathway compared to that during REM sleep, (2) neuronal calcium sensor (NCS-1) protein, which is over expressed in schizophrenia and bipolar disorder, modulates gamma band oscillations in the PPN in a concentration-dependent manner, (3) leptin, which undergoes resistance in obesity resulting in sleep dysregulation, decreases sodium currents in PPN neurons, accounting for its normal attenuation of waking, and (4) following our discovery of electrical coupling in the RAS, we hypothesize that there are cell clusters within the PPN that may act in concert. These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS.

Unified physical mechanism of frequency-domain controlled-source electromagnetic exploration on land and in ocean

NASA Astrophysics Data System (ADS)

Liu, Changsheng; Lin, Jun; Zhou, Fengdao; Hu, Ruihua; Sun, Caitang

2013-12-01

The frequency-domain controlled-source electromagnetic method (FDCSEM) has played an important role in the terrestrial and oceanic exploration. However, the measuring manners and the detecting abilities in two kinds of environment are much different. This paper analyses the electromagnetic theories of the FDCSEM exploration on land and in ocean, simulates the electromagnetic responses in the two cases based on a united physical and mathematical model, and studies the physical mechanism leading to these differences. In this study, the relationship between the propagation paths and the detecting ability is illuminated and the way to improve the detecting ability of FDCSEM is brought forward. In terrestrial exploration, FDCSEM widely adopts the measuring manner of controlled-source audio-frequency magnetotelluric method (CSAMT), which records the electromagnetic fields in the far zone in the broadside direction of an electric dipole source. This manner utilizes the airwave (i.e. the Earth surface wave) and takes the stratum wave as interference. It is sensitive to the conductive target but insensitive to the resistive one. In oceanic exploration, FDCSEM usually adopts the measuring manner of marine controlled-source electromagnetic method (MCSEM), which records the electromagnetic fields, commonly the horizontal electric fields, in the in-line direction of the electric dipole source. This manner utilizes the stratum wave (i.e. the seafloor wave and the guided wave in resistive targets) and takes the airwave as interference. It is sensitive to the resistive target but relatively insensitive to the conductive one. The numerical simulation shows that both the airwave and the stratum wave contribute to the FDCSEM exploration. United utilization of them will enhance the anomalies of targets and congregate the advantages of CSAMT and MCSEM theories. At different azimuth and different offset, the contribution of the airwave and the stratum wave to electromagnetic anomaly is different. Observation at moderate offset in the in-line direction is the best choice for the exploration of resistive targets, no matter the environment is land or shallow sea. It is also the best choice for the exploration of conductive targets in terrestrial environment. As for the conductive targets in shallow sea, observation at moderate offset in the broadside direction is better. Synthetic and felicitous utilization of the airwave and the stratum wave will optimize the performance of FDCSEM.

Frequency and voltage dependent electrical responses of poly(triarylamine) thin film-based organic Schottky diode

NASA Astrophysics Data System (ADS)

Anuar Mohamad, Khairul; Tak Hoh, Hang; Alias, Afishah; Ghosh, Bablu Kumar; Fukuda, Hisashi

2017-11-01

A metal-organic-metal (MOM) type Schottky diode based on poly (triarylamine) (PTAA) thin films has been fabricated by using the spin coating method. Investigation of the frequency dependent conductance-voltage (G-V-f) and capacitance-voltage (C-V-f) characteristics of the ITO/PTAA/Al MOM type diode were carried out in the frequency range from 12 Hz to 100 kHz using an LCR meter at room temperature. The frequency and bias voltage dependent electrical response were determined by admittance-based measured method in terms of an equivalent circuit model of the parallel combination of resistance and capacitance (RC circuit). Investigation revealed that the conductance is frequency and a bias voltage dependent in which conductance continuous increase as the increasing frequency, respectively. Meanwhile, the capacitance is dependent on frequency up to a certain value of frequency (100 Hz) but decreases at high frequency (1 - 10 kHz). The interface state density in the Schottky diode was determined from G-V and C-V characteristics. The interface state density has values almost constant of 2.8 x 1012 eV-1cm-2 with slightly decrease by increasing frequencies. Consequently, both series resistance and interface trap density were found to decrease with increasing frequency. The frequency dependence of the electrical responses is attributed the distribution density of interface states that could follow the alternating current (AC) signal.

Exploration of dynamic dipole polarizability of impurity doped quantum dots in presence of noise

NASA Astrophysics Data System (ADS)

Ghosh, Anuja; Bera, Aindrila; Saha, Surajit; Arif, Sk. Md.; Ghosh, Manas

2018-02-01

Present study strives to perform a rigorous exploration of dynamic dipole polarizability (DDP) of GaAs quantum dot (QD) containing dopant with special reference to influence of Gaussian white noise. Several physical quantities have been varied over a range to observe the modulations of the DDP profiles. Aforesaid physical quantities include magnetic field, confinement potential, dopant location, dopant potential, noise strength, aluminium concentration (only for Alx Ga1 - x As alloy QD), position-dependent effective mass (PDEM), position-dependent dielectric screening function (PDDSF), anisotropy, hydrostatic pressure (HP) and temperature. The DDP profiles reveal noticeable characteristics governed by the particular physical quantity involved, presence/absence of noise, the manner (additive/multiplicative) noise is applied to the system and the incoming photon frequency. As a general observation we have found that additive noise causing greater deviation of the DDP profile from noise-free state than its multiplicative neighbor. The study highlights viable means of harnessing DDP of doped QD under the governance of noise by appropriate adjustment of several relevant factors. The study merits importance in the light of technological applications of QD-based devices where noise appears as an integral component.

Vortex reconnection rate, and loop birth rate, for a random wavefield

NASA Astrophysics Data System (ADS)

Hannay, J. H.

2017-04-01

A time dependent, complex scalar wavefield in three dimensions contains curved zero lines, wave ‘vortices’, that move around. From time to time pairs of these lines contact each other and ‘reconnect’ in a well studied manner, and at other times tiny loops of new line appear from nowhere (births) and grow, or the reverse, existing loops shrink and disappear (deaths). These three types are known to be the only generic events. Here the average rate of their occurrences per unit volume is calculated exactly for a Gaussian random wavefield that has isotropic, stationary statistics, arising from a superposition of an infinity of plane waves in different directions. A simplifying ‘axis fixing’ technique is introduced to achieve this. The resulting formulas are proportional to the standard deviation of angular frequencies, and depend in a simple way on the second and fourth moments of the power spectrum of the plane waves. Reconnections turn out to be more common than births and deaths combined. As an expository preliminary, the case of two dimensions, where the vortices are points, is studied and the average rate of pair creation (and likewise destruction) per unit area is calculated.

Viscosity-dependent variations in the cell shape and swimming manner of Leptospira.

PubMed

Takabe, Kyosuke; Tahara, Hajime; Islam, Md Shafiqul; Affroze, Samia; Kudo, Seishi; Nakamura, Shuichi

2017-02-01

Spirochaetes are spiral or flat-wave-shaped Gram-negative bacteria that have periplasmic flagella between the peptidoglycan layer and outer membrane. Rotation of the periplasmic flagella transforms the cell body shape periodically, allowing the cell to swim in aqueous environments. Because the virulence of motility-deficient mutants of pathogenic species is drastically attenuated, motility is thought to be an essential virulence factor in spirochaetes. However, it remains unknown how motility practically contributes to the infection process. We show here that the cell body configuration and motility of the zoonotic spirochaete Leptospira changes depending on the viscosity of the medium. Leptospira swim and reverse the swimming direction by transforming the cell body. Motility analysis showed that the frequency of cell shape transformation was increased by increasing the viscosity of the medium. The increased cell body transformation induced highly frequent reversal of the swimming direction. A simple kinetic model based on the experimental results shows that the viscosity-induced increase in reversal limits cell migration, resulting in the accumulation of cells in high-viscosity regions. This behaviour could facilitate the colonization of the spirochaete on host tissues covered with mucosa.

Efficient FEM simulation of static and free vibration behavior of single walled boron nitride nanotubes

NASA Astrophysics Data System (ADS)

Giannopoulos, Georgios I.; Kontoni, Denise-Penelope N.; Georgantzinos, Stylianos K.

2016-08-01

This paper describes the static and free vibration behavior of single walled boron nitride nanotubes using a structural mechanics based finite element method. First, depending on the type of nanotube under investigation, its three dimensional nanostructure is developed according to the well-known corresponding positions of boron and nitride atoms as well as boron nitride bonds. Then, appropriate point masses are assigned to the atomic positions of the developed space frame. Next, these point masses are suitably interconnected with two-noded, linear, spring-like, finite elements. In order to simulate effectively the interactions observed between boron and nitride atoms within the nanotube, appropriate potential energy functions are introduced for these finite elements. In this manner, various atomistic models for both armchair and zigzag nanotubes with different aspect ratios are numerically analyzed and their effective elastic modulus as well as their natural frequencies and corresponding mode shapes are obtained. Regarding the free vibration analysis, the computed results reveal bending, breathing and axial modes of vibration depending on the nanotube size and chirality as well as the applied boundary support conditions. The longitudinal stiffness of the boron nitride nanotubes is found also sensitive to their geometric characteristics.

Effect of Salicylate on the Elasticity, Bending Stiffness, and Strength of SOPC Membranes

PubMed Central

Zhou, Yong; Raphael, Robert M.

2005-01-01

Salicylate is a small amphiphilic molecule which has diverse effects on membranes and membrane-mediated processes. We have utilized micropipette aspiration of giant unilamellar vesicles to determine salicylate's effects on lecithin membrane elasticity, bending rigidity, and strength. Salicylate effectively reduces the apparent area compressibility modulus and bending modulus of membranes in a dose-dependent manner at concentrations above 1 mM, but does not greatly alter the actual elastic compressibility modulus at the maximal tested concentration of 10 mM. The effect of salicylate on membrane strength was investigated using dynamic tension spectroscopy, which revealed that salicylate increases the frequency of spontaneous defect formation and lowers the energy barrier for unstable hole formation. The mechanical and dynamic tension experiments are consistent and support a picture in which salicylate disrupts membrane stability by decreasing membrane stiffness and membrane thickness. The tension-dependent partitioning of salicylate was utilized to calculate the molecular volume of salicylate in the membrane. The free energy of transfer for salicylate insertion into the membrane and the corresponding partition coefficient were also estimated, and indicated favorable salicylate-membrane interactions. The mechanical changes induced by salicylate may affect several biological processes, especially those associated with membrane curvature and permeability. PMID:15951377

Metabolic modulation of neuronal gamma-band oscillations.

PubMed

Vodovozov, Wadim; Schneider, Justus; Elzoheiry, Shehabeldin; Hollnagel, Jan-Oliver; Lewen, Andrea; Kann, Oliver

2018-05-28

Gamma oscillations (30-100 Hz) represent a physiological fast brain rhythm that occurs in many cortex areas in awake mammals, including humans. They associate with sensory perception, voluntary movement, and memory formation and require precise synaptic transmission between excitatory glutamatergic neurons and inhibitory GABAergic interneurons such as parvalbumin-positive basket cells. Notably, gamma oscillations are exquisitely sensitive to shortage in glucose and oxygen supply (metabolic stress), with devastating consequences for higher cognitive functions. Herein, we explored the robustness of gamma oscillations against changes in the availability of alternative energy substrates and amino acids, which is partially regulated by glial cells such as astrocytes. We used organotypic slice cultures of the rat hippocampus expressing acetylcholine-induced persistent gamma oscillations under normoxic recording conditions (20% oxygen fraction). Our main findings are (1) partial substitution of glucose with pyruvate and the ketone body β-hydroxybutyrate increases the frequency of gamma oscillations, even at different stages of neuronal tissue development. (2) Supplementation with the astrocytic neurotransmitter precursor glutamine has no effect on the properties of gamma oscillations. (3) Supplementation with glycine increases power, frequency, and inner coherence of gamma oscillations in a dose-dependent manner. (4) During these treatments switches to other frequency bands or pathological network states such as neural burst firing or synchronized epileptic activity are absent. Our study indicates that cholinergic gamma oscillations show general robustness against these changes in nutrient and amino acid composition of the cerebrospinal fluid; however, modulation of their properties may impact on cortical information processing under physiological and pathophysiological conditions.

Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes

PubMed Central

Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

2016-01-01

Following one of the world’s largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes. PMID:26907305

Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes.

PubMed

Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

2016-02-19

Following one of the world's largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

Proportional spike-timing precision and firing reliability underlie efficient temporal processing of periodicity and envelope shape cues

PubMed Central

Zheng, Y.

2013-01-01

Temporal sound cues are essential for sound recognition, pitch, rhythm, and timbre perception, yet how auditory neurons encode such cues is subject of ongoing debate. Rate coding theories propose that temporal sound features are represented by rate tuned modulation filters. However, overwhelming evidence also suggests that precise spike timing is an essential attribute of the neural code. Here we demonstrate that single neurons in the auditory midbrain employ a proportional code in which spike-timing precision and firing reliability covary with the sound envelope cues to provide an efficient representation of the stimulus. Spike-timing precision varied systematically with the timescale and shape of the sound envelope and yet was largely independent of the sound modulation frequency, a prominent cue for pitch. In contrast, spike-count reliability was strongly affected by the modulation frequency. Spike-timing precision extends from sub-millisecond for brief transient sounds up to tens of milliseconds for sounds with slow-varying envelope. Information theoretic analysis further confirms that spike-timing precision depends strongly on the sound envelope shape, while firing reliability was strongly affected by the sound modulation frequency. Both the information efficiency and total information were limited by the firing reliability and spike-timing precision in a manner that reflected the sound structure. This result supports a temporal coding strategy in the auditory midbrain where proportional changes in spike-timing precision and firing reliability can efficiently signal shape and periodicity temporal cues. PMID:23636724

Actin cytoskeleton as a putative target of the neem limonoid Azadirachtin A.

PubMed

Anuradha, Aritakula; Annadurai, Ramaswamy S; Shashidhara, L S

2007-06-01

Limonoids isolated from the Indian neem tree (Azadirachta indica) have been gaining global acceptance in agricultural applications and in contemporary medicine for their myriad but discrete properties. However, their mode of action is still not very well understood. We have studied the mode of action of Azadirachtin A, the major limonoid of neem seed extracts, using Drosophila melanogaster as the model system. Azadirachtin A induces moderate-to-severe phenotypes in different tissues in a dose-dependent manner. At the cellular level, Azadirachtin A induces depolymerization of Actin leading to arrest of cells and subsequently apoptosis in a caspase-independent manner. Azadirachtin A-induced phenotypes were rescued by the over-expression of Cyclin E in a tissue-dependent manner. Cyclin E, which caused global rescue of Azadirachtin A-induced phenotypes, also effected rearrangement of the actin filaments. These results suggest that probably actin is a target of Azadirachtin A activity.

Chronic cat allergen exposure induces a TH2 cell-dependent IgG4 response related to low sensitization.

PubMed

Renand, Amedee; Archila, Luis D; McGinty, John; Wambre, Erik; Robinson, David; Hales, Belinda J; Thomas, Wayne R; Kwok, William W

2015-12-01

In human subjects, allergen tolerance has been observed after high-dose allergen exposure or after completed allergen immunotherapy, which is related to the accumulation of anti-inflammatory IgG4. However, the specific T-cell response that leads to IgG4 induction during chronic allergen exposure remains poorly understood. We sought to evaluate the relationship between cat allergen-specific T-cell frequency, cat allergen-specific IgE and IgG4 titers, and clinical status in adults with cat allergy with and without cat ownership and the cellular mechanism by which IgG4 is produced. Fel d 1-, Fel d 4-, Fel d 7-, and Fel d 8-specific T-cell responses were characterized by CD154 expression after antigen stimulation. In allergic subjects without cat ownership, the frequency of cat allergen (Fel d 1 and Fel d 4)-specific TH2 (sTH2) cells correlates with higher IgE levels and is linked to asthma. Paradoxically, we observed that subjects with cat allergy and chronic cat exposure maintain a high frequency of sTH2 cells, which correlates with higher IgG4 levels and low sensitization. B cells from allergic, but not nonallergic subjects, are able to produce IgG4 after cognate interactions with sTH2 clones and Fel d 1 peptide or the Fel d 1 recombinant protein. These experiments suggest that (1) allergen-experienced B cells with the capacity to produce IgG4 are present in allergic subjects and (2) cat allergen exposure induces an IgG4 response in a TH2 cell-dependent manner. Thus IgG4 accumulation could be mediated by chronic activation of the TH2 response, which in turn drives desensitization. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Can Low Frequency Measurements Be Good Enough? - A Statistical Assessment of Citizen Hydrology Streamflow Observations

NASA Astrophysics Data System (ADS)

Davids, J. C.; Rutten, M.; Van De Giesen, N.

2016-12-01

Hydrologic data has traditionally been collected with permanent installations of sophisticated and relatively accurate but expensive monitoring equipment at limited numbers of sites. Consequently, the spatial coverage of the data is limited and costs are high. Achieving adequate maintenance of sophisticated monitoring equipment often exceeds local technical and resource capacity, and permanently deployed monitoring equipment is susceptible to vandalism, theft, and other hazards. Rather than using expensive, vulnerable installations at a few points, SmartPhones4Water (S4W), a form of Citizen Hydrology, leverages widely available mobile technology to gather hydrologic data at many sites in a manner that is repeatable and scalable. However, there is currently a limited understanding of the impact of decreased observational frequency on the accuracy of key streamflow statistics like minimum flow, maximum flow, and runoff. As a first step towards evaluating the tradeoffs between traditional continuous monitoring approaches and emerging Citizen Hydrology methods, we randomly selected 50 active U.S. Geological Survey (USGS) streamflow gauges in California. We used historical 15 minute flow data from 01/01/2008 through 12/31/2014 to develop minimum flow, maximum flow, and runoff values (7 year total) for each gauge. In order to mimic lower frequency Citizen Hydrology observations, we developed a bootstrap randomized subsampling with replacement procedure. We calculated the same statistics, along with their respective distributions, from 50 subsample iterations with four different subsampling intervals (i.e. daily, three day, weekly, and monthly). Based on our results we conclude that, depending on the types of questions being asked, and the watershed characteristics, Citizen Hydrology streamflow measurements can provide useful and accurate information. Depending on watershed characteristics, minimum flows were reasonably estimated with subsample intervals ranging from daily to monthly. However, maximum flows in most cases were poorly characterized, even at daily subsample intervals. In general, runoff volumes were accurately estimated from daily, three day, weekly, and even in some cases, monthly observations.

Expression of Inapproptriate Cadherins in Human Breast Carcinomas

DTIC Science & Technology

2000-08-01

fibroblast growth factor receptor signaling. * We showed that cadherin 11 acts in a manner... fibroblast growth factor receptor signaling; and that cadherin 11 promotes epithelial cell motility in a manner similar to N-cadherin. 28 N-Cadherin...levels of E-cadherin; and that N- cadherin-dependent motility may be mediated by fibroblast growth factor receptor signaling. 14. SUBJECT TERMS

Multibeam single frequency synthetic aperture radar processor for imaging separate range swaths

NASA Technical Reports Server (NTRS)

Jain, A. (Inventor)

1982-01-01

A single-frequency multibeam synthetic aperture radar for large swath imaging is disclosed. Each beam illuminates a separate ""footprint'' (i.e., range and azimuth interval). The distinct azimuth intervals for the separate beams produce a distinct Doppler frequency spectrum for each beam. After range correlation of raw data, an optical processor develops image data for the different beams by spatially separating the beams to place each beam of different Doppler frequency spectrum in a different location in the frequency plane as well as the imaging plane of the optical processor. Selection of a beam for imaging may be made in the frequency plane by adjusting the position of an aperture, or in the image plane by adjusting the position of a slit. The raw data may also be processed in digital form in an analogous manner.

Life-span extension by a metacaspase in the yeast Saccharomyces cerevisiae.

PubMed

Hill, Sandra Malmgren; Hao, Xinxin; Liu, Beidong; Nyström, Thomas

2014-06-20

Single-cell species harbor ancestral structural homologs of caspase proteases, although the evolutionary benefit of such apoptosis-related proteins in unicellular organisms is unclear. Here, we found that the yeast metacaspase Mca1 is recruited to the insoluble protein deposit (IPOD) and juxtanuclear quality-control compartment (JUNQ) during aging and proteostatic stress. Elevating MCA1 expression counteracted accumulation of unfolded proteins and aggregates and extended life span in a heat shock protein Hsp104 disaggregase- and proteasome-dependent manner. Consistent with a role in protein quality control, genetic interaction analysis revealed that MCA1 buffers against deficiencies in the Hsp40 chaperone YDJ1 in a caspase cysteine-dependent manner. Life-span extension and aggregate management by Mca1 was only partly dependent on its conserved catalytic cysteine, which suggests that Mca1 harbors both caspase-dependent and independent functions related to life-span control. Copyright © 2014, American Association for the Advancement of Science.

Assessing cortical synchronization during transcranial direct current stimulation: A graph-theoretical analysis.

PubMed

Mancini, Matteo; Brignani, Debora; Conforto, Silvia; Mauri, Piercarlo; Miniussi, Carlo; Pellicciari, Maria Concetta

2016-10-15

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that can alter cortical excitability and modulate behaviour in a polarity-dependent way. Despite the widespread use of this method in the neuroscience field, its effects on ongoing local or global (network level) neuronal activity are still not foreseeable. A way to shed light on the neuronal mechanisms underlying the cortical connectivity changes induced by tDCS is provided by the combination of tDCS with electroencephalography (EEG). In this study, twelve healthy subjects underwent online tDCS-EEG recording (i.e., simultaneous), during resting-state, using 19 EEG channels. The protocol involved anodal, cathodal and sham stimulation conditions, with the active and the reference electrodes in the left frontocentral area (FC3) and on the forehead over the right eyebrow, respectively. The data were processed using a network model, based on graph theory and the synchronization likelihood. The resulting graphs were analysed for four frequency bands (theta, alpha, beta and gamma) to evaluate the presence of tDCS-induced differences in synchronization patterns and graph theory measures. The resting state network connectivity resulted altered during tDCS, in a polarity-specific manner for theta and alpha bands. Anodal tDCS weakened synchronization with respect to the baseline over the fronto-central areas in the left hemisphere, for theta band (p<0.05). In contrast, during cathodal tDCS a significant increase in inter-hemispheric synchronization connectivity was observed over the centro-parietal, centro-occipital and parieto-occipital areas for the alpha band (p<0.05). Local graph measures showed a tDCS-induced polarity-specific differences that regarded modifications of network activities rather than specific region properties. Our results show that applying tDCS during the resting state modulates local synchronization as well as network properties in slow frequency bands, in a polarity-specific manner. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of remote sensing in tropical forests

NASA Technical Reports Server (NTRS)

Joyce, Armond T.; Luvall, J. C.; Sever, T.

1990-01-01

Cloud cover in tropical humid forests can pose serious operational constraints on Landsat TM and SPOT HRV instrumentation, given their respective orbital frequencies of 16 and 26 days. SAR data intrinsically precludes such problems; the increase of data acquisition frequency to daily rates, as with the NOAA AVHRR instrument, also bears consideration. It is deemed essential that SAR data-related research be expedited, in order to ascertain inherent SAR information for tropical forests in a timely and cost-effective manner.

Real-time open-loop frequency response analysis of flight test data

NASA Technical Reports Server (NTRS)

Bosworth, J. T.; West, J. C.

1986-01-01

A technique has been developed to compare the open-loop frequency response of a flight test aircraft real time with linear analysis predictions. The result is direct feedback to the flight control systems engineer on the validity of predictions and adds confidence for proceeding with envelope expansion. Further, gain and phase margins can be tracked for trends in a manner similar to the techniques used by structural dynamics engineers in tracking structural modal damping.

Theoretical analysis of optical poling and frequency doubling effect based on classical model

NASA Astrophysics Data System (ADS)

Feng, Xi; Li, Fuquan; Lin, Aoxiang; Wang, Fang; Chai, Xiangxu; Wang, Zhengping; Zhu, Qihua; Sun, Xun; Zhang, Sen; Sun, Xibo

2018-03-01

Optical poling and frequency doubling effect is one of the effective manners to induce second order nonlinearity and realize frequency doubling in glass materials. The classical model believes that an internal electric field is built in glass when it's exposed by fundamental and frequency-doubled light at the same time, and second order nonlinearity appears as a result of the electric field and the orientation of poles. The process of frequency doubling in glass is quasi phase matched. In this letter, the physical process of poling and doubling process in optical poling and frequency doubling effect is deeply discussed in detail. The magnitude and direction of internal electric field, second order nonlinear coefficient and its components, strength and direction of frequency doubled output signal, quasi phase matched coupled wave equations are given in analytic expression. Model of optical poling and frequency doubling effect which can be quantitatively analyzed are constructed in theory, which set a foundation for intensive study of optical poling and frequency doubling effect.

A spectrum of exercise training reduces soluble Aβ in a dose-dependent manner in a mouse model of Alzheimer's disease.

PubMed

Moore, Kaitlin M; Girens, Renee E; Larson, Sara K; Jones, Maria R; Restivo, Jessica L; Holtzman, David M; Cirrito, John R; Yuede, Carla M; Zimmerman, Scott D; Timson, Benjamin F

2016-01-01

Physical activity has long been hypothesized to influence the risk and pathology of Alzheimer's disease. However, the amount of physical activity necessary for these benefits is unclear. We examined the effects of three months of low and high intensity exercise training on soluble Aβ40 and Aβ42 levels in extracellular enriched fractions from the cortex and hippocampus of young Tg2576 mice. Low (LOW) and high (HI) intensity exercise training animals ran at speeds of 15m/min on a level treadmill and 32 m/min at a 10% grade, respectively for 60 min per day, five days per week, from three to six months of age. Sedentary mice (SED) were placed on a level, non-moving, treadmill for the same duration. Soleus muscle citrate synthase activity increased by 39% in the LOW group relative to SED, and by 71% in the HI group relative to LOW, indicating an exercise training effect in these mice. Soluble Aβ40 concentrations decreased significantly in an exercise training dose-dependent manner in the cortex. In the hippocampus, concentrations were decreased significantly in the HI group relative to LOW and SED. Soluble Aβ42 levels also decreased significantly in an exercise training dose-dependent manner in both the cortex and hippocampus. Five proteins involved in Aβ clearance (neprilysin, IDE, MMP9, LRP1 and HSP70) were elevated by exercise training with its intensity playing a role in each case. Our data demonstrate that exercise training reduces extracellular soluble Aβ in the brains of Tg2576 mice in a dose-dependent manner through an up-regulation of Aβ clearance. Copyright © 2015 Elsevier Inc. All rights reserved.

Repeated restraint stress enhances cue-elicited conditioned freezing and impairs acquisition of extinction in an age-dependent manner

PubMed Central

Zhang, Wei; Rosenkranz, J. Amiel

2013-01-01

Affective disorders are believed to involve dysfunction within the amygdala, a key structure for processing emotional information. Chronic stress may contribute to affective disorders such as depression and anxiety via its effects on the amygdala. Previous research has shown that chronic stress increases amygdala neuronal activity in an age-dependent manner. However, whether these distinct changes in amgydala neuronal activity are accompanied by age-dependent changes in amygdala-dependent affective behavior is unclear. In this study, we investigated how chronic stress impacts amgydala-dependent auditory fear conditioning in adolescent and adult rats in a repeated restraint model. We found that repeated restraint enhanced conditioned freezing in both adolescent and adult rats. But repeated restraint led to impaired acquisition of fear extinction only in adolescent rats. Along with previous findings, these results suggest that chronic stress may precipitate affective disorders via differential mechanisms, with different outcomes at different ages. PMID:23538069

Frequency-dependent learning achieved using semiconducting polymer/electrolyte composite cells

NASA Astrophysics Data System (ADS)

Dong, W. S.; Zeng, F.; Lu, S. H.; Liu, A.; Li, X. J.; Pan, F.

2015-10-01

Frequency-dependent learning has been achieved using semiconducting polymer/electrolyte composite cells. The cells composed of polymer/electrolyte double layers realized the conventional spike-rate-dependent plasticity (SRDP) learning model. These cells responded to depression upon low-frequency stimulation and to potentiation upon high-frequency stimulation and presented long-term memory. The transition threshold θm from depression to potentiation varied depending on the previous stimulations. A nanostructure resembling a bio-synapse in its transport passages was demonstrated and a random channel model was proposed to describe the ionic kinetics at the polymer/electrolyte interface during and after stimulations with various frequencies, accounting for the observed SRDP.Frequency-dependent learning has been achieved using semiconducting polymer/electrolyte composite cells. The cells composed of polymer/electrolyte double layers realized the conventional spike-rate-dependent plasticity (SRDP) learning model. These cells responded to depression upon low-frequency stimulation and to potentiation upon high-frequency stimulation and presented long-term memory. The transition threshold θm from depression to potentiation varied depending on the previous stimulations. A nanostructure resembling a bio-synapse in its transport passages was demonstrated and a random channel model was proposed to describe the ionic kinetics at the polymer/electrolyte interface during and after stimulations with various frequencies, accounting for the observed SRDP. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr02891d

Characterization of silodosin and naftopidil in the treatment of bladder dysfunction in the spontaneously hypertensive rat.

PubMed

Saito, Motoaki; Shimizu, Shogo; Ohmasa, Fumiya; Oikawa, Ryo; Tsounapi, Panagiota; Dimitriadis, Fotios; Kinoshita, Yukako; Satoh, Keisuke

2013-04-01

As increasing evidence suggest that α(1)-blockers prevent benign prostatic hyperplasia related overactive bladder and nocturia in the human, we investigated the effects of silodosin and naftopidil on hypertension-related bladder dysfunction in the spontaneously hypertensive rat (SHR) model. Twelve-week-old male SHRs received no treatment or treatment with silodosin (100 µg/kg, p.o.) or naftopidil (10 or 30 mg/kg, p.o.) once daily for 6 weeks. Wistar rats were used as normotensive controls. After 6-week treatment, voiding functions were estimated by metabolic cages (dark- and light-cycle separately) and cystometric studies. Furthermore, the bladder blood flow (BBF) was measured employing the hydrogen clearance method. SHRs showed significant increases in micturition frequency, and decreases in BBF and single voided volume in both metabolic cages and cystometrograms compared to the Wistar group. Treatment with silodosin normalized the decreased BBF, and treatment with naftopidil increased the BBF in a dose-dependent manner in the SHR group. Although treatment with silodosin and the high dose of naftopidil significantly inhibited micturition frequency in one day, only treatment with the high dose of naftopidil significantly inhibited micturition frequency and urine production in the light-cycle compared to the non-treated SHRs. Although treatment with silodosin and the high dose of naftopidil significantly increased single voided volume, only treatment with silodosin significantly inhibited non-voiding contractions in the cystometrgrams. Our data suggest that both silodosin and naftopidil improve hypertension-related bladder dysfunction in the SHR, and naftopidil but not silodosin improves urinary frequency in the light-cycle due to inhibition of urine production. Copyright © 2012 Wiley Periodicals, Inc.

Effects of extremely low frequency electromagnetic fields on distortion product otoacoustic emissions in rabbits.

PubMed

Budak, Bilgehan; Budak, Gürer G; Oztürk, Göknur Güler; Muluk, Nuray Bayar; Apan, Alpaslan; Seyhan, Nesrin

2009-06-01

Humans are continuously exposed to extremely low frequency (ELF), electromagnetic fields (EMF), transmitted from the common sources like power stations, electric transmission lines, communication and radio-television signal transmission units. The present study aimed to assess the effects of 50 Hz ELF-EMF of 5.068 and 10.182 kV/m electric fields, which refer to the lower and upper intensity limits beyond which hazardous effects can be observed, on the auditory functions of rabbits via Distortion Product Otoacoustic Emission (DPOAE) recordings. The study was performed on 20 healthy adult female New Zealand White rabbits randomly divided into two groups and applied 50 Hz ELF-EMF with either 5.068 kV/m (Group 1) or 10.182 kV/m (Group 2) of electric field for 3h/day during 14 days. DPOAE responses recorded on the 0th day before exposure (B-EMF) and on the 6th (A-EMF-6th) and 14th (A-EMF-14th) days after exposure (AE). Mean stimulus intensity and emission amplitudes at 1.0-8.0 kHz were analyzed. In Group 2 rabbits, on 6th and 14th days, the DPOAE amplitudes were observed as increased at 1.5-4.0 kHz (at 2.0 and 4.0 kHz significantly) than B-EMF values. At 6.0 kHz, A-EMF-14th amplitudes were significantly lower than A-EMF values. These results suggest that ELF EMFs might affect hearing functions by frequency dependent manner. Higher ELF EMFs exposure caused increase of cochlear activity. Ototoxic effect of 10.182 kV/m ELF EMFs may begin at the basal turn of the cochlea by reducing DPOAEs at high frequencies.

Gonadotropin-Releasing Hormone Pulse Sensitivity of Follicle-Stimulating Hormone-β Gene Is Mediated by Differential Expression of Positive Regulatory Activator Protein 1 Factors and Corepressors SKIL and TGIF1

PubMed Central

Mistry, Devendra S.; Tsutsumi, Rie; Fernandez, Marina; Sharma, Shweta; Cardenas, Steven A.; Lawson, Mark A.

2011-01-01

Gonadotropin synthesis and release is dependent on pulsatile stimulation by the hypothalamic neuropeptide GnRH. Generally, slow GnRH pulses promote FSH production, whereas rapid pulses favor LH, but the molecular mechanism underlying this pulse sensitivity is poorly understood. In this study, we developed and tested a model for FSHβ regulation in mouse LβT2 gonadotropes. By mining a previous microarray data set, we found that mRNA for positive regulators of Fshb expression, such as Fos and Jun, were up-regulated at slower pulse frequencies than a number of potential negative regulators, such as the corepressors Skil, Crem, and Tgif1. These latter corepressors reduced Fshb promoter activity whether driven by transfection of individual transcription factors or by treatment with GnRH and activin. Overexpression of binding or phosphorylation-defective ski-oncogene-like protein (SKIL) and TG interacting factor (TGIF1) mutants, however, failed to repress Fshb promoter activity. Knockdown of the endogenous repressors SKIL and TGIF1, but not cAMP response element-modulator, increased Fshb promoter activity driven by constant GnRH or activin. Chromatin immunoprecipitation analysis showed that FOS, SKIL, and TGIF1 occupy the FSHβ promoter in a cyclical manner after GnRH stimulation. Overexpression of corepressors SKIL or TGIF1 repressed induction of the Fshb promoter at the slow GnRH pulse frequency but had little effect at the fast pulse frequency. In contrast, knockdown of endogenous SKIL or TGIF1 selectively increased Fshb mRNA at the fast GnRH pulse frequency. Therefore, we propose a potential mechanism by which production of gonadotropin Fshb is modulated by positive transcription factors and negative corepressors with different pulse sensitivities. PMID:21659477

Variation in Tomato spotted wilt virus titer in Frankliniella occidentalis and its association with frequency of transmission.

PubMed

Rotenberg, Dorith; Krishna Kumar, Nallur K; Ullman, Diane E; Montero-Astúa, Mauricio; Willis, David K; German, Thomas L; Whitfield, Anna E

2009-04-01

Tomato spotted wilt virus (TSWV) is transmitted in a persistent propagative manner by Frankliniella occidentalis, the western flower thrips. While it is well established that vector competence depends on TSWV acquisition by young larvae and virus replication within the insect, the biological factors associated with frequency of transmission have not been well characterized. We hypothesized that the number of transmission events by a single adult thrips is determined, in part, by the amount of virus harbored (titer) by the insect. Transmission time-course experiments were conducted using a leaf disk assay to determine the efficiency and frequency of TSWV transmission following 2-day inoculation access periods (IAPs). Virus titer in individual adult thrips was determined by real-time quantitative reverse transcriptase-PCR (qRT-PCR) at the end of the experiments. On average, 59% of adults transmitted the virus during the first IAP (2 to 3 days post adult-eclosion). Male thrips were more efficient at transmitting TSWV multiple times compared with female thrips of the same cohort. However, females harbored two to three times more copies of TSWV-N RNA per insect, indicating that factors other than absolute virus titer in the insect contribute to a successful transmission event. Examination of virus titer in individual insects at the end of the third IAP (7 days post adult-eclosion) revealed significant and consistent positive associations between frequency of transmission and virus titer. Our data support the hypothesis that a viruliferous thrips is more likely to transmit multiple times if it harbors a high titer of virus. This quantitative relationship provides new insights into the biological parameters that may influence the spread of TSWV by thrips.

Cough and expiration reflexes elicited by inhaled irritant gases are intensified in ovalbumin-sensitized mice.

PubMed

Zhang, Cheng; Lin, Ruei-Lung; Hong, Jeff; Khosravi, Mehdi; Lee, Lu-Yuan

2017-05-01

This study was designed to determine the effect of active sensitization with ovalbumin (Ova) on cough responses to inhaled irritant gases in mice. Conscious mice moved freely in a recording chamber, while the pressure change in the chamber and audio and video signals of the mouse movements were recorded simultaneously to measure the frequencies of cough reflex (CR) and expiration reflex (ER). To further verify the accuracy of cough analysis, the intrapleural pressure was also recorded by a telemetry sensor surgically implanted in the intrapleural space in a subgroup of mice. During the irritant gas inhalation challenge, sulfur dioxide (SO 2 ; 200 and 400 ppm) or ammonia (NH 3 ; 0.1% and 0.2%) was drawn into the chamber at a constant flow rate for 8 min. Ova sensitization and sham sensitization with vehicle (Veh) were performed over a 25-day period in separate groups of mice. Our results showed that 1 ) both SO 2 and NH 3 inhalation challenges increased CR and ER frequencies in a concentration-dependent manner before Ova sensitization; 2 ) the baseline CR frequency was significantly elevated after Ova sensitization, accompanied by pronounced airway inflammation; and 3 ) Ova sensitization also markedly augmented the responses of CR and ER to both SO 2 and NH 3 inhalation challenges; in sharp contrast, the cough responses did not change after sham sensitization in the Veh group. In conclusion, Ova sensitization caused distinct and lingering increases in baseline cough frequency, and also intensified both CR and ER responses to inhaled irritant gases, which probably resulted from an allergic inflammation-induced hypersensitivity of airway sensory nerves. Copyright © 2017 the American Physiological Society.

Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures.

PubMed

Porter, R J; Partiot, A; Sachdeo, R; Nohria, V; Alves, W M

2007-04-10

To evaluate the efficacy and safety of retigabine 600, 900, and 1,200 mg/day administered three times daily as adjunctive therapy in patients with partial-onset seizures. A multicenter, randomized, double-blind, placebo-controlled trial was performed. After an 8-week baseline phase, patients were randomized to a 16-week double-blind treatment period (8-week forced titration and 8-week maintenance) followed by either tapering or entry into an open-label extension study. Primary efficacy was the percentage change from baseline in monthly seizure frequency and compared across treatment arms. Secondary efficacy comparisons included the proportion of patients experiencing >/=50% reduction in seizure frequency (responder rate), emergence of new seizure types, and physician assessment of global clinical improvement. Safety/tolerability assessments included adverse events (AEs), physical and neurologic examinations, and clinical laboratory evaluations. Efficacy analyses were performed on the intent-to-treat population. Of the 399 randomized patients, 279 (69.9%) completed the double-blind treatment period. The median percent change in monthly total partial seizure frequency from baseline was -23% for 600 mg/day, -29% for 900 mg/day, and -35% for 1,200 mg/day vs -13% for placebo (p < 0.001 for overall difference across all treatment arms). Responder rates for retigabine were 23% for 600 mg/day, 32% for 900 mg/day (p = 0.021), and 33% for 1,200 mg/day (p = 0.016), vs 16% for placebo. The most common treatment-emergent AEs were somnolence, dizziness, confusion, speech disorder, vertigo, tremor, amnesia, abnormal thinking, abnormal gait, paresthesia, and diplopia. Adjunctive therapy with retigabine is well tolerated and reduces the frequency of partial-onset seizures in a dose-dependent manner.

Genetic damage induced by a food coloring dye (sunset yellow) on meristematic cells of Brassica campestris L.

PubMed

Dwivedi, Kshama; Kumar, Girjesh

2015-01-01

We have performed the present piece of work to evaluate the effect of synthetic food coloring azo dye (sunset yellow) on actively dividing root tip cells of Brassica campestris L. Three doses of azo dye were administered for the treatment of actively dividing root tip cells, namely, 1%, 3%, and 5%, for 6-hour duration along with control. Mitotic analysis clearly revealed the azo dye induced endpoint deviation like reduction in the frequency of normal divisions in a dose dependent manner. Mitotic divisions in the control sets were found to be perfectly normal while dose based reduction in MI was registered in the treated sets. Azo dye has induced several chromosomal aberrations (genotoxic effect) at various stages of cell cycle such as stickiness of chromosomes, micronuclei formation, precocious migration of chromosome, unorientation, forward movement of chromosome, laggards, and chromatin bridge. Among all, stickiness of chromosomes was present in the highest frequency followed by partial genome elimination as micronuclei. The present study suggests that extensive use of synthetic dye should be forbidden due to genotoxic and cytotoxic impacts on living cells. Thus, there is an urgent need to assess potential hazardous effects of these dyes on other test systems like human and nonhuman biota for better scrutiny.

ON THE FOURIER AND WAVELET ANALYSIS OF CORONAL TIME SERIES

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

Auchère, F.; Froment, C.; Bocchialini, K.

Using Fourier and wavelet analysis, we critically re-assess the significance of our detection of periodic pulsations in coronal loops. We show that the proper identification of the frequency dependence and statistical properties of the different components of the power spectra provides a strong argument against the common practice of data detrending, which tends to produce spurious detections around the cut-off frequency of the filter. In addition, the white and red noise models built into the widely used wavelet code of Torrence and Compo cannot, in most cases, adequately represent the power spectra of coronal time series, thus also possibly causingmore » false positives. Both effects suggest that several reports of periodic phenomena should be re-examined. The Torrence and Compo code nonetheless effectively computes rigorous confidence levels if provided with pertinent models of mean power spectra, and we describe the appropriate manner in which to call its core routines. We recall the meaning of the default confidence levels output from the code, and we propose new Monte-Carlo-derived levels that take into account the total number of degrees of freedom in the wavelet spectra. These improvements allow us to confirm that the power peaks that we detected have a very low probability of being caused by noise.« less

Autoradiographic assay of mutants resistant to diphtheria toxin in mammalian cells in vitro

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

Ronen, A.; Gingerich, J.D.; Duncan, A.M.V.

1984-10-01

Diptheria toxin kills mammalian cells by ribosylating elongation factor 2, a protein factor necessary for protein synthesis. The frequency of cells able to form colonies in the presence of the toxin can be used as an assay for mutation to diphtheria toxin resistance. Resistance to diphtheria toxin can also be detected autoradiographically in cells exposed to (/sup 3/H)leucine after treatment with the toxin. In cultures of Chinese hamster ovary cells, the frequency of such resistant cells is increased by exposure of the cells to ..gamma..-rays, ultraviolet light, ethylnitrosourea, mitomycin c, ethidium bromide, and 5-bromo-2'-deoxyuridine in a dose- and time-dependent manner.more » The resistant cells form discrete microcolonies if they are allowed to divide several times before intoxication which indicates that they are genuine mutants. The assay is potentially adaptable to any cell population that can be intoxicated with diphtheria toxin and labeled with (/sup 3/H)leucine, whether or not the cells can form colonies. It may be useful, therefore, for measuring mutation rates in slowly growing or nondividing cell populations such as breast, brain, and liver, as well as in cells that do divide but cannot be readily cloned, such as the colonic epithelium. 23 references, 6 figures.« less

What Do We Know About the Influence of the Cerebellum on Walking Ability? Promising Findings from Transcranial Alternating Current Stimulation.

PubMed

Naro, Antonino; Milardi, Demetrio; Cacciola, Alberto; Russo, Margherita; Sciarrone, Francesca; La Rosa, Gianluca; Bramanti, Alessia; Bramanti, Placido; Calabrò, Rocco Salvatore

2017-08-01

Several cerebellar functions related to upper limb motor control have been studied using non-invasive brain stimulation paradigms. We have recently shown that transcranial alternating current stimulation (tACS) may be a promising approach in shaping the plasticity of cerebellum-brain pathways in a safe and effective manner. This study aimed to assess whether cerebellar tACS at different frequencies may tune M1-leg excitability and modify gait control in healthy human subjects. To this end, we tested the effects of different cerebellar tACS frequencies over the right cerebellar hemisphere (at 10, 50, and 300 Hz, besides a sham-tACS) on M1-leg excitability, cerebellum-brain inhibition (CBI), and gait parameters in a sample of 25 healthy volunteers. Fifty and 300 Hz tACS differently modified M1-leg excitability and CBI from both lower limbs, without significant gait perturbations. We hypothesize that tACS aftereffect may depend on a selective entrainment of distinct cerebellar networks related to lower limb motor functions. Therefore, cerebellar tACS might represent a useful tool to modulate walking training in people with cerebellum-related gait impairment, given that tACS may potentially reset abnormal cerebellar circuitries.

On the Fourier and Wavelet Analysis of Coronal Time Series

NASA Astrophysics Data System (ADS)

Auchère, F.; Froment, C.; Bocchialini, K.; Buchlin, E.; Solomon, J.

2016-07-01

Using Fourier and wavelet analysis, we critically re-assess the significance of our detection of periodic pulsations in coronal loops. We show that the proper identification of the frequency dependence and statistical properties of the different components of the power spectra provides a strong argument against the common practice of data detrending, which tends to produce spurious detections around the cut-off frequency of the filter. In addition, the white and red noise models built into the widely used wavelet code of Torrence & Compo cannot, in most cases, adequately represent the power spectra of coronal time series, thus also possibly causing false positives. Both effects suggest that several reports of periodic phenomena should be re-examined. The Torrence & Compo code nonetheless effectively computes rigorous confidence levels if provided with pertinent models of mean power spectra, and we describe the appropriate manner in which to call its core routines. We recall the meaning of the default confidence levels output from the code, and we propose new Monte-Carlo-derived levels that take into account the total number of degrees of freedom in the wavelet spectra. These improvements allow us to confirm that the power peaks that we detected have a very low probability of being caused by noise.

Quantification of MDL-induced signal degradation in MIMO-OFDM mode-division multiplexing systems.

PubMed

Tian, Yu; Li, Juhao; Zhu, Paikun; Wu, Zhongying; Chen, Yuanxiang; He, Yongqi; Chen, Zhangyuan

2016-08-22

Mode-division multiplexing (MDM) transmission over few-mode optical fiber has emerged as a promising technology to enhance transmission capacity, in which multiple-input-multiple-output (MIMO) digital signal processing (DSP) after coherent detection is used to demultiplex the signals. Compared with conventional single-mode systems, MIMO-MDM systems suffer non-recoverable signal degradation induced by mode-dependent loss (MDL). In this paper, the MDL-induced signal degradation in orthogonal-frequency-division-multiplexing (OFDM) MDM systems is theoretically quantified in terms of mode-average error vector magnitude (EVM) through frequency domain norm analysis. A novel scalar MDL metric is proposed considering the probability distribution of the practical MDM input signals, and a closed-form expression for EVM measured after zero-force (ZF) MIMO equalization is derived. Simulation results show that the EVM estimations utilizing the novel MDL metric remain unbiased for unrepeated links. For a 6 × 100 km 20-mode MDM transmission system, the estimation accuracy is improved by more than 90% compared with that utilizing traditional condition number (CN) based MDL metric. The proposed MDL metric can be used to predict the MDL-induced SNR penalty in a theoretical manner, which will be beneficial for the design of practical MIMO-MDM systems.

Incomplete data based parameter identification of nonlinear and time-variant oscillators with fractional derivative elements

NASA Astrophysics Data System (ADS)

Kougioumtzoglou, Ioannis A.; dos Santos, Ketson R. M.; Comerford, Liam

2017-09-01

Various system identification techniques exist in the literature that can handle non-stationary measured time-histories, or cases of incomplete data, or address systems following a fractional calculus modeling. However, there are not many (if any) techniques that can address all three aforementioned challenges simultaneously in a consistent manner. In this paper, a novel multiple-input/single-output (MISO) system identification technique is developed for parameter identification of nonlinear and time-variant oscillators with fractional derivative terms subject to incomplete non-stationary data. The technique utilizes a representation of the nonlinear restoring forces as a set of parallel linear sub-systems. In this regard, the oscillator is transformed into an equivalent MISO system in the wavelet domain. Next, a recently developed L1-norm minimization procedure based on compressive sensing theory is applied for determining the wavelet coefficients of the available incomplete non-stationary input-output (excitation-response) data. Finally, these wavelet coefficients are utilized to determine appropriately defined time- and frequency-dependent wavelet based frequency response functions and related oscillator parameters. Several linear and nonlinear time-variant systems with fractional derivative elements are used as numerical examples to demonstrate the reliability of the technique even in cases of noise corrupted and incomplete data.

Conjugal Transfer of the Pathogenicity Island ROD21 in Salmonella enterica serovar Enteritidis Depends on Environmental Conditions

PubMed Central

Salazar-Echegarai, Francisco J.; Tobar, Hugo E.; Nieto, Pamela A.; Riedel, Claudia A.; Bueno, Susan M.

2014-01-01

Unstable pathogenicity islands are chromosomal elements that can be transferred from one bacterium to another. Salmonella enterica serovar Enteritidis (S. Enteritidis) is a pathogenic bacterium containing such unstable pathogenicity islands. One of them, denominated ROD21, is 26.5 kb in size and capable of excising from the chromosome in certain culture conditions, as well as during bacterial infection of phagocytic cells. In this study we have evaluated whether ROD21 can be effectively transferred from one bacterium to another. We generated a donor and several recipient strains of S. Enteritidis to carry out transfer assays in liquid LB medium. These assays showed that ROD21 is effectively transferred from donor to recipient strains of S. Enteritidis and S. Typhimurium. When Escherichia coli was used as the recipient strain, ROD21 transfer failed to be observed. Subsequently, we showed that a conjugative process was required for the transfer of the island and that changes in temperature and pH increased the transfer frequency between Salmonella strains. Our data indicate that ROD21 is an unstable pathogenicity island that can be transferred by conjugation in a species-specific manner between Salmonellae. Further, ROD21 transfer frequency increases in response to environmental changes, such as pH and temperature. PMID:24705125

Predicting word-recognition performance in noise by young listeners with normal hearing using acoustic, phonetic, and lexical variables.

PubMed

McArdle, Rachel; Wilson, Richard H

2008-06-01

To analyze the 50% correct recognition data that were from the Wilson et al (this issue) study and that were obtained from 24 listeners with normal hearing; also to examine whether acoustic, phonetic, or lexical variables can predict recognition performance for monosyllabic words presented in speech-spectrum noise. The specific variables are as follows: (a) acoustic variables (i.e., effective root-mean-square sound pressure level, duration), (b) phonetic variables (i.e., consonant features such as manner, place, and voicing for initial and final phonemes; vowel phonemes), and (c) lexical variables (i.e., word frequency, word familiarity, neighborhood density, neighborhood frequency). The descriptive, correlational study will examine the influence of acoustic, phonetic, and lexical variables on speech recognition in noise performance. Regression analysis demonstrated that 45% of the variance in the 50% point was accounted for by acoustic and phonetic variables whereas only 3% of the variance was accounted for by lexical variables. These findings suggest that monosyllabic word-recognition-in-noise is more dependent on bottom-up processing than on top-down processing. The results suggest that when speech-in-noise testing is used in a pre- and post-hearing-aid-fitting format, the use of monosyllabic words may be sensitive to changes in audibility resulting from amplification.

Genetic Damage Induced by a Food Coloring Dye (Sunset Yellow) on Meristematic Cells of Brassica campestris L.

PubMed Central

Dwivedi, Kshama; Kumar, Girjesh

2015-01-01

We have performed the present piece of work to evaluate the effect of synthetic food coloring azo dye (sunset yellow) on actively dividing root tip cells of Brassica campestris L. Three doses of azo dye were administered for the treatment of actively dividing root tip cells, namely, 1%, 3%, and 5%, for 6-hour duration along with control. Mitotic analysis clearly revealed the azo dye induced endpoint deviation like reduction in the frequency of normal divisions in a dose dependent manner. Mitotic divisions in the control sets were found to be perfectly normal while dose based reduction in MI was registered in the treated sets. Azo dye has induced several chromosomal aberrations (genotoxic effect) at various stages of cell cycle such as stickiness of chromosomes, micronuclei formation, precocious migration of chromosome, unorientation, forward movement of chromosome, laggards, and chromatin bridge. Among all, stickiness of chromosomes was present in the highest frequency followed by partial genome elimination as micronuclei. The present study suggests that extensive use of synthetic dye should be forbidden due to genotoxic and cytotoxic impacts on living cells. Thus, there is an urgent need to assess potential hazardous effects of these dyes on other test systems like human and nonhuman biota for better scrutiny. PMID:25954313

Aluminum induces chromosome aberrations, micronuclei, and cell cycle dysfunction in root cells of Vicia faba.

PubMed

Yi, Min; Yi, Huilan; Li, Honghai; Wu, Lihua

2010-04-01

Aluminum (Al) exists naturally in air, water, and soil, and also in our diet. Al can be absorbed into the human body and accumulates in different tissues, which has been linked to the occurrence of Alzheimer's disease and various neurological disorders. By using Vicia cytogenetic tests, which are commonly used to monitor the genotoxicity of environmental pollutants, cytogenetic effects of aluminum (AlCl(3)) were investigated in this study. Present results showed that Al caused significant increases in the frequencies of micronuclei (MN) and anaphase chromosome aberrations in Vicia faba root tips exposed to Al over a concentration-tested range of 0.01-10 mM for 12 h. The frequency of micronucleated cells was higher in Al-treated groups at pH 4.5 than that at pH 5.8. Similarly, AlCl(3) treatment caused a decrease in the number of mitotic cells in a dose- and pH-dependent manner. The number of cells in each mitotic phase changed in Al-treated samples. Mitotic indices (MI) decreased with the increases of pycnotic cells. Our results demonstrate that aluminum chloride is a clear clastogenic/genotoxic and cytotoxic agent in Vicia root cells. The V. faba cytogenetic test could be used for the genotoxicity monitoring of aluminum water contamination.

Assessment of arsenic toxicity using Allium/Vicia root tip micronucleus assays.

PubMed

Wu, Lihua; Yi, Huilan; Yi, Min

2010-04-15

Arsenic is ubiquitous in the environment and is a potential human carcinogen. Its carcinogenicity has been demonstrated in several models. In this study, broad bean (Vicia faba L.) and common onion (Allium cepa L.), two plant species which are commonly used for detecting the genotoxic effects of environmental pollutants, were used to measure possible genotoxic effect of arsenite (0.3-30 mg/l). Present results showed that arsenite (As(III)) induced micronuclei (MN) formation in both Allium and Vicia root tips. MN frequency significantly increased in Vicia root cells exposed to 0.3-10 mg/l arsenite and in Allium root cells exposed to 1-30 mg/l arsenite, which indicated that Vicia root tip cells are more sensitive to arsenite than Allium. Mitotic index (MI) decreased in a concentration-dependent manner and showed significant differences in Vicia/Allium roots among treatments and the control, after exposure to 1-30 mg/l arsenite for at least 4 h. In the present study, MN frequency was positively associated with lipid peroxidation, which indicated that arsenite exposure can induce oxidative stress, cytotoxicity and genotoxicity in plant cells. The results also suggested that Vicia/Allium root micronucleus (MN) assays are simple, efficient and reproducible methods for the genotoxicity monitoring of arsenic water contamination. 2009 Elsevier B.V. All rights reserved.

Carvacrol modulates voltage-gated sodium channels kinetics in dorsal root ganglia.

PubMed

Joca, Humberto Cavalcante; Vieira, Daiana Cardoso Oliveira; Vasconcelos, Aliny Perreira; Araújo, Demetrius Antônio Machado; Cruz, Jader Santos

2015-06-05

Recent studies have shown that many of plant-derived compounds interact with specific ion channels and thereby modulate many sensing mechanisms, such as nociception. The monoterpenoid carvacrol (5-isopropyl-2-methylphenol) has an anti-nociceptive effect related to a reduction in neuronal excitability and voltage-gated Na(+) channels (NaV) inhibition in peripheral neurons. However, the detailed mechanisms of carvacrol-induced inhibition of neuronal NaV remain elusive. This study explores the interaction between carvacrol and NaV in isolated dorsal root ganglia neurons. Carvacrol reduced the total voltage-gated Na(+) current and tetrodotoxin-resistant (TTX-R) Na(+) current component in a concentration-dependent manner. Carvacrol accelerates current inactivation and induced a negative-shift in voltage-dependence of steady-state fast inactivation in total and TTX-R Na(+) current. Furthermore, carvacrol slowed the recovery from inactivation. Carvacrol provoked a leftward shift in both the voltage-dependence of steady-state inactivation and activation of the TTX-R Na(+) current component. In addition, carvacrol-induced inhibition of TTX-R Na(+) current was enhanced by an increase in stimulation frequency and when neurons were pre-conditioned with long depolarization pulse (5s at -50 mV). Taken all results together, we herein demonstrated that carvacrol affects NaV gating properties. The present findings would help to explain the mechanisms underlying the analgesic activity of carvacrol. Copyright © 2015 Elsevier B.V. All rights reserved.

Immunostimulatory Activity of Opuntia ficus-indica var. Saboten Cladodes Fermented by Lactobacillus plantarum and Bacillus subtilis in RAW 264.7 Macrophages.

PubMed

Hwang, Joon-Ho; Lim, Sang-Bin

2017-02-01

To increase the functionality of Opuntia ficus-indica var. saboten cladodes, it was fermented by Lactobacillus plantarum and Bacillus subtilis. Eighty percent methanol extracts were investigated for their effects on nitric oxide (NO) production, cytokine secretion, nuclear factor-κB (NF-κB) activity, and mitogen-activated protein kinase (MAPK) phosphorylation in RAW 264.7 cells. Methanol extracts of L. plantarum culture medium (LPCME) and B. subtilis culture medium (BSCME) did not affect lipopolysaccharide (LPS)-induced NO production but, at 500 μg/mL, increased interferon (IFN)-γ-induced NO production by 55.2 and 66.5 μM, respectively, in RAW 264.7 cells. In RAW 264.7 cells not treated with LPS and IFN-γ, LPCME did not affect NO production, but BSCME increased NO production significantly in a dose-dependent manner. In addition, BSCME induced the expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in RAW 264.7 cells in a dose-dependent manner. BSCME at 500 μg/mL increased TNF-α and IL-1β mRNA levels by 83.8% and 82.2%, respectively. BSCME increased NF-κB-dependent luciferase activity in a dose-dependent manner; 500 μg/mL BSCME increased activity 9.1-fold compared with the control. BSCME induced the phosphorylation of p38, c-JUN NH 2 -terminal protein kinase (JNK), and extracellular signal-regulated kinase (ERK) in a dose-dependent manner, but did not affect total ERK levels. In conclusion, BSCME exerted immunostimulatory effects, which were mediated by MAPK phosphorylation and NF-κB activation, resulting in increased TNF-α and IL-1β gene expression in RAW 264.7 macrophages. Therefore, BSCM shows promise for use as an immunostimulatory therapeutic.

On Noether's Theorem for the Invariant of the Time-Dependent Harmonic Oscillator

ERIC Educational Resources Information Center

Abe, Sumiyoshi; Itto, Yuichi; Matsunaga, Mamoru

2009-01-01

The time-dependent oscillator describing parametric oscillation, the concept of invariant and Noether's theorem are important issues in physics education. Here, it is shown how they can be interconnected in a simple and unified manner.

Effects of haloperidol on Kv4.3 potassium channels.

PubMed

Lee, Hong Joon; Sung, Ki-Wug; Hahn, Sang June

2014-10-05

Haloperidol is commonly used in clinical practice to treat acute and chronic psychosis, but it also has been associated with adverse cardiovascular events. We investigated the effects of haloperidol on Kv4.3 currents stably expressed in CHO cells using a whole-cell patch-clamp technique. Haloperidol did not significantly inhibit the peak amplitude of Kv4.3, but accelerated the decay rate of inactivation of Kv4.3 in a concentration-dependent manner. Thus, the effects of haloperidol on Kv4.3 were estimated from the integral of the Kv4.3 currents during the depolarization pulse. The Kv4.3 was decreased by haloperidol in a concentration-dependent manner with an IC50 value of 3.6 μM. Haloperidol accelerated the decay rate of Kv4.3 inactivation and activation kinetics in a concentration-dependent manner, thereby decreasing the time-to-peak. Haloperidol shifted the voltage dependence of the steady-state activation and inactivation of Kv4.3 in a hyperpolarizing direction. Haloperidol also caused an acceleration of the closed-state inactivation of Kv4.3. Haloperidol produced a use-dependent block of Kv4.3, which was accompanied by a slowing of recovery from the inactivation of Kv4.3. These results suggest that haloperidol blocks Kv4.3 by both interacting with the open state of Kv4.3 channels during depolarization and accelerating the closed-state inactivation at subthreshold membrane potentials. Copyright © 2014 Elsevier B.V. All rights reserved.

L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

PubMed

Cartwright, Stephanie P; Bill, Roslyn M; Hipkiss, Alan R

2012-01-01

The dipeptide L-carnosine (β-alanyl-L-histidine) has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose), 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

TALE activators regulate gene expression in a position- and strand-dependent manner in mammalian cells.

PubMed

Uhde-Stone, Claudia; Cheung, Edna; Lu, Biao

2014-01-24

Transcription activator-like effectors (TALEs) are a class of transcription factors that are readily programmable to regulate gene expression. Despite their growing popularity, little is known about binding site parameters that influence TALE-mediated gene activation in mammalian cells. We demonstrate that TALE activators modulate gene expression in mammalian cells in a position- and strand-dependent manner. To study the effects of binding site location, we engineered TALEs customized to recognize specific DNA sequences located in either the promoter or the transcribed region of reporter genes. We found that TALE activators robustly activated reporter genes when their binding sites were located within the promoter region. In contrast, TALE activators inhibited the expression of reporter genes when their binding sites were located on the sense strand of the transcribed region. Notably, this repression was independent of the effector domain utilized, suggesting a simple blockage mechanism. We conclude that TALE activators in mammalian cells regulate genes in a position- and strand-dependent manner that is substantially different from gene activation by native TALEs in plants. These findings have implications for optimizing the design of custom TALEs for genetic manipulation in mammalian cells. Copyright © 2013 Elsevier Inc. All rights reserved.

ERβ1 inhibits the migration and invasion of breast cancer cells through upregulation of E-cadherin in a Id1-dependent manner

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

Zhou, Yan; Ming, Jia; Xu, Yan

2015-02-06

Highlights: • Expression of ERβ1 was positively correlated with E-cadherin in breast cancer cell. • ERβ1 upregulates E-cadherin expression in breast cancer cell lines. • ERβ1 upregulates E-cadherin expression in a Id1-dependent manner. - Abstract: ERβ1 is a member of the nuclear receptor superfamily of ligand-regulated transcription factors. It plays an important role in regulating the progression of breast cancer. However, the mechanisms of ERβ1 in tumorigenesis, metastasis and prognosis are still not fully clear. In this study, we showed that the expression of ERβ1 was positively correlated with E-cadherin expression in breast cancer cell lines. In addition, we foundmore » that ERβ1 upregulates E-cadherin expression in breast cancer cell lines. Furthermore, we also found that ERβ1 inhibits the migration and invasion of breast cancer cells and upregulated E-cadherin expression in a Id1-dependent manner. Taken together, our study provides further understanding of the molecular mechanism of ERβ1 in tumor metastasis and suggests the feasibility of developing novel therapeutic approaches to target Id1 to inhibit breast cancer metastasis.« less

Resonant ultrasound spectroscopy

DOEpatents

Migliori, Albert

1991-01-01

A resonant ultrasound spectroscopy method provides a unique characterization of an object for use in distinguishing similar objects having physical differences greater than a predetermined tolerance. A resonant response spectrum is obtained for a reference object by placing excitation and detection transducers at any accessible location on the object. The spectrum is analyzed to determine the number of resonant response peaks in a predetermined frequency interval. The distribution of the resonance frequencies is then characterized in a manner effective to form a unique signature of the object. In one characterization, a small frequency interval is defined and stepped though the spectrum frequency range. Subsequent objects are similarly characterized where the characterizations serve as signatures effective to distinguish objects that differ from the reference object by more than the predetermined tolerance.

Study of micro piezoelectric vibration generator with added mass and capacitance suitable for broadband vibration

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

He, Qing, E-mail: hqng@163.com; Mao, Xinhua, E-mail: 30400414@qq.com; Chu, Dongliang, E-mail: 569256386@qq.com

This study proposes an optimized frequency adjustment method that uses a micro-cantilever beam-based piezoelectric vibration generator based on a combination of added mass and capacitance. The most important concept of the proposed method is that the frequency adjustment process is divided into two steps: the first is a rough adjustment step that changes the size of the mass added at the end of cantilever to adjust the frequency in a large-scale and discontinuous manner; the second step is a continuous but short-range frequency adjustment via the adjustable added capacitance. Experimental results show that when the initial natural frequency of amore » micro piezoelectric vibration generator is 69.8 Hz, then this natural frequency can be adjusted to any value in the range from 54.2 Hz to 42.1 Hz using the combination of the added mass and the capacitance. This method simply and effectively matches a piezoelectric vibration generator’s natural frequency to the vibration source frequency.« less

Image enhancement by non-linear extrapolation in frequency space

NASA Technical Reports Server (NTRS)

Anderson, Charles H. (Inventor); Greenspan, Hayit K. (Inventor)

1998-01-01

An input image is enhanced to include spatial frequency components having frequencies higher than those in an input image. To this end, an edge map is generated from the input image using a high band pass filtering technique. An enhancing map is subsequently generated from the edge map, with the enhanced map having spatial frequencies exceeding an initial maximum spatial frequency of the input image. The enhanced map is generated by applying a non-linear operator to the edge map in a manner which preserves the phase transitions of the edges of the input image. The enhanced map is added to the input image to achieve a resulting image having spatial frequencies greater than those in the input image. Simplicity of computations and ease of implementation allow for image sharpening after enlargement and for real-time applications such as videophones, advanced definition television, zooming, and restoration of old motion pictures.

Resonant acoustic transducer and driver system for a well drilling string communication system

DOEpatents

Chanson, Gary J.; Nicolson, Alexander M.

1981-01-01

The acoustic data communication system includes an acoustic transmitter and receiver wherein low frequency acoustic waves, propagating in relatively loss free manner in well drilling string piping, are efficiently coupled to the drill string and propagate at levels competitive with the levels of noise generated by drilling machinery also present in the drill string. The transmitting transducer incorporates a mass-spring piezoelectric transmitter and amplifier combination that permits self-oscillating resonant operation in the desired low frequency range.

Efficient dynamic coherence transfer relying on offset locking using optical phase-locked loop

NASA Astrophysics Data System (ADS)

Xie, Weilin; Dong, Yi; Bretenaker, Fabien; Shi, Hongxiao; Zhou, Qian; Xia, Zongyang; Qin, Jie; Zhang, Lin; Lin, Xi; Hu, Weisheng

2018-01-01

We design and experimentally demonstrate a highly efficient coherence transfer based on composite optical phaselocked loop comprising multiple feedback servo loops. The heterodyne offset-locking is achieved by conducting an acousto-optic frequency shifter in combination with the current tuning and the temperature controlling of the semiconductor laser. The adaptation of the composite optical phase-locked loop enables the tight coherence transfer from a frequency comb to a semiconductor laser in a fully dynamic manner.

Interactive wall turbulence control

NASA Technical Reports Server (NTRS)

Wilkinson, Stephen P.

1990-01-01

After presenting boundary layer turbulence physics in a manner that emphasizes the possible modification of structural surfaces in a way that locally alters the production of turbulent flows, an account is given of the hardware that could plausibly be employed to implement such a turbulence-control scheme. The essential system components are flow sensors, electronic processors, and actuators; at present, actuator technology presents the greatest problems and limitations. High frequency/efficiency actuators are required to handle three-dimensional turbulent motions whose frequency and intensity increases in approximate proportion to freestream speed.

Tuning of gravity-dependent and gravity-independent vertical angular VOR gain changes by frequency of adaptation

PubMed Central

2012-01-01

The gain of the vertical angular vestibulo-ocular reflex (aVOR) was adaptively increased and decreased in a side-down head orientation for 4 h in two cynomolgus monkeys. Adaptation was performed at 0.25, 1, 2, or 4 Hz. The gravity-dependent and -independent gain changes were determined over a range of head orientations from left-side-down to right-side-down at frequencies from 0.25 to 10 Hz, before and after adaptation. Gain changes vs. frequency data were fit with a Gaussian to determine the frequency at which the peak gain change occurred, as well as the tuning width. The frequency at which the peak gravity-dependent gain change occurred was approximately equal to the frequency of adaptation, and the width increased monotonically with increases in the frequency of adaptation. The gravity-independent component was tuned to the adaptive frequency of 0.25 Hz but was uniformly distributed over all frequencies when the adaptation frequency was 1–4 Hz. The amplitude of the gravity-independent gain changes was larger after the aVOR gain decrease than after the gain increase across all tested frequencies. For the aVOR gain decrease, the phase lagged about 4° for frequencies below the adaptation frequency and led for frequencies above the adaptation frequency. For gain increases, the phase relationship as a function of frequency was inverted. This study demonstrates that the previously described dependence of aVOR gain adaptation on frequency is a property of the gravity-dependent component of the aVOR only. The gravity-independent component of the aVOR had a substantial tuning curve only at an adaptation frequency of 0.25 Hz. PMID:22402654

Tuning of gravity-dependent and gravity-independent vertical angular VOR gain changes by frequency of adaptation.

PubMed

Yakushin, Sergei B

2012-06-01

The gain of the vertical angular vestibulo-ocular reflex (aVOR) was adaptively increased and decreased in a side-down head orientation for 4 h in two cynomolgus monkeys. Adaptation was performed at 0.25, 1, 2, or 4 Hz. The gravity-dependent and -independent gain changes were determined over a range of head orientations from left-side-down to right-side-down at frequencies from 0.25 to 10 Hz, before and after adaptation. Gain changes vs. frequency data were fit with a Gaussian to determine the frequency at which the peak gain change occurred, as well as the tuning width. The frequency at which the peak gravity-dependent gain change occurred was approximately equal to the frequency of adaptation, and the width increased monotonically with increases in the frequency of adaptation. The gravity-independent component was tuned to the adaptive frequency of 0.25 Hz but was uniformly distributed over all frequencies when the adaptation frequency was 1-4 Hz. The amplitude of the gravity-independent gain changes was larger after the aVOR gain decrease than after the gain increase across all tested frequencies. For the aVOR gain decrease, the phase lagged about 4° for frequencies below the adaptation frequency and led for frequencies above the adaptation frequency. For gain increases, the phase relationship as a function of frequency was inverted. This study demonstrates that the previously described dependence of aVOR gain adaptation on frequency is a property of the gravity-dependent component of the aVOR only. The gravity-independent component of the aVOR had a substantial tuning curve only at an adaptation frequency of 0.25 Hz.

Effect of low frequency magnetic fields on the growth of MNP-treated HT29 colon cancer cells

NASA Astrophysics Data System (ADS)

Spyridopoulou, K.; Makridis, A.; Maniotis, N.; Karypidou, N.; Myrovali, E.; Samaras, T.; Angelakeris, M.; Chlichlia, K.; Kalogirou, O.

2018-04-01

Recent investigations have attempted to understand and exploit the impact of magnetic field-actuated internalized magnetic nanoparticles (MNPs) on the proliferation rate of cancer cells. Due to the complexity of the parameters governing magnetic field-exposure though, individual studies to date have raised contradictory results. In our approach we performed a comparative analysis of key parameters related to the cell exposure of cancer cells to magnetic field-actuated MNPs, and to the magnetic field, in order to better understand the factors affecting cellular responses to magnetic field-stimulated MNPs. We used magnetite MNPs with a hydrodynamic diameter of 100 nm and studied the proliferation rate of MNPs-treated versus untreated HT29 human colon cancer cells, exposed to either static or alternating low frequency magnetic fields with varying intensity (40-200 mT), frequency (0-8 Hz) and field gradient. All three parameters, field intensity, frequency, and field gradient affected the growth rate of cells, with or without internalized MNPs, as compared to control MNPs-untreated and magnetic field-untreated cells. We observed that the growth inhibitory effects induced by static and rotating magnetic fields were enhanced by pre-treating the cells with MNPs, while the growth promoting effects observed in alternating field-treated cells were weakened by MNPs. Compared to static, rotating magnetic fields of the same intensity induced a similar extend of cell growth inhibition, while alternating fields of varying intensity (70 or 100 mT) and frequency (0, 4 or 8 Hz) induced cell proliferation in a frequency-dependent manner. These results, highlighting the diverse effects of mode, intensity, and frequency of the magnetic field on cell growth, indicate that consistent and reproducible results can be achieved by controlling the complexity of the exposure of biological samples to MNPs and external magnetic fields, through monitoring crucial experimental parameters. We demonstrate that further research focusing on the accurate manipulation of the aforementioned magnetic field exposure parameters could lead to the development of successful non-invasive therapeutic anticancer approaches.

Structural frequency functions for an impulsive, distributed forcing function

NASA Technical Reports Server (NTRS)

Bateman, Vesta I.

1987-01-01

The response of a penetrator structure to a spatially distributed mechanical impulse with a magnitude approaching field test force levels (1-2 Mlb) were measured. The frequency response function calculated from the response to this unique forcing function is compared to frequency response functions calculated from response to point forces of about 2000 pounds. The results show that the strain gages installed on the penetrator case respond similiarly to a point, axial force and to a spatially distributed, axial force. This result suggests that the distributed axial force generated in a penetration event may be reconstructed as a point axial force when the penetrator behaves in linear manner.

Safety assessment of probiotics for human use

USDA-ARS?s Scientific Manuscript database

The safety of probiotics is tied to their intended use, which includes consideration of the potential vulnerability of the consumer or patient, dose and duration of consumption, and both the manner and frequency of administration. Unique to probiotics is that they are living organisms when administ...

On the mechanism for PPAR agonists to enhance ABCA1 gene expression

PubMed Central

Ogata, Masaki; Tsujita, Maki; Hossain, Mohammad Anwar; Akita, Nobukatsu; Gonzalez, Frank J.; Staels, Bart; Suzuki, Shogo; Fukutomi, Tatsuya; Kimura, Genjiro; Yokoyama, Shinji

2009-01-01

Expression of ATP binding cassette transporter A1 (ABCA1), a major regulator of high density lipoprotein (HDL) biogenesis, is known to be up-regulated by the transcription factor liver X receptor (LXR) α, and expression is further enhanced by activation of the peroxisome proliferator activated receptors (PPARs). We investigated this complex regulatory network using specific PPAR agonists: four fibrates (fenofibrate, bezafibrate, gemfibrozil and LY518674), a PPAR δ agonist (GW501516) and a PPAR γ agonist (pioglitazone). All of these compounds increased the expression of LXRs, PPARs and ABCA1 mRNAs, and associated apoA-I-mediated lipid release in THP-1 macrophage, WI38 fibroblast and mouse fibroblast. When mouse fibroblasts lacking expression of PPAR α were examined, the effects of fenofibrate and LY518674 were markedly diminished while induction by other ligands were retained. The PPAR α promoter was activated by all of these compounds in an LXR α-dependent manner, and partially in a PPAR α-dependent manner, in mouse fibroblast. The LXR responsive element (LXRE)-luciferase activity was enhanced by all the compounds in an LXR α-dependent manner in mouse fibroblast. This activation was exclusively PPAR α-dependent by fenofibrate and LY518674, but nonexclusively by the others. We conclude that PPARs and LXRs are involved in the regulation of ABCA1 expression and HDL biogenesis in a cooperative signal transduction pathway. PMID:19201410

Regulation of alternative splicing by the circadian clock and food related cues

PubMed Central

2012-01-01

Background The circadian clock orchestrates daily rhythms in metabolism, physiology and behaviour that allow organisms to anticipate regular changes in their environment, increasing their adaptation. Such circadian phenotypes are underpinned by daily rhythms in gene expression. Little is known, however, about the contribution of post-transcriptional processes, particularly alternative splicing. Results Using Affymetrix mouse exon-arrays, we identified exons with circadian alternative splicing in the liver. Validated circadian exons were regulated in a tissue-dependent manner and were present in genes with circadian transcript abundance. Furthermore, an analysis of circadian mutant Vipr2-/- mice revealed the existence of distinct physiological pathways controlling circadian alternative splicing and RNA binding protein expression, with contrasting dependence on Vipr2-mediated physiological signals. This view was corroborated by the analysis of the effect of fasting on circadian alternative splicing. Feeding is an important circadian stimulus, and we found that fasting both modulates hepatic circadian alternative splicing in an exon-dependent manner and changes the temporal relationship with transcript-level expression. Conclusions The circadian clock regulates alternative splicing in a manner that is both tissue-dependent and concurrent with circadian transcript abundance. This adds a novel temporal dimension to the regulation of mammalian alternative splicing. Moreover, our results demonstrate that circadian alternative splicing is regulated by the interaction between distinct physiological cues, and illustrates the capability of single genes to integrate circadian signals at different levels of regulation. PMID:22721557

Non-specific actions of the non-peptide tachykinin receptor antagonists, CP-96,345, RP 67580 and SR 48968, on neurotransmission.

PubMed Central

Wang, Z. Y.; Tung, S. R.; Strichartz, G. R.; Håkanson, R.

1994-01-01

1. Three non-peptide tachykinin receptor antagonists, CP-96,345, RP 67580 and SR 48968, were found to inhibit the electrically-evoked, tachykinin-mediated contractile responses of the rabbit iris sphincter in a concentration-dependent fashion; the pIC50 values were 5.6 +/- 0.01, 5.4 +/- 0.07 and 4.8 +/- 0.03, respectively. 2. These antagonists also inhibited the electrically-evoked, parasympathetic response of the rabbit iris sphincter and the sympathetic response of the guinea-pig vas deferens in a concentration-dependent manner; the pIC50 values were 0.3-1.2 log units lower than those recorded for the tachykinin-mediated responses. 3. Two local anaesthetics, bupivacaine and oxybuprocaine, were also found to inhibit the tachykinin-mediated, cholinergic and sympathetic contractile responses in these tissues in a concentration-dependent manner; the concentration ranges for producing the inhibition were similar to those of the non-peptide tachykinin receptor antagonists. 4. On the sciatic nerves of frogs, the tachykinin receptor antagonists inhibited action potentials in a concentration-dependent manner; the potency of the three drugs was similar to that of bupivacaine. 5. Our results suggest that, in addition to blocking tachykinin receptors, the non-peptide tachykinin receptor antagonists, CP-96,345, RP 67580 and SR 48968, may exert non-specific inhibitory effects on neurotransmission. PMID:8012694

New insight into mitochondrial changes in vascular endothelial cells irradiated by gamma ray.

PubMed

Hu, Shunying; Gao, Yajing; Zhou, Hao; Kong, Fanxuan; Xiao, Fengjun; Zhou, Pingkun; Chen, Yundai

2017-05-01

To investigate alterations of mitochondria in irradiated endothelial cells to further elucidate the mechanism underlying radiation-induced heart disease. Experiments were performed using human umbilical vein endothelial cells (HUVECs). HUVECs were irradiated with single gamma ray dose of 0, 5, 10 and 20 Gy, respectively. Apoptosis was assessed by flow cytometry at 24, 48 and 72 h post-irradiation, respectively. The intracellular reactive oxygen species (ROS) was measured with 2',7'-dichlorofluorescein-diacetate (DCFH-DA) at 24 h post-irradiation. Mitochondrial membrane potential (ΔΨm) by JC-1 and the opening of mitochondrial permeability transition pore (mPTP) by a calcein-cobalt quenching method were detected at 24 h post-irradiation in order to measure changes of mitochondria induced by gamma ray irradiation. Gamma ray irradiation increased HUVECs apoptosis in a dose-dependent and time-dependent manner. Irradiation also promoted ROS production in HUVECs in a dose-dependent manner. At 24 h post-irradiation, the results showed that irradiation decreases ΔΨm, however, paradoxically, flow cytometry showed green fluorescence instensity higher in irradiated HUVECs than in control HUVECs in an irradiation dose-dependent manner which indicated gamma ray irradiation inhibited mPTP opening in HUVECs. Gamma ray irradiation induces apoptosis and ROS production of endothelial cells, and decreases ΔΨm meanwhile contradictorily inhibiting the opening of mPTP.

Iron alters cell survival in a mitochondria-dependent pathway in ovarian cancer cells

PubMed Central

Bauckman, Kyle; Haller, Edward; Taran, Nicholas; Rockfield, Stephanie; Ruiz-Rivera, Abigail; Nanjundan, Meera

2015-01-01

The role of iron in the development of cancer remains unclear. We previously reported that iron reduces cell survival in a Ras/mitogen-activated protein kinase (MAPK)-dependent manner in ovarian cells; however, the underlying downstream pathway leading to reduced survival was unclear. Although levels of intracellular iron, ferritin/CD71 protein and reactive oxygen species did not correlate with iron-induced cell survival changes, we identified mitochondrial damage (via TEM) and reduced expression of outer mitochondrial membrane proteins (translocase of outer membrane: TOM20 and TOM70) in cell lines sensitive to iron. Interestingly, Ru360 (an inhibitor of the mitochondrial calcium uniporter) reversed mitochondrial changes and restored cell survival in HEY ovarian carcinoma cells treated with iron. Further, cells treated with Ru360 and iron also had reduced autophagic punctae with increased lysosomal numbers, implying cross-talk between these compartments. Mitochondrial changes were dependent on activation of the Ras/MAPK pathway since treatment with a MAPK inhibitor restored expression of TOM20/TOM70 proteins. Although glutathione antioxidant levels were reduced in HEY treated with iron, extracellular glutamate levels were unaltered. Strikingly, oxalomalate (inhibitor of aconitase, involved in glutamate production) reversed iron-induced responses in a similar manner to Ru360. Collectively, our results implicate iron in modulating cell survival in a mitochondria-dependent manner in ovarian cancer cells. PMID:25697096

A new rate-dependent model for high-frequency tracking performance enhancement of piezoactuator system

NASA Astrophysics Data System (ADS)

Tian, Lizhi; Xiong, Zhenhua; Wu, Jianhua; Ding, Han

2017-05-01

Feedforward-feedback control is widely used in motion control of piezoactuator systems. Due to the phase lag caused by incomplete dynamics compensation, the performance of the composite controller is greatly limited at high frequency. This paper proposes a new rate-dependent model to improve the high-frequency tracking performance by reducing dynamics compensation error. The rate-dependent model is designed as a function of the input and input variation rate to describe the input-output relationship of the residual system dynamics which mainly performs as phase lag in a wide frequency band. Then the direct inversion of the proposed rate-dependent model is used to compensate the residual system dynamics. Using the proposed rate-dependent model as feedforward term, the open loop performance can be improved significantly at medium-high frequency. Then, combining the with feedback controller, the composite controller can provide enhanced close loop performance from low frequency to high frequency. At the frequency of 1 Hz, the proposed controller presents the same performance as previous methods. However, at the frequency of 900 Hz, the tracking error is reduced to be 30.7% of the decoupled approach.

Dynamically reconfigurable holographic metasurface aperture for a Mills-Cross monochromatic microwave camera.

PubMed

Yurduseven, Okan; Marks, Daniel L; Fromenteze, Thomas; Smith, David R

2018-03-05

We present a reconfigurable, dynamic beam steering holographic metasurface aperture to synthesize a microwave camera at K-band frequencies. The aperture consists of a 1D printed microstrip transmission line with the front surface patterned into an array of slot-shaped subwavelength metamaterial elements (or meta-elements) dynamically tuned between "ON" and "OFF" states using PIN diodes. The proposed aperture synthesizes a desired radiation pattern by converting the waveguide-mode to a free space radiation by means of a binary modulation scheme. This is achieved in a holographic manner; by interacting the waveguide-mode (reference-wave) with the metasurface layer (hologram layer). It is shown by means of full-wave simulations that using the developed metasurface aperture, the radiated wavefronts can be engineered in an all-electronic manner without the need for complex phase-shifting circuits or mechanical scanning apparatus. Using the dynamic beam steering capability of the developed antenna, we synthesize a Mills-Cross composite aperture, forming a single-frequency all-electronic microwave camera.

Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current

PubMed Central

Liu, Pin W.; Blair, Nathaniel T.

2017-01-01

Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC50 <100 μm) and block by the peptide inhibitor blood depressing substance I (BDS-I). There was a small component of Kv1-mediated current during AP repolarization, but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction, but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small-diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could mitigate the frequency-dependent decreases in conduction velocity typical of C-fiber axons. SIGNIFICANCE STATEMENT Small-diameter dorsal root ganglia (DRG) neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We found that action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. PMID:28877968

Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current.

PubMed

Liu, Pin W; Blair, Nathaniel T; Bean, Bruce P

2017-10-04

Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC 50 <100 μm) and block by the peptide inhibitor blood depressing substance I (BDS-I). There was a small component of Kv1-mediated current during AP repolarization, but this current did not show frequency-dependent reduction. In a small fraction of cells, there was a component of calcium-dependent potassium current that showed frequency-dependent reduction, but the contribution to overall potassium current reduction was almost always much smaller than that of Kv3-mediated current. These results show that Kv3 channels make a major contribution to spike repolarization in small-diameter DRG neurons and undergo frequency-dependent reduction, leading to spike broadening at moderate firing frequencies. Spike broadening from frequency-dependent reduction in Kv3 current could mitigate the frequency-dependent decreases in conduction velocity typical of C-fiber axons. SIGNIFICANCE STATEMENT Small-diameter dorsal root ganglia (DRG) neurons mediating nociception and other sensory modalities express many types of potassium channels, but how they combine to control firing patterns and conduction is not well understood. We found that action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. Copyright © 2017 the authors 0270-6474/17/379705-10$15.00/0.

Anti-diarrhoeal and anti-microbial activity of Flos populi (male inflorescence of Populus tomentosa Carrière) aqueous extracts.

PubMed

Xu, Qianqian; Shen, Zhiqiang; Wang, Yubo; Guo, Shijin; Li, Feng; Wang, Yanping; Zhou, Chunfeng

2013-07-09

Flos populi (male inflorescence of Populus tomentosa Carrière) has been traditionally used in East Asian countries for the treatment of various inflammatory diseases, strengthening the spleen and stomach, anti-rheumatic, anti-tumor and anti-diarrhoeal. To evaluate the in vivo or in vitro anti-diarrhoeal and anti-microbial activity of Flos populi aqueous extract. Acute toxicity of Flos populi aqueous extract (FPAE) was investigated. Castor oil-induced diarrhoea method was used to evaluate the anti-diarrhoeal activity, inhibition of defecation and diarrhoea were determined in mice, effects on castor oil-induced enteropooling, intestinal transit and intestinal fluid secretion in rats or mice. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of FPAE against strains of three clinical bacterial isolates and one reference strain were used to test the anti-microbial activity. The FPAE reduced the frequency of diarrhoea episodes and decreased the propulsion of charcoal meal through the gastrointestinal tract in a dose dependent manner. FPAE (100-500 mg/kg, p.o.) produced dose-dependent and significant (P<0.01) protection of mice against castor oil-induced diarrhoea. FPAE, dose-dependently and significantly (P< 0.01) delayed the onset of castor-oil induced diarrhoea, decreased the frequency of defecation, and reduced the severity of diarrhoea. Compared with control animals, FPAE, dose-dependently and significantly (P< 0.01) decreased the volume of castor oil-induced intestinal fluid secretion, and reduced the number, weight and wetness of faecal droppings. There was no deaths or abnormalities in behaviour seen in the acute toxicity test. The aqueous extract displayed anti-microbial effects to three species of bacteria in anti-microbial test. The findings of this study indicate that FPAE possesses anti-diarrhoeal property in rats and mice and confirm the ethnomedicinal use of Flos Populi as a valuable natural remedy for the treatment, management and/or control of diarrhoea. These results may support the fact that this plant is traditionally used to cure diarrhoea. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

Effect of the Fatigue Induced by a 110-km Ultramarathon on Tibial Impact Acceleration and Lower Leg Kinematics

PubMed Central

Giandolini, Marlene; Gimenez, Philippe; Temesi, John; Arnal, Pierrick J.; Martin, Vincent; Rupp, Thomas; Morin, Jean-Benoit; Samozino, Pierre; Millet, Guillaume Y.

2016-01-01

Ultramarathon runners are exposed to a high number of impact shocks and to severe neuromuscular fatigue. Runners may manage mechanical stress and muscle fatigue by changing their running kinematics. Our purposes were to study (i) the effects of a 110-km mountain ultramarathon (MUM) on tibial shock acceleration and lower limb kinematics, and (ii) whether kinematic changes are modulated according to the severity of neuromuscular fatigue. Twenty-three runners participated in the study. Pre- and post-MUM, neuromuscular tests were performed to assess knee extensor (KE) and plantar flexor (PF) central and peripheral fatigue, and a treadmill running bouts was completed during which step frequency, peak acceleration, median frequency and impact frequency content were measured from tibial acceleration, as well as foot-to-treadmill, tibia-to-treadmill, and ankle flexion angles at initial contact, and ankle range of motion using video analysis. Large neuromuscular fatigue, including peripheral changes and deficits in voluntary activation, was observed in KE and PF. MVC decrements of ~35% for KE and of ~28% for PF were noted. Among biomechanical variables, step frequency increased by ~2.7% and the ankle range of motion decreased by ~4.1% post-MUM. Runners adopting a non rearfoot strike pre-MUM adopted a less plantarflexed foot strike pattern post-MUM while those adopting a rearfoot strike pre-MUM tended to adopt a less dorsiflexed foot strike pattern post-MUM. Positive correlations were observed between percent changes in peripheral PF fatigue and the ankle range of motion. Peripheral PF fatigue was also significantly correlated to both percent changes in step frequency and the ankle angle at contact. This study suggests that in a fatigued state, ultratrail runners use compensatory/protective adjustments leading to a flatter foot landing and this is done in a fatigue dose-dependent manner. This strategy may aim at minimizing the overall load applied to the musculoskeletal system, including impact shock and muscle stretch. PMID:27031830

Stiffness and force in activated frog skeletal muscle fibers.

PubMed Central

Cecchi, G.; Griffiths, P. J.; Taylor, S.

1986-01-01

Single fibers, isolated intact from frog skeletal muscles, were held firmly very near to each end by stiff metal clasps fastened to the tendons. The fibers were then placed horizontally between two steel hooks inserted in eyelets of the tendon clasps. One hook was attached to a capacitance gauge force transducer (resonance frequency up to approximately 50 kHz) and the other was attached to a moving-coil length changer. This allowed us to impose small, rapid releases (complete in less than 0.15 ms) and high frequency oscillations (up to 13 kHz) to one end of a resting or contracting fiber and measure the consequences at the other end with fast time resolution at 4 to 6 degrees C. The stiffness of short fibers (1.8-2.6 mm) was determined directly from the ratio of force to length variations produced by the length changer. The resonance frequency of short fibers was so high (approximately 40 kHz) that intrinsic oscillations were not detectably excited. The stiffness of long fibers, on the other hand, was calculated from measurement of the mechanical resonance frequency of a fiber. Using both short and long fibers, we measured the sinusoids of force at one end of a contracting fiber that were produced by relatively small sinusoidal length changes at the other end. The amplitudes of the sinusoidal length changes were small compared with the size of step changes that produce nonlinear force-extension relations. The sinusoids of force from long fibers changed amplitude and shifted phase with changes in oscillation frequency in a manner expected of a transmission line composed of mass, compliance, and viscosity, similar to that modelled by (Ford, L. E., A. F. Huxley, and R. M. Simmons, 1981, J. Physiol. (Lond.), 311:219-249). A rapid release during the plateau of tetanic tension in short fibers caused a fall in force and stiffness, a relative change in stiffness that putatively was much smaller than that of force. Our results are, for the most part, consistent with the cross-bridge model of force generation proposed by Huxley, A. F., and R. M. Simmons (1971, Nature (Lond.), 213:533-538). However, stiffness in short fibers developed markedly faster than force during the tetanus rise. Thus our findings show the presence of one or more noteworthy cross-bridge states at the onset and during the rise of active tension towards a plateau in that attachment apparently is followed by a relatively long delay before force generation occurs. A set of equations is given in the Appendix that describes the frequency dependence of the applied sinusoid and its response. This model predicts that frequency dependent changes can be used as a measure of a change in stiffness. PMID:3955178

Effect of temperature- and frequency-dependent dynamic properties of rail pads on high-speed vehicle-track coupled vibrations

NASA Astrophysics Data System (ADS)

Wei, Kai; Wang, Feng; Wang, Ping; Liu, Zi-xuan; Zhang, Pan

2017-03-01

The soft under baseplate pad of WJ-8 rail fastener frequently used in China's high-speed railways was taken as the study subject, and a laboratory test was performed to measure its temperature and frequency-dependent dynamic performance at 0.3 Hz and at -60°C to 20°C with intervals of 2.5°C. Its higher frequency-dependent results at different temperatures were then further predicted based on the time-temperature superposition (TTS) and Williams-Landel-Ferry (WLF) formula. The fractional derivative Kelvin-Voigt (FDKV) model was used to represent the temperature- and frequency-dependent dynamic properties of the tested rail pad. By means of the FDKV model for rail pads and vehicle-track coupled dynamic theory, high-speed vehicle-track coupled vibrations due to temperature- and frequency-dependent dynamic properties of rail pads was investigated. Finally, further combining with the measured frequency-dependent dynamic performance of vehicle's rubber primary suspension, the high-speed vehicle-track coupled vibration responses were discussed. It is found that the storage stiffness and loss factor of the tested rail pad are sensitive to low temperatures or high frequencies. The proposed FDKV model for the frequency-dependent storage stiffness and loss factors of the tested rail pad can basically meet the fitting precision, especially at ordinary temperatures. The numerical simulation results indicate that the vertical vibration levels of high-speed vehicle-track coupled systems calculated with the FDKV model for rail pads in time domain are higher than those calculated with the ordinary Kelvin-Voigt (KV) model for rail pads. Additionally, the temperature- and frequency-dependent dynamic properties of the tested rail pads would alter the vertical vibration acceleration levels (VALs) of the car body and bogie in 1/3 octave frequencies above 31.5 Hz, especially enlarge the vertical VALs of the wheel set and rail in 1/3 octave frequencies of 31.5-100 Hz and above 315 Hz, which are the dominant frequencies of ground vibration acceleration and rolling noise (or bridge noise) caused by high-speed railways respectively. Since the fractional derivative value of the adopted rubber primary suspension, unlike the tested rail pad, is very close to 1, its frequency-dependent dynamic performance has little effect on high-speed vehicle-track coupled vibration responses.

Dynamic blocked transfer stiffness method of characterizing the magnetic field and frequency dependent dynamic viscoelastic properties of MRE

NASA Astrophysics Data System (ADS)

Poojary, Umanath R.; Hegde, Sriharsha; Gangadharan, K. V.

2016-11-01

Magneto rheological elastomer (MRE) is a potential resilient element for the semi active vibration isolator. MRE based isolators adapt to different frequency of vibrations arising from the source to isolate the structure over wider frequency range. The performance of MRE isolator depends on the magnetic field and frequency dependent characteristics of MRE. Present study is focused on experimentally evaluating the dynamic stiffness and loss factor of MRE through dynamic blocked transfer stiffness method. The dynamic stiffness variations of MRE exhibit strong magnetic field and mild frequency dependency. Enhancements in dynamic stiffness saturate with the increase in magnetic field and the frequency. The inconsistent variations of loss factor with the magnetic field substantiate the inability of MRE to have independent control over its damping characteristics.

Radiation-quality dependent cellular response in mutation induction in normal human cells.

PubMed

Suzuki, Masao; Tsuruoka, Chizuru; Uchihori, Yukio; Kitamura, Hisashi; Liu, Cui Hua

2009-09-01

We studied cellular responses in normal human fibroblasts induced with low-dose (rate) or low-fluence irradiations of different radiation types, such as gamma rays, neutrons and high linear energy transfer (LET) heavy ions. The cells were pretreated with low-dose (rate) or low-fluence irradiations (approximately 1 mGy/7-8 h) of 137Cs gamma rays, 241Am-Be neutrons, helium, carbon and iron ions before irradiations with an X-ray challenging dose (1.5 Gy). Helium (LET = 2.3 keV/microm), carbon (LET = 13.3 keV/microm) and iron (LET = 200 keV/microm) ions were produced by the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. No difference in cell-killing effect, measured by a colony forming assay, was observed among the pretreatment with different radiation types. In mutation induction, which was detected in the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus to measure 6-thioguanine resistant clones, there was no difference in mutation frequency induced by the X-ray challenging dose between unpretreated and gamma-ray pretreated cells. In the case of the pretreatment of heavy ions, X-ray-induced mutation was around 1.8 times higher in helium-ion pretreated and 4.0 times higher in carbon-ion pretreated cells than in unpretreated cells (X-ray challenging dose alone). However, the mutation frequency in cells pretreated with iron ions was the same level as either unpretreated or gamma-ray pretreated cells. In contrast, it was reduced at 0.15 times in cells pretreated with neutrons when compared to unpretreated cells. The results show that cellular responses caused by the influence of hprt mutation induced in cells pretreated with low-dose-rate or low-fluence irradiations of different radiation types were radiation-quality dependent manner.

Non-neuronal, slow GABA signalling in the ventrobasal thalamus targets δ-subunit-containing GABAA receptors

PubMed Central

Jiménez-González, Cristina; Pirttimaki, Tiina; Cope, David W; Parri, H R

2011-01-01

The rodent ventrobasal (VB) thalamus contains a relatively uniform population of thalamocortical (TC) neurons that receive glutamatergic input from the vibrissae and the somatosensory cortex, and inhibitory input from the nucleus reticularis thalami (nRT). In this study we describe γ-aminobutyric acid (GABA)A receptor-dependent slow outward currents (SOCs) in TC neurons that are distinct from fast inhibitory postsynaptic currents (IPSCs) and tonic currents. SOCs occurred spontaneously or could be evoked by hypo-osmotic stimulus, and were not blocked by tetrodotoxin, removal of extracellular Ca2+ or bafilomycin A1, indicating a non-synaptic, non-vesicular GABA origin. SOCs were more common in TC neurons of the VB compared with the dorsal lateral geniculate nucleus, and were rarely observed in nRT neurons, whilst SOC frequency in the VB increased with age. Application of THIP, a selective agonist at δ-subunit-containing GABAA receptors, occluded SOCs, whereas the benzodiazepine site inverse agonist β-CCB had no effect, but did inhibit spontaneous and evoked IPSCs. In addition, the occurrence of SOCs was reduced in mice lacking the δ-subunit, and their kinetics were also altered. The anti-epileptic drug vigabatrin increased SOC frequency in a time-dependent manner, but this effect was not due to reversal of GABA transporters. Together, these data indicate that SOCs in TC neurons arise from astrocytic GABA release, and are mediated by δ-subunit-containing GABAA receptors. Furthermore, these findings suggest that the therapeutic action of vigabatrin may occur through the augmentation of this astrocyte–neuron interaction, and highlight the importance of glial cells in CNS (patho) physiology. PMID:21395866

Assessing the Formation of Experience-Based Gender Expectations in an Implicit Learning Scenario

PubMed Central

Öttl, Anton; Behne, Dawn M.

2017-01-01

The present study investigates the formation of new word-referent associations in an implicit learning scenario, using a gender-coded artificial language with spoken words and visual referents. Previous research has shown that when participants are explicitly instructed about the gender-coding system underlying an artificial lexicon, they monitor the frequency of exposure to male vs. female referents within this lexicon, and subsequently use this probabilistic information to predict the gender of an upcoming referent. In an explicit learning scenario, the auditory and visual gender cues are necessarily highlighted prior to acqusition, and the effects previously observed may therefore depend on participants' overt awareness of these cues. To assess whether the formation of experience-based expectations is dependent on explicit awareness of the underlying coding system, we present data from an experiment in which gender-coding was acquired implicitly, thereby reducing the likelihood that visual and auditory gender cues are used strategically during acquisition. Results show that even if the gender coding system was not perfectly mastered (as reflected in the number of gender coding errors), participants develop frequency based expectations comparable to those previously observed in an explicit learning scenario. In line with previous findings, participants are quicker at recognizing a referent whose gender is consistent with an induced expectation than one whose gender is inconsistent with an induced expectation. At the same time however, eyetracking data suggest that these expectations may surface earlier in an implicit learning scenario. These findings suggest that experience-based expectations are robust against manner of acquisition, and contribute to understanding why similar expectations observed in the activation of stereotypes during the processing of natural language stimuli are difficult or impossible to suppress. PMID:28936186

Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome.

PubMed

Suvrathan, Aparna; Hoeffer, Charles A; Wong, Helen; Klann, Eric; Chattarji, Sumantra

2010-06-22

Fragile X syndrome (FXS), a common inherited form of mental impairment and autism, is caused by transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. Earlier studies have identified a role for aberrant synaptic plasticity mediated by the metabotropic glutamate receptors (mGluRs) in FXS. However, many of these observations are derived primarily from studies in the hippocampus. The strong emotional symptoms of FXS, on the other hand, are likely to involve the amygdala. Unfortunately, little is known about how exactly FXS affects synaptic function in the amygdala. Here, using whole-cell recordings in brain slices from adult Fmr1 knockout mice, we find mGluR-dependent long-term potentiation to be impaired at thalamic inputs to principal neurons in the lateral amygdala. Consistent with this long-term potentiation deficit, surface expression of the AMPA receptor subunit, GluR1, is reduced in the lateral amygdala of knockout mice. In addition to these postsynaptic deficits, lower presynaptic release was manifested by a decrease in the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs), increased paired-pulse ratio, and slower use-dependent block of NMDA receptor currents. Strikingly, pharmacological inactivation of mGluR5 with 2-methyl-6-phenylethynyl-pyridine (MPEP) fails to rescue either the deficit in long-term potentiation or surface GluR1. However, the same acute MPEP treatment reverses the decrease in mEPSC frequency, a finding of potential therapeutic relevance. Therefore, our results suggest that synaptic defects in the amygdala of knockout mice are still amenable to pharmacological interventions against mGluR5, albeit in a manner not envisioned in the original hippocampal framework.

Noradrenaline decreases spike voltage threshold and induces electrographic sharp waves in turtle medial cortex in vitro.

PubMed

Lorenzo, Daniel; Velluti, Julio C

2004-01-01

The noradrenergic modulation of neuronal properties has been described at different levels of the mammalian brain. Although the anatomical characteristics of the noradrenergic system are well known in reptiles, functional data are scarce. In our study the noradrenergic modulation of cortical electrogenesis in the turtle medial cortex was studied in vitro using a combination of field and intracellular recordings. Turtle EEG consists of a low voltage background interspersed by spontaneous large sharp waves (LSWs). Noradrenaline (NA, 5-40 microM) induced (or enhanced) the generation of LSWs in a dose-dependent manner. Pharmacological experiments suggest the participation of alpha and beta receptors in this effect. In medial cortex neurons NA induced a hyperpolarization of the resting potential and a decrease of input resistance. Both effects were observed also after TTX treatment. Noradrenaline increased the response of the cells to depolarizing pulses, resulting in an upward shift of the frequency/current relation. In most cells the excitability change was mediated by a decrease of the spike voltage threshold resulting in the reduction of the amount of depolarization needed to fire the cell (voltage threshold minus resting potential). As opposed to the mechanisms reported in mammalian neurons, no changes in the frequency adaptation or the post-train afterhyperpolarization were observed. The NA effects at the cellular level were not reproduced by noradrenergic agonists. Age- and species-dependent properties in the pharmacology of adrenergic receptors could be involved in this result. Cellular effects of NA in turtle cortex are similar to those described in mammals, although the increase in cellular excitability seems to be mediated by a different mechanism. Copyright 2004 S. Karger AG, Basel

A Wideband Fast Multipole Method for the two-dimensional complex Helmholtz equation

NASA Astrophysics Data System (ADS)

Cho, Min Hyung; Cai, Wei

2010-12-01

A Wideband Fast Multipole Method (FMM) for the 2D Helmholtz equation is presented. It can evaluate the interactions between N particles governed by the fundamental solution of 2D complex Helmholtz equation in a fast manner for a wide range of complex wave number k, which was not easy with the original FMM due to the instability of the diagonalized conversion operator. This paper includes the description of theoretical backgrounds, the FMM algorithm, software structures, and some test runs. Program summaryProgram title: 2D-WFMM Catalogue identifier: AEHI_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEHI_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 4636 No. of bytes in distributed program, including test data, etc.: 82 582 Distribution format: tar.gz Programming language: C Computer: Any Operating system: Any operating system with gcc version 4.2 or newer Has the code been vectorized or parallelized?: Multi-core processors with shared memory RAM: Depending on the number of particles N and the wave number k Classification: 4.8, 4.12 External routines: OpenMP ( http://openmp.org/wp/) Nature of problem: Evaluate interaction between N particles governed by the fundamental solution of 2D Helmholtz equation with complex k. Solution method: Multilevel Fast Multipole Algorithm in a hierarchical quad-tree structure with cutoff level which combines low frequency method and high frequency method. Running time: Depending on the number of particles N, wave number k, and number of cores in CPU. CPU time increases as N log N.

Fluoxetine Blocks Nav1.5 Channels via a Mechanism Similar to That of Class 1 Antiarrhythmics

PubMed Central

Poulin, Hugo; Bruhova, Iva; Timour, Quadiri; Theriault, Olivier; Beaulieu, Jean-Martin; Frassati, Dominique

2014-01-01

The voltage-gated Nav1.5 channel is essential for the propagation of action potentials in the heart. Malfunctions of this channel are known to cause hereditary diseases. It is a prime target for class 1 antiarrhythmic drugs and a number of antidepressants. Our study investigated the Nav1.5 blocking properties of fluoxetine, a selective serotonin reuptake inhibitor. Nav1.5 channels were expressed in HEK-293 cells, and Na+ currents were recorded using the patch-clamp technique. Dose-response curves of racemic fluoxetine (IC50 = 39 μM) and its optical isomers had a similar IC50 [40 and 47 μM for the (+) and (−) isomers, respectively]. Norfluoxetine, a fluoxetine metabolite, had a higher affinity than fluoxetine, with an IC50 of 29 μM. Fluoxetine inhibited currents in a frequency-dependent manner, shifted steady-state inactivation to more hyperpolarized potentials, and slowed the recovery of Nav1.5 from inactivation. Mutating a phenylalanine (F1760) and a tyrosine (Y1767) in the S6 segment of domain (D) IV (DIVS6) significantly reduced the affinity of fluoxetine and its frequency-dependent inhibition. We used a noninactivating Nav1.5 mutant to show that fluoxetine displays open-channel block behavior. The molecular model of fluoxetine in Nav1.5 was in agreement with mutational experiments in which F1760 and Y1767 were found to be the key residues in binding fluoxetine. We concluded that fluoxetine blocks Nav1.5 by binding to the class 1 antiarrhythmic site. The blocking of cardiac Na+ channels should be taken into consideration when prescribing fluoxetine alone or in association with other drugs that may be cardiotoxic or for patients with conduction disorders. PMID:25028482

Effective conductivity and permittivity of unsaturated porous materials in the frequency range 1 mHz–1GHz

PubMed Central

Revil, A

2013-01-01

A model combining low-frequency complex conductivity and high-frequency permittivity is developed in the frequency range from 1 mHz to 1 GHz. The low-frequency conductivity depends on pore water and surface conductivities. Surface conductivity is controlled by the electrical diffuse layer, the outer component of the electrical double layer coating the surface of the minerals. The frequency dependence of the effective quadrature conductivity shows three domains. Below a critical frequency fp, which depends on the dynamic pore throat size Λ, the quadrature conductivity is frequency dependent. Between fp and a second critical frequency fd, the quadrature conductivity is generally well described by a plateau when clay minerals are present in the material. Clay-free porous materials with a narrow grain size distribution are described by a Cole-Cole model. The characteristic frequency fd controls the transition between double layer polarization and the effect of the high-frequency permittivity of the material. The Maxwell-Wagner polarization is found to be relatively negligible. For a broad range of frequencies below 1 MHz, the effective permittivity exhibits a strong dependence with the cation exchange capacity and the specific surface area. At high frequency, above the critical frequency fd, the effective permittivity reaches a high-frequency asymptotic limit that is controlled by the two Archie's exponents m and n like the low-frequency electrical conductivity. The unified model is compared with various data sets from the literature and is able to explain fairly well a broad number of observations with a very small number of textural and electrochemical parameters. It could be therefore used to interpret induced polarization, induction-based electromagnetic methods, and ground penetrating radar data to characterize the vadose zone. PMID:23576823

NRIP enhances HPV gene expression via interaction with either GR or E2

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

Chang, Szu-Wei; Lu, Pei-Yu; Guo, Jih-Huong

We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, inmore » a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.« less

Arginase inhibition reduces interleukin-1β-stimulated vascular smooth muscle cell proliferation by increasing nitric oxide synthase-dependent nitric oxide production

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

Yoon, Jeongyeon; Ryoo, Sungwoo, E-mail: ryoosw08@kangwon.ac.kr

2013-06-07

Highlights: •Arginase inhibition suppressed proliferation of IL-1β-stimulated VSMCs in dose-dependent manner. •NO production from IL-1β-induced iNOS expression was augmented by arginase inhibition, reducing VSMC proliferation. •Incubation with cGMP analogues abolished IL-1β-dependent proliferation of VSMCs. -- Abstract: We investigated whether arginase inhibition suppressed interleukin (IL)-1β-stimulated proliferation in vascular smooth muscle cells (VSMCs) and the possible mechanisms involved. IL-1β stimulation increased VSMC proliferation, while the arginase inhibitor BEC and transfection of the antisense (AS) oligonucleotide against arginase I decreased VSMC proliferation and was associated with increased protein content of the cell cycle regulator p21Waf1/Cip1. IL-1β incubation induced inducible nitric oxide synthase (iNOS)more » mRNA expression and protein levels in a dose-dependent manner, but did not affect arginase I and II expression. Consistent with this data, IL-1β stimulation resulted in increase in NO production that was significantly augmented by arginase inhibition. The specific iNOS inhibitor 1400W abolished IL-1β-mediated NO production and further accentuated IL-1β-stimulated cell proliferation. Incubation with NO donors GSNO and DETA/NO in the presence of IL-1β abolished VSMCs proliferation and increased p21Waf1/Cip1 protein content. Furthermore, incubation with the cGMP analogue 8-Br-cGMP prevented IL-1β-induced VSMCs proliferation. In conclusion, arginase inhibition augmented iNOS-dependent NO production that resulted in suppression of IL-1β-induced VSMCs proliferation in a cGMP-dependent manner.« less

The calmodulin inhibitor CGS 9343B inhibits voltage-dependent K{sup +} channels in rabbit coronary arterial smooth muscle cells

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

Li, Hongliang; Hong, Da Hye; Kim, Han Sol

We investigated the effects of the calmodulin inhibitor CGS 9343B on voltage-dependent K{sup +} (Kv) channels using whole-cell patch clamp technique in freshly isolated rabbit coronary arterial smooth muscle cells. CGS 9343B inhibited Kv currents in a concentration-dependent manner, with a half-maximal inhibitory concentration (IC{sub 50}) value of 0.81 μM. The decay rate of Kv channel inactivation was accelerated by CGS 9343B. The rate constants of association and dissociation for CGS 9343B were 2.77 ± 0.04 μM{sup −1} s{sup −1} and 2.55 ± 1.50 s{sup −1}, respectively. CGS 9343B did not affect the steady-state activation curve, but shifted the inactivationmore » curve toward to a more negative potential. Train pulses (1 or 2 Hz) application progressively increased the CGS 9343B-induced Kv channel inhibition. In addition, the inactivation recovery time constant was increased in the presence of CGS 9343B, suggesting that CGS 9343B-induced inhibition of Kv channel was use-dependent. Another calmodulin inhibitor, W-13, did not affect Kv currents, and did not change the inhibitory effect of CGS 9343B on Kv current. Our results demonstrated that CGS 9343B inhibited Kv currents in a state-, time-, and use-dependent manner, independent of calmodulin inhibition. - Highlights: • We investigated the effects of CGS 9394B on Kv channels. • CGS 9394B inhibited Kv current in a state-, time-, and use-dependent manner. • Caution is required when using CGS 9394B in vascular function studies.« less

Anisotropy of the apparent frequency dependence of backscatter in formalin fixed human myocardium.

PubMed

Hall, C S; Verdonk, E D; Wickline, S A; Perez, J E; Miller, J G

1997-01-01

Measurements of the frequency dependence of ultrasonic backscatter are presented for specific angles of insonification for regions of infarcted and noninfarcted human myocardium. A 5-MHz transducer was used to insonify cylindrical cores taken from 7 noninfarcted regions and 12 infarcted regions of the left ventricular free wall of 6 formalin-fixed human hearts explanted because of ischemic cardiomyopathy. The dependence of apparent (uncompensated for diffraction effects and attenuation) backscatter on frequency was approximated by a power-law dependence, magnitude of B(f)2 = afn. Under ideal conditions in a lossless medium, the effect of not compensating for the effects of diffraction and attenuation leads to the value of n to be 2.0 for Rayleigh scatterers while the frequency dependence of the fully compensated backscatter coefficient would be f4. The value of n was determined over the frequency range, 3-7 MHz. Both nonifarcted and infarcted myocardium exhibited anisotropy of the frequency dependence of backscatter, with maxima occurring at angles that were perpendicular to the predominant myofiber direction and minima when parallel to the fibers. Perpendicular insonification yielded results for n of 1.8 +/- 0.1 for noninfarcted myocardium and 1.2 +/- 0.1 for infarcted myocardium while parallel insonification yielded results of 0.4 +/- 0.1 for noninfarcted and 0.0 +/- 0.1 for infarcted myocardium. The functional form of the angle-dependent backscatter is similar for both noninfarcted and infarcted myocardium, although the frequency dependence is clearly different for both tissue states for all angles of insonification. The results of this study indicate that the anisotropy of the frequency dependence of backscatter may play a significant role in ultrasonic imaging and is an important consideration for ultrasonic tissue characterization in myocardium.

Therapeutic potential of an anti-high mobility group box-1 monoclonal antibody in epilepsy.

PubMed

Zhao, Junli; Wang, Yi; Xu, Cenglin; Liu, Keyue; Wang, Ying; Chen, Liying; Wu, Xiaohua; Gao, Feng; Guo, Yi; Zhu, Junming; Wang, Shuang; Nishibori, Masahiro; Chen, Zhong

2017-08-01

Brain inflammation is a major factor in epilepsy, and the high mobility group box-1 (HMGB1) protein is known to contribute significantly to the generation of seizures. Here, we investigated the therapeutic potential of an anti-HMGB1 monoclonal antibody (mAb) in epilepsy. anti-HMGB1 mAb attenuated both acute seizure models (maximal electroshock seizure, pentylenetetrazole-induced and kindling-induced), and chronic epilepsy model (kainic acid-induced) in a dose-dependent manner. Meanwhile, the anti-HMGB1 mAb also attenuated seizure activities of human brain slices obtained from surgical resection from drug-resistant epilepsy patients. The mAb showed an anti-seizure effect with a long-term manner and appeared to be minimal side effects at even very high dose (no disrupted physical EEG rhythm and no impaired basic physical functions, such as body growth rate and thermoregulation). This anti-seizure effect of mAb results from its inhibition of translocated HMGB1 from nuclei following seizures, and the anti-seizure effect was absent in toll-like receptor 4 knockout (TLR4 -/- ) mice. Interestingly, the anti-HMGB1 mAb also showed a disease-modifying anti-epileptogenetic effect on epileptogenesis after status epileptics, which is indicated by reducing seizure frequency and improving the impaired cognitive function. These results indicate that the anti-HMGB1 mAb should be viewed as a very promising approach for the development of novel therapies to treat refractory epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Control of Inhibition by the Direct Action of Cannabinoids on GABAA Receptors.

PubMed

Golovko, Tatiana; Min, Rogier; Lozovaya, Natalia; Falconer, Caroline; Yatsenko, Natalia; Tsintsadze, Timur; Tsintsadze, Vera; Ledent, Catherine; Harvey, Robert J; Belelli, Delia; Lambert, Jeremy J; Rozov, Andrei; Burnashev, Nail

2015-09-01

Cannabinoids are known to regulate inhibitory synaptic transmission via activation of presynaptic G protein-coupled cannabinoid CB1 receptors (CB1Rs). Additionally, recent studies suggest that cannabinoids can also directly interact with recombinant GABAA receptors (GABAARs), potentiating currents activated by micromolar concentrations of γ-aminobutyric acid (GABA). However, the impact of this direct interaction on GABAergic inhibition in central nervous system is unknown. Here we report that currents mediated by recombinant GABAARs activated by high (synaptic) concentrations of GABA as well as GABAergic inhibitory postsynaptic currents (IPSCs) at neocortical fast spiking (FS) interneuron to pyramidal neuron synapses are suppressed by exogenous and endogenous cannabinoids in a CB1R-independent manner. This IPSC suppression may account for disruption of inhibitory control of pyramidal neurons by FS interneurons. At FS interneuron to pyramidal neuron synapses, endocannabinoids induce synaptic low-pass filtering of GABAAR-mediated currents evoked by high-frequency stimulation. The CB1R-independent suppression of inhibition is synapse specific. It does not occur in CB1R containing hippocampal cholecystokinin-positive interneuron to pyramidal neuron synapses. Furthermore, in contrast to synaptic receptors, the activity of extrasynaptic GABAARs in neocortical pyramidal neurons is enhanced by cannabinoids in a CB1R-independent manner. Thus, cannabinoids directly interact differentially with synaptic and extrasynaptic GABAARs, providing a potent novel context-dependent mechanism for regulation of inhibition. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Unsteady potential flow past a propeller blade section

NASA Technical Reports Server (NTRS)

Takallu, M. A.

1990-01-01

An analytical study was conducted to predict the effect of an oscillating stream on the time dependent sectional pressure and lift coefficients of a model propeller blade. The assumption is that as the blade sections encounter a wake, the actual angles of attack vary in a sinusoidal manner through the wake, thus each blade is exposed to an unsteady stream oscillating about a mean value at a certain reduced frequency. On the other hand, an isolated propeller at some angle of attack can experience periodic changes in the value of the flow angle causing unsteady loads on the blades. Such a flow condition requires the inclusion of new expressions in the formulation of the unsteady potential flow around the blade sections. These expressions account for time variation of angle of attack and total shed vortices in the wake of each airfoil section. It was found that the final expressions for the unsteady pressure distribution on each blade section are periodic and that the unsteady circulation and lift coefficients exhibit a hysteresis loop.

Effect of carbaryl on survival and development in Bombina orientalis (Boulenger) embryos.

PubMed

Kang, Han Seung; Park, Chan Jin; Gye, Myung Chan

2010-05-01

Bombina orientalis is one of the most common amphibians in the world and comprise a large proportion of their total number in Korea. B. orientalis, spawns in the farming regions at Spring when the massive application of agricultural chemicals occurs. Carbaryl, carbamate chemical is a slightly to highly toxic insecticide inhibiting acetylcholinesterase. The embryotoxicity and teratogenic effects of carbaryl on B. orientalis embryos were investigated at 5, 10, 50 and 100 muM. The survival rates of embryos at 312 h post fertilization were decreased with concentration dependent manner. Exposure to carbaryl produced 4 types of severe external abnormalities such as bent trunk, thick-set body, bent tail and ventral blister. At 5 muM carbaryl, a dose of no observed effect on embryonic survival, developmental abnormalities were significantly increased. The developmental abnormalities showed in order of frequency with bent trunk, thick-set body, bent tail and ventral blister. This result suggests that carbaryl is detrimental for embryonic survival and teratogenic by causing the axial skeletal defects in B. orientalis embryos.

Self-Organization of Embryonic Genetic Oscillators into Spatiotemporal Wave Patterns

PubMed Central

Tsiairis, Charisios D.; Aulehla, Alexander

2016-01-01

Summary In vertebrate embryos, somites, the precursor of vertebrae, form from the presomitic mesoderm (PSM), which is composed of cells displaying signaling oscillations. Cellular oscillatory activity leads to periodic wave patterns in the PSM. Here, we address the origin of such complex wave patterns. We employed an in vitro randomization and real-time imaging strategy to probe for the ability of cells to generate order from disorder. We found that, after randomization, PSM cells self-organized into several miniature emergent PSM structures (ePSM). Our results show an ordered macroscopic spatial arrangement of ePSM with evidence of an intrinsic length scale. Furthermore, cells actively synchronize oscillations in a Notch-signaling-dependent manner, re-establishing wave-like patterns of gene activity. We demonstrate that PSM cells self-organize by tuning oscillation dynamics in response to surrounding cells, leading to collective synchronization with an average frequency. These findings reveal emergent properties within an ensemble of coupled genetic oscillators. PMID:26871631

Localized removal of layers of metal, polymer, or biomaterial by ultrasound cavitation bubbles

PubMed Central

Fernandez Rivas, David; Verhaagen, Bram; Seddon, James R. T.; Zijlstra, Aaldert G.; Jiang, Lei-Meng; van der Sluis, Luc W. M.; Versluis, Michel; Lohse, Detlef; Gardeniers, Han J. G. E.

2012-01-01

We present an ultrasonic device with the ability to locally remove deposited layers from a glass slide in a controlled and rapid manner. The cleaning takes place as the result of cavitating bubbles near the deposited layers and not due to acoustic streaming. The bubbles are ejected from air-filled cavities micromachined in a silicon surface, which, when vibrated ultrasonically at a frequency of 200 kHz, generate a stream of bubbles that travel to the layer deposited on an opposing glass slide. Depending on the pressure amplitude, the bubble clouds ejected from the micropits attain different shapes as a result of complex bubble interaction forces, leading to distinct shapes of the cleaned areas. We have determined the removal rates for several inorganic and organic materials and obtained an improved efficiency in cleaning when compared to conventional cleaning equipment. We also provide values of the force the bubbles are able to exert on an atomic force microscope tip. PMID:23964308

Discrete Walsh Hadamard transform based visible watermarking technique for digital color images

NASA Astrophysics Data System (ADS)

Santhi, V.; Thangavelu, Arunkumar

2011-10-01

As the size of the Internet is growing enormously the illegal manipulation of digital multimedia data become very easy with the advancement in technology tools. In order to protect those multimedia data from unauthorized access the digital watermarking system is used. In this paper a new Discrete walsh Hadamard Transform based visible watermarking system is proposed. As the watermark is embedded in transform domain, the system is robust to many signal processing attacks. Moreover in this proposed method the watermark is embedded in tiling manner in all the range of frequencies to make it robust to compression and cropping attack. The robustness of the algorithm is tested against noise addition, cropping, compression, Histogram equalization and resizing attacks. The experimental results show that the algorithm is robust to common signal processing attacks and the observed peak signal to noise ratio (PSNR) of watermarked image is varying from 20 to 30 db depends on the size of the watermark.

Testing the genotoxicity of coking wastewater using Vicia faba and Hordeum vulgare bioassays.

PubMed

Dong, Yiru; Zhang, Jintun

2010-07-01

The coking wastewater induces severe environmental problems in China, however, its toxicity has not been well known. In the present study, the genotoxicity of coking wastewater was studied using Vicia faba and Hordeum vulgare root tip cytogenetic bioassays. Results show that the tested coking wastewater decreased the mitotic index, and significantly enhanced the frequencies of micronucleus, sister chromatid exchange and pycnotic cell in concentration-dependent manners. Exposure to the same concentration wastewater, the increasing ratios of above genetic injuries were higher in V. faba than that in H. vulgare. The results imply that coking wastewater is a genotoxic agent in plant cells and exposure to the wastewater in environment may pose a potential genotoxic risk to organisms. It also suggests that both bioassays can be used for testing the genotoxicity of coking wastewater, but the V. faba assay is more sensitive than H. vulgare assay during the process. Copyright (c) 2010. Published by Elsevier Inc.

Electroencephalogram-based indices applied to dogs' depth of anaesthesia monitoring.

PubMed

Brás, S; Georgakis, A; Ribeiro, L; Ferreira, D A; Silva, A; Antunes, L; Nunes, C S

2014-12-01

Hypnotic drug administration causes alterations in the electroencephalogram (EEG) in a dose-dependent manner. These changes cannot be identified easily in the raw EEG, therefore EEG based indices were adopted for assessing depth of anaesthesia (DoA). This study examines several indices for estimating dogs' DoA. Data (EEG, clinical end-points) were collected from 8 dogs anaesthetized with propofol. EEG was initially collected without propofol. Then, 100 ml h⁻¹ (1000 mg h⁻¹) of propofol 1% infusion rate was administered until a deep anaesthetic stage was reached. The infusion rate was temporarily increased to 200 ml h⁻¹ (2000 mg h⁻¹) to achieve 80% of burst suppression. The index performance was accessed by correlation coefficient with the propofol concentrations, and prediction probability with the anaesthetic clinical end-points. The temporal entropy and the averaged instantaneous frequency were the best indices because they exhibit: (a) strong correlations with propofol concentrations, (b) high probabilities of predicting anaesthesia clinical end-points. Copyright © 2014 Elsevier Ltd. All rights reserved.

Frequency-dependent polarization-angle-phase-shift in the microwave-induced magnetoresistance oscillations

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

Liu, Han-Chun; Ye, Tianyu; Mani, R. G.

2015-02-14

Linear polarization angle, θ, dependent measurements of the microwave radiation-induced oscillatory magnetoresistance, R{sub xx}, in high mobility GaAs/AlGaAs 2D electron devices have shown a θ dependence in the oscillatory amplitude along with magnetic field, frequency, and extrema-dependent phase shifts, θ{sub 0}. Here, we suggest a microwave frequency dependence of θ{sub 0}(f) using an analysis that averages over other smaller contributions, when those contributions are smaller than estimates of the experimental uncertainty.

Maintenance of genetic variation with a frequency-dependent selection model as compared to the overdominant model.

PubMed

Hedrick, P W

1972-12-01

A frequency-dependent selection model proposed by Huang, Singh and Kojima (1971) was found to be more effective at maintaining genetic variation in a finite population than the overdominant model. The fourth moment parameter of the distribution of unfixed states showed that there was a more platykurtic distribution for the frequency-dependent model. This agreed well with the expected gene frequency change found for an infinite population.

Tangeretin, a citrus polymethoxyflavonoid, induces apoptosis of human gastric cancer AGS cells through extrinsic and intrinsic signaling pathways.

PubMed

Dong, Yang; Cao, Aili; Shi, Jianrong; Yin, Peihao; Wang, Li; Ji, Guang; Xie, Jianqun; Wu, Dazheng

2014-04-01

Tangeretin, a natural polymethoxyflavone present in citrus peel oil, is known to have anticancer activities in breast cancer, colorectal carcinoma and lung carcinoma, yet, the underlying mechanisms of tangeretin in human gastric cancer AGS cells have not been investigated to date. In the present study, the apoptotic mechanisms of tangeretin in AGS cells were explored. It was observed that tangeretin increased the apoptotic rates of AGS cells following treatment with tangeretin for 48 h in a dose-dependent manner by Annexin V-FITC and PI double staining. In addition, characteristic apoptotic morphology such as nuclear shrinkage and apoptotic bodies was observed after Hoechst 33258 staining. Flow cytometric assay showed that treatment of AGS cells with tangeretin decreased the mitochondrial membrane potential (MMP) in a dose-dependent manner, which indicated that mitochondrial dysfunction was involved in the tangeretin-induced apoptosis. Caspase-3, -8 and -9 activities were increased by tangeretin in a dose-dependent manner. Western blotting showed that the protein levels of pro-apoptotic proteins including cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax, Bid, tBid, p53, p21/cip1, Fas and FasL were significantly upregulated by tangeretin. In addition, PFT-α (a p53 inhibitor) reduced the apoptotic rates and the expression of p53, p21, caspase-3 and caspase-9 induced by tangeretin, indicating that tangeretin-induced apoptosis was p53-dependent. In conclusion, these results suggest that tangeretin induces the apoptosis of AGS cells mainly through p53-dependent mitochondrial dysfunction and the Fas/FasL-mediated extrinsic pathway.

Brevicoryne brassicae aphids interfere with transcriptome responses of Arabidopsis thaliana to feeding by Plutella xylostella caterpillars in a density-dependent manner.

PubMed

Kroes, Anneke; Broekgaarden, Colette; Castellanos Uribe, Marcos; May, Sean; van Loon, Joop J A; Dicke, Marcel

2017-01-01

Plants are commonly attacked by multiple herbivorous species. Yet, little is known about transcriptional patterns underlying plant responses to multiple insect attackers feeding simultaneously. Here, we assessed transcriptomic responses of Arabidopsis thaliana plants to simultaneous feeding by Plutella xylostella caterpillars and Brevicoryne brassicae aphids in comparison to plants infested by P. xylostella caterpillars alone, using microarray analysis. We particularly investigated how aphid feeding interferes with the transcriptomic response to P. xylostella caterpillars and whether this interference is dependent on aphid density and time since aphid attack. Various JA-responsive genes were up-regulated in response to feeding by P. xylostella caterpillars. The additional presence of aphids, both at low and high densities, clearly affected the transcriptional plant response to caterpillars. Interestingly, some important modulators of plant defense signalling, including WRKY transcription factor genes and ABA-dependent genes, were differentially induced in response to simultaneous aphid feeding at low or high density compared with responses to P. xylostella caterpillars feeding alone. Furthermore, aphids affected the P. xylostella-induced transcriptomic response in a density-dependent manner, which caused an acceleration in plant response against dual insect attack at high aphid density compared to dual insect attack at low aphid density. In conclusion, our study provides evidence that aphids influence the caterpillar-induced transcriptional response of A. thaliana in a density-dependent manner. It highlights the importance of addressing insect density to understand how plant responses to single attackers interfere with responses to other attackers and thus underlines the importance of the dynamics of transcriptional plant responses to multiple herbivory.

Unsteady Pressures in a Transonic Fan Cascade Due to a Single Oscillating Airfoil

NASA Technical Reports Server (NTRS)

Lepicovsky, J.; McFarland, E. R.; Capece, V. R.; Hayden, J.

2002-01-01

An extensive set of unsteady pressure data was acquired along the midspan of a modern transonic fan blade for simulated flutter conditions. The data set was acquired in a nine-blade linear cascade with an oscillating middle blade to provide a database for the influence coefficient method to calculate instantaneous blade loadings. The cascade was set for an incidence of 10 dg. The data were acquired on three stationary blades on each side of the middle blade that was oscillated at an amplitude of 0.6 dg. The matrix of test conditions covered inlet Mach numbers of 0.5, 0.8, and 1.1 and the oscillation frequencies of 200, 300, 400, and 500 Hz. A simple quasiunsteady two-dimensional computer simulation was developed to aid in the running of the experimental program. For high Mach number subsonic inlet flows the blade pressures exhibit very strong, low-frequency, self-induced oscillations even without forced blade oscillations, while for low subsonic and supersonic inlet Mach numbers the blade pressure unsteadiness is quite low. The amplitude of forced pressure fluctuations on neighboring stationary blades strongly depends on the inlet Mach number and forcing frequency. The flowfield behavior is believed to be governed by strong nonlinear effects due to a combination of viscosity, compressibility, and unsteadiness. Therefore, the validity of the quasi-unsteady simplified computer simulation is limited to conditions when the flowfield is behaving in a linear, steady manner. Finally, an extensive set of unsteady pressure data was acquired to help development and verification of computer codes for blade flutter effects.

Resonance Tube Phonation in Water-the Effect of Tube Diameter and Water Depth on Back Pressure and Bubble Characteristics at Different Airflows.

PubMed

Wistbacka, Greta; Andrade, Pedro Amarante; Simberg, Susanna; Hammarberg, Britta; Södersten, Maria; Švec, Jan G; Granqvist, Svante

2018-01-01

Resonance tube phonation with tube end in water is a voice therapy method in which the patient phonates through a glass tube, keeping the free end of the tube submerged in water, creating bubbles. The purpose of this experimental study was to determine flow-pressure relationship, flow thresholds between bubble types, and bubble frequency as a function of flow and back volume. A flow-driven vocal tract simulator was used for recording the back pressure produced by resonance tubes with inner diameters of 8 and 9 mm submerged at water depths of 0-7 cm. Visual inspection of bubble types through video recording was also performed. The static back pressure was largely determined by the water depth. The narrower tube provided a slightly higher back pressure for a given flow and depth. The amplitude of the pressure oscillations increased with flow and depth. Depending on flow, the bubbles were emitted from the tube in three distinct types with increasing flow: one by one, pairwise, and in a chaotic manner. The bubble frequency was slightly higher for the narrower tube. An increase in back volume led to a decrease in bubble frequency. This study provides data on the physical properties of resonance tube phonation with the tube end in water. This information will be useful in future research when looking into the possible effects of this type of voice training. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Wireless sensor network

NASA Astrophysics Data System (ADS)

Perotti, Jose M.; Lucena, Angel R.; Mullenix, Pamela A.; Mata, Carlos T.

2006-05-01

Current and future requirements of aerospace sensors and transducers demand the design and development of a new family of sensing devices, with emphasis on reduced weight, power consumption, and physical size. This new generation of sensors and transducers will possess a certain degree of intelligence in order to provide the end user with critical data in a more efficient manner. Communication between networks of traditional or next-generation sensors can be accomplished by a Wireless Sensor Network (WSN) developed by NASA's Instrumentation Branch and ASRC Aerospace Corporation at Kennedy Space Center (KSC), consisting of at least one central station and several remote stations and their associated software. The central station is application-dependent and can be implemented on different computer hardware, including industrial, handheld, or PC-104 single-board computers, on a variety of operating systems: embedded Windows, Linux, VxWorks, etc. The central stations and remote stations share a similar radio frequency (RF) core module hardware that is modular in design. The main components of the remote stations are an RF core module, a sensor interface module, batteries, and a power management module. These modules are stackable, and a common bus provides the flexibility to stack other modules for additional memory, increased processing, etc. WSN can automatically reconfigure to an alternate frequency if interference is encountered during operation. In addition, the base station will autonomously search for a remote station that was perceived to be lost, using relay stations and alternate frequencies. Several wireless remote-station types were developed and tested in the laboratory to support different sensing technologies, such as resistive temperature devices, silicon diodes, strain gauges, pressure transducers, and hydrogen leak detectors.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism affects sympathetic tone in a gender-specific way.

PubMed

Chang, Chuan-Chia; Chang, Hsin-An; Chen, Tien-Yu; Fang, Wen-Hui; Huang, San-Yuan

2014-09-01

The Val/Val genotype of the brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) has been reported to affect human anxiety-related phenotypes. Substantial research has demonstrated that anxiety is associated with sympathetic activation, while sex steroid hormones have been shown to exert differential actions in regulating BDNF expression. Thus, we examined whether the BDNF variant modulates autonomic function in a gender-dependent manner. From 708 adults initially screened for medical and psychiatric illnesses, a final cohort of 583 drug-free healthy Han Chinese (355 males, 228 females; age 34.43±8.42 years) was recruited for BDNF genotyping (Val/Val: 136, 23.3%, Val/Met: 294, 50.4%, and Met/Met: 153, 26.2%). Time- and frequency-domain analyses of heart rate variability (HRV) were used to assess autonomic outflow to the heart. Significant genotype-by-gender interaction effects were found on HRV indices. Even after adjusting for possible confounders, male participants bearing the Val/Val genotype had significant increases in low frequency (LF), LF% and LF/high frequency (HF) ratio, indicating altered sympathovagal balance with increased sympathetic modulation, compared to male Met/Met homozygotes. Females, however, showed an opposite but non-significant pattern. These results suggest that the studied BDNF polymorphism is associated with sympathetic control in a gender-specific way. The findings here support the view that male subjects with the Val/Val genotype have increased risk of anxiety by association with sympathetic activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cell type- and activity-dependent extracellular correlates of intracellular spiking

PubMed Central

Perin, Rodrigo; Buzsáki, György; Markram, Henry; Koch, Christof

2015-01-01

Despite decades of extracellular action potential (EAP) recordings monitoring brain activity, the biophysical origin and inherent variability of these signals remain enigmatic. We performed whole cell patch recordings of excitatory and inhibitory neurons in rat somatosensory cortex slice while positioning a silicon probe in their vicinity to concurrently record intra- and extracellular voltages for spike frequencies under 20 Hz. We characterize biophysical events and properties (intracellular spiking, extracellular resistivity, temporal jitter, etc.) related to EAP recordings at the single-neuron level in a layer-specific manner. Notably, EAP amplitude was found to decay as the inverse of distance between the soma and the recording electrode with similar (but not identical) resistivity across layers. Furthermore, we assessed a number of EAP features and their variability with spike activity: amplitude (but not temporal) features varied substantially (∼30–50% compared with mean) and nonmonotonically as a function of spike frequency and spike order. Such EAP variation only partly reflects intracellular somatic spike variability and points to the plethora of processes contributing to the EAP. Also, we show that the shape of the EAP waveform is qualitatively similar to the negative of the temporal derivative to the intracellular somatic voltage, as expected from theory. Finally, we tested to what extent EAPs can impact the lowpass-filtered part of extracellular recordings, the local field potential (LFP), typically associated with synaptic activity. We found that spiking of excitatory neurons can significantly impact the LFP at frequencies as low as 20 Hz. Our results question the common assertion that the LFP acts as proxy for synaptic activity. PMID:25995352

Parental overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner.

PubMed

Otani, Koichi; Suzuki, Akihito; Matsumoto, Yoshihiko; Shibuya, Naoshi; Sadahiro, Ryoichi; Enokido, Masanori

2013-12-24

It has been suggested that dysfunctional attitudes, cognitive vulnerability to depression, have developmental origins. The present study examined the effects of parental rearing on dysfunctional attitudes in three areas of life with special attention to gender specificity. The subjects were 665 Japanese healthy volunteers. Dysfunctional attitudes were assessed by the 24-item Dysfunctional Attitude Scale, which has the Achievement, Dependency and Self-control subscales. Perceived parental rearing was assessed by the Parental Bonding Instrument, which has the Care and Protection subscales. Higher scores of the Achievement (β = 0.293, p < 0.01) and Dependency (β = 0.224, p < 0.05) subscales were correlated with higher scores of the Protection subscale in the combination of mother and daughter, but not in other combinations of parents and recipients. Scores of the Self-control subscale were not correlated with paternal or maternal rearing scores. The present study suggests that parental overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner.

Macroscopic Models of Local Field Potentials and the Apparent 1/f Noise in Brain Activity

PubMed Central

Bédard, Claude; Destexhe, Alain

2009-01-01

The power spectrum of local field potentials (LFPs) has been reported to scale as the inverse of the frequency, but the origin of this 1/f noise is at present unclear. Macroscopic measurements in cortical tissue demonstrated that electric conductivity (as well as permittivity) is frequency-dependent, while other measurements failed to evidence any dependence on frequency. In this article, we propose a model of the genesis of LFPs that accounts for the above data and contradictions. Starting from first principles (Maxwell equations), we introduce a macroscopic formalism in which macroscopic measurements are naturally incorporated, and also examine different physical causes for the frequency dependence. We suggest that ionic diffusion primes over electric field effects, and is responsible for the frequency dependence. This explains the contradictory observations, and also reproduces the 1/f power spectral structure of LFPs, as well as more complex frequency scaling. Finally, we suggest a measurement method to reveal the frequency dependence of current propagation in biological tissue, and which could be used to directly test the predictions of this formalism. PMID:19348744

Temperature dependence of frequency response characteristics in organic field-effect transistors

NASA Astrophysics Data System (ADS)

Lu, Xubing; Minari, Takeo; Liu, Chuan; Kumatani, Akichika; Liu, J.-M.; Tsukagoshi, Kazuhito

2012-04-01

The frequency response characteristics of semiconductor devices play an essential role in the high-speed operation of electronic devices. We investigated the temperature dependence of dynamic characteristics in pentacene-based organic field-effect transistors and metal-insulator-semiconductor capacitors. As the temperature decreased, the capacitance-voltage characteristics showed large frequency dispersion and a negative shift in the flat-band voltage at high frequencies. The cutoff frequency shows Arrhenius-type temperature dependence with different activation energy values for various gate voltages. These phenomena demonstrate the effects of charge trapping on the frequency response characteristics, since decreased mobility prevents a fast charge response for alternating current signals at low temperatures.

28Si total body irradiation injures bone marrow hematopoietic stem cells via induction of cellular apoptosis

NASA Astrophysics Data System (ADS)

Chang, Jianhui; Feng, Wei; Wang, Yingying; Allen, Antiño R.; Turner, Jennifer; Stewart, Blair; Raber, Jacob; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

2017-05-01

Long-term space mission exposes astronauts to a radiation environment with potential health hazards. High-energy charged particles (HZE), including 28Si nuclei in space, have deleterious effects on cells due to their characteristics with high linear energy transfer and dense ionization. The influence of 28Si ions contributes more than 10% to the radiation dose equivalent in the space environment. Understanding the biological effects of 28Si irradiation is important to assess the potential health hazards of long-term space missions. The hematopoietic system is highly sensitive to radiation injury and bone marrow (BM) suppression is the primary life-threatening injuries after exposure to a moderate dose of radiation. Therefore, in the present study we investigated the acute effects of low doses of 28Si irradiation on the hematopoietic system in a mouse model. Specifically, 6-month-old C57BL/6 J mice were exposed to 0.3, 0.6 and 0.9 Gy 28Si (600 MeV) total body irradiation (TBI). The effects of 28Si TBI on BM hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) were examined four weeks after the exposure. The results showed that exposure to 28Si TBI dramatically reduced the frequencies and numbers of HSCs in irradiated mice, compared to non-irradiated controls, in a radiation dose-dependent manner. In contrast, no significant changes were observed in BM HPCs regardless of radiation doses. Furthermore, irradiated HSCs exhibited a significant impairment in clonogenic ability. These acute effects of 28Si irradiation on HSCs may be attributable to radiation-induced apoptosis of HSCs, because HSCs, but not HPCs, from irradiated mice exhibited a significant increase in apoptosis in a radiation dose-dependent manner. However, exposure to low doses of 28Si did not result in an increased production of reactive oxygen species and DNA damage in HSCs and HPCs. These findings indicate that exposure to 28Si irradiation leads to acute HSC damage.

Qualitative models of seat discomfort including static and dynamic factors.

PubMed

Ebe, K; Griffin, M J

2000-06-01

Judgements of overall seating comfort in dynamic conditions sometimes correlate better with the static characteristics of a seat than with measures of the dynamic environment. This study developed qualitative models of overall seat discomfort to include both static and dynamic seat characteristics. A dynamic factor that reflected how vibration discomfort increased as vibration magnitude increased was combined with a static seat factor which reflected seating comfort without vibration. The ability of the model to predict the relative and overall importance of dynamic and static seat characteristics on comfort was tested in two experiments. A paired comparison experiment, using four polyurethane foam cushions (50, 70, 100, 120 mm thick), provided different static and dynamic comfort when 12 subjects were exposed to one-third octave band random vertical vibration with centre frequencies of 2.5 and 5.5 Hz, at magnitudes of 0.00, 0.25 and 0.50 m x s(-2) rms measured beneath the foam samples. Subject judgements of the relative discomfort of the different conditions depended on both static and dynamic characteristics in a manner consistent with the model. The effect of static and dynamic seat factors on overall seat discomfort was investigated by magnitude estimation using three foam cushions (of different hardness) and a rigid wooden seat at six vibration magnitudes with 20 subjects. Static seat factors (i.e. cushion stiffness) affected the manner in which vibration influenced the overall discomfort: cushions with lower stiffness were more comfortable and more sensitive to changes in vibration magnitude than those with higher stiffness. The experiments confirm that judgements of overall seat discomfort can be affected by both the static and dynamic characteristics of a seat, with the effect depending on vibration magnitude: when vibration magnitude was low, discomfort was dominated by static seat factors; as the vibration magnitude increased, discomfort became dominated by dynamic factors.

Intra-oral administration of rebamipide liquid prevents tongue injuries induced by X-ray irradiation in rats.

PubMed

Nakashima, Takako; Uematsu, Naoya; Sakurai, Kazushi

2017-07-01

Oral mucositis is a common and serious side effect in patients who undergo cytotoxic cancer therapies. The purpose of this study was to investigate the preventive effects of rebamipide on radiation-induced glossitis model in rats. Glossitis was induced by a single dose of 15 Gy of X-rays to the snouts of rats (day 0). A novel form of rebamipide liquid comprising its submicronized crystals was administered intra-orally. The preventive effect of rebamipide on tongue injuries was macroscopically evaluated on day 7 following irradiation. The pretreatment period, dosing frequency, and dose dependency of rebamipide were examined. Two percent rebamipide liquid, administered six times a day for 14 days from day -7 to day 6, significantly decreased the ulcer-like area. However, no significant effect was observed when rebamipide was given either from day -4 or from day -1. Four or six times daily, 2% rebamipide liquid significantly inhibited the ulcer-like injury area ratio, but not when given twice daily. Rebamipide liquid, 1, 2, and 4% six times daily significantly reduced the area ratios of total injury and ulcer-like injury in a dose-dependent manner. Gene expression and protein levels of proinflammatory cytokines and chemokines were dramatically elevated in the irradiated tongues of control rats on day 7 without rebamipide liquid treatment. They were dose-dependently and significantly suppressed in rebamipide-treated groups. Intra-oral administration of rebamipide liquid prevented oral mucositis dose-dependently accompanied by the suppression of inflammatory expression in the radiation-induced rats' glossitis model.

An asymptotic preserving unified gas kinetic scheme for frequency-dependent radiative transfer equations

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

Sun, Wenjun, E-mail: sun_wenjun@iapcm.ac.cn; Jiang, Song, E-mail: jiang@iapcm.ac.cn; Xu, Kun, E-mail: makxu@ust.hk

This paper presents an extension of previous work (Sun et al., 2015 [22]) of the unified gas kinetic scheme (UGKS) for the gray radiative transfer equations to the frequency-dependent (multi-group) radiative transfer system. Different from the gray radiative transfer equations, where the optical opacity is only a function of local material temperature, the simulation of frequency-dependent radiative transfer is associated with additional difficulties from the frequency-dependent opacity. For the multiple frequency radiation, the opacity depends on both the spatial location and the frequency. For example, the opacity is typically a decreasing function of frequency. At the same spatial region themore » transport physics can be optically thick for the low frequency photons, and optically thin for high frequency ones. Therefore, the optical thickness is not a simple function of space location. In this paper, the UGKS for frequency-dependent radiative system is developed. The UGKS is a finite volume method and the transport physics is modeled according to the ratio of the cell size to the photon's frequency-dependent mean free path. When the cell size is much larger than the photon's mean free path, a diffusion solution for such a frequency radiation will be obtained. On the other hand, when the cell size is much smaller than the photon's mean free path, a free transport mechanism will be recovered. In the regime between the above two limits, with the variation of the ratio between the local cell size and photon's mean free path, the UGKS provides a smooth transition in the physical and frequency space to capture the corresponding transport physics accurately. The seemingly straightforward extension of the UGKS from the gray to multiple frequency radiation system is due to its intrinsic consistent multiple scale transport modeling, but it still involves lots of work to properly discretize the multiple groups in order to design an asymptotic preserving (AP) scheme in all regimes. The current scheme is tested in a few frequency-dependent radiation problems, and the results are compared with the solutions from the well-defined implicit Monte Carlo (IMC) method. The UGKS is much more efficient than IMC, and the computational times of both schemes for all test cases are listed. The UGKS seems to be the first discrete ordinate method (DOM) for the accurate capturing of multiple frequency radiative transport physics from ballistic particle motion to the diffusive wave propagation.« less

Amplitude Variation of Bottom Simulating Reflection with Respect to Frequency - Transitional Base or Attenuation?

USGS Publications Warehouse

Lee, Myung W.

2007-01-01

The amplitude of a bottom simulating reflection (BSR), which occurs near the phase boundary between gas hydrate-bearing sediments and underlying gas-filled sediments, strongly depends on the frequency content of a seismic signal, as well as the impedance contrast across the phase boundary. A strong-amplitude BSR, detectable in a conventional seismic profile, is a good indicator of the presence of free gas beneath the phase boundary. However, the BSR as observed in low-frequency multichannel seismic data is generally difficult to identify in high-frequency, single-channel seismic data. To investigate the frequency dependence of BSR amplitudes, single-channel seismic data acquired with an air gun source at Blake Ridge, which is located off the shore of South Carolina, were analyzed in the frequency range of 10-240 Hz. The frequency-dependent impedance contrast caused by the velocity dispersion in partially gas saturated sediments is important to accurately analyze BSR amplitude. Analysis indicates that seismic attenuation of gas hydrate-bearing sediments, velocity dispersion, and a transitional base all contribute to the frequency-dependent BSR amplitude variation in the frequency range of 10-500 Hz. When velocity dispersion is incorporated into the BSR amplitude analysis, the frequency-dependent BSR amplitude at Blake Ridge can be explained with gas hydrate-bearing sediments having a quality factor of about 250 and a transitional base with a thickness of about 1 meter.

Frequency-dependent selection predicts patterns of radiations and biodiversity.

PubMed

Melián, Carlos J; Alonso, David; Vázquez, Diego P; Regetz, James; Allesina, Stefano

2010-08-26

Most empirical studies support a decline in speciation rates through time, although evidence for constant speciation rates also exists. Declining rates have been explained by invoking pre-existing niches, whereas constant rates have been attributed to non-adaptive processes such as sexual selection and mutation. Trends in speciation rate and the processes underlying it remain unclear, representing a critical information gap in understanding patterns of global diversity. Here we show that the temporal trend in the speciation rate can also be explained by frequency-dependent selection. We construct a frequency-dependent and DNA sequence-based model of speciation. We compare our model to empirical diversity patterns observed for cichlid fish and Darwin's finches, two classic systems for which speciation rates and richness data exist. Negative frequency-dependent selection predicts well both the declining speciation rate found in cichlid fish and explains their species richness. For groups like the Darwin's finches, in which speciation rates are constant and diversity is lower, speciation rate is better explained by a model without frequency-dependent selection. Our analysis shows that differences in diversity may be driven by incipient species abundance with frequency-dependent selection. Our results demonstrate that genetic-distance-based speciation and frequency-dependent selection are sufficient to explain the high diversity observed in natural systems and, importantly, predict decay through time in speciation rate in the absence of pre-existing niches.

40 CFR 122.26 - Storm water discharges (applicable to State NPDES programs, see § 123.25).

Code of Federal Regulations, 2010 CFR

2010-07-01

... pursuant to section 313 of title III of SARA; fertilizers; pesticides; and waste products such as ashes... and access areas, areas where pesticides, herbicides, soil conditioners and fertilizers are applied... location, manner and frequency in which pesticides, herbicides, soil conditioners and fertilizers are...

Student Teachers' Computer Use during Practicum.

ERIC Educational Resources Information Center

Wang, Yu-mei; Holthaus, Patricia

This study was designed to investigate the use of computers by student teachers in their practicums. Student teachers (n=120) in two public universities in the United States answered a questionnaire that covered: the manner and frequency of computer use, student teachers' perception of their training, their attitudes toward the role of the…

9 CFR 303.2 - Experimentation: Intensity of inspection coverage.

Code of Federal Regulations, 2014 CFR

2014-01-01

... inspection coverage. 303.2 Section 303.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... under the Act and regulations is required, the frequency with which and the manner in which meat food... by Program employees is to be based on considerations relevant to effective regulation of meat food...

47 CFR 27.3 - Other applicable rule parts.

Code of Federal Regulations, 2013 CFR

2013-10-01

... to the Wireless Communications Service include the following: (a) Part 0. This part describes the... authorization. (d) Part 5. This part contains rules prescribing the manner in which parts of the radio frequency...) Part 101. This part sets forth the requirements and conditions applicable to fixed microwave services...

47 CFR 27.3 - Other applicable rule parts.

Code of Federal Regulations, 2012 CFR

2012-10-01

... to the Wireless Communications Service include the following: (a) Part 0. This part describes the... authorization. (d) Part 5. This part contains rules prescribing the manner in which parts of the radio frequency...) Part 101. This part sets forth the requirements and conditions applicable to fixed microwave services...

47 CFR 27.3 - Other applicable rule parts.

Code of Federal Regulations, 2014 CFR

2014-10-01

... to the Wireless Communications Service include the following: (a) Part 0. This part describes the... authorization. (d) Part 5. This part contains rules prescribing the manner in which parts of the radio frequency...) Part 101. This part sets forth the requirements and conditions applicable to fixed microwave services...

Recovery of Phytophthora ramorum in plant tissue with mixed infections

USDA-ARS?s Scientific Manuscript database

This study was performed to investigate the frequency with which P. ramorum would be isolated from host tissue co-infected with P. ramorum as well as an indigenous Phytophthora species or P. kernoviae. Three separate experiments were tested in a similar manner using different combinations of pathog...

Maintenance of Genetic Variation with a Frequency-Dependent Selection Model as Compared to the Overdominant Model

PubMed Central

Hedrick, Philip W.

1972-01-01

A frequency-dependent selection model proposed by Huang, Singh and Kojima (1971) was found to be more effective at maintaining genetic variation in a finite population than the overdominant model. The fourth moment parameter of the distribution of unfixed states showed that there was a more platykurtic distribution for the frequency-dependent model. This agreed well with the expected gene frequency change found for an infinite population. PMID:4652882

Study on Frequency Dependency of ON-Resistance and Pulse-Loss Calculation of MOSFETs for Switch Mode Power Supply

NASA Astrophysics Data System (ADS)

Yamamura, Hideho; Sato, Ryohei; Iwata, Yoshiharu

Global efforts toward energy conservation, increasing data centers, and the increasing use of IT equipments are leading to a demand in reduced power consumption of equipments, and power efficiency improvement of power supply units is becoming a necessity. MOSFETs are widely used for their low ON-resistances. Power efficiency is designed using time-domain circuit simulators, except for transformer copper-loss, which has frequency dependency which is calculated separately using methods based on skin and proximity effects. As semiconductor technology reduces the ON-resistance of MOSFETs, frequency dependency due to the skin effect or proximity effect is anticipated. In this study, ON-resistance of MOSFETs are measured and frequency dependency is confirmed. Power loss against rectangular current pulse is calculated. The calculation method for transformer copper-loss is expanded to MOSFETs. A frequency function for the resistance model is newly developed and parametric calculation is enabled. Acceleration of calculation is enabled by eliminating summation terms. Using this method, it is shown that the frequency dependent component of the measured MOSFETs increases the dissipation from 11% to 32% at a switching frequency of 100kHz. From above, this paper points out the importance of the frequency dependency of MOSFETs' ON-resistance, provides means of calculating its pulse losses, and improves loss calculation accuracy of SMPSs.

The Frequency Spectral Properties of Electrode-Skin Contact Impedance on Human Head and Its Frequency-Dependent Effects on Frequency-Difference EIT in Stroke Detection from 10Hz to 1MHz.

PubMed

Yang, Lin; Dai, Meng; Xu, Canhua; Zhang, Ge; Li, Weichen; Fu, Feng; Shi, Xuetao; Dong, Xiuzhen

2017-01-01

Frequency-difference electrical impedance tomography (fdEIT) reconstructs frequency-dependent changes of a complex impedance distribution. It has a potential application in acute stroke detection because there are significant differences in impedance spectra between stroke lesions and normal brain tissues. However, fdEIT suffers from the influences of electrode-skin contact impedance since contact impedance varies greatly with frequency. When using fdEIT to detect stroke, it is critical to know the degree of measurement errors or image artifacts caused by contact impedance. To our knowledge, no study has systematically investigated the frequency spectral properties of electrode-skin contact impedance on human head and its frequency-dependent effects on fdEIT used in stroke detection within a wide frequency band (10 Hz-1 MHz). In this study, we first measured and analyzed the frequency spectral properties of electrode-skin contact impedance on 47 human subjects' heads within 10 Hz-1 MHz. Then, we quantified the frequency-dependent effects of contact impedance on fdEIT in stroke detection in terms of the current distribution beneath the electrodes and the contact impedance imbalance between two measuring electrodes. The results showed that the contact impedance at high frequencies (>100 kHz) significantly changed the current distribution beneath the electrode, leading to nonnegligible errors in boundary voltages and artifacts in reconstructed images. The contact impedance imbalance at low frequencies (<1 kHz) also caused significant measurement errors. We conclude that the contact impedance has critical frequency-dependent influences on fdEIT and further studies on reducing such influences are necessary to improve the application of fdEIT in stroke detection.

The Frequency Spectral Properties of Electrode-Skin Contact Impedance on Human Head and Its Frequency-Dependent Effects on Frequency-Difference EIT in Stroke Detection from 10Hz to 1MHz

PubMed Central

Zhang, Ge; Li, Weichen; Fu, Feng; Shi, Xuetao; Dong, Xiuzhen

2017-01-01

Frequency-difference electrical impedance tomography (fdEIT) reconstructs frequency-dependent changes of a complex impedance distribution. It has a potential application in acute stroke detection because there are significant differences in impedance spectra between stroke lesions and normal brain tissues. However, fdEIT suffers from the influences of electrode-skin contact impedance since contact impedance varies greatly with frequency. When using fdEIT to detect stroke, it is critical to know the degree of measurement errors or image artifacts caused by contact impedance. To our knowledge, no study has systematically investigated the frequency spectral properties of electrode-skin contact impedance on human head and its frequency-dependent effects on fdEIT used in stroke detection within a wide frequency band (10 Hz-1 MHz). In this study, we first measured and analyzed the frequency spectral properties of electrode-skin contact impedance on 47 human subjects’ heads within 10 Hz-1 MHz. Then, we quantified the frequency-dependent effects of contact impedance on fdEIT in stroke detection in terms of the current distribution beneath the electrodes and the contact impedance imbalance between two measuring electrodes. The results showed that the contact impedance at high frequencies (>100 kHz) significantly changed the current distribution beneath the electrode, leading to nonnegligible errors in boundary voltages and artifacts in reconstructed images. The contact impedance imbalance at low frequencies (<1 kHz) also caused significant measurement errors. We conclude that the contact impedance has critical frequency-dependent influences on fdEIT and further studies on reducing such influences are necessary to improve the application of fdEIT in stroke detection. PMID:28107524

P-type Ca2+ channels mediate excitatory and inhibitory synaptic transmitter release in crayfish muscle.

PubMed

Araque, A; Clarac, F; Buño, W

1994-05-10

The toxin fraction (FTX) and peptide omega-Aga-IVA from the venom of the funnel-web spider Agelenopsis aperta, as well as a synthetic analogue of FTX, specifically block the P-type voltage-dependent Ca2+ channel (VDCC). The effects of these toxins on synaptic transmission were studied in the neuromuscular synapses of the crayfish opener muscle, which has a single excitatory and a single inhibitory motoneuron. FTX selectively and reversibly blocked excitatory and inhibitory postsynaptic currents and potentials in a dose-dependent manner. FTX had no effect on (i) resting and postsynaptic membrane conductance, (ii) postsynaptic L-type VDCC, and (iii) both glutamate- and gamma-aminobutyric acid-induced postsynaptic responses. Mean amplitude and frequency of miniature postsynaptic potentials were unchanged by FTX. The postsynaptic VDCC was inhibited by nifedipine, a selective dihydropyridine antagonist of L-type VDCC, whereas synaptic transmission was unaffected. Transmission was also undisturbed by omega-conotoxin, suggesting that N-type VDCCs are not involved. The peptide omega-Aga-IVA blocked excitatory and inhibitory transmission without affecting postsynaptic VDCC. Synaptic transmission was also blocked by synthetic FTX. We conclude that presynaptic P-type VDCCs are involved in both evoked excitatory and inhibitory transmitter release in crayfish neuromuscular synapses.

P-type Ca2+ channels mediate excitatory and inhibitory synaptic transmitter release in crayfish muscle.

PubMed Central

Araque, A; Clarac, F; Buño, W

1994-01-01

The toxin fraction (FTX) and peptide omega-Aga-IVA from the venom of the funnel-web spider Agelenopsis aperta, as well as a synthetic analogue of FTX, specifically block the P-type voltage-dependent Ca2+ channel (VDCC). The effects of these toxins on synaptic transmission were studied in the neuromuscular synapses of the crayfish opener muscle, which has a single excitatory and a single inhibitory motoneuron. FTX selectively and reversibly blocked excitatory and inhibitory postsynaptic currents and potentials in a dose-dependent manner. FTX had no effect on (i) resting and postsynaptic membrane conductance, (ii) postsynaptic L-type VDCC, and (iii) both glutamate- and gamma-aminobutyric acid-induced postsynaptic responses. Mean amplitude and frequency of miniature postsynaptic potentials were unchanged by FTX. The postsynaptic VDCC was inhibited by nifedipine, a selective dihydropyridine antagonist of L-type VDCC, whereas synaptic transmission was unaffected. Transmission was also undisturbed by omega-conotoxin, suggesting that N-type VDCCs are not involved. The peptide omega-Aga-IVA blocked excitatory and inhibitory transmission without affecting postsynaptic VDCC. Synaptic transmission was also blocked by synthetic FTX. We conclude that presynaptic P-type VDCCs are involved in both evoked excitatory and inhibitory transmitter release in crayfish neuromuscular synapses. Images PMID:7910404

Modelling conflicts with cluster dynamics in networks

NASA Astrophysics Data System (ADS)

Tadić, Bosiljka; Rodgers, G. J.

2010-12-01

We introduce cluster dynamical models of conflicts in which only the largest cluster can be involved in an action. This mimics the situations in which an attack is planned by a central body, and the largest attack force is used. We study the model in its annealed random graph version, on a fixed network, and on a network evolving through the actions. The sizes of actions are distributed with a power-law tail, however, the exponent is non-universal and depends on the frequency of actions and sparseness of the available connections between units. Allowing the network reconstruction over time in a self-organized manner, e.g., by adding the links based on previous liaisons between units, we find that the power-law exponent depends on the evolution time of the network. Its lower limit is given by the universal value 5/2, derived analytically for the case of random fragmentation processes. In the temporal patterns behind the size of actions we find long-range correlations in the time series of the number of clusters and the non-trivial distribution of time that a unit waits between two actions. In the case of an evolving network the distribution develops a power-law tail, indicating that through repeated actions, the system develops an internal structure with a hierarchy of units.

Discovery of a vezatin-like protein for dynein-mediated early endosome transport

PubMed Central

Yao, Xuanli; Arst, Herbert N.; Wang, Xiangfeng; Xiang, Xin

2015-01-01

Early endosomes are transported bidirectionally by cytoplasmic dynein and kinesin-3, but how the movements are regulated in vivo remains unclear. Here our forward genetic study led to the discovery of VezA, a vezatin-like protein in Aspergillus nidulans, as a factor critical for early endosome distribution. Loss of vezA causes an abnormal accumulation of early endosomes at the hyphal tip, where microtubule plus ends are located. This abnormal accumulation depends on kinesin-3 and is due to a decrease in the frequency but not the speed of dynein-mediated early endosome movement. VezA-GFP signals are enriched at the hypha tip in an actin-dependent manner but are not obviously associated with early endosomes, thus differing from the early endosome association of the cargo adapter HookA (Hook in A. nidulans). On loss of VezA, HookA associates normally with early endosomes, but the interaction between dynein-dynactin and the early-endosome-bound HookA is significantly decreased. However, VezA is not required for linking dynein-dynactin to the cytosolic ∆C-HookA, lacking the cargo-binding C-terminus. These results identify VezA as a novel regulator required for the interaction between dynein and the Hook-bound early endosomes in vivo. PMID:26378255

Therapeutic targeting of RNA splicing in myelodysplasia.

PubMed

Kim, Young Joon; Abdel-Wahab, Omar

2017-07-01

Genomic analysis of patients with myelodysplastic syndromes (MDS) has identified that mutations within genes encoding RNA splicing factors represent the most common class of genetic alterations in MDS. These mutations primarily affect SF3B1, SRSF2, U2AF1, and ZRSR2. Current data suggest that these mutations perturb RNA splicing catalysis in a manner distinct from loss of function but how exactly the global changes in RNA splicing imparted by these mutations result in MDS is not well delineated. At the same time, cells bearing mutations in RNA splicing factors are exquisitely dependent on the presence of the remaining wild-type (WT) allele to maintain residual normal splicing for cell survival. The high frequency of these mutations in MDS, combined with their mutual exclusivity and noteworthy dependence on the WT allele, make targeting RNA splicing attractive in MDS. To this end, two promising therapeutic approaches targeting RNA splicing are being tested clinically currently. These include molecules targeting core RNA splicing catalysis by interfering with the ability of the SF3b complex to interact with RNA, as well as molecules degrading the auxiliary RNA splicing factor RBM39. The preclinical and clinical evaluation of these compounds are discussed here in addition to their potential as therapies for spliceosomal mutant MDS. Copyright © 2017 Elsevier Inc. All rights reserved.

A novel protein from edible fungi Cordyceps militaris that induces apoptosis.

PubMed

Bai, Ke-Chun; Sheu, Fuu

2018-01-01

Cordyceps militaris is a dietary therapeutic fungus that is an important model species in Cordyceps research. In this study, we purified a novel protein from the fruit bodies of C. militaris and designated it as Cordyceps militaris protein (CMP). CMP has a molecular mass of 18.0 kDa and is not glycosylated. Interestingly, CMP inhibited cell viability in murine primary cells and other cell lines in a time- and dose-dependent manner. Using trypan blue staining and a lactate dehydrogenase release assay, we showed that CMP caused cell death in the murine hepatoma cell line BNL 1MEA.7R.1. Furthermore, the frequency of BNL 1MEA.7R.1 cells at the sub-G1 stage was increased by CMP. Apoptosis, as determined by Annexin V and propidium iodide analysis, indicated that CMP could mediate BNL 1MEA.7R.1 apoptosis, but not necrosis. After coincubation with CMP, a decrease in mitochondria potential was detected using 3,3'-dihexyloxacarbocyanine iodide. These results suggest that CMP is a harmful protein that induces apoptosis through a mitochondrion-dependent pathway. Stability experiments demonstrated that heat treatment and alkalization degraded CMP and further destroyed its cell-death-inducing ability, implying that cooking is necessary for food containing C. militaris. Copyright © 2017. Published by Elsevier B.V.

Noise-induced switching near a depth two heteroclinic network and an application to Boussinesq convection.

PubMed

Ashwin, Peter; Podvigina, Olga

2010-06-01

We investigate the robust heteroclinic dynamics arising in a system of ordinary differential equations in R(4) with symmetry [Formula in text]. This system arises from the normal form reduction of a 1: squate root of 2 mode interaction for Boussinesq convection. We investigate the structure of a particular robust heteroclinic attractor with "depth two connections" from equilibria to subcycles as well as connections between equilibria. The "subcycle" is not asymptotically stable, due to nearby trajectories undertaking an "excursion," but it is a Milnor attractor, meaning that a positive measure set of nearby initial conditions converges to the subcycle. We investigate the dynamics in the presence of noise and find a number of interesting properties. We confirm that typical trajectories wind around the subcycle with very occasional excursions near a depth two connection. The frequency of excursions depends on noise intensity in a subtle manner; in particular, for anisotropic noise, the depth two connection may be visited much more often than for isotropic noise, and more generally the long term statistics of the system depends not only on the noise strength but also on the anisotropy of the noise. Similar properties are confirmed in simulations of Boussinesq convection for parameters giving an attractor with depth two connections. (c) 2010 American Institute of Physics.

EUCLIA—Exploring the UV/Optical Continuum Lag in Active Galactic Nuclei. I. A Model without Light Echoing

NASA Astrophysics Data System (ADS)

Cai, Zhen-Yi; Wang, Jun-Xian; Zhu, Fei-Fan; Sun, Mou-Yuan; Gu, Wei-Min; Cao, Xin-Wu; Yuan, Feng

2018-03-01

The tight interband correlation and the lag–wavelength relation among UV/optical continua of active galactic nuclei have been firmly established. They are usually understood within the widespread reprocessing scenario; however, the implied interband lags are generally too small. Furthermore, it is challenged by new evidence, such as that the X-ray reprocessing yields too much high-frequency UV/optical variation and that it fails to reproduce the observed timescale-dependent color variations among the Swift light curves of NGC 5548. In a different manner, we demonstrate that an upgraded inhomogeneous accretion disk model, whose local independent temperature fluctuations are subject to a speculated common large-scale temperature fluctuation, can intrinsically generate the tight interband correlation and lag across the UV/optical and be in nice agreement with several observational properties of NGC 5548, including the timescale-dependent color variation. The emergent lag is a result of the differential regression capability of local temperature fluctuations when responding to the large-scale fluctuation. An average speed of propagations as large as ≳15% of the speed of light may be required by this common fluctuation. Several potential physical mechanisms for such propagations are discussed. Our interesting phenomenological scenario may shed new light on comprehending the UV/optical continuum variations of active galactic nuclei.

REPRODUCING THE CORRELATIONS OF TYPE C LOW-FREQUENCY QUASI-PERIODIC OSCILLATION PARAMETERS IN XTE J1550–564 WITH A SPIRAL STRUCTURE

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

Varniere, Peggy; Vincent, Frederic H., E-mail: varniere@apc.univ-paris7.fr

While it has been observed that the parameters intrinsic to the type C low-frequency quasi-periodic oscillations are related in a nonlinear manner among themselves, there has been, up to now, no model to explain or reproduce how the frequency, the FWHM, and the rms amplitude of the type C low-frequency quasi-periodic oscillations behave with respect to one another. Here we are using a simple toy model representing the emission from a standard disk and a spiral such as that caused by the accretion–ejection instability to reproduce the overall observed behavior and shed some light on its origin. This allows usmore » to prove the ability of such a spiral structure to be at the origin of flux modulation over more than an order of magnitude in frequency.« less

Ordered structures and jet noise

NASA Technical Reports Server (NTRS)

Petersen, R. A.; Kaplan, R. E.; Laufer, J.

1974-01-01

A series of measurements of near field pressures and turbulent velocity fluctuations were made in a jet having a Reynolds number of about 50,000 in order to investigate more quantitatively the character and behavior of the large scale structures, and to ascertain their importance to the jet noise problem. It was found that the process of interaction between vortices can be inhibited by artificially exciting the shear layers with periodic disturbances of certain frequency. The turbulent fluctuation amplitudes measured at four diameters downstream decreased considerably. Finally, it was observed that the passage frequency of the structures decreased with x in a similar manner as the frequency corresponding to the maximum intensity radiation emanating from the same value of x.

Daucosterol inhibits cancer cell proliferation by inducing autophagy through reactive oxygen species-dependent manner.

PubMed

Zhao, Chuanke; She, Tiantian; Wang, Lixin; Su, Yahui; Qu, Like; Gao, Yujing; Xu, Shuo; Cai, Shaoqing; Shou, Chengchao

2015-09-15

This study aims to evaluate the anti-cancer effect of daucosterol and explore its possible mechanism. MTT and colony formation assay were performed to determine the effect of daucosterol on cancer cell proliferation in vitro. H22 allograft model was used for the assessment of its anti-cancer activity in vivo. Intracellular generation of reactive oxygen species (ROS) was measured using DCFH-DA probe with flow cytometry system and a laser scanning confocal microscope. LC3 (microtubule-associated protein 1 light chain 3)-II conversion was monitored with immunofluorescence and immunoblotting to demonstrate daucosterol-induced autophagy. We found that daucosterol inhibits the proliferation of human breast cancer cell line MCF-7 and gastric cancer cell lines MGC803, BGC823 and AGS in a dose-dependent manner. Furthermore, daucosterol inhibits murine hepatoma H22 cell growth in ICR mice. Daucosterol treatment induces intracellular ROS generation and autophagy, but not apoptotic cell death. Treatment with ROS scavenger GSH (reduced glutathione), NAC (N-acetyl-l-cysteine) or autophagy inhibitor 3-Methyladenine (3-MA) counteracted daucosterol-induced autophagy and growth inhibition in BGC823 and MCF-7 cancer cells. Daucosterol inhibits cancer cell proliferation by inducing autophagy through ROS-dependent manner and could be potentially developed as an anti-cancer agent. Copyright © 2015 Elsevier Inc. All rights reserved.

The contractile ring coordinates curvature-dependent septum assembly during fission yeast cytokinesis

PubMed Central

Zhou, Zhou; Munteanu, Emilia Laura; He, Jun; Ursell, Tristan; Bathe, Mark; Huang, Kerwyn Casey; Chang, Fred

2015-01-01

The functions of the actin-myosin–based contractile ring in cytokinesis remain to be elucidated. Recent findings show that in the fission yeast Schizosaccharomyces pombe, cleavage furrow ingression is driven by polymerization of cell wall fibers outside the plasma membrane, not by the contractile ring. Here we show that one function of the ring is to spatially coordinate septum cell wall assembly. We develop an improved method for live-cell imaging of the division apparatus by orienting the rod-shaped cells vertically using microfabricated wells. We observe that the septum hole and ring are circular and centered in wild-type cells and that in the absence of a functional ring, the septum continues to ingress but in a disorganized and asymmetric manner. By manipulating the cleavage furrow into different shapes, we show that the ring promotes local septum growth in a curvature-dependent manner, allowing even a misshapen septum to grow into a more regular shape. This curvature-dependent growth suggests a model in which contractile forces of the ring shape the septum cell wall by stimulating the cell wall machinery in a mechanosensitive manner. Mechanical regulation of the cell wall assembly may have general relevance to the morphogenesis of walled cells. PMID:25355954

Effects of celecoxib on cell apoptosis and Fas, FasL and Bcl-2 expression in a BGC-823 human gastric cancer cell line.

PubMed

Li, Qian; Peng, Jie; Liu, Ting; Zhang, Guiying

2017-09-01

Fas, which is an apoptotic-related protein, has an important role in cell apoptosis. Fas ligand (FasL) binds to Fas and activates apoptosis signal transduction. We previously demonstrated that the efficiency of celecoxib inhibited the proliferation and apoptosis of HT-29 colon cancer cell line. The BGC823 cell line was used as an experimental model to evaluate the potential role of celecoxib on gastric cancer cell apoptosis. Inhibitory effects of celecoxib on cell viability were determined by MTT assay. Cell apoptosis was evaluated by flow cytometric analysis and laser confocal microscopy. The results of the present study demonstrated that celecoxib inhibited the viability of BGC823 cells in a concentration- and time-dependent manner. Furthermore, the effect of BGC823 cells apoptosis was increased in a concentration-dependent manner. Western blotting was used to determine the protein expression levels of Fas, FasL, and B-cell lymphoma-2 (Bcl-2). During the celecoxib-induced apoptosis of BGC823 cells, celecoxib upregulated Fas expression and downregulated FasL and Bcl-2 expression in a concentration-dependent manner. These results suggest that celecoxib inhibited the growth and induced apoptosis of BGC823 gastric cancer cells by regulating the protein expression of Fas, FasL and Bcl-2.

ROS-mediated platelet generation: a microenvironment-dependent manner for megakaryocyte proliferation, differentiation, and maturation

PubMed Central

Chen, S; Su, Y; Wang, J

2013-01-01

Platelets have an important role in the body because of their manifold functions in haemostasis, thrombosis, and inflammation. Platelets are produced by megakaryocytes (MKs) that are differentiated from haematopoietic stem cells via several consecutive stages, including MK lineage commitment, MK progenitor proliferation, MK differentiation and maturation, cell apoptosis, and platelet release. During differentiation, the cells migrate from the osteoblastic niche to the vascular niche in the bone marrow, which is accompanied by reactive oxygen species (ROS)-dependent oxidation state changes in the microenvironment, suggesting that ROS can distinctly influence platelet generation and function in a microenvironment-dependent manner. The objective of this review is to reveal the role of ROS in regulating MK proliferation, differentiation, maturation, and platelet activation, thereby providing new insight into the mechanism of platelet generation, which may lead to the development of new therapeutic agents for thrombocytopenia and/or thrombosis. PMID:23846224

Nanoparticles modulate autophagic effect in a dispersity-dependent manner

NASA Astrophysics Data System (ADS)

Huang, Dengtong; Zhou, Hualu; Gao, Jinhao

2015-09-01

Autophagy plays a key role in human health and disease, especially in cancer and neurodegeneration. Many autophagy regulators are developed for therapy. Diverse nanomaterials have been reported to induce autophagy. However, the underlying mechanisms and universal rules remain unclear. Here, for the first time, we show a reliable and general mechanism by which nanoparticles induce autophagy and then successfully modulate autophagy via tuning their dispersity. Various well-designed univariate experiments demonstrate that nanomaterials induce autophagy in a dispersity-dependent manner. Aggregated nanoparticles induce significant autophagic effect in comparison with well-dispersed nanoparticles. As the highly stable nanoparticles may block autophagic degradation in autolysosomes, endocytosis and intracellular accumulation of nanoparticles can be responsible for this interesting phenomenon. Our results suggest dispersity-dependent autophagic effect as a common cellular response to nanoparticles, reveal the relationship between properties of nanoparticles and autophagy, and offer a new alternative way to modulate autophagy.

Platelet-derived growth factor regulates K-Cl cotransport in vascular smooth muscle cells.

PubMed

Zhang, Jing; Lauf, Peter K; Adragna, Norma C

2003-03-01

Platelet-derived growth factor (PDGF), a potent serum mitogen for vascular smooth muscle cells (VSMCs), plays an important role in membrane transport regulation and in atherosclerosis. K-Cl cotransport (K-Cl COT/KCC), the coupled-movement of K and Cl, is involved in ion homeostasis. VSMCs possess K-Cl COT activity and the KCC1 and KCC3 isoforms. Here, we report on the effect of PDGF on K-Cl COT activity and mRNA expression in primary cultures of rat VSMCs. K-Cl COT was determined as the Cl-dependent Rb influx and mRNA expression by semiquantitative RT-PCR. Twenty four-hour serum deprivation inhibited basal K-Cl COT activity. Addition of PDGF increased total protein content and K-Cl COT activity in a time-dependent manner. PDGF activated K-Cl COT in a dose-dependent manner, both acutely (10 min) and chronically (12 h). AG-1296, a selective inhibitor of the PDGF receptor tyrosine kinase, abolished these effects. Actinomycin D and cycloheximide had no effect on the acute PDGF activation of K-Cl COT, suggesting posttranslational regulation by the drug. Furthermore, PDGF increased KCC1 and decreased KCC3 mRNA expression in a time-dependent manner. These results indicate that chronic activation of K-Cl COT activity by PDGF may involve regulation of the two KCC mRNA isoforms, with KCC1 playing a dominant role in the mechanism of PDGF-mediated activation.

Flavonoids and Tannins from Smilax china L. Rhizome Induce Apoptosis Via Mitochondrial Pathway and MDM2-p53 Signaling in Human Lung Adenocarcinoma Cells.

PubMed

Fu, San; Yang, Yanfang; Liu, Dan; Luo, Yan; Ye, Xiaochuan; Liu, Yanwen; Chen, Xin; Wang, Song; Wu, Hezhen; Wang, Yuhang; Hu, Qiwei; You, Pengtao

2017-01-01

In vitro evidence indicates that Smilax china L. rhizome (SCR) can inhibit cell proliferation. Therefore, in the present study, we analyzed the effects in vitro of SCR extracts on human lung adenocarcinoma A549 cells. Our results showed that A549 cell growth was inhibited in a dose- and time-dependent manner after treatment with SCR extracts. Total flavonoids and total tannins from SCR induced A549 apoptosis in a dose-dependent manner, as shown by our flow cytometry analysis, which was consistent with the alterations in nuclear morphology we observed. In addition, the total apoptotic rate induced by total tannins was higher than the rate induced by total flavonoids at the same dose. Cleaved-caspase-3 protein levels in A549 cells after treatment with total flavonoids or total tannins were increased in a dose-dependent manner, followed by the activation of caspase-8 and caspase-9, finally triggering to PARP cleavage. Furthermore, total flavonoids and total tannins increased the expression of Bax, decreased the expression of Bcl-2, and promoted cytochrome [Formula: see text] release. Moreover, MDM2 and p-MDM2 proteins were decreased, while p53 and p-p53 proteins were increased, both in a dose-dependent manner, after A549 treatment with total flavonoids and total tannins. Finally, cleaved-caspase-3 protein levels in the total flavonoids or total tannins-treated H1299 (p53 null) and p53-knockdown A549 cells were increased. Our results indicated that total flavonoids and total tannins from SCR exerted a remarkable effect in reducing A549 growth through their action on mitochondrial pathway and disruption of MDM2-p53 balance. Hence, our findings demonstrated a potential application of total flavonoids and total tannins from SCR in the treatment of human lung adenocarcinoma.

AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

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

Liu, Xin, E-mail: fangfei6073@126.com; Zhu, Yanming, E-mail: ymzhu2001@neau.edu.cn; Zhai, Hong, E-mail: Zhai.h@neigaehrb.ac.cn

2012-06-15

Highlights: Black-Right-Pointing-Pointer AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. Black-Right-Pointing-Pointer AtPP2CG1 up-regulates the expression of marker genes in different pathways. Black-Right-Pointing-Pointer AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, andmore » abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2-3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter-GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.« less

Glucose and insulin do not decrease in a dose-dependent manner after increasing doses of mixed fibers that are consumed in muffins for breakfast.

PubMed

Willis, Holly J; Thomas, William; Eldridge, Alison L; Harkness, Laura; Green, Hilary; Slavin, Joanne L

2011-01-01

Conventional wisdom suggests that fiber consumption leads to lower postprandial glucose and insulin response. We hypothesized that increasing doses of mixed, viscous fiber would lower glucose and insulin levels in a dose-dependent manner. Healthy men (n = 10) and women (n = 10) with a body mass index of 24 ± 2 (mean ± SEM) participated in this double-blind, crossover study. On 4 separate visits, fasting subjects consumed an approximately 2093 kJ (500 calorie) muffin with 0, 4, 8, or 12 g of mixed fibers. Blood was drawn to measure glucose and insulin at regular intervals throughout a 3-hour test period. Area under the curve (AUC) glucose was significantly lower after 0 g of fiber than after 4, 8, or 12 g of fiber (arbitrary AUC units ± SEM: 25.3 ± 5.2 vs 44.6 ± 7.7, 49.7 ± 7.9, 51.5 ± 6.6, respectively; P < .006). Area under the curve glucose increased with increasing fiber doses (P for trend = .0003). Area under the curve insulin was higher after the 4-g dose than after the 0-, 8-, and 12-g doses (arbitrary AUC units ± SEM: 84.4 ± 8.0 vs 60.1 ± 6.5, 69.4 ± 8.7, 69.7 ± 8.5, respectively; P < .05); it did not change in a dose-dependent manner. Area under the curve glucose and AUC insulin did not correlate with each other. Glucose and insulin did not decrease in a dose-dependent manner after 0, 4, 8, and 12 g of mixed fibers were consumed in muffins for breakfast. The lack of differences was largely based on the individual variation in glucose response. Caution should be used when making general claims about the expected impact of fiber on glucose and insulin levels. Copyright © 2011 Elsevier Inc. All rights reserved.

Coherent-subspace array processing based on wavelet covariance: an application to broad-band, seismo-volcanic signals

NASA Astrophysics Data System (ADS)

Saccorotti, G.; Nisii, V.; Del Pezzo, E.

2008-07-01

Long-Period (LP) and Very-Long-Period (VLP) signals are the most characteristic seismic signature of volcano dynamics, and provide important information about the physical processes occurring in magmatic and hydrothermal systems. These events are usually characterized by sharp spectral peaks, which may span several frequency decades, by emergent onsets, and by a lack of clear S-wave arrivals. These two latter features make both signal detection and location a challenging task. In this paper, we propose a processing procedure based on Continuous Wavelet Transform of multichannel, broad-band data to simultaneously solve the signal detection and location problems. Our method consists of two steps. First, we apply a frequency-dependent threshold to the estimates of the array-averaged WCO in order to locate the time-frequency regions spanned by coherent arrivals. For these data, we then use the time-series of the complex wavelet coefficients for deriving the elements of the spatial Cross-Spectral Matrix. From the eigenstructure of this matrix, we eventually estimate the kinematic signals' parameters using the MUltiple SIgnal Characterization (MUSIC) algorithm. The whole procedure greatly facilitates the detection and location of weak, broad-band signals, in turn avoiding the time-frequency resolution trade-off and frequency leakage effects which affect conventional covariance estimates based upon Windowed Fourier Transform. The method is applied to explosion signals recorded at Stromboli volcano by either a short-period, small aperture antenna, or a large-aperture, broad-band network. The LP (0.2 < T < 2s) components of the explosive signals are analysed using data from the small-aperture array and under the plane-wave assumption. In this manner, we obtain a precise time- and frequency-localization of the directional properties for waves impinging at the array. We then extend the wavefield decomposition method using a spherical wave front model, and analyse the VLP components (T > 2s) of the explosion recordings from the broad-band network. Source locations obtained this way are fully compatible with those retrieved from application of more traditional (and computationally expensive) time-domain techniques, such as the Radial Semblance method.

High frequency measures of OHC nonlinear capacitance (NLC) and their significance: Why measures stray away from predictions

NASA Astrophysics Data System (ADS)

Santos-Sacchi, Joseph

2018-05-01

Measures of membrane capacitance (Cm) can be used to assess important characteristics of voltage-dependent membrane proteins (e.g., channels and transporters). In particular, a protein's time-dependent voltage-sensor charge movement is equivalently represented as a frequency-dependent component of Cm, telling much about the kinetics of the protein's conformational behavior. Recently, we have explored the frequency dependence of OHC voltage-dependent capacitance (aka nonlinear capacitance, NLC) to query rates of conformational switching within prestin (SLC26a5), the cell's lateral membrane molecular motor 1. Following removal of confounding stray capacitance effects, high frequency Cm measures using wide-band stimuli accurately reveal unexpected low pass behavior in prestin's molecular motions.

Frequency dependent Lg attenuation in south-central Alaska

USGS Publications Warehouse

McNamara, D.E.

2000-01-01

The characteristics of seismic energy attenuation are determined using high frequency Lg waves from 27 crustal earthquakes, in south-central Alaska. Lg time-domain amplitudes are measured in five pass-bands and inverted to determine a frequency-dependent quality factor, Q(f), model for south-central Alaska. The inversion in this study yields the frequency-dependent quality factor, in the form of a power law: Q(f) = Q0fη = 220(±30) f0.66(±0.09) (0.75≤f≤12Hz). The results from this study are remarkably consistent with frequency dependent quality factor estimates, using local S-wave coda, in south-central Alaska. The consistency between S-coda Q(f) and Lg Q(f) enables constraints to be placed on the mechanism of crustal attenuation in south-central Alaska. For the range of frequencies considered in this study both scattering and intrinsic attenuation mechanisms likely play an equal role.

Linear transformation of the encoding mechanism for light intensity underlies the paradoxical enhancement of cortical visual responses by sevoflurane.

PubMed

Arena, Alessandro; Lamanna, Jacopo; Gemma, Marco; Ripamonti, Maddalena; Ravasio, Giuliano; Zimarino, Vincenzo; De Vitis, Assunta; Beretta, Luigi; Malgaroli, Antonio

2017-01-01

The mechanisms of action of anaesthetics on the living brain are still poorly understood. In this respect, the analysis of the differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity might provide important and novel cues. Here we show that the anaesthetic sevoflurane strongly silences the brain but potentiates in a dose- and frequency-dependent manner the cortical visual response. Such enhancement arises from a linear scaling by sevoflurane of the power-law relation between light intensity and the cortical response. The fingerprint of sevoflurane action suggests that circuit silencing can boost linearly synaptic responsiveness presumably by scaling the number of responding units and/or their correlation following a sensory stimulation. General anaesthetics, which are expected to silence brain activity, often spare sensory responses. To evaluate differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity, we characterized their modulation by sevoflurane and propofol. Power spectra and the bust-suppression ratio from EEG data were used to evaluate anaesthesia depth. ON and OFF cortical responses were elicited by light pulses of variable intensity, duration and frequency, during light and deep states of anaesthesia. Both anaesthetics reduced spontaneous cortical activity but sevoflurane greatly enhanced while propofol diminished the ON visual response. Interestingly, the large potentiation of the ON visual response by sevoflurane was found to represent a linear scaling of the encoding mechanism for light intensity. To the contrary, the OFF cortical visual response was depressed by both anaesthetics. The selective depression of the OFF component by sevoflurane could be converted into a robust potentiation by the pharmacological blockade of the ON pathway, suggesting that the temporal order of ON and OFF responses leads to a depression of the latter. This hypothesis agrees with the finding that the enhancement of the ON response was converted into a depression by increasing the frequency of light-pulse stimulation from 0.1 to 1 Hz. Overall, our results support the view that inactivity-dependent modulation of cortical circuits produces an increase in their responsiveness. Among the implications of our findings, the silencing of cortical circuits can boost linearly the cortical responsiveness but with negative impact on their frequency transfer and with a loss of the information content of the sensory signal. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Contact-dependent depletion of hydrogen peroxide by catalase is a novel mechanism of myeloid-derived suppressor cell induction operating in human hepatic stellate cells.

PubMed

Resheq, Yazid J; Li, Ka-Kit; Ward, Stephen T; Wilhelm, Annika; Garg, Abhilok; Curbishley, Stuart M; Blahova, Miroslava; Zimmermann, Henning W; Jitschin, Regina; Mougiakakos, Dimitrios; Mackensen, Andreas; Weston, Chris J; Adams, David H

2015-03-15

Myeloid-derived suppressor cells (MDSC) represent a unique cell population with distinct immunosuppressive properties that have been demonstrated to shape the outcome of malignant diseases. Recently, human hepatic stellate cells (HSC) have been reported to induce monocytic-MDSC from mature CD14(+) monocytes in a contact-dependent manner. We now report a novel and unexpected mechanism by which CD14(+)HLADR(low/-) suppressive cells are induced by catalase-mediated depletion of hydrogen peroxide (H2O2). Incubation of CD14(+) monocytes with catalase led to a significant induction of functional MDSC compared with media alone, and H2O2 levels inversely correlated with MDSC frequency (r = -0.6555, p < 0.05). Catalase was detected in primary HSC and a stromal cell line, and addition of the competitive catalase inhibitor hydroxylamine resulted in a dose-dependent impairment of MDSC induction and concomitant increase of H2O2 levels. The NADPH-oxidase subunit gp91 was significantly increased in catalase-induced MDSC as determined by quantitative PCR outlining the importance of oxidative burst for the induction of MDSC. These findings represent a so far unrecognized link between immunosuppression by MDSC and metabolism. Moreover, this mechanism potentially explains how stromal cells can induce a favorable immunological microenvironment in the context of tissue oxidative stress such as occurs during cancer therapy. Copyright © 2015 by The American Association of Immunologists, Inc.

Equilibrium finite-frequency noise of an interacting mesoscopic capacitor studied in time-dependent density functional theory

NASA Astrophysics Data System (ADS)

Dittmann, Niklas; Splettstoesser, Janine; Helbig, Nicole

2018-03-01

We calculate the frequency-dependent equilibrium noise of a mesoscopic capacitor in time-dependent density functional theory (TDDFT). The capacitor is modeled as a single-level quantum dot with on-site Coulomb interaction and tunnel coupling to a nearby reservoir. The noise spectra are derived from linear-response conductances via the fluctuation-dissipation theorem. Thereby, we analyze the performance of a recently derived exchange-correlation potential with time-nonlocal density dependence in the finite-frequency linear-response regime. We compare our TDDFT noise spectra with real-time perturbation theory and find excellent agreement for noise frequencies below the reservoir temperature.

Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission.

PubMed

Sengupta, Ayesha; Bocchio, Marco; Bannerman, David M; Sharp, Trevor; Capogna, Marco

2017-02-15

The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT 2A and 5-HT 1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT 1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders. Therefore, it is essential to determine the physiological mechanisms through which 5-HT neurons in the dorsal raphe nuclei modulate amygdala circuits. Here, we combined optogenetic, electrophysiological, and pharmacological approaches to study the effects of activation of 5-HT axons in the basal nucleus of the amygdala (BA). We found that 5-HT neurons co-release 5-HT and glutamate onto BA neurons in a cell-type-specific and frequency-dependent manner. Therefore, we suggest that theories on the contribution of 5-HT neurons to amygdala function should be revised to incorporate the concept of 5-HT/glutamate cotransmission. Copyright © 2017 Sengupta et al.

Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission

PubMed Central

Bannerman, David M.

2017-01-01

The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10–20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT2A and 5-HT1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders. Therefore, it is essential to determine the physiological mechanisms through which 5-HT neurons in the dorsal raphe nuclei modulate amygdala circuits. Here, we combined optogenetic, electrophysiological, and pharmacological approaches to study the effects of activation of 5-HT axons in the basal nucleus of the amygdala (BA). We found that 5-HT neurons co-release 5-HT and glutamate onto BA neurons in a cell-type-specific and frequency-dependent manner. Therefore, we suggest that theories on the contribution of 5-HT neurons to amygdala function should be revised to incorporate the concept of 5-HT/glutamate cotransmission. PMID:28087766

Frequency-dependent sexual selection.

PubMed

O'Donald, P; Majerus, M E

1988-07-06

Sexual selection by female choice is expected to give rise to a frequency-dependent sexual advantage in favour of preferred male phenotypes: the rarer the preferred phenotypes, the more often they are chosen as mates. This 'rare-male advantage' can maintain a polymorphism when two or more phenotypes are mated preferentially: each phenotype gains an advantage when it is rarer than the others; no preferred phenotype can then be lost from the population. Expression of preference may be complete or partial. In models of complete preference, females with a preference always mate preferentially. Models of partial preference are more realistic: in these models, the probability that a female mates preferentially depends on the frequency with which she encounters the males she prefers. Two different 'encounter models' of partial preference have been derived: the O'Donald model and the Charlesworth model. The encounter models contain the complete preference model as a limiting case. In this paper, the Charlesworth model is generalized to allow for female preference of more than one male phenotype. Levels of frequency dependence can then be compared in the O'Donald and Charlesworth models. The complete preference model and both encounter models are formulated in the same genetical terms of preferences for dominant and recessive male phenotypes. Polymorphic equilibria and conditions for stability are derived for each of the three models. The models are then fitted to data of frequencies of matings observed in experiments with the two-spot ladybird. The complete preference model gives as good a fit as the encounter models to the data of these and other experiments. The O'Donald and Charlesworth encounter models are shown to produce a very similar frequency-dependent relation. Generally, as females become less choosy, they express their preference with more dependence on male frequency, whereas the resulting selection of the males becomes less frequency dependent. More choosy females are more constant in expressing their preference, producing greater frequency dependence in the selection of the males.

Control and Coordination of Frequency Responsive Residential Water Heaters

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

Williams, Tess L.; Kalsi, Karanjit; Elizondo, Marcelo A.

2016-07-31

Demand-side frequency control can complement traditional generator controls to maintain the stability of large electric systems in the face of rising uncertainty and variability associated with renewable energy resources. This paper presents a hierarchical frequency-based load control strategy that uses a supervisor to flexibly adjust control gains that a population of end-use loads respond to in a decentralized manner to help meet the NERC BAL-003-1 frequency response standard at both the area level and interconnection level. The load model is calibrated and used to model populations of frequency-responsive water heaters in a PowerWorld simulation of the U.S. Western Interconnection (WECC).more » The proposed design is implemented and demonstrated on physical water heaters in a laboratory setting. A significant fraction of the required frequency response in the WECC could be supplied by electric water heaters alone at penetration levels of less than 15%, while contributing to NERC requirements at the interconnection and area levels.« less

Assessing frequency-dependent site polarisabilities in linear response polarisable embedding

NASA Astrophysics Data System (ADS)

Nørby, Morten S.; Vahtras, Olav; Norman, Patrick; Kongsted, Jacob

2017-01-01

In this paper, we discuss the impact of using a frequency-dependent embedding potential in quantum chemical embedding calculations of response properties. We show that the introduction of a frequency-dependent embedding potential leads to further model complications upon solving the central equations defining specific molecular properties. On the other hand, we also show from a numerical point of view that the consequences of using such a frequency-dependent embedding potential is almost negligible. Thus, for the kind of systems and processes studied in this paper the general recommendation is to use frequency-independent embedding potentials since this leads to less complicated model issues. However, larger effects are expected if the absorption bands of the environment are closer to that of the region treated using quantum mechanics.

Modulation of NMDA and AMPA-Mediated Synaptic Transmission by CB1 Receptors in Frontal Cortical Pyramidal Cells

PubMed Central

Li, Qiang; Yan, Haidun; Wilson, Wilkie A.; Swartzwelder, H. Scott

2010-01-01

Although the endogenous cannabinoid system modulates a variety of physiological and pharmacological processes, the specific role of cannabinoid CB1 receptors in the modulation of glutamatergic neurotransmission and neural plasticity is not well understood. Using whole-cell patch clamp recording techniques, evoked or spontaneous excitatory postsynaptic currents (eEPSCs or sEPSCs) were recorded from visualized, layer II/III pyramidal cells in frontal cortical slices from rat brain. Bath application of the CB1 receptor agonist, WIN 55212-2 (WIN), reduced the amplitude of NMDA receptor-mediated EPSCs in a concentration-dependent manner. When co-applied with the specific CB1 antagonists, AM251 or AM281, WIN did not suppress NMDA receptor mediated EPSCs. WIN also reduced the amplitude of evoked AMPA receptor-mediated EPSCs, an effect that was also reversed by AM251. Both the frequency and amplitude of spontaneous AMPA receptor-mediated EPSCs were significantly reduced by WIN. In contrast, WIN reduced the frequency, but not the amplitude of miniature EPSCs, suggesting that the suppression of glutmatergic activity by CB1 receptors in the frontal neocortex is mediated by a pre-synaptic mechanism. Taken together, these data indicate a critical role for endocannabinoid signaling in the regulation of excitatory synaptic transmission in frontal neocortex, and suggest a possible neuronal mechanism whereby THC regulates cortical function. PMID:20420813

Heparin concentration is critical for cell culture with human platelet lysate.

PubMed

Hemeda, Hatim; Kalz, Jana; Walenda, Gudrun; Lohmann, Michael; Wagner, Wolfgang

2013-09-01

Culture media for mesenchymal stromal cells (MSCs) are generally supplemented with fetal bovine serum. Human platelet lysate (hPL) has been proven to be a very effective alternative without the risk of xenogeneic infections or immune reactions. In contrast to fetal bovine serum, hPL comprises plasma, and anticoagulants-usually unfractionated heparin (UFH)-need to be added to prevent gel formation. Cultures of MSCs in hPL media with various concentrations of UFH and enoxaparin, a low-molecular-weight heparin (LMWH), were systematically compared with regard to proliferation, fibroblastoid colony-forming unit frequency, immunophenotype and in vitro differentiation. At least 0.61 IU/mL UFH or 0.024 mg/mL LMWH was necessary for reliable prevention of coagulation of hPL pools used in this study. Higher concentrations impaired cellular proliferation in a dose-dependent manner even without benzyl alcohol, which is commonly added to heparins as a bacteriostatic agent. Colony-forming unit frequency was also reduced at higher heparin concentrations, particularly with LMWH, whereas no significant effect was observed on cellular morphology or immunophenotype. High concentrations of heparins reduced the in vitro differentiation toward adipogenic and osteogenic lineages. Heparin concentration is critical for culture of MSCs in hPL media; this is of particular relevance for cellular therapy where cell culture procedures need to be optimized and standardized. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Selective spectroscopic imaging of hyperpolarized pyruvate and its metabolites using a single-echo variable phase advance method in balanced SSFP

PubMed Central

Varma, Gopal; Wang, Xiaoen; Vinogradov, Elena; Bhatt, Rupal S.; Sukhatme, Vikas; Seth, Pankaj; Lenkinski, Robert E.; Alsop, David C.; Grant, Aaron K.

2015-01-01

Purpose In balanced steady state free precession (bSSFP), the signal intensity has a well-known dependence on the off-resonance frequency, or, equivalently, the phase advance between successive radiofrequency (RF) pulses. The signal profile can be used to resolve the contributions from the spectrally separated metabolites. This work describes a method based on use of a variable RF phase advance to acquire spatial and spectral data in a time-efficient manner for hyperpolarized 13C MRI. Theory and Methods The technique relies on the frequency response from a bSSFP acquisition to acquire relatively rapid, high-resolution images that may be reconstructed to separate contributions from different metabolites. The ability to produce images from spectrally separated metabolites was demonstrated in-vitro, as well as in-vivo following administration of hyperpolarized 1-13C pyruvate in mice with xenograft tumors. Results In-vivo images of pyruvate, alanine, pyruvate hydrate and lactate were reconstructed from 4 images acquired in 2 seconds with an in-plane resolution of 1.25 × 1.25mm2 and 5mm slice thickness. Conclusions The phase advance method allowed acquisition of spectroscopically selective images with high spatial and temporal resolution. This method provides an alternative approach to hyperpolarized 13C spectroscopic MRI that can be combined with other techniques such as multi-echo or fluctuating equilibrium bSSFP. PMID:26507361

Comparison of cytotoxic and genotoxic effects of plutonium-239 alpha particles and mobile phone GSM 900 radiation in the Allium cepa test.

PubMed

Pesnya, Dmitry S; Romanovsky, Anton V

2013-01-20

The goal of this study was to compare the cytotoxic and genotoxic effects of plutonium-239 alpha particles and GSM 900 modulated mobile phone (model Sony Ericsson K550i) radiation in the Allium cepa test. Three groups of bulbs were exposed to mobile phone radiation during 0 (sham), 3 and 9h. A positive control group was treated during 20min with plutonium-239 alpha-radiation. Mitotic abnormalities, chromosome aberrations, micronuclei and mitotic index were analyzed. Exposure to alpha-radiation from plutonium-239 and exposure to modulated radiation from mobile phone during 3 and 9h significantly increased the mitotic index. GSM 900 mobile phone radiation as well as alpha-radiation from plutonium-239 induced both clastogenic and aneugenic effects. However, the aneugenic activity of mobile phone radiation was more pronounced. After 9h of exposure to mobile phone radiation, polyploid cells, three-groups metaphases, amitoses and some unspecified abnormalities were detected, which were not registered in the other experimental groups. Importantly, GSM 900 mobile phone radiation increased the mitotic index, the frequency of mitotic and chromosome abnormalities, and the micronucleus frequency in a time-dependent manner. Due to its sensitivity, the A. cepa test can be recommended as a useful cytogenetic assay to assess cytotoxic and genotoxic effects of radiofrequency electromagnetic fields. Copyright © 2012 Elsevier B.V. All rights reserved.

Are Ecstasy Induced Serotonergic Alterations Overestimated For The Majority Of Users?

PubMed

Szigeti, Balázs; Winstock, Adam R; Erritzoe, David; Maier, Larissa J

2018-05-01

Neuroimaging studies imply that the regular use of ±3,4-methylenedioxymethamphetamine (MDMA), the major constituent of ecstasy pills, alters the brain's serotonergic system in a dose-dependent manner. However, the relevance of these findings remains unclear due to limited knowledge about the ecstasy/MDMA use pattern of real-life users. We examined the representativeness of ecstasy users enrolled in neuroimaging studies by comparing their ecstasy use habits with the use patterns of a large, international sample. A systematic literature search revealed 10 imaging studies that compare serotonin transporter levels in recreational ecstasy users to matched controls. To characterize the ecstasy use patterns we relied on the Global Drug Survey, the world's largest self-report database on drug use. The basis of the dose comparison were the Usual Amount (pills/session), Use Frequency (sessions/month) and Dose Intensity (pills/year) variables. Both the average Usual Amount (pills/session) and Use Frequency (sessions/month) of neuroimaging study participants corresponded to the top 5-10% of the Global Drug Survey sample and imaging participants, on average, consumed 720% more pills over a year than the Global Drug Survey participants. Our findings suggest that the serotonin brain imaging literature has focused on unusually heavy ecstasy use and therefore the conclusions from these studies are likely to overestimate the extent of serotonergic alterations experienced by the majority of people who use ecstays.

Temporal dynamics of divided spatial attention

PubMed Central

Garcia, Javier O.; Serences, John T.

2013-01-01

In naturalistic settings, observers often have to monitor multiple objects dispersed throughout the visual scene. However, the degree to which spatial attention can be divided across spatially noncontiguous objects has long been debated, particularly when those objects are in close proximity. Moreover, the temporal dynamics of divided attention are unclear: is the process of dividing spatial attention gradual and continuous, or does it onset in a discrete manner? To address these issues, we recorded steady-state visual evoked potentials (SSVEPs) as subjects covertly monitored two flickering targets while ignoring an intervening distractor that flickered at a different frequency. All three stimuli were clustered within either the lower left or the lower right quadrant, and our dependent measure was SSVEP power at the target and distractor frequencies measured over time. In two experiments, we observed a temporally discrete increase in power for target- vs. distractor-evoked SSVEPs extending from ∼350 to 150 ms prior to correct (but not incorrect) responses. The divergence in SSVEP power immediately prior to a correct response suggests that spatial attention can be divided across noncontiguous locations, even when the targets are closely spaced within a single quadrant. In addition, the division of spatial attention appears to be relatively discrete, as opposed to slow and continuous. Finally, the predictive relationship between SSVEP power and behavior demonstrates that these neurophysiological measures of divided attention are meaningfully related to cognitive function. PMID:23390315

Phenytoin attenuates the hyper-exciting neurotransmission in cultured embryonic cortical neurons.

PubMed

Chou, Ming-Yi; Lee, Chun-Yao; Liou, Horng-Huei; Pan, Chien-Yuan

2014-08-01

Phenytoin is an effective anti-epileptic drug that inhibits Na(+) channel activities; however, how phenytoin modulates synaptic transmission to soothe epileptic symptoms is not clear. To characterize the effects of phenytoin regulation on neurotransmission, we studied the electrophysical properties of cultured embryonic cortical neurons. Phenytoin inhibited the inward Na(+) current in a dose-dependent manner with an IC50 of 16.8 μM, and at 100 μM, the inhibitory effect of phenytoin on the Na(+) current was proportional to the frequency applied. In cultured neurons, phenytoin significantly decreased the action potential firing rate and the peak potential. To study the effect of phenytoin in neurotransmission, we measured the Ca(2+) responses from stimulated target neurons and their neighboring neurons. Phenytoin significantly suppressed the Ca(2+) responses evoked by strong stimulations in the target and neighboring neurons, and exerted a decreased inhibitory effect under moderate stimulation. Picrotoxin, a GABAA receptor antagonist, enhanced the recorded spontaneous excitatory postsynaptic current activities. After picrotoxin-induced enhancement, phenytoin had a more pronounced effect on the suppression of the spontaneous hyper-exciting excitatory postsynaptic current (>100 pA), but it only mildly inhibited the general excitatory postsynaptic current. Our results demonstrate that phenytoin suppresses the efficacy of neurotransmission especially for the high-frequency stimulation by reducing the Na(+) channel activity and can potentially alleviate epileptiform activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Temporal dynamics of divided spatial attention.

PubMed

Itthipuripat, Sirawaj; Garcia, Javier O; Serences, John T

2013-05-01

In naturalistic settings, observers often have to monitor multiple objects dispersed throughout the visual scene. However, the degree to which spatial attention can be divided across spatially noncontiguous objects has long been debated, particularly when those objects are in close proximity. Moreover, the temporal dynamics of divided attention are unclear: is the process of dividing spatial attention gradual and continuous, or does it onset in a discrete manner? To address these issues, we recorded steady-state visual evoked potentials (SSVEPs) as subjects covertly monitored two flickering targets while ignoring an intervening distractor that flickered at a different frequency. All three stimuli were clustered within either the lower left or the lower right quadrant, and our dependent measure was SSVEP power at the target and distractor frequencies measured over time. In two experiments, we observed a temporally discrete increase in power for target- vs. distractor-evoked SSVEPs extending from ∼350 to 150 ms prior to correct (but not incorrect) responses. The divergence in SSVEP power immediately prior to a correct response suggests that spatial attention can be divided across noncontiguous locations, even when the targets are closely spaced within a single quadrant. In addition, the division of spatial attention appears to be relatively discrete, as opposed to slow and continuous. Finally, the predictive relationship between SSVEP power and behavior demonstrates that these neurophysiological measures of divided attention are meaningfully related to cognitive function.

Early Visual Word Processing Is Flexible: Evidence from Spatiotemporal Brain Dynamics.

PubMed

Chen, Yuanyuan; Davis, Matthew H; Pulvermüller, Friedemann; Hauk, Olaf

2015-09-01

Visual word recognition is often described as automatic, but the functional locus of top-down effects is still a matter of debate. Do task demands modulate how information is retrieved, or only how it is used? We used EEG/MEG recordings to assess whether, when, and how task contexts modify early retrieval of specific psycholinguistic information in occipitotemporal cortex, an area likely to contribute to early stages of visual word processing. Using a parametric approach, we analyzed the spatiotemporal response patterns of occipitotemporal cortex for orthographic, lexical, and semantic variables in three psycholinguistic tasks: silent reading, lexical decision, and semantic decision. Task modulation of word frequency and imageability effects occurred simultaneously in ventral occipitotemporal regions-in the vicinity of the putative visual word form area-around 160 msec, following task effects on orthographic typicality around 100 msec. Frequency and typicality also produced task-independent effects in anterior temporal lobe regions after 200 msec. The early task modulation for several specific psycholinguistic variables indicates that occipitotemporal areas integrate perceptual input with prior knowledge in a task-dependent manner. Still, later task-independent effects in anterior temporal lobes suggest that word recognition eventually leads to retrieval of semantic information irrespective of task demands. We conclude that even a highly overlearned visual task like word recognition should be described as flexible rather than automatic.

Opinion-enhanced collaborative filtering for recommender systems through sentiment analysis

NASA Astrophysics Data System (ADS)

Wang, Wei; Wang, Hongwei

2015-10-01

The motivation of collaborative filtering (CF) comes from the idea that people often get the best recommendations from someone with similar tastes. With the growing popularity of opinion-rich resources such as online reviews, new opportunities arise as we can identify the preferences from user opinions. The main idea of our approach is to elicit user opinions from online reviews, and map such opinions into preferences that can be understood by CF-based recommender systems. We divide recommender systems into two types depending on the number of product category recommended: the multiple-category recommendation and the single-category recommendation. For the former, sentiment polarity in coarse-grained manner is identified while for the latter fine-grained sentiment analysis is conducted for each product aspect. If the evaluation frequency for an aspect by a user is greater than the average frequency by all users, it indicates that the user is more concerned with that aspect. If a user's rating for an aspect is lower than the average rating by all users, he or she is much pickier than others on that aspect. Through sentiment analysis, we then build an opinion-enhanced user preference model, where the higher the similarity between user opinions the more consistent preferences between users are. Experiment results show that the proposed CF algorithm outperforms baseline methods for product recommendation in terms of accuracy and recall.

Testosterone-induced benign prostatic hyperplasia rat and dog as facile models to assess drugs targeting lower urinary tract symptoms

PubMed Central

Li, Jing; Tian, Yanxin; Guo, Shimeng; Gu, Haifeng; Yuan, Qianting; Xie, Xin

2018-01-01

Benign prostatic hyperplasia (BPH) is an age-related disease, affecting a majority of elderly men worldwide. Medical management of BPH is an alternative to surgical treatment of this disease. Currently, α1-adrenergic receptor (α1-AR) antagonists are among the first line drugs to treat BPH by reducing the tension of urinary track and thus the obstructive symptoms in voiding. In drug development, old male dogs with spontaneous BPH are considered the golden standard of the animal models. However, old dogs (>6 years) are expensive and not all old dogs develop BPH. So it is necessary to develop more accessible animal models for drug efficacy evaluation. Here we describe the development of testosterone-induced BPH models in both rats and young adult dogs and their applications in the in vivo evaluation of α1-AR antagonist. The BPH rats and dogs induced by chronic testosterone treatment have significantly increased micturition frequency and reduced mean voided volume, very similar to the clinical symptoms of BPH patients. Silodosin, an α1-AR antagonist, significantly reduces the urinary frequency and increases the voided volume in BPH model animals in a dose-dependent manner. The results demonstrate that testosterone-induced BPH rat and dog models might provide a more efficient way to evaluate micturition behavior in anti-BPH drug studies. PMID:29351556

Estimation of Coda Wave Attenuation in Northern Morocco

NASA Astrophysics Data System (ADS)

Boulanouar, Abderrahim; Moudnib, Lahcen El; Padhy, Simanchal; Harnafi, Mimoun; Villaseñor, Antonio; Gallart, Josep; Pazos, Antonio; Rahmouni, Abdelaali; Boukalouch, Mohamed; Sebbani, Jamal

2018-03-01

We studied the attenuation of coda waves and its frequency and lapse-time dependence in northern Morocco. We analysed coda waves of 66 earthquakes recorded in this region during 2008 for four lapse time windows of length 30, 40, 50, and 60 s, and at five frequency bands with central frequency in the range of 0.75-12 Hz. We determined the frequency dependent Q c relation for the horizontal (NS and EW) and vertical (Z) component seismograms. We analyzed three-component broadband seismograms of 66 local earthquakes for determining coda-Q based on the single back-scattering model. The Q c values show strong frequency dependence in 1.5-12 Hz that is related to high degree of heterogeneity of the medium. The lapse time dependence of Q c shows that Q 0 ( Q c at 1 Hz) significantly increases with lapse time that is related to the depth dependence of attenuation and hence of the level of heterogeneity of the medium. The average frequency-dependent Q c( f) values are Qc = (143.75 ± 1.09)f^{(0.864 ± 0.006)}, Qc = (149.12 ± 1.08)f^{(0.85 ± 0.005)} and Qc = (140.42 ± 1.81)f^{(0.902 ± 0.004)} for the vertical, north-south and east-west components of motion, respectively. The frequency-dependent Q c(f) relations are useful for evaluating source parameters (Singh et al. 2001), which are the key inputs for seismic hazard assessment of the region.

Frequency dependence limits divergent evolution by favouring rare immigrants over residents.

PubMed

Bolnick, Daniel I; Stutz, William E

2017-06-08

Two distinct forms of natural selection promote adaptive biological diversity. Divergent selection occurs when different environments favour different phenotypes, leading to increased differences between populations. Negative frequency-dependent selection occurs when rare variants within a population are favoured over common ones, increasing diversity within populations. These two diversifying forces promote genetic variation at different spatial scales, and may act in opposition, but their relative effects remain unclear because they are rarely measured concurrently. Here we show that negative frequency-dependent selection within populations can favor rare immigrants over locally adapted residents. We reciprocally transplanted lake and stream ecotypes of threespine stickleback into lake and stream habitats, while manipulating the relative abundance of residents versus immigrants. We found negative frequency-dependence: survival was highest for the locally rare ecotype, rather than natives. Also, individuals with locally rare major histocompatibility complex (MHC) class IIb genotypes were infected by fewer parasites. This negative frequency-dependent selection will tend to favour rare immigrants over common residents, amplifying the effect of migration and undermining the efficacy of divergent natural selection to drive population differences. The only signal of divergent selection was a tendency for foreign fish to have higher parasite loads than residents, after controlling for MHC genotype rarity. Frequency-dependent ecological interactions have long been thought to promote speciation. Our results suggest a more nuanced view in which negative frequency dependence alters the fate of migrants to promote or constrain evolutionary divergence between populations.

Universal distribution of component frequencies in biological and technological systems

PubMed Central

Pang, Tin Yau; Maslov, Sergei

2013-01-01

Bacterial genomes and large-scale computer software projects both consist of a large number of components (genes or software packages) connected via a network of mutual dependencies. Components can be easily added or removed from individual systems, and their use frequencies vary over many orders of magnitude. We study this frequency distribution in genomes of ∼500 bacterial species and in over 2 million Linux computers and find that in both cases it is described by the same scale-free power-law distribution with an additional peak near the tail of the distribution corresponding to nearly universal components. We argue that the existence of a power law distribution of frequencies of components is a general property of any modular system with a multilayered dependency network. We demonstrate that the frequency of a component is positively correlated with its dependency degree given by the total number of upstream components whose operation directly or indirectly depends on the selected component. The observed frequency/dependency degree distributions are reproduced in a simple mathematically tractable model introduced and analyzed in this study. PMID:23530195

Molecular stress-inducing compounds increase osteoclast formation in a heat shock factor 1 protein-dependent manner.

PubMed

Chai, Ryan C; Kouspou, Michelle M; Lang, Benjamin J; Nguyen, Chau H; van der Kraan, A Gabrielle J; Vieusseux, Jessica L; Lim, Reece C; Gillespie, Matthew T; Benjamin, Ivor J; Quinn, Julian M W; Price, John T

2014-05-09

Many anticancer therapeutic agents cause bone loss, which increases the risk of fractures that severely reduce quality of life. Thus, in drug development, it is critical to identify and understand such effects. Anticancer therapeutic and HSP90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) causes bone loss by increasing osteoclast formation, but the mechanism underlying this is not understood. 17-AAG activates heat shock factor 1 (Hsf1), the master transcriptional regulator of heat shock/cell stress responses, which may be involved in this negative action of 17-AAG upon bone. Using mouse bone marrow and RAW264.7 osteoclast differentiation models we found that HSP90 inhibitors that induced a heat shock response also enhanced osteoclast formation, whereas HSP90 inhibitors that did not (including coumermycin A1 and novobiocin) did not affect osteoclast formation. Pharmacological inhibition or shRNAmir knockdown of Hsf1 in RAW264.7 cells as well as the use of Hsf1 null mouse bone marrow cells demonstrated that 17-AAG-enhanced osteoclast formation was Hsf1-dependent. Moreover, ectopic overexpression of Hsf1 enhanced 17-AAG effects upon osteoclast formation. Consistent with these findings, protein levels of the essential osteoclast transcription factor microphthalmia-associated transcription factor were increased by 17-AAG in an Hsf1-dependent manner. In addition to HSP90 inhibitors, we also identified that other agents that induced cellular stress, such as ethanol, doxorubicin, and methotrexate, also directly increased osteoclast formation, potentially in an Hsf1-dependent manner. These results, therefore, indicate that cellular stress can enhance osteoclast differentiation via Hsf1-dependent mechanisms and may significantly contribute to pathological and therapeutic related bone loss.

Unusual polarity-dependent patterns in a bent-core nematic liquid crystal under low-frequency ac field.

PubMed

Xiang, Ying; Zhou, Meng-jie; Xu, Ming-Ya; Salamon, Péter; Éber, Nándor; Buka, Ágnes

2015-04-01

Electric-field-induced patterns of diverse morphology have been observed over a wide frequency range in a recently synthesized bent-core nematic (BCN) liquid crystal. At low frequencies (up to ∼25 Hz), the BCN exhibited unusual polarity-dependent patterns. When the amplitude of the ac field was enhanced, these two time-asymmetrical patterns turned into time-symmetrical prewavylike stripes. At ac frequencies in the middle-frequency range (∼50-3000 Hz), zigzag patterns were detected whose obliqueness varied with the frequency. Finally, if the frequency was increased above 3 kHz, the zigzag pattern was replaced by another, prewavylike pattern, whose threshold voltage depended on the frequency; however, the wave vector did not. For a more complete characterization, material parameters such as elastic constants, dielectric permittivities, and the anisotropy of the diamagnetic susceptibility were also determined.

The nonstationary strain filter in elastography: Part I. Frequency dependent attenuation.

PubMed

Varghese, T; Ophir, J

1997-01-01

The accuracy and precision of the strain estimates in elastography depend on a myriad number of factors. A clear understanding of the various factors (noise sources) that plague strain estimation is essential to obtain quality elastograms. The nonstationary variation in the performance of the strain filter due to frequency-dependent attenuation and lateral and elevational signal decorrelation are analyzed in this and the companion paper for the cross-correlation-based strain estimator. In this paper, we focus on the role of frequency-dependent attenuation in the performance of the strain estimator. The reduction in the signal-to-noise ratio (SNRs) in the RF signal, and the center frequency and bandwidth downshift with frequency-dependent attenuation are incorporated into the strain filter formulation. Both linear and nonlinear frequency dependence of attenuation are theoretically analyzed. Monte-Carlo simulations are used to corroborate the theoretically predicted results. Experimental results illustrate the deterioration in the precision of the strain estimates with depth in a uniformly elastic phantom. Theoretical, simulation and experimental results indicate the importance of high SNRs values in the RF signals, because the strain estimation sensitivity, elastographic SNRe and dynamic range deteriorate rapidly with a decrease in the SNRs. In addition, a shift in the strain filter toward higher strains is observed at large depths in tissue due to the center frequency downshift.

Intruder detection system

NASA Technical Reports Server (NTRS)

Lee, R. D. (Inventor)

1973-01-01

An intruder detection system is described. The system contains a transmitter which sends a frequency modulated and amplitude modulated signal to a remote receiver in response to a geophone detector which responds to seismic impulses created by the intruder. The signal makes it possible for an operator to determine the number of intruders and the manner of movement.

Auditory Proprioceptive Integration: Effects of Real-Time Kinematic Auditory Feedback on Knee Proprioception

PubMed Central

Ghai, Shashank; Schmitz, Gerd; Hwang, Tong-Hun; Effenberg, Alfred O.

2018-01-01

The purpose of the study was to assess the influence of real-time auditory feedback on knee proprioception. Thirty healthy participants were randomly allocated to control (n = 15), and experimental group I (15). The participants performed an active knee-repositioning task using their dominant leg, with/without additional real-time auditory feedback where the frequency was mapped in a convergent manner to two different target angles (40 and 75°). Statistical analysis revealed significant enhancement in knee re-positioning accuracy for the constant and absolute error with real-time auditory feedback, within and across the groups. Besides this convergent condition, we established a second divergent condition. Here, a step-wise transposition of frequency was performed to explore whether a systematic tuning between auditory-proprioceptive repositioning exists. No significant effects were identified in this divergent auditory feedback condition. An additional experimental group II (n = 20) was further included. Here, we investigated the influence of a larger magnitude and directional change of step-wise transposition of the frequency. In a first step, results confirm the findings of experiment I. Moreover, significant effects on knee auditory-proprioception repositioning were evident when divergent auditory feedback was applied. During the step-wise transposition participants showed systematic modulation of knee movements in the opposite direction of transposition. We confirm that knee re-positioning accuracy can be enhanced with concurrent application of real-time auditory feedback and that knee re-positioning can modulated in a goal-directed manner with step-wise transposition of frequency. Clinical implications are discussed with respect to joint position sense in rehabilitation settings. PMID:29568259

Signaling pathway underlying the octopaminergic modulation of myogenic contraction in the cricket lateral oviduct.

PubMed

Tamashiro, Hirotake; Yoshino, Masami

2014-12-01

Octopamine (OA), a biogenic monoamine, is a neurotransmitter and neuromodulator in invertebrates. Here, we report the effect of OA on the spontaneous rhythmic contractions (SRCs) of the lateral oviduct of the cricket Gryllus bimaculatus and the possible signaling pathway involved. Application of OA increased both the frequency and amplitude of SRCs in a dose-dependent manner. The effect of OA was inhibited by subsequent application of the OA receptor antagonist epinastine, indicating that the action of OA is mediated by OA receptor. To investigate the predominant signaling pathway underlying the action of OA, we first examined a possible involvement of the cAMP/cAMP-dependent protein kinase A (PKA) signaling pathway. Application of the membrane-permeable cAMP analog 8-Br-cAMP had little effect on SRCs and the effect of OA was not influenced by subsequent application of the PKA inhibitor H89, indicating that the cAMP/PKA signaling pathway is not the predominant pathway in the action of OA. Next, we examined a possible involvement of the second messenger inositol 1,4,5-trisphosphate in the action of OA. The effect of OA on SRCs was inhibited by subsequent application of the phosphoinositide-specific phospholipase C (PLC) inhibitor U73122, indicating that the PLC pathway is involved in the action of OA. The OA-induced increase in the frequency of SRCs was inhibited by pretreatment of the cell with the ryanodine receptor antagonist tetracaine but was not significantly affected by the IP3 receptor antagonist 2-aminoethoxydiphenyl borate (2-APB). On the other hand, the OA-induced increase in the amplitude of SRCs was inhibited by pretreatment of the cells with 2-APB but was not significantly affected by tetracaine. Taken together, these results suggest that the OA-induced excitatory effect on SRCs is mediated by the PLC signaling pathway: Ca2+ release from IP3 receptors may contribute to the modulation of the amplitude of SRCs, whereas Ca2+ release from ryanodine receptors may contribute to the modulation of the frequency of SRCs. Copyright © 2014 Elsevier Ltd. All rights reserved.

ADP-ribosylation factor arf6p may function as a molecular switch of new end take off in fission yeast

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

Fujita, Atsushi

2008-02-01

Small GTPases act as molecular switches in a wide variety of cellular processes. In fission yeast Schizosaccharomyces pombe, the directions of cell growth change from a monopolar manner to a bipolar manner, which is known as 'New End Take Off' (NETO). Here I report the identification of a gene, arf6{sup +}, encoding an ADP-ribosylation factor small GTPase, that may be essential for NETO. arf6{delta} cells completely fail to undergo NETO. arf6p localizes at both cell ends and presumptive septa in a cell-cycle dependent manner. And its polarized localization is not dependent on microtubules, actin cytoskeletons and some NETO factors (bud6p,more » for3p, tea1p, tea3p, and tea4p). Notably, overexpression of a fast GDP/GTP-cycling mutant of arf6p can advance the timing of NETO. These findings suggest that arf6p functions as a molecular switch for the activation of NETO in fission yeast.« less

Anomalous frequency-dependent ionic conductivity of lesion-laden human-brain tissue

NASA Astrophysics Data System (ADS)

Emin, David; Akhtari, Massoud; Fallah, Aria; Vinters, Harry V.; Mathern, Gary W.

2017-10-01

We study the effect of lesions on our four-electrode measurements of the ionic conductivity of (˜1 cm3) samples of human brain excised from patients undergoing pediatric epilepsy surgery. For most (˜94%) samples, the low-frequency ionic conductivity rises upon increasing the applied frequency. We attributed this behavior to the long-range (˜0.4 mm) diffusion of solvated sodium cations before encountering intrinsic impenetrable blockages such as cell membranes, blood vessels, and cell walls. By contrast, the low-frequency ionic conductivity of some (˜6%) brain-tissue samples falls with increasing applied frequency. We attribute this unusual frequency-dependence to the electric-field induced liberation of sodium cations from traps introduced by the unusually severe pathology observed in samples from these patients. Thus, the anomalous frequency-dependence of the ionic conductivity indicates trap-producing brain lesions.

Non-Lorentzian ion cyclotron resonance line shapes arising from velocity-dependent ion-neutral collision frequencies

NASA Technical Reports Server (NTRS)

Whealton, J. H.; Mason, E. A.

1973-01-01

An asymptotic solution of the Boltzmann equation is developed for ICR absorption, without restrictions on the ion-neutral collision frequency or mass ratio. Velocity dependence of the collision frequency causes deviations from Lorentzian line shape.

Effects of aromaticity in cations and their functional groups on the temperature dependence of low-frequency spectrum

DOE PAGES

Kakinuma, Shohei; Ramati, Sharon; Wishart, James F.; ...

2018-05-21

We investigate the temperature dependence of low-frequency spectra in the frequency range of 0.3–200 cm -1 for ionic liquids (ILs) whose cations possess two systematically different cyclic groups, using femtosecond Raman-induced Kerr effect spectroscopy. The target ILs are bis(trifluoromethylsulfonyl)amide [NTf 2]– salts of 1-cyclohexylmethyl-1-methylpyrrolidinium [CHxmMPyrr] +, 1-cyclohexylmethyl-3-methylimidazolium [CHxmMIm] +, N-cyclohexylmethylpyridinium [CHxmPy]+, 1-benzyl-1-methylpyrrolidinium [BzMPyrr] +, 1-benzyl-3-methylimidazolium [BzMIm] +, and N-benzylpyridinium [BzPy] + cations. The aim of this study is to better understand the effects of aromaticity in the cations’ constituent groups on the temperature-dependent low-frequency spectral features of the ILs. The low-frequency spectra of these ILs are temperature dependent, but themore » temperature-dependent spectrum of [CHxmMPyrr][NTf 2] is different from that of other ILs. While [CHxmMPyrr][NTf 2] shows spectral changes with temperature in the low-frequency region below 50 cm -1, the other ILs also show spectral changes in the high-frequency region above 80 cm -1 (above 50 cm -1 in the case of [BzMPyrr][NTf 2]). We conclude that the spectral change in the low-frequency region is due to both the cation and anion, while the change in the high-frequency region is attributed to the red shift of the aromatic ring librations. On the basis of the plots of the first moment of the spectra vs. temperature, we found that the first moment of the low-frequency spectrum of the IL whose cation does not have an aromatic ring is less temperature dependent than that of the other ILs. However, the intrinsic first moment, the first moment at 0 K, of the low-frequency spectrum is governed by the absence or presence of a charged aromatic group, while a neutral aromatic group does not have much influence on determining the intrinsic first moment.« less

Effects of aromaticity in cations and their functional groups on the temperature dependence of low-frequency spectrum

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

Kakinuma, Shohei; Ramati, Sharon; Wishart, James F.

We investigate the temperature dependence of low-frequency spectra in the frequency range of 0.3–200 cm -1 for ionic liquids (ILs) whose cations possess two systematically different cyclic groups, using femtosecond Raman-induced Kerr effect spectroscopy. The target ILs are bis(trifluoromethylsulfonyl)amide [NTf 2]– salts of 1-cyclohexylmethyl-1-methylpyrrolidinium [CHxmMPyrr] +, 1-cyclohexylmethyl-3-methylimidazolium [CHxmMIm] +, N-cyclohexylmethylpyridinium [CHxmPy]+, 1-benzyl-1-methylpyrrolidinium [BzMPyrr] +, 1-benzyl-3-methylimidazolium [BzMIm] +, and N-benzylpyridinium [BzPy] + cations. The aim of this study is to better understand the effects of aromaticity in the cations’ constituent groups on the temperature-dependent low-frequency spectral features of the ILs. The low-frequency spectra of these ILs are temperature dependent, but themore » temperature-dependent spectrum of [CHxmMPyrr][NTf 2] is different from that of other ILs. While [CHxmMPyrr][NTf 2] shows spectral changes with temperature in the low-frequency region below 50 cm -1, the other ILs also show spectral changes in the high-frequency region above 80 cm -1 (above 50 cm -1 in the case of [BzMPyrr][NTf 2]). We conclude that the spectral change in the low-frequency region is due to both the cation and anion, while the change in the high-frequency region is attributed to the red shift of the aromatic ring librations. On the basis of the plots of the first moment of the spectra vs. temperature, we found that the first moment of the low-frequency spectrum of the IL whose cation does not have an aromatic ring is less temperature dependent than that of the other ILs. However, the intrinsic first moment, the first moment at 0 K, of the low-frequency spectrum is governed by the absence or presence of a charged aromatic group, while a neutral aromatic group does not have much influence on determining the intrinsic first moment.« less

Effects of aromaticity in cations and their functional groups on the temperature dependence of low-frequency spectrum

NASA Astrophysics Data System (ADS)

Kakinuma, Shohei; Ramati, Sharon; Wishart, James F.; Shirota, Hideaki

2018-05-01

In this study, we investigate the temperature dependence of low-frequency spectra in the frequency range of 0.3-200 cm-1 for ionic liquids (ILs) whose cations possess two systematically different cyclic groups, using femtosecond Raman-induced Kerr effect spectroscopy. The target ILs are bis(trifluoromethylsulfonyl)amide [NTf2]- salts of 1-cyclohexylmethyl-1-methylpyrrolidinium [CHxmMPyrr]+, 1-cyclohexylmethyl-3-methylimidazolium [CHxmMIm]+, N-cyclohexylmethylpyridinium [CHxmPy]+, 1-benzyl-1-methylpyrrolidinium [BzMPyrr]+, 1-benzyl-3-methylimidazolium [BzMIm]+, and N-benzylpyridinium [BzPy]+ cations. The aim of this study is to better understand the effects of aromaticity in the cations' constituent groups on the temperature-dependent low-frequency spectral features of the ILs. The low-frequency spectra of these ILs are temperature dependent, but the temperature-dependent spectrum of [CHxmMPyrr][NTf2] is different from that of other ILs. While [CHxmMPyrr][NTf2] shows spectral changes with temperature in the low-frequency region below 50 cm-1, the other ILs also show spectral changes in the high-frequency region above 80 cm-1 (above 50 cm-1 in the case of [BzMPyrr][NTf2]). We conclude that the spectral change in the low-frequency region is due to both the cation and anion, while the change in the high-frequency region is attributed to the red shift of the aromatic ring librations. On the basis of the plots of the first moment of the spectra vs. temperature, we found that the first moment of the low-frequency spectrum of the IL whose cation does not have an aromatic ring is less temperature dependent than that of the other ILs. However, the intrinsic first moment, the first moment at 0 K, of the low-frequency spectrum is governed by the absence or presence of a charged aromatic group, while a neutral aromatic group does not have much influence on determining the intrinsic first moment.

Mutual Information in Frequency and Its Application to Measure Cross-Frequency Coupling in Epilepsy

NASA Astrophysics Data System (ADS)

Malladi, Rakesh; Johnson, Don H.; Kalamangalam, Giridhar P.; Tandon, Nitin; Aazhang, Behnaam

2018-06-01

We define a metric, mutual information in frequency (MI-in-frequency), to detect and quantify the statistical dependence between different frequency components in the data, referred to as cross-frequency coupling and apply it to electrophysiological recordings from the brain to infer cross-frequency coupling. The current metrics used to quantify the cross-frequency coupling in neuroscience cannot detect if two frequency components in non-Gaussian brain recordings are statistically independent or not. Our MI-in-frequency metric, based on Shannon's mutual information between the Cramer's representation of stochastic processes, overcomes this shortcoming and can detect statistical dependence in frequency between non-Gaussian signals. We then describe two data-driven estimators of MI-in-frequency: one based on kernel density estimation and the other based on the nearest neighbor algorithm and validate their performance on simulated data. We then use MI-in-frequency to estimate mutual information between two data streams that are dependent across time, without making any parametric model assumptions. Finally, we use the MI-in- frequency metric to investigate the cross-frequency coupling in seizure onset zone from electrocorticographic recordings during seizures. The inferred cross-frequency coupling characteristics are essential to optimize the spatial and spectral parameters of electrical stimulation based treatments of epilepsy.

Adjusting for background mutation frequency biases improves the identification of cancer driver genes.

PubMed

Evans, Perry; Avey, Stefan; Kong, Yong; Krauthammer, Michael

2013-09-01

A common goal of tumor sequencing projects is finding genes whose mutations are selected for during tumor development. This is accomplished by choosing genes that have more non-synonymous mutations than expected from an estimated background mutation frequency. While this background frequency is unknown, it can be estimated using both the observed synonymous mutation frequency and the non-synonymous to synonymous mutation ratio. The synonymous mutation frequency can be determined across all genes or in a gene-specific manner. This choice introduces an interesting trade-off. A gene-specific frequency adjusts for an underlying mutation bias, but is difficult to estimate given missing synonymous mutation counts. Using a genome-wide synonymous frequency is more robust, but is less suited for adjusting biases. Studying four evaluation criteria for identifying genes with high non-synonymous mutation burden (reflecting preferential selection of expressed genes, genes with mutations in conserved bases, genes with many protein interactions, and genes that show loss of heterozygosity), we find that the gene-specific synonymous frequency is superior in the gene expression and protein interaction tests. In conclusion, the use of the gene-specific synonymous mutation frequency is well suited for assessing a gene's non-synonymous mutation burden.

Assessing the utility of frequency dependent nudging for reducing biases in biogeochemical models

NASA Astrophysics Data System (ADS)

Lagman, Karl B.; Fennel, Katja; Thompson, Keith R.; Bianucci, Laura

2014-09-01

Bias errors, resulting from inaccurate boundary and forcing conditions, incorrect model parameterization, etc. are a common problem in environmental models including biogeochemical ocean models. While it is important to correct bias errors wherever possible, it is unlikely that any environmental model will ever be entirely free of such errors. Hence, methods for bias reduction are necessary. A widely used technique for online bias reduction is nudging, where simulated fields are continuously forced toward observations or a climatology. Nudging is robust and easy to implement, but suppresses high-frequency variability and introduces artificial phase shifts. As a solution to this problem Thompson et al. (2006) introduced frequency dependent nudging where nudging occurs only in prescribed frequency bands, typically centered on the mean and the annual cycle. They showed this method to be effective for eddy resolving ocean circulation models. Here we add a stability term to the previous form of frequency dependent nudging which makes the method more robust for non-linear biological models. Then we assess the utility of frequency dependent nudging for biological models by first applying the method to a simple predator-prey model and then to a 1D ocean biogeochemical model. In both cases we only nudge in two frequency bands centered on the mean and the annual cycle, and then assess how well the variability in higher frequency bands is recovered. We evaluate the effectiveness of frequency dependent nudging in comparison to conventional nudging and find significant improvements with the former.

Analysis of Fresnel Zone Plates Focusing Dependence on Operating Frequency

PubMed Central

Fuster, José Miguel; Candelas, Pilar; Castiñeira-Ibáñez, Sergio; Pérez-López, Sergio

2017-01-01

The focusing properties of Fresnel Zone Plates (FZPs) against frequency are analyzed in this work. It is shown that the FZP focal length depends almost linearly on the operating frequency. Focal depth and focal distortion are also considered, establishing a limit on the frequency span at which the operating frequency can be shifted. An underwater FZP ultrasound focusing system is demonstrated, and experimental results agree with the theoretical analysis and simulations. PMID:29206137

Beating motion of a circular cylinder in vortex-induced vibrations

NASA Astrophysics Data System (ADS)

Shen, Linwei; Chan, Eng-Soon; Wei, Yan

2018-04-01

In this paper, beating phenomenon of a circular cylinder in vortex-induced vibration is studied by numerical simulations in a systematic manner. The cylinder mass coefficients of 2 and 10 are considered, and the Reynolds number is 150. Two distinctive frequencies, namely cylinder oscillation and vortex shedding frequencies, are obtained from the harmonic analysis of the cylinder displacement. The result is consistent with that observed in laboratory experiments. It is found that the cylinder oscillation frequency changes with the natural frequency of the cylinder while the reduced velocity is varied. The added-mass coefficient of the cylinder in beating motion is therefore estimated. Meanwhile, the vortex shedding frequency does not change dramatically in the beating situations. In fact, it is very close to 0.2. Accordingly, the lift force coefficient has two main components associated with these two frequencies. Besides, higher harmonics of the cylinder oscillation frequency appear in the spectrum of the lift coefficient. Moreover, the vortex shedding timing is studied in the beating motion by examining the instantaneous flow fields in the wake, and two scenarios of the vortex formation are observed.

Phloretin Inhibits Platelet-derived Growth Factor-BB-induced Rat Aortic Smooth Muscle Cell Proliferation, Migration, and Neointimal Formation After Carotid Injury.

PubMed

Wang, Dong; Wang, Qingjie; Yan, Gaoliang; Qiao, Yong; Tang, Chengchun

2015-05-01

Abnormal vascular smooth muscle cell proliferation and migration are key factors in many cardiovascular diseases. Here, we investigated the effects of phloretin on platelet-derived growth factor homodimer (PDGF-BB)-induced rat aortic smooth muscle cell (RASMC) proliferation, migration, and neointimal formation after carotid injury. Phloretin significantly inhibited the PDGF-BB-stimulated RASMC proliferation in a concentration-dependent manner (10-100 μM). Also, PDGF-BB-stimulated RASMC migration was inhibited by phloretin at 50 μM. Pretreating RASMC with phloretin dose-dependently inhibited PDGF-BB-induced Akt and p38 mitogen-activated protein kinases activation. Furthermore, phloretin increased p27 and decreased cyclin-dependent kinase 2, CDK4 expression, and p-Rb activation in PDGF-BB-stimulated RASMC in a concentration-dependent manner (10-50 μM). PDGF-BB-induced cell adhesion molecules and matrix metalloproteinase-9 expression were blocked by phloretin at 50 μM. Preincubation with phloretin dose-dependently reduced the intracellular reactive oxygen species production. In vivo study showed that phloretin (20 mg/kg) significantly reduced neointimal formation 14 days after carotid injury in rats. Thus, phloretin may have potential as a treatment against atherosclerosis and restenosis after vascular injury.

Voltage and frequency dependence of prestin-associated charge transfer

PubMed Central

Sun, Sean X.; Farrell, Brenda; Chana, Matthew S.; Oster, George; Brownell, William E.; Spector, Alexander A.

2009-01-01

Membrane protein prestin is a critical component of the motor complex that generates forces and dimensional changes in cells in response to changes in the cell membrane potential. In its native cochlear outer hair cell, prestin is crucial to the amplification and frequency selectivity of the mammalian ear up to frequencies of tens of kHz. Other cells transfected with prestin acquire voltage-dependent properties similar to those of the native cell. The protein performance is critically dependent on chloride ions, and intrinsic protein charges also play a role. We propose an electro-diffusion model to reveal the frequency and voltage dependence of electric charge transfer by prestin. The movement of the combined charge (i.e., anion and protein charges) across the membrane is described with a Fokker-Planck equation coupled to a kinetic equation that describes the binding of chloride ions to prestin. We found a voltage-and frequency-dependent phase shift between the transferred charge and the applied electric field that determines capacitive and resistive components of the transferred charge. The phase shift monotonically decreases from zero to -90 degree as a function of frequency. The capacitive component as a function of voltage is bell-shaped, and decreases with frequency. The resistive component is bell-shaped for both voltage and frequency. The capacitive and resistive components are similar to experimental measurements of charge transfer at high frequencies. The revealed nature of the transferred charge can help reconcile the high-frequency electrical and mechanical observations associated with prestin, and it is important for further analysis of the structure and function of this protein. PMID:19490917

Generalized Doppler and aberration kernel for frequency-dependent cosmological observables

NASA Astrophysics Data System (ADS)

Yasini, Siavash; Pierpaoli, Elena

2017-11-01

We introduce a frequency-dependent Doppler and aberration transformation kernel for the harmonic multipoles of a general cosmological observable with spin weight s , Doppler weight d and arbitrary frequency spectrum. In the context of cosmic microwave background (CMB) studies, the frequency-dependent formalism allows to correct for the motion-induced aberration and Doppler effects on individual frequency maps with different masks. It also permits to deboost background radiations with non-blackbody frequency spectra, like extragalactic foregrounds and CMB spectra with primordial spectral distortions. The formalism can also be used to correct individual E and B polarization modes and account for motion-induced E/B mixing of polarized observables with d ≠1 at different frequencies. We apply the generalized aberration kernel on polarized and unpolarized specific intensity at 100 and 217 GHz and show that the motion-induced effects typically increase with the frequency of observation. In all-sky CMB experiments, the frequency-dependence of the motion-induced effects for a blackbody spectrum are overall negligible. However in a cut-sky analysis, ignoring the frequency dependence can lead to percent level error in the polarized and unpolarized power spectra over all angular scales. In the specific cut-sky used in our analysis (b >4 5 ° ,fsky≃14 % ), and for the dipole-inferred velocity β =0.00123 typically attributed to our peculiar motion, the Doppler and aberration effects can change polarized and unpolarized power spectra of specific intensity in the CMB rest frame by 1 - 2 % , but we find the polarization cross-leakage between E and B modes to be negligible.

Anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation: frequency and power dependence.

PubMed

Gapeyev, A B; Mikhailik, E N; Chemeris, N K

2008-04-01

Using a model of acute zymosan-induced footpad edema in NMRI mice, the frequency and power dependence of anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR) was found. Single whole-body exposure of animals to EHF EMR at the intensity of 0.1 mW/cm(2) for 20 min at 1 h after zymosan injection reduced both the footpad edema and local hyperthermia on average by 20% at the frequencies of 42.2, 51.8, and 65 GHz. Some other frequencies from the frequency range of 37.5-70 GHz were less effective or not effective at all. At fixed frequency of 42.2 GHz and intensity of 0.1 mW/cm(2), the effect had bell-shaped dependence on exposure duration with a maximum at 20-40 min. Reduction of intensity to 0.01 mW/cm(2) resulted in a change of the effect dependence on exposure duration to a linear one. Combined action of cyclooxygenase inhibitor sodium diclofenac and EHF EMR exposure caused a partial additive effect of decrease in footpad edema. Combined action of antihistamine clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that arachidonic acid metabolites and histamine are involved in realization of anti-inflammatory effects of low-intensity EHF EMR. (c) 2007 Wiley-Liss, Inc.

Deformation of giant vesicles in AC electric fields —Dependence of the prolate-to-oblate transition frequency on vesicle radius

NASA Astrophysics Data System (ADS)

Antonova, K.; Vitkova, V.; Mitov, M. D.

2010-02-01

The electrodeformation of giant vesicles is studied as a function of their radii and the frequency of the applied AC field. At low frequency the shape is prolate, at sufficiently high frequency it is oblate and at some frequency, fc, the shape changes from prolate to oblate. A linear dependence of the prolate-to-oblate transition inverse frequency, 1/fc, on the vesicle radius is found. The nature of this phenomenon does not change with the variation of both the solution conductivity, σ, and the type of the fluid enclosed by the lipid membrane (water, sucrose or glucose aqueous solution). When σ increases, the value of fc increases while the slope of the line 1/fc(r) decreases. For vesicles in symmetrical conditions (the same conductivity of the inner and the outer solution) a linear dependence between σ and the critical frequency, fc, is obtained for conductivities up to σ=114 μS/cm. For vesicles with sizes below a certain minimum radius, depending on the solution conductivity, no shape transition could be observed.

Managing grazing of riparian areas in the Intermountain Region

Treesearch

Warren P. Clary; Bert F. Webster

1989-01-01

Concern about livestock grazing in riparian habitats and its effect upon riparian-dependent resources has resulted in numerous controversies about the appropriate management approach. This document provides guidance for grazing of riparian areas in a manner that should reduce both nonpoint source pollution and potential grazing impacts on other riparian-dependent...

HDAC Inhibition Modulates Hippocampus-Dependent Long-Term Memory for Object Location in a CBP-Dependent Manner

ERIC Educational Resources Information Center

Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

2011-01-01

Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation…

Exogenous fatty acids and niacin on acute prostaglandin D2 production in human myeloid cells.

PubMed

Montserrat-de la Paz, Sergio; Bermudez, Beatriz; Lopez, Sergio; Naranjo, Maria C; Romero, Yolanda; Bando-Hidalgo, Maria J; Abia, Rocio; Muriana, Francisco J G

2017-01-01

Niacin activates HCA 2 receptor that results in the release of PGD 2 . However, little is known on PGD 2 -producing cells and the role of fatty acids. Notably M-CSF macrophages exhibited a timely dependent PGD 2 production upon niacin challenge. Short pretreatment of M-CSF macrophages with autologous postprandial TRLs induced the down-regulation of HCA 2 gene and up-regulation of genes encoding COX1 and COX2 enzymes in a fatty acid-dependent manner. These effects were paralleled by a higher PGD 2 production with postprandial TRL-SFAs. The niacin-mediated transcriptional activity of all genes involved in PGD 2 biosynthesis was desensitized in a time-dependent manner by postprandial TRLs, leading to a decreased PGD 2 release. In vivo, the net excursions of PGD 2 in plasma followed similar fatty acid-dependent patterns as those found for PGD 2 release in vitro. The predominant fatty acid class in the diet acutely modulates PGD 2 biosynthetic pathway both in vitro and in vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

Parental overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner

PubMed Central

2013-01-01

Background It has been suggested that dysfunctional attitudes, cognitive vulnerability to depression, have developmental origins. The present study examined the effects of parental rearing on dysfunctional attitudes in three areas of life with special attention to gender specificity. Methods The subjects were 665 Japanese healthy volunteers. Dysfunctional attitudes were assessed by the 24-item Dysfunctional Attitude Scale, which has the Achievement, Dependency and Self-control subscales. Perceived parental rearing was assessed by the Parental Bonding Instrument, which has the Care and Protection subscales. Results Higher scores of the Achievement (β = 0.293, p < 0.01) and Dependency (β = 0.224, p < 0.05) subscales were correlated with higher scores of the Protection subscale in the combination of mother and daughter, but not in other combinations of parents and recipients. Scores of the Self-control subscale were not correlated with paternal or maternal rearing scores. Conclusions The present study suggests that parental overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner. PMID:24365104

3-D model-based Bayesian classification

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

Soenneland, L.; Tenneboe, P.; Gehrmann, T.

1994-12-31

The challenging task of the interpreter is to integrate different pieces of information and combine them into an earth model. The sophistication level of this earth model might vary from the simplest geometrical description to the most complex set of reservoir parameters related to the geometrical description. Obviously the sophistication level also depend on the completeness of the available information. The authors describe the interpreter`s task as a mapping between the observation space and the model space. The information available to the interpreter exists in observation space and the task is to infer a model in model-space. It is well-knownmore » that this inversion problem is non-unique. Therefore any attempt to find a solution depend son constraints being added in some manner. The solution will obviously depend on which constraints are introduced and it would be desirable to allow the interpreter to modify the constraints in a problem-dependent manner. They will present a probabilistic framework that gives the interpreter the tools to integrate the different types of information and produce constrained solutions. The constraints can be adapted to the problem at hand.« less

Spermidine promotes stress resistance in Drosophila melanogaster through autophagy-dependent and -independent pathways.

PubMed

Minois, N; Carmona-Gutierrez, D; Bauer, M A; Rockenfeller, P; Eisenberg, T; Brandhorst, S; Sigrist, S J; Kroemer, G; Madeo, F

2012-10-11

The naturally occurring polyamine spermidine (Spd) has recently been shown to promote longevity across species in an autophagy-dependent manner. Here, we demonstrate that Spd improves both survival and locomotor activity of the fruit fly Drosophila melanogaster upon exposure to the superoxide generator and neurotoxic agent paraquat. Although survival to a high paraquat concentration (20 mM) was specifically increased in female flies only, locomotor activity and survival could be rescued in both male and female animals when exposed to lower paraquat levels (5 mM). These effects are dependent on the autophagic machinery, as Spd failed to confer resistance to paraquat-induced toxicity and locomotor impairment in flies deleted for the essential autophagic regulator ATG7 (autophagy-related gene 7). Spd treatment did also protect against mild doses of another oxidative stressor, hydrogen peroxide, but in this case in an autophagy-independent manner. Altogether, this study establishes that the protective effects of Spd can be exerted through different pathways that depending on the oxidative stress scenario do or do not involve autophagy.

Dengue Virus Modulates the Unfolded Protein Response in a Time-dependent Manner*

PubMed Central

Peña, José; Harris, Eva

2011-01-01

Flaviviruses, such as dengue virus (DENV), depend on the host endoplasmic reticulum for translation, replication, and packaging of their genomes. Here we report that DENV-2 infection modulates the unfolded protein response in a time-dependent manner. We show that early DENV-2 infection triggers and then suppresses PERK-mediated eIF2α phosphorylation and that in mid and late DENV-2 infection, the IRE1-XBP1 and ATF6 pathways are activated, respectively. Activation of IRE1-XBP1 correlated with induction of downstream targets GRP78, CHOP, and GADD34. Furthermore, induction of CHOP did not induce apoptotic markers, such as suppression of anti-apoptotic protein Bcl-2, activation of caspase-9 or caspase-3, and cleavage of poly(ADP-ribose) polymerase. Finally, we show that DENV-2 replication is affected in PERK−/− and IRE1−/− mouse embryo fibroblasts when compared with wild-type mouse embryo fibroblasts. These results demonstrate that time-dependent activation of the unfolded protein response by DENV-2 can override inhibition of translation, prevent apoptosis, and prolong the viral life cycle. PMID:21385877

A Comparison of Two Mathematical Modeling Frameworks for Evaluating Sexually Transmitted Infection Epidemiology.

PubMed

Johnson, Leigh F; Geffen, Nathan

2016-03-01

Different models of sexually transmitted infections (STIs) can yield substantially different conclusions about STI epidemiology, and it is important to understand how and why models differ. Frequency-dependent models make the simplifying assumption that STI incidence is proportional to STI prevalence in the population, whereas network models calculate STI incidence more realistically by classifying individuals according to their partners' STI status. We assessed a deterministic frequency-dependent model approximation to a microsimulation network model of STIs in South Africa. Sexual behavior and demographic parameters were identical in the 2 models. Six STIs were simulated using each model: HIV, herpes, syphilis, gonorrhea, chlamydia, and trichomoniasis. For all 6 STIs, the frequency-dependent model estimated a higher STI prevalence than the network model, with the difference between the 2 models being relatively large for the curable STIs. When the 2 models were fitted to the same STI prevalence data, the best-fitting parameters differed substantially between models, with the frequency-dependent model suggesting more immunity and lower transmission probabilities. The fitted frequency-dependent model estimated that the effects of a hypothetical elimination of concurrent partnerships and a reduction in commercial sex were both smaller than estimated by the fitted network model, whereas the latter model estimated a smaller impact of a reduction in unprotected sex in spousal relationships. The frequency-dependent assumption is problematic when modeling short-term STIs. Frequency-dependent models tend to underestimate the importance of high-risk groups in sustaining STI epidemics, while overestimating the importance of long-term partnerships and low-risk groups.

Frequency dependent hub role of the dorsal and ventral right anterior insula.

PubMed

Wang, Yifeng; Zhu, Lixia; Zou, Qijun; Cui, Qian; Liao, Wei; Duan, Xujun; Biswal, Bharat; Chen, Huafu

2018-01-15

The right anterior insula (rAI) plays a crucial role in generating adaptive behavior by orchestrating multiple brain networks. Based on functional separation findings of the insula and spectral fingerprints theory of cognitive functions, we hypothesize that the hub role of the rAI is region and frequency dependent. Using the Human Connectome Project dataset and backtracking approach, we segregate the rAI into dorsal and ventral parts at frequency bands from slow 6 to slow 3, indicating the frequency dependent functional separation of the rAI. Functional connectivity analysis shows that, within lower than 0.198 Hz frequency range, the dorsal and ventral parts of rAI form a complementary system to synchronize with externally and internally-oriented networks. Moreover, the relationship between the dorsal and ventral rAIs predicts the relationship between anti-correlated networks associated with the dorsal rAI at slow 6 and slow 5, suggesting a frequency dependent regulation of the rAI to brain networks. These findings could improve our understanding of the rAI by supporting the region and frequency dependent function of rAI and its essential role in coordinating brain systems relevant to internal and external environments. Copyright © 2017 Elsevier Inc. All rights reserved.

Adenosine triphosphate regulates the activity of guinea pig Cav1.2 channel by direct binding to the channel in a dose-dependent manner.

PubMed

Feng, Rui; Xu, Jianjun; Minobe, Etsuko; Kameyama, Asako; Yang, Lei; Yu, Lifeng; Hao, Liying; Kameyama, Masaki

2014-05-01

The present study is to investigate the mechanism by which ATP regulates Cav1.2 channel activity. Ventricular tissue was obtained from adult guinea pig hearts using collagenase. Ca(2+) channel activity was monitored using the patch-clamp technique. Proteins were purified using wheat germ agglutinin-Sepharose, and the concentration was determined using the Coomassie brilliant blue technique. ATP binding to the Cav1.2 channel was examined using the photoaffinity method. EDA-ATP-biotin maintains Ca(2+) channel activity in inside-out membrane patches. ATP directly bound to the Cav1.2 channel in a dose-dependent manner, and at least two molecules of ATP bound to one molecule of the Cav1.2 channel. Low levels of calmodulin (CaM) increased ATP binding to the Cav1.2 channel, but higher levels of CaM decreased ATP binding to the Cav1.2 channel. In addition, Ca(2+) was another regulator for ATP binding to the Cav1.2 channel. Furthermore, ATP bound to GST-fusion peptides of NH2-terminal region (amino acids 6-140) and proximal COOH-terminal region (amino acids 1,509-1,789) of the main subunit (α1C) of the Cav1.2 channel. Our data suggest that ATP might regulate Cav1.2 channel activity by directly binding to the Cav1.2 channel in a dose-dependent manner. In addition, the ATP-binding effect to the Cav1.2 channel was both CaM- and Ca(2+) dependent.

The Development of a Viral Mediated CRISPR/Cas9 System with Doxycycline Dependent gRNA Expression for Inducible In vitro and In vivo Genome Editing

PubMed Central

de Solis, Christopher A.; Ho, Anthony; Holehonnur, Roopashri; Ploski, Jonathan E.

2016-01-01

The RNA-guided Cas9 nuclease, from the type II prokaryotic Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) adaptive immune system, has been adapted and utilized by scientists to edit the genomes of eukaryotic cells. Here, we report the development of a viral mediated CRISPR/Cas9 system that can be rendered inducible utilizing doxycycline (Dox) and can be delivered to cells in vitro and in vivo utilizing adeno-associated virus (AAV). Specifically, we developed an inducible gRNA (gRNAi) AAV vector that is designed to express the gRNA from a H1/TO promoter. This AAV vector is also designed to express the Tet repressor (TetR) to regulate the expression of the gRNAi in a Dox dependent manner. We show that H1/TO promoters of varying length and a U6/TO promoter can edit DNA with similar efficiency in vitro, in a Dox dependent manner. We also demonstrate that our inducible gRNAi vector can be used to edit the genomes of neurons in vivo within the mouse brain in a Dox dependent manner. Genome editing can be induced in vivo with this system by supplying animals Dox containing food for as little as 1 day. This system might be cross compatible with many existing S. pyogenes Cas9 systems (i.e., Cas9 mouse, CRISPRi, etc.), and therefore it likely can be used to render these systems inducible as well. PMID:27587996

Traveling Wave Modes of a Plane Layered Anelastic Earth

DTIC Science & Technology

2016-05-20

dependent anelastic moduli. The anelastic moduli must be frequency dependent and satisfy the Kramers- Kronig relations to preserve causality. The...the complex, frequency dependent moduli satisfy the Kramers- Kronig relations. Stable, well-behaved numerical algorithms exist for solving the complex

[Effect of chloride ion on corrosion of two commonly used dental alloys].

PubMed

Chen, Lei; Zhang, Weidan; Zhang, Yuanyuan

2014-11-01

To investigate the eff ect of chloride concentration on the corrosion of Co-Cr alloy and pure Ti in a simulated oral environment. The electrochemical corrosion tests of pure Ti and Co-Cr alloy were carried out in neutral artificial saliva solutions with different NaCl concentrations (0.9%, 2.0%, and 3.0%). Th e morphologies of corroded surface for pure Ti and Co-Cr alloy were observed by scanning electron microscope (SEM). Th e changes in the self-corrosion potentials (Ecorr) for pure Ti and Co-Cr alloy in three kinds of artificial saliva solutions was not obvious. However, the self-corrosion current densities (Icorr) of pure Ti were much lower than those of Co-Cr. The Icorr of Co-Cr alloy increased in a concentration-dependent manner of NaCl, whereas the breakdown potential (Eb) of Co-Cr alloy decreased in a concentration-dependent manner. Th e potential ranged for the breakdown of oxide film (Ev) was shortened in a concentration-dependent manner of NaCl. There was no obvious difference in the Icorr of pure Ti with different concentrations of NaCl. The breakdown potential was not seen according to the polarization curves. In a certain range, the increase of the concentration of Cl- leads to accelerate the corrosion behavior of Co-Cr alloy, but it does not affect pure Ti.

Aldosterone concentrations in saliva reflect the duration and severity of depressive episode in a sex dependent manner.

PubMed

Segeda, V; Izakova, L; Hlavacova, N; Bednarova, A; Jezova, D

2017-08-01

Evidence is accumulating that aldosterone may exert central actions and influence mental functions. The aim of the present study was to test the hypothesis that major depressive disorder affects the diurnal variation of salivary aldosterone and that aldosterone concentrations reflect the duration and severity of the depressive episode in a sex dependent manner. The sample consisted of 60 patients (37 postmenopausal women, 23 men) with major depressive disorder. Patients were examined two times, in acute depressive episode (admission to the hospital) and after reaching clinical remission (discharge). The samples of saliva were taken by the patients themselves twice a day (8.00-9.00 h in the morning and in the evening). Aldosterone concentrations were significantly higher in women compared to men and were significantly higher at the time of admission to the hospital compared to those at the discharge. Morning but not evening salivary aldosterone concentrations reflected the length of the depressive episode in women as well as the severity of the disorder in both sexes. Moreover, the patients with depression failed to exert known daily rhythmicity of aldosterone release. The present study brings several pieces of evidence suggesting the association of aldosterone with the pathophysiology of depression. Salivary aldosterone concentrations appear to reflect the outcome, the duration and the severity of the depressive episode in a sex dependent manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

Calcium signals and caspase-12 participated in paraoxon-induced apoptosis in EL4 cells.

PubMed

Li, Lan; Cao, Zhiheng; Jia, Pengfei; Wang, Ziren

2010-04-01

In order to investigate whether calcium signals participate in paraoxon (POX)-induced apoptosis in EL4 cells, real-time laser scanning confocal microscopy (LSCM) was used to detect Ca(2+) changes during the POX application. Apoptotic rates of EL4 cells and caspase-12 expression were also evaluated. POX (1-10nM) increased intracellular calcium concentration ([Ca(2+)]i) in EL4 cells in a dose-dependent manner at early stage (0-2h) of POX application, and apoptotic rates of EL4 cells after treatment with POX for 16h were also increased in a dose-dependent manner. Pre-treatment with EGTA, heparin or procaine attenuated POX-induced [Ca(2+)]i elevation and apoptosis. Additionally, POX up-regulated caspase-12 expression in a dose-dependent manner, and pre-treatment with EGTA, heparin or procaine significantly inhibited POX-induced increase of caspase-12 expression. Our results suggested that POX induced [Ca(2+)]i elevation in EL4 cells at the early stage of POX-induced apoptosis, which might involve Ca(2+) efflux from the endoplasmic reticulum (ER) and Ca(2+) influx from extracellular medium. Calcium signals and caspase-12 were important upstream messengers in POX-induced apoptosis in EL4 cells. The ER-associated pathway possibly operated in this apoptosis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Hedonic sensitivity to low-dose ketamine is modulated by gonadal hormones in a sex-dependent manner

PubMed Central

Saland, Samantha K.; Schoepfer, Kristin J.; Kabbaj, Mohamed

2016-01-01

We recently reported a greater sensitivity of female rats to rapid antidepressant-like effects of ketamine compared to male rats, and that ovarian-derived estradiol (E2) and progesterone (P4) are essential for this response. However, to what extent testosterone may also contribute, and whether duration of response to ketamine is modulated in a sex- and hormone-dependent manner remains unclear. To explore this, we systematically investigated the influence of testosterone, estradiol and progesterone on initiation and maintenance of hedonic response to low-dose ketamine (2.5 mg/kg) in intact and gonadectomized male and female rats. Ketamine induced a sustained increase in sucrose preference of female, but not male, rats in an E2P4-dependent manner. Whereas testosterone failed to alter male treatment response, concurrent administration of P4 alone in intact males enhanced hedonic response low-dose ketamine. Treatment responsiveness in female rats only was associated with greater hippocampal BDNF levels, but not activation of key downstream signaling effectors. We provide novel evidence supporting activational roles for ovarian-, but not testicular-, derived hormones in mediating hedonic sensitivity to low-dose ketamine in female and male rats, respectively. Organizational differences may, in part, account for the persistence of sex differences following gonadectomy and selective involvement of BDNF in treatment response. PMID:26888470

Oxytocin prevents cartilage matrix destruction via regulating matrix metalloproteinases.

PubMed

Wu, Yixin; Wu, Tongyu; Xu, Binbin; Xu, Xiaoyan; Chen, Honggan; Li, Xiyao

2017-05-06

Degradation of the extracellular matrix type II Collagen (Col II) induced by proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) is an important hallmark of Osteoarthritis (OA). Oxytocin (OT) is a well-known neurohypophysical hormone that is synthesized in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus. In this study, we have found that oxytocin receptor (OTR) was expressed in human primary chondrocytes, and the expression of which was reduced in chondrocytes from OA patients and in response to TNF-α treatment in a dose dependent manner. Notably, it was shown that TNF-α -induced degradation of Col II was restored by treatment with OT in a dose-dependent manner. In addition, TNF-α treatment (10 ng/mL) highly elevated the expression of MMP-1 and MMP-13 in SW1353 chondrocytes, which were reversed by OT in a dose dependent manner at both gene and protein expression levels. In addition, it was demonstrated that the JAK2/STAT1 pathway was involved in the restoration effects of OT in the degradation of Col II. Lastly, knockdown of OTR abolished the inhibitory effects of OT on the degradation of col II and the induction of MMP-1 and MMP-13 expression, suggesting the involvement of OTR. Our study implied the therapeutic potential of OT for cartilage degradation. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuron-derived orphan receptor 1 promoted human pulmonary artery smooth muscle cells proliferation.

PubMed

Wang, Chang-Guo; Lei, Wei; Li, Chang; Zeng, Da-Xiong; Huang, Jian-An

2015-05-01

As a transcription factor of the nuclear receptor superfamily, neuron-derived orphan receptor 1 (NOR1) is induced rapidly in response to various extracellular stimuli. But, it is still unclear its role in pulmonary artery smooth muscle cells proliferation. Human PASMCs were cultured in vitro and stimulated by serum. The special antisense oligodeoxynucleotides (AS-ODNs) were used to knockdown human NOR1 gene expression. Real-time PCR and Western-blot were used to evaluate the gene expression and protein levels. Fetal bovine serum (FBS) induced human PASMCs proliferation in a dose dependent manner. Furthermore, FBS promoted NOR1 gene expression in a dose dependent manner and a time dependent manner. 10% FBS induced a maximal NOR1 mRNA levels at 2 h. FBS also induced a significant higher NOR1 protein levels as compared with control. The NOR1 over-expressed plasmid significantly promoted DNA synthesis and cells proliferation. Moreover, the special AS-ODNs against human NOR1 not only prevented NOR1 expression but also inhibited DNA synthesis and cells proliferation significantly. The NOR1 over-expression plasmid could up-regulate cyclin D1 expression markedly, but the AS-ODNs inhibited cyclin D1 expression significantly. So, we concluded that NOR1 could promote human PASMCs proliferation. Cyclin D1 might be involved in this process.

Effect of tributyltin on testicular development in Sebastiscus marmoratus and the mechanism involved.

PubMed

Zhang, Jiliang; Zuo, Zhenghong; He, Chengyong; Cai, Jiali; Wang, Yuqing; Chen, Yixin; Wang, Chonggang

2009-07-01

Organotin compounds, such as tributyltin (TBT), that have been used as antifouling biocides can induce masculinization in female mollusks. However, few studies addressing the effects of TBT on fishes have been reported. The present study was conducted to investigate the effects of TBT at environmentally relevant concentrations (1, 10, and 100 ng/L) on testicular development in Sebastiscus marmoratus and to gain insight into its mechanism of action. After exposure for 48 d, the gonadosomatic index had decreased in a dose-dependent manner. Although the testosterone levels in the testes were elevated and the 17beta-estradiol levels were decreased, spermatogenesis was suppressed. Moreover, gamma-glutamyl transpeptidase activity (which is used as a Sertoli cell marker) was decreased in a dose-dependent manner after TBT exposure, and serious interstitial fibrosis was observed in the interlobular septa of the testes in the 100 ng/L TBT test group. Increases in the retinoid X receptors and peroxisome proliferator activated receptor gamma expression and the progressive enlargement of lipid droplets in the testes were observed after TBT exposure. Estrogen receptor alpha levels in the testes of the fish exposed to TBT decreased in a dose-dependent manner. The reduction of estrogen receptor alpha mRNA resulted from the decrease of 17beta-estradiol levels, and the progressive enlargement of lipid droplets may have contributed to the dysfunction of the Sertoli cells, which then disrupted spermatogenesis.

Oxymatrine inhibits the proliferation of prostate cancer cells in vitro and in vivo

PubMed Central

WU, CUNZAO; HUANG, WEIPING; GUO, YONG; XIA, PENG; SUN, XIANBIN; PAN, XIAODONG; HU, WEILIE

2015-01-01

Oxymatrine is an alkaloid, which is derived from the traditional Chinese herb, Sophora flavescens Aiton. Oxymatrine has been shown to exhibit anti-inflammatory, antiviral, and anticancer properties. The present study aimed to investigate the anticancer effects of oxymatrine in human prostate cancer cells, and the underlying molecular mechanisms of these effects. An MTT assay demonstrated that oxymatrine significantly inhibited the proliferation of prostate cancer cells in a time- and dose-dependent manner. In addition, flow cytometry and a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assay suggested that oxymatrine treatment may induce prostate cancer cell apoptosis in a dose-dependent manner. Furthermore, western blot analysis demonstrated a significant increase in the expression of p53 and bax, and a significant decrease in that of Bcl-2, in prostrate cancer cells in a dose-dependent manner. In vivo analysis demonstrated that oxymatrine inhibited tumor growth following subcutaneous inoculation of prostate cancer cells into nude mice. The results of the present study suggested that the antitumor properties of oxymatrine, may be associated with the inhibition of cell proliferation, and induction of apoptosis, via the regulation of apoptosis-associated gene expression. Therefore, the results may provide a novel approach for the development of prostate cancer therapy using oxymatrine, which is derived from the traditional Chinese herb, Sophora flavescens. PMID:25672672

Phenformin activates the unfolded protein response in an AMP-activated protein kinase (AMPK)-dependent manner.

PubMed

Yang, Liu; Sha, Haibo; Davisson, Robin L; Qi, Ling

2013-05-10

The cross-talk between UPR activation and metabolic stress remains largely unclear. Phenformin treatment activates the IRE1α and PERK pathways in an AMPK-dependent manner. AMPK is required for phenformin-mediated IRE1α and PERK activation. Our findings demonstrate the cross-talk between UPR and metabolic signals. Activation of the unfolded protein response (UPR) is associated with the disruption of endoplasmic reticulum (ER) homeostasis and has been implicated in the pathogenesis of many human metabolic diseases, including obesity and type 2 diabetes. However, the nature of the signals activating UPR under these conditions remains largely unknown. Using a method that we recently optimized to directly measure UPR sensor activation, we screened the effect of various metabolic drugs on UPR activation and show that the anti-diabetic drug phenformin activates UPR sensors IRE1α and pancreatic endoplasmic reticulum kinase (PERK) in both an ER-dependent and ER-independent manner. Mechanistically, AMP-activated protein kinase (AMPK) activation is required but not sufficient to initiate phenformin-mediated IRE1α and PERK activation, suggesting the involvement of additional factor(s). Interestingly, activation of the IRE1α (but not PERK) pathway is partially responsible for the cytotoxic effect of phenformin. Together, our data show the existence of a non-canonical UPR whose activation requires the cytosolic kinase AMPK, adding another layer of complexity to UPR activation upon metabolic stress.

[Effects of sinensetin on proliferation and apoptosis of human gastric cancer AGS cells].

PubMed

Dong, Yang; Ji, Guang; Cao, Aili; Shi, Jianrong; Shi, Hailian; Xie, Jianqun; Wu, Dazheng

2011-03-01

To study the effects and mechanisms of sinensetin on proliferation and apoptosis of human AGS gastric cancer cells. MTT assay was used to detect the growth inhibition rates of human AGS gastric cancer cells treated with sinsesectin in different concentrations and times. The cell cycle distribution was measured by flow cytometry. The apoptosis was examined by Annexin-FITC/PI staining and DNA fragment analysis. The apoptosis morphology was observed by inverted fluorescence microscope after Hoechst 33342 staining. The protein expressions of p21 and p53 were detected by western blot. MTT assay showed that sinensetin inhibited the growth of AGS gastric cancer cells in a dose- and time-dependent manner. Sinensetin blocked AGS cells in G2/ M and increased the apoptosis rates of AGS cells in a dose-dependent manner. DNA ladder was observed in cells treated with 60 micromol x L(-1) sinensetin for 48 h. The typical apoptotic morphological changes including cell nucleus shrinkage, chromatin condensation and apoptotic bodies were observed when treated with different dose of sinensetin. Western blot showed that sinensetin increased expressions of p53 and p21 in a dose-dependent manner. Sinensetin could inhibit human AGS gastric cancer cells proliferation and induce cell cycle block in G2/M phase and apoptosis. The up regulation of p53 and p21 protein might be one of the mechanisms.

Dexamethasone Enhances 1α,25-Dihydroxyvitamin D3 Effects by Increasing Vitamin D Receptor Transcription*

PubMed Central

Hidalgo, Alejandro A.; Deeb, Kristin K.; Pike, J. Wesley; Johnson, Candace S.; Trump, Donald L.

2011-01-01

Calcitriol, the active form of vitamin D, in combination with the glucocorticoid dexamethasone (Dex) has been shown to increase the antitumor effects of calcitriol in squamous cell carcinoma. In this study we found that pretreatment with Dex potentiates calcitriol effects by inhibiting cell growth and increasing vitamin D receptor (VDR) and VDR-mediated transcription. Treatment with actinomycin D inhibits Vdr mRNA synthesis, indicating that Dex regulates VDR expression at transcriptional level. Real time PCR shows that treatment with Dex increases Vdr transcripts in a time- and a dose-dependent manner, indicating that Dex directly regulates expression of Vdr. RU486, an inhibitor of glucocorticoids, inhibits Dex-induced Vdr expression. In addition, the silencing of glucocorticoid receptor (GR) abolishes the induction of Vdr by Dex, indicating that Dex increases Vdr transcripts in a GR-dependent manner. A fragment located 5.2 kb upstream of Vdr transcription start site containing two putative glucocorticoid response elements (GREs) was evaluated using a luciferase-based reporter assay. Treatment with 100 nm Dex induces transcription of luciferase driven by the fragment. Deletion of the GRE distal to transcription start site was sufficient to abolish Dex induction of luciferase. Also, chromatin immunoprecipitation reveals recruitment of GR to distal GRE with Dex treatment. We conclude that Dex increases VDR and vitamin D effects by increasing Vdr de novo transcription in a GR-dependent manner. PMID:21868377

Number Codes Readable by Magnetic-Field-Response Recorders

NASA Technical Reports Server (NTRS)

Woodard, Stanley E.; Taylor,Bryant D.

2009-01-01

A method of encoding and reading numbers incorporates some of the features of conventional optical bar coding and radio-frequency identification (RFID) tagging, but overcomes some of the disadvantages of both: (1) Unlike in conventional optical bar coding, numbers can be read without having a line of sight to a tag; and (2) the tag circuitry is simpler than the circuitry used in conventional RFID. The method is based largely on the principles described in Magnetic-Field-Response Measurement-Acquisition System (LAR-16908), NASA Tech Briefs, Vol. 30, No. 6 (June 2006) page 28. To recapitulate: A noncontact system includes a monitoring unit that acquires measurements from sensors at distances of the order of several meters. Each sensor is a passive radio-frequency (RF) resonant circuit in the form of one or more inductor(s) and capacitor(s). The monitoring unit a handheld unit denoted a magnetic field response recorder (MFRR) generates an RF magnetic field that excites oscillations in the resonant circuits resulting in the sensors responding with their own radiated magnetic field. The resonance frequency of each sensor is made to differ significantly from that of the other sensors to facilitate distinction among the responses of different sensors. The MFRR measures selected aspects of the sensor responses: in a typical application, the sensors are designed so that their resonance frequencies vary somewhat with the sensed physical quantities and, accordingly, the MFRR measures the resonance frequencies and variations thereof as indications of those quantities. In the present method, the resonance circuits are not used as sensors. Instead, the circuits are made to resonate at fixed frequencies that correspond to digits to be encoded. The number-encoding scheme is best explained by means of examples in which each resonant circuit consists of a spiral trace inductor electrically connected to a set of parallel-connected capacitors in the form of interdigitated electrode pairs (see figure). The inductor and capacitor(s) in each resonant circuit can be fabricated as a patterned thin metal film by means of established metal-deposition and -patterning techniques. The capacitance and, hence, the resonance frequency, depends on the number of interdigitated electrodes connected to the inductor. In a similar manner, sets of electrodes could be used.

Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain.

PubMed

Sawicki, C M; McKim, D B; Wohleb, E S; Jarrett, B L; Reader, B F; Norden, D M; Godbout, J P; Sheridan, J F

2015-08-27

Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b(+) cells (microglia/macrophages) and enriched GLAST-1(+)/CD11b(-) cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain region-dependent manner. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.